Association between chronic kidney disease and age-related macular degeneration: a Mendelian randomization study.

Purpose: Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent. Methods: Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers. Results: IVW results showed that CKD, eGFR were not associated with any type of AMD (p > 0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, p = 0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, p = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, p = 4.87 × 10-8), IgAN (OR: 1.373, 95% CI: 1.097-1.719, p = 0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, p = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, p = 1.57 × 10-4) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, p = 7.55 × 10-4) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, p = 7.56 × 10-4) and MN (OR: 1.071, 95% CI: 1.040-1.103, p = 5.48 × 10-6). Conclusion: This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.

Blood metabolites and chronic kidney disease: a Mendelian randomization study.

BACKGROUND: Human blood metabolites have demonstrated close associations with chronic kidney disease (CKD) in observational studies. Nonetheless, the causal relationship between metabolites and CKD is still unclear. This study aimed to assess the associations between metabolites and CKD risk. METHODS: We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 1400 blood metabolites and eight phenotypes (outcomes) (CKD, estimated glomerular filtration rate(eGFR), urine albumin to creatinine ratio, rapid progress to CKD, rapid decline of eGFR, membranous nephropathy, immunoglobulin A nephropathy, and diabetic nephropathy). The inverse variance weighted (IVW), MR-Egger, and weighted median were used to investigate the causal relationship. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, MR-PRESSO Global test, and leave-one-out analysis. Bonferroni correction was used to test the strength of the causal relationship. RESULTS: Through the MR analysis of 1400 metabolites and eight clinical phenotypes, a total of 48 metabolites were found to be associated with various outcomes. Among them, N-acetylleucine (OR = 0.923, 95%CI: 0.89-0.957, PIVW = 1.450 × 10-5) has a strong causal relationship with lower risk of CKD after the Bonferroni-corrected test, whereas Glycine to alanine ratio has a strong causal relationship with higher risk of CKD (OR = 1.106, 95%CI: 1.063-1.151, PIVW = 5.850 × 10-7). No horizontal pleiotropy and heterogeneity were detected. CONCLUSION: Our study offers groundbreaking insights into the integration of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for CKD. It underscores 48 metabolites as potential causal candidates, meriting further investigation.

Iron-related gene mutations driving global Mycobacterium tuberculosis transmission revealed by whole-genome sequencing.

BACKGROUND: Iron plays a crucial role in the growth of Mycobacterium tuberculosis (M. tuberculosis). However, the precise regulatory mechanism governing this system requires further elucidation. Additionally, limited studies have examined the impact of gene mutations related to iron on the transmission of M. tuberculosis globally. This research aims to investigate the correlation between mutations in iron-related genes and the worldwide transmission of M. tuberculosis. RESULTS: A total of 13,532 isolates of M. tuberculosis were included in this study. Among them, 6,104 (45.11%) were identified as genomic clustered isolates, while 8,395 (62.04%) were classified as genomic clade isolates. Our results showed that a total of 12 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, such as Rv1469 (ctpD, C758T), Rv3703c (etgB, G1122T), and Rv3743c (ctpJ, G676C). Additionally, seven SNPs, including Rv0104 (T167G, T478G), Rv0211 (pckA, A302C), Rv0283 (eccB3, C423T), Rv1436 (gap, G654T), ctpD C758T, and etgB C578A, demonstrated a positive correlation with transmission clades across different countries. Notably, our findings highlighted the positive association of Rv0104 T167G, pckA A302C, eccB3 C423T, ctpD C758T, and etgB C578A with transmission clades across diverse regions. Furthermore, our analysis identified 78 SNPs that exhibited significant associations with clade size. CONCLUSIONS: Our study reveals the link between iron-related gene SNPs and M. tuberculosis transmission, offering insights into crucial factors influencing the pathogenicity of the disease. This research holds promise for targeted strategies in prevention and treatment, advancing research and interventions in this field.

Association between fatty acid metabolism gene mutations and Mycobacterium tuberculosis transmission revealed by whole genome sequencing.

