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Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None, (Copyright © 2024. Published by Elsevier Inc.)

Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp 3 )-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.

An increase in fibrous connective tissue and a decrease in parenchymal cells in organ tissues are the primary pathological alterations linked to organ fibrosis. If fibrosis is not treated, organ structure is destroyed, function can decline, or even fail, posing a serious risk to human life and health. Numerous organs develop fibrosis, and organ fibroproliferative illnesses account for almost 45% of patient deaths from various diseases in the industrialized world, as well as a major cause of disability and mortality in many other diseases. Recently, it has become evident that histone modification is an important way to regulate gene expression in organ fibrosis. Histone modifications alter the structure of chromatin, thereby affecting gene accessibility. Histone acetylation modifications relax chromatin, making it easier for gene transcription factors to access DNA, thereby promoting gene transcription. In addition, histone modifications recruit other proteins to interact with chromatin to form complexes that further regulate gene expression. Histone methylation modifications recruit methylation-reading proteins that recognize methylation marks and alter gene expression status. It not only affects the normal physiological function of cells, but also plays an important role in organ fibrosis. This article reviews the important role played by histone modifications in organ fibrosis and potential therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Herein, visible light-induced, nickel-catalyzed direct functionalization of the Hantzsch esters (HEs) with readily accessible alkyl bromides has been successfully achieved by taking advantage of HE as the reductant and substrate through an aromatization-dearomatization process. In this strategy, the single electron reduction of alkyl bromides by reactive Ni(I) species is essential for the success of this late-stage transformation. A wide range of 4-alkyl-1,4-dihydropyridines were rapidly assembled in moderate to good yields under mild conditions, rendering this photoinduced approach attractive for synthetic and medicinal chemistry.

This study focuses on predicting mechanical fatigue in excavator turntables, critical components susceptible to failure due to variable operational loads. While conventional methods like finite element analysis(FEA) and multiaxial fatigue criteria have been used, they are limited by the complexity and cost of obtaining real operational load spectra. To address this challenge, our research presents a comprehensive approach that integrates multi-body dynamics modeling, finite element analysis, and MATLAB-based fatigue life prediction systems. Our methodology involves creating a finite element model for stress analysis, synthesizing load spectra from operational data, and utilizing Weibull distribution to analyze load magnitude probabilities. Subsequently, MATLAB imported the load spectrum and built the fatigue prediction framework to finalize the analysis. Furthermore, we have fully open-sourced our code on an open platform, incorporating default load profiles and predictive models within the code. Key findings pinpoint areas prone to stress concentration and fatigue. Key findings identify stress concentration areas and fatigue-prone regions, providing valuable insights for design optimization and durability improvement., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yantong Liu reports financial support was provided by 10.13039/501100002522Kunsan National University. Chen Xian reports financial support was provided by Shaanxi Province Department of Science and Technology. Young-chul Kim reports financial support was provided by 10.13039/501100002522Kunsan National University Department of Materials Science and Engineering. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Lower limb deep vein thrombosis (DVT) concurrent with pulmonary embolism (PE) is perilous, particularly in the elderly, exhibiting heterogeneity with thrombophilia mutations. Tailored treatment is essential, yet sudden deaths complicate causative factor elucidation. This report emphasizes genetic testing necessity in PE patients with thrombophilia indicators, facilitating cause identification, personalized treatment guidance, and family education., Case Presentation: This study details a 75-year-old Chinese woman with DVT and PE, where genetic testing identified thrombophilia, guiding personalized treatment decisions., Results: Upon admission, the patient, after over 10 days of bed rest, presented chest tightness, shortness of breath, and unilateral leg swelling. Diagnostic measures revealed DVT and a substantial PE. Genetic testing identified a PROS1 gene C200A>C mutation, reducing protein S activity. Following 2 weeks of anticoagulation and inferior vena cava filter insertion, the patient, discharged, initiated lifelong anticoagulant therapy. A 1-year follow-up showed no recurrent thrombotic events. Family members carrying the mutation received informed and educational interventions., Conclusion: Genetic testing for thrombophilic predisposition post-PE is crucial, elucidating etiology, guiding individualized treatment, and playing a pivotal role in family education., (© 2024. The Author(s).)

Herein, a dual photoredox/nickel catalyzed formylation of aryl bromide with commercially available 2,2-dimethoxy- N , N -dimethylethan-1-amine as an effective CO source has been successfully achieved, delivering a series of aromatic aldehydes in moderate to good yields. Compared with the traditional reductive carbonylation process, this newly designed synthetic protocol provides a straightforward toolbox to access aromatic aldehydes, obviating the use of carbon monoxide and stoichiometric reductants. Finally, the utility of this direct formylation reaction was demonstrated in the pharmaceutical analogue synthesis.

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of SUN YAT-SEN UNIVERSITY CANCER CENTER.)

Herein, a visible-light-induced nickel-catalyzed cross-coupling of aryl bromide with nitrile has been reported. By utilization of readily available nitriles as carbonyl precursors, a range of structurally diverse aryl ketones were facilely constructed. The synthetic simplicity, mild reaction conditions, and acidic functional group tolerance would broaden the synthetic utilities of this developed protocol as an expedient alternative to Grignard/organolithium protocols.

Brassinosteroid (BR) is a vital plant hormone that regulates plant growth and development. BRASSINAZOLE RESISTANT 1 (BZR1) is a key transcription factor in BR signaling, and its nucleocytoplasmic localization is crucial for BR signaling. However, the mechanisms that regulate BZR1 nucleocytoplasmic distribution and thus the homeostasis of BR signaling remain largely unclear. The vacuole is the largest organelle in mature plant cells and plays a key role in maintenance of cellular pH, storage of intracellular substances, and transport of ions. In this study, we uncovered a novel mechanism of BR signaling homeostasis regulated by the vacuolar H + -ATPase (V-ATPase) and BZR1 feedback loop. Our results revealed that the vha-a2 vha-a3 mutant (vha2, lacking V-ATPase activity) exhibits enhanced BR signaling with increased total amount of BZR1, nuclear-localized BZR1, and the ratio of BZR1/phosphorylated BZR1 in the nucleus. Further biochemical assays revealed that VHA-a2 and VHA-a3 of V-ATPase interact with the BZR1 protein through a domain that is conserved across multiple species. VHA-a2 and VHA-a3 negatively regulate BR signaling by interacting with BZR1 and promoting its retention in the tonoplast. Interestingly, a series of molecular analyses demonstrated that nuclear-localized BZR1 could bind directly to specific motifs in the promoters of VHA-a2 and VHA-a3 to promote their expression. Taken together, these results suggest that V-ATPase and BZR1 may form a feedback regulatory loop to maintain the homeostasis of BR signaling in Arabidopsis, providing new insights into vacuole-mediated regulation of hormone signaling., (Copyright © 2023 The Author. Published by Elsevier Inc. All rights reserved.)

