Extraction of Molecular-Frame Electron-Ion Differential Scattering Cross Sections Based on Elliptical Laser-Induced Electron Diffraction.

We extracted the molecular-frame elastic differential cross sections (MFDCSs) for electrons scattering from N_{2}^{+} based on elliptical laser-induced electron diffraction (ELIED), wherein the structural evolution is initialized by the same tunneling ionization and probed by incident angle-resolved laser-induced electron diffraction imaging. To establish ELIED, an intuitive interpretation of the ellipticity-dependent rescattering electron momentum distributions was first provided by analyzing the transverse momentum distribution. It was shown that the incident angle of the laser-induced returning electrons could be tuned within 20° by varying the ellipticity and handedness of the driving laser pulses. Accordingly, the incident angle-resolved DCSs of returning electrons for spherically symmetric targets (Xe^{+} and Ar^{+}) were successfully extracted as a proof-of-principle for ELIED. The MFDCSs for N_{2}^{+} were experimentally obtained at incident angles of 4° and 7°, which were well reproduced by the simulations. The ELIED approach is the only successful method so far for obtaining incident angle-resolved ionic MFDCS, which provides a new sensitive observable for the transient structure retrieval of N_{2}^{+}. Our results suggest that the ELIED has the potential to extract the structural tomographic information of polyatomic molecules with femtosecond and subangstrom spatiotemporal resolutions that can enable the visualization of the nuclear motions in complex chemical reactions as well as chiral recognition.

Coulomb focusing in attosecond angular streaking.

Angular streaking technique employs a close-to-circularly polarized laser pulse to build a mapping between the instant of maximum ionization and the most probable emission angle in the photoelectron momentum distribution, thereby enabling the probe of laser-induced electron dynamics in atoms and molecules with attosecond temporal resolution. Here, through the jointed experimental observations and improved Coulomb-corrected strong-field approximation statistical simulations, we identify that electrons emitted at different initial ionization times converge to the most probable emission angle due to the previously-unexpected Coulomb focusing triggered by the nonadiabatic laser-induced electron tunneling. We reveal that the Coulomb focusing induces the observed nonintuitive energy-dependent trend in the angular streaking measurements on the nonadiabatic tunneling, and that tunneling dynamics under the classically forbidden barrier can leave fingerprints on the resulting signals. Our findings have significant implications for the decoding of the intricate tunneling dynamics with attosecond angular streaking.

Long-term survival in patients with para-aortic metastatic cervical cancer receiving simultaneous integrated boost chemoradiation to positive lymph nodes: a single-center experience.

OBJECTIVES: To examine the benefits of extended-field chemoradiation with simultaneous integrated boost to positive lymph nodes, followed by image-guided adaptive brachytherapy in patients with cervical cancer with para-aortic metastasis. METHODS: This retrospective cohort study enrolled 143 patients diagnosed between January 2011 and July 2023 at a single center. Survival and recurrence were evaluated using the Kaplan-Meier method and log-rank test. Cox regression was employed to identify prognostic factors and adjust for confounding factors. Patients were then stratified according to neoadjuvant chemotherapy, and its impact on survival outcomes was evaluated. RESULTS: A total of 129 patients completed the entire treatment course. The 5-year overall survival rate was 57.6%, and the para-aortic failure rate was 6.8% after a median follow-up of 61 months (95% CI 49 to 82 months). Multivariate analysis indicated that neoadjuvant chemotherapy, larger primary tumor or pelvic/para-aortic lymph nodes, and lower hemoglobin nadir (for widespread metastasis-free survival only) predicted poorer survival. After propensity score matching, the 5-year para-aortic recurrence-free, widespread metastasis-free, and overall survival rates were 92.2% vs 92.8% (p=0.85), 50.8% vs 72.1% (p=0.007), and 47.5% vs 65.5% (p=0.037), respectively, in groups receiving neoadjuvant chemotherapy or not. Sixteen patients (12.4%) experienced grade 3-4 late toxicities. Patients who received neoadjuvant chemotherapy had a significantly higher incidence of grade 3-4 anemia and neutropenia than those who did not (45.2% vs 26.7% and 38.1% vs 21.8%, respectively), if including another 14 patients who discontinued treatment due to acute vomiting. CONCLUSION: Chemoradiation with simultaneous integrated boost to positive lymph nodes demonstrates favorable outcomes and acceptable late toxicities in para-aortic metastatic cervical cancer. Neoadjuvant chemotherapy has been shown to adversely affect outcomes, and acute vomiting is a major cause of treatment abortion.

