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Jui-Jen Chang,1,2,* Yi-Chen Wang,3,4,* Shu-Hui Yang,5,6 Ju-Yu Wu,7 Ming-Wei Chang,8 Hui-Min David Wang5,9– 11 1Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40447, Taiwan; 2Graduate Institute of Integrated Medicine, China Medical University, Taichung, 40447, Taiwan; 3Division of Cardiology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung City, 802, Taiwan; 4Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 807, Taiwan; 5Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, 402, Taiwan; 6Bachelor Program of Biotechnology, National Chung Hsing University, Taichung, 402, Taiwan; 7Doctoral Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, 402, Taiwan; 8Nanotechnology and Integrated Bioengineering Centre, University of Ulster, Belfast, BT15 1AB, Northern Ireland, UK; 9Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 10Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 404, Taiwan; 11Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan*These authors contributed equally to this workCorrespondence: Hui-Min David Wang, Graduate Institute of Biomedical Engineering, National Chung Hsing University, No. 145, Xingda Road, South Dist, Taichung City, 402, Taiwan, Tel +886-4-22840733#651 ; +886-935753718, Email davidw@dragon.nchu.edu.twBackground: Recently, the use of the tumor or its secretions as drug carriers has gradually become popular, with the advantages of high biocompatibility and enhanced drug delivery to specific cells. Melanoma is the most malignant tumor of all skin cancers; it is the most metastatic and, therefore, the most difficult to treat. The main purpose of this study is to develop nanovesicles with tumor cell membrane secretion properties to encapsulate target substances to enhance the therapeutic effect of cancer.Methods: Astaxanthin was selected as an anticancer drug due to our previous research finding that astaxanthin has extremely high antioxidant, anti-ultraviolet damage, and anti-tumor properties. The manufacturing method of the astaxanthin nanovesicle carrier is to mix melanoma cells and astaxanthin in an appropriate ratio and then remove the genetic material and inflammatory factors of cancer cells by extrusion.Results: In terms of results, after the co-culture of astaxanthin nanovesicles and melanoma cancer cells, it was confirmed that the ability of astaxanthin nanovesicles to inhibit the growth and metastasis of melanoma cancer cells was significantly better than the same amount of astaxanthin alone, and it had no effect on normal Human cells are also effective. There was no apparent harm on normal cells, indicating the ability of the vesicles to be selectively transported.Conclusion: Our findings illustrated the potential of astaxanthin nanovesicles as an anticancer drug. Keywords: melanoma, astaxanthin, nanoparticle

STUDY OBJECTIVES: Mycoplasma pneumoniae is a common cause of lower respiratory disease. Several studies have suggested that respiratory infection by M pneumoniae is associated with reactive airway disease and asthma. Interleukin (IL)-8 has been suggested to have a role in the pathogenesis of the allergic inflammation of bronchial asthma, and is well known to be expressed in bronchial epithelial cells. MEASUREMENTS: An examination was carried out into the effect of M pneumoniae lysate (MPL) and the role of mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinase (ERK) on IL-8 expression in human lung epithelial cells. A549 cells were seeded at a density of 5 x 10(4) cells per well and incubated in basal medium for a further 24 h. IL-8 levels were determined by an enzyme-linked immunosorbent assay. MAPK phosphorylation was assessed by Western blotting. RESULTS: In A549 cells, MPL induced IL-8 release in a time- and dose-dependent manner. Pretreatment with PD 98059, which blocks the activation of MAPK/ERK kinase 1, inhibited MPL-induced IL-8 production by 64.4% at 25 micromol/L. Stimulation of A549 cells by MPL also caused an increase in the activity of ERK, compared with the nonstimulated cells. The MPL stimulation had no effect on the activities of p38. CONCLUSION: These observations suggest that activation of ERK by MPL may be one of the mechanisms that result in an increase of the production of IL-8. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cutaneous neonatal lupus resembles subacute cutaneous lupus erythematosus (SCLE), and photosensitivity is a common symptom. Tumor necrosis factor alpha (TNFalpha) release by ultraviolet light-exposed keratinocytes may be exaggerated in SCLE patients who have the haplotype TNFalpha -308A;DRB1*03. Accordingly, this study was undertaken to seek genetic and histologic evidence for a role of TNFalpha in the pathogenesis of cutaneous neonatal lupus. METHODS: DNA was isolated from 83 children (22 with rash, 35 with congenital heart block [CHB], 26 unaffected siblings) and 58 mothers from the Research Registry for Neonatal Lupus. RESULTS: The -308A allele (associated with higher TNFalpha production), HLA-DRQB1*02, and HLA-DRB1*03 were each present in the majority of children with rash (64%, 68%, and 64%, respectively). The frequency of all 3 6p alleles occurring together in 1 individual was greater in children with rash than in children who had either CHB or no manifestation of neonatal lupus (59% versus 30%; P = 0.02). This association with neonatal lupus rash was equivalent to published findings in a cohort of patients with SCLE, but significantly greater than the association in patients with discoid lupus erythematosus. Prominent TNFalpha staining in the epidermis was observed in lesional skin from 3 children with rash, but not in skin from a healthy neonate. CONCLUSION: Taken together, the finding of a genetic predisposition to generate increased levels of TNFalpha following tissue injury and the histologic demonstration of TNFalpha in the target organ support the notion that this inflammatory cytokine plays a role in the pathogenesis of cutaneous neonatal lupus. Furthermore, the results of these studies provide evidence of a biologic link between neonatal lupus and the rash of SCLE. [ABSTRACT FROM AUTHOR]

