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The treatment of spinal cord injury aims to reconstruct the fiber connection and restore the interrupted neural pathways. Adipose mesenchymal stem cells (ADSCs) can promote the recovery of motor functions in spinal cord injury. However, poor survival of ADSCs and leakage outside of the injury site after local transplantation reduce the number of cells, which seriously attenuates the cumulative effect. We performed heterotopic transplantation on rats with severe spinal cord injury using human ADSCs loaded within self-assembly hydrogel RADA16-RGD (R: arginine; A: alanine; D: aspartic acid; G: glycine). Our results indicate that the combined transplantation of human ADSCs with RADA16-RGD improved the survival of ADSCs at the injured site. The inflammatory reaction was inhibited, with improved survival of the neurons and increased residual area of nerve fibers and myelin protein. The functional behaviors were promoted, as determined by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale score and electrophysiological measurements. ADSCs can promote the repair of spinal cord injury. This study provides new ideas for the treatment of spinal cord injury.

Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Aβ aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood–brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.

Background: Cancer-associated fibroblasts (CAFs) are of considerable importance in tumor progression by interacting with the tumor microenvironment. However, the hidden mechanism explaining how tumor cells interact with CAFs in the tumor mechanical microenvironment remains largely unknown. Methods: We highlighted exosomes as the mediator modulating the interaction between liver cancer cells and CAFs under mechanical conditions. The normal hepatic stellate cells LX2 were exposed to the medium or exosomes from the HepG2 cells with or without fluid shear stress subjection, and the CAFs activation markers were checked. To further explore the potential role of PI3K, which is active in liver fibrosis, the PI3K inhibitor was used. Results: The specific markers of CAFs, FAP, and α-SMA, increased in LX2 with subjection to the fluid shear stress-induced exosomes from HepG2 cells. In turn, the enriched IGF2 in the exosomes activated the IGF2-PI3K signaling pathway in LX2 cells. Conclusions: These findings reveal that fluid shear stress-induced liver cancer cells possess a stronger capacity to convert normal fibroblasts to CAFs than statically cultured liver cancer cells, and tumor-derived exosomes mediated the intercellular cross-talk between liver cancer cells and fibroblasts.

Precipitation is one of the many important natural factors impacting agriculture and natural resource management. Although statistics have been applied to investigate the non-stationary trend and the unpredictable variances of precipitation under climate change, existing methods usually lack a sound physical basis that can be generally applied in any location and at any time for future extrapolation, especially in tropical areas. Physically, the formation of precipitation is a result of ascending air which reduces air pressure and condenses moisture into drops, either by irregular terrain or atmospheric phenomena (e.g., via frontal lifting). Thus, in this paper, pressure change events (PCEs) will be used as a physical indicator of the stability of atmospheric systems to reveal the impact of temperature on precipitation in the tropical areas of Florida. By using data from both national and regional weather observation networks, this study segments the continuous observation series into PCE sequences for further analysis divided by dry and wet seasons. The results reveal that the frequency and intensity of PCE are highly associated with the occurrences of weather events. Decreasing pressure favors precipitation, and may turn extreme when the temperature and air moisture are sufficient to fuel the process. With similar intensity, decreasing pressure change events (DePCEs) generally bear a higher probability of precipitation (POP) and precipitation depth (PD) than increasing pressure change events (InPCEs). The frequency of alternating between InPCEs and DePCEs is subject to the temperature of the season and climate. Due to the seasonal fluctuations of weather characteristics, such as temperature and relative humidity, the dependence of extreme precipitation on these characteristics can be interpreted via PCE. A 7% increase rate of precipitation vs. temperature rise, determined by the Clausius—Clapeyron (C—C) relationship, can be observed from extreme precipitation with variances in the season and PCE types. Although indicated by other research, active vertical movement of air caused by a phase change in water at the frozen point is not pronounced in Florida. The response patterns of humidity to precipitation also vary by season and PCE types in extreme conditions. In summary, PCEs demonstrate reliable physical evidence of precipitation formation and can better associate the occurrence and intensity of extreme weather with other characteristics. In turn, such associations embody the underlying physical concepts present at any location in the world.

Heat-shrinkable materials, which are typically shape-memory polymers and irreversibly shrink in response to external heating stimuli, are vital for coating and protection applications in aerospace, micro-robotics, biomedical devices, and biomimetic systems. In these applications, they are often subjected to complex environmental conditions, such as thermal and mechanical loading, which induce a certain level of deformation. It is imperative to understand the resultant deformation and internal stress state under these loading conditions. Here we report a new class of heat-shrinkable metamaterials, which utilize photochemical expansion in 3D printing to release locally residual stress with the heat-shrinkage rate of 3–8%. Planar lattice metamaterials are designed to evolve into permanent heat-shrinkage status. The fundamental mechanisms that control heat-shrinkable behavior are identified and tested in thermal experiments. The photochemical expansion strain rises with the increase of layer printing time and nozzle proceeding direction. Furthermore, analytical predictions agree well with the experiments about the unrecoverable heat-shrinkable strain and the recoverable thermal strain of the proposed unit cell. The findings presented here enable heat-shrinkable metamaterials with simple fabrication and porosity, dramatically reducing required manufacture times and materials. Keywords: Residual stress, Metamaterial, Lattice, Heat-shrinkable, Photochemical expansion

This work presents a comparative study on the reliability of auxetic (re-entrant honeycomb) and non-auxetic (diamond lattice and conventional honeycomb) lattice composites. The analyzed specimen consists of two unidirectional carbon fiber reinforced composite (CFRP) face sheets and a 3D-printed polymeric core. Low velocity impact tests are conducted first to characterize the unit cell deformation pattern, and we further explore its influence on core structure behavior as well as sandwich panel performance. It is found that the re-entrant topology exhibits lower energy absorption capacity but superior robustness and durability. Consequently, the re-entrant panel performs best in both force mitigation and energy dissipation, provided that the impact energy is appropriate. Furthermore, employing re-entrant core not only stabilizes the occurrences of the face sheet penetration as the impact energy increases, but also grants the sandwich panel consistent behaviors under multi-cycle impacts. These unique performances are due to the global instability of the auxetic structure, which yields more compliant deformation and less stress concentration. Resultant discrepancies shall be interpreted with the sandwich core deformation for validation. These findings pave the way for developing new class of auxetic lattice composites, especially under cyclic loading conditions, through a combination of rational design and 3D printing. Keywords: Auxetic, Lattice, Reliability, Robustness, Durability, Low velocity impact

