Peripheral nerve-derived Sema3A promotes osteogenic differentiation of mesenchymal stem cells through the Wnt/ß-catenin/Nrp1 positive feedback loop.

Sensory nerves play a crucial role in maintaining bone homeostasis by releasing Semaphorin 3A (Sema3A). However, the specific mechanism of Sema3A in regulation of bone marrow mesenchymal stem cells (BMMSCs) during bone remodelling remains unclear. The tibial denervation model was used and the denervated tibia exhibited significantly lower mass as compared to sham operated bones. In vitro, BMMSCs cocultured with dorsal root ganglion cells (DRGs) or stimulated by Sema3A could promote osteogenic differentiation through the Wnt/ß-catenin/Nrp1 positive feedback loop, and the enhancement of osteogenic activity could be inhibited by SM345431 (Sema3A-specific inhibitor). In addition, Sema3A-stimulated BMMSCs or intravenous injection of Sema3A could promote new bone formation in vivo. To sum up, the coregulation of bone remodelling is due to the ageing of BMMSCs and increased osteoclast activity. Furthermore, the sensory neurotransmitter Sema3A promotes osteogenic differentiation of BMMSCs via Wnt/ß-catenin/Nrp1 positive feedback loop, thus promoting osteogenesis in vivo and in vitro.

Generative Adversarial Network Model to Classify Human Induced Pluripotent Stem Cell-Cardiomyocytes based on Maturation Level.

Objective: Our study develops a generative adversarial network (GAN)-based method that generates faithful synthetic image data of human cardiomyocytes at varying stages in their maturation process, as a tool to significantly enhance the classification accuracy of cells and ultimately assist the throughput of computational analysis of cellular structure and functions. Methods: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) were cultured on micropatterned collagen coated hydrogels of physiological stiffnesses to facilitate maturation and optical measurements were performed for their structural and functional analyses. Control groups were cultured on collagen coated glass well plates. These image recordings were used as the real data to train the GAN model. Results: The results show the GAN approach is able to replicate true features from the real data, and inclusion of such synthetic data significantly improves the classification accuracy compared to usage of only real experimental data that is often limited in scale and diversity. Conclusion: The proposed model outperformed four conventional machine learning algorithms with respect to improved data generalization ability and data classification accuracy by incorporating synthetic data. Significance: This work demonstrates the importance of integrating synthetic data in situations where there are limited sample sizes and thus, effectively addresses the challenges imposed by data availability.

"Loop-Neurorrhaphy Technique for Preventing Bone Resorption and Preserving Lower Lip Sensation in Mandibular Reconstruction using Vascularized Iliac Bone Flap: A Single-Center Randomized Clinical Trial".

BACKGROUND: The aim of this study was to investigate whether using an innervated vascularized iliac bone flap could effectively prevent bone resorption and maintain sensory function in the lower lip. METHODS: In the innervated group, the deep circumflex iliac artery and recipient vessels were anastomosed, with simultaneous microanastomosis of ilioinguinal nerve, mental nerve and inferior alveolar nerve. Conversely, the control group underwent solely vascular anastomosis. CT was utilized to assess bone quality. Sensory recovery of the lower lip was recorded using two-point discrimination and current perception threshold testing. RESULTS: The study comprised a total of 40 subjects, with each group accounting for 20 participants, equally distributed in terms of gender. Hounsfield unit loss was significantly lower in the innervated group (13.26±8.65 %) as compared to the control group (37.98±8.60 %) (P < 0.001). Moreover, two-point discrimination values were lower in the innervated group (15.11±8.39 mm) when compared to the control group (21.44±7.24 mm) (P = 0.02). The current perception threshold values for the innervated group were 176.19 ± 31.89, 64.21 ± 19.23, and 42.29 ± 18.96 in 2kHz, 250Hz, and 5Hz respectively, while in the control group, the current perception threshold values were 204.47 ± 36.99, 82.26 ± 27.29, and 58.89 ± 25.38 in 2kHz, 250Hz, and 5Hz (P =0.02, 0.02, and 0.03, respectively). CONCLUSIONS: The innervated vascularized iliac bone flap represents a safe and effective novel approach to preserving lower lip sensation and preventing bone resorption through functional mandibular reconstruction.

Characterization of key aroma-active compounds in different types of Douchi based on molecular sensory science approaches.

