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Jong Man Kim,* Jong Wook Oh,* Sangjin Kim, Jinsoo Rhu, Ji Soo Lee, Kyeong Sik Kim, Gyu-Seong Choi, Jae-Won JohDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea*These authors contributed equally to this workBackground: Tablet and capsule forms have advantages and disadvantages in the market. Generally, the tablet form (500 mg) of mycophenolate mofetil (MMF) is more convenient for drug ingestion and more cost-effective than the capsule form (250 mg). We examined the efficacy and safety of MMF in its different forms combined with tacrolimus in liver transplant recipients.Methods: A randomized controlled trial was performed to compare the efficacy and safety between the tablet form of MMF (tablet group) and the capsule form of MMF (capsule group) in liver transplant patients. One hundred sixteen patients were enrolled in the present study from 2014 to 2017. Fifty-six patients in the full-analysis set (FAS) population were in the capsule group and 60 were in the tablet group. The primary endpoint was incidence of biopsy-proven acute rejection (BPAR) by 24 weeks after liver transplantation (LT). Secondary endpoints were patient survival, serum creatinine level, and adverse events (AEs).Results: In the per-protocol population, 45 patients were in the tablet group and 49 were in the capsule group. There were no statistically significant differences in MMF dose, mycophenolic acid trough level, and tacrolimus trough level between the two groups. The incidence of BPAR at 24 weeks after randomization was 6.7% in the tablet group and 6.1% in the capsule group (P=0.627). All patients with BPAR responded well to steroid pulse therapy and increased tacrolimus. Serum creatine level and eGFR were not different between the two groups. The incidence of serious AEs was 7.2% in the tablet group and 7.6% in the capsule group, and none were related to formulation. There was no significant difference in incidence of discontinuations or serious AEs between the two groups.Conclusion: The present study suggests that the new tablet formulation can be a useful treatment option to maintain a consistent systemic exposure level of MMF, which may help reduce graft failure in liver transplant patients.Keywords: tacrolimus, liver transplantation, efficacy, immunosuppression

Yong Cheol Shin,1,* Won Jun Yang,1,* Jong Ho Lee,1 Jin-Woo Oh,2 Tai Wan Kim,3 Jong-Chul Park,4 Suong-Hyu Hyon,5 Dong-Wook Han1 1Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Republic of Korea; 2Department of Nanomaterials Engineering, College of Nanoscience and Nanotechnology, Pusan National University, Busan, Republic of Korea; 3Department of Design, College of Arts, Pusan National University, Busan, Republic of Korea; 4Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Center for Fiber and Textile Science, Kyoto Institute of Technology, Kyoto, Japan *These authors contributed equally to this work Abstract: This study concentrates on the development of biodegradable nanofiber membranes with controlled drug release to ensure reduced tissue adhesion and accelerated healing. Nanofibers of poly(lactic-co-glycolic acid) (PLGA) loaded with epigallocatechin-3-O-gallate (EGCG), the most bioactive polyphenolic compound in green tea, were electrospun. The physicochemical and biomechanical properties of EGCG-releasing PLGA (E-PLGA) nanofiber membranes were characterized by atomic force microscopy, EGCG release and degradation profiles, and tensile testing. In vitro antioxidant activity and hemocompatibility were evaluated by measuring scavenged reactive oxygen species levels and activated partial thromboplastin time, respectively. In vivo antiadhesion efficacy was examined on the rat peritonea with a surgical incision. The average fiber diameter of E-PLGA membranes was approximately 300–500 nm, which was almost similar to that of pure PLGA equivalents. E-PLGA membranes showed sustained EGCG release mediated by controlled diffusion and PLGA degradation over 28 days. EGCG did not adversely affect the tensile strength of PLGA membranes, whereas it significantly decreased the elastic modulus and increased the strain at break. E-PLGA membranes were significantly effective in both scavenging reactive oxygen species and extending activated partial thromboplastin time. Macroscopic observation after 1 week of surgical treatment revealed that the antiadhesion efficacy of E-PLGA nanofiber membranes was significantly superior to those of untreated controls and pure PLGA equivalents, which was comparable to that of a commercial tissue-adhesion barrier. In conclusion, the E-PLGA hybrid nanofiber can be exploited to craft strategies for the prevention of postsurgical adhesions. Keywords: nanofiber membrane, poly(lactic-co-glycolic acid), epigallocatechin-3-O-gallate, antiadhesion, tissue-adhesion barrier

Strict social isolation and physical distancing measures implemented during the COVID-19 pandemic had significant implications for the psychological well-being of middle-aged and older adults. This study aimed to investigate factors associated with depressive symptoms during the pandemic period among individuals who reported no significant depressive symptoms before the pandemic. Individuals from the Korean Longitudinal Study of Aging without a previous report of significant depressive symptoms across Waves 6 (2016) and 7 (2018) were investigated for the development of depressive symptoms in Wave 8 (2020). The multivariable logistic regression results revealed that both men and women who participated in social gatherings and physical exercise less than once a week were associated with an increase in the likelihood of depressive symptoms (odds ratio [OR] 2.88; 95% confidence interval [CI] 1.80-4.61 and OR 2.61; 95% CI 1.64-4.15, respectively for men and OR 2.58; 95% CI 1.80-3.70 and OR 1.51; 95% CI 1.02-2.23, respectively for women). In addition, unmarried men (OR 2.38; 95% CI 1.37-4.14) and women with one chronic disease (OR 1.98; 95% CI 1.14-3.43) or two or more chronic diseases (OR 2.28; 95% CI 1.31-3.99) reported a significant increase in the likelihood of depressive symptoms. Regular social gatherings and physical exercise were identified as key factors in mitigating depressive symptoms among middle-aged and older adults. The findings can inform the development of public health strategies that promote regular social interactions and physical activity to enhance the psychological resilience and overall well-being of middle-aged and older adults in the endemic era., Competing Interests: Declaration of competing interest Authors declare there is no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Tissue clearing enables deep imaging in various tissues by increasing the transparency of tissues, but there were limitations of immunostaining of the large-volume tissues such as the whole brain., Methods: Here, we cleared and immune-stained whole mouse brain tissues using a novel clearing technique termed high-speed clearing and high-resolution staining (HCHS). We observed neural structures within the cleared brains using both a confocal microscope and a light-sheet fluorescence microscope (LSFM). The reconstructed 3D images were analyzed using a computational reconstruction algorithm., Results: Various neural structures were well observed in three-dimensional (3D) images of the cleared brains from Gad-green fluorescent protein (GFP) mice and Thy 1-yellow fluorescent protein (YFP) mice. The intrinsic fluorescence signals of both transgenic mice were preserved after HCHS. In addition, large-scale 3D imaging of brains, immune-stained by the HCHS method using a mild detergent-based solution, allowed for the global topological analysis of several neuronal markers such as c-Fos, neuronal nuclear protein (NeuN), Microtubule-associated protein 2 (Map2), Tuj1, glial fibrillary acidic protein (GFAP), and tyrosine hydroxylase (TH) in various anatomical regions in the whole mouse brain tissues. Finally, through comparisons with various existing tissue clearing methodologies such as CUBIC, Visikol, and 3DISCO, it was confirmed that the HCHS methodology results in relatively less tissue deformation and higher fluorescence retention., Conclusion: In conclusion, the development of 3D imaging based on novel tissue-clearing techniques (HCHS) will enable detailed spatial analysis of neural and vascular networks present within the brain., (© 2024. Korean Tissue Engineering and Regenerative Medicine Society.)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on the viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression, notably, the decreased expression of the Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. This study demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

