Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats

Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction

An innovative EEG-based emotion recognition using a single channel-specific feature from the brain rhythm code method.

Efficiently recognizing emotions is a critical pursuit in brain–computer interface (BCI), as it has many applications for intelligent healthcare services. In this work, an innovative approach inspired by the genetic code in bioinformatics, which utilizes brain rhythm code features consisting of δ, θ, α, β, or γ, is proposed for electroencephalography (EEG)-based emotion recognition. These features are first extracted from the sequencing technique. After evaluating them using four conventional machine learning classifiers, an optimal channel-specific feature that produces the highest accuracy in each emotional case is identified, so emotion recognition through minimal data is realized. By doing so, the complexity of emotion recognition can be significantly reduced, making it more achievable for practical hardware setups. The best classification accuracies achieved for the DEAP and MAHNOB datasets range from 83–92%, and for the SEED dataset, it is 78%. The experimental results are impressive, considering the minimal data employed. Further investigation of the optimal features shows that their representative channels are primarily on the frontal region, and associated rhythmic characteristics are typical of multiple kinds. Additionally, individual differences are found, as the optimal feature varies with subjects. Compared to previous studies, this work provides insights into designing portable devices, as only one electrode is appropriate to generate satisfactory performances. Consequently, it would advance the understanding of brain rhythms, which offers an innovative solution for classifying EEG signals in diverse BCI applications, including emotion recognition

Exclusive real-time monitoring during recurrent laryngeal nerve dissection in conventional monitored thyroidectomy

Abstract During conventional intermittent intraoperative neuromonitoring (IONM) in thyroidectomy, recurrent laryngeal nerve (RLN) injury is detected by an electromyographic (EMG) loss of signal (LOS) after the nerve dissection. Exclusive continuous monitoring during the phase of RLN dissection may be helpful in detecting adverse EMG changes earlier. A total of 208 RLNs at risk were enrolled in this study. Standardized IONM procedures were followed. We continuously stimulated the RLN at the lower exposed end with a stimulator to exclusively monitor the real-time quantitative EMG change during RLN dissection. Once the amplitude decreased by more than 50% of the initial signal, the surgical maneuver was paused and the RLN was retested every minute for 10 minutes to determine amplitude recovery before restarting the dissection. The procedure was feasible in all patients. No LOS was encountered in this study. Nineteen RLNs had an amplitude reduction of more than 50%. Eighteen nerves showed gradual amplitude recovery (16 nerves had a traction injury and two nerves had a compression injury). After 10 minutes, the recovery was complete (i.e., >90%) in eight nerves, 70–90% in seven nerves, and 50–70% in three nerves. Among these 18 nerves, only one nerve developed temporary vocal palsy because it was exposed to unavoidable repeated nerve traction after restarting the dissection. Another nerve showed no gradual recovery from thermal injury, and developed temporary vocal palsy. The temporary and permanent palsy rates were 1% and 0%, respectively. During intermittent IONM, exclusive real-time monitoring of the RLN during dissection is an effective procedure to detect an adverse EMG change, and prevent severe RLN injuries that cause LOS

An innovative EEG-based emotion recognition using a single channel-specific feature from the brain rhythm code method

IntroductionEfficiently recognizing emotions is a critical pursuit in brain–computer interface (BCI), as it has many applications for intelligent healthcare services. In this work, an innovative approach inspired by the genetic code in bioinformatics, which utilizes brain rhythm code features consisting of δ, θ, α, β, or γ, is proposed for electroencephalography (EEG)-based emotion recognition.MethodsThese features are first extracted from the sequencing technique. After evaluating them using four conventional machine learning classifiers, an optimal channel-specific feature that produces the highest accuracy in each emotional case is identified, so emotion recognition through minimal data is realized. By doing so, the complexity of emotion recognition can be significantly reduced, making it more achievable for practical hardware setups.ResultsThe best classification accuracies achieved for the DEAP and MAHNOB datasets range from 83–92%, and for the SEED dataset, it is 78%. The experimental results are impressive, considering the minimal data employed. Further investigation of the optimal features shows that their representative channels are primarily on the frontal region, and associated rhythmic characteristics are typical of multiple kinds. Additionally, individual differences are found, as the optimal feature varies with subjects.DiscussionCompared to previous studies, this work provides insights into designing portable devices, as only one electrode is appropriate to generate satisfactory performances. Consequently, it would advance the understanding of brain rhythms, which offers an innovative solution for classifying EEG signals in diverse BCI applications, including emotion recognition

Immunoassays Based on Penicillium marneffei Mp1p Derived from Pichia pastoris Expression System for Diagnosis of Penicilliosis

