Blood-Glucose-Depleting Hydrogel Dressing as an Activatable Photothermal/Chemodynamic Antibacterial Agent for Healing Diabetic Wounds.

Poorly healing and nonhealing diabetic wounds are challenging to treat as the rapid growth of bacteria due to the high local glucose content can lead to persistent inflammation and poor angiogenesis. Herein, a smart hydrogel dressing composed of 3,3',5,5'-tetramethylbenzidine/ferrous ion/Pluronic F-127/glucose oxidase (TMB/Fe2+/PF127/GOx) is designed and demonstrated to consume blood glucose while accelerating wound healing by generating antibacterial agents in situ. The loaded GOx degrades blood glucose to provide hydrogen peroxide (H2O2) and gluconic acid to support the Fe2+-based Fenton reaction, and the generated hydroxyl radical (·OH) facilitates the oxidation of TMB. The color change from colorless to green caused by the oxidation of TMB in the blood glucose range between 1 and 10 mM can be monitored visually. Simultaneously, this process induced chemodynamic therapy (CDT) by the specific generation of hydroxyl radical (·OH) for killing bacteria. Moreover, the oxidized TMB shows strong absorption in the near infrared (NIR) region so that NIR light can be converted into heat efficiently for photothermal therapy (PTT). As a result, nearly 100% of Staphylococcus aureus and Escherichia coli are killed by synergistic PTT/CDT, and the infected skin wounds undergo complete repair along with downregulation of interleukin-6 (IL-6) and upregulation of the vascular endothelial growth factor (VEGF) and matrix metallopeptidase-2 (MMP-2). Different from traditional wound dressings that can give rise to secondary injury, the excellent thermosensitive properties arising from the sol/gel phase transition render the hydrogel dressing materials injectable, self-reparable, and removable on demand. The multifunctional hydrogel with hypoglycemic, chemodynamic, photothermal, antibacterial, and on-demand thermosensitive properties has immense potential in the treatment of diabetic wounds.

Hydrogen sulfide treatment increases the antioxidant capacity of fresh Lingwu Long Jujube (Ziziphus jujuba cv. Mill) fruit during storage.

Hydrogen sulfide (H2S) has been identified as an important gaseous signal molecule in plants. Here, we investigated the effects of H2S on postharvest senescence and antioxidant metabolism of Lingwu Long Jujube (Ziziphus jujuba cv. Mill) fruits (LLJF). Fumigation of Jujube fruits with H2S released from 0.4 mm NaHS could significantly prolong the postharvest shelf life of jujube fruits, reduce the decay rate of fruit, the weight loss of fruit, and inhibit the fruit loss, hardness, color, soluble solids, and titratable acidity. Compared with the control group, exogenous H2S fumigation significantly decreased the loss of chlorophyll, carotenoids, soluble protein, ascorbic acid, phenols, and flavonoids in jujube fruits during post-harvest storage. At the same time, H2S could significantly delay the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2) and superoxide anion (O2 ∙-) and promote catalase (CAT), superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase (POD) activity, and inhibit polyphenol oxidase (PPO) activity. To summarize, H2S can effectively alleviate postharvest senescence and decay of jujube fruits by regulating the ROS accumulation and antioxidant enzymes, and prolong the storage period of postharvest.

Constitutional delay of growth and puberty in female mice is induced by circadian rhythm disruption in utero.

Constitutional delay of growth and puberty (CDGP) refers to the late onset of puberty. CDGP is associated with poor psychosocial outcomes and elevated risk of cardiovascular and osteoporotic diseases, especially in women. The environmental factors that contribute to CDGP are poorly understood. Here, we investigated the effects of chronic circadian disturbance (CCD) during the fetal stage on the pubertal development of female mice. Compared to non-stressed female (NS-F) mice that were not exposed to CCD in utero, adolescent CCD female (CCD-F) mice exhibited phenotypes that were consistent with CDGP, including lower body weight, reduced levels of circulating gonadal hormones, decreased expression of gonadal hormones and steroid synthesis-related enzymes in the ovary and hypothalamus, irregular estrus cycles, and tardive vaginal introitus initial opening (VO) days (equivalent to the menarche). Phenotypic differences in the above-noted parameters were not observed in CCD-F mice once they had reached adulthood. The expression of genes involved in fatty acid metabolism was perturbed in the ovary and hypothalamus of CCD-F mice. In addition, the ovaries of these animals exhibited altered diurnal expression profiles of circadian clock genes. Together, our findings not only suggest that CCD during fetal development may result in delayed puberty in female mice, they also offer insights on potential mechanisms that underlie CDGP.

