How multiple air pollutants affect hand, foot, and mouth disease incidence in children: assessing effect modification by geographical context in multicity of Sichuan, southwest China.

BACKGROUND: Several studies have suggested a significant association of hand, foot, and mouth disease (HFMD) with ambient air pollutants. Existing studies have characterized the role of air pollutants on HFMD using only risk ratio measures while ignoring the attributable burden. And whether the geographical context (i.e., diverse topographic features) could modulate the relationships is unclear. METHODS: Daily reported childhood HFMD counts, ambient air pollution, and meteorological data during 2015-2017 were collected for each of 21 cities in Sichuan Province. A multistage analysis was carried out in different populations based on geographical context to assess effect modification by topographic conditions. We first constructed a distributed lag nonlinear model (DLNM) for each city to describe the relationships with risk ratio measures. Then, we applied a multivariate meta-regression to estimate the pooled effects of multiple air pollutants on HFMD from the exposure and lagged dimensions. Finally, attributable risks measures were calculated to quantify HFMD burden by air pollution. RESULTS: Based on 207554 HFMD cases in Sichuan Province, significant associations of HFMD with ambient air pollutants were observed mainly at relatively high exposure ranges. The effects of ambient air pollutants on HFMD are most pronounced on lag0 or around lag7, with relative risks gradually approaching the reference line thereafter. The attributable risks of O3 were much greater than those of other air pollutants, particularly in basin and mountain regions. CONCLUSIONS: This study revealed significant pooled relationships between multiple air pollutants and HFMD incidence from both exposure and lag dimensions. However, the specific effects, including RRs and ARs, differ depending on the air pollution variable and geographical context. These findings provide local authorities with more evidence to determine key air pollutants and regions for devising and implementing targeted interventions.

Rutin mitigates fluoride-induced nephrotoxicity by inhibiting ROS-mediated lysosomal membrane permeabilization and the GSDME-HMGB1 axis involved in pyroptosis and inflammation.

Fluoride is known to induce nephrotoxicity; however, the underlying mechanisms remain incompletely understood. Therefore, this study aims to explore the roles and mechanisms of lysosomal membrane permeabilization (LMP) and the GSDME/HMGB1 axis in fluoride-induced nephrotoxicity and the protective effects of rutin. Rutin, a naturally occurring flavonoid compound known for its antioxidative and anti-inflammatory properties, is primarily mediated by inhibiting oxidative stress and reducing proinflammatory markers. To that end, we established in vivo and in vitro models. In the in vivo study, rats were exposed to sodium fluoride (NaF) throughout pregnancy and up until 2 months after birth. In parallel, we employed in vitro models using HK-2 cells treated with NaF, n-acetyl-L-cysteine (NAC), or rutin. We assessed lysosomal permeability through immunofluorescence and analyzed relevant protein expression via western blotting. Our findings showed that NaF exposure increased ROS levels, resulting in enhanced LMP and increased cathepsin B (CTSB) and D (CTSD) expression. Furthermore, the exposure to NaF resulted in the upregulation of cleaved PARP1, cleaved caspase-3, GSDME-N, and HMGB1 expressions, indicating cell death and inflammation-induced renal damage. Rutin mitigates fluoride-induced nephrotoxicity by suppressing ROS-mediated LMP and the GSDME/HMGB1 axis, ultimately preventing fluoride-induced renal toxicity occurrence and development. In conclusion, our findings suggest that NaF induces renal damage through ROS-mediated activation of LMP and the GSDME/HMGB1 axis, leading to pyroptosis and inflammation. Rutin, a natural antioxidative and anti-inflammatory dietary supplement, offers a novel approach to prevent and treat fluoride-induced nephrotoxicity.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Influence of social and meteorological factors on hand, foot, and mouth disease in Sichuan Province.

