ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.

Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5'UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5'UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5'UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5'UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.

Urease-producing bacteria with plant growth-promoting ability that may tolerate and remove cadmium from aqueous solution.

Urease-producing bacteria (UPB) are widely present in soil and play an important role in soil ecosystems. In this study, 65 UPB strains were isolated from cadmium (Cd)-polluted soil around a lead-zinc mine in Yunnan Province, China. The Cd tolerance, removal of Cd from aqueous solution, production of indoleacetic acid (IAA) and plant growth-promoting effects of these materials were investigated. The results indicate that among the 65 UPB strains, four strains with IAA-producing ability were screened and identified as Bacillus thuringiensis W6-11, B. cereus C7-4, Serratia marcescens W11-10, and S. marcescens C5-6. Among the four strains, B. cereus C7-4 had the highest Cd tolerance, median effect concentration (EC50) of 59.94 mg/L. Under Cd 5 mg/L, S. marcescens C5-6 had the highest Cd removal from aqueous solution, up to 69.83%. Under Cd 25 mg/kg, inoculation with B. cereus C7-4 significantly promoted maize growth in a sand pot by increasing the root volume, root surface area, and number of root branches by 22%, 29%, and 20%, respectively, and plant height and biomass by 16% and 36%, respectively, and significantly increasing Cd uptake in the maize roots. Therefore, UPB is a potential resource for enhancing plant adaptability to Cd stress in plants with Cd-polluted habitats.

This study utilized urease-producing bacteria screened from the soil of lead zinc mining areas in Yunnan, China as the research object, enriching the microbial resources in Yunnan. In addition, this article verified the IAA production ability and cadmium removal ability of urease-producing bacteria, and screened out bifunctional urease-producing bacteria that have potential in cadmium pollution control and plant growth promotion.

[Study on mechanism of icariin-induced ferroptosis in HepG2 hepatoma carcinoma cells through PPARG/FABP4/GPX4 pathway].

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.

Inhibiting cardiac autophagy suppresses Zika virus replication.

Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient-dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. Furthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV.

Optical power degradation mechanisms in 271†nm AlGaN-based deep ultraviolet light-emitting diodes.

The degradation of AlGaN-based UVC LEDs under constant temperature and constant current stress for up to 500 hrs was analyzed in this work. During each degradation stage, the two-dimensional (2D) thermal distributions, I-V curves, optical powers, combining with focused ion beam and scanning electron microscope (FIB/SEM), were thoroughly tested and analyzed the properties and failure mechanisms of UVC LEDs. The results show that: 1) the opto-electrical characteristics measured before/during stress indicate that the increased leakage current and the generation of stress-induced defects increase the non-radiative recombination in the early stress stage, resulting in a decrease in optical power; 2) the increase of temperature caused by the deterioration of the Cr/Al layer of p-metal after 48 hrs of stress aggravates the optical power in UVC LEDs. The 2D thermal distribution in conjunction with FIB/SEM provide a fast and visual way to precisely locate and analyze the failure mechanisms of UVC LEDs.

Protective effects of MiR-146b in cerebral infarction via targeting SIRT1/FOXO1 signaling pathway.