BACKGROUND: Fatty acid metabolism greatly promotes the virulence and pathogenicity of Mycobacterium tuberculosis (M.tb). However, the regulatory mechanism of fatty acid metabolism in M.tb remains to be elucidated, and limited evidence about the effects of gene mutations in fatty acid metabolism on the transmission of M.tb was reported. RESULTS: Overall, a total of 3193 M.tb isolates were included in the study, of which 1596 (50%) were genomic clustered isolates. Most of the tuberculosis isolates belonged to lineage2(n = 2744,85.93%), followed by lineage4(n = 439,13.75%) and lineage3(n = 10,0.31%).Regression results showed that the mutations of gca (136,605, 317G > C, Arg106Pro; OR, 22.144; 95% CI, 2.591-189.272), ogt(1,477,346, 286G > C ,Gly96Arg; OR, 3.893; 95%CI, 1.432-10.583), and rpsA (1,834,776, 1235 C > T, Ala412Val; OR, 3.674; 95% CI, 1.217-11.091) were significantly associated with clustering; mutations in gca and rpsA were also significantly associated with clustering of lineage2. Mutation in arsA(3,001,498, 885 C > G, Thr295Thr; OR, 6.278; 95% CI, 2.508-15.711) was significantly associated with cross-regional clusters. We also found that 20 mutation sites were positively correlated with cluster size, while 11 fatty acid mutation sites were negatively correlated with cluster size. CONCLUSION: Our research results suggested that mutations in genes related to fatty acid metabolism were related to the transmission of M.tb. This research could help in the future control of the transmission of M.tb.

Association between two-component systems gene mutation and Mycobacterium tuberculosis transmission revealed by whole genome sequencing.

BACKGROUND: Two-component systems (TCSs) assume a pivotal function in Mycobacterium tuberculosis (M.tuberculosis) growth. However, the exact regulatory mechanism of this system needs to be elucidated, and only a few studies have investigated the effect of gene mutations within TCSs on M.tuberculosis transmission. This research explored the relationship between TCSs gene mutation and the global transmission of (M.tuberculosis). RESULTS: A total of 13531 M.tuberculosis strains were enrolled in the study. Most of the M.tuberculosis strains belonged to lineage4 (n=6497,48.0%), followed by lineage2 (n=5136,38.0%). Our results showed that a total of 36 single nucleotide polymorphisms (SNPs) were positively correlated with clustering of lineage2, such as Rv0758 (phoR, C820G), Rv1747(T1102C), and Rv1057(C1168T). A total of 30 SNPs showed positive correlation with clustering of lineage4, such as phoR(C182A, C1184G, C662T, T758G), Rv3764c (tcrY, G1151T), and Rv1747 C20T. A total of 19 SNPs were positively correlated with cross-country transmission of lineage2, such as phoR A575C, Rv1028c (kdpD, G383T, G1246C), and Rv1057 G817T. A total of 41 SNPs were positively correlated with cross-country transmission of lineage4, such as phoR(T758G, T327G, C284G), kdpD(G1755A, G625C), Rv1057 C980T, and Rv1747 T373G. CONCLUSIONS: Our study identified that SNPs in genes of two-component systems were related to the transmission of M. tuberculosis. This finding adds another layer of complexity to M. tuberculosis virulence and provides insight into future research that will help to elucidate a novel mechanism of M. tuberculosis pathogenicity.

Healthy City Community Space-Oriented Structural Planning and Management Optimization under COVID-19.

This work studies ways of Healthy City Construction (HCC) and Urban Governance Optimization (UGO) during the COVID-19 pandemic. The specific urban community space planning structure is proposed following a literature review on the healthy city's theoretical basis and historical development. Then, the proposed HCC-oriented community space structure is tested by surveying residents' physical and mental health and infectious risk using a questionnaire survey and Particle Swarm Optimization (PSO). Specifically, the particle fitness is calculated according to the original data conditions, and the community space with the highest fitness is determined. Based on the calculation, the community space's neighbors are investigated from different aspects through a questionnaire survey on patients' daily activities and community health security coverage. The results showed that: (1) The score of daily activities of community patients with respiratory diseases was 2312 before the implementation of the proposed community structure and 2715 after the implementation. Therefore, the service quality of residents increases after implementation. (2) The proposed HCC-oriented community space structure improves the physical self-control ability of chronic patients and helps them reduce their pain. This work aims to create a people-oriented healthy city community space, improve the city's "immune system," and regenerate the energy and environmental sustainability of the urban living environment.

