Effect of glycerin on the physical properties of polyvinyl alcohol/sodium alginate blend.

Because of the abundance of sodium resources, sodium-ion batteries (NIBs) offer a promising alternative electrochemical energy storage solution. One of the current roadblocks to the development of NIBs technology is a lack of electrode materials capable of reversibly storing/releasing sodium ions for a sufficiently long time. Thus, this work aims to study, theoretically, the effect of glycerin incorporation on polyvinyl alcohol (PVA)/sodium alginate (Na Alg) blend as electrode materials for NIBs. The electronic, thermal, and quantitative structure-activity relationship (QSAR) descriptors of polymer electrolytes based on a blend of PVA and Na Alg and glycerin are the main topics of this work. These properties are examined here using semi-empirical methods and the density functional theory (DFT). Bandgap energy (Eg) is examined because the structural analysis reveals details regarding the interactions between PVA/Na Alg and glycerin. The findings indicate that the addition of glycerin caused the Eg value to drop to 0.2814 eV. The molecular electrostatic potential surface, or MESP, shows the electron-rich and deficit regions throughout the electrolyte system as well as the distribution of molecular charges. Thermal parameters that are studied include enthalpy (H), entropy (ΔS), heat capacity (Cp), Gibbs' free energy (G), and heat of formation. Additionally, the study examines several QSAR descriptors, such as total dipole moment (TDM), total energy (E), ionization potential (IP), Log P, and Polarizability. The results show that H, ΔS, Cp, G, and TDM increased with increasing temperature and glycerin content. Meanwhile, heat of formation, IP, and E decreased, improving reactivity and polarizability. Additionally, the cell voltage increased to 2.488 V due to glycerin addition. The overall DFT and PM6 calculations of cost-effective PVA/Na Alg based glycerin electrolytes indicate that they can partially replace lithium-ion batteries due to their multifunctionality, but requires further improvement and investigations.

Case Report of Friedreich's Ataxia and ALG1-Related Biochemical Abnormalities in a Patient With Progressive Spastic Paraplegia.

Frataxin is an evolutionarily conserved mitochondrial protein responsible for iron homeostasis and metabolism. A deficiency of frataxin (encoded by FXN) leads to Friedreich's ataxia (FRDA), a progressive disorder that affects both the central and peripheral nervous systems, most commonly via a pathogenic GAA trinucleotide expansion. In contrast, pathogenic variants in ALG1 in humans cause a form of congenital disorder of glycosylation. Here, we present a 15-year-old boy with a clinical presentation that raised concern for complex hereditary spastic paraplegia (HSP), with motor features including progressive spastic paraparesis, cervical dystonia, cerebellar dysfunction, and diminished lower extremity reflexes. The proband was initially found to have a novel compound heterozygous variant in ALG1 on exome sequencing, along with N-glycan profiling revealing evidence of defective mannosylation and Western blot analysis demonstrating an 84% reduction in ALG1 expression. Although several of his clinical features could be explained by the ALG1 variant specifically or considered as part of the presentation of CDGs in general, there were additional phenotypes that suggested an alternative, or additional, genetic diagnosis. Subsequently, he was found to have biallelic pathogenic GAA repeat expansions in FXN on genome sequencing, leading to a diagnosis of FRDA. Given that FRDA explained all his clinical features, the ALG1 variant may have been a hypomorphic form and/or a biochemical phenotype. Our findings underscore the importance of considering FRDA as a differential diagnosis in cases of complex HSP and demonstrate the utility of unbiased genome sequencing approaches that include detection of trinucleotide repeat expansions for progressive motor disorders.

Identification of two novel variants in ALG11 causing congenital disorder of glycosylation.