To attain the differences in the flavor profile of Douchi, the key aroma-active compounds of three types of Douchi were investigated. The "Sauce-like", "Smoky", "Nutty", "Roast", "Caramel", and "Flower" of Douchi were favored by customers. Further, a total of 179 volatile compounds were identified using HS-SPME-GC-MS, and 29 aroma compounds were detected using GC-O-MS. Based on the quantification, 9, 13, and 10 compounds were regarded as aroma-active compounds in Yangjiang Douchi (YJ), Pingjiang Douchi (PJ), and Liuyang Douchi (LY), respectively. Moreover, the mixture of these aroma-active compounds successfully simulated the main aromas of PJ, LY, and YJ. And omission experiments confirmed that guaiacol was the key aroma compound for LY, benzene acetaldehyde, dimethyl trisulfide, and 2-acetyl pyrrole were important for YJ, benzene acetaldehyde and 3,5-diethyl-2-methyl pyrazine notably contributed to key aroma of PJ.

Distinctive mesenchymal-like neurofibroma stem cells shape NF1 clinical phenotypes controlled by BDNF microenvironment.

BACKGROUND: Neurofibroma type I (NF1) often presents with multiple clinical phenotypes due to mutations of NF1 gene. The aim of this study was to determine the phenotypic and therapeutic relevance of tumor microenvironment in NF1 patients. METHODS: Tumor stem cells (TSCs) from NF1 were isolated and cultured using fluorescence activated cell sorting (FACS) and colony formation experiments. Then, flow cytometry was used to detect the surface markers, osteogenic and adipogenic differentiation were performed as well. Its tumorigenesis ability was confirmed by subcutaneous tumorigenesis in nude mice. Immunohistochemical staining was performed on neurofibroma tissues from the head and trunk with different phenotypes. The expression of BDNF in neurofibroma tissues was detected by Elisa and immunohistochemical staining. Western Blotting was used to detect the expression of p38 MAPK pathway in TSCs. The effect of BDNF neutralizing antibody on the tumorigenesis of TSCs was observed. RESULTS: Herein, we advocate that NF1 contain a new subgroup of mesenchymal-like neurofibroma stem cells (MNSCs). Such colony-forming MNSCs preserved self-renewal, multiple differentiation and tumorigenic capabilities. More interestingly, the MNSCs isolated from neurofibroma tissues of the same patient with different phenotypes presented site-specific capabilities. Moreover, different levels of brain-derived neurotrophic factor (BDNF) in neurofibroma tissues can impact the MNSCs by activating the TrkB/p38 MAPK pathway. Systemic administration of BDNF neutralizing antibodies inhibited MNSCs' characteristics. CONCLUSIONS: We demonstrated that BDNF can modulate MNSCs and thereby controlling different tumor phenotypes between the head and trunk regions. Application of BDNF neutralizing antibodies may inhibit p38 MAPK pathway, therefore providing a promising strategy for managing NF1.

Segmental disturbance of white matter microstructure in predicting mild cognitive impairment in idiopathic Parkinson's disease: An individualized study based on automated fiber quantification tractography.

PURPOSE: The neurobiological mechanisms and an early identification of MCI in idiopathic Parkinson's disease (IPD) remain unclear. To investigate the abnormalities of types of white matter (WM) fiber tracts segmentally and establish reliable indicator in IPD-MCI. METHODS: Forty IPD with normal cognition (IPD-NCI), thirty IPD-MCI, and thirty healthy controls were included. Automated fiber quantification was applied to extract the fractional anisotropy (FA) and mean diffusivity (MD) values at 100 locations along the major fibers. Partial correlation was performed between diffusion values and cognitive performance. Furthermore, machine learning analyses were conducted to determine the imaging biomarker of MCI. Permutation tests were performed to evaluate the pointwise differences under the FWE correction. RESULTS: IPD-MCI had similar but more severe and widespread WM degeneration in the association, projection, and commissural fibers compared with IPD-NCI. Meanwhile, IPD-MCI showed distinct degeneration pattern in the association fibers. The FA of the anterior segment of right inferior fronto-occipital fasciculus (IFOF) was positively correlated with MoCA (P < 0.05) and executive function (P < 0.05). The MD of the middle and posterior segment of left superior longitudinal fasciculus (SLF) was negatively correlated with MoCA P < 0.05), executive (P < 0.05), visuospatial function (P < 0.05). Furthermore, the AUC of support vector machine model was 0.80 in the validation dataset. The FA of anterior segment of right IFOF contribute the most. CONCLUSION: This study demonstrated that regional tract-specific microstructural degeneration, especially the association fibers, can be used to predict MCI in IPD. Especially, the right IFOF may be a significant imaging biomarker in predicting IPD with MCI.

