Cerebrospinal Fluid Nitric Oxide Synthase is a Potential Mediator Between Cigarette Smoke Exposure and Sleep Disorders.

Objective: Cigarette smoking and low peripheral nitric oxide synthase (NOS) levels are strongly associated with sleep disorders. However, whether cerebrospinal fluid (CSF) NOS relates to sleep disorders and whether CSF NOS mediates the relationship between cigarette smoking and sleep disorders is unclear. Methods: We measured CSF levels of total NOS (tNOS) and its isoforms (inducible NOS [iNOS] and constitutive NOS [cNOS]) in 191 Chinese male subjects. We applied the Pittsburgh Sleep Quality Index (PSQI). Results: The PSQI scores of active smokers were significantly higher than those of non-smokers, while CSF tNOS, iNOS, and cNOS were significantly lower (all p < 0.001). CSF tNOS, iNOS, and cNOS were negatively associated with PSQI scores in the general population (all p < 0.001). Mediation analysis suggested that CSF tNOS, iNOS, and cNOS mediate the relationship between smoking and PSQI scores, and the indirect effect accounted for 78.93%, 66.29%, and 81.65% of the total effect, respectively. Conclusion: Cigarette smoking is associated with sleep disorders. Active smokers had significantly lower CSF levels of tNOS, iNOS, and cNOS. Furthermore, tNOS, iNOS, and cNOS mediate the relationship between cigarette smoking and sleep quality. This study provides insights into how cigarette smoke affects sleep disorders.

Increased expression of the kynurenine pathway in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine pathway (KP) have been suggested to contribute to the pathogenesis of central nervous system (CNS) infection. We hypothesized that KP may also be involved in parasitic eosinophilic meningitis. BALB/c mice were orally infected with 40 A. cantonensis L3, intraperitoneal dexamethasone at a dose of 500 µg/kg/day was administered from the seventh day of infection until the end of the study. The Evans blue method was used to analyze blood-brain barrier (BBB) dysfunction, and indoleamine 2,3-dioxygenase (IDO) proteins levels was measured by Western blot, immunohistochemistry (IHC), and immunofluorescence. Tryptophan and kynurenine concentrations were analyzed by IHC and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of Evans blue, IDO, tryptophan and kynurenine in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. BBB dysfunction was found in mice with eosinophilic meningitis. The administration of dexamethasone significantly decreased the amount of Evans blue. An increased IDO expression was shown in Western blot, IHC and immunofluorescence following 2-3 weeks infection. Increased tryptophan and kynurenine expressions in the brain and cerebrospinal fluid (CSF) were also found in IHC and LC-MS/MS studies. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine. In conclusion, A. cantonensis infection inducing BBB damage, then increased the influx of tryptophan into CSF. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine.

The effects of BDNF rs6265 and FGF21 rs11665896 polymorphisms on alcohol use disorder-related impulsivity in Han Chinese adults.

Introduction: Patients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD. Methods: We recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data. Results: The T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness (F = 9.15, p = 0.003, η2p = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness. Conclusion and significance: The combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (ca 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to ferroptosis and apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.

Monitoring the Season-Prevalence Relationship of Vairimorpha ceranae in Honey Bees (Apis mellifera) over One Year and the Primary Assessment of Probiotic Treatment in Taichung, Taiwan.

Microsporidiosis, which is caused by the pathogen Vairimorpha ceranae, is a prevalent disease in the honey bee (Apis mellifera) and might lead to significant adult honey bee mortality. In this study, we conducted an annual survey of the mature spore load of V. ceranae in the guts of nurse bees and forager bees in the apiary of National Chung Hsing University (NCHU) in Taiwan. The results indicated that, on average, honey bees hosted approximately 2.13 × 106 mature spore counts (MSCs)/bee in their guts throughout the entire year. The highest number of MSCs was 6.28 × 106 MSCs/bee, which occurred in April 2020, and the lowest number of MSCs was 5.08 × 105 MSCs/bee, which occurred in November 2020. Furthermore, the guts of forager bees had significantly higher (>58%) MSCs than those of nurse bees. To evaluate the potential of the probiotic to treat microsporidiosis, the lactic acid bacterium Leuconostoc mesenteroides TBE-8 was applied to honey bee colonies. A significant reduction (>53%) in MSCs following probiotic treatment was observed, indicating the potential of probiotic treatment for managing microsporidiosis. This research provided information on V. ceranae MSCs in the honey bee gut at NCHU in Taiwan and the MSCs' correlation with the annual season. Furthermore, a potential probiotic treatment for microsporidiosis was assessed for future management.

