A complex systems approach to mosaic loss of the Y chromosome.

Mosaic loss of Y chromosome (mLOY) is an acquired condition wherein a sizeable proportion of an organ's cells have lost their Y. Large-scale cohort studies have shown that mLOY is age-dependent and a strong risk factor for all-cause mortality and adverse outcomes of age-related diseases. Emerging multi-omics approaches that combine gene expression, epigenetic and mutational profiling of human LOY cell populations at single-cell levels, and contemporary work in in vitro cell and preclinical mouse models have provided important clues into how mLOY mechanistically contributes to disease onset and progression.

Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is currently the most aggressive subtype of breast cancer, characterized by high heterogeneity and strong invasiveness, and currently lacks effective therapies. PRMT5, a type II protein arginine methyltransferase, is upregulated in numerous cancers, including TNBC, and plays a critical role, marked it as an attractive therapeutic target. PROTAC (Proteolysis Targeting Chimeras) is an innovative drug development technology that utilizes the ubiquitin-proteasome system (UPS) to degrade target proteins, which is characterized by higher activity, enhanced safety, lower resistance, and reduced toxicity, offering significant value for clinical translation.

Juvenile hormone as a key regulator for asymmetric caste differentiation in ants.

Caste differentiation involves many functional traits that diverge during larval growth and metamorphosis to produce adults irreversibly adapted to reproductive division of labor. Investigating developmental differentiation is important for general biological understanding and has increasingly been explored for social phenotypes that diverge in parallel from similar genotypes. Here, we use ants to investigate the extent to which canalized worker development can be shifted toward gyne (virgin-queen) phenotypes by juvenile hormone (JH) treatment.

Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice.

Circadian disruption often arises prior to the onset of typical motor deficits in patients with Parkinson's disease (PD). It remains unclear whether such a prevalent non-motor manifestation would contribute to the progression of PD. Diffusible oligomeric alpha-synuclein (O-αSyn) is perceived as the most toxic and rapid-transmitted species in the early stages of PD.

Light-phase time-restricted feeding disrupts the muscle clock and insulin sensitivity yet potentially induces muscle fiber remodeling in mice.

Skeletal muscle plays a critical role in regulating systemic metabolic homeostasis. It has been demonstrated that time-restricted feeding (TRF) during the rest phase can desynchronize the suprachiasmatic nucleus (SCN) and peripheral clocks, thereby increasing the risk of metabolic diseases. However, the impact of dietary timing on the muscle clock and health remains poorly understood.

Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson's Disease.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present.

Presenilin-1, mutated in familial Alzheimer's disease, maintains genome stability via a γ-secretase dependent way.

Mutations in Presenilin-1 (PS1) account for over 80 % mutations linked to familial Alzheimer's disease (AD). However, the mechanisms of action of PS1 mutations in causing familial AD are not fully understood, limiting opportunities to develop targeted disease-modifying therapies for individuals carrying PS1 mutation. To gain more comprehensive insights into the impact of PS1 mutations on genome stability, we knocked down PS1 in SH-SY5Y, HMC3 and A549 cells.

Human fibroblasts facilitate the generation of iPSCs-derived mammary-like organoids.

Background: Breast cancer is the most common malignancy in women worldwide, and its treatment largely depends on mastectomy. Patients after mastectomy suffer from crippled body image, self-esteem, and quality of life. Post-mastectomy breast reconstruction can improve patients' psychosocial health.

A single-cell transcriptomic atlas tracking the neural basis of division of labour in an ant superorganism.

Ant colonies with permanent division of labour between castes and highly distinct roles of the sexes have been conceptualized to be superorganisms, but the cellular and molecular mechanisms that mediate caste/sex-specific behavioural specialization have remained obscure. Here we characterized the brain cell repertoire of queens, gynes (virgin queens), workers and males of Monomorium pharaonis by obtaining 206,367 single-nucleus transcriptomes. In contrast to Drosophila, the mushroom body Kenyon cells are abundant in ants and display a high diversity with most subtypes being enriched in worker brains, the evolutionarily derived caste.

Decoding and rejuvenating human ageing genomes: Lessons from mosaic chromosomal alterations.

One of the most curious findings emerged from genome-wide studies over the last decade was that genetic mosaicism is a dominant feature of human ageing genomes. The clonal dominance of genetic mosaicism occurs preceding the physiological and physical ageing and associates with propensity for diseases including cancer, Alzheimer's disease, cardiovascular disease and diabetes. These findings are revolutionizing the ways biologists thinking about health and disease pathogenesis.

Extract of bulbus of Fritillaria cirrhosa induces spindle multipolarity in human-derived colonic epithelial NCM460 cells through promoting centrosome fragmentation.

Bulbus of Fritillaria cirrhosa D. Don (BFC), an outstanding antitussive and expectorant herbal drug used in China and many other countries, has potential but less understood genotoxicity. Previously, we have reported that aqueous extract of BFC compromised the spindle assembly checkpoint and cytokinesis in NCM460 cells.

Small but strong: Mutational and functional landscapes of micronuclei in cancer genomes.