Auditory attentional load attenuates age-related audiovisual integration: An EEG study.

Studies have revealed that visual attentional load modulated audiovisual integration (AVI) greatly; however, auditory and visual attentional resources are separate to some degree, and task-irrelevant auditory information could arouse much faster and larger attentional alerting effects than visible information. Here, we aimed to explore how auditory attentional load influences AVI and how aging could have an effect. Thirty older and 30 younger adults participated in an AV discrimination task with an additional auditory distractor competing for attentional resources. The race model analysis revealed highest AVI in the low auditory attentional load condition (low > no > medium > high, pairwise comparison, all p ≤ 0.047) for younger adults and a higher AVI under the no auditory attentional-load condition (p = 0.008), but there was a lower AVI under the low (p = 0.019), medium (p < 0.001), and high (p = 0.021) auditory attentional-load conditions for older adults than for younger adults. The time-frequency analysis revealed higher theta- and alpha-band AVI oscillation under no and low auditory attentional-load conditions than under medium and high auditory attentional-load conditions for both older (all p ≤ 0.011) and younger (all p ≤ 0.024) adults. Additionally, Weighted Phase lag index (WPLI) analysis revealed higher theta-band and lower alpha-band global functional connectivity for older adults during AV stimuli processing (all p ≤ 0.031). These results suggested that the AVI was higher in the low attentional-load condition than in the no attentional-load condition but decreased inversely with increasing of attentional load and that there was a significant aging effect in older adults. In addition, the strengthened theta-band global functional connectivity in older adults during AV stimuli processing might be an adaptive phenomenon for age-related perceptual decline.

Screening of Medications for Idiopathic Membranous Nephropathy Using Glomerular Whole-Genome Sequencing.

Objective: To explore medications that have a therapeutic effect on idiopathic membranous nephropathy (IMN) using the Gene Expression Omnibus (GEO), the Connectivity Map (CMap) database, and bioinformatics approaches. Methods: IMN patients' glomerular whole-genome sequencing data were retrieved and screened in the GEO database, differentially expressed genes were identified using GEO2R analysis, a PPI network was built in the STRING database, node degree values were calculated, and topological analysis was performed using the degree value to identify core genes. The WebGestalt database was used to perform GO enrichment and KEGG pathway analyses on the core genes. Candidate medications for the therapy of IMN were collected from the CMap database, and the candidate medications were then searched and analyzed. Results: 113 core genes were identified by topological analysis from the 1157 genes that were shown to be differentially expressed. The enrichment analysis identified several important gene functions and signaling pathways related to IMN. Some possible medications for the treatment of IMN have been found using the CMap database. Naringin, with the lowest CMap score, meaningful P value, and specificity score, was predicted as the most likely medication. Conclusion: The GEO and CMap databases can be used to understand the molecular changes of IMN and to provide new ideas for medication research. However, medication candidates must undergo clinical and experimental testing.

Screening and Analysis of Potential Critical Gene in Acute Myocardial Infarction Based on a miRNA-mRNA Regulatory Network.

Background: MicroRNAs (miRNAs) have been shown to be involved in the initiation, progression, and prevention of acute myocardial infarction (AMI), but the underlying mechanism remains unclear. Objective: Through the GEO database, bioinformatics methods were used to explore the miRNA-mRNA regulatory relationship pairs associated with AMI and to elucidate the underlying mechanism. Methods: Using the R software Limma package, differential expression analysis was performed using the AMI-related miRNA chip dataset (GSE31568) and mRNA chip dataset (GSE159657) from the GEO database. The miRDB, miRWalk, miRTarBase, and TargetScan databases were used to predict potential downstream target genes regulated by differentially expressed miRNAs, and a miRNA-mRNA regulatory network was built with Cytoscape; GO function and KEGG pathway enrichment analyses of target genes were done with Funrich software, and the protein interaction network of target genes in the regulatory network was built with the STRING database. Results and Conclusions: A total of 187 differentially expressed miRNAs were experimentally screened, of which 91 were upregulated (such as hsa-miR-302b, hsa-miR-1299), and 96 were downregulated (such as hsa-miR-1201, hsa-miR-1283); 507 differentially expressed mRNAs were identified, of which 430 were upregulated (such as MRM1 and SFXN4), and 77 were downregulated (such as KCTD13 and CCDC134). And 16 miRNAs and 44 mRNAs were used for regulatory network construction. GO and KEGG enrichment analyses mainly focused on Integrins in angiogenesis, angiopoietin receptor Tie2-mediated signaling, and signaling events mediated by stem cell factor receptor (c-Kit). As hub genes in the PPI network, FGF2 and MMP2 may be key targets of AMI. The experimentally constructed miRNA-mRNA regulatory network found that hsa-miR-190b targets to inhibit FGF2, while hsa-miR-330-3p targets to regulate MMP2, which may mediate Integrins in angiogenesis, Angiopoietin receptor Tie2-mediated signaling pathway to induce AMI pathogenesis, providing strong data support and a research direction for the prevention and treatment of AMI.