Stress-induced nuclear translocation of ONAC023 improves drought and heat tolerance through multiple processes in rice.

Drought and heat are major abiotic stresses frequently coinciding to threaten rice production. Despite hundreds of stress-related genes being identified, only a few have been confirmed to confer resistance to multiple stresses in crops. Here we report ONAC023, a hub stress regulator that integrates the regulations of both drought and heat tolerance in rice. ONAC023 positively regulates drought and heat tolerance at both seedling and reproductive stages. Notably, the functioning of ONAC023 is obliterated without stress treatment and can be triggered by drought and heat stresses at two layers. The expression of ONAC023 is induced in response to stress stimuli. We show that overexpressed ONAC23 is translocated to the nucleus under stress and evidence from protoplasts suggests that the dephosphorylation of the remorin protein OSREM1.5 can promote this translocation. Under drought or heat stress, the nuclear ONAC023 can target and promote the expression of diverse genes, such as OsPIP2;7, PGL3, OsFKBP20-1b, and OsSF3B1, which are involved in various processes including water transport, reactive oxygen species homeostasis, and alternative splicing. These results manifest that ONAC023 is fine-tuned to positively regulate drought and heat tolerance through the integration of multiple stress-responsive processes. Our findings provide not only an underlying connection between drought and heat responses, but also a promising candidate for engineering multi-stress-resilient rice.

Effects of the commensal microbiota on spleen and mesenteric lymph node immune function: investigation in a germ-free piglet model.

Commensal microbial-host interaction is crucial for host metabolism, growth, development, and immunity. However, research on microbial-host immunity in large animal models has been limited. This study was conducted to investigate the effects of the commensal microbiota on immune function in two model groups: germ-free (GF) and specific-pathogen-free (SPF) piglets. The weight and organ index of the spleen of the GF piglet were larger than those in the SPF piglet (P < 0.05). The histological structure of the red pulp area and mean area of germinal centers were larger in the SPF piglet than in the GF piglet (P < 0.05), whereas the areas of staining of B cells and T cells in the spleen and mesenteric lymph nodes (MLNs) were lower in the GF piglet (P < 0.05). We identified immune-related genes in the spleen and MLNs using RNA sequencing, and used real-time quantitative PCR to analyze the expression of core genes identified in gene set enrichment analysis. The expression levels of genes in the transforming growth factor-ß/SMAD3 signaling pathway, Toll-like receptor 2/MyD88/nuclear factor-κB signaling pathway, and pro-inflammatory factor genes IL-6 and TNF-α in the spleen and MLNs were higher in the SPF piglet and in splenic lymphocytes compared with those in the GF and control group, respectively, under treatment with acetic acid, propionic acid, butyric acid, lipopolysaccharide (LPS), or concanavalin A (ConA). The abundances of plasma cells, CD8++ T cells, follicular helper T cells, and resting natural killer cells in the spleen and MLNs were significantly greater in the SPF piglet than in the GF piglet (P < 0.05). In conclusion, the commensal microbiota influenced the immune tissue structure, abundances of immune cells, and expression of immune-related pathways, indicating the importance of the commensal microbiota for spleen and MLNs development and function. In our study, GF piglet was used as the research model, eliminating the interference of microbiota in the experiment, and providing a suitable and efficient large animal research model for exploring the mechanism of "microbial-host" interactions.

Diversity and host interaction of the gut microbiota in specific pathogen-free pigs.

