Influence of diluent on antimicrobial activity of cinnamon bark essential oil vapor against Staphylococcus aureus and Salmonella enterica on a laboratory medium and beef jerky.

The influence of chemical diluents on the antimicrobial activity of plant essential oil (EO) vapors was evaluated. We first determined if vapors generated from 22 chemical diluents not containing EO had antimicrobial activities. Ethyl ether vapor retarded the growth of S. aureus. The minimal inhibitory concentrations (MICs) and the minimal lethal concentrations (MLCs) of cinnamon bark EO vapor, which was diluted in and generated from 21 diluents, against S. aureus and S. enterica were determined. Cinnamon bark EO vapor showed significantly (P ≤ 0.05) lower MICs against S. aureus when diluted in dimethyl sulfoxide (DMSO), ethanol, ethyl acetate, or jojoba oil, and against S. enterica when diluted in DMSO, ethanol, or jojoba oil, compared to those in other diluents. We compared antimicrobial activities of cinnamon bark EO vapor diluted in DMSO, ethanol, ethyl acetate, or jojoba oil against S. aureus and S. enterica on beef jerky as a food model. Antimicrobial activity was significantly (P ≤ 0.05) higher when vaporized from DMSO. These results indicate that antimicrobial activity of cinnamon bark EO vapor may vary significantly (P ≤ 0.05) depending on the type of diluent from which it is vaporized. These observations provide basic information when developing food and food-contact surface decontamination strategies using EO vapors.

FcRγ- NK Cell Induction by Specific Cytomegalovirus and Expansion by Subclinical Viral Infections in Rhesus Macaques.

"Adaptive" NK cells, characterized by FcRγ deficiency and enhanced responsiveness to Ab-bound, virus-infected cells, have been found in certain hCMV-seropositive individuals. Because humans are exposed to numerous microbes and environmental agents, specific relationships between hCMV and FcRγ-deficient NK cells (also known as g-NK cells) have been challenging to define. Here, we show that a subgroup of rhesus CMV (RhCMV)-seropositive macaques possesses FcRγ-deficient NK cells that stably persist and display a phenotype resembling human FcRγ-deficient NK cells. Moreover, these macaque NK cells resembled human FcRγ-deficient NK cells with respect to functional characteristics, including enhanced responsiveness to RhCMV-infected target in an Ab-dependent manner and hyporesponsiveness to tumor and cytokine stimulation. These cells were not detected in specific pathogen-free (SPF) macaques free of RhCMV and six other viruses; however, experimental infection of SPF animals with RhCMV strain UCD59, but not RhCMV strain 68-1 or SIV, led to induction of FcRγ-deficient NK cells. In non-SPF macaques, coinfection by RhCMV with other common viruses was associated with higher frequencies of FcRγ-deficient NK cells. These results support a causal role for specific CMV strain(s) in the induction of FcRγ-deficient NK cells and suggest that coinfection by other viruses further expands this memory-like NK cell pool.

Highly Resilient Dual-Crosslinked Hydrogel Adhesives Based on a Dopamine-Modified Crosslinker.

Hydrogels are promising material for wound dressing and tissue engineering. However, owing to their low tissue adhesion in a moist environment and lack of flexibility, hydrogels are still not widely applied in movable parts, such as joints. Herein, we report a dual-crosslinked hydrogel adhesive using a dopamine-modified and acrylate-terminated crosslinker, tri(ethylene glycol) diacrylate-dopamine crosslinker (TDC). The covalent crosslinking was formed by photopolymerization between acrylic acid (AA) and TDC, and the noncovalent crosslinking was formed by intermolecular dopamine-dopamine and dopamine-AA interactions. Our resultant hydrogel demonstrated strong tissue adhesion in a moist environment (approximately 71 kPa) and high mechanical resilience (approximately 94%) with immediate recovery at a 200% strain rate. Moreover, it accelerated wound healing upon dressing the wound site properly. Our study provides the potential for advanced polymer synthesis by introducing a functional crosslinking agent.

Animal Models of COVID-19: Nonhuman Primates.

With the advent of the novel SARS-CoV-2, the entire world has been thrown into chaos with severe disruptions from a normal life. While the entire world was going chaotic, the researchers throughout the world were struggling to contribute to the best of their capabilities to advance the understanding of this new pandemic and fast track the development of novel therapeutics and vaccines. While various animal models have helped a lot to understand the basic physiology, nonhman primates have been promising and much more successful in modelling human diseases compared to other available clinical models. Here we describe the different aspects of modelling the SARS-CoV-2 infection in NHPs along with the associated methods used in NHP immunology.

