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Genetic Diversity and Population Structure of Urban and Rural Goshawks.

Urbanization poses a growing threat to biodiversity with potential impacts on species' genetic diversity and population structure. The Eurasian goshawk (Astur gentilis) is traditionally a forest-dwelling raptor that has recently established breeding populations in urban environments such as Helsinki, Finland. Here, we investigated genetic diversity and population structure across urban, suburban, and rural goshawk populations in Finland using 10 microsatellite markers and 72 individuals sampled between 1990 and 2020. Genetic diversity, measured by heterozygosity and allelic richness, was similar among populations. Genetic differentiation was low to moderate (F ST = 0.022-0.074) and statistically non-significant. Despite urbanization, contemporary urban goshawks showed genetic similarity to adjacent contemporary non-urban goshawks, while greater differentiation was observed between temporally separated populations. Consistent with this pattern, clustering supported K = 2 as the primary level of genetic structure, separating the contemporary urban and surrounding populations from the earlier surrounding and rural populations. Given the limited marker set and sample sizes, these findings are interpreted as broad-scale patterns rather than definitive evidence of fine-scale population structure. Further studies using larger sample sizes and genome-wide markers are needed to resolve population connectivity and the longer-term genetic effects of urbanization.

Astur gentilis↗

Halosimplex yunnanense sp. nov., a novel haloarchaeon from an underground salt mine.

Strain J119T, a halophilic archaeon, was isolated from a salt mine sample collected in Yunnan Province, China. Cells are spherical (diameter 0.5-0.7 µm) or short‑rod‑shaped (0.4-0.5 × 0.7-0.8 µm), non‑motile, Gram‑stain‑negative, and can grow at 20-55°C (optimum 42°C), with NaCl tolerance ranging from 15% to 30% (w/v) (optimum 20%) and a pH growth range of 5.5-9.0 (optimum pH 7.0). Strain J119T's nearly complete 16S rRNA gene sequence (1,452 bp; accession MW736888.1) shows the highest sequence similarity (97.32%) to Halosimplex salinum YPL4T; this value is lower than the species boundary threshold of 98.65%. Its rpoB' gene (1,830 bp; NZ_JBTJEL000000000.1) shares the highest similarity (95.52%) with Halosimplex aquaticum XZYJT29T. Genomic analyses revealed that the average amino acid identity, average nucleotide identity and digital DNA-DNA hybridization values between strain J119T and strains YPL4T and XZYJT29T were 78.58%, 82.59%, 25.50% and 82.61%, 85.70%, 29.20%, respectively. The genomic DNA G + C content of strain J119T is 66.5%. Phenotypic, phylogenetic, and genome-based analyses suggest that strain J119T (= KCTC 4326T = MCCC 4K00178T) represents a novel species of the genus Halosimplex, for which the name Halosimplex yunnanense sp. nov. is proposed.

RNA, Ribosomal, 16S↗

Genomic and Structural Analysis of Gamete Recognition Proteins in a Broadcast Spawning Echinoderm Mesocentrotus franciscanus.

Gamete recognition proteins are expressed on the surfaces of sperm and eggs, where they mediate interactions between gametes. The genetic basis for gamete recognition proteins, as well as their structure and interactions, have yet to be fully resolved. Using a new high-quality de novo genome assembly for the sea urchin Mesocentrotus franciscanus, we investigated the genomic structure, expression, and protein forms of several gamete recognition proteins: sperm bindin, egg receptor for sperm (HSP110), and egg bindin receptor (EBR1), as well as the receptor for egg jelly (REJ) and its paralogs. To inform future population genetic and evolutionary studies, we resolve the genomic structure of the large EBR1 protein, identifying fewer tandem CUB-TSP1 repeats in EBR1 compared to the initial characterization of this protein. As expected for an egg receptor for sperm, EBR1 is highly expressed in female reproductive tissues (eggs and female gonad), compared to other tissues. In contrast, HSP110 shows similar levels of expression across male and female reproductive tissues, as well as across non-reproductive tissues and development stages. HSP110 might be a pleiotropic gene that in part influences fertilization. Using protein structural modeling and functional domain predictions, we propose hypotheses about potential interactions among EBR1, bindin, and HSP110 proteins that may provide insight into sperm-egg interactions in sea urchins. Resolving the genomic structure of genes encoding gamete recognition proteins, in combination with functional annotations and protein structural modeling, enables deeper investigation into the consequences of variation in gamete recognition proteins and the evolution of reproductive isolation.

