Lacidophilin tablets alleviate constipation through regulation of intestinal microflora by promoting the colonization of Akkermansia sps.

Constipation is a major health problem worldwide that requires effective and safe treatment options. Increasing evidence indicates that disturbances in gut microbiota may be a risk factor for constipation. Administration of lacidophilin tablets shows promising therapeutic potential in the treatment of inflammatory bowel disease owing to their immunomodulatory properties and regulation of the gut microbiota. The focus of this study was on investigating the ability of lacidophilin tablets to relieve constipation by modulating the gut microbiome. Rats with loperamide hydrochloride induced constipation were treated with lacidophilin tablets via intragastric administration for ten days. The laxative effect of lacidophilin tablets was then evaluated by investigating the regulation of intestinal microflora and the possible underlying molecular mechanism. Our results reveal that treatment with lacidophilin tablets increased the intestinal advancement rate, fecal moisture content, and colonic AQP3 protein expression. It also improved colonic microflora structure in the colonic contents of model rats mainly by increasing Akkermansia muciniphila and decreasing Clostridium_sensu_stricto_1. Transcriptome analysis indicated that treatment with lacidophilin tablets maintains the immune response in the intestine and promotes recovery of the intestinal mechanical barrier in the constipation model. Our study shows that lacidophilin tablets improve constipation, possibly by promoting Akkermansia colonization and by modulating the intestinal immune response.

[Distribution, Sources, and Ecological Risk Evaluation of Heavy Metals in Surface Sediments of Taihu Lake].

For the surface sediment samples of Taihu Lake in 2010, the eight physicochemical indices of pH, temperature, Eh, water content, porosity, grain size, total phosphorus, and Loss-on-ignition were measured and analyzed, along with the contents of nine heavy metals:Cu, Zn, Ni, Cr, Pb, Ba, Mn, Co, and V. The order of magnitudes of heavy metal content of surface sediments in Taihu Lake was:Mn>Ba>Zn>Cr>V>Ni>Pb>Cu>Co. This suggested that the contents of the nine heavy metals were beyond the background value, which had a close connection to the geology of the Taihu Lake Basin and were influenced by human activity to varying degrees. The clustering analysis and the spatial distribution of the heavy metals revealed that the concentrations of heavy metals in the North and South Taihu Lake sections decreased from the lake shore to the lake center, the concentrations of heavy metals in the West Taihu Lake section increased from the lake shore to the lake center, and the distribution of heavy metals in the center of the lake remained relatively uniform. According to the correlation study, the metal elements were positively correlated with one another to varying degrees, indicating that they originate from the same source of pollution. According to the PCA and PMF analyses, there were some different sources of heavy metals in Taihu Lake, in which the transportation and industrial complex source were the most important sources, the diagenesis was the second major source, and agriculture was the third major source. Furthermore, the heavy metal pollution was evaluated using the geoaccumulation and the potential ecological risk indices. This offers a solid theoretical backing for the future management of heavy metal pollution in Taihu Lake.

Evaluation of procedural pain for neonates in a neonatal intensive care unit: a single-centre study.

BACKGROUND: To evaluate the procedural pain experienced by neonates in a neonatal intensive care unit (NICU) setting and determine the corresponding pain grades. METHODS: Two experienced nurses independently used the Neonatal Infant Pain Scale (NIPS) to evaluate the neonatal pain during procedures taking place in the tertiary NICU and two level-two neonatal care units in the Children's Hospital of Zhejiang University School of Medicine. The mean and distribution of NIPS pain scores and the corresponding pain grades of participants when experiencing clinical painful procedures were analysed. RESULTS: A total of 957 neonates exposed to 15 common clinical painful procedures were included in the study. The clinical painful procedures experienced by 957 participants could be divided into three groups: severe pain (NIPS score 5-7: peripheral intravenous cannulation, arterial catheterisation, arterial blood sampling, peripherally inserted central catheter placement and nasopharyngeal suctioning), mild to moderate pain (NIPS score 3-4: finger prick, intramuscular injection, adhesive removal, endotracheal intubation suctioning, heel prick, lumbar puncture and subcutaneous injection) and no pain to mild pain (NIPS score 0-2: gastric tube insertion, enema and intravenous injection). CONCLUSIONS: The neonatal pain response to clinical procedures in NICU had certain pattern and preintervention drug analgesia could be taken for painful procedures with clustered high NIPS pain scores. Meanwhile, full coverage non-drug pain relief measures could be taken for procedures that are with scattered pain scores, and real-time pain evaluation should be provided to determine whether further drug analgesia is required.

