Early onset epileptic and developmental encephalopathy and MOGS variants: a new diagnosis in the whole exome sequencing (WES) ERA : Report of a new patient and review of the literature.

Mannosyl-oligosaccharide glucosidase - congenital disorder of glycosylation (MOGS-CDG) is determined by biallelic mutations in the mannosyl-oligosaccharide glucosidase (glucosidase I) gene. MOGS-CDG is a rare disorder affecting the processing of N-Glycans (CDG type II) and is characterized by prominent neurological involvement including hypotonia, developmental delay, seizures and movement disorders. To the best of our knowledge, 30 patients with MOGS-CDG have been published so far. We described a child who is compound heterozygous for two novel variants in the MOGS gene. He presented Early Infantile Developmental and Epileptic Encephalopathy (EI-DEE) in the absence of other specific systemic involvement and unrevealing first-line biochemical findings. In addition to the previously described features, the patient presented a Hirschprung disease, never reported before in individuals with MOGS-CDG.

MOGS-CDG: Quantitative analysis of the diagnostic Glc3 Man tetrasaccharide and clinical spectrum of six new cases.

Congenital disorders of glycosylation (CDG) are a clinically and biochemically heterogeneous subgroup of inherited metabolic disorders. Most CDG with abnormal N-glycosylation can be detected by transferrin screening, however, MOGS-CDG escapes this routine screening. Combined with the clinical heterogeneity of reported cases, diagnosing MOGS-CDG can be challenging. Here, we clinically characterize ten MOGS-CDG cases including six previously unreported individuals, showing a phenotype characterized by dysmorphic features, global developmental delay, muscular hypotonia, and seizures in all patients and in a minority vision problems and hypogammaglobulinemia. Glycomics confirmed accumulation of a Glc3 Man7 GlcNAc2 glycan in plasma. For quantification of the diagnostic Glcα1-3Glcα1-3Glcα1-2Man tetrasaccharide in urine, we developed and validated a liquid chromatography-mass spectrometry method of 2-aminobenzoic acid (2AA) labeled urinary glycans. As an internal standard, isotopically labeled 13 C6 -2AA Glc3 Man was used, while labeling efficiency was controlled by use of 12 C6 -2AA and 13 C6 -2AA labeled laminaritetraose. Recovery, linearity, intra- and interassay coefficients of variability of these labeled compounds were determined. Furthermore, Glc3 Man was specifically identified by retention time matching against authentic MOGS-CDG urine and compared with Pompe urine. Glc3 Man was increased in all six analyzed cases, ranging from 34.1 to 618.0 µmol/mmol creatinine (reference <5 µmol). In short, MOGS-CDG has a broad manifestation of symptoms but can be diagnosed with the use of a quantitative method for analysis of urinary Glc3 Man excretion.

Recent advances in process engineering and upcoming applications of metal-organic frameworks.

Progress in metal-organic frameworks (MOFs) has advanced from fundamental chemistry to engineering processes and applications, resulting in new industrial opportunities. The unique features of MOFs, such as their permanent porosity, high surface area, and structural flexibility, continue to draw industrial interest outside the traditional MOF field, both to solve existing challenges and to create new businesses. In this context, diverse research has been directed toward commercializing MOFs, but such studies have been performed according to a variety of individual goals. Therefore, there have been limited opportunities to share the challenges, goals, and findings with most of the MOF field. In this review, we examine the issues and demands for MOF commercialization and investigate recent advances in MOF process engineering and applications. Specifically, we discuss the criteria for MOF commercialization from the views of stability, producibility, regulations, and production cost. This review covers progress in the mass production and formation of MOFs along with future applications that are not currently well known but have high potential for new areas of MOF commercialization.

Epilepsy and movement disorders in CDG: Report on the oldest-known MOGS-CDG patient.

Congenital glycosylation disorders (CDG) are inherited metabolic diseases due to defective glycoprotein and glycolipid glycan assembly and attachment. MOGS-CDG is a rare disorder with seven patients from five families reported worldwide. We report on a 19-year-old girl with MOGS-CDG. At birth she presented facial dysmorphism, marked hypotonia, and drug-resistant tonic seizures. In the following months, her motility was strongly limited by dystonia, with forced posture of the head and of both hands. She showed a peculiar hyperkinetic movement disorder with a rhythmic and repetitive pattern repeatedly documented on EEG-polygraphy recordings. Brain MRI showed progressive cortical and subcortical atrophy. Epileptic spasms appeared in first months and ceased by the age of 7 years, while tonic seizures were still present at last assessment (19 years). We report the oldest-known MOGS-CDG patient and broaden the neurological phenotype of this CDG.