Objectives: Multiple factors associated with neural tube defects (NTDs) risk have been identified, yet there is little evidence on the possible effects of maternal stressful life events. In this study, we aimed to investigate the association between stressful life events during the periconceptional period and risk of NTDs in offspring., Methods: Relevant literature was searched in PubMed, Springer Link, ScienceDirect, and Cochrane Library up to July 2023. The pooled odds ratio (OR) and 95% confidence interval (CI) of NTDs risk with maternal stressful life events were estimated using a random effects model. Publication bias was assessed using Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot., Results: Analysis results showed that mothers who experienced stressful life events during the periconceptional period were at greater risk of having NTDs offspring (OR: 1.37, 95% CI: 1.08-1.73) than those who did not. In subgroup analysis, the pooled OR was 1.37 (1.13-1.67) and 1.73 (0.36-8.32) for with and without adjusting for folic acid supplementation in each included study, while was 1.37 (1.13-1.67) and 1.64 (0.39-6.88) for exposure time of three months preconception until three months post conception and one year preconception until three months post conception, respectively., Conclusions: This study suggests that maternal stressful life events during the periconceptional period are significantly associated with higher NTDs risk in offspring. Tailored approaches for evaluating the risk and policy of NTDs among women of childbearing age should emphasize individual stressful experiences before and during early pregnancy.

Herein, a direct cross-dehydrogenative C-H amination of indoles has been successfully achieved, enabled by the merger of photocatalysis with nickel catalysis. This developed process does not require stoichiometric oxidants and prefunctionalization of amine partners, providing a concise platform for C-N bond formation. Moreover, the synthetic practicality of this transformation was well revealed by its high step- and atom-economy, high reaction efficiency, and broad functional group tolerance.

Pulmonary fibrosis is a chronic and progressive fibrotic disease that results in impaired gas exchange, ventilation, and eventual death. The pro-fibrotic environment is instigated by various factors, leading to the transformation of epithelial cells into myofibroblasts and/or fibroblasts that trigger fibrosis. Epithelial mesenchymal transition (EMT) is a biological process that plays a critical role in the pathogenesis of pulmonary fibrosis. Epigenetic regulation of tissue-stromal crosstalk involving DNA methylation, histone modifications, non-coding RNA, and chromatin remodeling plays a key role in the control of EMT. The review investigates the epigenetic regulation of EMT and its significance in pulmonary fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A Giese reaction of aryl bromides with electron-deficient alkenes was developed, enabled by a dual catalyst system containing Ni II complex and Ir III photocatalyst. This protocol could accommodate a variety of aryl bromides and electron-deficient alkenes, delivering the conjugate adducts in up to 97% yield. The utilization of photoexcited (dtbbpy)Ni II (aryl)Br intermediate as an aryl radical source allows this novel transformation of aryl halides, thus expanding the chemical space of excited nickel catalysis.

Epigenetic has been implicated in pulmonary fibrosis. However, there is limited information regarding the biological role of the epigenetic reader MeCP2 in pulmonary fibrosis. The aim of this study was to investigate the role of MeCP2 and its target WIF1 in pulmonary fibrosis. The pathological changes and collagen depositions was analyzed by H&E, Masson's Trichrome Staining and Sirius Red staining. MeCP2, WIF1, α-SMA, Wnt1, β-catenin, and collagen I expression were analyzed by western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, respectively. The effects of MeCP2 on pulmonary fibrosis involve epigenetic mechanisms, using cultured cells, animal models, and clinical samples. Herein, our results indicated that MeCP2 level was up-regulated, while WIF1 was decreased in Bleomycin (BLM)-induced mice pulmonary fibrosis tissues, patients pulmonary fibrosis tissues and TGF-β1-induced lung fibroblast. Knockdown of MeCP2 by siRNA can rescue WIF1 downregulation in TGF-β1-induced lung fibroblast, inhibited lung fibroblast activation. The DNA methylation inhibitor 5-azadC-treated lung fibroblasts have increased WIF1 expression with reduced MeCP2 association. In addition, we found that reduced expression of WIF1 caused by TGF-β1 is associated with the promoter methylation status of WIF1. Moreover, in vivo studies revealed that knockdown of MeCP2 mice exhibited significantly ameliorated pulmonary fibrosis, decreased interstitial collagen deposition, and increased WIF1 expression. Taken together, our study showed that epigenetic reader MeCP2 repressed WIF1 facilitates lung fibroblast proliferation, migration and pulmonary fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A photoinduced, photocatalyst-free cyanoalkylation of nitrostyenes was explored, affording a series of cyanoalkylated alkenes in moderate to good yields. Mechanistic studies reveal that an electron donor-acceptor complex formed between O -aryl oximes and DIPEA is presumably involved in this process. The excellent functional group compatibility of this newly designed synthetic protocol allows for cyanoalkylation of structurally varied substrates, which offers an eco-friendly pathway for the assembly of cyanoalkylated alkenes.

