Two new quinoline alkaloid with neuroprotective activities from Xylaria longipes.

Two new quinoline alkaloids with an α, ß-unsaturated amide side chain, xylarinines A and B (1 and 2), were isolated from the ethyl acetate extracts of Xylaria longipes solid fermentation. The structures of these were primarily determined though NMR and HRESIMS data analysis. The absolute configuration of compound 1 was assigned using experimental and calculated ECD data. The neuroprotective effects of compounds 1 and 2 against glutamate-induced damage in PC12 cells were evaluated in vitro bioassay. The results demonstrated that both compounds significantly improved cell viability, inhibited apoptosis, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced intracellular reactive oxygen species (ROS) accumulation. These findings suggested that these mechanisms contribute to the neuroprotective effects of the compounds.

Human pluripotent stem cell-derived kidney organoids: Current progress and challenges.

Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advances in the generation of hPSC-derived kidney organoids, how these organoids contribute to the understanding of human kidney development and research in disease modeling. Additionally, the limitations, future research focus, and applications of hPSC-derived kidney organoids were highlighted.

A pair of new chromone enantiomers from Xylaria nigripes.

A pair of new chromone derivative enantiomers, (+)-xylarichromone A (1a) and (-)-xylarichromone A (1b), were isolated from the solid fermentation of Xylaria nigripes. The planar structure of 1 was determined by extensive NMR spectroscopic data, and its absolute configuration was assigned by comparison the ECD spectra with the known chromone derivatives. Compound 1 was the first chromone derivative reported from this medicinal fungus. The neuroprotective effects of 1 against oxygen and glucose deprivation (OGD) induced pheochromocytoma-12 cells (PC12) injury was investigated.

Peripheral clock gene oscillations are perturbed in neonatal and adult rat offspring raised under adverse limited bedding conditions.

Circadian (24-h) rhythms in the suprachiasmatic nucleus (SCN) are established in utero in rodents, but rhythmicity of peripheral circadian clocks appears later in postnatal development. Since peripheral oscillators can be influenced by maternal feeding and behavior, we investigated whether exposure to the adverse environmental conditions of limited bedding (LB) during postnatal life would alter rhythmicity in the SCN, adrenal gland and liver in neonatal (postnatal day PND10), juvenile (PND28) and adult rats. We also examined locomotor activity in adults. Limited bedding increased nursing time and slightly increased fragmentation of maternal behavior. Exposure to LB reduced the amplitude of Per2 in the SCN on PND10. Adrenal clock gene expression (Bmal1, Per2, Cry1, Rev-erbα, Dbp) and corticosterone secretion were rhythmic at all ages in NB offspring, whereas rhythmicity of Bmal1, Cry1 and corticosterone was abolished in neonatal LB pups. Circadian gene expression in the adrenal and liver was well established by PND28. In adults, liver expression of several circadian genes was increased at specific daytimes by LB and the microstructure of locomotor behavior was altered. Thus, changes in maternal care and behavior might provide important signals to the maturing peripheral oscillators and modify, in particular their output functions in the long-term.

Impact of bariatric surgery on glucose and lipid metabolism and liver and kidney function in food-induced obese diabetic rats.

BACKGROUND: Obesity usually causes diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects. AIM: To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats. METHODS: Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery (RYGB), sleeve gastrectomy (SG), or gastric banding (GB). Glucose and insulin tolerance tests, analyses of biochemical parameters, histological examination, western blot, and quantitative real-time polymerase chain reaction were conducted. RESULTS: In comparison to the sham operation group, the RYGB, SG, and GB groups had decreased body weight and food intake, reduced glucose intolerance and insulin insensitivity, downregulated biochemical parameters, alleviated morphological changes in the liver and kidneys, and decreased levels of protein kinase C ß/ P66shc. The effect in the RYGB group was better than that in the SG and GB groups. CONCLUSION: These results suggest that RYGB, SG and GB may be helpful for the treatment of foodborne obesity-induced DM.

The complete mitochondrial genome of Wellcomia compar (Spirurina: Oxyuridae) and its genome characterization and phylogenetic analysis.

