IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency.

Metabolic dysregulation is one of the most common causes of pediatric neurodegenerative disorders. However, how the disruption of ubiquitous and essential metabolic pathways predominantly affect neural tissue remains unclear. Here we use mouse models of a childhood neurodegenerative disorder caused by AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that mouse models of AMPD2 deficiency exhibit predominant degeneration of the hippocampal dentate gyrus, despite a general reduction of brain GTP levels. Neurodegeneration-resistant regions accumulate micron-sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis, while these filaments are barely detectable in the hippocampal dentate gyrus. Furthermore, we show that IMPDH2 filament disassembly reduces GTP levels and impairs growth of neural progenitor cells derived from individuals with human AMPD2 deficiency. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation, opening the possibility of exploring the induction of IMPDH2 assembly as a therapy for neurodegeneration.

Identification and phenotypic analysis of novel LTBP2 mutations in a Chinese cohort with congenital ectopia lentis.

Purpose: To evaluate the frequency of LTBP2 mutations and to elaborate on LTBP2-related clinical phenotypes in a Chinese congenital ectopia lentis (CEL) cohort. Methods: In total, 145 Chinese probands with CEL were recruited for this study and underwent ocular and systemic examinations. Whole-exome sequencing was used to identify mutations, and Sanger sequencing and bioinformatics analysis were further performed to verify pathogenic mutations. Results: Overall, biallelic mutations in LTBP2 involving eight novel mutations (c.4370-7_4370-9delTCT, c.4370-5C>G, c.3452G>A, c.2253delG, c.4114T>C, c.1251G>A, c.4760G>A, and c.620G>A) were identified in four CEL probands (4/145, 2.76%). Patients with LTBP2 mutations were characterized by a megalocornea, spherophakia, high myopia, and glaucoma instead of a flat cornea, high corneal astigmatism, cardiovascular and skeletal abnormalities that were reported in other gene mutations. A novel homozygous frameshift mutation was detected, and this type of mutation was found to cause more complicated ocular symptoms than others, ranging from the anterior segment to the fundus. Conclusion: This study reported the mutation frequency of the LTBP2 gene in a Chinese CEL cohort and provided novel insight into LTBP2-related genotype-phenotype associations in CEL.

Prevalence and distribution of acute gastrointestinal illness in the community of China: a population-based face-to-face survey, 2014-2015.

BACKGROUND: The true incidence of acute gastrointestinal illness in China is underrecognized by surveillance systems. The aims of this study were to estimate the incidence and prevalence of self-reported AGI in the community of China, and to investigate sociodemographic and epidemiological determinants of AGI. METHODS: We conducted a 12-months cross-sectional population-based survey in eight provinces of China during 2014-2015. The survey determined the prevalence and incidence of acute gastrointestinal illness (AGI) in the total permanent resident population in China according to the census of the population in 2010. The random multilevel population sample was stratified by geographic, population, and socioeconomic status. We used a recommended case definition of AGI, with diarrhea (three loose or watery stools) and/or any vomiting in a four-week recall. A face-to-face survey was conducted by selecting the member in the household with the most recent birthday. RESULTS: Among 56,704 sampled individuals, 948 (1,134 person-time) fulfilled the case definition; 98.5% reported diarrhea. This corresponds to 2.3% (95% CI:1.9%-2.8%) of an overall standardized four-week prevalence and 0.3 (95% CI: 0.23-0.34) episodes per person-year of annual adjusted incidence rate. There was no significant difference between males and females. The incidence rates were higher among urban residents, and in the spring and summer. In the whole study period, 50% of the cases sought medical care, of which 3.9% were hospitalized and 14.3% provided a biological sample for laboratory identification of the causative agent. Children aged 0-4 and young adults aged 15-24, people living in rural areas and people who traveled frequently had higher prevalence of AGI. CONCLUSION: Results showed that AGI represents a substantial burden in China, and will contribute to the estimation of the global burden of AGI. Complemented with data on the etiologies of AGI, these estimates will form the basis to estimate the burden of foodborne diseases in China.

Interaction among biofilter microbiome, fecal metabolome and water quality and regulation of sewage discharge in the recirculating aquaculture system of Apostichopus japonicus.

With the aggravation of environmental pollution caused by traditional culture of Apostichopus japonicus, the concept of A. japonicus recirculating aquaculture system (RAS) came into being. To plan the sewage discharge time reasonably, we explored the temporal variation of water quality, biofilter microbe and fecal metabolome in RAS and relevant mechanism. The results showed that monitored water quality in RAS were within the safe living range of A. japonicus. Proteobacteria and Desulfobacterota were dominant bacteria in biofilter. The RDA results and correlation heatmap showed that NH4-N and NO2-N significantly affected the microbial community composition. The expression pattern of fecal metabolites changed with the passage of time after feeding. And ROC curve analysis and VIP bar chart showed that there were inter group biomarkers with predictive performance, which could help to remind timely sewage discharge. Topological analysis of KEGG pathway enrichment showed that metabolic pathways such as alanine, aspartate and glutamate metabolism changed significantly after feeding (P < 0.01). Additionally, the correlation analysis results showed that biofilter microbe and fecal metabolites were related to water quality (P < 0.05). Combined with the above research results, this study concluded that the RAS could discharge sewage 25-30 h after feeding. These findings were of direct significance to the management of RAS environment and the protection of A. japonicus healthy growth.