Targeted and stimuli-responsive drug delivery enhances therapeutic efficacy and minimizes undesirable side effects of cancer treatment. Although cellulose nanocrystals (CNCs) are used as drug carriers because of their robustness, spindle shape, biocompatibility, renewability, and nontoxicity, the lack of programmability and functionality of CNCs-based platforms hampers their application. Thus, high adaptability and the capacity to form dynamic 3D nanostructures of DNA may be advantageous, as they can provide functionalities such as target-specific and stimuli-responsive drug release. Using DNA nanotechnology, the functional polymeric form of DNA nanostructures can be replicated using rolling circle amplification (RCA), and the biologically and physiologically stable DNA nanostructures may overcome the challenges of CNCs. In this study, multifunctional polymeric DNAs produced with RCA were strongly complexed with surface-modified CNCs via electrostatic interactions to form polymeric DNA-decorated CNCs (pDCs). Particle size, polydispersity, zeta potential, and biostability of the nanocomplexes were analyzed. As a proof of concept, the dynamic structural functionalities of DNA nanostructures were verified by observing cancer-targeted intracellular delivery and pH-responsive drug release. pDCs showed anticancer properties without side effects in vitro, owing to their aptamer and i-motif functionalities. In conclusion, pDCs exhibited multifunctional anticancer activities, demonstrating their potential as a promising hybrid nanocomplex platform for targeted cancer therapy., Competing Interests: Declaration of competing interest There are no competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A weak van der Waals (vdW) force in layered materials enables their isolation into thin flakes through mechanical exfoliation while sustaining their intrinsic electronic and optical properties. Here, we introduce a universal roll-printing method capable of producing vdW multilayer films on wafer-to-meter scale. This process uses sequential exfoliation and transfer of layered materials from the powder sources to target substrates through a repeated rolling of a cylindrical metal drum. We achieve uniformly coated films with a library of vdW powders on various mechanically rigid and flexible substrates. The printed films are configured into different devices including light-emitting diodes and photodetectors. The presented technique offers substantial benefits in terms of cost efficiency and a low thermal budget while offering high material quality.

Background: High hand hygiene (HH) workload is a commonly cited barrier to optimal HH performance. The objective of this study was to assess trends of HH workload as defined by HH opportunities (HHO) and performance rates over different timescales using automated HH monitoring system data., Methods: This multiyear retrospective observational study was conducted in 58 inpatient units located in 10 North American hospitals. HHO and HH rates were analyzed by time series mixed effects general additive model., Results: Median HH rates peaked at 50.0 between 6 and 7 AM with a trough of 38.2 at 5 PM. HHO over hours in a day were the highest at 184 per hospital unit per hour at 10 AM with a trough of 49.0 between 2 and 3 AM. Median rates for day and night shifts were 40.8 and 45.5, respectively (P = .078). Weekend day shift had the lowest median rate (39.4) compared with any other 12-hour shift (P < .1018). The median rates and HHO varied little across days in a week and months., Conclusions: HH workload and performance rates were negatively correlated and changed drastically over hours in a day. Hospitals should consider HH workload in the development and timely delivery of improvement interventions., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Despite the negative health impact of multiple risk-taking behaviors (RTBs), there is a lack of understanding of adolescents who are more prone to multiple RTBs. This study aimed to identify sociodemographic, mental, and physical health variables associated with increased susceptibility to multiple RTBs in each sex., Methods: Cross-sectional data from the 2020 and 2021 Korea Youth Risk Behavior Web-based Survey was used. A total of 106,979 Korean adolescents (55,460 men and 51,519 women) were assessed on five RTBs (alcohol use, smoking, sexual intercourse, illicit substance use, no seat belt wearing). In comparison to no RTB group, odds ratios of the relevant covariate factors were calculated in one RTB or multiple RTBs groups., Results: Male and female adolescents engaging in multiple RTBs were 6.4% and 3.8%, respectively. Increasing age, low subjective socioeconomic status, and living in rural areas were associated with multiple RTBs regardless of sex. All mental health variables except anxiety were associated with multiple RTBs in both sexes. Physical inactivity and obesity were associated with decreased odds of multiple RTBs in both sexes., Conclusion: This study identifies diverse factors associated with multiple RTBs of Korean adolescents and demonstrates existing sex differences. Age and mental health status are the most critical factors that distinguish multiple risk-taking groups from those involved in one or no RTB., Competing Interests: Declaration of competing interest The authors have no potential competing interests to declare for conducting this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study compared the anti-pseudomonal effects between nephrite-impregnated contact lenses (CLs) and conventional and cosmetic CLs., Methods: After inoculation with Pseudomonas aeruginosa (P.aeruginosa) , we counted the number of bacteria on the CL surface and observed each surface using atomic force microscopy (AFM) and scanning electron microscopy (SEM). To estimate potential harm of nephrite-impregnated CLs, we conducted a safety test using a rabbit model, treated with all CL types., Results: Both conventional and cosmetic CLs ( n  = 258 ± 2.9 × 10 4 , 368 ± 2.2 × 10 4 ) showed significantly decreased number of attached bacteria when compared with those without nephrite impregnation ( n  = 134 ± 0.8 × 10 4 , 238 ± 2.5 × 10 4 , p  < 0.0001, respectively). AFM and SEM revealed that P. aeruginosa was less attached to the nephrite-impregnated CLs than to the conventional and cosmetic CLs, although those with nephrite impregnation had rougher surface. In the safety test, there were no significant differences in the findings between four groups, and the clarity and stability of all corneas were preserved., Conclusions: Nephrite may be used as a next-generation substance to reduce infectious keratitis caused by P. aeruginosa when added to CLs.

