Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression.

In mammals, the transition from mitosis to meiosis facilitates the successful production of gametes. However, the regulatory mechanisms that control meiotic initiation remain unclear, particularly in the context of complex histone modifications. Herein, we show that KDM2A, acting as a lysine demethylase targeting H3K36me3 in male germ cells, plays an essential role in modulating meiotic entry and progression. Conditional deletion of Kdm2a in mouse pre-meiotic germ cells results in complete male sterility, with spermatogenesis ultimately arrested at the zygotene stage of meiosis. KDM2A deficiency disrupts H3K36me2/3 deposition in c-KIT+ germ cells, characterized by a reduction in H3K36me2 but a dramatic increase in H3K36me3. Furthermore, KDM2A recruits the transcription factor E2F1 and its co-factor HCFC1 to the promoters of key genes required for meiosis entry and progression, such as Stra8, Meiosin, Spo11, and Sycp1. Collectively, our study unveils an essential role for KDM2A in mediating H3K36me2/3 deposition and controlling the programmed gene expression necessary for the transition from mitosis to meiosis during spermatogenesis.

hnRNPH1 establishes Sertoli-germ cell crosstalk through cooperation with PTBP1 and AR, and is essential for male fertility in mice.

Spermatogenesis depends on the crosstalk of Sertoli cells (SCs) and germ cells. However, the gene regulatory network establishing the communications between SCs and germ cells remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) in SCs is essential for the establishment of crosstalk between SCs and germ cells. Conditional knockout of hnRNPH1 in mouse SCs leads to compromised blood-testis barrier function, delayed meiotic progression, increased germ cell apoptosis, sloughing of germ cells and, eventually, infertility of mice. Mechanistically, we discovered that hnRNPH1 could interact with the splicing regulator PTBP1 in SCs to regulate the pre-mRNA alternative splicing of the target genes functionally related to cell adhesion. Interestingly, we also found hnRNPH1 could cooperate with the androgen receptor, one of the SC-specific transcription factors, to modulate the transcription level of a group of genes associated with the cell-cell junction and EGFR pathway by directly binding to the gene promoters. Collectively, our findings reveal a crucial role for hnRNPH1 in SCs during spermatogenesis and uncover a potential molecular regulatory network involving hnRNPH1 in establishing Sertoli-germ cell crosstalk.

Cortical atrophy in early-stage patients with anti-NMDA receptor encephalitis: a machine-learning MRI study with various feature extraction.

Conventional brain magnetic resonance imaging (MRI) of anti-N-methyl-D-aspartate-receptor encephalitis (NMDARE) is non-specific, thus showing little differential diagnostic value, especially for MRI-negative patients. To characterize patterns of structural alterations and facilitate the diagnosis of MRI-negative NMDARE patients, we build two support vector machine models (NMDARE versus healthy controls [HC] model and NMDARE versus viral encephalitis [VE] model) based on radiomics features extracted from brain MRI. A total of 109 MRI-negative NMDARE patients in the acute phase, 108 HCs and 84 acute MRI-negative VE cases were included for training. Another 29 NMDARE patients, 28 HCs and 26 VE cases were included for validation. Eighty features discriminated NMDARE patients from HCs, with area under the receiver operating characteristic curve (AUC) of 0.963 in validation set. NMDARE patients presented with significantly lower thickness, area, and volume and higher mean curvature than HCs. Potential atrophy predominately presented in the frontal lobe (cumulative weight = 4.3725, contribution rate of 29.86%), and temporal lobe (cumulative weight = 2.573, contribution rate of 17.57%). The NMDARE versus VE model achieved certain diagnostic power, with AUC of 0.879 in validation set. Our research shows potential atrophy across the entire cerebral cortex in acute NMDARE patients, and MRI machine learning model has a potential to facilitate the diagnosis MRI-negative NMDARE.

Genome-wide characterization of the bHLH gene family in Gynostemma pentaphyllum reveals its potential role in the regulation of gypenoside biosynthesis.

