CD147 TagSNP is associated with the vulnerability to lung cancer in the Chinese population: a case-control study.

BACKGROUND: Lung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population. METHODS: A hospital-based case-control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses. RESULTS: Baseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype. CONCLUSIONS: CD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

Phylogenetic relationships and genetic diversity of the Korean endemic Phedimus latiovalifolius (Crassulaceae) and its close relatives.

Phedimus latiovalifolius (Y.N.Lee) D.C.Son & H.J.Kim is exclusively distributed in the high mountains in the Korean Peninsula, mainly along the Baekdudaegan mountain range. Despite its morphological and distributional distinction from other Phedimus Raf. species, its taxonomic identity and phylogenetic relationship with congeneric species remain unclear. This study employs genotyping-by-sequencing-derived genome-wide single nucleotide polymorphisms to establish the monophyly of P. latiovalifolius and its relationship with closely related species. Genetic diversity and population differentiation of P. latiovalifolius are also assessed to provide baseline genetic information for future conservation and management strategies. Our phylogenetic analyses robustly demonstrate the monophyletic nature of P. latiovalifolius, with P. aizoon (L.) 't Hart identified as its closest sister lineage. There is no genetic evidence supporting a hybrid origin of P. latiovalifolius from P. aizoon involving either P. ellacombeanus (Praeger) 't Hart or P. kamtschaticus (Fisch.) 't Hart. Population genetic analyses reveal two major groups within P. latiovalifolius. A higher genetic variation is observed in P. ellacombeanus than in the congeneric species. Notably, most of the genetic variation exists within P. latiovalifolius populations. Given its distribution and the potential role of Baekdudaegan as an East Asian Pleistocene refugia, P. latiovalifolius could be considered rare and endemic, persisting in the refugium across glacial/interglacial cycles.

Effective population size in field pea.

BACKGROUND: Effective population size (Ne) is a pivotal parameter in population genetics as it can provide information on the rate of inbreeding and the contemporary status of genetic diversity in breeding populations. The population with smaller Ne can lead to faster inbreeding, with little potential for genetic gain making selections ineffective. The importance of Ne has become increasingly recognized in plant breeding, which can help breeders monitor and enhance the genetic variability or redesign their selection protocols. Here, we present the first Ne estimates based on linkage disequilibrium (LD) in the pea genome. RESULTS: We calculated and compared Ne using SNP markers from North Dakota State University (NDSU) modern breeding lines and United States Department of Agriculture (USDA) diversity panel. The extent of LD was highly variable not only between populations but also among different regions and chromosomes of the genome. Overall, NDSU had a higher and longer-range LD than the USDA that could extend up to 500 Kb, with a genome-wide average r2 of 0.57 (vs 0.34), likely due to its lower recombination rates and the selection background. The estimated Ne for the USDA was nearly three-fold higher (Ne = 174) than NDSU (Ne = 64), which can be confounded by a high degree of population structure due to the selfing nature of pea. CONCLUSIONS: Our results provided insights into the genetic diversity of the germplasm studied, which can guide plant breeders to actively monitor Ne in successive cycles of breeding to sustain viability of the breeding efforts in the long term.

Dihydroorotase MoPyr4 is required for development, pathogenicity, and autophagy in rice blast fungus.

Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5'-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.

Whole genome sequencing and genomic characteristics analysis of carbapenem-resistant Acinetobacter baumannii clinical isolates in two hospitals in China.

Nosocomial outbreaks caused by carbapenem-resistant Acinetobacter baumannii (CRAB) strains are rapidly emerging worldwide and are cause for concern. Herein, we aimed to describe the genomic characteristics of CRAB strains isolated from two hospitals in China in 2023. The A. baumannii isolates were mainly collected from the ICU and isolated from the sputum (71.43%, 15/21), followed by urine (14.29%, 3/21). Twenty-one A. baumannii strains possessed a multidrug-resistant (MDR) profile, and whole-genome sequencing showed that they all carried blaOXA-23. Based on the Pasteur multilocus sequence typing (MLST) scheme, all strains were typed into a sequence type 2 (ST2). Based on the Oxford MLST scheme, six strains belonged to ST540, three of which were ST208, and four strains were assigned to ST784. Kaptive showed most of the strains (38.10%, 8/21) contained KL93. As for the lipoolygosaccharide (OC locus) type, OCL1c and OCL1d were identified, accounting for 33.33% (7/21) and 66.67% (14/21), respectively. Based on the BacWGSTdb server, we found that the strains belonging to ST540 and ST784 were all collected from China. However, the ST938 strains were isolated from Malaysia and Thailand. Comparative genomics analysis showed that the AB10 strain had a closed relationship with SXAB10-SXAB13 strains, suggesting the transmission happened in these two hospitals and other hospital in China. In addition, the 4300STDY7045869 strain, which was collected from Thailand, possessed near genetic relationship with our isolates in this study, suggesting the possible spread among various countries. Additionally, 3-237 single nucleotide polymorphisms were observed among these strains. In conclusion, this study conducted a genome-based study for A. baumannii strains collected from two hospitals in China and revealed their epidemiological and molecular features. Clone spreading occurred in these two hospitals. Hence, there is an urgent need for increased surveillance in hospitals and other clinical settings to prevent and control CRAB spreading.

Transcriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism.

BACKGROUND: Two important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE). METHODS: In this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls). FINDINGS: Sixteen genes showed an association with PDAC risk (FDR <0.10), including six genes not yet reported for PDAC risk (PPIP5K2, TFR2, HNF4G, LRRC10B, PRC1 and FBXL20) and ten previously reported genes (INHBA, SMC2, ABO, PDX1, MTMR6, ACOT2, PGAP3, STARD3, GSDMB, ADAM33). MR provided support for a causal effect of PDAC on T2D using genetic instruments in the HNF4G and PDX1 loci, and unidirectional causality of VTE on PDAC involving the ABO locus (OR 2.12, P < 1e-7). No evidence of a causal effect of PDAC on VTE was found. INTERPRETATION: These analyses identified candidate susceptibility genes and disease relationships for PDAC that warrant further investigation. HNF4G and PDX1 may induce PDAC-associated diabetes, whereas ABO may induce the causative effect of VTE on PDAC. FUNDING: National Institutes of Health (USA).

Associations of modifiable factors with risk of irritable bowel syndrome.

Background: Modifiable factors were found to be associated with the risk of irritable bowel syndrome (IBS) in observational studies, but whether these associations are causal is uncertain. We conducted a Mendelian randomization (MR) study to systematically explore the causal associations of modifiable factors with IBS. Methods: Summary-level statistical data for IBS was obtained from a genome-wide association study (GWAS) meta-analysis of UK Biobank (40,548 cases and 293,220 controls) and the international collaborative Bellygenes initiative (12,852 cases and 139,981 controls). Genetic instruments associated with the exposures at the genome-wide significance (p < 5 × 10-8) level were selected from previous GWASs. Mendelian randomization was performed using inverse-variance weighted (IVW) method, supplemented with several sensitivity analyses to evaluate potentially causal relationships between identified contributing factors and IBS. Furthermore, we applied another database from FinnGen (8,116 IBS cases and 276,683 controls) to testify the reliability of the significant associations. Results: Seven convincing modifiable factors were significantly associated with IBS after correction for multiple testing. Genetically predicted smoking initiation (OR = 1.12, 95% CI = 1.06-1.18, p = 1.03 × 10-4), alcohol consumption (OR = 0.47, 95% CI = 0.34-0.64, p = 3.49 × 10-6), sedentary behavior (OR = 1.17, 95% CI = 1.07-1.28, p = 4.02 × 10-4), chronotype (OR = 0.92, 95% CI = 0.88-0.96, p = 4.42 × 10-4), insomnia (OR = 1.19, 95% CI = 1.15-1.24, p = 7.59 × 10-19), education (OR = 0.80, 95% CI = 0.74-0.88, p = 5.34 × 10-7), and visceral adiposity (OR = 1.15, 95% CI = 1.06-1.24, p = 7.96 × 10-4). We additionally identified several suggestive factors, including serum magnesium, serum phosphorus, physical activity, lifetime smoking, intelligence, lean body mass, and body mass index (BMI). After pooling the effect estimates from FinnGen, the associations remained significant except for chronotype. Conclusion: This MR analysis verified several modifiable risk factors for IBS, thus prevention strategies for IBS should be considered from multiple perspectives on these risk factors.

Association between rs1799724 of TNF- α gene and early onset preeclampsia in Chinese: A pilot study.

Objective: To investigate the association between polymorphisms of TNF- α (rs1799724, rs1800629), VEGF (rs3025039) and VEGFR1 (rs 722503) and early onset preeclampsia (EOPE) in Chinese. Methods: A total of 132 EOPE patients from January 2016 to December 2018 at the Second Hospital of Tianjin Medical University were selected as the EOPE group, and 156 normal pregnant patients as the Control group. In both groups, 5 ml of peripheral venous blood was obtained after admission. The characteristics of genotype and allele distribution at the four SNPs in the study subjects were examined by matrix-assisted laser desorption ionization time-of-flight mass spectrometric genotyping. Results: The genotype frequency distribution and allele frequency distribution of rs1799724 were significantly different between the EOPE group and the Control group (P = 0.002，P = 0.003). The T allele was statistically associated with the development of EOPE under a dominant genetic model (P = 0.001). The genotype and allele frequency distributions of rs1800629, rs3025039, and rs 722503 did not differ significantly between the EOPE group and the Control group (P > 0.05). There was no linkage disequilibrium among rs1799724, rs1800629 and rs3025039 loci, the corresponding haploid cannot be formed. Conclusions: The rs1799724 of TNF- α gene is a genetic susceptibility locus for EOPE and may be a potential predictors of preeclampsia.

