A multifunctional chitosan based porous membrane for pH-responsive antibacterial activity and promotion of infected wound healing.

Unsatisfactory mechanical and antibacterial properties restricted the solo use of chitosan (CS) as a wound dressing. In this work, a novel CS/hydroxyapatite/ZIF-8 (CS/HAp/ZIF-8, CHZ-10) porous membrane was facilely constructed by in situ loading of ZIF-8 on CS/HAp. The advantages of the three compositions were rationally integrated, and the multifunctionality and practicality of this CS-based dressing were improved. HAp not only improved the mechanical strength and stability of CS, but also promoted cell proliferation and accelerated hemostasis with its released Ca2+. Meanwhile, ZIF-8 enhanced the antibacterial activity of CS by releasing antibacterial Zn2+ in a pH-responsive and sustainable manner, avoiding the bio-accumulation toxicity of heavy metals. Compared with CS/HAp and conventionally used gauze, CHZ-10 exhibited superior coagulation and hemolytic ability, as well as outstanding antibacterial activity against E. coli and S. aureus. Besides, both in vivo observation and histological evaluation demonstrated that CHZ-10 could not only effectively inhibit bacterial infection and reduce inflammation of the wound, but also promote its re-epithelialization, granulation, tissue formation and collagen fibre growth, leading to effectively enhanced wound-healing. This work provides a new method for the easy construction of multifunctional antibacterial dressings based on CS, showing promise for application in clinical wound care.

Enhancing peroxidase-like activity of AuNPs through headspace reaction: A signal amplification strategy for colorimetric and fluorescent sensing of trace Hg2.

BACKGROUND: Recently, headspace single-drop microextraction (HS-SDME) has attracted some attention for developing sensitive and selective colorimetric assays due to its excellent capability to reduce matrix interference and enrich analytes. However, the single droplet limits direct visual observation of color change and its quantitative measurement suffers from reduced optical path length. Therefore, amplifying the detection signals in both volume and intensity is an important and challenging task for improving the sensitivity, stability, and accuracy of such colorimetric analysis. RESULTS: In this study, a "headspace-nanoenzyme" (HS-NE) strategy was proposed that successfully addressed these challenges and enabled the colorimetric and fluorescent dual-mode detection of trace Hg2+. Atomic Hg0, generated via chemical vapor generation (CVG), underwent headspace reaction with AuNPs droplet to form Au@HgNPs, thus catalyzing the oxidation of o-phenylenediamine (OPD) in the presence of H2O2. The absorbance and fluorescence intensity of oxidized OPD were proportion to the concentration of Hg2+ in the sample solution. Due to the greatly enhanced peroxidase-like activity by Au@HgNPs, the limit of detection was as low as 0.98 nM and 0.21 nM for the colorimetric and fluorescent modes, respectively. The applicability of this assay was further demonstrated with determination of Hg2+ in real environmental and biological samples. Moreover, a convenient and cost-effective paper-based sensing platform was fabricated for rapid on-site detection of Hg2+. SIGNIFICANCE AND NOVELTY: This novel HS-NE strategy combines HS-SDME and nanoenzyme-based sensing to achieve dual effects of eliminating matrix interference and amplifying the measurement signal, resulting in improved accuracy, enhanced stability, high sensitivity, and exceptional selectivity, with great potential for on-site determination of trace Hg2+.

Concentration- and Self-Catalysis-Dominated Rapid Synthesis of Multifunctional UiO-66(Ce) for Dual-Mode Sensing of Tetracycline.

Simple and rapid synthesis of multifunctional metal-organic frameworks (MOFs) at room temperature (RT) with their multifunction controllable is still appealing for further expansion of the practical applications of MOFs. Herein, in this work, rapid RT synthesis of a multifunctional UiO-66(Ce) [M-UiO-66(Ce)] with both oxidase-like activity and fluorescence emission properties was facilely achieved within 15 min through a straightforward reactant concentration modulation and self-catalytic postmodification strategy. Appropriate concentrations of cerium ammonium nitrate or 1,4-benzenedicarboxylic acid (BDC) were beneficial for the synthesis of UiO-66(Ce) with better crystallization. During the postmodification process, through regulation of the self-photocatalysis of UiO-66(Ce), a high conversion rate from BDC to BDC-OH of up to 14% can be obtained, resulting in a significantly enhanced fluorescence signal of M-UiO-66(Ce) within 2 min. Moreover, M-UiO-66(Ce) enabled the accurate and reliable detection of tetracycline (TC) in real samples. Besides, the colorimetric and fluorescence modes complemented each other, expanding the linear range of TC detection and exhibiting its great potential for practical applications. This work provides new insights for the convenient and rapid synthesis of multifunctional materials based on MOFs, which is favorable for promoting the large-scale preparation of MOFs and their practical application in on-site environmental pollutant sensing.