BACKGROUND: Gynostemma pentaphyllum, an ancient Chinese herbal medicine, serves as a natural source of gypenosides with significant medicinal properties. Basic helix-loop-helix (bHLH) transcription factors play pivotal roles in numerous biological processes, especially in the regulation of secondary metabolism in plants. However, the characteristics and functions of the bHLH genes in G. pentaphyllum remain unexplored, and their regulatory role in gypenoside biosynthesis remains poorly elucidated. RESULTS: This study identified a total of 111 bHLH members in G. pentaphyllum (GpbHLHs), categorizing them into 26 subgroups based on shared conserved motif compositions and gene structures. Collinearity analysis illustrated that segmental duplications predominately lead to the evolution of GpbHLHs, with most duplicated GpbHLH gene pairs undergoing purifying selection. Among the nine gypenoside-related GpbHLH genes, two GpbHLHs (GpbHLH15 and GpbHLH58) were selected for further investigation based on co-expression analysis and functional prediction. The expression of these two selected GpbHLHs was dramatically induced by methyl jasmonate, and their nuclear localization was confirmed. Furthermore, yeast one-hybrid and dual-luciferase assays demonstrated that GpbHLH15 and GpbHLH58 could bind to the promoters of the gypenoside biosynthesis pathway genes, such as GpFPS1, GpSS1, and GpOSC1, and activate their promoter activity to varying degrees. CONCLUSIONS: In conclusion, our findings provide a detailed analysis of the bHLH family and valuable insights into the potential use of GpbHLHs to enhance the accumulation of gypenosides in G. pentaphyllum.

Efficacy and safety of different oral prednisone tapering courses in adult anti-NMDAR encephalitis: A multicenter prospective cohort study.

OBJECTIVE: In adult anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, corticosteroids are commonly used as first-line treatment. However, the optimal oral prednisone tapering (OPT) following intravenous methylprednisolone pulse therapy remains unclear. We aim to compare the efficacy and safety of different OPT courses in anti-NMDAR encephalitis. METHODS: The CHASE study, a multicenter prospective observational cohort study, enrolled patients with autoimmune encephalitis from October 2011 to March 2023. Patients were grouped based on oral prednisone tapering course: ≤3 months (Group ≤3 month), 3-6 months (Group 3-6 months, including 3 months), and >6 months (Group > 6 months). Kaplan-Meier plots were used to analyze time to relapse and time to total recovery within 2 years. RESULTS: Among 666 screened patients, 171 (median [IQR] age 27 [21.0-36.5] years, 55.0% female) met selection criteria. Responders at 3 months were prevalent in Group ≤3 months (OR 7.251 [95% CI 2.252 to 23.344] and Group 3-6 months (OR, 3.857 [95% CI 1.107 to 13.440] than in Group >6 months. Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at 12 months were higher in Group >6 months than in Group ≤3 months and Group 3-6 months (ß, -2.329 [95% CI -3.784 to -.875]; ß, -2.871 [95% CI -4.490, -1.253]). CASE seizures subscore was higher in Group >6 months than in Group 3-6 months (ß, -.452 [95% CI -.788 to -.116]). No significant difference in seizure freedom rates among the groups. Adverse events were higher in Group 3-6 months and Group >6 months than in Group ≤3 months (OR 6.045 [95% CI 2.352 to 15.538]; OR 6.782 [95% CI 1.911 to 24.073]). SIGNIFICANCE: Longer oral prednisone courses for adult patients with anti-NMDAR encephalitis did not show superior effects compared to shorter courses in improving modified Rankin Scale (mRS) scores and CASE scores, reducing the risk of relapse within 2 years, or achieving seizure freedom. Instead, extended prednisone courses may lead to more side effects- particularly weight gain. This outcome recommends evaluating the possibility of shortening the duration of oral prednisone after a thorough patient assessment.

Neurological complications during the Omicron COVID-19 wave in China: A cohort study.

BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.

The association between APOE gene polymorphisms and the risk, characteristics, and prognosis of epilepsy: A systematic review and meta-analysis.

