Salmonella Grumpensis Causing Diarrhea in Children - Shanghai Municipality, China, 2023.

What is already known about this topic?: Foodborne diseases are a growing public health concern with a notable disease burden in China. What is added by this report?: Two children with diarrhea visited a healthcare facility within 24 hours on August 1 and 2, 2023. Salmonella Grumpensis was detected in their stool samples by the public health laboratory. Whole genome sequencing (WGS) analysis revealed characteristics typical of outbreak strains. Although the origin of the outbreak was unknown, the possibility of a hidden shared infection was deemed feasible. What are the implications for public health practice?: It underscores the importance of thorough genomic surveillance to promptly detect emerging pathogens. Public health laboratories play a crucial role by utilizing advanced genomic technologies for accurate pathogen identification and timely warning systems.

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

Potential structure-function relationships of pectic polysaccharides from quinoa microgreens: Impact of various esterification degrees.

Pectic polysaccharides are one of the most vital functional ingredients in quinoa microgreens, which exhibit numerous health-promoting benefits. Nevertheless, the detailed information about the structure-function relationships of pectic polysaccharides from quinoa microgreens (QMP) remains unknown, thereby largely restricting their applications as functional foods or fortified ingredients. Therefore, to unveil the possible structure-function relationships of QMP, the mild alkali de-esterification was utilized to modify QMP, and then the correlations of esterification degrees of native and modified QMPs to their biological functions were systematically investigated. The results showed that the modified QMPs with different esterification degrees were successfully prepared by the mild alkali treatment, and the primary chemical structure (e.g., compositional monosaccharides and glycosidic linkages) of the native QMP was overall stable after the de-esterified modification. Furthermore, the results revealed that the antioxidant capacity, antiglycation effect, prebiotic potential, and immunostimulatory activity of the native QMP were negatively correlated to its esterification degree. In addition, both native and modified QMPs exerted immunostimulatory effects through activating the TLR4/NF-κB signaling pathway. These results are conducive to unveiling the precise structure-function relationships of QMP, and can also promote its applications as functional foods or fortified ingredients.

Poly(ethylene oxide)-based composite solid electrolyte for long cycle life solid-state lithium metal batteries: Improvement of interface stability through a dual mechanism.

Solid-state lithium metal batteries (SSLMBs) are promising candidates for safe and high-energy-density next-generation applications. However, harmful interfacial decomposition and uneven Li deposition lead to poor ion transport, a short cycle life, and battery failure. Herein, we propose a novel poly(ethylene oxide) (PEO)-based composite solid electrolyte (CSE) containing succinonitrile (SN) and zinc oxide (ZnO) nanoparticles (NPs), which improves interface stability through a dual mechanism. (1) By anchoring bis(trifluoromethanesulfonyl)imide (TFSI) anions to ZnO, a reliable solid electrolyte interface (SEI) later with abundant LiF can be obtained to inhibit interface decomposition. (2) The immobilization of escaping SN molecules in the SEI layer by ZnO NPs promotes the self-polymerization of SN and facilitates charge transfer through the interface. As a result, the ion conductivity of the stainless steel-symmetrical battery reaches 1.1 × 10-4 S cm-1 at room temperature, and a LiFePO4 (LFP) full battery exhibits ultrahigh stability (800 cycles) at 0.5 C. Thus, the present study provides valuable insights for the development of advanced PEO-based SSLMBs.

Predicting Schistosomiasis Intensity in Africa: A Machine Learning Approach to Evaluate the Progress of WHO Roadmap 2030.

