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Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA1-3. Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells4-7. Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA-chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an older transcriptomic signature and Alzheimers disease pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues.

Human mitochondrial DNA (mtDNA) encodes 37 essential genes and plays a critical role in mitochondrial and cellular functions. mtDNA is susceptible to damage by endogenous and exogenous chemicals. Damaged mtDNA molecules are counteracted by the redundancy, repair, and degradation of mtDNA. In response to difficult-to-repair or excessive amounts of DNA lesions, mtDNA degradation is a crucial mitochondrial genome maintenance mechanism. Nevertheless, the molecular basis of mtDNA degradation remains incompletely understood. Recently, mitochondrial transcription factor A (TFAM) has emerged as a factor in degrading damaged mtDNA containing abasic (AP) sites. TFAM has AP-lyase activity, which cleaves DNA at AP sites. Human TFAM and its homologs contain a higher abundance of Glu than that of the proteome. To decipher the role of Glu in TFAM-catalyzed AP-DNA cleavage, we constructed TFAM variants and used biochemical assays, kinetic simulations, and molecular dynamics (MD) simulations to probe the functional importance of E187 near a key residue K186. Our previous studies showed that K186 is a primary residue to cleave AP-DNA via Schiff base chemistry. Here, we demonstrate that E187 facilitates β-elimination, key to AP-DNA strand scission. MD simulations showed that extrahelical confirmation of the AP lesion and the flexibility of E187 in TFAM-DNA complexes facilitate AP-lyase reactions. Together, highly abundant Lys and Glu residues in TFAM promote AP-DNA strand scission, supporting the role of TFAM in AP-DNA turnover and implying the breadth of this process across different species.

[Objective] In the context of a large number of rural labors migrating to cities and towns, clarifying the impact of labor transfer on the green production efficiency of grains for farming households has important policy implications in promoting the steady improvement of green production efficiency and promoting sustainable development of agricultural ecology.[Methods] Based on the survey data of 770 grain-producing farming households from Hubei and Henan Provinces, this study used the data envelopment analysis-slacks-based measure (DEA-SBM) model to calculate the green production efficiency of grains, and used the Tobit model to demonstrate the impact of labor transfer and technology extension on the green production efficiency of grains.[Results] The research showed that labor transfer had an inhibitory effect on the green production efficiency of grains for farming households in both the temporal and spatial dimensions. Government green technology extension measures could promote the improvement of green production efficiency of grains and effectively alleviate the negative impact of labor transfer on green production efficiency of grains. The mitigating effect of technology extension services on the green production efficiency of farming households was limited by the age and income of farmers. For young and high-income farmers, its mitigating effect is insignificant. [Conclusion] Therefore, we should improve the rural labor security mechanism, expand the promotion channels of green production technologies, and focus on the promotion of green production technology for older and low-income farming households, to promote the improvement of green production efficiency of grains and effectively speed up the process of high-quality agricultural development.

Although high-throughput RNA sequencing (RNA-seq) has greatly advanced small non-coding RNA (sncRNA) discovery, the currently widely used complementary DNA library construction protocol generates biased sequencing results. This is partially due to RNA modifications that interfere with adapter ligation and reverse transcription processes, which prevent the detection of sncRNAs bearing these modifications. Here, we present PANDORA-seq (panoramic RNA display by overcoming RNA modification aborted sequencing), employing a combinatorial enzymatic treatment to remove key RNA modifications that block adapter ligation and reverse transcription. PANDORA-seq identified abundant modified sncRNAs-mostly transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs)-that were previously undetected, exhibiting tissue-specific expression across mouse brain, liver, spleen and sperm, as well as cell-specific expression across embryonic stem cells (ESCs) and HeLa cells. Using PANDORA-seq, we revealed unprecedented landscapes of microRNA, tsRNA and rsRNA dynamics during the generation of induced pluripotent stem cells. Importantly, tsRNAs and rsRNAs that are downregulated during somatic cell reprogramming impact cellular translation in ESCs, suggesting a role in lineage differentiation.