OBJECTIVE: Epilepsy is one of the most common neurological diseases. Current evidence suggests that the apolipoprotein E (APOE) gene may be related to epilepsy. The purpose was to explore whether the APOE gene is associated with the risk, characteristics, and prognosis of epilepsy. METHODS: The study was a systematic review and meta-analysis. We searched WANFANG, VIP, CNKI, Embase, CENTRAL, and Medline for relevant studies published in English and Chinese inception up to December 27, 2023. Studies containing both APOE genotypes or at least one type of APOE allele and epilepsy were included. RESULTS: A total of 46 studies were included. Fourteen studies reported APOE genotypes and epilepsy risk (2539 patients and 2847 controls). The meta-analyses showed that the APOE 4 was higher in epilepsy (OR [95 % CI] = 1.32 [1.07, 1.62], I2 = 30 %), the APOE 2 was lower in epilepsy (OR [95 % CI] = 0.73 [0.62, 0.87], I2 = 0 %), and the APOE 3 didn't differ between epilepsy and controls (OR [95 % CI] = 1.01 [0.86, 1.19], I2 = 29 %). Our findings highlight that the risk of epilepsy is different depending on the subtype, with the APOE gene being more associated with temporal lobe epilepsy, drug-refractory epilepsy, and late-onset epilepsy. Patients with the ɛ4 allele have an earlier onset, worse cognition, and are more likely to have a history of febrile convulsion. No association between the ɛ4 allele and psychiatric symptoms and seizure-free after surgery. INTERPRETATION: These findings will help inform the provision of epilepsy services, including clinical management an important option for epilepsy patients with cognitive impairment, temporal lobe epilepsy, late-onset epilepsy, and drug-refractory epilepsy. However, whether APOE gene testing should be used as a routine test in people with epilepsy remains to be determined.

Social support and the burden of physical and psychiatric comorbidities in the patients with late-onset epilepsy in China: A cross-sectional study.

INTRODUCTION: Epilepsy is the third most common neurological disorder in elderly people. Patients with epilepsy (PWEs) are more likely to have comorbidities. Social support is very important for PWEs. However, there are many gaps in the research on social support in older PWEs, especially the correlation between social support and comorbidities. METHODS: A cross-sectional study was conducted in three hospitals in China. Social support was assessed using the Social Support Rate Scale. The burden of physical comorbidities was assessed using the CCI, and global disability was assessed using the mRS. The NDDIE was used to assess depression, the GAD7 was used for anxiety, the CDR was used for cognitive status, and the NPI was used for psychotic symptoms. RESULTS: A total of 154 older PWEs participated in the study. There were 97 patients with at least one physical comorbidities. The burden of physical comorbidities was negatively correlated with overall social support (Adj. r = -0.35, P < 0.001) and global disability (Adj. r = -0.45, P < 0.001). In terms of psychiatric comorbidities, anxiety, depression, and cognitive status were not correlated with overall social support (Adj. r = -0.03, -0.02, and -0.11, P > 0.05). Psychotic symptoms were correlated with overall social support (Adj. r = -0.20, P < 0.05). The overall burden of psychiatric comorbidities was associated with overall social support (r = 0.30, P < 0.01). DISCUSSION: Neurologists and social workers should consider more personalized biopsychosocial care to improve the quality of life of older PWEs.

Co-transfer of IncFII/IncFIB and IncFII plasmids mediated by IS26 facilitates the transmission of mcr-8.1 and tmexCD1-toprJ1.

PURPOSE: This study aimed to characterise the whole-genome structure of two clinical Klebsiella pneumoniae strains co-harbouring mcr-8.1 and tmexCD1-toprJ1, both resistant to colistin and tigecycline. METHODS: K. pneumoniae strains TGC-02 (ST656) and TGC-05 (ST273) were isolated from urine samples of different patients hospitalised at separate times in 2021. Characterisation involved antimicrobial susceptibility testing (AST), conjugation assays, whole-genome sequencing (WGS), and bioinformatics analysis. Comparative genomic analysis was conducted on mcr-8.1-carrying and tmexCD1-toprJ1-carrying plasmids. RESULTS: Both K. pneumoniae isolates displayed a multidrug-resistant phenotype, exhibiting resistance or reduced susceptibility to ampicillin, ampicillin/sulbactam, cefazolin, aztreonam, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, apramycin, tigecycline and colistin. WGS analysis revealed that clinical strain TGC-02 carried the TmexCD1-toprJ1 gene on a 200-Kb IncFII/IncFIB-type plasmid, while mcr-8 was situated on a 146-Kb IncFII-type plasmid. In clinical strain TGC-05, TmexCD1-toprJ1 was found on a 300-Kb IncFIB/IncHI1B/IncR-type plasmid, and mcr-8 was identified on a 137-Kb IncFII/IncFIA-type plasmid. Conjugation experiments assessed the transferability of these plasmids. While transconjugants were not obtained for TGC-05 despite multiple screening with tigecycline or colistin, pTGC-02-tmex and pTGC-02-mcr8 from clinical K. pneumoniae TGC-02 demonstrated self-transferability through conjugation. Notably, the rearrangement of pTGC-02-tmex and pTGC-02-mcr8 via IS26-based homologous recombination was observed. Moreover, the conjugative and fusion plasmids of the transconjugant co-harboured the tmexCD1-toprJ1 gene cluster and mcr-8.1, potentially resulting from IS26-based homologous recombination. CONCLUSION: The emergence of colistin- and tigecycline-resistant K. pneumoniae strains is concerning, and effective surveillance measures should be implemented to prevent further dissemination.

