Free heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Red blood cells (RBCs) transfusion is related to perioperative neurocognitive disorders. The toxic effect of free heme has been identified in many pathologies. However, the underlying mechanisms of RBCs transfusion or free heme in cognitive impairment have not been clearly explored. Therefore, this research was conducted to determine the mechanism of free heme-induced neuroinflammation and cognitive impairment. METHODS: Rats were received intraperitoneal injection of hemin alone or combined with intracerebroventricular injection of Hemopexin (HPX), and MWM test was conducted to measure cognitive function. The amount of heme-HPX complexes was evaluated by flow cytometry for CD91 + cells. The microglial inflammatory response in rat brain was observed by immunofluorescence staining of Iba-1, and the inflammatory factors of TNF-α, IL-1ß and IL-6 in rat brain and BV2 cells were detected by ELISA analysis. Furthermore, neuronal apoptosis in HT22 cells alone and in HT22 + BV2 coculture system was detected by flow cytometry and immunofluorescence staining. Finally, western blot was conducted to detect TLR4/MyD88/NF-κB proteins in rat brain and BV2 cells treated with hemin or combined with pathway inhibitors. Additionally, the M1 surface marker CD86 was observed in BV2 cells to further confirm neuroinflammation. RESULTS: Intraperitoneal injection of hemin induced cognitive impairment, increase of CD91 + cells, up-regulation of TNF-α and IL-1ß, down-regulation of IL-6, activation of microglia, and activation of the TLR4/MyD88/NF-κB signaling pathway in rat brain. Significantly, intracerebroventricular injection of HPX reduced the above effects. Hemin induced boost of TNF-α, IL-1ß and IL-6 in BV2 cells, as well as apoptosis in HT22 cells. Notably, when HT22 cells were cocultured with BV2 cells, apoptosis was significantly increased. Hemin also induced activation of the TLR4/MyD88/NF-κB signaling pathway and increased the M1 surface marker CD86 in BV2 cells, and inhibiting this pathway reduced the inflammatory responses. CONCLUSIONS: Free heme induces cognitive impairment, and the underlying mechanism may involve neuronal apoptosis and microglial inflammation via the TLR4/MyD88/NF-κB signaling pathway. HPX may have potential therapeutic effects. Video Abstract.

Yanghanlia caeni gen. nov., sp. nov., a novel taxon within the family Alcaligenaceae isolated from sludge of a pesticide-manufacturing factory.

A Gram-stain-negative bacterium, designated LG-2T, was isolated from sludge collected at a pesticide-manufacturing factory in Jiangsu Province, PR China. Cells of strain LG-2T were strictly aerobic, non-motile and spherical. Growth was observed at 15-42 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.0) and 0-3.0 % (w/v) NaCl (optimum, 1.0 %). LG-2T showed 95.5-96.9 % 16S rRNA sequence similarity to type strains in the genera Pusillimonas, Bordetella, Parapusillimonas, Candidimonas and Paracandidimonas of the family Alcaligenaceae. The phylogenomic tree indicated that strain LG-2T was clustered in the family Alcaligenaceae and formed a clade with Paracandidimonas soli IMT-305T, while the phylogenetic trees based on 16S rRNA gene sequences indicated that strain LG-2T formed a distinct clade within the family Alcaligenaceae. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between LG-2T and its closely related type strains in the genera Pusillimonas, Bordetella, Parapusillimonas, Candidimonas and Paracandidimonas were 70.8-75.3, 18.9-23.7 and 59.6 %-69.3 %, respectively. The major cellular fatty acids were C16 : 0, C17 : 0 cyclo, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 2 (C12 : 0 aldehyde and/or unknown 10.928). The predominant menaquinone was Q-8. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, two aminophospholipids, three aminolipids and nine unknown polar lipids. The genome size of strain LG-2T was 3.2 Mb and the DNA G+C content was 63.4 mol%. On the basis of the phenotypic, phylogenetic and genomic results from this study, strain LG-2T represents a novel species of a new genus in the family Alcaligenaceae, for which the name Yanghanlia caeni gen. nov., sp. nov. is proposed, with strain LG-2T (=KCTC 8084T= CCTCC AB 2023123T) as the type strain.