Mesocentrotus franciscanus↗

An inducer-independent, single-plasmid CRISPR-Cas9 system for genome editing in Bacillus species.

Advances in molecular biology tools are essential for streamlining and accelerating genetic engineering of cells across industrial and academic applications. While CRISPR-Cas improves genome editing efficiency, current systems have limitations and are often host specific, which restricts their versatility. This study describes a versatile CRISPR-Cas9 system for genome editing in industrially relevant Bacillus species. By adapting the well-established pJOE8999 vector-based CRISPR-Cas9 genome editing system, we constructed an inducer-independent, broad-host-range genome editing system. It maintains the benefits of low toxicity to the target cell and the cloning host as well as the ease to use of a single-plasmid CRISPR-Cas9 system. We utilized the constitutive Sigma70-type promoter from the conserved veg gene of Bacillus, to develop and test the suitability of promoter variants of different strengths for Cas9 expression. Successful gene deletions in three different Bacillus species demonstrated the versatility of the modified system for this industrially important genus. This was further confirmed by the integration of a reporter gene fusion and the introduction of a single point mutation in the genome of Bacillus licheniformis. This one-step CRISPR-based transformation protocol developed in this study enables fast genome editing workflows with minimal hands-on time. KEY POINTS: • Editing and screening of promoter variants for balanced Cas9 expression in Bacillus. • Development of a versatile inducer-independent, single-plasmid CRISPR-Cas-based system. • Verification of the modified CRISPR-based system for genome editing in different Bacilli.

CRISPR-Cas Systems↗

Genomic Characterisation of Carbapenem-Resistant Klebsiella pneumoniae and Enterobacter hormaechei Clinical Isolates from Nigeria: Evidence of Resistance, Virulence, and Putative Plasmid-Mediated Gene Sharing.

The global proliferation of carbapenem-resistant Enterobacterales (CRE) constitutes one of the most urgent public health threats, yet high-resolution genomic data from sub-Saharan Africa remain critically scarce. We applied whole-genome sequencing (WGS) and comparative phylogenomics to characterise antimicrobial resistance determinants, virulence genes, and mobile genetic elements (MGEs) in three carbapenem-resistant clinical isolates originating from three tertiary hospitals (selected from a broader surveillance collection spanning four facilities) in Osun State, southwestern Nigeria. We purposively selected three isolates, two Klebsiella pneumoniae subsp. pneumoniae (K22, ST411; K31, ST17) and one Enterobacter hormaechei subsp. steigerwaltii (K32, ST45) from a broader surveillance collection of 27 carbapenem-non-susceptible Enterobacterales, to represent phenotypically and genotypically divergent lineages. Resistome analysis revealed extensive plasmid-associated β-lactam and aminoglycoside resistance in K31 (including blaCTX-M-15, blaOXA-1, and blaTEM-1). K32 harboured an intrinsic chromosomal blaACT-17 AmpC gene, while IS26 and ISEcp1 insertion sequences, consistent with transposon-mediated mobilisation, flanked its acquired aminoglycoside and sulfonamide resistance cassettes. K22 lacked detected acquired carbapenemase, ESBL, or plasmid-mediated AmpC genes, indicating that its carbapenem-resistant phenotype may involve non-carbapenemase mechanisms such as porin alteration or efflux-mediated reduced susceptibility; however, this mechanism requires confirmation by direct ompK35/ompK36 sequence analysis and/or phenotypic outer membrane protein profiling. Virulome profiling identified a broader repertoire of siderophore, adhesion, and biofilm genes in both K. pneumoniae isolates than in E. hormaechei. Phylogenomic analysis demonstrated that K22 and K31 cluster within the broader K. pneumoniae population framework but represent distinct high-risk lineages (ST411 and ST17) rather than a single clonal outbreak. Analysis also identified a shared plasmid backbone between K31 and K32, supporting interspecies horizontal gene transfer. These descriptive genomic findings identify clinically relevant resistance and virulence determinants in three purposively selected carbapenem-resistant Enterobacterales from Nigerian tertiary-care hospitals. The detection of shared resistance elements between K. pneumoniae and E. hormaechei suggests possible plasmid-mediated gene sharing. Still, larger WGS studies with long-read sequencing and patient-level epidemiological data are required to define transmission and dissemination patterns.

