Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

BACKGROUND: As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. METHODS: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. RESULTS: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12-74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92-1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. CONCLUSION: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

Batoclimab vs Placebo for Generalized Myasthenia Gravis: A Randomized Clinical Trial.

Importance: Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in the circulation and alleviate symptoms in patients with generalized MG. Objective: To examine the efficacy and safety profile of batoclimab, a monoclonal IgG1 antibody, in patients with generalized MG. Design, Setting, and Participants: This was a multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers in China. Adult patients 18 years or older with generalized MG were screened, and those who were antibody positive were enrolled. Intervention: Eligible patients received batoclimab or matching placebo in addition to standard of care. Each treatment cycle consisted of 6 weekly subcutaneous injections of batoclimab, 680 mg, or matching placebo followed by 4 weeks of observation. A second treatment cycle was conducted in patients who required continuing treatment. Main Outcome and Measure: The primary outcome was sustained improvement, as defined by a 3-point or greater reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline for 4 or more consecutive weeks in the first cycle in individuals who were positive for acetylcholine receptor or muscle-specific kinase antibodies. Results: A total of 178 adult patients with generalized MG were screened, 132 were randomly assigned, 131 tested positive for antibodies, and 1 tested negative for antibodies. A total of 132 patients (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) were enrolled. The rate of sustained MG-ADL improvement in the first cycle in antibody-positive patients was 31.3% (20 of 64) in the placebo group vs 58.2% (39 of 67) in the batoclimab group (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). The MG-ADL score diverged between the 2 groups as early as week 2. The mean (SE) maximum difference in MG-ADL score reduction occurred 1 week after the last dose (day 43, 1.7 [0.3] in the placebo group vs 3.6 [0.3] in the batoclimab group; group difference, -1.9; 95% CI, -2.8 to -1.0; nominal P < .001). The rates of treatment-related and severe treatment-emergent adverse events in patients were 36.9% (24 of 65) and 7.7% (5 of 65) in the placebo group vs 70.1% (47 of 67) and 3.0% (2 of 67) in the batoclimab group, respectively. Conclusions and Relevance: Batoclimab increased the rate of sustained MG-ADL improvement and was well tolerated in adult patients with generalized MG. Clinical effects and the extent of IgG reduction were similar to those previously reported for efgartigimod and rozanolixizumab. Future studies of large sample size are needed to further understand the safety profile of batoclimab. Trial Registration: ClinicalTrials.gov Identifier: NCT05039190.

Association between insulin resistance, metabolic syndrome and its components and lung cancer: a systematic review and meta-analysis.

BACKGROUND: A growing body of evidence points to the association between insulin resistance (IR), metabolic syndrome (MetS) and its components and lung cancer incidence, but remains controversial and unknown. METHODS: A systematic search was conducted through PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI) and Wanfang databases for the corresponding studies. Each study reported the risk estimate and 95% confidence intervals (CI) for lung cancer, and a fixed effects model or random effects model was used for outcome. RESULTS: We included 31 publications involving 6,589,383 people with 62,246 cases of lung cancer. Diabetes mellitus (DM) (RR = 1.11, 95% CI 1.06-1.16, P = 0.000) and IR (RR = 2.35, 95% CI 1.55-3.58, P = 0.000) showed a positive association with lung cancer risk. BMI (RR = 0.66, 95% CI 0.54-0.81, P = 0.000) and HDL-C (RR = 0.88, 95% CI 0.79-0.97, P = 0.010) were negatively correlated with lung cancer. MetS(RR = 0.99, 95% CI 0.90-1.09, P = 0.801), TC (RR = 0.93, 95% CI 0.81-1.06, P = 0.274), TG (RR = 0.99, 95% CI 0.88-1.12,P = 0.884), LDL-C (RR = 1.01, 95% CI 0.87-1.16, P = 0.928), hypertension (RR = 1.01, 95% CI 0.88-1.15, P = 0.928), FBG (RR = 1.02, 95% CI 0.92-1.13, P = 0.677) and obesity (RR = 1.11, 95% CI 0.92-1.35, P = 0.280) were not associated with lung cancer. CONCLUSION: Our study showed that the risk of lung cancer is correlated with DM, IR, BMI, and HDL-C. Timely control of these metabolic disorders may have a positive effect on preventing lung cancer. Trial registration Our study has been registered in the Prospective Register of Systematic Reviews (PROSPERO), ID: CRD42023390710.