Abstract Background Patients diagnosed with high-grade serous ovarian cancer (HGSOC) who received initial debulking surgery followed by platinum-based chemotherapy can experience highly variable clinical responses. A small percentage of women experience exceptional long-term survival (long term (LT), 10+ years), while others develop primary resistance to therapy and succumb to disease in less than 2 years (short term (ST)). To improve clinical management of HGSOC, there is a need to better characterize clinical and molecular profiles to identify factors that underpin these disparate survival responses. Methods To identify clinical and tumor molecular biomarkers associated with exceptional clinical response or resistance, we conducted an integrated clinical, exome, and transcriptome analysis of 41 primary tumors from LT (n = 20) and ST (n = 21) HGSOC patients. Results Younger age at diagnosis, no residual disease post debulking surgery and low CA125 levels following surgery and chemotherapy were clinical characteristics of LT. Tumors from LT survivors had increased somatic mutation burden (median 1.62 vs. 1.22 non-synonymous mutations/Mbp), frequent BRCA1/2 biallelic inactivation through mutation and loss of heterozygosity, and enrichment of activated CD4+, CD8+ T cells, and effector memory CD4+ T cells. Characteristics of ST survival included focal copy number gain of CCNE1, lack of BRCA mutation signature, low homologous recombination deficiency scores, and the presence of ESR1-CCDC170 gene fusion. Conclusions Our findings suggest that exceptional long- or short-term survival is determined by a concert of clinical, molecular, and microenvironment factors.

Abstract The pyramiding of resistance (R) genes provides broad-spectrum and durable resistance to plant diseases. However, the genetic basis for bacterial blight (BB) resistance remains unclear. The BB R gene pyramided line IRBB54, which expresses xa5 and Xa21, possessed a higher level of resistance than both single R gene lines. Large-scale genotyping of genetic markers in this study revealed similar genetic backgrounds among the near-isogenic lines (NILs), suggesting that resistance in the resistant NILs was mainly conferred by the individual R genes or the interaction between them. Transcriptome analysis demonstrated that more than 50% of the differentially expressed genes (DEGs), and more than 70% of the differentially expressed functions, were shared between IRBB54 and IRBB5 or IRBB21. Most of the DEGs in the resistant NILs were downregulated and are predicted to function in cellular and biological process. The DEGs common among the resistant NILs mainly showed non-additive expression patterns and enrichment in stress-related pathways. The differential expression of agronomic trait-controlled genes in the resistant NILs, especially in IRBB54, indicated the existence of potential side-effects resulting from gene pyramiding. Our findings contribute to the understanding of R gene pyramiding, as well as its effects on targeted and non-targeted trait(s).

Anxiety and depression are severe public health problems worldwide. The effects of ozone exposure on anxious and depressive symptoms remain largely unknown, especially in China. We evaluated the associations between ozone exposure and depression and anxiety among middle-aged and older adults across China. A multi-center community-based repeated measurement study among middle-aged and older adults was conducted from 2017 to 2018 in 11 provinces in China. The status of depression and anxiety was measured using Patient Health Questionnaire-9 (PHQ-9) and the generalized anxiety disorder seven-item (GAD-7) scale at the cut-off point of five, respectively. Concentrations of multiple ozone metrics were collected from real-time monitoring stations. The multilevel logistic regression model with random intercept was used to evaluate the effects of ambient ozone on anxiety and depression over different exposure windows. After adjusting for potential confounders, a 10 μ g /m ^3 increase in the three months moving average of ozone was associated with the risk of anxiety [odds ratio (OR) = 1.25; 95% confidence interval (CI): 1.15; 1.37] and depression (OR = 1.17; 95% CI: 1.08; 1.27). A significantly positive modification effect of temperature on associations between ozone and anxiety was also found, while there is no interaction for depression. Exposure-response curves showed that there may be a threshold for the effect of ozone exposure on anxiety and depression over the three months moving average concentrations, with similar patterns observed at different temperature levels. People over 65 years old were at significantly higher risks of ozone-associated depression, while anxiety was more strongly associated with ozone in hypertensive patients. Our study supports the theory that anxiety and depression is associated with mid-term ozone exposure in China, and temperatures significantly enhanced their associations. These findings may have significant implications for promoting prevention activities regarding mental disorders and approaches in reducing the disease burden by simultaneously controlling air pollution and mitigating climate change.

Three yeast strains, namely Cryptococcus albidus (Ca63), Cryptococcus albidus (Ca64), and Candida parapsilosis (Yett1006), and their combinations, including single yeast agent, two combined yeast strains, single yeast agent + NaHCO3, single yeast agent + chitosan, single yeast agent + ascorbic acid, and single yeast agent + konjac powder, were evaluated for their activity against Botrytis cinerea, the most economically important fungal pathogens causing postharvest disease of snap beans. In in vitro tests, no inhibition zone was observed in dual cultures of three yeast strains and B. cinerea. The mycelial growth inhibition rates of B. cinerea for Ca63, Ca64, and Yett1006 were 97%, 95%, and 97%, respectively. In in vivo tests, the optimal combination of the lowest disease index of snap beans with B. cinerea was Ca63 + Ca64, with a preventing effect of 75%. The decay rate and rust spots index of Ca64 + ascorbic acid combination were 25% and 20%, respectively, which were the lowest. The activities of defense-related enzymes increased, while malondialdehyde (MDA) content was suppressed in snap beans after different treatments. Our results highlight the potential of the three yeast strains and their combinations as new nonpolluting agents for the integrated control of B. cinerea on snap beans.

SiOx is considered as a promising anode for next-generation Li-ions batteries (LIBs) due to its high theoretical capacity; however, mechanical damage originated from volumetric variation during cycles, low intrinsic conductivity, and the complicated or toxic fabrication approaches critically hampered its practical application. Herein, a green, inexpensive, and scalable strategy was employed to fabricate NG/SiOx/NG (N-doped reduced graphene oxide) homogenous hybrids via a freeze-drying combined thermal decomposition method. The stable sandwich structure provided open channels for ion diffusion and relieved the mechanical stress originated from volumetric variation. The homogenous hybrids guaranteed the uniform and agglomeration-free distribution of SiOx into conductive substrate, which efficiently improved the electric conductivity of the electrodes, favoring the fast electrochemical kinetics and further relieving the volumetric variation during lithiation/delithiation. N doping modulated the disproportionation reaction of SiOx into Si and created more defects for ion storage, resulting in a high specific capacity. Deservedly, the prepared electrode exhibited a high specific capacity of 545 mAh g−1 at 2 A g−1, a high areal capacity of 2.06 mAh cm−2 after 450 cycles at 1.5 mA cm−2 in half-cell and tolerable lithium storage performance in full-cell. The green, scalable synthesis strategy and prominent electrochemical performance made the NG/SiOx/NG electrode one of the most promising practicable anodes for LIBs.

