Linked article: This Correspondence comments on van den Noort et al. Click here to view the article.
Linked article: Click here to see the Reply to this Correspondence.
A simple and cost effective sol–gel process for producing vanadium dioxide thin films was developed via thermolysis of V2O5·nH2O (n≈2) VV precursors prepared by dissolving vanadium powder or V2O5 ...powder in 30% hydrogen peroxide solutions. After spin-coating on fused silica substrates and annealing at 750°C in vacuum, without any intermediate gas reducing step, the major phase VO2(M, monoclinic phase) was found in both of the films based on V–H2O2 and V2O5–H2O2 precursor, exhibiting large transmittance changes (>40%) in the IR region (>2000nm) and small hysteresis loop width (<5°C) which were comparable to reported epitaxial VO2 films. The two films have similar metal-to-insulator transition temperature τC=62.5°C, lower than the classical value of 68°C for VO2 thin films. In addition, the method enables simple doping, as found for 0.56at.% W-doped VO2 films. This intrinsically simple solution process followed by one-step annealing makes it potentially useful in smart window applications.
► Cost effective and easy-handle V2O5–H2O2 precursor ► One-step annealing without inert/reducing atmosphere ► Flexible for doping
The skyrmion crystal (SkX) characterized by a triple-q helical spin modulation has been reported to be a unique topological state that competes with the single-q helimagnetic order in ...noncentrosymmetric materials with Dzyaloshinskii-Moriya (DM) interactions. Here, we report the discovery of a rich variety of multiple-q helimagnetic spin structures in the centrosymmetric cubic perovskite SrFeO3 without DM interactions. On the basis of neutron diffraction measurements, we have identified two types of robust multiple-q spin structures that appear in the absence of external magnetic fields: an anisotropic double-q spin spiral and an isotropic quadruple-q spiral hosting a three-dimensional lattice of topological singularities. The present system not only diversifies the family of SkX host materials but furthermore provides an experimental missing link between centrosymmetric lattices and topological helimagnetic order. It also offers perspectives for integration of SkXs into oxide electronic devices.
More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric ...variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses—EEHV2, EEHV3, EEHV6, and EEHV7—found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species.
It is known that multiple cationic charges are required to produce broad-spectrum antimicrobial photosensitizers (PS) for photodynamic inactivation (aPDI) or photodynamic therapy of bacteria and ...fungi. In the present study we describe the synthesis and aPDI testing of a set of derivatives prepared from the parent pheophytin molecule with different numbers of attached side arms (1-3) each consisting of five quaternized cationic groups (pentacationic), producing the corresponding Zn2+pheophorbide-a-N(C2N+C1C3)5 (Zn-Phe-N5+, 5 charges), Zn2+chlorin e6-N(C2N+C1C3)52 (Zn-Chl-N10+, 10 charges) and Zn2+mesochlorin e6-N(C2N+C1C3)53 (Zn-mChl-N15+, 15 charges). Moreover, a conjugate between Zn-Phe-N5+ and the antibiotic vancomycin called Van-Zn2+-m-pheophorbide-N(C2N+C1C3)5 (Van-Zn-mPhe-N5+) was also prepared. The aPDI activities of all compounds were based on Type-II photochemistry (1O2 generation). We tested these compounds against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Escherichia coli, and the fungal yeast Candida albicans. All three compounds were highly active against MRSA, giving eradication (≥6 logs of killing) with <1.0 μM and 10 J cm-2 of 415 nm light. The order of activity was Zn-Phe-N5+ > Zn-Chl-N10+ > Zn-mChl-N15+. In the case of E coli the activity was much lower (eradication was only possible with 50 μM Zn-mChl-N15+ and 20 J cm-2). The order of activity was the reverse of that found with MRSA (Zn-mChl-N15+ > Zn-Chl-N10+ > Zn-Phe-N5+). Activity against C. albicans was similar to E. coli with Zn-mChl-N15+ giving eradication. The activity of Van-Zn-mPhe-N5+ was generally lower than that of Zn-Phe-N5+ (except for E. coli). Red (660 nm) light was also effective as might be expected from the absorption spectra. An initial finding that Van-Zn-mPhe-N5+ might have higher activity against vancomycin resistant Enterococcus fecium (VRE) strains (compared to vancomycin sensitive strains) was disproved when it was found that VRE strains were also more sensitive to aPDI with Zn-Phe-N5+. The minimum inhibitory concentrations of Van-Zn-mPhe-N5+ were higher than those of Van alone, showing that the antibiotic properties of the Van moiety were lessened in the conjugate. In conclusion, Zn-Phe-N5+ is a highly active PS against Gram-positive species and deserves further testing. Increasing the number of cationic charges increased aPDI efficacy on C. albicans and Gram-negative E. coli.