Background: There is scarce data on the long-term mortality and associated prognostic factors in patients with dilated cardiomyopathy (DCM). The study aimed to investigate the all-cause mortality up to 15 years (mean 7.9 ± 5.7 years) in such patients, and the independent prognostic factors influencing their long-term mortality., Methods: One hundred and sixty-six consecutive patients with DCM were prospectively enrolled from 2002 to 2003. The mean age of patients was 59.5 ± 10.4 years, and approximately 57% were male. They were followed up by telephone or outpatient visit at least every three months until 2019 or all-cause death occurred. Predictors of mortality were identified using multivariate logistic regression analysis., Results: During the 15 years of follow-up, five patients were lost to follow-up, and the complete data records of 161 patients were included in the analysis. Patients were treated with angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin-receptor blocker (ARB), β-blockers, mineralocorticoid receptor antagonist (MRA), diuretics and digitalis from 2002 to 2004, and maintained at the maximum tolerated doses between 2004 and 2019. Our safety targets to maintain heart rate and blood pressure at 60-80 beats/min and 90-120/60-80 mmHg, respectively. All-cause mortality in the first five years was 55.9%. The independent risk factors for the 5-year mortality were age ≥ 70 years old (OR = 5.45, P = 0.006), systolic blood pressure (SBP) > 120 mmHg (OR = 3.63, P = 0.004), 6-minute walk distance (6MWD) < 450 m (OR = 3.84, P = 0.001). 15-year all-cause mortality was 65.8%. The independent risk factors for 15-year mortality were age ≥ 70 years old (OR = 16.07, P = 0.009), LVEF ≤ 35% (OR = 5.69, P = 0.003), and SBP > 120 mmHg (OR = 9.56, P < 0.001)., Conclusions: This study was the first to demonstrate the 15-year survival rate of 34% in DCM patients. The DCM patients' first five-year all-cause mortality decreased significantly after continuous standardized treatment and intensive management. The mortality then plateaued in the following 10 years. Age ≥ 70 years, LVEF ≤ 35%, and SBP > 120 mmHg were independent predictors of 15-year all-cause mortality., (Copyright and License information: Journal of Geriatric Cardiology 2022.)

Objective: The coronavirus disease 2019 (COVID-19) pandemic, a major public health crisis, harms individuals' mental health. This 3-wave repeated survey aimed to examine the prevalence and correlates of suicidal ideation at different stages of the COVID-19 pandemic in a large sample of college students in China., Methods: Using a repeated cross-sectional survey design, we conducted 3 online surveys of college students during the COVID-19 pandemic at 22 universities in Guandong, China. The 3 surveys were conducted during the outbreak period (T1: 3 February to 10 February 2020, N = 164,101), remission period (T2: 24 March to 3 April 2020, N = 148,384), and normalized prevention and control period (T3: 1 June to 15 June 2020, N = 159,187). Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. A range of suicide-related factors was assessed, including sociodemographic characteristics, depression, anxiety, insomnia, pre-existing mental health problems, and COVID-19-related factors., Results: The prevalence of suicidal ideation was 8.5%, 11.0% and 12.6% at T1, T2, and T3, respectively. Male sex (aOR: 1.35-1.44, Ps < 0.001), poor self-perceived mental health (aOR: 2.25-2.81, Ps < 0.001), mental diseases (aOR: 1.52-2.09, P < 0.001), prior psychological counseling (aOR: 1.23-1.37, Ps < 0.01), negative perception of the risk of the COVID-19 epidemic (aOR: 1.14-1.36, Ps < 0.001), depressive symptoms (aOR: 2.51-303, Ps < 0.001) and anxiety symptoms (aOR: 1.62-101.11, Ps < 0.001) were associated with an increased risk of suicidal ideation., Conclusion: Suicidal ideation appeared to increase during the COVID-19 pandemic remission period among college students in China. Multiple factors, especially mental health problems, are associated with suicidal ideation. Psychosocial interventions should be implemented during and after the COVID-19 pandemic to reduce suicide risk among college students., (© 2022. The Author(s).)

Objective: Little is known about the association between perceived social support (PSS) and suicidal ideation in Chinese adolescents. This study was to examine the association of perceived social support and suicidal ideation (SI) and the mediating role of depressive symptoms in a large sample of adolescents in China., Method: A total of 11,831 adolescents who participated in the baseline Shandong Adolescent Behavior & Health Cohort were included for analysis. Perceived social support, depressive symptoms, and other variables were assessed by a self-administrated questionnaire. Path analysis was used to estimate the association between PSS, depressive symptoms, and suicidal ideation., Results: The prevalence rate of SI in the past year was 12.5%. Suicidal ideation and depressive symptoms were significantly associated with low PSS from family, friends, and significant others. Path analysis revealed that depressive symptoms partially mediated the relationship between PSS from family, friends, and significant others and suicidal ideation. After controlling for covariates, the mediation effect proportion of depressive symptoms on the associations between perceived social support from family, friends, and significant others and SI ranged from 19.20% to 62.12%., Limitations: As this is a cross-sectional study, no causal relationship could be made., Conclusions: Depressive symptoms partially mediated the association between perceived social support and suicidal ideation. Longitudinal research is needed to better understand the association between social support and suicidal ideation in adolescents., (Copyright © 2022. Published by Elsevier B.V.)

Herein, a tunable iodization/deuterolysis protocol for phosphonium ylides by employing D 2 O as the deuterium source was designed. Notably, this process could be manipulated by tuning the base, thus leading to two valuable deuterated building blocks - benzyl iodides and aromatic aldehydes with broad substrate scope, good functional group compatibility and excellent deuteration degree. Concise syntheses of a series of deuterated drug analogues have been achieved based on the developed deuteration reaction platform.

A phosphine-mediated, well-designed Morita-Baylis-Hillman-type/Wittig cascade for the rapid assembly of a quinolinone framework from benzaldehyde derivatives is developed for the first time. By rationally combining I 2 /NIS-mediated cyclization, biologically relevant 3-(benzopyrrole/furan-2-yl) quinolinones were facilely synthesized in a one-pot process by starting from 3-styryl-quinolinones bearing an o -hydroxy/amino group, significantly expanding the chemical space of this privileged skeleton. Further utility of this protocol is illustrated by successfully performing this transformation in a catalytic manner through in situ reduction of phosphine oxide by phenylsilane.

A novel phosphine-catalysed, one-pot domino approach for the annulation of 2-formylphenyl alkynoates with activated methylene compounds to construct various cyclopentene-fused dihydrocoumarins is reported. This developed strategy provides a facile and efficient approach for the synthesis of structurally complex coumarins from inexpensive and readily available alkynoates.

