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Magnolia officinalis is widely used in Southeast Asian countries for the treatment of fever, headache, diarrhea, and stroke. Magnolol is a phenolic compound extracted from M. officinalis, with proven antibacterial, antioxidant, anti-inflammatory, and anticancer activities. In this study, we modified magnolol to synthesize a methoxylated derivative, 2-O-methylmagnolol (MM1), and investigated the use of MM1, and magnolol in the treatment of liver cancer. We found that both magnolol and MM1 exhibited inhibitory effects on the growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines and halted the cell cycle at the G1 phase. MM1 also demonstrated a substantially better tumor-suppressive effect than magnolol. Further analysis suggested that by inhibiting class I histone deacetylase expression in HCC cell lines, magnolol and MM1 induced p21 expression and p53 activation, thereby causing cell cycle arrest and inhibiting HCC cell growth, migration, and invasion. Subsequently, we verified the significant tumor-suppressive effects of magnolol and MM1 in an animal model. Collectively, these findings demonstrate the anti-HCC activities of magnolol and MM1 and their potential for clinical use.

Candida albicans is the most common cause of fungal infection. The emergence of drug resistance leads to the need for novel antifungal agents. We aimed to design naphthofuranquinone analogs to treat drug-resistant C. albicans for topical application on cutaneous candidiasis. The time-killing response, agar diffusion, and live/dead assay of the antifungal activity were estimated against 5-fluorocytosine (5-FC)- or fluconazole-resistant strains. A total of 14 naphthofuranquinones were compared for their antifungal potency. The lead compounds with hydroxyimino (TCH-1140) or O-acetyl oxime (TCH-1142) moieties were the most active agents identified, showing a minimum inhibitory concentration (MIC) of 1.5 and 1.2 μM, respectively. Both compounds were superior to 5-FC and fluconazole for killing planktonic fungi. Naphthofuranquinones efficiently diminished the microbes inside and outside the biofilm. TCH-1140 and TCH-1142 were delivered into C. albicans-infected keratinocytes to eradicate intracellular fungi. The compounds did not reduce the C. albicans burden inside the macrophages, but the naphthofuranquinones promoted the transition of fungi from the virulent hypha form to the yeast form. In the in vivo skin mycosis mouse model, topically applied 5-FC and TCH-1140 reduced the C. albicans load from 1.5 × 106 to 5.4 × 105 and 1.4 × 105 CFU, respectively. The infected abscess diameter was significantly decreased by TCH-1140 (3-4 mm) as compared to the control (8 mm). The disintegrated skin-barrier function induced by the fungi was recovered to the baseline by the compound. The data support the potential of TCH-1140 as a topical agent for treating drug-resistant C. albicans infection without causing skin irritation.

In the foreseeable future, coastal coral reef ecosystems are likely to face further increases in eutrophication. Lipids and fatty acids (FAs), as important components of corals, are becoming a hot topic to study the effects of eutrophication on corals. This study investigated the effects of nitrate (NO3–) enrichment (0, 5, 10, 20, and 40 μM) on the respiration, photosynthesis, and FA compositions of Pocillopora damicornis larvae. Our results showed that saturated FAs (SFAs) were the most abundant in P. damicornis larvae over all treatment groups, followed by polyunsaturated FAs (PUFAs). The unsaturated-to-SFA ratio (U/S) and unsaturation index (UI) reduced at low nitrate concentrations (20 μM). The UI and U/S levels were elevated due to the increased PUFAs levels and decreased SFA levels at higher nitrate concentrations. Compared with the N5 and N10 groups, the fluidity of the biomembrane of the larvae did not continue to decrease but instead increased at higher nitrate concentrations, indicating that the biomembrane restructuring in the larvae may have become ineffective. Moreover, respiration increased and the consumption of numerous lipids led to a significant decrease in TFAs. These could adversely affect the dispersal, settlement, and development of larvae. Overall, P. damicornis larvae can adapt to low levels of nitrate (

