Search

As the main lymphoid organ, the thymus degenerates with age. The loss of thymic epithelial cells is mainly related to thymus degeneration and reduced T cells development. As an insulin sensitizer, metformin is a first-line drug for the treatment of diabetes and has been shown to prolong the lifespan of mice, but the mechanism is still unclear. In this study, we explored the therapeutic effect of metformin on thymus degeneration in the accelerated aging mice, which was established by intraperitoneal injection D-galactose (120 mg/kg/day) for eight weeks. Metformin was intragastrically given with 100 or 300 mg/kg body weight per day, respectively, for six weeks. Histological examination showed that metformin administration could alleviate thymus atrophy caused by D-galactose. In addition, metformin therapy increased mitochondrial membrane potential, with a reduction in mitochondrial reactive oxygen species, MDA and SOD levels, and restored mitochondrial balance through enhanced expression of dynamin-related protein 1 (Drp1). Furthermore, metformin altered T lymphocyte subsets and cellular senescent cells; the expression of FoxN1, Aire and Sox2 of thymic epithelial cells also increased. Thus, metformin presented a positive effect on thymic degeneration through improving mitochondrial function. Taken together, these findings revealed an unexpected complexity in the anti-aging of this widely used drug.

Purpose The study explores the influences of nutrition-related factors (albumin, hemoglobin, and obesity) and lifestyles (physical activity, fruit and vegetable intake, smoking, and drinking) on the length of hospital stay in postoperative colorectal cancer patients. Methods This study is a cross-sectional design. A convenience sample of 106 preoperative colorectal cancer patients was recruited from a medical center in Taiwan. Data were collected using self-reported questionnaires and from patients' medical records. Results The median length of hospital stay was ten days with an interquartile range ( IQR) of 8–11.25 days. The results of the log-link Gamma generalized linear model showed that albumin ( B = −0.16, p = 0.007) and physical activity (B = −0.14, p = 0.001) were significant predictors of the length of hospital stay after controlling for demographics and disease characteristics. The influences of anemia, obesity, fruit and vegetable intake, smoking, and drinking on the length of hospital stay were insignificant. Conclusions Patients with hypoalbuminemia and a low level of physical activity undergo a more extended postoperative hospital stay. The study findings inform clinicians of the influencing factor of the patients' recovery and provide a foundation for developing interventions to decrease hospital stay length.

Background A vaccine against SARS-CoV-2 is of high urgency. Here the safety and immunogenicity induced by a DNA vaccine (INO-4800) targeting the full length spike antigen of SARS-CoV-2 are described. Methods INO-4800 was evaluated in two groups of 20 participants, receiving either 1.0 mg or 2.0 mg of vaccine intradermally followed by CELLECTRA® EP at 0 and 4 weeks. Thirty-nine subjects completed both doses; one subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose. ClinicalTrials.gov identifier: NCT04336410. Findings The median age was 34.5, 55% (22/40) were men and 82.5% (33/40) white. Through week 8, only 6 related Grade 1 adverse events in 5 subjects were observed. None of these increased in frequency with the second administration. No serious adverse events were reported. All 38 subjects evaluable for immunogenicity had cellular and/or humoral immune responses following the second dose of INO-4800. By week 6, 95% (36/38) of the participants seroconverted based on their responses by generating binding (ELISA) and/or neutralizing antibodies (PRNT IC50), with responder geometric mean binding antibody titers of 655.5 [95% CI (255.6, 1681.0)] and 994.2 [95% CI (395.3, 2500.3)] in the 1.0 mg and 2.0 mg groups, respectively. For neutralizing antibody, 78% (14/18) and 84% (16/19) generated a response with corresponding geometric mean titers of 102.3 [95% CI (37.4, 280.3)] and 63.5 [95% CI (39.6, 101.8)], in the respective groups. By week 8, 74% (14/19) and 100% (19/19) of subjects generated T cell responses by IFN-ɣ ELISpot assay with the median SFU per 106 PBMC of 46 [95% CI (21.1, 142.2)] and 71 [95% CI (32.2, 194.4)] in the 1.0 mg and 2.0 mg groups, respectively. Flow cytometry demonstrated a T cell response, dominated by CD8+ T cells co-producing IFN-ɣ and TNF-α, without increase in IL-4. Interpretation INO-4800 demonstrated excellent safety and tolerability and was immunogenic in 100% (38/38) of the vaccinated subjects by eliciting either or both humoral or cellular immune responses. Funding Coalition for Epidemic Preparedness Innovations (CEPI).

