Image_1_Case Report: Identification of Compound Heterozygous Mutations in a Patient With Late-Onset Glycogen Storage Disease Type II (Pompe Disease).TIF

Pompe disease is an autosomal recessive hereditary lysosomal disorder and correlated with acid α-glucosidase enzyme (GAA) deficiencies, which lead to accumulation of glycogen in all tissues, most notably in skeletal muscles. Adult late-onset Pompe disease (LOPD) is a slowly progressive disease of proximal myopathy with later involvement of the respiratory muscles, resulting in respiratory failure. In this study, we reported a 22-year-old Chinese woman with inability to withstand heavy physical activity since childhood, who presented with respiratory and ambulation weakness in 2 months. On admission, her bilateral upper limbs strength was 4/5 and lower limbs strength was 3/5 according to Medical Research Council (MRC) score. The patient had compound heterozygotes containing a newly identified 4 nt deletion of coding sequence (deletion nt 1411_1414) in one of the acid α-glucosidase alleles and a c.2238G>C (p.Trp746Cys) missense mutation. This deletion has been reported in infant-onset Pompe disease (IOPD) but not LOPD. Intriguingly, this deletion mutation was not found in the patient's family and was considered as pathogenic. Muscle biopsy showed scattered vacuoles with basophilic granules inside the subsarcolemmal area, which were strongly stained by periodic acid-Schiff (PAS). Laboratory tests revealed a significant increase of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). GAA level was 9.77 nmol/1 h/mg and was not sufficient for the diagnosis of GAA activity deficiency (0–3.78 nmol/1 h/mg). In summary, mutational analysis of GAA and muscle biopsy are crucial in the diagnosis of Pompe disease.</p

Image_3_Case Report: Identification of Compound Heterozygous Mutations in a Patient With Late-Onset Glycogen Storage Disease Type II (Pompe Disease).TIF

Pompe disease is an autosomal recessive hereditary lysosomal disorder and correlated with acid α-glucosidase enzyme (GAA) deficiencies, which lead to accumulation of glycogen in all tissues, most notably in skeletal muscles. Adult late-onset Pompe disease (LOPD) is a slowly progressive disease of proximal myopathy with later involvement of the respiratory muscles, resulting in respiratory failure. In this study, we reported a 22-year-old Chinese woman with inability to withstand heavy physical activity since childhood, who presented with respiratory and ambulation weakness in 2 months. On admission, her bilateral upper limbs strength was 4/5 and lower limbs strength was 3/5 according to Medical Research Council (MRC) score. The patient had compound heterozygotes containing a newly identified 4 nt deletion of coding sequence (deletion nt 1411_1414) in one of the acid α-glucosidase alleles and a c.2238G>C (p.Trp746Cys) missense mutation. This deletion has been reported in infant-onset Pompe disease (IOPD) but not LOPD. Intriguingly, this deletion mutation was not found in the patient's family and was considered as pathogenic. Muscle biopsy showed scattered vacuoles with basophilic granules inside the subsarcolemmal area, which were strongly stained by periodic acid-Schiff (PAS). Laboratory tests revealed a significant increase of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). GAA level was 9.77 nmol/1 h/mg and was not sufficient for the diagnosis of GAA activity deficiency (0–3.78 nmol/1 h/mg). In summary, mutational analysis of GAA and muscle biopsy are crucial in the diagnosis of Pompe disease.</p

Image_2_Case Report: Identification of Compound Heterozygous Mutations in a Patient With Late-Onset Glycogen Storage Disease Type II (Pompe Disease).TIF