To observe the therapeutic effect of micro ribonucleic acid (miR)-146b on brain tissue injury in rats with cerebral infarction (CI) by regulating the Sirtuin 1 (SIRT1)/forkhead box protein O1 (FOXO1) signaling pathway, a rat model of CI was established. Lentiviral cells were used to transfect and silence or overexpress miR-146b. The rats were divided into the miR-146b inhibitor group (Inhibitors), miR-146b mimic group (Mimics) and normal group (Control). Then quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the transfection rate of miR-146b in rat brain tissues in each group. The improved method was adopted to score the nerves of rats, and the infarction volume of rats in each group was determined. Subsequently, the levels of superoxide dismutase (SOD) and reactive oxygen species (ROS) in the brain tissues in each group were measured via enzyme-linked immunosorbent assay (ELISA), the apoptosis of nerve cells in the brain tissues was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and glial fibrillary acidic protein (GFAP), S100ß gene and SIRT1/FOXO1 pathway-related genes and proteins in the brain tissues were determined through qRT-PCR and Western blotting. MiR-146b exhibited a high expression in Mimics and an extremely low expression in Inhibitors. Rats in Mimics were normal in movement, and their neurological scores were close to those in Control. Rats in Inhibitors could walk normally, and their neurological scores were notably higher than those in other groups (P<0.05). In addition, Inhibitors had a remarkably larger CI volume (P<0.05), a remarkably increased ROS level and a significantly reduced SOD level compared with those in other groups. Moreover, TUNEL staining results manifested that apoptotic cells, especially glial cells, were notably increased in Inhibitors compared with those in Mimics. Besides, the messenger RNA (mRNA) expression levels of S100ß and GFAP in Inhibitors were higher than those in other groups (P<0.05). SIRT1 and FOXO1 genes were increased in Mimics, which were close to those in Control. According to Western blotting results, the protein expression levels of SIRT1 and FOXO1 in Mimics were notably higher than those in Inhibitors. MiR-146b can play a protective role in CI rats by activating the SIRT1/FOXO1 signaling pathway, lowering the oxidative stress level and reducing brain tissue apoptosis.

MiR-182 promotes apoptosis of neural cells in cerebral infarction rats by PI3K/AKT signaling pathway.

To explore the effects of micro ribonucleic acid (miR)-182 on the proliferation and apoptosis of neural cells in cerebral infarction rats and its underlying mechanism. The rat model of cerebral infarction was established, and neural cells were extracted accordingly. The cell proliferation ability was detected via cell counting kit-8 (CCK8) assay. In addition, the apoptosis rate was determined through flow cytometry and the activity of active caspase-3. Furthermore, the interaction between miR-182 and PI3K was explored via dual luciferase reporter assay, and the protein expression levels were observed via Western blotting. The neural cells in mouse brain tissues significantly decreased in the model group compared with that in the control group via HE stain. Additionally, the expression level of miR-182 was significantly increased in the model group compared with that in the control group. Furthermore, overexpression of miR-182 could inhibit the proliferation of neural cells through inducing cell apoptosis. Besides, the results of the luciferase reporter assay showed that the relative luciferase activity in neural cells could be inhibited by the transfection with miR-182 (P<0.05). Overexpression of miR-182 significantly reduced the protein expression levels of phosphatidylinositol 3-hydroxy kinase (PI3K) and p-AKT. MiR-182 induces apoptosis of neural cells through inhibiting the PI3K/AKT signaling pathway, which plays an important regulatory role in the apoptosis of neural cells in cerebral infarction rats.

Effect of oil exposure stages on the heat resistance of Salmonella enterica serovar Enteritidis phage type 30 in peanut flour.

The oil in low-moisture foods (LMFs) shows protective effects on bacteria during thermal processing. However, the circumstances under which this protective effect strengthens remain unclear. This study aimed to understand which step of the oil exposure to bacterial cells (inoculation, isothermal inactivation, or recovery and enumeration step) in LMFs can enhance their heat resistance. Peanut flour (PF) and defatted PF (DPF) were selected as the oil-rich and oil-free LMF models. Salmonella enterica Enteritidis Phage Type 30 (S. Enteritidis) was inoculated into four designated PF groups representing different oil exposure stages. It was isothermally treated to obtain heat resistance parameters. At a constant moisture content (aw,25°C = 0.32 ± 0.02) and controlled aw,85°C (0.32 ± 0.02), S. Enteritidis exhibited significantly high (p < 0.05) D values in oil-rich sample groups. For instance, the heat resistance values of S. Enteritidis in the PF-DPF and DPF-PF groups were D80°C of 138.22 ± 7.45 min and 101.89 ± 7.82 min; however, the D80°C in the DPF-DPF group was 34.54 ± 2.07 min. The oil addition after the thermal treatment also helped injured bacterial recovery in the enumeration. For instance, the D80°C, D85°C, and D90°C values in the DFF-DPF oil groups were 36.86 ± 2.30, 20.65 ± 1.23, and 7.91 ± 0.52 min, respectively, which were higher than those in the DPF-DPF group at 34.54 ± 2.07, 17.87 ± 0.78, and 7.10 ± 0.52 min. We confirmed that the oil protected S. Enteritidis in PF in all three stages: desiccation process, heat treatment, and recovery of bacterial cells in plates.

