Baicalin effects on rats with spinal cord injury by anti-inflammatory and regulating the serum metabolic disorder.

Baicalin had neuroprotective effects on inhibiting neuronal cell apoptosis induced by spinal cord ischemic injury. This study aimed to explore the protective effects of Baicalin on rats with spinal cord injury (SCI) and its mechanism of action. The recovery of spinal cord nerve function in rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) score and the combine behavioral score (CBS). The expressions of cytokines tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by the enzyme-linked immunosorbent assay method. Expressions of inflammation-related proteins were detected by Western blot. Multivariate statistical analysis was performed for serum metabolites. The BBB and CBS score results showed that Baicalin had a certain improvement on rats with SCI. SCI symptoms were significantly improved in low-dose and high-dose groups. The levels of TNF-α, IL-1ß, and IL-6 in the SCI group were significantly increased. The expressions of NF-κB p65, NF-κB p50, p-IκBα, and IKKα in the SCI group showed the opposite trend compared with the low-dose and high-dose groups. Compared with the sham group, glutamine, levels of 3-OH-butyrate, N-acetylaspartate, and glutathione were significantly reduced, and the levels of glutamate and betaine were significantly increased in the SCI group. When Baicalin was administered, the contents of glutamine synthase (GS) and glutaminase (GLS) were significantly reduced, indicating that Baicalin had the effect of improving GS and GLS. Baicalin has protective effects on improving SCI and lower extremity motor function, has a significant anti-inflammatory effect, and regulates the serum metabolic disorder caused by SCI in rats.

NCOA3 Loss Disrupts Molecular Signature of Chondrocytes and Promotes Posttraumatic Osteoarthritis Progression.

BACKGROUND/AIMS: Osteoarthritis (OA) is the most common joint disease. Recently, a novel variant near the nuclear receptor coactivator 3 (NCOA3) has been identified in association with greater risk of developing OA. However, how NCOA3 is regulated in chondrocytes and involved in OA pathogenesis remain elusive. METHODS: The expression and DNA methylation of NCOA3 in knee OA cartilage and in vitro dedifferentiated chondrocytes with or without rs6094710 SNP were analyzed by qRT-PCR, immunoblotting, methylation-specific PCR and bisulfite sequencing. NCOA3 was depleted by siRNA or shRNA or inhibited by a chemical inhibitor to assess its role in chondrocyte dedifferentiation or OA pathogenesis in posttraumatic OA animal model established by cruciate ligament transection surgery. RESULTS: We found that compared with normal counterparts, samples with rs6094710 SNP failed to upregulate NCOA3. Further evidence associated this phenotype with DNMT1-mediated hypermethylation in gene promoter region. Moreover, we showed that NCOA3 maintained the molecular signature of chondrocytes dedifferentiating in vitro or exposed to IL-1ß, nevertheless, NCOA3 appeared dispensable for preventing OA initiation, since NCOA3 loss did not trigger OA in young mice. Instead, NCOA3 loss promoted posttraumatic OA progression, and in parallel, enhanced NF-κB activation. Finally, the promoted posttraumatic OA progression was significantly retarded when administrated with NF-κB pathway inhibitor, suggesting that NCOA3 lose promotes posttraumatic OA at least partially by enhancing NF-κB activation. CONCLUSION: Thus, our findings indicate a critical role of NCOA3 in chondrocytes, and imply that manipulating NCOA3 might present a potential therapeutic approach to interfere OA progression.

Methods for Assessment of Memory Reactivation.

It has been suggested that reactivation of previously acquired experiences or stored information in declarative memories in the hippocampus and neocortex contributes to memory consolidation and learning. Understanding memory consolidation depends crucially on the development of robust statistical methods for assessing memory reactivation. To date, several statistical methods have seen established for assessing memory reactivation based on bursts of ensemble neural spike activity during offline states. Using population-decoding methods, we propose a new statistical metric, the weighted distance correlation, to assess hippocampal memory reactivation (i.e., spatial memory replay) during quiet wakefulness and slow-wave sleep. The new metric can be combined with an unsupervised population decoding analysis, which is invariant to latent state labeling and allows us to detect statistical dependency beyond linearity in memory traces. We validate the new metric using two rat hippocampal recordings in spatial navigation tasks. Our proposed analysis framework may have a broader impact on assessing memory reactivations in other brain regions under different behavioral tasks.

Solid-State Dewetting of Gold Aggregates/Islands on TiO2 Nanorod Structures Grown by Oblique Angle Deposition.

