Functions and mechanisms of RNA helicases in plants.

RNA helicases (RHs) are a family of ubiquitous enzymes that alter RNA structures and remodel ribonucleoprotein complexes typically using energy from the hydrolysis of ATP. RHs are involved in various aspects of RNA processing and metabolism, exemplified by transcriptional regulation, pre-mRNA splicing, miRNA biogenesis, liquid-liquid phase separation, and rRNA biogenesis, among other molecular processes. Through these mechanisms, RHs contribute to vegetative and reproductive growth, as well as abiotic and biotic stress responses throughout the life cycle in plants. In this review, we systematically characterize RH-featured domains and signature motifs in Arabidopsis. We also summarize the functions and mechanisms of RHs in various biological processes in plants with a focus on DEAD-box and DEAH-box RNA helicases, aiming to present the latest understanding of RHs in plant biology.

The difference of the retinal structural and microvascular characteristics in patients with MOGAD-ON and AQP4-ON.

BACKGROUND: Antibodies against myelin-oligodendrocyte-glycoprotein (MOG-Abs) associated disease (MOGAD) has been recognized as a disease entity. Optic neuritis (ON) is the most common symptom in MOGAD. To demonstrate the differences in retinal microvascular characteristics between patients with MOGAD-ON and aquaporin-4 antibody (AQP4-Ab) positive ON. METHODS: In a prospective study, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were used to measure retinal and microvascular parameters. RESULTS: Twenty-six MOGAD-ON eyes, 40 AQP4-ON eyes, and 60 control eyes were included in the study. The thickness of RNFL and GCC in MOGAD-ON eyes was significantly lower than that of HC (p < 0.001, respectively), but comparable to AQP4-ON eyes. The vessel density in retina capillary plexus (RCP) was reduced significantly in MOGAD-ON than that in AQP4-ON (p < 0.05, respectively). The visual accuracy was positively correlated with vessel density of superficial RCP in MOG-ON (p = 0.001) and positively correlated with the thickness of the inner retina layer in AQP4-ON (p < 0.001). CONCLUSION: The retinal neuro-axonal damages between MOGAD-ON and AQP4-ON were comparable. Unlike AQP4-ON eyes, microvascular densities were significantly reduced in MOGAD-ON and were positively correlated with the deterioration of visual acuity in MOGAD-ON. TRIAL REGISTRATION: Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE, NCT: 04106830).

Prediction of H3 K27M-mutant in midline gliomas by magnetic resonance imaging: a systematic review and meta-analysis.

PURPOSE: To summarize the predictive value of MRI for H3 K27M-mutant in midline gliomas using meta-analysis. METHODS: Systematic electronic searches of the PubMed, Embase, ISI Web of Science, and Cochrane Library up to Jun 31, 2021, were conducted by two experienced neuroradiologists with the keywords of "MRI," "Glioma," and "H3 K27M." The hierarchical summary receiver-operating characteristic (HSROC) model was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (LR +), negative likelihood ratio (LR -), and diagnostic odds ratio (DOR). Coupled forest plots were used to evaluate the heterogeneity of the included studies. RESULTS: Of seven original studies with a total of 593 patients, 240 glioma patients were included, with 45.5-70.6% H3 K27M-mutant gliomas. Using MRI, a pooled sensitivity of 0.78 (95% CI, 0.66-0.87), specificity of 0.85 (95% CI, 0.76-0.91), LR + of 5.07 (95% CI, 3.19-8.08), LR - of 0.26 (95% CI, 0.16-0.42), and DOR of 19.80 (95% CI, 9.28-42.28) were achieved for H3 K27M-mutant prediction. Significant heterogeneity was observed among the studies in terms of sensitivity (Q = 16.83, df = 7, p = 0.02; I2 = 58.40 [95% CI, 25.83-90.97]), LR - (Q = 16.61, df = 7, p = 0.02; I2 = 57.87 [95% CI, 24.81-90.93]), and DOR (Q = 14.05, df = 7, p = 0.05; I2 = 50.18 [95% CI, 10.06-90.31]). CONCLUSIONS: This meta-analysis demonstrated a clinical value of MRI to predict H3 K27M-mutant in midline gliomas with a pooled sensitivity of 0.78 and specificity of 0.85.

