Synthesis and Antibacterial Activity of Novel 4″-O-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains.

A series of novel 4″-O-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains was synthesized by coupling 6-deoxy-desosamine donors (18, 19) with 4″-OH of compounds 5a-c. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive and resistant pathogens, and compounds 21d and 21e displayed significant improvement of activities against resistant pathogens.

Antibacterial activities of a series of novel 5-O-(4', 6'-O-dimodified)-mycaminose 14-membered ketolides.

A series of novel 5-O-(4',6'-O-dimodified)-mycaminose 14-membered ketolides were assessed for their in vitro antibacterial activities against a panel of sensitive and resistant pathogens. Compound 1 and compound 2, two ester analogs, showed the best antibacterial activities against several macrolide-sensitive and macrolide-resistant strains. These results indicated that introducing ester to 6-OH and a small volume ether substituent to the 4-OH of mycaminose could improve the antibacterial activities of ketolides.

Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl side chains.

A series of quinoylalkyl side chains was designed and synthesized, followed by introduction into ketolides by coupling with building block 6 or 32. The corresponding targets 7a-n, 33b, and 33e were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.

Correlation between serum interleukin-6 level and type 1 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: This report aimed to explore the association between the change of circulating interleukin-6 (IL-6) in patients and the development of type 1 diabetes mellitus (T1DM). METHODS: Four databases (PubMed, CNKI, WanFang and Civip) were used to search and list all clinical case-control studies about serum IL-6 level in T1DM patients between Jan 1, 2000 and Aug 31, 2016. RESULTS: A total of 20 case-control studies with 1238 T1DM patients and 742 healthy controls were included in this study. Compared to healthy controls, the serum content of IL-6 in patients with T1DM was significantly greater (overall: SMD, 1.49; 95% CI, 1.04 to 1.93; p<0.001), and notably increased in all subgroup with different age, ethnic and disease duration (all p<0.001). Furthermore, the analysis in subgroup exhibited that serum levels of IL-6 in the age greater than 20-year old (SMD, 1.64; 95% CI, 0.57-2.71; p<0.001), the diseased duration among 0-10years (SMD, 2.43; 95% CI, 1.42-3.44; p<0.001) and the sorted American group (SMD, 1.68; 95% CI, 0.85-2.51; p<0.001) were higher than those in control groups. CONCLUSIONS: Patients with T1DM were found to be linked to elevated level of serum IL-6, which the age, ethnic and disease durations in T1DM patients had no effect on the serum IL-6 levels for promoting diabetes mellitus.

Cross-cultural Adaptation and Validation of the Simplified Chinese Version of the Knee Outcome Survey Activities of Daily Living Scale.

PURPOSE: To perform a cross-cultural adaptation and translation of the original version of the Activities of Daily Living Scale of the Knee Outcome Survey into Simplified Chinese and validate of the Simplified Chinese version. METHODS: The original version was translated and cross-culturally adapted into Simplified Chinese according to the guidelines and the recommendations of the American Academy of Orthopaedic Surgeons Outcome Committee. A total of 213 patients (96 male, 117 female) were selected to participate in our investigation. The inclusion criteria were as follows: 18 years of age and older, able to speak Chinese Mandarin and read Simplified Chinese, and referred to physical therapy for evaluation and treatment for a knee disorder. The exclusion criteria were as follows: patients who had disorders or impairments involving both knees, patients who had other conditions that could affect lower extremity function, patients with physical therapy related to the knee in the previous 1 month, and patients with psychological problems. Each participant was asked to complete the Knee Outcome Survey Activities of Daily Living Scale (KOS-ADLS), International Knee Documentation Committee Subjective Knee Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Short Form 36 forms and to provide baseline demographic data. Each participant completed the KOS-ADLS twice on 2 nonconsecutive days for reliability evaluation. A portion of the participants (n = 161) finished the KOS-ADLS a third time 4 weeks after physical treatment to test responsiveness. RESULTS: The original version of the KOS-ADLS was well adapted and translated into Simplified Chinese. Simplified Chinese of KOS-ADLS was shown to have good internal consistency (Cronbach's alpha = 0.855 to 0.929), great test-retest reliability (intraclass correlation coefficient = 0.935 to 0.961), high construct validity as we hypothesized (significant correlations with Short Form 36 subscales, Western Ontario and McMaster Universities Osteoarthritis Index, and International Knee Documentation Committee Subjective Knee Form), and high responsiveness (standard response means = 0.97 to 1.23, standard effect size = 0.81 to 0.91). CONCLUSIONS: Simplified Chinese of KOS-ADLS was shown to have good reliability, validity, and responsiveness for use in patients with knee disorders in China. LEVEL OF EVIDENCE: Level II, testing of previously developed diagnostic criteria in a series of consecutive patients with universally applied gold standard.