Video-Based versus On-Site Neonatal Pain Assessment in Neonatal Intensive Care Units: The Impact of Video-Based Neonatal Pain Assessment in Real-World Scenario on Pain Diagnosis and Its Artificial Intelligence Application.

BACKGROUND: Neonatal pain assessment (NPA) represents a huge global problem of essential importance, as a timely and accurate assessment of neonatal pain is indispensable for implementing pain management. PURPOSE: To investigate the consistency of pain scores derived through video-based NPA (VB-NPA) and on-site NPA (OS-NPA), providing the scientific foundation and feasibility of adopting VB-NPA results in a real-world scenario as the gold standard for neonatal pain in clinical studies and labels for artificial intelligence (AI)-based NPA (AI-NPA) applications. SETTING: A total of 598 neonates were recruited from a pediatric hospital in China. METHODS: This observational study recorded 598 neonates who underwent one of 10 painful procedures, including arterial blood sampling, heel blood sampling, fingertip blood sampling, intravenous injection, subcutaneous injection, peripheral intravenous cannulation, nasopharyngeal suctioning, retention enema, adhesive removal, and wound dressing. Two experienced nurses performed OS-NPA and VB-NPA at a 10-day interval through double-blind scoring using the Neonatal Infant Pain Scale to evaluate the pain level of the neonates. Intra-rater and inter-rater reliability were calculated and analyzed, and a paired samples t-test was used to explore the bias and consistency of the assessors' pain scores derived through OS-NPA and VB-NPA. The impact of different label sources was evaluated using three state-of-the-art AI methods trained with labels given by OS-NPA and VB-NPA, respectively. RESULTS: The intra-rater reliability of the same assessor was 0.976-0.983 across different times, as measured by the intraclass correlation coefficient. The inter-rater reliability was 0.983 for single measures and 0.992 for average measures. No significant differences were observed between the OS-NPA scores and the assessment of an independent VB-NPA assessor. The different label sources only caused a limited accuracy loss of 0.022-0.044 for the three AI methods. CONCLUSION: VB-NPA in a real-world scenario is an effective way to assess neonatal pain due to its high intra-rater and inter-rater reliability compared to OS-NPA and could be used for the labeling of large-scale NPA video databases for clinical studies and AI training.

Construction and validation of a predictive risk model for nosocomial infections with MDRO in NICUs: a multicenter observational study.

Objectives: This study aimed to construct and validate a predictive risk model (PRM) for nosocomial infections with multi-drug resistant organism (MDRO) in neonatal intensive care units (NICUs), in order to provide a scientific and reliable prediction tool, and to provide reference for clinical prevention and control of MDRO infections in NICUs. Methods: This multicenter observational study was conducted at NICUs of two tertiary children's hospitals in Hangzhou, Zhejiang Province. Using cluster sampling, eligible neonates admitted to NICUs of research hospitals from January 2018 to December 2020 (modeling group) or from July 2021 to June 2022 (validation group) were included in this study. Univariate analysis and binary logistic regression analysis were used to construct the PRM. H-L tests, calibration curves, ROC curves and decision curve analysis were used to validate the PRM. Results: Four hundred and thirty-five and one hundred fourteen neonates were enrolled in the modeling group and validation group, including 89 and 17 neonates infected with MDRO, respectively. Four independent risk factors were obtained and the PRM was constructed, namely: P = 1/ (1+ e-X), X = -4.126 + 1.089× (low birth weight) +1.435× (maternal age ≥ 35 years) +1.498× (use of antibiotics >7 days) + 0.790× (MDRO colonization). A nomogram was drawn to visualize the PRM. Through internal and external validation, the PRM had good fitting degree, calibration, discrimination and certain clinical validity. The prediction accuracy of the PRM was 77.19%. Conclusion: Prevention and control strategies for each independent risk factor can be developed in NICUs. Moreover, clinical staff can use the PRM to early identification of neonates at high risk, and do targeted prevention to reduce MDRO infections in NICUs.

