The synthesis and anti-tumour properties of novel 4-substituted phthalazinones as Aurora B kinase inhibitors.

A series of novel 4-substituted phthalazinones as Aurora B kinase inhibitors was synthesized and evaluated the anti-proliferative activities against A549, HCT116, MCF-7 and HepG2 cells. 1-(4-(2-((4-Oxo-3,4-dihydrophthalazin-1-yl)amino)ethyl) phenyl)-3-(3-(trifluoromethyl)phenyl)urea (17b) exhibited the most potent anti-proliferative activity against HCT116 cells with IC50 value of 4.35 ± 1.21 µM, as well as the moderate Aurora B inhibitory activity with the IC50 value of 142 nM. Furthermore, 17b inhibited the phosphorylation of Aurora B on Thr232, leading to cell cycle arrest in the G2/M phase by down-regulating the expression of CyclinB1 and Cdc2 proteins, and apoptosis by up-regulating the expression of BAD and Bax proteins in HCT116 cells. In addition, a docking study revealed that 17b could form key hydrogen bonds with Ala173, Glu171 and Glu177 in Aurora B. All the results reveal that 17b is worthy of further development as an Aurora B kinase inhibitor.

Association of klotho gene polymorphism and the regulation of calcium-phosphate metabolism disorders in patients with end-stage renal disease.

BACKGROUND: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown. METHODS: A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non-dialysis (A3, n = 55). The klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects. RESULTS: (i) Three genotypes (GG, GA and AA) of KL G-395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium-phosphate metabolism disorders. CONCLUSION: Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G-395A klotho gene polymorphism could be a risk factor on calcium-phosphate metabolism disorders in patients with ESRD.

[Epidemiological analysis of imported malaria in Xiaogan City from 2008 to 2013].

The epidemiological features of 27 imported malaria cases during 2008-2013 in Xiaogan were analyzed. Among the cases, 21(77.8%) were falciparum malaria,and 6(22.2%) were vivax malaria. Twenty-five (97.3%) cases were among 19-47 year-old males. The reported cases increased from 2010 to 2013, and there was no significant difference among seasons. The cases were reported from all the seven counties. Eleven cases (40.7%) were reported by Xiaonan District. Twenty-three cases were infected in Africa.

Motor experience modulates neural processing of lexical action language: Evidence from rugby players.

The perceptual symbol theory proposes a sensorimotor simulation in language processing, emphasizing the role of motor experience. However, the neural basis of motor experience on lexical-level language processing remains little known. In the current fMRI study, we compared brain activation and task-based functional connectivity in 28 rugby players and 28 novices during rugby- specialized and daily verb processing. Distinct differences were observed between the two groups in the bilateral superior temporal gyrus and left angular gyrus regions during specialized verb processing. Notably, intergroup functional connectivity was evident between the left superior temporal gyrus and the right precentral gyrus during specialized verb processing. This study contributes insights into the neural responses and connectivity patterns associated with motor experience at the lexical level, highlighting its potential impact on language processing.

Effects of acute exercise with different modalities on working memory in men with high and low aerobic fitness.

OBJECTIVES: This study aimed to determine the effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on working memory in individuals with high and low aerobic fitness. DESIGN: The protocol adopted a between-subjects crossover design. METHODS: Forty healthy male college students (mean age = 19.59 ± 1.00 years) were assigned to high fitness (n = 20) or low fitness (n = 20) groups based on their estimated maximum oxygen consumption (VO2max) in the 20 m shuttle run test. All participants were instructed to engage in three acute exercise interventions (10 min HIIE, 20 min HIIE, 20 min MICE) and a reading control intervention on separate days in a randomized order. A spatial 2-back task was performed before and after each intervention to assess working memory. RESULTS: Analyses of the 2-back task performance revealed that the working memory of high and low fitness participants benefited from different modalities of acute exercise. Specifically, reaction time in the 2-back task was significantly shorter after 20 min HIIE compared to pre-exercise in high fitness participants, whereas low fitness participants had significantly faster reaction time in the 2-back task after 20 min MICE and 10 min HIIE relative to pre-exercise. CONCLUSIONS: The effects of acute aerobic exercise on working memory are modulated by a combination of exercise modality and aerobic fitness. This finding has important implications for providing experimental evidence that participants choose appropriate exercise to undertake based on their level of aerobic fitness to improve cognitive performance.

