Smart Galactosidase-Responsive Antimicrobial Dendron: Towards More Biocompatible Membrane-Disruptive Agents.

Antimicrobial resistance is a global healthcare challenge that urgently needs the development of new therapeutic agents. Antimicrobial peptides and mimics thereof are promising candidates but mostly suffer from inherent toxicity issues due to the non-selective binding of cationic groups with mammalian cells. To overcome this toxicity issue, this work herein reports the synthesis of a smart antimicrobial dendron with masked cationic groups (Gal-Dendron) that could be uncaged in the presence of ß-galactosidase enzyme to form the activated Enz-Dendron and confer antimicrobial activity. Enz-Dendron show bacteriostatic activity toward Gram-negative (P. aeruginosa and E. coli) and Gram-positive (S. aureus) bacteria with minimum inhibitory concentration values of 96 µm and exerted its antimicrobial mechanism via a membrane disruption pathway, as indicated by inner and outer membrane permeabilization assays. Crucially, toxicity studies confirmed that the masked prodrug Gal-Dendron exhibited low hemolysis and is at least 2.4 times less toxic than the uncaged cationic Enz-Dendron, thus demonstrating the advantage of masking the cationic groups with responsive immolative linkers to overcome toxicity and selectivity issues. Overall, this study highlights the potential of designing new membrane-disruptive antimicrobial agents that are more biocompatible via the amine uncaging strategy.

One-Step Preparation of Magnetic Lipid Bubbles: Magnetothermal Effect Induces the Simultaneous Formation of Gas Nuclei and Self-Assembly of Phospholipids.

In recent years, enveloped micro-nanobubbles have garnered significant attention in research due to their commendable stability, biocompatibility, and other notable properties. Currently, the preparation methods of enveloped micro-nanobubbles have limitations such as complicated preparation process, large bubble size, wide distribution range, low yield, etc. There exists an urgent demand to devise a simple and efficient method for the preparation of enveloped micro-nanobubbles, ensuring both high concentration and a uniform particle size distribution. Magnetic lipid bubbles (MLBs) are a multifunctional type of enveloped micro-nanobubble combining magnetic nanoparticles with lipid-coated bubbles. In this study, MLBs are prepared simply and efficiently by a magneto internal heat bubble generation process based on the interfacial self-assembly of iron oxide nanoparticles induced by the thermogenic effect in an alternating magnetic field. The mean hydrodynamic diameter of the MLBs obtained was 384.9 ± 8.5 nm, with a polydispersity index (PDI) of 0.248 ± 0.021, a zeta potential of -30.5 ± 1.0 mV, and a concentration of (7.92 ± 0.46) × 109 bubbles/mL. Electron microscopy results show that the MLBs have a regular spherical stable core-shell structure. The superparamagnetic iron oxide nanoparticles (SPIONs) and phospholipid layers adsorbed around the spherical gas nuclei of the MLBs, leading the particles to demonstrate commendable superparamagnetic and magnetic properties. In addition, the effects of process parameters on the morphology of MLBs, including phospholipid concentration, phospholipid proportiona, current intensity, magnetothermal time, and SPION concentration, were investigated and discussed to achieve controlled preparation of MLBs. In vitro imaging results reveal that the higher the concentration of MLBs loaded with iron oxide nanoparticles, the better the in vitro ultrasound (US) imaging and magnetic resonance imaging (MRI) results. This study proves that the magneto internal heat bubble generation process is a simple and efficient technique for preparing MLBs with high concentration, regular structure, and commendable properties. These findings lay a robust foundation for the mass production and application of enveloped micro-nanobubbles, particularly in biomedical fields and other related domains.

Feature Matching of Microsecond-Pulsed Magnetic Fields Combined with Fe3O4 Particles for Killing A375 Melanoma Cells.

