Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Psychometric Properties of the Chinese Version of the ElectroConvulsive Therapy Cognitive Assessment: An Electroconvulsive Therapy-Specific Cognitive Screening Tool.

OBJECTIVES: Electroconvulsive therapy (ECT) is an effective somatic treatment, but it may be limited by cognitive adverse effects. The existing cognitive screening instruments often lack specificity to ECT-associated cognitive deficits. The ElectroConvulsive Therapy Cognitive Assessment was developed and validated in a clinical setting, but the reliability and validity of the Chinese version of ElectroConvulsive Therapy Cognitive Assessment (ECCA-C) have not been studied in a large clinical sample. METHODS: The ECCA-C and the Montreal Cognitive Assessment (MoCA) were administered to patients with major depressive disorder (MDD) undergoing ECT at 3 time points: pretreatment (baseline), before the fifth treatment, and 1 week posttreatment. The instruments were also administered to a sample of healthy subjects. RESULTS: Sixty-five patients with MDD and 50 age- and sex-matched healthy controls were recruited in this study. Overall, the patient group had statistically significantly lower MoCA and ECCA-C scores than the control group (both P values <0.001). The Cronbach α of the ECCA-C was 0.88 at baseline. Statistically significant decreases over time were observed in ECCA-C: pre-ECT (23.9 ± 4.0) > mid-ECT (21.3 ± 3.4) > post-ECT (18.7 ± 4.8) (all P values <0.001), whereas no statistically significant changes in MoCA scores were found at these 3 time points (F = 1.86, P = 0.165). A cutoff score of 26.5 on the ECCA-C was found to best differentiate between MDD patients and healthy controls. CONCLUSIONS: The ECCA-C showed satisfactory psychometric properties and may be a more sensitive instrument than the MoCA to assess cognitive impairment associated with ECT.

Cognitive reserve in patients with mood disorders: Validation study of the Chinese version of the cognitive reserve assessment scale in health.

BACKGROUND: Cognitive reserve (CR) is closely associated with cognitive and functional outcome, disease severity, progression and prognosis in psychiatric patients; however, it has not been extensively tested in mood disorders. This study examined the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH) in mood disorder patients. METHODS: Altogether 166 subjects were recruited, 44 with major depressive disorder (MDD), 64 with bipolar disorder (BD), and 58 healthy controls. CR was assessed using the CRASH and the Cognitive Reserve Questionnaire (CRQ). RESULTS: Internal consistency (Cronbach's alpha) was 0.779 for the CRASH. The Receiver Operating Characteristic (ROC) curve analysis revealed an area under the ROC curve (AUC) value of 0.73 (95 % CI: 0.647-0.809). The optimal cut-off score of 51 generated the best combination of sensitivity (0.78) and specificity (0.43) for discriminating between patients with mood disorders and healthy controls. The CRASH score was highly correlated with the CRQ score in both mood disorder patients (rs = 0.586, P < 0.001) and healthy controls (rs = 0.627, P < 0.001), indicating acceptable convergent validity for the CRASH. Within the mood disorder sample, the CRASH score was associated with functional outcomes (FAST: rs = -0.243, P = 0.011). CONCLUSIONS: The CRASH is a useful tool to measure CR in mood disorder with acceptable psychometric properties and could be used in both research and clinical practice.

Role of social organization engagement in high-risk groups intervention against HIV/AIDS: a case study from 176 cities of China.