Ruicaihuangia caeni gen. nov., sp. nov., a novel taxon within the family Microbacteriaceae isolated from sludge.

A Gram-stain-positive bacterium, designated YN-L-19T, was isolated from a sludge sample collected from a pesticide-manufacturing plant. Cells of YN-L-19T were strictly aerobic, non-spore-forming, non-motile and ovoid-shaped. Colonies were small, smooth and yellow. Growth occurred at 10-37 °C (optimum, 30 °C), pH 5.0-9.0 (optimum, 7.0) and 0-3.0 % (w/v) NaCl (optimum 0.5 %). Phylogenetic analysis based on genome and 16S rRNA gene sequences indicated that YN-L-19T was affiliated to the family Microbacteriaceae and most closely related to Diaminobutyricimonas aenilata, Terrimesophilobacter mesophilus, Planctomonas deserti and Curtobacterium luteum. The major cellular fatty acids of YN-L-19T were anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0 and C16 : 0. The predominant menaquinone was MK-7. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, glycolipid and one unidentified lipid. The average amino acid identity values between strain YN-L-19T and the related strains were 57.9-61.9 %, which were below the genus boundary (70 %). On the basis of the evidence presented in this study, strain YN-L-19T represents a novel species of a new genus in the family Microbacteriaceae, for which the name Ruicaihuangia caeni gen. nov., sp. nov. (type strain YN-L-19T=CCTCC AB 2022401T= KCTC 49935T) is proposed.

The effectiveness of therapeutic artmaking on depression, anxiety, quality of life, and psychological distress in cancer patients on chemotherapy: a systematic review of the literature.

OBJECTIVES: The purpose of this study was to evaluate the evidence of art therapy on depression, anxiety, quality of life, and mental distress in cancer patients undergoing chemotherapy. METHODS: A systematic literature search was conducted. A systematic search of online electronic databases including, PubMed/MEDLINE, Scopus Web of Science, PsycINFO, and EMBASE was performed using keywords extracted from Medical Subject Headings such as "Art Therapy," and "Neoplasms," "Cancer," and "Chemotherapy" from the earliest to January 11, 2023. A total of 3890 publications were assessed for relevance by title and abstract. The remaining 1298 articles were examined using three inclusion criteria: interventions were guided by an artist or art therapist, participants were actively involved in the creative process, and anxiety, depression, and/or quality of life were included as outcome measures. The methodological quality of the included studies was appraised using specific checklists. RESULT: A total of 495 patients with cancer undergoing chemotherapy participated in ten studies. Among the participants, 87.21% were female and 63.43% of them were in the intervention group. The mean age of the participants was 53.93 in five studies that reduced depression in cancer patients undergoing chemotherapy. Six studies investigated the effect of different art therapy methods on the anxiety of patients, which in four studies reduced their anxiety. Also, three studies investigated the effect of different art therapy methods on patients' distress, which in two studies reduced their distress. CONCLUSION: Art therapy had positive effects on depression, anxiety, quality of life, and psychological distress of cancer patients undergoing chemotherapy. Meanwhile, research on art therapy in cancer patients on chemotherapy is insufficient. We cannot conclude that art therapy benefits cancer patients on chemotherapy. More rigorous research is needed.

Paenibacillus lacisoli sp. nov., a mesotrione-degrading strain isolated from lakeside soil.

