Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.

Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.

Fibroblast growth factor 21 alleviates unilateral ureteral obstruction-induced renal fibrosis by inhibiting Wnt/ß-catenin signaling pathway.

Fibroblast growth factor 21 (FGF21) is a key regulator of energy metabolism. Recent studies suggested that serum FGF21 levels increase with declining renal function. However, the link between FGF21 and kidney diseases and the direct effect of FGF21 in renal fibrosis remains unclear. In this study, FGF21 was upregulated in unilateral ureteral obstruction (UUO)-induced renal fibrosis and cellular fibrosis induced by transforming growth factor-ß, and renal expression of FGF21 was positively correlated with fibrosis markers. Additionally, FGF21 was regulated by Wnt/ß-catenin signaling pathway. The knockdown and overexpression of FGF21 in mouse tubular epithelial cells demonstrated that FGF21 alleviates renal fibrosis by inhibiting the Wnt/ß-catenin signaling pathway. To investigate the effect of FGF21 on renal fibrosis in vivo, we established an overexpression model by injecting the plasmid in mice and found that FGF21 overexpression relieved UUO-induced renal fibrosis and renal inflammatory response. Taken together, FGF21 is upregulated with the activation of Wnt/ß-catenin signaling pathway and alleviates renal fibrosis by inhibiting the activation of Wnt/ß-catenin signaling pathway in a negative feedback mode. These results provide a new understanding for the source of elevated serum FGF21 in patients with chronic kidney disease and prove that FGF21 is a direct inhibitor of the progression of renal fibrosis, thus providing novel therapeutic intervention insights for renal fibrosis.

Text Dialogue Analysis for Primary Screening of Mild Cognitive Impairment: Development and Validation Study.

BACKGROUND: Artificial intelligence models tailored to diagnose cognitive impairment have shown excellent results. However, it is unclear whether large linguistic models can rival specialized models by text alone. OBJECTIVE: In this study, we explored the performance of ChatGPT for primary screening of mild cognitive impairment (MCI) and standardized the design steps and components of the prompts. METHODS: We gathered a total of 174 participants from the DementiaBank screening and classified 70% of them into the training set and 30% of them into the test set. Only text dialogues were kept. Sentences were cleaned using a macro code, followed by a manual check. The prompt consisted of 5 main parts, including character setting, scoring system setting, indicator setting, output setting, and explanatory information setting. Three dimensions of variables from published studies were included: vocabulary (ie, word frequency and word ratio, phrase frequency and phrase ratio, and lexical complexity), syntax and grammar (ie, syntactic complexity and grammatical components), and semantics (ie, semantic density and semantic coherence). We used R 4.3.0. for the analysis of variables and diagnostic indicators. RESULTS: Three additional indicators related to the severity of MCI were incorporated into the final prompt for the model. These indicators were effective in discriminating between MCI and cognitively normal participants: tip-of-the-tongue phenomenon (P<.001), difficulty with complex ideas (P<.001), and memory issues (P<.001). The final GPT-4 model achieved a sensitivity of 0.8636, a specificity of 0.9487, and an area under the curve of 0.9062 on the training set; on the test set, the sensitivity, specificity, and area under the curve reached 0.7727, 0.8333, and 0.8030, respectively. CONCLUSIONS: ChatGPT was effective in the primary screening of participants with possible MCI. Improved standardization of prompts by clinicians would also improve the performance of the model. It is important to note that ChatGPT is not a substitute for a clinician making a diagnosis.

Constructing an Ultra-Rapid Nanoconfinement-Enhanced Fluorescence Clinical Detection Platform by Using Machine Learning and Tunable DNA Xerogel "Probe".

Low mass transfer efficiency and unavoidable matrix effects seriously limit the development of rapid and accurate determination of biosensing systems. Herein, we have successfully constructed an ultra-rapid nanoconfinement-enhanced fluorescence clinical detection platform based on machine learning (ML) and DNA xerogel "probe", which was performed by detecting neutrophil gelatinase-associated lipocalin (NGAL, protein biomarker of acute kidney injury). By regulating pore sizes of the xerogels, the transfer of NGAL in xerogels can approximate that in homogeneous solution. Due to electrostatic attraction of the pore entrances, NGAL rapidly enriches on the surface and inside the xerogels. The reaction rate of NGAL and aptamer cross-linked in xerogels is also accelerated because of the nanoconfinement effect-induced increasing reactant concentration and the enhanced affinity constant KD between reactants, which can be promoted by ∼667-fold than that in bulk solution, thus achieving ultra-rapid detection (ca. 5 min) of human urine. The platform could realize one-step detection without sample pretreatments due to the antiligand exchange effect on the surface of N-doped carbon quantum dots (N-CQDs) in xerogels, in which ligand exchange between -COOH and underlying interfering ions in urine will be inhibited due to higher adsorption energy of -COOH on the N-CQD surface relative to the interfering ions. Based on the ML-extended program, the real-time analysis of the urine fluorescence spectra can be completed within 2 s. Interestingly, by changing DNA, aptamer sequences, or xerogel fluorescence intensities, the detection platform can be customized for targeted diseases.