Application of epicutaneo-cava catheters with 24G indwelling needles in very low birth weight infants: a safe and simple innovative technique.

Background: Epicutaneo-cava catheter (ECC) is an ideal venous access for very low birth weight (VLBW) infants. However, because veins of VLBW infants are thin, ECC catheter is difficult to insert, and the success rate of puncture is low. This study aimed to use ECC with 24G indwelling needles to improve the outcomes of VLBW infants. Methods: This retrospective study enrolled 121 VLBW infants (birthweight <1,500 g) who required ECC catheterization and were admitted to the Neonatal Intensive Care Unit of the Children's Hospital of Zhejiang University School of Medicine between January 2021 and December 2021. The patients were divided into the indwelling needle group and the conventional technique group according to the technique of ECC. The demographic and treatment data of the two groups were collected, and the success rate of first attempt cannulation of ECC and catheter-related complications of the two groups were analyzed and compared. Results: There were no significant differences in gender, age, and body weight between the two groups on the day of ECC insertion and venipuncture site. It can be seen through model analysis that the success rate of first-attempt cannulation of ECC in the indwelling needle group was significantly higher than in the conventional technique group. In contrast, average catheterization time and catheterization-related bleeding risk in the indwelling needle group were significantly lower than in the conventional technique group (p = 0.00,and 0.00, respectively). Infection during catheter placement, indwelling catheter duration and catheter-related infection between the two groups (p > 0.05). Conclusion: Application of ECC with 24G indwelling needles in VLBW infants can improve the success rate of first attempt cannulation of ECC, reduce the time of catheterization and the risk of bleeding, which may be popularized for widespread application.

Artificial Intelligence Based Pain Assessment Technology in Clinical Application of Real-World Neonatal Blood Sampling.

Background: Accurate neonatal pain assessment (NPA) is the key to neonatal pain management, yet it is a challenging task for medical staff. This study aimed to analyze the clinical practicability of the artificial intelligence based NPA (AI-NPA) tool for real-world blood sampling. Method: We performed a prospective study to analyze the consistency of the NPA results given by a self-developed automated NPA system and nurses' on-site NPAs (OS-NPAs) for 232 newborns during blood sampling in neonatal wards, where the neonatal infant pain scale (NIPS) was used for evaluation. Spearman correlation analysis and the degree of agreement of the pain score and pain grade derived by the NIPS were applied for statistical analysis. Results: Taking the OS-NPA results as the gold standard, the accuracies of the NIPS pain score and pain grade given by the automated NPA system were 88.79% and 95.25%, with kappa values of 0.92 and 0.90 (p < 0.001), respectively. Conclusion: The results of the automated NPA system for real-world neonatal blood sampling are highly consistent with the results of the OS-NPA. Considering the great advantages of automated NPA systems in repeatability, efficiency, and cost, it is worth popularizing the AI technique in NPA for precise and efficient neonatal pain management.

Eutrophication causes microbial community homogenization via modulating generalist species.

Eutrophication substantially influences the community structure of aquatic organisms and has become a major threat to biodiversity. However, whether eutrophication is linked to homogenization of microbial communities and the possible underlying mechanisms are poorly understood. Here, we studied bacterial and fungal communities from water and sediments of 40 shallow lakes in the Yangtze-Huaihe River basin, a representative area characterized by intensifying eutrophication in China, and further examined the beta diversity patterns and underlying mechanisms under eutrophication conditions. Our results indicate that eutrophication generally caused biotic homogenization of bacterial and fungal communities in both habitats showing decreased community variations for the sites with a higher trophic state index (TSI). In the two habitats, community dissimilarities were positively correlated with TSI changes for both taxonomic groups, while the local contribution to beta diversity (LCBD) remarkably declined with increasing TSI for the fungal community. These phenomena were consistent with the pivotal importance of the TSI in statistically accounting for beta diversity of bacterial and fungal communities in both habitats. In addition, we found that physicochemical factors such as water temperature and pH were also important for bacterial and fungal communities in water, while heavy metal elements were important for the communities in sediments. Interestingly, generalist species, rather than specialist species, were revealed to more dominantly affect the variations in beta diversity along the trophic gradient, which were quantified by Bray-Curtis dissimilarity and LCBD. Collectively, our findings reveal the importance of generalist species in contributing to the change of beta diversity of microbial communities along trophic gradients, which have profound implications for a comprehensive understanding of the effects of eutrophication on microbial community.