Pompe disease is an autosomal recessive hereditary lysosomal disorder and correlated with acid α-glucosidase enzyme (GAA) deficiencies, which lead to accumulation of glycogen in all tissues, most notably in skeletal muscles. Adult late-onset Pompe disease (LOPD) is a slowly progressive disease of proximal myopathy with later involvement of the respiratory muscles, resulting in respiratory failure. In this study, we reported a 22-year-old Chinese woman with inability to withstand heavy physical activity since childhood, who presented with respiratory and ambulation weakness in 2 months. On admission, her bilateral upper limbs strength was 4/5 and lower limbs strength was 3/5 according to Medical Research Council (MRC) score. The patient had compound heterozygotes containing a newly identified 4 nt deletion of coding sequence (deletion nt 1411_1414) in one of the acid α-glucosidase alleles and a c.2238G>C (p.Trp746Cys) missense mutation. This deletion has been reported in infant-onset Pompe disease (IOPD) but not LOPD. Intriguingly, this deletion mutation was not found in the patient's family and was considered as pathogenic. Muscle biopsy showed scattered vacuoles with basophilic granules inside the subsarcolemmal area, which were strongly stained by periodic acid-Schiff (PAS). Laboratory tests revealed a significant increase of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). GAA level was 9.77 nmol/1 h/mg and was not sufficient for the diagnosis of GAA activity deficiency (0–3.78 nmol/1 h/mg). In summary, mutational analysis of GAA and muscle biopsy are crucial in the diagnosis of Pompe disease.</p

Table_1_Investigation of Anxiety, Depression, Sleep, and Family Function in Caregivers of Children With Epilepsy.docx

Objective: Epilepsy is a chronic disease that places a heavy burden on caregivers. Previous studies have shown that caregivers of epilepsy patients often experience anxiety and depression; however, few comprehensive studies have assessed their sleep quality and family function. Based on the current understanding of the anxiety and depression state of caregivers in children with epilepsy, we further explored the caregivers' sleep and family function and evaluated the predictors of the depression state of caregivers.Methods: In this cross-sectional online anonymous survey, we sent an online questionnaire to the caregivers of children with epilepsy who visited our hospital. The QR code of the questionnaire was scanned at the follow-up course to conduct an online survey. The questionnaire contained questions about sociodemographic and clinical information, the Self-rating Anxiety Scale, Self-rating Depression Scale, Pittsburgh Sleep Quality Index, and the Family Assessment Device.Results: A total of 308 caregivers of children with epilepsy aged 0–12 years were included in this study. The mean age of children with epilepsy was 4.8 ± 3.18 years, and the average illness duration was 34.2 ± 29.18 months. Further, 47.1% of the children took three or more anti-seizure medications, and 43.2% were on ketogenic diet therapy. We found that in 77.9% of the cases, the subjects were the mothers, in 89% there was more than one co-caregiver, and in 51.9%, financial help was required. Further, 63.6% of the caregivers thought they could not get enough access to disease knowledge education, and 83.7% perceived epilepsy was a terrible disease. Our results also showed that 65.6% of the caregivers were in depression status, 41.9% were in anxiety status, and 49.0% had poor sleep quality. The proportion of unhealthy family functioning in each subscale was 45.1–96.1%, and the unhealthy behavior control function accounted for 96.1%. Binary logistic regression analysis of the data showed that without co-caregivers [odds ratio (OR), 5.193], free of anxiety status (OR, 0.063), good sleep quality (OR, 0.446), healthy family role dimension (OR, 0.344), and healthy family general functional dimension (OR, 0.259) were predictors of depression status in caregivers of children with epilepsy.Conclusion: Anxiety and depression status are common in caregivers of children with epilepsy, with depression status being more prominent. Moreover, a considerable proportion of caregivers had poor sleep quality and unhealthy family function. The caregivers' anxiety status, sleep quality, family role dimension, family general function dimension, and the number of co-caregivers were predictors of depression status in caregivers. In clinical practice, caregivers' anxiety and depression status, poor sleep quality, and unhealthy family functioning should be addressed along with the treatment of children with epilepsy.</p

