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.

Surveillance for foodborne disease outbreaks in China, 2003 to 2008.

Knowledge of implicated food vehicles and contributing factors derived from foodborne disease outbreak (FBDO) investigations allows consumers to be educated on decreasing high-risk behavior to reduce the risk of being affected by foodborne diseases. Food safety regulatory authorities also need summary of outbreak data, as these data indicate where the existing food supply system should be improved. To obtain information on epidemiology of FBDOs in China, FBDOs reported to the China National Foodborne Diseases Surveillance Network by 12 surveillance provinces that include 43% of the Chinese population was summarized. Between 2003 and 2008, 2795 FBDOs were reported, resulting in 62559 illnesses, 31261 hospitalizations, and 330 deaths. Outbreak size ranged from 2 to 464 cases, with a median of 14 cases. The outbreak rate had decreased from 1.37 per 1 million population in 2003 to 0.46 per 1 million population in 2008. Of the 2176 outbreaks with a single known etiology, bacteria (1051 outbreaks, 48%), man-made chemical hazards (550 outbreaks, 25%), and animal and plant toxins (536 outbreaks, 25%) were the main courses. Only one outbreak was caused by virus. Of the 1930 outbreaks with a single commodity, plant-based foods were the most common reported (930 outbreaks, 48%), followed by animal-based foods (590 outbreaks, 31%). Outbreaks most frequently occurred in private residences (32%), workplace cafeterias (21%), and restaurants (17%). The most common factor reported in the 2190 outbreaks with known contributing factors were improper cooking (510 outbreaks, 23%), contaminated ingredient (503 outbreaks, 23%), cross contamination (475 outbreaks, 22%) and improper storage (295 outbreaks, 13%). It is considered that FBDOs continue to be an important public health problem in China.

Differences in inactivation of Escherichia coli O157:H7 strains in ground beef following repeated high pressure processing treatments and cold storage.

High pressure processing (HPP) is a safe non-thermal processing method to effectively improve food safety. In this study, HPP treatment followed by cold storage was investigated to reduce Escherichia coli O157:H7 in ground beef. Experiments were conducted using ground beef contaminated with six E. coli O157:H7 strains one at a time or as a cocktail. Control and inoculated ground beef samples were HPP at 25 °C, 35 °C, and 45 °C, at 400 MPa and pre-determined number of pressure cycles totaling a holding time of 15 min. Optimum HPP parameters were 25 °C, 400 MPa at five pressure cycles of 3 min each which achieved a 5-log reduction of E. coli O157:H7 in ground beef. Storing HPP processed ground beef at 4 °C or -20 °C further decreased (P < 0.05) the E. coli O157:H7 population. An effective HPP treatment (5-log reduction) was developed that could be used post-processing to reduce the risk associated with E. coli O157:H7 contamination in ground beef.

Effect of aqueous media on the copper-ion-mediated phototoxicity of CuO nanoparticles toward green fluorescent protein-expressing Escherichia coli.

Quantitative comparison of different aqueous media on the phototoxicity of copper oxide nanoparticles (CuO NPs) is crucial for understanding their ecological effects. In this study, the phototoxicity of CuO NPs toward the green fluorescent protein-expressing Escherichia coli (GFP-E. coli) under UV irradiation (365 nm) was investigated in Luria-Bertani medium (LB), NaCl solution, deionized water (DI) and phosphate-buffered saline (PBS). The phototoxicity of CuO NPs toward GFP-E. coli decreased in the order of DI>NaCl>PBS>LB because of different released concentrations of Cu(2+). The 3h released Cu(2+) concentrations by 10mg/L CuO NPs in DI water, NaCl solution, LB medium, and PBS were 1946.3 ± 75.6, 1242.5 ± 47.6, 1023.4 ± 41.2, and 1162.1 ± 41.9 µg/L, respectively. Transmission electron microscope and laser scanning confocal microscope images of E. coli exposed to CuO NPs demonstrated that the released Cu(2+) resulted in fragmentation of bacterial cell walls, leakage of intracellular components, and finally death of bacteria in four media after UV light irradiation. In each medium, the bacterial mortality rate logarithmically increased with the releasing concentrations of Cu(2+) by CuO NPs (R(2)>0.90) exposed to 3h UV light. This study highlights the importance of taking into consideration of water chemistry when the phototoxicity of CuO NPs is assessed in nanotoxicity research.

The food retail revolution in China and its association with diet and health.