Taxonomic dependency of beta diversity components in benthic communities of bacteria, diatoms and chironomids along a water-depth gradient.

Community variation (i.e., beta diversity) along geographical gradients is a well-known ecological pattern, but the corresponding variation in beta diversity components (e.g., species turnover and nestedness) and underlying drivers remain poorly understood. Based on two alternative approaches (that is, the beta diversity partitioning proposed by Baselga and the Local Contributions to Beta Diversity (LCBD) partitioning proposed by Legendre), we examined the patterns of beta diversity components of lacustrine benthos, from bacteria to diatoms and chironomids, in the surface sediments along a 100-m water-depth gradient in Lugu Lake. We further quantified the relative importance of spatial, environmental and biotic variables in explaining water-depth patterns in beta diversity. Based on the Baselga's framework, there was a taxonomic dependency for the patterns of beta diversity components with water-depth, showing a significant species turnover pattern for bacteria, while diatoms and chironomids showed significant nestedness. This dependency was also evident in the patterns of community uniqueness with water-depth because based on Legendre's framework, the LCBD decreased with water depth for bacteria whereas increased with depth for diatoms. The total beta diversity and species turnover of bacteria could be explained by the pure effects of spatial, environmental and biotic variables. A total of 26.8% and 23.6% of the nestedness component of diatoms and chironomids was explained by environmental variables, respectively, while species turnover was mostly related to spatial variables. Bacteria total LCBD and species replacement were driven only by environmental variables. For diatoms and chironomids, however, most of the total LCBD and its two components were explained by spatial variables, and biotic variables were most important for the diatom replacement component. Our findings provide insights into the mechanisms responsible for community organizations along water-depth gradients from the perspective of beta diversity components.

Insertion of a 1.9F central venous catheter via the internal jugular vein in neonates.

OBJECTIVE: This study aimed to develop a technique for placing a 1.9 French (F) central venous catheter in the internal jugular vein of newborns. METHODS: In this retrospective study, punctures were performed with a modified ultrasound-guided Seldinger technique with 57 1.9F catheters in 48 newborns. Punctures were performed in the right internal jugular vein in 43 (75.4%) patients and in the left internal jugular vein in 14 (24.6%) patients. RESULTS: We included 33 (57.9%) boys and 24 (42.1%) girls, aged a median 38 days (range, 2-135 days). The puncture success rate was 100%. Catheterization duration was a median 14 days (range, 1-70 days). Among the catheters, 94.1% were removed after completion of therapy or upon death. Fifty-three (93%) patients experienced no complication, whereas a small amount of bleeding was observed in 2 (3.5%) patients, inflammation of puncture in 1 (1.8%) patient, and occlusion in 1 (1.8%) patient. The method of placement of 1.9F catheters in the internal jugular vein of newborns had a high success rate, with minimal trauma and few complications. CONCLUSIONS: Our method of placing a 1.9F central venous catheter in the internal jugular vein is suggested for level III to VI neonatal intensive care units.

Ursolic acid promotes apoptosis and mediates transcriptional suppression of CT45A2 gene expression in non-small-cell lung carcinoma harbouring EGFR T790M mutations.

BACKGROUND AND PURPOSE: In non-small-cell lung carcinoma (NSCLC) patients, the L858R/T790M mutation of the epithelial growth factor receptor (EGFR) is a major cause of acquired resistance to EGFR-TKIs treatment that limits their therapeutic efficacy. Identification of drugs that can preferentially kill the NSCLC harbouring L858R/T790M mutation is therefore critical. Here, we have evaluated the effects of ursolic acid, an active component isolated from herbal sources, on erlotinib-resistant H1975 cells that harbour the L858R/T790M mutation. EXPERIMENTAL APPROACH: Gene expression omnibus (GEO) profiles analyses was applied to detect differentially expressed genes in NSCLC cells harbouring EGFR mutation. AnnexinV-FITC/PI, TUNEL staining, MTT, wound healing, RT-PCR, qRT-PCR, western blots, immunostaining, dual-luciferase reporters and ChIP-PCR were utilized to investigate the effects of ursolic acid in vitro and in vivo. KEY RESULTS: The cancer/testis antigen family 45 member A2 (CT45A2) was highly expressed in H1975 cells. Ectopic expression of CT45A2 in H1975 cells increased cell proliferation and motility in vitro. Silencing the CT45A2 expression strongly attenuated H1975 cells motility and growth. The anti-cancer effect of ursolic acid was critically dependent on CT45A2 expression in H1975 cells. Ursolic acid suppressed CT45A2 gene transcription mediated by transcriptional factor TCF4 and ß-catenin signalling. CONCLUSIONS AND IMPLICATIONS: CT45A2 is a novel oncogene for NSCLC with an EGFR T790 mutation. Ursolic acid induced apoptosis and inhibited proliferation of H1975 cells by negatively regulating the ß-catenin/TCF4/CT45A2 signalling pathway. Therefore, ursolic acid may be a potential candidate treatment for NSCLC harbouring the EGFR-L858R/T790M mutation.