Exploring resting-state EEG oscillations in patients with Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVE: Quantitative resting-state electroencephalography (rs-EEG) is a convenient method for characterizing the functional impairments and adaptations of the brain that has been shown to be valuable for assessing many neurological and psychiatric disorders, especially in monitoring disease status and assisting neuromodulation treatment. However, it has not yet been explored in patients with neuromyelitis optica spectrum disorder (NMOSD). This study aimed to investigate the rs-EEG features of NMOSD patients and explore the rs-EEG features related to disease characteristics and complications (such as anxiety, depression, and fatigue). METHODS: A total of 32 NMOSD patients and 20 healthy controls (HCs) were recruited; their demographic and disease information were collected, and their anxiety, depression, and fatigue symptoms were evaluated. The rs-EEG power spectra of all the participants were obtained. After excluding the participants with low-quality rs-EEG data during processing, statistical analysis was conducted based on the clinical information and rs-EEG data of 29 patients and 19 HCs. The rs-EEG power (the mean spectral energy (MSE) of absolute power and relative power in all frequency bands, as well as the specific power for all electrode sites) of NMOSD patients and HCs was compared. Furthermore, correlation analyses were performed between rs-EEG power and other variables for NMOSD patients (including the disease characteristics and complications). RESULTS: The distribution of the rs-EEG power spectra in NMOSD patients was similar to that in HCs. The dominant alpha-peaks shifted significantly towards a lower frequency for patients when compared to HCs. The delta and theta power was significantly increased in the NMOSD group compared to that in the HC group. The alpha oscillation power was found to be significantly negatively associated with the degree of anxiety (reflected by the anxiety subscore of hospital anxiety and depression scale (HADS)) and the degree of depression (reflected by the depression subscore of HADS). The gamma oscillation power was revealed to be significantly positively correlated with the fatigue severity scale (FSS) score, while further analysis indicated that the electrode sites of almost the whole brain region showing correlations with fatigue. Regarding the disease variables, no statistically significant rs-EEG features were related to the main disease features in NMOSD patients. CONCLUSION: The results of this study suggest that the rs-EEG power spectra of NMOSD patients show increased slow oscillations and are potential biomarkers of widespread white matter microstructural damage in NMOSD. Moreover, this study revealed the rs-EEG features associated with anxiety, depression, and fatigue in NMOSD patients, which might help in the evaluation of these complications and the development of neuromodulation treatment. Quantitative rs-EEG analysis may play an important role in the management of NMOSD patients, and future studies are warranted to more comprehensively understand its application value.

Hyperoside Inhibits RNF8-mediated Nuclear Translocation of ß-catenin to Repress PD-L1 Expression and Prostate Cancer.

BACKGROUND: Hyperoside is a flavonol glycoside isolated from Hypericum perforatum L. that has inhibitory effects on cancer cells; however, its effects on prostate cancer (PCa) remain unclear. Therefore, we studied the anti-PCa effects of hyperoside and its underlying mechanisms in vitro and in vivo. AIM: This study aimed to explore the mechanism of hyperoside in anti-PCa. METHODS: 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl Tetrazolium Bromide (MTT), transwell, and flow cytometry assays were used to detect PCa cell growth, invasion, and cell apoptosis. Immunoblot analysis, immunofluorescence, immunoprecipitation, and quantitative real-time PCR (qRT-PCR) were used to analyze the antitumor mechanism of hyperoside. RESULTS: Hyperoside inhibited PCa cell growth, invasion, and cell cycle and induced cell apoptosis. Furthermore, RING finger protein 8 (RNF8), an E3 ligase that assembles K63 polyubiquitination chains, was predicted to be a direct target of hyperoside and was downregulated by hyperoside. Downregulation of RNF8 by hyperoside impeded the nuclear translocation of ß-catenin and disrupted the Wnt/ß-catenin pathway, which reduced the expression of the target genes c-myc, cyclin D1, and programmed death ligand 1 (PD-L1). Decreased PD-L1 levels contributed to induced immunity in Jurkat cells in vitro. Finally, in vivo studies demonstrated that hyperoside significantly reduced tumor size, inhibited PD-L1 and RNF8 expression, and induced apoptosis in tumor tissues of a subcutaneous mouse model. CONCLUSION: Hyperoside exerts its anti-PCa effect by reducing RNF8 protein, inhibiting nuclear translocation of ß-catenin, and disrupting the Wnt/ß-catenin pathway, in turn reducing the expression of PD-L1 and improving Jurkat cell immunity.