In Situ Hydrolysis of Block Copolymers at the Water-Oil Interface.

In situ manipulation of the chemical composition of block copolymers at the fluid interfaces affords a route by which the interfacial tension, the packing of the copolymers, and the penetration of the blocks into the two liquids can be controlled. Here, a series of linear block copolymers of poly(solketal methacrylate-b-styrene) (PSM-b-PS) are used, converting hydrophobic PSM block into a hydrophilic glycerol monomethacrylate (GM) block, that results in a marked decrease in the liquid-liquid interfacial tension. The kinetics of the first-order hydrolysis reaction was analyzed by monitoring the time-dependent interfacial tension as a function of pH, polymer concentration, molecular weight, and composition. Fluorescence recovery after photobleaching (FRAP) was used to measure the in-plane dynamics of the copolymers before and after hydrolysis. This work provides insights into a quantitative pathway by which in situ interfacial reactions may be performed and monitored in real time, completely changing the interfacial activity of the molecule.

Multiplexed CRISPR/Cas9-mediated metabolic engineering of γ-aminobutyric acid levels in Solanum lycopersicum.

In recent years, the type II CRISPR system has become a widely used and robust technique to implement site-directed mutagenesis in a variety of species including model and crop plants. However, few studies manipulated metabolic pathways in plants using the CRISPR system. Here, we introduced the pYLCRISPR/Cas9 system with one or two single-site guide RNAs to target the tomato phytoene desaturase gene. An obvious albino phenotype was observed in T0 regenerated plants, and more than 61% of the desired target sites were edited. Furthermore, we manipulated the γ-aminobutyric acid (GABA) shunt in tomatoes using a multiplex pYLCRISPR/Cas9 system that targeted five key genes. Fifty-three genome-edited plants were obtained following single plant transformation, and these samples represented single to quadruple mutants. The GABA accumulation in both the leaves and fruits of genomically edited lines was significantly enhanced, and the GABA content in the leaves of quadruple mutants was 19-fold higher than that in wild-type plants. Our data demonstrate that the multiplex CRISPR/Cas9 system can be exploited to precisely edit tomato genomic sequences and effectively create multisite knockout mutations, which could shed new light on plant metabolic engineering regulations.

Cytokines and Tissue Damage Biomarkers in First-Onset Neuromyelitis Optica Spectrum Disorders: Significance of Interleukin-6.

OBJECTIVE: We investigated the contribution of several cytokines in the pathogenesis of first-onset neuromyelitis optica spectrum disorder (NMOSD) and determined the differences between aquaporin 4 immunoglobulin G (AQP4-IgG)-positive and AQP4-IgG-negative subtypes. METHODS: We enrolled 18 NMOSD (10 AQP4-IgG-positive and 8 AQP4-IgG-negative) and 8 multiple sclerosis (MS) patients, whose serum and cerebrospinal fluid (CSF) samples were collected during the acute phase of the first onset before immunotherapy. Fifteen patients with other noninflammatory neurological diseases (OND) were also included. The serum and CSF levels of interleukin (IL)-6, IL-10, IL-17, IL-21, IL-23, transforming growth factor (TGF)-ß1 and the CSF levels of 3 biomarkers of axonal loss and astrocytic damage were measured using the human cytokine multiplex assay or ELISA. RESULTS: Serum levels of IL-10 and TGF-ß1 and CSF levels of IL-6, IL-10, and TGF-ß1 were significantly increased in first-onset NMOSD compared to in OND patients. In a subgroup analysis, the CSF levels of IL-6, neurofilament light protein (NFL), S100B, and glial fibrillary acidic protein (GFAP) were significantly more elevated in the AQP4-IgG-positive patients than in the AQP4-IgG-negative NMOSD patients. Correlations were found between the CSF cytokines and tissue damage biomarkers and the clinical findings in NMOSD patients. Notably, the CSF IL-6 level had the strongest correlation with the tissue damage biomarkers and it also correlated with CSF white blood cell (WBC) count. CONCLUSIONS: IL-6 plays a role in the pathogenetic process of NMOSD, especially in the AQP4-IgG-positive subtype. Distinct pathogenesis exists between AQP4-IgG-positive and AQP4-IgG-negative NMOSD in the initial phase of the disease.

