The optimal measurement period of actigraphy for circadian rhythm in relation to adiposity: A retrospective case-control study.

BACKGROUND: This study focused on the relationship between adiposity and Rest-Activity Rhythms (RAR), utilizing both parametric cosine-based models and non-parametric algorithms. The emphasis was on the impact of varying measurement periods (7-28 days) on this relationship. METHODS: We retrieved actigraphy data from two datasets, encompassing a diverse cohort recruited from an obesity outpatient clinic and a workplace health promotion program. Participants were required to wear a research-grade wrist actigraphy device continuously for a minimum of four weeks. The final dataset included 115 individuals (mean age 40.7 ± 9.5 years, 51 % female). We employed both parametric and non-parametric methods to quantify RAR using six standard variables. Additionally, the study evaluated the correlations between three key adiposity indices - Body Mass Index (BMI), Visceral Adipose Tissue (VAT) area, and Body Fat Percentage (BF%) - and circadian rhythm indicators, controlling for factors like physical activity, age, and gender. RESULTS: The obesity group displayed a significantly lower relative amplitude (RA) as per non-parametric algorithm findings, with a decreased amplitude noted in the parametric algorithm analysis, in comparison to the overweight and control groups. The relationship between circadian rhythm indicators and adiposity metrics over 7- to 28-day periods was examined. A notable negative correlation was observed between RA and both BMI and VAT, while correlation coefficients between adiposity indicators and non-parametric circadian parameters increased with extended durations of actigraphy data. Specifically, RA over a 28-day period was significantly correlated with BF%, a trend not seen in the 7-day measurement (p = 0.094) in multivariate linear regression. The strength of the correlation between BF% and 28-day RA was more pronounced than that in the 7-day period (p = 0.044). However, replacing RA with amplitude as per parametric cosinor fitting yielded no significant correlations for any of the measurement periods. CONCLUSION: The study concludes that a 28-day measurement period more effectively captures the link between disrupted circadian rhythms and adiposity. Non-parametric algorithms, in particular, were more effective in characterizing disrupted circadian rhythms, especially when extending the measurement period beyond the standard 7 days.

The immune landscape in apical periodontitis: From mechanism to therapy.

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.

DeePhafier: a phage lifestyle classifier using a multilayer self-attention neural network combining protein information.

Bacteriophages are the viruses that infect bacterial cells. They are the most diverse biological entities on earth and play important roles in microbiome. According to the phage lifestyle, phages can be divided into the virulent phages and the temperate phages. Classifying virulent and temperate phages is crucial for further understanding of the phage-host interactions. Although there are several methods designed for phage lifestyle classification, they merely either consider sequence features or gene features, leading to low accuracy. A new computational method, DeePhafier, is proposed to improve classification performance on phage lifestyle. Built by several multilayer self-attention neural networks, a global self-attention neural network, and being combined by protein features of the Position Specific Scoring Matrix matrix, DeePhafier improves the classification accuracy and outperforms two benchmark methods. The accuracy of DeePhafier on five-fold cross-validation is as high as 87.54% for sequences with length >2000bp.

Tröger's Base-Embedded Pillararenes─Macrocycles with Both Fixed and Conformational Chirality.

Tröger's base-embedded pillararenes (P[1]TB[3]A), which combine Tröger's base (TB) with dialkoxybenzene units, were prepared via a fragment-coupling macrocyclization strategy. The TB unit in macrocycle P[1]TB[3]A provides a fixed chiral source, while 1,4-alkoxybenzene segments flip quickly to change their arrangement, which could provide reversible conformational chirality for those macrocycles. This rare example of macrocycles holding both fixed and conformational chirality lays a good foundation for expanding pillararenes using the fixed chiral source.

Expanding the Surgical Armamentarium Through Meaningful Use of the Electronic Health Record.

This Viewpoint proposes several ways to innovate electronic health record (EHR) systems to address surgeon-specific needs and to improve clinicians' experience and health care quality.

Soft Crawling Microrobot Based on Flexible Optoelectronics Enabling Autonomous Phototaxis in Terrestrial and Aquatic Environments.

