Global birth prevalence of Pompe disease: A systematic review and meta-analysis.

BACKGROUND: Pompe disease, also known as Glycogen storage disease type II, is an autosomal recessive disorder caused by defects in alpha-glucosidase, resulting in abnormal glycogen accumulation. METHODS: To conduct a systematic review and meta-analysis of birth prevalence of Pompe disease, the MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of Pompe disease from inception until July 01, 2024. Meta-analysis was performed to estimate global birth prevalence of Pompe disease. The funnel plot was used to describe potential publication bias. RESULTS: Twenty-two studies, screened out of 945 records, were included for data extraction. Studies that fulfilled inclusion criteria involved 15 areas/countries. Global birth prevalence of Pompe disease was 2.0 cases (95% CI: 1.5-2.4) per 100,000 live births. Global birth prevalence of infantile-onset Pompe disease was 1.0 cases (95% CI: 0.5-1.5) per 100,000 live births. Global birth prevalence of late-onset Pompe disease was 2.4 cases (95% CI: 1.8-3.0) per 100,000 live births. The main limitations are that no study was assessed as high-quality and approximately half of the studies were from Europe. CONCLUSIONS: Quantitative data on the global epidemiology of Pompe disease could be the fundamental to evaluate the global efforts on building a better world for Pompe disease patients.

Targeted Therapy of Osteoarthritis via Intra-Articular Delivery of Lipid-Nanoparticle-Encapsulated Recombinant Human FGF18 mRNA.

Fibroblast growth factor 18 (FGF18) emerges as a promising therapeutic target for osteoarthritis (OA). In this study, a novel articular cavity-localized lipid nanoparticle (LNP) named WG-PL14 is developed. This optimized formulation has a nearly 30-fold increase in mRNA expression as well as better articular cavity enrichment compared to commercial lipids MC3 when performing intra-articular injection. Then, a mRNA sequence encoding recombinant human FGF18 (rhFGF18) for potential mRNA therapy in OA is optimized. In vitro assays confirm the translation of rhFGF18 mRNA into functional proteins within rat and human chondrocytes, promoting cell proliferation and extracellular matrix (ECM) synthesis. Subsequently, the therapeutic efficacy of the LNP-rhFGF18 mRNA complex is systematically assessed in a mouse OA model. The administration exhibits several positive outcomes, including an improved pain response, upregulation of ECM-related genes (e.g., AGRN and HAS2), and remodeling of subchondral bone homeostasis compared to a control group. Taken together, these findings underscore the potential of localized LNP-rhFGF18 mRNA therapy in promoting the regeneration of cartilage tissue and mitigating the progression of OA.

Solvation Regulation Reinforces Anion-Derived Inorganic-Rich Interphase for High-Performance Quasi-Solid-State Li Metal Batteries.

Solid-state polymer lithium metal batteries are an important strategy for achieving high safety and high energy density. However, the issue of Li dendrites and inherent inferior interface greatly restricts practical application. Herein, this study introduces tris(2,2,2-trifluoroethyl)phosphate solvent with moderate solvation ability, which can not only complex with Li+ to promote the in-situ ring-opening polymerization of 1,3-dioxolane (DOL), but also build solvated structure models to explore the effect of different solvation structures in the polymer electrolyte. Thereinto, it is dominated by the contact ion pair solvated structure with pDOL chain segments forming less lithium bonds, exhibiting faster kinetic process and constructing a robust anion-derived inorganic-rich interphase, which significantly improves the utilization rate of active Li and the high-voltage resistance of pDOL. As a result, it exhibits stable cycling at ultra-high areal capacity of 20 mAh cm-2 in half cells, and an ultra-long lifetime of over 2000 h in symmetric cells can be realized. Furthermore, matched with LiNi0.9Co0.05Mn0.05O2 cathode, the capacity retention after 60 cycles is as high as 96.8% at N/P value of 3.33. Remarkably, 0.7 Ah Li||LiNi0.9Co0.05Mn0.05O2 pouch cell with an energy density of 461 Wh kg-1 can be stably cycled for five cycles at 100% depth of discharge.