The Relative Abundance of Benthic Bacterial Phyla Along a Water-Depth Gradient in a Plateau Lake: Physical, Chemical, and Biotic Drivers.

Water-depth biodiversity gradient, one of the typical biogeographical patterns on Earth, is understudied for bacteria in freshwater ecosystems, and thus left the underlying mechanisms poorly understood especially for benthic bacteria. Here, we investigated the water-depth distribution of surface sediment bacterial phyla and their driving factors in Lake Lugu, a plateau lake in Southwest China. Our results revealed that the relative abundance of 11 dominant bacterial phyla showed various water-depth patterns, such as increasing, decreasing, hump-shaped, and U-shaped patterns. These patterns across phyla were consistent with their different niche positions of water depth, while the occupancy-abundance relationships were not dependent on phylum attributes. Consistently, phylum abundance was best explained by water depth; other physical and chemical factors, such as metal ion concentrations, SiO2, and pH, can also explain the variations in some bacterial phyla. Chemical variables were the main drivers of the dominant bacterial phyla. However, biotic variables also showed substantial importance for some phyla, such as Planctomycetes, Actinobacteria, and WS3. This work could provide new insights into the general water-depth patterns and underlying mechanisms of the relative abundance of bacterial phyla in freshwater ecosystems.

Using the synthesized peptide HAYED (5) to protect the brain against iron catalyzed radical attack in a naturally senescence Kunming mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the brain. It cannot be cured currently, and those suffering from AD place a great burden on their caregivers and society. AD is characterized by high levels of iron ions in the brain, which catalyze radicals that damage the neurons. Knowing that the Aß42 peptide precipitates iron by binding iron ions at amino acid residues D1, E3, H11, H13, and H14, we synthesized a 5-repeat (HAYED) sequence peptide. By treating iron-stressed SH-SY5Y cells with it and injecting it into the cerebrospinal fluid (CSF) of naturally senescence Kunming mouse, which displaying AD-similar symptoms such as learning and memory dysfunction, neuron degeneration and high level of iron in brain, we found that HAYED (5) decreased the iron and radical levels in the cell culture medium and in the CSF. Specially, the synthesized peptide prevented cell and brain damage. Furthermore, functional magnetic resonance imaging (fMRI), Morris water maze and passive avoidance tests demonstrated that the peptide ameliorated brain blood-oxygen metabolism and slowed cognitive loss in the experimental senescence mice, and clinical and blood tests showed that HAYED (5) was innoxious to the kidney, the liver and blood and offset the AD-associated inflammation and anemia.

Flexible Tactile Sensor Array Based on Aligned MWNTs-PU Composited Sub-Microfibers.

This present paper describes a novel method to fabricate tactile sensor arrays by producing aligned multi-walled carbon nanotubes (MWNTs)-polyurethane (PU) composite sub-microfiber (SMF) arrays with the electrospinning technique. The proposed sensor was designed to be used as the artificial skin for a tactile sensation system. Although thin fibers in micro- and nanoscale have many good mechanical characteristics and could enhance the alignment of MWNTs inside, the high impedance as a consequence of a small section handicaps its application. In this paper, unidirectional composite SMFs were fabricated orthogonally to the parallel electrodes through a low-cost method to serve as sensitive elements (SEs), and the impedances of SEs were measured to investigate the changes with deformation caused by applied force. The particular piezoresistive mechanism of MWNTs disturbed in SMF was analyzed. The static and dynamic test results of the fabricated tactile sensor were also presented to validate the performance of the proposed design.

