Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei.

Trypanosoma brucei is a protozoan parasite that causes Human African Trypanosomiasis (HAT), a neglected tropical disease (NTD) that is endemic in 36 countries in sub-Saharan Africa. Only a handful drugs are available for treatment, and these have limitations, including toxicity and drug resistance. Using the natural product, curcumin, as a starting point, several curcuminoids and related analogs were evaluated against bloodstream forms of T. b. brucei. A particular subset of dibenzylideneacetone (DBA) compounds exhibited potent in vitro antitrypanosomal activity with sub-micromolar EC50 values. A structure-activity relationship study including 26 DBA analogs was initiated, and several compounds exhibited EC50 values as low as 200 nM. Cytotoxicity counter screens in HEK293 cells identified several compounds having selectivity indices above 10. These data suggest that DBAs offer starting points for a new small molecule therapy of HAT.

A study on longitudinal relationship between ultrafine dust and the prevalence of depression.

BACKGROUND: Recently, the fine dust problem caused by rapid industrialization and science and technological development has emerged as a severe social issue worldwide. This also increases the interest in its effect on human life. In particular, there is a growing concern about the harm of fine dust in Korea. METHODS: This study is based on the PM 2.5 data from 2017 to 2021 provided by Air Korea to estimate changes in ultrafine dust. In addition, the data from the Community Health Survey provided by the Korea Centers for Disease Control and Prevention (KCDC) from 2017 to 2021 were used to examine the effect between the change in ultra-fine dust and the prevalence of depression. A total of 229 local governments were included in the analysis. The Latent Growth Modeling was carried out to estimate the change in ultra-fine dust and the prevalence of depressions and verify the relationship between ultra-fine dust and the prevalence of depression. RESULTS: The analysis result revealed that the ultra-fine dust concentration continued to decrease from 2017 to 2021. However, the depression prevalence increased from an average of 2.60% in 2017 to an average of 3.12% in 2021, suggesting the need for adequate and sufficient welfare policies for depression treatment. As a result of estimating the initial value and change rate of ultra-fine dust and depression prevalence, the higher the initial value of ultra-fine dust, the greater the decrease in ultra-fine dust. In terms of depression, the lower the initial value of the prevalence of depression, the larger the increase in depression prevalence. CONCLUSIONS: This study is significant in that it revealed the strong association of the longitudinal relationship between ultra-fine dust and depression, one of the biggest issues in Korea, by utilizing large-scale longitudinal data.

X-ray radiation-induced intestinal barrier dysfunction in human epithelial Caco-2 cell monolayers.

Radiation therapy and unwanted radiological or nuclear exposure, such as nuclear plant accidents, terrorist attacks, and military conflicts, pose serious health issues to humans. Dysfunction of the intestinal epithelial barrier and the leakage of luminal antigens and bacteria across the barrier have been linked to various human diseases. Intestinal permeability is regulated by intercellular structures, termed tight junctions (TJs), which are disrupted after radiation exposure. In this study, we investigated radiation-induced alterations in TJ-related proteins in an intestinal epithelial cell model. Caco-2 cells were irradiated with 2, 5, and 10 Gy and harvested 1 and 24 h after X-ray exposure. The trypan blue assay revealed that cell viability was reduced in a dose-dependent manner 24 h after X-ray exposure compared to that of non-irradiated cells. However, the WST-8 assay revealed that cell proliferation was significantly reduced only 24 h after radiation exposure to 10 Gy compared to that of non-irradiated cells. In addition, a decreased growth rate and increased doubling time were observed in cells irradiated with X-rays. Intestinal permeability was significantly increased, and transepithelial electrical resistance values were remarkably reduced in Caco-2 cell monolayers irradiated with X-rays compared to non-irradiated cells. X-ray irradiation significantly decreased the mRNA and protein levels of ZO-1, occludin, claudin-3, and claudin-4, with ZO-1 and claudin-3 protein levels decreasing in a dose-dependent manner. Overall, the present study reveals that exposure to X-ray induces dysfunction of the human epithelial intestinal barrier and integrity via the downregulation of TJ-related genes, which may be a key factor contributing to intestinal barrier damage and increased intestinal permeability.