Photoreduced Ag+ surrounding single poly(4-cyanostyrene) nanoparticles for undifferentiated SERS sensing and killing of bacteria.

Developing a rapid, low cost and sensitive sensing strategy for undifferentiated detection and fast killing of bacterial pathogens are critical to alleviating bacteria infections. Here, we propose a direct photoreduction method to synthesize the SERS tag by integrating poly(4-cyanostyrene) nanoparticles (NPs) and silver ions, which are applied as bio-sensing system for bacteria sensing and fast killing. Under a focused laser spot, silver ions on the surface of the poly(4-cyanostyrene) NPs could be photoreduced into Ag NPs, thereby causing the Raman signal amplification of poly(4-cyanostyrene) NPs up to 40 times, and there is a good linear correlation between the Raman intensity of poly(4-cyanostyrene) NPs and different concentrations of Ag+. Moreover, 4-mercaptophenylboronic acid, performing the same recognition function for both the Gram-positive and Gram-negative bacteria, is used as bridge between the bacteria and Ag+ by the inherent chemical bonding. Based on further constructed bio-sensing system, we achieved the quick count and killing of both Gram-positive bacteria, e.g., Staphylococcus aureus (S. aureus), and Gram-negative bacteria, e.g., Escherichia coli (E. coli). Notably, the sensing strategy can detect at least ∼100 cells of E. coli, ∼10 cells of S. aureus and ∼10 cells of their mixture in less than 40 min. The detection accuracy for actual samples can also reach over 80% and the bacteria were entirely killed by Ag+ after the detection, avoiding bacterial contamination in the environment. This novel method is anticipated to perform as a simple yet effective tool for fast and sensitive bacteria counting and killing.

Screening of ADHD symptoms in primary school students and investigation of parental awareness of ADHD and its influencing factors: A cross-sectional study.

Objective: The present study aimed to compare the differences in positive screening rates of attention deficit hyperactivity disorder (ADHD) symptoms between parents and teachers in the same sample of primary school students. Concurrently, parental awareness and information sources of ADHD were investigated, and possible relevant factors affecting parental awareness and their influence on positive screening rate of ADHD were analyzed. Methods: A cross-sectional study was conducted in Changchun, China, between September 2020 and January 2021. Parents of 1,118 primary school students and 24 head teachers were recruited in the survey. Data were collected through a structured self-administered questionnaire. It consisted of socio-demographic characteristics, ADHD symptom screening questionnaire, parental awareness, and information sources of ADHD. Results: Among the 1,118 primary school students, 30 (2.7%) and 60 (5.4%) students were positive for Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) screening in the parent version and teacher version, respectively. Parents had lower positive screening rates for ADHD symptoms than teachers. Relationship with children (mother, OR = 1.552, 95% CI = 1.104-2.180), bachelor degree or above of parents (OR = 1.526, 95% CI = 1.054-2.210), children's sex (girl, OR = 1.442, 95% CI = 1.093-1.904), and age (OR = 1.344, 95% CI = 1.030-1.754), children's grade (grade 2, OR = 0.522, 95% CI = 0.310-0.878; grade 3, OR = 0.388, 95% CI = 0.185-0.782), information sources of ADHD (medical staff, OR = 1.494, 95% CI = 1.108-2.015; family/relative/friend, OR = 1.547, 95% CI = 1.148-2.083; TV/Internet, OR = 3.200, 95% CI = 2.270-4.510) were the factors related to the parental awareness of ADHD. Conclusion: Parents and teachers of primary school students recognize ADHD symptoms differently. The positive screening rate of ADHD among teachers was significantly higher than that of parents. Relationship with children, educational level of parents, children's sex, age, and grade, and information sources of ADHD are the relevant factors affecting parental awareness of ADHD. More efforts should be made to disseminate ADHD knowledge through mass media, and medical staff. Fathers, parents with low educational level, and parents of grade 2 and 3 pupils should be encouraged to acquire more knowledge on ADHD to improve the early recognition rate of ADHD symptoms. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=54 072], identifier [ChiCTR2000033388].