One of the principal signaling pathway outcomes from brain-derived neurotrophic factor (BDNF) is the activation of antiapoptotic pathways. In addition to the role of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3 kinase, BDNF activates protein kinase CK2 to mediate its neuroprotective effect. The inhibition of CK2 activity has been shown to induce apoptosis. Although serum response element (SRE)-mediated transcription has been reported to be activated by BDNF and that the phosphorylation of serum response factor (SRF) by CK2 has been shown to enhance its DNA binding activity, the biological relevance of these interactions remains largely unclear. In the present study, we found that SRE-mediated transcription, CK2 activity, and SRF phosphorylation increased in PC12 cells under BDNF treatment. The transfection of CK2α siRNA blocked the enhancing effect of BDNF on SRE-mediated transcription, SRF phosphorylation, and Mcl-1 gene expression. Moreover, the blockade of CK2 diminished the antiapoptotic effects of BDNF on SRE-mediated transcription, Mcl-1 gene expression, and cell viability under rotenone-induced cytotoxicity. Our data may assist in the development of therapeutic strategies for inhibiting apoptosis during neurodegeneration.

Purpose Health self-management helps improve health-related quality of life and life satisfaction, as well as cancer survival. The study aim was to explore the essence of the health self-management experiences and support needs of colorectal cancer patients after surgeries. Methods The study was based on phenomenology research methodology. Purposive sampling was used to obtain a heterogeneous sample to provide rich information regarding the research questions. Participants were recruited from colorectal surgery outpatient clinics in a hospital in Taiwan. Data were collected by semi-structured in-depth interviews and analyzed by thematic content analysis. Strategies adapted from Lincoln and Guba were used to enhance the trustworthiness of the study. Results Ten participants, 5 males and 5 females, were interviewed. Their health self-management experience fell into 3 overarching themes and 9 related subthemes. Our results show that (1) seeking support when experiencing discomfort, (2) when life changes, re-adjust accordingly, and (3) staying positive and self-perseverance are the essences of the health self-management experiences and support needs of postoperative colorectal cancer patients. Conclusions Postoperative colorectal cancer patients experienced tremendous physical and psychosocial challenges after returning home from the hospital. Although burdened with multiple stressors, these patients were able to seek support, learning to practice self-care, facing cancer positively, and exhibit positive growth in life. Patients with colorectal cancer have to constantly adjust to the impacts of their diseases. The study results may provide as a reference for supporting postoperative adjustment and promoting health self-management among patients with colorectal cancer.

The analysis of sequence conservation is commonly used to predict functionally important sites in proteins. We have developed an approach that first identifies highly conserved sites in a set of orthologous sequences using a weighted substitution-matrix-based conservation score and then filters these conserved sites based on the pattern of conservation present in a wider alignment of sequences from the same family and structural information to identify surface-exposed sites. This allows us to detect specific functional sites in the target protein and exclude regions that are likely to be generally important for the structure or function of the wider protein family. We applied our method to two members of the serpin family of serine protease inhibitors. We first confirmed that our method successfully detected the known heparin binding site in antithrombin while excluding residues known to be generally important in the serpin family. We next applied our sequence analysis approach to neuroserpin and used our results to guide site-directed polyalanine mutagenesis experiments. The majority of the mutant neuroserpin proteins were found to fold correctly and could still form inhibitory complexes with tissue plasminogen activator (tPA). Kinetic analysis of tPA inhibition, however, revealed altered inhibitory kinetics in several of the mutant proteins, with some mutants showing decreased association with tPA and others showing more rapid dissociation of the covalent complex. Altogether, these results confirm that our sequence analysis approach is a useful tool that can be used to guide mutagenesis experiments for the detection of specific functional sites in proteins.