Regulating the Inner Helmholtz Plane with a High Donor Additive for Efficient Anode Reversibility in Aqueous Zn-Ion Batteries.

The performance of aqueous Zn ion batteries (AZIBs) is highly dependent on inner Helmholtz plane (IHP) chemistry. Notorious parasitic reactions containing hydrogen evolution reactions (HER) and Zn dendrites both originate from abundant free H2 O and random Zn deposition inside active IHP. Here, we report a universal high donor number (DN) additive pyridine (Py) with only 1 vol. % addition (Py-to-H2 O volume ratio), for regulating molecule distribution inside IHP. Density functional theory (DFT) calculations and molecular dynamics (MD) simulation verify that incorporated Py additive could tailor Zn2+ solvation sheath and exclude H2 O molecules from IHP effectively, which is in favor of preventing H2 O decomposition. Consequently, even at extreme conditions such as high depth of discharge (DOD) of 80 %, the symmetric cell based on Py additive can sustain approximately 500 h long-term stability. This efficient strategy with high DN additives furnishes a promising direction for designing novel electrolytes and promoting the practical application of AZIBs, despite inevitably introducing trace organic additives.

Regulating Interfacial Ion Migration via Wool Keratin Mediated Biogel Electrolyte toward Robust Flexible Zn-Ion Batteries.

Aqueous Zn-ion batteries (ZIBs) have emerged as a promising energy supply for next-generation wearable electronics, yet they are still impeded by the notorious growth of zinc dendrite and uncontrollable side reaction. While the rational design of electrolyte composition or separator decoration can effectively restrain zinc dendrite growth, synchronously regulating the interfacial electrochemical performance by tackling the physical delamination venture between electrode and electrolyte remains a major obstacle for high-performance wearable aqueous ZIB. Herein, a category of hybrid biogel electrolyte containing carrageenan and wool keratin (CWK) is put forward to regulate the interfacial electrochemistry in aqueous ZIB. Systematic electrochemical kinetics analyses and ex situ scanning electrochemical microscopy (SECM) characterizations achieve comprehensive understanding of the keratin enhanced interfacial Zn2+ redox reaction. Thanks to the keratin triggered selective ion permeability, the as-designed CWK hybrid biogel electrolyte manifests a promoted Zn2+ transference number and excellent reversibility of Zn plating/stripping and outstanding Zn utilization (average Coulombic efficiency ≈98%). More impressively, the CWK hybrid biogel electrolyte also demonstrates cathode side-reaction depression and strengthened interfacial adhesion while assembled into a quasi-solid-state flexible ZIB. This work offers a strategy to synchronously solve concurrent challenges for both of Zn anode and cathode toward realistic wearable aqueous ZIB.

Mutation spectrum and genotype-phenotype correlations in Chinese congenital ectopia lentis patients.

PURPOSE: To identify the spectrum and frequency of mutations in congenital ectopia lentis (CEL) and to investigate the correlations between genotype and clinical phenotype in Chinese CEL patients. METHODS: Ninety-three participants with CEL were enrolled from March 2017 to April 2020. Ocular and systemic examinations were performed for each included patient. Genomic DNA from the included patients was analysed by whole-exome sequencing to detect mutations. Clinical manifestations were compared for different mutation subgroups. RESULTS: Gene mutations were detected in 79 patients. Sixty-five were FBN1-associated, and most were related to Marfan syndrome (MFS). The FBN1 mutations mainly consisted of missense mutations (49/65) and were concentrated in the 5' region. Probands with missense mutations tend to show high corneal astigmatism (χ2 = 3.98, P = 0.046) and severe lens dislocation (t = 2.90, P = 0.006) compared to premature termination codon (PTC) mutations. CONCLUSIONS: Most Chinese CEL patients were identified as having FBN1 mutations. Those with missense mutations commonly showed severe ocular phenotypes; therefore, reinforced follow-up and long-term observation are required. These correlations implicated the crucial role of missense and cysteine-involving mutations in ocular phenotypes, which might be explained by dominant-negative and nonsense-mediated mRNA decay (NMD).

Detection of antibiotics in the urine of children and pregnant women in Jiangsu, China.

