Escherichia coli O157:H7 senses microbiota-produced riboflavin to increase its virulence in the gut.

Riboflavin is produced by most commensal bacteria in the human colon, where enterohemorrhagic Escherichia coli (EHEC) colonizes and causes diseases. Sensing environmental signals to site-specifically express the type-III secretion system (T3SS), which injects effectors into host cells leading to intestinal colonization and disease, is key to the pathogenesis of EHEC. Here, we reveal that EHEC O157:H7, a dominant EHEC serotype frequently associated with severe diseases, acquired a previously uncharacterized two-component regulatory system rbfSR, which senses microbiota-produced riboflavin to directly activate the expression of LEE genes encoding the T3SS in the colon. rbfSR is present in O157:H7 and O145:H28 but absent from other EHEC serotypes. The binding site of RbfR through which it regulates LEE gene expression was identified and is conserved in all EHEC serotypes and Citrobacter rodentium, a surrogate for EHEC in mice. Introducing rbfSR into C. rodentium enabled bacteria to sense microbiota-produced riboflavin in the mouse colon to increase the expression of LEE genes, causing increased disease severity in mice. Phylogenic analysis showed that the O55:H7 ancestor of O157:H7 obtained rbfSR which has been kept in O157:H7 since then. Thus, acquiring rbfSR represents an essential step in the evolution of the highly pathogenic O157:H7. The expression of LEE genes and cell attachment ability of other EHEC serotypes in the presence of riboflavin significantly increased when rbfSR was introduced into them, indicating that those serotypes are ready to use RbfSR to increase their pathogenicity. This may present a potential public health issue as horizontal gene transfer is frequent in enteric bacteria.

Multi-hierarchy Network Configuration Can Predict Brain States and Performance.

The brain is a hierarchical modular organization that varies across functional states. Network configuration can better reveal network organization patterns. However, the multi-hierarchy network configuration remains unknown. Here, we propose an eigenmodal decomposition approach to detect modules at multi-hierarchy, which can identify higher-layer potential submodules and is consistent with the brain hierarchical structure. We defined three metrics: node configuration matrix, combinability, and separability. Node configuration matrix represents network configuration changes between layers. Separability reflects network configuration from global to local, whereas combinability shows network configuration from local to global. First, we created a random network to verify the feasibility of the method. Results show that separability of real networks is larger than that of random networks, whereas combinability is smaller than random networks. Then, we analyzed a large data set incorporating fMRI data from resting and seven distinct tasking conditions. Experiment results demonstrates the high similarity in node configuration matrices for different task conditions, whereas the tasking states have less separability and greater combinability between modules compared with the resting state. Furthermore, the ability of brain network configuration can predict brain states and cognition performance. Crucially, derived from tasks are highlighted with greater power than resting, showing that task-induced attributes have a greater ability to reveal individual differences. Together, our study provides novel perspectives for analyzing the organization structure of complex brain networks at multi-hierarchy, gives new insights to further unravel the working mechanisms of the brain, and adds new evidence for tasking states to better characterize and predict behavioral traits.

Ratiometric Fluorescent Probe for Super-Resolution Imaging of Lysosome HClO in Ferroptosis Cells.

Ferroptosis is an iron-dependent programmed cell death that is characterized by the dysregulation of lipid reactive oxygen species (ROS) production, causing abnormal changes in hypochlorous acid (HClO) levels in lysosomes. Super-resolution imaging can observe the fine structure of the lysosome at the nanometer level; therefore, it can be used to detect lysosome HClO levels during ferroptosis at the suborganelle level. Herein, we utilize a ratiometric fluorescent probe, SRF-HClO, for super-resolution imaging of lysosome HClO. Structured-illumination microscopy (SIM) improves the accuracy of lysosome targeting and enables the probe SRF-HClO to be successfully applied to rapidly monitor the up-regulated lysosome HClO at the nanoscale during inflammation and ferroptosis. Importantly, the probe SRF-HClO can also detect HClO changes in inflammatory and ferroptosis mice and evaluate the inhibitory effect of ferroptosis on mice tumors.

Assessing Atherosclerosis by Super-Resolution Imaging of HClO in Foam Cells Using a Ratiometric Fluorescent Probe.