Efficacy of immunotherapy and prognosis in anti-LGI1 encephalitis patients: A meta-analysis.

OBJECTIVE: To assess the efficacy and safety of immunotherapy for LGI1 antibody encephalitis, and consider the predictors of poor outcomes following immunotherapy. METHODS: We searched PubMed and Embase for articles reporting the immunotherapy data of anti-LGI1 encephalitis patients. The proportions of patients with poor outcomes (modified Rankin Scale [mRS] score > 2) at 3 months, 12 months, and the last follow-up, as well as the odds ratio [OR] of predictors were pooled. RESULTS: The review included 162 articles with 1066 patients. The proportion of patients with poor functional outcomes was 21% at 3 months, 14% at 12 months, and 14% at the last follow-up after receiving immunotherapy. The proportion of patients with reported relapse was 16.6%. The mean duration from onset to the first relapse was 15.6 months. Predictors significantly associated with poor outcomes were age (increase of 1 year), the presence of cognitive impairment, and CSF LGI1 antibody positive. We did not find a statistically significant association between the worst mRS score in the acute phase, the presence of faciobrachial dystonic seizures (FBDS), days from symptom onset to immunotherapy, second-line treatment, maintenance immunotherapy, or follow-up time and outcomes. INTERPRETATION: Although most patients respond to immunotherapy, a minority of patients still have poor outcomes. Advanced age, cognitive impairment, and CSF LGI1 antibody positive are associated with an increased risk of poor outcomes. However, due to the insufficiency of the data, these conclusions need to be interpreted with caution.

The weekend effect in kidney transplantation outcomes: A meta-analysis.

OBJECTIVE: To determine whether kidney transplants performed during weekends have worse outcomes than those performed during weekdays. METHODS: For this systematic review, PubMed, EMBASE, and the Cochrane Library (January 2000 to January 2023) were searched. We examined the survival rates of patients and grafts for hospital inpatients admitted during weekends and those admitted during weekdays. To be included, the study had to be in English and had to provide discrete survival data around weekends versus weekdays, including patients who were admitted as inpatients over the weekend. RESULTS: Five studies (n = 163,506 patients) were examined. The hazards ratio (HR) of the survival rate of patients with weekend transplantation was 1.01 (95% confidence interval [CI], 0.96 to 1.06) when compared with patients with weekday transplantation. Patients who had renal transplant on weekends had an overall allograft survival HR of 1.01 (95% CI, 0.99 to 1.03) and death-censored allograft survival HR of 1.01 (95% CI, 0.98 to 1.04). Comparison of length of hospital stay, rejection, surgical complications, and vascular complications between renal transplants on weekends and those on weekdays showed no statistical difference. CONCLUSION: Hospital inpatients admitted for renal transplantation during weekends have a survival rate similar to that of inpatients admitted during weekdays. The weekend effect of renal transplantation was very weak; hence, transplantations done during weekends and weekdays are both appropriate.

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature.