Recent advances in plasmonic Prussian blue-based SERS nanotags for biological application.

The reliability and reproducibility of surface-enhanced Raman scattering (SERS) technology is still a great challenge in bio-related analysis. Prussian blue (PB)-based SERS tags have attracted increasing interest for improving these deficiencies due to its unique Raman band (near 2156 cm-1) in the Raman-silent region, providing zero-background bio-Raman labels without interference from endogenous biomolecules. Moreover, the stable PB shell consisting of multiple layers of CN- reporters ensure a stable and strong Raman signal output, avoiding the desorption of the Raman reporter from the plasmonic region by the competitive adsorption of the analyte. More importantly, they possess outstanding multiplexing potential in biological analysis owing to the adjustable Raman shift with unique narrow spectral widths. Despite more attention having been attracted to the structure and preparation of PB-based SERS tags for their better biological applications over the past five years, there is still a great challenge for SERS suitable for applications in the actual environment. The biological applications of PB-based SERS tags are comprehensively recounted in this minireview, mainly focusing on quantification analysis, multiple-spectral analysis and cell-imaging joint phototherapy. The prospects of PB-based SERS tags in clinical diagnosis and treatment are also discussed. This review aims to draw attention to the importance of SERS tags and provide a reference for the design and application of PB-based SERS tags in future bio-applications.

Silica Nanoparticles Disturb Ion Channels and Transmembrane Potentials of Cardiomyocytes and Induce Lethal Arrhythmias in Mice.

BACKGROUND: The toxicity of silica nanoparticles (SiNPs) on cardiac electrophysiology has seldom been evaluated. METHODS: Patch-clamp was used to investigate the acute effects of SiNP-100 (100 nm) and SiNP-20 (20 nm) on the transmembrane potentials (TMPs) and ion channels in cultured neonatal mouse ventricular myocytes. Calcium mobilization in vitro, cardiomyocyte ROS generation, and LDH leakage after exposure to SiNPs in vitro and in vivo were measured using a microplate reader. Surface electrocardiograms were recorded in adult mice to evaluate the arrhythmogenic effects of SiNPs in vivo. SiNP endocytosis was observed using transmission electron microscopy. RESULTS: Within 30 min, both SiNPs (10-8-10-6 g/mL) did not affect the resting potential and IK1 channels. SiNP-100 increased the action potential amplitude (APA) and the INa current density, but SiNP-20 decreased APA and INa density. SiNP-100 prolonged the action potential duration (APD) and decreased the Ito current density, while SiNP-20 prolonged or shortened the APD, depending on exposure concentrations and increased Ito density. Both SiNPs (10-6 g/mL) induced calcium mobilization but did not increase ROS and LDH levels and were not endocytosed within 10 min in cardiomyocytes in vitro. In vivo, SiNP-100 (4-10 mg/kg) and SiNP-20 (4-30 mg/kg) did not elevate myocardial ROS but increased LDH levels depending on dose and exposure time. The same higher dose of SiNPs (intravenously injected) induced tachyarrhythmias and lethal bradyarrhythmias within 90 min in adult mice. CONCLUSION: SiNPs (i) exert rapid toxic effects on the TMPs of cardiomyocytes in vitro largely owing to their direct interfering effects on the INa and Ito channels and Ca2+ homeostasis but not IK1 channels and ROS levels, and (ii) induce tachyarrhythmias and lethal bradyarrhythmias in vivo. SiNP-100 is more toxic than SiNP-20 on cardiac electrophysiology, and the toxicity mechanism is likely more complicated in vivo.