New Insights into the Roles of Nogo-A in CNS Biology and Diseases.

Nogos have become a hot topic for its well-known number Nogo-A's big role in clinical matters. It has been recognized that the expression of Nogo-A and the receptor NgR1 inhibit the neuron's growth after CNS injuries or the onset of the MS. The piling evidence supports the notion that the Nogo-A is also involved in the synaptic plasticity, which was shown to negatively regulate the strength of synaptic transmission. The occurrence of significant schizophrenia-like behavioral phenotypes in Nogo-A KO rats also added strong proof to this conclusion. This review mainly focuses on the structure of Nogo-A and its corresponding receptor-NgR1, its intra- and extra-cellular signaling, together with its major physiological functions such as regulation of migration and distribution and its related diseases like stroke, AD, ALS and so on.

Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome.

CONTEXT: Metabolic syndrome (MS) refers to the clustering of metabolic derangements that include hyperglycemia, dyslipidemia, hypertension, and chronic kidney impairment. Those conditions are well known as being synergistically responsible for morbidity from cardiovascular disease as well as for driving the global epidemic of type 2 diabetes. It is still unknown whether an exact unifying pathogenesis of MS exists. OBJECTIVE: The meta-analysis intended to analyze the use of Chinese medicine (CM) as a therapeutic tool to explore indirectly the unifying pathogenesis of MS. METHODS: PubMed, the Chinese National Knowledge Infrastructure (CNKI), and the Wanfang databases were systematically searched from inception to November 2013 for randomized, controlled trials (RCTs) that compared treatment efficacy for MS patients using the Wen Dan decoction (WDD), a CM formula, versus Western conventional therapeutics. OUTCOME MEASURES: Measurements included tests of the overall therapeutic efficacy of WDD for hyperglycemia, hypertension, dyslipidemia, and renal functions, and the study also analyzed adverse events. Data were expressed as weighted mean differences (WMDs), with 95% confidence intervals (95% CIs) and the odds ratio (OR). RESULTS: A total of 31 RCTs were included for meta-analysis, involving 2512 patients and including 1282 participants in the intervention groups. The pooled data favored WDD over the control treatments as follows: (1) hyperglycemia, with a WMD of -0.95 mmol/L (95% CI: -1.19 to -0.71); (2) hypertension, with a WMD of -7.40 mm Hg (95% CI: -9.86 to -4.93); (3) dyslipidemia: (a) total cholesterol (TC), with a WMD of -0.62 mmol/L (95% CI: -0.90 to -0.33); (b) triglycerides (TGs), with a WMD of -0.32 mmol/L (95% CI: -0.52 to -0.13); (c) low-density lipoproteins (LDPs), with a WMD of -0.22 mmol/L (95% CI: -0.41 to -0.02); and (d) high-density lipoproteins (HDPs), with a WMD of 0.10 mmol/L (95% CI: 0.03 to 0.17); and (4) of renal functions: (a) urea, with a WMD of -3.41 mmol/L (95% CI: -5.50 to -1.32) and (b) creatinine, with a WMD of -68.81 µmol/L (95% CI: -132.63 to -4.98). No statistical significance was documented in creatinine clearance between the 2 treatments with a WMD of 15.47 mL/min (95% CI: -7.71 to 38.64). The overall efficacy rate was 91.4% for WDD and 66.9% for the control treatments (OR: 5.33; 95% CI: 4.06 to 6.99). Adverse events were rare and minor. CONCLUSIONS: The consistent improvements found in metabolic profiles by use of the single herbal formula may indirectly imply a common pathogenesis in MS.