BACKGROUND: A high-risk prevention strategy is an effective way to fight against human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). The China AIDS Fund for Non-Governmental Organizations (CAFNGO) was established in 2015 to help social organizations intervene to protect high-risk populations in 176 cities. This study aimed to evaluate the role of social organizations in high-risk population interventions against HIV/AIDS. METHODS: This study was based on the CAFNGO program from 2016 to 2020. The collected data included the number and types of social organizations participating in high-risk group interventions and the amount of funds obtained by these organizations each year. We explored the factors influencing the number of newly diagnosed AIDS cases using a spatial econometric model. Furthermore, we evaluated the effectiveness of intervention activities by comparing the percentages of the individuals who initially tested positive, and the individuals who took the confirmatory test, as well as those who retested positive and underwent the treatment. RESULTS: Overall, from 2016 to 2020, the number of social organizations involved in interventions to protect HIV/AIDS high-risk populations increased from 441 to 532, and the invested fund increased from $3.98 to $10.58 million. The number of newly diagnosed cases decreased from 9128 to 8546 during the same period. Although the number of cities with overall spatial correlations decreased, the spatial agglomeration effect persisted in the large cities. City-wise, the number of social organizations (direct effect 19.13), the permanent resident population (direct effect 0.12), GDP per capita (direct effect 17.58; indirect effect - 15.38), and passenger turnover volume (direct effect 5.50; indirect effect - 8.64) were the major factors influencing new positive cases confirmed through the testing interventions performed by the social organizations. The initial positive test rates among high-risk populations were below 5.5%, the retesting rates among those who initially tested positive were above 60%, and the treatment rates among diagnosed cases were above 70%. CONCLUSIONS: The spatial effect of social organizations participating in interventions targeting high-risk populations funded by CAFNGO is statistically significant. Nevertheless, despite the achievements of these social organizations in tracking new cases and encouraging treatment, a series of measures should be taken to further optimize the use of CAFNGO. Working data should be updated from social organizations to CAFNGO more frequently by establishing a data monitoring system to help better track newly diagnosed AIDS cases. Multichannel financing should be expanded as well.

Territory aggression and energy budget in food-restricted striped hamsters.

Food resource availability is one of the most important factors affecting interindividual competition in a variety of animal species. However, the energy budget and territory aggression strategy of small mammals during periods of food restriction remain uncertain. In this study, metabolic rate, body temperature, territory aggression behavior, and fat deposit were measured in male striped hamster (Cricetulus barabensis) restricted by 20% of ad libitum food intake with or without supplementary methimazole. Serum thyroid hormone (tri-iodothyronine, T3 and thyroxine, T4), and cytochrome c oxidase (COX) activity in liver, brown adipose tissue, and skeletal muscle, were also measured. Attack latency, total attack times and duration, and the interval duration between attacks of resident hamsters were not significantly changed during food restriction, which was not significantly affected by supplementary methimazole. Metabolic rate and body temperature was significantly increased in food-restricted hamsters following introduction of an intruder, which was not completely blocked by supplementary methimazole. Serum T3 and T4 levels and BAT COX activity were not significantly changed following aggression, and were significantly decreased by supplementary methimazole. These findings suggest that striped hamsters increase energy expenditure for territory aggression during food restriction, and consequently lead to excessive energy depletion. Territory aggression behavior may decrease the capacity to cope with food shortage, which may be independent of thyroid hormone.

Validation of the 33-Item Hypomania Checklist-External Assessment in Screening Adolescents for Bipolar Disorder.

Background: Bipolar disorder (BD) is often misdiagnosed, leading to poor treatment outcomes. Thus, accurate assessment of BD is of great importance, including in BD adolescents. The aim of the study was to explore the psychometric properties of the 33-item Hypomania Checklist-External Assessment (HCL-33-EA) in depressed adolescents. Methods: The study was conducted between March and November 2020 in Beijing, China. Depressed adolescents aged between 13 and 17 years (N = 260) with BD (N = 147) or major depressive disorder (MDD) (N = 113) diagnosed according to the International Classification of Diseases, Tenth Revision (ICD-10) were recruited. Patients' hypomanic symptoms were assessed by their carers using the HCL-33-EA. Results: The HCL-33-EA showed high internal consistency (Cronbach's alpha = 0.82) with two factorial dimensions. The Receiver Operating Characteristic (ROC) curve analysis revealed an area under the ROC curve (AUC) value of 0.61 (95% confidence interval (CI): 0.54-0.67). The optimal cut-off score of 7 generated the best combination of sensitivity (0.81) and specificity (0.37) for discriminating between adolescents with BD and MDD. Conclusion: The HCL-33-EA, with a two-factor structure, seems to be a useful tool for screening for BD in depressed adolescents. However, the high sensitivity and low specificity of the HCL-33-EA at the optimal cut-off value of 7 indicate that the HCL-33-EA needs to be further refined for young patients.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

Predictors of rapid eye movement sleep behavior disorder in patients with Parkinson's disease based on random forest and decision tree.