Economic analysis of the circular economy based on waste plastic pyrolysis oil: a case of the university campus.

Recently, the concept of a circular economy for carbon neutrality is emerging. In particular, waste plastics are one of the key wastes, and efforts are being made to recycle them as energy rather than dispose of them. Accordingly, the technology of producing and utilizing pyrolysis oil from waste plastics attracts attention. As it is an early stage of technology development, however, there are not many demonstrations and papers that analyze the technology broadly. The goal of this study is to propose building a circular economy on a university campus through waste plastic pyrolysis oil technology. To show its feasibility, waste plastic pyrolysis oil technology is analyzed comprehensively from economic, environmental, and policy perspectives using the scenario analysis technique on the university campus level. A methodology of the scenario analysis technique enables predicting the uncertainties. Since plastic pyrolysis oil technologies and carbon neutrality are accompanied by many uncertainties, this technique is expected to be an appropriate methodology for this study. First, the amount of pyrolysis oil production from waste plastics from the campus is estimated. Then, the cost and carbon emissions from waste plastics are estimated if the pyrolysis oil technology is used instead of the traditional waste disposal process. As a result, the total economic profits of up to 425,484,022 won/year (354,570.01 $/year) are expected when a circular economy is built using waste plastic pyrolysis oil. In addition, it is also confirmed that greenhouse gas (GHG) emissions can be reduced by up to 840,891 kgCO2eq/year. The waste plastic pyrolysis oil satisfies Korea's gas pollutant standards and is consistent with the GHG reduction policy. It can be concluded that building a circular economy at the university campus level using waste plastic pyrolysis oil technology is suitable from economic, environmental, and policy perspectives.

A method for early diagnosis of lung cancer from tumor originated DNA fragments using plasma cfDNA methylome and fragmentome profiles.

Early detection is critical for minimizing mortality from cancer. Plasma cell-free DNA (cfDNA) contains the signatures of tumor DNA, allowing us to quantify the signature and diagnose early-stage tumors. Here, we report a novel tumor fragment quantification method, TOF (Tumor Originated Fragment) for the diagnosis of lung cancer by quantifying and analyzing both the plasma cfDNA methylation patterns and fragmentomic signatures. TOF utilizes the amount of ctDNA predicted from the methylation density information of each cfDNA read mapped on 6243 lung-tumor-specific CpG markers. The 6243 tumor-specific markers were derived from lung tumor tissues by comparing them with corresponding normal tissues and healthy blood from public methylation data. TOF also utilizes two cfDNA fragmentomic signatures: 1) the short fragment ratio, and 2) the 5' end-motif profile. We used 298 plasma samples to analyze cfDNA signatures using enzymatic methyl-sequencing data from 201 lung cancer patients and 97 healthy controls. The TOF score showed 0.98 of the area under the curve in correctly classifying lung cancer from normal samples. The TOF score resolution was high enough to clearly differentiate even the early-stage non-small cell lung cancer patients from the healthy controls. The same was true for small cell lung cancer patients.

Wafer-Scale Production of Transition Metal Dichalcogenides and Alloy Monolayers by Nanocrystal Conversion for Large-Scale Ultrathin Flexible Electronics.

Two-dimensional (2D) transition metal dichalcogenide (TMD) layers are unit-cell thick materials with tunable physical properties according to their size, morphology, and chemical composition. Their transition of lab-scale research to industrial-scale applications requires process development for the wafer-scale growth and scalable device fabrication. Herein, we report on a new type of atmospheric pressure chemical vapor deposition (APCVD) process that utilizes colloidal nanoparticles as process-scalable precursors for the wafer-scale production of TMD monolayers. Facile uniform distribution of nanoparticle precursors on the entire substrate leads to the wafer-scale uniform synthesis of TMD monolayers with the controlled size and morphology. Composition-controlled TMD alloy monolayers with tunable bandgaps can be produced by simply mixing dual nanoparticle precursor solutions in the desired ratio. We also demonstrate the fabrication of ultrathin field-effect transistors and flexible electronics with uniformly controlled performance by using TMD monolayers.

Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro, In Vivo and Clinical Studies.

Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM's severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed "indirect evidence"). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.

Toward a comprehensive understanding of global vegetation CO2 assimilation from space.

Large-scale global analysis of the relationship between growing season solar-induced chlorophyll fluorescence (SIF) and gross primary productivity (GPP), indicated by the GPP/SIF ratio, varied greatly with higher values found in wet-and-cold climate regions and lower values found in hot-and-dry climate regions. Such pattern has been shown to be most influenced by the environmental factor of moisture availability.

Facile Ferroelectric Phase Transition Driven by Si Doping in HfO2.

The recently discovered ferroelectricity in thin-film orthorhombic HfO2, which can be directly integrated into complementary metal-oxide semiconductor technology, has become an important research target. However, the use of orthorhombic HfO2 in practical devices has been limited by undesirable mixing with the monoclinic phase, which is nonpolar and thus degrades the ferroelectric properties. Here, we demonstrate that a Si dopant significantly stabilizes the ferroelectric phase because of its unique bonding characteristics, particularly its intrinsic tendency to form strong covalent bonds with O, thereby weakening the phase boundary to stabilize the ferroelectric orthorhombic phase over the nonpolar monoclinic phase, relatively. On the basis of our theoretical predictions, we conducted transmission electron microscopy measurements and confirmed that Si substitution doping indeed induced monoclinic structural components into the orthorhombic phase, which is a strong indication of the weakened phase boundary and subsequent facilitation of the ferroelectric transition. This work thus provides an atomic-scale picture for understanding the unique role of Si in promoting the ferroelectric phase and the dopant dependence on the wake-up effect in HfO2, offering a substantial advancement toward integrating ferroelectrics into practical devices.

Sonographic features of Rosai-Dorfman disease in the breast: A case report.

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is an uncommon histiocytic disease of the lymph nodes. Extranodal presentation, especially in breast parenchymal tissue, is rare. A 54-year-old woman presented with a painful and palpable lump in the right breast. Ultrasonography revealed an irregular, indistinct, hypoechoic mass with a hyperechoic halo. Pathological analysis revealed proliferation of large histiocytes and stromal fibrosis with emperipolesis and positive immunoreactivity for S-100 and CD68. The clinical and radiologic manifestations of Rosai-Dorfman disease may vary, and differentiation from other inflammatory diseases and malignancies is challenging; thus, accurate pathological diagnosis plays an important role in appropriate management.

Direct Observation of Redox Mediator-Assisted Solution-Phase Discharging of Li-O2 Battery by Liquid-Phase Transmission Electron Microscopy.

Li-O2 battery is one of the important next-generation energy storage systems, as it can potentially offer the highest theoretical energy density among battery chemistries reported thus far. However, realization of its high discharge capacity still remains challenging and is hampered by the nature of how the discharge products are formed, causing premature passivation of the air electrode. Redox mediators are exploited to solve this problem, as they can promote the charge transfer from electrodes to the solution phase. The mechanistic understanding of the fundamental electrochemical reaction involving the redox mediators would aid in the further development of Li-O2 batteries along with rational design of new redox mediators. Herein, we attempt to monitor the discharge reaction of a Li-O2 battery in real time by liquid-phase transmission electron microscopy (TEM). Direct in situ TEM observation reveals the gradual growth of toroidal Li2O2 discharge product in the electrolyte with the redox mediator upon discharge. Moreover, quantitative analyses of the growth profiles elucidate that the growth mechanism involves two steps: dominant lateral growth of Li2O2 into disclike structures in the early stage followed by vertical growth with morphology transformation into a toroidal structure.

