Spatial regulation of MCAK promotes cell polarization and focal adhesion turnover to drive robust cell migration

The asymmetric distribution of microtubule (MT) dynamics in migrating cells is important for cell polarization, yet the underlying regulatory mechanisms remain underexplored. Here, we addressed this question by studying the role of the MT depolymerase, MCAK (mitotic centromere-associated kinesin), in the highly persistent migration of RPE-1 cells. MCAK knockdown leads to slowed migration and poor directional movement. Fixed and live cell imaging revealed that MCAK knockdown results in excessive membrane ruffling as well as defects in cell polarization and the maintenance of a major protrusive front. Additionally, loss of MCAK increases the lifetime of focal adhesions by decreasing their disassembly rate. These functions correlate with a spatial distribution of MCAK activity, wherein activity is higher in the trailing edge of cells compared with the leading edge. Overexpression of Rac1 has a dominant effect over MCAK activity, placing it downstream of or in a parallel pathway to MCAK function in migration. Together, our data support a model in which the polarized distribution of MCAK activity and subsequent differential regulation of MT dynamics contribute to cell polarity, centrosome positioning, and focal adhesion dynamics, which all help facilitate robust directional migration

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial (vol 26, 46, 2022)

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Geo-Environmental Factors’ Influence on the Prevalence and Distribution of Dental Fluorosis: Evidence from Dali County, Northwest China

Residents living in areas with high fluorine environmental background will ingest excessive fluorine from the atmosphere, drinking water, food and other ways. Long-term effects of fluorine on the human body could cause people suffering from dental fluorosis and influence the sustainable development of the severe fluorosis areas. Previous studies have independently discussed the high fluoride environment in Dali County from the aspects of natural environment, drinking water quality and endemic fluorosis. This study carried out a detail investigation on dental fluorosis population in seven selected villages of Dali County, Shaanxi province, northwest China. The highest dental fluorosis index of 1.9 was found in Lianjia village located near the Anren depression, while the lowest dental fluorosis index of 0.0 was found in Jiaxi village near the Yellow River alluvium. Groundwater fluorine contents the range was 0.01 mg/L to 11.80 mg/L, with the highest value (2.6 mg/L) being observed in the 2nd terrace of Weihe River. The lowest groundwater fluorine content (0.8 mg/L) was observed in the Yellow River alluvium. Soil fluorine contents ranged from 1.18 mg/kg to 13.70 mg/kg, with its highest value (13.70 mg/kg) observed in Xinfeng village near the Anren depression. The lowest value of fluorine (1.18 mg/kg) was found in soil from the 1st terrace of Weihe River. As for the fluorine contents of corn, they ranged from 4.04 mg/kg to 7.72 mg/kg. The highest value (7.72 mg/kg) appeared in the 3rd terrace of Weihe River and the lowest value (4.04 mg/kg) in the 2nd terrace of Weihe River. The soil leaching was the dominant fluorine source of groundwater environment. Areas with severe dental fluorosis are located at the edge of the depression and the conjunction between steep slope and gentle slope. A poor correlation was found between the dental fluorosis index from the seven investigated villages and the corn fluorine content contrarily to the groundwater fluorine content, which positively correlated to the dental fluorosis index. Based on the obtained results, two recommendations were done to prevent and control dental fluorosis and accelerate the sustainable development in Dali County: to strengthen the use of low fluorine groundwater for drinking water supply, and to widely install the public water purifiers in the rural communities for purifying high-fluorine water to reduce the incidence of dental fluorosis in the population

Cumulative Effect and Content Variation of Toxic Trace Elements in Human Hair around Xiaoqinling Gold Mining Area, Northwestern China

The harm of toxic trace element polluted living environments to human health in mining areas has attracted extensive attention. In this study, human hair samples from a toxic trace element polluted area (village A) in a mineral processing area collected in 2015 and 2019 were studied in detail and the nonpolluted human hair samples from a contrast area (village B) with a relatively clean environment were also collected for comparison. The Hg and As in human hair samples were analyzed by Atomic Fluorescence Spectrometry (AFS) and the Pb, Cd, Cr, and Cu in human hair samples were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The single cumulative index (Pi) and the Nemerrow index (Pz) were used to evaluate the single and comprehensive cumulative pollution index. The results indicated that the average toxic trace element contents in human hair from different ages in the polluted area exhibited certain statistical significance. The average single cumulative indexes indicated a significant accumulation of Hg, Pb, and Cd in human hair of both genders and different ages from the polluted area, and the comprehensive cumulative pollution indexes revealed higher accumulation of toxic trace elements in the hair of males than in females. In general, the content of toxic trace elements in human hair from polluted area was still growing in accumulation. The high content of toxic trace elements in human hair shows a notable correlation with human health, and the environmental pollution in gold mining areas is seriously harmful to human health

Geo-Environmental Factors’ Influence on the Prevalence and Distribution of Dental Fluorosis: Evidence from Dali County, Northwest China