Construction and Bioinformatics Analysis of the miRNA-mRNA Regulatory Network in Diabetic Nephropathy.

Background: MicroRNA (miRNA) has been confirmed to be involved in the occurrence, development, and prevention of diabetic nephropathy (DN), but its mechanism of action is still unclear. Objective: With the help of the GEO database, bioinformatics methods are used to explore the miRNA-mRNA regulatory relationship pairs related to diabetic nephropathy and explain their potential mechanisms of action. Methods: The DN-related miRNA microarray dataset (GSE51674) and mRNA expression dataset (GSE30122) are downloaded through the GEO database, online analysis tool GEO2R is used for data differential expression analysis, TargetScan, miRTarBase, and miRDB databases are used to predict potential downstream target genes regulated by differentially expressed miRNAs, and intersection with differential genes is used to obtain candidate target genes. According to the regulatory relationship between miRNA and mRNA, the miRNA-mRNA relationship pair is clarified, and the miRNA-mRNA regulatory network is constructed using Cytoscape. DAVID is used to perform GO function enrichment analysis and KEGG pathway analysis of candidate target genes. By GeneMANIA prediction of miRNA target genes and coexpressed genes, the protein interaction network is constructed. Results and Conclusions. A total of 67 differentially expressed miRNAs were screened in the experiment, of which 42 were upregulated and 25 were downregulated; a total of 448 differentially expressed mRNAs were screened, of which 93 were upregulated and 355 were downregulated. Using TargetScan, miRTarBase, and miRDB databases to predict downstream targets of differentially expressed miRNAs, 2283 downstream target genes coexisting in 3 databases were predicted to intersect with differentially expressed mRNAs to obtain 96 candidate target genes. Finally, 44 miRNA-mRNA relationship pairs consisting of 12 differentially expressed miRNAs and 27 differentially expressed mRNAs were screened out; further analysis showed that miRNA regulatory network genes may participate in the occurrence and development of diabetic nephropathy through PI3K/Akt, ECM-receptor interaction pathway, and RAS signaling pathway.

Screening and Analysis of Key Genes in miRNA-mRNA Regulatory Network of Membranous Nephropathy.

Background: MicroRNAs (miRNAs) are confirmed to participate in occurrence, development, and prevention of membranous nephropathy (MN), but their mechanism of action is unclear. Objective: With the GEO database and the use of bioinformatics, miRNA-mRNA regulatory network genes relevant to MN were explored and their potential mechanism of action was explained. Methods: The MN-related miRNA chip data set (GSE51674) and mRNA chip data set (GSE108109) were downloaded from the GEO database. Differential analysis was performed using the GEO2R online tool. TargetScan, miRTarBase, and StarBase databases were used to predict potential downstream target genes regulated by differentially expressed miRNAs, and the intersection with differential genes were taken to obtain candidate target genes. According to the regulatory relationship between miRNA and mRNA, the miRNA-mRNA relationship pair was clarified and Cytoscape was used to construct a miRNA-mRNA regulatory network. WebGestalt was used to conduct enrichment analysis of the biological process of differential mRNAs in the regulatory network; FunRich analyzes the differential mRNA pathways in the miRNA-mRNA regulatory network. And the STRING database was used to construct a PPI network for candidate target genes, and Cytoscape visually analyzes the PPI network. Results: Experiments were conducted to screen differentially expressed miRNAs and mRNAs. There were 30 differentially expressed miRNAs, including 22 upregulated and 8 downregulated; and 1267 differentially expressed mRNAs, including 536 upregulated and 731 downregulated. Using TargetScan, miRTarBase, and StarBase databases to predict the downstream targets of differentially expressed miRNAs, 2957 downstream target genes coexisting in the 3 databases were predicted to intersect with differentially expressed mRNAs to obtain 175 candidate target genes. Finally, 36 miRNA-mRNA relationship pairs comprising 10 differentially expressed miRNAs and 27 differentially expressed mRNAs were screened out, and the regulatory network was constructed. Further analysis revealed that the miRNA regulatory network genes may be involved in the development of membranous nephropathy by mTOR, PDGFR-ß, LKB1, and VEGF/VEGFR signaling pathways. Conclusion: The miRNA regulatory network genes may participate in the regulation of podocyte autophagy, lipid metabolism, and renal fibrosis through mTOR, PDGFR-ß, LKB1, and VEGF/VEGFR signaling pathways, thereby affecting the occurrence and development of membranous nephropathy.