Abstract Auxetic materials exhibiting a negative Poisson’s ratio are of great research interest due to their unusual mechanical responses and a wide range of potential deployment. Efforts have been devoted to exploring novel 2D and 3D auxetic structures through rational design, optimization, and taking inspiration from nature. Here we report a 3D architected lattice system showing a negative Poisson’s ratio over a wide range of applied uniaxial stretch. 3D printing, experimental tests, numerical simulation, and analytical modeling are implemented to quantify the evolution of the Poisson’s ratio and reveal the underlying mechanisms responsible for this unusual behavior. We further show that the auxetic behavior can be controlled by tailoring the geometric features of the ligaments. The findings reported here provide a new routine to design architected metamaterial systems exhibiting unusual properties and having a wide range of potential applications.

Genetic profiling of multiple myeloma requires painful bone marrow biopsies. Here, the authors develop an alternative non-invasive method for sequencing of five oncogenes in circulating cell-free DNA from myeloma patients, demonstrating 96% concordance with bone marrow tumour profiling results.

Rutting is one of the dominant pavement distresses, hence, the accuracy of rut depth measurements can have a substantial impact on the maintenance and rehabilitation (M & R) strategies and funding allocation. Different computation algorithms such as straight-edge method and wire line method, which are based on the same raw data, may lead to rut depth estimation which are not always consistent. Therefore, there is an urgent need to assess the impact of algorithm types on the accuracy of rut depth computation. In this paper, a 13-point-based laser sensor detection technology, commonly accepted in China for rut depth measurements, was used to obtain a database of 85,000 field transverse profiles having three representative rutting shapes with small, medium and high severity rut levels. Based on the reconstruction of real transverse profiles, the consequences from two different algorithms were compared. Results showed that there is a combined effect of rut depth and profile shape on the rut depth computation accuracy. As expected, the difference between the results obtained with the two computation methods increases with deeper rutting sections: when the distress is above 15 mm (severe level), the average difference between the two computation methods is above 1.5 mm, normally, the wire line method provides larger results. The computation suggests that the rutting shapes have a minimal influence on the results. An in-depth analysis showed that the upheaval outside of the wheel path is a dominant shape factor which results in higher computation differences.

A leading cause of death worldwide is sepsis that develops as a dysregulated immune response to infection. Serious infection caused by methicillin-resistant Staphylococcus aureus (MRSA) increases the difficulty of treatment in septic patients. Host-directed therapy (HDT) is an emerging approach to bacterial infections. Xuebijing injection (XBJ), a commercialized injectable prescription from traditional Chinese medicine, has been used as adjuvant therapy for sepsis with a history of 15 years. Whether it plays a protective role in severe infection caused by antibiotic-resistant bacteria is still unknown. In this study, XBJ significantly improved the survival of MRSA-induced sepsis mice. In MRSA-infected mouse model, XBJ down-regulated the expression of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, MCP-1, MIP-2, and IL-10 in sera. Besides that, it decreased the bacterial load in spleens, livers, and alleviated tissue damage of lung, liver, and kidney. The combination of XBJ with vancomycin or dexamethasone exhibited a better down-regulatory role of the inflammatory response. Then, the protective mechanism of XBJ was further investigated. XBJ inhibited heat-killed MRSA-induced IL-6 and TNF-α production in mouse macrophages. XBJ also decreased Pam3CSK4 (a synthetic tripalmitoylated lipopeptide mimicking bacterial lipoproteins)-stimulated expression of IL-6, TNF-α, IL-1β, IL-12, etc. in mouse macrophages. Furthermore, XBJ down-regulated the activation of NF-κB, MAPK, and PI3K/Akt pathways in Pam3CSK4-stimulated mouse macrophages. In conclusion, our findings demonstrated that XBJ played a protective role in MRSA-challenged mice and down-regulated the inflammatory response and the activation of signaling pathways initiated by Pam3CSK4. It enlarged the clinical application of XBJ in the treatment of severe bacterial infection, e.g. caused by MRSA.

High spatiotemporal resolution fine particulate matter (PM2.5) simulations can provide important exposure data for the assessment of long-term and short-term health effects. Satellite-based aerosol optical depth (AOD) data, meteorological data, and topographic data have become key variables for PM2.5 estimation. In this study, a random forest model was developed and used to estimate the highest resolution (0.01° × 0.01°) daily PM2.5 concentrations in the Beijing-Tianjin-Hebei region. Our model had a suitable performance (cv-R2 = 0.83 and test-R2 = 0.86). The regional test-R2 value in southern Beijing-Tianjin-Hebei was higher than that in northern Beijing-Tianjin-Hebei. The model performance was excellent at medium to high PM2.5 concentrations. Our study considered meteorological lag effects and found that the boundary layer height of the one-day lag had the most important contribution to the model. AOD and elevation factors were also important factors in the modeling process. High spatiotemporal resolution PM2.5 concentrations in 2010–2016 were estimated using a random forest model, which was based on PM2.5 measurements from 2013 to 2016. Keywords: PM2.5 estimation, Human exposure, High spatiotemporal resolution, Machine learning

Background: Particle air pollution has adverse health effects, and low-cost monitoring among a large population group is an effective method for performing environmental health studies. However, concern about the accuracy of low-cost monitors has affected their popularization in monitoring projects. Objective: To calibrate a low-cost particle monitor (HK-B3, Hike, China) through a controlled exposure experiment. Methods: Our study used a MicroPEM monitor (RTI, America) as a standard particle concentration measurement device to calibrate the Hike monitors. A machine learning model was established to calibrate the particle concentration obtained by the low-cost PM2.5 monitors, and ten-fold validation was used to test the model. In addition, we used a linear regression model to compare the results of the machine learning model. A calibration method was established for the low-cost monitors, and it can be used to apply the monitors in future air pollution monitoring projects. Results: The values of the random forest model calibration results and observations were more condensed around the regression line y = 0.99x + 0.05, and the R squared value (R2 = 0.98) was higher than that for the linear regression (R2 = 0.87). The random forest model showed better performance than the traditional linear regression model. Conclusions: Our study provided an effective calibration method to support the accuracy of low-cost monitors. The machine learning method based on the calibration model established in our study can increase the effectiveness of future air pollution and health studies. Keywords: PM2.5, Low-cost, Monitor, Calibration, Random forest model