The processed food sector in low- and middle-income countries has grown rapidly. Little is understood about its effect on obesity. Using data from 14,976 participants aged two and older in the 2011 China Health and Nutrition Survey, this paper examines patterns of processed food consumption and their impacts on obesity while considering the endogeneity of those who purchase processed foods. A major assumption of our analysis of the impact of processed foods on overweight and obesity was that the consumption of processed foods is endogenous due to their accessibility and urbanicity levels. The results show that 74.5% of participants consumed processed foods, excluding edible oils and other condiments; 28.5% of participants' total daily energy intake (EI) was from processed foods. Children and teenagers in megacities had the highest proportion of EI (40.2%) from processed foods. People who lived in megacities or highly urbanized neighborhoods with higher incomes and educational achievement consumed more processed foods. When controlling for endogeneity, only the body mass index (BMI) and risk of being overweight of children ages two to eighteen are adversely associated with processed foods (+4.97 BMI units, 95% confidence interval (CI): 1.66-8.28; odds ratio (OR) = 3.63, 95% CI: 1.45-9.13). Processed food purchases represent less than a third of current Chinese food purchases. However, processed food purchases are growing at the rate of 50% per year, and we must begin to understand the implications for the future.

Fluorescent immunoassay for chloramphenicol based on the label-free polyadenine-mediated spherical nucleic acids triggered signal amplification.

A fluorescent immunosorbent assay incorporating signal amplification away from the surface of spherical nucleic acid (SNA) was developed for the detection of chloramphenicol (CAP). Through the conjugation of antibodies and poly-adenine (polyA) DNA onto the surface of gold nanoparticles (AuNPs), the fabrication of the nano-immunoprobe was achieved in a more straightforward and cost-effective manner. Moreover, a strategy utilizing the hybridization chain reaction (HCR) in the amplification step was devised, with particular attention given to the enzyme inhibition associated with SNA. The results demonstrated good performance on CAP detection with a linear range of 0.01-5 ng/L with a detection limit of 0.005 ng/L. The significance of this work mainly lies in the polyA-SNA-based immunoprobe and the thoughtful design to prevent enzyme inhibition.

Gut microbiota dynamics interacting with gastrointestinal evacuation of Apostichopus japonicus: novel insights into promising strategies for environmental improvement.

As an important input of environmental micropollutants into aquaculture environment, feed is now considered to be a critical factor in shaping gastrointestinal evacuation characteristics of animals. We analyzed the gastrointestinal evacuation characteristics and gut bacteria of Apostichopus japonicus within 30 h after feeding in recirculating aquaculture system (RAS) and explored the evacuation mechanism interacting by bacteria. The Gauss model was the most precise gastrointestinal evacuation curve, and 80% of gastrointestinal evacuation time was 27.81 h after feeding. Linear discriminant analysis effect size analysis revealed that gut microbial abundance associated significantly with time (P < 0.05), and 42 biomarkers that could predict gastrointestinal evacuation were totally detected, such as Lutibacter and Vibrio. Biomarkers at 25 h after feeding were related to harmful bacteria. A dynamic response between gastrointestinal content ratio and gut microbial abundance was detected. Taken together, we could discharge sewage about 25 h after feeding and carry out the next round of feeding activities.

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis.

AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P<0.001). The medians of physical, psychosocial and total health scores self-reported by the children were 68.75 (62.50, 81.25), 65.00 (60.00, 80.00) and 67.39 (60.87, 78.26) preoperatively and were 93.75 (87.50, 100.00), 90.00 (83.33, 96.67) and 89.13 (85.32, 95.65) postoperatively. The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children (P<0.001). All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents (P<0.001). In the physical functioning evaluation, the preoperative score reported by parents of girls was higher than parents of boys (P=0.041), and the postoperative score of girls was higher than that of boys (P=0.036). CONCLUSION: CEL is associated with significantly worse quality of life in preschool children. Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

Community Incidence Estimates of Five Pathogens Based on Foodborne Diseases Active Surveillance - China, 2023.