Summary
Background
Irritable bowel syndrome patients with diarrhoea (IBS‐D) often report intolerance to milk; however, the mechanism underlying these symptoms is unknown.
Aim
To assess the role of ...psychological factors, immune activation and visceral sensitivity on the development of lactose intolerance (LI) in IBS‐D patients.
Methods
Fifty‐five IBS‐D patients and 18 healthy controls (HCs) with lactase deficiency underwent a 20‐g lactose hydrogen breath test (LHBT). Patients were categorised as lactose malabsorption (LM; malabsorption only) or LI malabsorption plus increase in total symptom score (TSS). Measurements included (i) psychological status; (ii) enteric biopsies with quantification of mast cells (MCs), T‐lymphocytes and enterochromaffin cells; (iii) serum cytokines; (iv) rectal sensitivity before and after lactose ingestion.
Results
LI was more prevalent in IBS‐D patients than HCs 25/55 (46%) vs. 3/18 (17%), P = 0.029. IBS‐D patients with LI had (i) higher levels of anxiety than those with LM (P = 0.017) or HCs (P = 0.006); (ii) increased mucosal MCs compared with LM (P = 0.006) and HCs (P < 0.001); (iii) raised serum TNF‐α compared with LM (P = 0.034) and HCs (P < 0.001) and (iv) increased rectal sensitivity after lactose ingestion compared with LM (P < 0.001) or HCs (P < 0.001). Severity of abdominal symptoms after lactose ingestion was associated with the increase in visceral sensitivity after lactose intake (r = 0.629, P < 0.001), MCs (r = 0.650, P < 0.001) and anxiety (r = 0.519, P < 0.001).
Conclusions
IBS‐D patients with lactose intolerence are characterised by anxiety, mucosal immune activation and increased visceral sensitivity after lactose ingestion. The presence of these biomarkers may indicate an IBS phenotype that responds to dietary therapy and/or mast cell stabilisers (ClinicalTrials.gov Identifier: NCT01286597).
Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out ...photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine.
Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome resistant microbes.
We synthesized C60-fullerene (LC16) bearing decaquaternary chain and ...deca-tertiary-amino groups that facilitates electron-transfer reactions via the photoexcited fullerene. Addition of the harmless salt, potassium iodide (10 mM) potentiated the ultraviolet A (UVA) or white light-mediated killing of Gram-negative bacteria Acinetobacter baumannii, Gram-positive methicillin-resistant Staphylococcus aureus and fungal yeast Candida albicans by 1-2+ logs. Mouse model infected with bioluminescent Acinetobacter baumannii gave increased loss of bioluminescence when iodide (10 mM) was combined with LC16 and UVA/white light.
The mechanism may involve photoinduced electron reduction of (1)(C60>)* or (3)(C60>)* by iodide producing I· or I2 followed by subsequent intermolecular electron-transfer events of (C60>)-· to produce reactive radicals.