The addition reaction of thiol to vinyl azide has been extensively studied. Variously substituted aryl thiols are all viable for this coupling process. The scope of the other partner is successfully expanded from α-aryl vinyl azide to α-alkyl vinyl azide. A thiol-vinyl azide coupling/cyclization cascade is realized with substituted aryl vinyl azides carrying a 2-methoxycarbonyl group. The value of β-ketosulfide products was demonstrated by its application in S-heterocycle synthesis.

Compounds bearing fluorinated moieties are pervasive in a wide range of pharmaceuticals and agrochemicals. The installation of fluorinated units is a persistently vital task in synthetic chemistry, where facile and manipulable assays are highly demanding. Herein, we establish a general and programmable fluorination strategy for the modular assembly of mono- and difluoromethylarenes through the controllable deprotonation and fluorination of phosphonium ylides. Moreover, the rational combination of the reaction sequence allows the rapid construction of diversified fluorine-containing arenes.

A chemical investigation on the 95% ethanol extract of the aerial part of Gelsemium elegans resulted in the isolation of three new gelsedine-type indole alkaloids, 14 β -hydroxygelselenidine ( 1 ), 11-methoxygelseziridine ( 2 ), and 14 β -hydroxygelsedethenine ( 3 ). Structural elucidation of all the compounds was accomplished by spectral methods such as 1 D and 2 D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic activities against five human non-small-cell lung cancer cell lines. Consequently, alkaloid 3 exhibited cytotoxic activities for all tested tumor cell lines with IC 50 values from 8.3 to 9.8 μM. [Formula: see text].

Residual cancer after incomplete ablation remains a major problem for radiofrequency ablation (RFA). We aimed to investigate the synergetic treatment efficacy of RFA combined with ultrasonic cavitation for liver tumor. Sixty rabbits with VX2 liver tumor were randomly divided into three groups. Group A was control group without any treatment. Combined ultrasonic cavitation with RFA was performed for group B1. Group B2 underwent RFA alone. The histopathological results were compared at the 5th, 11th, and 18th day of experiment, and the survival time and metastasis were assessed. The tumor volume growth rate, percentage of necrosis area, microvessel density, and apoptosis index showed significant differences among these groups at the 5th day, 11th day, and 18th day of experiment (P < .05). In contrast, the difference of metastatic score was not significant at the 5th and 11th day (P > .05). At the 18th day, the metastatic score of group A was significant higher than that of group B1 (P < .05), whereas the differences between group A and group B2, or group B1 and group B2 were not significant (P > .05). The median/range interquartile of survival time in groups A, B1, and B2 were 25/8 days, 50/19 days, and 48/20 days, respectively, and there was significant difference between groups A and B1 or B2 (P < .05). The difference between groups B1 and B2 was not significant (P > .05). Ultrasonic cavitation after incomplete RFA for liver tumor improved the antitumor effect, which could be considered as a potentially useful combined therapeutic strategy for liver malignancy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension independently predict cardiovascular events, the underlying mechanisms are still controversial. The aim of the study was to investigate the relationships between orthostatic changes and organ damage in subjects over 60 years old., Methods: This is a prospective observational cohort study. One thousand nine hundred and ninety-seven subjects over 60 years old were enrolled. Participants were grouped according to whether they had a drop ≥ 20 mmHg in systolic or ≥ 10 mmHg in diastolic BP (orthostatic hypotension), an increase in mean orthostatic systolic blood pressure ≥ 20 mm Hg (orthostatic hypertension), or normal changes within 3 min of orthostatism. Multiple regression modeling was used to investigate the relationship between orthostatic hypotension, orthostatic hypertension and subclinical organ damage with adjustment for confounders., Results: Orthostatic hypotension and orthostatic hypertension were found in 461 (23.1%) and 189 (9.5%) participants, respectively. Measurement of carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (baPWV), clearance of creatinine, and microalbuminuria were associated with orthostatic hypotension; measurement of IMT and baPWV were associated with orthostatic hypertension in a cruse model. After adjustment, IMT [odds ratio (OR), 95% confidence interval (CI) per one-SD increment: 1.385, 1.052-1.823; P = 0.02], baPWV (OR = 1.627, 95% CI: 1.041-2.544; P = 0.033) and microalbuminuria (OR = 1.401, 95% CI: 1.002-1.958; P = 0.049) were still associated with orthostatic hypotension, while orthostatic hypertension was only associated with IMT (OR = 1.730, 95% CI: 1.143-2.618; P = 0.009)., Conclusions: Orthostatic hypotension seems to be independently correlated with increased carotid atherosclerosis, arterial stiffness and renal damage in subjects over 60 years old. Orthostatic hypertension correlates with carotid atherosclerosis only.

A copper catalyzed intramolecular 1,2-carboboration of o-aldiminyl cinnamate has been realized in both regio- and stereoselective fashions. This reaction provides a convenient entry to highly valuable and otherwise challenging cis-2,3,4-trisubstituted tetrahydroquinolines carrying a 4-boryl group. An unusual non-Michael addition intermediate or alternatively, a cyclic enolate is proposed to account for the intriguing all-cis configuration in the final products.

Background and Objective: The health behaviors of hypertensive stroke patients in China are not satisfactory. In this study, we tested the effect of a Health Belief Model Comprehensive Reminder System on health behaviors and blood pressure control in hypertensive ischemic stroke patients after occurrence and hospital discharge., Methods: A randomized, parallel-group, assessor-blinded experimental design yielded participation of 174 hospitalized hypertensive ischemic stroke patients. The intervention consisted of face-to-face and telephone health belief education, a patient calendar handbook, and weekly automated short-message services. Data were collected at baseline and 3 months after discharge., Results: Three months after discharge, the intervention group showed statistically, significantly better health behaviors for physical activity, nutrition, low-salt diet, and medication adherence. The intervention group also had statistically, significantly decreased systolic blood pressure and increased blood pressure control rate. Smoking and alcohol use behaviors were not affected., Conclusion: At 3 months, use of the Comprehensive Reminder System based on the Health Belief Model, yielded improvement in most health behaviors and blood pressure control in hypertensive ischemic stroke patients. Continued implementation of this intervention protocol is warranted to determine the long-term effect. Smoking and alcohol use behaviors need to be targeted with a different intervention.