Two novel complexes, {Cu2[5-(NO2)sal]2 (DMF)4}2 (1) and {Co[5-(NO2)sal] (H2O)3}2 (2), have been prepared and characterized by elemental analysis, IR spectrum, and X-ray single-crystal diffraction. Complex 1 is a four nuclear Cu(II) complex and belongs to monoclinic system with space group C 2/c, a = 23.541(2) A, b = 14.8150(12) A, c = 22.459(2) A, β = 104.361(2)°, V = 7588.0(12) A3, D c = 1.368 Mg/m3, Z = 4, F(000) = 3216, R 1 = 0.0826, wR 2 = 0.2212 [I>2σ(I)] Every Cu(II) atom is six-coordinated by three O atoms from two 5-(NO2)sal and two O atoms from two DMF and one bridged O atom. The distance of Cu···Cu are 4.5027(14), 5.817(2), and 5.526(2) A. Complex 2 is a dinuclear Co(II) complex and belongs to monoclinic system with space group P 21/c, a = 10.9003(9) A, b = 13.6938(15) A, c = 6.6781(5) A, β = 91.223(1)°, V = 996.59(16) A3, D c = 1.748 Mg/m3, Z = 2, F(000) = 596, R 1 = 0.1058, wR 2 = 0.3098 [I>2σ(I)] Every Co(II) atom is six-coordinated by two O atoms from one 5-(NO2)sal and three O atoms from th...

The golf course industry has become increasingly aware of potential problems related to pesticide and fertilizer movement from soil into surface water and groundwater . The objective of this study was to monitor and analysis the pollution level and scope, varying pattern, diffusion characteristics and the impact on the lake which are influenced by the Spring City Golf Course located in the catchment area of Yangzonghai Lake. It produced data on the quality of the surface water bodies, groundwater and soil environment including nitrogen, phosphorus, pesticides and heavy metal , and proposed some control measures in the last part.

An M[X]/G/1 retrial G-queue with single vacation and unreliable server is investigated in this paper. Arrivals of positive customers form a compound Poisson process, and positive customers receive service immediately if the server is free upon their arrivals; Otherwise, they may enter a retrial orbit and try their luck after a random time interval. The arrivals of negative customers form a Poisson process. Negative customers not only remove the customer being in service, but also make the server under repair. The server leaves for a single vacation as soon as the system empties. In this paper, we analyze the ergodical condition of this model. By applying the supplementary variables method, we obtain the steady-state solutions for both queueing measures and reliability quantities.

A new Schiff base, N,N′-bis(4-methoxy-benzylidene)-1,4-bis(3-aminopropyl)piperazine (BMBA), has been synthesized by the reaction of 1,4-bis(3-aminopropyl)piperazine and 4-methoxy-benzaldehyde in methanol solution. The title compound was characterized by elemental analysis, IR spectrum, 1H NMR, 13C NMR and X-ray single crystal diffraction analyses. The compound crystallizes in the monoclinic system with space group C2/c and a = 24.071(5), b = 9.4035(19), c = 11.263(2) A, β = 96.787(2)°, V = 2531.6(9) A3, D c = 1.193 g/cm3, M r = 454.60, Z = 4, F (000) = 984, μ = 0.079 mm−1, R 1 = 0.0693, and ωR 2 = 0.2269. In the crystal structure, molecules of BMBA and water of crystallization are linked through intermolecular O2W–H2′···N2 hydrogen bond, forming a 1D hydrogen bonding network that generates planar “ribbons” running parallel to the c-axis. Furthermore, the antibacterial activity of title compound was investigated preliminary by agar diffusion method, and it exhibited certain inhibited effect against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. A new Schiff base, N,N′-bis(4-methoxy-benzylidene)-1,4-bis(3-aminopropyl)piperazine, has been synthesized by the reaction of 1,4-bis(3-aminopropyl)piperazine and 4-methoxy-benzaldehyde in methanol solution, and characterized by elemental analysis, IR spectrum, 1H NMR, 13C NMR and X-ray single crystal diffraction analyses. Furthermore, the antibacterial activity was investigated by agar diffusion method, and the results indicated that the Schiff base was active relatively against Escherichia coli, Staphylococcus aureus and Bacillus subtilis.

