Search

The overactivation of transposable elements (TEs) is a significant threat to male reproduction, particularly during the delicate process of spermatogenesis. Here, we report that zinc finger protein ZCCHC8—a key component of the nuclear exosome targeting (NEXT) complex that is involved in ribonucleic acid (RNA) surveillance—is required for TE silencing during spermatogenesis. Loss of ZCCHC8 results in delayed meiotic progression and reduced production of round spermatids (RS). We observed that young long-interspersed nuclear element (LINE1, L1) subfamilies that are targeted by ZCCHC8 were upregulated in both spermatogonial stem cells (SSC) and pachytene spermatocytes (PS) of Zcchc8 null testes. Further study found that a reduced H3K9me3 modification in SSC and elevated H3 lysine 4 trimethylation in the PS of Zcchc8 KO mice occurred upon young L1, especially L1Md_A, which may have contributed to impairment of the chromatin condensation from PS to RS during spermatogenesis. This study highlights the crucial role of RNA surveillance-mediated chromatin repression by the NEXT complex during spermatogenesis. [ABSTRACT FROM AUTHOR]

The inhomogeneity of spectral pixel response is an unavoidable phenomenon in hyperspectral imaging, which is mainly manifested by the existence of inhomogeneity banding noise in the acquired hyperspectral data. It must be carried out to get rid of this type of striped noise since it is frequently uneven and densely distributed, which negatively impacts data processing and application. By analyzing the source of the instrument noise, this work first created a novel non-uniform noise removal method for a spatial dimensional push sweep hyperspectral imaging system. Clean and clear medical hyperspectral brain tumor tissue images were generated by combining scene-based and reference-based non-uniformity correction denoising algorithms, providing a strong basis for further diagnosis and classification. The precise procedure entails gathering the reference dark background image for rectification and the actual medical hyperspectral brain tumor image. The original hyperspectral brain tumor image is then smoothed using a weighted least squares algorithm model embedded with bilateral filtering (BLF-WLS), followed by a calculation and separation of the instrument fixed-mode fringe noise component from the acquired reference dark background image. The purpose of eliminating non-uniform fringe noise is achieved. In comparison to other common image denoising methods, the evaluation is based on the subjective effect and unreferenced image denoising evaluation indices. The approach discussed in this paper, according to the experiments, produces the best results in terms of the subjective effect and unreferenced image denoising evaluation indices (MICV and MNR). The image processed by this method has almost no residual non-uniform noise, the image is clear, and the best visual effect is achieved. It can be concluded that different denoising methods designed for different noises have better denoising effects on hyperspectral images. The non-uniformity denoising method designed in this paper based on a spatial dimension push-sweep hyperspectral imaging system can be widely used. [ABSTRACT FROM AUTHOR]

In recent years, the incidence of thyroid cancer has rapidly increased. To address the issue of the inefficient diagnosis of thyroid cancer during surgery, we propose a rapid method for the diagnosis of benign and malignant thyroid nodules based on hyperspectral technology. Firstly, using our self-developed thyroid nodule hyperspectral acquisition system, data for a large number of diverse thyroid nodule samples were obtained, providing a foundation for subsequent diagnosis. Secondly, to better meet clinical practical needs, we address the current situation of medical hyperspectral image classification research being mainly focused on pixel-based region segmentation, by proposing a method for nodule classification as benign or malignant based on thyroid nodule hyperspectral data blocks. Using 3D CNN and VGG16 networks as a basis, we designed a neural network algorithm (V3Dnet) for classification based on three-dimensional hyperspectral data blocks. In the case of a dataset with a block size of 50 × 50 × 196, the classification accuracy for benign and malignant samples reaches 84.63%. We also investigated the impact of data block size on the classification performance and constructed a classification model that includes thyroid nodule sample acquisition, hyperspectral data preprocessing, and an algorithm for thyroid nodule classification as benign and malignant based on hyperspectral data blocks. The proposed model for thyroid nodule classification is expected to be applied in thyroid surgery, thereby improving surgical accuracy and providing strong support for scientific research in related fields. [ABSTRACT FROM AUTHOR]

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs. [ABSTRACT FROM AUTHOR]