A modular inquiry-based semester theme that integrates data science education and bioinformatics in protein structure function courses.

BACKGROUND: With an exponential growth in biological data and computing power, familiarity with bioinformatics has become a demanding and popular skill set both in academia and industry. There is a need to increase students' competencies to be able to take on bioinformatic careers, to get them familiarized with scientific professions in data science and the academic training required to pursue them, in a field where demand outweighs the supply. METHODS: Here we implemented a set of bioinformatic activities into a protein structure and function course of a graduate program. Concisely, students were given hands-on opportunities to explore the bioinformatics-based analyses of biomolecular data and structural biology via a semester-long case study structured as inquiry-based bioinformatics exercises. Towards the end of the term, the students also designed and presented an assignment project that allowed them to document the unknown protein that they identified using bioinformatic knowledge during the term. RESULTS: The post-module survey responses and students' performances in the lab module imply that it furthered an in-depth knowledge of bioinformatics. Despite having not much prior knowledge of bioinformatics prior to taking this module students indicated positive feedback. CONCLUSION: The students got familiar with cross-indexed databases that interlink important data about proteins, enzymes as well as genes. The essential skillsets honed by this research-based bioinformatic pedagogical approach will empower students to be able to leverage this knowledge for their future endeavours in the bioinformatics field.

The promoter polymorphism rs3918226 of endothelial nitric oxide synthase gene as a novel susceptibility marker for peripheral artery disease.

OBJECTIVES: This pilot study aimed to investigate the association between the single nucleotide polymorphism (SNP) rs3918226 in the promoter of the nitric oxide synthase (NOS3) gene and the risk of peripheral artery disease (PAD). METHODS: DNA samples from 1263 unrelated subjects of Slavic origin, including 620 patients with PAD and 643 controls, were genotyped for the SNP rs3918226 using the MassArray-4 system. RESULTS: The rs3918226 polymorphism was found to be strongly associated with an increased risk of PAD regardless of coronary artery disease, hypertension, or cigarette smoking (OR=2.86, 95%CI 1.89-4.32, Pperm<0.0001). The SNP-PAD association was in almost three times stronger in females (OR=8.31 95%CI 3.07-22.48) than in males (OR=1.79 95%CI 1.10-2.93). SNP rs3918226 was correlated with ankle brachial index (ABI) and total plasma cholesterol in patients with PAD (Рperm<0.05). The NOS3 polymorphism was closely associated with SNPs rs7692387 and rs13139571 in GUCY1A3 to determine the risk of PAD, suggesting that the rs3918226 polymorphism may disrupt signaling in the nitric oxide-soluble guanylyl cyclase pathway. Diplotypes with wild-type alleles, such as NOS3 rs3918226-C/C×GUCY1A1 rs7692387G/G and NOS3 rs3918226-C/C×GUCY1A1 rs13139571C/C, showed strong protection against disease risk (FDR≤0.001). Functional SNP annotation revealed that the allele rs3918226-T was associated with decreased expression of NOS3, most strongly in the tibial arteries than in the coronary artery or aorta. CONCLUSIONS: The present study is the first to show that the rs3918226 polymorphism of NOS3 is a novel susceptibility marker for peripheral artery disease. Further research in independent populations is necessary to reproduce the association between polymorphism rs3918226 and disease risk.

Serum S-adenosylhomocysteine, rather than homocysteine, is associated with hepatocellular carcinoma survival: a prospective cohort study.