Objective: To investigate diagnostic value of ultrasonography scores (US) and contrast-enhanced ultrasonography (CEUS) in evaluating rheumatoid arthritis (RA) activity. Methods: 39 patients with RA were included and the metacarpophalangeal, proximal interphalangeal, wrist, elbow and knee joints of them were examined by high frequency ultrasound. The severe joints and the related indexes (synovial thickness, synovial blood flow, joint effusion and bone erosion) were exposed. Then scores (0~3) were obtained and the sum was calculated. For 12 patients of the 39, 2.4 ml SonoVue was intravenously injected with observation of synovial enhancing. ROIs time-intensity curve (TIC) was obtained and the parameters including area under curve (AUC), peak intensity (PI) and time to peak (TTP) were analyzed. For 39 patients, the relationships among each parameters, ultrasonography scores, DAS28 scores and biochemical examinations (ESR, CRP, RF, anti-CCP) were analyzed. Results: The US were significantly correlated with DAS28 Scores (r=0.823, P

A surge of prolactin (PRL) occurs in female rats during proestrus in response to elevated estradiol and progesterone levels. Dopamine is the primary hypothalamic inhibitor of PRL secretion from the pituitary. Using double-label immunocytochemistry, we investigated the pattern of estrogen receptor-alpha (ER-alpha) immunoreactivity in dopaminergic neurons in the arcuate nucleus (ARC) and the periventricular nucleus (PeVN) during the proestrous PRL surge and compared it to that during diestrus, when PRL levels are constantly low. Our results showed that during diestrus80% of dopaminergic neurons in the ARC were also positive for ER-alpha, and this colocalization percentage decreased significantly during proestrus. By contrast,15% of dopaminergic neurons in the PeVN expressed ER-alpha, and the low percentage of ER-alpha expression was unchanged throughout proestrus and diestrus. Results from estrogen plus progesterone treated ovariectomized rats showed similar patterns of ER-alpha expression within the ARC and the PeVN and, once again, compared with the control group, had a significant reduction in ER-alpha immunoreactivity in dopaminergic neurons in the ARC, but not in the PeVN. These results provide an anatomic basis that dopaminergic neurons in the ARC and the PeVN are functionally different regarding to ER-alpha expression. Our study also supports the hypothesis that dopaminergic neurons in the ARC are an important neuronal population responsive to estrogen by changing the expression of ER-alpha in those neurons. This modification of sensitivity of dopaminergic neurons in the ARC in response to ovarian steroids may be an important molecular mechanism involved in PRL regulation, including the regulation of the proestrous surge of PRL.

Nitric oxide (NO)-containing neurons have been localized in various parts of the central nervous system including the hypothalamus. NO plays an important role in the regulation of reproductive activities including sexual behavior and pituitary hormone secretion. To test the hypothesis that NO-containing neurons in specific brain areas may respond to the stimulus of mating and participate in integrating the tactile information in the hypothalamus, this study used Fos as a marker of neuronal activity. Proestrous rats receiving intromissions (mated group) from males or mounts-without-intromission (mounted group) were sacrificed along with rats taken directly from their home cage (control group) 90 min after the beginning of mating or mounting. NOergic neurons were labeled by histochemical reaction for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). The presence of activated NO-producing (double-stained NADPH-d/Fos) neurons was quantitatively assessed in several brain areas before and after mating. The results showed that mating-with-intromissions induced a significant increase in the percentage of NADPH-d/Fos colabeled neurons in the medial preoptic area (mPOA) and the magnocellular component of the paraventricular nucleus (PVNm) compared to mounts-without-intromission or control treatment. Both mating and mounting induced Fos expression in NADPH-d-positive cells in the ventromedial nucleus of hypothalamus (VMN). In contrast, the expression of Fos in the NADPH-d-positive neurons in the supraoptic nucleus (SON) and the parvocellular portion of the paraventricular nucleus (PVNp) was not influenced by either mating or mounting although abundant NO-containing neurons were found in the two brain areas. The second experiment of the study examined whether NOergic neurons in these brain areas are influenced directly by estrogen by determining the number of NADPH-d-positive neurons that contained the estrogen receptor alpha (ERalpha), the classical ER. Double labeled NADPH-d/ERalpha neurons were observed in several brain areas including the mPOA and VMN while few, if any, NADPH-d-positive neurons in the SON, PVNm or PVNp contained ERalpha. The results suggest that the activated NOergic neurons in these brain areas may be involved in processing and integrating the mating stimulus. Further investigation is required to determine the physiological role of the mating-activated NOergic activity in specific mating-induced changes in reproductive neuroendocrinology.

Pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) is suppressed by alpha-adrenergic antagonists in ovariectomized (OVX) rabbits, thus suggesting that initiation of GnRH pulses requires the presence of norepinephrine (NE) stimulation. Terminals of NE neurons are located in proximity with GnRH cells in the hypothalamus, including the arcuate nucleus-median eminence (AME) region. Synaptic NE molecules may be catabolized or transported back to NE terminals (i.e. reuptake) via specific NE transporter proteins (NET). Thus, the amount of synaptic NE acting on GnRH cells is a function of the rate of NE release, metabolism and reuptake. Hypothetically, the rise and fall of a GnRH pulse may be associated with the similar fluctuations of synaptic NE release and/or NET activity. To test this hypothesis, we examined the effects of AME administration of desipramine (DMI, a specific NET blocking drug) on GnRH release. First, we delivered 0.2-10 mM doses of DMI continuously for 1 h via an AME microdialysis (microD) system into intact male rabbits. We found that each AME-DMI infusion, between dosages of 1 mM and 10 mM, stimulated a GnRH pulse, and that the size of these GnRH pulses were proportional to the dosage of DMI. To confirm the specificity of DMI on NET, we measured catecholamine content in microD samples by HPLC. The temporal (60 min) DMI induced a pattern of NE release that included a rising limb within the first 20-30 min; although NE returned to baseline values within the period of DMI treatment. Neither epinephrine nor dopamine levels were changed by DMI. Second, a median dose of DMI (5 mM) was given by microD for 60 min in four separate rabbit models: gonadal intact females (F-INT), intact males (M-INT), gonadectomized females (F-GDX) and castrated males (M-GDX). Individual microD samples were measured for NE and GnRH. Regardless of gender or gonadal status, 5 mM of DMI concomitantly induced a pulse-like release of NE and GnRH. Furthermore, the response of GnRH to DMI was greater in GDX rabbits than in INT animals of both genders. Third, we administered DMI (5 mM) for 30 min via a push-pull perfusion (PPP) system during four repeated 90 min intervals, in either F-INT or ovariectomized (F-GDX) females, and measured GnRH in PPP samples. In both F-INT and F-GDX, each DMI challenge induced a GnRH pulse. In F-INT, all sequential DMI-induced GnRH pulses were nearly equal in size. In contrast, in F-GDX, the first DMI-induced GnRH pulse was greater than subsequent ones. Collectively, these observations are consistent with the concept of noradrenergic regulation of pulsatile GnRH release, and we conclude that the temporal activity of NET may be an integral part of the mechanism by which GnRH pulses operate.

The analysis of sequence conservation is commonly used to predict functionally important sites in proteins. We have developed an approach that first identifies highly conserved sites in a set of orthologous sequences using a weighted substitution-matrix-based conservation score and then filters these conserved sites based on the pattern of conservation present in a wider alignment of sequences from the same family and structural information to identify surface-exposed sites. This allows us to detect specific functional sites in the target protein and exclude regions that are likely to be generally important for the structure or function of the wider protein family. We applied our method to two members of the serpin family of serine protease inhibitors. We first confirmed that our method successfully detected the known heparin binding site in antithrombin while excluding residues known to be generally important in the serpin family. We next applied our sequence analysis approach to neuroserpin and used our results to guide site-directed polyalanine mutagenesis experiments. The majority of the mutant neuroserpin proteins were found to fold correctly and could still form inhibitory complexes with tissue plasminogen activator (tPA). Kinetic analysis of tPA inhibition, however, revealed altered inhibitory kinetics in several of the mutant proteins, with some mutants showing decreased association with tPA and others showing more rapid dissociation of the covalent complex. Altogether, these results confirm that our sequence analysis approach is a useful tool that can be used to guide mutagenesis experiments for the detection of specific functional sites in proteins.

