OBJECTIVE: The Colorado potato beetle, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae) is the most widespread insect pest that causes major economic losses, especially on potatoes. Due to heavy insecticide use, this species now resists most pesticides, posing a significant control challenge. Frequent pesticide application also harms non-target organisms, the environment, and human health. Hence, utilizing biocontrol agents like entomopathogenic fungi (EPF) offers a viable alternative for pest management. The aim of this study was to identify and characterize new EPF strains isolated from soil samples and evaluate their efficacy against adult L. decemlineata under laboratory conditions.
RESULTS: Soil samples were collected in potato fields or uncultivated areas adjacent to the field in the Czech Republic and EPF strains were isolated using a modified Tenebrio bait method. A total of 20 fungal strains were isolated and identified using morphological and molecular markers based on the 28S rRNA, ITS and elongation factor 1-alpha gene sequences as Beauveria bassiana (Bals.-Criv.) Vuill., Beauveria brongniartii (Sacc.) Petch and Cordyceps fumosorosea (Wize) Kepler, B. Shrestha & Spatafora (Hypocreales: Cordycipitaceae), Purpureocillium lilacinum (Thom.) Luangsa-ard, Houbraken, Hywel-Jones & Samson (Hypocreales: Ophiocordycipitaceae), Metarhizium brunneum (Petch) and Metarhizium robertsii Bisch., Rehner & Humber (Hypocreales: Clavicipitaceae). The bioassays revealed high variability among virulence of these strains against L. decemlineata with the shortest median time to death (LT50 = 5.0 days) in M. robertsii strain MAN3b.
CONCLUSIONS: Results shown that some EPF strains, particularly those of genera Metarhizium, can be promising biocontrol agents against the Colorado potato beetle.

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OBJECTIVE: The objective is to develop a natural and stable anti-oxidative stress and anti-ageing ingredient. In this study, we evaluated the changes in white tea leaves fermented with Eurotium cristatum PLT-PE and Saccharomyces boulardii PLT-HZ and their efficacy against skin oxidative stress.
METHODS: We employed untargeted metabolomics technology to analyse the differential metabolites between tea extract (TE) and fermented tea extract (FTE). In vitro, using H2O2-induced HaCaT cells, we evaluated cell vitality, ROS, and inflammatory factors (TNF-α, IL-1β, and IL-6). Additionally, we verified the effects on the extracellular matrix and nuclear DNA using fibroblasts or reconstructed skin models. We measured skin hydration, elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio in volunteers after using an emulsion containing 3% FTE for 28 and 56 days.
RESULTS: Targeted metabolomics analysis of white tea leaves yielded more than 20 differential metabolites with antioxidant and anti-inflammatory activities, including amino acids, polypeptides, quercetin, and liquiritin post-fermentation. FTE, compared to TE, can significantly reduce reactive oxygen species (ROS) and protect against oxidative stress-induced skin damage in H2O2-induced HaCaT cells. FTE can inhibit H2O2-induced collagen degradation by suppressing the MAPK/c-Jun signalling pathway and can also mitigate the reactive oxygen species damage to nuclear DNA. Clinical studies showed that the volunteers\' stratum corneum water content, skin elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio significantly improved from the baseline after 28 and 56 days of FTE use.
CONCLUSIONS: This study contributes to the growing body of literature supporting the protective effects against skin oxidative stress and ageing from fermented plant extracts. Moreover, our findings might inspire multidisciplinary efforts to investigate new fermentation techniques that could produce even more potent anti-ageing solutions.
OBJECTIVE: L\'objectif est de développer un ingrédient naturel et stable contre le stress oxydatif et anti‐âge. Dans cette étude, nous avons évalué les modifications dans les feuilles de thé blanc fermentées avec la PLT‐PE Eurotium cristatum et la PLT‐HZ Saccharomyces boulardii et leur efficacité contre le stress oxydatif cutané. MÉTHODES: Nous avons utilisé une technologie de métabolomique non ciblée pour analyser les métabolites différentiels entre l\'extrait de thé (ET) et l\'extrait de thé fermenté (ETF). In vitro, à l\'aide de cellules HaCaT induites par l\'H2O2, nous avons évalué la vitalité cellulaire, les ERO et les facteurs inflammatoires (TNF‐α, IL‐1β, and IL‐6). Nous avons également vérifié les effets sur la matrice extracellulaire et l\'ADN nucléaire à l\'aide de fibroblastes ou de modèles cutanés reconstruits. Nous avons mesuré l\'hydratation de la peau, l\'élasticité, la surface de rides, le rapport des surfaces de rides, la surface d\'érythème, et le rapport des surfaces d\'érythème chez des volontaires ayant utilisé une émulsion contenant 3% d\'ETF pendant 28 et 56 jours. RÉSULTATS: L\'analyse métabolomique ciblée des feuilles de thé blanc a révélé plus de 20 métabolites différentiels ayant des activités antioxydantes et anti‐inflammatoires, notamment des acides aminés, des polypeptides, de la quercétine et de la liquiritine après fermentation. Par rapport à l\'ET, l\'ETF peut réduire significativement les espèces réactives de l\'oxygène (ERO) et protéger contre les lésions cutanées induites par le stress oxydatif dans les cellules HaCaT induites par l\'H2O2. L\'ETF peut inhiber la dégradation du collagène induite par l\'H2O2 en supprimant la voie de signalization MAPK/c‐Jun et peut également atténuer les dommages causés par les espèces réactives de l\'oxygène à l\'ADN nucléaire. Les études cliniques ont montré que la teneur en eau de la couche cornée des volontaires, l\'élasticité de la peau, la surface de rides, le rapport des surfaces de rides, la surface d\'érythème et le rapport des surfaces d\'érythème se sont significativement améliorés par rapport à la référence après 28 et 56 jours d\'utilisation d\'ETF.
CONCLUSIONS: Cette étude contribue au corpus croissant de littérature soutenant les effets protecteurs des extraits de plantes fermentées contre le stress oxydatif cutané et le vieillissement. En outre, nos résultats pourraient inspirer des efforts pluridisciplinaires pour étudier de nouvelles techniques de fermentation susceptibles de produire des solutions anti‐âge encore plus puissantes.