Wellcomia compar (Spirurina: Oxyuridae) is a pinworm that infects wild and captive porcupines. Despite clear records of its morphological structure, its genetics, systematics, and biology are poorly understood. This study aimed to determine the complete mitochondrial (mt) genome of W. compar and reconstruct its phylogenetic relationship with other nematodes. We sequenced the complete mt genome of W. comparand conducted phylogenetic analyses using concatenated coding sequences of 12 protein-coding genes (PCGs) by maximum likelihood and Bayesian inference. The complete mt genome is 14,373 bp in size and comprises 36 genes, including 12 protein-coding, two rRNA and 22 tRNA genes. Apart from 28 intergenic regions, one non-coding region and one overlapping region also occur. A comparison of the gene arrangements of Oxyuridomorpha revealed relatively similar features in W. compar and Wellcomia siamensis. Phylogenetic analysis also showed that W. compar and W. siamensis formed a sister group. In Oxyuridomorpha the genetic distance between W. compar and W. siamensis was 0.0805. This study reports, for the first time, the complete W. compar mt genome sequence obtained from Chinese porcupines. It provides genetic markers for investigating the taxonomy, population genetics, and phylogenetics of pinworms from different hosts and has implications for the diagnosis, prevention, and control of parasitic diseases in porcupines and other animals.

Bacterial diversity in water from Xifeng Hot Spring in China.

The Xifeng Hot Spring is one of the eight largest hot springs in China, which is rich in radon gas and sulphur in karst scenery. Little is known about the microbiota structure in the spring. The water was collected from three sites containing the outlet of spring water discharge site (OWD), spring pool for tourist (SPT) and sewage effluent pool (SEP) in the Xifeng Hot Spring and further analyzed by culture-independent technique and culture-dependent method. A total of 57 phyla were identified from the water samples. The dominate phyla at OWD was Bacteroidetes (46.93%), while it was Proteobacteria in both sites of SEP and SPT with relative richness of 61.9% and 94.9%, respectively. Two bacteria, Deinococcus and Hymenobacter, that confirmed to be radiation-resistant, seven sulphur bacteria and three thermophilic bacteria were detected from Xifeng Hot Spring. Furthermore, it was found that genus Flavobacterium was susceptible to environmental change with abundance of 11 ~ 2825 times higher in OWD than the other two groups. Compared bacteria from the OWD group with that from 14 hot springs in six countries, total 94 unique genera bacteria were found out from the Xifeng Hot Spring including four thiometabolism-related bacteria (Propionispira, Desulforegula, Desulfobacter and Desulfococcus) and the thermophilic bacterium (Symbiobacterium). Using microbial culturing and isolation technology, sixteen strains were isolated from the water samples of three sites. The diversity of microbiota was abundant and variable along with the niche changed in conditions and surroundings. It indicated that numbers of valuable bacteria resources could be explored from the special surroundings of Xifeng Hot Spring.

Two pairs of new isobenzofuranone enantiomers from a soil-derived fungus Penicillium canescens DWS225.

Two pairs of new isobenzofuranone derivative enantiomers, (±)-penicifurans E (1) and (±)-penicifurans F (2), together with four know compounds (3-6) were isolated from the solid fermentation of Penicillium canescens DWS225. The structures of these enantiomers were elucidated by extensive NMR spectroscopic data, and their absolute configurations were assigned by the experimental and calculated ECD data. The neuroprotective effects of all the isolates against oxygen-glucose deprivation/reperfusion injury in pheochromocytoma-12 cells (PC12) were investigated.

Synergistic effects of lipopolysaccharide and rotenone on dopamine neuronal damage in rats.

INTRODUCTION: The etiology of Parkinson's disease (PD) is still unknown. Until now, oxidative stress and neuroinflammation play a crucial role in the pathogenesis of PD. However, the specific synergistic role of oxidative stress and neuroinflammation in the occurrence and development of PD remains unclear. METHODS: The changes in motor behavior, dopamine (DA) neurons quantification and their mitochondrial respiratory chain, glial cells activation and secreted cytokines, Nrf2 signaling pathway, and redox balance in the brain of rats were evaluated. RESULTS: Lipopolysaccharide (LPS)-induced neuroinflammation and rotenone (ROT)-induced oxidative stress synergistically aggravated motor dysfunction, DA neuron damage, activation of glial cells, and release of related mediators, activation of Nrf2 signaling and destruction of oxidative balance. In addition, further studies indicated that after ROT-induced oxidative stress caused direct damage to DA neurons, LPS-induced inflammatory effects had stronger promoting neurotoxic effects on the above aspects. CONCLUSIONS: Neuroinflammation and oxidative stress synergistically aggravated DA neuronal loss. Furtherly, oxidative stress followed by neuroinflammation caused more DA neuronal loss than neuroinflammation followed by oxidative stress.

A Nomogram for Optimizing Sarcopenia Screening in Community-dwelling Older Adults: AB3C Model.

