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Basic helix-loop-helix (bHLH) transcription factors play central regulatory roles in plant development and responses to environmental stress. However, the evolutionary dynamics of the bHLH gene family in Rosaceae fruit species remain largely unexplored. In particular, the expression profiles and functional roles of PybHLH genes during stone cell formation in pear fruit are not well understood. In this study, a total of 910 bHLH genes were identified across seven Rosaceae species-Asian pear, European pear, apple, peach, sweet cherry, Japanese apricot, and strawberry-with 198 genes detected in pear (Pyrus spp.). The PybHLH genes were classified into 13 major clusters (A-M) comprising 17 subfamilies. Inter-species collinearity analyses revealed strong macrosyntenic conservation among apple, Asian pear, and European pear. Whole-genome duplication (WGD) and dispersed duplication (DSD) were identified as the main drivers of bHLH gene family expansion. Transcriptome analysis across multiple tissues identified eight PybHLH genes with specific expression in fruit flesh. Integration of differential expression data during stone cell development with a co-expression network of lignin biosynthetic genes further narrowed down four PybHLH candidates associated with lignification. Among them, RT-qPCR and transient expression assays confirmed that PybHLH182 positively regulates stone cell lignification. This study presents the first comprehensive analysis of the bHLH gene family across seven Rosaceae species, clarifying the evolutionary trajectory of bHLHs and the tissue-specific expression patterns of PybHLHs. The Maloideae subfamily maintains gene family stability via WGD and DSD, whereas the genus Prunus drives gene divergence through frequent genomic rearrangements. Meanwhile, PybHLH182 was identified as a core regulator governing stone cell formation in pear fruits. These findings provide a theoretical basis for molecular breeding of Rosaceae fruit trees and elucidating the mechanisms underlying pear fruit quality formation.

Background: Nijmegen breakage syndrome-like disorder (NBSLD) is a rare chromosomal instability syndrome caused by biallelic pathogenic variants in RAD50, which is a key component of the MRE11-RAD50-NBS1 (MRN) complex involved in DNA double-strand break repair. Merely few cases have been reported worldwide, and its phenotypic spectrum remains incompletely defined.

Case presentation: We report a 6-year-old Chinese boy, who presented with bilateral cryptorchidism, severe microcephaly, growth retardation, multiple café-au-lait macules, brachydactyly, and distinctive craniofacial features, including a sloping forehead, midface prominence, and receding mandible. Mild intellectual impairment was confirmed on formal neurocognitive testing. The immunological assessment revealed borderline lymphopenia without overt immunodeficiency.

Genetic findings: Whole-exome sequencing (WES) identified compound heterozygosity for two variants in RAD50 (NM_005732.3): a paternally inherited frameshift variant c.2165_2166insT (p.Lys722Asnfs*6) and a maternally inherited splice-site variant c.3752 + 4_3752 + 7dup. The minigene splicing assay revealed that the latter disrupts normal splicing, leading to partial intron retention and a premature stop codon (p.Ile1252*).

Diagnosis and treatment: Based on the clinical features and molecular confirmation, the patient was diagnosed with NBSLD. Allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as a potential therapeutic option for DNA damage repair disorders. However, it is not presently required for this patient, who is managed with regular surveillance.

Outcome and significance: The present case expands the clinical and mutational spectrum of RAD50-associated NBSLD. It emphasizes the importance of combining clinical assessment, genomic analysis, and functional assays for the accurate diagnosis of rare chromosomal breakage disorders.

Muscle larva of the mammalian parasitic nematode Trichinella spp. resides in a single cell called a nurse cell (NC). Despite originating from muscle cells the NC is of the non-muscular type. Its only role is to sustain muscle larva throughout the host's life. Our previous studies documented cellular senescence as the main phenomenon associated with the NC development and its long-term maintenance. Cell-cycle arrest of the NC was underpinned by p57 Kip2 cyclin-dependent kinase inhibitor (CDKI) expression. Since p16 INK4a and p21 Cip1 CDKIs are recommended as the key markers of growth arrest in in situ senescence examination their expression and localization in the NC-larva complexes were followed in the current study. A model of murine trichinellosis was employed. CDKN2a gene encoding p16 INK4a and CDKN1a gene encoding p21 Cip1 were upregulated in the mature NC at 7-month old infection. However, only p16 INK4a was upregulated on the protein level during the NC development at 26-day old infection, as well as in the mature NC at 7-month old infection. Both CDKIs localized to the larva at two time points of infection. It is hypothesized that Trichinella muscle larvae may absorb mammalian CDKIs while encysted in the NCs. These CDKIs may exert growth-inhibitory role in the parasite and/or if transferred to the offspring they may participate in the establishment of new NCs in the next host. These hypotheses await functional validation.

Background: Adaptor-related protein complex 1 subunit mu 2 (AP1M2) has been has been shown to be overexpressed in breast cancer tissues. However, whether AP1M2 regulates triple-negative breast cancer (TNBC) progression and chemoresistance is unknown.

Methods: The expression of AP1M2 and pre-B-cell leukaemia homeobox 1 (PBX1) was analyzed by qRT-PCR or western blot. Cell proliferation, migration, invasion, docetaxel resistance, and apoptosis were analyzed using CCK8 assay, colony formation assay, EdU assay, transwell assay, wound healing assay and flow cytometry. Dual-luciferase reporter assay was used to assess the interaction between AP1M2 and PBX1.

Results: AP1M2 had increased expression in TNBC cells, and its knockdown suppressed TNBC cell proliferation, migration, invasion, and enhanced docetaxel sensitivity. In terms of mechanism, PBX1 bound to AP1M2 promoter region to enhance its transcription. The rescue experiments revealed that overexpression of AP1M2 could abolish the suppressive effect of PBX1 knockdown on TNBC cell proliferation, migration, invasion, and docetaxel resistance.

Conclusion: PBX1-mediated AP1M2 facilitates cell proliferation, migration, invasion, and docetaxel resistance to accelerate TNBC malignant behavior, providing a novel target for TNBC treatment.