Rapid Photoresponsive Switchable Pressure-Sensitive Adhesive Containing Azobenzene for the Mini-Light Emitting Diode Transfer Process.

Materials that can switch adhesive properties based on external stimuli are required in several industries for temporary bonding or transfer processes. Previously studied materials achieve this under restricted conditions (hydration, heat, and long switching times), and some materials have limitations related to reuse because of irreversible reactions or residue formation on substrates. Herein, a rapid photoresponsive switchable pressure-sensitive adhesive (PSA) fabricated using an acrylic polymer and an aliphatic monomer containing azobenzene is reported. The adhesion force of the proposed PSA can be switched by photoisomerizing the azobenzene moiety. The process induces the transition of surface energy and modulus of the PSA. Ultraviolet and visible light irradiation can switch the probe tack force from 200 to 4 kPa within 15-30 s. Adhesion switching is possible in a state wherein the PSA remains adhered to a substrate. Mini-LEDs are selectively transferred from the carrier PSA to a polydimethylsiloxane substrate following the process of partial adhesion switching of the PSA. The novel and switchable PSA, which exhibits a selective and repeatable adhesion switching property and high switching ratio when stimulated by light stimuli, may be potentially used to realize the mini-LED or micro-LED transfer processes.

Photoresponsive, switchable, pressure-sensitive adhesives: influence of UV intensity and hydrocarbon chain length of low molecular weight azobenzene compounds.

Unlike traditional adhesives with a fixed adhesive force, switchable adhesives, which have an adhesive force that can be adjusted by external stimuli, are specifically designed to be released according to user demand, or to enable the transfer of fine electronic devices. Previously developed switchable adhesives have limitations such as a slow switching rate, narrow adhesion modulation range, or the lack of reusability. Thus, we fabricated switchable pressure-sensitive adhesives (PSAs) that can overcome these limitations. The adhesive force of each switchable PSA, which comprises an azobenzene-containing acrylic polymer and low molecular weight compounds, was designed to be activated/deactivated via ultraviolet (UV) and visible light irradiation. The adhesive force and UV intensity required for the switch were found to be dependent on the aliphatic chain length of the compound. The adhesive force of the SP-C10, i.e., a switchable PSA containing a azobenzene compound with an aliphatic chain of 10 hydrocarbons, increased to 3.5 N from nearly zero in response to only 30 s of low-level (25 mW cm-2) UV irradiation. Additionally, SP-C10 did not lose its adhesive force even after 30 cycles of repeated adhesion switching. The mechanism of adhesion switching influenced by UV intensity and the structure of low molecular weight azobenzene compounds are also reported.

Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets.

Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

Antiretroviral therapy does not reduce tuberculosis reactivation in a tuberculosis-HIV coinfection model.

While the advent of combination antiretroviral therapy (ART) has significantly improved survival, tuberculosis (TB) remains the leading cause of death in the HIV-infected population. We used Mycobacterium tuberculosis/simian immunodeficiency virus-coinfected (M. tuberculosis/SIV-coinfected) macaques to model M. tuberculosis/HIV coinfection and study the impact of ART on TB reactivation due to HIV infection. Although ART significantly reduced viral loads and increased CD4+ T cell counts in blood and bronchoalveolar lavage (BAL) samples, it did not reduce the relative risk of SIV-induced TB reactivation in ART-treated macaques in the early phase of treatment. CD4+ T cells were poorly restored specifically in the lung interstitium, despite their significant restoration in the alveolar compartment of the lung as well as in the periphery. IDO1 induction in myeloid cells in the inducible bronchus-associated lymphoid tissue (iBALT) likely contributed to dysregulated T cell homing and impaired lung immunity. Thus, although ART was indispensable for controlling viral replication, restoring CD4+ T cells, and preventing opportunistic infection, it appeared inadequate in reversing the clinical signs of TB reactivation during the relatively short duration of ART administered in this study. This finding warrants the modeling of concurrent treatment of TB and HIV to potentially reduce the risk of reactivation of TB due to HIV to inform treatment strategies in patients with M. tuberculosis/HIV coinfection.

