A series of new amino (NH)-type hydrogen-bonding (H-bonding) compounds comprising 2-(2′-aminophenyl)benzothiazole and its extensive derivatives were designed and synthesized. Unlike in the hydroxyl ...(OH)-type H-bonding systems, one of the amino hydrogens can be replaced with electron-donating/withdrawing groups. This, together with a versatile capability for modifying the parent moiety, makes feasible the comprehensive spectroscopy and dynamics studies of amino-type excited-state intramolecular proton transfer (ESIPT), which was previously inaccessible in the hydroxyl-type ESIPT systems. Empirical correlations were observed among the hydrogen-bonding strength (the N–H bond distances and proton acidity), ESIPT kinetics, and thermodynamics, demonstrating a trend that the stronger N–H···N hydrogen bond leads to a faster ESIPT, as experimentally observed, and a more exergonic reaction thermodynamics. Accordingly, ESIPT reaction can be harnessed for the first time from a highly endergonic type (i.e., prohibition) toward equilibrium with a measurable ESIPT rate and then to the highly exergonic, ultrafast ESIPT reaction within the same series of amino-type intramolecular H-bond system.
ortho‐Methyl effects are exploited to tune steric hindrance between side‐chain N,N′‐diaryls and polycyclic dihydrodibenzoa,cphenazine, and in turn control the conformations of ...N,N′‐diphenyl‐dihydrodibenzoa,cphenazine (DPAC) and its ortho‐methyl derivatives Mx‐My (x=0, 1 or 2, y=1 or 2, x and y correlate with the number of methyl groups in the ortho‐positiond of N,N′‐diphenyl). The magnitude of steric hindrance increases as x and y increase, and the V‐shaped dihydrodibenzoa,cphenazine skeleton is gradually tuned from a bent (DPAC) to planar (M2‐M2) structure in the ground state. As a result, the relaxation of the excited‐state structure of DPAC and its numerous analogues could be mimicked by model structures Mx‐My, demonstrating for the first time the the conformation change from bent‐to‐planar and hence a large range of energy‐gap tuning of polycyclic conjugated structures controlled by the steric hindrance.
Six (D)PAC: ortho‐Methyl effects are exploited to tune the steric hindrance between side‐chain N,N′‐diaryls and polycyclic dihydrodibenzoa,cphenazine, and in turn control the conformation and color of N,N′‐diphenyl‐dihydrodibenzoa,cphenazine (DPAC) and its ortho‐methyl derivatives. The results show that simple insertion of a small methyl group overcomes the energy barrier to planarization in the ground state.
Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)‐positive patients. Incidence of and associated factors ...with early seroreversion (loss of seroresponse) among HIV‐positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV‐positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case‐control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow‐up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow‐up of 611 days. In a case‐control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio aOR, 1.703; 95% confidence interval CI, 1.292‐2.323, per 10‐kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067‐7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020‐0.154) and 0.837 (95% CI, 0.704‐0.979, per 100‐cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two‐dose HAV vaccination occurred in 3.9% of HIV‐positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV‐positive adults with predictors of early seroreversion.
Changes in mitochondrial dynamics (fusion and fission) are known to occur during stem cell differentiation; however, the role of this phenomenon in tissue aging remains unclear. Here, we report that ...mitochondrial dynamics are shifted toward fission during aging of Drosophila ovarian germline stem cells (GSCs), and this shift contributes to aging‐related GSC loss. We found that as GSCs age, mitochondrial fragmentation and expression of the mitochondrial fission regulator, Dynamin‐related protein (Drp1), are both increased, while mitochondrial membrane potential is reduced. Moreover, preventing mitochondrial fusion in GSCs results in highly fragmented depolarized mitochondria, decreased BMP stemness signaling, impaired fatty acid metabolism, and GSC loss. Conversely, forcing mitochondrial elongation promotes GSC attachment to the niche. Importantly, maintenance of aging GSCs can be enhanced by suppressing Drp1 expression to prevent mitochondrial fission or treating with rapamycin, which is known to promote autophagy via TOR inhibition. Overall, our results show that mitochondrial dynamics are altered during physiological aging, affecting stem cell homeostasis via coordinated changes in stemness signaling, niche contact, and cellular metabolism. Such effects may also be highly relevant to other stem cell types and aging‐induced tissue degeneration.
Aging shifts mitochondrial balance toward fission; fragmented mitochondria with low membrane potential (△Ψ), and ROS levels, along with decreased BMP signaling causing GSC loss. Marf depletion induces highly fragmented mitochondria with low fatty acid (FA) oxidation, causing oil droplet (LD) accumulation, and attenuated BMP signaling that cause GSC loss. Drp1 depletion generates elongated mitochondria and increased E‐cadherin expression to strengthen GSC competitiveness for niche occupancy.
Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal ...degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye's accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic
mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.
Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that causes severe morbidity and mortality. Up to date, there is no approved or licensed vaccine or antiviral ...medicines can be used to treat MERS-CoV-infected patients. Here, we analyzed the antiviral activities of resveratrol, a natural compound found in grape seeds and skin and in red wine, against MERS-CoV infection.