BACKGROUND AND OBJECTIVES: Sleep disorders related to Parkinson's disease (PD) have recently attracted increasing attention, but there are few clinical reports on the correlation of Parkinson's disease patients with rapid eye movement (REM) sleep behavior disorder (RBD). Therefore, this study conducted a cognitive function examination for Parkinson's disease patients and discussed the application effect of three algorithms in the screening of influencing factors and risk prediction effects. METHODS: Three algorithms (logistic regression, machine learning-based regression trees and random forest) were used to establish a prediction model for PD-RBD patients, and the application effects of the three algorithms in the screening of influencing factors and the risk prediction of PD-RBD were discussed. RESULTS: The subjects included 169 patients with Parkinson's disease (Parkinson's disease with RBD [PD-RBD] = 69 subjects; Parkinson's disease without RBD [PD-nRBD] = 100 subjects). This study compared the predictive performance of RF, decision tree and logistic regression, selected a final model with the best model performance and proposed the importance of variables in the final model. After the analysis, the accuracy of RF (83.05%) was better than that of the other models (decision tree = 75.10%, logistic regression = 71.62%). PQSI, Scopa-AUT score, MoCA score, MMSE score, AGE, LEDD, PD-course, UPDRS total score, ESS score, NMSQ, disease type, RLSRS, HAMD, UPDRS III and PDOnsetage are the main variables for predicting RBD, along with increased weight. Among them, PQSI is the most important factor. The prediction model of Parkinson's disease RBD that was established in this study will help in screening out predictive factors and in providing a reference for the prognosis and preventive treatment of PD-RBD patients. CONCLUSIONS: The random forest model had good performance in the prediction and evaluation of PD-RBD influencing factors and was superior to decision tree and traditional logistic regression models in many aspects, which can provide a reference for the prognosis and preventive treatment of PD-RBD patients.

A comparison of the 33-item Hypomania Checklist with the 33-item Hypomania Checklist-external assessment for the detection of bipolar disorder in adolescents.

BACKGROUND: Adolescents with bipolar disorder (BD) are often misdiagnosed as having major depressive disorder (MDD), which delays appropriate treatment and leads to adverse outcomes. The aim of this study was to compare the performance of the 33-item Hypomania Checklist (HCL-33) with the 33-item Hypomania Checklist- external assessment (HCL-33-EA) in adolescents with BD or MDD. METHODS: 147 adolescents with BD and 113 adolescents with MDD were consecutively recruited. The HCL-33 and HCL-33-EA were completed by patients and their carers, respectively. The sensitivity, positive predictive value (PPV), specificity, negative predictive value (NPV), and area under the curve (AUC) were calculated and compared between the two instruments, using cut-off values based on the Youden's index. RESULTS: The total scores of the HCL-33 and HCL-33-EA were positively and significantly correlated (rs = 0.309, P < 0.001). Compared to the HCL-33, the HCL-33-EA had higher sensitivity and NPV (HCL-33: sensitivity = 0.58, NPV = 0.53; HCL-33-EA: sensitivity = 0.81, NPV = 0.60), while the HCL-33 had higher specificity and PPV (HCL-33: specificity = 0.61, PPV = 0.66; HCL-33-EA: specificity = 0.37, PPV = 0.63). CONCLUSION: Both the HCL-33 and HCL-33-EA seem to be useful for screening depressed adolescents for BD. The HCL-33-EA would be more appropriate for distinguishing BD from MDD in adolescents due to its high sensitivity in Chinese clinical settings.