Pathogenic bacteria infection is a major public health problem due to the high morbidity and mortality rates, as well as the increased expenditure on patient management. Although there are several options for antimicrobial therapy, their efficacy is limited because of the occurrence of drug-resistant bacteria. Many conventional antibiotics have failed to show significant amelioration in overall survival of infectious patients. Nanomedicine for delivering antibiotics provides an opportunity to improve the efficiency of the antibacterial regimen. Nanosystems used for antibiotic delivery and targeting to infection sites render some benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged antibiotic half-life, tissue targeting, and minimal adverse effects. The nanocarriers' sophisticated material engineering tailors the controllable physicochemical properties of the nanoparticles for bacterial targeting through passive or active targeting. In this review, we highlight the recent progress on the development of antibacterial nanoparticles loaded with antibiotics. We systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for bacterial eradication. Passive targeting by modulating the nanoparticle structure and the physicochemical properties is an option for efficient drug delivery to the bacteria. In addition, active targeting, such as magnetic hyperthermia induced by iron oxide nanoparticles, is another efficient way to deliver the drugs to the targeted site. The nanoparticles are also designed to respond to the change in environment pH or enzymes to trigger the release of the antibiotics. This article offers an overview of the benefits of antibacterial nanosystems for treating infectious diseases.

We developed a time-dependent stochastic neutral model for predicting diverse temporal trajectories of biodiversity change in response to ecological disturbance (i.e. habitat destruction) and dispersal dynamic (i.e. emigration and immigration). The model is general and predicts how transition behaviours of extinction may accumulate according to a different combination of random drift, immigration rate, emigration rate and the degree of habitat destruction. We show that immigration, emigration, the areal size of the destroyed habitat and initial species abundance distribution (SAD) can impact the total biodiversity loss in an intact local area. Among these, the SAD plays the most deterministic role, as it directly determines the initial species richness in the local target area. By contrast, immigration was found to slow down total biodiversity loss and can drive the emergence of species credits (i.e. a gain of species) over time. However, the emigration process would increase the extinction risk of species and accelerate biodiversity loss. Finally but notably, we found that a shift in the emigration rate after a habitat destruction event may be a new mechanism to generate species credits.

Soil invertebrates and microorganisms are two major drivers of litter decomposition. Even though the importance of invertebrates and microorganisms in biogeochemical soil cycles and soil food webs has been studied, the effects of invertebrates on fungi are not well understood compared to other organisms. In this work, we investigated the effects of soil invertebrates on fungi as a factor that cannot be ignored in the study of nutrient cycling. The result showed the grazing of isopods on white-rot fungi was transitive and persistent. The grazed fungi appeared “compensatory” growing. The biomass of fungi increased after grazing. The activities of enzymes associated with nutrient cycling were increased under grazing. The zymography images showed the enzyme hotspots and activities also increased significantly in the grazing area. The results suggest that invertebrate grazing can significantly increase the fungal biomass and enzyme activity, accelerating litter decomposition in the unreached grazer area. The grazing effects of invertebrate plays an important role in promoting the nutrient cycling of the forest ecosystem. We believe that this study will be a good reference related to showing the relationship between soil invertebrates, fungi and soil biogeochemical cycles.