ABSTRACT To characterize the diversity and richness and explore the function and structure of swine gut microbiome and resistome in common pig-farming feedlots, we sampled and metagenomic sequenced the feces of pigs from four different industrialized feedlots located in four distant provinces across China. Surprisingly, more than half of the nonredundant genes (1,937,648, 54.3%) in the current catalogue were newly found compared with the previously published reference gene catalogue (RGC) of the pig gut microbiome. Additionally, 16 high-completeness draft genomes were obtained by analyzing the dominant species on each feedlot. Notably, seven of these species often appeared in the human body sites. Despite a smaller number of nonredundant genes, our study identified more antibiotic resistance genes than those available in the RGC. Tetracycline, aminoglycoside, and multidrug resistance genes accounted for nearly 70% of the relative abundance in the current catalogue. Slightly higher sharing ratios were shown between the industrialized feedlot pig gut microbiomes and human gut microbiomes than that between the RGC and human counterpart (14.7% versus 12.6% in genes and 94.1% versus 87.7% in functional groups, respectively). Furthermore, a remarkably high number of the antibiotic resistance proteins (n =141) were identified to be shared by the pig, human, and mouse resistome, indicating the potential for horizontal transfer of resistance genes. Of the antibiotic resistance proteins shared by pigs and humans, 50 proteins were related to tetracycline resistance, and 49 were related to aminoglycoside resistance. IMPORTANCE The gut microbiota is believed to be closely related to many important physical functions in the host. Comprehensive data on mammalian gut metagenomes has facilitated research on host-microbiome interaction mechanisms, but less is known about pig gut microbiome, especially the gut microbiome in industrialized feedlot pigs, compared with human microbiome. On the other hand, pig production, as an important source of food, is believed to exacerbate the antibiotic resistance in humans due to the abuse of antibiotics in pig production in various parts of the world. This study delineates an intricate picture of swine gut microbiome and antibiotic resistome in industrialized feedlots and may provide insight for the pig producing industry.

Dendritic cells (DCs) play pivotal roles in T-cell homeostasis and activation, and metabolic programing has been recently linked to DC development and function. However, the metabolic underpinnings corresponding to distinct DC functions remain largely unresolved. Here, we demonstrate a special metabolic-epigenetic coupling mechanism orchestrated by tuberous sclerosis complex subunit 1 (TSC1)-mechanistic target of rapamycin (mTOR) for homeostatic DC function. Specific ablation of Tsc1 in the DC compartment (Tsc1DC-KO) largely preserved DC development but led to pronounced reduction in naïve and memory-phenotype cluster of differentiation (CD)8+ T cells, a defect fully rescued by concomitant ablation of mTor or regulatory associated protein of MTOR, complex 1 (Rptor) in DCs. Moreover, Tsc1DC-KO mice were unable to launch efficient antigen-specific CD8+ T effector responses required for containing Listeria monocytogenes and B16 melanomas. Mechanistically, our data suggest that the steady-state DCs tend to tune down de novo fatty acid synthesis and divert acetyl-coenzyme A (acetyl-CoA) for histone acetylation, a process critically controlled by TSC1-mTOR. Correspondingly, TSC1 deficiency elevated acetyl-CoA carboxylase 1 (ACC1) expression and fatty acid synthesis, leading to impaired epigenetic imprinting on selective genes such as major histocompatibility complex (MHC)-I and interleukin (IL)-7. Remarkably, tempering ACC1 activity was able to divert cytosolic acetyl-CoA for histone acetylation and restore the gene expression program compromised by TSC1 deficiency. Taken together, our results uncover a crucial role for TSC1-mTOR in metabolic programing of the homeostatic DCs for T-cell homeostasis and implicate metabolic-coupled epigenetic imprinting as a paradigm for DC specification.

Abstract A CRISPR/Cas9 system has emerged as a powerful tool for gene editing to treat genetic mutation related diseases. Due to the complete endothelial barrier, effective delivery of the CRISPR/Cas9 system to vasculatures remains a challenge for in vivo gene editing of genetic vascular diseases especially in aorta. Herein, it is reported that CHO‐PGEA (cholesterol (CHO)‐terminated ethanolamine‐aminated poly(glycidyl methacrylate)) with rich hydroxyl groups can deliver a plasmid based pCas9‐sgFbn1 system for the knockout of exon 10 in Fbn1 gene. This is the first report of a polycation‐mediated CRISPR/Cas9 system for gene editing in aorta of adult mice. CHO‐PGEA/pCas9‐sgFbn1 nanosystems can effectively contribute to the knockout of exon 10 in Fbn1 in vascular smooth muscle cells in vitro, which leads to the change of the phosphorylation of Smad2/3 and the increased expression of two downstream signals of Fbn1: Mmp‐2 and Ctgf. For in vivo application, the aortic enrichment of CHO‐PGEA/Cas9‐sgFbn1 is achieved by administering a pressor dose of angiotensin II (Ang II). The effects of the pCas9‐sgFbn1 system targeting Fbn1 demonstrate an increase in the expression of Mmp‐2 and Ctgf in aorta. Thus, the combination of CHO‐PGEA/pCas9‐sgFbn1 nanosystems with Ang II infusion can provide the possibility for in vivo gene editing in aorta.

Microbial exposure during early life plays a pivotal role in modulating the health and intestinal development of the host. Our recent study showed that the low-birth-weight (LBW) piglets harbored a different fecal microbiota compared to normal-birth-weight (NBW) piglets during early life with a lower abundance of the genus Lactobacillus. Considering the spatial variations in gut microbiota at distinct gut locations, this study was designed to further investigate the differences in the microbiota composition and predominant Lactobacillus species in the ileum and colon between LBW and NBW piglets during early life, including day 7 (D7), day 21 (D21, before weaning), and day 35 (D35, 2 weeks after weaning). Compared with the normal group, LBW piglets harbored a significantly lower proportion of short-chain fatty acids producing microbes, such as Ruminococcaceae and Prevotellaceae in the ileum on D7, Alistipes and Lachnospiraceae in the colon on D7, Blautia in the colon on D21, and Ruminiclostridium 9 in the colon on D35. The relative abundance of the phylum Bacteroidetes was also declined in both ileum and colon of LBW piglets on D7. Meanwhile, the levels of total SCFAs on D7, D21, and D35, acetate and valerate on D7 and D21, propionate on D21, and lactate on D21 and D35, were also declined in the colon of LBW piglets. Moreover, functional alterations in the gut microbiota of LBW piglets were characterized by differentially abundant microbial genes involved in multiple pathways such as amino acid metabolism, energy metabolism, replication and repair, and metabolism of cofactors and vitamins in the colon. Additionally, lower numbers of L. salivarius on D7 and L. amylovorus on D21 resided in the colon of LBW piglets compared to those in the normal ones. Collectively, LBW piglets have altered bacterial communities, microbial metabolism and gene functions in the ileum and colon during early life, especially the colonic community. This work will help to develop novel ideas in identifying the reliable biomarkers affecting the gut microbiota development in LBW piglets during early life and facilitate the development of new nutritional interventions.