Identification and characterization of novel mutations in MOGS in a Chinese patient with infantile spams.

Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of disorders caused by the defects in the synthesis and processing of glycoproteins. CDG is caused by mannosyl-oligosaccharide glucosidase (MOGS) deficiency, and is an extremely rare type, and only six patients have been reported. Here, we report a patient from China with facial dysmorphism, infantile spams, developmental delay, low vison, and abnormal liver function and low immunoglobulin. Brain MRI showed hypoplasia of the corpus callosum and slightly wide sulci at bilateral frontal parietal lobes. Compound heterozygous mutations of (c.1694G>A: R565Q and c.1619G>A: R540H) in exon 4 of MOGS gene (NM_006302.2) were identified by whole exome sequencing. Further investigation showed that the gene expression of MOGS in patients' peripheral blood was decreased. We observed that two mutations were associated with lower protein expression of MOGS, cell growth, and cell cycle in transiently transfected Hela cells. We also noticed that cell cycle-related proteins, ß-catenin, cyclin D1, and C-myc, were decreased in mutant cells. In conclusion, our study suggested whole exome sequencing, and genes associated with CDGs should be analyzed in patients with infantile spams and multiple system involvement, and mutant MOGS-impaired cell cycle progression. Our work broadens the mutation spectrum of MOGS gene.

Abrogation of glucosidase I-mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder.

Glucosidase I (GI) removes the outermost glucose from protein-linked Glc3Man9GlcNAc2 (G3M9) in the endoplasmic reticulum (ER). Individuals with congenital disorders of glycosylation MOGS-CDG bear mutations in the GI-encoding gene (gls1). Although GI absence has been reported to produce lethality in Schizosaccharomyces pombe yeasts, here we obtained two viable Δgls1 mutants, one with a very sick but not lethal phenotype (Δgls1-S) and the other with a healthier one (Δgls1-H). The sick strain displayed only G3M9 as an ER protein-linked oligosaccharide, whereas the healthier strain had both G3M9 and Man9GlcNAc2 The lipid-linked oligosaccharide patterns of the two strains revealed that the most abundantly formed glycans were G3M9 in Δgls1-S and Glc2Man9GlcNAc2 in Δgls1-H, suggesting reduced Alg10p glucosyltransferase activity in the Δgls1-H strain. A mutation in the alg10+ gene was indeed observed in this strain. Our results indicated that abrogated G3M9 deglucosylation was responsible for the severe defects observed in Δgls1-S cells. Further studies disclosed that the defects could not be ascribed to disruption of glycoprotein entrance into calnexin-folding cycles, inhibition of the oligosaccharyltransferase by transfer reaction products, or reduced proteasomal degradation of misfolded glycoproteins. Lack of triglucosylated glycoprotein deglucosylation neither significantly prevented glycan elongation in the Golgi nor modified the overall cell wall monosaccharide composition. Nevertheless, it resulted in a distorted cell wall and in the absence of underlying ER membranes. Furthermore, Golgi expression of human endomannosidase partially restored normal growth in Δgls1-S cells. We propose that accumulation of G3M9-bearing glycoproteins is toxic and at least partially responsible for defects observed in MOGS-CDG.

Based on Fe and Ni prepared organic colloidal materials as efficient oxide nanozymes for chemiluminescence detection of GSH and Hg(II) ions.

Metal-organic gels (MOGs) are a type of metal-organic colloid material with a large specific surface area, loose porous structure, and open metal active sites. In this work, FeNi-MOGs were synthesized by the simple one-step static method, using Fe(III) and Ni(II) as the central metal ions and terephthalic acid as the organic ligand. The prepared FeNi-MOGs could effectively catalyze the chemiluminescence of luminol without the involvement of H2O2, which exhibited good catalytic activity. Then, the multifunctional detected platform was constructed for the detection of GSH and Hg2+, based on the antioxidant capacity of GSH, and the strong affinity between mercury ion (Hg2+) and GSH which inactivated the antioxidant capacity of GSH. The experimental limits of detection (LOD) for GSH and Hg2+ were 76 nM and 210 nM, and the detection ranges were 2-100 µM and 8-4000 µM, respectively. The as-proposed sensor had good performance in both detection limit and detection range of GSH and Hg2+, which fully met the needs of daily life. Surprisingly, the sensor had low detection limits and an extremely wide detection range for Hg2+, spanning five orders of magnitude. Furthermore, the detection of mercury ions in actual lake water and GSH in human serum showed good results, with recovery rates ranging from 90.10 % to 105.37 %, which proved that the method was accurate and reliable. The as-proposed sensor had great potential as the platform for GSH and Hg2+ detection applications.