Prevalence and risk factors of deep venous thrombosis in patients with longitudinally extensive transverse myelitis: one center data from China.

OBJECTIVE: Deep venous thrombosis (DVT) is a severe complication in longitudinally extensive transverse myelitis (LETM) patients. It may interfere with LETM treatment and delay the recovery of the spinal dysfunction. However, there is less data about the prevalence and risk factors of DVT in patients with LETM. We analyzed data retrospectively to ascertain the prevalence of DVT and the clinical risk factors for DVT. METHODS: Clinical data on 255 LETM patients were collected from medical records. All patients were performed color Doppler ultrasound(US) to screen DVT in both lower extremities when admitted. Clinical characteristics of LETM patients with DVT were compared with those without DVT using corresponding statistical methods. Multivariate logistic regression was performed to identify risk factors related to DVT. RESULTS: DVT were found in 11.8% patients with LETM. Univariate analysis showed that age, muscle force and elevated baseline D-dimer were risk factors for DVT. After multivariate logistic regression, age, dyslipidemia, segments of lesions, and elevated baseline D-dimer remained significant independent risk factors. CONCLUSIONS: DVT is common in patients with LETM and related to patient's age, dyslipidemia, segments of lesions, and elevated baseline D-dimer. Early recognition of DVT and thrombosis prophylaxis are appropriate in patients with LETM.

Association between TPMT*3C and decreased thiopurine S-methyltransferase activity in patients with neuromyelitis optica spectrum disorders in China.

AIM OF THE STUDY: Thiopurines are effective drugs in treating neuromyelitis optica spectrum disorders and other diseases. Thiopurines' toxicity is mainly imputed to thiopurine S-methyltransferase activity. In Chinese population, the most common and important variation of thiopurine S-methyltransferase is TPMT*3C (rs1142345). This study aims to reveal the association between thiopurine S-methyltransferase activity and genetic polymorphisms of thiopurine S-methyltransferase in patients with neuromyelitis optica spectrum disorders in China. MATERIAL AND METHODS: A liquid chromatography tandem mass/mass method was used to evaluate the thiopurine S-methyltransferase activity by using 6-mercapthioprine as the substrate in human erythrocyte haemolysate via 1 h incubation at 37 °C to form its methylated product 6-methylmercaptopurine. The amount of 6-methylmercaptopurine was adjusted by haematocrit and normalized to 8 × 108 erythrocytes. The selected polymorphisms of thiopurine S-methyltransferase were identified using MassARRAY system (Sequenom) and multiple SNaPshot technique. RESULTS: In 69 patients with neuromyelitis optica spectrum disorders, thiopurine S-methyltransferase activity was 80.29-154.53 (127.51 ± 16.83) pmol/h/8 × 108 erythrocytes. TPMT*3C (rs1142345) was associated with lower thiopurine S-methyltransferase activity (BETA = -25.37, P = 0.011). Other selected variants were not associated with thiopurine S-methyltransferase activity. CONCLUSIONS: TPMT*3C affects TPMT activity in Chinese patients with neuromyelitis optica spectrum disorders. Further studies are warranted to confirm the results. ABBREVIATIONS: TPRs = thiopurines; NMOSD = neuromyelitis optica spectrum disorders; TPMT = thiopurine S-methyltransferase; LC-MS/MS = liquid chromatography tandem mass/mass; 6-MMP = 6-methylmercaptopurine; IS = internal standard; SNP = single nucleotide polymorphism; MAF = minor allele frequency; HWE = Hardy-Weinberg equilibrium; BETA = regression coefficients; UTR-3 = untranslated region 3.