The combination of magnetic fields and magnetic nanoparticles (MNPs) to kill cancer cells by magneto-mechanical force represents a novel therapy, offering advantages such as non-invasiveness, among others. Pulsed magnetic fields (PMFs) hold promise for application in this therapy due to advantages such as easily adjustable parameters; however, they suffer from the drawback of narrow pulse width. In order to fully exploit the potential of PMFs and MNPs in this therapy, while maximizing therapeutic efficacy within the constraints of the narrow pulse width, a feature-matching theory is proposed, encompassing the matching of three aspects: (1) MNP volume and critical volume of Brownian relaxation, (2) relaxation time and pulse width, and (3) MNP shape and the intermittence of PMF. In the theory, a microsecond-PMF generator was developed, and four kinds of MNPs were selected for in vitro cell experiments. The results demonstrate that the killing rate of the experimental group meeting the requirements of the theory is at least 18% higher than the control group. This validates the accuracy of our theory and provides valuable guidance for the further application of PMFs in this therapy.

The effect of ultrasonic power on the physicochemical properties and antioxidant activities of frosted figs pectin.

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.

Robust Hydrogel Actuators Functioning in Multi-Environments Enabled by Thermo-Responsive Polymer Nanoparticle Coatings on Hydrogel Surfaces.

Hydrogel actuators with anisotropic structures exhibit reversible responsiveness upon the trigger of various external stimuli, rendering them promising for applications in many fields including artificial muscles and soft robotics. However, their effective operation across multiple environments remains a persistent challenge, even for widely studied thermo-responsive polymers like poly(N-isopropyl acrylamide) (PNIPAm). Current attempts to address this issue are hindered by complex synthetic procedures or specific substrates. This study introduces a straightforward methodology to grow a thin, dense PNIPAm nanoparticle layer on diverse hydrogel surfaces, creating a highly temperature-sensitive hydrogel actuator. This actuator demonstrates adaptability across various environments, including water, oil, and open air, owing to its distinct structure facilitating self-water circulation during actuation. The thin PNIPAm layer consists of interconnected PNIPAm nanoparticles synthesized via in situ interfacial precipitation polymerization, seamlessly bonded to the hydrogel substrate through an interfacial layer containing hybrid hydrogel/PNIPAm nanoparticles. This unique anisotropic structure ensures exceptional structural stability without interfacial delamination, even enduring harsh treatments such as freezing, ultrasonic irradiation, and prolonged water immersion. Remarkably, PNIPAm films on hydrogel surfaces which enable programmable 3D actuation can also be precisely patterned. This synthetic approach opens a novel pathway for fabricating advanced hydrogel actuators with broad-ranging applications.

Preliminary Exploration of the Biophysical Mechanisms of Pulsed Magnetic Field- Induced Cell Permeabilization.

Pulsed magnetic field treatment can enhance cell membrane permeability, allowing large molecular substances that normally cannot pass through the cell membrane to enter the cell. This research holds significant prospects for biomedical applications. However, the mechanism underlying pulsed magnetic field-induced cell permeabilization remains unclear, impeding further progress in research related to pulsed magnetic field. Currently, hypotheses about the mechanism are struggling to explain experimental results. Therefore, this study developed a parameter-adjustable pulsed magnetic field generator and designed experiments. Starting from the widely accepted hypothesis of "induced electric fields by pulsed magnetic field," we conducted a preliminary exploration of the biophysical mechanisms underlying pulsed magnetic field-induced cell permeabilization. Finally, we have arrived at an intriguing conclusion: under the current technical parameters, the impact of the pulsed magnetic field itself is the primary factor influencing changes in cell membrane permeability, rather than the induced electric field. This conclusion holds significant implications for understanding the biophysical mechanisms behind pulsed magnetic field therapy and its potential biomedical applications.

Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital facial malformation with a complex, incompletely understood origin. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, potentially shedding light on NSCL/P's etiology. This study aimed to identify critical lncRNAs and construct regulatory networks to unveil NSCL/P's underlying molecular mechanisms. Integrating gene expression profiles from the Gene Expression Omnibus (GEO) database, we pinpointed 30 dysregulated NSCL/P-associated lncRNAs. Subsequent analyses enabled the creation of competing endogenous RNA (ceRNA) networks, lncRNA-RNA binding protein (RBP) interaction networks, and lncRNA cis and trans regulation networks. RT-qPCR was used to examine the regulatory networks of lncRNA in vivo and in vitro. Furthermore, protein levels of lncRNA target genes were validated in human NSCL/P tissue samples and murine palatal shelves. Consequently, two lncRNAs and three mRNAs: FENDRR (log2FC = - 0.671, P = 0.040), TPT1-AS1 (log2FC = 0.854, P = 0.003), EIF3H (log2FC = - 1.081, P = 0.041), RBBP6 (log2FC = 0.914, P = 0.037), and SRSF1 (log2FC = 0.763, P = 0.026) emerged as potential contributors to NSCL/P pathogenesis. Functional enrichment analyses illuminated the biological functions and pathways associated with these lncRNA-related networks in NSCL/P. In summary, this study comprehensively delineates the dysregulated transcriptional landscape, identifies associated lncRNAs, and reveals pivotal sub-networks relevant to NSCL/P development, aiding our understanding of its molecular progression and setting the stage for further exploration of lncRNA and mRNA regulation in NSCL/P.

Reducing nitrogen loss from farmland by layered double hydroxide-supported carbon dots-enhanced ammonium immobilization.

It remains a significant challenge to develop a kind of cost-effective and eco-friendly adsorbent with strong immobilization capabilities for ammonium in farmland. In this work, we employed Ca/Al layered double hydroxide-supported carbon dots (CDs@Ca/Al-LDHs) as a novel and efficient adsorbent for ammonium immobilization both in aqueous and soil environments. Such a composite could exhibit a high adsorption capacity towards ammonium in solution, which was four times higher than zeolite and three times higher than biochar under the same conditions. The mechanism investigations revealed that electrostatic interactions between the negatively charged CDs and the positively charged ammonium played a key role in the adsorption. In 30-day leaching experiments, the fabricated composite cumulatively reduced ammonium and nitrate by 6.3% and 9.7%, respectively at a dosage of 0.1% (w/w). Incubation experiments further confirmed that the developed composite could effectively inhibit ammonia volatilization and nitrification by immobilizing the ammonium within soil matrices. Our results demonstrated that CDs@Ca/Al-LDHs represented a promising candidate for cost-effective and eco-friendly immobilization of excess ammonium from over-fertilized farmland.

Rapid, Tough, and Trigger-Detachable Hydrogel Adhesion Enabled by Formation of Nanoparticles In Situ.

Integrating hydrogel with other materials is always challenging due to the low mass content of hydrogels and the abundance of water at the interfaces. Adhesion through nanoparticles offers characteristics such as ease of use, reversibility, and universality, but still grapples with challenges like weak bonding. Here, a simple yet powerful strategy using the formation of nanoparticles in situ is reported, establishing strong interfacial adhesion between various hydrogels and substrates including elastomers, plastics, and biological tissue, even under wet conditions. The strong interfacial bonding can be formed in a short time (60 s), and gradually strengthened to 902 J m-2 adhesion energy within an hour. The interfacial layer's construction involves chain entanglement and other non-covalent interactions like coordination and hydrogen bonding. Unlike the permanent bonding seen in most synthetic adhesives, these nanoparticle adhesives can be efficiently triggered for removal by acidic solutions. The simplicity of the precursor diffusion and precipitation process in creating the interfacial layer ensures broad applicability to different substrates and nanoparticle adhesives without compromising robustness. The tough adhesion provided by nanoparticles allows the hydrogel-elastomer hybrid to function as a triboelectric nanogenerator (TENG), facilitating reliable electrical signal generation and output performance due to the robust interface.

Associations of sugar-sweetened, artificially sweetened, and naturally sweet juices with Alzheimer's disease: a prospective cohort study.