Laser Welding Multimodel Quality Forecast Method Based on Dynamic Geometric Features of the Molten Pool.

Laser welding quality forecast is highly significant during the laser manufacturing process. However, extracting the dynamic characteristics of the molten pool in the short laser welding process makes predicting of the welding quality in real time difficult. Accordingly, this study proposes a multimodel quality forecast (MMQF) method based on dynamic geometric features of molten pool to forecast the welding quality in real time. For extraction of geometric features of molten pool, an improved fully convolutional neural network is proposed to segment the collected dynamic molten pool images during the entire welding process. In addition, several dynamic geometric features of the molten pool are extracted by using the minimum enclosed rectangle algorithm with an evaluation of the performance by several statistical indexes. With regard to forecasting the welding quality, a nonlinear quadratic kernel logistic regression model is proposed by mapping the linear inseparable features to the high dimensional space. Experimental results show that the MMQF method can make an effective and stable forecast of welding quality. It performs well under small data and can satisfy the requirement of real-time forecast.

Identification of Functional Modules and Key Pathways Associated with Innervation in Graft Bone-CGRP Regulates the Differentiation of Bone Marrow Mesenchymal Stem Cells via p38 MAPK and Wnt6/ß-Catenin.

Bone resorption occurs after bone grafting, however, contemporaneous reconstruction of the innervation of the bone graft is a potential treatment to maintain the bone mass of the graft. The innervation of bone is an emerging research topic. To understand the potential molecular mechanisms of bone innervation after bone grafting, we collected normal iliac bone tissue as well as bone grafts with or without innervation from nine patients 1 year after surgery and performed RNA sequencing. We identified differentially expressed genes) from these samples and used the gene ontology and Kyoto Encyclopedia of Genes and Genomes databases for functional enrichment and signaling pathway analysis. In parallel, we established protein-protein interaction networks to screen functional modules. Based on bioinformatic results, we validated in vitro the osteogenic differentiation potential of rat bone marrow mesenchymal stem cells (BMMSCs) after calcitonin gene-related peptide (CGRP) stimulation and the expression of p38 MAPK and Wnt6/ß-catenin pathways during osteogenesis. Our transcriptome analysis of bone grafts reveals functional modules and signaling pathways of innervation which play a vital role in the structural and functional integration of the bone graft. Simultaneously, we demonstrate that CGRP regulates the differentiation of BMMSCs through p38 MAPK and Wnt6/ß-catenin.

The efficacy and safety of SARS-CoV-2 vaccines mRNA1273 and BNT162b2 might be complicated by rampant C-to-U RNA editing.

The SARS-CoV-2 RNA vaccines are smartly designed to increase the synonymous codon usage by introducing multiple U-to-C mutations. This design would elevate the translation efficiency of vaccine RNAs. However, we found evidence to reason that the designed cytidines might be converted to uridines again by C-to-U RNA deamination in host cells. This C-to-U mechanism might be a main factor that affects the efficacy and safety of RNA vaccines.

[Evaluation of the effect of simultaneous neuralized iliac bone flap on the preservation of lower lip and chin sensation during mandibular reconstruction].

PURPOSE: To evaluate the effect of reconstructing inferior alveolar nerve and preserving the sensation of lower lip and chin in repairing mandibular defect by simultaneous neuralized iliac bone flap. METHODS: Patients with continuous mandibular defects requiring reconstruction were randomly assigned to the innervated(IN) group and the control(CO) group by random number table. In the IN group, the deep circumflex iliac artery and recipient vessels were anastomosed microscopically during mandible reconstruction, and the ilioinguinal nerve(IN), mental nerve(MN) and inferior alveolar nerve(IAN) were anastomosed at the same time. In the CO group, only vascular anastomosis was performed without nerve reconstruction. During the operation, the nerve electrical activity after nerve anastomosis was detected by nerve monitor, and the sensory recovery of lower lip was recorded by two-point discrimination(TPD), current perception threshold (CPT) and Touch test sensory evaluator(TTSE) test. SPSS 26.0 software package was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 20 patients were included, with 10 patients in each group. All the flaps survived in both groups, and no serious complications such as flap crisis occurred, and no obvious complications occurred in the donor site. The results of TPD test, CPT test and TTSE test all indicated that the degree of postoperative hypoesthesia in the IN group was less(P＜0.05). CONCLUSIONS: Simultaneous nerve anastomosis vascularized iliac bone flap can effectively preserve the feeling of lower lip and improve the postoperative quality of life of patients. It is a safe and effective technique.