Analysis of Comprehensive Nursing in the Treatment of Elderly Patients with Thoracolumbar Vertebral Body Compression Fractures by Percutaneous Vertebroplasty.

Objective: To explore and analyze the comprehensive nursing effect of percutaneous vertebroplasty (PVP) in the treatment of elderly patients with thoracolumbar vertebral compression fractures. Methods: This study recruited elderly patients with thoracolumbar vertebral compression fractures who were diagnosed in Lujiang County People's Hospital from January 2020 to December 2022 and underwent PVP. Finally, a total of 80 cases were included in this study. All patients were randomly divided into two treatment groups: the observation group and the control group. The patients in the control group were given routine nursing measures, and the patients in the observation group were given comprehensive nursing intervention. The baseline characteristics of the two groups of patients were recorded thoroughly, and relevant indicators such as clinical indicators, functional recovery, pain relief, and occurrence of complications were observed and compared between the two groups. Results: The recovery time of the patients in the observation group, including the time of getting out of bed and the time of hospitalization, was significantly shorter than that of the control group [OR = 0.61 (95%CI: 0.44 - 0.83); OR = 0.70 (95%CI: 0.51 - 0.96)] P < .05; the JOA score of the observation group was significantly higher than that of the control group after treatment (RR = 1.28 (95%CI: 1.16 - 1.42)); the vas scores of the patients at each time point were lower than those of the control group [OR = 0.60 (95%CI: 0.43 - 0.84); OR = 0.57 (95%CI: 0.41 - 0.80); OR = 0.61 (95%CI: 0.44 - 0.85); OR = 0.72 (95%CI: 0.52 - 0.99)]; the incidence of complications in the observation group was significantly lower than that of the control group OR = 0.27 (95%CI: 0.10 - 0.72). Conclusion: The implementation of comprehensive nursing has a clear application effect on PVP in the treatment of elderly patients with thoracolumbar vertebral compression fractures. It can effectively speed up patients' movement speeds, reduce the overall length of hospitalization, and promote the recovery of thoracolumbar spine function. It can also relieve the patient's pain faster, reduce the possibility of complications, and have a positive impact on the patient's prognosis, which is worthy of clinical application.

Single-cell RNA sequencing reveals diverse B cell phenotypes in patients with anti-NMDAR encephalitis.

BACKGROUNDS: Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune disorder characterized by prominent psychiatric symptoms. Although the role of NMDAR antibodies in the disease has been extensively studied, the phenotype of B cell subsets is still not fully understood. METHODS: We utilized single-cell RNA sequencing, single-cell B cell receptor sequencing (scBCR-seq), bulk BCR sequencing, flow cytometry, and enzyme-linked immunosorbent assay to analyze samples from both NMDAR-E patients and control individuals. RESULTS: The cerebrospinal fluid (CSF) of NMDAR-E patients showed significantly increased B cell counts, predominantly memory B (Bm) cells. CSF Bm cells in NMDAR-E patients exhibited upregulated expression of differential expression genes (DEGs) associated with immune regulatory function (TNFRSF13B and ITGB1), whereas peripheral B cells upregulated DEGs related to antigen presentation. Additionally, NMDAR-E patients displayed higher levels of IgD- CD27- double negative (DN) cells and DN3 cells in peripheral blood (PB). In vitro, DN1 cell subsets from NMDAR-E patients differentiated into DN2 and DN3 cells, while CD27+ and/or IgD+ B cells (non-DN) differentiated into antibody-secreting cells (ASCs) and DN cells. NR1-IgG antibodies were found in B cell culture supernatants from patients. Differential expression of B cell IGHV genes in CSF and PB of NMDAR-E patients suggests potential antigen class switching. CONCLUSION: B cell subpopulations in the CSF and PB of NMDAR-E patients exhibit distinct compositions and transcriptomic features. In vitro, non-DN cells from NMDAR-E can differentiate into DN cells and ASCs, potentially producing NR1-IgG antibodies. Further research is necessary to investigate the potential contribution of DN cell subpopulations to NR1-IgG antibody production.