Optimal decision-making in relieving global high temperature-related disease burden by data-driven simulation.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization.

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of several pain-related substrates in spinal cord dorsal horn and are critically involved in the modification of pain transmission. The current study demonstrated that protein tyrosine phosphatase 1B (PTP1B), a unique endoplasmic reticulum-resident member of PTP family, displayed an activity-dependent increase in its protein expression and synaptic localization in spinal dorsal horn of adult male rats. PTP1B interacted with the Src Homology 3 (SH3) domain of Synapse-Associated Protein 102 (SAP102), one of the postsynaptic scaffolding proteins that anchored PTP1B at postsynaptic sites. The SAP102-tethered PTP1B augmented the synaptic transmission mediated specifically by GluN2B subunit-containing N-methyl-D-aspartate subtype glutamate receptors. Interference with PTP1B activity or disruption of its interaction with SAP102 attenuated GluN2B-mediated nociceptive transmission and ameliorated pain sensitization induced by intraplantar injection of Complete Freund's Adjuvant. These data suggested that the activity-dependent synaptic redistribution of PTP1B served as an important mechanism regulating GluN2B receptor activity and that manipulation of PTP1B synaptic targeting might represent an effective approach for the treatment of chronic inflammatory pain.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Infectious disease control: from health security strengthening to health systems improvement at global level.

Since the twenty first century, the outbreaks of global infectious diseases have caused several public health emergencies of international concern, imposing an enormous impact on population health, the economy, and social development. The COVID-19 pandemic has once again exposed deficiencies in existing global health systems, emergency management, and disease surveillance, and highlighted the importance of developing effective evaluation tools. This article outlines current challenges emerging from infectious disease control from the perspective of global health, elucidated through influenza, malaria, tuberculosis, and neglected tropical diseases. The discordance among government actors and absent data sharing platforms or tools has led to unfulfilled targets in health system resilience and a capacity gap in infectious disease response. The current situation calls for urgent action to tackle these threats of global infectious diseases with joined forces through more in-depth international cooperation and breaking governance barriers from the purview of global health. Overall, a systematic redesign should be considered to enhance the resilience of health systems, which warrants a great need to sustain capacity-building efforts in emergency preparedness and response and raises an emerging concern of data integration in the concept of One Health that aims to address shared health threats at the human-animal-environment interface.

Allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia and pulmonary eosinophilia: A case report.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an immune-related pulmonary disease caused by sensitization of airway by Aspergillus fumigatus. The disease manifests as bronchial asthma and recurring pulmonary shadows, which may be associated with bronchiectasis. The diagnosis of ABPA mainly depends on serological, immunological, and imaging findings. Pathological examination is not necessary but may be required in atypical cases to exclude pulmonary tuberculosis, tumor, and other diseases through lung biopsy. CASE SUMMARY: An 18-year-old man presented with recurrent wheezing, cough, and peripheral blood eosinophilia. Chest computed tomography showed pulmonary infiltration. There was a significant increase in eosinophils in bronchoalveolar lavage fluid. There was no history of residing in a parasite-endemic area or any evidence of parasitic infection. Pathologic examination of bronchoalveolar lavage fluid excluded fungal and mycobacterial infections. The patient was receiving medication for comorbid diseases, but there was no temporal correlation between medication use and clinical manifestations, which excluded drug-induced etiology. Histopathological examination of lung biopsy specimen showed no signs of eosinophilic granulomatosis with polyangiitis, IgG4-related diseases, or tumors. The diagnosis of ABPA was considered based on the history of asthma and the significant increase in serum Aspergillus fumigatus-specific immunoglobulin (Ig)E. Eosinophil-related diseases were excluded through pathological biopsy, which showed typical pathological manifestations of ABPA. CONCLUSION: The possibility of ABPA should be considered in patients with poorly controlled asthma, especially those with eosinophilia, lung infiltration shadows, or bronchiectasis. Screening for serum IgE, Aspergillus fumigatus-specific IgE and IgG, and alveolar lavage can help avoid misdiagnosis.