Formation of TiO2@Carbon Core/Shell Nanocomposites from a Single Molecular Layer of Aromatic Compounds for Photocatalytic Hydrogen Peroxide Generation.

In this article, we demonstrate that TiO2@carbon core/shell (TiO2@C) nanocomposite photocatalysts prepared by carbonizing a single molecular layer of aromatic compounds adsorbed on the surface of TiO2 nanoparticles selectively enhance the generation of hydrogen peroxide (H2O2). Atomically thin carbon shells have been formed directly on the surface of TiO2 nanoparticles through pyrolytic decarboxylation of the adsorbed aromatic compounds, benzoic acid (BA), and 1-naphthoic acid (NA), which yields two types of TiO2@C nanocomposites, TiO2@C(BA) and TiO2@C(NA). Raman spectroscopy shows that the as-obtained nanocomposites have similar degrees of graphitization (D/G band ratio), regardless of the type of aromatic precursors, but TiO2@C(NA) contains more oxygenic species than TiO2@C(BA) (D*/G band ratio). Such oxygenic species predominantly exist in the form of epoxide groups, as determined by attenuated total reflection infrared spectroscopy. The sp2 carbon atoms near the epoxide groups in the carbon shell can act as active sites for the two-electron reduction of O2. Therefore, TiO2@C(NA) can generate H2O2 more efficiently than TiO2@C(BA). Furthermore, the carbon shells retard the reconsumption of the generated H2O2 by inhibiting the adsorption of H2O2 on the surface of TiO2 nanoparticles, thereby improving the photocatalytic efficiency of H2O2 generation. Finally, we have shown the durability and reproducibility of our TiO2@C-based photocatalytic systems. We believe that our research may offer a potentially improved strategy for H2O2 generation and other photocatalytic applications.

Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection.

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals.

Effects of aerobic and resistance exercises on circulating apelin-12 and apelin-36 concentrations in obese middle-aged women: a randomized controlled trial.

BACKGROUND: The risk for obesity-related diseases increases with the prevalence of obesity. In obesity, adipokines secreted from adipose tissue induce inflammation, causing adverse effects. Recently, adipokines such as apelin, visfatin, and chemerin have been studied. Long-term resistance training improves health in middle-aged women by improving metabolic risk factors, body composition, and muscle strength. However, there is still a lack of evidence on the association of apelin concentration with different exercise types in middle-aged obese women This study aimed to investigate the effects of 8 weeks of aerobic and resistance exercises on apelin-12 and apelin-36 levels and thereby verify the effects of different exercise types in obese, middle-aged women. METHODS: Participants were middle-aged women aged 50-61 years, with no experience of systematic exercise in the last 6 months, and met the WHO obesity criteria for the Asia-Pacific region of waist circumference ≥ 80 cm and body fat percentage ≥ 30%. Subjects were selected and allocated to the aerobic exercise, resistance exercise, or no exercise group by block randomization. Body weight, body fat, and body mass index were measured by bioelectrical impedance analysis. Analysis of variance, the t-test, and Tukey's post-hoc test were performed. RESULTS: A total of 24 participants were selected with eight participants in each group. Both aerobic and resistance exercises were effective in altering the physical composition, showing significant decreases in weight, waist circumference, BMI, and body fat. The aerobic and resistance exercise group showed a significant, positive change in apelin-12 levels. CONCLUSIONS: In obese individuals, aerobic and resistance exercise were effective in improving obesity and reducing blood apelin-12 concentration, which is closely correlated with indicators of metabolic syndrome. Future research should focus on comparing the response of apelin to exercise in obese subjects treated with only dietary control and the response in the obese subjects of different ages and sex. TRIAL REGISTRATION: No. 1040917-201,506-BR-153-04 , Clinical Research Information Service (CRIS), Republic of Korea (05 October 2018, retrospectively registered).

Defect-Induced Fluorescence of Silica Nanoparticles for Bioimaging Applications.

With biocompatibility, biodegradability, and high functionality, silica nanoparticles (SNPs) have been widely investigated for various biomedical applications. However, lack of optical fluorescence has limited the application of SNPs as a degradable imaging agent. Here, we hydrothermally synthesized fluorescent SNPs by artificially generating optically active defect centers using tetraethyl orthosilicate and (3-aminopropyl)trimethoxysilane. The synthesized SNPs demonstrated strong blue photoluminescence originating from the dioxasilyrane (=Si(O2)) and silylene (=Si:) defect centers with the aid of aminopropyl groups. Furthermore, phosphorescence was observed at 459 nm, indicating the presence of silylene in SNPs. Finally, these SNPs have been successfully utilized as a fluorescent probe for bioimaging of normal, cancer, and macrophage cells.