Long noncoding RNA LINC00482 silencing sensitizes non-small cell lung cancer cells to cisplatin by downregulating CLASRP via E2F1.

Long noncoding RNA LINC00482 (LINC00482) is dysregulated in non-small cell lung cancer cells (NSCLC). Herein, this research examined the actions and specific mechanisms of LINC00482 in cisplatin (DDP) resistance in NSCLC. LINC00482 expression was assessed using RT-qPCR in clinical NSCLC tissues and cell lines. Knockdown and ectopic expression assays were conducted in A549 and HCC44 cells, followed by determination of cell proliferation with CCK-8 and clone formation assays, apoptosis with flow cytometry, and DDP sensitivity. The association between LINC00482, E2F1, and CLASRP was evaluated with dual-luciferase reporter, ChIP, and RIP assays. The role of LINC00482 in NSCLC was confirmed in nude mice. NSCLC tissues and cells had upregulated LINC00482 expression. LINC00482 was mainly localized in the cell nucleus, and LINC00482 recruited E2F1 to enhance CLASRP expression in NSCLC cells. LINC00482 knockdown enhanced the DDP sensitivity and apoptosis of NSCLC cells while reducing cell proliferation, which was negated by overexpressing CLASRP. LINC00482 knockdown restricted tumor growth and enhanced DDP sensitivity in NSCLC in vivo. LINC00482 silencing downregulated CLASRP through E2F1 to facilitate the sensitivity to DDP in NSCLC.

Somatic symptoms and related disorders in a large cohort of people with epilepsy: A cohort study.

OBJECTIVE: This study was undertaken to characterize somatic symptoms and related disorders (SSD) in epilepsy. METHODS: Adults with epilepsy under active follow-up at a tertiary epilepsy center were consecutively enrolled. The diagnosis of SSD was performed by an experienced psychologist based on the structured clinical interview for Statistical Manual of Mental Disorders, 5th edition. Detailed social/demographic data, epilepsy features, psychiatric features, life quality, disability, and economic burden were collected and compared between people with SSD and those without. Bodily distress syndrome checklist, Somatic Symptom Disorder-B Criteria Scale, Patient Health Questionnaire-9, and Generalized Anxiety Disorder seven-item scale (GAD-7) were used to evaluate SSD individuals' somatic symptoms, symptom-related psychological distress, and depressive and anxious symptoms. Quality of life and disability were assessed by Quality of Life in Epilepsy Inventory 31 (QOLIE-31) and World Health Organization Disability Assessment Schedule V.2.0 (WHO DAS 2.0). A risk prediction nomogram was generated using least absolute shrinkage and selection operator (LASSO) analysis and validated. RESULTS: One hundred fifty of 631 participants (24%) were diagnosed with SSD. In people with SSD, the top three most common somatic symptoms were memory impairment, headache, and dizziness (85%, 80%, and 78%, respectively), and multiple systems were involved in most (82%) people with SSD. Compared with people without SSD, those with SSD had lower QOLIE-31 total scores, and higher WHO DAS 2.0 scores and disease economic burdens. LASSO analysis suggested that a history of severe traumatic brain injury, hippocampal sclerosis, low seizure worry and medication effects scores on QOLIE-31, multiple systems affected by somatic symptoms, and a high GAD-7 score were risk factors of SSD. The nomogram was validated for good accuracy in the training and testing cohorts. SIGNIFICANCE: SSD are likely to be a common comorbidity in epilepsy and harm epilepsy prognosis. Our risk prediction nomogram was successfully developed but needs further validation in larger cohorts.

One-Step Electrodeposition of Polyaniline Nanorods on Carbon Cloth for High-Performance Flexible Supercapacitors.