Aims: The present study describes the derivation and validation of the Chronic Heart Failure Severity Index (CHFSI)., Main Methods: The CHFSI was derived using data obtained from a single-center prospective cohort study (2000-2014) that enrolled 756 patients. Logistic regression was used to identify independent predictors of mortality and quality of life over a 15-year follow-up period., Key Findings: The score was validated at the first 5-year (n = 644), second 5-year (n = 364), and third 5-year (n = 262). Independent predictors of mortality were older age (OR = 2.04, P < 0.001), etiology score (OR = 2.61, P < 0.001), faster heart rate (OR = 1.46, P = 0.027), higher systolic blood pressure (OR = 2.35, P < 0.001), and left ventricular ejection fraction ≤45% (OR = 1.97, P = 0.018). The derived CHFSI predicted the mortality, and the AUC for the logistic model was 0.78 (95% confidence interval = 0.74-0.81, P < 0.001). Based on the logistic model, an integer scoring system was derived. Patients were classified into three groups: low risk (0-7 points), intermediate risk (8-11 points) and high risk (≥12 points) groups. The cumulative mortality for 15 years was 45.5% (125/275), 84.0% (204/243), and 100% (99/99), respectively (P < 0.001). The 6-min walk test revealed a significant difference in quality of life among patients in the low, medium and high risk groups (all, P < 0.0001)., Significance: The CHFSI is a very useful clinical predictive tool that identifies patients at risk of future mortality and their quality of life across healthcare systems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Enterocytozoon bieneusi, the most important and common microsporidian species, inhabits in most animals and humans causing diarrhea and systemic diseases. The objectives of the present study were to examine the prevalence and genetic variability of E. bieneusi in pigs in Shaanxi province, northwestern China. A total of 560 pig faecal samples were collected from five different farms in Shaanxi province and molecularly characterized using multilocus genotyping (MLST) technology. High E. bieneusi infection rate (78.9%) was observed in these samples. 12 known and 22 possible novel ITS genotypes were identified, with the novel SZZD1 as the predominant genotype distributed in all age groups and pig farms. 32 (including 11 known and 21 novel ones) of them belong to the zoonotic group 1. MLST analysis showed that 109 ITS positive samples formed 87 distinct multilocus genotypes (MLGs). An incomplete linkage disequilibrium (LD) and clonal genetic structure of E. bieneusi were found in pigs in Shaanxi province. These findings indicated the complex population structures of E. bieneusi in pigs in Shaanxi province and provided baseline data for better understanding of the epidemiological status of E. bieneusi in this province., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cryptosporidium parvum is one of the most important enteric protozoan pathogens, responsible for severe diarrhea in immunocompromised human and livestock. However, few effective agents were available for controlling this parasite. Accumulating evidences suggest that long non-coding RNA (lncRNA) played key roles in many diseases through regulating the gene expression. Here, the expression profiles of lncRNAs and mRNAs were analyzed in HCT-8 cells infected with C. parvum IId subtype using microarray assay. A total of 821 lncRNAs and 1,349 mRNAs were differentially expressed in infected cells at 24 h post infection (pi). Of them, all five types of lncRNAs were identified, including 22 sense, 280 antisense, 312 intergenic, 44 divergent, 33 intronic lncRNAs, and 130 lncRNAs that were not found the relationship with mRNAs' location. Additionally, real-time polymerase chain reactions of 10 lncRNAs and 10 mRNAs randomly selected were successfully confirmed the microarray results. The co-expression and target prediction analysis indicated that 27 mRNAs were cis -regulated by 29 lncRNAs and 109 were trans -regulated by 114 lncRNAs. These predicted targets were enriched in several pathways involved in the interaction between host and C. parvum , e.g., hedgehog signaling pathway, Wnt signaling pathway, and tight junction, suggesting that these differentially expressed lncRNAs would play important regulating roles during the infection of C. parvum IId subtype.

Background: Generally, tea plants are grown in acid soil which is rich in aluminum (Al) and fluoride (F). A recent publication showed that pretreatment with Al(3+) promoted F accumulation in tea plants by increasing endogenous Ca(2+) and calmodulin (CaM). A high level of F in tea leaves not only impairs tea quality but also might pose a health risk for people drinking tea regularly. Therefore it is important to try to find some clues which might be beneficial in controlling F accumulation in tea plants grown in acid soil (Al(3+) )., Results: It was found that diisothiocyanostilbene-2,2-disulfonic acid (DIDS) significantly reduced Al(3+) -promoted F accumulation in tea plants. Additionally, Al(3+) plus DIDS treatment stimulated significantly higher Ca(2+) efflux and decreased the CaM level in tea roots compared with Al(3+) treatment. Besides, significantly higher depolarization of membrane potential was shown in tea roots treated with Al(3+) plus DIDS than in those treated with Al(3+) , as well as higher net total H(+) efflux and plasma membrane H(+) -ATPase activity., Conclusion: Al(3+) -promoted F accumulation in tea plants was inhibited by an anion channel inhibitor DIDS. Ca(2+) /CaM and membrane potential depolarization may be the components involved in this process. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Tea plant is known to be a hyper-accumulator of fluoride (F). Over-intake of F has been shown to have adverse effects on human health, e.g., dental fluorosis. Thus, understanding the mechanisms fluoride accumulation and developing potential approaches to decrease F uptake in tea plants might be beneficial for human health. In the present study, we found that pretreatment with the anion channel inhibitor NPPB reduced F accumulation in tea plants. Simultaneously, we observed that NPPB triggered Ca(2+) efflux from mature zone of tea root and significantly increased relative CaM in tea roots. Besides, pretreatment with the Ca(2+) chelator (EGTA) and CaM antagonists (CPZ and TFP) suppressed NPPB-elevated cytosolic Ca(2+) fluorescence intensity and CaM concentration in tea roots, respectively. Interestingly, NPPB-inhibited F accumulation was found to be significantly alleviated in tea plants pretreated with either Ca(2+) chelator (EGTA) or CaM antagonists (CPZ and TFP). In addition, NPPB significantly depolarized membrane potential transiently and we argue that the net Ca(2+) and H⁺ efflux across the plasma membrane contributed to the restoration of membrane potential. Overall, our results suggest that regulation of Ca(2+)-CaM and plasma membrane potential depolarization are involved in NPPB-inhibited F accumulation in tea plants.