BACKGROUND: Emerging evidence suggested that S-adenosylhomocysteine (SAH) may be a better serum biomarker for cardiovascular disease than homocysteine (Hcy). However, the role of SAH in hepatocellular carcinoma (HCC) prognosis remains unclear. OBJECTIVES: We aimed to prospectively explore the relationships between serum SAH and related metabolites (Hcy, S-adenosylmethionine [SAM]) with HCC survival, and to evaluate the effect modifications by gene polymorphisms in one-carbon metabolism key enzymes. METHODS: We included 1,080 newly diagnosed HCC patients from the Guangdong Liver Cancer Cohort. Serum SAH, Hcy, and SAM were measured utilizing HPLC-MS/MS. Gene polymorphisms in one-carbon metabolism key enzymes were identified using competitive allele-specific PCR (KASP). Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariate Cox proportional hazards models. RESULTS: After a median follow-up of 3.6 years, 601 deaths occurred, with 552 (92%) attributed to HCC. Multivariable analysis revealed that patients in the highest quartile of serum SAH concentrations were significantly associated with worse survival compared to those in the lowest quartile, with HRs of 1.58 (95% CI: 1.19, 2.10; P-trend = 0.002) for LCSS and 1.54 (95% CI: 1.18, 2.02; P-trend = 0.001) for OS. There were no significant interactions between serum SAH concentrations and genetic variants of one-carbon metabolism key enzymes. No significant associations were found between serum Hcy, SAM concentrations and SAM/SAH ratio with LCSS or OS. CONCLUSIONS: Higher serum SAH concentrations, rather than homocysteine, were independently associated with worse survival in HCC patients, regardless of the genetic variants of one-carbon metabolism key enzymes. These findings suggesting that SAH may serve as a novel metabolism-related prognostic biomarker for HCC.

Molecular basis and functional consequences of the interaction between the Base Excision Repair DNA glycosylase NEIL1 and RPA.

NEIL1 is a DNA glycosylase that recognizes and initiates base excision repair of oxidized bases. The ubiquitous ssDNA binding scaffolding protein, replication protein A (RPA), modulates NEIL1 activity in a manner that depends on DNA structure. Interaction between NEIL1 and RPA has been reported, but the molecular basis of this interaction has yet to be investigated. Using a combination of NMR spectroscopy and isothermal titration calorimetry (ITC), we show that NEIL1 interacts with RPA through two contact points. An interaction with the RPA32C protein recruitment domain was mapped to a motif in the common interaction domain (CID) of NEIL1 and a dissociation constant (Kd) of 200 nM was measured. A substantially weaker secondary interaction with the tandem RPA70AB ssDNA binding domains was also mapped to the CID. Together these two contact points reveal NEIL1 has a high overall affinity (Kd ∼ 20 nM) for RPA. A homology model of the complex of RPA32C with the NEIL1 RPA binding motif in the CID was generated and used to design a set of mutations in NEIL1 to disrupt the interaction, which was confirmed by ITC. The mutant NEIL1 remains catalytically active against a thymine glycol lesion in duplex DNA in vitro. Testing the functional effect of disrupting the NEIL1-RPA interaction in vivo using a Fluorescence Multiplex-Host Cell Reactivation (FM-HCR) reporter assay revealed an unexpected role for NEIL1 in nucleotide excision repair. These findings are discussed in the context of the role of NEIL1 in replication-associated repair.

Mechanistic insights into mesenchymal-amoeboid transition as an intelligent cellular adaptation in cancer metastasis and resistance.

Malignant cell plasticity is an important hallmark of tumor biology and crucial for metastasis and resistance. Cell plasticity lets cancer cells adapt to and escape the therapeutic strategies, which is the leading cause of cancer patient mortality. Epithelial cells acquire mobility via epithelial-mesenchymal transition (EMT), whereas mesenchymal cells enhance their migratory ability and clonogenic potential by acquiring amoeboid characteristics through mesenchymal-amoeboid transition (MAT). Tumor formation, progression, and metastasis depend on the tumor microenvironment (TME), a complex ecosystem within and around a tumor. Through increased migration and metastasis of cancer cells, the TME also contributes to malignancy. This review underscores the distinction between invasion pattern morphological manifestations and the diverse structures found within the TME. Furthermore, the mechanisms by which amoeboid-associated characteristics promote resistance and metastasis and how these mechanisms may represent therapeutic opportunities are discussed.

Association between primary biliary cholangitis with diabetes and cardiovascular diseases: A bidirectional multivariable Mendelian randomization study.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs). METHODS: Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836). RESULTS: SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models. CONCLUSION: Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.

Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.

