Age, sex, and APOE gene-specific associations between dynapenic obesity and dementia in a large cohort.

OBJECTIVE: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort. METHODS: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses. RESULTS: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026). CONCLUSIONS: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders.

Relationship Between the Gut Microbiota and Neurological Deficits in Patients With Cerebral Ischemic Stroke.

OBJECTIVE: The aim of the paper was to investigate the composition and structure of intestinal flora in patients with cerebral ischemic stroke (CIS), and to investigate the relationship between gut microbiota (GM) and different levels of stroke severity. METHODS: In this study, 47 CIS patients (16 mild, 21 moderate, and 10 severe) and 15 healthy controls were included. General information, clinical data, and behavioral scores of the enrolled subjects were collected. Deoxyribonucleic acid in fecal intestinal flora was extracted and detected using high-throughput Illumina 16S ribosomal ribonucleic acid sequencing technology. Finally, the correlation between the community composition of intestinal microbiota and National Institutes of Health Stroke Scale (NIHSS) score in CIS patients was analyzed. RESULTS: Compared with healthy controls, there was no statistically significant difference in Alpha diversity among CIS patients, but the principal coordinate analysis showed significant differences in the composition of the GM among stroke patients with different degrees of severity and controls. In CIS patients, Streptococcus was significantly enriched, and Eshibacter-Shigella, Bacteroides, and Agathobacter were significantly down-regulated (P < .05). In addition, the relative abundance of Blautia was negatively correlated with the NIHSS score. CONCLUSIONS: Our results show that different degrees of CIS severity exert distinct effects on the intestinal microbiome. This study reveals the intestinal microecological changes after brain injury from the perspective of brain-gut axis. Intestinal microorganisms not only reveal the possible pathological process and indicate the severity of neurologic impairment, but also make targeted therapy possible for CIS patients.

Impact of sarcopenic obesity on heart failure in people with type 2 diabetes and the role of metabolism and inflammation: A prospective cohort study.

AIMS: We aimed to prospectively evaluate the association of sarcopenic obesity (SO) with the incidence risk of heart failure (HF), and the mediating role of metabolomics and inflammation in people with type 2 diabetes (T2D). METHODS: 22,496 participants with T2D from the UK Biobank were included. SO was defined as the combination of obesity (body mass index ≥30 kg/m2) and sarcopenia (grip strength <27 kg in male or <16 kg in female). The incident HF was identified through linked hospital records. Cox proportional hazard regression models were used to estimate the associations. Mediation analysis was conducted to evaluate the mediating effect of the "metabolomic risk score" of HF, which was derived from 168 plasma metabolites through LASSO regression, and five inflammatory markers (e.g., C-reactive protein [CRP] level) on the aforementioned associations. RESULTS: 1946 (8.7 %) participants developed HF during a median follow-up of 12.0 years. Compared to participants with neither obesity nor sarcopenia, those with obesity & non-sarcopenia (hazard ratio [HR]: 1.80, 95 % confidence interval [CI]: 1.62, 2.00), sarcopenia & non-obesity (HR: 1.90, 95 % CI: 1.56, 2.31) and SO (HR: 2.29, 95 % CI: 1.92, 2.73) showed a higher risk of HF. The metabolomic risk score (20.0 %) and CRP (20.4 %) meditated this association. CONCLUSIONS: SO was associated with an increased risk of HF in people with T2D and metabolomics and inflammation partially mediated this association. Our findings suggest the importance of managing obesity and muscle strength simultaneously in preventing HF among people with T2D and shed light on the underlying mechanisms.

Dietary patterns, metabolomics and frailty in a large cohort of 120 000 participants.