Dysphagia (difficulty in swallowing) is a common clinical symptom associated with many diseases, such as stroke, multiple sclerosis, neuromuscular diseases, and cancer. Its complications include choking, aspiration, malnutrition, cachexia, and dehydration. The goal in dysphagia management is to provide adequate nutrition and hydration while minimizing the risk of choking and aspiration. It is important to advance the individual toward oral feeding in a timely manner to enhance the recovery of swallowing function and preserve the quality of life. Current clinical assessments of dysphagia are limited in providing adequate guidelines for oral feeding. Mathematical modeling of the fluid dynamics of pharyngeal bolus transport provides a unique opportunity for studying the physiology and pathophysiology of swallowing. Finite element analysis (FEA) is a special case of computational fluid dynamics (CFD). In CFD, the flow of a fluid in a space is modeled by covering the space with a grid and predicting how the fluid moves from grid point to grid point. FEA is capable of solving problems with complex geometries and free surfaces. A preliminary pharyngeal model has been constructed using FEA. This model incorporates literature-reported, normal, anatomical data with time-dependent pharyngeal/ upper esophageal sphincter (UES) wall motion obtained from videofluorography (VFG). This time-dependent wall motion can be implemented as a moving boundary condition in the model. Clinical kinematic data can be digitized from VFG studies to construct and test the mathematical model. The preliminary model demonstrates the feasibility of modeling pharyngeal bolus transport, which, to our knowledge, has not been attempted before. This model also addresses the need and the potential for CFD in understanding the physiology and pathophysiology of the pharyngeal phase of swallowing. Improvements of the model are underway. Combining the model with individualized clinical data should potentially improve the management of dysphagia. [ABSTRACT FROM AUTHOR]

Background: There is need to identify evidence-based early childhood obesity prevention programs that are feasible and demonstrate cost-effectiveness for a broader health impact. This scale-out study leveraged community-engaged principles to compare the feasibility and cost-effectiveness of three delivery modes of a childhood obesity prevention family meals program (Simple Suppers) that demonstrated positive impacts on child and caregiver diet/nutritional health-related outcomes in a previous experimental trial tested among elementary-aged children. Methods: This three-arm (in-person, online, hybrid) pre-(T0) and post-(T1)-test study included families recruited from Head Start. Forty-five families (45 caregivers; 55 children) completed the study. The program was adapted to families with younger children (3-5 years). During the 8-week program, participants received weekly group education and meals through in-person, online, or hybrid format. Feasibility outcomes were attendance, acceptability (post-test survey; focus groups), fidelity, and cost (food; staff). Participant outcomes were related to diet/nutritional health. Kruskal-Wallis test was used to compare T0 to T1 differences in participant outcomes across delivery modes. Qualitative data were analyzed using thematic analysis. Cost-effectiveness was calculated as the net-cost of the program by changes in outcomes. Results: Overall attendance was 51.2%, and higher for in-person (72.0%) and hybrid (59.7%). Program satisfaction rate was highest for hybrid (93.0%), as well as program fidelity (96.7%). Focus group results revealed areas of program improvement, behavior change, and program approval. Cost was lowest for hybrid ($17.09/family). Children in the hybrid group had a reduced waist circumference ( p = 0.02) versus in-person and online groups. Conclusion: The hybrid mode of Simple Suppers demonstrated the greatest scaling potential for a broader public health impact.

Dermatologic disease can result in disability. In part two of this continuing medical education (CME) article, we highlight disabilities that may result from dermatologic conditions. We introduce guidelines for caring for patients with disabilities including how to identify, assess, and document patients' disabilities and provide patient-centered care and support., (Copyright © 2024. Published by Elsevier Inc.)

Disability is common amongst dermatologic patients. Herein, we review the epidemiology of disability and terminology used to refer to patients with disabilities. We discuss different forms of disability, including cognitive, motor, visual and hearing, and review how dermatology practices can better accommodate patients with disabilities to optimize care., (Copyright © 2024. Published by Elsevier Inc.)

Broad discussion is needed to chart a path forward.

Competing Interests: None disclosed.