Epidemiological studies of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) with Alzheimer's disease (AD) have provided controversial findings. Furthermore, little is known about the association between pure fruit/vegetable juices and AD. The present study aims to estimate the associations of SSBs, ASBs, and pure fruit/vegetable juices with AD, and to evaluate the theoretical effects of replacing SSBs and ASBs with the different consumption of pure fruit/vegetable juices on the risk of AD. This prospective cohort study of the UK Biobank included 206,606 participants aged 39-72 years free of dementia at baseline between 2006 and 2010. Dietary intake of SSBs, ASBs, and pure fruit/vegetable juices (naturally sweet juices) were collected using a 24-h dietary recall questionnaire completed between 2009 and 2012. Incident AD was identified by medical and mortality records. Cox proportional hazard models and substitution models were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 699 cases of AD were identified over a median follow-up of 9.5 years. The consumption of SSBs and ASBs (> 2 units/d) were associated with a higher risk of AD. However, participants who drank > 1-2 units/d of pure fruit/vegetable juices were associated with a lower risk of AD. In substitution models, replacing SSBs with an equivalent consumption of pure fruit/vegetable juices could be associated with a risk reduction of AD.

Biomimetic Electronic Skin through Hierarchical Polymer Structural Design.

Human skin comprises multiple hierarchical layers that perform various functions such as protection, sensing, and structural support. Developing electronic skin (E-skin) with similar properties has broad implications in health monitoring, prosthetics, and soft robotics. While previous efforts have predominantly concentrated on sensory capabilities, this study introduces a hierarchical polymer system that not only structurally resembles the epidermis-dermis bilayer structure of skin but also encompasses sensing functions. The system comprises a polymeric hydrogel, representing the "dermis", and a superimposed nanoporous polymer film, forming the "epidermis". Within the film, interconnected nanoparticles mimic the arrangement of interlocked corneocytes within the epidermis. The fabrication process employs a robust in situ interfacial precipitation polymerization of specific water-soluble monomers that become insoluble during polymerization. This process yields a hybrid layer establishing a durable interface between the film and hydrogel. Beyond the structural mimicry, this hierarchical structure offers functionalities resembling human skin, which includes (1) water loss protection of hydrogel by tailoring the hydrophobicity of the upper polymer film; (2) tactile sensing capability via self-powered triboelectric nanogenerators; (3) built-in gold nanowire-based resistive sensor toward temperature and pressure sensing. This hierarchical polymeric approach represents a potent strategy to replicate both the structure and functions of human skin in synthetic designs.

Light-Switchable Biocatalytic Covalent-Organic Framework Nanomotors for Aqueous Contaminants Removal.

Self-propelled nanomotors represent a promising class of adaptable and versatile technologies with broad applications in the realms of biomedicine and environmental remediation. Herein, we report a biocatalytic nanomotor based on a covalent-organic framework (COF) that demonstrates intelligent and switchable motion triggered by a blue-to-red light switch. Consequently, when exposed to blue light, the nanomotor significantly enhances the removal of contaminants in aqueous solutions due to its elevated mobility. Conversely, it effectively deactivates its motion and contaminant removal upon exposure to red light. This study explores the heterogeneous assembly strategy of the COF-based nanomotor and its light-controlled propulsion performance and provides a novel strategy for the regulation of movement, offering valuable insights for the design and practical applications of nanomotors.

Advances in the study of myeloid-derived suppressor cells in infectious lung diseases.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells capable of inhibiting T-cell responses. MDSCs have a crucial role in the regulation of the immune response of the body to pathogens, especially in inflammatory response and pathogenesis during anti-infection. Pathogens such as bacteria and viruses use MDSCs as their infectious targets, and even some pathogens may exploit the inhibitory activity of MDSCs to enhance pathogen persistence and chronic infection of the host. Recent researches have revealed the pathogenic significance of MDSCs in pathogens such as bacteria and viruses, despite the fact that the majority of studies on MDSCs have focused on tumor immune evasion. With the increased prevalence of viral respiratory infections, the resurgence of classical tuberculosis, and the advent of medication resistance in common bacterial pneumonia, research on MDSCs in these illnesses is intensifying. The purpose of this work is to provide new avenues for treatment approaches to pulmonary infectious disorders by outlining the mechanism of action of MDSCs as a biomarker and therapeutic target in pulmonary infectious diseases.

Comparison of methods for detecting protein extracted from excess activated sludge.