Floristic changes and environmental drivers of soil fungi and archaea in different salt-tolerant plant communities in the intertidal habitat of coastal wetlands.

Microorganisms are crucial elements of terrestrial ecosystems, which play significant roles in improving soil physicochemical properties, providing plant growth nutrients, degrading toxic and harmful chemicals, and biogeochemical cycling. Variations in the types and quantities of root exudates among different plants greatly alter soil physicochemical properties and result in variations in the diversity, structure, and function of soil microorganisms. Not much is understood about the differences of soil fungi and archaea communities for different plant communities in coastal wetlands, and their response mechanisms to environmental changes. In this study, fungal and archaea communities in soils of Suaeda salsa, Phragmites australis, and Spartina alterniflora in the intertidal habitat of coastal wetlands were selected for research. Soil fungi and archaea were analyzed for diversity, community structure, and function using high throughput ITS and 16S rRNA gene sequencing. The study revealed significant differences in fungi and archaea's diversity and community structure in the rhizosphere soil of three plant communities. At the same time, there is no significant difference in the functional groups. SOM, TP, AP, MC, EC and SOM, TN, TP, AP, MC, EC are the primary environmental determinants affecting changes in soil fungal and archaeal communities, respectively. Variations in the diversity, community structure, and ecological functions of fungi and archaea can be used as indicators characterizing the impact of external disturbances on the soil environment, providing a theoretical foundation for the effective utilization of soil microbial resources, thereby achieving the goal of environmental protection and health promotion.

Clinical characteristics of BRAT1-related disease: a systematic literature review.

BACKGROUND: BRAT1 (BRCA1-associated ataxia telangiectasia mutated activator 1) is involved in many important biological processes, including DNA damage response and maintenance of mitochondrial homeostasis. Dysfunctional BRAT1 causes variable clinical phenotypes, which hinders BRAT1-related disease from recognition and diagnosis. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was the guideline for this systematic review. MEDLINE was searched by terms ("BAAT1" and "BRAT1") from inception until June 21, 2022. RESULTS: Twenty-eight studies, screened out of 49 records, were included for data extraction. The data from fifty patients with mutated BRAT1 were collected. There are 3 high relevant phenotypes, 4 medium relevant phenotypes and 3 low relevant phenotypes. Eye-related abnormal features were most frequently reported: 27 abnormal features were observed. Thirty-nine kinds of pathogenic nucleotide change in BRAT1 were reported. Top three common mutations of BRAT1 were c.638_639insA (16 cases), c.1395G > A (5 cases) and c.294dupA (4 cases). Homozygous mutations in BRAT1 presented a more severe phenotype than those who are compound heterozygotes. CONCLUSIONS: This is the first comprehensive systematic review to present quantitative data about clinical characteristics of BRAT1-related disease, which helps doctors to recognize and diagnose it easier.

Role of mitochondria in neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic encephalopathy, an important cause of death as well as long-term disability in survivors, is caused by oxygen and glucose deprivation, and limited blood flow. Following hypoxic-ischemic injury in the neonatal brain, three main biochemical damages (excitotoxicity, oxidative stress, and exacerbated inflammation) are triggered. Mitochondria are involved in all three cascades. Mitochondria are the nexus of metabolic pathways to offer most of the energy that our body needs. Hypoxic-ischemic injury affects the characteristics of mitochondria, including dynamics, permeability, and ATP production, which also feed back into the process of neonatal hypoxic-ischemic encephalopathy. Mitochondria can be a cellular hub in inflammation, which is another main response of the injured neonatal brain. Some treatments for neonatal hypoxic-ischemic encephalopathy affect the function of mitochondria or target mitochondria, including therapeutic hypothermia and erythropoietin. This review presents the main roles of mitochondria in neonatal hypoxic-ischemic encephalopathy and discusses some potential treatments directed at mitochondria, which may foster the development of new therapeutic strategies for this encephalopathy.

4-octyl itaconate ameliorates ventilator-induced lung injury.