Tb3+-Based Off-On Fluorescent Platform for Multicolor and Dosage-Sensitive Visualization of Bacterial Spore Marker.

Developing a novel strategy for the sensitive and rapid detection of pathogenic bacterial spores in field or on-site settings will be helpful in minimizing their potential threats to human health, environmental safety, and food safety. In this study, Tb3+ was combined with glutathione (GSH)-modified copper nanoclusters (CuNCs), and an aggregation-induced emission (AIE) fluorescent probe based on Tb-GSH-CuNCs was fabricated for dipicolinic acid (DPA, a pathogenic bacterial spore marker) sensing. Making use of the competitive binding of Tb3+ between GSH-CuNCs and DPA, a multicolor sensing of DPA was facilely realized without introducing fluorescent materials as the reference. Due to an "off-on" response mechanism of the AIE fluorescent probe, this multicolor response to DPA exhibited a feature of rich color gradients and highly discriminative color change, allowing a dosage-sensitive visual quantification of DPA. The DPA with a concentration even as low as 0.5 µM can still be identified by the naked eye. Moreover, together with a smartphone app, which can extract the R (red), G (green), and B (blue) values from the probe system, a portable platform can be established for sensitive DPA quantification in the range of 0.5-70 µM, showing great potential for the practical monitoring of DPA in field or on-site settings.

Whole Transcriptome Sequencing of Peripheral Blood Shows That Immunity/GnRH/PI3K-Akt Pathways Are Associated With Opioid Use Disorder.

Background: Opioid use disorder (OUD), which is most commonly exhibited as addiction, is a persistent chronic disease that places a burden on families and society. Various peripheral traits have been linked to OUD in the past, but research on this topic is insufficient. Methods: Seven male patients with OUD and 7 male healthy controls with matched demographic and clinical data were enrolled in this study. Peripheral blood RNA was used to construct an rRNA-removed library and a small RNA library. The peripheral transcriptomic differences between the two groups were investigated using RNA-seq. Differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) were identified by bioinformatics methods, and functional enrichment analysis with differentially expressed RNAs was performed to investigate the potential biological mechanisms of OUD. Results: A total of 229 mRNAs (115 upregulated, 114 downregulated), 416 lncRNAs (191 upregulated, 225 downregulated), 17 circRNAs (16 upregulated, 1 downregulated) and 74 miRNAs (42 upregulated, 32 downregulated) were differentially expressed between the OUD group and the healthy control group. Functional enrichment analysis with differentially expressed mRNAs showed that immunity, GnRH secretion, and PI3K-Akt signaling pathways were associated with OUD. Immunity-, JAK-STAT-, and insulin-related pathways were enriched in functional enrichment analysis of target genes predicted by differentially expressed miRNAs. Conclusion: We identified hundreds of differentially expressed genes that were enriched in immunity, GnRH secretion and PI3K-Akt signaling pathways. Some genes with significant changes might be used as potential biomarkers for progression and treatment of OUD.

Possible Avoidant Personality Disorder Magnifies the Association Between Bullying Victimization and Depressive Symptoms Among Chinese University Freshmen.

BACKGROUND: Bullying victimization has been associated with depressive symptoms in Chinese university students. This study examined the moderating effect of possible avoidant personality disorder (APD) on association between bullying victimization and depressive symptoms in university freshmen. METHODS: A total of 1,453 freshmen were recruited from a comprehensive university in Wuhan, China, and administered a self-report questionnaire. The APD subscale of Personality Diagnostic Questionnaire-Version 4 and Beck Depression Inventory were used to measure the presence of possible APD and depressive symptoms, respectively. The moderating effect of possible APD was examined by testing the statistical significance of the interaction between victimization and possible APD in multiple logistic regression analysis. RESULTS: The prevalence of depressive symptoms was 24.8%. In multiple logistic regression analysis, the interaction between bullying victimization and possible APD was significantly associated with depressive symptoms (OR: 1.80, P = 0.029). Subsequent subgroup analyses according to the status of possible APD showed that, the victimization-depression association was stronger among freshmen with possible APD (OR: 3.23, P < 0.001) than those without possible APD (OR: 1.82, P = 0.001). CONCLUSION: In Chinese university freshmen, bullying victimization is significantly associated with depressive symptoms, and possible APD magnifies the victimization-depression association. Bullied freshmen, particularly freshmen with possible APD, could be considered as the target group of campus-based depression intervention programs.