[Study on effects of different habitat processing methods of Salviae Miltiorrhizae Radix et Rhizoma in rats with acute myocardial ischemia].

To investigate the effects of different habitat processing methods of Salviae Miltiorrhizae Radix et Rhizoma on acute myocardial ischemia induced by pituitrin in rats. In this experiment, the tail vein injection of pituitrin was used to induce acute myocardial ischemia in rats. Electrocardiograph(ECG) heart rate and ΔST changes were recorded, and the levels of creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH), superoxide dismutase(SOD) and malondialdehyde(MDA) in serum of rats were detected to comprehensively evaluate the effects of six processing methods of Salviae Miltiorrhizae Radix et Rhizoma on serum biochemical indexes of rats with acute myocardial injury. The ECG results showed that the Salviae Miltiorrhizae Radix et Rhizoma dried in a drying oven had a good effect on the improvement of heart rate and ΔST of electrocardiogram after ischemia, and all the other groups had some protective effects to different degrees. The results of biochemical indexes in serum of each group after ischemia showed that the activity of CK-MB decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in a drying oven after sweating and losing weight in a drying oven, high-dose group with drying in the shade and low-dose group with drying in the shade. The activity of LDH decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in the shade and low-dose group of drying in the shade. The activity of SOD increased most significantly in Salviae Miltiorrhizae Radix et Rhizoma low-dose group with drying in sun, low-dose group with drying in sun after sweating and losing weight in sun, and low-dose group with drying in a drying oven. The activity of MDA decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma low-dose group with drying in sun. The comprehensive scoring results showed that the highest score was obtained in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in the shade while the scores of other treatment groups were higher than that of the model group. It could be seen that the Salviae Miltiorrhizae Radix et Rhizoma dried in a drying oven had a good improvement effect on electrocardiograph indexes after acute myocardial injury, the Salviae Miltiorrhizae Radix et Rhizoma dried in the shade had a good improvement effect on serum myocardial enzymes after acute myocardial injury, and the other processing methods had a certain protective effect on myocardial injury. The six processing methods evaluated by pharmacodynamics showed that the Salviae Miltiorrhizae Radix et Rhizoma dried in the shade and dried in a drying oven had good efficacy.

Contribution of DNA methylation in chronic stress-induced cardiac remodeling and arrhythmias in mice.

It is recognized that stress can induce cardiac dysfunction, but the underlying mechanisms are not well understood. The present study aimed to test the hypothesis that chronic negative stress leads to alterations in DNA methylation of certain cardiac genes, which in turn contribute to pathologic remodeling of the heart. We found that mice that were exposed to chronic restraint stress (CRS) for 4 wk exhibited cardiac remodeling toward heart failure, as characterized by ventricular chamber dilatation, wall thinning, and decreased contractility. CRS also induced cardiac arrhythmias, including intermittent sinus tachycardia and bradycardia, frequent premature ventricular contraction, and sporadic atrioventricular conduction block. Circulating levels of stress hormones were elevated, and the cardiac expression of tyrosine hydroxylase, a marker of sympathetic innervation, was increased in CRS mice. Using reduced representation bisulfite sequencing, we found that although CRS did not lead to global changes in DNA methylation in the murine heart, it nevertheless altered methylation at specific genes that are associated with the dilated cardiomyopathy (DCM) (e.g., desmin) and adrenergic signaling of cardiomyocytes (ASPC) (e.g., adrenergic receptor-α1) pathways. We conclude that CRS induces cardiac remodeling and arrhythmias, potentially through altered methylation of myocardial genes associated with the DCM and ASPC pathways.-Zhang, P., Li, T., Liu, Y.-Q., Zhang, H., Xue, S.-M., Li, G., Cheng, H.-Y.M., Cao, J.-M. Contribution of DNA methylation in chronic stress-induced cardiac remodeling and arrhythmias in mice.

[Research advance in allelopathy effect and mechanism of terrestrial plants in inhibition of Microcystis aeruginosa.] / é™†ç”Ÿæ¤ç‰©åŒ–æ„ŸæŠ‘åˆ¶é“œç»¿å¾®å›Šè—»ä½œç”¨æ•ˆåº”åŠæœºåˆ¶ç ”ç©¶è¿›å±•.

The inhibition of algae reproduction and control of harmful algal bloom are the primary challenges in the ecological restoration of eutrophicated water. It is urgent to inhibit algae over-reproduction in green and effective ways, one of which is the use of plant allelopathic effect. How-ever, few study focused on allelochemicals of terrestrial plants. Here, we introduced inhibition of Microcystis aeruginosa over-reproduction by allelochemicals from three categories of terrestrial plants, including herbaceous plants (Compositae/Papaveraceae, Liliaceae, Graminaceae), woody plants, and Chinese medicine plants. The classification, separation and identification of alleloche-micals from terrestrial plants that could be used for the inhibition of M. aeruginosa were summarized. Finally, the allelopathic mechanism to inhibit M. aeruginosa was discussed in detail to support the development of algistat. We also proposed some suggestions for the further development of algistat.

[Study on the specific immunity induced by dendritic cell vaccine loading allogenic microvascular endothelial cell bEnd.3 antigen against U14 cervical cancer cell in mice].

OBJECTIVE: To explore the specific cellular and humoral immunity induced by dendritic cells (DC) vaccine loading allogenic microvascular endothelial cell bEnd.3 antigen against U14 cervical cancer cell of mice. METHODS: Mouse brain microvascular endothelial cell bEnd.3 was cultured and identified for preparation endothelial cell bEnd.3 antigen. The level of mRNA expression of vascular endothelial growth factor receptor 2 (VEGF-R2) and integrin αV was detected by reverse transcription (RT)-PCR. The BALB/c mice were immuned with DC loading bEnd.3 antigen 4 times in 4 weeks (bEnd.3-DC group), while the mice only were immuned with DC or injected with phosphate buffer saline (PBS group) as control group. One week after last vaccination, U14 cervical cancer cells were injected subcutaneously into the mice. The tumor size, cytotoxic T lymphocyte (CTL) response of spleen lymphocytes in vitro, the percentage of CD3+CD8+ surface markers of spleen lymphocytes, and the titer of serum antibody were detected. The specific immunity was examined by immunocytochemistry and western blot. RESULTS: The expression of VEGF-R2 and integrin αV gene in bEnd.3 cells were expressed highly. After the vaccine was injected, the tumors of mice in PBS group grew faster than those in other groups, while the tumors in bEnd.3-DC group grew slowly and disappeared after 2 weeks. The volume of tumors in DC group grew slower than those in PBS group [(0.11 ± 0.13) cm³ versus (3.38 ± 0.34) cm³]. The CTL response of spleen lymphocytes in vitro showed that bEnd.3-DC cells could kill bEnd.3 cells, the special lysis rate was more than 60%. The percentage of CD3+CD8+ spleen lymphocytes in bEnd.3-DC group [(38.6 ± 0.7)%] was higher than those in other groups (P < 0.05). The titer of serum antibody of bEnd.3-DC group was 1:3200, while it was 1:800 in DC group and there were not any in PBS group. Immunocytochemistry analysis indicated there were specific antigen-antibody reaction to bEnd.3 cell in bEnd.3-DC group. Western blot analysis revealed that there were specific bands at 220,000 (VEGF-R2). CONCLUSIONS: bEnd.3-DC vaccine can inhibit the tumor growth of U14 cervical cancer cell of mice, which indicates that the special cellular and humoral immunity are induced by bEnd.3-DC antigen which maybe have some antigens in bEnd.3 cells that reacts with endothelial cell proliferation-related antigens.

[Effects of precipitation and interspecific competition on Quercus mongolica and pinus koraiensis seedlings growth].