Concentration, spatial distribution, and health risk assessment of PFASs in serum of teenagers, tap water and soil near a Chinese fluorochemical industrial plant.

Discharges released from fluorochemical industrial plants lead to severe contamination of the environment with per- and polyfluoroalkyl substances (PFASs), which may pose risks to human health. In this study, 187 serum samples from teenagers (age = 14 years), 22 tap water samples and 40 soil samples were collected in areas within 0-11 km of a fluorochemical industrial plant in Huantai County, Shandong Province, and concentrations of 18 PFASs were quantified by UPLC-MS/MS. Perfluorooctanoic acid (PFOA) was found to be predominant, concentrations of which ranged from 40.4 to 845 ng/mL in serum, from 2.88 to 19.3 ng/L in tap water, from 4.40 to 189 ng/g in soil, and accounting for 84.1-98.6%, 15.9-79.8%, and 73.8-96.7% of the total PFASs, respectively. Statistical analysis demonstrated that concentrations of perfluorinated carboxylic acids (PFCAs) in soil (C5-C9) and serum (C8-C10) were associated with the industrial plant. And PFOA concentrations in tap water were not relevant to the industrial plant, which were comparable with the non-contaminated area and lower than the threshold value recommended by U.S. EPA (70 ng/mL), indicating that the contribution to the high concentration of serum PFOA of local teenagers by drinking water was limited. Moreover, PFCAs in soil only made a limited contribution to the serum PFCAs of local residents by direct inhalation and dermal exposure, but the potential health risk by the soil via food chain should be paid attention to. Furthermore, health risk assessment demonstrated that high concentrations of PFOA in serum could pose potential health risk to local teenagers. Therefore, effective measures should be taken to attenuate the health risks caused by the industrial plant to local residents, and further epidemiological studies should be carried out in the future.

[An assessment of white matter development in preterm infants with bronchopulmonary dysplasia using diffusion tensor imaging].

OBJECTIVE: To assess white matter development in preterm infants with bronchopulmonary dysplasia (BPD) using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of diffusion tensor imaging (DTI). METHODS: Ninety-six infants with a gestational age of ≤32 weeks and a birth weight of <1 500 g who were admitted to the neonatal intensive care unit within 24 hours after birth from August 2016 to April 2019 and underwent head MRI and DTI before discharge were enrolled. According to the discharge diagnosis, they were divided into BPD group with 48 infants and non-BPD group with 48 infants. The two groups were compared in terms of FA and ADC values of the same regions of interest on DTI image. RESULTS: There were no significant differences in the incidence rates of periventricular/intraventricular hemorrhage, periventricular leukomalacia, and punctate white matter lesions between the two groups (P>0.05). Compared with the non-BPD group, the BPD group had significantly lower FA values and significantly higher ADC values of the posterior limb of the internal capsule, the splenium of the corpus callosum, the occipital white matter, the cerebellum, and the cerebral peduncle (P<0.05). Compared with the non-BPD group, the BPD group had a significantly higher frequency of apnea, a significantly higher proportion of infants with pneumonia or mechanical ventilation, and a significantly longer duration of assisted ventilation (P<0.05). CONCLUSIONS: BPD may has potential adverse effects to white matter development in preterm infants, leading to delayed white matter development. Therefore, it is necessary to pay attention to the neurological function of these infants.

Integrative graph regularized matrix factorization for drug-pathway associations analysis.

Pathway-based drug discovery can give full consideration to the efficacy of compounds in the systemic physiological environment. The recently emerged drug-pathway association identification approaches gain popularity due to its potential to decipher the mechanism of action and the targets of compounds. In this study, we propose a novel drug-pathway association identification method: Integrative Graph regularized Matrix Factorization (IGMF). It employs graph regularization to encode data geometrical information and prevent possible overfitting in prediction. Furthermore, it achieves parts-based and sparse data representation by imposing L1-norm regularization on the objective function. Empirical studies demonstrate that IGMF has strong advantages in identifying more new drug-pathway associations compared to its peer methods. It further shows a good capability to unveil the intrinsic structures of data. As an effective drug-pathway discovery method, it will inspire new analytics methods in this subfield.