Plasma proteins are promising biomarkers and potential drug targets for stroke. This study aimed to explore whether there is a causal relationship between plasma proteins and subtypes of stroke using a Mendelian randomization (MR) approach. A two-sample bidirectional Mendelian randomization approach was employed to investigate the causal link between plasma proteins and stroke. Data on plasma proteins were obtained from three studies, including INTERVAL, and pooled stroke information was sourced from the MEGASTROKE consortium and the UK Biobank dataset, covering four subtypes of stroke. MR analyses were primarily conducted using inverse variance weighting, and sensitivity analyses were also performed. Finally, potential reverse causality was assessed using bidirectional MR. We identified two proteins causally associated with stroke: one as a potential therapeutic target and another as a protective factor. CXCL8 was found to be positively associated with the risk of developing large-artery atherosclerotic (LAA) stroke (OR, 1.005; 95% CI 1.001 to 1.010; p = 0.022), whereas TNFRSF11b was negatively correlated with the risk of developing LAA stroke (OR, 0.937; 95% CI 0.892 to 0.984; p = 0.010), independently of other stroke subtypes. Reverse bivariate analysis did not indicate that ischemic stroke was causally associated with CXCL8 and TNFRSF11b. There is a causal relationship between CXCL8 and TNFRSF11b with LAA stroke, independent of other subtypes. This study offers a new perspective on the genetics of stroke.

BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1.
METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis.
RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations.
CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.

Although age-dependent alterations in urinary magnesium (Mg2+) excretion have been described, the underlying mechanism remains elusive. As heritability significantly contributes to variations in urinary Mg2+excretion, we measured urinary Mg2+ excretion at different ages in a cohort of genetically variable Diversity Outbred (DO) mice. Compared to animals aged 6 months, an increase in Mg2+ excretion was observed at 12 and 18 months. Quantitative trait locus (QTL) analysis revealed an association of a locus on chromosome 10 with Mg2+ excretion at 6 months of age, with Oit3 (encoding oncoprotein-induced transcript 3; OIT3) as our primary candidate gene. To study the possible role of OIT3 in renal Mg2+ handling, we generated and characterized Oit3 knockout (Oit3-/-) mice. Although a slightly lower serum Mg2+ concentration was present in male Oit3-/- mice, this effect was not observed in female Oit3-/- mice. Additionally, urinary Mg2+ excretion and the expression of renal magnesiotropic genes was unaltered in Oit3-/- mice. For animals aged 12 and 18 months, QTL analysis revealed an association with a locus on chromosome 19, which contains the gene encoding TRPM6, a known Mg2+ channel involved in renal Mg2+ reabsorption. Comparison with RNAseq data revealed that Trpm6 mRNA expression is inversely correlated with the QTL effect, implying that TRPM6 may be involved in age-dependent changes in urinary Mg2+ excretion in mice. In conclusion, we show here that variants in Oit3 and Trpm6 are associated with urinary Mg2+ excretion at distinct periods in life, although OIT3 is unlikely to affect renal Mg2+ handling.

Human ascariasis is a soil-transmitted helminthiasis and remains a neglected tropical disease. Ascaris suum has the potential to cause cross-infections between humans and pigs. In this study, we present a rare case of a patient with asymptomatic infection by Ascaris suum. A 66-year-old male underwent colonoscopy, and a white linear worm body was found in the hepatic curvature. The worm was collected by aspiration and submitted to the laboratory for parasite identification. The patient had no symptoms related to parasitic infection. The worm was highly suspected to be of the genus Ascaris. Because of the difficulty of morphological classification, genetic analysis was performed. From PCR-restriction fragment length polymorphism results and sequence analysis of the internal transcribed spacer-1 region, it was determined to be A. suum. The experience with rapid differentiation of A. suum by performing genetic analysis will be useful for future examinations of parasitic infections.