Exposure to low concentrations of antibiotics links to multiple health hazards, such as drug resistance of bacteria, and childhood obesity. In this study, seven antibiotics were measured in the urine of 107 children and 126 pregnant women in Jiangsu Province by ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). The overall urinary antibiotics detection rate was 38.6%. Most (98.3%) of the participants' antibiotics concentrations were no more than 10 ng/mL. Children had a significantly higher detection rate than pregnant women (47.7% vs. 31.0%, P = 0.009), as well as the concentration (95th percentile: 6.49 vs. 4.08 ng/mL, P = 0.002). The detection rates of individual antibiotics ranged from 0.4% to 15.0%, and the concentrations ranged from lower than the limit of detection (LOD) through up to 31.96 ng/mL individually. Two or more antibiotics were detected in 11.2% of the urines. Tetracyclines were more frequently detected than phenicols (30.9% vs.12.4%). Oxytetracycline was the most frequently detected (15.0%). Multivariate logistic regression showed that consuming puffed food every day was associated with a significantly increased likelihood of detection, and higher concentration of overall antibiotics, and of doxycycline. Children were more likely to be detected of doxycycline and florfenicol, and to have elevated concentration of doxycycline, compared with pregnant women. This study highlights the relatively heavier antibiotics exposure in children, and a possible impact of puffed food on it, which needs to be warranted in future studies.

Characterization of Human Origin Salmonella Serovar 1,4,[5],12:i:- in Eastern China, 2014 to 2018.

The prevalence of Salmonella serovar 1,4,[5],12:i:- among diarrhea patients has increased considerably in many countries around the world, including China. However, the characterization of this serovar of human origin has been less reported from China. We characterized 76 isolates of Salmonella 1,4,[5],12:i:- gained from diarrhea patients from 2014 to 2018 in the Jiangsu Province of eastern China. These isolates fell into a single-sequence type (ST34) determined by multilocus sequence typing (MLST), and into 44 pulsed-field gel electrophoresis band patterns, with 1 pattern (JSSMM015) comprising 12 isolates (15.9%). By means of PCR-based assays, the seven prophage located virulence genes were detected in our Salmonella 1,4,[5],12:i:- isolates with a high rate of gipA, gtgB, sspH1, sspH2, sodC1, and gtgE (93.4-97.4%), and with a moderate rate of sopE (42.1%). In contrast, none of the five plasmid-borne virulence genes (spvC, pefA, mig5, rck, and srgA) was identified. We tested the isolates' susceptibility to 18 antibiotics of 9 categories using the VITEK 2 system. A high proportion (89.5%) of the isolates were multidrug resistant (MDR) strains with full resistance to cefazolin, cefotetan, amikacin, gentamycin, and tobramycin, followed by resistance to ampicillin (88.2%) and ampicillin/sulbactam (80.3%). The resistance to piperacillin/tazobactam, ceftazidime, cefepime, and levofloxacin was scarce (2.6-9.2%). Notably, an isolate from 2018 was resistant to carbapenems. blaTEM-1B and aac(6')-Ib-cr were the most common drug resistance genes presented in cephalosporin- and fluoroquinolone-resistant strains. All Salmonella 1,4,[5],12:i:- isolates were capable of forming biofilm, with 13.2% of them having strong ability. However, no association was indicated between the scale of biofilm formation ability and MDR. Our results indicate that the combination of these characteristics may together provide a selective and competitive advantage to those Salmonella 1,4,[5],12:i:- isolates, contributing to their increasing prevalence observed worldwide.

Long non-coding RNA LINC01194 promotes the proliferation, migration and invasion of lung adenocarcinoma cells by targeting miR-641/SETD7 axis.

BACKGROUND: It is increasingly evidenced that long non-coding RNAs (lncRNAs) play an important role in various diseases. LncRNA LINC01194 acts as an oncogene in several cancer types. Nevertheless, the role of LINC01194 in lung adenocarcinoma (LUAD) has not yet been revealed. METHODS: qRT-PCR was used to detect the expression of LINC01194, miR-641 and SETD7 mRNA, while western blot was exploited to examine SETD7 protein level. Cell proliferation was detected by colony formation and EdU assays. Transwell assays detected cell migration and invasion. TUNEL assay and flow cytometry analysis were used to detect cell apoptosis. RIP, RNA pull down and luciferase reporter assays detected the binding among LINC01194, miR-641 and SETD7. RESULTS: LINC01194 was significantly upregulated in LUAD tissues and cell lines. Knockdown of LINC01194 resulted in decreased cell proliferation, migration and invasion, and increased apoptosis. Mechanistic experiments unveiled that LINC01194 augmented SETD7 expression in LUAD cells by competitively interacting with miR-641. Rescue experiments showed that miR-641 inhibition and SETD7 overexpression rescued the repressing impacts on LUAD cell proliferation, migration and invasion caused by LINC01194 knockdown. CONCLUSION: LINC01194 promotes the progression of LUAD by enhancing miR-641-targeted SETD7. The LINC01194/miR-641/SETD7 axis might provide new molecular targets for treating LUAD.