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Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant Lactococcus lactis strain expressing the Ling-Zhi immunomodulatory protein ( L. lactis -LZ8). This study investigated the anti-atherosclerotic effects of L. lactis -LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of L. lactis -LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving L. lactis -LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the L. lactis -LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the L. lactis -LZ8 group. Our studies underscore LZ8's role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD.

Background: Molecular testing of thyroid nodules is an essential tool to help risk stratify nodules with indeterminate cytology. Although ThyroSeq testing has been around for over a decade, there is a paucity of long-term follow-up data on cytologically indeterminate nodules that are determined to be molecularly negative or low-risk. The objective of this study is to assess the outcomes of nodules with indeterminate cytology (Bethesda III or IV) and negative or low-risk ThyroSeq results., Methods: This is a single academic institution retrospective cohort study. Patients with at least one thyroid nodule sampled with fine-needle aspiration who underwent ThyroSeq testing from 2012 to 2018 and had negative or low-risk ThyroSeq results on a cytologically indeterminate sample (n = 159 patients, 167 nodules) were included in the study. Outcomes include the false-negative rate and negative predictive value of each test version, as well as follow-up length for each nodule., Results: There were 159 patients with a mean age of 58 years (7-84 years) included in this study; the majority were female (81.8%). The mean follow-up was 4.0 years. Of 167 nodules, three were found to be malignant on resection (1.8%). The negative predictive value for the entire cohort was 98.2% and it was 89.3% for the surgical series., Conclusion: ThyroSeq testing has good negative predictive value and can help risk stratify cytologically indeterminate nodules. Routine follow-up allows for safe monitoring of nodules for features suggestive of malignancy., (© 2024 American Cancer Society.)

Issue Addressed: Nostalgia-the bittersweet reliving of the past-has been linked to social connection and psychological wellbeing. Although food consumption is often an intrinsically social experience, relatively little research has examined how individuals experience and understand how food consumption relates to feelings of nostalgia, food and mood., Methods: In the current study, semi-structured interviews were conducted with eight Australians from varying cultural backgrounds to explore their experiences with nostalgia, food and mood., Results: Reflexive thematic analysis identified three key themes from the data: (i) The bittersweet experiences of food-evoked nostalgia-individuals' descriptions of food-evoked nostalgia and how it impacted their mood both positively and negatively (ii) social connection and identity continuity-participants' description of food-evoked nostalgia and how this provides an opportunity for social connection and identity continuity throughout life, which positively influences mood, and (iii) the role and relationship of food-evoked nostalgia and mood-individual descriptions of the important role that nostalgic food plays in their life, in addition to their relationship with food, and how this impacts mood., Conclusions: Understanding the positive component of nostalgic foods allowed individuals to bolster positive mood states with food-evoked nostalgia, increasing their quality of life. SO WHAT?: Understanding the link between food-evoked nostalgia and mood has significant implications, suggesting that negative mood states altered by nostalgic foods may result in positive mood states. Appropriate use of food-evoked nostalgia may increase the quality of life for individuals experiencing low mood states., (© 2024 The Author(s). Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Purpose: Atopic march is defined as the development of atopic dermatitis in early childhood. We recently developed an atopic march mouse model through skin sensitization with aeroallergens from house dust mites and cockroaches. Using this model, this study aimed to evaluate the oral immunotherapy efficacy of Lactococcus lactis harboring specific antigens on the progression of atopic march., Methods: Dust mite major allergen Der p 2 and cockroach Per a 2-372 were expressed in L. lactis as a fusion recombinant clone (D2P2). L. lactis -D2P2 was administered intragastrically to Aeroallergen patch-sensitized mice once a day for a total of 35 times. The immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of lungs and skin were evaluated., Results: Our data showed that L. lacti s-D2P2 significantly lowered total immunoglobulin E levels, decreased scratch bouts, and relieved AHR compared with the control mice. Histological analysis of the skin and lung tissue demonstrated the therapeutic effects of L. lactis -D2P2 to modulate immune responses via decreased eosinophil infiltration and reduced expression of key cytokines, interleukin (IL)-31 and IL-13, respectively., Conclusions: The results imply that mucosal allergen-specific immunotherapy of L. lactis -D2P2 is a more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. This study provides a promising platform for the development of novel oral protein-based vaccines in the early prevention of allergies., 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.)

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA , de novo lipogenesis-related genes ACACA and FASN , and MYC . FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis. NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).

In general (i.e. in heteronormative and cisgendered samples), authenticity appears protective against threats to well-being. Authenticity may also, in part, protect well-being against the minority stressors experienced by sexually minoritized (LGB; lesbian, gay, and bisexual) individuals. In this scoping review, we examined the relation between authenticity and well-being in LGB samples experiencing minority stress. We hypothesized that (i) LGB minority stress relates to decreased authenticity (i.e. inauthenticity), (ii) authenticity relates to increased well-being, and (iii) authenticity influences the relation between LGB minority stress and well-being. We identified 17 studies ( N  = 4,653) from systematic searches across Medline, ProQuest, PsycINFO, and Scopus using terms related to sexual identity, minority stress, authenticity, and well-being. In almost all studies, proximal (but not distal) stress was associated with inauthenticity, and inauthenticity with decreased well-being. In all but one study, the association between proximal stress and well-being was associated with inauthenticity. Although these results are consistent with our hypotheses, the included studies were limited in scope and heterogenous in their methods, instruments, and samples, restricting conclusions regarding mediation or moderation. The results require replication, well-powered direct comparisons between LGB and non-LGB samples, and consideration of the varied ways authenticity can be conceptualized and measured.