Pigs are widely used as animal models in various studies related to humans. The interaction between the gut microbiota and the host has significant effects on the host's health and disease status. However, although there have been many studies investigating the pig gut microbiota, the findings have been inconsistent due to variations in rearing conditions. Interactions between the gut microbiota and host have not been fully explored in pigs. Specific pathogen-free (SPF) pigs are ideal non-primate large animals to study the interactions between the gut microbiota and the host. In this study, we performed high-throughput sequencing analysis of the gut microbiota and the gut tissue transcriptome of six SPF pigs to provide a systematic understanding of the composition, function, and spatial distribution of gut microbiota in SPF pigs. We identified significant differences in microbial diversity and functionality among different gastrointestinal tract sites. Metagenomics data analysis revealed significant differences in alpha diversity and beta diversity of microbiota in different gastrointestinal sites of SPF pigs. Additionally, transcriptomic data indicated significant differences in gene expression as well as KEGG and GO functional enrichment between the small intestine and large intestine. Furthermore, by combining microbial metagenomics and host transcriptomics analyses, specific correlations were found between gut microbiota and host genes. These included a negative correlation between the TCN1 gene and Prevotella dentalis, possibly related to bacterial metabolic pathways involving vitamin B12, and a positive correlation between the BDH1 gene and Roseburia hominis, possibly because both are involved in fatty acid metabolism. These findings lay the groundwork for further exploration of the co-evolution between the microbiota and the host, specifically in relation to nutrition, metabolism, and immunity. In conclusion, we have elucidated the diversity of the gut microbiota in SPF pigs and conducted a detailed investigation into the interactions between the gut microbiota and host gene expression. These results contribute to our understanding of the intricate dynamics between the gut microbiota and the host, offering important references for advancements in life science research, bioproduct production, and sustainable development in animal husbandry.

A double-stranded RNA binding protein enhances drought resistance via protein phase separation in rice.

Drought stress significantly impacts global rice production, highlighting the critical need to understand the genetic basis of drought resistance in rice. Here, through a genome-wide association study, we reveal that natural variations in DROUGHT RESISTANCE GENE 9 (DRG9), encoding a double-stranded RNA (dsRNA) binding protein, contribute to drought resistance. Under drought stress, DRG9 condenses into stress granules (SGs) through liquid-liquid phase separation via a crucial α-helix. DRG9 recruits the mRNAs of OsNCED4, a key gene for the biosynthesis of abscisic acid, into SGs and protects them from degradation. In drought-resistant DRG9 allele, natural variations in the coding region, causing an amino acid substitution (G267F) within the zinc finger domain, increase DRG9's binding ability to OsNCED4 mRNA and enhance drought resistance. Introgression of the drought-resistant DRG9 allele into the elite rice Huanghuazhan significantly improves its drought resistance. Thus, our study underscores the role of a dsRNA-binding protein in drought resistance and its promising value in breeding drought-resistant rice.

Haplotype-resolved 3D chromatin architecture of the hybrid pig.

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter-enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.

The boundary of posterior to level V region and the theoretical feasibility of irradiation dose reduction of level Va in nasopharyngeal carcinoma.

The lymph node involvement in the posterior to level V (PLV) region is mainly observed in nasopharyngeal carcinoma (NPC). Recently, we have reported the distribution of metastatic lymph nodes in the PLV region and there are correlations between the neck node levels (NNL) of NPC, but what is the boundary of the PLV region and how to delineate it remains unclear, and we further to elaborate whether the bilateral level Va should be covered as intermediate-risk nodal regions (CTVn2, about 60 Gy equivalent) for all T and N categories based on these correlations. A total of 1021 consecutive NPC patients with N1-3 stage from January 2012 to December 2020 were reviewed. The lymph node metastasis level of each patient was evaluated according to the updated guidelines proposed in 2013. According to the distribution pattern of lymph node metastasis and the anatomical structure in the PLV region, the boundaries of PLV region was delineated, and whether it is appropriate to cover the bilateral level Va as CTVn2 for all the NPC patients was further discussed. The correlations of level Va with other NNL were studied using logistic regression model. The cranial boundary of PLV region is the caudal border of cricoid cartilage, the caudal boundary is the plane serratus anterior muscle begins to appear, the anterior boundary is the anterior border of trapezius, and the posterior boundary is the convergence of levator scapulae and trapezius. Laterally, the PLV region is limited by the medial edge of trapezius and medially by the lateral surface of levator scapulae. The nodal spread in level Va is based on the lymph node metastasis of level IIb in NPC. The PLV region is a missing NNL of head and neck tumors, especially in NPC. The proposed boundaries of the PLV region can provide a preliminary proposal for the further revision of NNL in head and neck tumors. It is theoretically feasible to reduce the prophylactic irradiation dose of the bilateral level Va in patients with N0 stage or with isolated metastases in level VIIa.