Picosecond or nanosecond-domain non-ablative lasers generate faster photothermal effects and cause less injury than microsecond lasers. In this study, we investigated the enhancing effect of 1064 nm picosecond- and nanosecond-domain neodymium (Nd):yttrium–aluminum–garnet (YAG) lasers on the cutaneous delivery of cosmeceutical peptides. Microsecond-domain fractional ablative CO2 and fully ablative erbium (Er):YAG lasers were also used for comparison. In the Franz diffusion cell study, pig or mouse skin was treated with a laser before exposure to palmitoyl tripeptide (PT)-1, PT-38, and copper tripeptide (CT)-1 at a concentration of 150 μM. Psoriasiform, atopic dermatitis (AD)-like, and photoaged skins were also developed as permeation barriers. The non-ablative laser elicited the ultrastructural disruption of the stratum corneum and epidermal vacuolation. All laser modalities significantly increased the skin permeation of peptides in vitro. The non-ablative laser chiefly enhanced peptide delivery to the receptor compartment, whereas the ablative laser mainly increased the intracutaneous peptide deposition. The picosecond- and nanosecond-domain Nd:YAG lasers elevated the amount of PT-1 in the receptor up to 40- and 22-fold compared with untreated skin, respectively. Laser treatment promoted peptide delivery in barrier-deficient and inflamed skins, although this enhancement effect was less than that observed in healthy skin. Fluorescence microscopy indicated the capability of the non-ablative laser to deliver peptides to deeper skin strata. The ablative laser confined the peptide distribution in the epidermis. Confocal microscopy showed that peptides penetrated the skin along the microdots created by the fractional Nd:YAG and CO2 lasers. The skin barrier function determined by transepidermal water loss suggested quick recovery when using a nanosecond-domain laser (within 4 h). A longer period was needed for the skin treated with the fully ablative Er:YAG laser (76−84 h). Nanosecond non-ablative laser-facilitated peptide delivery may become an efficient and safe approach for cosmeceutical applications.

Background/Aims: 2-O-methylmagnolol (MM1), a derivative of magnolol bearing one methoxy moiety, has been shown to display improved anti-tumor activity against skin cancers. In this study, we examined the anti-tumor effects of magnolol and MM1 on oral squamous cell carcinoma (OSCC). Methods: Trypane blue staining and clonogenic assays were performed to determine the cytotoxic effects of magnolol and MM1 in OSCC cells. Migration and matrigel invasion assays were carried out to examine the metastasis effects of magnolol and MM1 in OSCC cells. IL6-stimulation, Western blot, and immunohistochemistry were used to investigate the IL-6/STAT3 signaling and apoptosis. A bioluminescent mouse model of orthotopically implanted SAS cells was used to determine the anti-tumor activity of MM1 in vivo. Results: MM1 displays greater activity than magnolol on affecting the cytotoxicity, migration, and invasion of OSCC cells cultured in vitro. The improved anti-tumor activity of MM1 was shown to associate with its greater activity to inhibit STAT3 signaling and to induce apoptosis in the OSCC. In addition, we presented evidence that MM1 is effective in inhibiting the growth of orthotopic implanted OSCC cells in vivo. Conclusion: Our data indicate that MM1 displays greater anti-tumor activity than magnolol in OSCC and is an attractive agent to be further explored for its potential clinical application.

Abstract Background Cilomilast is a phosphodiesterase 4 (PDE4) inhibitor for treating inflammatory lung diseases. This agent has a narrow therapeutic index with significant adverse effects on the nervous system. This study was conducted to entrap cilomilast into PEGylated phosphatidylcholine-rich niosomes (phosphatiosomes) to improve pulmonary delivery via the strong affinity to pulmonary surfactant film. Neutrophils were used as a cell model to test the anti-inflammatory activity of phosphatiosomes. In an in vivo approach, mice were given lipopolysaccharide to produce acute lung injury. The surface charge in phosphatiosomes that influenced the anti-inflammatory potency is discussed in this study. Results The average diameter of the phosphatiosomes was about 100 nm. The zeta potential of anionic and cationic nanovesicles was − 35 and 32 mV, respectively. Cilomilast in both its free and nanocapsulated forms inhibited superoxide anion production but not elastase release in activated neutrophils. Cationic phosphatiosomes mitigated calcium mobilization far more effectively than the free drug. In vivo biodistribution evaluated by organ imaging demonstrated a 2-fold ameliorated lung uptake after dye encapsulation into the phosphatiosomes. The lung/brain distribution ratio increased from 3 to 11 after nanocarrier loading. The intravenous nanocarriers deactivated the neutrophils in ALI, resulting in the elimination of hemorrhage and alveolar wall damage. Only cationic phosphatiosomes could significantly suppress IL-1β and TNF-α in the inflamed lung tissue. Conclusions These results suggest that phosphatiosomes should further be investigated as a potential nanocarrier for the treatment of pulmonary inflammation.