Background: Hypertension is a major worldwide public health problem. Previous studies have indicated that ambient temperature is associated with blood pressure (BP), but the nature of this association remains unclear. Objective: The objective of this meta-analysis was to investigate the relationship between ambient temperature and BP. Methods: We performed a systematic search of the literature indexed in PubMed, Web of Science, and ScienceDirect between 1980 and 2016. The pooled effect sizes for exposure to low/moderate temperatures, as well as high-temperature exposure, were calculated using a random-effects model. Results: Fifteen studies were included in this meta-analysis. Twelve of these reported the effects of low/moderate-temperature exposure, two reported the effects of high-temperature exposure, and one reported the effects of both low/moderate- and high-temperature exposure. For low/moderate-temperature exposure, 1°C decrease in temperature was associated with 0.40 mmHg (95% confidence interval [CI]: 0.34–0.46) increase in systolic BP and 0.13 mmHg (95% CI: 0.08–0.18) increase in diastolic BP. For high-temperature exposure, the relationship between BP and temperature was not statistically significant. Conclusion: For low/moderate-temperature exposure, a decrease in temperature was associated with an increase in BP. In contrast, the relationship between high-temperature exposure and BP was not statistically significant.

Objective: To observe the hemostatic effect of the Spleen-invigorating, Qi-replenishing and Blood-arresting Formula on simvastatin-induced zebrafish hemorrhage model compared with that of the Heat-clearing and Blood-cooling Formula. Methods: AB strain wild type zebrafish were treated with 0.5 μM simvastatin for 24 hours to establish the zebrafish hemorrhage model. Under strictly blind experimental conditions, the zebrafish were then treated with experimental agents in different concentration within the maximum non-lethal dose. The intervention effect of the Spleen-invigorating, Qi-replenishing and Blood-arresting Formula was comprehensively assessed by examining the main observational parameters such as the bleeding reduction rate and hemostatic rate while referring to the additional parameters such as blood flow, improvement rate of blood flow, velocity of movement, improvement rate of motion under spleen-qi deficiency. Results: Hemostatic effect: The bleeding rate and hemostatic rate in the zebrafish were respectively, 30%, 15%, 45%, 40% and 60%, 80%, 40%, 47% when equal concentration of 500 μg/mL, 1000 μg/mL were used. This showed that the experimental herbs B1 was superior to B2 in decreasing the bleeding rate and improving hemostatic effect in the zebrafish. Improvement of blood flow: With equal concentration, the experimental herb B1 was superior to B2 in increasing the blood flow and improvement rate of blood flow in hemorrhagic zebrafish. Promotion of the improvement of motion: With equal concentration of 500 μg/mL and 1000 μg/mL, the experimental herb B1 was superior to B2 in promoting the velocity of motion in the zebrafish and promoting the improvement rate of motion. Conclusion: The manifestations of simvastatin-induced zebrafish hemorrhage are basically similar to that of failure of the spleen to control blood in human beings. The Spleen-invigorating, Qi-replenishing and Blood-arresting Formula has good hemostatic effect on simvastatin-induced hemorrhage in the zebrafish. It also boasts the functions of improving blood flow and velocity of motion in the hemorrhagic zebrafish. Such a conclusion provides the experimental basis for the treatment of the syndrome of failure of the spleen to control blood by this formula.

Objective(s): The main objective of this study was to investigate the variations of β-endorphin (β-EP), vasoactive intestinal peptide (VIP), serotonin (5-HT) and norepinephrine (NE) of immune thrombocytopenia (ITP) mice as well as the regulatory mechanism of prednison. Materials and Methods: Sixty BALB/c mice were randomly divided into control group, model group and prednison intervention group. ITP mice model was duplicated by injecting with glycoprotein-antiplatelet serum (GP-APS) except in control group. After ITP disease model was successful established, prednison was used in prednison intervention group. The β-EP, VIP, 5-HT and NE contents of ITP mice were detected by enzyme linked immunosorbent assay (ELISA). Results:Compared with the values in control group, the detection values of VIP and 5-HT in model group declined, while the detection values of β-EP and NE increased. Compared with prednison intervention group, the detection values of VIP and 5-HT in model group increased, while the detection values of β-EP and NE showed no significant change. Conclusion: In this study, the β-EP, VIP, 5-HT and NE contents in ITP mice injected with GP-APS were changed by prednison. It shows that prednison as the first-line therapy for ITP with effective hemostasis function is likely to increasing the contents of VIP and 5-HT. These results suggest the therapeutic value of prednison for the treatment of ITP.

The low cost β-zeolite and ethylenediamine modified β-zeolite (EDA@β-zeolite) were prepared by self-assembly method and used for Cu(II) removal from contaminated aqueous solution. Removal ability of β-zeolite toward Cu(II) was greatly improved after ethylenediamine (EDA) modification, the removal performance was greatly affected by environmental conditions. XPS results illustrated that the amide group played important role in the removal process by forming complexes with Cu(II). The EDA@β-zeolite showed desirable recycling ability. The finding herein suggested that the proposed composite is a promising and suitable candidate for the removal of Cu(II) from contaminated natural wastewater and aquifer.

The frequency and intensity of high-temperature events continue to increase, resulting in a surge of pathogenicity and mortality. People with low levels of risk perception and adaptability, such as the elderly, suffer more from high temperatures. Effective intervention measures may lead to reduced levels of high temperature-related risk. The purpose of this study was to compare changes in temperature exposure, risk perception and coping behaviors under different intervention methods. Herein we conducted three different interventions including education, subsidies for electricity and uses of spray-cooling appliances as well as collected data about temperature exposure, risk perception, and coping behaviors. Before and after the experiment, we evaluated the intervention effectiveness with a number of variables related to alerting human responses under high temperatures. We conducted nonparametric tests for paired samples and generalized linear mixed effect models. Compared with subsidy support and outdoor spray-cooling methods, education is more effective as it leads to lower levels of temperature exposure, higher levels of risk perception, and more behavioral responses. The subsidy support intervention is useful in increasing risk perception and promoting home cooling practices as well. In comparison, spray cooling barely contributes to the reduction of personal temperature exposure. The encouragement of risk-related education and continued government subsidy may prevent elderly individuals from experiencing high-temperature exposure.