Organocatalytic Enantioselective Synthesis of Seven-Membered Ring with Inherent Chirality.

Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).

An intronic enhancer of Cebpa regulates adipocyte differentiation and adipose tissue development via long-range loop formation.

Cebpa is a master transcription factor gene for adipogenesis. However, the mechanisms of enhancer-promoter chromatin interactions controlling Cebpa transcriptional regulation during adipogenic differentiation remain largely unknown. To reveal how the three-dimensional structure of Cebpa changes during adipogenesis, we generated high-resolution chromatin interactions of Cebpa in 3T3-L1 preadipocytes and 3T3-L1 adipocytes using circularized chromosome conformation capture sequencing (4C-seq). We revealed dramatic changes in chromatin interactions and chromatin status at interaction sites during adipogenic differentiation. Based on this, we identified five active enhancers of Cebpa in 3T3-L1 adipocytes through epigenomic data and luciferase reporter assays. Next, epigenetic repression of Cebpa-L1-AD-En2 or -En3 by the dCas9-KRAB system significantly down-regulated Cebpa expression and inhibited adipocyte differentiation. Furthermore, experimental depletion of cohesin decreased the interaction intensity between Cebpa-L1-AD-En2 and the Cebpa promoter and down-regulated Cebpa expression, indicating that long-range chromatin loop formation was mediated by cohesin. Two transcription factors, RXRA and PPARG, synergistically regulate the activity of Cebpa-L1-AD-En2. To test whether Cebpa-L1-AD-En2 plays a role in adipose tissue development, we injected dCas9-KRAB-En2 lentivirus into the inguinal white adipose tissue (iWAT) of mice to suppress the activity of Cebpa-L1-AD-En2. Repression of Cebpa-L1-AD-En2 significantly decreased Cebpa expression and adipocyte size, altered iWAT transcriptome, and affected iWAT development. We identified functional enhancers regulating Cebpa expression and clarified the crucial roles of Cebpa-L1-AD-En2 and Cebpa promoter interaction in adipocyte differentiation and adipose tissue development.

A multiclass extreme gradient boosting model for evaluation of transcriptomic biomarkers in Alzheimer's disease prediction.

BACKGROUND: Patients with young-onset Alzheimer's disease (AD) (before the age of 50 years old) often lack obvious imaging changes and amyloid protein deposition, which can lead to misdiagnosis with other cognitive impairments. Considering the association between immunological dysfunction and progression of neurodegenerative disease, recent research has focused on identifying blood transcriptomic signatures for precise prediction of AD. METHODS: In this study, we extracted blood biomarkers from large-scale transcriptomics to construct multiclass eXtreme Gradient Boosting models (XGBoost), and evaluated their performance in distinguishing AD from cognitive normal (CN) and mild cognitive impairment (MCI). RESULTS: Independent testing with external dataset revealed that the combination of blood transcriptomic signatures achieved an area under the receiver operating characteristic curve (AUC of ROC) of 0.81 for multiclass classification (sensitivity = 0.81; specificity = 0.63), 0.83 for classification of AD vs. CN (sensitivity = 0.72; specificity = 0.73), and 0.85 for classification of AD vs. MCI (sensitivity = 0.77; specificity = 0.73). These candidate signatures were significantly enriched in 62 chromosome regions, such as Chr.19p12-19p13.3, Chr.1p22.1-1p31.1, and Chr.1q21.2-1p23.1 (adjusted p < 0.05), and significantly overrepresented by 26 transcription factors, including E2F2, FOXO3, and GATA1 (adjusted p < 0.05). Biological analysis of these signatures pointed to systemic dysregulation of immune responses, hematopoiesis, exocytosis, and neuronal support in neurodegenerative disease (adjusted p < 0.05). CONCLUSIONS: Blood transcriptomic biomarkers hold great promise in clinical use for the accurate assessment and prediction of AD.

Control of rice ratooning ability by a nucleoredoxin that inhibits histidine kinase dimerization to attenuate cytokinin signaling in axillary buds.