Assessment of integrated patterns of human-animal-environment health: a holistic and stratified analysis.

BACKGROUND: Data-driven research is a very important component of One Health. As the core part of the global One Health index (GOHI), the global One Health Intrinsic Drivers index (IDI) is a framework for evaluating the baseline conditions of human-animal-environment health. This study aims to assess the global performance in terms of GOH-IDI, compare it across different World Bank regions, and analyze the relationships between GOH-IDI and national economic levels. METHODS: The raw data among 146 countries were collected from authoritative databases and official reports in November 2021. Descriptive statistical analysis, data visualization and manipulation, Shapiro normality test and ridge maps were used to evaluate and identify the spatial and classificatory distribution of GOH-IDI. This paper uses the World Bank regional classification and the World Bank income groups to analyse the relationship between GOH-IDI and regional economic levels, and completes the case studies of representative countries. RESULTS: The performance of One Health Intrinsic Driver in 146 countries was evaluated. The mean (standard deviation, SD) score of GOH-IDI is 54.05 (4.95). The values (mean SD) of different regions are North America (60.44, 2.36), Europe and Central Asia (57.73, 3.29), Middle East and North Africa (57.02, 2.56), East Asia and Pacific (53.87, 5.22), Latin America and the Caribbean (53.75, 2.20), South Asia (52.45, 2.61) and sub-Saharan Africa (48.27, 2.48). Gross national income per capita was moderately correlated with GOH-IDI (R2 = 0.651, Deviance explained = 66.6%, P < 0.005). Low income countries have the best performance in some secondary indicators, including Non-communicable Diseases and Mental Health and Health risks. Five indicators are not statistically different at each economic level, including Animal Epidemic Disease, Animal Biodiversity, Air Quality and Climate Change, Land Resources and Environmental Biodiversity. CONCLUSIONS: The GOH-IDI is a crucial tool to evaluate the situation of One Health. There are inter-regional differences in GOH-IDI significantly at the worldwide level. The best performing region for GOH-IDI was North America and the worst was sub-Saharan Africa. There is a positive correlation between the GOH-IDI and country economic status, with high-income countries performing well in most indicators. GOH-IDI facilitates researchers' understanding of the multidimensional situation in each country and invests more attention in scientific questions that need to be addressed urgently.

Assessing food security performance from the One Health concept: an evaluation tool based on the Global One Health Index.

BACKGROUND: Food systems instantiate the complex interdependencies across humans, physical environments, and other organisms. Applying One Health approaches for agri-food system transformation, which adopts integrated and unifying approaches to optimize the overall health of humans, animals, plants, and environments, is crucial to enhance the sustainability of food systems. This study develops a potential assessment tool, named the global One Health index-Food Security (GOHI-FS), aiming to evaluate food security performance across countries/territories from One Health perspective and identify relevant gaps that need to be improved for sustainable food systems. METHODS: We comprehensively reviewed existing frameworks and elements of food security. The indicator framework of GOHI-FS was conceptualized following the structure-process-outcome model and confirmed by expert advisory. Publicly available data in 2020 was collected for each indicator. The weighting strategy was determined by the Fuzzy Analytical Hierarchy Process. The data for each indicator was normalized and aggregated by weighted arithmetic mean. Linear regressions were performed to evaluate the associations of GOHI-FS with health and social-economic indicators. RESULTS: The GOHI-FS includes 5 first-level indicators, 19 second-level indicators and 45 third-level indicators. There were 146 countries/territories enrolled for evaluation. The highest average score of first-level indicators was Nutrition (69.8) and the lowest was Government Support and Response (31.3). There was regional heterogeneity of GOHI-FS scores. Higher median scores with interquartile range (IQR) were shown in North America (median: 76.1, IQR: 75.5-76.7), followed by Europe and Central Asia (median: 66.9, IQR: 60.1-74.3), East Asia and the Pacific (median: 60.6, IQR: 55.5-68.7), Latin America and the Caribbean (median: 60.2, IQR: 57.8-65.0), Middle East and North Africa (median: 56.6, IQR: 52.0-62.8), South Asia (median: 51.1, IQR: 46.7-53.8), and sub-Saharan Africa (median: 41.4, IQR: 37.2-46.5). We also found significant associations between GOHI-FS and GDP per capita, socio-demographic index, health expenditure and life expectancy. CONCLUSIONS: GOHI-FS is a potential assessment tool to understand the gaps in food security across countries/territories under the One Health concept. The pilot findings suggest notable gaps for sub-Saharan Africa in numerous aspects. Broad actions are needed globally to promote government support and response for food security.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Tackling global health security by building an academic community for One Health action.