Asthma and atopic dermatitis (AD) are representative chronic diseases in childhood. This study aimed to investigate the impact of preterm birth on the incidence and severity of asthma and AD in children, as well as to identify neonatal risk factors for asthma and AD. We used health claims data recorded between 2007 and 2014 in the Korean National Health Insurance Service database. We recruited 2,224,476 infants born between 2007 and 2014 and divided them into three groups: 3518 of extremely preterm (EP) infants (< 28 weeks of gestational age (GA)), 82,579 of other preterm (OP) infants (28-36 weeks of GA), and 2,138,379 of full-term (FT) infants (> 37 weeks of GA). We defined asthma as > 3 episodes of clinical visits in a year before 6 years of age, early asthma as onset at < 2 years of age, and severe asthma as > 1 event of status asthmaticus or admission to a hospital via an emergency room. AD was defined as ≥ 3 diagnoses in a year before 6 years of age, early AD as onset at < 2 years of age, and severe AD as prescription of high-potency topical steroids or immunosuppressants. An association of preterm birth with asthma and AD was assessed using inverse probability of treatment-weighted multivariable Cox regression analysis. Cardiorespiratory conditions, such as respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, and pulmonary hypertension, significantly increased the risk of asthma. Specifically, bronchopulmonary dysplasia emerged as a significant risk factor for both severe and early-onset asthma (odds ratio (OR) 1.36, 95% CI 1.21-1.37 for severe asthma; OR 1.55, 95% CI 1.30-1.85 for early asthma), while it was associated with a decreased risk of AD (OR 0.86, 95% CI 0.80-0.92). Neonatal sepsis, jaundice, and retinopathy of prematurity were also identified as significant risk factors for later asthma. A stepwise increase in the risk of asthma with an increasing degree of prematurity was observed, with the OP group showing an adjusted hazard ratio (aHR) of 1.24 (95% CI: 1.22-1.26) and the EP group showing an aHR of 1.51 (95% CI: 1.41-1.63). Conversely, preterm birth was inversely associated with the risk of AD, with aHRs of 0.73 (95% CI: 0.67-0.79) for the OP group and 0.88 (95% CI: 0.87-0.89) for the EP group. Conclusion Preterm children have a significantly higher risk of asthma and lower risk of AD, with cardiorespiratory conditions significantly increasing the risk of asthma. Thus, we highlight the need for targeted respiratory management strategies for this high-risk population. What is Known: •Asthma and atopic dermatitis are prevalent chronic diseases in childhood, reducing the quality of life of children. •Preterm birth was associated with an increased risk of asthma, but few large nationwide studies. •Research on the relationship between preterm birth and pediatric atopic dermatitis is controversial, with few large nationwide studies. What is New: • Preterm children, especially born before 28 weeks of gestational age, had a significantly higher risk of asthma and lower risk of atopic dermatitis. • Cardiorespiratory comorbidities such as RDS, BPD, PDA, and pulmonary hypertension in neonatal period are prominent risk factors for asthma. • Preterm children are vulnerable to both early-onset and severe asthma., (© 2024. The Author(s).)

Understanding somatic mutations and structural variations in domestic pigs (Sus scrofa domestica) is critical due to their increasing importance as model organisms in biomedical research. In this study, we conducted a comprehensive analysis through whole-genome sequencing of skin, organs, and blood samples. By examining two pig pedigrees, we investigated the inheritance and sharedness of structural variants among fathers, mothers, and offsprings. Utilizing single-cell clonal expansion techniques, we observed significant variations in the number of somatic mutations across different tissues. An in-house developed pipeline enabled precise filtering and analysis of these mutations, resulting in the construction of individual phylogenetic trees for two pigs. These trees explored the developmental relationships between different tissues, revealing insights into clonal expansions from various anatomical locations. This study enhances the understanding of pig genomes, affirming their increasing value in clinical and genomic research, and provides a foundation for future studies in other animals, paralleling previous studies in mice and humans. This approach not only deepens our understanding of mammalian genomic variations but also strengthens the role of pigs as a crucial model in human health and disease research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer has become a consistent concern globally and increasingly fatal. Malignant melanoma is a rising concern, with its increased mortality. Kaempferia parviflora Wall. ex Baker ( K. parviflora (KP)), commonly known as black ginger, is well known for its medicinal contributions. For the first time, in the following study we investigated the antimelanoma potential of Laos KP extracts in human cell lines. KP extracts (KPE) in methanol, DCM, and ethyl acetate showed strong cell inhibition in both melanomas, with KPE-DCM being particularly effective in inhibiting melanoma cell migration, invasion, and proliferation by inducing cell cycle arrest and apoptosis, while KPE-Hexane exhibited a low cell inhibition rate and a more limited effect. KPE affected the increased expression of caspase-3, PARP andBax and the decreased expression of the BcL-2, Mu-2-related death-inducing gene (MUDENG, MuD) protein. Furthermore, KPE enhanced apoptotic cells in the absence and presence of the pancaspase inhibitor Z-VAD-FMK. Interestingly, these apoptotic cells were significantly suppressed by the caspase inhibitor. Moreover, elevated mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels, suggestive of KPE's mitochondrial-mediated apoptosis in melanoma cells, were also confirmed. KPE treatment increased MMP levels, and upregulated the generation of ROS in A375 cells but not in A2058 cells. However, pretreatment with an ROS scavenger (NAC) suppressed KPE-induced cell death and ROS generation. These results clearly pointed out KPE-induced mitochondrial-mediated apoptotic cell death as the mechanism behind the inhibition of the human melanoma cells. Future studies exploring the role of specific ROS sources and their interaction with mitochondrial dynamics could deepen the existing understanding on KPE-induced apoptosis.

Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10 -8 per base pair) and a turnover frequency of 10-20 per year, which are fundamental components shaping the landscape of mtDNA mosaicism over a lifetime. The expansion of mtDNA-truncating mutations toward homoplasmy was substantially suppressed. Our findings provide comprehensive insights into the origins, dynamics and functional consequences of mtDNA mosaicism in human somatic cells., (© 2024. The Author(s).)