Elevational variation in metabolic rate, feeding capacity and their associations in the Asiatic toad Bufo gargarizans.

Foraging behavior is known to place demands on the metabolic characteristics of anurans. Active foragers feeding on sedentary prey typically have high aerobic capacity and low anaerobic capacity, whereas sit-and-wait foragers feeding on active and mobile prey have the opposite pattern. Thus, the energetic demands of foraging may influence their metabolic adaptations to harsh environments, such as high elevations. Anurans that engage in active foraging have been found to increase maximum metabolic rate (MMR) and aerobic scope (AS, the difference between MMR and resting metabolic rate, RMR) at high elevations. However, data are lacking in amphibian ambush foragers. In this study, we examined the RMR, MMR, AS, and feeding capacity of a sit-and-wait forager ─the Asiatic toad (Bufo gargarizans), from two populations that are in close geographic proximity but differ by 1350 m in elevation. Our results show that there is no elevational variation in RMR and feeding capacity in either males or females. However, there are sex-specific variations in MMR and AS along an elevational gradient; females from high elevations have lower MMR and smaller net AS than their counterparts from low elevations while males maintain similar MMR and net AS across elevations. Furthermore, aerobic performances do not appear to be associated with feeding capacity at either the individual or population level. Our results support the hypothesis that sit-and-wait foragers may not increase their aerobic capacity as a strategy in hypoxic and low food availability environments and the role of sex in these adaptive adjustments should not be overlooked.

Clinical outcome and peripheral immune profile of myasthenic crisis with omicron infections: A prospective cohort study.

The impact of Omicron infections on the clinical outcome and immune responses of myasthenia gravis (MG) remained largely unknown. From a prospective multicenter MG cohort (n = 189) with 197 myasthenic crisis (MC), we finally included 41 independent MG patients to classify into two groups: the Omicron Group (n = 13) and the Control Group (n = 28). In this matched cohort study, all-cause mortality was 7.69% (1/13) in Omicron Group and 14.29% (4/28) in Control Group. A higher proportion of elevated serum IL-6 was identified in the Omicron Group (88.89% vs 52.38%, P = 0.049). In addition, the proportions of CD3+CD8+T in lymphocytes and Tregs in CD3+CD4+ T cells were significantly elevated in the Omicron Group (both P = 0.0101). After treatment, the Omicron Group exhibited a marked improvement in MG-ADL score (P = 0.026) and MG-QoL-15 (P = 0.0357). MCs with Omicron infections were associated with elevated serum IL-6 and CD3+CD8+T response. These patients tended to present a better therapeutic response after fast-acting therapies and anti-IL-6 treatment.

Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1.

Despite the unique ability of pioneer transcription factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called ChIP-ISO to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1. Combining ChIP-ISO with in vitro and neural network analyses, we find that 1) FOXA1 binding is strongly affected by co-binding TFs AP-1 and CEBPB, 2) FOXA1 and AP-1 show binding cooperativity in vitro, 3) FOXA1's binding is determined more by local sequences than chromatin context, including eu-/heterochromatin, and 4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding.

Myasthenic crisis in thymoma-associated myasthenia gravis: a multicenter retrospective cohort study.

Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently associated with transient worsening of MG and even acute respiratory failure, namely myasthenic crisis (MC). However, little is known about the clinical features and outcomes of MC in thymoma-associated MG patients. We performed a retrospective cohort study in MG patients recruited from 9 independent tertiary neuromuscular centers in China from Jan 2015, through Oct 2022. Overall, 156 MC from 149 MG patients with positive anti-acetylcholine receptor (AChR) antibodies were finally analyzed. Next, these patients were divided into two subgroups: the TMG group (n = 60 MCs, 58 patients) and the non-thymoma-associated MG group (n = 96 MCs, 91 patients). Compared with non-thymoma-associated MG, TMG patients had a significantly shorter disease duration from symptom onset to the crisis (17.95±40.9 vs 51.31±60.61 months, P<0.0001), a larger proportion of MGFA IVa as the initial onset clinical classification (6.67% vs 0, P = 0.0205), and a longer hospital stay (39.24±22.09 [6-111] vs. 33.2 ± 23.42 days [7-120]; P = 0.0317) during the crisis. Within the TMG group, the hospital stay was significantly longer in patients with unresected thymoma compared to that in postoperative myasthenic crisis (POMC) (47.68±24.9 [6-111] vs. 34.21±18.87 days [12-82]; P = 0.0257). Early identification of the MG categories may provide some hints in tailoring therapeutic strategies to improve the prognosis.