The PICASSO Cohort: baseline characteristics of a cohort of men who have sex with men and male-to-female transgender women at high risk for syphilis infection in Lima, Peru.

BACKGROUND: Men who have sex with men (MSM) and male-to-female transgender women (transwomen) are disproportionately at risk of syphilis infection in Peru. METHODS: From 2013 to 2014, MSM and transwomen seeking human immunodeficiency virus (HIV) or sexually transmitted infection (STI) testing and/or treatment were recruited into a 2-year observational cohort study to determine predictors of recently acquired syphilis infection (defined as a rapid plasma reagin [RPR] titer ≥1:16 and a reactive treponemal antibody test) in Lima, Peru. At baseline, interviewers collected sociodemographic, behavioral, and medical characteristics from participants. All cohort participants were tested for syphilis, HIV, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) infection. Using cross-sectional analyses, bivariate and multivariate models were used to determine factors associated with recently acquired syphilis infection and calculate adjusted prevalence ratios. RESULTS: We recruited 401 participants, 312 MSM and 89 transwomen, with median ages of 29.0 and 32.5 years old (interquartile ranges: 23.3, 37.4 and 27.2, 39.5, respectively). The prevalence of recently acquired syphilis infection at baseline was 16.8% for MSM and 6.7% for transwomen. Among MSM and transwomen, 30.1 and 33.7% were infected with HIV, 18.6 and 24.7% were infected with CT, and 14.2 and 19.1% were infected with NG, respectively. Co-infection rates among MSM with recently acquired syphilis infection included: 44.2% with HIV, 40.4% with CT (32.7% with anal CT and 7.7% with pharyngeal CT), and 19.2% with NG (11.5% with anal NG and 7.7% with pharyngeal NG). Co-infection rates among transwomen with recently acquired syphilis infection included: 66.7% with HIV, 0% with CT, and 16.7% with anal NG. In multivariate analysis among the entire cohort, recently acquired syphilis infection was independently associated with younger age (adjusted prevalence ratio [aPR] = 0.96, 95% confidence interval [CI] = 0.93-0.99), receptive role during anal sex (aPR = 2.56, 95% CI = 1.05-6.25), prior HIV diagnosis (aPR = 1.70, 95% CI = 1.11-2.61), anal CT or NG infection (aPR = 1.69, 95% CI = 1.09-2.60), and prior syphilis diagnosis (aPR = 3.53, 95% CI = 2.20-5.68). CONCLUSIONS: We recruited a cohort of MSM and transwomen who had a high prevalence of recently acquired syphilis infection in Lima, Peru. Recently acquired syphilis infection was associated with socio-demographic characteristics, sexual risk, and sexually transmitted co-infections.

Protease IV, a quorum sensing-dependent protease of Pseudomonas aeruginosa modulates insect innate immunity.

In Pseudomonas aeruginosa, quorum sensing (QS) plays an essential role in pathogenesis and the QS response controls many virulence factors. Using a mealworm, Tenebrio molitor as a host model, we found that Protease IV, a QS-regulated exoprotease of P. aeruginosa functions as a key virulence effector causing the melanization and death of T. molitor larvae. Protease IV was able to degrade zymogens of spätzle processing enzyme (SPE) and SPE-activating enzyme (SAE) without the activation of the antimicrobial peptide (AMP) production. Since SPE and SAE function to activate spätzle, a ligand of Toll receptor in the innate immune system of T. molitor, we suggest that Protease IV may interfere with the activation of the Toll signaling. Independently of the Toll pathway, the melanization response, another innate immunity was still generated, since Protease IV directly converted Tenebrio prophenoloxidase into active phenoloxidase. Protease IV also worked as an important factor in the virulence to brine shrimp and nematode. These results suggest that Protease IV provides P. aeruginosa with a sophisticated way to escape the immune attack of host by interfering with the production of AMPs.

Anthranilate deteriorates the structure of Pseudomonas aeruginosa biofilms and antagonizes the biofilm-enhancing indole effect.

