Artificial intelligence-based perioperative safety verification system improved the performance of surgical safety verification execution.

OBJECTIVE: To explore the application effect of the artificial intelligence-based (AI-based) perioperative safety verification system in the performance of safety verification execution in urological and general surgeries. METHODS: The surgical checklists of 141 urological and general surgical patients from September to December 2019 in Hangzhou Children's Hospital were selected as the control group, and 71 surgical checklists for urological and general surgeries that the applied AI-based perioperative safety verification system from August to September 2022 were chosen as the experimental group. We compared the execution rate and standardization rate of safety verification as well as the satisfaction of surgeons, nurses, and anesthesiologists between the two groups. RESULTS: The execution rate and standardization rate of surgical safety verification in the experimental group were higher than those in the control group (both P<0.05). In addition, the satisfaction of surgeons, nurses, and anesthesiologists was also higher in the experimental group (all P<0.05). CONCLUSION: The AI-based perioperative safety verification system can improve the execution and standardization rates of surgical verifications, and also enhance the satisfaction of surgical participants.

Species diversity and major host/substrate associations of the genus Akanthomyces (Hypocreales, Cordycipitaceae).

Akanthomyces, a group of fungi with rich morphological and ecological diversity in Cordycipitaceae (Ascomycota, Hypocreales), has a wide distribution amongst diverse habitats. By surveying arthropod-pathogenic fungi in China and Southeast Asia over the last six years, nine Akanthomyces spp. were found and identified. Five of these were shown to represent four known species and an undetermined species of Akanthomyces. Four of these were new species and they were named A.kunmingensis and A.subaraneicola from China, A.laosensis from Laos and A.pseudonoctuidarum from Thailand. The new species were described and illustrated according to the morphological characteristics and molecular data. Akanthomycesaraneogenus, which was isolated from spiders from different regions in China, Thailand and Vietnam, was described as a newly-recorded species from Thailand and Vietnam. The phylogenetic positions of the nine species were evaluated, based on phylogenetic inferences according to five loci, namely, ITS, nrLSU, TEF, RPB1 and RPB2. In this study, we reviewed the research progress achieved for Akanthomyces regarding its taxonomy, species diversity, geographic distribution and major host/substrate associations. The morphological characteristics of 35 species in Akanthomyces, including four novel species and 31 known taxa, were also compared.

Exogenous Spermidine and Amino-Ethoxyvinylglycine Improve Nutritional Quality via Increasing Amino Acids in Rice Grains.

Polyamines and ethylene are key regulators of the growth and development, quality formation, and stress response of cereal crops such as rice. However, it remains unclear whether the application of these regulators could improve the nutritional quality via increasing amino acids in rice grains. This study examined the role of exogenous polyamines and ethylene in regulating amino acid levels in the milled rice of earlier-flowered superior grain (SG) and later-flowered inferior grain (IG). Two rice varieties were field grown, and either 1 mmol L-1 spermidine (Spd) or 50 µmol L-1 amino-ethoxyvinylglycine (AVG) was applied to panicles at the early grain-filling stage. The control check (CK) was applied with deionized water. The results showed that the Spd or AVG applications significantly increased polyamine (spermine (Spm) and Spd) contents and decreased ethylene levels in both SG and IG and significantly increased amino acid levels in the milled rice of SG and IG relative to the CK. Collectively, the application of Spd or AVG can increase amino acid-based nutritional quality and grain yield via increasing polyamine (Spm and Spd) contents and reducing ethylene levels in both SG and IG of rice.

Involvement of brassinosteroids and abscisic acid in spikelet degeneration in rice under soil drying during meiosis.

Spikelet degeneration in rice (Oryza sativa L.) is a serious physiological defect, and can be regulated by soil moisture status and phytohormones. This study investigated the possibility that brassinosteroids (BRs) in collaboration with abscisic acid (ABA) are involved in mediating the effect of soil drying during meiosis on spikelet degeneration in rice. Three rice cultivars were field grown and three irrigation regimes including well watered (WW), moderate soil drying (MD), and severe soil drying (SD) were imposed during meiosis. MD significantly decreased spikelet degeneration in comparison with WW, due mainly to the alleviation in oxidative damage via enhancing ascorbate-glutathione (AsA-GSH) cycle activity in young panicles, and SD exhibited the opposite effects. Enhanced AsA-GSH cycle strength, decreased oxidative stress, and spikelet degeneration rate were closely associated with the synergistically elevated BR and ABA levels in young panicles in MD. In contrast, low BR and excessive ABA levels led to an increase in spikelet degeneration in SD. The three cultivars exhibited the same tendencies. The intrinsic link among AsA-GSH cycle, oxidative stress, spikelet degeneration rate, and BR and ABA levels was further verified by using transgenic rice lines and chemical regulators. BRs or ABA play a unique role in regulating spikelet degeneration. Synergistically increased BR and ABA levels in MD could work together to strengthen AsA-GSH cycle activity, leading to a reduction in oxidative damage and spikelet degeneration. On the other hand, a severe imbalance between low BR and excessive ABA levels may have contributed to the opposite effects in SD.