LC-MS/MS Analysis of Erythrocyte Thiopurine Nucleotides and Their Association With Genetic Variants in Patients With Neuromyelitis Optica Spectrum Disorders Taking Azathioprine.

BACKGROUND: Azathioprine is a first-line drug in treating neuromyelitis optica spectrum disorders (NMOSD). To exhibit its bioactivity, azathioprine needs to be converted to thiopurine nucleotides (TPNs) including 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) that are affected by genetic polymorphisms. This study aims to develop an LC-MS/MS method for the analysis of erythrocyte concentrations of TPNs and to evaluate their associations with variants of various genes (MTHFR, TPMT, HLA, SLC29A1, SLC28A2, SLC28A3, ABCB1, and ABCC4) in patients with NMOSD. METHODS: Erythrocyte 6-TGNs and 6-MMPNs were converted to their free bases 6-thioguanine and 6-methylmercaptopurine derivative by 1-hour acid hydrolysis at 95°C. An LC-MS/MS method was developed, validated, and used to study 32 patients with NMOSD to determine these free bases. Genetic variants were identified by MassARRAY (Sequenom) and multiple SNaPshot techniques. The associations between genetic variants and the concentrations of TPNs or the 6-MMPNs:6-TGNs ratio were evaluated by PLINK software using linear regression. RESULTS: Methanol and water were used for separation with a total run time of 6.5 minutes. The lowest limit of quantification was 0.1 µmol/L with an injection volume of 10 µL. rs10868138 (SLC28A3) was associated with a higher erythrocyte concentration of 6-TGNs (P = 0.031), whereas rs12378361 (SLC28A3) was associated with a lower erythrocyte concentration of 6-TGNs (P = 0.0067). rs507964 (SLC29A1) was significantly associated with a lower erythrocyte concentration of 6-MMPNs (P = 0.024) and a lower 6-MMPNs:6-TGNs ratio (P = 0.029). CONCLUSIONS: An LC-MS/MS method for the analysis of erythrocyte TPNs was developed, validated, and used to study 32 patients with NMOSD. SLC29A1 and SLC28A3 were associated with the erythrocyte concentrations of TPNs and 6-MMPNs:6-TGNs ratio. Further studies are needed to confirm these results.

Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating autoimmune diseases in the central nervous system (CNS) that are characterized by a high relapse rate and the presence of anti-aquaporin 4 antibodies (AQP4-IgG) in the serum. Azathioprine (AZA) is a first-line immunomodulatory drug that is widely used for the treatment of patients with NMOSD. However, the efficacy and safety of AZA vary in different individuals. METHOD: Thirty-two patients with NMOSD who regularly took AZA were enrolled in the study at Beijing Tiantan Hospital, Capital Medical University. The efficacy of AZA was evaluated using the expanded disability status scale (EDSS) and the annual relapse rate (ARR). The erythrocyte concentrations of AZA metabolites were detected using an LC-MS/MS method. RESULTS: The erythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) were 202.03 ± 63.35 pmol/8*108 RBC and 1618.90 ± 1607.06 pmol/8*108 RBC, respectively. After the patients had received AZA therapy for more than one year, the EDSS score decreased from 5.21 ± 0.24 to 2.57 ± 0.33 (p < 0.0001), and the ARR decreased from 1.41 ± 0.23 to 0.36 ± 0.09 (p < 0.0001). The 6-TGN and 6-MMPN levels were significantly different between the non-relapsed and relapsed groups (p < 0.0001, p = 0.006, respectively). A higher ARR was significantly correlated with higher erythrocyte concentrations of 6-TGNs (p < 0.0001) and 6-MMPNs (p = 0.004). CONCLUSION: AZA can reduce the EDSS score and ARR in NMOSD patients. Additionally, the efficacy of AZA is significantly related to the erythrocyte concentrations of 6-TGNs and 6-MMPNs. Within the safe upper limits, a higher concentration of 6-TGNs is associated with better efficacy of AZA. TRIAL REGISTRATION NUMBER: ISRCTN16551495 , retrospectively registered on May 22, 2017.