Atherosclerosis (AS) is the leading cause of cardiovascular disease. Foam cells, with elevated lipid droplets (LDs) and HClO levels, are the main components of the atherosclerotic plaques that are characteristic of AS. Super-resolution imaging can be used to visualize the distribution of LDs in foam cells at the nanometer level, facilitating the identification of LDs and HClO. In the present study, we report the development of a ratiometric fluorescent probe, SFL-HClO, for super-resolution imaging of LDs and HClO. Super-resolution imaging with this probe revealed the precise structure of LDs at the suborganelle level. Moreover, the fluorescence behavior of SFL-HClO on the surface of LDs verified its excellent performance in detecting HClO in the foam cells. SFL-HClO can sequentially and specifically respond to LDs and HClO via "turn-on" and ratiometric signal output, respectively, thus contributing to precise imaging of foam cells. Importantly, we demonstrate that SFL-HClO can be used to report on upregulated HClO in atherosclerotic plaques in the aorta of AS mice, providing a suitable fluorescent tool for early atherosclerotic disease assessment.

An L-type lectin receptor-like kinase promotes starch accumulation during rice pollen maturation.

Starch accumulation is key for the maturity of rice pollen grains; however, the regulatory mechanism underlying this process remains unknown. Here, we have isolated a male-sterile rice mutant, abnormal pollen 1 (ap1), which produces nonviable pollen grains with defective starch accumulation. Functional analysis revealed that AP1 encodes an active L-type lectin receptor-like kinase (L-LecRLK). AP1 is localized to the plasma membrane and its transcript is highly accumulated in pollen during the starch synthesis phase. RNA-seq and phosphoproteomic analysis revealed that the expression/phosphorylation levels of numerous genes/proteins involved in starch and sucrose metabolism pathway were significantly altered in the mutant pollen, including a known rice UDP-glucose pyrophosphorylase (OsUGP2). We further found that AP1 physically interacts with OsUGP2 to elevate its enzymatic activity, likely through targeted phosphorylation. These findings revealed a novel role of L-LecRLK in controlling pollen maturity via modulating sucrose and starch metabolism.

Low Temperature Synthesis of 2D p-Type α-In2Te3 with Fast and Broadband Photodetection.

2D A 2 III B 3 VI ${\mathrm{A}}_2^{{\mathrm{III}}}{\mathrm{B}}_3^{{\mathrm{VI}}}$ compounds (A = Al, Ga, In, and B = S, Se, and Te) with intrinsic structural defects offer significant opportunities for high-performance and functional devices. However, obtaining 2D atomic-thin nanoplates with non-layered structure on SiO2/Si substrate at low temperatures is rare, which hinders the study of their properties and applications at atomic-thin thickness limits. In this study, the synthesis of ultrathin, non-layered α-In2Te3 nanoplates is demonstrated using a BiOCl-assisted chemical vapor deposition method at a temperature below 350 °C on SiO2/Si substrate. Comprehensive characterization results confirm the high-quality single crystal is the low-temperature cubic phase α-In2Te3 , possessing a noncentrosymmetric defected ZnS structure with good second harmonic generation. Moreover, α-In2Te3 is revealed to be a p-type semiconductor with a direct and narrow bandgap value of 0.76 eV. The field effect transistor exhibits a high mobility of 18 cm2 V-1 s-1, and the photodetector demonstrates stable photoswitching behavior within a broadband photoresponse from 405 to 1064 nm, with a satisfactory response time of τrise = 1 ms. Notably, the α-In2Te3 nanoplates exhibit good stability against ambient environments. Together, these findings establish α-In2Te3 nanoplates as promising candidates for next-generation high-performance photonics and electronics.

Colloidal Synthesis of Carbon Dot-ZnSe Nanoplatelet Van der Waals Heterostructures for Boosting Photocatalytic Generation of Methanol-Storable Hydrogen.