Background: There is evidence that global anthropogenic climate change may be impacting floral phenology and the temporal and spatial characteristics of aero-allergenic pollen. Given the extent of current and future climate uncertainty, there is a need to strengthen predictive pollen forecasts., Methods: The study aims to use CatBoost (CB) and deep learning (DL) models for predicting the daily total pollen concentration up to 14 days in advance for 23 cities, covering all five continents. The model includes the projected environmental parameters, recent concentrations (1, 2 and 4 weeks), and the past environmental explanatory variables, and their future values., Results: The best pollen forecasts include Mexico City (R 2 (DL&#95;7) ≈ .7), and Santiago (R 2 (DL&#95;7) ≈ .8) for the 7th forecast day, respectively; while the weakest pollen forecasts are made for Brisbane (R 2 (DL&#95;7) ≈ .4) and Seoul (R 2 (DL&#95;7) ≈ .1) for the 7th forecast day. The global order of the five most important environmental variables in determining the daily total pollen concentrations is, in decreasing order: the past daily total pollen concentration, future 2 m temperature, past 2 m temperature, past soil temperature in 28-100 cm depth, and past soil temperature in 0-7 cm depth. City-related clusters of the most similar distribution of feature importance values of the environmental variables only slightly change on consecutive forecast days for Caxias do Sul, Cape Town, Brisbane, and Mexico City, while they often change for Sydney, Santiago, and Busan., Conclusions: This new knowledge of the ecological relationships of the most remarkable variables importance for pollen forecast models according to clusters, cities and forecast days is important for developing and improving the accuracy of airborne pollen forecasts., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Gene regulatory elements drive complex biological phenomena and their mutations are associated with common human diseases. The impacts of human regulatory variants are often tested using model organisms such as mice. However, mapping human enhancers to conserved elements in mice remains a challenge, due to both rapid enhancer evolution and limitations of current computational methods. We analyze distal enhancers across 45 matched human/mouse cell/tissue pairs from a comprehensive dataset of DNase-seq experiments, and show that while cell-specific regulatory vocabulary is conserved, enhancers evolve more rapidly than promoters and CTCF binding sites. Enhancer conservation rates vary across cell types, in part explainable by tissue specific transposable element activity. We present an improved genome alignment algorithm using gapped-kmer features, called gkm-align, and make genome wide predictions for 1,401,803 orthologous regulatory elements. We show that gkm-align discovers 23,660 novel human/mouse conserved enhancers missed by previous algorithms, with strong evidence of conserved functional activity., (© 2024. The Author(s).)

While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine., Competing Interests: Declaration of interests Y.S.J. is the co-founder and chief genomics officer of Inocras, Inc. J.S.L. is the co-founder and chief innovation officer of Inocras, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The use of naturally sourced organic materials with chirality, such as the M13 bacteriophage, holds intriguing implications, especially in the field of nanotechnology. The chirality properties of bacteriophages have been demonstrated through numerous studies, particularly in the analysis of liquid crystal phase transitions, developing specific applications. However, exploring the utilization of the M13 bacteriophage as a template for creating chiral nanostructures for optics and sensor applications comes with significant challenges. In this study, the chirality of the M13 bacteriophage was leveraged as a valuable tool for generating helical hybrid structures by combining it with nanoparticles through an evaporation-induced three-dimensional (3D) printing process. Utilizing on the self-assembly property of the M13 bacteriophage, metal nanoparticles were organized into a helical chain under the influence of the M13 bacteriophage at the meniscus interface. External parameters, including nanoparticle shape, the ratio between the bacteriophage and nanoparticles, and pulling speed, were demonstrated as crucial factors affecting the fabrication of helical nanostructures. This study aimed to explore the potential of chiral nanostructure fabrication by utilizing the chirality of the M13 bacteriophage and manipulating external parameters to control the properties of the resulting hybrid structures.

The colorimetric sensor-based electronic nose has been demonstrated to discriminate specific gaseous molecules for various applications, including health or environmental monitoring. However, conventional colorimetric sensor systems rely on RGB sensors, which cannot capture the complete spectral response of the system. This limitation can degrade the performance of machine learning analysis, leading to inaccurate identification of chemicals with similar functional groups. Here, we propose a novel time-resolved hyperspectral (TRH) data set from colorimetric array sensors consisting of 1D spatial, 1D spectral, and 1D temporal axes, which enables hierarchical analysis of multichannel 2D spectrograms via a convolution neural network (CNN). We assessed the outstanding classification performance of the TRH data set compared to an RGB data set by conducting a relative humidity (RH) concentration classification. The time-dependent spectral response of the colorimetric sensor was measured and trained as a CNN model using TRH and RGB sensor systems at different RH levels. While the TRH model shows a high classification accuracy of 97.5% for the RH concentration, the RGB model yields 72.5% under identical conditions. Furthermore, we demonstrated the detection of various functional volatile gases with the TRH system by using experimental and simulation approaches. The results reveal distinct spectral features from the TRH system, corresponding to changes in the concentration of each substance.

This systematic review and meta-analysis aimed to investigate the prevalence of self-reported sleep disturbances in people living with HIV considering the effects of age, depression, anxiety, CD4 cell counts, time since HIV diagnosis, study region, and the instruments used to measure sleep disturbances. We searched PubMed, PsycINFO, and EMBASE to include eligible articles. In this meta-analysis of 43 studies, the pooled prevalence of self-reported sleep disturbances was 52.29% (95% confidence interval 47.69-56.87). The subgroup analyses revealed that variations in the sleep measurements and study region significantly contributed to the observed heterogeneity. In the meta-regression analyses, higher proportions of participants with depression or anxiety and longer times since HIV diagnosis were significantly associated with a higher prevalence of self-reported sleep disturbances after adjusting for mean age. Our findings emphasise the substantial burden of sleep disturbances in people living with HIV and identified comorbid depression and anxiety and the time since HIV diagnosis as significant moderators. These results underscore the importance of considering these factors when designing tailored screening programmes for high-risk patients and implementing early interventions to prevent and mitigate sleep disturbances in people living with HIV., (© 2024. The Author(s).)