BACKGROUND: Hand, foot and mouth disease (HFMD) caused by a variety of enteroviruses remains a major public health problem in China. Previous studies have found that social factors may contribute to the inconsistency of the relationship patterns between meteorological factors and HFMD, but the conclusions are inconsistent. The influence of social factors on the association between meteorology and HFMD is still less well understood. We aimed to analyze whether social factors affected the effect of meteorological factors on HFMD in Sichuan Province. METHOD: We collected daily data on HFMD, meteorological factors and social factors in Sichuan Province from 2011 to 2017. First, we used a Bayesian spatiotemporal model combined with a distributed lag nonlinear model to evaluate the exposure-lag-response association between meteorological factors and HFMD. Second, by constructing the interaction of meteorological factors and social factors in the above model, the changes in the relative risk (RR) under different levels of social factors were evaluated. RESULTS: The cumulative exposure curves for average temperature, relative humidity, and HFMD were shaped like an inverted "V" and a "U" shape. As the average temperature increased, the RR increased and peaked at 19 °C (RR 1.020 [95% confidence interval CI 1.004-1.050]). The urbanization rate, per capita gross domestic product (GDP), population density, birth rate, number of beds in health care centers and number of kindergartens interacted with relative humidity. With the increase in social factors, the correlation curve between relative humidity and HFMD changed from an "S" shape to a "U" shape. CONCLUSIONS: Relative humidity and average temperature increased the risk of HFMD within a certain range, and social factors enhanced the impact of high relative humidity. These results could provide insights into the combined role of environmental factors in HFMD and useful information for regional interventions.

Cross-talk between autophagy and ferroptosis contributes to the liver injury induced by fluoride via the mtROS-dependent pathway.

Fluoride can induce hepatotoxicity, but the mechanisms responsible are yet to be investigated. This study sought to investigate the role and mechanism of mitochondrial reactive oxygen species (mtROS), autophagy, and ferroptosis in fluoride-induced hepatic injury with a focus on the role of mtROS-mediated cross-talk between autophagy and ferroptosis. To this end, an in vivo Sprague-Dawley rat model and in vitro BRL3A cells were exposed to sodium fluoride (NaF). The results revealed that NaF exposure diminished the mitochondrial membrane potential, increased mtROS production and TOMM20 expression, and induced autophagic flux blockage and ferroptosis in vivo and in vitro. Furthermore, the autophagy activator (RAPA) enhanced GPX4 expression while inhibiting ACSL4 expression, reduced the accumulation of ferrous ions in BRL3A cells, and restored lipid peroxidation levels, thus inhibiting ferroptosis. Fer-1, a ferritinase inhibitor, downregulated the expression of LC3-II and p62, increased the number of autolysosomes while decreasing the number of autophagosomes, and alleviated the blockage of autophagic flux by improving autophagic degradation. These results suggest the occurrence of a cross-talk between autophagy and ferroptosis. The mtROS inhibitor (Mito-TEMPO) could alleviate autophagic flux blockage and inhibit ferroptosis in NaF-induced liver injury. In addition, the cross-talk between NaF-induced autophagy and ferroptosis was dependent on the mtROS pathway.

TFE3-mediated impairment of lysosomal biogenesis and defective autophagy contribute to fluoride-induced hepatotoxicity.

Excessive fluoride exposure can cause liver injury, but the specific mechanisms need further investigation. We aimed to explore the role of impaired lysosomal biogenesis and defective autophagy in fluoride-induced hepatotoxicity and its potential mechanisms, focusing on the role of transcription factor E3 (TFE3) in regulating hepatocyte lysosomal biogenesis. To this end, we established a Sprague-Dawley (SD) rat model exposed to sodium fluoride (NaF) and a rat liver cell line (BRL3A) model exposed to NaF. The results showed that NaF exposure diminished liver function and led to apoptosis as well as autophagosome accumulation and impaired autophagic degradation. In addition, NaF exposure caused compromised lysosome biogenesis and decreased lysosomal degradation, and inhibited TFE3 nuclear translocation. Notably, the mTOR inhibitors rapamycin (RAPA) and Ad-TFE3 promoted lysosomal biogenesis and enhanced lysosomal degradation function. Furthermore, RAPA and Ad-TFE3 reduced NaF-induced apoptosis by alleviating impaired autophagic degradation. In conclusion, NaF impairs lysosomal biogenesis by inhibiting TFE3 nuclear translocation, decreasing lysosomal degradation function, resulting in impaired autophagic degradation, and ultimately inducing apoptosis. Therefore, TFE3 may be a promising therapeutic target for fluoride-induced hepatotoxicity.

PRKAA1 induces aberrant mitophagy in a PINK1/Parkin-dependent manner, contributing to fluoride-induced developmental neurotoxicity.