Rice ratooning, the fast outgrowth of dormant buds on stubble, is an important cropping practice in rice production. However, the low ratooning ability (RA) of most rice varieties restricts the application of this cost-efficient system, and the genetic basis of RA remains unknown. In this study, we dissected the genetic architecture of RA by a genome-wide association study in a natural rice population. Rice ratooning ability 3 (RRA3), encoding a hitherto not characterized nucleoredoxin involved in reduction of disulfide bonds, was identified as the causal gene of a major locus controlling RA. Overexpression of RRA3 in rice significantly accelerated leaf senescence and reduced RA, whereas knockout of RRA3 significantly delayed leaf senescence and increased RA and ratoon yield. We demonstrated that RRA3 interacts with Oryza sativa histidine kinase 4 (OHK4), a cytokinin receptor, and inhibits the dimerization of OHK4 through disulfide bond reduction. This inhibition ultimately led to decreased cytokinin signaling and reduced RA. In addition, variations in the RRA3 promoter were identified to be associated with RA. Introgression of a superior haplotype with weak expression of RRA3 into the elite rice variety Guichao 2 significantly increased RA and ratoon yield by 23.8%. Collectively, this study not only uncovers an undocumented regulatory mechanism of cytokinin signaling through de-dimerization of a histidine kinase receptor-but also provides an eximious gene with promising value for ratoon rice breeding.

Directly imaging excited state-resolved transient structures of water induced by valence and inner-shell ionisation.

Real-time imaging of transient structure of the electronic excited state is fundamentally critical to understand and control ultrafast molecular dynamics. The ejection of electrons from the inner-shell and valence level can lead to the population of different excited states, which trigger manifold ultrafast relaxation processes, however, the accurate imaging of such electronic state-dependent structural evolutions is still lacking. Here, by developing the laser-induced electron recollision-assisted Coulomb explosion imaging approach and molecular dynamics simulations, snapshots of the vibrational wave-packets of the excited (A) and ground states (X) of D2O+ are captured simultaneously with sub-10 picometre and few-femtosecond precision. We visualise that θDOD and ROD are significantly increased by around 50∘ and 10 pm, respectively, within approximately 8 fs after initial ionisation for the A state, and the ROD further extends 9 pm within 2 fs along the ground state of the dication in the present condition. Moreover, the ROD can stretch more than 50 pm within 5 fs along autoionisation state of dication. The accuracies of the results are limited by the simulations. These results provide comprehensive structural information for studying the fascinating molecular dynamics of water, and pave the way towards to make a movie of excited state-resolved ultrafast molecular dynamics and light-induced chemical reaction.

H2 formation via non-Born-Oppenheimer hydrogen migration in photoionized ethane.

Neutral H2 formation via intramolecular hydrogen migration in hydrocarbon molecules plays a vital role in many chemical and biological processes. Here, employing cold target recoil ion momentum spectroscopy (COLTRIMS) and pump-probe technique, we find that the non-adiabatic coupling between the ground and excited ionic states of ethane through conical intersection leads to a significantly high yield of neutral H2 fragment. Based on the analysis of fingerprints that are sensitive to orbital symmetry and electronic state energies in the photoelectron momentum distributions, we tag the initial electronic population of both the ground and excited ionic states and determine the branching ratios of H2 formation channel from those two states. Incorporating theoretical simulation, we established the timescale of the H2 formation to be ~1300 fs. We provide a comprehensive characterization of H2 formation in ionic states of ethane mediated by conical intersection and reveals the significance of non-adiabatic coupling dynamics in the intramolecular hydrogen migration.

Pharmacological effects and mechanisms of YiYiFuZi powder in chronic heart disease revealed by metabolomics and network pharmacology.

Introduction: YiYiFuZi powder (YYFZ) is a classical formula in Chinese medicine, which is commonly used clinically for the treatment of Chronic Heart Disease (CHD), but it's pharmacological effects and mechanism of action are currently unclear. Methods: An adriamycin-induced CHD model rat was established to evaluate the pharmacological effects of YYFZ on CHD by the results of inflammatory factor level, histopathology and echocardiography. Metabolomic studies were performed on rat plasma using UPLC-Q-TOF/MS to screen biomarkers and enrich metabolic pathways; network pharmacology analysis was also performed to obtain the potential targets and pathways of YYFZ for the treatment of CHD. Results: The results showed that YYFZ significantly reduced the levels of TNF-α and BNP in the serum of rats, alleviated the disorder of cardiomyocyte arrangement and inflammatory cell infiltration, and improved the cardiac function of rats with CHD. The metabolomic analysis identified a total of 19 metabolites, related to amino acid metabolism, fatty acid metabolism, and other metabolic pathways. Network pharmacology showed that YYFZ acts through PI3K/Akt signaling pathway, MAPK signaling pathway and Ras signaling pathway. Discussion: YYFZ treatment of CHD modulates blood metabolic pattern and several protein phosphorylation cascades but importance specific changes for therapeutic effect require further studies.