A Gram-stain-positive, facultatively anaerobic, rod-shaped bacterium, designated JX-17T, was isolated from a soil sample collected in Jiangxi Province, PR China. Growth was observed at 15-48 °C (optimum 37 °C), at pH 5.0-9.0 (optimum pH 7.0) and with 0-6.0% (w/v) NaCl (optimum 1.0%). Strain JX-17T could degrade approximately 50% of 50 mg/L mesotrione within 2 days of incubation, but could not use mesotrione as sole carbon source for growth. Strain JX-17T showed less than 95.3% 16S rRNA gene sequence similarity with type strains of the genus Paenibacillus. In the phylogenetic tree based on 16S rRNA gene and genome sequences, strain JX-17T formed a distinct lineage within the genus Paenibacillus. The ANI values between JX-17T and the most closely related type strains P. lentus CMG1240T and P. farraposensis UY79T were 70.1% and 71.4%, respectively, and the dDDH values between them were 19.0% and 23.3%, respectively. The major cellular fatty acids were anteiso-C15:0, iso-C16:0, anteiso-C17:0 and C16:0, the predominant respiratory quinone was MK-7, the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified glycolipid, an aminophospholipid and a phosphatidylinositol. The diagnostic diamino acid of the peptidoglycan was meso-diaminopimelic acid, and the DNA G + C content was 50.1 mol%. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain JX-17T represents a novel species within the genus Paenibacillus, for which the name Paenibacillus lacisoli sp. nov is proposed, with strain JX-17T (= GDMCC 1.3962T = KCTC 43568T) as the type strain.

Predictability comparison of sizing parameters for postoperative vault after implantable Collamer lens implantation.

PURPOSE: This study aims to assess the accuracy of three parameters (white-to-white distance [WTW], angle-to-angle [ATA], and sulcus-to-sulcus [STS]) in predicting postoperative vault and to formulate an optimized predictive model. METHODS: In this retrospective study, a cohort of 465 patients (comprising 769 eyes) who underwent the implantation of the V4c implantable Collamer lens with a central port (ICL) for myopia correction was examined. Least absolute shrinkage and selection operator (LASSO) regression and classification models were used to predict postoperative vault. The influences of WTW, ATA, and STS on predicting the postoperative vault and ICL size were analyzed and compared. RESULTS: The dataset was randomly divided into training (80%) and test (20%) sets, with no significant differences observed between them. The screened variables included only seven variables which conferred the largest signal in the model, namely, lens thickness (LT, estimated coefficients for logistic least absolute shrinkage of -0.20), STS (-0.04), size (0.08), flat K (-0.006), anterior chamber depth (0.15), spherical error (-0.006), and cylindrical error (-0.0008). The optimal prediction model depended on STS (R2=0.419, RMSE=0.139), whereas the least effective prediction model relied on WTW (R2=0.395, RMSE=0.142). In the classified prediction models of the vault, classification prediction of the vault based on STS exhibited superior accuracy compared to ATA or WTW. CONCLUSIONS: This study compared the capabilities of WTW, ATA, and STS in predicting postoperative vault, demonstrating that STS exhibits a stronger correlation than the other two parameters.

STING inhibitors target the cyclic dinucleotide binding pocket.

Cytosolic DNA activates cGAS (cytosolic DNA sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling, which triggers interferon and inflammatory responses that help defend against microbial infection and cancer. However, aberrant cytosolic self-DNA in Aicardi-Goutière's syndrome and constituently active gain-of-function mutations in STING in STING-associated vasculopathy with onset in infancy (SAVI) patients lead to excessive type I interferons and proinflammatory cytokines, which cause difficult-to-treat and sometimes fatal autoimmune disease. Here, in silico docking identified a potent STING antagonist SN-011 that binds with higher affinity to the cyclic dinucleotide (CDN)-binding pocket of STING than endogenous 2'3'-cGAMP. SN-011 locks STING in an open inactive conformation, which inhibits interferon and inflammatory cytokine induction activated by 2'3'-cGAMP, herpes simplex virus type 1 infection, Trex1 deficiency, overexpression of cGAS-STING, or SAVI STING mutants. In Trex1-/- mice, SN-011 was well tolerated, strongly inhibited hallmarks of inflammation and autoimmunity disease, and prevented death. Thus, a specific STING inhibitor that binds to the STING CDN-binding pocket is a promising lead compound for STING-driven disease.

Reassembly of Peptide Nanofibrils on Live Cell Surfaces Promotes Cell-Cell Interactions.