Self-reported oral health habits, knowledge and conditions of schoolchildren and adolescents in mainland China.

To determine the oral health habits, knowledge and conditions of students in China and investigate the impact of associated factors. A self-reported online questionnaire was distributed through social networks in mainland China to assess the oral health habits, knowledge, and conditions of students aged 6-20 years attending primary, middle, and high schools. Factors potentially associated with oral health, such as oral health habits of their parents, family education level, and economic regions, were analyzed using McNemar's and Chi-square tests. Within one month, 5561 valid questionnaires were retrieved from all 31 provinces or equivalent regions in mainland China. The results showed that 46.9% of students suffered from bleeding when brushing their teeth, while only 11.8% reported professional teeth cleaning at a dental clinic. Soda beverages were widely consumed among them (75.4%). A significant minority of students brushed their teeth less than twice daily (22.8%) and for about 2 minutes each time (19.3%). Only 21.9% of the students had preventive oral health care. Students' toothbrushing habits and knowledge about interdental cleaning tools were associated with parental habits (p < 0.001). Overall, students from families with higher educational backgrounds and eastern China had better oral health habits, knowledge, and conditions. There is a need to pay more attention to gingival health and caries prevention among schoolchildren and adolescents in mainland China. Improving parental oral hygiene habits could have a positive impact on the oral health of students. Further research on oral health among students is needed in the middle and western regions of China.

Synthesis of Cyclopropenes and Fluorinated Cyclopropanes via Michael Initiated Ring Closure of Alkyl Triflones.

A facile synthesis of cyclopropenes and fluorinated cyclopropanes from readily available alkyl triflones was developed. The reaction, regardless of electronic effect, gave products in good to excellent yields and moderate diastereoselectivity. The mechanism may involve tandem Michael addition of triflones/intramolecular nucleophilic cyclization (elimination of -SO2 CF3 )/elimination of fluoride.

Selective Inhibition of PTP1B by New Anthraquinone Glycosides from Knoxia valerianoides.

Protein tyrosine phosphatase 1B (PTP1B) is highly validated as a therapeutic target for type 2 diabetes. However, active site-directed PTP1B inhibitors generally suffer from poor selectivity and bioavailability. Inspired by the identification of a unique anthraquinone-coumarin hybrid from Knoxia valerianoides exhibiting good specificity for PTP1B over the highly homologous T-cell protein tyrosine phosphatase (TCPTP), further chemical investigation of this plant species led to the isolation of nine new anthraquinone glycosides (1-9) and two known ones (10 and 11). Structures were characterized by a combination of spectroscopic analyses and chemical methods. All compounds showed PTP1B inhibitory activities with IC50 values ranging from 1.05 to 13.74 µM. Compounds 4 and 8 exhibited greater than 64-fold selectivity over TCPTP. Enzyme kinetic studies revealed that compounds 4 and 7 behaved as mixed-type inhibitors. Docking studies predicted similar binding modes of these compounds at the allosteric site positioned between helices α3 and α6.

Comprehensive Analysis of the Effect of 20(R)-Ginsenoside Rg3 on Stroke Recovery in Rats via the Integrative miRNA-mRNA Regulatory Network.

MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNAs. Recent research has proven that miRNAs play an essential role in the occurrence and development of ischemic stroke. Our previous studies confirmed that 20(R)-ginsenosideRg3 [20(R)-Rg3] exerts beneficial effects on cerebral ischemia-reperfusion injury (CIRI), but its molecular mechanism has not been elucidated. In this study, we used high-throughput sequencing to investigate the differentially expressed miRNA and mRNA expression profiles of 20(R)-Rg3 preconditioning to ameliorate CIRI injury in rats and to reveal its potential neuroprotective molecular mechanism. The results show that 20(R)-Rg3 alleviated neurobehavioral dysfunction in MCAO/R-treated rats. Among these mRNAs, 953 mRNAs were significantly upregulated and 2602 mRNAs were downregulated in the model group versus the sham group, whereas 437 mRNAs were significantly upregulated and 35 mRNAs were downregulated in the 20(R)-Rg3 group in contrast with those in the model group. Meanwhile, the expression profile of the miRNAs showed that a total of 283 differentially expressed miRNAs were identified, of which 142 miRNAs were significantly upregulated and 141 miRNAs were downregulated in the model group compared with the sham group, whereas 34 miRNAs were differentially expressed in the 20(R)-Rg3 treatment group compared with the model group, with 28 miRNAs being significantly upregulated and six miRNAs being significantly downregulated. Furthermore, 415 (391 upregulated and 24 downregulated) differentially expressed mRNAs and 22 (17 upregulated and 5 downregulated) differentially expressed miRNAs were identified to be related to 20(R)-Rg3's neuroprotective effect on stroke recovery. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that 20(R)-Rg3 could modulate multiple signaling pathways related to these differential miRNAs, such as the cGMP-PKG, cAMP and MAPK signaling pathways. This study provides new insights into the protective mechanism of 20(R)-Rg3 against CIRI, and the mechanism may be partly associated with the regulation of brain miRNA expression and its target signaling pathways.

[Air Temperature Affects the Hospital Admission for Cardiovascular Diseases among Rural Residents in Dingxi City].

Objective To explore the effect of air temperature on the hospitalization of rural residents with cardiovascular diseases and its lag effect in Dingxi city. Methods The meteorological data and air pollution data of Dingxi city from 2018 to 2019,as well as the daily hospitalization data of rural residents due to cardiovascular diseases,were collected.The distributed lag non-linear models were employed to analyze the relationship between daily mean air temperature and the number of inpatients with cardiovascular diseases.Meanwhile,stratified analysis was carried out according to gender,age,and disease. Results There was a non-linear relationship between air temperature and the number of hospitalized rural residents with cardiovascular diseases in Dingxi city.The exposure-response curve approximated a bell shape.The curves for different cardiovascular diseases appeared similar shapes,with different temperature thresholds.Low temperature(-7 ℃) and moderately low temperature(0 ℃) exhibited a cumulative lag effect on the number of patients hospitalized with cardiovascular diseases.With a cumulative lag of 7 days at -7 ℃ and 14 days at 0 ℃,the RR values peaked,which were 1.121(95% CI=1.002-1.255) and 1.198(95% CI=1.123-1.278),respectively.With a cumulative lag of 14 days at 0 ℃,the RR values were 1.034(95% CI=1.003-1.077) and 1.039(95% CI=1.004-1.066) for the number of hospitalized patients with ischemic heart disease and heart rhythm disorders,respectively.The cumulative lag effects of moderately high temperature(17 ℃) and high temperature(21 ℃) on ischemic heart disease,heart rhythm disorders,and cerebrovascular disease all peaked on that day.Specifically,the RR values at 17 ℃ and 21 ℃ were 1.148(95% CI=1.092-1.206) and 1.176(95% CI=1.096-1.261) for ischemic heart disease,1.071(95% CI=1.001-1.147) and 1.112(95% CI=1.011-1.223) for heart rhythm disorders,and 1.084(95% CI=1.025-1.145) and 1.094(95% CI=1.013-1.182) for cerebrovascular disease,respectively.There was no cumulative lag effect of air temperature on the number of hospitalized patients with heart failure.In addition,stratified analysis showed that low temperature(-7 ℃) and moderately low temperature(0 ℃) affected the number of hospitalized female patients with cardiovascular diseases,and only moderately low temperature(0 ℃) affected males.The cumulative lag effect of high temperature on females was higher than that on males.Air temperature exhibited a stronger impact on female patients than on male patients. Additionally,the population aged<65 years old was more sensitive to low temperature and high temperature than that aged ≥65 years old. Conclusions Air temperature changes increase the hospitalization risk of rural residents with cardiovascular diseases in Dingxi city,which presents a lag effect.The effects of air temperature on patients hospitalized due to cardiovascular diseases varied among different etiologies,genders,and ages.It is necessary to emphasize on the impact of temperature changes on health in residents,especially for key populations such as females,people aged<65 years old,and those with ischemic heart disease.