OBJECTIVES: Sarcopenia is associated with significantly higher mortality risk, and earlier detection of sarcopenia has remarkable public health benefits. However, the model that predicts sarcopenia in the community has yet to be well identified. The study aimed to develop a nomogram for predicting the risk of sarcopenia and compare the performance with 3 sarcopenia screen models in community-dwelling older adults in China. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 966 community-dwelling older adults. METHODS: A total of 966 community-dwelling older adults were enrolled in the study, with 678 participants grouped into the Training Set and 288 participants grouped into the Validation Set according to a 7:3 randomization. Predictors were identified in the Training Set by univariate and multivariate logistic regression and then combined into a nomogram to predict the risk of sarcopenia. The performance of this nomogram was assessed by calibration, discrimination, and clinical utility. RESULTS: Age, body mass index, calf circumference, congestive heart failure, and chronic obstructive pulmonary disease were demonstrated to be predictors for sarcopenia. The nomogram (named as AB3C model) that was constructed based on these predictors showed excellent calibration and discrimination in the Training Set with an area under the receiver operating characteristic curve (AUC) of 0.930. The nomogram also showed perfect calibration and discrimination in the Validation Set with an AUC of 0.897. The clinical utility of the nomogram was supported by decision curve analysis. Comparing the performance with 3 sarcopenia screen models (SARC-F, Ishii, and Calf circumference), the AB3C model outperformed the other models regarding sensitivity and AUC. CONCLUSIONS AND IMPLICATIONS: AB3C model, an easy-to-apply and cost-effective nomogram, was developed to predict the risk of sarcopenia, which may contribute to optimizing sarcopenia screening in community settings.

Neuroprotective methylsuccinic acid and enoic acid derivatives from the fungus Xylaria longipes.

Three undescribed methylsuccinic acid derivatives, xylaril acids A-C, and two undescribed enoic acid derivatives, xylaril acids D-E, were isolated from the fungus Xylaria longipes. The structures of the undescribed compounds were deduced by spectroscopic means, including HRESIMS and 1D/2D NMR spectroscopy, as well as ECD calculations. The absolute configuration of xylaril acids A was further determined by single-crystal X-ray diffraction experiments. All the isolated compounds displayed neuroprotective activities against oxygen-glucose deprivation/reperfusion injury in PC12 cells by enhancing cell viability and inhibiting cell apoptosis.

A UPLC-Q-TOF/MS and network pharmacology method to explore the mechanism of Anhua fuzhuan tea intervention in nonalcoholic fatty liver disease.

The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.

Fundus image classification using Inception V3 and ResNet-50 for the early diagnostics of fundus diseases.

Purpose: We aim to present effective and computer aided diagnostics in the field of ophthalmology and improve eye health. This study aims to create an automated deep learning based system for categorizing fundus images into three classes: normal, macular degeneration and tessellated fundus for the timely recognition and treatment of diabetic retinopathy and other diseases. Methods: A total of 1,032 fundus images were collected from 516 patients using fundus camera from Health Management Center, Shenzhen University General Hospital Shenzhen University, Shenzhen 518055, Guangdong, China. Then, Inception V3 and ResNet-50 deep learning models are used to classify fundus images into three classes, Normal, Macular degeneration and tessellated fundus for the timely recognition and treatment of fundus diseases. Results: The experimental results show that the effect of model recognition is the best when the Adam is used as optimizer method, the number of iterations is 150, and 0.00 as the learning rate. According to our proposed approach we, achieved the highest accuracy of 93.81% and 91.76% by using ResNet-50 and Inception V3 after fine-tuned and adjusted hyper parameters according to our classification problem. Conclusion: Our research provides a reference to the clinical diagnosis or screening for diabetic retinopathy and other eye diseases. Our suggested computer aided diagnostics framework will prevent incorrect diagnoses caused by the low image quality and individual experience, and other factors. In future implementations, the ophthalmologists can implement more advanced learning algorithms to improve the accuracy of diagnosis.

N6­methyladenosine­induced long non­coding RNA PVT1 regulates the miR­27b­3p/BLM axis to promote prostate cancer progression.