Nature regulates cellular interactions through the cell-surface molecules and plasma membranes. Despite advances in cell-surface engineering with diverse ligands and reactive groups, modulating cell-cell interactions through scaffolds of the cell-binding cues remains a challenging endeavor. Here, we assembled peptide nanofibrils on live cell surfaces to present the ligands that bind to the target cells. Surprisingly, with the same ligands, reducing the thermal stability of the nanofibrils promoted cellular interactions. Characterizations of the system revealed a thermally induced fibril disassembly and reassembly pathway that facilitated the complexation of the fibrils with the cells. Using the nanofibrils of varied stabilities, the cell-cell interaction was promoted to different extents with free-to-bound cell conversion ratios achieved at low (31%), medium (54%), and high (93%) levels. This study expands the toolbox to generate desired cell behaviors for applications in many areas and highlights the merits of thermally less stable nanoassemblies in designing functional materials.

Stressors, emotions, and social support systems among respiratory nurses during the Omicron outbreak in China: a qualitative study.

BACKGROUND: Respiratory nurses faced tremendous challenges when the Omicron variant spread rapidly in China from late 2022 to early 2023. An in-depth understanding of respiratory nurses' experiences during challenging times can help to develop better management and support strategies. The present study was conducted to explore and describe the work experiences of nurses working in the Department of Pulmonary and Critical Care Medicine (PCCM) during the Omicron outbreak in China. METHODS: This study utilized a descriptive phenomenological method. Between January 9 and 22, 2023, semistructured and individual in-depth interviews were conducted with 11 respiratory nurses at a tertiary hospital in Wuhan, Hubei Province. A purposive sampling method was used to select the participants, and the sample size was determined based on data saturation. The data analysis was carried out using Colaizzi's method. RESULTS: Three themes with ten subthemes emerged: (a) multiple stressors (intense workload due to high variability in COVID patients; worry about not having enough ability and energy to care for critically ill patients; fighting for anxious clients, colleagues, and selves); (b) mixed emotions (feelings of loss and responsibility; feelings of frustration and achievement; feelings of nervousness and security); and (c) a perceived social support system (team cohesion; family support; head nurse leadership; and the impact of social media). CONCLUSION: Nursing managers should be attentive to frontline nurses' needs and occupational stress during novel coronavirus disease 2019 (COVID-19) outbreaks. Management should strengthen psychological and social support systems, optimize nursing leadership styles, and proactively consider the application of artificial intelligence (AI) technologies and products in clinical care to improve the ability of nurses to effectively respond to future public health crises.

γ-Glutamyltransferase-Activatable Fluoro-Photoacoustic Reporter for Highly Sensitive Diagnosis of Acute Liver Injury and Tumor.

γ-Glutamyltransferase (GGT) has been recognized as an important clinical biomarker that is closely related to many diseases. Visualizing the GGT fluctuation facilitates early disease-related diagnosis and therapy. Herein, an activated probe (NIR-GGT) for the imaging of GGT activity was prepared. The probe consists of a stable NIR fluorophore with the tunable amino group decorated with the γ-glutamate group as a GGT-sensing unit linked by a self-elimination group. NIR-GGT can sensitively recognize GGT and cause a strong turn-on fluorescent and photoacoustic signal. The up-regulation of the GGT expression in acetaminophen-induced acute liver injury was imaged using NIR-GGT. The probe can track changes in the GGT level in the early stages of drug-induced acute liver injury (DIALI) and its remedy process by fluorescent and photoacoustic dual-modality imaging with a high temporal-spatial resolution. NIR-GGT can also be used to differentiate between tumor and para-carcinowa tissues in vivo. The probe may be a potential tool for the diagnosis of early-stage DIALI and accurate tumor resection in the clinical field.

Enhancing the Selectivity of Leucine Aminopeptidase Near-Infrared Fluorescent Probes for Assisting in Surgical Tumor Resection.

Selective fluorescence imaging of analytes is a challenge for monitoring diseases as homologues interfere with the imaging agents. Leucine aminopeptidase (LAP), a kind of protease, is related to tumor pathogenesis. The known LAP fluorescent probes based on leucine recognition have limited selectivity. Herein, a selective t-butyl-alanine recognition unit for LAP through the ligand regulation strategy is prepared as a new near-infrared (NIR) fluorescent probe (DCM-LAP) having a large Stokes shift of 214 nm and a high sensitivity with a detection limit of 168 mU/L. DCM-LAP has an enhanced response toward LAP with NIR fluorescence at 656 nm based on intramolecular charge transfer. The probe is selective without being interfered with by biological enzymes including the aminopeptidase N (APN). DCM-LAP can image LAP activity in living cells. It can also visualize the cell invasion and migration processes. DCM-LAP is employed in the real-time imaging of LAP in tumor-bearing nude mice and guides in the accurate resection of breast tumors. It also distinguishes tumor tissues from normal with a high tumor-to-normal ratio (9.8). The DCM-LAP probe can thus assist in the investigations of LAP-associated clinical disease.