Many organisms move directly toward light for prey hunting or navigation, which is called phototaxis. Mimicking this behavior in robots is crucially important in the energy industry and environmental exploration. However, the phototaxis robots with rigid bodies and sensors still face challenges in adapting to unstructured environments, and the soft phototaxis robots often have high requirements for light sources with limited locomotion performance. Here, we report a 3.5 g soft microrobot that can perceive the azimuth angle of light sources and exhibit rapid phototaxis locomotion autonomously enabled by three-dimensional flexible optoelectronics and compliant shape memory alloy (SMA) actuators. The optoelectronics is assembled from a planar patterned flexible circuit with miniature photodetectors, introducing the self-occlusion to light, resulting in high sensing ability (error < 3.5°) compared with the planar counterpart. The actuator produces a straightening motion driven by an SMA wire and is then returned to a curled shape by a prestretched elastomer layer. The actuator exhibits rapid actuation within 0.1 s, a significant degree of deformation (curvature change of ∼87 m-1) and a blocking force of ∼0.4 N, which is 68 times its own weight. Finally, we demonstrated the robot is capable of autonomously crawling toward a moving light source in a hybrid aquatic-terrestrial environment without human intervention. We envision that our microrobot could be widely used in autonomous light tracking applications.

The Prognosis of Patients with Myocardial Infarction after Light Therapy: A Preliminary Study.

BACKGROUND: Patients with myocardial infarction (MI) can have disturbed sleep, but little is known about the efficacy of light therapy on sleep and prognosis of patients with MI. We conducted a randomized controlled study to investigate its efficacy. MATERIAL AND METHODS: This preliminary study included 34 patients with MI. They were randomized into the blue light and the white light groups during their stay in intensive care unit. 17 age and gender matched healthy controls were also enrolled. Actigraphy was used to evaluate objective sleep since enrollment. Delirium scales were used to screen delirium. Lab work-up including vitamin D level was performed at the baseline and discharge. We used Mann-Whitney U test or Wilcoxon signed-rank test to compare the difference between the MI group and the healthy control group, and the group difference after receiving light therapy. RESULTS: Patients with MI had significantly lower vitamin D level than healthy controls (p<0.001). They also had significantly poorer sleep, as indicated by actigraphy parameters including sleep onset latency (p=0.01), sleep efficiency (p=0.002), wake after sleep onset (p<0.001) and awake times (p=0.002). No significant group difference was found by actigraphy after light therapy except a non-significant higher relative amplitude of the blue light group (p=0.061). Besides, vitamin D level of the blue light group increased significantly (p1=0.047, p2=0.045). CONCLUSIONS: Patients with MI had poorer sleep, highlighting the needs to develop interventions. Significantly increased vitamin D level and a non-significant better rest-active rhythm after light therapy suggest its potential with sleep and prognosis which warrants further investigation.

Anatomical and physiological responses of roots and rhizomes in Oryza longistaminata to soil water gradients.

BACKGROUND AND AIMS: Roots and rhizomes are critical for the adaptation of clonal plants to soil water gradients. Oryza longistaminata, a rhizomatous wild rice, is of particular interest for perennial rice breeding due to its resilience under abiotic stress conditions. While root responses to soil flooding are well-studied, rhizome responses to water gradients remain underexplored. We hypothesize that physiological integration of Oryza longistaminata mitigates heterogeneous water deficit stress through interconnected rhizomes, and both roots and rhizomes respond to contrasting water conditions. METHODS: We investigated the physiological integration between mother plants and ramets, measuring key photosynthetic parameters (photosynthetic and transpiration rate, and stomatal conductance) using an Infrared Gas Analyzer. Moreover, root and rhizome responses to three water regimes (flooding, well-watered, and water deficit) were examined by measuring radial water loss and apparent permeance to O2, along with histochemical and anatomical characterization. KEY RESULTS: Our experiment highlights the role of physiological integration via interconnected rhizomes in mitigating water deficit stress. Severing rhizome connections from mother plants or ramets exposed to water deficit conditions led to significant decreases in key photosynthetic parameters, underscoring the importance of rhizome connections in bidirectional stress mitigation. Additionally, O. longistaminata rhizomes exhibited constitutive suberized and lignified apoplastic barriers, while such barriers were induced in roots under water stress. Anatomically, both rhizomes and roots respond similarly to water gradients, showing thinner diameters under water deficit conditions and larger diameters under flooding conditions. CONCLUSION: Our findings indicate that physiological integration through interconnected rhizomes helps alleviate water deficit stress when either the mother plant or the ramet is experiencing water deficit, while the counterpart is in control conditions. Moreover, O. longistaminata can adapt to various soil water regimes by regulating anatomical and physiological traits of roots and rhizomes.