Methanol is not only a promising liquid hydrogen carrier but also an important feedstock chemical for chemical synthesis. Catalyst design is vital for enabling the reactions to occur under ambient conditions. This study reports a new class of van der Waals heterojunction photocatalyst, which is synthesized by hot-injection method, whereby carbon dots (CDs) are grown in situ on ZnSe nanoplatelets (NPLs), i.e., metal chalcogenide quantum wells. The resultant organic-inorganic hybrid nanoparticles, CD-NPLs, are able to perform methanol dehydrogenation through CH splitting. The heterostructure has enabled light-induced charge transfer from the CDs into the NPLs occurring on a sub-nanosecond timescale, with charges remaining separated across the CD-NPLs heterostructure for longer than 500 ns. This resulted in significantly heightened H2 production rate of 107 µmole·g-1·h-1 and enhanced photocurrent density up to 34 µA cm-2 at 1 V bias potential. EPR and NMR analyses confirmed the occurrence of α-CH splitting and CC coupling. The novel CD-based organic-inorganic semiconductor heterojunction is poised to enable the discovery of a host of new nano-hybrid photocatalysts with full tunability in the band structure, charge transfer, and divergent surface chemistry for guiding photoredox pathways and accelerating reaction rates.

Identification of Ligands for Ion Channels: TRPM2.

Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, nonselective cation channel with a widespread distribution throughout the body. It is involved in many pathological and physiological processes, making it a potential therapeutic target for various diseases, including Alzheimer's disease, Parkinson's disease, and cancers. New analytical techniques are beneficial for gaining a deeper understanding of its involvement in disease pathogenesis and for advancing the drug discovery for TRPM2-related diseases. In this work, we present the application of collision-induced affinity selection mass spectrometry (CIAS-MS) for the direct identification of ligands binding to TRPM2. CIAS-MS circumvents the need for high mass detection typically associated with mass spectrometry of large membrane proteins. Instead, it focuses on the detection of small molecules dissociated from the ligand-protein-detergent complexes. This affinity selection approach consolidates all affinity selection steps within the mass spectrometer, resulting in a streamlined process. We showed the direct identification of a known TRPM2 ligand dissociated from the protein-ligand complex. We demonstrated that CIAS-MS can identify binding ligands from complex mixtures of compounds and screened a compound library against TRPM2. We investigated the impact of voltage increments and ligand concentrations on the dissociation behavior of the binding ligand, revealing a dose-dependent relationship.

Development of a virus-based affinity ultrafiltration method for screening virus-surface-protein-targeted compounds from complex matrixes: Herbal medicines as a case study.

Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus-based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus-based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC-derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti-H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.

Regulatory function and mechanism research for m6A modification WTAP via SUCLG2-AS1- miR-17-5p-JAK1 axis in AML.

Acute myeloid leukemia (AML), characterized by the abnormal accumulation of immature marrow cells in the bone marrow, is a malignant tumor of the blood system. Currently, the pathogenesis of AML is not yet clear. Therefore, this study aims to explore the mechanisms underlying the development of AML. Firstly, we identified a competing endogenous RNA (ceRNA) SUCLG2-AS1-miR-17-5p-JAK1 axis through bioinformatics analysis. Overexpression of SUCLG2-AS1 inhibits proliferation, migration and invasion and promotes apoptosis of AML cells. Secondly, luciferase reporter assay and RIP assay validated that SUCLG2-AS1 functioned as ceRNA for sponging miR-17-5p, further leading to JAK1 underexpression. Additionally, the results of MeRIP-qPCR and m6A RNA methylation quantification indicted that SUCLG2-AS1(lncRNA) had higher levels of m6A RNA methylation compared with controls, and SUCLG2-AS1 is regulated by m6A modification of WTAP in AML cells. WTAP, one of the main regulatory components of m6A methyltransferase complexes, proved to be highly expressed in AML and elevated WTAP is associated with poor prognosis of AML patients. Taken together, the WTAP-SUCLG2-AS1-miR-17-5p-JAK1 axis played essential roles in the process of AML development, which provided a novel therapeutic target for AML.

Hippocampal Glutamate Levels and Their Correlation With Subregion Volume in School-Aged Children With MRI-Negative Epilepsy: A Preliminary Study.