Tea plant (Camellia sinensis (L.) O. kuntze) is known to be a fluoride (F) and aluminum (Al(3+)) hyper-accumulator. Previous study showed that pre-treatment of Al(3+) caused a significant increase of F accumulation in tea plants. However, less is known about the intricate network of Al(3+) promoted F accumulation in tea plants. In this study, the involvement of endogenous Ca(2+) and CaM in Al(3+) pretreatment-promoted F accumulation in tea plants was investigated. Our results showed that Al(3+) induced the inverse change of intracellular Ca(2+) fluorescence intensity and stimulated Ca(2+) trans-membrane transport in the mature zone of tea root. Also, a link between internal Ca(2+) and CaM was found in tea roots under the presence of Al(3+). In order to investigate whether Ca(2+) and CaM were related to F accumulation promoted by Al(3+) pretreatment, Ca(2+) chelator EGTA and CaM antagonists CPZ and TFP were used. EGTA, CPZ, and TFP pretreatment inhibited Al(3+)-induced increase of Ca(2+) fluorescence intensity and CaM content in tea roots, and also significantly reduced Al(3+)-promoted F accumulation in tea plants. Taken together, our results suggested that the endogenous Ca(2+) and CaM are involved in Al(3+) pretreatment-promoted F accumulation in tea roots., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

This study aimed to examine the association between sleep disturbance and attempted suicide in rural China. The study group included 409 suicide attempters from six rural counties in Shandong Province, China and an equal number of controls matched on age, sex, and residency. Sleep disturbance was assessed by the item "sleep restless" in the Center for Epidemiologic Studies Depression Scale. Sleep disturbance was reported more frequently in suicide attempters than in controls (1-2 days/week, 9.0% vs. 4.4%; 3-4 days/week, 11.5% vs. 2.4%; ≥5 days/week, 30.3% vs. 7.5%, χ 2= 128.72, p < 0.001). Suicide risk was significantly associated with increased frequency of sleep disturbance (OR = 3.98, 95% CI = 1.62-9.74 for 1-2 days/week; OR = 3.28, 95% CI = 1.21-8.84 for 3-4 days/week; OR = 2.41, 95% CI = 1.26-4.60 for ≥5 days/week) even after adjusting for potential psychosocial confounding factors and mental disorders. This finding may have important implications for early intervention and prevention of suicide.

Aim: To perform a profiling analysis of changes in intestinal microRNA (miRNA) expression during hypothermic circulatory arrest (HCA)., Methods: A total of eight piglets were randomly divided into HCA and sham operation (SO) groups. Under general anesthesia, swine in the HCA group were subjected to hypothermic cardiopulmonary bypass at 24 °C followed by 80 min of circulatory arrest, and the reperfusion lasted for 180 min after cross-clamp removal. The counterparts in the SO group were only subjected to median sternotomy. Histopathological analysis was used to detect mucosal injury, and Pick-and-Mix custom miRNA real-time polymerase chain reaction (PCR) panels containing 306 unique primer sets were utilized to assay unpooled intestinal samples harvested from the two groups., Results: The intestinal mucosa of the animals that were subjected to 24 °C HCA exhibited representative ischemic reperfusion injury of grade 2 or 3 according to the Chiu score. Such intestinal mucosal injuries, with the subepithelial space and epithelial layer lifting away from the lamina propria, were accompanied by shortened and irregular villi. On the contrary, the intestinal mucosa remained normal in the sham-operated animals. In total, twenty-five miRNAs were differentially expressed between the two groups (15 upregulated and 10 downregulated in the HCA group). Among these, eight miRNAs (miR-122, miR-221-5p, miR-31, miR-421-5p, miR-4333, miR-499-3p, miR-542 and let-7d-3p) were significantly dysregulated (four higher and four lower). The expression of miR-122 was significantly (5.37-fold) increased in the HCA group vs the SO group, indicating that it may play a key role in HCA-induced mucosal injury., Conclusion: Exposure to HCA caused intestinal miRNA dysregulation and barrier dysfunction in swine. These altered miRNAs might be related to the protection or destruction of the intestinal barrier.

Objective: This study aimed to examine the association between negative life events (NLEs) and attempted suicide in rural China., Methods: Six rural counties were selected from disease surveillance points in Shandong province, China. A total of 409 suicide attempters in rural areas between October 1, 2009, and March 31, 2011, and an equal number of matched controls were interviewed. We compared negative life events experienced within 1 month, 1-3 months, 3-6 months, and 6-2 months prior to attempted suicide for cases and prior to interview for controls. We used multivariate logistic regression to examine the association between NLEs and attempted suicide., Results: Suicide attempters experienced more NLEs within the last year prior to suicide attempt than controls prior to interview (83.1% vs. 33.5%). There was a significant dose-response relationship between NLEs experienced within the last year and increased risk of attempted suicide. Timing of NLEs analysis showed that NLEs experienced in the last month and 6-12 months prior to suicide attempt were significantly associated with elevated risk of attempted suicide, even after adjusting for mental disorders and demographic factors. Of NLEs, quarrelling with spouse, quarrelling with other family members, conflicting with friends or neighbors, family financial difficulty, and serious illness were independently related to attempted suicide., Conclusion: NLEs are significantly associated with increased risk for attempted suicide in rural China. Stress management and intervention may be important to prevent suicidal behavior in rural China.

The authors recruited 401 suicide attempters from general hospitals and 409 matched non-attempters to evaluate the psychometric properties of the Beck Hopelessness Scale (BHS) in rural China. All participants completed the BHS, Center for Epidemiologic Studies Depression Scale (CES-D), and Trait Anxiety Inventory (TAI). Suicide attempters had higher BHS scores than non-attempters. Cronbach's alpha coefficients were satisfactory and BHS scores significantly correlated to CES-D and TAI scores. Confirmatory factor analysis supported a four-factor model for suicide attempters and a five-factor model for non-attempters. The BHS is satisfactory in assessing hopelessness among suicide attempters in rural China.