Frontiers of Hydroxyapatite Composites in Bionic Bone Tissue Engineering.

Bone defects caused by various factors may cause morphological and functional disorders that can seriously affect patient's quality of life. Autologous bone grafting is morbid, involves numerous complications, and provides limited volume at donor site. Hence, tissue-engineered bone is a better alternative for repair of bone defects and for promoting a patient's functional recovery. Besides good biocompatibility, scaffolding materials represented by hydroxyapatite (HA) composites in tissue-engineered bone also have strong ability to guide bone regeneration. The development of manufacturing technology and advances in material science have made HA composite scaffolding more closely related to the composition and mechanical properties of natural bone. The surface morphology and pore diameter of the scaffold material are more important for cell proliferation, differentiation, and nutrient exchange. The degradation rate of the composite scaffold should match the rate of osteogenesis, and the loading of cells/cytokine is beneficial to promote the formation of new bone. In conclusion, there is no doubt that a breakthrough has been made in composition, mechanical properties, and degradation of HA composites. Biomimetic tissue-engineered bone based on vascularization and innervation show a promising future.

Plasmonic nanosensors for point-of-care biomarker detection.

Advancement of materials along with their fascinating properties play increasingly important role in facilitating the rapid progress in medicine. An excellent example is the recent development of biosensors based on nanomaterials that induce surface plasmon effect for screening biomarkers of various diseases ranging from cancer to Covid-19. The recent global pandemic re-confirmed the trend of real-time diagnosis in public health to be in point-of-care (POC) settings that can screen interested biomarkers at home, or literally anywhere else, at any time. Plasmonic biosensors, thanks to its versatile designs and extraordinary sensitivities, can be scaled into small and portable devices for POC diagnostic tools. In the meantime, efforts are being made to speed up, simplify and lower the cost of the signal readout process including converting the conventional heavy laboratory instruments into lightweight handheld devices. This article reviews the recent progress on the design of plasmonic nanomaterial-based biosensors for biomarker detection with a perspective of POC applications. After briefly introducing the plasmonic detection working mechanisms and devices, the selected highlights in the field focusing on the technology's design including nanomaterials development, structure assembly, and target applications are presented and analyzed. In parallel, discussions on the sensor's current or potential applicability in POC diagnosis are provided. Finally, challenges and opportunities in plasmonic biosensor for biomarker detection, such as the current Covid-19 pandemic and its testing using plasmonic biosensor and incorporation of machine learning algorithms are discussed.

Metabolomics-based study of the potential interventional effects of Xiao-Xu-Ming Decoction on cerebral ischemia/reperfusion rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao-Xu-Ming Decoction (XXMD) is a classical Chinese medicinal compound for the treatment of ischemic stroke, which has good efficacy in clinical studies and also plays a neuroprotective role in pharmacological studies. AIM OF THE STUDY: The purpose of this study is to investigate the potential and integral interventional effects of XXMD on cerebral ischemia/reperfusion rat model. MATERIALS AND METHODS: In this study, 1H NMR metabolomics was used, combined with neurological functional assessments, cerebral infarct area measurements, and pathological staining including Nissl staining, immunofluorescence staining of NeuN and TUNEL, and immunohistochemical staining of MCT2, to analyze the metabolic effects of XXMD in the treatment of an ischemia/reperfusion rat model. RESULTS: It's observed that XXMD treatment could improve the neurological deficit scores and reduce the cerebral infarct areas on cerebral ischemia/reperfusion rat model. The pathological staining results performed that XXMD treatment could improve the decrease of Nissl bodies and the expression of NeuN and MCT2, reduce the high expression of TUNEL. In 1H NMR study, it revealed that the metabolic patterns among three experimental groups were different, the level of lactate, acetate, NAA, glutamate, and GABA were improved to varying degrees in different brain area. CONCLUSION: Our findings indicated that XXMD has positive effect on neuroprotection and improvement of metabolism targeting cerebral ischemic injury in rats, which showed great potential for ischemic stroke.

Bisphosphorylation of anhydrides - convenient access to bisphosphonates with a P-O-C-P motif.