Aiming at the variation of precipitation pattern caused by global warming, a field simulation experiment was conducted to study the effects of 30% increase (+W) and decrease (-W) of precipitation on the morphology, growth, and biomass partitioning of mono- and mixed cultured seedlings of Quercus mongolica and Pinus koraiensis, the two dominant tree species in temperate broad-leaved Korean pine mixed forest in Changbai Mountains. Comparing with monoculture, mixed culture increased the canopy width and main root length of Q. mongolica seedlings, but decreased the basal diameter, plant height, leaf number, and dry masses of root, stem, leaf and whole plant of P. koraiensis seedlings significantly. Treatment (-W) increased the stem/mass ratio while decreased the main root length of Q. mongolica seedlings, and decreased the main root length, leaf number, dry masses of leaf and whole plant, and leaf/mass ratio, while increased the stem/mass ratio of P. koraiensis seedlings significantly, compared with treatment CK. Treatment (+W) had no significant effect on these indices of the two species. At early growth stage, interspecific competition and precipitation pattern had significant effects on the morphology and growth of the seedlings, and the responses were much stronger for P. koraiensis than for Q. mongolica.

Poly[bis-[µ-1-cyclo-propyl-6-fluoro-4-oxido-7-(1-piperazin-yl)-1,4-dihydro-quinoline-3-carboxyl-ato]nickel(II)].

In the title compound, [Ni(C(17)H(17)FN(3)O(3))(2)](n), the Ni(II) atom exists in a distorted trans-NiN(2)O(4) octa-hedral geometry defined by two monodentate N-bonded and two bidentate O,O-bonded 1-cyclo-propyl-6-fluoro-4-oxido-7-(1-piperazin-yl)-1,4-dihydro-quinoline-3-carboxyl-ate (ciprofloxacinium) monoanions. The extended two-dimensional structure is a square grid. The Ni atom lies on a center of inversion.

[With genechip technique to investigate HLA-DQB1 gene polymorphisms in south and north regions of China].

OBJECTIVE: To research and compare HLA-DQB1 gene frequency(GF) and polymorphism distribution between south and north population of Chinese in China. METHODS: Combining PCR-sequence specific primers(SSP) and sequence specific oligonucleotide probe(SSOP) techniques and DNA Microarray Kit for HLA-DQB1 Low Res Genotyping from Shenzhen Yi-Shengtang Biological LTD. Co. was used to type HLA-DQB1 gene polymorphisms of 700 individuals living in south China and 320 individuals in north China. RESULTS: We inspected 10 alleles of HLA-DQB1 and got a series of comprehensive and accurate statistic data. CONCLUSION: It is tested that HLA-DQB1*02, 05, 0601, 0602, 0603 gene frequencies are different obviously(P<0.05) between south and north Chinese. And those data will be useful to kinds of research associated with disease relevant and anthropology research.

[Evaluation on reducing effect of eye drop on herpes simplex virus-I in vitro].

OBJECTIVE: To observe the effect of herbal eye drop Reduqing (clearing toxic heat) on herpes simplex virus (HSV) on the cytopathic effect in cell culture in vitro. METHODS: The maximal non-toxic Reduqing eye drop concentration added to cell culture infected with 100 and 10TCID50 of herpes simplex virus? (HSV-1) to observe the inhibitory effect of the medicine on HSV-I induced cytopathic effect. RESULTS: The Reduqing eye drop at maximal non-toxic concentration could obviously inhibit the cytopatic effect induced by 100TCID50 and 10TCID50 HSV-I. No statistically significant difference was found when compared with 0.1% acyclovir eye drop (P>0.05), on cytopathic effect occurred with boty eye drops. However, there was significant difference when compared with control group(P<0.05). The inhibitory effect of concentrations of Reduqing at 500,000 and 63,000 microg/L was stronger than that of 2,000,000 and 1,000,000 microg/L (P 0.01). The maximal tolerable concentration of Reduqing eye drop by the cell was 2,000,000 microg/L (1:80 dilution), which was higher than that of 5,000 microg/L(1:400 dilution) acyclovir eye drop. CONCLUSIONS: These results suggest that Reduqing eye drop could markedly inhibit the cytopathic effects caused by HSV-I. The Reduqing eye drop showed remarkably low toxic effect to the cells as compared to acyclovir eye drop.