Background & Aims: Transarterial chemoembolization (TACE) is recommended as standard care for intermediate hepatocellular carcinoma (HCC). We analyse the rationality and effectiveness of TACE with BCLC B stage HBV-related HCC in a large cohort., Methods: A total of 1516 patients with BCLC B stage from 7724 HBV-related HCCs who received TACE as initial treatment were retrospectively studied. The treatment response was assessed by the mRECIST criteria. The overall survival was calculated with life-table method and compared with the Mantel-Cox test. The prognostic factors were assessed using Cox proportional hazards., Results: The 1-, 3- and 5-year overall survival rates were 84%, 29% and 19% respectively for all patients. Alpha-foetoprotein, Child-Pugh classification, tumour size and number were independent prognostic factors. The 5-year survival for patients with CR, PR, SD and PD were 39%, 19%, 2% and 0%, respectively (P < 0.0001). Child-Pugh A liver function (P = 0.002) and smaller tumour (P < 0.0001) were associated with CR/PR response. After TACE, the 5-year survival rates for patients who received surgical resection, local ablation, repeated TACE and other therapies were 52%, 29%, 12%, 10% respectively (P < 0.0001). In 328 CR patients, the prognosis of 151 patients received surgical resection is better than 177 patients not undergo liver resection (5-year survival: 52% & 27%, P < 0.0001)., Conclusions: Transarterial chemoembolization is a safe and efficacious treatment for BCLC B stage HBV-related HCC. A low AFP level, small tumour, low tumour number and good liver function predicted good survival. Tumour response after initial TACE, an independent prognostic factor of overall survival, was associated with tumour extent and influenced subsequent treatment., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The tea plant is a fluoride (F) and aluminum (Al) hyperaccumulator. High concentrations of F and Al have always been found in tea leaves without symptoms of toxicity, which may be related to the special localization of F and Al in tea leaves. In this study, we for the first time determined the subcellular localization of F and Al in tea roots and leaves and provided evidence of the detoxification mechanisms of high concentrations of F and Al in tea plants. Results revealed that 52.3 and 71.8% of the total F accumulated in the soluble fraction of tea roots and leaves, and vacuoles contained 98.1% of the total F measured in the protoplasts of tea leaves. Cell walls contained 69.8 and 75.2% of the total Al detected in the tea roots and leaves, respectively, and 73.2% of Al sequestered in cell walls was immobilized by pectin and hemicellulose components. Meanwhile, 88.3% of the Al measured in protoplasts was stored in the vacuoles of tea leaves. Our results suggested that the subcellular distributions of F and Al in tea plants play two important roles in the detoxification of F and Al toxicities. First, most of the F and Al was sequestered in the vacuole fractions in tea leaves, which could reduce their toxicities to organelles. Second, Al can be immobilized in the pectin and hemicellulose components of cell walls, which could suppress the uptake of Al by tea roots.

Aim: To investigate the outcome of living donor liver transplantation (LDLT) recipients transplanted with small-for-size grafts (SFSGs)., Methods: Between November 2001 and December 2010, 196 patients underwent LDLT with right lobe liver grafts at our center. Recipients were divided into 2 treatment groups: group A with an actuarial graft-to-recipient weight ratio (aGRWR) < 0.8% (n = 45) and group B with an aGRWR ≥ 0.8% (n = 151). We evaluated serum liver function markers within 4 wk after transplantation. We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients, the donors and the transplantation procedures based upon a review of their medical records., Results: Small-for-size syndrome (SFSS) developed in 7 of 45 patients (15.56%) in group A and 9 of 151 patients (5.96%) in group B (P = 0.080). The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation, albeit not significantly. The cumulative 1-, 3- and 5-year liver graft survival rates were 82.22%, 71.11% and 71.11% for group A and 81.46%, 76.82%, and 75.50% for group B patients, respectively (P = 0.623). However, univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival (P < 0.001). Furthermore, multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival., Conclusion: Our study suggests that LDLT recipients with an aGRWR < 0.8% may have liver graft outcomes comparable to those who received larger size grafts. Further studies are required to ascertain the safety of using SFSGs.

Aim: To investigate the value of two-dimensional (2D) and three-dimensional (3D) double contrast-enhanced ultrasonography (DCUS) imaging for evaluation of gastric lesions., Methods: 2D and 3D DCUS imaging with both oral and intravenous administrations of contrast agents was used to assess gastroscopiclly-confirmed gastric lesions in 46 patients with benign and malignant diseases. Initially, liquid-based ultrasound contrast agent (Xinzhang®) was given orally at dose of 500-600 mL for conventional ultrasound examination of the gastric lesions, and then a microbubble-based contrast agent (SonoVue) was injected intravenously at dose of 1.2-2.4 mL in bolus fashion to assess the perfusion pattern of the lesions using contrast imaging modes. The parameters derived from time-intensity curves including the arrival time (AT), time to peak (TTP), peak intensity (PI) and enhanced intensity (EI) were measured on the 2D DCUS imaging. 3D DCUS of the lesions was acquired to demonstrate the value of this imaging mode., Results: There were 22 cases with benign lesions including chronic gastritis (n = 5), gastric ulcer (n = 9), gastric polyps (n = 3), gastric stromal tumors (n = 5), and 24 cases with malignant lesions including gastric cancer (n = 20), gastric cardia carcinoma (n = 3) and post-operative recurrent gastric cancer (n = 1) in the study. The oral contrast-enhanced ultrasonography (CEUS) imaging of the stomach clearly demonstrated the anatomy of the stomach and morphologic features of gastric lesions. With optimal scanning window and imaging display under oral CEUS, intravenous CEUS clearly showed the perfusion of gastric lesions with various characteristic manifestations. Both 2D and 3D DCUS images clearly demonstrated normal gastric wall as a three-layer structure, from the inside out, hyperechoic mucosa, hypoechoic muscularis and hyperechoic serosa, respectively. There were statistical significant differences of AT (8.68 ± 2.06 vs 10.43 ± 2.75, P = 0.017), PI (34.64 ± 6.63 vs 29.58 ± 8.22, P = 0.023) and EI (29.72 ± 6.69 vs 22.66 ± 7.01, P = 0.001) between malignant lesions and normal gastric wall. However, no differences of AT, PI and EI between benign lesions and normal gastric wall tissue were found. 3D DCUS could intuitively display morphological features and vascularities of the lesions with multiplanar and volume views. 3D DCUS imaging provided comprehensive information complementary to 2D imaging. The crater or wellhead appearances and feeding vessels as well as distorted nourishing vasculature of gastric carcinoma were better seen with 3D imaging than 2D imaging., Conclusion: DCUS imaging can simultaneously display the anatomic and perfusion features of gastric lesions. 3D DCUS can provide additional information to 2D DCUS for evaluation of gastric lesions.