The predicted increase in the frequency of extreme climatic events in the future may have a negative effect on cereal production, but our understanding of the historical trends of high-temperature events associated with climate change and their long-term impact on summer maize yield is limited. Based on an analysis of historical climate and summer maize yield data from 1980 to 2016 in the Huang-Huai-Hai (3H) region of China, we calculated two high-temperature event indices, namely, high-temperature hours (HTH) and high-temperature degrees (HTD, the sum of the differences between 35 °C and above), and then investigated the temporal trend of high-temperature events from maize heading to maturity and their impact on the yield of summer maize. Our results indicated that the air temperature showed a significant upward trend when heading into the maturity period of summer maize in the 3H region from 1980–2016 and that the increase was greater in the northern Huang-Huai-Hai (N3H) region than in the southern Huang-Huai-Hai (S3H) region. The intensity of high-temperature events when heading into the maturity period increased considerably from 1980 to 2016 in the 3H region, especially in the S3H region. The HTH and HTD increased by 1.30 h and 0.80 °C per decade in the S3H region, respectively. Moreover, a sensitivity analysis of panel data showed that the increases in HTH and HTD when heading into the maturity period had a consistent negative effect on yield in S3H and N3H regions; this effect was more obvious in the S3H region. In the S3H region, a 1 h increase in HTH was found to be associated with a 0.45–1.13% decrease in yield and a 1 °C increase in HTD could result in a yield loss of 1.34–4.29%. High-temperature events were detrimental to summer maize production, and the severity of this effect was projected to increase in the 3H region. In this study, we used two indices (HTH and HTD) to quantify the impact of high-temperature events on summer maize yield during the critical growth phase (heading to maturity) at a small timescale (hours and days). The results of this study can provide a reference for policymakers to use in the formulation of corresponding climate change adaptation strategies.

Summary: Background: Air pollution and its adverse effects on public health remain a considerable problem in China, where policies have been implemented to improve the situation. We aimed to estimate the disease burden associated with particulate matter (PM)2·5 across China for 2020 and 2030 to identify the populations and regions most at risk, quantify the health benefits of air quality improvement targets, and determine the effect of population growth and ageing on this disease burden. Methods: In this modelling study, we investigated premature deaths associated with PM2·5 across China on the basis of air quality scenarios proposed by the expert group involved in the formulation of the 13th Five-Year Plan for Eco-Environmental Protection and population scenarios based on the Shared Socioeconomic Pathways of the Intergovernmental Panel on Climate Change. We used the integrated exposure–response model used for the Global Burden of Disease Study to estimate the number of PM2·5-related premature deaths under each scenario. Findings: The projected health benefits of the air-quality-improving targets are substantial, and could reduce the number of PM2.5-related premature deaths in China by approximately 129 278 by 2020 and 217 988 by 2030, compared with 2010. However, since China's population is increasing and ageing, the number of PM2.5-related premature deaths was estimated to increase by 84 102 by 2020 and by 244 191 by 2030, indicating that the health benefits induced by air quality improvements could be offset by the effect of the population increasing in size and ageing. Interpretation: To reduce the future disease burden in China, targets that are stricter than the interim target and stringent policies to improve air quality and protect public health are needed, especially for at-risk population groups, such as older individuals (aged >55 years) and patients with cardiovascular diseases, particularly in regions with a high disease burden. Funding: National Key Research and Development Program of China, National Natural Science Foundation of China, Beijing Natural Science Foundation, National High-level Talents Special Support Plan of China for Young Talents, and Special Foundation of Basic Science and Technology Resources Survey of Ministry of Science and Technology of China.

The high overpotentials for oxygen reduction reaction (ORR) create an extremely negative impact on the energy efficiency of the air-based battery systems. To overcome this problem, binuclear ball-type metallophthalocyanines containing methoxy substituents (M2Pc2(EP)4, M = Fe(II), Co(II) and Zn(II)) were wrapped with polystyrene sodium sulfonate (PSS) modified graphene oxide (GO), using a facilely “solvothermal π-π assembly” method to prepare M2Pc2(EP)4/PSS-Gr composites. Compared with the commercial Pt/C catalysts, the M2Pc2(EP)4/PSS-Gr composites enhanced the catalytic activity of oxygen reduction reaction. The π electron conjugated structure of the MN4-type phthalocyanine macrocyclic system strongly influenced the one-step four-electron electrocatalytic process of the M2Pc2(EP)4/PSS-Gr composites. Moreover, the π-π interactions between the M2Pc2(EP)4 and PSS-Gr dramatically enhanced the π electron density in the conjugated structure and oxygen could be reduced more easily. The electrocatalytic activity test was displayed in the order of Fe2Pc2(FP)4/PSS-Gr > Co2Pc2(EP)4/PSS-Gr > Zn2Pc2(EP)4/PSS-Gr. The results indicated that the catalytic performance of M2Pc2Rn could be enhanced by the modification of π electron conjugated structure of M2Pc2(EP)4 and carbon materials.