Objectives: Accumulating evidences show that the regulatory network of m6A modification is essential for mammalian spermatogenesis. However, as an m6A reader, the roles of YTHDF2 remain enigmatic due to the lack of a proper model. Here, we employed the germ cell conditional knockout mouse model and explored the function of YTHDF2 in spermatogenesis. Materials and methods: Ythdf2 germ cell conditional knockout mice were obtained by crossing Ythdf2‐floxed mice with Vasa‐Cre and Stra8‐Cre mice. Haematoxylin and eosin (HE) staining, immunofluorescent staining and Western blotting were used for phenotyping. CASA, IVF and ICSI were applied for sperm function analysis. RNA‐seq, YTHDF2‐RIP‐seq and quantitative real‐time PCR were used to explore transcriptome changes and molecular mechanism analysis. Results: Our results showed that YTHDF2 was highly expressed in spermatogenic cells. The germ cell conditional knockout males were sterile, and their sperm displayed malformation, impaired motility, and lost fertilization ability. During differentiated spermatogonia transiting to pachytene spermatocyte, most m6A‐modified YTHDF2 targets that were degraded in control germ cells persisted in pachytene spermatocytes of Ythdf2‐vKO mice. These delayed mRNAs were mainly enriched in pathways related to the regulation of transcription, and disturbed the transcriptome of round spermatid and elongated spermatid subsequently. Conclusion: Our data demonstrate that YTHDF2 facilitates the timely turnover of phase‐specific transcripts to ensure the proper progression of spermatogenesis, which highlights a critical role of YTHDF2 in spermatogenesis. [ABSTRACT FROM AUTHOR]

Microbial interactions affect community stability and niche spaces in all ecosystems. However, it is not clear what factors influence these interactions, leading to changes in species fitness and ecological niches. Here, we utilized 16 monocultures and their corresponding pairwise co-cultures to measure niche changes among 16 cultivable bacterial species in a wide range of carbon sources, and we used resource availability as a parameter to alter the interactions of the synthetic bacterial community. Our results suggest that metabolic similarity drives niche deformation between bacterial species. We further found that resource limitation resulted in increased microbial inhibition and more negative interactions. At high resource availability, bacteria exhibited little inhibitory potential and stronger facilitation (in 71% of cases), promoting niche expansion. Overall, our results show that metabolic similarity induces different degrees of resource competition, altering pairwise interactions within the synthetic community and potentially modulating bacterial niches. This framework may lay the basis for understanding complex niche deformation and microbial interactions as modulated by metabolic similarity and resource availability.IMPORTANCEUnderstanding the intricate dynamics of microbial interactions is crucial for unraveling the stability and ecological roles of diverse ecosystems. However, the factors driving these interactions, leading to shifts in species fitness and ecological niches, remain inadequately explored. We demonstrate that metabolic similarity serves as a key driver of niche deformation between bacterial species. Resource availability emerges as a pivotal parameter, affecting interactions within the community. Our findings reveal heightened microbial inhibition and more negative interactions under resource-limited conditions. The prevalent facilitation is observed under conditions of high resource availability, underscoring the potential for niche expansion in such contexts. These findings emphasize that metabolic similarity induces varying degrees of resource competition, thereby altering pairwise interactions within the synthetic community and potentially modulating bacterial niches. Our workflow has broad implications for understanding the roles of metabolic similarity and resource availability in microbial interactions and for designing synthetic microbial communities., Competing Interests: The authors declare no conflict of interest.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs., (©The Author(s) 2023. Published by Oxford University Press on behalf of Higher Education Press.)

N 6 -methyladenosine (m 6 A) is the most common internal modification in eukaryotic mRNA. It is dynamically installed and removed, and acts as a new layer of mRNA metabolism, regulating biological processes including stem cell pluripotency, cell differentiation, and energy homeostasis. m 6 A is recognized by selective binding proteins; YTHDF1 and YTHDF3 work in concert to affect the translation of m 6 A-containing mRNAs, YTHDF2 expedites mRNA decay, and YTHDC1 affects the nuclear processing of its targets. The biological function of YTHDC2, the final member of the YTH protein family, remains unknown. We report that YTHDC2 selectively binds m 6 A at its consensus motif. YTHDC2 enhances the translation efficiency of its targets and also decreases their mRNA abundance. Ythdc2 knockout mice are infertile; males have significantly smaller testes and females have significantly smaller ovaries compared to those of littermates. The germ cells of Ythdc2 knockout mice do not develop past the zygotene stage and accordingly, Ythdc2 is upregulated in the testes as meiosis begins. Thus, YTHDC2 is an m 6 A-binding protein that plays critical roles during spermatogenesis.