The Immediate and Sustained Effects of Moderate-Intensity Continuous Exercise and High-Intensity Interval Exercise on Working Memory.

This study investigated the immediate and delayed effects of moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) on working memory. Fifty healthy young adults (mean age = 19.96 ± 1.03 years) engaged in (1) a MICE session, 20 min of continuous running on a treadmill at an intensity of 40-59% of heart rate reserve (HRR); (2) a HIIE session, 10 sets of 1 min running at an intensity of 90% HRR, interspersed by 1 min self-paced walking at 50% HRR; and (3) a control session, resting in a chair and reading books for 24 min. A spatial 2-back task was performed to assess working memory before, immediately after and 30 min after each intervention. Reaction time in the 2-back task was significantly reduced immediately after both MICE and HIIE interventions. The enhanced working memory associated with HIIE sustained for 30 min after the exercise, whereas the beneficial effects associated with MICE returned to the pre-exercise level at 30 min after the exercise. These results suggest that although both MICE and HIIE enhance working memory in young adults, the positive effect sustains longer in HIIE than that in MICE. The current study extends the existing knowledge base by suggesting that improvements in working memory with HIIE last longer than with MICE.

Effects of Acute Exercise on Cognitive Flexibility in Young Adults with Different Levels of Aerobic Fitness.

This study aimed to evaluate the effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on cognitive flexibility in young adults with differing levels of aerobic fitness. Sixty-six young adults were grouped into high- and low-fit groups based on their final running distance on the 20 m Progressive Aerobic Cardiovascular Endurance Run (PACER) test. Individuals participated in a 10 min HIIE, a 20 min HIIE, a 20 min MICE, and a control session (reading quietly in a chair) in a counterbalanced order. The more-odd shifting task was completed before and approximately 5 min after each intervention to assess cognitive flexibility. The results showed that young adults with a high fitness level gained greater benefits in terms of switch cost from the 20 min HIIE, while low-fitness participants benefited more from the 10 min HIIE and the 20 min MICE. These findings suggest that aerobic fitness may influence the effect of acute HIIE and MICE on cognitive flexibility. Young adults should consider individual fitness level when adopting time-effective and appropriate exercise routines to improve cognitive flexibility.

Sustained Effects of High-Intensity Interval Exercise and Moderate-Intensity Continuous Exercise on Inhibitory Control.

This study examined the immediate and sustained effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) bouts on inhibitory control in young adults. Participants (n = 41) engaged in (1) a session of HIIE, involving 10 one-minute runs on a treadmill at an intensity targeting 85-90% HRmax interspersed with self-paced walking at 60% HRmax; (2) a session of MICE, involving a 20 min run on a treadmill at an intensity of 60-70% HRmax; and (3) a control session, involving 24 min of resting on separate days in a counterbalanced order. Using a flanker task, inhibitory control was assessed before the intervention (t0), immediately after the session (t1), and then at 30 min (t2), 60 min (t3), and 90 min (t4) after the session. During the flanker task, the response time (RT) for incongruent trials immediately after HIIE was significantly shortened compared to that before exercise. This shortened RT was sustained for 90 min post-exercise during recovery from HIIE. Interference scores of RT were also reduced after HIIE, benefitting inhibitory control, and were maintained for 90 min post-exercise. Reduced accuracy interference scores were recorded following HIIE compared to the control session. Improvements in inhibitory control elicited by HIIE were sustained for at least 90 min post-exercise. In contrast, an improvement in inhibitory control was not observed during the MICE session. HIIE might represent a time-efficient approach for enhancing inhibitory control.

Comparison of the Sustainability Effects of High-Intensity Interval Exercise and Moderate-Intensity Continuous Exercise on Cognitive Flexibility.