Anchoring and Upgrading Ultrafine NiPd on Room-Temperature-Synthesized Bifunctional NH2 -N-rGO toward Low-Cost and Highly Efficient Catalysts for Selective Formic Acid Dehydrogenation.

Hydrogen is widely considered to be a sustainable and clean energy alternative to the use of fossil fuels in the future. Its high hydrogen content, nontoxicity, and liquid state at room temperature make formic acid a promising hydrogen carrier. Designing highly efficient and low-cost heterogeneous catalysts is a major challenge for realizing the practical application of formic acid in the fuel-cell-based hydrogen economy. Herein, a simple but effective and rapid strategy is proposed, which demonstrates the synthesis of NiPd bimetallic ultrafine particles (UPs) supported on NH2 -functionalized and N-doped reduced graphene oxide (NH2 -N-rGO) at room temperature. The introduction of the NH2 N group to rGO is the key reason for the formation of the ultrafine and well-dispersed Ni0.4 Pd0.6 UPs (1.8 nm) with relatively large surface area and more active sites. Surprisingly, the as-prepared low-cost NiPd/NH2 -N-rGO dsiplays excellent hydrophilicity, 100% H2 selectivity, 100% conversion, and remarkable catalytic activity (up to 954.3 mol H2 (mol catalyst)-1 h-1 ) for FA decomposition at room temperature even with no additive, which is much higher than that of the best catalysts so far reported.

Prenatal assessment of pulmonary maturity on 3-D ultrasound.

AIM: The aim of this study was to assess the feasibility and accuracy of 3-D ultrasound indices to evaluate fetal lung maturity, and to establish a normal reference for fetal lung volume (FLV) and fetal lung-to-liver intensity ratio (FLLIR) in a Chinese population. METHODS: A total of 1022 pregnant women with singleton pregnancy were prospectively studied between June 2008 to June 2011. Ultrasound examination was performed. The breathing-related nasal fluid flow (BRNFF) spectrum, FLV, pulmonary artery blood flow parameters, and echo intensity of the lung were calculated. Phosphoglycerides in the amniotic fluid were measured on thin layer chromatography. RESULTS: FLLIR and FLV were positively and linearly correlated with gestational age (F = 0.915, 0.846). Indicators of fetal lung maturity included FLLIR >1.1, FLV >50 mL, and regular BRNFF spectrum, with positive likelihood ratios of 12.28, 11.78, and 11.63, independently. CONCLUSION: Ultrasound indices, including FLLIR, FLV and BRNFF may serve as useful alternatives to amniotic fluid phospholipids in analyzing fetal lung maturity in Chinese patients.

[Pollution Characteristics and Risk Assessment of Polybrominated Diphenyl Ethers in the Surface Sediments from Middle Reaches of the Yangtze River].

Polybrominated diphenyl ethers (PBDEs) are highly lipophilic compounds with high toxicity and long-term bioaccumulation, which have strong affinities to suspended particulates in water. So PBDEs are easily adsorbed to sediments, and cause potential risks to human beings and aquatic ecosystem. In order to investigate the levels and patterns of PBDEs in the Yangtze River, 13 surface sediment samples were collected from the middle reaches of the regions and the concentrations of 9 PBDE congeners in the sediments were determined using High Resolution Gas Chromatography/High Resolution Mass Spectrometry (HRGC/HRMS). The total concentrations of PBDEs ranged from 46.1 to 326 pg · g⁻¹ dry weight. BDE-99 and BDE-47 were the dominant PBDE congeners, which averagely contributed 51.6% and 19.6%, respectively. The concentrations of PBDEs were relatively low compared to those in other studies. The total organic carbon (TOC) was also analyzed in this study, and the results indicated that there was no obvious positive correlation between the levels of PBDEs and TOC. In addition, based on the PBDEs concentration levels, the ecotoxicological risks of PBDEs contamination in surface sediments of the Yangtze River were evaluated by the quotient method. The results showed that the levels of PBDEs were considerably low and these compounds should have no risk to human health.