Site-Specific Three-Color Labeling of α-Synuclein via Conjugation to Uniquely Reactive Cysteines during Assembly by Native Chemical Ligation.

Single-molecule fluorescence is widely used to study conformational complexity in proteins, and has proven especially valuable with intrinsically disordered proteins (IDPs). Protein studies using dual-color single-molecule Förster resonance energy transfer (smFRET) are now quite common, but many could benefit from simultaneous measurement of multiple distances through multi-color labeling. Such studies, however, have suffered from limitations in site-specific incorporation of more than two dyes per polypeptide. Here we present a fully site-specific three-color labeling scheme for α-synuclein, an IDP with important putative functions and links to Parkinson disease. The convergent synthesis combines native chemical ligation with regiospecific cysteine protection of expressed protein fragments to permit highly controlled labeling via standard cysteine-maleimide chemistry, enabling more global smFRET studies. Furthermore, this modular approach is generally compatible with recombinant proteins and expandable to accommodate even more complex experiments, such as by labeling with additional colors.

G protein-coupled receptor kinase-2-deficient mice are protected from dextran sodium sulfate-induced acute colitis.

G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase and plays a key role in different disease processes. Previously, we showed that GRK2 knockdown enhances wound healing in colonic epithelial cells. Therefore, we hypothesized that ablation of GRK2 would protect mice from dextran sodium sulfate (DSS)-induced acute colitis. To test this, we administered DSS to wild-type (GRK2+/+) and GRK2 heterozygous (GRK+/-) mice in their drinking water for 7 days. As predicted, GRK2+/- mice were protected from colitis as demonstrated by decreased weight loss (20% loss in GRK2+/+ vs. 11% loss in GRK2+/-). lower disease activity index (GRK2+/+ 9.1 vs GRK2+/- 4.1), and increased colon lengths (GRK2+/+ 4.7 cm vs GRK2+/- 5.3 cm). To examine the mechanisms by which GRK2+/- mice are protected from colitis, we investigated expression of inflammatory genes in the colon as well as immune cell profiles in colonic lamina propria, mesenteric lymph node, and in bone marrow. Our results did not reveal differences in immune cell profiles between the two genotypes. However, expression of inflammatory genes was significantly decreased in DSS-treated GRK2+/- mice compared with GRK2+/+. To understand the mechanisms, we generated myeloid-specific GRK2 knockout mice and subjected them to DSS-induced colitis. Similar to whole body GRK2 heterozygous knockout mice, myeloid-specific knockout of GRK2 was sufficient for the protection from DSS-induced colitis. Together our results indicate that deficiency of GRK2 protects mice from DSS-induced colitis and further suggests that the mechanism of this effect is likely via GRK2 regulation of inflammatory genes in the myeloid cells.

Multifunctional Photonic Nanomaterials for Diagnostic, Therapeutic, and Theranostic Applications.

The last decade has seen dramatic progress in the principle, design, and fabrication of photonic nanomaterials with various optical properties and functionalities. Light-emitting and light-responsive nanomaterials, such as semiconductor quantum dots, plasmonic metal nanoparticles, organic carbon, and polymeric nanomaterials, offer promising approaches to low-cost and effective diagnostic, therapeutic, and theranostic applications. Reasonable endeavors have begun to translate some of the promising photonic nanomaterials to the clinic. Here, current research on the state-of-the-art and emerging photonic nanomaterials for diverse biomedical applications is reviewed, and the remaining challenges and future perspectives are discussed.

Molecular Markers for Interspecies Transmission of Avian Influenza Viruses in Mammalian Hosts.