Genomic Comparison of Two Species of Samsoniella with Other Genera in the Family Cordycipitaceae.

Whole genomes of Samsoniella hepiali ICMM 82-2 and S. yunnanensis YFCC 1527 were sequenced and annotated, as well as compared with whole genome sequences of other species in the family Cordycipitaceae. S. hepiali ICMM 82-2, S. hepiali FENG and S. yunnanensis YFCC 1527 had 54, 57 and 58 putative secondary metabolite biosynthetic gene clusters, respectively. S. hepiali had one unique domain and S. yunnanensis YFCC 1527 six. Both S. hepiali and S. yunnanensis YFCC 1527 had curvupallide-B, fumosorinone and fujikurin putative biosynthetic gene clusters. C. javanica had biosynthetic gene clusters for fumonisin. The 14 genomes had common domains, namely A-P-C-P-C and KS-AT-DH-ER-KR-ACP. The A-P-C-P-C domain may be involved in the biosynthesis of dimethylcoprogen. The maximum likelihood and the Bayesian inference trees of KS-AT-DH-ER-KR-ACP were highly consistent with the multigene phylogenetic tree for the 13 species of Cordycipitaceae. This study facilitates the discovery of novel biologically active SMs from Cordycipitaceae using heterologous expression and gene knockdown methods.

Nitrogen enrichment ameliorates the stimulatory effects of reduced salinity on photosynthesis and growth of phytoplankton assemblages in the northern South China sea.

Anthropogenic activities and climate change are exacerbating the occurrence of extreme rainfall that normally brings large amounts of nutrient-rich freshwater from the land to the sea, resulting in acute salinity decrease and nutrient increase. To evaluate the effects of such changes in salinity and nutrients, we tracked the changes in photosynthetic efficiency and growth of phytoplankton assemblages from the northern South China Sea at 5 salinity levels and at an intermediate salinity level with 3 or 4 nitrogen concentrations. The results showed that the reduction of salinity reduced the maximum photochemical quantum yield (FV/FM) of photosystem II of phytoplankton within a short-term cultivation (i.e. 24-72 h), followed by a stimulatory effect. The reducing effect of reduced salinity lasted longer in the nearshore area than in the offshore area, so the stimulatory effect occurred later in the former area. Nitrogen enrichment mitigated the negative effect of reduced salinity in short-term cultivation and showed a positive effect on FV/FM in long-term cultivation. Moreover, both reduced salinity and enriched nitrogen stimulated phytoplankton growth after an acclimation period. Our results suggest that the reduced salinity stresses phytoplankton in the short term, which is mitigated by nitrogen enrichment, but benefits them in the long term. This sheds light on how phytoplankton thrive and even flourish in coastal or estuarine environments where salinity and nutrients typically covary strongly after extreme rainfall.

Morphology, phylogeny and host specificity of two new Ophiocordyceps species belonging to the "zombie-ant fungi" clade (Ophiocordycipitaceae, Hypocreales).

Species of the genus Ophiocordyceps, which include species able to manipulate the behaviour of ants, are known as the "zombie-ant fungi" and have attracted much attention over the last decade. They are widespread within tropical, subtropical and even temperate forests worldwide, with relatively few reports from subtropical monsoon evergreen broad-leaved forest. Fungal specimens have been collected from China, occurring on ants and producing hirsutella-like anamorphs. Based on a combination of morphological characters, phylogenetic analyses (LSU, SSU, TEF1a, RPB1 and RPB2) and ecological data, two new species, Ophiocordycepstortuosa and O.ansiformis, are identified and proposed herein. Ophiocordycepstortuosa and O.ansiformis are recorded on the same species of Colobopsis ant, based on phylogenetic analyses (COI), which may be sharing the same host. Ophiocordycepstortuosa and O.ansiformis share the morphological character of producing lanceolate ascospores. They have typical characteristics distinguished from other species. The ascospore of O.tortuosa are tortuously arranged in the ascus and the ascospore of O.ansiformis have a structure like a handle-shape in the middle. Our molecular data also indicate that O.tortuosa and O.ansiformis are clearly distinct from other species.