Objective: To examine the associations of dietary patterns with frailty and whether metabolic signatures (MSs) mediate these associations. Methods: We used UK Biobank data to examine (1) the associations of four dietary patterns (i.e., alternate Mediterranean diet [aMED], Recommended Food Score [RFS], Dietary Approaches to Stop Hypertension [DASH] and Mediterranean-DASH Intervention for Neurodegenerative Delay [MIND] diet) with frailty (measured by the frailty phenotype and the frailty index) using multivariable logistic regression (analytic sample 1: N = 124 261; mean age = 57.7 years), and (2) the mediating role of MSs (weighted sums of the metabolites selected from 168 plasma metabolites using the LASSO algorithm) in the above associations via mediation analysis (analytic sample 2: N = 26 270; mean age = 57.7 years). Results: Four dietary patterns were independently associated with frailty (all P < 0.001). For instance, compared to participants in the lowest tertile for RFS, those in the intermediate (odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.74, 0.89) and highest (OR: 0.62; 95% CI: 0.56, 0.68) tertiles had a lower risk of frailty. We found that 98, 68, 123 and 75 metabolites were associated with aMED, RFS, DASH and MIND, respectively, including 16 common metabolites (e.g., fatty acids, lipoproteins, acetate and glycoprotein acetyls). The MSs based on these metabolites partially mediated the association of the four dietary patterns with frailty, with the mediation proportion ranging from 26.52% to 45.83%. The results were robust when using another frailty measure, the frailty index. Conclusions: The four dietary patterns were associated with frailty, and these associations were partially mediated by MSs. Adherence to healthy dietary patterns may potentially reduce frailty development by modulating metabolites.

Accelerated Bone Regeneration on the Metal Surface through Controllable Surface Potential.

Surface potential is rarely investigated as an independent factor in influencing tissue regeneration on the metal surface. In this work, the surface potential on the titanium (Ti) surface was designed to be tailored and adjusted independently, which arises from the ferroelectricity and piezoelectricity of poled poly(vinylidene fluoride-trifluoroethylene) (PVTF). Notably, it is found that such controllable surface potential on the metal surface significantly promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro as well as bone regeneration in vivo. In addition, the intracellular calcium ion (Ca2+) concentration measurement further proves that such controllable surface potential on the metal surface could activate the transmembrane calcium channels and allow the influx of extracellular Ca2+ into the cytoplasm. That might be the reason for improved osteogenic differentiation of BMSCs and bone regeneration. These findings reveal the potential of the metal surface with improved bioactivity for stimulation of osteogenesis and show great prospects for fabricable implantable medical devices with adjustable surface potential.

Gene set enrichment analysis identifies immune subtypes of kidney renal clear cell carcinoma with significantly different molecular and clinical properties.

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy, marked by a high abundance of tumor-infiltrating lymphocytes (TILs) and an unfavorable prognosis upon metastasis. Numerous studies have demonstrated that KIRC possesses a tumor microenvironment that is highly heterogeneous, and this is associated with significant variations in the effectiveness of most first-line drugs administered to KIRC patients. Therefore, it is crucial to classify KIRC based on the tumor microenvironment, although these subtyping techniques are still inadequate. Methods: By applying gene set enrichment scores of 28 immune signatures, we conducted a hierarchical clustering of KIRC and determined its immune subtypes. In addition, we conducted a comprehensive exploration of the molecular and clinical features of these subtypes, including survival prognosis, proliferation, stemness, angiogenesis, tumor microenvironment, genome instability, intratumor heterogeneity, and pathway enrichment. Results: Through cluster analysis, two immune subtypes of KIRC were identified and termed Immunity-High (Immunity-H) and Immunity-Low (Immunity-L). This clustering outcome was consistent in four independent KIRC cohorts. The subtype Immunity-H exhibited elevated levels of TILs, tumor aneuploidy, homologous recombination deficiency, stemness, and proliferation potential, along with a poorer prognosis for survival. Despite this, the Immunity-L subtype demonstrated elevated intratumor heterogeneity and a stronger angiogenesis signature in contrast to Immunity-H. According to the results of pathway enrichment analysis, the Immunity-H subtype was found to be highly enriched in immunological, oncogenic, and metabolic pathways, whereas the Immunity-L subtype was highly enriched in angiogenic, neuroactive ligand-receptor interaction, and PPAR pathways. Conclusions: Based on the enrichment of immune signatures in the tumor microenvironment, KIRC can be categorized into two immune subtypes. The two subtypes demonstrate considerably distinct molecular and clinical features. In KIRC, an increase in immune infiltration is linked to a poor prognosis. Patients with Immunity-H KIRC may exhibit active responses to PPAR and immune checkpoint inhibitors, whereas patients with Immunity-L may manifest favorable responses to anti-angiogenic agents and immune checkpoint inhibitors. The immunological classification provides molecular insights into KIRC immunity, as well as clinical implications for the management of this disease.