BACKGROUND: Penicillium marneffei is a dimorphic fungus endemic in Southeast Asia. It can cause fatal penicilliosis in humans, particularly in HIV-infected people. Diagnosis of this infection is difficult because its clinical manifestations are not distinctive. Specialized laboratory tests are necessary to establish a definitive diagnosis for successful management. We have demonstrated previously that a cell wall mannoprotein Mp1p, abundant in P. marneffei, is a potential biomarker for diagnosis of P. marneffei infections. In the present study, we describe immunoassays based on Mp1p derived from the yeast Pichia pastoris expression system. METHODOLOGY/PRINCIPAL FINDINGS: We generated monoclonal antibodies (MAbs) and rabbit polyclonal antibodies (PAbs) against Mp1p expressed in P. pastoris. Subsequently, we developed two Mp1p antigen capture ELISAs which employed MAbs for both the capture and detecting antibodies (MAb-MAb pair) or PAbs and MAbs as the capture and detecting antibodies (PAbs-MAb pair) respectively. The two Mp1p antigen ELISAs detected Mp1p specifically in cultures of P. marneffei yeast phase at 37-40 degrees C and had no cross-reaction with other tested pathogenic fungi. The sensitivities and specificities of the two antigen assays were found to be 55% (11/20) and 99.6% (538/540) for MAb-MAb Mp1p ELISA, and 75% (15/20) and 99.4% (537/540) for PAbs-MAb Mp1p ELISA performed using 20 sera with culture-confirmed penicilliosis, and 540 control sera from 15 other mycosis patients and 525 healthy donors. Meanwhile, we also developed an anti-Mp1p IgG antibody ELISA with an evaluated sensitivity of 30% (6/20) and a specificity of 98.5% (532/540) using the same sera. Furthermore, combining the results of Mp1p antigen and antibody detection improved the sensitivity of diagnosis to 100% (20/20). CONCLUSIONS/SIGNIFICANCE: Simultaneous detection of antigen and antibody using the immunoassays based on Mp1p derived from P. pastoris greatly improves detection sensitivity. The procedures should be useful for the routine diagnosis of penicilliosis.published_or_final_versio

Common Features in Electronic Structure of the Fe-Based Layered Superconductors from Photoemission Spectroscopy

High resolution photoemission measurements have been carried out on non-superconducting LaOFeAs parent compound and various superconducting R(O1-xFx)FeAs (R=La, Ce and Pr) compounds. We found that the parent LaOFeAs compound shows a metallic character. Through extensive measurements, we have identified several common features in the electronic structure of these Fe-based compounds: (1). 0.2 eV feature in the valence band; (2). A universal 13~16 meV feature; (3). A clear Fermi cutoff showing zero leading-edge shift in the superconducting state;(4). Lack of superconducting coherence peak(s); (5). Near EF spectral weight suppression with decreasing temperature. These universal features can provide important information about band structure, superconducting gap and pseudogap in these Fe-based materials.Comment: 5 pages,4 figure

DNA Methylation and Histone Modifications Regulate De Novo Shoot Regeneration in Arabidopsis by Modulating WUSCHEL Expression and Auxin Signaling

Plants have a profound capacity to regenerate organs from differentiated somatic tissues, based on which propagating plants in vitro was made possible. Beside its use in biotechnology, in vitro shoot regeneration is also an important system to study de novo organogenesis. Phytohormones and transcription factor WUSCHEL (WUS) play critical roles in this process but whether and how epigenetic modifications are involved is unknown. Here, we report that epigenetic marks of DNA methylation and histone modifications regulate de novo shoot regeneration of Arabidopsis through modulating WUS expression and auxin signaling. First, functional loss of key epigenetic genes—including METHYLTRANSFERASE1 (MET1) encoding for DNA methyltransferase, KRYPTONITE (KYP) for the histone 3 lysine 9 (H3K9) methyltransferase, JMJ14 for the histone 3 lysine 4 (H3K4) demethylase, and HAC1 for the histone acetyltransferase—resulted in altered WUS expression and developmental rates of regenerated shoots in vitro. Second, we showed that regulatory regions of WUS were developmentally regulated by both DNA methylation and histone modifications through bisulfite sequencing and chromatin immunoprecipitation. Third, DNA methylation in the regulatory regions of WUS was lost in the met1 mutant, thus leading to increased WUS expression and its localization. Fourth, we did a genome-wide transcriptional analysis and found out that some of differentially expressed genes between wild type and met1 were involved in signal transduction of the phytohormone auxin. We verified that the increased expression of AUXIN RESPONSE FACTOR3 (ARF3) in met1 indeed was due to DNA demethylation, suggesting DNA methylation regulates de novo shoot regeneration by modulating auxin signaling. We propose that DNA methylation and histone modifications regulate de novo shoot regeneration by modulating WUS expression and auxin signaling. The study demonstrates that, although molecular components involved in organogenesis are divergently evolved in plants and animals, epigenetic modifications play an evolutionarily convergent role in this process

SEPTIN12 Genetic Variants Confer Susceptibility to Teratozoospermia

It is estimated that 10–15% of couples are infertile and male factors account for about half of these cases. With the advent of intracytoplasmic sperm injection (ICSI), many infertile men have been able to father offspring. However, teratozoospermia still remains a big challenge to tackle. Septins belong to a family of cytoskeletal proteins with GTPase activity and are involved in various biological processes e.g. morphogenesis, compartmentalization, apoptosis and cytokinesis. SEPTIN12, identified by c-DNA microarray analysis of infertile men, is exclusively expressed in the post meiotic male germ cells. Septin12+/+/Septin12+/− chimeric mice have multiple reproductive defects including the presence of immature sperm in the semen, and sperm with bent neck (defect of the annulus) and nuclear DNA damage. These facts make SEPTIN12 a potential sterile gene in humans. In this study, we sequenced the entire coding region of SEPTIN12 in infertile men (n = 160) and fertile controls (n = 200) and identified ten variants. Among them is the c.474 G>A variant within exon 5 that encodes part of the GTP binding domain. The variant creates a novel splice donor site that causes skipping of a portion of exon 5, resulting in a truncated protein lacking the C-terminal half of SEPTIN12. Most individuals homozygous for the c.474 A allele had teratozoospermia (abnormal sperm <14%) and their sperm showed bent tail and de-condensed nucleus with significant DNA damage. Ex vivo experiment showed truncated SEPT12 inhibits filament formation in a dose-dependent manner. This study provides the first causal link between SEPTIN12 genetic variant and male infertility with distinctive sperm pathology. Our finding also suggests vital roles of SEPT12 in sperm nuclear integrity and tail development