Comparison of 6-mercaptopurine with 6-thioguanine for the analysis of thiopurine S-methyltransferase activity in human erythrocyte by LC-MS/MS.

Thiopurines (TPDs) are first-line drugs in treating neuromyelitis optica spectrum disorders (NMOSD). Evaluation of thiopurine S-methyltransferase activity (TPMT), a major determinant of TPD toxicity, before TPD treatment using 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrate was suggested. However, the equivalent of the two substrates in TPMT activity evaluation was unknown, and an alternative substrate was required in TPMT activity evaluation in patients who were already taking 6-MP or 6-TG. Before evaluating the agreement of 6-MP and 6-TG in TPMT activity measurement in patients with NMOSD, the affinity of the two substrates for the active center of TPMT should be established. A computer-based simulation indicated that 6-MP and 6-TG had similar affinities for the two active sites of TPMT. According to the guidelines, an LC-MS/MS method was developed and validated to evaluate the TPMT activity in human erythrocyte hemolysate using 6-MP or 6-TG as substrates via 1 h incubation at 37°C. The method was applied in 81 patients with NMOSD. Evaluated by Bland-Altman plot, 6-methylmercaptopurine and 6-methylthioguanine represented TPMT activities were in agreement with each other. Further studies are warranted to confirm the results.

Atypical MRI features in familial adult onset Alexander disease: case report.

BACKGROUND: Alexander disease (AxD) is a rare neurological disease, especially in adults. It shows variable clinical and radiological features. CASE PRESENTATION: We diagnosed a female with AxD presenting with paroxysmal numbness of the limbs at the onset age of 28-year-old, progressing gradually to spastic paraparesis at age 30. One year later, she had ataxia, bulbar paralysis, bowel and bladder urgency. Her mother had a similar neurological symptoms and died within 2 years after onset (at the age of 47), and her maternal aunt also had similar but mild symptoms at the onset age of 54-year-old. Her brain magnetic resonance imaging (MRI) showed abnormal signals in periventricular white matter with severe atrophy in the medulla oblongata and thoracic spinal cord, and mild atrophy in cervical spinal cord, which is unusual in the adult form of AxD. She and her daughter's glial fibrillary acidic protein (GFAP) gene analysis revealed the same heterozygous missense mutation, c.1246C > T, p.R416W, despite of no neurological symptoms in her daughter. CONCLUSIONS: Our case report enriches the understanding of the familial adult AxD. Genetic analysis is necessary when patients have the above mentioned symptoms and signs, MRI findings, especially with family history.

Sunflower-like missing-linker covalent organic framework for efficient extraction of non-steroidal anti-inflammatory drugs.

As excellent crystalline materials, covalent organic frameworks (COFs) are widely used in drug adsorption. In this work, a defective engineering strategy was proposed for designing and preparing the functionalized end-capping monomer and missing-linker COFs. The missing-linker COF 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde compound with glycidyltrimethyl ammonium chloride modified benzene-1,4-diamine (TpPa-GTA) was synthesized through Schiff base reaction with wide pore size distribution for adsorption of four nonsteroidal anti-inflammatory drugs (NSAIDs). The adsorption process follows pseudo-second-order kinetics, and the four drugs reached adsorption equilibrium within 10 min. The sunflower-like structure helps to promote intraparticle diffusion during the adsorption process, thereby realizing the rapid adsorption of TpPa-GTA. The equilibrium isotherms fit well with both the Freundlich and Langmuir models, with a maximum adsorption capacity of 83.3-315 mg g-1 calculated from the Langmuir model. Based on the detection results of Zeta potential and XPS, the adsorption mechanism was inferred, and the rapid capture of NSAIDs in the wide pH range of 4.0 to 7.5 was realized under electrostatic interaction, hydrogen bonding, and π-π interaction. The detection of lake and river samples using the missing adapter TpPa-GTA has a recovery rate of 84.2-117%, which provides a new approach to the adsorption of pollutants with COFs.

Stochastic processes drive the diversity and composition of methanogenic community in a natural mangrove ecosystem.