BACKGROUND: Congenital disorders of glycosylation (CDG) represent a heterogeneous group of rare inherited metabolic disorders due to abnormalities in protein or lipid glycosylation pathways, affecting multiple systems, and frequently being accompanied by neurological symptoms. ALG11-CDG, also known as CDG-1p, arises from a deficiency in a specific mannosyltransferase encoded by the ALG11 gene. To date, only 17 cases have been documented, and these patients have prominent clinical phenotypes, including seizures, developmental delay, and microcephaly. METHODS: We describe a novel case of a four-month-old boy from a Chinese family exhibiting developmental delay, seizures, and microcephaly. Trio whole-exome sequencing (WES) and subsequent Sanger sequencing were employed to identify the potential genetic cause, and functional study was performed to evaluate the pathogenicity of genetic variant identified. RESULTS: Trio WES unveiled novel compound heterozygous variants: c.1307G>T (p.G436V) and c.1403G>A (p.R468H) within exon 4 of the ALG11 gene, inherited from the father and mother, respectively. Subsequent in vitro functional analysis revealed decreased stability of the mutant protein and concurrent hypoglycosylation of GP130, a hyperglycosylated protein. CONCLUSIONS: Our findings not only expand the clinical and variant spectrum of ALG11-CDG, but also emphasize the importance of WES as a first-tier genetic test in determining the molecular diagnosis.

Ferrous sulfate remodels the properties of sodium alginate-based hydrogel and facilitates the healing of wound infection caused by MRSA.

Frequent occurrence of wound infection caused by multiple-resistant bacteria (MRB) has posed a serious challenge to the current healthcare system relying on antibiotics. The development of novel antimicrobial materials with high safety and efficacy to heal wound infection is of great importance in combating this crisis. Herein, we prepared a promising antibacterial hydrogel by cross-linking ferrous ions (Fe2+) with the deprotonated carboxyl anion in sodium alginate (Na-ALG) to cure wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, ferrous-modified Na-ALG (Fe-ALG) hydrogel demonstrated better properties compared to the traditional Na-ALG-based hydrogels, including injectability, self-healing, appropriate fluidity, high-water retention, potent MRSA-killing efficacy, and excellent biocompatibility. Importantly, the addition of Fe2+ enhances the antibacterial efficacy of the Na-ALG hydrogel, enabling it to effectively eliminate MRSA and accelerate the healing of antibiotic-resistant bacterial-infected wounds in a remarkably short period (10 days). This modification not only facilitates wound closure and fur generation, but also mitigates systemic inflammation, thereby effectively impeding the spread of MRSA to the lungs. Taken together, Fe-ALG hydrogel is a promising therapeutic material for treating wound infections by Staphylococcus aureus, especially by antibiotic-resistant strains like MRSA.

Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype-Phenotype Correlation.

BACKGROUND: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date. METHODS: We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant. RESULTS: All three males have a de novo mutation, infantile spasms, DEE, drug-resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13. CONCLUSION: The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype-phenotype correlation.

The circular RNA circ_0001742 regulates colorectal carcinoma proliferation and migration via the MicroRNA-431-5p/ALG8 axis.

Background: Accumulating studies have found that circular RNAs (circRNAs) have a regulatory effect in a variety of tumors. However, to date, the relationship between specific circRNAs and colorectal cancer (CRC) remains elusive. Methods: An RNA-sequencing method based on different metastatic potential of CRC cell lines was applied to evaluate the circRNA expression profile. Additionally, we conducted a series of experiments to assess the relationship between circRNAs and CRC progression. Results: Circ_0001742 was upregulated in CRC cells with high metastatic potential, and circ_0001742 overexpression was observed to facilitate proliferation, migration and metastasis while knockdown will inhibit. More importantly, we found that circ_0001742 acted as a sponge for miR-431-5p, thus affecting ALG8 levels and the development of CRC. Conclusions: This study demonstrated an essential function for the circ_0001742/miR-431-5p/ALG8 axis in CRC development, and it may be a promising therapeutic target for CRC.

ALG3 predicts poor prognosis and increases resistance to anti-PD-1 therapy through modulating PD-L1 N-link glycosylation in TNBC.