Engineering Nanoparticle Antitoxins Utilizing Aromatic Interactions

Methicillin resistant Staphylococcus aureus (MRSA) is a highly virulent bacterium capable of inflicting severe infections. This pathogen has a long history of developing resistance to antibacterial drugs, and many phenotypes are capable of disabling the host immune response by releasing peptide and protein toxins with the capacity to lyse human polymorphonuclear neutrophils. The peptide phenol-soluble modulin α3 (PSMα3) has been identified as an important toxin released by the most virulent strains of MRSA. A library of polymer nonaparticles was synthesized by precipitation polymerization and screened for their ability to bind and neutralize this toxin. To generate high affinity, monomers were chosen to compliment the functional groups of PSMα3. Nanoparticles incorporating aromatic monomers provided a high affinity for the peptide and were effective at neutralizing its toxicity in vitro

Data_Sheet_2_Exosome-Induced Regulation in Inflammatory Bowel Disease.PDF

An exosome (30–150 nm size) is a cell-derived vesicle. Exosome-induced regulation in inflammatory bowel disease (IBD) is becoming increasingly popular due to their potential functions of exosomal pathways. Exosomes, which are involved in the regulation of IBD, can be released from various cell types, or found in many physiological fluids, and plants. The specific functions of exosomes in IBD primarily depend on the internal functional components, including RNAs, proteins, and other substances. However, exosome-induced transport mechanisms involving cell-cell communications or cell-environment interactions are also very important. Recent studies have revealed that exosome crosstalk mechanisms may influence major IBD-related pathways, such as immune responses, barrier functions, and intestinal flora. This review highlights the advancements in the biology of exosome secretions and their regulation in IBD. The functional roles of exosomal components, including nucleic acids, proteins, and some other components, are the main focus of this review. More animal and clinical research is needed to study the functions of exosomes on IBD. Designing new drug dosage form using exosome-like-structure may provide new insights into IBD treatment. This review suggests a potential significance for exosomes in IBD diagnosis and treatment.</p

Data_Sheet_1_Exosome-Induced Regulation in Inflammatory Bowel Disease.PDF

An exosome (30–150 nm size) is a cell-derived vesicle. Exosome-induced regulation in inflammatory bowel disease (IBD) is becoming increasingly popular due to their potential functions of exosomal pathways. Exosomes, which are involved in the regulation of IBD, can be released from various cell types, or found in many physiological fluids, and plants. The specific functions of exosomes in IBD primarily depend on the internal functional components, including RNAs, proteins, and other substances. However, exosome-induced transport mechanisms involving cell-cell communications or cell-environment interactions are also very important. Recent studies have revealed that exosome crosstalk mechanisms may influence major IBD-related pathways, such as immune responses, barrier functions, and intestinal flora. This review highlights the advancements in the biology of exosome secretions and their regulation in IBD. The functional roles of exosomal components, including nucleic acids, proteins, and some other components, are the main focus of this review. More animal and clinical research is needed to study the functions of exosomes on IBD. Designing new drug dosage form using exosome-like-structure may provide new insights into IBD treatment. This review suggests a potential significance for exosomes in IBD diagnosis and treatment.</p

Sampling time points and treatments for 2018 RNA-seq data.

Each time point includes the following samples: 3 biological replicates (6 apples per replicate) used for RNA-Seq, a texture analysis of 9 apple fruit at pullout, and a texture analysis of 9 apple fruit after a 7d ripening period (stored in air at 20°C).</p

Compressed RNA-seq gene expression matrices.

Gene expression matrices of Malus domestica fruit reported in this study. Counts are reported as Transcripts per Million (TPM) reads. (ZIP)</p

The effects of citicoline on Hypoxia/OGD induced changes in the mRNA level of TJPs in endothelial cells.

<p>(<b>A</b>) mRNA level of ZO-1 and occludin in HUVECs. (<b>B</b>) mRNA levels of claudin-5 and ZO-1 in bEnd.3s. Both high and low dose of citicoline increase the expression, while high-dose is more effective when compared to low dose. ^∧∧<i>P</i><0.01, ^∧∧∧<i>P</i><0.001 <i>vs.</i> control; *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 <i>vs.</i> model; ^##<i>P</i><0.01, ^###<i>P</i><0.001 <i>vs.</i> low citicoline; ^∼∼∼<i>P</i><0.001 <i>vs.</i> hypoxia, n = 3/group.</p