Progress in Research and Application of Metal-Organic Gels: A Review.

In recent years, metal-organic gels (MOGs) have attracted much attention due to their hierarchical porous structure, large specific surface area, and good surface modifiability. Compared with MOFs, the synthesis conditions of MOGs are gentler and more stable. At present, MOGs are widely used in the fields of catalysis, adsorption, energy storage, electrochromic devices, sensing, analysis, and detection. In this paper, literature metrology and knowledge graph visualization analysis are adopted to analyze and summarize the literature data in the field of MOGs. The visualization maps of the temporal distribution, spatial distribution, authors and institutions' distribution, influence of highly cited literature and journals, keyword clustering, and research trends are helpful to clearly grasp the content and development trend of MOG materials research, point out the future research direction for scholars, and promote the practical application of MOGs. At the same time, the paper reviews the research and application progress of MOGs in recent years by combining keyword clustering, time lines, and emergence maps, and looks forward to their challenges, future development trend, and application prospects.

MOGS promotes stemness acquisition and invasion via enhancing NOTCH1-glycosylation dependent NOTCH pathway in colorectal cancer.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, and about half of CRC patients eventually succumb to tumor metastasis. Despite this, treatment options for metastatic colon cancer remain severely limited, reflected by a 12% 5-year overall survival rate. Increasing evidence suggests that cancer stem cells (CSCs) are pivotal in driving CRC metastasis. Our study found a significant upregulation of MOGS in metastatic colorectal cancer, with high MOGS expression inversely correlating with patient prognosis. Additionally, MOGS enhances the NOTCH pathway, thus promoting stemness in CRC cells, both in vitro and in vivo. Mechanistically, MOGS may facilitate the maturation of NOTCH1 protein by promoting NOTCH1 glycosylation. Correspondingly, silencing MOGS markedly reduced invasion and stemness of CRC cells in vivo. In summary, our findings highlight the critical role of MOGS in fostering stemness and activating the NOTCH pathway in colorectal cancer cells. Disrupting the function of the MOGS/NOTCH could represent a feasible therapeutic strategy for CRC management.

Strategic self-limiting production of infectious HIV particles by CRISPR in permissive cells.

Post-translational glycosylation of the HIV-1 envelope protein involving precursor glycan trimming by mannosyl oligosaccharide glucosidase (MOGS) is critically important for morphogenesis of virions and viral entry. Strategic editing of the MOGS gene in T lymphocytes and myeloid origin cells harboring latent proviral DNA results in the production of non-infectious particles upon treatment of cells with latency reversal agents. Controlled activation of CRISPR-MOGS by rebound HIV-1 mitigates production of infectious particles that exhibit poor ability of the virus to penetrate uninfected cells. Moreover, exclusive activation of CRISPR in cells infected with HIV-1 alleviates concern for broad off-target impact of MOGS gene ablation in uninfected cells. Combination CRISPR treatment of peripheral blood lymphocytes prepared from blood of people with HIV-1 (PWH) tailored for editing the MOGS gene (CRISPR-MOGS) and proviral HIV-1 DNA (CRISPR-HIV) revealed a cooperative impact of CRISPR treatment in inhibiting the production of infectious HIV-1 particles. Our design for genetic inactivation of MOGS by CRISPR exhibits no detectable off-target effects on host cells or any deleterious impact on cell survival and proliferation. Our findings offer the development of a new combined gene editing-based cure strategy for the diminution of HIV-1 spread after cessation of antiretroviral therapy (ART) and its elimination.

Metabolism-related MOGS Gene is Dysregulated After Peripheral Nerve Injury and Negatively Regulates Schwann Cell Plasticity.