OBJECTIVE: The aim of this study was to assess the prognostic significance of α-1,3-mannitrotransferase (ALG3) in triple-negative breast cancer (TNBC) and investigate its impact and potential mechanism on the efficacy of anti-PD-1 therapy. METHODS: Bioinformatics analysis was used to examine the expression of ALG3 in cancer patients using UACLAN and other databases. The associations of the ALG3 gene and the clinicopathological features of breast cancer were examined with bc-GenExMiner database. Correlation between ALG3 expression and survival was further established utilizing the Kaplan-Meier Plotter database. Immunohistochemistry (IHC) was used to analyze the expression of ALG3 in cohort of breast cancer patients from Hubei cancer hospital to confirmed the prognostic value of ALG3 in TNBC. The effect of ALG3 on the levels of infiltrating immune cells was also analyzed. And the mutation module within cBioPortal was utilized to visualize ALG3 mutations in BRCA. The CRISPR/Cas9 technique was used to establish ALG3 low-expression TNBC cell lines. Influence of ALG3 expression on cancer cell proliferation and chemotherapeutic responsiveness was scrutinized in vitro. Animal models were constructed to evaluate the alteration of tumor sensitivity to anti-PD-1 therapy with decreased ALG3 expression. And flow cytometry and IHC were used to investigate the tumor immune microenvironment. Association of PD-L1 Glycosylation and ALG3 expression were also investigated by western blot. RESULTS: ALG3 expression was elevated in TNBC and was strikingly linked to unfavorable clinical features such as lymphatic node metastasis, high NPI, advanced stage and age, etc. Furthermore, high ALG3 expression was associated with shorter OS in TNBC patients. Mechanistically, ALG3 expression was negatively correlated with the infiltration of CD8+ T cells, CD4+ T cells, and NK cells. ALG3-KO cells had increased sensitivity to chemotherapeutic agents. In animal models, the volume of ALG3-KO tumors was lower than the control group with immunotherapy. ALG3-KO tumors showed an increased proportion of CD8+ T cells, while a decreased proportion of regulatory T cells and M2-type macrophages. The expression level of PD-L1 protein was not affected by ALG3 level, but the glycosylation level was significantly decreased in tumor. Similarly, the glycosylation level of PD-L1 is reduced in ALG3-KO cell in vitro. Additionally, ALG3 knockout lead to reduced tolerance of tumor cells to IFN-γ, thereby enhancing the efficacy of immunotherapy. CONCLUSION: ALG3 is a potential biomarker for poor prognosis of TNBC and may reduce the efficacy of immunotherapy by modulating the tumor microenvironment and glycosylation of PD-L1.

Nutrient removal in floating and vertical flow constructed wetlands using aluminium dross: An innovative approach to mitigate eutrophication.

On global scale, eutrophication is one of the most prevalent environmental threats to water quality, primarily caused by elevated concentration of nutrients in wastewater. This study utilizes aluminum dross (AD), an industrial waste, to create a value-added material by improving its operational feasibility and application for removing phosphate and ammonium from water. The operational challenges of AD such as its powdered nature and effective operation under only extreme pH conditions were addressed by immobilizing in calcium alginate to form calcium alginate aluminium dross (Ca-Alg-Al dross) beads. These Ca-Alg-Al dross beads were further tested for phosphate and ammonium removal from natural wastewater in two different aqueous environment systems: (i) vertical flow constructed wetlands (VF-CWs) followed by Ca-Alg-Al dross beads fixed bed system and (ii) Ca-Alg-Al dross beads mounted floating constructed wetlands (FCW) for remediating polluted lentic ecosystems. Our results show maximum phosphate and ammonium removal of 85 ± 0.41 % and 93.44 %, respectively, in VF-CWs followed by Ca-Alg-Al dross beads fixed bed system. The Ca-Alg-Al dross beads mounted FCW system achieved maximum phosphate removal of 79.18 ± 8.56 % and ammonium removal of 65.45 ± 21.04 %. Furthermore, the treated water from the FCW system was assessed for its potential to inhibit algal growth by artificially inoculating treated water with natural algae to simulate eutrophic conditions. Interestingly, treated water from the FCW system was found capable of arresting the algal growth. Besides, scanning electron microscopy with energy dispersive X-ray (SEM-EDX) and Fourier transform infrared (FTIR) spectroscopy confirmed the functional groups and surface properties and probable participation of multiple mechanisms including ion exchange, electrostatic attraction, and ligand complexation for phosphate and ammonium removal. Overall, these results offer a promising way to utilize AD for high-end applications in wastewater treatment.