Prostate cancer (PCa) is one of the most fundamental causes of cancer­related mortality and morbidity among males. However, the underlying mechanisms have not yet been fully clarified. The present study aimed to investigate the effects of plasmacytoma variant translocation 1 (PVT1) on the malignant behaviors of PCa cells and to explore the possible molecular mechanisms involved. The expression levels of PVT1 and microRNA (miRNA/miR)­27b­3p in PCa tissues and cell lines were measured using reverse­transcritpion­quantitative polymerase chain reaction. Methyltransferase 3 (METTL3)­mediated PVT1 N6­methyladenosine (m6A) modifications were detected using RNA immunoprecipitation (RIP) and RNA pull­down assays. Bioinformatics analysis was used to predict the interactions of miR­27b­3p with PVT1 and bloom syndrome protein (BLM), and these interactions were validated using RIP, dual­luciferase reporter and biotin pull­down assays. The functional importance of miR­27b­3p, PVT1 and BLM within PCa cells was assessed through the in vitro utilization of Cell Counting Kit­8, Transwell, wound healing and colony formation assays, and the in vivo use of a mouse xenograft model. The results revealed the high expression level of PVT1 in PCa tissues and cells, and epigenetic analyses revealed the upregulation of PVT1 expression following METTL3­mediated m6A modification. PVT1 overexpression induced PCa cells to become more proliferative, migratory and invasive, whereas PVT1 knockdown led to the opposite phenotype. Furthermore, miR­27b­3p was found to target both PVT1 and BLM, and PVT1 functioned to sequester miR­27b­3p within cells, thereby indirectly promoting the BLM expression level. BLM overexpression reversed the adverse effects of PVT1 knockdown on the migratory, proliferative and invasive capabilities of PCa cells in vitro and in vivo. The overexpression of PVT1 contributed to the aggressive phenotype of PCa cells by regulating the miR­27b­3p/BLM axis. On the whole, the findings of the present study may provide novel potential targets for the treatment of PCa.

Classification optimization of traditional Chinese medicine materials based on additive physical properties of powder / 中国中药杂志

According to the method of predicting the physical properties of oily powder based on the additive physical properties of Chinese medicinal powder, Dioscoreae Rhizoma and calcined Ostreae Concha with high sieve rate and good fluidity were mixed and crushed with Persicae Semen, Platycladi Semen, Raphani Semen, Ziziphi Spinosae Semen, and other typical oily materials with high fatty oil content in proportion to obtain 23 mixed powders. Fifteen physical properties such as bulk density, water absorption, and maximum torque force were measured, and the physical properties of typical oily powders were predicted. When the mixing and grinding ratio was in the range of 5∶1-1∶1, the r value in the correlation equation between the weighted average score of the mixed powder and the powder proportion ranged from 0.801 to 0.986, and the linearity was good, indicating that the method of predicting the physical properties of oily powder based on the additive physical properties of traditional Chinese medicine(TCM)powder was feasible. The results of cluster analysis showed that the classification boundaries of the five kinds of TCM materials were clear, and the similarity of the physical fingerprints of powdery and oily materials decreased from 80.6% to 37.2%, which solved the problem of fuzzy classification boundaries of powdery and oily materials due to the lack of representativeness of oily material model drugs. The classification of TCM materials was optimized, laying a foundation for optimizing the prediction model of the prescription of personalized water-paste pills.

Prognostic nomogram for primary splenic lymphoma: a SEER database-based study.

This study aimed to establish a nomogram model based on the clinicopathological factors affecting the prognosis of patients with primary splenic lymphoma (PSL) to predict the overall survival (OS) and cancer-specific survival (CSS) of patients. A total of 4074 patients diagnosed with PSL were included in this study. Among them, 4052 cases from the SEER (Surveillance, Epidemiology, and End Results) database were randomized into a training set and an internal validation set in a 7:3 ratio. Another 22 patients from the First Affiliated Hospital of Xi'an Jiaotong University were used as an external validation set. The prognostic factors affecting the OS and CSS of patients were analyzed using univariate and multivariate Cox regression models. Survival analysis was performed using Kaplan-Meier (KM) method and compared by Log-rank test. Then, a nomogram model was established to predict OS and CSS. Finally, the model was validated both internally and externally using the concordance index (C-index), receiver operating characteristic curve (ROC), and calibration curve to evaluate its predictive value, and the decision curve analysis (DCA) was conducted to assess its clinical utility. Our results showed that the model displayed a good prediction ability. In the training set, the OS rates at 1, 3, and 5 years were 85.9%, 75.8% and 70.1%, respectively, while the CSS rates at 1, 3, and 5 years were 91.9%, 86.2% and 82.3%, respectively. Predictors in the prediction model of OS included age, sex, marital status, Ann Arbor stage, histology, surgery, chemotherapy and year at diagnosis. On the other hand, predictors in the model of CSS included age, Ann Arbor stage, histology, chemotherapy, and year at diagnosis. Internal and external validation of the nomogram model showed that the C-index for predicting OS was 0.678 (0.662, 0.694) in the training set, 0.672 (0.648, 0.696) in the internal validation set, and 0.704 (0.565, 0.843) in the external validation set; the C-index for predicting CSS was 0.685 (0.661, 0.709) in the training set, 0.683 (0.650, 0.716) in the internal validation set, and 0.676 (0.488, 0.864) in the external validation set. The calibration curves for several groups showed good consistency, and DCA suggested its clinical usability. In conclusion, the nomogram constructed in this study has a good predictive value for the survival of patients with PSL, and can be a clinically applicable and practical prediction tool, facilitating rapid and accurate individualized predictions of the patient survival.