Background: Only 15 patients of autoimmune encephalitis with metabotropic glutamate receptor 5 (mGluR5) antibodies have been reported worldwide since 2011, mostly from western countries. Patients with different genetic backgrounds are necessary to further clarify the clinical phenotype and prognosis of this rare disease. Objective: We initially describe a case series from China to confirm the previous findings, expand the clinical phenotype, and identify the prognostic factors of autoimmune encephalitis with mGluR5 antibodies. Methods: Observational data with follow-up were prospectively collected from autoimmune encephalitis patients with mGluR5 antibodies. Clinical information and outcomes on current and previously reported cases were combined and analyzed. Results: We identified five patients (median age 35 years); two were female. The main clinical manifestations were behavioral/personality changes (five of five, 100%) and cognitive disorders (four of five, 80%), accompanied with other neurologic symptoms. Hypoventilation occurred in two (40%) patients, which was life-threatening. One patient had meningoencephalitis, suggesting a new phenotype in anti-mGluR5 encephalitis. All patients received immunotherapy. At the last follow-up (median 18 months), two (40%) patients showed complete recovery, two (40%) patients showed partial recovery, and one (20%) patient died. One (20%) patient had multiple relapses. Together with the 15 previously reported cases, associated tumors occurred in seven of 12 (58%) Western patients vs. one of eight (13%) Chinese patients. Modified Rankin Scale (mRS) scores at the last follow-up (median 31 months) were available in 16 patients. Patients with bad outcomes (mRS > 2, n = 4) were more likely to have hypoventilation at onset and higher mRS scores at peak of the disease. Conclusions: In patients with different genetic background, as Chinese, the clinical phenotype of anti-mGluR5 encephalitis is similar. Fewer paraneoplastic cases were observed in Chinese patients. Most patients showed good responses to immunotherapy and cancer treatment. The clinical outcomes were favorable in most patients.

Limitations on knowledge of autoimmune encephalitis and barriers to its treatment among neurologists: a survey from western China.

BACKGROUND: Autoimmune encephalitis (AE) is a group of severe antibody-mediated brain diseases. The understanding of clinical management of AE has developed rapidly. However, the knowledge level of AE and barriers to effective treatment among neurologists remains unstudied. METHODS: We conducted a questionnaire survey among neurologist in western China on knowledge of AE, treatment practices, and perspectives on barriers to treatment. RESULTS: A total of 1113 neurologists were invited and 690 neurologists from 103 hospitals completed the questionnaire with a response rate of 61.9%. Respondents correctly answered 68.3% of medical questions about AE. Some respondents (12.4%) never assayed for diagnostic antibodies if patients had suspected AE. Half (52.3%) never prescribed immunosuppressants for AE patients, while another 7.6% did not know whether they should do so. Neurologists who never prescribed immunosuppressants were more likely to have less education, a less senior job title, and to practice in a smaller setting. Neurologists who did not know whether to prescribe immunosuppressants were associated with less AE knowledge. The most frequent barrier to treatment, according to respondents, was financial cost. Other barriers to treatment included patient refusal, insufficient AE knowledge, lack of access to AE guidelines, drugs or diagnostic test, etc. CONCLUSION: Neurologists in western China lack AE knowledge. Medical education around AE is urgent needed and should be more targeted to individuals with less educated level or working in non-academic hospitals. Policies should be developed to increase the availability of AE related antibody testing or drugs and reduce the economic burden of disease.

Ribosomal S6 Kinase Regulates the Timing and Entrainment of the Mammalian Circadian Clock Located in the Suprachiasmatic Nucleus.

Previous work in the suprachiasmatic nucleus (SCN), the locus of the principal circadian clock, has shown that the activation state of the ERK/MAPK effector p90 ribosomal S6 kinase (RSK) is responsive to photic stimulation and is modulated across the circadian cycle. These data raise the prospect that RSK signaling contributes to both SCN clock timing and entrainment. Here, we found marked expression of the three main RSK isoforms (RSK1/2/3) within the SCN of C57/Bl6 mice. Further, using a combination of immunolabeling and proximity ligation assays, we show that photic stimulation led to the dissociation of RSK from ERK and the translocation of RSK from the cytoplasm to the nucleus. To test for RSK functionality following light treatment, animals received an intraventricular infusion of the selective RSK inhibitor, SL0101, 30 min prior to light (100 lux) exposure during the early circadian night (circadian time 15). Notably, the disruption of RSK signaling led to a significant reduction (∼45 min) in the phase delaying effects of light, relative to vehicle-infused mice. To test the potential contribution of RSK signaling to SCN pacemaker activity, slice cultures from a per1-Venus circadian reporter mouse line were chronically treated with SL0101. Suppression of RSK signaling led to a significant lengthening of the circadian period (∼40 min), relative to vehicle-treated slices. Together, these data reveal that RSK functions as a signaling intermediate that regulates light-evoked clock entrainment and the inherent time keeping properties of the SCN.

Salt-induced phosphoproteomic changes in the subfornical organ in rats with chronic kidney disease.