Psychiatric assessment and therapy in an adolescent with ALG6-CDG: a six-month follow-up case report.

ALG6-congenital disorder of glycosylation (ALG6-CDG) is a complex of rare inherited disorders caused by mutations in the ALG6 gene, which encodes the α-1,3-glucosyltransferase enzyme required for N-glycosylation. ALG6-CDG affects multiple systems and exhibits clinical heterogeneity. Besides developmental delays and neurological signs and symptoms, behavioral and psychological symptoms are also an important group of clinical features of ALG6-CDG. Here, we present the case of a 17-year-old Chinese girl with ALG6-CDG who first visited the psychiatric department with apathy, language reduction, and substupor symptoms. The psychiatric assessments and treatment processes performed are described and discussed in this report. During diagnostic process, we found a novel mutation, c.849delT, in ALG6 by whole-exome sequencing. The patient's symptoms improved with escitalopram and risperidone treatment. However, above a certain dosage, she was sensitive to extrapyramidal side effects. This study accumulates clinical experience for diagnosing and treating ALG6-CDG and improves our understanding of this rare genetic disorder.

Asymmetric Hydrogel Electrolyte Featuring a Customized Anode and Cathode Interfacial Chemistry for Advanced Zn-I2 Batteries.

An integrated asymmetric hydrogel electrolyte with a tailored composition and chemical structure on the cathode/anode-electrolyte interface is designed to boost the cost-effective, high-energy Zn-I2 battery. Such a configuration concurrently addresses the parasitic reactions on the Zn anode side and the polyiodide shuttle issue afflicting the cathode. Specifically, the Zn2+-cross-linked sodium alginate and carrageenan dual network (Carra-Zn-Alg) is adopted to guide the Zn2+ transport, achieving a dendrite-free morphology on the Zn surface and ensuring long-term stability. For the cathode side, the poly(vinyl alcohol)-strengthened poly(3,4-ethylenedioxythiophene)polystyrenesulfonate hydrogel (PVA-PEDOT) with high conductivity is employed to trap polyiodide and accelerate electron transfer for mitigating the shuttle effect and facilitating I2/I- redox kinetics. Attributing to the asymmetrical architecture with a customized interfacial chemistry, the optimized Zn-I2 cell exhibits a superior Coulombic efficiency of 99.84% with a negligible capacity degradation at 0.1 A g-1 and an enhanced stability of 10 000 cycles at 5 A g-1. The proposed asymmetric hydrogel provides a promising route to simultaneously resolve the distinct challenges encountered by the cathode and anode interfaces in rechargeable batteries.

Structure, ingredient, and function-based biomimetic scaffolds for accelerated healing of tendon-bone interface.