Sugar-sweetened beverage (SSB) consumption is strongly associated with obesity. Autonomous motivation and self-efficacy, key concepts of self-determination theory, may influence SSB consumption. Low-income mothers of young children experience disproportionate rates of obesity. Whether autonomous motivation and self-efficacy are associated with SSB consumption in low-income mothers of young children is unknown. This exploratory secondary data analysis explored whether autonomous motivation or self-efficacy were associated with SBB consumption using data from a lifestyle intervention for low-income, overweight or obese mothers with young children. Participants (N = 311) completed surveys assessing autonomous motivation, self-efficacy, and SSB consumption at baseline, after the 16-week intervention, and at 3-month follow-up. Using baseline data, we performed linear regression models to explore associations of self-efficacy and autonomous motivation with SSB consumption. We also performed mixed effects models to explore whether autonomous motivation or self-efficacy were associated with SSB consumption over time. At baseline, a one-point increase in autonomous motivation and self-efficacy were associated with 4.36 (p < 0.001) and 6.43 (p = 0.025) fewer ounces of SSB consumption per day, respectively. In longitudinal models, SSB consumption decreased over time. Change in SSB consumption was associated with self-efficacy (B = -4.88; p = 0.015) and autonomous motivation (B = -2.29; p = 0.008). Our findings suggest self-efficacy and autonomous motivation may influence SSB consumption among mothers of young children with overweight and obesity. Further investigation should explore if self-efficacy and autonomous motivation have long-term effects on SSB consumption., (© 2024 The Author(s). Research in Nursing & Health published by Wiley Periodicals LLC.)

This study introduces a synthetic biology approach that reprograms the yeast mating-type switching mechanism for tunable cell differentiation, facilitating synthetic microbial consortia formation and cooperativity. The underlying mechanism was engineered into a genetic logic gate capable of inducing asymmetric sexual differentiation within a haploid yeast population, resulting in a consortium characterized by mating-type heterogeneity and tunable population composition. The utility of this approach in microbial consortia cooperativity was demonstrated through the sequential conversion of xylan into xylose, employing haploids of opposite mating types each expressing a different enzyme of the xylanolytic pathway. This strategy provides a versatile framework for producing and fine-tuning functionally heterogeneous yet isogenic yeast consortia, furthering the advancement of microbial consortia cooperativity and offering additional avenues for biotechnological applications., (© 2024. The Author(s).)

Background: Bone grafting is the standard treatment for critical bone defects, but autologous grafts have limitations like donor site morbidity and limited availability, while commercial artificial grafts may have poor integration with surrounding bone tissue, leading to delayed healing. Magnesium deficiency negatively impacts angiogenesis and bone repair. Therefore, incorporating magnesium into a synthetic biomaterial could provide an excellent bone substitute. This study aims to evaluate the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM), which could serve as an excellent bone substitute by incorporating magnesium., Methods: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well., Results: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 minutes and a compressive strength of 4.39±0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis., Conclusion: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%., (© 2024. The Author(s).)

Peripheral nerve regeneration and functional recovery rely on the chemical, physical, and structural properties of nerve guidance conduits (NGCs). However, the limited support for long-distance nerve regeneration and axonal guidance has hindered the widespread use of NGCs. This study introduces a novel nerve guidance conduit with oriented lateral walls, incorporating multi-walled carbon nanotubes (MWCNTs) within core-shell fibers prepared in a single step using a modified electrohydrodynamic (EHD) printing technique to promote peripheral nerve regeneration. The structured conduit demonstrated exceptional stability, mechanical properties, and biocompatibility, significantly enhancing the functionality of NGCs. In vitro cell studies revealed that RSC96 cells adhered and proliferated effectively along the oriented fibers, demonstrating a favorable response to the distinctive architectures and properties. Subsequently, a rat sciatic nerve injury model demonstrated effective efficacy in promoting peripheral nerve regeneration and functional recovery. Tissue analysis and functional testing highlighted the significant impact of MWCNT concentration in enhancing peripheral nerve regeneration and confirming well-matured aligned axonal growth, muscle recovery, and higher densities of myelinated axons. These findings demonstrate the potential of oriented lateral architectures with coaxial MWCNT fibers as a promising approach to support long-distance regeneration and encourage directional nerve growth for peripheral nerve repair in clinical applications., (© 2024 Wiley‐VCH GmbH.)

Mutations in the orphan transporter MFSD7c (also known as Flvcr2), are linked to Fowler syndrome. Here, we used Mfsd7c knockout (Mfsd7c -/- ) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood-brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7c -/- embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers of Mfsd7c -/- embryos. Thus, we hypothesized that MFSD7c regulates the level of choline in the brain. Indeed, expression of human MFSD7c in cells significantly increased choline uptake. Interestingly, we showed that choline uptake by MFSD7c is greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch clamp analysis showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c was shown to be conserved in vertebrates, but not in yeasts. We demonstrated that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. We also showed that several missense mutations identified in patients exhibiting Fowler syndrome had abolished or reduced choline transport activity. Mice lacking Mfsd7c in endothelial cells of the central nervous system suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c was required for exporting choline derived from lysophosphatidylcholine in the brain. Collectively, our work identifies MFSD7c as a choline exporter at the BBB and provides a foundation for future work to reveal the disease mechanisms of Fowler syndrome., (© 2024. The Author(s).)