Summary: Background: Evidence from cohort studies in North America and Europe indicates that long-term exposure to fine particulate matter (PM2·5) is associated with an increased mortality risk. However, this association has rarely been quantified at higher ambient concentrations. We estimated the hazard ratio (HR) for all-cause mortality from long-term exposure to PM2·5 in a well established Chinese cohort of older adults. Methods: The Chinese Longitudinal Healthy Longevity Survey (CLHLS) is a prospective cohort study of men and women aged 65 years and older enrolled in 2008 and followed up through 2014 for mortality events. We studied individuals for whom residential locations were available in 2008 for linkage to 1 km grids of PM2·5 concentrations, derived from satellite remote sensing. Cox proportional hazards models were used to estimate the effect of long-term exposure to PM2·5 on all-cause mortality, controlling for age, sex, smoking status, drinking status, physical activity, body-mass index, household income, marital status, and education. We then used our results to estimate premature mortality related to PM2·5 exposure in the population aged 65 years and older in China in 2010. Findings: 13 344 individuals in the CLHLS cohort had data for all timepoints, yielding follow-up data for 49 440 person-years. In a 3-year window, these individuals were exposed to a median PM2·5 concentration of 50·7 μg/m3 (range 6·7–113·3). The overall HR for a 10 μg/m3 increase in this value was 1·08 (95% CI 1·06–1·09). In stratified analyses, HRs were higher in rural than in urban locations, in southern versus northern regions, and with exposure to lower versus higher PM2·5 concentrations. Based on the overall HR, we estimated that 1 765 820 people aged 65 years and older in China in 2010 had premature mortality related to PM2·5 exposure. Interpretation: Long-term exposure to PM2·5 is associated with an increased risk of all-cause mortality among adults aged 65 years and older in China, but the magnitude of the risk declines as the concentration of PM2·5 increases. Funding: National Natural Science Foundation of China, National High-Level Talents Special Support Plan of China for Young Talents, US National Aeronautics and Space Administration, and the Columbia University Global Policy Initiative.

Low-birth-weight (LBW) piglets are at a high-risk for postnatal growth failure, mortality, and metabolic disorders later in life. Early-life microbial exposure is a potentially effective intervention strategy for modulating the health and metabolism of the host. Yet, it has not been well elucidated whether the gut microbiota development in LBW piglets is different from their normal littermates and its possible association with metabolite profiles. In the current study, 16S rRNA gene sequencing and metabolomics was used to investigate differences in the fecal microbiota and metabolites between LBW and normal piglets during early-life, including day 3 (D3), 7 (D7), 14 (D14), 21 (D21, before weaning), and 35 (D35, after birth). Compared to their normal littermates, LBW piglets harbored low proportions of Faecalibacterium on D3, Flavonifractor on D7, Lactobacillus, Streptococcus, and Prevotella on D21, as well as Howardella on D21 and D35. However, the abundance of Campylobacter on D7 and D21, Prevotella on D14 and D35, Oscillibacter and Moryella on D14 and D21, and Bacteroides on D21 was significantly higher in LBW piglets when compared with normal piglets. The results of the metabolomics analysis suggested that LBW significantly affected fecal metabolites involved in fatty acid metabolism (e.g., linoleic acid, α-linolenic acid, and arachidonic acid), amino acid metabolism (e.g., valine, phenylalanine, and glutamic acid), as well as bile acid biosynthesis (e.g., glycocholic acid, 25-hydroxycholesterol, and chenodeoxycholic acid). Spearman correlation analysis revealed a significant negative association between Campylobacter and N1-acetylspermine on D7, Moryella and linoleic acid on D14, Prevotella and chenodeoxycholic acid on D21, and Howardella and phenylalanine on D35, respectively. Collectively, LBW piglets have a different gut bacterial community structure when compared with normal-birth-weight (NBW) piglets during early-life, especially from 7 to 21 days of age. Also, a distinctive metabolic status in LBW piglets might be partly associated with the altered intestinal microbiota. These findings may further elucidate the factors potentially associated with the impaired growth and development of LBW piglets and facilitate the development of nutritional interventions.

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), which mainly causes pulmonary injury and tubercles. Although macrophages are generally considered to harbor the main cells of M. tuberculosis, new evidence suggests that neutrophils are rapidly recruited to the infected lung. M. tuberculosis itself, or its early secreted antigenic target protein 6 (ESAT-6), can induce formation of neutrophil extracellular traps (NETs). However, NETs trap mycobacteria but are unable to kill them. The role of NETs’ formation in the pathogenesis of mycobacteria remains unclear. Here, we report a new M. tuberculosis extracellular factor, bifunctional enzyme Rv0888, with both nuclease and sphingomyelinase activities. Rv0888 sphingomyelinase activity can induce NETs’ formation in vitro and in the lung of the mice and enhance the colonization ability of Mycobacterium smegmatis in the lungs of mice. Mice infected by M. smegmatis harboring Rv0888 sphingomyelinase induced pathological injury and inflammation of the lung, which was mainly mediated by NETs, induced by Rv0888 sphingomyelinase, associated protein (myeloperoxidase) triggered caspase-3. In summary, the study sheds new light on the pathogenesis of mycobacteria and reveals a novel target for TB treatment.

Objective: This study investigated the regulatory effect of non-classical immune parameters on immune thrombocytopenic purpura (ITP) mice by a spleen-invigorating, qi-replenishing and blood-containing formula (SQBF). Method: A total of 80 BALB/c mice were randomly divided into four equal groups (20 mice each): control group, model group, prednisone group and spleen-invigorating, qi-replenishing and blood-containing (SQBF) group. Mice in the model group, prednisone group, and SQBF group were administered anti-platelet serum to induce ITP. The dynamic variations of platelet counts in ITP mice were measured with an automatic blood analyzer before modeling and 48 h, and 8, 12 and 15 days following APS injection. Levels of β-endorphin (β-EP), vasoactive intestinal peptide (VIP) and salivary IgA (SIgA) were detected by enzyme-linked immunosorbent assay (ELISA) on 15th day of experiment. Results: SQBF enhanced peripheral blood platelet counts in ITP mice similar to that of prednisone, and both groups showed a statistically significant response compared with the model group (P

Background. The HIN-200 family genes in humans have been linked to several autoimmune diseases—particularly to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recently, its human counterpart gene cluster, the Ifi200 family in mice, has been linked to spontaneous arthritis disease (SAD). However, many immune-mediated diseases (including RA and SLE) show gender difference. Understanding whether or not and how these genes play a role in sex difference in immune-mediated diseases is essential for diagnosis/treatment. Methods. This study takes advantage of the whole genome gene expression profiles of recombinant inbred (RI) strain populations from female and male mice to analyze potential sex differences in a variety of genes in disease pathways. Expression levels and regulatory QTL of Ifi200 family genes between female and male mice were first examined in a large mouse population, including RI strains derived from C57BL/6J, DBA/2J (BXD), and classic inbred strains. Sex similarities and differences were then analyzed for correlations with gene expression levels between genes in the Ifi200 family and four selected gene sets: known immune Ifi200 pathway-related genes, lupus-relevant genes, osteoarthritis- (OA-) and RA-relevant genes, and sex hormone-related genes. Results. The expression level of Ifi202b showed the most sex difference in correlation with known immune-related genes (the P value for Ifi202b is 0.0004). Ifi202b also showed gender difference in correlation with selected sex hormone genes, with a P value of 0.0243. When comparing coexpression levels between Ifi200 genes and lupus-relevant genes, Ifi203 and Ifi205 showed significant sex difference (P values: 0.0303 and 0.002, resp.). Furthermore, several key genes (e.g., Csf1r, Ifnb1, IL-20, IL-22, IL-24, Jhdm1d, Csf1r, Ifnb1, IL-20, IL-22, IL-24, and Tgfb2 that regulate sex differences in immune diseases) were discovered. Conclusions. Different genes in the Ifi200 family play different roles in sex difference among dissimilar pathways of these four gene groups.