BACKGROUND: One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet. MAIN TEXT: The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation. CONCLUSIONS: The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.

Zinc at cytotoxic concentrations affects posttranscriptional events of gene expression in cancer cells.

Zinc at cytotoxic concentrations has been shown to regulate gene transcription in cancer cells, though zinc's involvement in posttranscriptional regulation is less characterized. In this study, we investigated the involvement of cytotoxic zinc in the posttranscriptional steps of gene expression. Clioquinol, a well-established zinc ionophore, was used to raise intracellular zinc to reported cytotoxic levels. The MCF-7 human cancer cell line was applied as a cell model system. Several parameters were used as indictors of posttranscriptional regulation, including p-body formation, microRNA profiling, expression level of proteins known to regulate mRNA degradation, microRNA processing, and protein translation. p-body formation was observed in MCF-7 cells using several molecules known as p-body components. Clioquinol plus zinc enhanced p-body assembly in MCF-7 cells. This enhancement was zinc-specific and could be blocked by a high affinity zinc chelator. The enhancement does not seem to be due to a stress response, as paclitaxel, a commonly used chemotherapeutic, did not cause enhanced p-body formation at a highly cytotoxic concentration. microRNA profiling indicated that clioquinol plus zinc globally down-regulates microRNA expression in this model system, which is associated with the reduced expression of Dicer, an enzyme key to microRNA maturation, and Ago2, a protein essential for microRNA stability. This study demonstrates that ionophoric zinc can induce cytotoxicity in cancer cells by globally regulating posttranscriptional events.

[Distribution of chromium in whole blood and urine among general population in China between year 2009 and 2010].

OBJECTIVE: To evaluate the chromium (Cr) levels in blood and urine among general population in China between 2009 and 2010, and thereby to analyze its prevalent features. METHODS: From year 2009 to 2010, a total of 11 983 subjects of general population aged between 6 and 60 year-old were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and 11 983 blood samples and 11 853 urine samples were also collected. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to test the Cr level both in blood and urine; and the Cr distribution in blood and urine among groups of population in different ages, genders and districts, were then analyzed. RESULTS: Among general population in China, the geometric mean (GM) of Cr concentration in blood was 1.19 µg/L, with median at 1.74 µg /L and 95% percentile at 5.59 µg/L. The Cr concentration in blood among males and females were separately 1.18 µg/L and 1.20 µg/L(P > 0.05); while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 µg/L (P < 0.01), respectively; and the figures in populations from eastern, central and western China were 1.00, 1.70 and 1.98 µg/L (P < 0.01), respectively. Among general population, the GM of Cr concentration in urine was 0.53 µg/L, with median was lower than 0.42 µg/L and 95% percentile at 3.53 µg/L. The Cr concentration in urine among males and females were separately 0.52 µg/L and 0.53 µg/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52 and 0.46 µg/L (P < 0.01), respectively;and the figures in populations from eastern, central and western China were 0.58, < 0.42 and 0.60 µg/L (P < 0.01), respectively. CONCLUSION: The study reported the Cr levels in blood and urine among general population in China, and thereby provided basic data evidence for the following Cr biological monitoring studies in near future.