Nigeria↗

Advancing the Deciphering of Host-Microbe Crosstalk with Spatial Omics: A Mini-Review.

Host-microbe crosstalk refers to the reciprocal influences between a host and its resident or invading microorganisms. This crosstalk plays important roles in maintaining host health, regulating physiological functions, and coordinating responses to infection. The rapid rise of spatial omics is transforming how this crosstalk is studied in both animals and plants. Unlike traditional bulk omics, which homogenize tissues and erase spatial context, spatial methods preserve in situ organization and can simultaneously capture molecular information from hosts and microbes. As a result, researchers can characterize the spatial organization of colonization and infection, identify spatial associations between microbial niches and host cell states, and visualize local host response gradients across intact tissues. Current spatial omics technologies encompass sequencing-based, imaging-based, and hybrid platforms. Spatial multi-omics approaches enable the joint measurement or integration of gene expression, protein abundance, and metabolite distributions. Although spatial association alone does not establish causality, spatial omics provides a high-resolution framework for characterizing host-microbe relationships within intact tissues and generating spatially constrained, testable hypotheses. When combined with perturbation experiments and complementary experimental evidence, these hypotheses can contribute to mechanistic interpretation of host-microbe crosstalk. Here, we review spatial omics technologies, compare their suitability and major trade-offs for host-microbe studies, and discuss computational strategies, analytical challenges, and future prospects.

Multiomics↗

Molecular mechanisms and agronomic strategies for thermotolerance in chili pepper (Capsicum annuum L.).

Heat stress is a primary environmental constraint on chili pepper (Capsicum annuum L.) productivity and fruit quality across global agricultural systems. Elevated temperatures adversely affect plant growth, flowering, fruit set, pod morphology, physiology, and metabolism. The severity of these impacts varies with the duration and intensity of heat exposure and with the stage of plant development. Reproductive development is especially vulnerable, resulting in compromised fruit formation and a decline in productivity. Heat stress disturbs photosynthesis, cellular structure integrity, and membrane stability through oxidative stress. Chili plants counter heat stress through complex molecular networks that encompass activation of antioxidant systems, heat shock protein (HSP) synthesis, osmolyte biosynthesis, and stress-responsive transcription factor expression. Recent advancements in genomics, transcriptomics, and metabolomics have elucidated fundamental regulatory pathways governing thermotolerance, highlighting the importance of heat-responsive genes, including CaHSPs, CaWRKYs, and CaNACs. This comprehensive review integrates contemporary understanding of physiological, biochemical, and molecular heat stress responses in chili pepper. Additionally, it evaluates potential agronomic and breeding strategies to strengthen crop adaptation to escalating global temperatures.

Capsicum↗

Scion-based drought stress memory affects potato response to water deficit.