BACKGROUND: Abnormal levels of glutamate constitute a key pathophysiologic mechanism in epilepsy. The use of glutamate chemical exchange saturation transfer (GluCEST) imaging to measure glutamate levels in pediatric epilepsy is rarely reported in research. PURPOSE: To investigate hippocampal glutamate level variations in pediatric epilepsy and the correlation between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional, prospective. SUBJECTS: A total of 38 school-aged pediatric epilepsy patients with structurally normal MRI as determined by at least two independent radiologists (60% males; 8.7 ± 2.5 years; including 20 cases of focal pediatric epilepsy [FE] and 18 cases of generalized pediatric epilepsy [GE]) and 17 healthy controls (HC) (41% males; 9.0 ± 2.5 years). FIELD STRENGTH/SEQUENCE: 3.0 T; 3D magnetization prepared rapid gradient echo (MPRAGE) and 2D turbo spin echo GluCEST sequences. ASSESSMENT: The relative concentration of glutamate was calculated through pixel-wise magnetization transfer ratio asymmetry (MTRasym) analysis of the GluCEST data. Hippocampal subfield volumes were computed from MPRAGE data using FreeSurfer. STATISTICAL TESTS: This study used t tests, one-way analysis of variance, Kruskal-Wallis tests, and Pearson correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The MTRasym values of both the left and right hippocampi were significantly elevated in GE (left: 2.51 ± 0.23 [GE] vs. 2.31 ± 0.12 [HCs], right: 2.50 ± 0.22 [GE] vs. 2.27 ± 0.22 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly elevated in FE (2.49 ± 0.28 [ipsilateral] vs. 2.29 ± 0.16 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly increased compared to the contralateral hippocampus in FE (2.49 ± 0.28 [ipsilateral] vs. 2.35 ± 0.34 [contralateral]). No significant differences in hippocampal volume were found between different groups (left hippocampus, P = 0.87; right hippocampus, P = 0.87). DATA CONCLUSION: GluCEST imaging have potential for the noninvasive measurement of glutamate levels in the brains of children with epilepsy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Endometrium procurement and transplantation restores fertility in rats.

RESEARCH QUESTION: Can rat endometrium be successfully procured and transplanted, and can a similar method be used to procure human endometrium? DESIGN: Rat endometrium was procured using an endometrium stripping method and transplanted into female Sprague-Dawley rats. Macroscopic and histological changes, endometrial receptivity-related protein concentrations and fertility were assessed. Additionally, a preliminary experiment was conducted to procure human endometrium using a similar method. RESULTS: Endometrium was successfully procured from both rats and humans, which contained intact endometrium and parts of the adjacent inner annulus myometrium. Endometrium auto-transplantation was conducted in rats and the procedure lasted a total of 41.3 ± 5.7 min with a mean blood loss of 0.09 ± 0.04 g. The transplanted endometrium survived well, but a fibrotic zone formed between the transplant and recipient tissue. Compared with sham rats, those with endometrium transplantation had similar endometrial thickness and endometrial gland numbers but reduced vascular density at 8 weeks after surgery. Endometrium transplantation also retained expression of the endometrial receptivity-related proteins leukaemia inhibitory factor and vascular endothelial growth factor. In contrast to non-pregnancy in the stripped horn, a mean of 5.0 ± 2.7 fetuses developed in the transplanted horn, and full-term live fetuses were conceived in the horns with transplanted endometrium. CONCLUSIONS: Endometrium procurement by stripping method can obtain an intact and functional endometrium, and endometrium transplantation can reconstruct the uterine cavity and restore fertility in rats.

Malassezia gallinae sp. nov., a new basidiomycetous yeast species isolated from skins of chickens.

Species of Malassezia are lipid-dependent yeasts and integral components of the skin microbiome. Most of the currently known species are isolated from mammals. However, the presence and distribution of Malassezia yeasts on the skin of avian species have not been fully understood or elucidated. During a survey on the occurrence of Malassezia species in chickens, 23 Malassezia strains isolated from the healthy skins of chickens may represent two candidate new species of this genus based on the sequence analysis of the internal transcribed spacer (ITS) (including 5.8S rRNA) and the D1/D2 domains of 26S rRNA. The combined ITS and D1/D2 phylogenetic analysis showed that those two candidate new species were closely related to Malassezia slooffiae, and differed from the type of M. slooffiae by 51-62 nucleotides in the ITS region and four nucleotides in the D1/D2 domains, respectively. Based on the phylogenetic analysis and the phenotypic comparison, we propose a new species, named Malassezia gallinae sp. nov., to include the 21 isolated strains.

Malassezia are lipophilic yeasts. Few species were isolated from birds, especially from poultry. We described a new Malassezia species with 21 strains isolated from chicken skins. This study revealed that chickens are normal hosts of Malassezia.

α-(N-Alkyl-N-heteroarenium)-α-diazoacetates: synthesis and reactivity of a novel class of 'onium' diazo compounds.