Background: Tendon-bone interface (TBI) repair is slow and challenging owing to its hierarchical structure, gradient composition, and complex function. In this work, enlightened by the natural characteristics of TBI microstructure and the demands of TBI regeneration, a structure, composition, and function-based scaffold was fabricated. Methods: The biomimetic scaffold was designed based on the "tissue-inducing biomaterials" theory: (1) a porous scaffold was created with poly-lactic-co-glycolic-acid, nano-hydroxyapatite and loaded with BMP2-gelatinmp to simulate the bone (BP); (2) a hydrogel was produced from sodium alginate, type I collagen, and loaded with TGF-ß3 to simulate the cartilage (CP); (3) the L-poly-lactic-acid fibers were oriented to simulate the tendon (TP). The morphology of tri-layered constructs, gelation kinetics, degradation rate, release kinetics and mechanical strength of the scaffold were characterized. Then, bone marrow mesenchymal stem cells (MSCs) and tenocytes (TT-D6) were cultured on the scaffold to evaluate its gradient differentiation inductivity. A rat Achilles tendon defect model was established, and BMSCs seeded on scaffolds were implanted into the lesionsite. The tendon-bone lesionsite of calcaneus at 4w and 8w post-operation were obtained for gross observation, radiological evaluation, biomechanical and histological assessment. Results: The hierarchical microstructures not only endowed the scaffold with gradual composition and mechanical properties for matching the regional biophysical characteristics of TBI but also exhibited gradient differentiation inductivity through providing regional microenvironment for cells. Moreover, the scaffold seeded with cells could effectively accelerate healing in rat Achilles tendon defects, attributable to its enhanced differentiation performance. Conclusion: The hierarchical scaffolds simulating the structural, compositional, and cellular heterogeneity of natural TBI tissue performed therapeutic effects on promoting regeneration of TBI and enhancing the healing quality of Achilles tendon. The translational potential of this article: The novel scaffold showed the great efficacy on tendon to bone healing by offering a structural and compositional microenvironment. The results meant that the hierarchical scaffold with BMSCs may have a great potential for clinical application.

A Novel Monoallelic ALG5 Variant Causing Late-Onset ADPKD and Tubulointerstitial Fibrosis.

Introduction: Monoallelic variants in the ALG5 gene encoding asparagine-linked glycosylation protein 5 homolog (ALG5) have been recently shown to disrupt polycystin-1 (PC1) maturation and trafficking via underglycosylation, causing an autosomal dominant polycystic kidney disease-like (ADPKD-like) phenotype and interstitial fibrosis. In this report, we present clinical, genetic, histopathologic, and protein structure and functional correlates of a new ALG5 variant, p.R79W, that we identified in 2 distant genetically related Irish families displaying an atypical late-onset ADPKD phenotype combined with tubulointerstitial damage. Methods: Whole exome and targeted sequencing were used for segregation analysis of available relatives. This was followed by immunohistochemistry examinations of kidney biopsies, and targeted (UMOD, MUC1) and untargeted plasma proteome and N-glycomic studies. Results: We identified a monoallelic ALG5 variant [GRCh37 (NM_013338.5): g.37569565G>A, c.235C>T; p.R79W] that cosegregates in 23 individuals, of whom 18 were clinically affected. We detected abnormal localization of ALG5 in the Golgi apparatus of renal tubular cells in patients' kidney specimens. Further, we detected the pathological accumulation of uromodulin, an N-glycosylated glycosylphosphatidylinositol (GPI)-anchored protein, in the endoplasmic reticulum (ER), but not mucin-1, an O- and N-glycosylated protein. Biochemical investigation revealed decreased plasma and urinary uromodulin levels in clinically affected individuals. Proteomic and glycoproteomic profiling revealed the dysregulation of chronic kidney disease (CKD)-associated proteins. Conclusion: ALG5 dysfunction adversely affects maturation and trafficking of N-glycosylated and GPI anchored protein uromodulin, leading to structural and functional changes in the kidney. Our findings confirm ALG5 as a cause of late-onset ADPKD and provide additional insight into the molecular mechanisms of ADPKD-ALG5.

Synthesis and characterization of a novel TiO2@chitosan/alginate nanocomposite sponge for highly efficient removal of As(V) ions from aqueous solutions: Adsorption isotherm, kinetics, experiment and adsorption mechanism optimization using Box-Behnken design.