A female case report of LGMD2B with compound heterozygous mutations of the DYSF gene and asymptomatic mutation of the X-linked DMD gene.

We report the case of a 31-year-old Chinese woman with a chief complaint of weakness in the lower limbs, which was diagnosed as limb-girdle muscular dystrophy 2B (LGMD2B) with compound heterozygous mutations of the DYSF gene. Meanwhile, this woman is an asymptomatic carrier with the mutation of the X-linked DMD gene. The electromyography, muscle MRI, and muscle biopsy indicated a chronic myogenic injury with dysferlin deletion. As a result of genetic testing, compound heterozygous G-to-T base substitution at position 5,497 in exon 49 of the DYSF gene, leading to a codon change from glutamic acid to termination codon at position 1,833, and a heterozygous C-to-G base change at position 4,638 + 8 in intron 42 of the DYSF gene with a consequence of splice, which has never been reported, were identified as candidate causative mutations. Unfortunately, DMD gene mutation c.3921+12A>G of the DMD gene on the X chromosome was also found in this patient. Finally, the patient was diagnosed as LGMD2B clinically and genetically. In the previous 2 years, the patient's lower limb weakness became slightly worse, resulting in even the total distance walked than before. Fortunately, during the follow-up, her son had not shown slowness or limitation of movement. Genetic testing by next-generation sequencing confirmed the final diagnosis of LGMD2B, and we identified the novel compound heterozygous variants in the DYSF gene, which is of great significance to the accurate diagnosis of genetically coded diseases. Much attention needs to be paid in clinics toward hereditary neuromuscular diseases with multiple pathogenic gene mutations. Genetic counseling and clinical follow-up should be the priorities in future, and promising treatments are also worth exploring.

The biodiversity of Aspergillus flavus in stored rice grain leads to a decrease in the overall aflatoxin B1 production in these species.

Aspergillus flavus is a significant fungus that poses a threat to food safety by producing mycotoxins in various crops. In this study, A. flavus isolates were obtained from storage rice collected from seven provinces in southern China, and their AFB1 production, biosynthesis genes presence, and diversity were detected. Results showed that 56 out of the 81 A. flavus isolates produced detectable levels of AFB1, and 71 isolates (87.6 %) possessed aflR gene in their AF synthesis gene cluster, while only 41 isolates (50.6 %) had the ver-1 gene present. Genetic diversity analysis using inter-simple sequence repeats (ISSR) markers revealed seven main clusters among the isolates and the genetic similarity coefficients of 81 A. flavus isolates ranged from 0.53 to 1.00. Additionally, coculture assays were conducted using two toxigenic and two atoxigenic isolates from the same grain depot to investigate the effect of intraspecific inhibition on AFB1 production and to assess the AFB1 contamination risk of storage rice. The in situ results demonstrated that the atoxigenic isolates effectively inhibited the AFB1 contamination of toxigenic isolates. These findings provide insight into the genetic diversity of A. flavus isolates populations and highlight the potential food safety hazards of them in stored rice grain in China.

Efficacy and safety of totally laparoscopic gastrectomy with uncut Roux-en-Y for gastric cancer: a dual-center retrospective study.

BACKGROUND: Uncut Roux-en-Y (URY) effectively alleviates the prevalent complexities connected with RY, such as Roux-en-Y stasis syndrome (RSS). Nevertheless, for gastric cancer (GC) patients, it is still controversial whether URY has an impact on long-term prognosis and whether it has fewer afferent loop recanalization. Therefore, compare whether URY and RY have differences in prognosis and long-term complications of GC patients undergoing totally laparoscopic gastrectomy (TLG). METHODS: We analyzed the data of patients who underwent TLG combined with digestive tract reconstruction from dual-center between 2016 and 2022. Only patients undergoing URY and RY were selected for analysis. Relapse-free survival (RFS) and overall survival (OS) were estimated. Bias between the groups was reduced by propensity score matching (PSM). The Cox proportional hazard regression model was used to further analyze the influence of URY on prognosis. RESULTS: Two hundred forty two GC patients were enrolled. The URY had significantly shorter operation time, liquid food intake time, and in-hospital stays than the RY (P < 0.001). The URY had fewer long-term and short-term postoperative complications than the RY, especially with regard to RSS, reflux esophagitis, and reflux gastritis. The 3-year and 5-year OS of the URY group and the RY group before PSM: 87.5% vs. 65.6% (P < 0.001) and 81.4% vs. 61.7% (P = 0.001). PSM and Cox multivariate analysis confirmed that compared to RY, URY can improve the short-term and long-term prognosis of GC patients. CONCLUSION: TLG combined with URY for GC, especially for advanced, older, and poorly differentiated patients, may promote postoperative recovery and improve long-term prognosis.