Analysis and Optimization of the Milling Performance of an Industry-Scale VSM via Numerical Simulations.

Vertical stirred mills (VSM) are widely used for powder processing in many situations like mechanical alloying preparation and raw material crushing and shaping. Many structural and operational parameters like stirrer helix angle and rotating speed have great significance on VSM performance, especially in a large industry-scale situation. Therefore, it becomes essential to investigate these parameters systematically to obtain high energy efficiency and good product quality. In this work, the discrete element method (DEM) was used to examine the effects of stirrer helix angle (α), stirrer diameter (d), and rotating speed (n) on the grinding performance in an industrial VSM, and then the response surface method (RSM) was employed for multi-objective optimization in the VSM. It is found that a media vortex phenomenon may happen near the stirring shaft. The media collisions are significantly influenced by α, d, and n. Through multi-objective optimization design (MOD), the power consumption (P) of the stirrer reduced by 8.09%. The media collision energy (E) increased by 9.53%. The energy conversion rate (R) rises by 20.70%. The collision intensity and frequency are both improved. This optimization method can help determine good operating parameters based on certain structures.

Visit-to-visit HbA1c variability, dementia, and hippocampal atrophy among adults without diabetes.

OBJECTIVES: Adults without diabetes are not completely healthy; they are probably heterogeneous with several potential health problems. The management of hemoglobin A1c (HbA1c) is crucial among patients with diabetes; but whether similar management strategy is needed for adults without diabetes is unclear. Thus, this study aimed to investigate the associations of visit-to-visit HbA1c variability with incident dementia and hippocampal volume among middle-aged and older adults without diabetes, providing potential insights into this question. METHODS: We conducted a prospective analysis for incident dementia in 10,792 participants (mean age 58.9 years, 47.8 % men) from the UK Biobank. A subgroup of 3793 participants (mean age 57.8 years, 48.6 % men) was included in the analysis for hippocampal volume. We defined HbA1c variability as the difference in HbA1c divided by the mean HbA1c over the 2 sequential visits ([latter - former]/mean). Dementia was identified using hospital inpatient records with ICD-9 codes. T1-structural brain magnetic resonance imaging was conducted to derive hippocampal volume (normalized for head size). The nonlinear and linear associations were examined using restricted cubic spline (RCS) models, Cox regression models, and multiple linear regression models. RESULTS: During a mean follow-up (since the second round) of 8.4 years, 90 (0.8 %) participants developed dementia. The RCS models suggested no significant nonlinear associations of HbA1c variability with incident dementia and hippocampal volume, respectively (All P > 0.05). Above an optimal cutoff of HbA1c variability at 0.08, high HbA1c variability (increment in HbA1c) was associated with an increased risk of dementia (Hazard Ratio, 1.88; 95 % Confidence Interval, 1.13 to 3.14, P = 0.015), and lower hippocampal volume (coefficient, -96.84 mm3, P = 0.037), respectively, in models with adjustment of covariates including age, sex, etc. Similar results were found for a different cut-off of 0. A series of sensitivity analyses verified the robustness of the findings. CONCLUSIONS: Among middle-aged and older adults without diabetes, increasing visit-to-visit HbA1c variability was associated with an increased dementia risk and lower hippocampal volume. The findings highlight the importance of monitoring and controlling HbA1c fluctuation in apparently healthy adults without diabetes.