[Lignans from Agrimonia pilosa].

Thirteen lignans were isolated from 60% ethanol extract of Agrimonia pilosa by column chromatography over silica gel, ODS, and MCI and preparative high performance liquid chromatography(HPLC). Their chemical structures were identified by physiochemical properties and spectral data as(7S,8S)-threo-4,7,9,9'-tetrahydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan(1),(+)-4,9,9'-trihydroxy-3-methoxy-3',7-epoxy-8,4'-oxyneolignan(2), dihydrodehydro-diconiferyl alcohol(3), 4,9,9'-trihydroxy-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan(4),(-)-secoisolariciresinol(5), 4,7,9,9'-tetrahydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan(6),(+)-isolariciresinol(7), 4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan(8), burselignan(9),(-)-evofolin B(10), icariol A2(11), ciwujiatone(12), and(+)-4″,4-dihydroxy-3,3',3″,3,5,5'-hexamethoxy-7,9';7',9-diepoxy-4,8″;4',8-bisoxy-8,8'-dineolignan-7″,7,9″,9-tetraol(13). Compound 1 was a new compound, and compounds 1-13 were isolated from Agrimonia plant for the first time. This study can enrich the chemical components in A. pilosa and provide material conditions for the follow-up study of its biological activity and the elucidation of its pharmacodynamic substances.

Moisture Content of Bacterial Cells Determines Thermal Resistance of Salmonella enterica Serotype Enteritidis PT 30.

Salmonella spp. are resilient bacterial pathogens in low-moisture foods. There has been a general lack of understanding of critical factors contributing to the enhanced thermal tolerance of Salmonella spp. in dry environments. In this study, we hypothesized that the moisture content (XW ) of bacterial cells is a critical intrinsic factor influencing the resistance of Salmonella spp. to thermal inactivation. We selected Salmonella enterica serotype Enteritidis PT 30 to test this hypothesis. We first produced viable freeze-dried S. Enteritidis PT 30, conditioned the bacterial cells to different XW s (7.7, 9.2, 12.4, and 15.7 g water/100 g dry solids), and determined the thermal inactivation kinetics of those cells at 80°C. The results show that the D-value (the time required to achieve a 1-log reduction) decreased exponentially with increasing XW We further measured the water activities (aw) of the freeze-dried S. Enteritidis PT 30 as influenced by temperatures between 20 and 80°C. By using those data, we estimated the XW of S. Enteritidis PT 30 from the published papers that related the D-values of the same bacterial strain at 80°C with the aw of five different food and silicon dioxide matrices. We discovered that the logarithmic D-values of S. Enteritidis PT 30 in all those matrices also decreased linearly with increasing XW of the bacterial cells. The findings suggest that the amount of moisture in S. Enteritidis PT 30 is a determining factor of its ability to resist thermal inactivation. Our results may help future research into fundamental mechanisms for thermal inactivation of bacterial pathogens in dry environments.IMPORTANCE This study established a logarithmic relationship between the thermal death time (D-value) of S. Enteritidis PT 30 and the moisture content (XW ) of the bacterial cells by conducting thermal inactivation tests on freeze-dried S Enteritidis PT 30. We further verified this relationship using literature data for S. Enteritidis PT 30 in five low-moisture matrices. The findings suggest that the XW of S. Enteritidis PT 30, which is rapidly adjusted by microenvironmental aw, or relative humidity, during heat treatments, is the key intrinsic factor determining the thermal resistance of the bacterium. The quantitative relationships reported in this study may help guide future designs of industrial thermal processes for the control of S. Enteritidis PT 30 or other Salmonella strains in low-moisture foods. Our findings highlight a need for further fundamental investigation into the role of water in protein denaturation and the accumulation of compatible solutes during thermal inactivation of bacterial pathogens in dry environments.

Magnetic hydrogel with long in situ retention time for self-regulating temperature hyperthermia.