The World Health Organization (WHO) 2030 Roadmap aims to eliminate schistosomiasis as a public health issue, targeting reductions in the heavy intensity of infections. Previous studies, however, have predominantly used prevalence as the primary indicator of schistosomiasis. We introduce several machine learning (ML) algorithms to predict infection intensity categories, using morbidity prevalence, with the aim of assessing the elimination of schistosomiasis in Africa, as outlined by the WHO. We obtained morbidity prevalence and infection intensity data from the Expanded Special Project to Eliminate Neglected Tropical Diseases, which spans 12 countries in sub-Saharan Africa. We then used a series of ML algorithms to predict the prevalence of infection intensity categories for Schistosoma haematobium and Schistosoma mansoni, with morbidity prevalence and several relevant environmental and demographic covariates from remote-sensing sources. The optimal model had high accuracy and stability; it achieved a mean absolute error (MAE) of 0.02, a root mean square error (RMSE) of 0.05, and a coefficient of determination (R2) of 0.84 in predicting heavy-intensity prevalence for S. mansoni; and an MAE of 0.02, an RMSE of 0.04, and an R2 value of 0.81 for S. haematobium. Based on this optimal model, we found that most areas in the surveyed countries have not achieved the target of the WHO road map for 2030. The ML algorithms used in our analysis showed a high overall predictive power in estimating infection intensity for each species, and our methods provided a low-cost, effective approach to evaluating the disease target in Africa set in the WHO road map for 2030.

Acupuncture for cognitive impairment after stroke: A systematic review and meta-analysis.

Objective: Acupuncture as an alternative therapy for post-stroke cognitive impairment (PSCI) has emerged as a research focus. The inclusion of additional external treatments in many previous studies prevents a clear, direct assessment of acupuncture's impact on PSCI. In order to prevent patients from developing hypersensitivity to other treatments and misinterpreting acupuncture's true therapeutic value, this study establish stricter intervention criteria and exclude therapies beyond acupuncture. The review aimed to offering a clearer evaluation of acupuncture's efficacy and safety in PSCI treatment. Methods: This research involved a comprehensive search for randomized controlled trials (RCTs) across eight databases, adhering to the Cochrane Systematic Reviewer's Handbook 5.1.0 for risk-of-bias and quality assessments. A meta-analysis was conducted using RevMan 5.3 software. Results: The inclusion of 18 publications, totaling 1361 patients, was achieved. The meta-analysis demonstrated a significantly higher overall efficacy of acupuncture for PSCI compared to controls (OR = 4.06, 95 % CI 2.86-5.76, Z = 7.82). Notable statistical differences were observed in the Montreal Cognitive Assessment scores (MD = 2.32, 95 % CI 1.68-2.97, Z = 7.10) and the Mini-Mental State Examination scores (MD = 2.02, 95 % CI 1.06-2.98, Z = 4.13) between the groups. Improvements in the Barthel Index scores were noted for the experimental group (MD = 5.70, 95 % CI 4.68-6.72, Z = 10.92). Conclusion: Integrating acupuncture with Western medications offers significant benefits for treating PSCI over Western medications alone. However, the long-term efficacy of acupuncture in PSCI treatment and its potential in reducing recurrence rates remain undetermined. Further high-standard RCTs are essential to explore acupuncture's effectiveness in PSCI treatment more thoroughly.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Creation of memory-memory entanglement in a metropolitan quantum network.

Towards realizing the future quantum internet1,2, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research.

Effects of replacing fishmeal with soybean meal on the immune and antioxidant capacity, and intestinal metabolic functions of red swamp crayfish Procambarus clarkii.