Our study suggests that the activated ICOS+PD‐1+Tfh cells are involved in the disease activity of UC, and the underlying mechanisms may be through promoting the differentiation of functional B cells ...caused by elevated serum IL‐4 and IL‐21. Furthermore, activated ICOS+PD‐1+Tfh cells, together with PD‐1+Tfh cells or not, are reliable biomarkers for UC disease activity monitoring.
Summary
Inducible co‐stimulator‐positive (ICOS) and programmed cell death 1‐positive (PD‐1) are important markers for follicular helper T cells (Tfh); however, their roles and clinical values in ulcerative colitis (UC) remain unknown. In this study, we recruited 68 UC patients and 34 healthy controls. Circulating ICOS+, PD‐1+ and ICOS+PD‐1+ Tfh subsets were analyzed by flow cytometry. Twelve active UC patients achieving remission after treatment with 5‐aminosalicylic acid were followed‐up and Tfh subset changes were analyzed. Serum immunoglobulin (Ig)G, C‐reactive protein (CRP), interleukin (IL)‐4 and IL‐21 levels and B cell subsets were analyzed and Mayo scores were calculated. Correlation analyses were performed between Tfh subsets and the clinical indicators. Receiver operating characteristic (ROC) curves were generated to evaluate the efficiency of Tfh subsets for disease monitoring. We found that levels of ICOS+, PD‐1+ and ICOS+PD‐1+ Tfh cells were significantly increased in active UC and significantly decreased when achieving clinical remission. Activated ICOS+PD‐1+Tfh cells were positively correlated with serum CRP and Mayo scores. Furthermore, ICOS+PD‐1+ Tfh cells were significantly correlated with circulating new memory B cells and plasmablasts, as well as serum IgG, IL‐4 and IL‐21. ROC analyses showed that when ICOS+PD‐1+ Tfh cells were used in combination with PD‐1+ Tfh cells, the diagnostic efficacy in distinguishing active UC from stable remission patients was higher than that of any one used alone, with area under curve (AUC) value 0·931. Our findings suggest that increased ICOS+PD‐1+ Tfh cells are associated with the activation of B cells in the pathogenesis of UC, and may be a potential biomarker for UC disease monitoring.
Mutations in SCN1A, the gene encoding the α subunit of Nav1.1 channel, can cause epilepsies with wide ranges of clinical phenotypes, which are associated with the contrasting effects of channel ...loss-of-function or gain-of-function. In this project, CRISPR/Cas9- and TALEN-mediated genome-editing techniques were applied to induced pluripotent stem cell (iPSC)-based-disease model to explore the mechanism of epilepsy caused by SCN1A loss-of-function mutation. By fluorescently labeling GABAergic subtype in iPSC-derived neurons using CRISPR/Cas9, we for the first time performed electrophysiological studies on SCN1A-expressing neural subtype and monitored the postsynaptic activity of both inhibitory and excitatory types. We found that the mutation c.A5768G, which led to no current of Nav1.1 in exogenously transfected system, influenced the properties of not only Nav current amount, but also Nav activation in Nav1.1-expressing GABAergic neurons. The two alterations in Nav further reduced the amplitudes and enhanced the thresholds of action potential in patient-derived GABAergic neurons, and led to weakened spontaneous inhibitory postsynaptic currents (sIPSCs) in the patient-derived neuronal network. Although the spontaneous excitatory postsynaptic currents (sEPSCs) did not change significantly, when the frequencies of both sIPSCs and sEPSCs were further analyzed, we found the whole postsynaptic activity transferred from the inhibition-dominated state to excitation in patient-derived neuronal networks, suggesting that changes in sIPSCs alone were sufficient to significantly reverse the excitatory level of spontaneous postsynaptic activity. In summary, our findings fill the gap of our knowledge regarding the relationship between SCN1A mutation effect recorded on exogenously transfected cells and on Nav1.1-expressing neurons, and reveal the physiological basis underlying epileptogenesis caused by SCN1A loss-of-function mutation.
PDF