This study aims to investigate the causal relationship between primary Sjögren\'s syndrome (SS) and multiple sclerosis (MS) using a two-sample Mendelian randomization (MR) analysis to provide insights into their common mechanisms and implications for therapeutic strategies. We utilized data from Genome-Wide Association Studies (GWAS) for primary SS (1,290 cases and 213,145 controls) and MS (4,888 cases and 10,395 controls), restricted to European ancestry. Instrumental variables (IVs) were selected based on genetic variants associated with primary SS. The primary MR method was Inverse Variance Weighted (IVW), supplemented by MR Egger, Weighted Median, Simple Mode, and Weighted Mode algorithms to assess the bidirectional causal relationships between MS and primary SS. Sensitivity analyses, including MR-PRESSO and leave-one-out analysis, were conducted to ensure the robustness of our findings. After excluding SNPs with pleiotropic effects, 42 and 5 SNPs were identified as robust IVs for primary SS and MS, respectively. Our analysis revealed a significant protective effect of MS on primary SS, with IVW showing an OR of 0.896 (95% CI: 0.841-0.954, P = 0.001). No significant heterogeneity or horizontal pleiotropy was detected, supporting the reliability of the results. Our findings suggest a potential protective effect of MS against primary SS, indicating a negative causal association between these two autoimmune diseases. This adds valuable genetic evidence to the understanding of the complex interplay between primary SS and MS, offering new avenues for research and therapeutic interventions.

UNASSIGNED: This research explores the causal association between circulating inflammatory markers and the development of sciatica, a common and debilitating condition. While previous studies have indicated that inflammation may be a factor in sciatica, but a thorough genetic investigation to determine a cause-and-effect relationship has not yet been carried out. Gaining insight into these interactions may uncover novel treatment targets.
UNASSIGNED: We utilized data from the OpenGWAS database, incorporating a large European cohort of 484,598 individuals, including 4,549 sciatica patients. Our study focused on 91 distinct circulating inflammatory markers. Genetic variations were employed as instrumental variables (IVs) for these markers. The analysis was conducted using inverse variance weighting (IVW) as the primary method, supplemented by weighted median-based estimation. Validation of the findings was conducted by sensitivity studies, utilizing the R software for statistical computations.
UNASSIGNED: The analysis revealed that 52 out of the 91 inflammatory markers studied showed a significant causal association with the risk of developing sciatica. Key markers like CCL2, monocyte chemotactic protein-4, and protein S100-A12 demonstrated a positive correlation. In addition, there was no heterogeneity or horizontal pleiotropy in these results. Interestingly, a reverse Mendelian randomization analysis also indicated potential causative effects of sciatica on certain inflammatory markers, notably Fms-related tyrosine kinase 3 ligands.
UNASSIGNED: The study provides robust evidence linking specific circulating inflammatory markers with the risk of sciatica, highlighting the role of inflammation in its pathogenesis. These findings could inform future research into targeted treatments and enhance our understanding of the biological mechanisms underlying sciatica.

A total of 3,860 accessions from the global in trust clonal potato germplasm collection w3ere genotyped with the Illumina Infinium SolCAP V2 12K potato SNP array to evaluate genetic diversity and population structure within the potato germplasm collection. Diploid, triploid, tetraploid, and pentaploid accessions were included representing the cultivated potato taxa. Heterozygosity ranged from 9.7% to 66.6% increasing with ploidy level with an average heterozygosity of 33.5%. Identity, relatedness, and ancestry were evaluated using hierarchal clustering and model-based Bayesian admixture analyses. Errors in genetic identity were revealed in a side-by-side comparison of in vitro clonal material with the original mother plants revealing mistakes putatively occurring during decades of processing and handling. A phylogeny was constructed to evaluate inter- and intraspecific relationships which together with a STRUCTURE analysis supported both commonly used treatments of potato taxonomy. Accessions generally clustered based on taxonomic and ploidy classifications with some exceptions but did not consistently cluster by geographic origin. STRUCTURE analysis identified putative hybrids and suggested six genetic clusters in the cultivated potato collection with extensive gene flow occurring among the potato populations, implying most populations readily shared alleles and that introgression is common in potato. Solanum tuberosum subsp. andigena (ADG) and S. curtilobum (CUR) displayed significant admixture. ADG likely has extensive admixture due to its broad geographic distribution. Solanum phureja (PHU), Solanum chaucha (CHA)/Solanum stenotomum subsp. stenotomum (STN), and Solanum tuberosum subsp. tuberosum (TBR) populations had less admixture from an accession/population perspective relative to the species evaluated. A core and mini core subset from the genebank material was also constructed. SNP genotyping was also carried out on 745 accessions from the Seed Savers potato collection which confirmed no genetic duplication between the two potato collections, suggesting that the collections hold very different genetic resources of potato. The Infinium SNP Potato Array is a powerful tool that can provide diversity assessments, fingerprint genebank accessions for quality management programs, use in research and breeding, and provide insights into the complex genetic structure and hybrid origin of the diversity present in potato genetic resource collections.