Clinical and video-polysomnographic characterization of restless sleep disorder in adult patients.

Adults with restless sleep disorder (RSD) have never been studied clinically and polysomnographically. This study aimed to describe the clinical manifestation, duration, and distribution of sleep-related movements in adult patients with restless sleep disorder. Patients who had performed VPSG from Jan 2021 to Jan 2022 and met the diagnosis criteria of RSD were enrolled in the study. Patients' bed partners were also interviewed or telephoned in identifying this disorder. Scoring of movements during sleep was according to the diagnosis criteria of RSD and scoring of large muscle group movements during sleep proposed by the International RLS Study Group in 2020 and 2021, respectively. The clinical manifestation, the distribution of sleep stage as well as the types and duration of the movements were carefully recorded and analyzed. We included ten patients in the study with a mean age of 27.6 years (range 22-38). There was a male prevalence in adults with RSD. The study highlighted the findings from video-polysomnography, which indicated frequent sleep-related movements occurring throughout the Night. These movements were most prominent during N1 and N2 sleep stage, followed by REM sleep, while fewer movements were observed during N3 sleep. Adults with RSD experienced significant daytime functioning impairments, including non-refreshing sleep, daytime fatigue/sleepiness, and mood disturbance. Two of the patients in the study were diagnosed with anxiety and depression, further underscoring the impact of RSD on mental health. Adult patients also suffer from severe RSD, and the RSD that originates in childhood tends to persist into adulthood. In these cases, longer duration of the disease and poor sleep quality may be associated with an increased risk of developing psychiatric comorbidities. Our cases represent an objectively documented type of RSD in younger adult patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00524-1.

Microstate-based brain network dynamics distinguishing temporal lobe epilepsy patients: A machine learning approach.

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients.

Machine learning-Based model for prediction of Narcolepsy Type 1 in Patients with Obstructive Sleep Apnea with Excessive Daytime Sleepiness.

Background: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1. Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early. Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP). Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA. Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices.

Plant beneficial traits of endophytic bacteria associated with fennel (Foeniculum vulgare Mill.).

In this study, we used 16S rRNA gene sequence analysis to describe the diversity of cultivable endophytic bacteria associated with fennel (Foeniculum vulgare Mill.) and determined their plant-beneficial traits. The bacterial isolates from the roots of fennel belonged to four phyla: Firmicutes (BRN1 and BRN3), Proteobacteria (BRN5, BRN6, and BRN7), Gammaproteobacteria (BRN2), and Actinobacteria (BRN4). The bacterial isolates from the shoot of fennel represented the phyla Proteobacteria (BSN1, BSN2, BSN3, BSN5, BSN6, BSN7, and BSN8), Firmicutes (BSN4, BRN1, and BRN3), and Actinobacteria (BRN4). The bacterial species Bacillus megaterium, Bacillus aryabhattai, and Brevibacterium frigoritolerans were found both in the roots and shoots of fennel. The bacterial isolates were found to produce siderophores, HCN, and indole-3-acetic acid (IAA), as well as hydrolytic enzymes such as chitinase, protease, glucanase, and lipase. Seven bacterial isolates showed antagonistic activity against Fusarium culmorum, Fusarium solani, and Rhizoctonia. solani. Our findings show that medicinal plants with antibacterial activity may serve as a source for the selection of microorganisms that exhibit antagonistic activity against plant fungal infections and may be considered as a viable option for the management of fungal diseases. They can also serve as an active part of biopreparation, improving plant growth.

Discovery of Oxidized p-Terphenyls as Phosphodiesterase 4 Inhibitors from Marine-Derived Fungi.