Identification of novel pathways and immune profiles related to sarcopenia.

Introduction: Sarcopenia is a progressive deterioration of skeletal muscle mass strength and function. Methods: To uncover the underlying cellular and biological mechanisms, we studied the association between sarcopenia's three stages and the patient's ethnicity, identified a gene regulatory network based on motif enrichment in the upregulated gene set of sarcopenia, and compared the immunological landscape among sarcopenia stages. Results: We found that sarcopenia (S) was associated with GnRH, neurotrophin, Rap1, Ras, and p53 signaling pathways. Low muscle mass (LMM) patients showed activated pathways of VEGF signaling, B-cell receptor signaling, ErbB signaling, and T-cell receptor signaling. Low muscle mass and physical performance (LMM_LP) patients showed lower enrichment scores in B-cell receptor signaling, apoptosis, HIF-1 signaling, and the adaptive immune response pathways. Five common genes among DEGs and the elastic net regression model, TTC39DP, SLURP1, LCE1C, PTCD2P1, and OR7E109P, were expressed between S patients and healthy controls. SLURP1 and LCE1C showed the highest expression levels among sarcopenic Chinese descent than Caucasians and Afro-Caribbeans. Gene regulatory analysis of top upregulated genes in S patients yielded a top-scoring regulon containing GATA1, GATA2, and GATA3 as master regulators and nine predicted direct target genes. Two genes were associated with locomotion: POSTN and SLURP1. TTC39DP upregulation was associated with a better prognosis and stronger immune profile in S patients. The upregulation of SLURP1 and LCE1C was associated with a worse prognosis and weaker immune profile. Conclusion: This study provides new insight into sarcopenia's cellular and immunological prospects and evaluates the age and sarcopenia-related modifications of skeletal muscle.

Review of rehabilitation protocols for brachial plexus injury.

Brachial plexus injury (BPI) is one of the most serious peripheral nerve injuries, resulting in severe and persistent impairments of the upper limb and disability in adults and children alike. With the relatively mature early diagnosis and surgical technique of brachial plexus injury, the demand for rehabilitation treatment after brachial plexus injury is gradually increasing. Rehabilitation intervention can be beneficial to some extent during all stages of recovery, including the spontaneous recovery period, the postoperative period, and the sequelae period. However, due to the complex composition of the brachial plexus, location of injury, and the different causes, the treatment varies. A clear rehabilitation process has not been developed yet. Rehabilitation therapy that has been widely studied focusing on exercise therapy, sensory training, neuroelectromagnetic stimulation, neurotrophic factors, acupuncture and massage therapy, etc., while interventions like hydrotherapy, phototherapy, and neural stem cell therapy are less studied. In addition, rehabilitation methods in some special condition and group often neglected, such as postoperative edema, pain, and neonates. The purpose of this article is to explore the potential contributions of various methods to brachial plexus injury rehabilitation and to provide a concise overview of the interventions that have been shown to be beneficial. The key contribution of this article is to form relatively clear rehabilitation processes based on different periods and populations, which provides an important reference for the treatment of brachial plexus injuries.

Enhanced M2 Polarization of Oriented Macrophages on the P(VDF-TrFE) Film by Coupling with Electrical Stimulation.