Spatial-temporal distribution of pulmonary tuberculosis registered in Fuling District of Chongqing during the 13th Five-Year Plan period / 中国热带医学

@#Abstract: Objective To analyze the spatial-temporal characteristics of the active pulmonary tuberculosis (PTB) and the pathogenic positive PTB in Fuling District of Chongqing during the 13th Five-Year Plan period, so as to explore the clustering areas, and provide scientific basis for the precise prevention and control of tuberculosis in Fuling District. Methods The PTB registration data of 27 townships in Fuling District from 2016 to 2020 were collected. The descriptive analysis were used to describe the temporal and spatial distribution characteristics of patients, SaTScan9.0 and ArcGis10.6 was used for spatial-temporal scanning analysis and local auto-correlation analysis. The results were visualized by ArcGis10.6. Results A total of 4 038 case of active PTB patients were registered and a downward trend was observed in PTB during the 13th Five-Year Plan period in Fuling District. The average annual registration rate of PTB was 70.17/100 000, and the annual PTB registration rate declined by 8.21%. The peak of active PTB and etiological positive PTB were mainly concentrated in March and June respectively. The top five streets of cumulative active PTB patients registered were Lizhi street, Dunren street, Chongyi street, Ma 'an street and Jiangdong street, accounting for 60.18% of the total registered PTB patients during the 13th Five-Year Plan period. The top three average annual registration rates were Dunren street (101.35/100 000), Chongyi street (101.34/100 000) and Wulingshan Township (99.21/100 000). The registered PTB from 2016 to 2020 showed a global auto-correlation (Moran's I=0.64, P<0.0001). The "high-high" area of active PTB and the etiological positive PTB all covered Lizhi street, Jiangdong street and Longqiao street. By scanning analysis of spatial-temporal, the primary cluster of active PTB concentrated in the main urban area south of the Yangtze River in Fuling during January 2016 to December 2017, and the primary cluster of pathogenic positive PTB concentrated in the main urban area south of the Yangtze River in Fuling and Jiangdong street during January 2019 to December 2020. Conclusions During the 13th Five-Year Plan period, there was the spatial-temporal clustering of PTB in Fuling District, which mainly gathered in the main urban area south of the Yangtze River in Fuling district and surrounding streets centered on Lizhi street.

[Analysis of absorbed constituents and network pharmacology research of Xiaoer Fupi Granules].

Xiaoer Fupi Granules, a refined version of the classical prescription Shenling Baizhu Powder, has the effect of invigora-ting spleen, replenishing Qi, harmonizing stomach and resolving accumulation and is commonly used to treat Qi deficiency in spleen and stomach, disordered transportation and transformation, and indigestion of children. However, its medicinal constituents and mechanism remain unclear. We studied the main active constituents and action mechanism of Xiaoer Fupi Granules by integrating network pharmacology and prototype constituent analysis in vivo. This study will help to increase the reliability of database analysis results and lay a foundation for precise medication and mining of quality control markers. On the basis of Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine(BATMAN-TCM), the "key chemical constituents-target" network was constructed. Ultra-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS) was employed to analyze the absorbed constituents in rat urine and plasma, so as to validate the network. Further, we used BATMAN-TCM to construct the "absorbed constituents-target-pathway" network and explore the functioning mechanism of Xiaoer Fupi Granules. A total of 86 chemical constituents of Xiaoer Fupi Granules were predicted via BATMAN-TCM, among which only 18.6% were detected in rat plasma and urine. Accor-ding to the "absorbed constituents-target-pathway" network, 8 chemical constituents such as stearic acid and caprylic acid capable of regulating gastric acid and insulin secretion may be the critical constituents of Xiaoer Fupi Granules in invigorating spleen and harmonizing stomach. This study identified the critical active constituents and predicted the action mechanism of Xiaoer Fupi Granules, providing the reference for the research on the material basis of Xiaoer Fupi Granules.

Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND: Abnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC-related NIID in China. METHODS: Patients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy. RESULTS: In the 247 patients with NOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=-0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission. CONCLUSIONS: NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.

Two New C21 Steroidal Glycosides from Selaginella Braunii Baker.

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.