Methanogens are considered to be crucial components of mangrove ecosystems with ecological significance. However, understanding the assembly processes of methanogenic communities in mangrove ecosystems is relatively insufficient. In the current study, a natural mangrove in a protection zone was employed to investigate the diversity and assembly processes of methanogenic community by using amplicon high-throughput sequencing, a null model as well as a neutral community model. The results showed that methanogenic community in mangrove sediments were highly diverse, with the predominance of methylotrophic Methanolobus, and hydrogenotrophic Methanogenium, Methanospirillum. The diversity, composition, and gene abundance varied obviously across the mangrove sampling sites, whereas the measured environmental variables exhibited a negligible effect. Null model showed that the values of beta nearest-taxon index were mostly between -2 and 2, indicating that stochastic processes contributed more than deterministic processes driving the methanogenic community assembly in mangrove sediments. Neutral community model revealed a high estimated migration rate of methanogenic community, further substantiating the significance of stochastic processes. Among the keystone species identified in network analysis, methanogens affiliated to hydrogenotrophic Methanospirillum may have a crucial role in maintaining the structure and function of methanogenic community. Notably, these keystone species were almost unaffected by measured environmental factors, indicating that the methanogenic community in mangrove sediments is more likely to be affected by stochastic processes. This study deepens the understanding of the diversity and assembly of methanogenic community in mangrove sediments, and provides clues to maintain mangrove ecosystem functioning.

Baicalin inhibits monosodium urate crystal-induced pyroptosis in renal tubular epithelial cell line through Panx-1/P2X7 pathways: Molecular docking, molecular dynamics, and in vitro experiments.

Pyroptosis is a programmed cell death process that frequently occurs in many diseases, including hyperuricemic nephropathy (HN). In HN, a range of stimuli mediates inflammation, leading to the activation of inflammasomes and the production of gasdermin D (GSDMD). Baicalin (BA), a natural flavonoid renowned for its antioxidant and anti-inflammatory properties, was investigated for its role in HN in this study. Initially, HN-like inflammation and pyroptosis were induced in HK-2 cells with treatment of monosodium urate (MSU), followed by the BA treatment. The expression of pyroptosis-associated genes, Panx-1 and P2X7, at both mRNA and protein levels was assessed through real-time polymerase chain reaction (RT-qPCR) and Western blotting (WB) without or with BA treatment. The results showed that expression of Panx-1 and P2X7 at mRNA and protein levels was increased in MSU-treated HK-2 cells, which subsequently decreased upon the BA treatment. Further experiments showed that BA could combine NLRP3 inflammasome and GSDMD, destabilizing GSDMD protein. Moreover, BA protected the cell membrane from MSU-induced damage, as evidenced by Hoechst 33342 and PI double staining, lactate dehydrogenase (LDH) assays, and electron microscopy observations. These results suggest that BA is involved in the regulating Panx-1/P2X7 pathways and thus inhibits pyroptosis, highlighting its potential therapeutic effect for HN.

Parallel degradome-seq and DMS-MaPseq substantially revise the miRNA biogenesis atlas in Arabidopsis.

MicroRNAs (miRNAs) are produced from highly structured primary transcripts (pri-miRNAs) and regulate numerous biological processes in eukaryotes. Due to the extreme heterogeneity of these structures, the initial processing sites of plant pri-miRNAs and the structural rules that determine their processing have been predicted for many miRNAs but remain elusive for others. Here we used semi-active DCL1 mutants and advanced degradome-sequencing strategies to accurately identify the initial processing sites for 147 of 326 previously annotated Arabidopsis miRNAs and to illustrate their associated pri-miRNA cleavage patterns. Elucidating the in vivo RNA secondary structures of 73 pri-miRNAs revealed that about 95% of them differ from in silico predictions, and that the revised structures offer clearer interpretation of the processing sites and patterns. Finally, DCL1 partners Serrate and HYL1 could synergistically and independently impact processing patterns and in vivo RNA secondary structures of pri-miRNAs. Together, our work sheds light on the precise processing mechanisms of plant pri-miRNAs.