Adsorption of Cu2+ and mechanism by natural biofilm.

The biofilm culturing device fixed on the slides was vertically placed in the commonly called small Li Lake of Jiangnan University. The adsorption experiment of Cu2+ was carried out by mature biofilm. Besides, scanning electron microscope (SEM), polymerase chain reaction and denaturing gradient gel electrophoresis (PCR-DGGE), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy spectrum (SEM-EDX) were used to analysis the effect of Cu2+ on the morphological structure of biofilm. The result indicated that when the initial concentration of Cu2+ was 5 mg·L-1, the absorption capacity of Cu2+ by unit mass biofilm is the maximum. More extracellular polymeric substances (EPS) were released by biofilm due to the stimulation of Cu2+. EPS was beneficial to the adsorption of Cu2+ by biofilm. After the adsorption of Cu2+, the bacterial diversity index decreased, while there were no significant differences in microbial communities on biofilm. Moreover, the main groups combining Cu2+ were the hydroxyl groups and amide groups in S-EPS and B-EPS. Ion exchange is a mechanism of the adsorption of Cu2+ by EPS.

[Influence of Hydraulic Retention Time on the Treatment of Polluted River Water by an Activated Carbon Rotating Biological Contactor].

The study combined activated carbon with a rotating biological contactor. The activated carbon adsorption experiments were conducted and the biofilm was formed by using the river water directly. The effects of different hydraulic retention times on the removal of NH4+-N, TP, and permanganate index and on the biofilm properties were investigated at the optimum rotational speed of the disc. Experimental results are as follows. The Freundlich isotherm showed that activated carbon had better adsorption properties for NH4+-N, TP, and permanganate index in water.When the disk speed was 3 r·min-1, the removal efficiency was the best, and the removal rates of NH4+-N, TP and permanganate index were the best at 86.05%, 81.28%, and 77.09%, respectively. In addition, there was a significant linear correlation between the hydraulic retention time and the removal of NH4+-N and TP (R2>0.9), respectively. The removal rates of NH4+-N and TP at different hydraulic retention times were significantly different (P<0.05), but the permanganate index was not (P>0.05).Hydraulic retention time had effects on the biofilm activity, protein and polysaccharide contents,and the three-dimensional fluorescence peaks of S-EPS, LB-EPS, and TB-EPS of the biofilm.

Toosendanin inhibits adipogenesis by activating Wnt/ß-catenin signaling.

Toosendanin (TSN), a triterpenoid extracted from Melia toosendan, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. However, its anti-adipogenic effect remains unknown. Here, we found that TSN dose-dependently attenuated lipid accumulation in preadipocytes 3T3-L1 as evidenced by Oil Red O staining. TSN also significantly downregulated mRNA and protein levels of adipocytokines (adiponectin and leptin), CCAAT/enhancer binding proteins α (C/EBP-α), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase, and acetyl-CoA carboxylase in adipocytes. To understand the mechanism, we observed that TSN effectively activated Wnt/ß-catenin pathway, in which TSN increased low density lipoprotein receptor related protein 6, disheveled 2, ß-catenin, and cyclin D1 expression levels, while it inactivated glycogen synthase kinase 3ß by enhancing its phosphorylation. Moreover, TSN reduced weight of gonadal white fat and serum triacylglycerol (TAG) content in high-fat diet (HFD)-fed mice. Interestingly, the in vivo studies also demonstrated that TSN promoted the expression of ß-catenin, but accordingly repressed C/EBP-α and PPAR-γ expression in HFD-induced mice. Overall, TSN is capable of inhibiting the lipogenesis of adipocytes by activating the Wnt/ß-catenin pathway, suggesting potential application of TSN as a natural anti-obesity agent.

miR-1224-5p Enhances Hepatic Lipogenesis by Targeting Adenosine Monophosphate-Activated Protein Kinase α1 in Male Mice.