Bioinformatics analysis of high-intensity intermittent exercise for prevention of myocardial infarction.

The mechanism of target interaction involving high-intensity interval training (HIIT) in improving prognosis of myocardial infarction (MI) remains unclear. This study aimed to establish a visual network of "HIIT-target-disease" by referring to the methods of pharmacological disease and drug bioinformatic analysis, to explore the potential targets, and key targets and predict the potential biological mechanism of high-intensity intermittent exercise in preventing and treating myocardial infarction. Public data resources such as OMIM, NCBI and GeneCards were used to find potential targets of high-intensity intermittent exercise and myocardial infarction. Key targets of overlap between exercise and disease were determined according to the Relevance score values analyzed by GeneCards. The visual network diagram of "HIIT - Multi-target-disease" was constructed by Cytoscape. A total of 4820 disease targets and 528 high-intensity intermittent exercise targets were screened out, and 444 overlapped targets were obtained, including 425 protein targets. Five core protein targets were selected: IL10, PPARA, TNF, IL6, and STAT3. It may pass PI3K-AKT signaling pathway, Insulin resistance pathway, T-cell signaling pathway, TNF signaling pathway, and JAX-STAT signaling pathway and other pathways play a role. Our study comprehensively elucidated the potential targets, key targets and molecular mechanisms of high-intensity intermittent exercise in improving the prognosis of myocardial infarction, and proved that high-intensity intermittent exercise can act on multiple targets and multiple pathways to play a good preventive and therapeutic effect on myocardial infarction, providing scientific theoretical basis for revealing the mechanism of high-intensity intermittent exercise in the prevention and treatment of cardiovascular disease.

Characterization of Cancer Stem Cells in Laryngeal Squamous Cell Carcinoma by Single-cell RNA Sequencing.

Cancer stem cells (CSCs) constitute a pivotal element within the tumor microenvironment (TME), driving the initiation and progression of cancer. However, the identification of CSCs and their underlying molecular mechanisms in laryngeal squamous cell carcinoma (LSCC) remains a formidable challenge. We employed single-cell RNA sequencing of matched primary tumor tissues, paracancerous tissues, and local lymph nodes from three LSCC patients. Two distinct clusters of stem cells originating from epithelial populations were delineated and verified as CSCs and normal stem cells (NSCs), respectively. CSCs were abundant in the paracancerous tissues compared to the tumor tissues. CSCs showed high expression of stem cell marker genes such as PROM1, ALDH1A1, and SOX4, and increased the activity of tumor-related hypoxia, Wnt/ß-catenin, and Notch signaling pathways. We then explored the intricate crosstalk between CSCs and the TME cells and identified targets within the TME that related with CSCs. We also found eight marker genes of CSCs that correlated significantly with the prognosis of LSCC patients. Furthermore, bioinformatics analyses showed that drugs such as erlotinib, OSI-027, and ibrutinib selectively targeted the CSC-specifically expressed genes. In conclusion, our results represent the first comprehensive characterization of CSCs properties in LSCC at the single-cell level.

Comparison of genomic prediction accuracy using different models for egg production traits in Taiwan country chicken.