Excess utilization of plant protein sources in animal feed has been found to adversely affect the antioxidant properties and immunity of animals. While the role of gut microbes in plant protein-induced inflammation has been identified in various models, the specific mechanisms regulating gut microbes in crustaceans remain unclear. Accordingly, this study was designed to investigate the effects of replacing fishmeal with soybean meal (SM) on the hepatopancreas antioxidant and immune capacities, and gut microbial functions of crayfish, as well as the potential microbial regulatory mechanisms. 750 crayfish (4.00 g) were randomly divided into five groups: SS0, SS25, SS50, SS75, and SS100, and fed diets with different levels of soybean meal substituted for fishmeal for six weeks. High SM supplementation proved detrimental to maintaining hepatopancreas health, as indicated by an increase in hemolymph MDA content, GPT, and GOT activities, the observed rupture of hepatopancreas cell basement membranes, along with the decreased number of hepatopancreatic F cells. Moreover, crayfish subjected to high SM diets experienced obvious inflammation in hepatopancreas, together with up-regulated mRNA expression levels of nfkb, alf, and tlr (p<0.05), whereas the lzm mRNA expression level exhibited the highest value in the SS25 group. Furthermore, hepatopancreas antioxidant properties highly attenuated by the level of dietary SM substitution levels, as evidenced by the observed increase in MDA content (p<0.05), decrease in GSH content (p<0.05), and inhabitation of SOD, CAT, GPx, and GST activities (p<0.05), along with down-regulated hepatopancreas cat, gpx, gst, and mmnsod mRNA expression levels via inhibiting nrf2/keap1 pathway. Functional genes contributing to metabolism identified that high SM diets feeding significantly activated lipopolysaccharide biosynthesis, revealing gut dysfunction acted as the cause of inflammation. The global microbial co-occurrence network further indicated that the microbes contributing more to serum indicators and immunity were in module eigengene 17 (ME17). A structural equation model revealed that the genes related to alf directly drove the serum enzyme activities through microbes in ME17, with OTU399 and OTU533 identified as major biomarkers and classified into Proteobacteria that secrete endotoxins. To conclude, SM could replace 25 % of fishmeal in crayfish diets without negatively affecting immunity, and antioxidant capacity. Excessive SM levels contributed to gut dysfunction and weakened the innate immune system of crayfish.

Association between coffee and caffeine intake and risk of COPD: Findings based on NHANES 2007-2012.

BACKGROUND: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. OBJECTIVES: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012. METHODS: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. RESULTS: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. CONCLUSIONS: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms.

Impacts of ultrasound-assisted Fenton degradation and alkaline de-esterification on structural properties and biological effects of pectic polysaccharides from Tartary buckwheat leaves.

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) leaf has abundant rhamnogalacturonan-I enriched pectic polysaccharides, which exert various health-promoting effects. Nevertheless, the potential relationship between the chemical structure and the biological function of pectic polysaccharides from Tartary buckwheat leaves (TBP) remains unclear. Therefore, to bridge the gap between the chemical structure and the biological function of TBP, the impacts of ultrasound-assisted Fenton degradation (UFD) and mild alkaline de-esterification (MAD) on structural properties and biological effects of TBP were systematically studied. Compared with the native TBP (molecular mass, 9.537 × 104 Da), the molecular masses of degraded TBPs (TBP-MMW, 4.811 × 104 Da; TBP-LMW, 2.101 × 104 Da) were significantly reduced by the UFD modification, while their primary chemical structures were overall stable. Besides, compared with the native TBP (esterification degree, 22.73 %), the esterification degrees of de-esterified TBPs (TBP-MDE, 14.27 %; TBP-LDE, 6.59 %) were notably reduced by the MAD modification, while their primary chemical structures were also overall stable. Furthermore, the results revealed that both UFD and MAD modifications could significantly improve the antioxidant, antiglycation, and immunostimulatory effects of TBP. Indeed, TBP's biological effects were negatively correlated to its molecular mass and esterification degree, while positively linked to its free uronic acids. The findings demonstrate that both UFD and MAD modifications are promising techniques for the structural modification of TBP, which can remarkedly promote its biological effects. Besides, the present results are conducive to better understanding TBP's structure-bioactivity relationship.

Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study.

BACKGROUND: The study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk. METHODS: The present study involved 28,974 UK Biobank participants aged 50-74y (2006-2010) at baseline (2006-2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life's Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z_rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z_rev-dementia effect. The total effect was decomposed into "mediation only" or pure indirect effect (PIE), "interaction only" or interaction referent (INTREF), "neither mediation nor interaction" or controlled direct effect (CDE), and "both mediation and interaction" or mediated interaction (INTMED). RESULTS: The study found poorer CVH assessed by LE8z_rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03-1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z_rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z_rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730). CONCLUSION: Dementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained ∼ 54 % of the total effect.