Electrical stimulation (ES) has been considered a promising strategy in regulating intracellular communication, membrane depolarization, ion transport, etc. Meanwhile, cell topography, such as the alignment and elongation in anisotropic orientation, also plays a critical role in triggering mechanotransduction as well as the cellular fate. However, coupling of ES and cell orientation to regulate the polarization of macrophages is yet to be explored. In this work, we intended to explore the polarization of macrophages on a poly(vinylidene fluoride-trifluoroethylene [P(VDF-TrFE)] film with intrinsic microstripe roughness, which was covered on indium tin oxide planar microelectrodes. We found that mouse bone marrow-derived macrophages (BMDMs) cultured on a P(VDF-TrFE) film exhibited an elongated morphology aligned with the microstripe crystal whisker, but their polarization behavior was not affected. However, the elongated cells were susceptible to ES and upregulated their M2 polarization, as verified by the related expression of phenotype markers, cytokines, and genes, while not affecting M1 polarization. This is due to the increased expression of the M2 polarization receptor interleukin-4Rα on the surface of elongated BMDMs, while the M1 polarization receptor toll-like receptor 4 was not affected. Thus, M2 polarization was singularly enhanced after activation of polarization by ES. The combination of surface morphology and ES to promote M2 single polarization in this work provides a new perspective for regulating macrophage polarization in the field of immunotherapy.

Self-Assembly of Selenium-Doped Carbon Quantum Dots as Antioxidants for Hepatic Ischemia-Reperfusion Injury Management.

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.

Electrical stimulation therapy for peripheral nerve injury.

Peripheral nerve injury is common and frequently occurs in extremity trauma patients. The motor and sensory impairment caused by the injury will affect patients' daily life and social work. Surgical therapeutic approaches don't assure functional recovery, which may lead to neuronal atrophy and hinder accelerated regeneration. Rehabilitation is a necessary stage for patients to recover better. A meaningful role in non-pharmacological intervention is played by rehabilitation, through individualized electrical stimulation therapy. Clinical studies have shown that electrical stimulation enhances axon growth during nerve repair and accelerates sensorimotor recovery. According to different effects and parameters, electrical stimulation can be divided into neuromuscular, transcutaneous, and functional electrical stimulation. The therapeutic mechanism of electrical stimulation may be to reduce muscle atrophy and promote muscle reinnervation by increasing the expression of structural protective proteins and neurotrophic factors. Meanwhile, it can modulate sensory feedback and reduce neuralgia by inhibiting the descending pathway. However, there are not many summary clinical application parameters of electrical stimulation, and the long-term effectiveness and safety also need to be further explored. This article aims to explore application methodologies for effective electrical stimulation in the rehabilitation of peripheral nerve injury, with simultaneous consideration for fundamental principles of electrical stimulation and the latest technology. The highlight of this paper is to identify the most appropriate stimulation parameters (frequency, intensity, duration) to achieve efficacious electrical stimulation in the rehabilitation of peripheral nerve injury.

Long-Term Lower Limb Motor Function Correlates with Middle Cerebellar Peduncle Structural Integrity in Sub-Acute Stroke: A ROI-Based MRI Cohort Study.

Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial stroke. However, the role of CCD in lower limb recovery after stroke is still unknown. In this study, using a region-of-interest-based analysis of diffusion tensor imaging (DTI), a total of 44 cases of stroke within 3 months onset were enrolled for assessment of the cerebral peduncle (CP) and middle cerebellar peduncles (MCP) in CCD. Compared with the control group, the fractional anisotropy ratio (rFA) and laterality index (LI) of the CP and MCP in the stroke group significantly decreased. The rFA of the MCP (unaffected side/affected side) showed a more significant correlation with 1-year paresis grading (PG), lower extremity PG, upper extremity PG, National Institutes of Health Stroke Scale (NIHSS), and functional independence measure (FIM) motor item score, in comparison to the rFA of the CP (affected side/unaffected side) (r = -0.698 vs. r = -0.541, r = -0.651 vs. r = -0.386, r = -0.642 vs. r = -0.565, r = -0.519 vs. r = -0.403, and r = 0.487 vs. r = 0.435, respectively). Furthermore, the LI of the CP had a more significant association with 1-year Brunel Balance Assessment (BBA), upper extremity PG, and Modified Rankin Scale (mRS) as compared to the LI of the MCP (r = 0.573 vs. r = 0.452; r = -0.554 vs. r = -0.528; and r = -0.494 vs. r = -0.344, respectively). We set the cutoff point for the MCP rFA at 0.925 (sensitivity: 79% and specificity: 100%) for predicting lower extremity motor function prognosis and found the receiver operating characteristic (ROC) curve of MCP rFA was larger than that of CP rFA (0.893 vs. 0.737). These results reveal that the MCP may play a significant role in the recovery of walking ability after stroke.