As the most widely distributed scavenger birds on the Qinghai-Tibetan Plateau, Himalayan vultures (Gyps himalayensis) feed on the carcasses of various wild and domestic animals, facing the dual selection pressure of pathogens and antibiotics and are suitable biological sentinel species for monitoring antibiotic resistance genes (ARGs). This study used metagenomic sequencing to comparatively investigate the ARGs and mobile genetic elements (MGEs) of wild and captive Himalayan vultures. Overall, the resistome of Himalayan vultures contained 414 ARG subtypes resistant to 20 ARG types, with abundances ranging from 0.01 to 1,493.60 ppm. The most abundant resistance type was beta-lactam (175 subtypes), followed by multidrug resistance genes with 68 subtypes. Decreases in the abundance of macrolide-lincosamide-streptogramin (MLS) resistance genes were observed in the wild group compared with the zoo group. A total of 75 genera (five phyla) of bacteria were predicted to be the hosts of ARGs in Himalayan vultures, and the clinical (102 ARGs) and high-risk ARGs (35 Rank I and 56 Rank II ARGs) were also analyzed. Among these ARGs, twenty-two clinical ARGs, nine Rank I ARG subtypes, sixteen Rank II ARG subtypes were found to differ significantly between the two groups. Five types of MGEs (128 subtypes) were found in Himalayan vultures. Plasmids (62 subtypes) and transposases (44 subtypes) were found to be the main MGE types. Efflux pump and antibiotic deactivation were the main resistance mechanisms of ARGs in Himalayan vultures. Decreases in the abundance of cellular protection were identified in wild Himalayan vultures compared with the captive Himalayan vultures. Procrustes analysis and the co-occurrence networks analysis revealed different patterns of correlations among gut microbes, ARGs, and MGEs in wild and captive Himalayan vultures. This study is the first step in describing the characterization of the ARGs in the gut of Himalayan vultures and highlights the need to pay more attention to scavenging birds. [ABSTRACT FROM AUTHOR]

Since the socio-economic reform in 1978, rural China has undergone drastic spatial restructuring, and the trend of multifunctional development and dynamic evolution of settlements in the countryside have become increasingly obvious. Functions and settlements are the important parts of rural areas. Rural multifunction is a new perspective to explore the diversified development paths of the countryside, and rural settlements provide basic support for rural multifunction. Clarifying the complex coupling coordination relationship between rural functional diversification (RFD) and rural settlement evolution (RSE), and identifying the spatial heterogeneity of their interactions is the key to promoting the rural revitalization strategy. This study analyzes the spatiotemporal changes in rural functions and rural settlements at the township level, alongside assessing various forms and the extent of coupled development. Therein, we consider the advantages of different coupling types of townships and propose four development paths for rural settlements to improve the adaptability of rural functions and settlements. The results show that: (1) The functions and settlements in the study area are characterized by significant spatial and temporal dynamics, indicating that the traditional mountainous countryside is in a process of rapid development and change. (2) The coupling coordination degree of RFD and RSE increases yearly, generally transitioning from the moderate imbalance to the basic coordination stage, and the coordinated townships have obvious spatial agglomeration. (3) Based on the elasticity coefficient model, this paper summarizes four coupling models of RFD and RSE to guide the optimization of rural settlement development paths. This research provides scientific guidance for developing countries in the spatial planning of rural territories and the optimization of rural settlements. [ABSTRACT FROM AUTHOR]

Objective To study on preoperative diagnosis of papillary thyroid carcinoma (PTC) with Bethesda Ⅴ thyroid nodules retrospectively and to explore the differences of clinical parameters between Bethesda Ⅴ and Ⅵ thyroid nodules. Methods The clinical data of 430 patients were analyzed. Results Univariate analysis showed that there were significant differences of Bethesda Ⅴ nodules in nodule boundary, tumor size and echo between PTC group of 159 cases and benign group of 20 cases (P