Homocysteine thiolactone (HTL), a toxic metabolite of homocysteine (Hcy) in hyperhomocysteinemia (HHcy), is known to modify protein structure and function, leading to protein damage through formation of N-Hcy-protein. HTL has been highly linked to HHcy-associated cardiovascular and neurodegenerative diseases. The protective role of HTL hydrolases against HTL-associated vascular toxicity and neurotoxicity have been reported. Although several endogeneous enzymes capable of hydrolyzing HTL have been identified, the primary enzyme responsible for its metabolism remains unclear. In this study, three human carboxylesterases were screened to explore new HTL hydrolase and human carboxylesterase 1 (hCES1) demonstrates the highest catalytic activity against HTL. Given the abundance of hCES1 in the liver and the clinical significance of its single-nucleotide polymorphisms (SNPs), six common hCES1 nonsynonymous coding SNP (nsSNPs) variants were examined and characterized for their kinetic parameters. Variants E220G and G143E displayed 7.3-fold and 13.2-fold lower catalytic activities than its wild-type counterpart. In addition, the detailed catalytic mechanism of hCES1 for HTL hydrolysis was computational investigated and elucidated by Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) method. The function of residues E220 and G143 in sustaining its hydrolytic activity of hCES1 was analyzed, and the calculated energy difference aligns well with experimental-derived results, supporting the validity of our computational insights. These findings provide insights into the potential protective role of hCES1 against HTL-associated toxicity, and warrant future studies on the possible association between specific genetic variants of hCES1 with impaired catalytic function and clinical susceptibility of HTL-associated cardiovascular and neurodegenerative diseases.

Genetic Variants in the Fat Mass and Obesity-Associated Gene and Risk of Obesity/Overweight in Children and Adolescents: A Systematic Review and Meta-Analysis.

OBJECTIVE: The variations in the single-nucleotide polymorphisms (SNPs) of the fat mass and obesity (FTO)-associated gene have been linked to being overweight or obese in children. In this research a thorough examination was performed to elucidate the connection between various FTO gene SNPs and overweight or obesity in children and adolescents. METHOD: We searched PubMed, Google scholar, Web of Science and Scopus until January 2024 to find studies that investigate the association between different SNPs of FTO gene and the risk of overweight/obesity in children and adolescents. After filtering the relevant studies, meta-analysis was used to quantify the association of FTO gene SNPs within different genetic inheritance models. RESULTS: We have identified 32 eligible studies with 14,930 obese/overweight cases and 24,765 healthy controls. Our recessive model showed a significant association with rs9939609 (OR: 1.56, 95% CI: 1.20; 2.02, p < 0.01) and rs1421085 (OR: 1.77, 95% CI: 1.14; 2.75, p < 0.01). Besides, in the homozygote model, rs1421085 showed the highest association (OR: 2.32, 95% CI: 1.38; 3.89, p < 0.01) with the risk of obesity in a population of children and adolescents. Moreover, there are other SNPs of FTO genes, such as rs9921255, rs9928094 and rs9930333, which showed a positive association with obesity and overweight. However, their effects were evaluated in very few numbers of studies. CONCLUSION: In this study, we have found that the FTO rs9939609 and rs1421085 are associated to an increased risk of obesity among children and adolescents. Besides, the findings of this study further reaffirmed the established link between rs9939609 and obesity in children and adolescents.

Multiplexing Imaging of Closely Located Single-Nucleotide Mutations in Single Cells via Encoded in situ PCR.

Mutation accumulation in RNAs results in closely located single-nucleotide mutations (SNMs), which is highly associated with the drug resistance of pathogens. Imaging of SNMs in single cells has significance for understanding the heterogeneity of RNAs that are related to drug resistance, but the direct "see" closely located SNMs remains challenging. Herein, we designed an encoded ligation-mediated in situ polymerase chain reaction method (termed enPCR), which enabled the visualization of multiple closely located SNMs in bacterial RNAs. Unlike conventional ligation-based probes that can only discriminate a single SNM, this method can simultaneously image different SNMs at closely located sites with single-cell resolution using modular anchoring probes and encoded PCR primers. We tested the capacity of the method to detect closely located SNMs related to quinolone resistance in the gyrA gene of Salmonella enterica (S. enterica), and found that the simultaneous detection of the closely located SNMs can more precisely indicate the resistance of the S. enterica to quinolone compared to the detection of one SNM. The multiplexing imaging assay for SNMs can serve to reveal the relationship between complex cellular genotypes and phenotypes.

Corrigendum: Patterns of within-host spread of Chlamydia trachomatis between vagina, endocervix and rectum revealed by comparative genomic analysis.

[This corrects the article DOI: 10.3389/fmicb.2023.1154664.].

A comparative study of the effect of high-pressure and low temperature on the crystal structure of lithium xanthinate hydrate.

The crystal structure of lithium xanthinate hydrate was studied by single crystal X-ray diffraction and Raman spectroscopy on cooling to 100 K and under compression to 5.3 GPa. A phase transition at ∼4 GPa is observed. No phase transitions occur on cooling. Anisotropy of lattice strain and changes in intermolecular interactions are compared.

Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study.

Introduction: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation. Methods: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments. Results: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland. Conclusion: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.