Ventilator-induced lung injury (VILI) disturbs the disordered immune system and causes persistent inflammatory damage. 4-octyl itaconate (OI) is a synthetic cell-permeable itaconate derivative with antioxidant and anti-inflammatory effects. In this study, we assessed whether OI protects against VILI. OI was intraperitoneally injected for three days before mechanical ventilation (MV; 20 ml/kg at 70 breaths/min) for 2 h. Mouse lung vascular endothelial cells (MLVECs) were pretreated with OI (62.5, 125, and 250 µM) prior to cyclic stretch for 4 h. We found that OI attenuated VILI and inflammatory response. OI also increased superoxide dismutase, nuclear factor E2-related factor 2, and heme oxygenase-1 levels, and decreased reactive oxygen species and malondialdehyde levels. Furthermore, OI inhibited the expression of NLR family pyrin domain-containing 3 (NLRP3), caspase-1 p20, apoptosis-associated speck-like protein containing a CARD, and N-terminal fragment of gasdermin D. Therefore, OI attenuates VILI, potentially by suppressing oxidative stress and NLRP3 activation.

Fabrication of ACP-CCS-PVA composite membrane for a potential application in guided bone regeneration.

The barrier membranes of guided bone regeneration (GBR) have been widely used in clinical medicine to repair bone defects. However, the unmatched mechanical strength, unsuitable degradation rates, and insufficient regeneration potential limit the application of the current barrier membranes. Here, amorphous calcium phosphate-carboxylated chitosan-polyvinyl alcohol (ACP-CCS-PVA) composite membranes are fabricated by freeze-thaw cycles, in which the ATP-stabilized ACP nanoparticles are uniformly distributed throughout the membranes. The mechanical performance and osteogenic properties are significantly improved by the ACP incorporated into the CCS-PVA system, but excess ACP would suppress cell proliferation and osteogenic differentiation. Our work highlights the pivotal role of ACP in GBR and provides insight into the need for biomaterial fabrication to balance mechanical strength and mineral content.

Investigation on Wire Electrochemical Discharge Micro-Machining.

With the development of MEMS, the machining demand and requirements for difficult-to-machine metal micro parts are getting higher. Microelectric discharge machining is an effective method to process difficult-to-machine metals. However, the recast layer caused by high temperatures in microelectric discharge machining affects the properties of machined materials. Here, we propose the wire electrochemical discharge micro-machining (WECDMM) and develop a new electrolyte system, which removes the recast layer. In this study, the mechanism of WECDMM was elucidated. The electrolyte was optimized through a comparison experiment, and NaNO3-glycol solution was determined as the best electrolyte. The influences of key process parameters including the conductivity of the electrolyte, pulse voltage, pulse-on time and wire feed rate were analyzed on the slit width, standard deviation, the radius of fillet at the entrance of the slit and roughness. Typical microstructures were machined, which verified the machining ability of WECDMM.

Immunity and Immune Evasion Mechanisms of Epstein-Barr Virus.

Epstein-Barr virus (EBV) is the first human oncogenic virus to be identified, which evades the body's immune surveillance through multiple mechanisms that allow long-term latent infection. Under certain pathological conditions, EBVs undergo a transition from the latent phase to the lytic phase and cause targeted dysregulation of the host immune system, leading to the development of EBV-related diseases. Therefore, an in-depth understanding of the mechanism of developing an immune response to EBV and the evasion of immune recognition by EBV is important for the understanding of the pathogenesis of EBV, which is of great significance for finding strategies to prevent EBV infection, and developing a therapy to treat EBV-associated diseases. In this review, we will discuss the molecular mechanisms of host immunological responses to EBV infection and the mechanisms of EBV-mediated immune evasion during chronic active infection.

Performance of wetland applied to ecological remediation of abandoned fish ponds: A case study in Gonghu Bay, Tai lake.