This research uses a novel TiO2@CSC.Alg composite sponge was created by encasing TiO2 nanoparticles in the natural polymers alginate and chitosan, resulting in a nanocomposite that is both ecologically friendly and biocompatible. Using the generated nanocomposite as a new environmentally friendly adsorbent, As(V) heavy metal ions were effectively removed from aqueous media. The following techniques were used to analyse the physicochemical properties of the obtained materials: pHZPC, FTIR, XRD, BET, SEM, and XPS. Utilizing nitrogen adsorption/desorption isotherms, the TiO2@CSC.Alg composite sponge's textural properties were identified. This revealed a BET surface area of 168.42 m2/g and a total pore volume of 1.18 cc/g, indicating its porous nature and potential for high adsorption capacity. Examine the effects of temperature, pH, dose, and beginning concentration on adsorption. The adsorption characteristics were determined based on equilibrium and adsorption kinetics measurements. The adsorption process was both pseudo-second-order (PSOE) and Langmuir isothermally fit. Chemisorption was the adsorption method since the adsorption energy was 25.45 kJ·mol-1. An endothermic and spontaneous adsorption process was indicated by more metal being absorbed as the temperature increased. The optimal conditions for adsorption were optimized via Box-Behnken design software to be pH of 5 in the solution, a dosage of 0.02 g of the TiO2@CSC.Alg composite sponge per 25 mL, and an arsenate (As(V)) solution the adsorption capacity was 202.27 mg/g are ideal for efficient adsorption. These parameters are critical in achieving the maximum adsorption capacity of the composite sponge for arsenate, which could be beneficial for water purification applications. Utilizing Design-Expert software's response surface methodology (RSM) and Box-Behnken design (BBD), the adsorption process was optimized with the fewest planned tests. After six successive cycles of adsorption and desorption, the adsorbent stability was confirmed by the adsorbent reusability test without any noticeable decrease in removal efficacy. Additionally, it displayed good efficiency, the same XRD and XPS data before and after reuse, and no change in chemical composition.

ALG5 Regulates STF-62247-Induced Milk Fat Synthesis via the mTOR Signaling Pathway.

Milk fat content is a critical indicator of milk quality. Exploring the key regulatory genes involved in milk fat synthesis is essential for enhancing milk fat content. STF-62247 (STF), a thiazolamide compound, has the potential to bind with ALG5 and upregulate lipid droplets in fat synthesis. However, the effect of STF on the process of milk fat synthesis and whether it acts through ALG5 remains unknown. In this study, the impact of ALG5 on milk fat synthesis and its underlying mechanism were investigated using bovine mammary epithelial cells (BMECs) and mouse models through real-time PCR, western blotting, Oil Red O staining, and triglyceride analysis. Experimental findings revealed a positive correlation between STF and ALG5 with the ability to synthesize milk fat. Silencing ALG5 led to decreased expression of FASN, SREBP1, and PPARγ in BMECs, as well as reduced phosphorylation levels in the PI3K/AKT/mTOR signaling pathway. Moreover, the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway were restored when ALG5 silencing was followed by the addition of STF. These results suggest that STF regulates fatty acid synthesis in BMECs by affecting the PI3K/AKT/mTOR signaling pathway through ALG5. ALG5 is possibly a new factor in milk fat synthesis.

Sodium alginate-encapsulated nano-iron oxide coupled with copper-based MOFs (Cu-BTC@Alg/Fe3O4): Versatile composites for eco-friendly and effective elimination of Rhodamine B dye in wastewater purification.

