catena-Poly[[(3-methyl­sulfanyl-1,2,4-thia­diazole-5-thiol­ato)sodium]di-μ-aqua-κ4 O:O]

The crystal structure of the title compound, [Na(C3H3N2S3)(H2O)2]n, features polymeric chains made up of O⋯O edge-shared NaSN(H2O)4 units running along the b axis. The Na+ ion and all non-H atoms of the thia­diazole ligand lie on a mirror plane

Arbitrarily primed sequence-related amplified polymorphism (AP-SRAP)

Sequence-related amplified polymorphism (SRAP) is a new-type molecular technique that targets coding sequences in the genome and results in a moderate number of co-dominant markers. Based on the SRAP program, the random primer combinations of SRAP, amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) were used as new primers in marker analysis. We defined this technique as arbitrarily primed sequence-related amplified polymorphism (AP-SRAP). Of 256 tested AP-SRAP primers, 37.6% primers produced polymorphic patterns from the DNA of one or more species, which showed that AP-SRAP is an effective method to screen markers. Additionally, 80 SRAP primers were used to screen markers in seven plant species (Chinese cabbage, Chinese kale, eggplant, pepper, cucumber, rose and lily), which indicated obvious polymorphism. The primers of AP-SRAP combine simply and reliably. It can overcome the limitation of the number of standard SRAP primers, make greater use of the supply of alternative primers, and potentially reduce laboratory costs. We expect that AP-SRAP may be of wide application in identity testing, population studies, linkage analysis and genome mapping.Keywords: Arbitrarily primed amplification, DNA markers, plantsAfrican Journal of Biotechnology Vol. 12(29), pp. 4588-459

Hepatoprotective effect of Fufang-Huanglu oral liquid on α- naphthylisothiocyanate-induced hepatitis jaundice in mice

Purpose: To investigate the effect of Fufang-Huanglu Oral Liquid (HOL) on hepatitis jaundice in mice.Methods: A total of 72 mice were divided into 6 groups (n = 12): normal group,  control group (model group), positive-treated group, and 3 HOL treatment groups (7.5, 15 and 30 mL/kg). Mice in normal and control groups received normal saline (20 mL/kg) orally, while positive and HOL-treated mice were orally administered Huganning tablets (1.0 g/kg) and HOL (7.5, 15 and 30 mL/kg), respectively. After 8 days, all mice (except normal group) were orally administered  α-naphthylisothiocyanate (ANIT, 100 mg/kg) to induce hepatitis jaundice, and sacrificed 2 days after drug administration. Serum GPT, GOT and TNF-α, as well as liver index, MDA, SOD and lipid profiles were determined.Results: The results showed that HOL, at all doses, significantly decreased liver index, serum GPT, serum SGOT and serum  TNF-α (p < 0.01). HOL also significantly decreased MDA, total cholesterol, TC and triglycerides, TG (p < 0.01), but increased  liver SOD (p < 0.01). Histological results indicate that HOL ameliorated liver injury induced by ANIT.Conclusion: These results showed that HOL possesses significant hepatoprotective effects against liver injury.Keywords: Fufang-Huanglu Oral Liquid, Hepatoprotective, Mice, Hepatitis, Jaundice, α-Naphthylisothiocyanate, Liver inde

Agonist and antagonist effects of aripiprazole on D<inf>2</inf>-like receptors controlling rat brain dopamine synthesis depend on the dopaminergic tone