The current work was to evaluate the lipase-catalyzed acidolysis of corn oil with caprylic acid (CA) in organic system under bath ultrasonic pretreatment and to analyze the physicochemical properties of structured lipids (SLs). Under optimum conditions (Novozym 40086 lipase, 200 W ultrasound power, 10 min ultrasound pretreatment time, 12% dosage of lipase, Triacylglycerol (TAG)/Free fatty acids (FFA): 1/8, 40 °C for 6 h), a 45.55% CA incorporation was obtained (named SLs-U). The highest CA incorporation was 32.75% for conventional method at reaction time of 10 h (named SLs-N). The predominant TAG types of SLs were MLM (medium-, long- and medium-chain-type TAGs) and MLL (medium-, long- and long-chain-type TAGs). X-ray diffraction analysis revealed that both SLs-U and SLs-N present β form. Differential scanning calorimetry (DSC) analysis showed that both SLs-U and SLs-N show a lower melting and crystallization temperature than corn oil. This study suggested that bath ultrasonic pretreatment can accelerate lipase-catalyzed acidolysis synthesis of MLM structured lipids in an organic system, and two kinds of structured lipids show similar physicochemical properties.

Effects of marine microalga Chlorella pyrenoidosa 55% ethanol extract (CPE55) on lipid metabolism, gut microbiota and regulation mechanism in high fat diet-fed induced hyperlipidaemia rats were investigated. Structure characterizations of major compounds in CPE55 were determined by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The compositions of gut microbiota in rats were analyzed by high-throughput next-generation 16S rRNA gene sequencing. Oral administration with CPE55 markedly alleviated dyslipidemia through improving adverse blood lipid profile and inhibiting hepatic lipid accumulation and steatosis. CPE55 has downregulated the gene expression levels of acetyl CoA carboxylase, sterol regulatory element-binding transcription factor-1c, and 3-hydroxy-3-methyl glutaryl coenzyme A reductase and upregulated adenosine 5′-monophosphate-activated protein kinase-α. It has also improved the abundance of bacteria Alistipes, Prevotella, Alloprevotella, and Ruminococcus1 and decreased the abundances of Turicibacter and Lachnospira. Turicibacter and Lachnospira were both positive correlations of metabolic phenotypes. The findings above illustrated that CPE55 might be developed as food ingredients to ameliorate lipid metabolic disorders and hyperlipidaemia.

The Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction energy profile has been frequently used to interpret the mechanisms controlling colloid attachment/detachment and aggregation/disaggregation behavior. This study highlighted a type of energy profile that is characterized by a shallow primary energy well (i.e., comparable to the average kinetic energy of a colloid) at a small separation distance and a monotonic decrease of interaction energy with separation distance beyond the primary energy well. This energy profile is present due to variations of height, curvature, and density of discrete physical heterogeneities on collector surfaces. The energy profile indicates that colloids can be spontaneously detached from the shallow primary energy well by Brownian diffusion. The spontaneous detachment from primary minima was unambiguously confirmed by conducting laboratory column transport experiments involving flow interruptions for two model colloids (polystyrene latex microspheres) and engineered nanoparticles (fullerene C60 aggregates). Whereas the spontaneous detachment has been frequently attributed to attachment in secondary minima in the literature, our study indicates that the detached colloids could be initially attached at primary minima. Our study further suggests that the spontaneous disaggregation from primary minima is more significant than spontaneous detachment because the primary minimum depth between colloid themselves is lower than that between a colloid and a collector surface.

To identify differential protein expression pattern associated with polycystic ovary syndrome (PCOS).Twenty women were recruited for the study, ten with PCOS as a test group and ten without PCOS as a control group. Differential in-gel electrophoresis (DIGE) analysis and mass spectroscopy were employed to identify proteins that were differentially expressed between the PCOS and normal ovaries. The differentially expressed proteins were further validated by western blot (WB) and immunohistochemistry (IHC).DIGE analysis revealed eighteen differentially expressed proteins in the PCOS ovaries of which thirteen were upregulated, and five downregulated. WB and IHC confirmed the differential expression of membrane-associated progesterone receptor component 1 (PGRMC1), retinol-binding protein 1 (RBP1), heat shock protein 90B1, calmodulin 1, annexin A6, and tropomyosin 2. Also, WB analysis revealed significantly (P

Lipids and lipid-metabolizing esterases/lipases are highly important for the mycobacterial life cycle and, possibly, for mycobacterial virulence. In this study, we expressed 10 members of the Lip family of Mycobacterium tuberculosis. Among the 10 proteins, LipL displayed a significantly high enzymatic activity for the hydrolysis of long-chain lipids. The optimal temperature for the lipase activity of LipL was demonstrated to be 37°C, and the optimal pH was 8.0. The lipase active center was not the conserved motif G-x-S-x-G, but rather the S-x-x-K and GGG motifs, and the key catalytic amino acid residues were identified as G50, S88, and K91, as demonstrated through site-directed mutagenesis experiments. A three-dimensional modeling structure of LipL was constructed, which showed that the GGG motif was located in the surface of a pocket structure. Furthermore, the subcellular localization of LipL was demonstrated to be on the mycobacterial surface by Western blot analysis. Our results revealed that the LipL protein could induce a strong humoral immune response in humans and activate a CD8+ T cell-mediated response in mice. Overall, our study identified and characterized a novel lipase denoted LipL from M. tuberculosis, and demonstrated that LipL functions as an immunogen that activates both humoral and cell-mediated responses.

We study a delayed SIR epidemic model and get the threshold value which determines the global dynamics and outcome of the disease. First of all, for any τ, we show that the disease-free equilibrium is globally asymptotically stable; when R01, the disease will persist. However, for any τ≠0, the existence conditions for Hopf bifurcations at the endemic equilibrium are obtained. Besides, we compare the delayed SIR epidemic model with nonlinear incidence rate to the one with bilinear incidence rate. At last, numerical simulations are performed to illustrate and verify the conclusions.