Chronic fluoride exposure can cause developmental neurotoxicity, however the precise mechanisms remain unclear. To explore the mechanism of mitophagy in fluoride-induced developmental neurotoxicity, specifically focusing on PRKAA1 in regulating the PINK1/Parkin pathway, we established a Sprage Dawley rat model with continuous sodium fluoride (NaF) exposure and an NaF-treated SH-SY5Y cell model. We found that NaF exposure increased the levels of LC3-Ⅱ and p62, impaired autophagic degradation, and subsequently blocked autophagic flux. Additionally, NaF exposure increased the expression of PINK1, Parkin, TOMM-20, and Cyt C and cleaved PARP in vivo and in vitro, indicating NaF promotes mitophagy and neuronal apoptosis. Meanwhile, phosphoproteomics and western blot analysis showed that NaF treatment enhanced PRKAA1 phosphorylation. Remarkably, the application of both 3-methyladenosine (3-MA; autophagy inhibitor) and dorsomorphin (DM; AMPK inhibitor) suppressed NaF-induced neuronal apoptosis by restoring aberrant mitophagy. In addition, 3-MA attenuated an increase in p62 protein levels and NaF-induced autophagic degradation. Collectively, our findings indicated that NaF causes aberrant mitophagy via PRKAA1 in a PINK1/Parkin-dependent manner, which triggers neuronal apoptosis. Thus, regulating PRKAA1-activated PINK1/Parkin-dependent mitophagy may be a potential treatment for NaF-induced developmental neurotoxicity.

The inhibition of TRPML1/TFEB leads to lysosomal biogenesis disorder, contributes to developmental fluoride neurotoxicity.

Fluoride is capable of inducing developmental neurotoxicity; regrettably, the mechanism is obscure. We aimed to probe the role of lysosomal biogenesis disorder in developmental fluoride neurotoxicity-specifically, the regulating effect of the transient receptor potential mucolipin 1 (TRPML1)/transcription factor EB (TFEB) signaling pathway on lysosomal biogenesis. Sprague-Dawley rats were given fluoridated water freely, during pregnancy to the parental rats to 2 months after delivery to the offspring. In addition, neuroblastoma SH-SY5Y cells were treated with sodium fluoride (NaF), with or without mucolipin synthetic agonist 1 (ML-SA1) or adenovirus TFEB (Ad-TFEB) intervention. Our findings revealed that NaF impaired learning and memory as well as memory retention capacities in rat offspring, induced lysosomal biogenesis disorder, and decreased lysosomal degradation capacity, autophagosome accumulation, autophagic flux blockade, apoptosis, and pyroptosis. These changes were evidenced by the decreased expression of TRPML1, nuclear TFEB, LAMP2, CTSB, and CTSD, as well as increased expression of LC3-II, p62, cleaved PARP, NLRP3, Caspase1, and IL-1ß. Furthermore, TRPML1 activation and TFEB overexpression both restored TFEB nuclear protein expression and promoted lysosomal biogenesis while enhancing lysosomal degradation capacity, recovering autophagic flux, and attenuating NaF-induced apoptosis and pyroptosis. Taken together, these results show that NaF promotes the progression of developmental fluoride neurotoxicity by inhibiting TRPML1/TFEB expression and impeding lysosomal biogenesis. Notably, the activation of TRPML1/TFEB alleviated NaF-induced developmental neurotoxicity. Therefore, TRPML1/TFEB may be promising markers of developmental fluoride neurotoxicity.

Molecularly Imprinted Nanomaterials with Stimuli Responsiveness for Applications in Biomedicine.

The review aims to summarize recent reports of stimuli-responsive nanomaterials based on molecularly imprinted polymers (MIPs) and discuss their applications in biomedicine. In the past few decades, MIPs have been proven to show widespread applications as new molecular recognition materials. The development of stimuli-responsive nanomaterials has successfully endowed MIPs with not only affinity properties comparable to those of natural antibodies but also the ability to respond to external stimuli (stimuli-responsive MIPs). In this review, we will discuss the synthesis of MIPs, the classification of stimuli-responsive MIP nanomaterials (MIP-NMs), their dynamic mechanisms, and their applications in biomedicine, including bioanalysis and diagnosis, biological imaging, drug delivery, disease intervention, and others. This review mainly focuses on studies of smart MIP-NMs with biomedical perspectives after 2015. We believe that this review will be helpful for the further exploration of stimuli-responsive MIP-NMs and contribute to expanding their practical applications especially in biomedicine in the near future.