A novel strategy of bisphosphorylation of anhydrides with P(O)-H reagents via a DMAP-catalyzed and DBU-promoted process has been developed. These one-step transformations proceed efficiently to provide convenient access to a variety of P-O-C-P motif containing organophosphorus compounds. In addition, the gram-scale synthesis and the efficient recovery of the by-product highlight the sustainability and applicability of this method.

Glucosamine suppresses oxidative stress and induces protective autophagy in osteoblasts by blocking the ROS/Akt/mTOR signaling pathway.

Oxidative stress is the crucial pathogenic factor in osteoporosis. Cell autophagy, a major form of self-digestion, plays critical functions in different forms of stress by devouring harmful cytosolic proteins or organelles for the renewal of organelles and to maintain cellular homeostasis. Glucosamine (GlcN) has been widely utilized in treatments for patients with osteoarthritis-related joint pain. It has potential antioxidant effects and its pharmacological effect in osteoblasts remains unclear. The present study aimed to investigate whether autophagy participates in the protective effects of GlcN in osteoblasts under oxidative stress and the possible mechanism. First of all, MC3T3-E1 cells were treated with hydrogen peroxide (H2 O2 ) to induce oxidative stress, as assessed by viability assays, apoptosis, the intracellular reactive oxygen species production. GlcN was capable of inducing autophagy and protected osteoblasts from those cytotoxic effects. Moreover, it significantly attenuated H2 O2 -induced oxidative stress as measured by malondialdehyde, glutathione, nitrite, and superoxide dismutase levels. Importantly, the autophagy level increased in osteoblasts treated with GlcN as represented by an increase in both Beclin1 expression and the LC3 II/I ratio. Immunofluorescence analysis of autophagosomes also confirmed the above results. In addition, GlcN decreased the mammalian target of rapamycin (mTOR) and protein kinase B (Akt). However, the Akt activator (SC79) suppressed the autophagy level induced by GlcN in osteoblasts. Consequently, the antioxidant effects of GlcN were mediated, at least in part, by enhancing autophagy through the Akt/mTOR pathway. These results suggested that GlcN might be a promising candidate for osteoporosis treatment.

Heart-on-Chip for Combined Cellular Dynamics Measurements and Computational Modeling Towards Clinical Applications.

Organ-on-chip or micro-engineered three-dimensional cellular or tissue models are increasingly implemented in the study of cardiovascular pathophysiology as alternatives to traditional in vitro cell culture. Drug induced cardiotoxicity is a key issue in drug development pipelines, but the current in vitro and in vivo studies suffer from inter-species differences, high costs, and lack of reliability and accuracy in predicting cardiotoxicity. Microfluidic heart-on-chip devices can impose a paradigm shift to the current tools. They can not only recapitulate cardiac tissue level functionality and the communication between cells and extracellular matrices but also allow higher throughput studies conducive to drug screening especially with their added functionalities or sensors that extract disease-specific phenotypic, genotypic, and electrophysiological information in real-time. Such electrical and mechanical components can tailor the electrophysiology and mechanobiology of the experiment to better mimic the in vivo condition as well. Recent advancements and challenges are reviewed in the fabrication, functionalization and sensor assisted mechanical and electrophysiological measurements, numerical and computational modeling of cardiomyocytes' behavior, and the clinical applications in drug screening and disease modeling. This review concludes with the current challenges and perspectives on the future of such organ-on-chip platforms.

Correlation Between Severity of Illness and Levels of Free Triiodothyronine, Interleukin-6, and Interleukin-10 in Patients with Acute Pancreatitis.

BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.

Novel loop neurorrhaphy technique to preserve lower lip sensate in mandibular reconstruction using an innervated vascularized iliac bone flap.