The protein contents of hydrolyzed sludge supernatant are commonly determined with the Kjeldahl method, but this method suffers from complicated operations, long process times, and large quantities of chemicals consumed. In this paper, the Lowry, bicinchoninic acid (BCA), and Bradford methods were used to test the precision and spiked recovery of proteins from sludge supernatants hydrolyzed by alkaline-thermal hydrolysis (ATH), enzymatic hydrolysis (EH), and ultrasound-assisted enzymatic hydrolysis (UEH), and the results were compared with those obtained with the Kjeldahl method. For all the hydrolytic processes, the sludge protein values determined with the three tested methods were within 0.05 of each other, which met the experimental requirement for accuracy. Both the Lowry and BCA methods had recovery rates of 95-105%, while the Bradford method showed large deviations and was not highly reliable. The three protein determination methods showed significant differences with the Kjeldahl method (P<0.05). However, the relative deviation between the Kjeldahl and BCA methods was the smallest (3-5%), followed by those between the Kjeldahl and the Lowry (11-21%) and Bradford methods (21-90%), and the causes of the deviations were analyzed based on the protein hydrolysate components and the mechanisms for the different detection methods. On the basis of these results, the BCA method was chosen as the most appropriate quantification method for use with sludge protein extraction, and it was used to analyze the protein contents extracted from residual sludge samples obtained from two sewage treatment plants. The reliability of the method was verified, and this lays a foundation for the extraction and reclamation of sludge proteins.

Consumption of coffee and tea with all-cause and cause-specific mortality: a prospective cohort study.

BACKGROUND: Previous studies suggested that moderate coffee and tea consumption are associated with lower risk of mortality. However, the association between the combination of coffee and tea consumption with the risk of mortality remains unclear. This study aimed to evaluate the separate and combined associations of coffee and tea consumption with all-cause and cause-specific mortality. METHODS: This prospective cohort study included 498,158 participants (37-73 years) from the UK Biobank between 2006 and 2010. Coffee and tea consumption were assessed at baseline using a self-reported questionnaire. All-cause and cause-specific mortalities, including cardiovascular disease (CVD), respiratory disease, and digestive disease mortality, were obtained from the national death registries. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 12.1 years, 34,699 deaths were identified. The associations of coffee and tea consumption with all-cause and cause-specific mortality attributable to CVD, respiratory disease, and digestive disease were nonlinear (all P nonlinear < 0.001). The association between separate coffee consumption and the risk of all-cause mortality was J-shaped, whereas that of separate tea consumption was reverse J-shaped. Drinking one cup of coffee or three cups of tea per day seemed to link with the lowest risk of mortality. In joint analyses, compared to neither coffee nor tea consumption, the combination of < 1-2 cups/day of coffee and 2-4 cups/day of tea had lower mortality risks for all-cause (HR, 0.78; 95% CI: 0.73-0.85), CVD (HR, 0.76; 95% CI: 0.64-0.91), and respiratory disease (HR, 0.69; 95% CI: 0.57-0.83) mortality. Nevertheless, the lowest HR (95% CI) of drinking both < 1-2 cup/day of coffee and ≥ 5 cups/day of tea for digestive disease mortality was 0.42 (0.34-0.53). CONCLUSIONS: In this large prospective study, separate and combined coffee and tea consumption were inversely associated with all-cause and cause-specific mortality.

Wrinkling and restabilization of a hyperelastic PDMS membrane at finite strain.

Wrinkles are commonly observed in uniaxially stretched hyperelastic membranes and eventually disappear with the increase of stretching. The widely used scheme at present assumes the material parameters to be empirical values and straightforwardly considers some constitutive models to explore the wrinkling and restabilization behavior. However, this simple treatment may cause deviation from experiment by ignoring the applicability of the models and the authenticity of the input parameters, prompting us to report based on realistic material parameters. This paper presents an experimental, theoretical and numerical investigation on the wrinkling and restabilization behavior of hyperelastic materials. By fitting experimental stress-strain curves of PDMS films, we confirm that the 3-term Ogden model bears a closer resemblance to the experimental data than the widely used neo-Hookean, Mooney-Rivlin, and Arruda-Boyce models under certain circumstances. The simulation results indicate that different constitutive models quantitatively affect the critical buckling strain, wrinkling amplitudes, and restabilization points. Furthermore, the isolated central bifurcation point solved by Koiter stability theory agrees well with the simulation and experimental results. A 3D phase diagram of stability boundaries was established to gain a comprehensive insight into the effects of geometric parameters (length, width, and thickness) on wrinkling.