Phylogeny and species delimitations in the economically, medically, and ecologically important genus Samsoniella (Cordycipitaceae, Hypocreales).

Samsoniella is a ubiquitous genus of cosmopolitan arthropod-pathogenic fungi in the family Cordycipitaceae. The fungi have economic, medicinal, and ecological importance. Prior taxonomic studies of these fungi relied predominantly on phylogenetic inferences from five loci, namely, the nuclear ribosomal small and large subunits (nr SSU and nr LSU), the 3' portion of translation elongation factor 1 alpha (3P_TEF), and RNA polymerase II subunits 1 and 2 (RPB1 and RPB2). Despite many new species being described, not all of the recognized species inside this group formed well-supported clades. Thus, the search for new markers appropriate for molecular phylogenetic analysis of Samsoniella remains a challenging problem. In our study, we selected the internal transcribed spacer regions of the rDNA (ITS rDNA) and seven gene regions, namely, 3P_TEF, the 5' portion of translation elongation factor 1 alpha (5P_TEF), RPB1, RPB2, γ-actin (ACT), ß-tubulin (TUB), and a gene encoding a minichromosome maintenance protein (MCM7), as candidate markers for species identification. Genetic divergence comparisons showed that the ITS, RPB2, ACT, and TUB sequences provided little valuable information with which to separate Samsoniella spp. In contrast, sequence data for 3P_TEF, 5P_TEF, RPB1, and MCM7 provided good resolution of Samsoniella species. The phylogenetic tree inferred from combined data (5P_TEF + 3P_TEF + RPB1 + MCM7) showed well-supported clades for Samsoniella and allowed for the delimitation of 26 species in this genus. The other two species (S.formicae and S.lepidopterorum) were not evaluated, as they had abundant missing data.

Effects of Salt Stress on Grain Yield and Quality Parameters in Rice Cultivars with Differing Salt Tolerance.

Rice yield and grain quality are highly sensitive to salinity stress. Salt-tolerant/susceptible rice cultivars respond to salinity differently. To explore the variation in grain yield and quality to moderate/severe salinity stress, five rice cultivars differing in degrees of salt tolerance, including three salt-tolerant rice cultivars (Lianjian 5, Lianjian 6, and Lianjian 7) and two salt-susceptible rice cultivars (Wuyunjing 30 and Lianjing 7) were examined. Grain yield was significantly decreased under salinity stress, while the extent of yield loss was lesser in salt-tolerant rice cultivars due to the relatively higher grain filling ratio and grain weight. The milling quality continued to increase with increasing levels. There were genotypic differences in the responses of appearance quality to mild salinity. The appearance quality was first increased and then decreased with increasing levels of salinity stress in salt-tolerant rice but continued to decrease in salt-susceptible rice. Under severe salinity stress, the protein accumulation was increased and the starch content was decreased; the content of short branched-chain of amylopectin was decreased; the crystallinity and stability of the starch were increased, and the gelatinization temperature was increased. These changes resulted in the deterioration of cooking and eating quality of rice under severe salinity-stressed environments. However, salt-tolerant and salt-susceptible rice cultivars responded differently to moderate salinity stress in cooking and eating quality and in the physicochemical properties of the starch. For salt-tolerant rice cultivars, the chain length of amylopectin was decreased, the degrees of order of the starch structure were decreased, and pasting properties and thermal properties were increased significantly, whereas for salt-susceptible rice cultivars, cooking and eating quality was deteriorated under moderate salinity stress. In conclusion, the selection of salt-tolerant rice cultivars can effectively maintain the rice production at a relatively high level while simultaneously enhancing grain quality in moderate salinity-stressed environments. Our results demonstrate specific salinity responses among the rice genotypes and the planting of salt-tolerant rice under moderate soil salinity is a solution to ensure rice production in China.

Hepatotoxicity assessment investigations on PFASs targeting L-FABP using binding affinity data and machine learning-based QSAR model.