Extracellular vesicles (EVs) are membrane-surrounded vesicles released by various cell types into the extracellular microenvironment. Although EVs vary in size, biological function, and components, their importance in cancer progression and the potential use of EV molecular species to serve as novel cancer biomarkers have become increasingly evident. Cancer cells actively release EVs into surrounding tissues, which play vital roles in cancer progression and metastasis, including invasion and immune modulation. EVs released by cancer cells are usually chosen as a gateway in the search for biomarkers for cancer. In this review, we mainly focused on molecular profiling of EV protein constituents from breast cancer, emphasizing mass spectrometry (MS)-based proteomic approaches. To further investigate the potential use of EVs as a source of breast cancer biomarkers, we have discussed the use of these proteins as predictive marker candidates. Besides, we have also summarized the key characteristics of EVs as potential therapeutic targets in breast cancer and provided significant information on their implications in breast cancer development and progression. Information provided in this review may help understand the recent progress in understanding EV biology and their potential role as new noninvasive biomarkers as well as emerging therapeutic opportunities and associated challenges., (© 2024 The Authors. Proteomics published by Wiley‐VCH GmbH.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a 'highly transmissible respiratory pathogen, leading to severe multi-organ damage. However, knowledge regarding SARS-CoV-2-induced cellular alterations is limited. In this study, we report that SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral infection. SARS-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNA-nucleocapsid cluster, thereby abnormally promoting mitochondrial elongation and the OXPHOS process, followed by enhancing ATP production. Furthermore, SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking, contributing to abnormal OXPHOS process and viral propagation. Approved EGFR inhibitors remarkably reduce SARS-CoV-2 propagation, among which vandetanib exhibits the highest antiviral efficacy. Treatment of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation, thereby resulting in the reduction of SARS-CoV-2 propagation. Furthermore, oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung inflammation. Vandetanib also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern, including alpha, beta, delta and omicron, in in vitro cell culture experiments. Taken together, our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation, suggesting that EGFR is an attractive host target for combating COVID-19., (© 2024. The Author(s).)

The effects of COVID-19 vaccination on short-term and long-term cerebrovascular risks among COVID-19 survivors remained unknown. We conducted a national multi-center retrospective cohort study with 151 597 vaccinated and 151 597 unvaccinated COVID-19 patients using the TriNetX database, from January 1, 2020 to December 31, 2023. Patients baseline characteristics were balanced with propensity score matching (PSM). The outcomes were incident cerebrovascular diseases occurred between 1st and 30th days (short-term) after COVID-19 diagnosis. Nine subgroup analyses were conducted to explore potential effect modifications. We performed six sensitivity analyses, including evaluation of outcomes between 1st to 180th days, accounting for competing risk, and incorporating different variant timeline to test the robustness of our results. Kaplan-Meier curves and Log-Rank tests were performed to evaluate survival difference. Cox proportional hazards regressions were adopted to estimate the PSM-adjusted hazard ratios (HR). The overall short-term cerebrovascular risks were lower in the vaccinated group compared to the unvaccinated group (HR: 0.66, 95% CI: 0.56-0.77), specifically cerebral infarction (HR: 0.62, 95% CI: 0.48-0.79), occlusion and stenosis of precerebral arteries (HR: 0.74, 95% CI: 0.53-0.98), other cerebrovascular diseases (HR: 0.57, 95% CI: 0.42-0.77), and sequelae of cerebrovascular disease (HR: 0.39, 95% CI:0.23-0.68). Similarly, the overall cerebrovascular risks were lower in those vaccinated among most subgroups. The long-term outcomes, though slightly attenuated, were consistent (HR: 0.80, 95% CI: 0.73-0.87). Full 2-dose vaccination was associated with a further reduced risk of cerebrovascular diseases (HR: 0.63, 95% CI: 0.50-0.80) compared to unvaccinated patients. Unvaccinated COVID-19 survivors have significantly higher cerebrovascular risks than their vaccinated counterparts. Thus, clinicians are recommended to monitor this population closely for stroke events during postinfection follow-up., (© 2024 Wiley Periodicals LLC.)

The purpose of this study is to investigate the association between handgrip strength (HGS) and health-related quality of life (HRQoL), demonstrating HGS as an effective indicator for evaluating HRQoL of patients with cancer. Analyzing 1657 Korean adult cancer patients (644 males, 1013 females) aged ≥ 20 years from the Korea National Health and Nutrition Examination Survey (2014-2019), HGS was standardized based on body mass index and categorized by sex. HRQoL was assessed using the Euro Quality of Life-5-Dimension 3-Level version (EQ-5D-3L) Index. Lower relative HGS was associated with decreased HRQoL in female patients, while no significant association was found in male patients. The lowest quartile of relative HGS exhibited a 2.5-fold decrease in HRQoL compared to the highest quartile (OR 2.50, 95% CI 1.59-3.95, p < 0.001). Both male and female patients with cancer were affected by age, subjective health perception, and stress recognition regarding HRQoL. This study suggests that HGS may be associated with the HRQoL of female patients with cancer, emphasizing that the HGS measurement can be effectively utilized as a pivotal tool for evaluating HRQoL in female patients with cancer., (© 2024. The Author(s).)

We developed a novel electrochemical sensor for the detection of alfuzosin (AFZ), a drug used to treat benign prostatic hyperplasia, using a double-shelled Co 3 O 4 /NiCo 2 O 4 nanocomposite-modified electrode. The nanocomposites were synthesized using a template-assisted approach, with zeolitic imidazole framework-67 (ZIF-67) as the sacrificial template, involving the formation of uniform ZIF-67/Ni-Co layered double hydroxide (LDH) hollow structures followed by calcination to achieve the final nanocomposite. The nanocomposite was characterized by various techniques and showed high porosity, large surface area, and good conductivity. The nanocomposite-modified electrode exhibited excellent electrocatalytic activity towards AFZ oxidation, with a wide linear range of 5-180 µM and a low limit of detection of 1.37 µM. The sensor also demonstrated good repeatability, reproducibility, and stability selectivity in the presence of common interfering substances. The sensor was successfully applied to determine the AFZ in pharmaceutical tablets and human serum samples, with satisfactory recoveries. Our results suggest that the double-shelled Co 3 O 4 /NiCo 2 O 4 nanocomposite is a promising material for the fabrication of electrochemical sensors for AFZ detection.

Optical encryption using coloration and photoluminescent (PL) materials can provide highly secure data protection with direct and intuitive identification of encrypted information. Encryption capable of independently controlling wavelength-tunable coloration as well as variable light intensity PL is not adequately demonstrated yet. Herein, a rewritable PL and structural color (SC) display suitable for dual-responsive optical encryption developed with a stimuli-responsive SC of a block copolymer (BCP) photonic crystal (PC) with alternating in-plane lamellae, of which a variety of 3D and 2D perovskite nanocrystals is preferentially self-assembled with characteristic PL, is presented. The SC of a BCP PC is controlled in the visible range with different perovskite precursor doping times. The perovskite nanocrystals developed in the BCP PC are highly luminescent, with a PL quantum yield of ≈33.7%, yielding environmentally stable SC and PL dual-mode displays. The independently programmed SC and PL information is erasable and rewritable. Dual-responsive optical encryption is demonstrated, in which true Morse code information is deciphered only when the information encoded by SCs is properly combined with PL information. Numerous combinations of SC and PL realize high security level of data anticounterfeiting. This dual-mode encryption display offers novel optical encryption with high information security and anti-counterfeiting., (© 2024 Wiley‐VCH GmbH.)