C23H22N2O4, monoclinic, P21/c (no. 14), a = 17.7478(4) Å, b = 10.0041(2) Å, c = 24.4749(6) Å, β = 111.111(2)°, V = 4053.88(17) Å3, Z = 8, Rgt(F) = 0.0614, wRref(F2) = 0.1749, T = 290 K.

C67H49Cl3N6O18, triclinic, P1̄ (no. 2), a = 12.3281(4) Å, b = 15.8887(5) Å, c = 16.9037(6) Å, α = 89.015(2)°, β = 77.885(3)°, γ = 72.021(3)°, V = 3075.20(19) Å3, Z = 2, Rgt(F) = 0.0658, wRref(F2) = 0.1558, T = 291.2(3) K.

Shanyou You No. 1, a new peanut variety with super high yield was bred by EMS (ethylmethane sulfonate) mutagenesis with the dried seeds of Shanyou 212 as the materials by Shantou Institute of Agricultural Science. It passed the national peanut variety identification and Guangdong crop variety approval in 2014, with the identification number of Guopingjian Peanut 2014014 and the approval number of Yueshenyou 2014001. It obtained the new plant variety right in 2017, with the variety right number of CNA20140907.4. In 2018, it passed the national non-major crop variety registration with the registration number of GPD Peanut (2018) 440280. The yield of this variety was outstanding. In the national (southern district) regional test of peanut varieties and the regional test of the new peanut varieties being planted in spring in Guangdong Province, the dry pod yields was 4 590.08 kg/hm² and 4 112.85kg/hm², respectively, which were 11.20% and 15.25% higher than that of the control Shanyou 523. It had the oil content of 49.31%-53.45% and protein content of 21.40%-26.58%. It was highly resistant to the rust and leaf spot diseases, and susceptible to bacterial wilt, with strong lodging resistance, drought resistance, and waterlogging resistance. The variety is suitable to be planted in spring and autumn in the water-drought rotation plough land and dry sloping fields in Guangdong, as well as in spring in the peanut production areas in western Guangxi, Fujian, Yunnan, southern Jiangxi, and southern Hunan. During the cultivation, the attention should be paid to the selection of soil property, timely sowing, reasonable close planting, strengthening the fertilizer and water management, and timely prevent and control of weeds, diseases, insect pests and rodent harm. [ABSTRACT FROM AUTHOR]

A known species, Scirula papilataLin, 1997 based on samples collected from Hubei Province, China, is redescribed with the detailed illustration and the first description of males. [ABSTRACT FROM AUTHOR]

Biofilm formation is an important virulence factor for the opportunistic microorganisms that elicit skin infections. The recalcitrant feature of biofilms and their antibiotic tolerance impose a great challenge on the use of conventional therapies. Most antibacterial agents have difficulty penetrating the matrix produced by a biofilm. One novel approach to address these concerns is to prevent or inhibit the formation of biofilms using nanoparticles. The advantages of using nanosystems for antibiofilm applications include high drug loading efficiency, sustained or prolonged drug release, increased drug stability, improved bioavailability, close contact with bacteria, and enhanced accumulation or targeting to biomasses. Topically applied nanoparticles can act as a strategy for enhancing antibiotic delivery into the skin. Various types of nanoparticles, including metal oxide nanoparticles, polymeric nanoparticles, liposomes, and lipid-based nanoparticles, have been employed for topical delivery to treat biofilm infections on the skin. Moreover, nanoparticles can be designed to combine with external stimuli to produce magnetic, photothermal, or photodynamic effects to ablate the biofilm matrix. This study focuses on advanced antibiofilm approaches based on nanomedicine for treating skin infections. We provide in-depth descriptions on how the nanoparticles could effectively eliminate biofilms and any pathogens inside them. We then describe cases of using nanoparticles for antibiofilm treatment of the skin. Most of the studies included in this review were supported by in vivo animal infection models. This article offers an overview of the benefits of nanosystems for treating biofilms grown on the skin.