In local chickens targeted for niche markets, genotyping costs are relatively high due to the small population size and diverse breeding goals. The single-step genomic best linear unbiased prediction (ssGBLUP) model, which combines pedigree and genomic information, has been introduced to increase the accuracy of genomic estimated breeding value (GEBV). Therefore, this model may be more beneficial than the genomic BLUP (GBLUP) model for genomic selection in local chickens. Additionally, the single-step genome-wide association study (ssGWAS) can be used to extend the ssGBLUP model results to animals with available phenotypic information but without genotypic data. In this study, we compared the accuracy of (G)EBVs using the pedigree-based BLUP (PBLUP), GBLUP, and ssGBLUP models. Moreover, we conducted single-SNP GWAS (SNP-GWAS), GBLUP-GWAS, and ssGWAS methods to identify genes associated with egg production traits in the NCHU-G101 chicken to understand the feasibility of using genomic selection in a small population. The average prediction accuracy of (G)EBV for egg production traits using the PBLUP, GBLUP, and ssGBLUP models is 0.536, 0.531, and 0.555, respectively. In total, 22 suggestive- and 5% Bonferroni genome-wide significant-level SNPs for total egg number (EN), average laying rate (LR), average clutch length, and total clutch number are detected using 3 GWAS methods. These SNPs are mapped onto Gallus gallus chromosomes (GGA) 4, 6, 10, 18, and 25 in NCHU-G101 chicken. Furthermore, through SNP-GWAS and ssGWAS methods, we identify 2 genes on GGA4 associated with EN and LR: ENSGALG00000023172 and PPARGC1A. In conclusion, the ssGBLUP model demonstrates superior prediction accuracy, performing on average 3.41% than the PBLUP model. The implications of our gene results may guide future selection strategies for Taiwan Country chickens. Our results highlight the applicability of the ssGBLUP model for egg production traits selection in a small population, specifically NCHU-G101 chicken in Taiwan.

Interpretation of immediately released health information: Informing patient medical education in breast oncology.

BACKGROUND: The Cures Act mandated immediately released health information. In this study, we investigated patient comprehension of mammography reports and the utility of online resources to aid report interpretation. METHODS: Patients who received a normal mammogram from February to April 2022 were invited to complete semi-structured interviews paired with health literacy questionnaires to assess patient's report comprehension before and after internet search. RESULTS: Thirteen selected patients via purposeful sampling completed interviews. Most patients described their initial understanding of the mammography report as "good" and improved to between "good" and "very good" after an internet search. Patients suggested "a little column on the side" for medical terminology, "an extra prompt" for making an appointment, or a recommendation for "good sites" to improve mammography reports. CONCLUSION: Patients varied in their ability to independently interpret medical reports and seek additional resources. While online resources marginally improved patient understanding, actionable and clear resources are needed.

Autonomic modulation by SGLT2i or DPP4i in patients with diabetes favors cardiovascular outcomes as revealed by skin sympathetic nerve activity.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are important second-line treatments for patients with type 2 diabetes mellitus (T2DM). Patients taking SGLT2i have favorable cardiovascular outcomes via various mechanisms, including autonomic nervous system (ANS) modulation. This study aimed to use neuro-electrocardiography (neuECG) to test the effects of SGLT2i or DPP4i on the ANS. Methods: Patients with T2DM, who did not reach target hemoglobin (Hb)A1C levels despite metformin treatment, were enrolled. SGLT2i or DPP4i were prescribed randomly unless a compelling indication was present. NeuECG and heart rate were recorded for 10 min before and after a 3-month treatment. The patients were treated according to standard practice and the obtained data for skin sympathetic nerve activity (SKNA) and ANS entropy were analyzed offline. Results: We enrolled 96 patients, of which 49 received SGLT2i and 47 received DPP4i. The baseline parameters were similar between the groups. No adverse event was seen during the study period. In the burst analysis of SKNA at baseline, all parameters were similar. After the 3-month treatment, the firing frequency was higher in SGLT2i group (0.104 ± 0.045 vs 0.083 ± 0.033 burst/min, p < 0.05), with increased long firing duration (7.34 ± 3.66 vs 5.906 ± 2.921, p < 0.05) in 3-s aSKNA scale; the other parameters did not show any significant change. By symbolic entropy, the most complex patterns (Rank 3) were found to be significantly higher in SGLT2i-treated patients than in DDP4i-treated group (0.084 ± 0.028 vs 0.07 ± 0.024, p = 0.01) and the direction of change in Rank 3, after SGLT2i treatment, was opposite to that observed in the DDP4i group (0.012 ± 0.036 vs. -0.005 ± 0.037, p = 0.024). Our findings demonstrated the favorable autonomic modulation by SGLTi and the detrimental effects of DPP4i on ANS. Conclusion: We demonstrated the autonomic modulation by SGLTi and DPP4i using SKNA in patients with DM, which might provide insights into the favorable outcomes of SGLT2i. Furthermore, we refined the analytical methods of neuECG, which uses SKNA to evaluate autonomic function.