Development of a tool for monitoring the jaw-opening pace and preliminary comparison the pace between young and old ages.

OBJECTIVES: Studies have demonstrated that high-speed jaw-opening exercises are effective in improving swallowing function. However, there has been no objective tool available for monitoring jaw-opening pace. This study aimed to develop an objective tool for monitoring and validating jaw-opening pace and compare it between young and old ages from different age groups. MATERIALS AND METHODS: A load cell plug-in jaw pad connected to an automatic recording and analysis system was used to record jaw-opening motions for offline analysis. We recruited 58 healthy volunteers from different age groups (20-39 y/o; 40-59y/o; 60-79y/o). During a 2-min recording session, each participant was instructed to fully open and close their jaw as quickly as possible while wearing a sensor. Bland-Altman plot, paired t-test and Pearson's correlation test were used to compare the number of jaw-opening motions between manual counting and automatic software analysis. The number of jaw-opening motions during the 2-min recording was compared between the three age groups. RESULTS: Automated analysis of jaw-opening pace was efficient and equally comparable with the traditional manual counting method across the three age groups. A declining trend in jaw-opening pace among the old age group was found but with no statistically significant difference. CONCLUSIONS: A jaw-opening motion monitoring tool with reliable automatic pace analysis software was validated in young and old ages. The jaw-opening pace demonstrated a tendency to decline with age. CLINICAL RELEVANCE: This monitoring tool can also be used to provide visual feedback during jaw-opening motion training in pace control.

A potential novel cancer immunotherapy: Agonistic anti-CD40 antibodies.

CD40, a novel immunomodulatory cancer therapy target, is expressed by B cells, macrophages, and dendritic cells (DCs) and mediates cytotoxic T cell priming through the CD40 ligand. Some tumors show promising responses to monotherapy or combination therapy with agonistic anti-CD40 antibodies. The development of improved anti-CD40 antibodies makes CD40 activation an innovative strategy in cancer immunotherapy. In this review, we trace the history of CD40 research and summarize preclinical and clinical findings. We emphasize the ongoing development of improved anti-CD40 antibodies and explore strategies for effective combination therapies. Guided by predictive biomarkers, future research should identify patient populations benefiting the most from CD40 activation.

Impulsivity and aggression in alcohol withdrawal syndrome is modulated by the interaction of ZNF804A and mTOR polymorphism.

Alcohol withdrawal syndrome (AWS) is a poorly studied phenotype of alcohol use disorder. Understanding the relationship between allelic interactions and AWS-related impulsivity and aggression could have significant implications. This study aimed to investigate the main and interacting effects of ZNF804A and mTOR on impulsivity and aggression during alcohol withdrawal. 446 Chinese Han adult males with alcohol dependence were included in the study. Impulsivity and aggression were assessed, and genomic DNA was genotyped. Single gene analysis showed that ZNF804A rs1344706 (A allele/CC homozygote) and mTOR rs1057079 (C allele/TT homozygote) were strongly associated with AWS-related impulsivity and aggression. In the allelic group, MANOVA revealed a significant gene x gene interaction, suggesting that risk varied systematically depending on both ZNF804A and mTOR alleles. Additionally, a significant interactive effect of ZNF804A rs1344706 and mTOR rs7525957 was found on motor impulsivity and physical aggression, and the ZNF804A rs1344706 gene variant had significant effects on motor impulsivity and physical aggression only in mTOR rs7525957 TT homozygous carriers. The study showed that specific allelic combinations of ZNF804A and mTOR may have protective or risk-enhancing effects on AWS-related impulsivity and aggression.

Enhanced serum levels of tumor necrosis factor-α, interleukin-1ß, and -6 in sarcopenia: alleviation through exercise and nutrition intervention.