Serine protease NAL1 exerts pleiotropic functions through degradation of TOPLESS-related corepressor in rice.

NARROW LEAF 1 (NAL1) is a breeding-valuable pleiotropic gene that affects multiple agronomic traits in rice, although the molecular mechanism is largely unclear. Here, we report that NAL1 is a serine protease and displays a novel hexameric structure consisting of two ATP-mediated doughnut-shaped trimeric complexes. Moreover, we identified TOPLESS-related corepressor OsTPR2 involved in multiple growth and development processes as the substrate of NAL1. We found that NAL1 degraded OsTPR2, thus modulating the expression of downstream genes related to hormone signalling pathways, eventually achieving its pleiotropic physiological function. An elite allele, NAL1A, which may have originated from wild rice, could increase grain yield. Furthermore, the NAL1 homologues in different crops have a similar pleiotropic function to NAL1. Our study uncovers a NAL1-OsTPR2 regulatory module and provides gene resources for the design of high-yield crops.

Dynamic chromatin architecture of the porcine adipose tissues with weight gain and loss.

Using an adult female miniature pig model with diet-induced weight gain/weight loss, we investigated the regulatory mechanisms of three-dimensional (3D) genome architecture in adipose tissues (ATs) associated with obesity. We generated 249 high-resolution in situ Hi-C chromatin contact maps of subcutaneous AT and three visceral ATs, analyzing transcriptomic and chromatin architectural changes under different nutritional treatments. We find that chromatin architecture remodeling underpins transcriptomic divergence in ATs, potentially linked to metabolic risks in obesity development. Analysis of chromatin architecture among subcutaneous ATs of different mammals suggests the presence of transcriptional regulatory divergence that could explain phenotypic, physiological, and functional differences in ATs. Regulatory element conservation analysis in pigs and humans reveals similarities in the regulatory circuitry of genes responsible for the obesity phenotype and identified non-conserved elements in species-specific gene sets that underpin AT specialization. This work provides a data-rich tool for discovering obesity-related regulatory elements in humans and pigs.

Decoding the transcriptome of muscular dystrophy due to Ptrf deficiency using single-nucleus RNA sequencing.

Lacking PTRF (polymerase I and transcript release factor), an essential caveolae component, causes a secondary deficiency of caveolins resulting in muscular dystrophy. The transcriptome responses of different types of muscle fibers and mononuclear cells in skeletal muscle to muscular dystrophy caused by Ptrf deletion have not been explored. Here, we created muscular dystrophy mice by Ptrf knockout and applied single-nucleus RNA sequencing (snRNA-seq) to unveil the transcriptional changes of the skeletal muscle at single-nucleus resolution. 11 613 muscle nuclei (WT, 5838; Ptrf KO, 5775) were classified into 12 clusters corresponding to 11 nuclear types. Trajectory analysis revealed the potential transition between type IIb_1 and IIb_2 myonuclei upon muscular dystrophy. Functional enrichment analysis indicated that apoptotic signaling and enzyme-linked receptor protein signaling pathway were significantly enriched in type IIb_1 and IIb_2 myonuclei of Ptrf KO, respectively. The muscle structure development and the PI3K-AKT signaling pathway were significantly enriched in type IIa and IIx myonuclei of Ptrf KO. Meanwhile, metabolic pathway analysis showed a decrease in overall metabolic pathway activity of myonuclei subtypes upon muscular dystrophy, with the most decrease in type IIb_1 myonuclei. Gene regulatory network analysis found that the activity of Mef2c, Mef2d, Myf5, and Pax3 regulons was enhanced in type II myonuclei of Ptrf KO, especially in type IIb_2 myonuclei. In addition, we investigated the transcriptome changes in adipocytes and found that muscular dystrophy enhanced the lipid metabolic capacity of adipocytes. Our findings provide a valuable resource for exploring the molecular mechanism of muscular dystrophy due to Ptrf deficiency.