A composite film made of a stable gold nanoparticle (NP) array with well-controlled separation and size atop a TiO2 nanorod film was fabricated via the oblique angle deposition (OAD) technique. The fabrication of the NP array is based on controlled, Rayleigh-instability-induced, solid-state dewetting of as-deposited gold aggregates on the TiO2 nanorods. It was found that the initial spacing between as-deposited gold aggregates along the vapor flux direction should be greater than the TiO2 interrod spacing created by 80° OAD to control dewetting and produce NP arrays. A numerical investigation of the process was conducted using a phase-field modeling approach. Simulation results showed that coalescence between neighboring gold aggregates is likely to have caused the uncontrolled dewetting in the 80° deposition, and this could be circumvented if the initial spacing between gold aggregates is larger than a critical value smin. We also found that TiO2 nanorod tips affect dewetting dynamics differently than planar TiO2. The topology of the tips can induce contact line pinning and an increase in the contact angle along the vapor flux direction to the supported gold aggregates. These two effects are beneficial for the fabrication of monodisperse NPs based on Rayleigh-instability-governed self-assembly of materials, as they help to circumvent the undesired coalescence and facilitate the instability growth on the supported material. The findings uncover the application potential of OAD as a new method to fabricate structured films as template substrates to mediate dewetting. The reported composite films would have uses in optical coatings and photocatalytic systems, taking advantage of their ability to combine plasmonic nanostructures within a nanostructured dielectric film.

Efficient Dual Mechanisms Boost the Efficiency of Ternary Solar Cells with Two Compatible Polymer Donors to Exceed 19.

Ternary strategyopens a simple avenue to improve the power conversion efficiency (PCE) of organic solar cells (OSCs). The introduction of wide bandgap polymer donors (PDs) as third component canbetter utilize sunlight and improve the mechanical and thermal stability of active layer. However, efficient ternary OSCs (TOSCs) with two PDs are rarely reported due to inferior compatibility and shortage of efficient PDs match with acceptors. Herein, two PDs-(PBB-F and PBB-Cl) are adopted in the dual-PDs ternary systems to explore the underlying mechanisms and improve their photovoltaic performance. The findings demonstrate that the third components exhibit excellent miscibility with PM6 and are embedded in the host donor to form alloy-like phase. A more profound mechanism for enhancing efficiency through dual mechanisms, that are the guest energy transfer to PM6 and charge transport at the donor/acceptor interface, has been proposed. Consequently, the PM6:PBB-Cl:BTP-eC9 TOSCs achieve PCE of over 19%. Furthermore, the TOSCs exhibit better thermal stability than that of binary OSCs due to the reduction in spatial site resistance resulting from a more tightly entangled long-chain structure. This work not only provides an effective approach to fabricate high-performance TOSCs, but also demonstrates the importance of developing dual compatible PD materials.

Autophagy induces hair follicle stem cell activation and hair follicle regeneration by regulating glycolysis.

BACKGROUND: Hair follicle stem cells (HFSCs) typically remain quiescent and are activated only during the transition from telogen to anagen to ensure that the hair follicle enters a new cycle. The metabolic behavior of stem cells in tissues is regulated by macroautophagy/autophagy, and changes in HFSC metabolism directly affect their activation and maintenance. However, the role of autophagy in the regulation of HFSC metabolism and function remains unclear. METHODS: Back skin samples were obtained from mice at different hair follicle cycle stages, and immunofluorescence staining was used to monitor autophagy in HFSCs. Mouse and human hair follicles were treated with rapamycin (Rapa, an autophagy activator) or 3-methyladenine (3-MA, an autophagy inhibitor). The effects of autophagy on the hair follicle cycle and HFSC were investigated by imaging, cell proliferation staining, and HFSC-specific marker staining. The influence and mechanism of autophagy on HFSC metabolism were explored using RNA sequencing, real-time polymerase chain reaction, immunohistochemical staining, and detection of lactate and glucose concentrations. Finally, the influence of autophagy-induced glycolysis on HFSC and the hair follicle cycle was verified by stem cell characteristics and in vivo functional experiments. RESULTS: Autophagy in HFSC was highest during the transition from telogen to anagen. Inhibiting autophagy with 3-MA led to early entry into catagen and prolonged telogen, whereas Rapa promoted autophagy and hair growth. Autophagy activated HFSC by increasing the expression and activity of HFSC lactate dehydrogenase (Ldha), thereby transforming HFSC metabolism into glycolysis. Inhibition of Ldha expression counteracted the effects of autophagy. CONCLUSIONS: Autophagy activated HFSC by promoting the transition from HFSC metabolism to glycolysis, ultimately initiating the hair follicle cycle and promoting hair growth.

Evaluation of platelet-rich plasma plus basic fibroblast growth factor combined with minoxidil in the treatment of androgenetic alopecia: A randomized controlled trial.