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants that have been detected in various environmental media and human serum, but their safety assessment remains challenging. PFASs may accumulate in liver tissues and cause hepatotoxicity by binding to liver fatty acid binding protein (L-FABP). Therefore, evaluating the binding affinity of PFASs to L-FABP is crucial in assessing the potential hepatotoxic effects. In this study, two binding sites of L-FABP were evaluated, results suggested that the outer site possessed high affinity to polyfluoroalkyl sulfates and the inner site preferred perfluoroalkyl sulfonamides, overall, the inner site of L-FABP was more sensitive to PFASs. The binding affinity data of PFASs to L-FABP were used as training set to develop a machine learning model-based quantitative structure-activity relationship (QSAR) for efficient prediction of potentially hazardous PFASs. Further Bayesian Kernel Machine Regression (BKMR) model disclosed flexibility as the determinant molecular property on PFASs-induced hepatotoxicity. It can influence affinity of PFASs to target protein through affecting binding conformations directly (individual effect) as well as integrating with other molecular properties (joint effect). Our present work provided more understanding on hepatotoxicity of PFASs, which could be significative in hepatotoxicity gradation, administration guidance, and safer alternatives development of PFASs.

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease.

OBJECTIVES: The aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD. METHODS: We performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results. RESULTS: We identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD. TOP2A_B cells and TOP2A_T cells had stemness signatures, and trajectory analysis showed that TOP2A_B cells may differentiate into IgG4+plasma cells and that TOP2A_T cells may differentiate into T follicular helper (Tfh) cells. ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD. CONCLUSION: Our data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.

Effects of a Nanonetwork-Structured Soil Conditioner on Microbial Community Structure.

Fertilizer application can increase yields, but nutrient runoff may cause environmental pollution and affect soil quality. A network-structured nanocomposite used as a soil conditioner is beneficial to crops and soil. However, the relationship between the soil conditioner and soil microbes is unclear. We evaluated the soil conditioner's impact on nutrient loss, pepper growth, soil improvement, and, especially, microbial community structure. High-throughput sequencing was applied to study the microbial communities. The microbial community structures of the soil conditioner treatment and the CK were significantly different, including in diversity and richness. The predominant bacterial phyla were Pseudomonadota, Actinomycetota, and Bacteroidota. Acidobacteriota and Chloroflexi were found in significantly higher numbers in the soil conditioner treatment. Ascomycota was the dominant fungal phylum. The Mortierellomycota phylum was found in significantly lower numbers in the CK. The bacteria and fungi at the genus level were positively correlated with the available K, available N, and pH, but were negatively correlated with the available P. Our results showed that the loss of nutrients controlled by the soil conditioner increased available N, which improved soil properties. Therefore, the microorganisms in the improved soil were changed. This study provides a correlation between improvements in microorganisms and the network-structured soil conditioner, which can promote plant growth and soil improvement.

The translocase of the inner mitochondrial membrane 22-2 is required for mitochondrial membrane function during Arabidopsis seed development.

The carrier translocase (also known as translocase of the inner membrane 22; TIM22 complex) is an important component of the mitochondrial protein import apparatus. However, the biological functions of AtTIM22-2 in Arabidopsis remain poorly defined. Here, we report studies on two tim22-2 mutants that exhibit defects in embryo and endosperm development, leading to seed abortion. AtTIM22-2, which was localized in mitochondria, was widely expressed in embryos and in various seedling organs. Loss of AtTIM22-2 function resulted in irregular mitochondrial cristae, decreased respiratory activity, and a lower membrane potential, together with changes in gene expression and enzyme activity related to reactive oxygen species (ROS) metabolism, leading to increased accumulation of ROS in the embryo. The levels of transcripts encoding mitochondrial protein import components were also altered in the tim22-2 mutants. Furthermore, mass spectrometry, bimolecular fluorescence complementation and co-immunoprecipitation assays revealed that AtTIM22-2 interacted with AtTIM23-2, AtB14.7 (a member of Arabidopsis OEP16 family encoded by At2G42210), and AT5G27395 (mitochondrial inner membrane translocase complex, subunit TIM44-related protein). Taken together, these results demonstrate that AtTIM22-2 is essential for maintaining mitochondrial membrane functions during seed development. These findings lay the foundations for a new model of the composition and functions of the TIM22 complex in higher plants.