The ENCODE Consortium's efforts to annotate noncoding cis-regulatory elements (CREs) have advanced our understanding of gene regulatory landscapes. Pooled, noncoding CRISPR screens offer a systematic approach to investigate cis-regulatory mechanisms. The ENCODE4 Functional Characterization Centers conducted 108 screens in human cell lines, comprising >540,000 perturbations across 24.85 megabases of the genome. Using 332 functionally confirmed CRE-gene links in K562 cells, we established guidelines for screening endogenous noncoding elements with CRISPR interference (CRISPRi), including accurate detection of CREs that exhibit variable, often low, transcriptional effects. Benchmarking five screen analysis tools, we find that CASA produces the most conservative CRE calls and is robust to artifacts of low-specificity single guide RNAs. We uncover a subtle DNA strand bias for CRISPRi in transcribed regions with implications for screen design and analysis. Together, we provide an accessible data resource, predesigned single guide RNAs for targeting 3,275,697 ENCODE SCREEN candidate CREs with CRISPRi and screening guidelines to accelerate functional characterization of the noncoding genome., (© 2024. The Author(s).)

Excessive alcohol consumption has been consistently linked to depression. This study, utilizing nationwide samples from the Korea National Health and Nutrition Examination Survey (n = 21,440) examined the association between drinking behaviors and depressive symptoms while also exploring the influence of sleep duration on this relationship. Demographic, socioeconomic, and health-related factors were included as covariates in the multivariable logistic regression analysis to assess their relationships with depressive symptoms. Based on their sleep duration, the participants were divided into subgroups to explore how sleep duration affects the relationship between drinking behaviors and depressive symptoms. Moderate alcohol consumption (1-4 times a month) was associated with reduced likelihood of experiencing depressive symptoms in women (p = 0.024), with a similar trend observed among men (p = 0.001). Men who started consuming alcohol before the age of 19 had a higher likelihood of experiencing depressive symptoms (p = 0.048). Only women who consumed more alcohol per occasion (≥ 7 drinks) had higher odds of depressive symptoms (p = 0.001). This study revealed complex factors that influence depressive symptoms, including alcohol consumption and sleep duration. This highlights the importance of tailored interventions based on sleep duration and sociodemographic characteristics for preventing and treating depression., (© 2024. The Author(s).)

The surface-enhanced Raman scattering (SERS) technique has garnered significant interest due to its ultrahigh sensitivity, making it suitable for addressing the growing demand for disease diagnosis. In addition to its sensitivity and uniformity, an ideal SERS platform should possess characteristics such as simplicity in manufacturing and low analyte consumption, enabling practical applications in complex diagnoses including cancer. Furthermore, the integration of machine learning algorithms with SERS can enhance the practical usability of sensing devices by effectively classifying the subtle vibrational fingerprints produced by molecules such as those found in human blood. In this study, we demonstrate an approach for early detection of breast cancer using a bottom-up strategy to construct a flexible and simple three-dimensional (3D) plasmonic cluster SERS platform integrated with a deep learning algorithm. With these advantages of the 3D plasmonic cluster, we demonstrate that the 3D plasmonic cluster (3D-PC) exhibits a significantly enhanced Raman intensity through detection limit down to 10 -6 M (femtomole-(10 -17 mol)) for p -nitrophenol (PNP) molecules. Afterward, the plasma of cancer subjects and healthy subjects was used to fabricate the bioink to build 3D-PC structures. The collected SERS successfully classified into two clusters of cancer subjects and healthy subjects with high accuracy of up to 93%. These results highlight the potential of the 3D plasmonic cluster SERS platform for early breast cancer detection and open promising avenues for future research in this field.

Stem cell technology holds immense potential for revolutionizing medicine, particularly in regenerative treatment for heart disease. The unique capacity of stem cells to differentiate into diverse cell types offers promise in repairing damaged tissues and implanting organs. Ensuring the quality of differentiated cells, essential for specific functions, demands in-depth analysis. However, this process consumes time and incurs substantial costs while invasive methods may alter stem cell features during differentiation and deplete cell numbers. To address these challenges, we propose a non-invasive strategy, using cellular respiration, to assess the quality of differentiation-induced stem cells, notably cardiovascular stem cells. This evaluation employs an electronic nose (E-Nose) and neural pattern separation (NPS). Our goal is to assess differentiation-induced cardiac stem cells (DICs) quality through E-Nose data analysis and compare it with standard commercial human cells (SCHCs). Sensitivity and specificity were evaluated by interacting SCHCs and DICs with the E-Nose, achieving over 90% classification accuracy. Employing selective combinations optimized by NPS, E-Nose successfully classified all six cell types. Consequently, the relative similarity among DICs like cardiomyocytes, endothelial cells with SCHCs was established relied on comparing response data from the E-Nose sensor without resorting to complex evaluations., Competing Interests: Declaration of competing interest I also declare on my honor that the information disclosed in this submission is true and complete to the best of my and our knowledge., (Copyright © 2023. Published by Elsevier B.V.)