A scion-based stress memory signal, which was derived from drought-primed potato plants, was transmitted to new potato plants generated through vegetative reproduction. This affected potato tuber yield. Drought is one of the most significant threats to agricultural productivity worldwide. The cultivated potato (Solanum tuberosum L.) is a crop species that is sensitive to drought stress. This study investigated the impact of scion-based drought stress memory on tuber yield, physiological parameters, gene expression, and DNA methylation in the vegetative progeny of grafted plants. The tuber progeny plants remembered the drought stress signal transmitted from the drought-primed scion. Significant changes were observed in the expression of genes, primarily those related to photosynthetic metabolic pathways, as well as those associated with chromatin remodeling, DNA repair, and the plant's response to abiotic stresses. The gene expression landscape corresponded with variability in chlorophyll fluorescence parameters. In the first and the second generation of vegetatively propagated plants, scion-based memory had a positive effect on tuber yield. This was achieved by buffering the decline in yield caused by drought, as compared to plants grown under control conditions. Whole-genome bisulfite sequencing analysis revealed no correlation between changes in DNA methylation and gene expression. Drought-induced alterations in DNA methylation were erased in the second progeny generation. We propose that there is a direct causal relationship between scion-based memory of drought stress and photosynthetic efficiency, as well as potato tuber productivity.

Solanum tuberosum↗

Genomic signatures of host-range divergence in the generalist Beauveria bassiana and the specialist Beauveria brongniartii.

Entomopathogenic fungi of the genus Beauveria are widely used biological control agents that infect diverse insect hosts and can also associate with plants as rhizosphere colonizers and endophytes. Within this genus, Beauveria bassiana is a cosmopolitan generalist, whereas Beauveria brongniartii exhibits a narrower host range, primarily targeting soil-dwelling coleopteran larvae with limited evidence of plant colonization. To explore genomic differentiation associated with this ecological divergence, the commercially exploited B. brongniartii strain BIPESCO2 and B. bassiana ATHUM 4946 were sequenced using Oxford Nanopore technology, followed by comparative genomic analyses across multiple strains. Orthology identified species-specific gene families, although overall genome architecture and core gene content were highly conserved. The CAZyme repertoires were nearly identical, indicating retention of a versatile enzymatic toolkit supporting plant association, saprotrophy, and insect pathogenicity. In contrast, biosynthetic gene clusters displayed substantial variation, including structural remodeling of Beauveria-specific virulence-associated clusters and expansion of type I polyketide synthase clusters in B. brongniartii. Effector prediction revealed a conserved core of largely uncharacterized proteins alongside species-specific orthogroups enriched in adhesion-, immunity-, and cuticle-interaction domains. Together, these findings indicate that host-range divergence in Beauveria is associated with compartmentalized genomic differentiation, particularly in secondary metabolism and a limited subset of lineage-specific virulence factors, rather than in the conserved core infection machinery.

Beauveria↗

Increasing bird diversity in a landscape in transition.

Rural depopulation across Mediterranean uplands has driven farmland extensification and landscape transitions, yet their medium-term impacts on birds remain poorly understood. We resurveyed 213 selected 2 km × 2 km grid cells in the Côa River basin (western Iberia) in 2023-2024, following protocols comparable to those applied in 1999-2005, ensuring consistent sampling across periods. Median alpha diversity increased by five species, a 28% gain, with total abundance rising as common taxa became more widespread. Gains were predominantly driven by forest-associated and generalist species, while farmland specialists showed stagnation or slight declines. We discuss how landscape transitions contributed to these biodiversity patterns including lower human density, reduced grazing pressure, and altered disturbance regimes. However, significant avian diversity gains occurred within apparently stable forest-cover mosaics, potentially masking broader ecological shifts.

Animals↗

Non-linear predictive modeling and comprehensive meta-analysis of rectal temperature in Santa Inês sheep: a systematic review of thermal challenges and biometerological trends.