This study examined the immediate and sustained effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on cognitive flexibility in young adults. Participants (n = 56) engaged in (1) a session of HIIE, involving 10 sets of one-minute treadmill running at an intensity targeting 90% heart rate reserve (HRR) interspersed with self-paced walking at 50% HRR; (2) a session of MICE, involving a 20 min treadmill running at an intensity of 40-59% HRR; and (3) a control session, involving 24 min of resting on separate days in a counterbalanced order. Using a more-odd shifting task, cognitive flexibility was assessed before the intervention (t0), immediately after the session (t1), and then at 30 min (t2) after the session. During the more-odd shifting task, the switch cost of response time (RT) immediately after the HIIE was significantly reduced compared to that before exercise, suggesting beneficial effects on cognitive flexibility. Additionally, the impacts of HIIE were maintained for 30 min post-exercise. However, improved cognitive flexibility was not observed until 30 min after the MICE intervention. HIIE might represent a time-efficient approach for enhancing cognitive flexibility.

The complete chloroplast genome sequence of Quercus chungii (Fagaceae).

Quercus chungii F.P.Metcalf, a rare oak with endemic to southern China, belongs to the compound trichome base (CTB) lineage in the Cyclobalanopsis section. The complete chloroplast genome of the species was assembled and annotated in this study. The circular genome was 160,731 bp in size, presenting a typical quadripartite structure including one large single-copy region (LSC, 90,140 bp), one small single-copy region (SSC, 18,911 bp), and two copies of inverted repeat regions (IRs, 25,840 bp). It encoded a total of 113 unique genes, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The maximum-likelihood (ML) phylogenetic tree reconstructed by IQ-TREE indicated that Q. chungii was more closely related to Q. myrsinifolia and Q. sichourensis.

The complete chloroplast genome sequence of Quercus schottkyana, and comparative analysis with related species.

In this study, we sequenced the complete chloroplast genome of Quercus schottkyana. The circular genome is 160,746 bp in size, featuring a typical quadripartite structure comprising one large single-copy region (LSC, 90,136 bp), one small single-copy region (SSC, 18,942 bp), and two copies of inverted repeat regions (IRs, 25,834 bp). The genome contains 131 genes, including 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes. The overall GC content is 36.90%. The maximum likelihood phylogenetic tree reconstructed using IQ-TREE indicated that Q. schottkyana has a closer relationship with Quercus sichourensis and Quercus acuta.

MiR-422a in gastric cancer cells directly targets CDC40 and modulates cell proliferation.

MicroRNAs have been shown to be involved in a variety of different human cancers, including gastric cancer, functioning as post-transcriptional regulators of oncogenes or tumor suppressors. This study aimed to clarify the role of miR-422a in gastric cancer and further elucidate the pathogenesis thereof. To this end, miR-422a expression was initially determined in gastric cancer tissues and cells. Our results showed decreased miR-422a and increased cell division cycle 40 (CDC40) expression in gastric cancer. Dual-luciferase reporter assay further confirmed that miR-422a targeted CDC40. Altogether, this study showed that miR-422a downregulated CDC40, thereby affecting cell cycle progression. Moreover, restoration of miR-422a inhibited gastric cancer cell proliferation. In summary, this study has been the first to show that miR-422a was associated with CDC40 levels in human gastric cancer cells and that disease development may be attributed to CDC40.

The MAndarin spoken word-Picture IDentification test in noise-Adaptive (MAPID-A) measures subtle speech-recognition-in-noise changes and spatial release from masking in very young children.