Induction of Thymus Atrophy and Disruption of Thymocyte Development by Fipronil through Dysregulation of IL-7-Associated Genes.

The susceptibility of the immune system to immunotoxic chemicals is evident, particularly in the thymus, a vital primary immune organ prone to atrophy due to exposure to toxicants. Fipronil (FPN), a widely used insecticide, is of concern due to its potential neurotoxicity, hepatotoxicity, and immunotoxicity. Our previous study showed that FPN disturbed the antigen-specific T-cell functionality in vivo. As T-cell lineage commitment and thymopoiesis are closely interconnected with the normal function of the T-cell-mediated immune responses, this study aims to further examine the toxic effects of FPN on thymocyte development. In this study, 4-week-old BALB/c mice received seven doses of FPN (1, 5, 10 mg/kg) by gavage. Thymus size, medulla/cortex ratio, total thymocyte counts, double-positive thymocyte population, and IL-7-positive cells decreased dose-dependently. IL-7 aids the differentiation of early T-cell precursors into mature T cells, and several essential genes contribute to the maturation of T cells in the thymus. Foxn1 ensures that the thymic microenvironment is suitable for the maturation of T-cell precursors. Lyl1 is involved in specifying lymphoid cells and maintaining T-cell development in the thymus. The c-Kit/SCF collaboration fosters a supportive thymic milieu to promote the formation of functional T cells. The expression of IL-7, IL-7R, c-Kit, SCF, Foxn1, and Lyl1 genes in the thymus was significantly diminished in FPN-treated groups with the concordance with the reduction of IL-7 signaling proteins (IL-7, IL-7R, c-KIT, SCF, LYL1, FOXO3A, and GABPA), suggesting that the dysregulation of T-cell lineage-related genes may contribute to the thymic atrophy induced by FPN. In addition, FPN disturbed the functionality of thymocytes with an increase of IL-4 and IFN-γ production and a decrease of IL-2 secretion after T-cell mitogen stimulation ex vivo. Collectively, FPN significantly deregulated genes related to T-cell progenitor differentiation, survival, and expansion, potentially leading to impaired thymopoiesis.

Self-healing and injectable chitosan/konjac glucomannan hydrogel with pH response for controlled protein release.

Dynamic hydrogels with the features of injection, self-healing, and remodeling at the target site have been developed as smart multifunctional biomaterials for drug delivery. However, most self-healing injectable hydrogels are difficult to control protein release after implantation, owing to the deficiency of pH responsiveness, which reduces the bioavailability of proteins. Herein, we propose a facile strategy to endow pH responsiveness into a dynamic hydrogel with both self-healing and injectable capabilities, by crosslinking biomacromolecular backbones via dual pH sensitive dynamic covalent bond. Particularly, oxidized konjac glucomannan (OKGM) can be crosslinked with poly (aspartic hydrazide) (PAHy) and N-carboxyethyl chitosan (CEC) to form dynamic acylhydrazone bonds and imide bonds, respectively, endowing the hydrogel with pH responsiveness and dynamic behaviors. Specifically, PAHy facilitates the formation of acylhydrazone bonds, improving the mechanical properties and pH sensitivity while reducing the degradation behavior of the hydrogels under physiological conditions. Kinetics indicate that the release of bovine serum albumin follows Fick diffusion under different pH conditions. The pH responsive hydrogel with self-healing injectable capabilities has the potential to be used as a controllable and sustain release carrier for protein drugs.

The systematic role of pancreatic cancer exosomes: distant communication, liquid biopsy and future therapy.