Aim: To explore the link between the RBP4 rs3758539 genotype and metabolic syndrome risk factors and whether the impact of this genetic variation displays any potential race discrepancy., Materials and Methods: This meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (registration no. CRD42023407999). PubMed, Web of Science, Embase, Cochrane Library, Google Scholar, Airiti Library and CINAHL databases were used for the study search until October 2023. We evaluated the methodological quality using the Joanna Briggs Institute checklist and determined the correlation using a random-effects meta-analysis., Results: The results indicated that individuals with the rs3758539 GA/AA genotype had a higher risk profile, including lower high-density lipoprotein levels [correlation: -0.045, 95% confidence interval (CI): -0.080 to -0.009, p = .015, I 2  = 46.9%] and higher body mass index (correlation: 0.117, 95% CI: 0.036-0.197, p = .005, I 2  = 82.0%), body fat (correlation: 0.098, 95% CI: 0.004-0.191, p = .041, I 2  = 64.0%), and low-density lipoprotein levels (correlation: 0.074, 95% CI: 0.010-0.139, p = .024, I 2  = 0%), of developing metabolic syndrome than those with the GG genotype. The subgroup analysis maintained a significantly positive correlation between the rs3758539 GA/AA genotype and body mass index (correlation: 0.163, 95% CI: 0.031-0.289, p = .016, I 2  = 88.9%) but a negative correlation with high-density lipoprotein levels (correlation: -0.047, 95% CI: -0.087 to -0.006, p = .025, I 2  = 65.7%) in the Asian group only., Conclusion: The current meta-analysis supports a significant link between the RBP4 rs3758539 GA/AA genotype and the metabolic syndrome., (© 2024 John Wiley & Sons Ltd.)

Background: Volatile organic compounds (VOC) are major indoor air pollutants. Previous studies reported an association between VOC exposure and allergic diseases. Here, we aimed to explore the relationship between VOC exposure and atopic dermatitis (AD) in adults., Methods: We prospectively enrolled 31 adult AD patients and 11 healthy subjects as controls. Urine metabolite levels of VOCs, including 1.3-butadiene, acrylamide, benzene, toluene, and xylene, were all determined with liquid chromatography-mass spectrometry. The relationship between AD and log-transformed urine levels of VOC metabolites were examined using a multivariate linear regression model adjusted for age and sex. We also treated mouse bone marrow-derived cells (BMMCs) with 1,3-butadiene and toluene and measured the release of β-hexosaminidase., Results: Our results demonstrated that creatinine-corrected urine levels of N-Acetyl-S- (3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), and N-Acetyl-S-(benzyl)-L-cysteine (BMA) were all elevated in AD patients compared with controls. In a multivariate linear regression model, creatinine-corrected urine levels of BMA (a toluene metabolite) and DHBMA (a 1,3-butadiene metabolite) appeared elevated in AD patients, although statistical significance was not reached after correction for multiple comparisons. In addition, 1,3-butadiene and toluene could stimulate BMMCs to degranulate as much as compound 48/80., Conclusions: Some VOCs, such as 1,3-butadiene and toluene, might be associated with AD pathogenesis in adults.

Flavonoids exhibit health-promoting benefits against multiple chronic diseases, including cancer. Apigenin (4',5,7-trihydroxyflavone), one flavonoid present in fruits and vegetables, is potentially applicable to chemoprevention. Despite considerable progress in the therapeutic regimen of liver cancer, its prognosis remains poor. MED28, a Mediator subunit for transcriptional activation, is implicated in the development of several types of malignancy; however, its role in liver cancer is unknown at present. In liver cancer, the AKT/mammalian target of rapamycin (mTOR) is one major pathway involved in the oncogenic process. The aim of this study is to investigate the role of apigenin and MED28 in AKT/mTOR signaling in liver cancer. We first identified a connectivity score of 92.77 between apigenin treatment and MED28 knockdown in several cancer cell lines using CLUE, a cloud-based software platform to assess connectivity among compounds and genetic perturbagens. Higher expression of MED28 predicted a poorer survival prognosis; MED28 expression in liver cancer tissue was significantly higher than that of normal tissue, and it was positively correlated with tumor stage and grade in The Cancer Genome Atlas Liver Cancer (TCGA-LIHC) data set. Knockdown of MED28 induced cell cycle arrest and suppressed the AKT/mTOR signaling in two human liver cancer cell lines, HepG2 and Huh 7, accompanied by less lipid accumulation and lower expression and nuclear localization of sterol regulatory element binding protein 1 (SREBP1). Apigenin inhibited the expression of MED28, and the effect of apigenin mimicked that of the MED28 knockdown. On the other hand, the AKT/mTOR signaling was upregulated when MED28 was overexpressed. These data indicated that MED28 was associated with the survival prognosis and the progression of liver cancer by regulating AKT/mTOR signaling and apigenin appeared to inhibit cell growth through MED28-mediated mTOR signaling, which may be applicable as an adjuvant of chemotherapy or chemoprevention in liver cancer.

Background: Craniospinal irradiation (CSI) poses a challenge to treatment planning due to the large target, field junction, and multiple organs at risk (OARs) involved. The aim of this study was to evaluate the performance of knowledge-based planning (KBP) in CSI by comparing original manual plans (MP), KBP RapidPlan initial plans (RP I ), and KBP RapidPlan final plans (RP F ), which received further re-optimization to meet the dose constraints., Patients and Methods: Dose distributions in the target were evaluated in terms of coverage, mean dose, conformity index (CI), and homogeneity index (HI). The dosimetric results of OARs, planning time, and monitor unit (MU) were evaluated., Results: All MP and RP F plans met the plan goals, and 89.36% of RP I plans met the plan goals. The Wilcoxon tests showed comparable target coverage, CI, and HI for the MP and RP F groups; however, worst plan quality was demonstrated in the RP I plans than in MP and RP F . For the OARs, RP F and RP I groups had better dosimetric results than the MP group ( P < 0.05 for optic nerves, eyes, parotid glands, and heart). The planning time was significantly reduced by the KBP from an average of 677.80 min in MP to 227.66 min ( P < 0.05) and 307.76 min ( P < 0.05) in RP I , and RP F , respectively. MU was not significantly different between these three groups., Conclusions: The KBP can significantly reduce planning time in CSI. Manual re-optimization after the initial KBP is recommended to enhance the plan quality., (© 2024 Wei-Ta Tsai et al., published by Sciendo.)