This study explores the effectiveness of Alginate-coated nano­iron oxide combined with copper-based MOFs (Cu-BTC@Alg/Fe3O4) composites for the sustainable and efficient removal of Rhodamine B (RhB) dye from wastewater through adsorption and photocatalysis. Utilizing various characterization techniques such as FTIR, XRD, SEM, and TEM, we confirmed the optimal synthesis of this composite. The composites exhibit a significant surface area of approximately 160 m2 g-1, as revealed by BET analysis, resulting in an impressive adsorption capacity of 200 mg g-1 and a removal efficiency of 97 %. Moreover, their photocatalytic activity is highly effective, producing environmentally friendly degradation byproducts, thus underlining the sustainability of Cu-BTC@Alg/Fe3O4 composites in dye removal applications. Our investigation delves into kinetics and thermodynamics, revealing a complex adsorption mechanism influenced by both chemisorption and physisorption. Notably, the adsorption kinetics indicate equilibrium attainment within 100 min across all initial concentrations, with the pseudo-second-order kinetic model fitting the data best (R2 ≈ 0.999). Furthermore, adsorption isotherm models, including Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich, elucidate the adsorption behavior, with the Temkin and Dubinin-Radushkevich models showing superior accuracy compared to the Langmuir model (R2 ≈ 0.98 and R2 ≈ 0.96, respectively). Additionally, thermodynamic analysis reveals a negative Gibbs free energy value (-6.40 kJ mol-1), indicating the spontaneity of the adsorption process, along with positive enthalpy (+24.3 kJ mol-1) and entropy (+82.06 kJ mol-1 K) values, suggesting an endothermic and disorderly process at the interface. Our comprehensive investigation provides insights into the optimal conditions for RhB adsorption onto Cu-BTC@Alg/Fe3O4 composites, highlighting their potential in wastewater treatment applications.

ALG13-Congenital Disorder of Glycosylation (ALG13-CDG): Updated clinical and molecular review and clinical management guidelines.

ALG13-Congenital Disorder of Glycosylation (CDG), is a rare X-linked CDG caused by pathogenic variants in ALG13 (OMIM 300776) that affects the N-linked glycosylation pathway. Affected individuals present with a predominantly neurological manifestation during infancy. Epileptic spasms are a common presenting symptom of ALG13-CDG. Other common phenotypes include developmental delay, seizures, intellectual disability, microcephaly, and hypotonia. Current management of ALG13-CDG is targeted to address patients' symptoms. To date, less than 100 individuals have been reported with ALG13-CDG. In this article, an international group of experts in CDG reviewed all reported individuals affected with ALG13-CDG and suggested diagnostic and management guidelines for ALG13-CDG. The guidelines are based on the best available data and expert opinion. Neurological symptoms dominate the phenotype of ALG13-CDG where epileptic spasm is confirmed to be the most common presenting symptom of ALG13-CDG in association with hypotonia and developmental delay. We propose that ACTH/prednisolone treatment should be trialed first, followed by vigabatrin, however ketogenic diet has been shown to have promising results in ALG13-CDG. In order to optimize medical management, we also suggest early cardiac, gastrointestinal, skeletal, and behavioral assessments in affected patients.

Deep pan-cancer analysis and multi-omics evidence reveal that ALG3 inhibits CD8+ T cell infiltration by suppressing chemokine secretion and is associated with 5-fluorouracil sensitivity.

BACKGROUND: α-1,3-mannosyltransferase (ALG3) holds significance as a key member within the mannosyltransferase family. Nevertheless, the exact function of ALG3 in cancer remains ambiguous. Consequently, the current research aimed to examine the function and potential mechanisms of ALG3 in various types of cancer. METHODS: Deep pan-cancer analyses were conducted to investigate the expression patterns, prognostic value, genetic variations, single-cell omics, immunology, and drug responses associated with ALG3. Subsequently, in vitro experiments were executed to ascertain the biological role of ALG3 in breast cancer. Moreover, the link between ALG3 and CD8+ T cells was verified using immunofluorescence. Lastly, the association between ALG3 and chemokines was assessed using qRT-PCR and ELISA. RESULTS: Deep pan-cancer analysis demonstrated a heightened expression of ALG3 in the majority of tumors based on multi-omics evidence. ALG3 emerges as a diagnostic and prognostic biomarker across diverse cancer types. In addition, ALG3 participates in regulating the tumor immune microenvironment. Elevated levels of ALG3 were closely linked to the infiltration of bone marrow-derived suppressor cells (MDSC) and CD8+ T cells. According to in vitro experiments, ALG3 promotes proliferation and migration of breast cancer cells. Moreover, ALG3 inhibited CD8+ T cell infiltration by suppressing chemokine secretion. Finally, the inhibition of ALG3 enhanced the responsiveness of breast cancer cells to 5-fluorouracil treatment. CONCLUSION: ALG3 shows potential as both a prognostic indicator and immune infiltration biomarker across various types of cancer. Inhibition of ALG3 may represent a promising therapeutic strategy for tumor treatment.