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

Abstract Background The species pool concept was formulated over the past several decades and has since played an important role in explaining multi-scale ecological patterns. Previous statistical methods were developed to identify species pools based on broad-scale species range maps or community similarity computed from data collected from many areas. No statistical method is available for estimating species pools for a single local community (sampling area size may be very small as ≤ 1 km2). In this study, based on limited local abundance information, we developed a simple method to estimate the area size and richness of a species pool for a local ecological community. The method involves two steps. In the first step, parameters from a truncated negative trinomial model characterizing the distributional aggregation of all species (i.e., non-random species distribution) in the local community were estimated. In the second step, we assume that the unseen species in the local community are most likely the rare species, only found in the remaining part of the species pool, and vice versa, if the remaining portion of the pool was surveyed and was contrasted with the sampled area. Therefore, we can estimate the area size of the pool, as long as an abundance threshold for defining rare species is given. Since the size of the pool is dependent on the rarity threshold, to unanimously determine the pool size, we developed an optimal method to delineate the rarity threshold based on the balance of the changing rates of species absence probabilities in the sampled and unsampled areas of the pool. Results For a 50 ha (0.5 km2) forest plot in the Barro Colorado Island of central Panama, our model predicted that the local, if not regional, species pool for the 0.5 km2 forest plot was nearly the entire island. Accordingly, tree species richness in this pool was estimated as around 360. When the sampling size was smaller, the upper bound of the 95% confidence interval could reach 418, which was very close to the flora record of tree richness for the island. A numerical test further demonstrated the power and reliability of the proposed method, as the true values of area size and species richness for the hypothetical species pool have been well covered by the 95% confidence intervals of the true values. Conclusions Our method fills the knowledge gap on estimating species pools for a single local ecological assemblage with little information. The method is statistically robust and independent of sampling size, as proved by both empirical and numerical tests.

Acute lung injury (ALI) is a respiratory disease that is associated with neutrophil activation. Neutrophil elastase released from activated neutrophils has been reported to cause lung tissue damage and contribute to the inflammatory response in ALI. In this study, aqueous extracts of Kochia scoparia fruits, a traditional botanical medicine and food garnish in Asia, showed a selective inhibitory effect on human neutrophil elastase (IC50, 79.53 ± 4.26 μg mL−1). Using bioactivity-guided fractionation, the polysaccharide fraction (KSWP, molecular weight > 300 kDa) was identified, and its protective effects against ALI were investigated. The results showed that KSWP protected mice from lipopolysaccharide-induced ALI by reducing elastase activity, neutrophil infiltration, pro-inflammatory cytokines, and neutrophil NET formation. In addition, KSWP showed high safety parameters in toxicity tests. These results conclusively demonstrate the high potency of KSWP as a component of functional foods or botanical products in the prevention of ALI.

Abstract Formyl peptide receptor 1 (FPR1) mediates bacterial and mitochondrial N-formyl peptides-induced neutrophil activation. Therefore, FPR1 is an important therapeutic target for drugs to treat septic or sterile inflammatory diseases. Honokiol, a major bioactive compound of Magnoliaceae plants, possesses several anti-inflammatory activities. Here, we show that honokiol exhibits an inhibitory effect on FPR1 binding in human neutrophils. Honokiol inhibited superoxide anion generation, reactive oxygen species formation, and elastase release in bacterial or mitochondrial N-formyl peptides (FPR1 agonists)-activated human neutrophils. Adhesion of FPR1-induced human neutrophils to cerebral endothelial cells was also reduced by honokiol. The receptor-binding results revealed that honokiol repressed FPR1-specific ligand N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein binding to FPR1 in human neutrophils, neutrophil-like THP-1 cells, and hFPR1-transfected HEK293 cells. However, honokiol did not inhibit FPR2-specific ligand binding to FPR2 in human neutrophils. Furthermore, honokiol inhibited FPR1 agonist-induced calcium mobilization as well as phosphorylation of p38 MAPK, ERK, and JNK in human neutrophils. In conclusion, our data demonstrate that honokiol may have therapeutic potential for treating FPR1-mediated inflammatory diseases.