BACKGROUND: Platelet-rich plasma plus basic fibroblast growth factor (PRPF) has been confirmed to be a safe and valuable therapy for androgenetic alopecia (AGA). However, the efficacy of PRPF combined with minoxidil treatment remains unknown. OBJECTIVE: To assess the efficacy of combined PRPF and minoxidil treatment for AGA. METHODS: In this prospective, randomized controlled trial, 75 patients with AGA were randomly divided into three groups and were administered the following treatments: Group 1, direct intradermal PRPF injection; Group 2, topical minoxidil 5% twice daily; and Group 3, PRPF injection combined with minoxidil. The PRPF injection was performed three times, 1 month apart. Hair growth parameters were evaluated using a trichoscope until the sixth month of the study. Patient satisfaction and side effects were recorded during the follow-up. RESULTS: All patients showed improvements (p < 0.05) in hair count, terminal hair, and decrease in telogen hair ratio after treatment. The efficacy of PRPF complex therapy revealed significant improvements (p < 0.05) in hair count, terminal hair and growth rate, compared with monotherapy. LIMITATIONS: Small sample size, short follow-up time and lack of quantification of GFs in PRPF. CONCLUSION: The effect of complex therapy exceed both the effects of PRPF monotherapy and minoxidil treatment, which can be a beneficial AGA treatment strategy.

The AR/miR-221/IGF-1 pathway mediates the pathogenesis of androgenetic alopecia.

Androgenetic alopecia (AGA) affects more than half of the adult population worldwide and is primarily caused by the binding of dihydrotestosterone (DHT) to androgen receptors (AR). However, the mechanisms by which AR affects hair follicles remain unclear. In our study, we found that miR-221 significantly suppressed hair growth and the proliferation of dermal papilla cells (DPCs) and dermal sheath cells (DSCs) in AGA patients. Interestingly, miR-221 and AR were mainly co-located in the same part of the hair follicle. Mechanistic analysis revealed that AR directly promoted the transcription of miR-221, which in turn suppressed IGF-1 expression, leading to the inactivation of the MAPK pathway in DPCs and the PI3K/AKT pathway in DSCs. In AGA patients, miR-221 expression was positively correlated with AR expression and negatively correlated with IGF-1 expression. Our findings indicate that miR-221, as a direct target of AR, plays a crucial role in the pathogenesis of AGA, making it a novel biomarker and potential therapeutic target for treating AGA.

Cement Leakage in Vertebral Compression Fractures Between Unilateral and Bilateral Percutaneous Vertebral Augmentation: A Meta-Analysis.

AIM: Cement leakage remains a significant clinical problem associated with vertebroplasty and kyphoplasty procedures, with uncontrolled cement flow in the posterior direction causing leakage into the vertebral veins or spinal canal that leads to potentially serious clinical complications. This meta-analysis compared the incidences of cement leakage between unilateral and bilateral percutaneous vertebral augmentation (PVA) in the treatment of osteoporosis vertebral compression fractures. MATERIAL AND METHODS: Pertinent studies were identified by a search of the PubMed, Embase, and Web of Science databases up to December 2020. The risk ratio (RR) or weighted mean difference (WMD) was applied to combine the results, and a random-effects or a fixed-effects model was used to pool the results depending on the heterogeneity among studies. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: A total of 16 trials (including 9 RCTs and 7 cohort studies) met the inclusion criteria and were included in this meta-analysis. The incidences of cement leakage were similar between the bilateral PVA and unilateral PVA groups (RR = 0.80, 95%CI: 0.57, 1.11; P = 0.182) but unilateral PVA required less cement volume (WMD = -1.34 ml, 95%CI: -1.87, -0.81; P 0.001). Subgroup analysis revealed that the incidence of cement leakage was significantly lower in the unilateral PKP group than in the bilateral PKP group (RR = 0.65, 95%CI: 0.44, 0.97; P = 0.034). CONCLUSION: The incidences of cement leakage were similar between unilateral and bilateral PVA, but unilateral PVA required less cement. More large-scale studies are needed to verify our findings.

Exploring EEG microstates for affective computing: decoding valence and arousal experiences during video watching.