Dengue presents a major public health concern in over 100 countries due to the absence of an effective vaccine and antiviral therapy against all four dengue virus (DENV) serotypes. Several antiviral peptides were previously reported to inhibit at least three or all four DENV serotypes. Chemical modifications such as d-amino acid substitutions, polyethylene glycol (PEG)ylation, and cyclization could be applied to peptides to improve their biological activities and stability in serum. The PEGylated peptide 3 (PEG-P3) was identified to be the most promising antiviral candidate as it demonstrated good inhibitory effects against all four DENV serotypes during the pre- and post-infection stages, Based on the RP-HPLC and LC/MS analysis, peptide 4 was identified to be more stable in human serum than peptide 3, with 78.9 % and 41.6 % of the peptides remaining after 72 h of incubation in human serum, respectively. Both peptides were also able to retain their antiviral activities against specific DENV serotypes after 72 h incubation in human serum. PEG-P3 was found to be more stable than the unmodified peptide 3 with 89.4 % of PEG-P3 remaining in the human serum after 72 h of incubation. PEG-P3 was able to retain its inhibitory effects against DENV-1 to 4 after 72 h of incubation in human serum. This study provided insights into the antiviral activities and stabilities of the unmodified and chemically modified peptides in human serum., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The hand, food, and mouth disease (HFMD) is primarily caused by Enterovirus A71 (EV-A71). EV-A71 outbreaks in the Asia Pacific have been associated with severe neurological disease and high fatalities. Currently, there are no FDA-approved antivirals for the treatment of EV-A71 infections. In this study, the SP81 peptide, derived from the VP1 capsid protein of EV-A71 was shown to be a promising antiviral candidate for the treatment of EV-A71 infections. SP81 peptide was non-toxic to RD cells up to 45 μM, with a half-maximal cytotoxic concentration (CC 50 ) of 90.32 μM. SP81 peptide exerted antiviral effects during the pre- and post-infection stages with 50% inhibitory concentrations (IC 50 ) of 4.529 μM and 1.192 μM, respectively. Direct virus inactivation of EV-A71 by the SP81 peptide was also observed with an IC 50 of 8.076 μM. Additionally, the SP81 peptide exhibited direct virus inactivation of EV-A71 at 95% upon the addition of the SP81 peptide within 5 min. This study showed that the SP81 peptide exhibited significant inhibition of EV-A71 and could serve as a promising antiviral agent for further clinical development against EV-A71 infections., 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 Inc. All rights reserved.)

Background: Polycyclic aromatic hydrocarbons are one of the major pathogenic components in air pollution. Previous studies have demonstrated an association between air pollution and atopic dermatitis., Objective: We sought to explore the relationship between polycyclic aromatic hydrocarbons exposure and adult atopic dermatitis., Methods: We prospectively recruited 23 adult patients with atopic dermatitis and 11 healthy controls. Plasma levels of inflammatory cytokines were determined using enzyme-linked immunosorbent assay. Expression levels of aryl hydrocarbon receptor, which mediates the effect of polycyclic aromatic hydrocarbons, and cytokines in peripheral blood nuclear cells (PBMCs) were measured using reverse transcription polymerase chain reaction. Urine levels of 16 polycyclic aromatic hydrocarbon metabolites were determined by gas chromatography- tandem mass spectrometry., Results: Patients with atopic dermatitis had lower levels of interleukin (IL)-5 and IL-23, and lower PBMC messenger RNA expression levels of interferon-> than the healthy controls. Plasma levels of IL-22 were moderately and positively associated with the SCORAD index. Creatinine-corrected urine levels of 9-hydroxyfluorene and 2-hydroxyphenanthrene were elevated in the atopic dermatitis group. However the difference was not statistically significant after Bonferroni correction., Conclusions: Our results demonstrated that the polycyclic aromatic hydrocarbons fluorene and phenanthrene are potentially associated with the pathogenesis of atopic dermatitis in adults.

Background: Women in the postpartum period come under multi-level pressure to return to pre-pregnancy body shape and size. This pressure can lead to reduced body image satisfaction, self-esteem, and mood. In this systematic review we explored the influences and outcomes of body dissatisfaction during the postpartum period., Methods: Four databases were searched using keywords: postpart* OR postnatal OR peripart* OR 'new mother' OR 'breast feed*' AND 'body image' OR 'body dissatisf*' OR 'body satisf*' OR 'body attitude' OR 'body shape'., Results: The influences and outcomes of body image dis/satisfaction in the postpartum period from 55 international studies were found to align within four of the five factors of the socioecological model. Intrapersonal factors: weight and body shape concerns, mental health and stressors, attitudes and behaviours, and protective coping skills and interventions. Interpersonal factors: social support (partner, family, and friends) and sexual functioning. Institutional factors: experiences with the healthcare system and returning to work. Societal factors: culture and ethnicity, media influences and social norms such as the thin ideal., Conclusions: A focus on intrapersonal factors alone is insufficient to understand women's experiences of body dis/satisfaction during the postpartum period. This suggests a need for better education and policy practices in pre-natal and postpartum care directed at body image and education to dispel societal norms such as the thin ideal. Doing so shifts the focus to include interpersonal, institutional, and societal influences alongside intrapersonal experiences. Research is needed to explore the utility and efficacy of broader approaches for women during this vulnerable life period.