To restore the abandoned fish ponds to "near natural" state, the wetland restoration was carried out in Gonghu Bay lakeside, and its long-term performance of controlling external load was studied for 5 years. The findings showed that water quality and biodiversity had been improved dramatically after the preliminary transformation. The concentrations of permanganate index (CODMn), total nitrogen (TN), and total phosphorus (TP) obviously decreased from 12.91 mg L-1 to 4.32 mg L-1, from 3.46 mg L-1 to 1.42 mg L-1, and from 0.27 mg L-1 to 0.04 mg L-1, respectively. The proportion of Cyanophyta was effectively reduced from 31.82% to 18.89%, and favored the growth of diatoms (31.82%-37.78%) to be the dominant algae species. Aquatic plant species and coverage gradually increased from 16 to 56 and from 5% to 60%, respectively. An in-deep monitoring done for 5 years (2013-2017) showed that the wetland achieved a satisfactory removal efficiency of 58.95% for TN, 64.60% for TP, and up to 77.83% for chlorophyll-a. Besides, three pollution scenarios, such as stormwater runoff, algal bloom, and continuous water transfer, were selected to explore the tolerance of the wetland to the suddenly increased pollution loads. The results dedicated that even if the inlet load was up to 1.0 × 105 m3 d-1, the removal rate coefficients of wetland for chlorophyll-a, TP, and TN were 0.135-0.239 d-1, 0.041-0.112 d-1, and 0.030-0.109 d-1, respectively, which were equivalent to the well-running wetlands. This study confirmed that the wetland was not only a promising ecological remediation technique to contaminated abandoned fish ponds, but also could withstand high pollution load, which had the prospect of sustainable utilization.

Global Epidemiology of Gaucher Disease: an Updated Systematic Review and Meta-analysis.

BACKGROUND: Gaucher disease [GD], an autosomal recessive lysosomal storage disorder, is characterized by progressive lysosomal storage of glucocerebroside in macrophages predominantly in bone, bone marrow, liver, and spleen. Meta-analysis of global GD epidemiology was not available before this study. METHODS: To provide a systematic review and meta-analysis of birth prevalence and prevalence of GD in multiple countries. MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of GD from inception until July 21, 2021. Meta-analysis, adopting a random-effects logistic model, was performed to estimate the birth prevalence and prevalence of GD. RESULTS: Eighteen studies that were screened of 1874 records were included for data extraction. The studies that fulfilled the criteria for inclusion involved 15 areas/countries. The global birth prevalence of GD was 1.5 cases [95% confidence interval: 1.0 to 2.0] per 100,000 live births. The global prevalence of GD was 0.9 cases [95% confidence interval: 0.7 to 1.1] per 100,000 inhabitants. CONCLUSIONS: This is the first comprehensive systematic review that presented quantitative data of GD global epidemiology. Quantitative data on global epidemiology of GD could be the fundamental to evaluate the global efforts on building a better world for GD patients.

Angiorganoid: vitalizing the organoid with blood vessels.

The emergence of the organoid simulates the native organs and this mini organ offers an excellent platform for probing multicellular interaction, disease modeling and drug discovery. Blood vessels constitute the instructive vascular niche which is indispensable for organ development, function and regeneration. Therefore, it is expected that the introduction of infiltrated blood vessels into the organoid might further pump vitality and credibility into the system. While the field is emerging and growing with new concepts and methodologies, this review aims at presenting various sources of vascular ingredients for constructing vascularized organoids and the paired methodology including de- and recellularization, bioprinting and microfluidics. Representative vascular organoids corresponding to specific tissues are also summarized and discussed to elaborate on the next generation of organoid development.

Silencing of immunoglobulin superfamily containing leucine-rich repeat inhibits gastric cancer cell growth and metastasis by regulating epithelial-mesenchymal transition.