Cysteine-Activatable Near-Infrared Fluorescent Probe for Dual-Channel Tracking Lipid Droplets and Mitochondria in Epilepsy.

Dual-channel fluorescent probes could respond to a specific target and emit different wavelengths of fluorescence before and after the response. Such probes could alleviate the influence caused by the variation of the probe concentration, excitation intensity, and so on. However, for most dual-channel fluorescent probes, the probe and fluorophore faced spectral overlap, which reduced sensitivity and accuracy. Herein, we introduced a cysteine (Cys)-responsive and near-infrared (NIR) emissive AIEgen (named TSQC) with good biocompatibility to dual-channel monitor Cys in mitochondria and lipid droplets (LDs) during cell apoptosis through wash-free fluorescence bio-imaging. TSQC can label mitochondria with bright fluorescence around 750 nm, and after reacting with Cys, the reaction product TSQ could spontaneously target LDs with emissions around 650 nm. Such spatially separated dual-channel fluorescence responses could significantly improve detection sensitivity and accuracy. Furthermore, the Cys-triggered dual-channel fluorescence imaging in LDs and mitochondria during apoptosis induced by UV light exposure, H2O2, or LPS treatment is clearly observed for the first time. Besides, we also report here that TSQC can be used to image subcellular Cys in different cell lines by measuring the fluorescence intensities of different emission channels. In particular, TSQC shows superior utility for the in vivo imaging of apoptosis in acute and chronic epilepsy mice. In brief, the newly designed NIR AIEgen TSQC can respond to Cys and separate two fluorescence signals to mitochondria and LDs, respectively, to study Cys-related apoptosis.

Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption.

OBJECTIVES: Neuroinflammation has been suggested that affects the processing of depression. There is renewed interest in berberine owing to its anti-inflammatory effects. Herein, we investigated whether berberine attenuate depressive-like behaviors via inhibiting NLRP3 inflammasome activation in mice model of depression. METHODS: Adult male C57BL/6N mice were administrated corticosterone (CORT, 20 mg/kg/day) for 35 days. Two doses (100 mg/kg/day and 200 mg/kg/day) of berberine were orally administrated from day 7 until day 35. Behavioral tests were performed to measure the depression-like behaviors alterations. Differentially expressed gene analysis was performed for RNA-sequencing data in the prefrontal cortex. NLRP3 inflammasome was measured by quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence labeling. The neuroplasticity and synaptic function were measured by immunofluorescence labeling, Golgi-Cox staining, transmission electron microscope, and whole-cell patch-clamp recordings. RESULTS: The results of behavioral tests demonstrated that berberine attenuated the depression-like behaviors induced by CORT. RNA-sequencing identified that NLRP3 was markedly upregulated after long-term CORT exposure. Berberine reversed the concentrations of peripheral and brain cytokines, NLRP3 inflammasome elicited by CORT in the prefrontal cortex and hippocampus were decreased by berberine. In addition, the lower frequency of neuronal excitation as well as the dendritic spine reduction were reversed by berberine treatment. Together, berberine increases hippocampal adult neurogenesis and synaptic plasticity induced by CORT. CONCLUSION: The anti-depressants effects of berberine were accompanied by reduced the neuroinflammatory response via inhibiting the activation of NLRP3 inflammasome and rescued the neuronal deterioration via suppression of impairments in synaptic plasticity and neurogenesis.

Advances in Multifunctional Chemotherapeutic Prodrugs for Near-infrared Fluorescence Imaging-guided Therapy.