BACKGROUND: Spatial release of masking (SRM) is a measure of an individual's ability to perform speech-noise segregation, which is usually quantified by the extent of improvement of the individual's speech recognition performance when the noise is switched from a spatially co-located position (e.g., speech and noise both presented from the front) to a spatially separated position (e.g., speech presented from the front and noise presented from the right side) with reference to the target speech. SRM is a combined measure of head shadow and binaural unmasking benefits. SRM has only been investigated in young children at group level but not at individual participant level in the international literature due to the lack of reliable speech recognition test materials able to detect subtle statistically significant within-participant changes in speech-recognition-in-noise thresholds. METHOD: The performance to signal-to-noise ratio (P-SNR) functions of twenty-four disyllabic words were obtained from 40 native Mandarin-speaking children aged 3.6-6.2 years with reported normal speech, language and hearing. The test items' difficulty levels were homogenized by adjusting the speech intensity level of each item so that the adjusted signal-to-noise ratio for 50% correct score (SNR-50%) point of each item would overlap at the mean SNR-50% point of all test items. In the MAPID-A, the homogenized test items were randomly presented in an adaptive testing procedure at a fixed noise intensity level, but the speech intensity level of the upcoming test item varied in 2-dB SNR steps depending on the recognition result of the previous test item. The SNR reversal point is marked by a change from a decrease to an increase in the SNR or vice versa. Two successive SNR reversal points marked the boundaries of an excursion. The mid-points from 12 excursions (in dB SNR) were averaged to produce the adaptive SNR-50% measure (aSNR-50%). RESULTS: The aSNR-50% results were obtained from another 12 children aged 4.8-5.3 years with reported normal speech, language and hearing. The average 99% confidence interval (CI) of all participants' mean aSNR-50% values was ±1.61 dB SNR; therefore, 3.22 dB SNR was the average critical difference required to confirm a significant difference in the scores obtained from the same participant between two test conditions. Statistically significant within-participant SRM was identified in 95% of the participants; in other words, aSNR-50% obtained from the spatially separated condition outperformed aSNR-50% obtained from the spatially co-located condition. The adaptive testing procedure was highly reliable, with an within-participant test-retest reliability of 90.6%. and significantly limited testing time to an average of 4.2 min. This research study has fulfilled its aim on detecting subtle within-participant SRM in very young children starting from 4 years of age with a reliable statistical procedure. MAPID-A offers a reliable and efficient clinical tool to investigate speech-recognition-in-noise and SRM performances in young Mandarin-speaking children. CONCLUSIONS: The narrow CIs, high test-retest reliability, and short testing time has proven that the MAPID-A is a promising sensitive, reliable and time-efficient clinical tool to detect subtle within-participant speech-recognition-in-noise changes in children as young as 4-5 years. The MAPID-A offers a clinical tool to behaviorally track young children's development in speech-recognition-in-noise and SRM, and to potentially review the development of the auditory neural pathway and the cerebral dominance for speech-recognition-in-noise in young children.

Gutuo Jiejiu decoction improves survival of patients with severe alcoholic hepatitis: A retrospective cohort study.

AIM: To verify the value of Gutuo Jiejiu decoction in improving the survival of patients with severe alcoholic hepatitis (SAH). METHODS: We performed a retrospective cohort study in consecutive patients diagnosed with SAH at the Teaching Hospital of Chengdu University of Traditional Chinese Medicine and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. The traditional Chinese medicine formula Gutuo Jiejiu decoction was employed as an exposure factor. Patients from the Teaching Hospital of Chengdu University of Traditional Chinese Medicine who had been treated with Gutuo Jiejiu decoction + prednisone were assigned to an observation group, and patients from Shuguang Hospital, Shanghai University of Traditional Chinese Medicine who had been treated with prednisone alone were selected as a control group. A retrospective analysis was performed by comparing age, alcohol intake, and clinical parameters of liver injury before and after treatment. Additionally, the 3- and 12-mo survival rates and the occurrence of complications were analyzed. RESULTS: One hundred and twenty-eight eligible patients were selected from 175 cases with SAH, of which 68 were assigned to the observation group and the other 60 to the control group. No significant difference was found in the patients' baseline characteristics (P > 0.05). However, significant improvements of 90-d survival rate [56/68 (82.4%) vs 27/60 (45.0%), P = 0.0000] and 365-d survival rate [48/68 (70.6%) vs 13/60 (21.7%), P = 00000] were observed in the observation group after treatment. After the first 3 mo of treatment, more improvements in the clinical parameters and scoring systems related to liver injury occurred in the observation group than in the control group (P < 0.05). After treatment for 12 mo, the differences in the clinical parameters and scoring systems related to liver injury between the two groups were more significant (P < 0.05). No significant differences in complications and adverse effects were found between the two groups. CONCLUSION: Gutuo Jiejiu decoction could improve the survival rates and clinical parameters of liver injury in patients with SAH, and may represent a new option for treating SAH.

[Applications of nuclear magnetic resonance in the study of soil-plant-atmosphere continuum].