The U.S. Global Change Research Program, Fourth National Climate Assessment reports that it is extremely likely that human activities, especially emissions of greenhouse gases, are the dominant cause of the observed warming since the mid-20th century. There are no convincing alternative explanations supported by observational evidence., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Metabolome analysis has gained widespread application in disease diagnosis owing to its ability to provide comprehensive information, including disease phenotypes. In this study, we utilized 3D superstructures fabricated through evaporation-induced microprinting to analyze the metabolome for glaucoma diagnosis. 3D superstructures offer the following advantages: high hotspot density per unit volume of the structure extending from two to three dimensions, excellent signal repeatability due to the reproducibility and defect tolerance of 3D printing, and high thermal stability due to the PVP-enclosed capsule form. Leveraging the superior optical properties of the 3D superstructure, we aimed to classify patients with glaucoma. The signal obtained from the 3D superstructure was employed in a Deep Neural Network (DNN) classification model to accurately classify glaucoma patients. The sensitivity and specificity of the model were determined as 92.05% and 93.51%, respectively. Additionally, the fabrication of 3D superstructures can be performed at any stage, significantly reducing measurement time. Furthermore, their thermal stability allows for the analysis of smaller samples. One notable advantage of 3D superstructures is their versatility in accommodating different target materials. Consequently, they can be utilized for a wide range of metabolic analyses and disease diagnoses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Pollen forecasting systems can provide information for coping with respiratory allergies. They estimate daily pollen production, dispersal, deposition, and removal based on daily weather conditions to predict daily pollen concentrations and provide allergy warnings. As of 2023, the Korea Meteorological Administration (KMA) provides 2-day forecast of allergenic pollens. However, unlike these models, long-term analysis of annual observations of tree pollen reveal annual variations. Therefore, in this study, we aimed to develop annual prediction models for allergenic tree pollens based on long-term multi-site pollen and meteorological data., Methods: Daily pollen concentrations were observed using Hirst-type volumetric spore traps at nine sites in Korea from 1998 to 2021, and daily weather data from the closest KMA stations were utilized. Models were developed to predict the seasonal pollen integral of seven tree species based on monthly mean temperature, wind speed, and total precipitation using three variable selection methods: 1) the t -test based key variable screening followed by linear regression with stepwise procedure (TM), 2) direct linear regression with stepwise procedure from the full variable model (FM), and 3) LASSO regression from the full variable model (LM)., Results: Data obtained during 1998-2017 and 2018=2021 were utilized for model development and validation, respectively. The root mean squared error, mean absolute error, mean error, and coefficient of determination (R²) revealed that the TM models were best suited for actual forecasting, even though R² in the TM model was lower than those of the FM and LM models., Conclusions: The annual variation model in this study can be integrated with the daily pollen forecast model by controlling the annual pollen potential, and the accuracy of the daily forecast can be improved accordingly., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Abstract: Black out rage gallons (BORGs) are a troublesome drinking pattern emerging on social media platforms. The prevalence of BORGs has been increasing on college campuses and is demonstrating significant consequences. There is no known research on BORGs in addiction treatment settings. We suggest that future research will be necessary to understand their implication. Troublesome binge drinking is not a new problem among colleges. However, social media has seemed to ignite such trends., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

l-Histidine plays significant roles in the food and pharmaceutical industries, and its demand has been steadily increasing recently. As demand for l-histidine continues, the development of eco-friendly processes is required. To pursue this goal, D-galactose, a primary component of red algae, was employed as a carbon source for synthesizing l-histidine. To harness this marine biomass, κ-carrageenan was preferentially hydrolyzed to obtain D-galactose using κ-carrageenase (CgkA) and iduronate-2-sulfatase (IdsA3). Subsequently, l-histidine production was enhanced by modifying precursor pathways in Corynebacterium glutamicum. The resulting strain, TDPH6 exhibited a remarkable 2.15-fold increase in l-histidine production compared to TDP. Furthermore, a galactose utilization system was introduced and named TDPH6G2. During fermentation, this strain efficiently consumed 100 % of the D-galactose and synthesized 0.395 g/L of l-histidine. In conclusion, this study presents a sustainable approach to L-histidine synthesis by introducing a galactose utilization system into C. glutamicum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Gender incongruence (GI) is a condition in which an individual's gender identity, role, and expression differ from their assigned sex. This study aimed to evaluate when GI first arises in transgender and non-binary individuals seeking hormone therapy and their years living untreated in South Korea., Methods: This retrospective study analyzed GI patients seeking gender-affirming hormone therapy (GAHT) or surgery between 2015 and 2021. The recorded data included gender identity, legal transition status, age of onset of GI, age at the initiation of therapy, and total therapy duration., Results: In total, 337 patients were enrolled, including 149 (44.2%) transgender men, 153 (45.4%) transgender women, and 35 (10.4%) non-binary individuals. The mean age of onset of GI was 10.6 years (standard deviation, 5.1). Of the total patients, 29% had an onset of GI before age 6 years (preschool), 61% before age 12 (elementary-school), and 87% before age 15 (middle-school). Patients lived with GI for almost 14 years before GAHT initiation at a median age of 23.0 years. 90% of transgender men, 82.3% of transgender women, and 85% of non-binary patients disclosed their gender identities to their families. Regarding social transition, 31.5% of transgender men, 16.3% of transgender women, and none of the non-binary patients (P<0.005) changed their legal gender markers., Conclusion: Many transgender and non-binary individuals experience GI early in life. These findings emphasized the need for early evaluation, timely gender-affirming care, and more accessible legal processes for gender marker changes in South Korea, aiming to enhance the safety and well-being of these individuals.

With the increasing challenge of controlling infectious diseases due to the emergence of antibiotic-resistant strains, the importance of discovering new antimicrobial agents is rapidly increasing. Animal venoms contain a variety of functional peptides, making them a promising platform for pharmaceutical development. In this study, a novel toxin peptide with antibacterial and anti-inflammatory activities was discovered from the spider venom gland transcriptome by implementing computational approaches. Lycotoxin-Pa2a (Lytx-Pa2a) showed homology to known-spider toxin, where functional prediction indicated the potential of both antibacterial and anti-inflammatory peptides without hemolytic activity. The colony-forming assay and minimum inhibitory concentration test showed that Lytx-Pa2a exhibited comparable or stronger antibacterial activity against pathogenic strains than melittin. Following mechanistic studies revealed that Lytx-Pa2a disrupts both cytoplasmic and outer membranes of bacteria while simultaneously inducing the accumulation of reactive oxygen species. The peptide exerted no significant toxicity when treated to human primary cells, murine macrophages, and bovine red blood cells. Moreover, Lytx-Pa2a alleviated lipopolysaccharide-induced inflammation in mouse macrophages by suppressing the expression of inflammatory mediators. These findings not only suggested that Lytx-Pa2a with dual activity can be utilized as a new antimicrobial agent for infectious diseases but also demonstrated the implementation of in silico methods for discovering a novel functional peptide, which may enhance the future utilization of biological resources.