Many machine learning applications in bioinformatics currently rely on matching gene identities when analyzing input gene signatures and fail to take advantage of preexisting knowledge about gene functions. To further enable comparative analysis of OMICS datasets, including target deconvolution and mechanism of action studies, we develop an approach that represents gene signatures projected onto their biological functions, instead of their identities, similar to how the word2vec technique works in natural language processing. We develop the Functional Representation of Gene Signatures (FRoGS) approach by training a deep learning model and demonstrate that its application to the Broad Institute's L1000 datasets results in more effective compound-target predictions than models based on gene identities alone. By integrating additional pharmacological activity data sources, FRoGS significantly increases the number of high-quality compound-target predictions relative to existing approaches, many of which are supported by in silico and/or experimental evidence. These results underscore the general utility of FRoGS in machine learning-based bioinformatics applications. Prediction networks pre-equipped with the knowledge of gene functions may help uncover new relationships among gene signatures acquired by large-scale OMICs studies on compounds, cell types, disease models, and patient cohorts., (© 2024. The Author(s).)

Topic: Early-life experiences, the transmission of health and disease within families, and the influence of cumulative risks as well as protective factors throughout life shape the trajectory of health, including mental health. Long-term health trajectories established early in life are influenced by biologic, social, and environmental factors. Negative trajectories may be more salient if exposures to adversity occur during critical developmental periods., Purpose: The purpose of this brief is to (a) review pediatric health disparities related to depression and the intergenerational transmission of pediatric depression using a Life Course Health Development (LCHD) model and (b) provide recommendations for pediatric mental health research., Sources: Peer-reviewed papers available for PubMed, CINAL, and Medline. Other sources include published books, papers, and gray materials., Conclusions: The LCHD model is a perspective to guide and foster new scientific inquiry about the development of mental health outcomes over the life course. The model enables synthesis of mental health, nursing, and public health, linking mental health prevention, risk reduction, and treatment in children., (© 2024 The Authors. Journal of Child and Adolescent Psychiatric Nursing published by Wiley Periodicals LLC.)

Addressing urgent environmental challenges, this commentary emphasizes the need for green, bio-based solutions in chemical production from renewable feedstocks. It highlights advanced metabolic engineering of microbial strains and the use of microbial consortia as innovative approaches for efficient resource recovery. These strategies aim to enhance the conversion of diverse renewable feedstocks, including agricultural residues, industrial by-products, and greenhouse gases, into value-added chemicals. This article discusses cutting-edge techniques in renewable feedstock upcycling, utilizing both engineered unicellular and multicellular systems. It advocates a paradigm shift in sustainable biomanufacturing, focusing on transforming renewable resources into value-added products. This approach is crucial for developing a circular bioeconomy, aligning with global efforts to mitigate environmental impacts., Competing Interests: The authors declare no conflict of interest. Matthew Wook Chang is the Editor-in-Chief for Biotechnology Notes and was not involved in the editorial review or the decision to publish this article., (© 2024 The Authors.)

Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. The mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: the M.S. laboratory has received unrelated research funding in sponsored research agreements from ArgenX BV, Moderna, 7Hills Pharma and Phio Pharmaceuticals which has no competing interest with this work. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus and Pfizer, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work., (Copyright: © 2024 Diego et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Organ-on-chip (OOC) technology is an innovative approach that reproduces human organ structures and functions on microfluidic platforms, offering detailed insights into intricate physiological processes. This technology provides unique advantages over conventional in vitro and in vivo models and thus has the potential to become the new standard for biomedical research and drug screening. In this mini-review, we compare OOCs with conventional models, highlighting their differences, and present several applications of OOCs in biomedical research. Additionally, we highlight advancements in OOC technology, particularly in developing multiorgan systems, and discuss the challenges and future directions of this field., Competing Interests: The authors declare no conflict of interest. Matthew Wook Chang is the Editor-in-Chief for Biotechnology Notes and was not involved in the editorial review or the decision to publish this article., (© 2024 The Authors.)

Competing Interests: None disclosed.

The study purpose was to examine whether adolescents who participated in organized physical activity (PA) programs differed from nonparticipants in motivation, social support, and self-efficacy related to PA; PA (min/hr); and sedentary screen time behavior. Thirty-nine 5th-7th grade adolescents participated in organized PA programs; 41 did not. Approximately 56.3% were Black, and 52.5% had annual family incomes <$20,000. Compared to nonparticipants, those who participated reported significantly higher social support ( M  = 2.32 vs. 3.13, p  < .001) and fewer hours watching television or movies on a usual weekend day ( M  = 2.49 vs. 1.59, p  = .016); and had higher accelerometer-measured vigorous PA ( M  = 0.58 vs. 1.04, p  = .009) and moderate-to-vigorous PA ( M  = 2.48 vs. 3.45, p  = .035). Involving adolescents in organized PA programs may be important for improving their moderate-to-vigorous PA, vigorous PA, and related psychosocial factors, as well as reducing sedentary screen time behavior., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chromosome-level design-build-test-learn cycles (chrDBTLs) allow systematic combinatorial reconfiguration of chromosomes with ease. Here, we established chrDBTL with a redesigned synthetic Saccharomyces cerevisiae chromosome XV , synXV . We designed and built synXV to harbor strategically inserted features, modified elements, and synonymously recoded genes throughout the chromosome. Based on the recoded chromosome, we developed a method to enable chrDBTL: CRISPR-Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE). CRIMiRE allowed the creation of customized wild-type/synthetic combinations, accelerating genotype-phenotype mapping and synthetic chromosome redesign. We also leveraged synXV as a "build-to-learn" model organism for translation studies by ribosome profiling. We conducted a locus-to-locus comparison of ribosome occupancy between synXV and the wild-type chromosome, providing insight into the effects of codon changes and redesigned features on translation dynamics in vivo . Overall, we established synXV as a versatile reconfigurable system that advances chrDBTL for understanding biological mechanisms and engineering strains., Competing Interests: J.D.B. is a founder and director of CDI Labs, Inc.; a founder of and consultant to Neochromosome, Inc.; and a founder of, scientific advisory board member of, and consultant to ReOpen Diagnostics, LLC and serves or served on the scientific advisory boards of the following: Sangamo, Inc.; Logomix, Inc.; Modern Meadow, Inc.; Rome Therapeutics, Inc.; Sample6, Inc.; Tessera Therapeutics, Inc.; and the Wyss Institute., (© 2023 The Authors.)

Changes in the transcriptomes of human tissues with advancing age are poorly cataloged. Here, we sought to identify the coding and long noncoding RNAs present in cultured primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22-89 years old) who participated in the GESTALT (Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing) study of the National Institute on Aging, NIH. Using high-throughput RNA sequencing and a linear regression model, we identified 1437 coding RNAs (mRNAs) and 1177 linear and circular long noncoding (lncRNAs) that were differentially abundant as a function of age. Gene set enrichment analysis (GSEA) revealed select transcription factors implicated in coordinating the transcription of subsets of differentially abundant mRNAs, while long noncoding RNA enrichment analysis (LncSEA) identified RNA-binding proteins predicted to participate in the age-associated lncRNA profiles. In summary, we report age-associated changes in the global transcriptome, coding and noncoding, from healthy human skin fibroblasts and propose that these transcripts may serve as biomarkers and therapeutic targets in aging skin., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Educating pediatric eczema patients and caregivers on appropriate product selection and avoidance of common irritants or allergens is a crucial aspect of eczema management. This study surveyed 80 pediatric caregivers in an academic pediatric dermatology clinic to assess influential factors in caregivers' selection of pediatric eczema-care products and identify ways to improve patient counseling on appropriate product selection and avoidance of common irritants or allergens. Caregivers frequently reported positive perceptions of commonly recommended ingredients for eczema but had inconsistent perceptions of fragrant plant oils and extracts, regardless of previous counseling on fragrance avoidance. These findings demonstrate uncertainty and misperceptions perpetuated by product labeling and a need for improved counseling strategies for avoiding fragrance and excessive product costs., (© 2023 Wiley Periodicals LLC.)

An 8-year-old female with chronic oral candidiasis and severe seborrheic dermatitis was found to have a heterozygous mutation (p.R14X c.40 C>T) of the IL-17RC gene, which was predicted to possibly represent a new pathogenic variant via truncation or nonsense-mediated mRNA decay. Given previously reported IL-17RC-related disorders are autosomal recessive, we would expect an affected individual to have two mutated alleles whereas our patient was heterozygous. Given the overlapping clinical picture, this variant could be responsible for altered immunity against both Candida and Malassezia species. This is the first report to our knowledge of chronic oral candidiasis and severe seborrheic dermatitis in a patient with a heterozygous variant (p.R14X c.40 C>T) for the IL-17RC gene., (© 2023 Wiley Periodicals LLC.)