What is already known about this topic?: Foodborne diseases, representing significant food safety and public health challenges globally, are not well-documented in terms of incidence, particularly for cases characterized by acute gastroenteritis (AGI) in China. What is added by this report?: This study developed a pyramid model to estimate the incidence of five pathogens, stratified by gender and age. The estimated incidences per 100,000 people with 95% uncertainty intervals (UI) are as follows: Norovirus, 3,188.28 (95% UI: 2,518.03, 7,296.96); Salmonella spp., 1,295.59 (95% UI: 1,002.62, 1,573.11); diarrheagenic E. coli (DEC), 782.62 (95% UI: 651.19, 932.05); Vibrio parahaemolyticus, 404.06 (95% UI: 342.19, 468.93); and Shigella spp., 26.73 (95% UI: 21.05, 33.46). What are the implications for public health practice?: This study elucidates the incidence rates across various gender and age groups, thereby identifying priority populations for targeted preventive interventions aimed at reducing disease burden. These insights are crucial for the development of public health policies and management of food safety risks.

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 AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that AMPD deficiency in mice primarily leads to hippocampal dentate gyrus degeneration despite causing a generalized reduction of brain GTP levels. Remarkably, we found that neurodegeneration resistant regions accumulate micron sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis. In contrast, IMPDH2 filaments are barely detectable in the hippocampal dentate gyrus, which shows a progressive neuroinflammation and neurodegeneration. Furthermore, using a human AMPD2 deficient neural cell culture model, we show that blocking IMPDH2 polymerization with a dominant negative IMPDH2 variant, impairs AMPD2 deficient neural progenitor growth. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation in neurons with available GTP precursor molecules, providing resistance to neurodegeneration. Our findings open the possibility of exploring the involvement of IMPDH2 assembly as a therapeutic intervention for neurodegeneration.

Risk factors associated with food consumption and food-handling habits for sporadic listeriosis: a case-control study in China from 2013 to 2022.

The prevalence of listeriosis in China has been increasing in recent years. Listeriosis primarily spreads through contaminated food. However, the resilient causative organism, Listeria monocytogenes, and its extended incubation period pose challenges in identifying risk factors associated with food consumption and food-handling habits. This study aimed to identify the risk factors associated with food consumption and food-handling habits for listeriosis in China. A matched case-control study (1:1 ratio) was conducted, which enrolled all eligible cases of listeriosis between 1 January 2013 and 31 December 2022 in China. Basic information and possible risk factors associated with food consumption and food-handling habits were collected. Overall, 359 patients were enrolled, including 208 perinatal and 151 non-perinatal cases. Univariate and multivariable logistic analyzes were performed for the perinatal group. For the perinatal and non-perinatal groups, ice cream and Chinese cold dishes were the high-risk foods for listeriosis (odds ratio (OR) 2.09 95% confidence interval (CI): 1.23-3.55; OR 3.17 95% CI: 1.29-7.81), respectively; consumption of leftovers and pet ownership were the high-risk food-handling habits (OR 1.92 95% CI: 1.03-3.59; OR 3.00 95% CI: 1.11-8.11), respectively. In both groups, separation of raw and cooked foods was a protective factor (OR 0.27 95% CI: 0.14-0.51; OR 0.35 95% CI: 0.14-0.89), while refrigerator cleaning reduced the infection risk by 64.94-70.41% only in the perinatal group. The identification of high-risk foods and food-handling habits for listeriosis is important for improving food safety guidelines for vulnerable populations.

Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency.

Dysregulated lipid homeostasis is emerging as a potential cause of neurodegenerative disorders. However, evidence of errors in lipid homeostasis as a pathogenic mechanism of neurodegeneration remains limited. Here, we show that cerebellar neurodegeneration caused by Sorting Nexin 14 (SNX14) deficiency is associated with lipid homeostasis defects. Recent studies indicate that SNX14 is an interorganelle lipid transfer protein that regulates lipid transport, lipid droplet (LD) biogenesis, and fatty acid desaturation, suggesting that human SNX14 deficiency belongs to an expanding class of cerebellar neurodegenerative disorders caused by altered cellular lipid homeostasis. To test this hypothesis, we generated a mouse model that recapitulates human SNX14 deficiency at a genetic and phenotypic level. We demonstrate that cerebellar Purkinje cells (PCs) are selectively vulnerable to SNX14 deficiency while forebrain regions preserve their neuronal content. Ultrastructure and lipidomic studies reveal widespread lipid storage and metabolism defects in SNX14-deficient mice. However, predegenerating SNX14-deficient cerebella show a unique accumulation of acylcarnitines and depletion of triglycerides. Furthermore, defects in LD content and telolysosome enlargement in predegenerating PCs suggest lipotoxicity as a pathogenic mechanism of SNX14 deficiency. Our work shows a selective cerebellar vulnerability to altered lipid homeostasis and provides a mouse model for future therapeutic studies.