The electrochemical performance of the carbon cloth (CC)-based electrodes is determined by the kind, content, morphology, and size of the modified pseudocapacitive materials, as well as the interaction with CC. Also, such structural parameters were mainly dependent on the deposition condition. More uniform polyaniline (PANI) could be obtained by electrochemical polymerization in comparison to chemical oxidation polymerization. However, two steps of electrodeposition were usually needed for nucleation and growth. Here, based on the comprehensive optimization of the electrodeposition condition, well-defined PANI nanorods anchored on the functionalized carbon cloth (FCC) as flexible electrodes (FCC@PANI) were synthesized by a facile one-step electrochemical polymerization. Compared with the FCC electrode, the resultant FCC@PANI-4 sample possessed good cycling stability (98.3% capacitance retention after 10,000 cycles), higher specific capacitances of 2312 mF cm-2 (1.0 mA cm-2) and 107 F g-1 (1.0 A g-1) with the boosting ratio in the areal specific capacitance (CA), and mass specific capacitances (Cm) of 169 and 181%, respectively. The improvement in both specific capacitance and cycling stability was obtained by the strong interaction between the FCC and the modified PANI nanorods with enhanced utilization efficiency of electroactive materials. Furthermore, the symmetric solid-state device assembled using the FCC@PANI-4 electrode delivered a maximum energy density of 0.079 mWh cm-2 at a power density of 0.363 mW cm-2.

Patient characteristics and outcome in patients with anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis.

OBJECTIVE: Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis is a rare subtype of autoimmune encephalitis. We report patients diagnosed with anti-AMPAR encephalitis in western China, focusing on their clinical presentations, imaging results, treatment strategies, and prognosis. METHODS: Data from patients diagnosed with anti-AMPAR encephalitis in the neurology center of West China Hospital from August 2018 to July 2021 were retrospectively collected and analyzed. Based on the diagnostic criteria of autoimmune encephalitis, nine cases were included. RESULTS: Four patients (44%) were males, and the median age at presentation was 54 years (range, 25-85). Short-term memory loss was the most common initial symptom. Additional types of autoantibodies were identified in three patients. After presentation, four patients were found to have tumors: two with small cell lung cancer, one with ovarian teratoma, and one with thymoma. All patients accepted first-line immune therapy, and follow-up was available from 8 patients (median 20 weeks, range 4-78). At the last follow-up, three patients showed good outcomes (modified Rankin scale [mRS] 0-2; 37.5%). Five patients showed poor outcomes (mRS 3-6; 62.5%): two had minimal changes and remained hospitalized, two had residual severe cognitive impairments, and one patient died during follow-up. Outcomes were worse among patients with tumors. Finally, only one patient experienced relapse during follow-up. CONCLUSION: Anti-AMPAR encephalitis should be considered in the differential diagnosis for middle- and senior-aged patients who present with predominantly acute or subacute short-term memory impairment. The long-term prognosis is correlated with the presence of a tumor.

UHRF1 is indispensable for meiotic sex chromosome inactivation and interacts with the DNA damage response pathway in mice†.

During male meiosis, the constitutively unsynapsed XY chromosomes undergo meiotic sex chromosome inactivation (MSCI), and the DNA damage response (DDR) pathway is critical for MSCI establishment. Our previous study showed that UHRF1 (ubiquitin-like, with PHD and ring finger domains 1) deletion led to meiotic arrest and male infertility; however, the underlying mechanisms of UHRF1 in the regulation of meiosis remain unclear. Here, we report that UHRF1 is required for MSCI and cooperates with the DDR pathway in male meiosis. UHRF1-deficient spermatocytes display aberrant pairing and synapsis of homologous chromosomes during the pachytene stage. In addition, UHRF1 deficiency leads to aberrant recruitment of ATR and FANCD2 on the sex chromosomes and disrupts the diffusion of ATR to the XY chromatin. Furthermore, we show that UHRF1 acts as a cofactor of BRCA1 to facilitate the recruitment of DDR factors onto sex chromosomes for MSCI establishment. Accordingly, deletion of UHRF1 leads to the failure of meiotic silencing on sex chromosomes, resulting in meiotic arrest. In addition to our previous findings, the present study reveals that UHRF1 participates in MSCI, ensuring the progression of male meiosis. This suggests a multifunctional role of UHRF1 in the male germline.

Highly Efficient Solvothermal Synthesis of Poly(1,5-diaminoanthraquinone) Nanoflowers for Energy and Environmental Applications.

