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The Drosophila lymph gland is an ideal model for studying hematopoiesis, and unraveling the mechanisms of Drosophila hematopoiesis can improve our understanding of the pathogenesis of human hematopoietic malignancies. Bone morphogenetic protein (BMP) signaling is involved in a variety of biological processes and is highly conserved between Drosophila and mammals. Decapentaplegic (Dpp)/BMP signaling is known to limit posterior signaling center (PSC) cell proliferation by repressing the protooncogene dmyc . However, the role of two other TGF-β family ligands, Glass bottom boat (Gbb) and Screw (Scw), in Drosophila hematopoiesis is currently largely unknown. Here, we showed that the loss of Gbb in the cortical zone (CZ) induced lamellocyte differentiation by overactivation of the EGFR and JNK pathways and caused excessive differentiation of plasmatocytes, mainly by the hyperactivation of EGFR. Furthermore, we found that Gbb was also required for preventing the hyperproliferation of the lymph glands by inhibiting the overactivation of the Epidermal Growth Factor Receptor (EGFR) and c-Jun N-terminal Kinase (JNK) pathways. These results further advance our understanding of the roles of Gbb protein and the BMP signaling in Drosophila hematopoiesis and the regulatory relationship between the BMP, EGFR, and JNK pathways in the proliferation and differentiation of lymph gland hemocytes.

Purpose: The effectiveness of robot-assisted gait training (RAGT) in children with cerebral palsy (CP), especially in terms of improving the performance of daily activities, remains unclear. Therefore, we aimed to investigate the effectiveness of RAGT in children with CP., Methods: In this single-center, single-blinded, randomized cross-over trial, we enrolled 20 children with CP with Gross Motor Function Classification System (GMFCS) levels II-IV (13 males; age range, 6.75 ± 2.15 years). The participants were randomized into the RAGT/standard care (SC) ( n = 10) and SC/RAGT/SC sequence groups ( n = 10). Using a Walkbot-K system, the RAGT program comprised 3 × 30-min sessions/week for 6 weeks with a continued SC program. The SC program comprised 2-4 conventional physiotherapy sessions/week for 6 weeks. The Gross Motor Function Measure-88 (GMFM-88), the pediatric functional independence measure (WeeFIM), and the Canadian occupational performance measure (COPM) scores were assessed pre- and post-RAGT or SC periods and treatment, period, follow-up, and carry-over effects were analyzed. Energy expenditure and body composition were measured pre- and post-RAGT., Results: Significant treatment effects were observed in dimensions D and E of the GMFM (D: p = 0.018; E: p = 0.021) scores, WeeFIM mobility subtotal ( p = 0.007), and COPM performance ( p < 0.001) and satisfaction ( p = 0.001) measure scores. The period, follow-up, and carry-over effects were not statistically significant. The gross energy cost significantly decreased ( p = 0.041) and the skeletal muscle mass increased ( p = 0.014) at post-RAGT assessment. The factors associated with functional outcomes showed significant improvements in the GMFM D scores and were mainly observed in children with GMFCS levels II-III compared to those classified at level IV ( p = 0.038)., Conclusion: RAGT had training benefits for children with CP. Specifically, it improved locomotor function and functional capability for daily activities. These effects were better in ambulatory children with CP. However, as SC interventions continued during the RAGT period, these improvements may be also related to multiple treatment effects.

AMP-activated protein kinase (AMPK) has been implicated in contractility changes in bladders with partial bladder outlet obstruction (PBOO), but the role of AMPK in the contractile response of normal bladder remains unclear. We investigated the phosphorylation of AMPKα and expression of the involved upstream AMPK kinases (AMPKKs) in a model of bladders with PBOO and sought to determine whether the pharmacological inhibition of these two factors affected detrusor contractility in normal bladders, using female Sprague-Dawley rats. Cystometry and Western blot analysis were performed in rats that were subjected to PBOO induction or a sham operation. Cystometry was performed in normal rats that received selective inhibitors of AMPKα and Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKKβ) (compound C and STO-609, respectively) at doses determined in the experiments. In the PBOO bladders, bladder weight and micturition pressure (MP) were higher and AMPKα phosphorylation (T172) and CaMKKβ expression was significantly reduced. Compound C and STO-609 increased MP. The increased contractile response in bladders with PBOO-induced hypertrophy was related to decreased CaMKKβ/AMPK signaling activity, and the pharmacological inhibition of this pathway in normal bladders increased detrusor contractility, implying a role of CaMKKβ/AMPK signaling in the bladder in the regulation of detrusor contractility.

The current study targets the chemical constituents of Caesalpinia decapetala (Roth) Alston and investigates the bioactivities of the isolated compounds. Fourteen known compounds were isolated using column chromatography, and structural identification was performed by physical and spectral analyses. The biological activities of the compounds were also evaluated by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 2,2-diphenlyl-1-picrylhydrazyl (DPPH) assays. Emodin (6), baicalein (9), and apigenin (12) displayed antitumor activities against the MGC-803 cell line, while quercetin (2), rutin (5), baicalein (9), and epicatechin (13) showed stronger DPPH scavenging activities compared with ascorbic acid. Andrographolide (1), quercetin (2), bergenin (4), rutin (5), emodin (6), betulin (7), baicalein (9), polydatin (10), salicin (11), and apigenin (12), were obtained from C. decapetala (Roth) Alston for the first time.

The involuntary dual control systems of the autonomic nervous system (ANS) in the bladder of awake spontaneously hypertensive rats (SHRs) were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO) objectively as a core symptom of an overactive bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%). DO frequency decreased from 0.98 ± 0.22 min(-1) to 0.28 ± 0.19 min(-1) (p < 0.01), and DO pressure decreased from 3.82 ± 0.57 cm H(2)O to 1.90 ± 0.86 cm H(2)O (p < 0.05). This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required.

Asymmetric addition under mild conditions of dialkyl phosphites on aldimines derived from cinnamaldehyde catalyzed by the inexpensive chiral organocatalyst (R)-3,3'-[4-fluorophenyl](2)-1,1'-binaphthol phosphate has been found effective to give new alpha-amino-phosphonates 9 in moderate yields (30-65%) and enantiomeric excess (8.4%-61.9%).

Alkyl 2-cyano-3-methylthio-3-phosphonylacrylates were synthesized by the reaction of alkyl 2-cyano-3,3-dimethylthioacrylates with dialkyl phosphites. The structures of the new compounds were characterized by elemental analyses, IR, 1H-, 13C- and 31P-NMR spectral data. These compounds were tested in vitro against pathogenic fungi, namely, Fusarium graminearum, Cytospora mandshurica and Fusarium oxysporum. Amongst all compounds, 2d and 2t were found to be effective against the tested fungi at 50 microg/mL. A half-leaf method was used to determine the in vivo protective, inactivation and curative efficacies of the title products against tobacco mosaic virus (TMV). Title compounds 2a and 2b were found to possess good in vivo curative, protection and inactivation effects against TMV with inhibitory rates at 500 mg/L of 60.0, 89.4 and 56.5 and 64.2, 84.2 and 61.2 %, respectively. To the best of our knowledge, this is the first report on the antiviral and antifungal activity of alkyl 2-cyano-3-methylthio-3-phosphonylacrylates.