Supported by grants SAF2006-08240, SAF2009-12510, and Red de Trastornos Adictivos RD06/0001/0015. G.F.M. was the recipient of a CSC fellowship.Background: The atypical antipsychotic drug aripiprazole binds with high affinity to a number of G protein coupled receptors, including dopamine D2 receptors, where its degree of efficacy as a partial agonist remains controversial. Methods: We examined the properties of aripiprazole at D2-like autoreceptors by monitoring the changes of dopamine synthesis in adult rat brain striatal minces incubated ex vivo. The effects of the dopaminergic tone on the properties of aripiprazole were assayed by comparing a basal condition (2 mM K+, low dopaminergic tone) and a stimulated condition (15 mM K+ where dopamine release mimics a relatively higher dopaminergic tone). We also used 2 reference compounds: quinpirole showed a clear agonistic activity and preclamol (S-(-)-PPP) showed partial agonism under both basal and stimulated conditions. Results: Aripiprazole under the basal condition acted as an agonist at D2-like autoreceptors and fully activated them at about 10 nM, inhibiting dopamine synthesis similarly to quinpirole. Higher concentrations of aripiprazole had effects not restricted to D2-like autoreceptor activation. Under the stimulated (15 mM K+) condition, nanomolar concentrations of aripiprazole failed to decrease dopamine synthesis but could totally block the effect of quinpirole. Conclusions: Under high dopaminergic tone, aripiprazole acts as a D2-like autoreceptor antagonist rather than as an agonist. These data show that, ex vivo, alteration of dopaminergic tone by depolarization affects the actions of aripiprazole on D2-like autoreceptors. Such unusual effects were not seen with the typical partial agonist preclamol and are consistent with the hypothesis that aripiprazole is a functionally selective D2R ligand

Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function

BACKGROUND: Molecular and cellular mechanisms of neuropeptide-Y (NPY)-mediated gender-difference in blood pressure (BP) regulation are largely unknown. METHODS: Baroreceptor sensitivity (BRS) was evaluated by measuring the response of BP to phenylephrine/nitroprusside. Serum NPY concentration was determined using ELISA. The mRNA and protein expression of NPY receptors were assessed in tissue and single-cell by RT-PCR, immunoblot, and immunohistochemistry. NPY was injected into the nodose while arterial pressure was monitored. Electrophysiological recordings were performed on nodose neurons from rats by patch-clamp technique. RESULTS: The BRS was higher in female than male and ovariectomized rats, while serum NPY concentration was similar among groups. The sex-difference was detected in Y1R, not Y2R protein expression, however, both were upregulated upon ovariectomy and canceled by estrogen replacement. Immunostaining confirmed Y1R and Y2R expression in myelinated and unmyelinated afferents. Single-cell PCR demonstrated that Y1R expression/distribution was identical between A- and C-types, whereas, expressed level of Y2R was ~15 and ~7 folds higher in Ah- and C-types than A-types despite similar distribution. Activation of Y1R in nodose elevated BP, while activation of Y2R did the opposite. Activation of Y1R did not alter action potential duration (APD) of A-types, but activation of Y2R- and Y1R/Y2R in Ah- and C-types frequency-dependently prolonged APD. N-type ICa was reduced in A-, Ah- and C-types when either Y1R, Y2R, or both were activated. The sex-difference in Y1R expression was also observed in NTS. CONCLUSIONS: Sex- and afferent-specific expression of Neuropeptide-Y receptors in baroreflex afferent pathway may contribute to sexual-dimorphic neurocontrol of BP regulation

Identification of DAPK1 Promoter Hypermethylation as a Biomarker for Intra-Epithelial Lesion and Cervical Cancer: A Meta-Analysis of Published Studies, TCGA, and GEO Datasets

Background: Promoter hypermethylation in death-associated protein kinase 1 (DAPK1) gene has been long linked to cervical neoplasia, but the established results remained controversial. Here, we performed a meta-analysis to assess the associations of DAPK1 promoter hypermethylation with low-grade intra-epithelial lesion (HSIL), high-grade intra-epithelial lesion (HSIL), cervical cancer (CC), and clinicopathological features of CC.Methods: Published studies with qualitative methylation data were initially searched from PubMed, Web of Science, EMBASE, and China National Knowledge Infrastructure databases (up to March 2018). Then, quantitative methylation datasets, retrieved from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, were pooled to validate the results of published studies.Results: In a meta-analysis of 37 published studies, DAPK1 promoter hypermethylation progressively increased the risk of LSIL by 2.41-fold (P = 0.012), HSIL by 7.62-fold (P &lt; 0.001), and CC by 23.17-fold (P &lt; 0.001). Summary receiver operating characteristic curves suggested a potential diagnostic value of DAPK1 promoter hypermethylation in CC, with a large area-under-the-curve of 0.83, a high specificity of 97%, and a moderate sensitivity of 59%. There were significant impacts of DAPK1 promoter hypermethylation on histological type (odds ratio (OR) = 3.53, P &lt; 0.001) and FIGO stage of CC (OR = 2.15, P = 0.003). Then, a pooled analysis of nine TCGA and GEO datasets, covering 13 CPG sites within DAPK1 promoter, identified eight CC-associated sites, six sites with diagnostic values for CC (pooled specificities: 74–90%; pooled sensitivities: 70–81%), nine loci associated with the histological type of CC, and all 13 loci with down-regulated effects on DAPK1 mRNA expression.Conclusion: The meta-analysis suggests that DAPK1 promoter hypermethylation is significantly associated with the disease severity of cervical neoplasia. DAPK1 methylation detection exhibits a promising ability to discriminate CC from cancer-free controls

Semileptonic BcB_c decays and Charmonium distribution amplitude

In this paper we study the semileptonic decays of the $B_c$ meson in the Light-Cone Sum Rule (LCSR) approach. The result for each channel depends on the corresponding distribution amplitude of the final meson. For the case of $B_c$ decaying into a pseudoscalar meson, to twist-3 accuracy only the leading twist distribution amplitude (DA) is involved if we start from a chiral current. If we choose a suitable chiral current in the vector meson case, the main twist-3 contributions are also eliminated and we can consider the leading twist contribution only. The leading twist distribution amplitudes of the charmonium and other heavy mesons are given by a model approach in the reasonable way. Employing this charmonium distribution amplitude we find the cross section $\sigma(e^+e^-\to J/\psi+\eta_c)\simeq22.8 {fb}$ which is consistent with Belle and BaBar's data. Based on this model, we calculate the form factors for various $B_c$ decay modes in the corresponding regions. Extrapolating the form factors to the whole kinetic regions, we get the decay widths and branching ratios for various $B_c$ decay modes including their $\tau$ modes when they are kinematically accessible.Comment: Changed content partially, Added references, 16 pages,2 figure

Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as an adjuvant therapy for ctDNA-positive gastric and gastroesophageal junction adenocarcinoma: a protocol for a randomized, controlled, multicenter phase II clinical trial (EXPLORING study)

BackgroundThe efficacy of current adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. ctDNA could serve as a potential marker to identify patients who are at higher risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly improve clinical outcome, albeit such evidence is rare in GA/GEJA. Here, we intend to explore the clinical benefit of the reinforcement of adjuvant immunotherapy and antiangiogenics alongside with chemotherapy in patients who are deemed in high risk of recurrence by ctDNA analysis, which might shed light on further improvements in adjuvant therapy for GA/GEJA.Methods/DesignThis study is designed as a prospective, multicenter, randomized, controlled phase II study in patients histologically or cytologically diagnosed with GA/GEJA who underwent D2 gastrectomy and achieved R0 or R1 resection. From February 2022, a total of 300 stage III patients will be enrolled and subjected according to ctDNA sequencing results, and those with positive results will subsequently be randomized 1:1 to arm A or B. Patients in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while patients in arm B will receive XELOX alone for 6-8 cycles. ctDNA-negative patients will be assigned to arm C, and patients who are ctDNA positive but failed in randomization will be assigned to arm D. Patients in arms C and D will receive the investigator’s choice of therapy. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the DFS of ctDNA positive patients versus ctDNA negative patients, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules on the treatment response, adverse events (AEs), and the impact of nutrition status or exercise on recurrence.DiscussionWe expect that ctDNA would be a strong prognostic factor and ctDNA-positive patients are at higher risk of relapse than ctDNA-negative patients. The addition of anlotinib and penpulimab to XELOX, may contribute to delaying relapse in ctDNA-positive patients.Trial registrationhttps://www.clinicaltrials.gov, identifier NCT05494060