This study aims to investigate the immunoglobulin superfamily containing leucine-rich repeat (ISLR) expression in gastric cancer (GC) and ISLR's underlying mechanisms regulation of GC progression. Through The Cancer Genome Atlas (TCGA) cohort datasets, we analyzed the ISLR expression in GC tumor tissues and normal tissues. ISLR expression in GC tissues and cells was determined using quantitative real-time polymerase chain reaction. Cell viability, proliferation, migration, and invasion assays were performed in GC cells transfected with sh-ISLR, ISLR plasmids, or controls. TCGA results showed that ISLR expression was higher in GC tumor tissues compared to normal tissues, and its expression levels were related to lymph node metastasis, tumor size, and clinical stage. ISLR was highly expressed in tumor cells. ISLR knockdown suppressed cell viability, proliferation, migration, and invasion in HGC-27 cells, whereas ISLR overexpression led to opposite effects in AGS cells. Gene Set Enrichment Analysis showed that ISLR could activate the epithelial-mesenchymal transition (EMT) signaling pathway. Silencing of ISLR suppressed EMT in HGC-27 cells and overexpression of ISLR promoted EMT in AGS cells. ISLR was overexpressed in both GC cell lines and tumor tissues, and our study first showed that silencing of ISLR inhibited GC cell growth and metastasis by reversing EMT.

Update of treatment for Gaucher disease.

Gaucher disease (GD), the most common lysosomal disorders, is a rare autosomal recessive hereditary disease that is caused by deficiency of glucosylceramidase. For now, there are five approved therapies for GD, which are used to treat thousands of patients with GD. Despite success of approved therapies, many unresolved issues attract academic institutions and industry to develop potential therapies to resolve them. This paper updated the latest information about approved therapies and potential curative therapies.

Tannic acid induces dentin biomineralization by crosslinking and surface modification.

It is currently known that crosslinking agents can effectively improve the mechanical properties of dentin by crosslinking type I collagen. However, few scholars have focused on the influence of crosslinking agents on the collagen-mineral interface after crosslinking. Analysis of the Fourier transform infrared spectroscopy (FTIR) results showed that hydrogen bonding occurs between the tannic acid (TA) molecule and the collagen. The crosslinking degree of TA to collagen reached a maximum 41.28 ± 1.52. This study used TA crosslinked collagen fibers to successfully induce dentin biomineralization, and the complete remineralization was achieved within 4 days. The crosslinking effect of TA can improve the mechanical properties and anti-enzyme properties of dentin. The elastic modulus (mean and standard deviation) and hardness values of the remineralized dentin pretreated with TA reached 19.1 ± 1.12 GPa and 0.68 ± 0.06 GPa, respectively, which were close to those of healthy dentin measurements, but significantly higher than those of dentin without crosslinking (8.91 ± 1.82 GPa and 0.16 ± 0.01 GPa). The interface energy between the surface of collagen fibers and minerals decreased from 10.59 mJ m-2 to 4.19 mJ m-2 with the influence of TA. The current work reveals the importance of tannic acid crosslinking for dentin remineralization while providing profound insights into the interfacial control of biomolecules in collagen mineralization.

The Incidence and Characteristics of Perinatal Stroke in Beijing: A Multicenter Study.

Objective: To assess the incidence, risk factors, and clinical characteristics of perinatal stroke in Beijing. Methods: This multicenter prospective study included all the live births from 17 representative maternal delivery hospitals in Beijing from March 1, 2019 to February 29, 2020. Neonates with a stroke were assigned to the study group. Clinical data, including general information, clinical manifestations, and risk factors, were collected. Up until 18 months after birth, neonates were routinely assessed according to the Ages and Stages Questionnaire (ASQ) and/or the Bayley scale. Statistical analysis was done using the chi-squared, t-tests, and logistic regression analysis using SPSS version 26.0. Outcomes: In total, 27 cases were identified and the incidence of perinatal stroke in Beijing was 1/2,660 live births, including 1/5,985 for ischemic stroke and 1/4,788 for hemorrhagic stroke. Seventeen cases (62.96%) of acute symptomatic stroke and convulsions within 72 h (10 cases, 37.04%) were the most common presentations. Ten patients showed no neurological symptoms and were found to have had a stroke through routine cranial ultrasonography after being hospitalized for non-neurological diseases. The risk factors include primiparity, placental or uterine abruption/acute chorioamnionitis, intrauterine distress, asphyxia, and severe infection. In the study group, 11.1% (3/27) of patients had adverse neurodevelopmental outcomes. The patients in the study group had lower scores for the ASQ than those in the control group in the communication, gross, and fine motor dimensions. Conclusion: The incidence of perinatal stroke in Beijing was consistent with that in other countries. Routine neuroimaging of infants with risk factors may enable identification of asymptomatic strokes in more patients. Patients who have suffered from a stroke may have neurological sequelae; therefore, early detection, treatment, and regular follow-ups are beneficial for improving their recovery outcomes.