A systematic and bibliometric review, combined with a meta-analysis, was used to adjust an equation for estimating the physiological responses of Santa Inês sheep subjected to different thermal challenges. The systematic review compiled data on physiological responses and the thermal environment, which were then used in the meta-analysis to adjust regression models. The bibliometric analysis mapped the relationships among studies, highlighting their usefulness in interpreting research findings and biases. Addressing prior methodological critiques, the core of this study involves replacing the linear approach with a non-linear segmented regression model to accurately define the Thermal Neutral Zone (TNZ). The Segmented Regression Model was crucial, establishing the upper limit of the Thermal Neutral Zone (TNZ) at an air temperature (tair) of 34.64 °C, where trectal begins to increase abruptly. The model, while identifying a biologically significant breakpoint, exhibited a moderate Multiple R-squared of 0.3529, highlighting the high heterogeneity and methodological variability in the current Santa Inês literature. This non-linear approach offers a biologically superior tool for identifying the onset of thermal distress.

Animals↗

The complete genomic sequence of a novel member of the genus Caulimovirus isolated from Dregea volubilis.

A novel caulimovirus was identified from diseased leaves of Dregea volubilis exhibiting yellowing and vein-associated chlorosis in Yuanjiang County, Yunnan Province, China. The virus was tentatively named Dregea volubilis caulimovirus 1 (DVCaV1). The complete genome sequence of DVCaV1, determined by de novo assembly of high-throughput sequencing data, comprises 8,160 bp of circular double-stranded DNA containing two intergenic regions and seven open reading frames (ORFs). These ORFs encode (in order) a movement protein (MP), an aphid transmission factor (ATF), a virion-associated protein (VAP), a coat protein (CP), a polymerase polyprotein (Pol, containing protease, reverse transcriptase, and RNase H domains), a transactivator/viroplasmin (TAV) protein, and a hypothetical protein of unknown function. Sequence comparisons revealed the highest nucleotide similarity with strawberry vein banding virus (SVBV; NC_001725). Phylogenetic analysis confirmed DVCaV1 as a member of the genus Caulimovirus, with SVBV as its closest known relative. According to current ICTV species demarcation criteria for the genus Caulimovirus (host range and > 20% nucleotide sequence divergence in the polymerase region), DVCaV1 represents a novel species. This is, to our knowledge, the first report of a caulimovirus detected in naturally symptomatic Dregea volubilis.

Genome, Viral↗

Complete genome sequence of a novel alternavirus infecting Fusarium falciforme.

We present the complete genome sequence of a novel alternavirus, tentatively named "Fusarium falciforme alternavirus 1 (FfAV1)", isolated from Fusarium falciforme. The host, F. falciforme strain Fod375, was isolated from a soil sample in Spain in 2012 and was found to be infected with a virus containing a tetra-segmented double-stranded (ds) RNA genome. The genome segments, designated as dsRNA1 (3529 bp), dsRNA2 (2641 bp), dsRNA3 (2459 bp), and dsRNA4 (1471 bp), each possess a single open reading frame (ORF). The protein predicted from dsRNA1 contains the typical domains of an RNA-dependent RNA polymerase (RdRP) homologous to those of previously reported alternaviruses, while the protein predicted from dsRNA3 shows homology to alternavirus capsid proteins. The proteins encoded by dsRNA2 and dsRNA4 are of unknown function. All predicted proteins exhibited the highest sequence identity with their counterparts in Hebei alternavirus and Marquandomyces marquandii alternavirus 1. Phylogenetic analysis supported the placement of this FfAV1 isolate within the genus Alternavirus. Considering these results, we propose that FfAV1, along with the two closely related unassigned alternaviruses, represents a new species within the genus.

Genome, Viral↗

Molecular characterization and genome sequence analysis of Dichroa emaravirus, a putative novel member of the genus Emaravirus.