Micronuclei, small spatially-separated, nucleus-like structures, are a common feature of human cancer cells. There are considerable heterogeneities in the sources, structures and genetic activities of micronuclei. Accumulating evidence suggests that micronuclei and main nuclei represent separate entities with respect to DNA replication, DNA damage sensing and repairing capacity because micronuclei are not monitored by the same checkpoints nor covered by the same nuclear envelope as the main nuclei.

Understanding the birth of rupture-prone and irreparable micronuclei.

Micronuclei are extra-nuclear bodies mainly derived from ana-telophase lagging chromosomes/chromatins (LCs) that are not incorporated into primary nuclei at mitotic exit. Unlike primary nuclei, most micronuclei are enclosed by nuclear envelope (NE) that is highly susceptible to spontaneous and irreparable rupture. Ruptured micronuclei act as triggers of chromothripsis-like chaotic chromosomal rearrangements and cGAS-mediated innate immunity and inflammation, raising the view that micronuclei play active roles in human aging and tumorigenesis.

Mosaic loss of human Y chromosome: what, how and why.

Y chromosome (ChrY), the male-specific sex chromosome, has been considered as a genetic wasteland. Aging-related mosaic loss of ChrY (LOY) has been known for more than half a century, but it was constantly considered as a neutral karyotype related to normal aging. These views have been challenged with genome-wide association studies identifying mosaic LOY in human somatic cells is the most commonly acquired mutation in male's genome and is associated with a wide spectrum of human diseases including cancer, Alzheimer's disease, and cardiovascular disease.

Genetic basis of ruminant headgear and rapid antler regeneration.

Ruminants are the only extant mammalian group possessing bony (osseous) headgear. We obtained 221 transcriptomes from bovids and cervids and sequenced three genomes representing the only two pecoran lineages that convergently lack headgear. Comparative analyses reveal that bovid horns and cervid antlers share similar gene expression profiles and a common cellular basis developed from neural crest stem cells.

High concentration of sugars is genotoxic to folate-deficient cells.

Patients with type 2 diabetes mellitus (T2DM) are associated with an elevated, but poorly understood baseline of genomic instability (GIN). Expert panels are still debating on whether hyperglycemia is the key element in conferring this high GIN. Since high blood glucose and low blood folate are prevalent in T2DM, we hypothesized that high glucose may work with low folate to induce GIN.

Geraniin Differentially Modulates Chromosome Stability of Colon Cancer and Noncancerous Cells by Oppositely Regulating their Spindle Assembly Checkpoint.

Geraniin has been reported to specifically induce apoptosis in multiple human cancers, but the underlying mechanism is poorly defined. The spindle assembly checkpoint (SAC) is a surveillance system to ensure high-fidelity chromosome segregation during mitosis. Weakening of SAC to enhance chromosome instability (CIN) can be therapeutic because very high levels of CIN are lethal.

Biphasic regulation of spindle assembly checkpoint by low and high concentrations of resveratrol leads to the opposite effect on chromosomal instability.

Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin possessing numerous health-promoting effects. Chromosomal instability (CIN), usually results from defective spindle assembly checkpoint (SAC), is a major contributor to many diseases. While it's recently recognized that RSV exhibits a nonlinear dose response for disease prevention, whether it's the case for its role in CIN remains unknown.

[Design and synthesis of imine compound for metal cation logical gates recognition and setup of double-control fluorescent molecule switch].

The Schiff base's reduced product N,N-bis(4-methoxybenzyl) ethane-1,2-diamine, which was used as a receptor L, was designed and synthesized for the first time in the present article. It was found that Cu2+ and Fe3+ could quench L in fluorescence observably and Zn2+ and Cd2+ could enhance L remarkably. So the two pair metal cation could set up "OR" logical gate relation with the receptor molecule L, then a logical recognition system be formed.

[Synthesis, characterization and interaction with ct-DNA of four novel secondary amine complexes].

A novel ligand(L), (N, N'-bis (4-methylbenzyl) ethane-1, 2-diamine), and its transition metal(II) complex, [ML2 (H2O)2]2+ x 2NO3- (M = Cu(II), Co(II, Ni(II), Zn(II)), have been synthesized and characterized by elemental analysis, IR and 1H NMR. The crystal structure of the Cu-L complex was characterized by X-ray single crystal diffraction, and the results showed a regular octahedral structure in which each metal ion is six--coordinated with four nitrogen atoms from two ligands and two oxygen atoms from two water molecules. The interaction of the complex with calf thymus DNA was investigated by UV spectroscopy and fluorescence spectroscopy, and the results suggest that the complex binds to DNA by electrostatic interaction mode.

Evaluation of diethylenetriaminepentaacetic acid-manganese(II) complexes modified by narrow molecular weight distribution of chitosan oligosaccharides as potential magnetic resonance imaging contrast agents.

Novel conjugates of narrow molecular weight distribution of chitosan oligosaccharides (CSn; n=6, 8, 11) with manganese-diethylenetriaminepentaacetic acid (Mn-DTPA) as potential magnetic resonance imaging (MRI) contrast agents were synthesized. The structures were characterized by means of Fourier transform infrared spectra, (13)C nuclear magnetic resonance, size exclusion chromatography and inductively coupled plasma atomic emission spectrometry. The characterization results showed that Mn-DTPA was successfully linked to aminated CSn by an amide function.