The blood-brain barrier (BBB) is a protective element of the neurovascular unit (NVU) surrounded by astrocytes, pericytes, extracellular matrix, and the tight junctional complex, which play a fundamental role in brain homeostasis. Due to its impeccable structural architecture, the BBB is referred to as the brain's gatekeeper, a near-impenetrable barrier to therapeutics. This review summarises the significant strides that have been made in the last 5 years towards circumventing the BBB and developing efficient drug delivery systems. Challenges associated with several CNS disorders related to BBB failure and exploitation of this unique NVU component for targeted treatment of brain-related disorders are also discussed., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The etiology of inflammatory bowel diseases (IBDs) frequently results in the uncontrolled inflammation of intestinal epithelial linings and the local environment. Here, we hypothesized that interferon-driven immunomodulation could promote anti-inflammatory effects. To test this hypothesis, we engineered probiotic Escherichia coli Nissle 1917 (EcN) to produce and secrete a type III interferon, interferon lambda 1 (IFNL1), in response to nitric oxide (NO), a well-known colorectal inflammation marker. We then validated the anti-inflammatory effects of the engineered EcN strains in two in vitro models: a Caco-2/Jurkat T cell coculture model and a scaffold-based 3D coculture IBD model that comprises intestinal epithelial cells, myofibroblasts, and T cells. The IFNL1-expressing EcN strains upregulated Foxp3 expression in T cells and thereafter reduced the production of pro-inflammatory cytokines such as IL-13 and -33, significantly ameliorating inflammation. The engineered strains also rescued the integrity of the inflamed epithelial cell monolayer, protecting epithelial barrier integrity even under inflammation. In the 3D coculture model, IFNL1-expressing EcN treatment enhanced the population of regulatory T cells and increased anti-inflammatory cytokine IL-10. Taken together, our study showed the anti-inflammatory effects of IFNL1-expressing probiotics in two in vitro IBD models, demonstrating their potential as live biotherapeutics for IBD immunotherapy.

Background: Episodic future thinking (EFT) has shown efficacy in laboratory settings. We conducted a pilot goal-oriented EFT (GoEFT) intervention in a real-world setting to help low-income overweight or obese mothers lose weight. This paper presents intervention acceptability and efficacy., Methods: The study used a single-group, before-after design. During the 3-week intervention, participants (N = 15) completed weekly web-based lessons and online health coaching sessions to manage stress and emotion, eat healthier, and be more physically active. Participants completed online surveys at baseline and immediately after the intervention. They also completed an interview to evaluate intervention acceptability. We applied paired t-tests to evaluate efficacy and used content analysis to discover interview themes., Results: Participants consistently identified the intervention as acceptable, noting the usefulness of pre-written goals, GoEFT strategies, and goal progress evaluations. The intervention effectively promoted weight loss ( d = -0.69), fruit and vegetable intake ( d = 0.45-0.49), and emotion control ( d = 0.71). It also reduced fat ( d = -0.51) and added sugar intake ( d = -0.48) and alleviated stress ( d = -0.52). Moreover, the intervention increased autonomous motivation ( d = 0.75-0.88) and self-efficacy ( d = 0.46-0.61)., Conclusion: The GoEFT intervention was acceptable to participants, showing strong preliminary efficacy.

Purpose: Investigate the associations between psychosocial factors and physical activity., Design: Secondary data analysis utilizing baseline data of a large-scale community-based randomized controlled lifestyle behavior intervention., Setting: The Special Supplemental Program for Women, Infants, and Children in Michigan, USA., Subjects: Low-income overweight or obese mothers with young children (N = 740, 65% response rate)., Measures: Survey data were collected via phone interview. Predictors included self-efficacy, autonomous motivation, emotional coping, and social support. Self-reported leisure physical activity was the outcome variable. Covariates were age, race, smoking, employment, education, body mass index, and postpartum status., Analysis: A multiple linear regression model was applied., Results: Self-efficacy ( β = .32, 95% CI = .11, .52, P = .003) and autonomous motivation ( β = .10, 95% CI = .03, .17, P = .005) were positively associated with physical activity. However, emotional coping and social support were not associated with physical activity., Conclusion: Future research should examine the longitudinal association of key psychosocial factors with physical activity.

Background: Implementing lifestyle behavior programs in real-world settings challenges researchers. The Special Supplemental Nutrition Program for Women, Infants, and Children ( WIC) has implemented and sustained Mothers In Motion ( MIM )'s client videos for clients to promote healthy lifestyle behaviors, and train-the-trainer videos, for personnel to enhance motivational interviewing techniques since 2015 and 2016, respectively. This paper describes the implementation processes and the results of client video implementation acceptability by WIC personnel., Methods: To document the implementation process, we applied the Framework for Adaptation and Modifications to Evidence-Based Implementation Strategies (FRAME-IS). To evaluate implementation acceptability, we conducted semi-structured interviews with 15 WIC personnel. A qualitative analysis was conducted to identify the common themes., Results: The facilitators for client video implementation were the inclusion of the target audience and family members addressing daily challenges, easy implementation, and compatibility with daily practice. While videos online facilitated implementation, videos in DVD format could challenge implementation., Conclusions: Future lifestyle intervention programs aimed for future implementation in community settings may consider the inclusion of the target audience and their family members and take into consideration easy implementation and compatibility.