Prior statin use in acute ischemic stroke patients with mechanical thrombectomy: A prospective cohort study in China.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has been proven to be effective for selected patients with acute ischemic stroke (AIS). However, conflicting findings have suggested the association between prior statin use and outcomes in AIS patients with MT, with a particular lack of information in the Chinese population. Via a prospective cohort study, we explored the safety and efficacy of prior statin use in Chinese AIS patients with MT. METHODS: We consecutively enrolled AIS patients treated with MT from the First Affiliated Hospital of Chengdu Medical College and Nanjing First Hospital between June 2015 and June 2022 who were under prior statin use or not. Safety and efficacy outcomes were prospectively followed. The primary outcomes were defined as 90-day favorable outcomes (mRS score 0-2). Secondary outcomes included successful recanalization (TICI≥2b), early neurological improvement (decrease of National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points at 24 h), symptomatic intracerebral hemorrhage (sICH), and death at 90 days. RESULTS: We enrolled 334 patients in total, 50 of whom (15.0%) undertaken statins administration before AIS. 117 (35.0%) patients had favorable outcomes at 90 days, 288 (86.2%) patients had successful recanalization, 108 (32.3%) patients achieved early neurological improvement, 41 (12.3%) patients had sICH and 73 (21.9%) patients died within 90 days. The 90-day favorable outcomes were not significantly different (adjusted OR=0.853, 95% CI 0.449-1.620, P = 0.626) between prior statins use group and no statins use group. There was no significant difference in recanalization (adjusted OR=1.466, 95% CI 0.536-4.009, P = 0.456), early neurological improvement (adjusted OR=1.568, 95% CI 0.811-3.032, P = 0.181), sICH (adjusted OR=0.850, 95% CI 0.325-2.224, P = 0.741), ICH (adjusted OR=1.029, 95% CI 0.479-2.490, P = 0.942), and 90-day mortality (adjusted OR=0.381, 95% CI 0.091-1.586, P = 0.185) between the two groups. CONCLUSIONS: Prior statin use may be safe for Chinese AIS patients with MT, but its efficacy warrants further research.

Digital finance and performance in innovation: Evidence from universities.

This study evaluated 72 universities' performance innovation during 2011 to 2019 of panel data, using the data envelopment analysis-Malmquist method. The study used benchmark regression to analyse the relationship between digital finance and the universities' innovation performance. The aim was to improve innovation performance and promote national innovation across countries. According to the results of the empirical analysis, digital finance positively affects innovation performance. That finding was confirmed through advanced robustness test evaluation, such as limited information maximum likelihood, two-stage least squares, and interactive fixed effects. Moreover, based on information theory, the digital finance influence mechanism improves credit demand and financial efficiency. Additionally, innovation performance survived spatial overflow effects. Lastly, the paper concludes with some implications for improving digital financial coverage and constructing innovation networks among universities.

Dual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1C.

The SWR1C chromatin remodeling enzyme catalyzes the ATP-dependent exchange of nucleosomal histone H2A for the histone variant H2A.Z, a key variant involved in a multitude of nuclear functions. How the 14-subunit SWR1C engages the nucleosomal substrate remains largely unknown. Numerous studies on the ISWI, CHD1, and SWI/SNF families of chromatin remodeling enzymes have demonstrated key roles for the nucleosomal acidic patch for remodeling activity, however a role for this nucleosomal epitope in nucleosome editing by SWR1C has not been tested. Here, we employ a variety of biochemical assays to demonstrate an essential role for the acidic patch in the H2A.Z exchange reaction. Utilizing asymmetrically assembled nucleosomes, we demonstrate that the acidic patches on each face of the nucleosome are required for SWR1C-mediated dimer exchange, suggesting SWR1C engages the nucleosome in a "pincer-like" conformation, engaging both patches simultaneously. Loss of a single acidic patch results in loss of high affinity nucleosome binding and nucleosomal stimulation of ATPase activity. We identify a conserved arginine-rich motif within the Swc5 subunit that binds the acidic patch and is key for dimer exchange activity. In addition, our cryoEM structure of a Swc5-nucleosome complex suggests that promoter proximal, histone H2B ubiquitinylation may regulate H2A.Z deposition. Together these findings provide new insights into how SWR1C engages its nucleosomal substrate to promote efficient H2A.Z deposition.

Biosurfactant from Pseudomonas fragi enhances the competitive advantage of Pseudomonas but reduces the overall spoilage ability of the microbial community in chilled meat.

Biosurfactants from Pseudomonas spp. have been reported to exhibit antibacterial and anti-adhesive properties, but their role during meat spoilage remains unclear. In this study, the biosurfactant was isolated from an isolate of Pseudomonas fragi with strong spoilage potential, and its surface tension and emulsification ability were determined. The chemical and microbial characteristics of the biosurfactant-treated meat samples were periodically analyzed. The results demonstrated that the biosurfactant produced by P. fragi could reduce surface tension and showed good emulsification properties. For the in situ spoilage trials, biosurfactant from P. fragi changed the microbial diversity on meat, helping Pseudomonas establish a dominant position in the population. However, biosurfactant treatment caused chicken meat to exhibit a weaker spoilage state, as indicated by the growth of psychrophilic microorganisms, total volatile basic nitrogen (TVBN) and meat color. These results provide practical information for understanding the role of P. fragi biosurfactant during chilled meat storage.

Longitudinal course of hyperintensity on diffusion weighted imaging in adult-onset neuronal intranuclear inclusion disease patients.

Background: High signals on diffusion weighted imaging along the corticomedullary junction (CMJ) have demonstrated excellent diagnostic values for adult-onset neuronal intranuclear inclusion disease (NIID). However, the longitudinal course of diffusion weighted imaging high intensities in adult-onset NIID patients has rarely been investigated. Methods: We described four NIID cases that had been discovered using skin biopsy and NOTCH2NLC gene testing, after diffusion weighted imaging exhibiting the distinctive corticomedullary junction high signals. Then using complete MRI data from NIID patients, we analyzed the chronological diffusion weighted imaging alterations of those individuals that had been published in Pub Med. Results: We discussed 135 NIID cases with comprehensive MRI data, including our four cases, of whom 39 had follow-up outcomes. The following are the four primary diffusion weighted imaging dynamic change patterns: (1) high signal intensities in the corticomedullary junction were negative on diffusion weighted imaging even after an 11-year follow-up (7/39); (2) diffusion weighted imagings were initially negative but subsequently revealed typical findings (9/39); (3) high signal intensities vanished during follow-up (3/39); (4) diffusion weighted imagings were positive at first and developed in a step-by-step manner (20/39). We discovered that NIID lesions eventually damaged the deep white matter, which comprises the cerebral peduncles, brain stem, middle cerebellar peduncles, paravermal regions, and cerebellar white matter. Conclusion: The longitudinal dynamic changes in NIID of diffusion weighted imaging are highly complex. We find that there are four main patterns of dynamic changes on diffusion weighted imaging. Furthermore, as the disease progressed, NIID lesions eventually involved the deep white matter.

The nutritional risk in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: The effect of nutrition on chronic autoimmune diseases is well known. This study is the first to assess the nutritional status of patients with neuromyelitis optica spectrum disorder (NMOSD) by administering the Mini Nutritional Assessment (MNA), to explore the impacts of nutrition on patients' quality of life and to identify the factors associated with the nutritional status of NMOSD patients. METHODS: Our study enrolled 70 NMOSD patients and 66 healthy controls. The following data were assessed: demographic information, disease features, and composite evaluations of life status, including nutrition, sleep, anxiety/depression, fatigue, and quality of life. Then, statistical analysis was performed. RESULTS: The MNA score of NMOSD patients was 20.4 ± 3.3, which was significantly lower than that of HCs (23.3 ± 2.5, P = 0.002), especially for the dimensions of global evaluation and anthropometric assessment. Nearly 85% of patients were at risk of malnutrition or had definite malnutrition. The total MNA score was positively correlated with the patient's quality of life (P<0.01). Lower MNA scores were correlated with gender (P = 0.02), longer disease duration (P<0.001), more severe anxiety (P = 0.004), more severe depression (P = 0.003), more severe sleep disturbances (P<0.001), and more severe fatigue (P = 0.01). Sleep disturbance was revealed to be a significant independent factor for the NMOSD patients' malnutritional risk (P = 0.001). CONCLUSIONS: These results suggest that the risk of malnutrition is very high in NMOSD patients and that malnutrition is closely related to their quality of life. Malnutrition among NMOSD patients is caused by a combination of various physiological and psychological factors. A multifaceted and personalized intervention is required to improve the prognosis of NMOSD.