Regulation of metabolism in pancreatic ductal adenocarcinoma via nanotechnology-enabled strategies.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with insidious onset and early distal metastasis. Metabolic reprogramming, the autonomous changes in cellular bioenergetics driven by aberrant genetic events and crosstalk between cancer and non-cancer cells in the desmoplastic microenvironment, is pivotal for the rapid progression of PDAC. As an attractive therapeutic target, nucleoside metabolism is regulated by various anti-metabolic drugs for the clinical treatment of PDAC. Despite various challenges, such as poor drug delivery efficiency and off-target side effects, metabolic modification and intervention are emerging as promising strategies for PDAC therapy, enabled by the rapid development of nanotechnology-based drug delivery strategies. In this review, we discuss the metabolic characteristics of PDAC and highlight how the development of nanomedicine has boosted the development of new therapeutics for PDAC by modulating critical targets in metabolic reprogramming.

Catalytic deAMPylation in AMPylation-inhibitory/assistant forms of FICD protein.

DeAMPylation, as a reversible reaction of AMPylation and mediated by the endoplasmic reticulum-localized enzyme FICD (filamentation induced by cAMP domain protein, also known as HYPE), is an important process in protein posttranslational modifications (PTMs). Elucidating the function and catalytic details of FICD is of vital importance to provide a comprehensive understanding of protein folding homeostasis. However, the detailed deAMPylation mechanism is still unclear. Furthermore, the role of a conserved glutamine (Glu234), that plays an inhibitory role in the AMPylation response, is still an open question in the deAMPylation process. In the present work, the elaborated deAMPylation mechanisms with AMPylation-inhibitory/assistant forms of FICD (wild type and Glu234Ala mutant) were investigated based on the QM(DFT)/MM MD approach. The results revealed that deAMPylation was triggered by proton transfer from protonated histidine (His363) to AMPylated threonine, instead of a nucleophilic attack of water molecules adding to the phosphorus of AMP. The free energy barrier of deAMPylation in the wild type (∼17.3 kcal/mol) is consistent with that in the Glu234Ala mutant of FICD (∼17.1 kcal/mol), suggesting that the alteration of the Glu234 residue does not affect the deAMPylation reaction and indirectly verifying the inducement of deAMPylation in FICD. In the wild type, the proton in the nucleophilic water molecule is transferred to Glu234, whereas it is delivered to Asp367 through the hydrogen-bond network of coordinated water molecules in the Glu234Ala mutant. The present findings were inspirational for understanding the catalytic and inhibitory mechanisms of FICD-mediated AMP transfer, paving the way for further studies on the physiological role of FICD protein.

Brassinosteroids mediate moderate soil-drying to alleviate spikelet degeneration under high temperature during meiosis of rice.

This study tested the hypothesis that brassinosteroids (BRs) mediate moderate soil-drying (MD) to alleviate spikelet degeneration under high temperature (HT) stress during meiosis of rice (Oryza sativa L.). A rice cultivar was pot-grown and subjected to normal temperature (NT) and HT treatments during meiosis, and two irrigation regimes including well-watered (WW) and MD were imposed to the plants simultaneously. The MD effectively alleviated the spikelet degeneration and yield loss under HT stress mainly via improving root activity and canopy and panicle traits including higher photosynthetic capacity, tricarboxylic acid cycle activity, and antioxidant capacity than WW. These parameters were regulated by BRs levels in plants. The decrease in BRs levels at HT was due mainly to the enhanced BRs decomposition, and the MD could rescue the BRs deficiency at HT via enhancing BRs biosynthesis and impeding decomposition. The connection between BRs and HT was verified by using rice BRs-deficient mutants, transgenic rice lines, and chemical regulators. Similar results were obtained in the open-air field experiment. The results suggest that BRs can mediate the MD to alleviate spikelet degeneration under HT stress during meiosis mainly via enhancing root activity, canopy traits, and young panicle traits of rice.

Cell type-specific DNA methylome signatures reveal epigenetic mechanisms for neuronal diversity and neurodevelopmental disorder.