Atopic dermatitis (AD) is a complex, chronic inflammatory skin disease. An estimated 57.5% of asthmatic patients and 50.7% of rhinitis patients are allergic to cockroaches in Taiwan. However, the role of cockroaches in the pathogenesis of AD is undetermined. Oral tolerance might be another strategy for protecting against AD and allergic inflammation by regulating T helper 2 (Th2) immune responses. Aim to examine the underlying immunologic mechanism, we developed an AD-like murine model by skin-brushing with cockroach Per a 2. We also investigated whether the systemic inflammation of AD in this murine model could be improved by specific tolerance to Lactococcus lactis-expressing Per a 2, which was administered orally. Repeated painting of Per a 2 without adjuvant to the skin of mice resulted in increased total IgE, Per a 2-specific IgE, and IgG1, but not IgG2a. In addition, epidermal thickening was significantly increased, there were more scratch episodes, and there were increases in total white blood cells (eosinophil, neutrophil, and lymphocyte) and Th2 cytokines (Interleukin (IL)-4, IL-5, IL-9, and IL-13) in a dose-dependent manner. The results revealed that oral administration of L. lactis-Per a 2 ameliorated Per a 2-induced scratch behavior and decreased the production of total IgE, Per a 2-specific IgE, and IgG1. Furthermore, L. lactis-Per a 2 treatment also suppressed inflammatory infiltration, expressions of thymic stromal lymphopoietin (TSLP) and IL-31 in skin lesions, and downregulated splenic IL-4 and IL-13 in Per a 2-induced AD mice. This study provides evidence supporting that repeated brushing of aeroallergens to the skin leads to atopic dermatitis phenotypes and oral allergen-specific immune tolerance can ameliorate AD-like symptoms and systemic inflammation and prevent progression of atopic march., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee 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.)

The progression of allergic diseases from atopic dermatitis in childhood to other allergic conditions such as asthma in later life is often referred to as the atopic march. In order to study the relationship between cutaneous sensitization by aeroallergen and atopic march, we established a mouse model to test the hypothesis using American cockroaches and house dust mites as the model allergens. Mice were sensitized via skin with native cockroach extract (CraA) or recombinant Per a 2 and Der p 2 proteins without adjuvant. Each mouse was subjected to a total of three 1-week patching sensitizations with a 2-week interval in between each application. The resulting immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of skin lesions and nasal mucosa were evaluated. In mice, application of CraA, rPer a 2, and rDer p 2 aeroallergens through skin patching induced significantly high levels of both total IgE and specific IgEs. The epicutaneous sensitization after a subsequent allergen challenge showed a significant increase in scratch bouts, AHR, epidermal thickness, and eosinophil counts in the skin compared with the control mice. In addition, stimulation of murine splenocytes with allergens increased higher levels of Th2 cytokines, anti-inflammatory cytokines, and chemokines excretion. Our study provides evidence supporting that epicutaneous sensitization to aeroallergens also led to nasal and airway symptoms comparable to atopic march as described in humans. We hope this new allergy model will be useful in the development of new preventive and therapeutic strategies aimed at stopping the atopic march., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Lee 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.)

Objectives: Complications of endoscopic sinus/nasal turbinate surgery include postoperative hemorrhage, synechiae formation, and poor wound healing. Our primary objectives were to evaluate whether a topical hydrogel based on self-assembling RADA16 peptides: i) reduces bleeding and synechiae formation, and ii) supports wound healing, using a sheep nasal surgery model., Methods: Thirty sheep received endoscopic surgery-created bilateral nasal mucosal injuries on the middle turbinate/opposing septum. Injuries were randomly assigned RADA16, Gelatin-thrombin, or no treatment. Outcomes included intra-operative hemostasis, scar tissue/synechiae formation and wound healing at 2 weeks and the 6-week study terminus, and histopathology., Results: Intra-operative hemostasis time improved with RADA16 and Gelatin-thrombin versus Control wounds (139.7±56.2 s, 145.4±58.1 s, and 224.0±69.9 s, respectively; p < 0.0001 for both comparisons). Two-week synechiae scores (maximum 4 points) were similar in Controls (2.9±1.8 points) and Gelatin-thrombin (3.1±1.6 points) wounds (p > 0.05), but were reduced in RADA16 sites by 91% versus Controls and 92% versus Gelatin-thrombin treatment (0.3±0.6 points; p < 0.0001 for both comparisons). Six-week synechiae scores were similar in Control (1.1±1.7 points) and Gelatin-thrombin (1.7±2.0 points) wounds (p > 0.05), but reduced 100% in RADA16-treated wounds. Synechiae occurred in fewer RADA16-treated sites at 2 weeks (20%) versus Gelatin-thrombin (80%) and Controls (75%; p < 0.01) and at 6 weeks (0%, 50% and 35%, respectively; p < 0.01). RADA16 was associated with significantly lower 6-week histopathology scores, driven by reduced submucosal fibrosis and angiogenesis., Conclusion: Although RADA16 and Gelatin-thrombin similarly accelerated hemostasis in this sheep endoscopic sinus surgery model, only RADA16 reduced postoperative synechiae formation at 2 weeks with an absence of synechiae at 6 weeks. Histology suggested RADA16 enhanced mucosal regeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no other potential conflicts of interest, financial or otherwise, related to the research described in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Dengue is a major global health threat causing 390 million dengue infections and 25,000 deaths annually. The lack of efficacy of the licensed Dengvaxia vaccine and the absence of a clinically approved antiviral against dengue virus (DENV) drive the urgent demand for the development of novel anti-DENV therapeutics. Various antiviral agents have been developed and investigated for their anti-DENV activities. This review discusses the mechanisms of action employed by various antiviral agents against DENV. The development of host-directed antivirals targeting host receptors and direct-acting antivirals targeting DENV structural and non-structural proteins are reviewed. In addition, the development of antivirals that target different stages during post-infection such as viral replication, viral maturation, and viral assembly are reviewed. Antiviral agents designed based on these molecular mechanisms of action could lead to the discovery and development of novel anti-DENV therapeutics for the treatment of dengue infections. Evaluations of combinations of antiviral drugs with different mechanisms of action could also lead to the development of synergistic drug combinations for the treatment of dengue at any stage of the infection.

