Widespread slow oscillations support interictal epileptiform discharge networks in focal epilepsy.

Interictal epileptiform discharges (IEDs) often co-occur across spatially-separated cortical regions, forming IED networks. However, the factors prompting IED propagation remain unelucidated. We hypothesized that slow oscillations (SOs) might facilitate IED propagation. Here, the amplitude and phase synchronization of SOs preceding propagating and non-propagating IEDs were compared in 22 patients with focal epilepsy undergoing intracranial electroencephalography (EEG) evaluation. Intracranial channels were categorized into the irritative zone (IZ) and normal zone (NOZ) regarding the presence of IEDs. During wakefulness, we found that pre-IED SOs within the IZ exhibited higher amplitudes for propagating IEDs than non-propagating IEDs (delta band: p = 0.001, theta band: p < 0.001). This increase in SOs was also concurrently observed in the NOZ (delta band: p = 0.04). Similarly, the inter-channel phase synchronization of SOs prior to propagating IEDs was higher than those preceding non-propagating IEDs in the IZ (delta band: p = 0.04). Through sliding window analysis, we observed that SOs preceding propagating IEDs progressively increased in amplitude and phase synchronization, while those preceding non-propagating IEDs remained relatively stable. Significant differences in amplitude occurred approximately 1150 ms before IEDs. During non-rapid eye movement (NREM) sleep, SOs on scalp recordings also showed higher amplitudes before intracranial propagating IEDs than before non-propagating IEDs (delta band: p = 0.006). Furthermore, the analysis of IED density around sleep SOs revealed that only high-amplitude sleep SOs demonstrated correlation with IED propagation. Overall, our study highlights that transient but widely distributed SOs are associated with IED propagation as well as generation in focal epilepsy during sleep and wakefulness, providing new insight into the EEG substrate supporting IED networks.

A region-specific modulation of sleep slow waves on interictal epilepsy markers in focal epilepsy.

OBJECTIVE: Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy. METHODS: Simultaneous polysomnography was performed in 45 patients with drug-resistant focal epilepsy during intracranial electroencephalographic recording. Scalp SSWs and intracranial spikes and ripples (80-250 Hz) were detected; ripples were classified as type I (co-occurring with spikes) or type II (occurring alone). The Hilbert transform was used to analyze the distributions of spikes and ripples in the phases of SSWs. RESULTS: Thirty patients with discrete seizure-onset zone (SOZ) and discernable sleep architecture were included. Intracranial spikes and ripples accumulated around the negative peaks of SSWs and increased with SSW amplitude. Phase analysis revealed that spikes and both ripple subtypes in SOZ were similarly facilitated by SSWs exclusively during down state. In exclusively irritative zones outside SOZ (EIZ), SSWs facilitated spikes and type I ripples across a wider range of phases and to a greater extent than those in SOZ. The type II and type I ripples in EIZ were modulated by SSWs in different patterns. Ripples in normal zones decreased specifically during the up-to-down transition and then increased after the negative peak of SSW, with a characteristically high post-/pre-negative peak ratio. SIGNIFICANCE: SSWs modulate interictal events in an amplitude-dependent and region-specific pattern. Pathological ripples and spikes were facilitated predominantly during the cortical down state. Coupling analysis of SSWs could improve the discrimination of pathological and physiological ripples and facilitate seizure localization.

Up-regulation of PPAR-γ involved in the therapeutic effect of icariin on cigarette smoke-induced inflammation.