Pancreatic cancer remains one of the most lethal diseases worldwide. Cancer-derived exosomes, benefiting from the protective role of the lipid membrane, exhibit remarkable stability in the circulatory system. These exosomes, released by tumor microenvironment, contain various biomolecules such as proteins, RNAs, and lipids that plays a pivotal role in mediating distant communication between the local pancreatic tumor and other organs or tissues. They facilitate the transfer of oncogenic factors to distant sites, contributing to the compromised body immune system, distant metastasis, diabetes, cachexia, and promoting a microenvironment conducive to tumor growth and metastasis in pancreatic cancer patients. Beyond their intrinsic roles, circulating exosomes in peripheral blood can be detected to facilitate accurate liquid biopsy. This approach offers a novel and promising method for the diagnosis and management of pancreatic cancer. Consequently, circulating exosomes are not only crucial mediators of systemic cell-cell communication during pancreatic cancer progression but also hold great potential as precise tools for pancreatic cancer management and treatment. Exosome-based liquid biopsy and therapy represent promising advancements in the diagnosis and treatment of pancreatic cancer. Exosomes can serve as drug delivery vehicles, enhancing the targeting and efficacy of anticancer treatments, modulating the immune system, and facilitating gene editing to suppress tumor growth. Ongoing research focuses on biomarker identification, drug delivery systems, and clinical trials to validate the safety and efficacy of exosome-based therapies, offering new possibilities for early diagnosis and precision treatment in pancreatic cancer. Leveraging the therapeutic potential of exosomes, including their ability to deliver targeted drugs and modulate immune responses, opens new avenues for innovative treatment strategies.

Herlyn-Werner-Wunderlich Syndrome Complicated with Vesicovaginal Fistula: A Rare Case Report.

Herlyn-Werner-Wunderlich (HWW) syndrome is characterized by obstructed hemivagina and ipsilateral renal anomaly, a rare congenital anomaly of the genitourinary tract, resulting from malformations of the renal tract associated with Müllerian duct anomalies. The initial symptoms of HWW frequently present after menarche and may be nonspecific, leading to a delayed diagnosis. We presented a 19-year-old female with 3-year hematuria and abdominal pain. The final diagnosis of HWW syndrome with a rare vesicovaginal fistula was made. The treatment of HWW syndrome typically involves surgical intervention. The primary treatment is resection or removal of the obstructed vaginal septum. The patient underwent excision of vaginal septum and vaginal reconstruction via hysteroscopy, as well as repair of the vesicovaginal fistula. The patient improved well after surgery and fully recovered without sequelae after 3 months. In addition, unilateral renal agenesis is one of congenital abnormalities of the kidney and urinary tract, which are the most frequent cause of chronic kidney disease (CKD) in children. This report describes a patient of HWW syndrome with rarely combined vesicovaginal fistula, and highlights the importance of early recognition and management to prevent associated complications.

Precision probiotics supplement strategy in aging population based on gut microbiome composition.

With the increasing prevalence of age-related chronic diseases burdening healthcare systems, there is a pressing need for innovative management strategies. Our study focuses on the gut microbiota, essential for metabolic, nutritional, and immune functions, which undergoes significant changes with aging. These changes can impair intestinal function, leading to altered microbial diversity and composition that potentially influence health outcomes and disease progression. Using advanced metagenomic sequencing, we explore the potential of personalized probiotic supplements in 297 older adults by analyzing their gut microbiota. We identified distinctive Lactobacillus and Bifidobacterium signatures in the gut microbiota of older adults, revealing probiotic patterns associated with various population characteristics, microbial compositions, cognitive functions, and neuroimaging results. These insights suggest that tailored probiotic supplements, designed to match individual probiotic profile, could offer an innovative method for addressing age-related diseases and functional declines. Our findings enhance the existing evidence base for probiotic use among older adults, highlighting the opportunity to create more targeted and effective probiotic strategies. However, additional research is required to validate our results and further assess the impact of precision probiotics on aging populations. Future studies should employ longitudinal designs and larger cohorts to conclusively demonstrate the benefits of tailored probiotic treatments.