Peptides are a rapid-growing class of therapeutics with unique and desirable physicochemical properties. Due to disadvantages such as low membrane permeability and susceptibility to proteolytic degradation, peptide-based drugs have limited bioavailability, a short half-life, and rapid in vivo elimination. Various strategies can be applied to improve the physicochemical properties of peptide-based drugs to overcome limitations such as limited tissue residence time, metabolic instability, and low permeability. Applied strategies including backbone modifications, side chain modifications, conjugation with polymers, modification of peptide termini, fusion to albumin, conjugation with the Fc portion of antibodies, cyclization, stapled peptides, pseudopeptides, cell-penetrating peptide conjugates, conjugation with lipids, and encapsulation in nanocarriers are discussed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

PUFA status is highly implicated in cognitive development and metabolic disorder-related diseases. Genetic variants of FADS genes encoding enzymes that catalyze the rate-limiting steps of PUFA biosynthesis appear to be associated with n-3 and n-6 PUFA contents. Therefore, we conducted the first systematic review and meta-analysis to explore the association of the A-allele carriers of the FADS1 rs174556 with PUFA status. The PRISMA guidelines were followed. The literature search was conducted up to November 2022 in PubMed, Web of Science, Embase, Cochrane Library, Airiti Library, and CINAHL. The Joanna Briggs Institute checklists were used to assess the methodological quality. The correlation with 95% CIs was determined by a random-effect meta-analysis. Eleven studies that met the inclusion criteria and acceptable quality were included in this systematic review. The data on PUFA contents were collected when they were mainly analyzed using blood samples and breast milk. Results of the meta-analysis on eight studies (one randomized controlled trial, one cohort study, and six cross-sectional studies) showed that the A-allele carriers of rs174556 were significantly negatively correlated with the concentrations of AA (P = 0.001), EPA (P = 0.004), and DHA (P = 0.025). However, ALA and LA were not associated with the A-allele carriers. To clarify the discrepancy, we further divided the studies into blood samples and breast milk subgroups. The subgroup analysis revealed that the A-allele carriers of rs174556 were significantly positively correlated with LA (P = 0.031) and negatively correlated with AA (P = 0.001), EPA (P = 0.036), and DHA (P < 0.001) in the blood sample group, but not in the breast milk group. The current meta-analysis proved that the A-allele carriers of the FADS1 rs174556 appeared to be highly associated with lower concentrations of AA, EPA, and DHA but higher LA in the blood samples. The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO:CRD42022363978). Adv Nutr 2023;x:xx-xx., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dengue infections pose a critical threat to public health worldwide. Since there are no clinically approved antiviral drugs to treat dengue infections caused by the four dengue virus (DENV) serotypes, there is an urgent need to develop effective antivirals. Peptides are promising antiviral candidates due to their specificity and non-toxic properties. The DENV envelope (E) protein was selected for the design of antiviral peptides due to its importance in receptor binding and viral fusion to the host cell membrane. Twelve novel peptides were designed to mimic regions containing critical amino acid residues of the DENV E protein required for interaction with the host. A total of four peptides were identified to exhibit potent inhibitory effects against at least three or all four DENV serotypes. Peptide 3 demonstrated all three modes of action: cell protection and inhibition of post-infection against all four DENV serotypes, whereas direct virus-inactivating effects were only observed against DENV-2, 3, and 4. Peptide 4 showed good direct virus-inactivating effects against DENV-2 (74.26%) as well as good inhibitions of DENV-1 (80.37%) and DENV-4 (72.22%) during the post-infection stage. Peptide 5 exhibited direct virus-inactivating effects against all four DENV serotypes, albeit at lower inhibition levels against DENV-1 and DENV-3. It also exhibited highly significant inhibition of DENV-4 (89.31%) during post-infection. Truncated peptide 5F which was derived from peptide 5 showed more significant inhibition of DENV-4 (91.58%) during post-infection and good direct virus-inactivating effects against DENV-2 (77.55%) at a lower concentration of 100 μM. Peptide 3 could be considered as the best antiviral candidate for pre- and post-infection treatments of DENV infections in regions with four circulating dengue serotypes. However, if the most predominant dengue serotype for a particular region could be identified, peptides with significantly high antiviral activities against that particular dengue serotype could serve as more suitable antiviral candidates. Thus, peptide 5F serves as a more suitable antiviral candidate for post-infection treatment against DENV-4., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Neck dissection is a commonly performed procedure for oncologic control of head and neck malignancy. With contemporary modified radical and selective neck dissections, haematoma, wound infection, tissue necrosis, chyle leak and injury involving the marginal mandibular, hypoglossal, vagus or accessory nerves are commonly described complications. Although the phrenic nerve courses within the surgical planes explored during a neck dissection and has a vital function in innervating the diaphragm, few studies have been performed to investigate the exact incidence of post-operative phrenic nerve paresis. This study aims to review the literature as to the rate of phrenic nerve injury following neck dissection., Methods: A systematic literature review was conducted from 2000 to 2022 including studies reporting on phrenic nerve paresis following neck dissection., Results: In total, 11 studies were included. The reported rate of immediate post-operative phrenic nerve paresis ranged from 0% to 5.3%, with an average rate of 0.613% (12/1959). The reported rate of phrenic nerve paresis at follow-up (1 month-127 months) ranged from 0% to 4.7%, with an average rate of 1.035% (5/483). There were no cases of bilateral phrenic nerve paresis reported in this period., Conclusions: Phrenic nerve paresis is an uncommon complication following neck dissection, often asymptomatic and potentially underreported. Bilateral phrenic nerve paresis is exceedingly rare. Injury can be avoided by staying superficial to the prevertebral fascia when dissecting around the anterior scalene muscle. Routine phrenic nerve integrity monitoring is not commonly utilized but may aid intra-operative phrenic nerve identification or confirmation of function., (© 2023 Royal Australasian College of Surgeons.)