OBJECTIVES: Subfornical organ (SFO) is vital in chronic kidney disease (CKD) progression caused by high salt levels. The current study investigated the effects of high salt on phosphoproteomic changes in SFO in CKD rats. METHODS: 5/6 nephrectomized rats were fed a normal-salt diet (0.4%) (NC group) or a high-salt diet (4%) (HC group) for three weeks, while sham-operated rats were fed a normal-salt diet (0.4%) (NS group). For phosphoproteomic analysis of SFO in different groups, TiO2 enrichment, isobaric tags for relative and absolute quantification (iTRAQ) labeling, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used. RESULTS: There were 6808 distinct phosphopeptides found, which corresponded to 2661 phosphoproteins. NC group had 168 upregulated and 250 downregulated phosphopeptides compared to NS group. Comparison to NC group, HC group had 154 upregulated and 124 downregulated phosphopeptides. Growth associated protein 43 (GAP43) and heat shock protein 27 (Hsp27) were significantly upregulated phosphoproteins and may protect against high-salt damage. Differential phosphoproteins with tight functional connection were synapse proteins and microtubule-associated proteins, implying that high-salt diet disrupted brain's structure and function. Furthermore, differential phosphoproteins in HC/NC comparison group were annotated to participate in GABAergic synapse signaling pathway and aldosterone synthesis and secretion, which attenuated inhibitory neurotransmitter effects and increased sympathetic nerve activity (SNA). DISCUSSION: This large scale phosphoproteomic profiling of SFO sheds light on how salt aggravates CKD via the central nervous system.

Phosphatidylinositol (3,5)-bisphosphate machinery regulates neurite thickness through neuron-specific endosomal protein NSG1/NEEP21.

Phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] is a critical signaling phospholipid involved in endolysosome homeostasis. It is synthesized by a protein complex composed of PIKfyve, Vac14, and Fig4. Defects in PtdIns(3,5)P2 synthesis underlie a number of human neurological disorders, including Charcot-Marie-Tooth disease, child onset progressive dystonia, and others. However, neuron-specific functions of PtdIns(3,5)P2 remain less understood. Here, we show that PtdIns(3,5)P2 pathway is required to maintain neurite thickness. Suppression of PIKfyve activities using either pharmacological inhibitors or RNA silencing resulted in decreased neurite thickness. We further find that the regulation of neurite thickness by PtdIns(3,5)P2 is mediated by NSG1/NEEP21, a neuron-specific endosomal protein. Knockdown of NSG1 expression also led to thinner neurites. mCherry-tagged NSG1 colocalized and interacted with proteins in the PtdIns(3,5)P2 machinery. Perturbation of PtdIns(3,5)P2 dynamics by overexpressing Fig4 or a PtdIns(3,5)P2-binding domain resulted in mislocalization of NSG1 to nonendosomal locations, and suppressing PtdIns(3,5)P2 synthesis resulted in an accumulation of NSG1 in EEA1-positive early endosomes. Importantly, overexpression of NSG1 rescued neurite thinning in PtdIns(3,5)P2-deficient CAD neurons and primary cortical neurons. Our study uncovered the role of PtdIns(3,5)P2 in the morphogenesis of neurons, which revealed a novel aspect of the pathogenesis of PtdIns(3,5)P2-related neuropathies. We also identified NSG1 as an important downstream protein of PtdIns(3,5)P2, which may provide a novel therapeutic target in neurological diseases.

Inhibition of calpain9 attenuates peritoneal dialysis-related peritoneal fibrosis.

Aim: Peritoneal dialysis is a common renal replacement method for end-stage renal disease. Long-term peritoneal dialysis leads to peritoneal dialysis-related peritoneal fibrosis, which leads to a cessation of treatment. Calpain is a protein belonging to calcium-dependent endopeptidase family and plays an important role in extracellular matrix remodeling. Here, we evaluated the effect of calpain in peritoneal dialysis-related peritoneal fibrosis. Methods: We established two animal models of peritoneal fibrosis and inhibited the activity of Calpain, and then collected peritoneal tissue to evaluate the progress of fibrosis and the changes of Calpain and ß-catenin. We obtained Rat peritoneal mesothelial cells and Human peritoneal mesothelial cell line and stimulated with TGF-ß to produce extracellular matrix. Next we inhibited Calpain activity or reduced Calpain9 expression, and then assessed changes in extracellular matrix and ß-catenin. Results: Inhibition of calpain activity attenuated chlorhexidine glucose and peritoneal dialysis-induced peritoneal thickening and ß-catenin expression in mice. In addition, compared with the control group, when primary rat peritoneal mesothelial cells or human peritoneal mesothelial cells were treated with transforming growth factor beta, down-regulation of calpain activity inhibited the expression of Fibronectin and Collagen I, and increased the expression of E-cadherin. These changes could be adjusted after silencing calpain9. Finally, calpain9 deficiency was associated with down-regulation of Fibronectin and ß-catenin in human peritoneal mesothelial cells. Conclusion: Our results suggest that calpain9 may be a key molecule in mediating peritoneal dialysis-related peritoneal fibrosis.