MicroRNAs are potential therapeutic targets for metabolic diseases. Here, miR-1224-5p was highly expressed in the livers of mice fed a high-fat diet (HFD) and in obese (ob/ob) mice. To examine the potential role of miR-1224-5p, we constructed liver-specific adenoviral vectors expressing either an miR-1224-5p inhibitor sequence or miR-1224-5p mimic sequences. After tail-vein vector injection, HFD-fed mice were examined for expression of lipogenic genes. We found that miR-1224-5p inhibitors significantly attenuated hepatic lipogenesis and steatosis in HFD-fed mice, whereas miR-1224-5p mimicked promoted lipid accumulation in the liver of chow-fed C57BL/6 mice. Additional in vitro studies demonstrated that downregulation of miR-1224-5p in HepG2 and primary hepatocytes led to a reduction of cellular triglycerides after treatment with an oleic acid and palmitic acid mixture. Importantly, this study also identified adenosine monophosphate-activated protein kinase (AMPK)-α1 as a direct target of miR-1224-5p. miR-1224-5p binding to the 3' untranslated region of AMPKα1 suppressed expression of the AMPKα1 protein and its downstream molecules. Metformin, an activator of AMPK, also inhibited hepatic expression of miR-1224-5p. Together, these findings indicate that miR-1224-5p promotes hepatic lipogenesis by suppressing AMPKα1 expression and suggest that miR-1224-5p inhibitors warrant further investigation as potential therapeutic tools in the treatment of nonalcoholic fatty liver disease.

Continuously Growing Ultrathick CrN Coating to Achieve High Load-Bearing Capacity and Good Tribological Property.

Continuous growth of traditional monolayer CrN coatings up to 24 h is successfully achieved to fabricate ultrathickness of up to 80 µm on the 316 stainless steel substrate using a multiarc ion plating technique. The microstructures, mechanical properties, and tribological properties evolution with the CrN coating continuously growing was evaluated in detail. The transmission electron microscopy observations and inverse Fourier-filtered images reveal a relaxation mechanism during the continuous growth of CrN coating, which can lead to a decrease in the residual stress when coating growth time exceeds 5 h. The scratch test and friction test results both show that the load-bearing capacity of coating is significantly increased as CrN coatings growing thicker. During the scratch test, the ultrathick CrN coating of thickness 80.6 µm is not failed under the load of 180 N, and the dominant failure mechanism is the cohesive failure including wedge spallation and cracking. The dry-sliding friction test results show the mean coefficient of friction and the wear rate of ultrathick CrN are respectively decreased by 17.2 and 56.8% at most compared with the thin coating (thickness is 5.4 µm). The ultrahigh load-bearing capacity and excellent tribological property are attributed to the relaxation mechanism and limited contact pressure as the coating grows continuously.

Prevalence of mild cognitive impairment and its subtypes in community-dwelling residents aged 65 years or older in Guangzhou, China.

BACKGROUND: Prevalence of mild cognitive impairment (MCI) has been reported substantial variations, and mostly in Western countries. Less is known about MCI in the south of China. The study is to estimate the prevalence of MCI and its subtypes in residents aged 65year or older in community-dwelling residents of Guangzhou, China. METHODS: The study was a community-based, cross-sectional study conducted in rural and urban areas of Guangzhou between April and October 2009. Eight communities were randomly selected using a cluster sampling method. Each elderly was interviewed with Montreal Cognitive Assessment, the Mini-Mental state examination, Auditory Verbal Learning Test, the Clinical Dementia Rating scale et al. MCI was classified as amnestic MCI (a-MCI) or nonamnestic MCI (na-MCI). RESULTS: 2427 individuals were contacted, but in-person interviews were conducted with 2111 participants. 299 participants with MCI were identified. The prevalence of MCI, a-MCI and na-MCI was 14.2%, 12.2%, 2.0% respectively. The prevalence of MCI and a-MCI increased with age, decreased with education level, and was higher in rural areas than in urban areas. The difference of prevalence of MCI and a-MCI between women with men wasn't statistically significant(MCIχ2=1.0, OR 0.9, 95%CI=0.6-1.2; a-MCIχ2=1.0, OR 0.9, 95%CI=0.6-1.2), when controlling for education by logistic regression analysis. CONCLUSIONS: The results suggest that 14.2% of elderly individuals are affected by MCI in Guangzhou, China. And MCI was dominated by a-MCI. The prevalence of MCI and a-MCI increased with age, decreased with education level, and was higher in the rural population compared to the urban population.