Aim: Magnetic hydrogels (MHGs) have been proposed to avoid the redistribution and loss of magnetic nanoparticles (MNPs) when administrated by intratumoral injection. However, the requirement of complex cooling systems and temperature monitoring systems still hinder the clinical application of MHGs. This study investigates the feasibility of developing an MHG to realize the self-regulation of hyperthermia temperature. Methods: The MHG was developed by dispersing the MNPs with self-regulating temperature property into the temperature-sensitive hydrogel through physical crosslinking. The MHG's gelation temperature was tested by measuring the storage modulus and loss modulus on a rotational rheometer. The biocompatibility of the MHG and MNPs was characterized by CCK-8 assay against HaCaT cells. The in vivo magnetic heating property was examined through monitoring the temperature in the MHG on mice back upon the application of the alternating magnetic field (400 ± 5 Oe, 100 ± 5 kHz) every week for successive six weeks. Results: The gelation temperature of the MHG falls in 28.4°C-37.4°C. At in vivo applied concentration of 80 mg/mL, the MHG exhibits over 80% cell viability after 72 h, significantly higher than 50% cell viability of the MNPs (p<0.001). The MHG's stable magnetic hyperthermia temperatures in vivo are in the range of 43.4°C-43.8°C. Conclusions: The developed MHG can be injected using a syringe and will solidify upon body temperature. The biocompatibility is improved after the MNPs being made into MHG. The MHG can self-regulate the temperature for six weeks, exhibiting application potential for self-regulating temperature hyperthermia.

The study of Wilson disease in pregnancy management.

INTRODUCTION: Pregnancy management in women with Wilson disease (WD) remains an important clinical problem. This research was conducted to investigate how to avoid worsening of WD symptoms during pregnancy and increase pregnancy success in women with WD by identifying the best pregnancy management approaches in these patients. PATIENTS AND METHODS: The clinical data of 117 pregnancies among 75 women with WD were retrospectively analyzed. Related information of the fetus was also recorded and analyzed. At the same time, regression analysis was performed for data of 22 pregnant women without WD, as normal controls. RESULTS: Of a total of 117 pregnancies among the 75 women with WD and 31 pregnancies among the 22 control womenincluded in this study, there were 108 successful pregnancies and 9 spontaneous abortions. Among the 108 successful pregnancies, 97 women a history of copper chelation therapy before pregnancy; all 97 women stopped anti-copper therapy during pregnancy. The nine women with spontaneous abortion had no pre-pregnancy history of copper displacement therapy. The incidence of lower limb edema was higher in the WD group than in normal controls (P = 0.036). Compared with the control group, there was a higher proportion in the WD group of male infants (P = 0.022) and lower average infant birth weight (t = 3.514, P = 0.001). CONCLUSION: It is relatively safe for women with WD patients to become pregnant. The best management method for pregnancy in women with WD may be intensive pre-pregnancy copper chelation therapy and no anti-copper treatment during pregnancy.

A novel approach of torque control for maxillary displaced incisors.

Effective torque control is crucial for the successful treatment of impacted incisors; however, torque control is often a challenge with the use of conventional bracket systems, especially when the adjacent teeth require opposite torque managements. A novel approach of torque control for adjacent anterior teeth is introduced in this case report. A 12-year-old boy had an impacted maxillary right central incisor with the adjacent teeth severely displaced. The treatment plan was to regain space and pull the impacted incisor into the dentition. An upper removable appliance was first used to regain space for the impacted central incisor, followed by a spontaneous eruption of the impacted incisor. Subsequently, fixed appliances were bonded to level and align the dentition. However, the crown of the maxillary right central incisor was found to be tipped lingually, while the maxillary right lateral incisor was tipped labially. Traditional torque control, including torque bend and the use of a Warren spring, were first used for the correction, but they were ineffective due to the overlap of the root apex of the maxillary central incisor and lateral incisor. After the roots were separated with a V-shaped curve, auxiliary brackets were bonded on the gingival one-third areas of the maxillary incisors and canine with nickel-titanium wires used for the torque control. This approach of using the auxiliary brackets and wires was demonstrated to be efficient and effective in the torque control of adjacent anterior teeth with opposite torque control requirements. The final result and the 2-year follow-up records demonstrated the proper torque of anterior teeth and good and stable dental and profile esthetics.