Central catecholaminergic systems play an important role in the control of reproductive activities including sexual behavior, luteinizing hormone (LH) and prolactin secretion. It has been reported that catecholaminergic neurons in the locus coeruleus (A6) are activated by mating in rabbits and ferrets, animals known as reflex ovulators. This study used Fos as a marker of neuronal activity to examine whether brainstem catecholaminergic neurons are activated by mating in the spontaneous ovulator, the female rat. Proestrous rats receiving intromissions (mated group) from males or mounts-without-intromission (mounted group) were sacrificed along with rats taken directly from their home cage (control group) 90 min after the beginning of mating or mounting. Double-label immunocytochemistry was used to examine the expression of c-Fos in catecholaminergic neurons labeled by tyrosine hydroxylase (TH) antibody, or adrenergic neurons labeled by phenylethanolamine-N-methyl transferase (PNMT) antibody. Double label immunofluorescent immunohistochemistry was used to determine the number of neurons containing the estrogen receptor (ERalpha) that were activated by mating in these brain areas. The results showed that mating-with-intromissions induced a significant increase in the percentage of TH/Fos colabeled neurons in both A1 and A2 cells compared to mounting-without-intromission or control. In both these areas, over 50% ERalpha-ir neurons were activated after mating while mounting-without-intromission did not affect the percentage of colabeled Fos/ERalpha neurons. In A6 region, neither the expression of Fos nor the percentage of TH/Fos colabeled cells was influenced by either mating or mounting compared to controls. The percentage of PNMT-containing neurons colabeled with Fos was not different in C1 and C2 among the three experimental groups. The results indicate that catecholaminergic neurons were activated by mating in A1 and A2 but not in adjoining adrenergic C1 and C2 cells. In contrast to the findings that catecholaminergic neurons in A6 are activated by mating in induced ovulators, mating did not affect neuronal activity in A6 neurons in the female rat. In A1 and A2 areas, a high percentage of neurons containing ERalpha were activated by mating suggesting both tactile and hormonal information may converge on these populations of neurons. The activated catecholaminergic neurons in A1 and A2 may be an important pathway by which sensory information generated during sexual interaction modulates both behavior and pituitary function.

This work measured the dilution heat of phosphatidylcholine (PC) vesicles incorporated with various amounts of cholesterol using isothermal titration calorimetry (ITC). The interaction potential between these PC vesicles was analyzed and the changing size of the PC vesicles response to various shear force and the zeta potential of the PC vesicles were also measured and discussed along with the ITC results. Experimental data indicate that the repulsive surface potential and the repulsive electrostatic force increases as cholesterol is incorporated into the bilayer. This phenomenon can be attributed to the decrease in the binding ability between the PC vesicular surfaces and the cations in the buffer solution. Incorporating cholesterol into the bilayer promotes the repulsive surface potential (or energy barrier) between the PC vesicles from the surface potential viewpoint. Additionally, incorporating cholesterol into the bilayer makes the PC vesicles more rigid and sustains more severe shear stress in our shear forces studies. This work also reveals that temperature and PC vesicular stability are correlated with each other. The stability of PC vesicles are likely to decline with a rise in the temperature, and the elevated temperature effect is evidence of the rigidity or curvature of the PC vesicles. Furthermore, the repulsive surface potential (or energy barrier) between the PC vesicles declines with a rise in temperature.

In the title compound, [Cu(2)(C(19)H(24)N(2)O(4))(2)(H(2)O)(2)].2H(2)O, the asymmetric unit consists of one half of the bis{mu-6,6'-dimethoxy-2,2'-[propane-1,2-diylbis(iminomethylene)]diphenolato}bis[aquacopper(II)] complex and two water molecules. Two Cu(II) centres are bridged through a pair of phenolate groups, resulting in a complex with a centrosymmetric structure, with the centre of inversion at the middle of the Cu(2)O(2) plane. The Cu atoms are in a slightly distorted square-pyramidal coordination environment (tau = 0.07). The average equatorial Cu-O bond length and the axial Cu-O bond length are 1.928 (3) and 2.486 (3) A, respectively. The Cu-O(water) bond length is 2.865 (4) A, so the compound could be described as having a weakly coordinating water molecule at each Cu(II) ion and two solvent water molecules per dimetallic unit. The Cu...Cu distance and Cu-O-Cu angle are 3.0901 (10) A and 87.56 (10) degrees , respectively. The molecules are linked into a sheet by O-H...O and C-H...O hydrogen bonds parallel to the [001] plane.