Treatment of alkyl α-(N-heteroaryl)-α-diazoacetates with alkylating reagents affords diazoacetate N-heteroarenium salts. These novel 'onium' diazo compounds are mostly yellow solids, displaying increased thermal and acid stability. Their tetrafluoroborates undergo rhodium catalyzed [2 + 1] and Doyle-Kirmse reactions under mild conditions, suggesting the N-quaternization an effective means of elimination of N-coordination caused catalyst toxicity.

Water Scarcity Assessment of Hydropower Plants in China under Climate Change, Sectoral Competition, and Energy Expansion.

Hydropower plays a pivotal role in low-carbon electricity generation, yet many projects are situated in regions facing heightened water scarcity risks. This research devised a plant-level Hydropower Water Scarcity Index (HWSI), derived from the ratio of water demand for electricity generation to basin-scale available runoff water. We assessed the water scarcity of 1736 hydropower plants in China for the baseline year 2018 and projected into the future from 2025 to 2060. The results indicate a notable increase in hydropower generation facing moderate to severe water scarcity (HWSI >0.05), rising from 10% in 2018 to 24-34% of the national total (430-630 TWh), with a projected peak in the 2030s-2040s under the most pessimistic scenarios. Hotspots of risk are situated in the southwest and northern regions, primarily driven by decreased river basin runoff and intensified sectoral water use, rather than by hydropower demand expansion. Comparative analysis of four adaptation strategies revealed that sectoral water savings and enhancing power generation efficiency are the most effective, potentially mitigating a high of 16% of hydropower risks in China. This study provides insights for formulating region-specific adaptation strategies and assessing energy-water security in the face of evolving environmental and societal challenges.

Informing Urban Flood Risk Adaptation by Integrating Human Mobility Big Data During Heavy Precipitation.

Understanding the impact of heavy precipitation on human mobility is critical for finer-scale urban flood risk assessment and achieving sustainable development goals #11 to build resilient and safe cities. Using ∼2.6 million mobile phone signal data collected during the summer of 2018 in Jiangsu, China, this study proposes a novel framework to assess human mobility changes during rainfall events at a high spatial granularity (500 m grid cell). The fine-scale mobility map identifies spatial hotspots with abnormal clustering or reduced human activities. When aggregating to the prefecture-city level, results show that human mobility changes range between -3.6 and 8.9%, revealing varied intracity movement across cities. Piecewise structural equation modeling analysis further suggests that city size, transport system, and crowding level directly affect mobility responses, whereas economic conditions influence mobility through multiple indirect pathways. When overlaying a historical urban flood map, we find such human mobility changes help 23 cities reduce 2.6% flood risks covering 0.45 million people but increase a mean of 1.64% flood risks in 12 cities covering 0.21 million people. The findings help deepen our understanding of the mobility pattern of urban dwellers after heavy precipitation events and foster urban adaptation by supporting more efficient small-scale hazard management.

A Screening of 10,240 NatureBank Fractions Identifies Nematicidal Activity in Agelasine-Containing Extracts from Sponges.

Nematode infections affect a fifth of the human population, livestock, and crops worldwide, imposing a burden to global public health and economies, particularly in developing nations. Resistance to commercial anthelmintics has increased over the years in livestock infections and driven the pursuit for new drugs. We herein present a rapid, cost-effective, and automated assay for nematicide discovery using the free-living nematode Caenorhabditis elegans to screen a highly diverse natural product library enriched in bioactive molecules. Screening of 10,240 fractions obtained from extracts of various biological sources allowed the identification of 7 promising hit fractions, all from marine sponges. These fractions were further assayed for nematicidal activity against the sheep nematode parasite Haemonchus contortus and for innocuity in zebrafish. The most active extracts against parasites and innocuous toward vertebrates belong to two chemotypes. High-performance liquid chromatography (HPLC) coupled with nuclear magnetic resonance (NMR) revealed that the most abundant compound in one chemotype is halaminol A, an aminoalcohol previously identified in a small screen against H. contortus. Terpene-nucleotide hybrids known as agelasines predominate in the other chemotype. This study reinforces the power of C. elegans for nematicide discovery from large collections and the potential of the chemical diversity derived from marine invertebrate biota.

Altered higher-order coupling between brain structure and function with embedded vector representations of connectomes in schizophrenia.