Using time-series Sentinel-1 data for soil prediction on invaded coastal wetlands.

Coastal soils are particularly sensitive to nonnative species invasion. In this context, spatially explicit soil information is essential for improving the knowledge of the role of soil in changing environments, supporting coastal sustainable management. Synthetic-aperture radar (SAR) data provides an attractive opportunity to monitor soil because the acquisition of images is independent of weather and daylight. However, SAR has not been commonly used for soil prediction. In this study, we firstly investigated the temporal variation of vegetation canopy and the soil-vegetation relationship using Sentinel-1 data in an invaded coastal wetland. And then we built 3D models to predict soil properties at multiple depths. A total of 16 Sentinel-1 images were acquired in a growing season. A series of soil physicochemical properties were examined including soil bulk density, texture, organic/inorganic carbon, pH, salinity, total nitrogen, and C/N ratio, relating to three depth layers in the top 1-m depth. Our results showed that time-series Sentinel-1 data can capture temporal characteristics of vegetation, and VH/VV was more sensitive to the vegetation growth than VH and VV. The soil-vegetation relationship captured by time-series SAR data was beneficial to predict soil properties, especially for soil chemical properties. The models provided permissible prediction accuracy, with an average RPD of 0.99. We concluded that the prior understanding of the temporal variation of SAR data is essential for developing practical soil prediction strategy. Our results highlight that SAR has the potential to predict a diverse set of soil properties in coastal wetlands with dense vegetation cover.

Hypercapnia induces IL-1ß overproduction via activation of NLRP3 inflammasome: implication in cognitive impairment in hypoxemic adult rats.

BACKGROUND: Cognitive impairment is one of common complications of acute respiratory distress syndrome (ARDS). Increasing evidence suggests that interleukin-1 beta (IL-1ß) plays a role in inducing neuronal apoptosis in cognitive dysfunction. The lung protective ventilatory strategies, which serve to reduce pulmonary morbidity for ARDS patients, almost always lead to hypercapnia. Some studies have reported that hypercapnia contributes to the risk of cognitive impairment and IL-1ß secretion outside the central nervous system (CNS). However, the underlying mechanism of hypercapnia aggravating cognitive impairment under hypoxia has remained uncertain. This study was aimed to explore whether hypercapnia would partake in increasing IL-1ß secretion via activating the NLRP3 (NLR family, pyrin domain-containing 3) inflammasome in the hypoxic CNS and in aggravating cognitive impairment. METHODS: The Sprague-Dawley (SD) rats that underwent hypercapnia/hypoxemia were used for assessment of NLRP3, caspase-1, IL-1ß, Bcl-2, Bax, and caspase-3 expression by Western blotting or double immunofluorescence, and the model was also used for Morris water maze test. In addition, Z-YVAD-FMK, a caspase-1 inhibitor, was used to treat BV-2 microglia to determine whether activation of NLRP3 inflammasome was required for the enhancing effect of hypercapnia on expressing IL-1ß by Western blotting or double immunofluorescence. The interaction effects were analyzed by factorial ANOVA. Simple effects analyses were performed when an interaction was observed. RESULTS: There were interaction effects on cognitive impairment, apoptosis of hippocampal neurons, activation of NLRP3 inflammasome, and upregulation of IL-1ß between hypercapnia treatment and hypoxia treatment. Hypercapnia + hypoxia treatment caused more serious damage to the learning and memory of rats than those subjected to hypoxia treatment alone. Expression levels of Bcl-2 were reduced, while that of Bax and caspase-3 were increased by hypercapnia in hypoxic hippocampus. Hypercapnia markedly increased the expression of NLRP3, caspase-1, and IL-1ß in hypoxia-activated microglia both in vivo and in vitro. Pharmacological inhibition of NLRP3 inflammasome activation and release of IL-1ß might ameliorate apoptosis of neurons. CONCLUSIONS: The present results suggest that hypercapnia-induced IL-1ß overproduction via activating the NLRP3 inflammasome by hypoxia-activated microglia may augment neuroinflammation, increase neuronal cell death, and contribute to the pathogenesis of cognitive impairments.