Ca2+-sensor ALG-2 engages ESCRTs to enhance lysosomal membrane resilience to osmotic stress.

Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how cells respond to osmotic stress within lysosomes. Using sensitive assays of lysosomal leakage and rupture, we examine acute effects of the osmotic disruptant glycyl-L-phenylalanine 2-naphthylamide (GPN). Our findings reveal that low concentrations of GPN rupture a small fraction of lysosomes, but surprisingly trigger Ca2+ release from nearly all. Chelating cytoplasmic Ca2+ makes lysosomes more sensitive to GPN-induced rupture, suggesting a role for Ca2+ in lysosomal membrane resilience. GPN-elicited Ca2+ release causes the Ca2+-sensor Apoptosis Linked Gene-2 (ALG-2), along with Endosomal Sorting Complex Required for Transport (ESCRT) proteins it interacts with, to redistribute onto lysosomes. Functionally, ALG-2, but not its ESCRT binding-disabled ΔGF122 splice variant, increases lysosomal resilience to osmotic stress. Importantly, elevating juxta-lysosomal Ca2+ without membrane damage by activating TRPML1 also recruits ALG-2 and ESCRTs, protecting lysosomes from subsequent osmotic rupture. These findings reveal that Ca2+, through ALG-2, helps bring ESCRTs to lysosomes to enhance their resilience and maintain organelle integrity in the face of osmotic stress.

Case report: Novel genotype of ALG2-CDG and confirmation of the heptasaccharide glycan (NeuAc-Gal-GlcNAc-Man2-GlcNAc2) as a specific diagnostic biomarker.

This report outlines the case of a child affected by a type of congenital disorder of glycosylation (CDG) known as ALG2-CDG (OMIM 607906), presenting as a congenital myasthenic syndrome (CMS) caused by variants identified in ALG2, which encodes an α1,3-mannosyltransferase (EC 2.4.1.132) involved in the early steps of N-glycosylation. To date, fourteen cases of ALG2-CDG have been documented worldwide. From birth, the child experienced perinatal asphyxia, muscular weakness, feeding difficulties linked to an absence of the sucking reflex, congenital hip dislocation, and hypotonia. Over time, additional complications emerged, such as inspiratory stridor, gastroesophageal reflux, low intake, recurrent seizures, respiratory infections, an inability to maintain the head upright, and a global developmental delay. Whole genome sequencing (WGS) revealed the presence of two ALG2 variants in compound heterozygosity: a novel variant c.1055_1056delinsTGA p.(Ser352Leufs*3) and a variant of uncertain significance (VUS) c.964C>A p.(Pro322Thr). Additional studies, including determination of carbohydrate-deficient transferrin (CDT) revealed a mild type I CDG pattern and the presence of an abnormal transferrin glycoform containing a linear heptasaccharide consisting of one sialic acid, one galactose, one N-acetyl-glucosamine, two mannoses and two N-acetylglucosamines (NeuAc-Gal-GlcNAc-Man2-GlcNAc2), ALG2-CDG diagnostic biomarker, confirming the pathogenicity of these variants.

Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.

Congenital disorders of glycosylation (CDG) are a group of rare autosomal recessive genetic disorders caused by pathogenic variants in genes coding for N-glycosylated glycoproteins, which play a role in folding, degrading, and transport of glycoproteins in their pathway. ALG12-CDG specifically is caused by biallelic pathogenic variants in ALG12. Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities. In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder. We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing.