MnFe layered double hydroxides confined MnOx for peroxymonosulfate activation: A novel manner for the selective production of singlet oxygen.

Singlet oxygen (1O2) is a reactive species for the selective degradation of stubborn organic pollutants. Given its resistance to harsh water environment, the effective and exclusive generation of 1O2 is acknowledged as a key strategy to mitigate water production costs and ensure water supply safety. Herein, we synthesized MnOx intercalated MnFe layered double hydroxides (MF-MnOx) to selectively produce 1O2 through the activation of PMS. The distinctive confined structure endowed MF-MnOx with a special pathway for the PMS activation. The direct oxidation of BPA on the intercalated MnOx induced the charge imbalance in the MnFe-LDH layer, resulting in the selective generation of 1O2. Moreover, acceptable activity deterioration of MF-MnOx was observed in a 10 h continuous degradation test in actual water, substantiating the application potential of MF-MnOx. This work presents a novel catalyst for the selective production of 1O2, and evaluates its prospects in the remediation of micro-polluted water.

Glycyrrhizin protects against diosbulbin B-induced hepatotoxicity by inhibiting the metabolic activation of diosbulbin B.

Diosbulbin B (DIOB), isolated from herbal medicine Dioscorea bulbifera L. (DB), could induce severe liver injury, and its toxicology was closely associated with CYP3A4-mediated metabolic oxidation of furan moiety to the corresponding cis-enedial reactive metabolite. Glycyrrhizin (GL), the major bioactive ingredient in licorice, can inhibit the activity of CYP3A4. Thus, GL may ameliorate hepatotoxicity of DIOB when GL and DIOB are co-administrated. The study aimed to investigate the protective effect of GL on DIOB-induced hepatotoxicity and the underlying mechanism. Biochemical and histopathological analysis demonstrated that GL alleviated DIOB-induced hepatotoxicity in a dose-dependent manner. In vitro study with mouse liver microsomes (MLMs) demonstrated that GL reduced the formation of metabolic activation-derived pyrrole-glutathione (GSH) conjugates from DIOB. Toxicokinetic studies showed that the pretreatment with GL caused the increase of AUCs and Cmax of DIOB in blood of mice, resulting in accelerating the accumulation of DIOB in the circulation. In addition, the pretreatment with GL alleviated DIOB-induced hepatic GSH depletion. In summary, GL ameliorated DIOB-induced hepatotoxicity, possibly related to the inhibition of the metabolic activation of DIOB. Thus, development of a standardized combination of DIOB with GL may protect patients from DIOB-induced liver injury.

Isaacs syndrome with LGI1 and CASPR2 antibodies after HPV vaccination: A case report.

RATIONALE: Isaacs syndrome is peripheral nerve hyperexcitability characterized by spontaneous muscle twitching and rigidity and is often associated with antibodies to CASPR2 (contactin-associated protein-like 2) and LGI1 (leucine-rich glioma-inactivated 1). But it is a rare Isaacs syndrome with LGI1 and CASPR2 antibodies after human papilloma virus (HPV) vaccination. PATIENT CONCERNS: The patient presented with limb pain, muscle twitching, numbness in the extremities and around the mouth, and hand rash after the second dose of HPV vaccine. DIAGNOSES: Laboratory tests indicated positive for LGI1 antibodies, CASPR2 antibodies, anti-phosphatidylserine/prothrombin antibodies and anti-sulfatide antibodies, TPO and ATG, IgG E. The patient post-M-wave discharges were seen on F-wave examination of the posterior tibial nerve in both lower limbs. We diagnosis the patient with Isaacs syndrome. INTERVENTIONS: Treatment with the intravenous immunoglobulin (IVIG) treatment, after 5 days of IVIG therapy (0.4 mg/kg/day), the rash on the hand disappeared, the pain was relieved, the sleep improved. OUTCOMES: After 3 Courses of treatment, the clinical manifestations of the nervous system disappeared and negative responsibility antibodies profile. LESSONS: This case report suggests a possible adverse reaction to HPV vaccination, which could be treated by attempting several periods of IVIG therapy. The underlying immune mechanisms need to be studied with further extensive data.

Protection of schisantherin A against dictamnine-induced hepatotoxicity: Pharmacokinetic insights.

Dictamnine (DIC), as the most abundant furoquinoline alkaloid ingredient of the herbal medicine Cortex Dictamni (CD), can induce severe liver injury. A previous study found that DIC-induced liver injury was initiated by cytochrome P4503A (CYP3A)-mediated metabolic activation and subsequent formation of adducts with cellular proteins. Schisantherin A (SchA) is the major lignan component of the herbal medicine Schisandra chinensis (SC). SC is frequently combined with CD used in numerous Chinese medicinal formulas for the treatment of eczema and urticaria. Furthermore, SC could protect against CD-induced hepatotoxicity. The objective of the study was to investigate the protective effect of SchA on DIC-induced hepatotoxicity based on pharmacokinetic interactions. The studies found that SchA exerted a protective effect on DIC-induced hepatotoxicity in a dose-dependent manner. Pharmacokinetic studies showed that pretreatment with SchA enhanced the area under concentration-time curve (AUC) and maximal concentration (Cmax ) values of DIC in the serum and liver tissue of mice, indicating that SchA could augment the accumulation of DIC in the circulation. In vitro metabolism assays with mouse liver microsomes (MLMs) showed that SchA reduced the production of DIC-glutathione (GSH) conjugate. In addition, SchA significantly reduced the excretion of DIC-GSH conjugate in the urine of mice and relieved hepatic GSH depletion induced by DIC. These results suggested that SchA could inhibit the metabolic activation of DIC in vitro and in vivo. In summary, our findings showed that the observed pharmacokinetic interactions might be attributable to the inhibition of the metabolism of DIC by SchA, which might be responsible for the protection of SchA against DIC-induced hepatotoxicity. Therefore, the development of a standardized combination of DIC and SchA may protect patients from DIC-induced liver injury.

Glycyrrhetinic acid ameliorates diosbulbin B-induced hepatotoxicity in mice by modulating metabolic activation of diosbulbin B.

Exposure to diosbulbin B (DBB), the primary component of the herbal medicine Dioscorea bulbifera L. (DB), can cause liver injury in humans and experimental animals. A previous study found DBB-induced hepatotoxicity was initiated by CYP3A4-mediated metabolic activation and subsequent formation of adducts with cellular proteins. The herbal medicine licorice (Glycyrrhiza glabra L.) is frequently combined with DB used in numerous Chinese medicinal formulas in an effort to protect against DB-elicited hepatotoxicity. Importantly, glycyrrhetinic acid (GA), the major bioactive ingredient in licorice, inhibits CYP3A4 activity. The study aimed to investigate the protection of GA against DBB-induced hepatotoxicity and the underlying mechanism. Biochemical and histopathological analysis showed GA alleviated DBB-induced liver injury in a dose-dependent manner. In vitro metabolism assay with mouse liver microsomes (MLMs) indicated that GA decreased the generation of metabolic activation-derived pyrrole-glutathione (GSH) conjugates from DBB. Toxicokinetic studies demonstrated that GA increased maximal serum concentration (Cmax ) and area under the serum-time curve (AUC) of DBB in mice. In addition, GA attenuated hepatic GSH depletion caused by DBB. Further mechanistic studies showed that GA reduced the production of DBB-derived pyrroline-protein adducts in a dose-dependent manner. In conclusion, our findings demonstrated that GA exerted protective effect against DBB-induced hepatotoxicity, mainly correlated with suppressing the metabolic activation of DBB. Therefore, the development of a standardized combination of DBB with GA may protect patients from DBB-induced hepatotoxicity.

The association between liver fibrosis and depression in patients after ischemic stroke.

BACKGROUND AND OBJECTIVE: Liver fibrosis has been considered a predictor of cardiovascular disease. This study aimed to evaluate whether the degree of liver fibrosis is related to post-stroke depression (PSD) at 3 months follow-up. METHODS: We prospectively and continuously enrolled patients with first-ever ischemic stroke from June 2020 to January 2022. Liver fibrosis was measured after admission by calculating the Fibrosis-4 index (FIB-4) and stratified into two categories (< 2.67 versus ≥ 2.67). Patients with a 17-item Hamilton Depression Scale score > 7 were further evaluated using the Chinese version of the structured clinical interview of DSM-IV, for diagnosing PSD at 3 months. RESULTS: A total of 326 patients (mean age 66.6 years, 51.5% male) were recruited for the study. As determined by the FIB-4 score, 80 (24.5%) patients had advanced liver fibrosis. During the follow-up, PSD was observed in 91 patients, which accounted for 27.9% (95% confidence interval [CI] 25.5%-30.5%) of the cohort. The prevalence of advanced liver fibrosis was higher in PSD patients than those without PSD (40.0% versus 24.0%; P = 0.006). After adjustment for covariates in the multivariate logistic analysis, advanced fibrosis was significantly associated with PSD (odds ratio [OR], 1.88; 95% CI, 1.03-3.42; P = 0.040). Similar results were found when the FIB-4 was analyzed as a continuous variable. CONCLUSIONS: This study found that advanced liver fibrosis was associated with an increased risk of 3-month PSD. FIB-4 score may be valuable for screening depressive symptoms in ischemic stroke patients.

Clinical characteristics and prognosis of anti-GABABR encephalitis: A single-center experience.

The purpose of this study was to assess the demographic data, clinical manifestations, cerebrospinal fluid (CSF), hematology, brain magnetic resonance imaging, electroencephalograms, and therapy and prognosis related to anti-gamma-aminobutyric acid B (anti-GABABR) encephalitis. We retrospectively examined the demographic data, clinical manifestations, laboratory results, brain magnetic resonance imaging, electroencephalograms, and therapy and prognosis of 6 patients with anti-GABABR encephalitis. We used the clinical data of patients with anti-GABABR encephalitis admitted to the Department of Neurology of Mianyang Central Hospital obtained from January 2017 to September 2020. Six patients with anti-GABABR encephalitis were included. Generalized tonic-clonic seizure was the first clinical symptom in 5 patients, while 1 patient first showed behavior disorder. After the first clinical symptom attack, 2 patients developed a memory deficit, 4 cases showed cognitive decline, 3 cases showed behavior disorder, 1 patient developed status epilepticus and only 1 patient returned to normal. CSF testing indicated normal intracranial pressure in 5 patients and elevated pressure in only 1 patient. Additionally, the cerebrospinal fluid tests revealed slight leukocytosis in all patients and elevated protein levels in 5 patients. The anti-GABABR antibody was positive in both serum and CSF in all patients. Brain magnetic resonance imaging showed limbic system lesions in 4 patients. Long-term electroencephalograms revealed abnormal waves in half of the patients. All patients were treated with high dosages of methylprednisolone, which was combined with intravenous immunoglobulin in 2 patients; symptoms were improved in 4 patients, 1 patient showed no significant change and 1 patient with status epilepticus died of severe pneumonia during hospitalization. Epilepsy is the most common initial symptom in patients of anti-GABABR encephalitis. Many patients are also affected by tumors. Early immunotherapy can achieve excellent effects, the long-term prognosis is good for most patients.

The Emerging Role of the Interaction of Extracellular Vesicle and Autophagy-Novel Insights into Neurological Disorders.

Eukaryotic cells release different types of extracellular vesicles (EVs), including exosomes, apoptotic bodies and microvesicles. EVs carry proteins, lipids and nucleic acids specific to cells and cell states. Autophagy is an intracellular degradation process, which, along with EVs, can significantly affect the development and progression of neurological diseases and, therefore, has been the hotspot. Generally, EVs and autophagy are closely associated. EVs and autophagy can interact with each other. On the one hand, the level of autophagy in target cells is closely related to the secretion and transport of EVs. In another, the application of EVs provides a great opportunity for adjuvant treatment of neurological disorders, for which autophagy is an excellent target. EVs can release their cargos into target cells, which, in turn, regulate the autophagic level of target cells through autophagy-related proteins directly and the non-coding RNA, signal transducer and activator of transcription 3 (STAT3), phosphodiesterase enzyme (PDE) 1-B, etc. signaling pathways indirectly, thus regulating the development of related neurological disorders.

Disorder Genes Regulate the Progression of Ischemic Stroke through the NF-κB Signaling Pathway.

Stroke is an acute cerebrovascular disease, including ischemic and hemorrhagic stroke. Stroke is the second leading cause of death after ischemic heart disease, which accounts for 9% of the global death toll. To explore the molecular mechanisms of the effects of the dysregulated factors, in the GEO database, we obtained transcriptome data from 24 h/72 h of mice with ischemic stroke and 24 h/72 h of normal mice. We then performed differential gene analysis, coexpression analysis, enrichment analysis, and regulator prediction bioinformatics analysis to identify the potential genes. We made a comparison between the ischemic stroke 72 h and the ischemic stroke for 24 h, and 5103 differential genes were obtained (p < 0.05). Four functional barrier modules were obtained by weighted gene coexpression network analysis. The critical genes of each module were ASTL, Zfp472, Fmr1 gene, and Nap1l1. The results of the enrichment analysis showed ncRNA metabolism, microRNAs in cancer, and biosynthesis of amino acids. These three functions and pathways have the most considerable count value. The regulators of the regulatory dysfunction module were predicted by pivotal analysis of TF and noncoding RNA, and critical regulators including NFKB1 (NF-κB1), NFKBIA, CTNNB1, and SP1 were obtained. Finally, the pivotal target gene found that CTNNB1, NFKB1, NFKBia, and Sp1 are involved in 18, 32, 2, and 60 target genes, respectively. Therefore, we believe that NFKB1 and Sp1 have a potential role in the progression of ischemic stroke. The NFKB signaling pathway promotes inflammatory cytokines and regulates the progression of ischemic stroke.

A novel quantitative method for diabetic cardiac autonomic neuropathy assessment in type 1 diabetic mice.

In this work, we used a sensitive and noninvasive computational method to assess diabetic cardiovascular autonomic neuropathy (DCAN) from pulse oximeter (photoplethysmographic; PPG) recordings from mice. The method, which could be easily applied to humans, is based on principal dynamic mode (PDM) analysis of heart rate variability (HRV). Unlike the power spectral density, PDM has been shown to be able to separately identify the activities of the parasympathetic and sympathetic nervous systems without pharmacological intervention. HRV parameters were measured by processing PPG signals from conscious 1.5- to 5-month-old C57/BL6 control mice and in Akita mice, a model of insulin-dependent type 1 diabetes, and compared with the gold-standard Western blot and immunohistochemical analyses. The PDM results indicate significant cardiac autonomic impairment in the diabetic mice in comparison to the controls. When tail-cuff PPG recordings were collected and analyzed starting from 1.5 months of age in both C57/Bl6 controls and Akita mice, onset of DCAN was seen at 3 months in the Akita mice, which persisted up to the termination of the recording at 5 months. Western blot and immunohistochemical analyses also showed a reduction in nerve density in Akita mice at 3 and 4 months as compared to the control mice, thus, corroborating our PDM data analysis of HRV records. Western blot analysis of autonomic nerve proteins corroborated the PPG-based HRV analysis via the PDM approach. In contrast, traditional HRV analysis (based on either the power spectral density or time-domain measures) failed to detect the nerve rarefaction.

Assessment of diabetic cardiac autonomic neuropathy in type I diabetic mice.