A colorimetric assay for the determination of trace arsenic based on in-situ formation of AuNPs with synergistic effect of arsine and iodide.

In this work, we propose a colorimetric assay for the determination of trace arsenic based on in-situ formation of AuNPs with the synergistic effect of arsine (AsH3) and iodide. AsH3, generated by hydride generation of AsIII in the sample or standard solution, enters into the HAuCl4 solution containing polyvinyl alcohol (PVA) and KI, and then reacts rapidly to form AuNPs, resulting in the solution color changing from light yellow to pink. Hydride generation applied here not only produces a strong reducing agent AsH3, but also effectively reduces matrix interference. The introduction of I- promotes the reaction by reducing the Au precursor from trivalent state to monovalent state, thus accelerating the formation of AuNPs with AsH3 and improving the sensitivity for the detection of arsenic. Trace AsIII as low as 10 µg L-1 in 3 mL sample solution can produce the change in color visible to the naked eye. Moreover, the use of the stabilizer PVA and the gaseous strong-reducing agent AsH3 evenly dispersed in the reaction solution lead to the formation of well-distributed and fine AuNPs of size changing little with the dosage of AsH3. The whole analysis process only takes 30 min under ambient condition without complicated synthesis and pretreatment. The proposed assay is simple, stable, sensitive and selective, providing a convenient and cost-effective choice for on-site trace arsenic detection in real samples.

A facile photochemical strategy for the synthesis of high-performance amorphous MoS2 nanoparticles.

It is difficult to avoid the formation of polysulfides by traditional chemical methods, and the synthesis of high purity amorphous MoS2 nanomaterials under ambient conditions is still a challenging task. Here we present a new and facile photochemical strategy for the synthesis of amorphous MoS2 nanomaterials, which is achieved by irradiating a mixed solution containing ammonium molybdate, formic acid and sodium sulfide simply with a Xe lamp for 3 min. The mechanism study reveals that the key step in this synthesis is the photolysis of formic acid to produce free radicals which can rapidly reduce Mo6+ to Mo4+, which then combines with S2- to form MoS2 and inhibits the formation of S-S2- by preventing S2- from participating in the reduction reaction. In addition, the results of a series of experiments indicate that the as-prepared amorphous MoS2 features a small particle size, uniform morphology and relatively large specific surface area, and shows excellent performance in the removal of inorganic heavy metal ions (mercury, lead and cadmium ions) and organic pollutants (rhodamine B and tetracycline), catalase catalysis and a lithium battery anode, showing its great potential and broad application prospects in the fields of environmental remediation, clean energy and green catalysis.

Nano-emulsion as a vaccine adjuvant can enhance the humoral immunity against influenza in aged and young mice / 中华微生物学和免疫学杂志

Objective@#To evaluate the immunogenicity of split influenza H1N1 vaccine formulated with an oil-in-water nano-emulsion adjuvant in aged mice and young mice.@*Methods@#A nano-emulsion adjuvant formulated split influenza H1N1 vaccine was used to immunize aged and young mice through intramuscular injection. Each mouse was immunized with 0.012 μg of hemagglutinin (HA) twice with an interval of 28 d. Hemagglutination inhibition (HI) titers in serum were measured 27 d after first immunization. Serum HI, IgG1 and IgG2a titers were detected 14 d after the last immunization. No adjuvant-formulated vaccine and normal saline (NS) were used to set up control groups. Virus challenge test was carried out using 10 times the median lethal dose (LD50) of A/Puerto Rico/8/34 (H1N1) strain two weeks after the last immunization and the protective effects were assessed through measuring the dynamic changes in body weight and survival rate.@*Results@#Higher levels of serum HI, IgG1 and IgG2a antibodies and higher HI antibody conversion rates were induced in the adjuvant groups, especially in the aged mice group, than in the control groups. Nano-emulsion adjuvant improved the immunogenicity of HA and mouse immunity to A/Puerto Rico/8/34 (H1N1).@*Conclusions@#Nano-emulsion adjuvant could enhance the immunogenicity of influenza antigens, especially in aged mice.