Epidemiological and intervention studies in nutritional psychiatry suggest that the risk of mood disorders is associated with what we eat. However, few studies use a person-centred approach to explore the food and mood relationship. In this qualitative study of 50 Australian participants, we explored individuals' experiences with food and mood as revealed during focus group discussions. Using a thematic template analysis, we identified three themes in the food and mood relationship: (i) social context: familial and cultural influences of food and mood , (ii) social economics: time, finance, and food security , and (iii) food nostalgia: unlocking memories that impact mood . Participants suggested that nutrients, food components or food patterns may not be the only way that food impacts mood. Rather, they described the social context of who, with, and where food is eaten, and that time, finances, and access to healthy fresh foods and bittersweet memories of foods shared with loved ones all impacted their mood. Findings suggest that quantitative studies examining the links between diet and mood should look beyond nutritional factors and give increased attention to the cultural, social, economic, and identity aspects of diet.

Current observational and interventional studies in nutritional psychiatry suggest that healthy dietary patterns rich in fresh whole foods could protect against depressive symptoms, and that unhealthy dietary patterns high in ultra-processed and refined foods could contribute to depressive symptoms. However, no studies have explored detailed subjective accounts behind the food and mood relationship. This study aimed to uncover unknown factors in the human experience with food and mood. Using a phenomenological framework, this focus group study applied thematic template analysis to accounts of over 50 Australians aged between 18 and 72. Three themes were identified from the transcript of the focus groups: (i) reactive and proactive relationships with food, (ii) acknowledgement of individual diversity relating to eating and mental health, and (iii) improving mood by removing food restriction and eating intuitively. The data highlights the complexity of the relationship between food and mood that extends beyond biological mechanisms which could be used to extend current epidemiological and intervention studies in the field of dietary patterns and depression.

Dengue is a mosquito-borne disease which causes significant public health concerns in tropical and subtropical countries. Dengue virus (DENV) has evolved various strategies to manipulate the innate immune responses of the host such as 'hiding' in the ultrastructure of the host, interfering with the signaling pathway through RNA modifications, inhibiting type 1 IFN production, as well as inhibiting STAT1 phosphorylation. DENV is also able to evade the adaptive immune responses of the host through antigenic variation, antigen-dependent enhancement (ADE), partial maturation of prM proteins, and inhibition of antigen presentation. miRNAs are important regulators of both innate and adaptive immunity and they have been shown to play important roles in DENV replication and pathogenesis. This makes them suitable candidates for the development of anti-dengue therapeutics. This review discusses the various strategies employed by DENV to evade innate and adaptive immunity. The role of miRNAs and DENV non-structural proteins (NS) are promising targets for the development of anti-dengue therapeutics., 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 © 2022 Lee, Voon, Lim, Chua and Poh.)

Inadequate vitamin D status may increase the risk of developing multiple types of cancer. Epidemiological studies suggest an inverse association between 25-hydroxyvitamin D 3 (25(OH)D 3 ) and malignancy, including colorectal cancer. Previous studies have suggested that MED28, a Mediator subunit involved in transcriptional regulation, is associated with the growth of colorectal cancer cells; however, its role in the progression of metastasis such as epithelial-mesenchymal transition (EMT) and cell migration of colorectal cancer is unclear at present. The aim of this study was to investigate a potentially suppressive effect of calcitriol, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), a bioactive form of vitamin D, and the role of MED28 in the progression of EMT in human colorectal cancer cells. Suppression of MED28 increased the expression of E-cadherin and reduced the expression of several mesenchymal and migration biomarkers and Wnt/ β -catenin signaling molecules, whereas overexpression of MED28 enhanced the EMT features. Calcitriol suppressed the expression of MED28, and the effect of calcitriol mirrored that of MED28 silencing. Our data indicate that calcitriol attenuated MED28-mediated cell growth and EMT in human colorectal cancer cells, underlining the significance of MED28 in the progression of colorectal cancer and supporting the potential translational application of calcitriol., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Chun-Yin Huang et al.)