Long-term air pollution levels modify the relationships between short-term exposure to meteorological factors, air pollution and the incidence of hand, foot and mouth disease in children: a DLNM-based multicity time series study in Sichuan Province, China.

BACKGROUND: Epidemiological studies have investigated the short-term effects of meteorological factors and air pollution on the incidence of hand, foot, and mouth disease (HFMD). Several meteorological indicators, such as relative humidity and the diurnal temperature range (DTR), significantly modify the relationship between short-term exposure to temperature and HFMD incidence. However, it remains unclear whether (and how) long-term air pollution levels modify the short-term relationships of HFMD incidence with meteorological factors and air pollution. METHODS: We obtained daily data on meteorological factors, air pollutants, and HFMD counts in children from 21 prefecture-level cities in Sichuan Province in Southwest China from 2015 to 2017. First, we constructed a distributed lag nonlinear model (DLNM) at each prefecture-level site to evaluate the short-term impacts of meteorological variables and air pollutants on HFMD incidence. Then, we assessed the pooled effects of the exposures and incorporated long-term city-specific air pollutant indicators as meta-predictors to examine their potential modification effects by performing multivariate meta-regression models. RESULTS: We found that long-term SO2 and CO concentrations significantly modified the short-term relationships between climatic variables and HFMD incidence. Specifically, high concentrations of CO (P = 0.027) and SO2 (P = 0.039) reduced the risk of HFMD at low temperatures. The relationship between relative humidity and HFMD incidence was weakened at high SO2 concentrations (P = 0.024), especially when the relative humidity was below the median level. When the minimum relative humidity (32%) was compared to the median relative humidity (77%), the risk ratio (RR) was 0.77 (95% CI: 0.51-1.17) in the 90th percentile of SO2 (19.6 µg/m3) and 0.41 (95% CI: 0.27-0.64) in the 10th percentile of SO2 (10.6 µg/m3). CONCLUSION: Our results indicated that long-term SO2 and CO levels modified the short-term associations between HFMD incidence in children and meteorological variables. These findings may inform health authorities to optimize targeted public health policies including reducing ambient air pollution and reinforcing self-protective actions to weaken the adverse health impacts of environmental factors on HFMD incidence.

Co-exposure of polystyrene microplastics and iron aggravates cognitive decline in aging mice via ferroptosis induction.

The objective of this study was to investigate the effects of co-exposure of iron and microplastics (MPs) on the cognitive function of aged humans and animals. It was already known that individual iron or MPs exposure can initiate potential neurotoxicity. However, the combined effect of MPs and iron remained to be elucidated. In this study, the toxicity of iron, MPs, co-treatment of MPs & iron, and the underlying mechanisms were evaluated in vivo. Our findings suggest that 5 µm MPs could enter the aging mice brain and accumulate in cortex and hippocampus. In addition, MPs and iron have a good binding ability, therefore, co-exposure of MPs & iron cause significant iron overload and cognitive deficits as compared to control and individual treatments of iron and MPs. Moreover, the lipid peroxidation and inflammation, which are involved in ferroptosis, get significantly elevated by co-exposure of iron and MPs. Taken together, our results provide compelling evidence that co-exposure of iron and MPs could aggravate the cognitive impairment via disturbing brain iron homeostasis and inducing ferroptosis in cognitive-related brain areas, what's more, the results warn that MPs may act as vectors of pollutants (mostly heavy metals) increasing the health burden on body.

How to improve infectious disease prediction by integrating environmental data: an application of a novel ensemble analysis strategy to predict HFMD.

This study proposed a novel ensemble analysis strategy to improve hand, foot and mouth disease (HFMD) prediction by integrating environmental data. The approach began by establishing a vector autoregressive model (VAR). Then, a dynamic Bayesian networks (DBN) model was used for variable selection of environmental factors. Finally, a VAR model with constraints (CVAR) was established for predicting the incidence of HFMD in Chengdu city from 2011 to 2017. DBN showed that temperature was related to HFMD at lags 1 and 2. Humidity, wind speed, sunshine, PM10, SO2 and NO2 were related to HFMD at lag 2. Compared with the autoregressive integrated moving average model with external variables (ARIMAX), the CVAR model had a higher coefficient of determination (R2, average difference: + 2.11%; t = 6.2051, P = 0.0003 < 0.05), a lower root mean-squared error (-24.88%; t = -5.2898, P = 0.0007 < 0.05) and a lower mean absolute percentage error (-16.69%; t = -4.3647, P = 0.0024 < 0.05). The accuracy of predicting the time-series shape was 88.16% for the CVAR model and 86.41% for ARIMAX. The CVAR model performed better in terms of variable selection, model interpretation and prediction. Therefore, it could be used by health authorities to identify potential HFMD outbreaks and develop disease control measures.