Cellular metabolism is essentially linked to tissue remodeling and organ regeneration. MOGS, a gene that encodes cellular metabolism-related protein mannosyl-oligosaccharide glucosidase, was found to be upregulated in nerve segments after peripheral nerve injury. Bioinformatic analyses identified upstream regulators of MOGS and MOGS-associated genes and indicated the significant involvement of cellular metabolism in peripheral nerve regeneration. Functional assessment showed that siRNA-mediated knockdown of MOGS led to elevated proliferation, migration, and differentiation of Schwann cells, indicating the negative regulation of MOGS on Schwann cell plasticity. Schwann cells transfected with MOGS siRNA also showed lower expression of fatty acid synthase (FASN), demonstrating that dysregulated MOGS in Schwann cells may affect neuronal behavior through the metabolic coupling between Schwann cells and axons. Taken together, this study demonstrated that MOGS may be a key regulating factor of Schwann cells and neuronal phenotype during peripheral nerve regeneration.

A visual peroxidase mimicking aptasensor based on Pt nanoparticles-loaded on iron metal organic gel for fumonisin B1 analysis in corn meal.

A visual colorimetric aptasensor combining platinum nanoparticles (Pt NPs) loaded on Fe-based metal organic gel (Fe-MOG) as peroxidase mimics with magnetic separation technique was designed for the detection of fumonisin B1 (FB1). Interestingly, based on the inherent properties of Fe-MOG such as porous nanostructures, abundant Fe2+/Fe3+ active metal centers and synergetic effect between Pt NPs and Fe-MOG, Pt NPs/Fe-MOG composites can be employed as excellent peroxidase mimetic enzyme to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. This process was accompanied by a color variation of the solution from colorless to blue. Kinetic analysis showed that the Pt NPs/Fe-MOG composites make an effective peroxidase mimic with low Michaelis constant (Km), high substrate binding affinity and rapid catalytic velocity (Vm). Furthermore, the Pt NPs/Fe-MOG based colorimetric aptasensor was used to detect FB1. The prepared Pt NPs/Fe-MOG achieved lower detection limit (2.7 pg/mL, 3σ/k) with a wide linear range of 0.01-2000.0 ng/mL. Finally, as a proof of concept of the rapidity and the simplicity of this colorimetric aptasensor, Pt NPs/Fe-MOG was used for the detection of FB1 in real corn samples.

Updated clinical and glycomic features of mannosyl-oligosaccharide glucosidase deficiency: Two case reports.

BACKGROUND: Mannosyl-oligosaccharide glucosidase (MOGS) deficiency is an extremely rare type of congenital disorder of glycosylation (CDG), with only 12 reported cases. Its clinical, genetic, and glycomic features are still expanding. Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG. CASE SUMMARY: We collected comprehensive clinical information, and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry. Novel dysmorphic features included an enlarged tongue, forwardly rotated earlobes, a birth mark, overlapped toes, and abnormal fat distribution. Novel imaging findings included pericardial effusion, a deep interarytenoid groove, mild congenital subglottic stenosis, and laryngomalacia. Novel laboratory findings included peripheral leukocytosis with neutrophil predominance, elevated C-reactive protein and creatine kinase, dyslipidemia, coagulopathy, complement 3 and complement 4 deficiencies, decreased proportions of T lymphocytes and natural killer cells, and increased serum interleukin 6. Glycosylation studies showed a significant increase of hypermannosylated glycopeptides (Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5) and hypersialylated glycopeptides. A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile. CONCLUSION: We confirmed abnormal glycomics in 1 patient, expanding the clinical and glycomic spectrum of MOGS-CDG. We also postulated a compensatory glycosylation pathway, leading to a possible serum biomarker for future diagnosis.

Luminescent cellulose-based porous binary metal-organic gels in an adsorption bed for effective adsorption and sensitive detection of chlortetracycline hydrochloride.