Following the identification of SARS-CoV-2, screening for air travel helped mitigate spread, yet lessons learned from a case study of air travel within Canada display enhanced techniques to better identify infected individuals, informing future responsive screening. While international travel bans limit infectious spread beyond a country's borders, such measures are hardly sustainable economically and infrequently address domestic travel. Here, we describe a case study from Canada, where a diagnostic laboratory at point of travel conducted real-time PCR-based detection of SARS-CoV-2 in support of existing interventions, including clinical and epidemiological questionnaires, and temperature checks. All mining workers departing from a populated urban area flying to one of two sites (Site A and B) in a remote northern Canadian region, which we deemed "at-risk", because healthcare services are limited and vulnerable to epidemics. Data collected between June and November 2020 on 15,873 clinical samples, indicate that molecular diagnosis allowed for identification of 13 infected individuals, who would have otherwise been missed by using solely nonpharmaceutical interventions. Overall, no outbreaks, COVID-19-related or other, were detected at the point of travel up to December 2021 since the implementation of the laboratory, suggesting this screening process is an effective means to protect at-risk communities. The success of this study suggests a process more practical than travel bans or an unfocused screening of air travelers everywhere., (© 2022. The Author(s).)

Objective: To present a case of giant cholesteatoma and review of the contemporary literature., Patients: A 61-year-old male presented with foul-smelling discharge from his right ear in the setting of a previous canal wall down mastoidectomy. Otomicroscopy demonstrated a mastoid cavity filled with infected keratinous debris. Neuro-imaging revealed soft tissue inflammatory changes in the mastoid cavity, with involvement of the temporomandibular joint (TMJ) and parotid gland and tegmen erosion. Biopsies showed evidence of desquamated epithelium consistent with cholesteatoma, with no malignant cells identified. Audiogram demonstrated a mean hearing loss of 65 dB on the right ear and an air-bone gap of 45 dB. Review of literature was also performed on giant cholesteatoma., Interventions: He underwent a modified Fisch Type B infratemporal fossa approach to completely remove the cholesteatoma and a vascularized free flap was utilized to fill the surgical defect., Main Outcome Measures: Complete extirpation of choles-teatoma and resolution of otorrhoea., Results: Repeat imaging showed complete removal of cholesteatoma and clinically there was resolution of the otorrhea. Review of the literature has shown a lack of consensus around the definition of giant cholesteatoma. Most cases in the literature demonstrated extensive involvement of anatomical spaces beyond the confines of the temporal bone to qualify for the diagnosis of giant cholesteatoma., Conclusions: Giant cholesteatoma should be suspected in cases of recurrent ear discharge following canal wall down mastoidectomy. The case we report add to the literature to benefit future patients in preoperative counseling and better inform management., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu 3+ and Gd 3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract-fucoidan was extracted from the same brown algae-Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 μg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 μg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized., (© 2022. The Author(s).)

Objectives: Pressure to lose weight can increase the risk of developing disordered eating behaviours, negative body image and depressive symptomatology. Eating intuitively may counteract these negative outcomes. This research examined the unique relationship between intuitive eating and disordered eating on body mass index (BMI), body image and depressive symptoms for women of young children., Methods: A survey of women with a child aged between six and 48 months, included the Intuitive Eating Scale, Eating Attitudes Test-26, Body Shape Questionnaire and Edinburgh Postnatal Depression Scale. Multivariate analysis of variance (MANOVA) was conducted as an omnibus test to estimate the effect of intuitive and disordered eating on BMI, negative body image and depressive symptoms., Results: Of the 419 sample (M age = 32.06), 32% were classified with disordered and 32% with intuitive eating. MANOVA and regression analysis found disordered eating positively associated with depressive symptoms, (β = 0.303) and negative body image (β = 0.318). Intuitive eating was associated with lower depressive symptoms (β =  - 0.183) and negative body image (β =  - 0.615). Disordered eating (β =  - 0.194) and intuitive eating (β =  - 0.586) both contributed to lower BMI, with the association stronger for intuitive eating., Conclusion: The early parenting period involves a high risk for developing disordered eating behaviours. Eating patterns are modifiable factors, illustrating the potential for positive and preventive health outcomes through adopting intuitive eating behaviours. There is an opportunity for healthcare professionals to promote physical and psychological health including for women in the early parenting period., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To perform a systematic review of the diagnosis and treatment of patients with pulsatile tinnitus secondary to middle ear myoclonus., Databases Reviewed: PubMed, EMBASE, and Scopus., Methods: A systematic review was performed using standardized methodology. Computerized and manual searches were performed to identify studies of all ages (patients) who had middle ear myoclonus (intervention). All study designs were assessed. Extracted data included demographics, clinical features, duration of followup as well as the diagnosis and reversibility of symptoms with medical or surgical intervention. Studies were included if they included subjects with middle ear myoclonus. Exclusion criteria included letters/commentaries and reviews., Results: Twenty articles representing 115 subjects with middle ear myoclonus were included. The mean age was 29.7 (range 6-67). The follow-up period ranged from 5 weeks to 36 months. Primary treatment consists of medical therapy utilising anxiolytics, antiepileptics, botulinum toxin and surgical treatment involving division of middle ear muscular tendon(s). In total, 60 patients underwent middle ear muscular tenotomies, with division of both stapedius and tensor tympani tendons being the most prevalent (88%). Limitations in the data arose from study design, related comorbidities such as palatal myoclonus, and concomitant drug administration. No study provided any objective criteria to diagnose this condition or evaluate post-treatment outcome., Conclusion: Middle ear myoclonus is an entity that is poorly assessed in the literature. There is a lack of consensus regarding the criteria and strategies for both diagnosing and treating this condition. Although level of evidence of current studies remains modest, it is felt that a stepwise approach is deemed best, with therapeutic decisions being made on an individual basis, evaluating each patient's specific circumstances and priorities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Allergic airway disease is the most common chronic airway inflammatory disorder in developed countries. House dust mite, cockroach, and mold are the leading allergens in most tropical and subtropical countries, including Taiwan. As allergen avoidance is difficult for patients allergic to these perennial indoor allergens, allergen-specific immunotherapy (ASIT) is the only available allergen-specific and disease-modifying treatment. However, for patients sensitized to multiple allergens, ASIT using each corresponding allergen is cumbersome. In the present study, we developed a recombinant L. lactis vaccine against the three most common indoor aeroallergens and investigated its effectiveness for preventing respiratory allergy and safety in mice. Three recombinant clones of Der p 2 (mite), Per a 2 (roach), and Cla c 14 (mold) were constructed individually in pNZ8149 vector and then electroporated into host strain L.lactis NZ3900. BALB/c mice were fed with the triple vaccine 5 times per week for 4 weeks prior to sensitization. The effectiveness and safety profile were then determined. Oral administration of the triple vaccine significantly alleviated allergen-induced airway hyper-responsiveness in the vaccinated mice. The allergen-specific IgG2a was upregulated. IL-4 and IL-13 mRNA expressions as well as inflammatory cell infiltration in the lungs decreased significantly in the vaccinated groups. No body weight loss or abnormal findings in the liver and kidneys were found in any of the groups of mice. This is the first report to describe a triple-aeroallergen vaccine using a food-grade lactococcal expression system. We developed a convenient oral delivery system and intend to extend this research to develop a vaccination that can be self-administered at home by patients., Competing Interests: The authors have declared that no competing interests exist.