BACKGROUND: This study aimed to introduce a novel loop neurorrhaphy technique using an innervated vascularized iliac bone flap (VIBF) with vascularized ilioinguinal nerve (IIN) to reconstruct the inferior alveolar nerve (IAN) and preserve lower lip sensation simultaneously with mandibular reconstruction. METHODS: This study prospectively included patients who underwent mandibular reconstruction using VIBF from May 2018 to April 2020. Subjects were allocated into two groups: (1) Group I; innervated VIBF with loop neurorrhaphy (IIN doubly anastomosed with IAN and mental nerve), (2) Group II (control); conventional VIBF. Evaluation was done with operative time, intraoperative indocyanine green (ICG), lower lip sensory assessment (two-point discrimination [TPD] test and current perception threshold [CPT]), and drooling. RESULTS: Twelve patients were included; 6 in each group, (7 males and 5 females), age ranging from 18 to 57 years (average: 36.75 years). In all cases, intraoperative perfusion of IIN was confirmed by ICG. Group I showed a statistically significant more flap harvesting time compared with group II (mean difference, 5.67 min; P = 0.0091). There was a significant difference in sensory recovery favoring group I (P < 0.05). The TPD results in group I showed an average of 9.8 ± 6.9 mm and 6.2 ± 5.7 mm on operated and non-operated sides, while Group II showed a poor sensory recovery, and the TPD showed an average of 24.6 ± 6.7 mm and 8.4 ± 2.3 mm on operated and non-operated sides. The CPT results showed a significant difference between both groups. In Group I, the extent of drooling was 3.16 ± 0.75, while in Group II, the score was 1.6 ± 0.81, revealing a significant difference favoring Group I. CONCLUSIONS: Concurrent mandibular reconstruction using VIBF and loop neurorrhaphy with vascularized IIN to reconstruct IAN successfully restore lower jaw form and preserve lip sensation.

Correlation between Palpitations below the Heart in Traditional Chinese Medicine and Autonomic Nerve Function Based on Heart Rate Variability: A Case-Control Study.

OBJECTIVE: To explore the autonomic nerve rhythm and the correlation between palpitations below the heart (PBTH) and autonomic nerve function in patients with PBTH based on heart rate variability (HRV). METHODS: The outpatients or ward patients of Wenzhou Hospital of Traditional Chinese Medicine were collected and divided into two groups: the PBTH group and the normal group. The HRV of each group was detected. Single-factor statistical methods, Spearman correlation analysis, and logistic regression were used to describe and analyze the rhythm and characteristics of autonomic nerves in patients with PBTH and the correlation between PBTH and autonomic nerve function. RESULTS: (1) In the comparison of HRV in different time periods in the same group, the SDNN, RMSSD, pNN50, TP, and HF in the PBTH group at night were significantly higher than those in the daytime (P < 0.01), while the LF/HF ratio was significantly lower than that in the daytime (P < 0.01). (2) In the comparison of HRV between the two groups in the same time period, the RMSSD and pNN50 of the PBTH group during the daytime period were significantly higher than those of the normal control group (P < 0.05), and the LF/HF was significantly lower than that of the normal group (P < 0.05). (3) In the Spearman correlation analysis, PBTH was significantly correlated with RMSSD, pNN50, and LF/HF ratio in the daytime period, with correlation coefficients of 0.424, 0.462, and -0.524, respectively (P < 0.05). (4) Logistic regression analysis showed that the decrease of LF/HF ratio during the daytime period was an independent risk factor for PBTH in TCM (OR = 0.474, 95% CI: 0.230-0.977, P < 0.05). CONCLUSIONS: The changes in parasympathetic nerve function in patients with PBTH have a circadian rhythm, which is characterized by increased activity during the nighttime. At the same time, the autonomic nerve activity of people with PBTH during the daytime is unbalanced, and the decrease of LF/HF ratio during the day is an independent high risk factor for PBTH.

Synthesis, Characterization, Immune Regulation, and Antioxidative Assessment of Yeast-Derived Selenium Nanoparticles in Cyclophosphamide-Induced Rats.

This article introduces an environmentally friendly and more economical method for preparing red selenium nanoparticles (Se-NPs) with high stability, good biocompatibility, and narrow size using yeast as a bio-reducing agent with high antioxidant, immune regulation, and low toxicity than inorganic and organic Se. The yeast-derived Se-NPs were characterized by scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The results revealed spherical-shaped particles of Se-NPs with an average diameter of 71.14 ± 18.17 nm, an amorphous structure, and surface enhancement with an organic shell layer, that provide precise geometry and stability in the formation of bio-inert gray or black Se-NPs instead of red Se-NPs. Furthermore, the addition of 0.3-0.8 mg/kg Se-NPs in the feed significantly improved the health of mice. As Se-NPs stimulated the oxidative state of mice, it significantly increased the level of GSH-Px, SOD, and AOC, and decreased the level of MDA. The yeast-derived Se-NPs alleviated the immunosuppression induced by cyclophosphamide, whereas protected the liver, spleen, and kidney of mice, stimulated the humoral immune potential of the mice, and significantly increased the levels of I g M, IgA, and I g G. These results indicated that the yeast-derived Se-NPs, as a trace element feed additive, increased the defense of the animal against oxidative stress and infectious diseases and therefore Se-NPs can be used as a potential antibiotic substitute for animal husbandry.