In the last decade, a wide range of avian influenza viruses (AIVs) have infected various mammalian hosts and continuously threaten both human and animal health. It is a result of overcoming the inter-species barrier which is mostly associated with gene reassortment and accumulation of mutations in their gene segments. Several recent studies have shed insights into the phenotypic and genetic changes that are involved in the interspecies transmission of AIVs. These studies have a major focus on transmission from avian to mammalian species due to the high zoonotic potential of the viruses. As more mammalian species have been infected with these viruses, there is higher risk of genetic evolution of these viruses that may lead to the next human pandemic which represents and raises public health concern. Thus, understanding the mechanism of interspecies transmission and molecular determinants through which the emerging AIVs can acquire the ability to transmit to humans and other mammals is an important key in evaluating the potential risk caused by AIVs among humans. Here, we summarize previous and recent studies on molecular markers that are specifically involved in the transmission of avian-derived influenza viruses to various mammalian hosts including humans, pigs, horses, dogs, and marine mammals.

Understanding Mind-Body Interaction from the Perspective of East Asian Medicine.

OBJECTIVE: Attempts to understand the emotion have evolved from the perspective of an independent cognitive system of the mind to that of an interactive response involving the body. This study aimed to quantify and visualize relationships between different emotions and bodily organ systems from the perspective of East Asian medicine. METHODS: Term frequency-inverse document frequency (tf-idf) method was used to quantify the significance of Five Viscera and the gallbladder relative to seven different emotions through the classical medical text of DongUiBoGam. Bodily organs that corresponded to different emotions were visualized using a body template. RESULTS: The emotions had superior tf-idf values with the following bodily organs: anger with the liver, happiness with the heart, thoughtfulness with the heart and spleen, sadness with the heart and lungs, fear with the kidneys and the heart, surprise with the heart and the gallbladder, and anxiety with the heart and the lungs. Specific patterns between the emotions and corresponding bodily organ systems were identified. CONCLUSION: The present findings will further the current understanding of the relationship between the mind and body from the perspective of East Asian medicine. Western medicine characterizes emotional disorders using "neural" language while East Asian medicine uses "somatic" language.

Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice.

G protein-coupled receptor kinase-6 (GRK6) is a serine/threonine kinase that is important in inflammatory processes. In this study, we examined the role of GRK6 in Escherichia coli-induced lung infection and inflammation using GRK6 knockout (KO) and wild-type (WT) mice. Intratracheal instillation of E. coli significantly enhanced bacterial load in the bronchoalveolar lavage (BAL) of KO compared with WT mice. Reduced bacterial clearance in the KO mice was not due to an intrinsic defect in neutrophil phagocytosis or killing but as a result of reduced neutrophil numbers in the KO BAL. Interestingly, neutrophil numbers in the lung were increased in the KO compared with WT mice, suggesting a potential dysfunction in transepithelial migration of neutrophils from the lungs to the bronchoalveolar space. This effect was selective for lung tissue because peritoneal neutrophil numbers were similar between the two genotypes following peritoneal infection. Although neutrophil expression of CXCR2/CXCR3 was similar between WT and KO, IL-17A expression was higher in the KO compared with WT mice. These results suggest that enhanced neutrophil count in the KO lungs but reduced numbers in BAL are likely due to transepithelial migration defect and/or altered chemokines/cytokines. Together, our studies suggest a previously unrecognized and novel role for GRK6 in neutrophil migration specific to pulmonary tissue during bacterial infection.

More than DeQi: Spatial Patterns of Acupuncture-Induced Bodily Sensations.

Acupuncture uses needles to stimulate certain parts of the body, inducing a specific sensation, termed DeQi, which regard as essential for acupuncture's therapeutic effect. Here, we used the newly developed tool, bodily sensation mapping, to investigate the spatial configuration of acupuncture-induced sensations throughout the body. Twenty-five participants randomly received acupuncture stimulation or tactile stimulation using a von Frey filament at four different acupoints (HT7, PC6, ST36, and SP10) on the left side of the body. Subjects evaluated the characteristics of DeQi sensations and marked the areas of induced sensations on a body outline. We compared the psychophysical responses of DeQi sensations and visualized the spatial patterns of these sensations using statistical parametric mapping. We found greater intensity of DeQi sensations following acupuncture stimulation compared with tactile stimulation, with relatively small differences among the four acupoints. The sensation maps exhibited similar spatial patterns for acupuncture and tactile stimulation in the areas close to the stimulated sites. However, acupuncture was associated with additional sensations in areas remote from the stimulated sites. This study demonstrates that acupuncture stimulation produces greater DeQi sensations than tactile stimulation and results in the spreading of sensations to areas remote from the stimulus sites. Investigating the spatial patterns of acupuncture-induced sensations may be crucial for understanding the underlying mechanisms of acupuncture.