Sphingomyelin synthase (SMS) catalyzes the synthesis of sphingomyelin (SM) and is required for maintenance of plasma membrane microdomain fluidity. Of the two isoforms of mammalian SMS, SMS1 is mostly present in the trans-Golgi apparatus, whereas SMS2 is predominantly found at the plasma membrane. SMS2 has a role in receptor mediated response to inflammation in macrophages, however, the role of SMS2 in vascular permeability, pulmonary edema, and lung injury have not been investigated. To define the role of SMS activation in lung injury, we utilized a lipopolysaccharide (LPS)-induced lung edema model. SMS activity was measured and correlated with the severity of lung injury. Within 4 h of LPS treatment, SMS activity was increased significantly and remained upregulated up to 24 h. Comparison of LPS-induced lung injury in SMS2 knockout (SMS2(-/-)) and wild-type littermate control mice showed that inflammation, cytokine induction, and lung injury were significantly inhibited in SMS2(-/-) mice. Our results suggest that a deficiency of SMS2 can diminish the extent of pulmonary edema and lung injury. Furthermore, we show that depletion of SMS2 was sufficient to decrease MAP kinase-JNK activation, severity of LPS-induced pulmonary neutrophil influx, and inflammation, suggesting a novel role of SMS2 activation in lung injury.

Objective: The phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in ovarian cancer cell survival and proliferation. The aim of this study was to determine whether the suppression of the PI3K catalytic subunit p110alphainhibits the growth of ovarian cancer cells in vitro and in vivo., Methods: The short hairpin RNA (shRNA) was used to knock down the expression of p110alpha in SKOV3 human ovarian cancer cells. The effects of shRNA on cell viability and apoptosis in vitro were assessed using the MTT assay and flow-cytometric analysis. Furthermore, the growth inhibition capacity of shRNA on ovarian carcinoma xenografts was tested in nude mice. Tumor cell proliferation, apoptosis and angiogenesis were measured by proliferating cell nuclear antigen, TUNEL and CD31 immunohistochemistry, respectively., Results: Using sequence-specific shRNA, we have silenced the expression of p110alpha in SKOV3 cells. shRNA-mediated knockdown of p110alpha correlated in vitro with decreased cell viability and increased apoptosis. Furthermore, inhibition of p110alpha significantly delayed the growth of ovarian carcinoma xenografts, and ultimately resulted in decreased cell proliferation, induction of apoptosis as well as a reduction in microvessel density., Conclusions: Our findings suggest that shRNA-directed targeting of p110alpharaises the potential of its application in human ovarian cancer therapy., (Copyright 2009 S. Karger AG, Basel.)

Microtubules are a major structural component of the cytoskeleton and participate in cell division, intracellular transport, and cell morphogenesis. In the present study, 795 cotton tubulin expressed sequence tags were analysed and 19 beta-tubulin genes (TUB) cloned from a cotton cDNA library. Among the group, 12 cotton TUBs (GhTUBs) are reported for the first time here. Transcription profiling revealed that nine GhTUBs were highly expressed in elongating fibre cells as compared with fuzzless-lintless mutant ovules. Treating cultured wild-type cotton ovules with exogenous phytohormones showed that individual genes can be induced by different agents. Gibberellin induced expression of GhTUB1 and GhTUB3, ethylene induced expression of GhTUB5, GhTUB9, and GhTUB12, brassinosteroids induced expression of GhTUB1, GhTUB3, GhTUB9, and GhTUB12, and lignoceric acid induced expression of GhTUB1, GhTUB3, and GhTUB12. When GhTUBs were transformed into the Saccharomyces cerevisiae inviable mutant, tub2, which is deficient in beta-tubulin, one ovule-specific and eight of nine fibre-preferential GhTUBs rescued this lethality. This study suggests that the proteins encoded by cotton GhTUBs are involved during cotton fibre development.

Objective: To study how hepatitis B virus(HBV) 'a' determinant hotpoint mutations were influecing the hepatitis B vaccine efficacy., Methods: Primers were designed in HBV conservative region, and the degenerate probes for detecting 16 'a' determinant hotpoint mutations were developed for gene chips. Sensitivity and specificity of the gene chips were evaluated by clone sequencing. Sera of 47 pairs of mothers and infants with immune failure and 323 mothers of children with immune protection of HB vaccine were detected by the gene chips., Results: Result from clone sequencing demonstrated that the gene chips were specific for the detection of 'a' determinant hotpoint mutations. The wild type of HBV was still dominant, with the prevalence of 78.66%, and the mutation frequencies of 126A, 145R, 126S-1, 126S-2, 129H, 144A, and 129R were 11.27%, 5.76%, 5.28%, 4.56%, 1.20%, 0.72% and 0.24%, respectively. The prevalence of 126A mutation was significantly higher than that of other mutations(P < 0.01). No significant differences were found in mother-infant transmission rates of 126A, 126S-1, 126S-2 and 145R variants., Conclusion: The currently available hepatitis B vaccine could block mother-infant transmission of 126A, 126S and 145R variants. It appears that there is no need to develop a new hepatitis B vaccine against 126 and 145 variants at present, but the consistent epidemiological surveillance on HBV mutants should be carried out.