Early steps of cancer initiation and metastasis, while critical for understanding disease mechanisms, are difficult to visualize and study. Here, we describe an approach to study the processes of initiation, progression, and metastasis of prostate cancer (PC) in a genetically engineered RapidCaP mouse model, which combines whole-organ imaging by serial two-photon tomography (STPT) and post hoc thick-section immunofluorescent (IF) analysis. STPT enables the detection of single tumor-initiating cells within the entire prostate, and consequent IF analysis reveals a transition from normal to transformed epithelial tissue and cell escape from the tumor focus. STPT imaging of the liver and brain reveal the distribution of multiple metastatic foci in the liver and an early-stage metastatic cell invasion in the brain. This imaging and data analysis pipeline can be readily applied to other mouse models of cancer, offering a highly versatile whole-organ platform to study in situ mechanisms of cancer initiation and progression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Plant-based dietary patterns (vegan and vegetarian) are often considered 'healthy' and have been associated with broad health benefits, including decreased risk of obesity and ill health (cardiovascular disease, blood glucose and type II diabetes). However, the association between plant-based diets and mood disorders such as depression remains largely equivocal. This cross-sectional study of 219 adults aged 18-44 (M=31.22, SD=7.40) explored the associations between an estimate of overall plant-based diet quality and depression in vegans (n=165) and vegetarians (n=54). Overall plant-based diet quality was associated with depressive symptoms in vegans and vegetarians F(1, 215)=13.71, p<0.001 accounting for 6% of the variation in depressive symptoms. For those without depression, higher diet quality was protective against depressive symptoms F(1, 125)=6.49, p=0.012. Conversely, for those with depression no association with diet quality was found F(1, 89)=0.01, p=0.963. These findings suggest that a high-quality plant-based diet may be protective against depressive symptoms in vegans and vegetarians. In line with emerging research between food and mental health, higher-quality dietary patterns are associated with a reduced risk of depressive symptoms. Given the rapidly increasing rate of vegan and vegetarian food products within Australia, understanding the potential mechanisms of effects through which a plant-based diet may influence depressive symptoms is required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Minor spliceosome inhibition due to mutations in RNU4ATAC are linked to primary microcephaly. Ablation of Rnu11, which encodes a minor spliceosome snRNA, inhibits the minor spliceosome in the developing mouse pallium, causing microcephaly. There, cell cycle defects and p53-mediated apoptosis in response to DNA damage resulted in loss of radial glial cells (RGCs), underpinning microcephaly. Here, we ablated Trp53 to block cell death in Rnu11 cKO mice. We report that Trp53 ablation failed to prevent microcephaly in these double knockout (dKO) mice. We show that the transcriptome of the dKO pallium was more similar to the control compared with the Rnu11 cKO. We find aberrant minor intron splicing in minor intron-containing genes involved in cell cycle regulation, resulting in more severely impaired mitotic progression and cell cycle lengthening of RGCs in the dKO that was detected earlier than in the Rnu11 cKO. Furthermore, we discover a potential role of p53 in causing DNA damage in the developing pallium, as detection of γH2aX+ was delayed in the dKO. Thus, we postulate that microcephaly in minor spliceosome-related diseases is primarily caused by cell cycle defects., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Increasing lines of evidence indicate that the biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D 3 ), prevents cancer progression by reducing cell proliferation, increasing cell differentiation, and inhibiting angiogenesis, among other potential roles. Cancer cells in solid tumors preferably undergo the "Warburg effect" to support cell growth by upregulating glycolysis, and the glycolytic intermediates further serve as building blocks to generate biomass. The objective of the current study is to investigate whether calcitriol affects glucose metabolism and cell growth in human colorectal cancer cells. Calcitriol reduced the expression of cyclin D1 and c-Myc. In addition, calcitriol reduced the expression of glucose transporter 1 (GLUT1) and key glycolytic enzymes and decreased extracellular acidification rate but increased oxygen consumption rate in human colorectal cancer cells. In a subcutaneous HT29 xenograft NOD/SCID mouse model, the volume and weight of the tumors were smaller in the calcitriol groups as compared with the control group, and the expression levels of GLUT1 and glycolytic enzymes, hexokinase 2 and lactate dehydrogenase A, were also lower in the calcitriol groups in a dose-responsive manner. Our data indicate that calcitriol suppresses glycolysis and cell growth in human colorectal cancer cells, suggesting an inhibitory role of the biologically active form of vitamin D in colorectal cancer progression.