Association of Sarcopenia with Cognitive Function and Dementia Risk Score: A National Prospective Cohort Study.

The relationship between skeletal muscle and cognitive disorders has drawn increasing attention. This study aims to examine the associations of sarcopenia with cognitive function and dementia risk score. Data on 1978 participants (aged 65 years and older) from the 2011 wave of the China Health and Retirement Longitudinal Study, with four follow-up waves to 2018, were used. Cognitive function was assessed by four dimensions, with a lower score indicating lower cognitive function. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM), with a higher score indicating a greater risk. Sarcopenia was defined when low muscle mass plus low muscle strength or low physical performance were met. We used generalized estimating equations to examine the associations of sarcopenia. In the fully adjusted models, sarcopenia was significantly associated with lower cognitive function (standardized, ß = -0.15; 95% CIs: -0.26, -0.04) and a higher BDRM score (standardized, ß = 0.42; 95% CIs: 0.29, 0.55). Our findings may provide a new avenue for alleviating the burden of cognitive disorders by preventing sarcopenia.

Photothermal extracellular matrix based nanocomposite films and their effect on the osteogenic differentiation of BMSCs.

Mild thermal stimulation in vivo could induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, nano-functionalized photothermal extracellular matrix (ECM) nanocomposite films were obtained through adding graphene during cell culture, so that graphene could directly integrate with the ECM secreted by cells. Owing to the similarity of the ECM to the in vivo microenvironment and the apparent photothermal effect of graphene nanoflakes, heat could be generated and transferred at the material-cell interface in a biomimetic way. It was demonstrated that such nanocomposite films achieved an interface temperature rise with light illumination. This could be easily sensed by BMSCs through the ECM. According to alkaline phosphatase, osteogenic related gene expression, mineral deposition, and upregulated expression of heat shock protein (HSP70) and p-ERK, composite films with proper illumination significantly promoted the differentiation of BMSCs into osteoblasts. This work endeavors to study the thermal regulation of BMSC differentiation and provide a new perspective on biocompatible osteo-implant materials which can be remotely controlled.

Role of prebiotics in enhancing the function of next-generation probiotics in gut microbiota.

With the development of high-throughput DNA sequencing and molecular analysis technologies, next-generation probiotics (NGPs) are increasingly gaining attention as live bacterial therapeutics for treatment of diseases. However, compared to traditional probiotics, NGPs are much more vulnerable to the harsh conditions in the human gastrointestinal tract, and their functional mechanisms in the gut are more complex. Prebiotics have been confirmed to play a critical role in improving the function and viability of traditional probiotics. Defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, prebiotics are also important for NGPs. This review summarizes potential prebiotics for use with NGPs and clarifies their characteristics and functional mechanisms. Then we particularly focus on illustrating the protective effects of various prebiotics by enhancing the antioxidant capacity and their resistance to digestive fluids. We also elucidate the role of prebiotics in regulating anti-bacterial effects, intestinal barrier maintenance, and cross-feeding mechanisms of NPGs. With the expanding range of candidate NGPs and prebiotic substrates, more studies need to be conducted to comprehensively elucidate the interactions between prebiotics and NGPs outside and inside hosts, in order to boost their nutritional and healthcare applications.

Electrochemical deposition of Ppy/Dex/ECM coatings and their regulation on cellular responses through electrical controlled drug release.