[Levels distribution and risk assessment of the indicator and dioxin-like polychlorinated biphenyls in ten different species of marine fish of Bohai Bay, China].

Polychlorinated biphenyls (PCBs) are highly lipohilic compounds with high metabolic persistence and toxicity. PCBs tend to accumulate in the aquatic food chain and make fish a source of various environmental toxicants to humans. Industries in the Bohai Bay include iron and steel smelting, cement manufacturing and waste incineration, which are potential emission sources of PCBs. In this study, risks and potential effects of PCBs in the Bohai Bay were assessed. Twelve dioxin-like polychlorinated biphenyls (dl-PCBs) and seven indicator PCBs in marine fish samples were analyzed by High Resolution Gas Chromatography/High Resolution Mass Spectrometry (HRGC/HRMS). The concentrations of dl-PCBs in marine fishes ranged from 28.9 pg x g(-1) to 1067.6 pg x g(-1) wet weight. The concentrations of indicator PCBs were between 185.5 pg x g(-1) and 8 371.7 pg x g(-1) wet weight. PCB-118 and PCB-105 were the major congeners of the dl-PCBs congeners, which contributed 41% - 56% and 15% - 21%, respectively. The predominant indicator PCBs were PCB-153 and PCB-138, which contributed 27% and 22%, respectively. The concentrations of dl-PCBs and indicator PCBs were relatively low as compared with those in other studies.

The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma.

BACKGROUND & AIMS: Recent evidence suggests that hepatocellular carcinoma can be classified into certain molecular subtypes with distinct prognoses based on the stem/maturational status of the tumor. We investigated the transcription program deregulated in hepatocellular carcinomas with stem cell features. METHODS: Gene and protein expression profiles were obtained from 238 (analyzed by microarray), 144 (analyzed by immunohistochemistry), and 61 (analyzed by qRT-PCR) hepatocellular carcinoma cases. Activation/suppression of an identified transcription factor was used to evaluate its role in cell lines. The relationship of the transcription factor and prognosis was statistically examined. RESULTS: The transcription factor SALL4, known to regulate stemness in embryonic and hematopoietic stem cells, was found to be activated in a hepatocellular carcinoma subtype with stem cell features. SALL4-positive hepatocellular carcinoma patients were associated with high values of serum alpha fetoprotein, high frequency of hepatitis B virus infection, and poor prognosis after surgery compared with SALL4-negative patients. Activation of SALL4 enhanced spheroid formation and invasion capacities, key characteristics of cancer stem cells, and up-regulated the hepatic stem cell markers KRT19, EPCAM, and CD44 in cell lines. Knockdown of SALL4 resulted in the down-regulation of these stem cell markers, together with attenuation of the invasion capacity. The SALL4 expression status was associated with histone deacetylase activity in cell lines, and the histone deacetylase inhibitor successfully suppressed proliferation of SALL4-positive hepatocellular carcinoma cells. CONCLUSIONS: SALL4 is a valuable biomarker and therapeutic target for the diagnosis and treatment of hepatocellular carcinoma with stem cell features.

When the lowest energy does not induce native structures: parallel minimization of multi-energy values by hybridizing searching intelligences.