Preliminary evaluation of adjuvant effects of cyclic dinucleotides ( CDN ) on immune responses to nasal spray influenza vaccine / 中华微生物学和免疫学杂志

Objective To analyze the immunostimulatory effects of cyclic dinucleotides ( CDN) on immune responses to a nasal spray influenza split virus vaccine and to evaluate its potential as a mucosal ad-juvant. Methods A H1N1 influenza split virus vaccine combined with different CDN was used for mouse immunization. Each mouse was intranasally immunized twice with 4. 5μg of hemagglutinin (HA) and 10μg of CDN with an interval of 21 d. Titers of hemagglutination inhibition ( HI) antibodies in serum, secretory IgA ( sIgA) in bronchoalveolar lavage fluid and IgG in serum were detected 21 d after the last immunization. Immunostimulatory activities of different CDN were compared. Effects of cyclic di-GMP ( c-di-GMP) and ch-itosan (CSN) on the immunogenicity of H1N1 and H7N9 influenza split vaccines were analyzed and com-pared. H1N1 influenza split vaccine combined with c-di-GMP or CSN was used to immunize mice. Three weeks after the last immunization, these mice were challenged with 10 times the median lethal dose ( LD50 ) of A/Puerto Rico/8/34 (H1N1) influenza virus. Survival rates of the mice were observed for 14 d. Results All three CDN induced high levels of HI antibodies and IgG in serum and sIgA in BALF. HI antibody sero-conversion rates were also higher than those of the control groups. c-di-GMP was superior to CSN in enhan-cing the immunogenicity of H1N1 and H7N9 antigens as higher titers of HI antibodies in serum and sIgA in BALF were induced. Conclusions CDN could enhance the immunogenicity of influenza antigens with better efficacy than CSN adjuvant.

Characteristics and potentials of stem cells derived from human degenerated nucleus pulposus: potential for regeneration of the intervertebral disc.

BACKGROUND: Eliminating the symptoms during treatment of intervertebral disc degeneration (IVDD) is only a temporary solution that does not cure the underlying cause. A biological method to treat this disorder may be possible by the newly discovered nucleus pulposus derived stem cells (NPDCs). However, the uncertain characteristics and potential of NPDCs calls for a comprehensive study. METHODS: In the present study, nucleus pulposus samples were obtained from 5 patients with IVDD undergoing discectomy procedure and NPDCs were harvested using fluorescence activated cell sorting (FACS) by the co-expression of GD2+ and Tie2+. After in vitro expansion, the properties of NPDCs were compared with those of bone marrow mesenchyme stem cells (BMSCs) from the same subjects. RESULTS: NPDCs performed similar properties in cell colony-forming ability, cell proliferation rate, cell cycle and stem cell gene expression similar to those of BMSCs. In addition, NPDCs could be differentiated into osteoblasts, adipocytes, and chondrocytes, and are found to be superior in chondrogenesis but inferior in adipocyte differentiation. CONCLUSIONS: NPDCs derived from the degenerated intervertebral disc still keep the regeneration ability similar to BMSCs. Besides, the superior capacity in chondrogenesis may provide a promising cell candidate for cell-based regenerative medicine and tissue engineering in IVDD.

Tuning the properties of the metal-organic framework UiO-67-bpy via post-synthetic N-quaternization of pyridine sites.

A new UiO-67-type zirconium metal organic framework (MOF) material UiO-67-bpy-Me (bpy = 2,2-bipyridine-4,4'-dicarboxylic acid, Me = methyl) was prepared by N-quaternization of the pyridine sites in UiO-67-bpy. After N-quaternization, the pristine neutral framework turned cationic while its high thermal and chemical stabilities were primarily preserved. Fast and enhanced anionic dye adsorption was observed in UiO-67-bpy-Me. In addition, despite the decrease in surface area and pore volume, UiO-67-bpy-Me exhibited an evident increase in CO2 uptake compared to UiO-67-bpy. The enhancement was ascribed to the strong interactions between CO2 and the N-quaternized framework. More importantly, as the N-quaternization has changed the electronic structure of the organic linker. UiO-67-bpy-Me showed optical absorption up to ca. 800 nm with a large red shift of 450 nm compared to the pristine UiO-67-bpy (ca. 350 nm). The extended optical absorption may lead to more efficiency in light utilization. A proof-of-concept demonstration showed that UiO-67-bpy-Me could more efficiently catalyze methyl-orange degradation under UV-Vis light irradiation than the pristine UiO-67-bpy. These findings demonstrate that N-quaternization could serve as a facile post-synthetic modification method to tune the chemical/physical properties of free pyridyl-containing MOFs.