Anthranilate and indole are alternative degradation products of tryptophan, depending on the bacterial species. While indole enhances the biofilm formation of Pseudomonas aeruginosa, we found that anthranilate, the tryptophan degradation product of P. aeruginosa, had an opposite effect on P. aeruginosa biofilm formation, in which anthranilate deteriorated the mushroom structure of biofilm. The anthranilate effect on biofilm formation was differentially exerted depending on the developmental stage and the presence of shear force. Anthranilate slightly accelerated the initial attachment of P. aeruginosa at the early stage of biofilm development and appeared to build more biofilm without shear force. But anthranilate weakened the biofilm structure in the late stage, deteriorating the mushroom structure of biofilms with shear force to make a flat biofilm. To investigate the interplay of anthranilate with indole in biofilm formation, biofilms were cotreated with anthranilate and indole, and the results showed that anthranilate antagonized the biofilm-enhancing effect of indole. Anthranilate was able to deteriorate the preformed biofilm. The effect of anthranilate and indole on biofilm formation was quorum sensing independent. AntR, a regulator of anthranilate-degrading metabolism was synergistically activated by cotreatment with anthranilate and indole, suggesting that indole might enhance biofilm formation by facilitating the degradation of anthranilate. Anthranilate slightly but significantly affected the cyclic diguaniylate (c-di-GMP) level and transcription of major extracellular polysaccharide (Psl, Pel, and alginate) operons. These results suggest that anthranilate may be a promising antibiofilm agent and antagonize the effect of indole on P. aeruginosa biofilm formation.

Theaflavins enhance intestinal barrier of Caco-2 Cell monolayers through the expression of AMP-activated protein kinase-mediated Occludin, Claudin-1, and ZO-1.

We investigated the effect of theaflavins (TFs) on membrane barrier of Caco-2 cells. For fluorescein-transport experiments, the apparent permeability (Papp) of fluorescein in Caco-2 cells pretreated with 20 µM TFs were significantly decreased compared with that in untreated cells. Although the respective monomeric catechins did not show any Papp reduction, purpurogallin pretreatment resulted in a significant Papp reduction similar to that of TF-3'-O-gallate (TF3'G) pretreatment. This indicates that the benzotropolone moiety may play a crucial role in the Papp reduction or tight junction (TJ)-closing effect induced by TFs. In TF-3'-O-gallate-pretreated Caco-2 cells, fluorescein transport was completely restored by compound C (AMPK inhibitor). In addition, TF3'G significantly increased both the mRNA and protein expression of TJ-related proteins (occludin, claudin-1, and ZO-1) as well as the phosphorylation of AMPK. It was, thus, concluded that TFs could enhance intestinal barrier function by increasing the expression of TJ-related proteins through the activation of AMPK in Caco-2 cells.

Consumer preferences for telemedicine devices and services in South Korea.

OBJECTIVE: The scope of healthcare has been expanding from caring for sick people to keeping people from becoming sick, and telemedicine will play a significant role in this new healthcare paradigm. This study investigated consumer preferences and willingness to pay for attributes of telemedicine services in South Korea. A market simulation was conducted to examine the market shares of alternative services and their relationships to the perceived usefulness of service types and preferred device types. MATERIALS AND METHODS: Using a conjoint survey, we collected data on consumer preferences for six telemedicine service attributes. Data analysis used the Bayesian mixed logit model. The market simulation estimated the probabilities of a specific service alternative being chosen using estimated model coefficients. RESULTS: Wearable devices were the most preferred, followed by smart-home and smartphone devices. Consumers perceived managing blood glucose to be the most useful telemedicine service, followed by monitoring oxygen saturation and blood pressure. The market simulation indicated that consumer preferences for device types were associated with the types of chronic diseases for which management through telemedicine services is perceived to be useful. CONCLUSIONS: As the focus of healthcare moves from treating patients to keeping individuals healthy, a key factor for the successful deployment of telemedicine services is understanding consumer perceptions and attitudes. The results of this study revealed the dynamics of consumer preferences with regard to service attributes.