Hydrangea febrifuga (syn. Dichroa febrifuga) is a traditional medicinal plant distributed in China and Southeast Asia, and febrifugine, one of its principal bioactive constituents, has served as an important lead compound for antimalarial drug development. Viral infections may adversely affect the quality of medicinal plants; however, no emaravirus has previously been reported from H. febrifuga. Here, high-throughput sequencing was performed on H. febrifuga leaves exhibiting mosaic symptoms collected in Yunnan Province, China. Combined with RT-PCR, Sanger sequencing, and 5'/3' rapid amplification of cDNA ends (RACE), five full-length genomic RNA segments of a putative novel emaravirus, tentatively designated Dichroa emaravirus (DEV), were identified and characterized. The five negative-sense single-stranded RNA (-ssRNA) segments have a combined length of 12,971 nt and encode an RNA-dependent RNA polymerase (RdRp), glycoprotein precursor (GP), nucleocapsid protein (NP), movement protein (MP), and an uncharacterized accessory protein, P5. The maximum amino acid sequence identities of DEV P1-P4 with recognized emaraviruses were 73.90%, 51.82%, 65.60%, and 81.30%, respectively, whereas P5 showed a maximum identity of 49.16% with its closest homolog. Thus, three of the four core proteins had maximum identities below 80%, consistent with the current ICTV species demarcation criterion for the genus Emaravirus. Maximum-likelihood phylogenetic analyses based on the four core proteins further supported the placement of DEV within the genus Emaravirus (family Fimoviridae). These results support DEV as a putative novel emaravirus and represent the first report of an emaravirus associated with H. febrifuga.

Genome, Viral↗

Isolation and characterization of a novel Schitoviridae phage VipHU7 that infects Vibrio parahaemolyticus.

In recent years, various bacteriophages that infect Vibrio spp. have been isolated and characterized. However, many characteristics concerning their infection mechanisms remain unknown. Here, we isolated and characterized a novel phage, VipHU7, that infects Vibrio parahaemolyticus. The morphology of VipHU7 was examined using transmission electron microscopy, which demonstrated that it has a short, noncontractile tail characteristic of podoviruses. VipHU7 formed clear plaques with halo zones on a bacterial lawn of V. parahaemolyticus MFS 1101, and host range analysis revealed that it had a limited host range. Analysis of the propagation and one-step growth curve of VipHU7 in liquid medium indicated that its replication rate increases in the presence of divalent cations, which did not affect its adsorption. Genome sequencing revealed that the VipHU7 genome is 76,454 bp long, with a 38.48% GC content and 112 predicted open reading frames. VipHU7 has a genomic structure similar to that of other Varunavirus phages that infect Vibrio spp. VIRIDIC analysis showed that the intergenomic similarity between VipHU7 and Vibrio phage BUCT194 was 83.7%, indicating that VipHU7 is a novel species belonging to the family Schitoviridae and genus Varunavirus.

Vibrio parahaemolyticus↗

Seed shattering habit in millets and the secrets of the abscission layer - a comprehensive review.

Though seed shattering continues to be a significant barrier affecting yield stability and harvesting efficiency in millets and other grasses, millets are increasingly acknowledged as climate-resilient, nutrient-rich 2007cereal crops with the potential to strengthen global nutritional and food security under the combined pressures of climate change, population growth, and limited natural resources. Since strong artificial selection favoured non-shattering phenotypes during domestication, seed shattering, an adaptive trait in wild species that promotes seed dispersal through the formation and activation of specialised abscission layers, became a distinguishing feature of cultivated cereals. With a focus on the morphological, physiological, hormonal, and genetic modulation of the abscission zone, this article summarizes the state of the art regarding seed shattering in millets. Abscission layer morphology, location, and lignification vary greatly among grasses, from well-defined lignified zones in rice and sorghum to non-lignified and anatomically subtle zones in Setaria and Panicum species. Cell wall-modifying enzymes like polygalacturonases, cellulases, expansins, and pectin methylesterases that mediate middle lamella degradation are modulated by coordinated hormonal signalling involving auxin, ethylene, and abscisic acid, which controls the timing and progression of cell separation at the physiological level. Domestication-related genes, including SH1, qSH1, SH4, and LES1, demonstrate convergent evolutionary mechanisms controlling abscission layer development in a variety of grass lineages at the molecular level. Understanding these regulatory networks has been greatly enhanced by recent developments in transcriptomics, functional genomics, and genome sequencing in both model species and underused millets. The role of millets as climate-smart cereals for sustainable future agriculture is reinforced by the integration of anatomical, physiological, and genetic insights, which offer a solid basis for targeted breeding and genome-editing strategies intended to improve seed retention, enhance yield stability, and increase harvest efficiency.