Bone tissue engineering requires a material that can simultaneously promote osteogenic differentiation and anti-inflammatory effects at specific times in response to a series of problems after bone implantation. In this study, the porous network-like titanium matrix was constructed and polypyrrole/dexamethasone (Ppy/Dex) composite coatings with three-dimensional nano-network structure were prepared by electrochemical deposition. The biocompatibility of the composite coatings was further improved by the composite of the extracellular matrix (ECM). The Ppy/Dex/ECM composite coatings released Dex by changing the redox state of Ppy under the electrical stimulation of negative pulses, achieving a drug release controlled by electric field. In terms of osteogenic differentiation, the Ppy/Dex/ECM composite coatings exhibited the best osteogenic activity under electrical controlled release, indicating the synergistic effect of Dex and ECM on osteogenic differentiation. In terms of anti-inflammatory properties, ECM exhibited simultaneous inhibition of both pro- and anti-inflammatory process, while Dex demonstrated significant promotion of anti-inflammatory processes. In this work, the effect of electrical controlled drug release on osteogenic differentiation and inflammation in the ECM cell microenvironment was achieved by preparing Ppy/Dex/ECM composite coatings, which is of great significance for bone tissue engineering and regenerative medicine.

An integrated analysis of gut microbiota and the brain transcriptome reveals host-gut microbiota interactions following traumatic brain injury.

OBJECTIVES: Recent evidence suggests that there is a link between gut and brain via microbial, immune, endocrine and neural signaling pathways, but the changes of gut-brain axis following brain trauma has not yet been clearly shown. The aim of this study was to reveal the gut microbiota and transcriptomic profile of the cerebral cortex in traumatic brain injury (TBI) mice. METHODS: A controlled cortical impact (CCI) device was used to establish a TBI model. Behavioral testing and histopathological analysis were performed. The gut microbiota was analyzed by 16S rRNA sequencing, and gene expression in the cerebral cortex was detected by whole-transcriptome sequencing (RNA-Seq) 7 days after TBI. RESULTS: The analysis of 16S rRNA sequencing data indicated that TBI increased the relative abundance of Bifidobacterium. The TBI group showed a disturbance in intestinal flora. RNA-Seq analysis identified 523 differentially expressed genes (481 upregulated and 42 downregulated) in the cerebral cortex of the TBI group compared with the sham group. Cluster analysis revealed 93 immune system process-related genes and 55 inflammatory response-related genes that were differentially expressed. CONCLUSIONS: This manuscript reports pathogenic changes via the gut-brain axis driven by TBI, which confer persistent symptoms and susceptibility to neurodegeneration.

Polarized P(VDF-TrFE) film promotes skin wound healing through controllable surface potential.

Surface potential of biomaterials is found to be important for wound healing. Here, poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) films with different surface potentials and piezoelectric responses were prepared and explored for the effect of surface potential on wound healing. The crystalline state of P(VDF-TrFE) films were characterized with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transformed infrared spectroscopy (FTIR), illustrated that the electric polarization will promote the crystallization of the ß phase of P(VDF-TrFE), in which the content of ß phase increased from 82.9 % to 86.8 % compared with the control. Then, Kelvin potential and piezoelectric coefficient d33 were to evaluate surface potential and polarization performance. Moreover, bovine serum albumin (BSA) adsorption and cell culture results showed that high surface potential can promote protein adsorption as well as fibroblast proliferation and macrophage polarization. Finally, in vivo experiments indicated that high voltage polarized P(VDF-TrFE) films can generate higher dynamic potential up to 2.3 V, and promoted wound healing from the phases of inflammation, proliferation and remodeling, the wound healing rate of which was 88.8 % ± 0.8 %, significantly higher than 79.1 % ± 2.5 % and 86.4 % ± 1.8 % of blank and control. In general, this work revealed that polarized P(VDF-TrFE) films can promote wound healing, shed light on designing wound healing materials with similar properties.