Residents living in areas with high fluorine environmental background will ingest excessive fluorine from the atmosphere, drinking water, food and other ways. Long-term effects of fluorine on the human body could cause people suffering from dental fluorosis and influence the sustainable development of the severe fluorosis areas. Previous studies have independently discussed the high fluoride environment in Dali County from the aspects of natural environment, drinking water quality and endemic fluorosis. This study carried out a detail investigation on dental fluorosis population in seven selected villages of Dali County, Shaanxi province, northwest China. The highest dental fluorosis index of 1.9 was found in Lianjia village located near the Anren depression, while the lowest dental fluorosis index of 0.0 was found in Jiaxi village near the Yellow River alluvium. Groundwater fluorine contents the range was 0.01 mg/L to 11.80 mg/L, with the highest value (2.6 mg/L) being observed in the 2nd terrace of Weihe River. The lowest groundwater fluorine content (0.8 mg/L) was observed in the Yellow River alluvium. Soil fluorine contents ranged from 1.18 mg/kg to 13.70 mg/kg, with its highest value (13.70 mg/kg) observed in Xinfeng village near the Anren depression. The lowest value of fluorine (1.18 mg/kg) was found in soil from the 1st terrace of Weihe River. As for the fluorine contents of corn, they ranged from 4.04 mg/kg to 7.72 mg/kg. The highest value (7.72 mg/kg) appeared in the 3rd terrace of Weihe River and the lowest value (4.04 mg/kg) in the 2nd terrace of Weihe River. The soil leaching was the dominant fluorine source of groundwater environment. Areas with severe dental fluorosis are located at the edge of the depression and the conjunction between steep slope and gentle slope. A poor correlation was found between the dental fluorosis index from the seven investigated villages and the corn fluorine content contrarily to the groundwater fluorine content, which positively correlated to the dental fluorosis index. Based on the obtained results, two recommendations were done to prevent and control dental fluorosis and accelerate the sustainable development in Dali County: to strengthen the use of low fluorine groundwater for drinking water supply, and to widely install the public water purifiers in the rural communities for purifying high-fluorine water to reduce the incidence of dental fluorosis in the population

Identification and analysis of CYP450 genes from transcriptome of Lonicera japonica and expression analysis of chlorogenic acid biosynthesis related CYP450s

Background Lonicera japonica is an important medicinal plant that has been widely used in traditional Chinese medicine for thousands of years. The pharmacological activities of L. japonica are mainly due to its rich natural active ingredients, most of which are secondary metabolites. CYP450s are a large, complex, and widespread superfamily of proteins that participate in many endogenous and exogenous metabolic reactions, especially secondary metabolism. Here, we identified CYP450s in L. japonica transcriptome and analyzed CYP450s that may be involved in chlorogenic acid (CGA) biosynthesis. Methods The recent availability of L. japonica transcriptome provided opportunity to identify CYP450s in this herb. BLAST based method and HMM based method were used to identify CYP450s in L. japonica transcriptome. Then, phylogenetic analysis, conserved motifs analysis, GO annotation, and KEGG annotation analyses were conducted to characterize the identified CYP450s. qRT-PCR was used to explore expression patterns of five CGA biosynthesis related CYP450s. Results In this study, 151 putative CYP450s with complete cytochrome P450 domain, which belonged to 10 clans, 45 families and 76 subfamilies, were identified in L. japonica transcriptome. Phylogenetic analysis classified these CYP450s into two major branches, A-type (47%) and non-A type (53%). Both types of CYP450s had conserved motifs in L. japonica. The differences of typical motif sequences between A-type and non-A type CYP450s in L. japonica were similar with other plants. GO classification indicated that non-A type CYP450s participated in more molecular functions and biological processes than A-type. KEGG pathway annotation totally assigned 47 CYP450s to 25 KEGG pathways. From these data, we cloned two LjC3Hs (CYP98A subfamily) and three LjC4Hs (CYP73A subfamily) that may be involved in biosynthesis of CGA, the major ingredient for pharmacological activities of L. japonica. qRT-PCR results indicated that two LjC3Hs exhibited oppositing expression patterns during the flower development and LjC3H2 exhibited a similar expression pattern with CGA concentration measured by HPLC. The expression patterns of three LjC4Hs were quite different and the expression pattern of LjC4H3 was quite similar with that of LjC3H1. Discussion Our results provide a comprehensive identification and characterization of CYP450s in L. japonica. Five CGA biosynthesis related CYP450s were cloned and their expression patterns were explored. The different expression patterns of two LjC3Hs and three LjC4Hs may be due to functional divergence of both substrate and catalytic specificity during plant evolution. The co-expression pattern of LjC3H1 and LjC4H3 strongly suggested that they were under coordinated regulation by the same transcription factors due to same cis elements in their promoters. In conclusion, this study provides insight into CYP450s and will effectively facilitate the research of biosynthesis of CGA in L. japonica

Preparation of Attapulgite/CoFe2O4 Magnetic Composites for Efficient Adsorption of Tannic Acid from Aqueous Solution

The use of attapulgite (ATP)-based materials for adsorption of pollutants from water and wastewater has received growing attention. However, recovering ATP-based adsorbents remains a challenge. In this study, a magnetic adsorbent ATP/CoFe2O4 with high tannic acid (TA) adsorptive capacity was fabricated via a facile co-precipitation approach and was well characterized. The loaded CoFe2O4 particles were embedded into the adsorbent surfaces to allow magnetic separability. For this material, its TA adsorption kinetics, isotherm behavior, and magnetic separation efficiency are reported. The developed magnetic composites had rapid sorption kinetics of 3 h, high sorption capacity of 109.36 mg/g, and good magnetic separation efficiency of 80%. The used ATP/CoFe2O4 was successfully regenerated by NaOH and reused five times without a substantial reduction in TA removal and magnetic performance. Intermolecular hydrogen bonding formation and surface complexation were identified as the sorption mechanisms of TA by ATP/CoFe2O4