Mitigation effect of hesperidin on X-ray radiation-induced intestinal barrier dysfunction in Caco-2 cell monolayers.

The tight junctions (TJs) and barrier function of the intestinal epithelium are highly sensitive to radiation. However, polyphenols can be used to reverse the effects of radiation. Here, we investigated the effects of hesperidin (hesperetin-7-rhamnoglucoside) on X-ray-induced intestinal barrier dysfunction in human epithelial Caco-2 monolayers. To examine whether hesperidin mitigated the effects of X-ray exposure (2 Gy), cell survival was evaluated and intestinal barrier function was assessed by measuring the transepithelial flux, apparent permeability coefficient (Papp), and barrier integrity. Hesperidin improved the survival of Caco-2 cell monolayers and attenuated X-ray exposure-induced intestinal barrier dysfunction. For fluorescein transport experiments, transepithelial flux and Papp of fluorescein in control group were significantly elevated by X-ray, but were restored to near control by 10 µM hesperidin pretreatment. Further, X-ray exposure decreased the barrier integrity and TJ interruption by reducing TJ-related proteins occludin and claudin-4, whereas cell monolayers pretreated with hesperidin before X-ray exposure were reinstated to control level. It was concluded that hesperidin treatment before X-ray exposure alleviated X-ray-induced intestinal barrier dysfunction through regulation of TJ-related proteins. These results indicate that hesperidin prevents and mitigates X-ray-induced intestinal barrier dysfunction.

Transformative Multifunction Deep Ultraviolet Photodetectors for On-Demand Applications: From Fast Optical Communication to Tunable In-Sensor Photocurrent Integration.

The strategic utilization of photodetectors' transient response could open new frontiers from free-space optical communication to the emerging field of neuromorphic optoelectronics. Contrarily, while communication requires a fast response, neuromorphic applications benefit from a slow and integrative transient photocurrent. By integrating these functionalities in a single device, this study unveils a photodetector with tunable responses, bridging the gap between optical communication and neuromorphic sensing and creating a versatile platform with on-demand applications. Particularly, a Ga2O3-based photodetector was designed, exhibiting a photocurrent on/off ratio close to 104, high responsivity of 0.43 A/W, and detectivity 1.22 × 1013 Jones under deep ultraviolet illumination (λ ∼ 260 nm). The photodetector demonstrates transient time-dependent on operational voltage, ranging from 10-4 to 0.2 s. The underlying mechanism is attributed to the voltage-dependent balance between photocarrier generation and defect-related recombination, as revealed by electrostatic force microscopy. Additionally, we have demonstrated potential applications, including digital Morse code interpretation, tunable integration of optical inputs within the sensor, one-time readouts, and effective analog Morse code reading. Furthermore, the effectiveness of input information recognition using analog integration, even with anomalies, was demonstrated. This work establishes a versatile approach for tunable in-sensor optical processing, potentially useful for a wide range of applications, from free-space optical communication to neuromorphic sensing.

Understanding the Interplay of Religion, Social Relationships, and Depressive Symptoms in Later Life: An Analysis of Dynamics in Individual and Dyadic Contexts.

This study examined how religious participation at the individual level and the dyadic religious similarity at the couple level influenced depressive symptoms via social relationships among older Korean couples aged 65 and above. The sample included 1,191 couples from the seventh assessment of the Korean Longitudinal Study of Ageing. The findings indicated that older adults who participated in religious activities more frequently showed lower levels of depressive symptoms through increased social interactions and marital satisfaction. Additionally, older couples with similar religious backgrounds showed higher levels of marital satisfaction than those without similar religious backgrounds, subsequently leading to lower levels of depressive symptoms. Overall, the associations between religion and depressive symptoms were similar for both genders. The findings provided insights into potential mechanisms leading to later-life depressive symptoms at both the individual and couple levels in terms of religion and social relationships and informed practical implications for older couples' marital relationships.