Improvement of Pacific White Shrimp (Litopenaeus vannamei) Drying Characteristics and Quality Attributes by a Combination of Salting Pretreatment and Microwave.

This study investigated the effects of salting pretreatment and microwave (MW) power on drying characteristics, water distribution and quality attributes of Pacific white shrimp (Litopenaeus vannamei). With increasing salt concentration (0-8%, w/v) and MW power (300-900 W), the drying time of shrimp was shortened by 15.15-28.57%, compared with the untreated samples. Regarding the quality of dried shrimp, increasing the salt concentration and MW power increased the hardness (from 13,073.6 to 24,556.5 g), while the springiness, color parameters and astaxanthin content showed an initial decrease but a later increase trend. Low field nuclear magnetic resonance (LF-NMR) demonstrated that the T2 curve of the pretreated samples moved toward the negative x-axis and the immobilized water content decreased with increasing salt concentration. E-nose showed that volatile components were different and could be obviously distinguished at different salt concentrations and MW powers. Raman spectroscopy illustrated that the protein secondary structure of dried shrimp was altered by salting pretreatment and drying conditions, and the lowest conversion degree of α-helix to ß-sheet of dried shrimp was obtained at the salt concentration of 4% (w/v) and MW power of 500 W. By comprehensively considering the drying time and quality attributes, the combination of 4% (w/v) salt and 500 W MW power was concluded as the best drying conditions for shrimp using a microwave. The results could provide an innovative combination of salt pretreatment and MW drying with suitable processing conditions for producing high-quality dried shrimp.

A Bibliometric and Visualized Analysis of Uremic Cardiomyopathy From 1990 to 2021.

Background: Uremic cardiomyopathy is commonly presented in chronic kidney disease (CKD), and it severely affects the prognosis of patients with CKD. In the past few decades, the investigation of uremic cardiomyopathy has developed rapidly. However, no report has summarized the situation of uremic cardiomyopathy research to date. This study aimed to evaluate the state of uremic cardiomyopathy research in the last 30 years and identify important topics and achievements, as well as emerging trends through bibliometric analysis. Materials and Methods: Publications related to uremic cardiomyopathy were collected from Science Citation Index Expanded. HistCite, VOSviewer, CiteSpace, and the Bibliometrix Package were used for bibliometric analysis and visualization, including the analysis of the overall distribution of the annual publication, leading countries, and active institutions and authors, core journals, co-cited references, and keywords. Results: A total of 2,403 studies related to uremic cardiomyopathy were obtained, and progress related to uremic cardiomyopathy was slower in past 3 years. A total of 10,077 authors from 2,697 institutions in 89 countries or regions reported investigations on uremic cardiomyopathy. The United States of America was the most productive and the most cited country. Myles Wolf, Joseph I Shapiro, and Carmine Zoccali published most articles in uremic cardiomyopathy, and journals in nephrology possessed core status in the field. Phosphate metabolism was the hotspot in uremic cardiomyopathy research in recent years, and future progress may concentrate on phosphate metabolism, endogenous natriuretic factors, and novel biomarkers. Conclusion: The United States of America and European countries played central roles in uremic cardiomyopathy research, while Chinese scholars should be more involved in this field. Global publications on uremic cardiomyopathy have entered platform stage, and the fibroblast growth factor-23-klotho axis remained a hotspot in this field. Endogenous natriuretic factors and novel biomarkers may be potential directions in future investigations.

Irisin, a fascinating field in our times.

Irisin is a muscle-secreted hormone that is generated by cleavage of membrane protein FNDC-5 (fibronectin type III domain-containing protein 5). Irisin is considered to be a mediator of exercise-induced metabolic improvements, such as browning of white adipose tissue, and is known to alleviate several chronic non-metabolic diseases. Thus, irisin may be an ideal therapeutic target for metabolic and non-metabolic diseases. However, several controversies regarding irisin have hindered its clinical translation. We review the generation, regulation (especially in exercise), and metabolic as well as therapeutic effects of irisin on metabolic and non-metabolic diseases. Furthermore, we discuss controversies regarding irisin and highlight potential future research directions.