Detection of Defects in Geomembranes Using Quasi-Active Infrared Thermography.

High-density polyethylene geomembranes are employed as covers for the sewage treatment lagoons at Melbourne Water Corporation's Western Treatment Plant, to harvest the biogas produced during anaerobic degradation, which is then used to generate electricity. Due to its size, inspecting the cover for defects, particularly subsurface defects, can be challenging, as well as the potential for the underside of the membrane to come into contact with different substrates, viz. liquid sewage, scum (consolidated solid matter), and biogas. This paper presents the application of a novel quasi-active thermography inspection method for subsurface defect detection in the geomembrane. The proposed approach utilises ambient sunlight as the input thermal energy and cloud shading as the trigger for thermal transients. Outdoor laboratory-scale experiments were conducted to study the proposed inspection technique. A pyranometer was used to measure the intensity of solar radiation, and an infrared thermal camera was used to measure the surface temperature of the geomembrane. The measured temperature profile was analysed using three different algorithms for thermal transient analysis, based on (i) the cooling constant from Newton's law of cooling, (ii) the peak value of the logarithmic second derivative, and (iii) a frame subtraction method. The outcomes from each algorithm were examined and compared. The results show that, while each algorithm has some limitations, when used in combination the three algorithms could be used to distinguish between different substrates and to determine the presence of subsurface defects.

Sulfur Induces Resistance against Canker Caused by Pseudomonas syringae pv. actinidae via Phenolic Components Increase and Morphological Structure Modification in the Kiwifruit Stems.

Bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has led to considerable losses in all major kiwifruit-growing areas. There are no commercial products in the market to effectively control this disease. Therefore, the defense resistance of host plants is a prospective option. In our previous study, sulfur could improve the resistance of kiwifruit to Psa infection. However, the mechanisms of inducing resistance remain largely unclear. In this study, disease severity and protection efficiency were tested after applying sulfur, with different concentrations in the field. The results indicated that sulfur could reduce the disease index by 30.26 and 31.6 and recorded high protection efficiency of 76.67% and 77.00% after one and two years, respectively, when the concentration of induction treatments was 2.0 kg/m3. Ultrastructural changes in kiwifruit stems after induction were demonstrated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the activities of phenylalanine ammonia-lyase (PAL), peroxidase (POD) and polyphenol oxidase (PPO), and the accumulation of lignin were determined by biochemical analyses. Our results showed that the morphological characteristics of trichomes and lenticels of kiwifruit stem were in the best defensive state respectively when the sulfur concentration was 3.0 kg/m3 and 1.5 kg/m3. Meanwhile, in the range of 0.5 to 2.0 kg/m3, the sulfur could promote the chloroplast and mitochondria of kiwifruit stems infected with Psa to gradually return to health status, increasing the thickness of the cell wall. In addition, sulfur increased the activities of PAL, POD and PPO, and promoted the accumulation of lignin in kiwifruit stems. Moreover, the sulfur protection efficiency was positively correlated with PPO activity (p < 0.05) and lignin content (p < 0.01), which revealed that the synergistic effect of protective enzyme activity and the phenolic metabolism pathway was the physiological effect of sulfur-induced kiwifruit resistance to Psa. This evidence highlights the importance of lignin content in kiwifruit stems as a defense mechanism in sulfur-induced resistance. These results suggest that sulfur enhances kiwifruit canker resistance via an increase in phenolic components and morphology structure modification in the kiwifruit stems. Therefore, this study could provide insights into sulfur to control kiwifruit canker caused by Psa.

Dynamic Synthetic Biointerfaces: From Reversible Chemical Interactions to Tunable Biological Effects.