Potential common molecular mechanisms between Sjögren syndrome and inclusion body myositis: a bioinformatic analysis and in vivo validation.

Background: Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy that typically affects the quadriceps and finger flexors. Sjögren's syndrome (SS), an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands has been reported to share common genetic and autoimmune pathways with IBM. However, the exact mechanism underlying their commonality remains unclear. In this study, we investigated the common pathological mechanisms involved in both SS and IBM using a bioinformatic approach. Methods: IBM and SS gene expression profiles were obtained from the Gene Expression Omnibus (GEO). SS and IBM coexpression modules were identified using weighted gene coexpression network analysis (WGCNA), and differentially expressed gene (DEG) analysis was applied to identify their shared DEGs. The hidden biological pathways were revealed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, protein-protein interaction (PPI) networks, cluster analyses, and hub shared gene identification were conducted. The expression of hub genes was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). We then analyzed immune cell abundance patterns in SS and IBM using single-sample gene set enrichment analysis (ssGSEA) and investigated their association with hub genes. Finally, NetworkAnalyst was used to construct a common transcription factor (TF)-gene network. Results: Using WGCNA, we found that 172 intersecting genes were closely related to viral infection and antigen processing/presentation. Based on DEG analysis, 29 shared genes were found to be upregulated and enriched in similar biological pathways. By intersecting the top 20 potential hub genes from the WGCNA and DEG sets, three shared hub genes (PSMB9, CD74, and HLA-F) were derived and validated to be active transcripts, which all exhibited diagnostic values for SS and IBM. Furthermore, ssGSEA showed similar infiltration profiles in IBM and SS, and the hub genes were positively correlated with the abundance of immune cells. Ultimately, two TFs (HDGF and WRNIP1) were identified as possible key TFs. Conclusion: Our study identified that IBM shares common immunologic and transcriptional pathways with SS, such as viral infection and antigen processing/presentation. Furthermore, both IBM and SS have almost identical immune infiltration microenvironments, indicating similar immune responses may contribute to their association.

Intraoperative and postoperative short-term outcomes of intracorporeal anastomosis versus extracorporeal anastomosis in laparoscopic right hemicolectomy.

Background: Intracorporeal anastomosis (IA) is a difficult but popular anastomotic approach for reconstruction of digestive tract after laparoscopic right hemicolectomy, which may reduce some limitations faced during extracorporeal anastomosis (EA). Methods: A retrospective review of 78 patients who underwent laparoscopic right hemicolectomy by a veteran surgeon in a high-volume public tertiary hospital, including 50 patients with IA and 28 patients with EA. The intraoperative-related factors and short-term results of the two anastomotic approaches were compared. Results: There was no significant difference in demographics and clinical characteristics between the two groups (P>0.05). The intraoperative blood loss was less (P=0.010) and the incision length was shorter (P<0.001) in the intracorporeal group. Postoperative farting time was faster (P=0.005) and postoperative pain score (VAS) was lower (P<0.001) in IA group. Although the anastomotic time of IA was shorter (P<0.001), the operative time of the two groups were similar. And number of lymph nodes harvested, NLR from POD1 to POD3, postoperative hospital stay and overall hospital stay between the two groups were comparable. Except for significant difference in abdominal infection rate, the Clavien-Dindo classification and the incidence of other postoperative complications were not statistically different. Moreover, the morbidity of abdominal infection decreased with time in the IA group (P=0.040). Conclusion: IA is a reliable and feasible procedure, which has faster anastomotic time, earlier return of bowel function and superior postoperative comfort of patient, compared to EA. The postoperative complication rate of IA is similar to that of EA, and may be improved with the IA technical maturity of surgeons, which potentially contributes to the development of ERAS.