BACKGROUND: Protein structure prediction (PSP), which is usually modeled as a computational optimization problem, remains one of the biggest challenges in computational biology. PSP encounters two difficult obstacles: the inaccurate energy function problem and the searching problem. Even if the lowest energy has been luckily found by the searching procedure, the correct protein structures are not guaranteed to obtain. RESULTS: A general parallel metaheuristic approach is presented to tackle the above two problems. Multi-energy functions are employed to simultaneously guide the parallel searching threads. Searching trajectories are in fact controlled by the parameters of heuristic algorithms. The parallel approach allows the parameters to be perturbed during the searching threads are running in parallel, while each thread is searching the lowest energy value determined by an individual energy function. By hybridizing the intelligences of parallel ant colonies and Monte Carlo Metropolis search, this paper demonstrates an implementation of our parallel approach for PSP. 16 classical instances were tested to show that the parallel approach is competitive for solving PSP problem. CONCLUSIONS: This parallel approach combines various sources of both searching intelligences and energy functions, and thus predicts protein conformations with good quality jointly determined by all the parallel searching threads and energy functions. It provides a framework to combine different searching intelligence embedded in heuristic algorithms. It also constructs a container to hybridize different not-so-accurate objective functions which are usually derived from the domain expertise.

Laboratory assessment of uptake and toxicity of lanthanum (La) in the leaves of Hydrocharis dubia (Bl.) Backer.

Increasing amounts of lanthanum (La) is released into aquatic environments. However, little information is available on the influence of La on aquatic plants. In this study, physiological and ultrastructural responses of Hydrocharis dubia (Bl.) Backer leaves to elevated concentrations of La (up to 160 µM) were investigated. The accumulation of La was found to be increased in a concentration-dependent manner. La disturbed the intrinsic balance of nutrient elements (P, Mg, Ca, Fe, K, and Zn). Pigment content decreased with the rise of the La concentrations and the EC(50) value for chlorophyll was 20 µM on day 7. The antioxidants (superoxide dismutase, peroxidase, catalase, reduced ascorbate, and reduced glutathione) exhibited varied response to the La treatments. Malondialdehyde content enhanced gradually at all La concentrations. The enhancement in proline content was found in a concentration-dependent manner. The amounts of three polypeptides with apparent molecular weights of 61.9, 51.5, and 16.7 kDa, respectively, were gradually diminished, as well as one existing polypeptides with apparent molecular weight of 22.3 kDa, elevating in response to increasing La concentrations. Significant damage to the chloroplast, mitochondrion, and nucleus was imposed by La indicated a general disarray in the cellular functions. The negative effects of La on H. dubia unequivocally indicate that La could exert an adverse influence on aquatic ecosystem and should lead to a more careful discharge of such elements into water environment.

O-H bond dissociation enthalpies of oximes: a theoretical assessment and experimental implications.

By using a multilayer composite ab initio method ONION-G3B3, we calculated O-H bond dissociation enthalpies (BDEs) of 58 oximes that were measured experimentally. Experimental BDEs derived from thermal decomposition kinetics and calorimetric measurements were found to be consistent with the theory. However, the electrochemical method was found to give questionably high BDEs possibly due to errors in the measurement of pKa's or redox potentials. Subsequently, the performances of a variety of DFT functionals including B3LYP, B3P86, B3PW91, BHandH, BHandHLYP, BMK, PBE1PBE, MPW1KCIS, mPWPW91, MPW1B95, and MPW1K were tested to calculate oxime O-H BDEs, where ROBHandHLYP was found to be the most accurate. By using this method, we calculated O-H BDEs of over 140 oximes in a systematic fashion. All of the calculated O-H BDEs fell in the range from 76.8 to 89.8 kcal/mol. An amino group on the azomethine carbon was found to strengthen the O-H bond, whereas bulky alkyl substituents on oximes decreased O-H BDEs due to their large steric-strain-relieving effects in the process of O-H bond cleavage. Para substituents had little effect on the BDEs of benzaldoximes and phenyl methyl ketoximes. Finally, on the basis of a spin distribution calculation, aryl-, alkyl-, and carbonyl-substituted iminoxyl radicals were found to be sigma-radicals, whereas amino-substituted iminoxyl radicals were of pi-structure.