Abscission Layer↗

Reversible exacerbation of parkinsonism during epirubicin-cyclophosphamide chemotherapy in a patient with PTEN hamartoma tumor syndrome and young-onset Parkinson's disease.

BACKGROUND: PTEN hamartoma tumor syndrome (PHTS), caused by germline loss-of-function variants in PTEN, typically manifests as macrocephaly, neurodevelopmental disorders, and cancer susceptibility. Parkinson's disease has not been recognized as part of its known neurological spectrum. METHODS: We describe the clinical course of a patient with a germline PTEN nonsense variant (p.Arg130Ter) who developed young-onset Parkinson's disease before being diagnosed with bilateral breast cancer. RESULTS: The patient developed asymmetric, levodopa-responsive parkinsonism at 35 years of age, with reduced bilateral striatal dopamine transporter uptake. During two cycles of epirubicin-cyclophosphamide chemotherapy, her previously well-controlled parkinsonism showed reproducible and severe exacerbations. Symptoms began several days after chemotherapy, reached their maximum severity approximately one week after treatment, and resolved completely within approximately two weeks without modification of her antiparkinsonian medications. No dehydration, electrolyte disturbance, infection, or exposure to dopamine-receptor antagonists was identified. The chemotherapy regimen was discontinued after the second episode because of the reproducible temporal association. CONCLUSIONS: This case demonstrates reproducible, fully reversible exacerbations of parkinsonism during epirubicin-cyclophosphamide chemotherapy in a patient with PHTS and young-onset Parkinson's disease. These episodes may reflect transient vulnerability of dopaminergic neurons to chemotherapy-related systemic stress, although the causal role of PTEN haploinsufficiency remains uncertain.

Humans↗

METTL14 alleviates pyroptosis of placental trophoblasts in gestational diabetes mellitus through the lncRNA MEG8/WNT7A axis via m6A modification.

Gestational diabetes mellitus (GDM) is a pregnancy complication associated with abnormal placental trophoblast function. Pyroptosis has been implicated in GDM pathogenesis, yet the role of m6A modification in this process remains unclear. We hypothesized that METTL14 regulates trophoblast pyroptosis through m6A-dependent modulation of the lncRNA MEG8/WNT7A axis. This study investigated the mechanism of METTL14 in pyroptosis of placental trophoblasts in GDM. HG-treated HTR8/SVneo cells were used as a cell model. METTL14, WNT7A, and lncRNA MEG8 expression was detected by RT-qPCR and western blot. Placental damage, cell injury, and pyroptosis markers were assessed. YTHDF2-mediated m6A enrichment on lncRNA MEG8, the interaction between lncRNA MEG8 and EZH2, and H3K27me3 enrichment on the WNT7A promoter were analyzed. Results showed that lncRNA MEG8 was upregulated, while METTL14 and WNT7A were downregulated. METTL14 overexpression reduced placental damage and trophoblast pyroptosis. Mechanistically, METTL14 suppressed lncRNA MEG8 expression through YTHDF2-mediated m6A methylation. Reduced lncRNA MEG8 decreased EZH2 recruitment to the WNT7A promoter, lowered H3K27me3 levels, and consequently promoted WNT7A expression. Rescue experiments confirmed that lncRNA MEG8 overexpression or WNT7A knockdown attenuated the suppressive effect of METTL14 on pyroptosis. In conclusion, METTL14 acts as an upstream regulator that inhibits trophoblast pyroptosis and ameliorates GDM-induced damage through the lncRNA MEG8/WNT7A axis via YTHDF2-mediated m6A modification, highlighting METTL14 as a potential therapeutic target.

Humans↗