Dynamic synthetic biointerface is a new concept of biomaterials with smart surface properties capable of controlled display of bioactive ligands, dynamic modulation of cell-biomaterial interactions, and subsequently clever manipulation of fundamental cell behaviors like adhesion, migration, proliferation, differentiation, apoptosis, and so on. As mimics of the extracellular matrix (ECM), such molecularly dynamic biointerfaces have attracted increasing attention because of their tunable biological effects with great significance in in situ cell biology, tissue engineering, drug targeting, and cell isolation for cancer theranostics. Approaches to control bioligand presentation on materials mainly rely on surface functionalization with dynamic or reversible chemical linkers to which the ligands are tethered. Photoelectric-transformable or photocleavable chemistry, host-guest supramolecular chemistry, and multiple noncovalent interactions were initially employed for fabrication of dynamic synthetic biointerfaces. However, the external stimuli required in these systems, including electrochemical potential, electrochemical reaction, and near-infrared or UV light, are mostly invasive to living cells; and few of them are able to respond to the stimuli occurring in natural biological processes. In addition, most of current systems focused only on the control of cell adhesion, other cell behaviors like migration, differentiation and apoptosis have rarely been explored. Therefore, the development of novel synthetic biointerfaces that permit access to noninvasive control of diverse cell behaviors still represents a key challenge in biomaterials science. Our group pioneers the use of reversible covalent bonds, metal coordinative interactions, and the molecular affinity of molecularly imprinted synthetic receptors as the dynamic driving forces for the fabrication of smart biointerfaces. Several typical biological stimuli, such as glycemic volatility, body temperature fluctuations, regional disparity of pH values, and specific biomolecules, were tactfully involved in our systems. In this Account, we highlight the strategies we have used on the exploitation of dynamic synthetic biointerfaces based on the above three types of reversible chemical interactions. While our attention has been focused on biologically stimuli-responsive or other noninvasive ligand presentation, the versatility of dynamic synthetic biointerfaces in control of cell adhesion, directing cell differentiation, and targeting cell apoptosis has also been successfully demonstrated. In addition, a paradigm shift of dynamic synthetic biointerfaces from macroscopic to microscopic scale (e.g., nanobiointerfaces) was conceptually demonstrated in our research. The potential applications of these developed dynamic systems, including fundamental cell biology, surface engineering of biomaterials, scaffold-free tissue engineering, cell-based cancer diagnosis, and drug targeting cancer therapy, were also introduced, respectively. Although the development of dynamic synthetic biointerfaces is still in its infancy, we strongly believe that further efforts in this field will play a continuously and increasingly significant role in bridging the gap between chemistry and biology.

Effect of Coagulation Bath Temperature on Mechanical, Morphological, and Thermal Properties of Cellulose/Antarctic Krill Protein Composite Fibers.

Cellulose (C) and Antarctic krill protein (AKP) were dissolved at low temperature, and then C/AKP composite fibers were prepared by wet spinning. In this paper, the effect of coagulation bath temperature on the properties of C/AKP composite fibers were studied by FT-IR, XRD, DSC, and other tests. The results showed that, when the temperature of the coagulation bath increased from 5 to 25 °C, the intermolecular hydrogen bond content of the C/AKP composite fibers increased from 28.20% to 31.33%. When the coagulation bath temperature is 15 °C, the breaking strength of the composite fibers is 1.64cN/dtex, which is 12% higher than that of the composite fibers at room temperature. At this temperature, the crystallinity of the composite fibers is improved, the thermal stability is slightly improved, and the surface morphology is smoother. Inspiringly, when zinc sulfate is added to the coagulation bath, the formation process of the fibers is milder. Moreover, the C/AKP composite fibers have excellent antibacterial activity against Escherichia coli and Staphylococcus aureus.

Short-term effects of rainfall on childhood hand, foot and mouth disease and related spatial heterogeneity: evidence from 143 cities in mainland China.

BACKGROUND: Numerous studies have demonstrated the potential association between rainfall and hand, foot and mouth disease (HFMD), but the results are inconsistent. This study aimed to quantify the relationship between rainfall and HFMD based on a multicity study and explore the potential sources of spatial heterogeneity. METHODS: We retrieved the daily counts of childhood HFMD and the meteorological variables of the 143 cities in mainland China between 2009 and 2014. A common time series regression model was applied to quantify the association between rainfall and HFMD for each of the 143 cities. Then, we adopted the meta-regression model to pool the city-specific estimates and explore the sources of heterogeneity by incorporating city-specific characteristics. RESULTS: The overall pooled estimation suggested a nonlinear exposure-response relationship between rainfall and HFMD. Once rainfall exceeded 15 mm, the HFMD risk stopped increasing linearly and began to plateau with the excessive risk ratio (ERR) peaking at 21 mm of rainfall (ERR = 3.46, 95% CI: 2.05, 4.88). We also found significant heterogeneity in the rainfall-HFMD relationships (I2 = 52.75%, P < 0.001). By incorporating the city-specific characteristics into the meta-regression model, temperature and student density can explain a substantial proportion of spatial heterogeneity with I2 statistics that decreased by 5.29 and 6.80% at most, respectively. CONCLUSIONS: Our findings verified the nonlinear association between rainfall and HFMD. The rainfall-HFMD relationship also varies depending on locations. Therefore, the estimation of the rain-HFMD relationship of one location should not be generalized to another location.