Four new p-terphenyl derivatives, talaroterphenyls A-D (1-4), together with three biosynthetically related known ones (5-7), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Compounds 1-3 are rare p-terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1-7 were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes (ttpB-ttpE). These p-terphenyls (1-7) and 36 marine-derived terphenyl analogues (8-43) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1-5, 14, 17, 23, and 26 showed notable activities with IC50 values of 0.40-16 µM. The binding pattern of p-terphenyl inhibitors 1-3 with PDE4 were explored by molecular docking analysis. Talaroterphenyl A (1), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-ß1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1 could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5-20 µM. This study suggests that the oxidized p-terphenyl 1, as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.

New Cyclic Pentapeptides from the Mangrove-Derived Aspergillus fumigatus GXIMD 03099.

Four new cyclic pentapeptides, avellanins D-G (1-4), together with four known compounds (5-8), were isolated from a mangrove-derived Aspergillus fumigatus GXIMD 03099 fungus from Acanthus ilicifolius L. Their structures were elucidated by analysis of HRESIMS, NMR, and ESI-MS/MS data. Their absolute configurations were determined by X-ray diffraction analysis and Marfey's method. Compounds 1-8 were screened for insecticidal and antibacterial activities. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with an LC50 value of 86.6 µM; compound 4 had weak activity against Vibrio harveyi with an MIC value of 5.85 µM.

Development and validation of a machine learning model for prediction of comorbid major depression disorder among narcolepsy type 1.

BACKGROUND: Major depression disorder (MDD) forms a common psychiatric comorbidity among patients with narcolepsy type 1 (NT1), yet its impact on patients with NT1 is often overlooked by neurologists. Currently, there is a lack of effective methods for accurately predicting MDD in patients with NT1. OBJECTIVE: This study utilized machine learning (ML) algorithms to identify critical variables and developed the prediction model for predicting MDD in patients with NT1. METHODS: The study included 267 NT1 patients from four sleep centers. The diagnosis of comorbid MDD was based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). ML models, including six full models and six compact models, were developed using a training set. The performance of these models was compared in the testing set, and the optimal model was evaluated in the testing set. Various evaluation metrics, such as Area under the receiver operating curve (AUC), precision-recall (PR) curve and calibration curve were employed to assess and compare the performance of the ML models. Model interpretability was demonstrated using SHAP. RESULT: In the testing set, the logistic regression (LG) model demonstrated superior performance compared to other ML models based on evaluation metrics such as AUC, PR curve, and calibration curve. The top eight features used in the LG model, ranked by feature importance, included social impact scale (SIS) score, narcolepsy severity scale (NSS) score, total sleep time, body mass index (BMI), education years, age of onset, sleep efficiency, sleep latency. CONCLUSION: The study yielded a straightforward and practical ML model for the early identification of MDD in patients with NT1. A web-based tool for clinical applications was developed, which deserves further verification in diverse clinical settings.

Ilicicolin C suppresses the progression of prostate cancer by inhibiting PI3K/AKT/mTOR pathway.

Aberrant activation of the PI3K/AKT pathway is a driving factor in the development of prostate cancer. Therefore, inhibiting the function of the PI3K/AKT signaling pathway is a strategy for the treatment of prostate cancer. Ilicicolin C is an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Which has anti-inflammatory activity, but its activity against prostate cancer has not yet been elucidated. MTT assay, plate clone-formation assay, flow cytometry and real-time cell analysis technology were used to detect the effects of ilicicolin C on cell viability, proliferation, apoptosis and migration of prostate cancer cells. Molecular docking software and surface plasmon resonance technology were used to analyze the interaction between ilicicolin C and PI3K/AKT proteins. Western blot assay was performed to examine the changes in protein expression. Finally, QikProp software was used to simulate the process of ilicicolin C in vivo, and a zebrafish xenograft model was used to further verify the anti-prostate cancer activity of ilicicolin C in vivo. Ilicicolin C showed cytotoxic effects on prostate cancer cells, with the most significant effect on PC-3 cells. Ilicicolin C inhibited proliferation and migration of PC-3 cells. It could also block the cell cycle and induce apoptosis in PC-3 cells. In addition, ilicicolin C could bind to PI3K/AKT proteins. Furthermore, ilicicolin C inhibited the expression of PI3K, AKT and mTOR proteins and could also regulate the expression of downstream proteins in the PI3K/AKT/mTOR signaling pathway. Moreover, the calculations speculated that ilicicolin C was well absorbed orally, and the zebrafish xenograft model confirmed the in vivo anti-prostate cancer effect of ilicicolin C. Ilicicolin C emerges as a promising marine compound capable of inducing apoptosis of prostate cancer cells by counteracting the aberrant activation of PI3K/AKT/mTOR, suggesting that ilicicolin C may be a viable candidate for anti-prostate cancer drug development. These findings highlight the potential of ilicicolin C against prostate cancer and shed light on its mechanism of action.

Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

Two Novel Alkaliphilic Species Isolated from Saline-Alkali Soil in China: Halalkalibacter flavus sp. nov., and Halalkalibacter lacteus sp. nov.

The degradation of farmland in China underscores the need for developing and utilizing saline-alkali soil. Soil health relies on microbial activity, which aids in the restoration of the land's ecosystem, and hence it is important to understand microbial diversity. In the present study, two Gram-stain-positive strains HR 1-10T and J-A-003T were isolated from saline-alkali soil. Preliminary analysis suggested that these strains could be a novel species. Therefore, the taxonomic positions of these strains were evaluated using polyphasic analysis. Phylogenetic and 16S rRNA gene sequence analysis indicated that these strains should be assigned to the genus Halalkalibacter. Cell wall contained meso-2,6-diaminopimelic acid. The polar lipids present in both strains were diphosphatidyl-glycerol, phosphatidylglycerol, and an unidentified phospholipid. The major fatty acids (>10%) were anteiso-C15:0, C16:0 and iso-C15:0. Average nucleotide identity and digital DNA#x2013;DNA hybridization values were below the threshold values (95% and 70%, respectively) for species delineation. Based on the above results, the strains represent two novel species of the genus Halalkalibacter, for which the names Halalkalibacter flavus sp. nov., and Halalkalibacter lacteus sp. nov., are proposed. The type strains are HR 1-10T (=GDMCC 1.2946T = MCCC 1K08312T = JCM 36285T), and J-A-003T (=GDMCC 1.2949T = MCCC 1K08417T = JCM 36286T).

Discovery of Antibacterial Compounds against Xanthomonas citri subsp. citri from a Marine Fungus Aspergillus terreus SCSIO 41202 and the Mode of Action.

Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a severe citrus disease. Currently, copper-containing pesticides are widely used to manage this disease, posing high risks to the environment and human health. This study reports the discovery of naturally occurring anti-Xcc compounds from a deep-sea fungus, Aspergillus terreus SCSIO 41202, and the possible mode of action. The ethyl acetate extract of A. terreus was subjected to bioassay-guided isolation, resulting in the discovery of eight anti-Xcc compounds (1-8) with minimum inhibitory concentrations (MICs) ranging from 0.078 to 0.625 mg/mL. The chemical structures of these eight metabolites were determined by integrative analysis of various spectroscopic data. Among these compounds, Asperporonin A (1) and Asperporonin B (2) were identified as novel compounds with a very unusual structural skeleton. The electronic circular dichroism was used to determine the absolute configurations of 1 and 2 through quantum chemical calculation. A bioconversion pathway involving pinacol rearrangement was proposed to produce the unusual compounds (1-2). Compound 6 exhibited an excellent anti-Xcc effect with a MIC value of 0.078 mg/mL, which was significantly more potent than the positive control CuSO4 (MIC = 0.3125 mg/mL). Compound 6 inhibited cell growth by disrupting biofilm formation, destroying the cell membrane, and inducing the accumulation of reactive oxygen species. In vivo tests indicated that compound 6 is highly effective in controlling citrus canker disease. These results indicate that compounds 1-8, especially 6, have the potential as lead compounds for the development of new, environmentally friendly, and efficient anti-Xcc pesticides.