Conventional chemotherapy (CT) is associated with severe side effects and inducible resistance, making it difficult to meet clinical requirements, forcing the development of new multifunctional prodrugs for precision medicine. In recent decades, researchers and clinicians have focused on developing of multifunctional chemotherapeutic prodrugs with tumor-targeting capability, activatable and traceable chemotherapeutic activity, as a powerful tool to improve theranostic outcomes in cancer treatment. The conjugates of near-infrared (NIR) organic fluorophores and chemotherapy reagents create an exciting avenue for real-time monitoring of drug delivery and distribution, as well as the combination of chemotherapy and photodynamic therapy (PDT). Therefore, there are great opportunities for researchers to conceive and exploit multifunctional prodrugs that can visualize chemo-drugs release and tumor treatment in vivo. In this review, the design strategy and the recent progress of multifunctional organic chemotherapeutic prodrugs for activating NIR fluorescence imaging-guided therapy are described and discussed in detail. Finally, the prospects and challenges of multifunctional chemotherapeutic prodrugs for NIR fluorescence imaging-guided therapy are provided.

miR-132-3p promotes heat stimulation-induced esophageal squamous cell carcinoma tumorigenesis by targeting KCNK2.

Epidemiological evidence supports that consumption of high-temperature food and beverages is an important risk factor for esophageal squamous cell carcinoma (ESCC); however, the underlying mechanism still remains unclear. Here, we established a series of animal models and found that drinking 65°C water can promote esophageal tumor progression from preneoplastic lesions to ESCC. RNA sequencing data showed that miR-132-3p was highly expressed in the heat stimulation group compared with controls. Further study verified that miR-132-3p were upregulated in human premalignant lesion tissues of the esophagus, ESCC tissues, and cells. Overexpression of miR-132-3p could promote ESCC cell proliferation and colony formation, whereas knockdown of miR-132-3p could inhibit ESCC progression in vitro and in vivo. Importantly, dual-luciferase reporter assays showed that miR-132-3p could bind with the 3'-untranslated region of KCNK2 and inhibit KCNK2 gene expression. Knockdown or overexpression of KCNK2 could promote or suppress ESCC progression in vitro. These data suggest that heat stimulation can promote ESCC progression and miR-132-3p mediated this process by directly targeting KCNK2.

Prediction of H3K27M Alteration Status in Brainstem Glioma Using Multi-Shell Diffusion MRI Metrics.

BACKGROUND: Multi-shell diffusion characteristics may help characterize brainstem gliomas (BSGs) and predict H3K27M status. PURPOSE: To identify the diffusion characteristics of BSG patients and investigate the predictive values of various diffusion metrics for H3K27M status in BSG. STUDY TYPE: Prospective. POPULATION: Eighty-four BSG patients (median age 10.5 years [IQR 6.8-30.0 years]) were included, of whom 56 were pediatric and 28 were adult patients. FIELD STRENGTH/SEQUENCE: 3 T, multi-shell diffusion imaging. ASSESSMENT: Diffusion kurtosis imaging and neurite orientation dispersion and density imaging analyses were performed. Age, gender, and diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis, intracellular volume fraction (ICVF), orientation dispersion index, and isotropic volume fraction (ISOVF), were compared between H3K27M-altered and wildtype BSG patients. STATISTICAL TESTS: Chi-square test, Mann-Whitney U test, multivariate analysis of variance (MANOVA), step-wise multivariable logistic regression. P-values <0.05 were considered significant. RESULTS: 82.4% pediatric and 57.1% adult patients carried H3K27M alteration. In the whole group, the H3K27M-altered BSGs demonstrated higher FA, AK and lower RD, ISOVF. The combination of age and median ISOVF showed fair performance for H3K27M prediction (AUC = 0.78). In the pediatric group, H3K27M-altered BSGs showed higher FA, AK, MK, ICVF and lower RD, MD, ISOVF. The combinations of median ISOVF, 5th percentile of FA, median MK and median MD showed excellent predictive power (AUC = 0.91). In the adult group, H3K27M-altered BSGs showed higher ICVF and lower RD, MD. The 75th percentile of RD demonstrated fair performance for H3K27M status prediction (AUC = 0.75). DATA CONCLUSION: Different alteration patterns of diffusion measures were identified between H3K27M-altered and wildtype BSGs, which collectively had fair to excellent predictive value for H3K27M alteration status, especially in pediatric patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Minocycline, a classic antibiotic, exerts psychotropic effects by normalizing microglial neuroinflammation-evoked tryptophan-kynurenine pathway dysregulation in chronically stressed male mice.