Status and transport of water in plant body are the main contents of study of soil-plant-atmosphere continuum (SPAC), as well as the base for use and regulation of agricultural water. The process of water transport in plant can be deeply influenced by the environments. Thus, plant needs to adjust its water status to accommodate the environmental change to sustain its own growth and development. Traditional methods for plant water monitoring, such as evaporation flux, pressure chamber, high pressure flow meter, heat pulse, and so on, usually cause damage or even destruction of plant body and disturb the original water status. Thus, they are not able to truly and precisely detect and reflect the real water status of plant. Nuclear magnetic resonance (NMR) is a non-destructive and non-invasive technique which can be used for the measurement of water molecular displacement, and transportation. This study aimed to provide an overview of the applications of NMR technique in the study of water distribution and transport in plant roots and stems, as well as the water content in plant cells and tissues. In addition, the existing main problems and possible solutions were analyzed for the applications of NMR in SPAC studies. Several important issues were proposed for the acquisition of more precise and reliable detection signals. It was suggested that the NMR technique would probably make important progress in the relevant fields such as plant water physiology, plantenvironment interactions, and water metabolism. In general, the application of NMR in SPAC system study was still in its infancy in China. The deeper application and expansion of NMR in SPAC study would depend on the development of portable and open NMR equipment that could be easily applied for different plants in field.

Moxibustion for Primary Dysmenorrhea at Different Interventional Times: A Systematic Review and Meta-Analysis.

Primary dysmenorrhea (PD) is one of the most common diseases in gynecology at present. Some clinical trials have reported the effects of moxibustion and confirmed temporal factors are the important elements influencing the efficacy of moxibustion. However, no systematic review has yet been conducted. In this study, we assessed the effects of moxibustion in patients with PD enrolled in randomized controlled trials (RCTs) and the difference among different intervention times to start moxibustion. We extracted data for studies searched from 10 electronic databases and evaluated the methodological quality of the included studies. We discussed three outcomes: effective rate, pain remission, and the level of PGF2α in serum. Current clinical researches showed that, compared with nonmoxibustion treatments for PD, moxibustion leads to higher effective rate and lower level of PGF2α in serum. However, there was no difference in using moxibustion to treat PD at different intervention times. Based on the theory of Chinese medicine and the results of this study, choosing 5 ± 2 days before menstruation to start moxibustion can achieve good efficacy for PD patients. However, more high-quality RCTs are needed to confirm the conclusions.

[Research advances on anti-ANGPT2 antibody in acute myeloid leukemia].

Angiopoietin2( ANGPT2 ) plays an important role in tumor angiopoiesis. ANGPT2 antagonises ANGPT1 resulting in an effect on the stability of blood vessels, which promotes tumor growth, invasion, proliferation as well as relating to tumor vascular density. A lot of researches published papers about anti-ANGPT2 for the treatment of tumor, and have made some progresses. In this review, the role of ANGPT2 in the pathogenesis of acute myelogenous leukemia (AML), including its effects on proliferation of leukemia cells, bone marrow angiopoiesis, tumor invasion and metastasis are briefly summarised in order to provide the basis for targeted ANGPT2 in treatment of AML.

Topochemistry of alkaline, alkaline-peroxide and hydrotropic pretreatments of common reed to enhance enzymatic hydrolysis efficiency.

Common reed was studied as raw material for sugar bioconversion. The low temperature alkaline, alkaline-peroxide and hydrotropic pretreatments were employed to overcome the recalcitrance of reed before enzymatic hydrolysis. After pretreatments, lignin was efficiently decreased from the fiber cell wall. Xylan was significantly reduced by hydrotropic pretreatment as well. The surface chemical compositions of reed before and after pretreatments were investigated by X-ray spectroscopy (XPS) and time of flight secondary ion mass spectrometry (ToF-SIMS). Reed had a high surface coverage by lignin. Hydrotropic pretreatment was outstanding to decrease the surface coverage by lignin and expose the polysaccharides to fiber surface. The surface lignin reduction was also supported by attenuated total reflectance (ATR)-FTIR results. Furthermore, the topochemical modification of the fiber wall by hydrotropic pretreatment could improve the fiber digestibility, and thus the maximum glucan and xylan yields with the cellulase dosage of 20 FPU/g raised to 93.1% and 25.5%, respectively.