Icariin (ICA) might be a potential anti-inflammatory medication in a variety of diseases including COPD, and previous studies showed that ICA could attenuate cigarette smoke (CS)-induced inflammation by inhibiting nuclear factor (NF)-κB. Peroxisome proliferator-activated receptor (PPAR) γ, a nuclear hormone receptor, has been reported to play a critical role in the inflammatory process in COPD. Whether PPAR-γ is involved in the anti-inflammatory effect of icariin on COPD has scarcely been explored. This study aimed at investigating the role of ICA in PPAR-γ expression in the CS-induced model, and then elucidating the therapeutic effects of ICA on COPD based on the PPARγ-NF-κB signaling pathway. The Beas-2B cells and H292 cells were induced with cigarette smoke extract (CSE) for 8 h after treatment with ICA for 16 h. The PPARγ expression and NF-κB pathway-related indicators were detected by western blotting, cellular immunofluorescence, and Real-time PCR. The PPARγ knock down or T0070907-treated Beas-2B cells were constructed to further investigate the relationship between the inhibition of NF-κB by ICA and PPARγ. A COPD model was established by CS exposure for 6 months, and ICA (40 mg/kg) was administrated by gastric perfusion. Then, the pulmonary function, lung histology, inflammatory cytokine levels, and protein expressions were detected. We found ICA up-regulated PPARγ protein expression in both Beas-2B cells and H292 cells, and it improved CSE-induced PPARγ down regulation and NF-κB activation. Furthermore, the inhibition of NF-κB pathway by ICA was partially dependent on PPARγ in the PPARγ knock down or T0070907-treated Beas-2B cells, suggesting that ICA attenuated CSE-induced inflammatory responses were associated with modulating the PPARγ-NF-κB pathway. Moreover, ICA showed similar effects on PPARγ and NF-κB expressions in the COPD model, and it effectively ameliorated the pulmonary function and lung inflammatory infiltration in the COPD rat model. Conclusively, the therapeutic effect of ICA on COPD was indirectly achieved by reducing airway inflammation, which was partially associated with modulating the PPARγ-NF-κB signaling pathway.

Integrative Analysis of DNA Methylation and Gene Expression Data Identifies Potential Biomarkers and Functional Epigenetic Modules for SARS-CoV-2.

To integrate gene expression and DNA methylation data and find the potential role of DNA methylation in the invasion and replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We first conducted differential expression and methylation analysis between the coronavirus disease of 2019 (COVID-19) and healthy controls. FEM was employed to identify functional epigenetic modules, from which a diagnostic model for COVID-19 was built. SKA1 and WSB1 modules were identified, with SKA1 module enriched in COVID-19 replication and transcription, and WSB1 module related to ubiquitin-protein activity. The differentially expressed or differentially methylated genes in these two modules could be used to distinguish COVID-19 from healthy controls, with AUC reaching 1 and 0.98 for SKA1 and WSB1 modules, respectively. Two epigenetically activated genes (CENPM and KNL1) from the SKA1 module were upregulated in HPV- or HBV-positive tumor samples and were found to be significantly associated with the survival of tumor patients. In conclusion, the identified FEM modules and potential signatures play an essential role in the replication and transcription of coronavirus.

Inhibition of HSPA8 by rifampicin contributes to ferroptosis via enhancing autophagy.

BACKGROUND AND AIM: Rifampicin is the most common pathogenic factor in anti-tuberculosis drug-induced liver injury (AT-DILI), the mechanisms that it promotes hepatocyte damage in AT-DILI are not yet to be thoroughly elucidated. In this study, we investigated the potential molecular mechanisms for ferroptosis involving rifampicin hepatotoxicity. METHODS: Animal and cell injury models of rifampicin were constructed, and the toxicity of rifampicin was assessed by physicochemical staining and cell viability assay. Next, flow cytometry was employed to detect changes in ferroptosis-related markers, and Western blotting was used to detect protein expression. Then, the important role of autophagy and ferroptosis was verified with small molecule compound intervention. RESULTS: We found that ferritinophagy-induced ferroptosis participates in the toxicity of rifampicin, and the mechanism is that rifampicin precisely activates high-throughput autophagy, which leads to the massive degradation of ferritin and the increase of free iron. Moreover, rifampicin exhibited conspicuous inhibition of Human 71 kDa heat shock cognate protein (HSPA8) that is intimately associated with Microtubule-associated protein light chain 3 isoform B (LC3B) expression, in turn, HSPA8 inducer attenuated intracellular autophagy flux. Of note, inducing HSPA8 or inhibition of autophagy and ferroptosis considerably relieved the hepatotoxicity of rifampicin in mouse model. CONCLUSIONS: The present study highlights the crucial roles of the HSPA8 and autophagy in ferroptotic cell death driving by rifampicin, particularly illumines multiple promising regulatory nodes for therapeutic interventions in diseases involving AT-DILI.

Cholecystokinin release triggered by NMDA receptors produces LTP and sound-sound associative memory.

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK-/- mice lacked neocortical LTP and showed deficits in a cue-cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue-cue associative memory.

Role of eosinophils in the diagnosis and prognostic evaluation of COVID-19.

Severe acute respiratory syndrome coronavirus 2 is responsible for the coronavirus disease 2019 (COVID-19) epidemic, which has severely affected global public health security. However, the diagnosis and treatment of the disease need further exploration. Therefore, this retrospective analysis was conducted on multiple indicators of peripheral blood in patients with COVID-19 to determine the role of leukocytes, lymphocytes, and eosinophils in the diagnosis and prognostic evaluation of COVID-19. Baseline information and clinical records of 40 patients were collected, including demographic data, disease status, medication, and laboratory routine. The correlation between the inspection indicators and disease classification, as well as prognostic factors, was analyzed. Decreased eosinophils were detected in 33 out of 40 patients with COVID-19 on admission, while lymphocytes and eosinophils were inversely related to the severity of the disease, according to the Spearman's correlation coefficient. Thus, it could be deduced that eosinophils have better sensitivity for the diagnosis of COVID-19 and play a major role similar to lymphocytes in assessing the prognosis of patients.

Cortical Excitability in Temporal Lobe Epilepsy with Bilateral Tonic-Clonic Seizures.

OBJECTIVE: We investigated motor cortical excitability (CE) in unilateral temporal lobe epilepsy (TLE) and its relationship to bilateral tonic-clonic seizure (BTCS) using paired-pulse transcranial magnetic stimulation (TMS). METHODS: In this cross-sectional study, we enrolled 46 unilateral TLE patients and 16 age-and sex-matched healthy controls. Resting motor thresholds (RMT); short-interval intracortical inhibition (SICI, GABAA receptor-mediated); facilitation (ICF, glutamatergic-mediated) with interstimulus intervals (ISIs) of 2, 5, 10, and 15 ms; and long-interval intracortical inhibition (LICI, GABAB receptor-mediated) with ISIs of 200-400 ms were measured via paired-pulse TMS. Comparisons were made between controls and patients with TLE, and then among the TLE subgroups (no BTCS, infrequent BTCS and frequent BTCS subgroup). RESULTS: Compared with controls, TLE patients had higher RMT, lower SICI and higher LICI in both hemispheres, and higher ICF in the ipsilateral hemisphere. In patients with frequent BTCS, cortical hyperexcitability in the ipsilateral hemisphere was found in a parameter-dependent manner (SICI decreased at a stimulation interval of 5 ms, and ICF increased at a stimulation interval of 15 ms) compared with patients with infrequent or no BTCS. CONCLUSIONS: Our results demonstrate that motor cortical hyper-excitability in the ipsilateral hemisphere underlies the epileptogenic network of patients with active BTCS, which is more extensive than those with infrequent or no BTCS.

Study on the activity of recombinant mutant tissue-type plasminogen activator fused with the C-terminal fragment of hirudin.

In the present study, bifunctional fusion proteins were designed by fusing the kringle 2 and protease domains of tissue-type plasminogen activator (tPA) to the C-terminal fragment of hirudin. The thrombolytic and anticoagulant activities of these recombinant proteins from mammalian cells were investigated using in vitro coagulation models and chromogenic assays. The results showed that all assayed tPA mutants retained catalytic activity. The C-terminal fragment of hirudin may have weak affinity to thrombin and thus was insufficient to suppress thrombin-mediated fibrin agglutination. The strength of the thrombolytic activity only relied on the selected tPA sequences, and the fibrinolytic efficiency of single-chain protein significantly decreased. Our data indicate that truncated tPA combined with a hirudin peptide may provide a framework for the further development of a new antithrombotic agent.

Inhibition of airway remodeling and inflammatory response by Icariin in asthma.

BACKGROUND: Icariin (ICA) is the major active ingredient extracted from Chinese herbal medicine Epimedium, which has the effects of improving cardiovascular function, inducing tumor cell differentiation and increasing bone formation. It is still rarely reported that ICA can exert its therapeutic potential in asthma via anti-airway remodeling. The point of the study was to estimate the role of ICA in anti-. airway remodeling and its possible mechanism of action in a mouse ovalbumin. (OVA)-induced asthma model. METHODS: Hematoxylin and Eosin Staining were performed for measuring airway remodeling related indicators. ELISA, Western blot and Immunohistochemistr-. y (IHC) were used for analyzing the level of protein. RT-PCR was used for analyzing the level of mRNA. RESULTS: On days 1 and 8, mice were sensitized to OVA by intraperitoneal injection. From day 16 to day 43, previously sensitized mice were exposed to OVA once daily by nebulizer. Interventions were performed orally with ICA (ICA low, medium and high dose groups) or dexamethasone 1 h prior to each OVA exposure. ICA improves pulmonary function, attenuates pulmonary inflammation and airway remodeling in mice exposed to OVA. Histological and Western blot analysis of the lungs show that ICA suppressed transforming growth factor beta 1 and vascular endothelial growth factor expression. Increase in interleukin 13 and endothelin-1 in serum and bronchoalveolar lavage fluid in OVA-induced asthmatic mice are also decreased by ICA. ICA attenuates airway smooth muscle cell proliferation, as well as key factors in the MAPK/Erk pathway. CONCLUSIONS: The fact that ICA can alleviate OVA-induced asthma at least partly through inhibition of ASMC proliferation via MAPK/Erk pathway provides a solid theoretical basis for ICA as a replacement therapy for asthma. These data reveal the underlying reasons of the use of ICA-rich herbs in Traditional Chinese Medicine to achieve good results in treating asthma.

Emotional Distress Correlates Among Patients With Chronic Nonspecific Low Back Pain: A Hierarchical Linear Regression Analysis.

BACKGROUND: Chronic low back pain (CLBP) has become a worldwide health concern, and emotional distress is an important issue for CLBP management. However, it remains poorly understood how emotional distress happens and develops. This study aimed to systematically explore the correlates of emotional distress in patients with CLBP. METHODS: The study was a multisite, cross-sectional survey with a sample of 252 patients with CLBP in urban communities. A battery of questionnaires was used to collect data. Univariate analysis, Pearson correlation analysis, and hierarchical linear regression analysis were performed. RESULTS: The mean score of emotional distress among 252 patients with CLBP was 13.85 ± 6.50. Hierarchical regression analysis indicated that the demographic factors, psychobehavioral factors, and social support of patients with CLBP were associated with their emotional distress, uniquely explaining 16.5%, 18.4%, and 6.2% of the variance, respectively. Five factors were found to be associated with patients' emotional distress: pain intensity (ß = 0.257, P < 0.001), passive coping (ß = 0.297, P < 0.001), active coping (ß = -0.254, P < 0.001), self-efficacy (ß = -0.155, P = 0.005), and social support (ß = -0.268, P < 0.001). CONCLUSIONS: Patients with CLBP suffered from clinically significant emotional distress. Patients' demographics, psychobehavioral factors, and social support were all related to emotional distress. The findings help us to identify the characteristics of patients with CLBP at high risk for emotional distress and to formulate corresponding countermeasures. LAY SUMMARY: This study aimed to explored the correlates of emotional distress of patients with chronic low back pain (CLBP) by hierarchical linear regression analysis. The study found that patients' demographic factors, psycho-behavioral factors, and social support were associated with their emotional distress, uniquely explaining 16.5%, 18.4%, and 6.2% of the variance, respectively. Pain intensity, passive coping, active coping, self-efficacy, and social support were detected as significant correlates.

The Influence of Self-Efficacy, Fear-Avoidance Belief, and Coping Styles on Quality of Life for Chinese Patients with Chronic Nonspecific Low Back Pain: A Multisite Cross-Sectional Study.

BACKGROUND: As a bio-psycho-social issue, chronic low back pain (CLBP) has been a significant topic in health management, and patients' quality of life (QOL) is gaining extensive attention. Self-efficacy, pain fear-avoidance belief (FAB), and coping styles play important roles in the QOL of CLBP patients. However, it remains unclear how self-efficacy and FAB influence QOL through specific coping styles. This study aimed to explore the influencing paths of self-efficacy, FAB, and coping styles on the QOL of patients with CLBP. METHODS: This study relies on a multisite, cross-sectional design involving 221 CLBP patients. Stepwise multiple regression and structural equation modeling were employed. RESULTS: CLBP patients lived with a poor global QOL. Self-efficacy played a direct, positive role in predicting QOL for patients with CLBP (ß = 0.35), and it also played an indirect, positive role in predicting QOL (ß = 0.19) through active coping styles (ß = 0.31). FAB played a direct, negative role in predicting QOL (ß = -0.33), and it also played an indirect, negative role in predicting QOL (ß = -0.32) through passive coping styles (ß = 0.32). CONCLUSIONS: Self-efficacy and FAB are both directly and indirectly related to global QOL, and coping styles are important mediating variables. Self-efficacy and active coping are protective factors for the QOL of CLBP patients, while FAB and passive coping are risk factors. Health education strategies are recommended by medical personnel to enhance CLBP patients' pain self-efficacy, decrease pain FAB, and modify pain coping styles, so that their global QOL can be improved.

Activation of 5-HT2A/C receptor reduces glycine receptor-mediated currents in cultured auditory cortical neurons.

Glycine receptors (GlyRs) permeable to chloride only mediate tonic inhibition in the cerebral cortex where glycinergic projection is completely absent. The functional modulation of GlyRs was largely studied in subcortical brain regions with glycinergic transmissions, but the function of cortical GlyRs was rarely addressed. Serotonin could broadly modulate many ion channels through activating 5-HT2 receptor, but whether cortical GlyRs are subjected to serotonergic modulation remains unexplored. The present study adopted patch clamp recordings to examine functional regulation of strychnine-sensitive GlyRs currents in cultured cortical neurons by DOI (2,5-Dimethoxy-4-iodoamphetamine), a 5-HT2A/C receptor agonist. DOI caused a concentration-dependent reduction of GlyR currents with unchanged reversal potential. This reduction was blocked by the selective receptor antagonists (ritanserin and risperidone) and G protein inhibitor (GDP-ß-s) demonstrated that the reducing effect of DOI on GlyR current required the activation of 5-HT2A/C receptors. Strychnine-sensitive tonic currents revealed the inhibitory tone mediated by nonsynaptic GlyRs, and DOI similarly reduced the tonic inhibition. The impaired microtube-dependent trafficking or clustering of GlyRs was thought to be involved in that nocodazole as a microtube depolymerizing drug largely blocked the inhibition mediated by 5-HT2A/C receptors. Our results suggested that activation of 5-HT2A/C receptors might suppress cortical tonic inhibition mediated by GlyRs, and the findings would provide important insight into serotonergic modulation of tonic inhibition mediated by GlyRs, and possibly facilitate to develop the therapeutic treatment of neurological diseases such as tinnitus through regulating cortical GlyRs.

Comparison of Serum Human Epididymis Protein 4 and Carbohydrate Antigen 125 as Markers in Endometrial Cancer: A Meta-Analysis.

OBJECTIVES: For patients with endometrial cancer (EC), the screening value of serum human epididymis protein 4 (HE4) remains controversial. We performed meta-analyses to compare the screening accuracy of serum HE4 and carbohydrate antigen 125 (CA125) for EC. MATERIALS AND METHODS: A search of diagnostic test studies was performed in 5 English databases: Pubmed, Cochrane Library, Web of Science, Science Direct, and Elton Bryan Stephens Co or EBSCO; and 2 Chinese databases including China National Knowledge Infrastructure or CNKI and VIP (Weipu Database), from their inception dates to early July 2015. Two reviewers independently selected trials, conducted critical appraisal, and extracted data. Meta-analyses were performed to compare the screening accuracy between HE4 and CA125. Summary receiver operating characteristic curve and the area under the summary receiver operating characteristic curve were performed. Subgroup analysis, meta-regression, sensitivity analysis, and Egger plot and the Egger test were also conducted. RESULTS: Twenty-one studies were identified, and the methodological quality was generally fair. Meta-analyses revealed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratios for HE4 in screening EC were 0.56, 0.89, 6.41, 0.49, and 14.82, respectively, whereas the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for CA125 in screening EC were 0.32, 0.81, 2.15, 0.83, and 2.74, respectively. The areas under the summary receiver operating characteristic curves for HE4 and CA125 were 0.7778 and 0.5474, respectively. CONCLUSIONS: This study indicates that serum HE4 may be superior to CA125 in screening accuracy of EC. This conclusion has to be interpreted cautiously owing to high heterogeneity and some limitations.

Mutation rate analysis at 19 autosomal microsatellites.

Previous studies have demonstrated that a large sample size is needed to reliably estimate population- and locus-specific microsatellite mutation rates. Therefore, we conducted a long-term collaboration study and performed a comprehensive analysis on the mutation characteristics of 19 autosomal short tandem repeat (STR) loci. The STR loci located on 15 of 22 autosomal chromosomes were analyzed in a total of 21,106 samples (11,468 parent-child meioses) in a Chinese population. This provided 217,892 allele transfers at 19 STR loci. An overall mutation rate of 1.20 × 10(-3) (95% CI, 1.06-1.36 × 10(-3) ) was observed in the populations across 18 of 19 STR loci, except for the TH01 locus with no mutation found. Most STR mutations (97.7%) were single-step mutations, and only a few mutations (2.30%) comprised two and multiple steps. Interestingly, approximately 93% of mutation events occur in the male germline. The mutation ratios increased with the paternal age at child birth (r = 0.99, p<0.05), but not maternal age. Last, with the combination analysis of the data from the southern Chinese population, we drew a picture of 19 STR mutations in China. In conclusion, the data from this study will provide useful information in parentage testing, kinship analysis, and population genetics.

Knockdown of TXNIP alleviates gestational diabetes mellitus by activating autophagy to regulate cell proliferation and apoptosis in high glucose-treated trophoblasts.

Dysregulated thioredoxin-interacting protein (TXNIP) has been observed in women with gestational diabetes mellitus (GDM), but the specific role of TXNIP in GDM and the underlying mechanism remain unclear. HTR-8/SVneo cells were treated with high glucose to mimic the injured trophoblasts of GDM. In vitro, TXNIP knockdown was performed by siRNA. RTqPCR was performed to determine the expression of the corresponding genes. Cell proliferation and apoptosis were measured using CCK-8, EdU and Annexin V/PI assays. The autophagosome number was assessed using transmission electron microscopy. The expression of the autophagy substrate sequestosome 1 (P62) was evaluated by immunofluorescence. Autophagy-related proteins, including P62, light chain 3 (LC3)-I, and LC3-II, were analysed by Western blotting. HTR-8/Svneo cells treated with high glucose demonstrated reduced proliferation, increased apoptosis, decreased autophagosome formation and overall decreased autophagy. However, knockdown of TXNIP reversed the effects of HG on HTR-8/Svneo cells. However, the effect of TXNIP knockdown on HG-treated HTR-8/Svneo cells was inhibited by 3-methyladenine (3-MA) (widely used as an inhibitor of autophagy). We concluded that knockdown of TXNIP has the potential to enhance the activity of high glucose-treated human trophoblasts through autophagic activation, thereby improving pregnancy outcomes in patients with GDM.

The Immunomodulatory effect of exosomes in diabetes: a novel and attractive therapeutic tool in diabetes therapy.

Exosomes carry proteins, metabolites, nucleic acids and lipids from their parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes.

Seizures and electrophysiological features in familial cortical myoclonic tremor with epilepsy 1.