Molecular environment and atypical function: What do we know about enzymes associated with Mucopolysaccharidoses?

Mucopolysaccharidoses are a group of lysosomal storage disorders caused by deficiency of enzymes involved in glycosaminoglycans degradation. Relationship between mucopolysaccharidoses and related enzymes has been clarified clearly. Based on such relationship, lots of therapies have been commercialized or are in the process of research and development. However, many potential treatments failed, because those treatments did not demonstrate expected efficacy or safety data. Molecular environment of enzyme, which is essential for their expression and activity, is fundamental for efficacy of therapy. In addition to enzyme activities, mucopolysaccharidoses-related enzymes have other atypical functions, such as regulation, which may cause side effects. This review tried to discuss molecular environment and atypical function of enzymes that are associated with mucopolysaccharidoses, which is very important for the efficacy and safety of potential therapies.

Glaucoma in mucopolysaccharidoses.

Mucopolysaccharidoses are a group of lysosomal storage disorders that are caused by deficiency of enzymes involved in glycosaminoglycans degradation. Due to low prevalence and high childhood mortality, researches on mucopolysaccharidoses were mainly focused on the fatal manifestations. With the development of treatments, more and more mucopolysaccharidoses patients were treated by approved therapies, thereby getting prolonged life span and improved quality of life. Abnormal accumulation of glycosaminoglycans in the eye may block trabecular meshwork, thicken sclera and change mechanical behavior of lamina cribrosa, which, by increasing intraocular pressure and damaging optic nerve, could cause glaucoma. Glaucoma was the leading cause of irreversible blindness worldwide, but it was rarely reported in mucopolysaccharidoses patients. Although non-fatal, it seriously affected quality of life. Prevalence of glaucoma in mucopolysaccharidoses patients (ranged from 2.1 to 12.5%) indicated that glaucoma in patients with mucopolysaccharidoses was worthy of attention and further study, thereby improving the quality of life for MPSs patients.

Global epidemiology of mucopolysaccharidosis type III (Sanfilippo syndrome): an updated systematic review and meta-analysis.

OBJECTIVES: Mucopolysaccharidosis III, an autosomal recessive lysosomal storage disorder, is characterized by progressive mental retardation and behavioral problems. Meta-analysis of global mucopolysaccharidosis III epidemiology, which serves as a fundamental reference for public health decision-making, was not available prior to this study. To provide a systematic review and meta-analysis of birth prevalence of mucopolysaccharidosis III in multiple countries. METHODS: MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of mucopolysaccharidosis III from inception until 1st July, 2020. A checklist adapted from STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) was used to assess the quality of all studies involved. Meta-analysis, adopting a random effects logistic model, was performed to estimate pooled birth prevalence of mucopolysaccharidosis III and its subtypes. RESULTS: Twenty-five studies screened out of 1,826 records were included for data extraction. The pooled global mucopolysaccharidosis III birth prevalence was 0.76 cases (95% CI: 0.57-0.96) per 100,000 live births. The pooled global birth prevalence of mucopolysaccharidosis III subtypes (A, B, and C) was 0.52 cases (95% CI: 0.33-0.72), 0.21 cases (95% CI: 0.12-0.30) and 0.01 cases (95% CI: 0.005-0.02) per 100,000 live births, respectively. CONCLUSIONS: Based on the global population size (7.8 billion) and the life span of patients, there would be 12-19 thousand mucopolysaccharidosis III patients worldwide. To our knowledge, this is the first comprehensive systematic review that presented quantitative data fundamental for evidence-based public health decision-making by evaluating global epidemiology of mucopolysaccharidosis III.