C21H21N3O4S, triclinic, P1̄ (no. 2), a = 9.4256(9) Å, b = 10.1906(9) Å, c = 11.6539(9) Å, α = 101.896(7)°, β = 104.770(8)°, γ = 93.271(8)°, V = 1052.01(16) Å3, Z = 2, Rgt(F) = 0.0469, wRref(F2) = 0.1354, T = 293(2) K.

Atopic dermatitis (AD) is an inflammatory skin disease that is usually accompanied by Staphylococcus aureus infection due to cutaneous barrier-function damage. Benzenoid compounds from Antrodia cinnamomea are known to exhibit antibacterial and anti-inflammatory activities. This study sought to investigate the potential of benzenoids for treating bacteria-infected AD. The compounds were screened against methicillin-resistant S. aureus (MRSA). Coenzyme Q0 (CoQ0), a key ingredient in A. cinnamomea, showed the strongest MRSA growth inhibition. We further tested the inhibitory effect of CoQ0 on planktonic and biofilm MRSA. The work was also performed to explore the potential effectiveness of CoQ0 on AD using activated keratinocytes and in vivo experimental AD mice as the models. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CoQ0 against MRSA were 7.81 μg/ml. CoQ0 was found to eradicate biofilm MRSA efficiently and reduce the biofilm thickness. CoQ0 killed MRSA by inhibiting DNA polymerase and topoisomerases. A proteomic assay showed that CoQ0 also reduced the ribosomal proteins. In the anti-inflammation study, CoQ0 was found to downregulate the expression of interleukin (IL)-6, chemokine (C-C motif) ligand (CCL)5, and CCL17 in HaCaT cells. CoQ0 at 0.5 μg/ml could recover the filaggrin decreased by HaCaT activation to the normal control. We established a bacteria-infected AD-like model in mice using ovalbumin (OVA) and topically applied MRSA. Topical CoQ0 delivery lessened the MRSA presence in the AD-like lesions by >90%. The erythema, barrier function, and epidermal thickness of the AD-like wounds were improved by CoQ0 through the reduction of IL-1β, IL-4, IL-6, IL-10, interferon (IFN)-γ, and by neutrophil infiltration in the lesional skin. CoQ0 is therefore regarded as effective in mitigating AD symptoms associated with bacterial load.

Human glioma facilitates an impaired anti-tumor immunity response, including defects in circulation of T lymphocytes. The level of CD8+ T-cell activation acts as an immune regulator associated with disease progression. However, little is known about the characteristics of peripheral and tumor-infiltrating CD8+ T cells in patients with glioma. In this study, we examined the level of CD8+ T-cell activation in a group of 143 patients with glioma and determined that peripheral CD3+ T cells decreased in accordance with disease severity. The patients' peripheral CD8+ T-cell populations were similar to that of healthy donors, and a small amount of CD8+ tumor-infiltrating lymphocytes was identified in glioma tissues. An increase in activated CD8+ T cells, characterized as CD38+HLA-DR+, and their association with disease progression were identified in the patients' peripheral blood and glioma, and shown to display enriched CCR5+ and TNFR2+ expression levels. Ex vivo examination of CD38+HLA-DR+CD8+ T cells indicated that this subset of cells displayed stronger secretion of IFN-γ and IL-2 before and after a 6-h stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin (ION) relative to healthy CD38+HLA-DR+CD8+ T cells, indicating the functional feasibility of CD38+HLA-DR+CD8+ T cells. Higher CCL5 protein and mRNA levels were identified in glioma tissues, which was consistent with the immunohistochemistry results revealing both CCL5 and CD38+HLA-DR+CD8+ T cell expression. Patients' CCR5+CD38+HLA-DR+CD8+ T cells were further validated and shown to display increases in CD45RA+CCR7− and T-bet+ accompanied by substantial CD107-a, IFN-γ, and Granzyme B levels in response to glioma cells.