Structural analysis and in vitro fermentation characteristics of an Avicennia marina fruit RG-I pectin as a potential prebiotic.

Avicennia marina (Forssk.) Vierh. is a highly salt-tolerant mangrove, and its fruit has been traditionally used for treating constipation and dysentery. In this study, a pectin (AMFPs-0-1) was extracted and isolated from this fruit for the first time, its structure was analyzed, and the effects on the human gut microbiota were investigated. The results indicated that AMFPs-0-1 with a molecular weight of 798 kDa had a backbone consisting of alternating →2)-α-L-Rhap-(1→ and →4)-α-D-GalpA-(1→ residues and side chains composed of →3-α-L-Araf-(1→-linked arabinan with a terminal ß-L-Araf, →5-α-L-Araf-(1→-linked arabinan, and →4)-ß-D-Galp-(1→-linked galactan that linked to the C-4 positions of all α-L-Rhap residues in the backbone. It belongs to a type I rhamnogalacturonan (RG-I) pectin but has no arabinogalactosyl chains. AMFPs-0-1 could be consumed by human gut microbiota and increase the abundance of some beneficial bacteria, such as Bifidobacterium, Mitsuokella, and Megasphaera, which could help fight digestive disorders. These findings provide a structural basis for the potential application of A. marina fruit RG-I pectic polysaccharides in improving human intestinal health.

Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells.

Two new cytochalasin derivatives, peniotrinins A (1) and B (2), three new citrinin derivatives, peniotrinins C-E (4, 5, 7), and one new tetramic acid derivative, peniotrinin F (12), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 µM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer.

Response of microbial diversity and function to the degradation of Barkol Saline Lake.

Barkol Lake, a shrinking hypersaline lake situated in the northeast of Xinjiang, China, has experienced the exposure of its riverbed and the gradual drying up of its original sediment due to climate change and human activities, resulting in the formation of alkaline soils. These changes have correspondingly altered the physicochemical characteristics of the surrounding environment. Microorganisms play a crucial role, with special functioning involved in various nutrient cycling and energy transfer in saline lake environments. However, little is known about how the microbial community dynamics and metabolic functions in this shrinking saline lake relate to the degradation process. To address this knowledge gap, a cultivation-independent method of amplicon sequencing was used to identify and analyze the microbial community and its potential ecological functions in the sediment and degraded area. The microbial community diversity was found to be significantly lower in the degraded areas than in the sediment samples. The Pseudomonadota was dominant in Barkol Saline Lake. The abundance of Desulfobacterota and Bacillota in the degraded areas was lower than in the lake sediment, while Pseudomonadota, Acidobacteriota, and Actinobacteriota showed an opposite trend. The ßNTI showed that microbial community assembly was primarily associated with deterministic processes in Barkol Saline Lake ecosystems and stochastic processes at the boundary between sediment and degraded areas. Functional predictions showed that sulfur metabolism, particularly sulfate respiration, was much higher in sediment samples than in the degraded areas. Overall, these findings provided a possible perspective for us to understand how microorganisms adapt to extreme environments and their role in saline lakes under environmental change.

Titanium catalyzed [2σ + 2π] cycloaddition of bicyclo[1.1.0]-butanes with 1,3-dienes for efficient synthesis of stilbene bioisosteres.

Natural stilbenes have shown significant potential in the prevention and treatment of diseases due to their diverse pharmacological activities. Here we present a mild and effective Ti-catalyzed intermolecular radical-relay [2σ + 2π] cycloaddition of bicyclo[1.1.0]-butanes and 1,3-dienes. This transformation enables the synthesis of bicyclo[2.1.1]hexane (BCH) scaffolds containing aryl vinyl groups with excellent regio- and trans-selectivity and broad functional group tolerance, thus offering rapid access to structurally diverse stilbene bioisosteres.

Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC-MS method.