BACKGROUND: Limited research has been conducted on the post-intervention inflammatory status in sarcopenic patients, despite previous studies revealing elevated pro-inflammatory markers. This study aimed to investigate the potential elevation of specific pro-inflammatory cytokines in sarcopenic patients and evaluate the effects of exercise and nutritional support interventions on these cytokine levels. METHODS: In this post-hoc analysis of a randomized controlled trial (RCT), 57 individuals with sarcopenia from the RCT and 57 non-sarcopenic participants from the same geriatric community cohort that did not participate in the RCT were enrolled. Grip strength and body composition measurements were recorded. Tumor necrotizing factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-15 levels were assessed at baseline for both groups and after a 12-week intervention consisting of resistive exercise and supplementation with branched-chain amino acids, calcium, and vitamin D3 in the patients with sarcopenia. RESULTS: The sarcopenic group demonstrated significantly lower body weight, body mass index, grip strength, and skeletal muscle mass index. Moreover, sarcopenic patients exhibited higher levels of TNF-α (p=0.007), IL-1ß (p<0.001), and IL-6 (p<0.001), while no significant difference was observed in IL-15 (p=0.345) between participants with and those without sarcopenia. Following the intervention, the sarcopenic group experienced significant improvements in grip strength and skeletal muscle mass index with a notable reduction in TNF-α (p=0.003), IL-1ß (p=0.012) and IL-6 (p=0.001) levels. CONCLUSIONS: Sarcopenic patients exhibit elevated levels of TNF-α, IL-1ß, and IL-6, which declined after nutrition support and exercise interventions. However, further research is necessary to evaluate the long-term impact of these interventions on cytokine levels.

Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy.

The immune checkpoint inhibitor (ICI), anti-programmed death-1 (anti-PD-1), has shown moderate efficacy in some patients with head and neck squamous cell carcinoma (HNSCC). Because of this, it is imperative to establish a mouse tumor model to explore mechanisms of antitumor immunity and to develop novel therapeutic options. Here, we examined the 4-nitroquinoline-1-oxide (4NQO)-induced oral squamous cell carcinoma (OSCC) model for genetic aberrations, transcriptomic profiles, and immune cell composition at different pathologic stages. Genomic exome analysis in OSCC-bearing mice showed conservation of critical mutations found in human HNSCC. Transcriptomic data revealed that a key signature comprised of immune-related genes was increased beginning at the moderate dysplasia stages. We first identified that macrophage composition in primary tumors differed across pathologic stages, leading to an oncogenic evolution through a change in the M1/M2 macrophage ratio during tumorigenesis. We treated the 4NQO-induced OSCC-bearing mice with anti-PD-1 and agonistic anti-CD40, which modulated multiple immune responses. The growth of tumor cells was significantly decreased by agonistic anti-CD40 by promoting an increase in the M1/M2 ratio. By examining cross-species genomic conservation in human and mouse tumors, our study demonstrates the molecular mechanisms underlying the development of OSCC and the regulation of contributing immune-related factors, and aims to facilitate the development of suitable ICI-based treatments for patients with HNSCC.

Phosphate burden induces vascular calcification through a NLRP3-caspase-1-mediated pyroptotic pathway.

AIMS: The aim of this study is to clarify the role of NLRP3 inflammasome in phosphate burden-induced vascular smooth muscle cell (VSMC) calcification. MAIN METHODS: VSMC calcification was induced using a high concentration of inorganic phosphate. After pharmacological inhibition or genetic silencing of the NLRP3 inflammasome, pyroptosis, or potassium efflux, the cells were examined by RT-qPCR, immunofluorescence, and western blotting to identify the NLRP3-mediated pathway for VSMC calcification. KEY FINDINGS: Calcified VSMCs with α-smooth muscle actin (α-SMA) disarray presented features of pyroptosis, including caspase-1 maturation, cleaved gasdermin D (GSDMD), and a high supernatant level of lactate dehydrogenase A. Pharmacological inhibitions of caspase-1 and pyroptosis attenuated VSMC calcification, whereas interleukin-1ß receptor antagonism did not. Unlike canonical NLRP3 activation, osteogenic VSMCs did not upregulate NLRP3 expression. However, NLRP3 genetic silencing or inhibitions, which targets different domains of the NLRP3 protein, could ameliorate VSMC calcification by aborting caspase-1 and GSDMD activation. Furthermore, potassium efflux through the inward-rectifier potassium channel, and not through the P2X7 receptor, triggered NLRP3 inflammasome activation and VSMC calcification. SIGNIFICANCE: In the present study, we identified a potassium efflux-triggered NLRP3-caspase-1-mediated pyroptotic pathway for VSMC calcification that is unique and different from the canonical NLRP3 inflammasome activation. Therefore, targeting this pathway may serve as a novel therapeutic strategy for vascular calcification.