Methicillin-resistant Staphylococcus aureus (MRSA) is the primary microbe responsible for skin infections that are particularly difficult to eradicate. This study sought to inhibit planktonic and biofilm MRSA using furanoquinone-derived compounds containing imine moiety. A total of 19 furanoquinone analogs were designed, synthesized, and assessed for anti-MRSA potency. Among 19 compounds, (Z)-4-(hydroxyimino)naphtho[1,2-b]furan-5(4H)-one (HNF) and (Z)-4-(acetoxyimino)naphtho[1,2-b]furan-5(4H)-one (ANF) showed antibacterial activity superior to the others based on an agar diffusion assay. HNF and ANF exerted a bactericidal effect with a minimum inhibitory concentration (MIC) of 9.7 ∼ 19.5 and 2.4 ∼ 9.7 μg/ml, respectively. Both compounds were able to reduce the MRSA count by 1,000-fold in biofilm as compared to the control. In vivo efficacy was evaluated using a mouse model of skin infection. Topical application of lead compounds significantly suppressed abscess occurrence and the MRSA burden, and also ameliorated the skin-barrier function. The biochemical assay indicated the compounds’ inhibition of DNA polymerase and gyrase. In silico docking revealed a favorable interaction of the compounds with DNA polymerase and gyrase although the binding was not very strong. The total DNA analysis and proteomic data suggested a greater impairment of some proteins by HNF than ANF. In general, HNF and ANF were similarly potent in MRSA inhibition in vitro and in vivo. The findings demonstrated that there was room for structural modification of furanoquinone compounds that could be used to identify anti-MRSA agent candidates.

AbstractIn autonomous driving vehicles, the heterogeneity between human and automation agents can cause conflicts in decision-making and behaviour due to the difference in perception of hazardous situations. Augmented Reality Human-Machine Interfaces (AR-HMI) provide an opportunity to support driving performance by enabling drivers to intuitively access shared perception and explanation of the automated vehicle. One possible approach to AR-HMI design is to simplify the information of driving tasks based on vehicle context understanding, although there is currently a lack of systematic understanding of how collaborative mechanisms or cognitive features contribute to AR-HMI information design. Therefore, this work develops an augmented reality cognitive interface design method for autonomous driving. It aims to identify novel collaborative interface information visualization and provide a common language and inspiration for the design space. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Objective: To compare utilization patterns for patients with newonset neck pain by initial provider specialty. Summary of Background Data: Initial provider specialty has been associated with distinct care patterns among patients with acute back pain; little is known about care patterns among patients with acute neck pain. Methods: De-identified administrative claims and electronic health record data were derived from the Optum Labs Data Warehouse, which contains longitudinal health information on over 200M enrollees and patients representing a mixture of ages and geographical regions across the United States. Patients had outpatient visits for new-onset neck pain from October 1, 2016 to September 30, 2019, classified by initial provider specialty. Utilization was assessed during a 180-day follow-up period, including subsequent neck pain visits, diagnostic imaging, and therapeutic interventions. Results: The cohort included 770,326 patients with new-onset neck pain visits. The most common initial provider specialty was chiropractor (45.2%), followed by primary care (33.4%). Initial provider specialty was strongly associated with the receipt of subsequent neck pain visits with the same provider specialty. Rates and types of diagnostic imaging and therapeutic interventions during follow-up also varied widely by initial provider specialty. While uncommon after initial visits with chiropractors (≤2%), CT, or MRI scans occurred in over 30% of patients with initial visits with emergency physicians, orthopedists, or neurologists. Similarly, 6.8% and 3.4% of patients initially seen by orthopedists received therapeutic injections and major surgery, respectively, compared with 0.4% and 0.1% of patients initially seen by a chiropractor. Conclusion: Within a large national cohort, chiropractors were the initial provider for a plurality of patients with new-onset neck pain. Compared with patients initially seen by physician providers, patients treated initially by chiropractors or therapists received fewer and less costly imaging services and were less likely to receive invasive therapeutic interventions during follow-up. [ABSTRACT FROM AUTHOR]