Investigating the electroencephalography (EEG) correlates of human emotional experiences has attracted increasing interest in the field of affective computing. Substantial progress has been made during the past decades, mainly by using EEG features extracted from localized brain activities. The present study explored a brain network-based feature defined by EEG microstates for a possible representation of emotional experiences. A publicly available and widely used benchmarking EEG dataset called DEAP was used, in which 32 participants watched 40 one-minute music videos with their 32channel EEG recorded. Four quasi-stable prototypical microstates were obtained, and their temporal parameters were extracted as features. In random forest regression, the microstate features showed better performances for decoding valence (model fitting mean squared error (MSE) = 3.85±0.28 and 4.07 ± 0.30, respectively, p = 0.022) and comparable performances for decoding arousal (MSE = 3.30±0.30 and 3.41 ±0.31, respectively, p = 0.169), as compared to conventional spectral power features. As microstate features describe neural activities from a global spatiotemporal dynamical perspective, our findings demonstrate a possible new mechanism for understanding human emotion and provide a promising type of EEG feature for affective computing.

[Understanding and prevention of D-dimer elevation in coronavirus disease 2019 in traditional Chinese medicine].

2019 Novel coronavirus (2019-nCoV) infection caused a pandemic in the world. From the reported cases in the literatures, the level of D-dimer in patients with coronavirus disease 2019 (COVID-19) is positively correlated with the severity of illness, which needs the attention of clinical workers. According to Western medicine, the increase of D-dimer is related to the hyperactivity of fibrinolytic system and the shortening of prothrombin time (PT), resulting in excessive production and degradation of plasma fibrin and hypercoagulable state of blood, while traditional Chinese medicine (TCM) believes that the above syndromes belong to the pathogenesis of "blood stasis" according to TCM theories. Over the years, TCM has a significant effect on promoting blood circulation, removing blood stasis and improving microcirculation. This article reviews the mechanism, clinical significance, understanding of TCM and common methods of promoting blood circulation and removing blood stasis caused by 2019-nCoV, in order to provide ideas for the prevention and treatment of impaired blood coagulation in patients with COVID-19.

Prognostic value of total bilirubin in patients with acute myocardial infarction: A meta-analysis.

BACKGROUND: Experimental data obtained in animal models supported the protective role of bilirubin. However, clinical studies regarding the prognostic role of total bilirubin in patients with acute myocardial infarction (AMI) are conflicting. We, therefore, undertook this meta-analysis to evaluate the prognostic value of serum total bilirubin in AMI patients. METHODS: Relevant studies were searched from PubMed and EMBASE databases up to April 15, 2018. Studies evaluating the outcomes in relation to serum total bilirubin in AMI patients and reporting multivariable-adjusted risk estimate of the prognostic value were eligible. The outcome measures were major adverse cardiac events (MACEs), cardiovascular death, and all-cause mortality. RESULTS: Six studies involving 14,554 AMI patients were identified. Meta-analysis indicated that higher total bilirubin was associated with an increased risk of MACEs (risk ratio [RR] 1.65; 95% confidence intervals [CI] 1.25-2.19) and cardiovascular death (RR 2.12; 95%CI 1.24-3.64). However, higher serum total bilirubin did not significantly increase all-cause mortality risk (RR 1.31; 95%CI 0.75-2.28). Subgroup analyses by the types of AMI and study design supported the pooled results. CONCLUSIONS: Higher serum total bilirubin level is a predictor of MACEs and cardiovascular death in patients with AMI. However, interpretation of these findings should be with caution due to the impact of cardiac dysfunction after AMI.

Dynamics of motor cortical activity during naturalistic feeding behavior.

OBJECTIVE: The orofacial primary motor cortex (MIo) plays a critical role in controlling tongue and jaw movements during oral motor functions, such as chewing, swallowing and speech. However, the neural mechanisms of MIo during naturalistic feeding are still poorly understood. There is a strong need for a systematic study of motor cortical dynamics during feeding behavior. APPROACH: To investigate the neural dynamics and variability of MIo neuronal activity during naturalistic feeding, we used chronically implanted micro-electrode arrays to simultaneously recorded ensembles of neuronal activity in the MIo of two monkeys (Macaca mulatta) while eating various types of food. We developed a Bayesian nonparametric latent variable model to reveal latent structures of neuronal population activity of the MIo and identify the complex mapping between MIo ensemble spike activity and high-dimensional kinematics. MAIN RESULTS: Rhythmic neuronal firing patterns and oscillatory dynamics are evident in single-unit activity. At the population level, we uncovered the neural dynamics of rhythmic chewing, and quantified the neural variability at multiple timescales (complete feeding sequences, chewing sequence stages, chewing gape cycle phases) across food types. Our approach accommodates time-warping of chewing sequences and automatic model selection, and maps the latent states to chewing behaviors at fine timescales. SIGNIFICANCE: Our work shows that neural representations of MIo ensembles display spatiotemporal patterns in chewing gape cycles at different chew sequence stages, and these patterns vary in a stage-dependent manner. Unsupervised learning and decoding analysis may reveal the link between complex MIo spatiotemporal patterns and chewing kinematics.