It has been shown that the functional dependency of the brain exists in both direct and indirect regional relationships. Therefore, it is necessary to map higher-order coupling in brain structure and function to understand brain dynamic. However, how to quantify connections between not directly regions remains unknown to schizophrenia. The word2vec is a common algorithm through create embeddings of words to solve these problems. We apply the node2vec embedding representation to characterize features on each node, their pairwise relationship can give rise to correspondence relationships between brain regions. Then we adopt pearson correlation to quantify the higher-order coupling between structure and function in normal controls and schizophrenia. In addition, we construct direct and indirect connections to quantify the coupling between their respective functional connections. The results showed that higher-order coupling is significantly higher in schizophrenia. Importantly, the anomalous cause of coupling mainly focus on indirect structural connections. The indirect structural connections play an essential role in functional connectivity-structural connectivity (SC-FC) coupling. The similarity between embedded representations capture more subtle network underlying information, our research provides new perspectives for understanding SC-FC coupling. A strong indication that the structural backbone of the brain has an intimate influence on the resting-state functional.

Predictive value of persistent antibodies at 6 months for relapse in neuronal surface antibody-associated autoimmune encephalitis.

BACKGROUND: For patients with neuronal surface antibody-associated autoimmune encephalitis (NSAE) whose clinical symptoms gradually improve, the recommended course of immunotherapy in China is about 6 months. We aim to explore the relationship between persistent antibody positivity when immunotherapy is discontinued at 6 months and subsequent relapse. METHODS: Prospective inclusion of NSAE patients with clinical remission after 6-month immunotherapy. Their antibody titers and other clinical data were collected at onset and 6 months later. Based on the antibody test results at 6 months, patients were divided into an antibody-persistent group and an antibody-negative conversion group, and then the rate of relapse between the two groups were compared. RESULTS: The study included 28 NSAE patients who were antibody-positive at diagnosis. After 6-month immunotherapy, there were 16 (57.1%) cases with persistent antibodies and 12 (42.9%) cases with antibody-negative conversion. In the acute phase of onset, seizures were more common in patients with persistent antibodies (87.5% vs. 50.0%, p = 0.044). During a mean follow-up period of 22 months, patients with persistent antibodies were more likely to experience relapse than those with antibody-negative conversion (37.5% vs. 0.0%, p = 0.024). There were no significant differences in antibody types, CSF findings, results of MRI and EEG, tumor combination, immunotherapy, and long-term outcome between the two groups (p > 0.05). CONCLUSIONS: For patients with persistent antibodies when immunotherapy is discontinued at 6 months, persistent antibody positivity was associated with a higher relapse rate.

Origin and significance of leucine-rich glioma-inactivated 1 antibodies in cerebrospinal fluid.

BACKGROUND: Whether antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) in cerebrospinal fluid (CSF) are partially transferred from serum and the impact of CSF-LGI1-Ab positivity on clinical features and prognosis are unclear. Therefore, we aim to investigate the differences in serum titers, clinical features, and outcomes between LGI1-Ab CSF-positive and LGI1-Ab CSF-negative patients. METHODS: Retrospective analysis of serum titers and clinical features according to CSF LGI1-Ab status. In addition, univariate and multivariate logistic regression were performed to identify predictors of worse outcomes. RESULTS: A total of 60 patients with anti-LGI1 encephalitis and positive serum LGI1-Abs were identified, of whom 8 (13.3%) patients were excluded due to the absence of CSF LGI1-Ab testing. Among the remaining 52 patients, 33 (63.5%) were positive for LGI1-Abs in CSF. CSF-positive patients were more likely to have high serum titers (≥ 1:100) than CSF-negative patients (p = 0.003), and Spearman's correlation analysis showed a positive correlation between CSF and serum titers in CSF-positive patients (r2 = 0.405, p = 0.019). Psychiatric symptoms and hyponatremia were more frequent in CSF-positive patients (p < 0.05). Both univariate and multivariate logistic regression analyses showed that CSF LGI1-Ab positivity and delayed immunotherapy are independent risk factors for incomplete recovery (modified Rankin Scale (mRS) > 0 at last follow-up). CONCLUSIONS: LGI1-Ab CSF-positive patients have higher serum titers, and their CSF titers are positively correlated with serum titers, indicating a possible peripheral origin of CSF LGI1-Abs. CSF-positive patients more often present with psychiatric symptoms, hyponatremia, and worse outcomes, suggesting more severe neuronal damage.