The dysregulation of tryptophan-kynurenine pathway (TKP) is extensively involved in the pathophysiology of Alzheimer's disease, depression, and neurodegenerative disorders. Minocycline, a classic antibiotic, may exert psychotropic effects associated with the modulation of TKP. In this study, we examined the effects of minocycline in improving behaviour and modulating TKP components in chronically stressed male mice. Following repeated treatment with 22.5 mg/kg and 45 mg/kg minocycline for 27 days, the stressed mice particularly with higher dose displayed significant improvement on cognitive impairment, depression- and anxiety-like behaviour. Minocycline suppressed stress-induced overexpression of pro-inflammatory cytokines and restored anti-inflammatory cytokines. Chronic stress dramatically suppressed blood and prefrontal cortical levels of the primary substrate tryptophan (TRP), the neuroprotective metabolite kynurenic acid (KYNA), and KYNA/KYN ratio, but increased the intermediate kynurenine (KYN), 3-hydroxykynurenine (3-HK), KYN/TRP ratio, and the neurotoxic metabolite quinolinic acid (QUIN). Minocycline partially or completely reversed changes in these components. Minocycline also inhibited stress-induced overexpression of QUIN-related enzymes, indoleamine 2, 3-dioxygenase 1(iDO-1), kynureninase (KYNU), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilate 3,4-dioxygenase (3-HAO), but rescued the decreased expression of kynurenine aminotransferase (KAT) in brain regions. Behavioral improvements were correlated with multiple TKP metabolites and enzymes. These results suggest that the psychotropic effects of minocycline are mainly associated with the restoration of biodistribution of the primary substrate in the brain and normalization of neuroinflammation-evoked TKP dysregulation.

Shiella aurantiaca gen. nov., sp. nov., a novel bacterium isolated from activated sludge, and proposal of Shiellaceae fam. nov.

A novel Gram-stain-negative, long rod-shaped, aerobic, non-motile, non-spore-forming and orange-pigmented bacterium, designated LB-30T, was isolated from activated sludge. Growth was observed at 15-40 °C (optimum 30 °C), pH 6.0-9.0 (optimum 7.0) and salinities of 0-3.0 % (w/v; optimum 2.0 %). LB-30T showed less than 89.9 % sequence similarities to the recognized taxa of the order Cytophagales. The results of phylogenetic analysis based on 16S rRNA gene sequences and phylogenomic tree indicated that LB-30T formed a distinct lineage within the order Cytophagales. The average amino acid identity (AAI) values between LB-30T and members of the related families Cyclobacteriaceae, Fulvivirgaceae, Roseivirgaceae, Reichenbachiellaceae, Cesiribacteraceae, Cytophagaceae and Hymenobacteraceae in the order Cytophagales were 50.5-54.6 %. The sole respiratory quinone of LB-31T was menaquinone 7 (MK-7). The major polar lipids were phosphatidylethanolamine, aminolipid and four unidentified lipids. The major fatty acids were iso-C15 : 0, iso-C15 : 1G and iso-C17 : 0 3-OH. The DNA G+C content was 43.8 mol%, calculated from the genome sequence. On the basis of differences in the phenotypic, physiological and biochemical characteristics, and distinct phylogenetic relationships, strain LB-30T is proposed to represent a novel species in a novel genus for which the name Shiella aurantiaca gen. nov., sp. nov is proposed, within a novel family Shiellaceae fam. nov. of the order Cytophagales. The type strain is LB-30T (=GDMCC 1.3629T= KCTC 92689T).

Jeotgalibaca caeni sp. nov., isolated from biochemical tank sludge.