Poly(1,5-diaminoanthraquinone) (PDAA) has attracted more interest because of its unique molecular structure. However, the lower polymerization yield limits its practical application. Here, the solvothermal chemically oxidative polymerization of 1,5-diaminoanthraquinone (DAA) was developed, and the well-defined PDAA nanoflowers were obtained with a high yield of 72.6% within 16 h. The PDAA nanoflower-based flexible film electrodes were fabricated with expandable graphene as conductive support, delivering a capacitance of 277 F g-1 and 258 mF cm-2 at 0.5 A g-1 (1 mA cm-2) and superior cycling stability with retention of 99% after 10000 cycles. The flexible symmetric solid-state supercapacitors (SSSCs) possessed a high capacitance of 52.5 F g-1 at 0.25 A g-1 and 96.6 mF cm-2 at 1 mA cm-2 and had only a 14% capacitance loss after 10000 cycles at 0.1 V s-1 as well as excellent flexibility. Besides, the PDAA nanoflowers could be used as self-separable adsorbent for methylene blue (MB) with a capacity of 93.8 mg g-1 at pH 9.

Typical linear radial periventricular enhancement in a patient with glial fibrillary acidic protein (GFAP) astrocytopathy.

OBJECTIVE: We describe an unusual case of corticosteroid-responsive autoimmune meningoencephalomyelitis with linear perivascular gadolinium enhancement but in the absence of anti- glial fibrillary acidic protein (GFAP) antibodies (ABs) in the cerebral spinal fluid (CSF). METHODS: The patient's clinical symptoms, brain magnetic resonance imaging (MRI) features, serum and CSF analysis and treatment were reviewed. RESULTS: A 47-year-old female experienced a subacute course with bilateral lower limbs weakness, unsteady walking, and dysuria. Brain MRI revealed typical radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter; MRI spine revealed lesions distributed in the entire spinal cord. Immunohistochemical staining of a brain biopsy revealed CD3+ T cells and CD20+ B cells cuffing around brain vessels, accompanied by CD68+ macrophages. CSF was negative for anti-GFAP ABs while serum was positive for anti-GFAP ABs (1:100). The patient responded well to corticosteroid. CONCLUSIONS: There are no uniform diagnostic criteria for autoimmune GFAP astrocytopathy. Our case suggested the importance of typical MRI findings in the diagnosis of this rare disease. Early treatments are very important to alleviate symptoms.

The detection of up-regulated anti-thyroid antibodies and autoimmune thyroid diseases in patients with autoimmune encephalitis: a retrospective study of 221 patients.

OBJECTIVE: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE. METHODS: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses. RESULTS: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE. CONCLUSIONS: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.

Evaluation of di-rhamnolipid biosurfactants production by a novel Pseudomonas sp. S1WB: Optimization, characterization and effect on petroleum-hydrocarbon degradation.

Rhamnolipid biosurfactants are multifunctional compounds that can play an indispensable role in biotechnological, biomedical, and environmental bioremediation-related fields, and have attracted significant attention in recent years. Herein, a novel strain Pseudomonas sp. S1WB was isolated from an oil-contaminated water sample. The biosurfactants produced by this strain have capabilities to reduce surface tension (SFT) at 32.75 ± 1.63 mN/m and emulsified 50.2 ± 1.13 % in liquid media containing 1 % used engine oil (UEO) as the sole carbon source. However, the lowest SFT reduction (28.25 ± 0.21), highest emulsification index (60.15 ± 0.07), and the maximum yields (900 mg/L) were achieved under optimized conditions; where, the glucose/urea and glycerol/urea combinations were found efficient carbon and nitrogen substrates for improved biosurfactants production. Biosurfactants product was characterized using ultra-high performance liquid chromatography-mass spectrometry (UHPLC- MS) and detected various di- rhamnolipids congeners. In addition, the di-rhamnolipids produced by S1WB strain was found highly stable in terms of surface activity and EI indices at different environmental factors i.e. temperature, pH and various NaCl concentrations, where, emulsifying property was found high stable till 30 days of incubation. Moreover, the stain was capable to degrade hydrocarbon at 42.2 ± 0.04 %, and the Gas chromatography- mass spectrometry (GC-MS) profile showed the majority of peak intensities of hydrocarbons have been completely degraded compared to control.