Photothermal nanozymes to self-augment combination cancer therapy by dual-glutathione depletion and hyperthermia/acidity-activated hydroxyl radical generation.

Chemodynamic therapy (CDT) has emerged as a promising strategy for tumor treatment. Nevertheless, the low Fenton catalytic efficiency and the high concentration of glutathione (GSH) in cancer cells largely decline antitumor efficacy of CDT. To self-augment antitumor effect of the CDT by combining with photothermal therapy (PTT), the unique photothermal nanozymes that doubly depleted GSH, and generated massive hydroxyl radicals (·OH) in the hyperthermia/acidity-activated manner were developed. Through the coordination of Fe3+ ions with PEGylated chitosan (PEG-CS)-modified polydopamine (PDA) nanoparticles, the attained Fe3+@PEG-CS/PDA nanozymes showed outstanding colloidal stability, photothermal conversion efficiency and acidity-triggered Fe3+ release. By GSH-mediated valence states transition of Fe3+ ions and Michael reaction between GSH and quinone-rich PDA, the nanozymes sufficiently executed dual depletion of GSH with the elevated temperature.Under mimic tumor acidity and near-infrared (NIR) irradiation condition, the endocytosed nanozymes effectively converted intracellular H2O2 into toxic ·OH upon amplified Fenton reaction, thereby potently killing 4T1 cancer cells and RAW 264.7 cells. Importantly, the nanozymes prominently suppressed 4T1 tumor growth in vivo and metastasis of cancer cells by CDT/PTT combination therapy without significant systemic toxicity. Our study provides novel visions in design of therapeutic nanozymes with great clinical translational prospect for tumor treatment.

A feature extraction free approach for protein interactome inference from co-elution data.

Protein complexes are key functional units in cellular processes. High-throughput techniques, such as co-fractionation coupled with mass spectrometry (CF-MS), have advanced protein complex studies by enabling global interactome inference. However, dealing with complex fractionation characteristics to define true interactions is not a simple task, since CF-MS is prone to false positives due to the co-elution of non-interacting proteins by chance. Several computational methods have been designed to analyze CF-MS data and construct probabilistic protein-protein interaction (PPI) networks. Current methods usually first infer PPIs based on handcrafted CF-MS features, and then use clustering algorithms to form potential protein complexes. While powerful, these methods suffer from the potential bias of handcrafted features and severely imbalanced data distribution. However, the handcrafted features based on domain knowledge might introduce bias, and current methods also tend to overfit due to the severely imbalanced PPI data. To address these issues, we present a balanced end-to-end learning architecture, Software for Prediction of Interactome with Feature-extraction Free Elution Data (SPIFFED), to integrate feature representation from raw CF-MS data and interactome prediction by convolutional neural network. SPIFFED outperforms the state-of-the-art methods in predicting PPIs under the conventional imbalanced training. When trained with balanced data, SPIFFED had greatly improved sensitivity for true PPIs. Moreover, the ensemble SPIFFED model provides different voting schemes to integrate predicted PPIs from multiple CF-MS data. Using the clustering software (i.e. ClusterONE), SPIFFED allows users to infer high-confidence protein complexes depending on the CF-MS experimental designs. The source code of SPIFFED is freely available at: https://github.com/bio-it-station/SPIFFED.

One-Year Medical Utilization and Mortality in Home Health and Nursing Home Care Recipients from Northern Taiwan.