We performed MTT and neutral red uptake assays to assess the survival rates of MERS-infected Vero E6 cells. In addition, quantitative PCR, western blotting, and immunofluorescent assays determined the intracellular viral RNA and protein expression. For viral productivity, we utilized plaque assays to confirm the antiviral properties of resveratrol against MERS-CoV.
Resveratrol significantly inhibited MERS-CoV infection and prolonged cellular survival after virus infection. We also found that the expression of nucleocapsid (N) protein essential for MERS-CoV replication was decreased after resveratrol treatment. Furthermore, resveratrol down-regulated the apoptosis induced by MERS-CoV in vitro. By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV.
In this study, we first demonstrated that resveratrol is a potent anti-MERS agent in vitro. We perceive that resveratrol can be a potential antiviral agent against MERS-CoV infection in the near future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The recent progress of efficiency improvement, emission color tuning, and lifetime elongation of blue organic light-emitting diodes (OLEDs) is reviewed. The latter is one of the most important ...bottlenecks for OLED development. The current status of blue light-emitting material design with emission mechanisms such as fluorescence (F), phosphorescence (Ph), thermally activated delayed fluorescence (TADF), and hybridized local and charge transfer (HLCT) is introduced in the first part of this review. Compared to red and green devices, the long exciton lifetime of the high energy triplet exciton in a blue OLED is the one of the main issues. To avoid the accumulation of high energy triplet excitons in the emitter for blue OLEDs, assisted triplet-triplet fluorescence (TTF) and Hyperfluorescence™ are employed to harvest the triplet excitons. In the second part of this review, we focus on issues from an application viewpoint: what are the requirements of blue OLEDs for display and lighting technologies in terms of efficiency, color, and lifetime? Key performance metrics of blue OLEDs with different technologies over time are summarized. Independent of technology, the trend is similar: the external quantum efficiency improves for the first stage of research, followed by color tuning, and then finally lifetime elongation. The state-of-the-art device performance of blue OLEDs with various emission mechanisms is illustrated. Although Ph- and TADF-emission based devices show satisfactory efficiency and electroluminescence (EL) spectra, despite having a lower efficiency TTF-emission based devices are the mainstream for real applications due to their relatively long operation lifetime. Blue Ph-OLEDs have the potential for lighting applications with suitable material selection and device design. We collected the published results and tried our best to make a fair comparison of the operation lifetime among different technologies. Finally, we discuss the possible future outlook from different viewpoints including new materials, device designs, and applications of blue OLEDs.
Emission mechanisms for OLEDs and their characteristics.
Green tea and its bioactive components, especially polyphenols, possess many health-promoting and disease-preventing benefits, especially anti-inflammatory, antioxidant, anticancer, and metabolic ...modulation effects with multi-target modes of action. However, the effect of tea polyphenols on immune function has not been well studied. Moreover, the underlying cellular and molecular mechanisms mediating immunoregulation are not well understood. This review summarizes the recent studies on the immune-potentiating effects and corresponding mechanisms of tea polyphenols, especially the main components of (–)-epigallocatechin-3-gallate (EGCG) and (–)-epicatechin-3-gallate (ECG). In addition, the benefits towards immune-related diseases, such as autoimmune diseases, cutaneous-related immune diseases, and obesity-related immune diseases, have been discussed.
We propose a new concept exploiting thermally activated delayed fluorescence (TADF) molecules as photosensitizers, storage units and signal transducers to harness solar thermal energy. Molecular ...composites based on the TADF core phenoxazine-triphenyltriazine (PXZ-TRZ) anchored with norbornadiene (NBD) were synthesized, yielding compounds PZDN and PZTN with two and four NBD units, respectively. Upon visible-light excitation, energy transfer to the triplet state of NBD occurred, followed by NBD → quadricyclane (QC) conversion, which can be monitored by changes in steady-state or time-resolved spectra. The small S
-T
energy gap was found to be advantageous in optimizing the solar excitation wavelength. Upon tuning the molecule's triplet state energy lower than that of NBD (61 kcal/mol), as achieved by another composite PZQN, the efficiency of the NBD → QC conversion decreased drastically. Upon catalysis, the reverse QC → NBD reaction occurred at room temperature, converting the stored chemical energy back to heat with excellent reversibility.
A favorable interplay between cancer cells and the tumor microenvironment (TME) facilitates the outgrowth of metastatic tumors. Because of the distinct initiating processes between primary and ...metastatic tumors, we investigate the differences in tumor-associated macrophages (TAMs) from primary and metastatic cancers. Here we show that dual expression of M1 and M2 markers is noted in TAMs from primary tumors, whereas predominant expression of M2 markers is shown in metastatic TAMs. At metastatic sites, TAMs secrete interleukin-35 (IL-35) to facilitate metastatic colonization through activation of JAK2-STAT6-GATA3 signaling to reverse epithelial-mesenchymal transition (EMT) in cancer cells. In primary tumors, inflammation-induced EMT upregulates IL12Rβ2, a subunit of the IL-35 receptor, in cancer cells to help them respond to IL-35 during metastasis. Neutralization of IL-35 or knockout of IL-35 in macrophages reduces metastatic colonization. These results indicate the distinct TMEs of primary and metastatic tumors and provide potential targets for intercepting metastasis.
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