The life expectancy benefits on respiratory diseases gained by reducing the daily concentration of particulate matter to attain different air quality standard targets: findings from a 5-year time-series study in Tianjin, China.

The short-term effects of particulate matter (PM) on years of life lost (YLL) have been confirmed by several studies; however, little attention has been paid to the effects of PM on life expectancy from respiratory diseases (RD), especially at the city level. A generalized additive model (GAM) was used to assess the associations between daily PM and YLL of the RD and chronic obstructive pulmonary diseases (COPD) in Tianjin from 2015 to 2019. Then the daily avoidable YLL, attributable fraction, and potential life expectancy benefits (PLEB) of RD and COPD by reducing the daily concentration of PM2.5 and PM10 to attain the Chinese and World Health Organization (WHO) air quality standard targets were estimated during 2015-2019. The stratified analyses by gender were also conducted. A total of 18279 RD and 7767 COPD deaths were included in this study. Per 10 µg/m3 increments in PM2.5 and PM10 at lag1 were significantly associated with 0.83(95%CI: 0.11, 1.55) years and 0.57(95%CI: 0.06, 1.08) years increasing in YLL of total RD and 0.48 (95%CI: 0.07, 0.90) years and 0.30 (95%CI: 0.01, 0.60) years increasing in YLL of total COPD. If the daily PM2.5 and PM10 concentrations decreased to attain the Chinese and WHO air quality standard targets, 0.06-0.39 years PLEB due to total RD and 0.08-0.53 years PLEB due to COPD could be gained. And more PLEB on RD could be gained by decreasing the daily PM concentrations to attain the WHO air quality standard targets than that of attaining the Chinese air quality standard targets. These evidence-based findings emphasize the importance of the Chinese PM-related guideline updating and may have implications for PM-related policy-making.

Assessment of shallow aquifer vulnerability to fluoride contamination using modified AHP-DRASTICH model as a tool for effective groundwater management, a case study in Yuncheng Basin, China.

Vulnerability assessment is an effective tool for the precaution of groundwater quality to specific pollutants. Groundwater fluoride pollution is severe and universal in the world, however, the method of groundwater risk assessment to fluorine is never built. The objective of this study was to establish an effective method to assess the potential level of groundwater vulnerability to fluoride by a modification of the typical DRASTIC model. The hydrogeochemical (H) factor (pH and TDS) was designed as a complementary parameter in the DRASTICH model. The weights of the parameters were revised by Analytical Hierarchy Process (AHP) method. The built AHP-DRASTICH model was applied to evaluate the groundwater vulnerability to fluoride contamination in Yuncheng basin, northern China, where groundwater with high fluoride concentration occurred extensively. The assessment result indicates that about 40 percent of the area belonged to relatively high and high vulnerability zones, which mainly distributed at the central part of the basin with strong evaporation and longer water-rock interaction time. The AHP-DRASTICH model shows a stronger positive correlation between risk scores and F concentration, giving better vulnerability assessment to F pollution compared with DARSTIC and DRASTICH models. The AHP-DRASTICH model is reliable and useful for guiding government and policy maker to take effective actions protecting groundwater from specific pollution.

The relationship between social support and Internet addiction among Chinese college freshmen: A mediated moderation model.

Purpose: Internet addiction has become a worldwide mental health problem, and this problem is particularly prominent in China. Although current studies have shown that social support is closely related to Internet addiction, the mechanism of the relationship between the two is not clear at present. This study aimed to find out the influencing factors and the mechanism of Internet addiction among college freshmen, and to form scientific prevention and intervention plan on this basis. Method: This study adopts the cluster sampling method to select 322 college freshmen in a typical postsecondary school in Shandong Province, using Chinese Internet Addiction Scale (CIAS), Social Support Rating Scale (SSRS), and Network-related Maladaptive Cognition Scale (NRMCS) to investigate the relationship between social support, network-related maladaptive cognition, gender, and the degree of Internet addiction. Results: The findings of this study are as follows: (1) After controlling age and family location, social support had a significant negative predictive effect on Internet addiction; (2) Gender acted as a moderator between the relationship of social support and Internet addiction; and (3) Additionally, the moderating effect of gender was completely mediated by network-related maladaptive cognition. Conclusion: There is a mediated moderating effect between social support and Internet addiction. That is, gender plays a moderating role between social support and Internet addiction, and this moderating effect is mediated by network maladaptive cognition.