N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC-MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. Despite low bioavailability (0.024%), N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs.

Secofumitremorgins C and D, a pair of atropisomers from saltern-derived fungus Aspergillus fumigatus GXIMD00544.

A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.

A cross-sectional, multicenter survey of the prevalence and influencing factors for migraine in epilepsy.

OBJECTIVES: Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy. METHODS: Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine. RESULTS: A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068-1.975; p = 0.018), focal and focal to bilateral tonic-clonic seizures (OR = 1.583, 95% CI: 1.090-2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282-3.063; p = 0.002) were the influencing factors for migraine. However, <10% of patients with epilepsy received analgesics for migraine. SIGNIFICANCE: Approximately 20% of patients with epilepsy screened positive for migraine. Being female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were the influencing factors for migraine. Neurologists should pay more attention to the screening and management of the migraine among patients with epilepsy in China. PLAIN LANGUAGE SUMMARY: Epilepsy and migraine are common chronic neurological disease with shared pathophysiological mechanisms and therapeutic options. However, migraine is often underestimated among patients with epilepsy. This multicenter study aimed to evaluate the prevalence of migraine and current status of treatment. In this study, approximately 20% of patients with epilepsy screened positive for migraine. Female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were identified as independent influencing factors for migraine. Despite the high prevalence, the treatment for migraine was not optimistic, neurologists should pay more attention to the screening and management of migraine.

Neuroprotective azaphilones from a deep-sea derived fungus Penicillium sp. SCSIO41030.

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived Penicillium sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 µM and 20 µM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aß25-35-induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 µM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aß25-35-induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.

Prevalence and molecular characterization of Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis in dairy cattle in Ningxia, northwestern China.

Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis are common intestinal pathogens that infect humans and animals. To date, research regarding these three protozoa in the Ningxia Hui Autonomous Region (Ningxia) has mostly been limited to a single pathogen, and comprehensive data on mixed infections are unavailable. This study aimed to evaluate the zoonotic potential of these three protozoa. In this study, small subunit ribosomal RNA (SSU rRNA) and 60 kDa glycoprotein (gp60) genes of Cryptosporidium; internal transcribed spacer (ITS) gene of E. bieneusi; and SSU rRNA, glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis were examined. DNA extraction, polymerase chain reaction, and sequence analysis were performed on fecal samples collected from 320 dairy cattle at three intensive dairy farms in Ningxia in 2021 to determine the prevalence and genetic characteristics of these three protozoa. The findings revealed that 61.56% (197/320) of the samples were infected with at least one protozoan. The overall prevalence of Cryptosporidium was 19.38% (62/320), E. bieneusi was 41.56% (133/320), and G. duodenalis was 29.38% (94/320). This study identified four Cryptosporidium species (C. bovis, C. andersoni, C. ryanae, and C. parvum) and the presence of mixed infections with two or three Cryptosporidium species. C. bovis was the dominant species in this study, while the dominant C. parvum subtypes were IIdA15G1 and IIdA20G1. The genotypes of E. bieneusis were J, BEB4, and I alongside the novel genotypes NX1-NX8, all belonging to group 2, with genotype J being dominant. G. duodenalis assemblages were identified as assemblages E, A, and B, and a mixed infection involving assemblages A + E was identified, with assemblage E being the dominant one. Concurrently, 11 isolates formed 10 different assemblage E multilocus genotypes (MLGs) and 1 assemblage A MLG and assemblage E MLGs formed 5 subgroups. To the best of our knowledge, this is the first report on mixed infection with two or three Cryptosporidium species in cattle in Ningxia and on the presence of the C. parvum subtype IIdA20G1 in this part of China. This study also discovered nine genotypes of E. bieneusis and novel features of G. duodenalis assemblages in Ningxia. This study indicates that dairy cattle in this region may play a significant role in the zoonotic transmission of Cryptosporidium spp., E. bieneusi, and G. duodenalis.