Uric acid disequilibrium is implicated in chronic hyperuricemia-related diseases. Long-term monitoring and lowering of serum uric acid levels may be crucial for diagnosis and effective management of these conditions. However, current strategies are not sufficient for accurate diagnosis and successful long-term management of hyperuricemia. Moreover, drug-based therapeutics can cause side effects in patients. The intestinal tract plays an important role in maintaining healthy serum acid levels. Hence, we investigated the engineered human commensal Escherichia coli as a novel method for diagnosis and long-term management of hyperuricemia. To monitor changes in uric acid concentration in the intestinal lumen, we developed a bioreporter using the uric acid responsive synthetic promoter, pucpro , and uric acid binding Bacillus subtilis PucR protein. Results demonstrated that the bioreporter module in commensal E. coli can detect changes in uric acid concentration in a dose-dependent manner. To eliminate the excess uric acid, we designed a uric acid degradation module, which overexpresses an E. coli uric acid transporter and a B. subtilis urate oxidase. Strains engineered with this module degraded all the uric acid (250 µM) found in the environment within 24 h, which is significantly lower ( p < 0.001) compared to wild type E. coli . Finally, we designed an in vitro model using human intestinal cell line, Caco-2, which provided a versatile tool to study the uric acid transport and degradation in an environment mimicking the human intestinal tract. Results showed that engineered commensal E. coli reduced ( p < 0.01) the apical uric acid concentration by 40.35% compared to wild type E. coli . This study shows that reprogramming E. coli holds promise as a valid alternative synthetic biology therapy to monitor and maintain healthy serum uric acid levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gencer, Mancuso, Chua, Ling, Costello, Chang and March.)

Since its inception, synthetic biology has overcome many technical barriers but is at a crossroads for high-precision biological design. Devising ways to fully utilize big biological data may be the key to achieving greater heights in synthetic biology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kitano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study is aimed to fabricate tetanus toxoid laden microneedle patches by using a polymeric blend comprising of polyvinyl pyrrolidone and sodium carboxymethyl cellulose as base materials and sorbitol as a plasticizer. The tetanus toxoid was mixed with polymeric blend and patches were prepared by using vacuum micromolding technique. Microneedle patches were evaluated for physical attributes such as uniformity of thickness, folding endurance, and swelling profile. Morphological features were assessed by optical and scanning electron microscopy. In vitro performance of fabricated patches was studied by using bicinchoninic acid assay (BCA). Insertion ability of microstructures was studied in vitro on model skin parafilm and in vivo in albino rat. In vivo immunogenic activity of the formulation was assessed by recording immunoglobulin G (IgG) levels, interferon gamma (IFN-γ) levels, and T-cell (CD4 + and CD8 + ) count following the application of dosage forms. Prepared patches, displaying sharp-tipped and smooth-surfaced microstructures, remained intact after 350 ± 36 foldings. Optimized microneedle patch formulation showed ~ 74% swelling and ~ 85.6% vaccine release within an hour. The microneedles successfully pierced parafilm. Histological examination of microneedle-treated rat skin confirmed disruption of epidermis without damaging the underneath vasculature. A significant increase in IgG levels (~ 21%), IFN-γ levels (~ 30%), CD4 + (~ 41.5%), and CD8 + (~ 48.5%) cell count was observed in tetanus vaccine-loaded microneedle patches treated albino rats with respect to control (untreated) group at 42nd day of immunization. In conclusion, tetanus toxoid-loaded microneedle patches can be considered as an efficient choice for transdermal delivery of vaccine without inducing pain commonly experienced with hypodermic needles., (© 2022. Controlled Release Society.)