Aims: We aimed to develop a virtual reality-based smartphone application that improves patient safety competency among nursing students in terms of knowledge, attitudes and confidence in patient safety management. We also sought to evaluate the effects and utility of the application in improving patient safety competency., Design: A parallel, randomized controlled pre- and post-test trial was conducted to test the effects of knowledge, attitudes and performance confidence in patient safety management., Methods: Participants were randomly allocated to the experimental (n = 22), in which nursing students received a two-week mobile web-based training programme covering key topics in patient safety management or the control group (n = 22), in which nursing students received a training booklet. Participants completed a pre-test and two post-test questionnaires to assess the program's impact. The evaluation tools were patient safety management knowledge, attitude and patient safety management performance confidence scale. Data analysis was performed using descriptive statistics, homogeneity test for pre-test, unpaired t-test and repeated measures ANOVA., Results: Patient safety competency in the experimental group improved significantly in terms of knowledge (from 11.68 to 18.55, p < 0.000), attitude (from 3.38 to 4.01; p < 0.005) and performance confidence (from 3.93 to 4.52; p < 0.000) compared with the control group. Our findings suggest that mobile app-based education using virtual reality may be effective in enhancing patient safety management in nursing education., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Sensors for detecting infinitesimal amounts of chemicals in air have been widely developed because they can identify the origin of chemicals. These sensing technologies are also used to determine the variety and freshness of fresh food and detect explosives, hazardous chemicals, environmental hormones, and diseases using exhaled gases. However, there is still a need to rapidly develop portable and highly sensitive sensors that respond to complex environments. Here, we show an efficient method for optimising an M13 bacteriophage-based multi-array colourimetric sensor for multiple simultaneous classifications. Apples, which are difficult to classify due to many varieties in distribution, were selected for classifying targets. M13 was adopted to fabricate a multi-array colourimetric sensor using the self-templating process since a chemical property of major coat protein p8 consisting of the M13 body can be manipulated by genetic engineering to respond to various target substances. The twenty sensor units, which consisted of different types of manipulated M13, exhibited colour changes because of the change of photonic crystal-like nanostructure when they were exposed to target substances associated with apples. The classification success rate of the optimal sensor combinations was achieved with high accuracy for the apple variety (100%), four standard fragrances (100%), and aging (84.5%) simultaneously. We expect that this optimisation technique can be used for rapid sensor development capable of multiple simultaneous classifications in various fields, such as medical diagnosis, hazardous environment monitoring, and the food industry, where sensors need to be developed in response to complex environments consisting of various targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2023. Published by Elsevier B.V.)

This study investigated the role of phospholipase D (PLD) in retinal ischemia-reperfusion (I/R) injury using an oxygen-glucose deprivation/reperfusion (OGD/R) model commonly used in retinal I/R injury research. To create an in vitro cellular I/R model, pharmacological inhibitors and small interfering RNA (siRNA) were used to target PLD1 and PLD2 in retinal pigment epithelial (RPE) cells. Treatment with PLD inhibitors and siRNA reduced reactive oxygen species (ROS) and malondialdehyde (MDA) induced by OGD/R in RPE cells and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), indicating a reduction in oxidative damage and improvement in the antioxidant system. Next, we showed that inhibiting PLD1 or PLD2 reduced intracellular iron levels and lipid peroxidation, which are critical factors in ferroptosis. Additionally, PLD1 and PLD2 modulated the expression of proteins involved in the regulation of ferroptosis, including GPX4, SLC7A11, FTH1, and ACSL4. We also investigated the roles of PLD1 and PLD2 in preventing pyroptosis, another form of programmed cell death associated with inflammation. Our study found that OGD/R significantly increased the production of pro-inflammatory cytokines and activated caspase-1, NLRP3, ASC, cleaved-caspase 1 (C-caspase-1), and GSDMD-N in RPE cells, indicating pyroptosis induction. However, PLD1 and PLD2 inhibition or knockdown significantly inhibited the production of pro-inflammatory cytokines and activation of the NLRP3 inflammasome, Taken together, our findings support the hypothesis that the PLD signaling pathway plays a key role in OGD/R-induced ferroptosis and pyroptosis induction and may be a potential therapeutic target for preventing or treating retinal dysfunction and degeneration., (© 2023 John Wiley & Sons Ltd.)

Seaweed extracts and their specific polysaccharides are widely known for their ability to act as reducing and capping agents during nanoparticle synthesis. Their application is highly favored in green synthesis methods, owing to their eco-friendliness, cost-effectiveness, and remarkable time and energy efficiency. In this study, fucoidan extracted from Undaria pinnatifida sporophyll (UPS) is introduced as a polysaccharide that effectively serves as a dual-function reducing and capping agent for the synthesis of gold nanoparticles (AuNPs). Results from various analyses indicate that AuNPs derived from UPS extract display a uniform spherical shape with an average size of 28.34 ± 1.15 nm and a zeta potential of -37.49 ± 2.13 mV, conclusively confirming the presence of Au. The FT-IR spectra distinctly revealed the characteristic fucoidan bands on the stabilized UPS-AuNPs surface. A 1 H-NMR analysis provided additional confirmation by revealing the presence of specific fucoidan protons on the UPS-AuNPs surface. To comprehensively evaluate the impact of UPS extract, UPS-AuNPs, and fucoidan on the biological properties of adipocytes, a rigorous comparative analysis of lipid droplet formation and morphology was conducted. Our findings revealed that adipocytes treated with UPS extract, fucoidan, and UPS-AuNPs, in that order, exhibited a reduction in the total lipid droplet surface area, maximum Ferret diameter, and overall Nile red staining intensity when compared to mature white adipocytes. Furthermore, our analysis of the effects of UPS extracts, UPS-AuNPs, and fucoidan on the expression of key markers associated with white adipose tissue browning, such as UCP1, PGC1a, and PRDM16, demonstrated increased mRNA and protein expression levels in the following order: UPS-AuNPs > fucoidan > UPS extracts. Notably, the production of active mitochondria, which play a crucial role in enhancing energy expenditure in beige adipocytes, also increased in the following order: UPS-AuNPs > fucoidan > UPS extract. These findings underscore the pivotal role of UPS extract, fucoidan, and UPS-AuNPs in promoting adipocyte browning and subsequently enhancing energy expenditure.

The escalating prevalence of antibiotic-resistant bacteria poses an immediate and grave threat to public health. Antimicrobial peptides (AMPs) have gained significant attention as a promising alternative to conventional antibiotics. Animal venom comprises a diverse array of bioactive compounds, which can be a rich source for identifying new functional peptides. In this study, we identified a toxin peptide, Lycotoxin-Pa1a (Lytx-Pa1a), from the transcriptome of the Pardosa astrigera spider venom gland. To enhance its functional properties, we employed an in silico approach to design a novel hybrid peptide, KFH-Pa1a, by predicting antibacterial and cytotoxic functionalities and incorporating the amino-terminal Cu(II)- and Ni(II) (ATCUN)-binding motif. KFH-Pa1a demonstrated markedly superior antimicrobial efficacy against pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa , compared to Lytx-Pa1a. Notably, KFH-Pa1a exerted several distinct mechanisms, including the disruption of the bacterial cytoplasmic membrane, the generation of intracellular ROS, and the cleavage and inhibition of bacterial DNA. Additionally, the hybrid peptide showed synergistic activity when combined with conventional antibiotics. Our research not only identified a novel toxin peptide from spider venom but demonstrated in silico-based design of hybrid AMP with strong antimicrobial activity that can contribute to combating MDR pathogens, broadening the utilization of biological resources by incorporating computational approaches., Competing Interests: The authors declare no conflict of interest.