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)-rich ADEVs in patients with AQP4-Abs-positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE130-149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor-related protein 1 (LRP1) could block the restorative effects of APOE130-149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE-/- mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.

Fabrication of mixed-mode amphoteric ß-cyclodextrin polymer for the simultaneous extraction of acidic and alkaline drugs.

A multifunctional mixed-mode ß-CD polymer adsorbent PNVCD-SIM containing amphoteric ions and multiple functional groups was prepared. Its physicochemical properties were characterized by scanning electron microscope (SEM), 1H nuclear magnetic resonance (1H NMR), 13C NMR, Fourier transform infrared spectroscopy (FT-IR), nitrogen adsorption-desorption test, elemental analysis (EA), and thermogravimetry and differential scanning calorimetry (TGA-DSC). The acidic indomethacin and alkaline promethazine were selected to evaluate the adsorption properties of PNVCD-SIM at different pH. Under optimal neutral pH conditions, the adsorption performance of PNVCD-SIM on acidic NSAIDs, alkaline phenothiazine, and neutral steroid hormone drugs was investigated. The results showed that PNVCD-SIM exhibited excellent diversified adsorption properties for acidic, alkaline, and neutral mixed drug components through the synergistic effects of ß-CD inclusion, electrostatic interaction, hydrogen bond, π-π conjugation, and π-cation effect. The adsorption mechanism was consistent with the pseudo-second-order kinetic model and Langmuir isotherm model. Under the optimized conditions, a dispersive solid phase extraction method combined with high-performance liquid chromatography (dSPE-HPLC) using PNVCD-SIM as the adsorbent was established. The simultaneous extraction and detection of acidic-alkaline multi-component drugs in actual urine and lake water samples were successfully realized. This study provides new insight into the design and preparation of mixed-mode adsorption materials suitable for the rapid analysis and detection of multiple analytes.

Deep learning models for cancer stem cell detection: a brief review.

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are a subset of tumor cells that persist within tumors as a distinct population. They drive tumor initiation, relapse, and metastasis through self-renewal and differentiation into multiple cell types, similar to typical stem cell processes. Despite their importance, the morphological features of CSCs have been poorly understood. Recent advances in artificial intelligence (AI) technology have provided automated recognition of biological images of various stem cells, including CSCs, leading to a surge in deep learning research in this field. This mini-review explores the emerging trend of deep learning research in the field of CSCs. It introduces diverse convolutional neural network (CNN)-based deep learning models for stem cell research and discusses the application of deep learning for CSC research. Finally, it provides perspectives and limitations in the field of deep learning-based stem cell research.

Ecological sustainability assessment of building glass industry in China based on the point of view of raw material emergy and chemical composition.

Severe environmental destruction is being driven by excessive resource consumption in the industrial production process. Therefore, there is a necessity to evaluate the sustainability of the production system. In this study, the emergy method has been adopted to assess the flat building glass production in China based on raw material and chemical composition. A series of problems including key contributors, primary sustainable indexes, unit emergy value (UEVs), sensitivity ratios, and waste impact was studied. The results illustrate that (1) the nonrenewable resources and imported resources showed the dominant impacts. (2) Silica sand and sandstone were the foremost items for the raw material angle emergy. (3) Excessive EIR, serious ELR, and tiny ESI were the main contributors to the unsustainability of the evaluated system. (4) Four UEVs were revealed, which are 1.69E + 12sej/kg, 1.80E + 12sej/kg, 1.60E + 12sej/kg, and 1.71E + 12sej/kg, respectively. (5) The nonrenewable resources showed the biggest fluctuation (7.09%), followed by imported resources (1.62%) in view of the raw material perspective; for the chemical composition, the nonrenewable resources were 7.15%, and imported resources were 1.49%, respectively. (6) Waste gas emissions were found as the major emergy contributor to the economic loss. Furthermore, positive solutions were discussed for improving the sustainability of glass production, including the proportion increase of renewable energy, recycling material replacement, and promotion of energy-saving equipment.