Three novel (Fe-Eu) JLUE-MOGs were successfully fabricated through a solvothermal method and employed to construct the double-effect system for antibiotics adsorption and detection. The characterizations highlighted the properties of ample active sites, large surface areas and hierarchical porous structures, which did contribute to superb and rapid chlortetracycline hydrochloride (CTC) adsorption by JLUE-MOGs. Besides, the effects of initial pH values, JLUE-MOG dosages and co-existing inorganic ions on the CTC adsorption could be explained by pore filling, π-π EDA interaction, electrostatic interaction, water affinity as well as hydrogen bonding. Moreover, the optimized condition was cross-explored by response surface methodology (RSM) with tiny differences compared to actual experiments. In addition, fluorescent JLUE-MOG-7 was implemented for sensitive recognition of CTC and reflecting adsorption processes. Furthermore, shaping JLUE-MOG-7@cellulose aerogels were fabricated as filter materials for applying into an adsorption bed. The breakthrough process was fitted well by Bohart-Adams model and Thomas model, along with recognizable fluorescence changes of immobilized adsorbents. This work develops efficient and luminescent powder-like JLUE-MOGs for antibiotics adsorptive enrichment and sensitive detection. More importantly, immobilized JLUE-MOG@cellulose aerogels, as promising and alternative adsorbents with real-time fluorescence changes, can be utilized for continuously pollutants removal in real wastewater treatment.

Congenital disorders of glycosylation type IIb with MOGS mutations cause early infantile epileptic encephalopathy, dysmorphic features, and hepatic dysfunction.

AIM: MOGS mutations cause congenital disorders of glycosylation type IIb (CDG-IIb or GCS1-CDG). The specific manifestations caused by the mutations in this gene remain unknown. We aimed to describe the clinical features of CDG- IIb and the effectiveness of urinary oligosaccharide analysis in the diagnosis of CDG- IIb. METHODS: Patient 1 was analyzed with whole-exome sequencing (WES) to identify the causative gene of intractable epilepsy and severe developmental delay. After detecting MOGS mutation in patient 1, we analyzed patients 2 and 3 who were siblings and had clinical features similar to those in patient 1. Urinary oligosaccharide analysis was performed to confirm CDG- IIb diagnosis in patient 1. The clinical features of these patients were analyzed and compared with those in eight published cases. RESULTS: Our three patients presented with early infantile epileptic encephalopathy, generalized hypotonia, hepatic dysfunction and dysmorphic features. In two cases, compound heterozygous mutations in MOGS were identified by WES. Isolation and characterization of the urinary oligosaccharide was performed in one of these cases to confirm the diagnosis of CDG-IIb. Although the isoelectric focusing of transferrin (IEF-T) of serum in this patient was normal, urinary excretion of Hex4 corresponding to Glc3Man was observed by mass spectrometry. CONCLUSION: This report provides clinical manifestations of CDG-IIb with MOGS mutation. CDG-IIb shows a normal IEF profile of serum transferrin and cannot be detected by structural analysis of the patient's glycoproteins. Characterization of urinary oligosaccharides should be considered to detect this disorder.

In Situ Synthesis of Gold Nanoparticles/Metal-Organic Gels Hybrids with Excellent Peroxidase-Like Activity for Sensitive Chemiluminescence Detection of Organophosphorus Pesticides.

Until now, despite much progress in the study of metal-organic gels (MOGs), the modification of transition-metal containing MOGs with noble metal nanoparticles (NPs) is far from fully developed. Herein, iron-based MOGs nanosheet hybrids with gold NPs (AuNPs) immobilization were first synthesized by a facile in situ grown strategy at ambient conditions. It is found that the as-prepared AuNPs/MOGs (Fe) hybrids exhibited enhanced mimicking peroxidase-like activity, making them endowed with outstanding performance in chemiluminescence (CL) field in the presence of H2O2. The remarkable CL enhancement by AuNPs/MOGs (Fe) hybrids was attributed to the modification of AuNPs on MOGs (Fe) nanosheets, which could synergistically accelerate the CL reaction by speeding up the generation of OH•, O2•-, and 1O2. Accordingly, a sensitive CL detection of organophosphorus pesticides was successfully achieved by the AuNPs/MOGs (Fe) hybrids CL enhancing system in the range of 5-800 nM with a detection limit of 1 nM. We envision that this highly active and novel enzyme mimetic catalyst can be applicable to other extended AuNPs/MOGs (Fe) hybrid-based CL systems for sensitive detection of various analytes.

Synchronous multifocal osteogenic sarcoma on multimodality imaging including bone scintigraphy.

Multifocal osteosarcoma is diagnosed when there are two or more lesions in the skeleton without presence of pulmonary metastases. It is further classified as synchronous type when the patient is demonstrated to have more than one lesion simultaneously at presentation and is known as Synchronous Multifocal Osteogenicsarcoma (MOGS). We report a case of synchronous MOGS showing its multimodality imaging findings including nuclear scan findings with pathological correlation.