Diabetic cardiac autonomic neuropathy (DCAN) is one of the most common complications of diabetes. One reason why the pathogenesis of DCAN is unclear is that non-invasive assessment of DCAN in humans and animals has been problematic. To overcome this limitation, we utilized a sensitive and non-invasive method to assess cardiac autonomic dysregulation from ECG records. The method, which could be easily applied to humans, is based on principal dynamic mode (PDM) analysis of heart rate variability (HRV). The method is unique, in that is able to separately identify the activities of the parasympathetic and sympathetic systems without pharmacological intervention. In our study, ECG was measured via telemetry in ten sex- and age-matched (4 month old male) C57 (n=5) and Akita (n=5) mice, a model of insulin-dependent type 1 diabetes. The results indicate significant reduced cardiac autonomic function in the diabetic mice in comparison to the controls. Further, both immunohistochemical and Western blot analyses show a reduction in nerve density in Akita mice as compared to the control mice, thus, corroborating our PDM data analysis of HRV records.

A novel approach to monitor nonstationary dynamics in physiological signals: application to blood pressure, pulse oximeter, and respiratory data.

We propose a parametric time-varying (TV) algorithm which utilizes sinusoids as the basis functions which are then projected onto sets of Legendre and Walsh functions for the purpose of monitoring nonstationary dynamics. The proposed algorithm is a general-purpose algorithm that has the potential to be widely applicable to various physiological signals, but is especially well-suited for tracking blood pressure (BP), pulse oximeter, and respiratory signals, as they all exhibit periodic oscillations with TV dynamics. The proposed algorithm's efficacy was verified using both simulation examples and application to experimental data from all of the above-mentioned sources. Our results show that the method can: (1) accurately monitor abrupt frequency changes even when the data are contaminated with significant noise, (2) accurately monitor the BP and pulse oximeter signals, and (3) provide accurate estimation of respiratory rates derived directly from pulse oximeter recordings.

Estimating time-varying nonlinear autoregressive model parameters by minimizing hypersurface distance.

A nonleast-squares (non-LS) based method is presented for modeling time-varying (TV) nonlinear systems. The proposed method combines basis function technique and minimization of hypersurface distance (MHD) to combat TV and nonlinear dynamics, respectively. The performance of TVMHD is compared to the LS and total LS methods using simulation examples as well as human heart rate data recorded during different body positions. With all data, TVMHD significantly outperforms the two other methods by a factor of one order of magnitude; the LS-based methods require double the number of parameters than TVMHD requires to obtain similar residual error values. The significance of TVMHD is that due to its accurate parameter estimates concomitant with a fewer number of parameters, we now have the possibility of pinpointing parameters that may be of physiological importance, where such application will be especially useful in discriminating diseased conditions. Furthermore, our algorithm allows discrimination of model terms, which are TV or time invariant, by examining those basis function coefficients that are designed to capture TV dynamics. However, it should be noted that the main disadvantage of TVMHD is that it requires significantly greater computational time than the LS-based methods.

Autonomic nervous nonlinear interactions lead to frequency modulation between low- and high-frequency bands of the heart rate variability spectrum.

Cardiac sympathetic and parasympathetic neural activities have been found to interact with each other to efficiently regulate the heart rate and maintain homeostasis. Quantitative and noninvasive methods used to detect the presence of interactions have been lacking, however. This may be because interactions among autonomic nervous systems are nonlinear and nonstationary. The goal of this work was to identify nonlinear interactions between the sympathetic and parasympathetic nervous systems in the form of frequency and amplitude modulations in human heart rate data. To this end, wavelet analysis was performed, followed by frequency analysis of the resultant wavelet decomposed signals in several frequency brackets defined as very low frequency (f < 0.04 Hz), low frequency (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.4 Hz). Our analysis suggests that the HF band is significantly modulated by the LF band in the heart rate data obtained in both supine and upright body positions. The strength of modulations is stronger in the upright than supine position, which is consistent with elevated sympathetic nervous activities in the upright position. Furthermore, significantly stronger frequency modulation than in the control condition was also observed with the cold pressor test. The results with the cold pressor test, as well as the body position experiments, further demonstrate that the frequency modulation between LF and HF is most likely due to sympathetic and parasympathetic nervous interactions during sympathetic activations. The modulation phenomenon suggests that the parasympathetic nervous system is frequency modulated by the sympathetic nervous system. In this study, there was no evidence of amplitude modulation among these frequencies.