OBJECTIVES: Home health care (HHC) and nursing home care (NHC) are mainstays of long-term service in the aged population. Therefore, we aimed to investigate the factors associated with 1-year medical utilization and mortality in HHC and NHC recipients in Northern Taiwan. DESIGN: This study employed a prospective cohort design. SETTING AND PARTICIPANTS: We enrolled 815 HHC and NHC participants who started receiving medical care services from the National Taiwan University Hospital, Beihu Branch between January 2015 and December 2017. METHODS: Multivariate Poisson regression modeling was used to quantify the relationship between care model (HHC vs NHC) and medical utilization. Cox proportional-hazards modeling was used to estimate hazard ratios and factors associated with mortality. RESULTS: Compared with NHC recipients, HHC recipients had higher 1-year utilization of emergency department services [incidence rate ratio (IRR) 2.04, 95% CI 1.16-3.59] and hospital admissions (IRR 1.49, 95% CI 1.14-1.93), as well as longer total hospital length of stay (LOS) (IRR 1.61, 95% CI 1.52-1.71) and LOS per hospital admission (IRR 1.31, 95% CI 1.22-1.41). Living at home or in a nursing home did not affect the 1-year mortality. CONCLUSIONS AND IMPLICATIONS: Compared with NHC recipients, HHC recipients had a higher number of emergency department services and hospital admissions, as well as longer hospital LOS. Policies should be developed to reduce emergency department and hospitalization utilization in HHC recipients.

Delay from Screening to Diagnosis in Autism Spectrum Disorder: Results from a Large National Health Research Network.

To examine delay from developmental screening to autism diagnosis, we used real-world health care data from a national research network to estimate the time between these events. We found an average delay of longer than 2 years from first screening to diagnosis, with no significant differences observed by sex, race, or ethnicity.

Frontier Review of the Molecular Mechanisms and Current Approaches of Stem Cell-Derived Exosomes.

Exosomes are effective therapeutic vehicles that may transport their substances across cells. They are shown to possess the capacity to affect cell proliferation, migration, anti-apoptosis, anti-scarring, and angiogenesis, via the action of transporting molecular components. Possessing immense potential in regenerative medicine, exosomes, especially stem cell-derived exosomes, have the advantages of low immunogenicity, minimal invasiveness, and broad clinical applicability. Exosome biodistribution and pharmacokinetics may be altered, in response to recent advancements in technology, for the purpose of treating particular illnesses. Yet, prior to clinical application, it is crucial to ascertain the ideal dose and any potential negative consequences of an exosome. This review focuses on the therapeutic potential of stem cell-derived exosomes and further illustrates the molecular mechanisms that underpin their potential in musculoskeletal regeneration, wound healing, female infertility, cardiac recovery, immunomodulation, neurological disease, and metabolic regulation. In addition, we provide a summary of the currently effective techniques for isolating exosomes, and describe the innovations in biomaterials that improve the efficacy of exosome-based treatments. Overall, this paper provides an updated overview of the biological factors found in stem cell-derived exosomes, as well as potential targets for future cell-free therapeutic applications.

The neural correlates of emotional conflict monitoring as an early manifestation of affective and cognitive declines in persons with Type 2 diabetes.

Patients with Type 2 diabetes are known to be more susceptible to experience dementia and depression/anxiety. The neural circuits of emotional conflict monitoring, as indicated by a Stroop task, might become altered in terms of cognitive and affective impairments in diabetes. This study investigated alterations in the emotional conflict monitoring and associations of corresponding brain activities with metabolic parameters in persons with Type 2 diabetes. Participants with normal cognitive and affective functioning, including 40 persons with Type 2 diabetes and 30 non-diabetes control subjects, underwent a functional MRI paradigm with the face-word emotional Stroop task and detailed cognitive and affective assessments, including the Montreal Cognitive Assessment and Beck Anxiety Inventory. Compared with the controls, people with diabetes exhibited stronger emotional interference, as indicated by differential reaction times between congruent and incongruent trials (Δcon). Δcon was correlated with Montreal Cognitive Assessment test scores and fasting glucose levels. People with diabetes demonstrated altered brain activation and functional connectivity in the neural network for emotional conflict monitoring. The neural network for emotional conflict monitoring mediated the association of pancreatic function with anxiety scores as well as the relationship between Δcon and Montreal Cognitive Assessment scores. Results suggested that alterations in the neural network underlying emotional conflict monitoring might present before clinically measurable cognitive and affective decrements were apparent, thereby bridging the gap between dementia and anxiety/depression in persons with diabetes.

A network analysis of difficulties in emotion regulation, anxiety, and depression for adolescents in clinical settings.

