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Jing Ye,1,2 Yunhui Lv,2 Hui Xie,3 Kun Lian,4 Xiufeng Xu1 1Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Sleep Medicine Center, The First People’s Hospital of Yunnan, Kunming, Yunnan, People’s Republic of China; 3Department of Traumatology, The First People’s Hospital of Yunnan, Kunming, Yunnan, People’s Republic of China; 4Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Xiufeng Xu, Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, No. 295 of Xichang Road, Kunming City, Yunnan Province, People’s Republic of China, Email xfxu2004@sina.comBackground: Obstructive sleep apnea (OSA) patients commonly experience high rates of depression. This study aims to examine the oral microbiota characteristics of OSA and those with comorbid major depressive disorder (OSA+MDD) patients.Methods: Participants were enrolled from Aug 2022 to Apr 2023. Polysomnography, psychiatrist interviews, and scales were used to diagnose OSA and MDD. Oral samples were collected from participants by rubbing swabs on buccal mucosa, palate, and gums. Oral microbiota was analyzed via whole-genome metagenomics and bioinformatic analysis followed sequencing. Venous blood was drawn to detect plasma inflammatory factor levels.Results: The study enrolled 33 OSA patients, 28 OSA+MDD patients, and 28 healthy controls. Significant differences were found in 8 phyla, 229 genera, and 700 species of oral microbiota among the three groups. Prevotellaceae abundance in the OSA and OSA+MDD groups was significantly lower than that in healthy controls. Linear discriminant analysis effect size (LEfSe) analysis showed that Streptococcaceae and Actinobacteria were the characteristic oral microbiota of the OSA and OSA+MDD groups, respectively. KEGG analysis indicates 30 pathways were changed in the OSA and OSA+MDD groups compared with healthy controls, and 23 pathways were changed in the OSA group compared with the OSA+MDD group. Levels of IL-6 in the OSA+MDD group were significantly higher than in the healthy group, correlating positively with the abundance of Schaalia, Campylobacter, Fusobacterium, Alloprevotella, and Candidatus Nanosynbacter in the oral, as well as with Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores.Conclusion: Significant differences in oral microbiota populations and gene function were observed among the three groups. OSA patients were characterized by a decreased abundance of Prevotellaceae and an increased abundance of Streptococcaceae. OSA+MDD patients had an increased abundance of Actinobacteria. IL-6 might regulate the relationship between depression and the oral microbiota in OSA+MDD patients.Keywords: obstructive sleep apnea, major depressive disorder, oral microbiota, whole-genome metagenomic analysis, inflammatory factors

Osteosarcoma is the commonest malignant bone tumor of children and adolescents and is characterized by a high risk of recurrence despite multimodal therapy, especially in metastatic disease. This suggests the presence of clinically undetected cancer cells that persist, leading to cancer recurrence. We sought to evaluate the utility of peripheral blood exosomes as a more sensitive yet minimally invasive blood test that could aid in evaluating treatment response and surveillance for potential disease recurrence. We extracted exosomes from the blood of pediatric osteosarcoma patients at diagnosis (n=7) and after neoadjuvant chemotherapy (n=5 subset), as well as from age-matched cancer-free controls (n=3). We also obtained matched tumor biopsy samples (n=7) from the cases. Exosome isolation was verified by CD9 immunoblot and characterized on electron microscopy. Profiles of 780 cancer-related transcripts were analysed in mRNA from exosomes of osteosarcoma patients at diagnosis and control patients, matched post-chemotherapy samples, and matched primary tumor samples. Peripheral blood exosomes of osteosarcoma patients at diagnosis were significantly smaller than those of controls and overexpressed extracellular matrix protein gene THBS1 and B cell markers MS4A1 and TCL1A. Immunohistochemical staining of corresponding tumor samples verified the expression of THBS1 on tumor cells and osteoid matrix, and its persistence in a treatment-refractory patient, as well as the B cell origin of the latter. These hold potential as liquid biopsy biomarkers of disease burden and host immune response in osteosarcoma. Our findings suggest that exosomes may provide novel and clinically-important insights into the pathophysiology of cancers such as osteosarcoma.

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ΔL∼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of ∼50 events of strong EMIC wave-driven precipitation. Most reside at L∼5-7 at dusk, while a smaller subset exists at L∼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of ∼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to ∼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At ∼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with 1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

Abstract Background Diabetes is known to increase morbidity and 30-day mortality in adults undergoing non-cardiac surgery, but longer term outcomes are less studied. This study was done to explore how undiagnosed and known diabetes affect 30-day and one-year morbidity and mortality outcomes. The secondary aim was to study the prevalence of undiagnosed diabetics in our perioperative Asian surgical population. Methods A retrospective cohort study of 2106 patients aged > 45 years undergoing non-cardiac surgery in a single tertiary hospital was performed. Undiagnosed diabetics were identified (HbA1c ≥6.5% or fasting blood glucose ≥126 mg/dL) and relevant demographic, clinical and surgical data were analyzed to elicit the relationship to adverse outcomes. Univariate analysis was first performed to identify significant variables with p-values ≤0.1, which were then analyzed using multiple logistic regression to calculate the adjusted odds ratio. Results The prevalence of undiagnosed diabetes was 7.4%. The mean and median HbA1c of known diabetics were 7.9 and 7.5%, while the mean and median HbA1c for undiagnosed diabetics were 7.2 and 6.8% respectively. 36.4% of known diabetics and 20.5% of undiagnosed diabetics respectively had a random blood glucose > 200 mg/dL. Undiagnosed diabetics had a three-fold increase in 1-year mortality compared to non-diabetics (adjusted OR 3.46(1.80–6.49) p

Zhong Q Wang,1,2 Yongmei Yu,1,2 Xian H Zhang,1,2 Z Elizabeth Floyd,3 Anik Boudreau,2 Kun Lian,4 William T Cefalu1,21Nutrition and Diabetes Research Laboratory, 2Botanical Research Center, 3Ubiquitin Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA; 4The Center for Energy and Environmental Studies, Southern University, Baton Rouge, LA, USAAim: To compare the effects of dietary fibers on hepatic cellular signaling in mice.Methods: Mice were randomly divided into four groups (n = 9/group): high-fat diet (HFD) control, cellulose, psyllium, and sugarcane fiber (SCF) groups. All mice were fed a HFD with or without 10% dietary fiber (w/w) for 12 weeks. Body weight, food intake, fasting glucose, and fasting insulin levels were measured. At the end of the study, hepatic fibroblast growth factor (FGF) 21, AMP-activated protein kinase (AMPK) and insulin signaling protein content were determined.Results: Hepatic FGF21 content was significantly lowered, but βKlotho, fibroblast growth factor receptor 1, fibroblast growth factor receptor 3, and peroxisome proliferator-activated receptor alpha proteins were significantly increased in the SCF group compared with those in the HFD group (P < 0.01). SCF supplementation also significantly enhanced insulin and AMPK signaling, as well as decreased hepatic triglyceride and cholesterol in comparison with the HFD mice. The study has shown that dietary fiber, especially SCF, significantly attenuates lipid accumulation in the liver by enhancing hepatic FGF21, insulin, and AMPK signaling in mice fed a HFD.Conclusion: This study suggests that the modulation of gastrointestinal factors by dietary fibers may play a key role in both enhancing hepatic multiple cellular signaling and reducing lipid accumulation.Keywords: dietary fiber, FGF21, insulin signaling, AMPK, GLP-1, PI 3K