Effects of ERK/p38 MAPKs signaling pathways on MTA-mediated osteo/odontogenic differentiation of stem cells from apical papilla: a vitro study.

BACKGROUND: Stem cells from apical papilla (SCAP) located in the root apex of immature permanent teeth are a reliable cell source for pulp-dentine complex regeneration. Mineral trioxide aggregate (MTA) is a biocompatible material which has been widely used in endodontic treatments. The aim of this study was to elucidate the regulatory role of MTA in the proliferation and differentiation of SCAP. METHODS: Cell viability was detected by Cell counting kit-8. Characteristics of SCAP were confirmed by Flow cytometric (FCM) analysis and alizarin red staining. Then, MTA-mediated osteo/odontogenic differentiation of SCAP was investigated by reverse transcription polymerase chain reaction. The effect of MAPKs on MTA-mediated osteo/odontogenic differentiation was evaluated by western blot analysis. RESULTS: There was no significant difference in cell viability between the control group and the group with lower concentrations of MTA. However, higher concentrations of MTA could inhibit proliferation of SCAP. It is demonstrated that the ALP activity were enhanced, the mRNA and protein expression of BSP, OCN, DSPP, Runx2 were up-regulated. In addition, phosphorylation proteins of ERK, p38 were activated through western blot analysis. CONCLUSIONS: MTA at appropriate concentration could enhance osteo/odontogenic differentiation of SCAP by activating p38 and ERK signaling pathways. This study provides a new idea for the clinical application of MTA and the treatment of endodontic diseases.

Three-dimensional printing biotechnology for the regeneration of the tooth and tooth-supporting tissues.

The tooth and its supporting tissues are organized with complex three-dimensional (3D) architecture, including the dental pulp with a blood supply and nerve tissues, complex multilayer periodontium, and highly aligned periodontal ligament (PDL). Mimicking such 3D complexity and the multicellular interactions naturally existing in dental structures represents great challenges in dental regeneration. Attempts to construct the complex system of the tooth and tooth-supporting apparatus (i.e., the PDL, alveolar bone, and cementum) have made certain progress owing to 3D printing biotechnology. Recent advances have enabled the 3D printing of biocompatible materials, seed cells, and supporting components into complex 3D functional living tissue. Furthermore, 3D bioprinting is driving major innovations in regenerative medicine, giving the field of regenerative dentistry a boost. The fabrication of scaffolds via 3D printing is already being performed extensively at the laboratory bench and in clinical trials; however, printing living cells and matrix materials together to produce tissue constructs by 3D bioprinting remains limited to the regeneration of dental pulp and the tooth germ. This review summarizes the application of scaffolds for cell seeding and biofabricated tissues via 3D printing and bioprinting, respectively, in the tooth and its supporting tissues. Additionally, the key advantages and prospects of 3D bioprinting in regenerative dentistry are highlighted, providing new ideas for dental regeneration.

Molecularly imprinted polymers as receptor mimics for selective cell recognition.

Molecularly imprinted polymers (MIPs) have now earned the reputation as "artificial receptors" or "plastic antibodies". As the mimics of natural receptors, MIPs are reminiscent of some basic functions of natural receptors in living systems, e.g., the ability to interact with or recognize cells. The latest decade has witnessed a great advance in MIPs from simple molecular extraction to efficient cell recognition, implying that MIP-based synthetic receptors are approaching to be perfectly functioning replicates of their natural counterparts. With the most emerging development in molecular imprinting, MIP-mediated cell recognition has now shown great promise in cell biology research, theranostics and regenerative medicine. This tutorial review provides a panoramic view of current MIPs for both microorganism and mammalian cell recognition. The most representative developments of MIP-mediated cell recognition, from initial imprinting strategies to eventual bio-related applications, are highlighted.