BACKGROUND: Difficulties in emotion regulation (DER) are widely considered to underlie anxiety and depression. Given the prevalence of anxiety and depression in adolescents and the fact that adolescence is a key period for the development of emotion regulation ability, it is important to examine how DER is related to anxiety and depression in adolescents in clinical settings. METHODS: In the present study, we assessed 209 adolescents in clinical settings using the Difficulties in Emotion Regulation Scale (DERS) and the Hospital Anxiety and Depression Scale (HADS) and examined the associations between six components of DER and 14 symptoms of anxiety and depression. We used network analysis, constructed circular and multidimensional scaling (MDS) networks, and calculated network centrality, bridge centrality, and stability of centrality indices. RESULTS: The results showed that: (1) The global centrality index shows that the Strategy component (i.e., lack of access to strategies) is the center in the whole network, ranking highest in strength, closeness, betweenness, and expected influence. (2) The MDS network showed a closeness of anxiety and depression symptoms, while Awareness component (i.e., lack of emotional awareness) stayed away from other DER components, but Awareness is close to some depression symptoms. (3) The bridge nodes of three groups, Strategy from DERS, Worry and Relax from anxiety symptoms, and Cheerful and Slow from depression symptoms, had the strongest relationships with the other groups. CONCLUSION: Lack of access to strategies remains in the center not only in DER but also in the DER-anxiety-depression network, while lack of awareness is close to depression but not to anxiety. Worrying thoughts and inability to relax are the bridging symptoms for anxiety, while lack of cheerful emotions and slowing down are the bridging symptoms for depression. These findings suggest that making emotion regulation strategies more accessible to patients and reducing these bridging symptoms may yield the greatest rewards for anxiety and depression therapy.

Inguinal Fat Compensates Whole Body Metabolic Functionality in Partially Lipodystrophic Mice with Reduced PPARγ Expression.

Peroxisome proliferator-activated receptor γ (PPARγ) gene mutations in humans and mice lead to whole-body insulin resistance and partial lipodystrophy. It is unclear whether preserved fat depots in partial lipodystrophy are beneficial for whole-body metabolic homeostasis. We analyzed the insulin response and expression of metabolic genes in the preserved fat depots of PpargC/- mice, a familial partial lipodystrophy type 3 (FPLD3) mouse model resulting from a 75% decrease in Pparg transcripts. Perigonadal fat of PpargC/- mice in the basal state showed dramatic decreases in adipose tissue mass and insulin sensitivity, whereas inguinal fat showed compensatory increases. Preservation of inguinal fat metabolic ability and flexibility was reflected by the normal expression of metabolic genes in the basal or fasting/refeeding states. The high nutrient load further increased insulin sensitivity in inguinal fat, but the expression of metabolic genes became dysregulated. Inguinal fat removal resulted in further impairment of whole-body insulin sensitivity in PpargC/- mice. Conversely, the compensatory increase in insulin sensitivity of the inguinal fat in PpargC/- mice diminished as activation of PPARγ by its agonists restored insulin sensitivity and metabolic ability of perigonadal fat. Together, we demonstrated that inguinal fat of PpargC/- mice plays a compensatory role in combating perigonadal fat abnormalities.

Effect of polysaccharide derived from dehulled adlay on regulating gut microbiota and inhibiting Clostridioides difficile in an in vitro colonic fermentation model.

Human body can digest only a few sugars with a low degree of polymerization. The rest of the carbohydrates become food for gastrointestinal symbiotic bacteria, affecting gut microbiota composition and human health. Adlay is a medicinal and food homologous crop. The study aims to determine whether dehulled adlay-derived polysaccharide regulates gut microbiota and barrier function to against Clostridioides difficile infection. Major molecular weight of adlay polysaccharide is 27 kDa. The growth of next-generation probiotics were promoted by adlay polysaccharides. In colonic fermentation model, the ratio of C. difficile was decreased when adding the condition medium of adlay polysaccharides-treated fecal microbiota. In addition, adlay polysaccharide promoted the expression of tight junction proteins and mucin in intestinal cells. This study shows that adlay polysaccharide can be used as prebiotics to regulate microbiota and maintain barrier function, which has the potential to be developed as novel functional food ingredients to protect intestinal health.