OBJECTIVES: To investigate and characterize epileptic seizures and electrophysiological features of familial cortical myoclonic tremor with epilepsy (FCMTE) type 1 patients in a large Chinese cohort. METHODS: We systematically evaluated 125 FCMTEtype 1 patients carrying the pentanucleotide (TTTCA) repeat expansion in the SAMD12 gene in China. RESULTS: Among the 28 probands, epileptic seizures (96.4%, 27/28) were the most common reason for an initial clinic visit. Ninety-seven (77.6%, 97/125) patients had experienced seizures. The seizures onset age was 36.5 ± 9.0 years, which was 6.9 years later than cortical tremors. The seizures were largely rare (<1/year, 58.8%) and occasional (1-6/year, 37.1%). Prolonged prodromes were reported in 57.7% (56/97). Thirty-one patients (24.8%, 31/125) reported photosensitivity history, and 79.5% (31/39) had a photoparoxysmal response. Interictal epileptiform discharges (IEDs) were recorded in 69.1% (56/81) of patients. Thirty-three patients showed generalized IEDs and 72.7% (24/33) were occipitally dominant, while 23 patients presented with focal IEDs with 65.2% (15/23) taking place over the occipital lobe. Overnight EEG of FCMTE patients displayed paradoxical sleep-wake fluctuation, with a higher average IED index of 0.82 ± 0.88/min during wakefulness and a lower IED index of 0.04 ± 0.06/min during non-rapid eye movement sleep stages I-II. INTERPRETATION: FCMTE type 1 has a benign course of epilepsy and distinct clinical and electrophysiological features. In addition to a positive family history and cortical myoclonus tremor, the seizure prodromes, specific seizure triggers, photosensitivity, distribution of IEDs, and unique fluctuations during sleep-wake cycle are cues for proper genetic testing and an early diagnosis of FCMTE.

Factors affecting accommodation hosts' willingness to use ground-source heat pumps (GSHPs).

Clean energy products have increased market share over the past few years. The ground-source heat pumps (GSHPs), however, do not enjoy such a favorable status in China. This research uses the theory of planned behavior to investigate accommodation operators' readiness to adopt GSHPs and the factors that impact their decision. A total of 251 accommodation operators across the nation were investigated. The results show that, financial benefits and policy privilege play a significant positive role in promoting the installation of GSHPs, while the deterrents include installation cost, installation condition, and technical maturity. Unlike previous studies, environmental awareness does not contribute significantly. The insights reached in this research can be used to guide future improvements in ground source heat pump technology, as well as serve as a resource for relevant government departments in developing effective marketing campaigns.

Baicalin Inhibits Airway Smooth Muscle Cells Proliferation through the RAS Signaling Pathway in Murine Asthmatic Airway Remodeling Model.

Background: Studies that looked at asthma airway remodeling pathogenesis and prevention have led to the discovery of the rat sarcoma viral oncogene (RAS) signaling pathway as a key mechanism that controls airway smooth muscle cell (ASMC) proliferation. Baicalin has great anti-inflammatory, proliferation-inhibited, and respiratory disease-relieving properties. However, the inhibitory effects and mechanisms of baicalin on ASMC-mediated airway remodeling in mice are still poorly understood. Methods: After establishing the asthmatic mice model by ovalbumin (OVA) and interfering with baicalin, airway remodeling characteristics such as airway resistance, mRNA, and protein expression levels of remodeling-related cytokines were measured by histopathological assessment, quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot. Further efforts on detailed mechanisms were used antibody arrays to compare the expression and activation of proteins involved in the RAS signaling pathway. In addition, validation experiments were performed in ASMC proliferation model and low-expression cells of the target gene by using shRNA. Results: In OVA-induced asthmatic mice model, baicalin significantly reduced the infiltration of inflammatory cells in lung tissue, attenuated airway resistance, and decreased mRNA and protein expression levels of remodeling-related cytokines such as interleukin-13 (IL-13), vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGF-ß1), matrix metallopeptidase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1). The results of antibody arrays involved in RAS signaling pathway revealed that OVA and baicalin administration altered the activation of protein kinase C alpha type (PKC-α), A-rapidly accelerated fibrosarcoma (A-RAF), mitogen-activated protein kinase 2 (MEK2), extracellular regulated MAP kinase (ERK), MAPK interacting serine/threonine kinase 1 (MNK1), and ETS transcription factor 1 (ELK1). The above results were further verified in the ASMC proliferation model. A-RAF silencing (shA-RAF) could promote ASMC proliferation and downregulate p-MEK2, p-ERK, p-MNK1, and p-ELK1 expression. Conclusion: The effects of baicalin against airway remodeling and ASMC proliferation might partially be achieved by suppressing the RAS signaling pathway. Baicalin may be a new therapeutic option for managing airway remodeling in asthma patients.