Corrigendum: Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis.

[This corrects the article DOI: 10.3389/fimmu.2023.1181697.].

Harnessing Multiscale Physiochemical Interactions on Nanobiointerface for Enhanced Stress Resilience in Rice.

Nanoagrochemicals present promising solutions for augmenting conventional agriculture, while insufficient utilization of nanobiointerfacial interactions hinders their field application. This work investigates the multiscale physiochemical interactions between nanoagrochemicals and rice (Oryza sativa L.) leaves and devises a strategy for elevating targeting efficiency of nanoagrochemicals and stress resilience of rice. We identified multiple deposition behaviors of nanoagrochemicals on hierarchically structured leaves and demonstrated the crucial role of leaf microarchitectures. A transition from the Cassie-Baxter to the Wenzel state significantly changed the deposition behavior from superlattice assembly, ring-shaped aggregation to uniform monolayer deposition. By fine-tuning the formulation properties, we achieved a 415.9-fold surge in retention efficiency, and enhanced the sustainability of nanoagrochemicals by minimizing loss during long-term application. This biointerface design significantly relieved the growth inhibition of Cd(II) pollutant on rice plants with a 95.2% increase in biomass after foliar application of SiO2 nanoagrochemicals. Our research elucidates the intricate interplay between leaf structural attributes, nanobiointerface design, and biological responses of plants, fostering field application of nanoagrochemicals.

A facile and intelligent detection method for diclazuril based on a stable dual emissive Eu3+-dopped metal-organic framework.

Diclazuril (DIC) is a broad-spectrum anti-coccidiosis drug of the triazine class, widely used in poultry farming. The overuse of DIC may lead to its accumulation in animal bodies, which may enter the food chain and threaten human health. In this work, we fabricated a stable Eu3+-doped UiO-66 fluorescence sensor (EuUHIPA-30) for the sensitive detection of DIC. Among 20 veterinary drugs, the fluorescence of EuUHIPA-30 selectively responds to DIC, with a low detection limit (0.19 µM) and fast response (10 s). EuUHIPA-30 is recyclable and can detect DIC in chicken and eggs with good recoveries. Moreover, a smartphone-integrated paper-based sensor enables the instrument-free, rapid, visual, and intelligent detection of DIC in chickens and eggs. This work provides a promising candidate for practical fluorescent DIC sensing in animal-derived food to promote food safety.

m6A-methylated Lonp1 drives mitochondrial proteostasis stress to induce testicular pyroptosis upon environmental cadmium exposure.

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

Pathways explaining racial/ethnic and socio-economic disparities in brain white matter integrity outcomes in the UK Biobank study.

Pathways explaining racial/ethnic and socio-economic status (SES) disparities in white matter integrity (WMI) reflecting brain health, remain underexplored, particularly in the UK population. We examined racial/ethnic and SES disparities in diffusion tensor brain magnetic resonance imaging (dMRI) markers, namely global and tract-specific mean fractional anisotropy (FA), and tested total, direct and indirect effects through lifestyle, health-related and cognition factors using a structural equations modeling approach among 36,184 UK Biobank participants aged 40-70 y at baseline assessment (47% men). Multiple linear regression models were conducted, testing independent associations of race/ethnicity, socio-economic and other downstream factors in relation to global mean FA, while stratifying by Alzheimer's Disease polygenic Risk Score (AD PRS) tertiles. Race (Non-White vs. White) and lower SES predicted poorer WMI (i.e. lower global mean FA) at follow-up, with racial/ethnic disparities in FAmean involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across tract-specific FA outcomes, with SES-FAmean total effect being partially mediated (41% of total effect = indirect effect). Furthermore, the association of poor cognition with FAmean was markedly stronger in the two uppermost AD PRS tertiles compared to the lower tertile (T2 and T3: ß±SE: -0.0009 ± 0.0001 vs. T1: ß±SE: -0.0005 ± 0.0001, P < 0.001), independently of potentially confounding factors. Race and lower SES were generally important determinants of adverse WMI outcomes, with partial mediation of socio-economic disparities in global mean FA through lifestyle, health-related and cognition factors. The association of poor cognition with lower global mean FA was stronger at higher AD polygenic risk.

Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer.

Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary thyroid carcinomas. While some cases of FNMTC are associated with familial multi-organ tumor predisposition syndromes, the majority occur independently. The genetic mechanisms underlying non-syndromic FNMTC remain unclear. Initial studies utilized SNP linkage analysis to identify susceptibility loci, including the 1q21 locus, 2q21 locus, and 4q32 locus, among others. Subsequent research employed more advanced techniques such as Genome-wide Association Study and Whole Exome Sequencing, leading to the discovery of genes such as IMMP2L, GALNTL4, WDR11-AS1, DUOX2, NOP53, MAP2K5, and others. But FNMTC exhibits strong genetic heterogeneity, with each family having its own pathogenic genes. This is the first article to provide a chromosomal landscape map of susceptibility genes associated with non-syndromic FNMTC and analyze their potential associations. It also presents a detailed summary of variant loci, characteristics, research methodologies, and validation results from different countries.

Clinicopathological characteristics and gene mutations in 11 patients with lipoprotein glomerulopathy.

OBJECTIVE: Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. METHODS: Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. RESULTS: The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. CONCLUSION: LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.

Causal relationship between feelings and cognitive decline: An univariable and multivariable Mendelian randomization study.

BACKGROUND: While the impact of depression on cognition is well-documented, the relationship between feelings and cognition has received limited attention. AIM: To explore the potential association between feelings and cognition with a two-sample Mendelian randomization (MR) analysis. METHODS: Our analysis utilized genome-wide association data on various feelings (fed-up feelings, n = 453071; worrier/anxious feelings, n = 450765; guilty feelings, n = 450704; nervous feelings, n = 450700; sensitivity/hurt feelings, n = 449419; miserableness, n = 454982; loneliness/isolation, n = 455364; happiness, n = 152348) in the European population and their impact on cognitive functions (intelligence, n = 269867). Conducting a univariable MR (UVMR) analysis to assess the relationship between feelings and cognition. In this analysis, we applied the inverse variance weighting (IVW), weighted median, and MR Egger methods. Additionally, we performed sensitivity analysis (leave-one-out analysis), assessed heterogeneity (using MR-PRESSO and Cochran's Q test), and conducted multiple validity test (employing MR-Egger regression). Subsequently, a multivariable MR (MVMR) analysis was employed to examine the impact of feelings on cognition. IVW served as the primary method in the multivariable analysis, complemented by median-based and MR-Egger methods. RESULTS: In this study, UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition (OR = 0.63, 95%CI: 0.43-0.92, P = 0.017). After adjustment of other feelings using MVMR, a direct adverse causal effect on cognition was observed (ORMVMR = 0.39, 95%CI: 0.17-0.90, PMVMR = 0.027). While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis (ORUVMR = 0.64, 95%CI: 0.42-0.97, PUVMR = 0.037), this effect disappeared after adjusting for other feelings (ORMVMR = 1.42, 95%CI: 0.43-4.74, PMVMR = 0.569). These findings were generally consistent across MV-IVW, median-based, and MR-Egger analyses. MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition, presenting a challenge in identifying the effect. Notably, this study did not demonstrate any significant impact of guilty feelings, nervous feelings, miserableness, or loneliness/isolation on cognition. Due to a limited number of instrumental variables for happiness, this study was unable to analyze the relationship between happiness and cognition. CONCLUSION: This MR study finds that sensitivity/hurt feelings are associated with cognitive decline, while the link between worrier/anxious feelings and cognition remains inconclusive. Insufficient evidence supports direct associations between happiness, guilty feelings, nervous feelings, miserableness, loneliness/isolation, and cognition.