Long-term seizure outcomes in patients with autoimmune encephalitis: A prospective observational registry study update.

OBJECTIVE: This study was undertaken to update and evaluate long-term seizure outcomes in patients with autoimmune encephalitis (AE) based on a large cohort study with long follow-up. METHODS: In this prospective observational registry study, we analyzed data from patients with AE mediated by common types of neuronal surface antibodies (anti-N-methyl-d-aspartate receptor [NMDAR], anti-leucine-rich glioma-inactivated 1 [LGI1]/contactin-associated protein-like 2 [Caspr2], anti-γ-aminobutyric acid type B receptor [GABAB R]). All patients were recruited from the Department of Neurology at West China Hospital between October 2011 and June 2019, and data were collected prospectively on their demographic and clinical characteristics, treatment strategy, and seizure outcomes, with a median follow-up of 42 months (range = 6-93 months). Potential risk factors associated with seizure recurrence were also assessed. RESULTS: Of 320 AE patients, 75.9% had acute seizures, among whom >90% of patients had their last seizure within 12 months of disease onset. During our follow-up, 21 (9.3%) patients experienced seizure recurrence. Patients with anti-GABAB R encephalitis had a higher cumulative incidence of seizure recurrence than those with anti-NMDAR (log-rank p = .03) or anti-LGI1/Caspr2 encephalitis (log-rank p = .04). Among patients with anti-NMDAR encephalitis, women had a significantly higher cumulative incidence of seizure recurrence than men (log-rank p = .01). Interictal epileptiform discharges (IEDs) or seizures captured on continuous electroencephalogram (EEG) in the acute phase were identified as potential risk factors for seizure recurrence (p = .04, p = .007). Among 163 patients with ≥24 months of follow-up, five (3.1%) showed persistent seizures and required ongoing antiseizure medications despite aggressive immunotherapy. SIGNIFICANCE: Seizure recurrence occurred in a small number of patients and chronic epilepsy occurred in 3.1% of patients during prolonged follow-up. Across all types of AE, risk factors for seizure recurrence were IEDs or seizures captured on EEG in the acute phase; for anti-NMDAR encephalitis, female sex was also a risk factor.

Fibroblast growth factor 21: A "rheostat" for metabolic regulation?

Fibroblast growth factor 21 is an evolutionarily conserved factor that plays multiple important roles in metabolic homeostasis. During the past two decades, extensive investigations have improved our understanding of its delicate metabolic roles and identified its pharmacological potential to mitigate metabolic disorders. However, most clinical trials have failed to obtain the desired results, which raises issues regarding its clinical value. Fibroblast growth factor 21 is dynamically regulated by nutrients derived from food intake and hepatic/adipose release, which in turn act on the central nervous system, liver, and adipose tissues to influence food preference, hepatic glucose, and adipose fatty acid output. Based on this information, we propose that fibroblast growth factor 21 should not be considered merely an anti-hyperglycemia or anti-obesity factor, but rather a means of balancing of nutrient fluctuations to maintain an appropriate energy supply. Hence, the specific functions of fibroblast growth factor 21 in glycometabolism and lipometabolism depend on specific metabolic states, indicating that its pharmacological effects require further consideration.

Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis.

Metastasis is the leading cause of death for colorectal cancer (CRC) patients, and the spreading tumor cells adhesion to endothelial cells is a critical step for extravasation and further distant metastasis. Previous studies have documented the important roles of gut microbiota-host interactions in the CRC malignancy, and Fusobacterium nucleatum (F. nucleatum) was reported to increase proliferation and invasive activities of CRC cells. However, the potential functions and underlying mechanisms of F. nucleatum in the interactions between CRC cells and endothelial cells and subsequent extravasation remain unclear. Here, we uncovered that F. nucleatum enhanced the adhesion of CRC cells to endothelial cells, promoted extravasation and metastasis by inducing ICAM1 expression. Mechanistically, we identified that F. nucleatum induced a new pattern recognition receptor ALPK1 to activate NF-κB pathway, resulting in the upregulation of ICAM1. Interestingly, the abundance of F. nucleatum in tumor tissues of CRC patients was positively associated with the expression levels of ALPK1 and ICAM1. Moreover, high expression of ALPK1 or ICAM1 was significantly associated with a shorter overall survival time of CRC patients. This study provides a new insight into the role of gut microbiota in engaging into the distant metastasis of CRC cells.