DNA methylation plays a critical function in establishing and maintaining cell identity in brain. Disruption of DNA methylation-related processes leads to diverse neurological disorders. However, the role of DNA methylation characteristics in neuronal diversity remains underexplored. Here, we report detailed context-specific DNA methylation maps for GABAergic, glutamatergic (Glu) and Purkinje neurons, together with matched transcriptome profiles. Genome-wide mCH levels are distinguishable, while the mCG levels are similar among the three cell types. Substantial CG-differentially methylated regions (DMRs) are also seen, with Glu neurons experiencing substantial hypomethylation events. The relationship between mCG levels and gene expression displays cell type-specific patterns, while genic CH methylation exhibits a negative effect on transcriptional abundance. We found that cell type-specific CG-DMRs are informative in terms of represented neuronal function. Furthermore, we observed that the identified Glu-specific hypo-DMRs have a high level of consistency with the chromatin accessibility of excitatory neurons and the regions enriched for histone modifications (H3K27ac and H3K4me1) of active enhancers, suggesting their regulatory potential. Hypomethylation regions specific to each cell type are predicted to bind neuron type-specific transcription factors. Finally, we show that the DNA methylation changes in a mouse model of Rett syndrome, a neurodevelopmental disorder caused by the de novo mutations in MECP2, are cell type- and brain region-specific. Our results suggest that cell type-specific DNA methylation signatures are associated with the functional characteristics of the neuronal subtypes. The presented results emphasize the importance of DNA methylation-mediated epigenetic regulation in neuronal diversity and disease.

Age of onset correlates with clinical characteristics and prognostic outcomes in neuromyelitis optica spectrum disorder.

Objective: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease preferentially affects the optic nerve and the spinal cord. The first attack usually occurs in the third or fourth decade, though patients with disease onset in the fifties or later are not uncommon. This study aimed to investigate the clinical characteristics and prognosis in patients with different age of onset and to explore the correlations between age of onset and clinical characteristics and prognostic outcomes. Method: We retrospectively reviewed the medical records of 298 NMOSD patients diagnosed according to the 2015 updated version of diagnostic criteria. Patients were divided into early-onset NMOSD (EO-NMOSD) (<50 years at disease onset) and late-onset NMOSD (LO-NMOSD) (≥50 years at disease onset) based on the age of disease onset. LO-NMOSD patients were divided into two subgroups: relative-late-onset NMOSD (RLO-NMOSD) (50~70 years at disease onset) and very-late-onset NMOSD (≥70 years at disease onset). Clinical characteristics, laboratory findings, neuroimaging features, and prognostic outcomes were investigated. Results: Compared to EO-NMOSD patients, patients with LO-NMOSD showed more frequent transverse myelitis (TM) (58.20% vs. 36.00%, p = 0.007) while less frequent optic neuritis (ON) (23.10% vs. 34.80%, p = 0.031) and brainstem/cerebral attacks (7.50% vs. 18.30%, p = 0.006) as the first attack. Patients with LO-NMOSD showed less frequent relapses, higher Expanded Disability Status Scale (EDSS) score at the last follow-up, fewer NMOSD-typical brain lesions, and longer segments of spinal cord lesions. Patients with older onset age showed a higher proportion of increased protein levels in cerebrospinal fluid during the acute phase of attacks. Age at disease onset positively correlated with length of spinal cord lesions at first attack and at last follow-up, negatively correlated with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up), irrespective of AQP4-IgG serostatus. Patients with older age at disease onset progressed to severe motor disability sooner, and age of onset positively correlated with EDSS score at the last follow-up, irrespective of AQP4-IgG serostatus. Conclusion: Age of disease onset affects clinical characteristics and prognosis outcomes of patients with NMOSD.

Phylogeny and Systematics of the Genus Tolypocladium (Ophiocordycipitaceae, Hypocreales).

The taxonomy and phylogeny of the genus Tolypocladium are herein revised based on the most comprehensive dataset to date. Two species-level phylogenies of Tolypocladium were constructed: a single-gene phylogeny (ITS) of 35 accepted species and a multigene phylogeny (nrSSU, nrLSU, tef-1α, rpb1, and rpb2) of 27 accepted species. Three new species, Tolypocladium pseudoalbum sp. nov., Tolypocladium subparadoxum sp. nov., and Tolypocladium yunnanense sp. nov., are described in the present study. The genetic divergences of four markers (ITS, tef-1α, rpb1 and rpb2) among Tolypocladium species are also reported. The results indicated that species of Tolypocladium were best delimited by rpb1 sequence data, followed by the sequence data for the rpb2, tef-1α, and ITS provided regions. Finally, a key to the 48 accepted species of Tolypocladium worldwide is provided.