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis.

Background: Congenital anomalies are increasingly becoming a global pediatric health concern, which requires immediate attention to its early diagnosis, preventive strategies, and efficient treatments. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (Gnai3) gene mutation has been demonstrated to cause congenital small jaw deformity, but the functions of Gnai3 in the disease-specific microRNA (miRNA) upregulations and their downstream signaling pathways during osteogenesis have not yet been reported. Our previous studies found that the expression of Mir24-2-5p was significantly downregulated in the serum of young people with overgrowing mandibular, and bioinformatics analysis suggested possible binding sites of Mir24-2-5p in the Gnai3 3'UTR region. Therefore, this study was designed to investigate the mechanism of Mir24-2-5p-mediated regulation of Gnai3 gene expression and explore the possibility of potential treatment strategies for bone defects. Methods: Synthetic miRNA mimics and inhibitors were transduced into osteoblast precursor cells to regulate Mir24-2-5p expression. Dual-luciferase reporter assay was utilized to identify the direct binding of Gnai3 and its regulator Mir24-2-5p. Gnai3 levels in osteoblast precursor cells were downregulated by shRNA (shGnai3). Agomir, Morpholino Oligo (MO), and mRNA were microinjected into zebrafish embryos to control mir24-2-5p and gnai3 expression. Relevant expression levels were determined by the qRT-PCR and Western blotting. CCK-8 assay, flow cytometry, and transwell migration assays were performed to assess cell proliferation, apoptosis, and migration. ALP, ARS and Von Kossa staining were performed to observe osteogenic differentiation. Alcian blue staining and calcein immersions were performed to evaluate the embryonic development and calcification of zebrafish. Results: The expression of Mir24-2-5p was reduced throughout the mineralization process of osteoblast precursor cells. miRNA inhibitors and mimics were transfected into osteoblast precursor cells. Cell proliferation, migration, osteogenic differentiation, and mineralization processes were measured, which showed a reverse correlation with the expression of Mir24-2-5p. Dual-luciferase reporter gene detection assay confirmed the direct interaction between Mir24-2-5p and Gnai3 mRNA. Moreover, in osteoblast precursor cells treated with Mir24-2-5p inhibitor, the expression of Gnai3 gene was increased, suggesting that Mir24-2-5p negatively targeted Gnai3. Silencing of Gnai3 inhibited osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization. Promoting effects of osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization by low expression of Mir24-2-5p was partially rescued upon silencing of Gnai3. In vivo, mir24-2-5p Agomir microinjection into zebrafish embryo resulted in shorter body length, smaller and retruded mandible, decreased cartilage development, and vertebral calcification, which was partially rescued by microinjecting gnai3 mRNA. Notably, quite similar phenotypic outcomes were observed in gnai3 MO embryos, which were also partially rescued by mir24-2-5p MO. Besides, the expression of phospho-JNK (p-JNK) and p-p38 were increased upon Mir24-2-5p inhibitor treatment and decreased upon shGnai3-mediated Gnai3 downregulation in osteoblast precursor cells. Osteogenic differentiation and mineralization abilities of shGnai3-treated osteoblast precursor cells were promoted by p-JNK and p-p38 pathway activators, suggesting that Gnai3 might regulate the differentiation and mineralization processes in osteoblast precursor cells through the MAPK signaling pathway. Conclusions: In this study, we investigated the regulatory mechanism of Mir24-2-5p on Gnai3 expression regulation in osteoblast precursor cells and provided a new idea of improving the prevention and treatment strategies for congenital mandibular defects and mandibular protrusion.