Sustained Auditory Attentional Load Decreases Audiovisual Integration in Older and Younger Adults.

The modulation of attentional load on the perception of auditory and visual information has been widely reported; however, whether attentional load alters audiovisual integration (AVI) has seldom been investigated. Here, to explore the effect of sustained auditory attentional load on AVI and the effects of aging, nineteen older and 20 younger adults performed an AV discrimination task with a rapid serial auditory presentation task competing for attentional resources. The results showed that responses to audiovisual stimuli were significantly faster than those to auditory and visual stimuli (AV > V ≥ A, all p < 0.001), and the younger adults were significantly faster than the older adults under all attentional load conditions (all p < 0.001). The analysis of the race model showed that AVI was decreased and delayed with the addition of auditory sustained attention (no_load > load_1 > load_2 > load_3 > load_4) for both older and younger adults. In addition, AVI was lower and more delayed in older adults than in younger adults in all attentional load conditions. These results suggested that auditory sustained attentional load decreased AVI and that AVI was reduced in older adults.

Exogenous Bimodal Cues Attenuate Age-Related Audiovisual Integration.

Previous studies have demonstrated that exogenous attention decreases audiovisual integration (AVI); however, whether the AVI is different when exogenous attention is elicited by bimodal and unimodal cues and its aging effect remain unclear. To clarify this matter, 20 older adults and 20 younger adults were recruited to conduct an auditory/visual discrimination task following bimodal audiovisual cues or unimodal auditory/visual cues. The results showed that the response to all stimulus types was faster in younger adults compared with older adults, and the response was faster when responding to audiovisual stimuli compared with auditory or visual stimuli. Analysis using the race model revealed that the AVI was lower in the exogenous-cue conditions compared with the no-cue condition for both older and younger adults. The AVI was observed in all exogenous-cue conditions for the younger adults (visual cue > auditory cue > audiovisual cue); however, for older adults, the AVI was only found in the visual-cue condition. In addition, the AVI was lower in older adults compared to younger adults under no- and visual-cue conditions. These results suggested that exogenous attention decreased the AVI, and the AVI was lower in exogenous attention elicited by bimodal-cue than by unimodal-cue conditions. In addition, the AVI was reduced for older adults compared with younger adults under exogenous attention.

An innovative method for oxidative degradation of chitosan with molecular oxygen catalyzed by metal phthalocyanine in neutral ionic liquid.

A novel aqueous solution-ionic liquid biphasic catalytic system was established for the oxidative degradation of chitosan under mild conditions. In this process, the environmentally acceptable and inexpensive molecular oxygen was first used as oxidant, the metal phthalocyanine was immobilized in ionic liquid as catalyst, and the aqueous solution as medium carried the reactants and the products. Under vigorous stirring and heating, the reactants fully contacted the catalysts in the emulsion and chitosan efficiently degraded into water-soluble materials. At the end of the reaction, the catalytic system could be easily separated by simple decantation and could also be reused in subsequent runs without apparent change in activity. These characters are in favor of the elimination of pollution and the reduction of the economic cost in the large-scale production of the water-soluble chitosan derivatives in chemical industry.