Tranexamic acid (TXA) effectively reduces blood loss and transfusion risk during total joint arthroplasty. Additionally, intraoperative irrigation with various antiseptic solutions is often utilized for the management and prevention of surgical site infection. However, interactions between various antiseptic solutions and TXA have not been investigated. The purpose of this in vitro study is to evaluate the stability of TXA in the presence of common orthopedic antiseptic solutions. Five antiseptic solutions-0.1% chlorhexidine (CHX) gluconate, 10% povidone-iodine (BTD), 0.5% sodium hypochlorite (Dakin's), 3% hydrogen peroxide (H 2 O 2 ), and 1.5% H 2 O 2 -and a 0.9% normal saline (NS) control were obtained. A stock 100 mg/ml TXA solution was diluted in each antiseptic solution to a concentration of 10.0 mg/ml to generate reference standard and stability samples. TXA stability in each solution was measured using high performance liquid chromatography at t = 0 and t = 120 min and reported as mean percent of theoretical concentration (MPT) with associated relative standard deviation (RSD). All experiments were performed in triplicate at room temperature. At t = 0 min, TXA remained stable when mixed with 0.9% NS, 0.1% CHX, 10% BTD, 3% H 2 O 2 , and 1.5% H 2 O 2 (MPT range: 102.0%-105.0%, RSD range: 0.80%-2.92%). Only 0.5% Dakin's led to significant degradation of TXA at t = 0 min (MPT: 14.3%, RSD:1.28%). At t = 120 min, TXA stability persisted for all compounds except Dakin's 0.5% (MPT: 18.4%, RSD: 28.7%). TXA efficacy may be significantly diminished when 0.5% Dakin's is used as an intraoperative irrigation solution. CHX, BTD, and H 2 O 2 do not degrade TXA., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Candida albicans is an opportunistic pathogen, with its infection as one of the causes of morbidity or mortality. Notably, the probiotic yeast Saccharomyces cerevisiae var. boulardii has shown the potential to fight against Candida infections. In this study, we aimed to engineer a commercial boulardii strain to produce medium-chain fatty acids (MCFAs) with antagonistic effects against C. albicans . First, we identified and characterized a boulardii strain and created its auxotrophic strain Δura3 . Next, we constructed and expressed a heterologous MCFA biosynthetic pathway under the control of inducible and constitutive promoters. Aside from examining MCFA production and secretion, we confirmed MCFAs' effects on C. albicans' anti-biofilm and anti-hyphal formations and the immunomodulatory effect of MCFA-containing supernatants on Caco-2 cells. We found that under constitutive promoters, the engineered boulardii strain constitutively produced and secreted a mixture of C6:0, C8:0, and C10:0. The secreted MCFAs then reduced biofilm and hyphal formations in C. albicans SC5314. We also confirmed that MCFAs upregulated the expression of virulence-related genes in SC5314. Furthermore, we found that the constitutively produced MCFAs in the supernatant induced the upregulation of immune response genes in Caco-2 cells co-cultured with SC5314, indicating MCFAs' roles in immunomodulation. Overall, the engineered boulardii strain produced and secreted MCFAs, as well as demonstrated antagonistic effects against C. albicans SC5314 and immune-modulatory effects in Caco-2. To our knowledge, this represents the first study tackling the metabolic engineering of a commercial probiotic yeast strain to constitutively produce and secrete MCFAs showing anti- Candida effects. Our study forms the basis of the potential development of a live biotherapeutics probiotic yeast against Candida infections through metabolic engineering strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ling, Liu, Sam, Shen, Chai and Chang.)

Transcription factor programs mediating the immune response to coronavirus disease 2019 (COVID-19) are not fully understood. Capturing active transcription initiation from cis-regulatory elements such as enhancers and promoters by capped small RNA sequencing (csRNA-seq), in contrast to capturing steady-state transcripts by conventional RNA-seq, allows unbiased identification of the underlying transcription factor activity and regulatory pathways. Here, we profile transcription initiation in critically ill COVID-19 patients, identifying transcription factor motifs that correlate with clinical lung injury and disease severity. Unbiased clustering reveals distinct subsets of cis-regulatory elements that delineate the cell type, pathway-specific, and combinatorial transcription factor activity. We find evidence of critical roles of regulatory networks, showing that STAT/BCL6 and E2F/MYB regulatory programs from myeloid cell populations are activated in patients with poor disease outcomes and associated with COVID-19 susceptibility genetic variants. More broadly, we demonstrate how capturing acute, disease-mediated changes in transcription initiation can provide insight into the underlying molecular mechanisms and stratify patient disease severity., Competing Interests: Declaration of interests A.M. is funded by the NIH. He reports income from Livanova, Equillium, and Corvus related to medical education. ResMed provided a philanthropic donation to UC San Diego. S.C. has consulted for Avalia, Roche, and GlaxoSmithKline., (Published by Elsevier Inc.)

Nucleic acid detection is crucial for monitoring diseases for which rapid, sensitive, and easy-to-deploy diagnostic tools are needed. CRISPR-based technologies can potentially fulfill this need for nucleic acid detection. However, their widespread use has been restricted by the requirement of a protospacer adjacent motif in the target and extensive guide RNA optimization. In this study, we developed FELICX, a technique that can overcome these limitations and provide a useful alternative to existing technologies. FELICX comprises flap endonuclease, Taq ligase and CRISPR-Cas for diagnostics (X) and can be used for detecting nucleic acids and single-nucleotide polymorphisms. This method can be deployed as a point-of-care test, as only two temperatures are needed without thermocycling for its functionality, with the result generated on lateral flow strips. As a proof-of-concept, we showed that up to 0.6 copies/μL of DNA and RNA could be detected by FELICX in 60 min and 90 min, respectively, using simulated samples. Additionally, FELICX could be used to probe any base pair, unlike other CRISPR-based technologies. Finally, we demonstrated the versatility of FELICX by employing it for virus detection in infected human cells, the identification of antibiotic-resistant bacteria, and cancer diagnostics using simulated samples. Based on its unique advantages, we envision the use of FELICX as a next-generation CRISPR-based technology in nucleic acid diagnostics., Competing Interests: Declaration of competing interest N.A., J.L.F., H.L., I.Y.H. and M.W.C have filed a patent application through the National University of Singapore based on the work described in this manuscript. The remaining authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)