A Gram-stain-positive, coccoid-shaped, non-spore-forming, facultatively anaerobic bacterium, designated YN-L-12T, was isolated from the activate sludge of a pesticide plant. Colonies on tryptone soya agar were small, white, opaque and circular. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain YN-L-12T belonged to the genus of Jeotgalibaca, and showed the highest similarity to Jeotgalibaca arthritidis 1805-02T (97.0 %), followed by Jeotgalibaca ciconiae H21T32T (96.5 %), Jeotgalibaca porci 1804-02T (95.6 %) and Jeotgalibaca dankookensis EX-07T (95.4 %). The strain grew at 15-37 °C (optimum, 30 °C), with 0-6.5 % (w/v) NaCl (optimum, 0.5 %) and at pH 7-9 (optimum, pH 7.5). The major fatty acids were C18 : 1 ω9c, C16 : 1 ω9c and C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, glycolipid and an unidentified lipid. The DNA G+C content of the strain was 41.1 mol%. Average nucleotide identity values between strain YN-L-12T and J. arthritidis 1805-02T and J. ciconiae H21T32T were 72.8 and 72.3 %, respectively. The digital DNA-DNA hybridization values between YN-L-12T and J. arthritidis 1805-02T and J. ciconiae H21T32T were 24.1 and 20.3 %, respectively. According to the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain YN-L-12T represents a novel species of the genus Jeotgalibaca, for which the name Jeotgalibaca caeni sp. nov. is proposed, with strain YN-L-12T (=KCTC 43533T=CCTCC AB 2022400T) as the type strain.

Amide proton transfer-weighted imaging and derived radiomics in the classification of adult-type diffuse gliomas.

OBJECTIVES: To evaluate the utility of amide proton transfer-weighted (APTw) MRI imaging and its derived radiomics in classifying adult-type diffuse glioma. MATERIALS AND METHODS: In this prospective study, APTw imaging was performed on 129 patients with adult-type diffuse gliomas. The mean APTw-related metrics (chemical exchange saturation transfer ratio (CESTR), CESTR normalized with the reference value (CESTRnr), and relaxation-compensated inverse magnetization transfer ratio (MTRRex)) and radiomic features within 3D tumor masks were extracted. APTw-radiomics models were developed using a support vector machine (SVM) classifier. Sensitivity analysis with tumor area of interest, different histogram cutoff values, and other classifiers were conducted. RESULTS: CESTR, CESTRnr, and MTRRex in glioblastomas were all significantly higher (p < 0.0003) than those of oligodendrogliomas and astrocytomas, with no significant difference between oligodendrogliomas and astrocytomas. The APTw-related metrics for IDH-wildtype and high-grade gliomas were significantly higher (p < 0.001) than those for the IDH-mutant and low-grade gliomas, with area under the curve (AUCs) of 0.88 for CESTR. The CESTR-radiomics models demonstrated accuracies of 84% (AUC 0.87), 83% (AUC 0.83), 90% (AUC 0.95), and 84% (AUC 0.86) in predicting the IDH mutation status, differentiating glioblastomas from astrocytomas, distinguishing glioblastomas from oligodendrogliomas, and determining high/low grade prediction, respectively, but showed poor performance in distinguishing oligodendrogliomas from astrocytomas (accuracy 63%, AUC 0.63). The sensitivity analysis affirmed the robustness of the APTw signal and APTw-derived radiomics prediction models. CONCLUSION: APTw imaging, along with its derived radiomics, presents a promising quantitative approach for prediction IDH mutation and grading adult-type diffuse glioma. CLINICAL RELEVANCE STATEMENT: Amide proton transfer-weighted imaging, a quantitative imaging biomarker, coupled with its derived radiomics, offers a promising non-invasive approach for predicting IDH mutation status and grading adult-type diffuse gliomas, thereby informing individualized clinical diagnostics and treatment strategies. KEY POINTS: • This study evaluates the differences of different amide proton transfer-weighted metrics across three molecular subtypes and their efficacy in classifying adult-type diffuse glioma. • Chemical exchange saturation transfer ratio normalized with the reference value and relaxation-compensated inverse magnetization transfer ratio effectively predicts IDH mutation/grading, notably the first one. • Amide proton transfer-weighted imaging and its derived radiomics holds potential to be used as a diagnostic tool in routine clinical characterizing adult-type diffuse glioma.