Evaluation of immunogenicity of an immune complexed hepatitis B vaccine / 中华微生物学和免疫学杂志

Objective To evaluate the immunogenicity of an immune complexed hepatitis B vac-cine ( HBsAg-HBIG immune complexes , IC) in mouse and cynomolgus monkeys by using recombinant hepa-titis B vaccine ( Saccharomyces cerevisiae, HBsAg) as the control .Methods BALB/c mice were vaccinated with single dose of IC and single dose of HBsAg respectively and then serum samples were collected at differ -ent time points for the detection of dynamic anti-HBs by using ELISA .The serum anti-HBs titers in BALB/c mice vaccinated with different immunization strategies were also analyzed .ELISPOT assay was performed to detect the numbers of IFN-γSFC and IFN-γpositive rate in splenocytes of BALB/c mice intramuscularly im-munized with IC, HBsAg or standard hepatitis B vaccine at 5μg/mouse.ED50 was measured to evaluate the stability of IC.Twelve cynomolgus monkeys were equally divided into two groups and immunized with high dose (100 μg) and low dose (20 μg) of IC respectively and then , serum anti-HBs levels at different time points were detected .Results The serum anti-HBs titers in IC immunized group at different time points were higher than those immunized with HBsAg .Moreover, the anti-HBs titer induced by two doses of IC reached a level comparable to that elicited by three doses of HBsAg .ELISPOT assay showed that both the numbers of IFN-γSFC and IFN-γpositive rate were the highest in IC immunized group as compared with those immunized with HBsAg and standard hepatitis B vaccine .IC had a lower ED50 than HBsAg, indicating a good long term stability .Cynomolgus monkeys immunized with high or low dose of IC produced high levels of anti-HBs titer during a long time period .Conclusion IC has a higher immunogenicity inducing both hu-moral immunity and cellular immunity as compared with HBsAg or standard hepatitis B vaccine .

Effect of AOT-assisted multi-walled carbon nanotubes on antibacterial activity.

The dispersing power of surfactant-modified multiwalled carbon nanotubes (MWCNTs) and their effect on the antibacterial activity were examined. The MWCNTs were modified using a dioctyl sodium sulfosuccinate (AOT) surfactant. UV-vis spectroscopy and transmission electron microscopy (TEM) were used to characterize the dispersion of MWCNTs in the aqueous phase. Fourier transform infrared spectroscopy confirmed the results of UV-vis spectroscopy and TEM, indicating that the AOT molecules had been adsorbed successfully onto the MWCNT surface. The highly dispersed AOT-modified MWCNTs showed strong antibacterial activity to Streptococcus mutans. The fluorescence images showed that the AOT-modified MWCNTs were capable of capturing bacteria and forming cell aggregates as well as killing them. The optical density growth curves and colony-forming units assays confirmed that the antibacterial activity of the AOT-modified MWCNTs was concentration-dependent and treatment time-dependent. This finding might be useful for applications of AOT-modified MWCNTs as an antibacterial agent to eliminate pathogens from a biocontaminated water phase.

Treatment of advanced non-small cell lung cancer with extracorporeal high frequency thermotherapy combined with Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and benefit response of extracorporeal high frequency thermotherapy (EHFT) combined with Chinese medicine (CM) in the treatment of patients with advanced nonsmall cell lung cancer.</p><p><b>METHODS</b>The study adopted a prospective, small sample and randomized controlled method, and the advanced non-small cell lung cancer patients were assigned to two groups according to the table of random digits, one having the treatment of EHFT combined with CM (the treatment group), the other only with CM (the control group). The patients in the treatment group were treated with EHFT one hour once per day, together with CM differentiation decoction, 250 mL orally taken, twice daily for 14 days as one cycle, and 3-4 cycles was performed. The patients in the control group were treated only with CM differentiation decoction using the same dose as the treatment group. The efficacies were evaluated after three to four cycles of treatment. Primary endpoints were disease control rate (DCR) and time to progression (TTP). Secondary endpoints were overall survival time and 1-year survival rate.</p><p><b>RESULTS</b>Sixty-six patients accomplished the study. After the patients underwent different treatments, none of the patients got a complete response or partial response in both groups. In the treatment group, DCR was 72.2%, and 10 had progression of disease (28.8%), while the DCR of the control group was 63.3%, and 11 had progression of disease (36.7%); there was a significant statistical difference (P <0.05), suggesting that the combined regimen had superiority on the DCR. As for long-term efficacy, the median survival time (MST) of the treatment group was 7.5 months, TTP was 5.5 months, and 1-year survival rate was 21.4 %; in the control group, the results were 6.8 months, 4.5 months and 16.6% respectively. There was significant statistical difference on TTP (P <0.05), but no difference on MST or 1-year survival rate.</p><p><b>CONCLUSION</b>EHFT combined with CM differentiation has better tolerance and short-term efficacy in the treatment of patients with advanced NSCLC.</p>