A prolactin (PRL) surge occurs in the female rat during proestrus in response to elevated estradiol levels. The elevated release of ovarian steroids on the day of proestrus is also associated with sexual receptivity. Mating triggers twice-daily PRL surges that supplant the proestrous PRL surge and are responsible for maintaining luteal function during the first half of pregnancy. In order to understand the neuronal mechanisms controlling the proestrous- and mating-induced PRL surges, we examined patterns of Fos expression by immunocytochemistry in specific brain regions as a measure of neuronal activity. Intact female rats were sacrificed at 09.00, 15.00, and 18.00 h on the day of proestrus and the day of diestrus. Brain tissues were also collected at 21.00 h on the day of proestrus from rats receiving intromissions or mounts from males or taken directly from their homecage. On the day of proestrus, the number of neurons expressing Fos in the medial preoptic area (mPOA), medial amygdaloid nucleus (mAMYG), and ventromedial nucleus of the hypothalamus (VMH) was few and was associated with low plasma PRL levels at 09.00 h; however, the number of Fos-positive cells in these brain regions significantly increased at 15.00 and 18.00 h when the proestrous PRL surge occurred. Mating during the evening of proestrus resulted in a dramatic increase in the number of Fos-positive cells in the mPOA, mAMYG, and VMH as well as in the arcuate nucleus (ARC). Nonmated animals in diestrus showed low and unchanged PRL levels and Fos expression in all the brain areas throughout the day. These results suggest that the mPOA, mAMYG, VMH and ARC may be important brain sites for the integration of stimuli associated with proestrous- and mating-induced PRL surges.

The title compound, [Ni(C19H25N2O4)(C2H6O)(H2O)]NO3, assembles into centrosymmetric dinuclear complexes through a pair of strong O—H⋯O hydrogen bonds.

In the title compound, C18H26N2O42+·2NO3−, the ions are linked into two chains by C—H⋯O hydrogen bonds; these chains are linked into sheets parallel to (001). The asymmetric unit consists of one cation, two half-cations and four anions. Two of the cations have a centre of symmetry at the mid-point of the central C—C bond.

In the title compound, [Ce(C18H22N2O4)2], the Ce atoms are eight-coordinate and there are three independent mol­ecules in the asymmetric unit. Two tetra­dentate N,N′-(2-hydr­oxy-3-methoxy­benz­yl)ethane-1,2-diamine ligands are coordinated to each CeIV atom. The mol­ecules are linked into a chain by three C—H⋯O hydrogen bonds. Neighbouring chains are connected by van der Waals forces, resulting in a three-dimensional network.

Mol­ecules of the title compound, C24H26N4, are linked by C—H⋯N hydrogen bonds, forming a C(5) chain along the [010] direction. Neighboring chains are connected by four C—H⋯π inter­actions, resulting in the formation of a three-dimensional network.

In the title compound, C22H20N2O4, the mol­ecule is centrosymmetric. The mol­ecules are linked by one C—H⋯O and one C—H⋯π inter­action into an [001] chain of R22(30) rings and an [010] chain of R22(22) rings.

The title compound, C22H28N2O4, is a potential multidentate azomethine ligand. The asymmetric unit contains two half-molecules, each molecule lying on a centre of symmetry. The mol­ecules are linked into sheets and a three-dimensional network by C—H⋯O hydrogen bonds and van der Waals forces.

In the title compound, C17H16N2, the 1,4-diazepine ring adopts a distorted boat conformation, in which the sum of the inter­nal angles is 809°. The mol­ecules are linked by a pair of C—H⋯N hydrogen bonds into a C22(14) chain along the [10\overline{1}] direction.

In the title compound, [Yb(NO3)3(C12H8N2)2], two bidentate 1,10-phenanthroline ligands and three bidentate nitrate anions are coordinated to the Yb cation. A crystallographic twofold rotation axis passes through the Yb atom and one nitrate group. The mol­ecules are linked into a three-dimensional network by five C—H⋯O hydrogen bonds.

The title compound, C17H16Cl2N2, adopts a `vault' conformation. The mol­ecules are linked by a pair of C—H⋯N hydrogen bonds into a centrosymmetric dimer with an R22(18) ring. These dimers are linked by a weak centrosymmetric π–π inter­action into a chain along the [001] direction, and these chains are connected by van der Waals inter­actions, resulting in a three-dimensional network structure.

In the title compound, C12H11NO3, the mol­ecules have one intra­molecular C—H⋯O hydrogen bond and are linked by N—H⋯O and C—H⋯O hydrogen bonds. Neighbouring sheets are linked by π–π stacking inter­actions.

In the title compound, C18H17N3O4, the mol­ecule has a trans configuration; the dihedral angle between the benzene rings is 34.4 (1)°. The mol­ecules are linked into centrosymmetric dimers with edge-fused [R21(6)][R22(10)][R21(6)] rings by C—H⋯O hydrogen bonds, and these dimers are linked by C—H⋯O weak inter­actions into a ribbon along [101]. Adjacent ribbons are linked into a three-dimensional network structure by π–π stacking inter­actions.