To explore the mechanism of Shihu Mixture (SHM) for improving diabetic cardiomyopathy. Thirty male SD rats were randomized into 3 groups (n=10) for type 2 diabetes mellitus modeling by high-fat and -sugar feeding for 12 weeks and intraperitoneal streptozotocin injection, followed by treatment with daily gavage of normal saline (model group), metformin solution, or SHM extract for 4 weeks, with 10 normally fed rats as the normal control group. Fasting blood glucose and cardiac weight index of the rats were monitored, and their TG, TC, LDL-C, HDL-C, and LDH levels were determined; serum and myocardial levels of BNP, CRP, TNF‑α and IL-6 were detected with ELISA. Myocardial pathological changes and ultrastructures of myocardial mitochondria and autophagosomes were examined with HE and Masson staining and transmission electron microscopy. Myocardial expressions of Sirt3, FoxO3a, PINK1, Parkin, P62, and LC3 mRNAs and proteins were detected with RT-qPCR, Western blotting, and immunohistochemistry. Compared with those in the control group, the rats in the other 3 groups showed significantly increased fasting blood glucose, cardiac weight index, serum TC, TG, LDL-C, LDH, CRP and BNP levels and myocardial levels of TNF‑α and IL-6 with lowered HDL-C level, obvious myocardial and mitochondrial pathologies, and dysregulated expression of Sirt3, FoxO3a, p-FoxO3a, PINK1, Parkin, LC3 and P62. Treatment of the rat models with SHM extract significantly reduced fasting blood glucose level and cardiac weight index, lowered the levels of LDH, CRP, BNP, TNF‑α, IL-6, TC, TG, and LDL-C, increased HDL-C level, alleviated myocardial and mitochondrial damages, promoted autophagosome formation, and improved dysregulation of mitochondrial autophagy-related gene expression, showing similar effects to metformin. SHM alleviates myocardial damage and improves mitochondrial function in rats with diabetic cardiomyopathy by regulating the mitochondrial autophagy pathway through Sirt3.

Immunotherapy has demonstrated limited efficacy in immunologically "cold" breast cancers characterized by absent T-cell infiltration and inadequate interferon signaling. The purpose of this work is to propose and articulate a mechanistic and therapeutic framework in which mitochondrial stress is deliberately harnessed to convert immunologically "cold" breast tumors into "hot," T cell-inflamed, immunotherapy-responsive lesions. This review synthesizes emerging evidence positioning mitochondrial stress as a strategic lever to transform these immune-excluded tumors into inflamed, therapy-responsive lesions. We examine how mitochondrial dysfunction triggers cytosolic release of mitochondrial DNA (mtDNA), a potent damage-associated molecular pattern that activates the cGAS-STING pathway, initiating type I interferon responses and secretion of T-cell-recruiting chemokines such as CCL5 and CXCL10. This axis functions as a "double-edged sword"-while acute activation converts "cold" tumors into "hot" immune-responsive states, chronic engagement drives immunosuppressive cytokine networks and therapeutic resistance, with outcomes varying across breast cancer subtypes. We explore six combination therapeutic strategies: mitochondrial poisons, radiotherapy/chemotherapy, PARP/ATR inhibitors, metabolic reprogramming agents, mitochondrial quality control modulators, and localized mitochondrial stress induction, each paired with immune checkpoint blockade. The review emphasizes "controlled ignition" as a paradigm whereby precisely dosed mitochondrial stress amplifies tumor antigenicity and favorable cytokine landscapes while avoiding chronic immunosuppression. Cytokine networks emerge as both integrators and therapeutic targets of mitochondrial-immune crosstalk. Future advances require mapping subtype-specific thresholds, developing tumor-restricted delivery systems, and implementing biomarker-guided trials to safely harness mitochondrial stress, potentially redefining these organelles as programmable immunological adjuvants in breast cancer therapy.

The transcription factor Nurr1 (NR4A2) serves as an essential element in dopaminergic neuron development since it functions predominantly in the substantia nigra, which becomes severely affected during Parkinson's disease (PD) and Alzheimer's disease (AD). Nurr1 regulates dopamine synthesis, survival-promoting, and oxidative stress genes that affect mitochondrial formation. Nurr1 binds to PGC-1α, allowing for mitochondrial activity regulation. This relationship supports mitochondrial biogenesis. Post-translational changes, including phosphorylation and acetylation, modify Nurr1 transcriptional regulation in order to enhance its ability to regulate mitochondrial genes. The assessment examines Nurr1's involvement in dopaminergic neuron development and mitochondrial formation while showing its role in reducing oxidative damage for an extensive understanding of its neurological disease functionality. Nurr1 serves as a therapeutic candidate for analysis, while the review explores obstacles and potential paths for using Nurr1-based treatments against Parkinson's disease alongside Alzheimer's disease and other neurodegenerative disorders. The extensive research utilized multiple databases, PubMed, Scopus, Medline, and EMBASE, with keywords "Nurr1," "NR4A2," "Neurodegenerative disorders," "Mitochondrial biogenesis," "Oxidative stress," "Parkinson's disease," "Alzheimer's disease," and "Therapeutic target." The analysis examined published research regarding Nurr1-mediated control of dopaminergic function and survival and mitigation of neurological and mitochondrial deficits within the past decade. Nurr1's interactions with important co-regulators like PGCα, its post-translational changes, and its effects on neuroinflammation have also received particular focus. In neurodegenerative illnesses, mitochondrial dysfunction adds to neuronal damage. Nurr1's regulation of mitochondrial biogenesis helps recover mitochondrial function, alleviate oxidative stress, and sustain neuronal survival. Dysregulation of Nurr1 expression is connected to decreased mitochondrial activity and accelerated neurodegeneration.

The type species of the trematode genus Skrjabinolecithum, S. spasskii, a parasite of mullets in the Russian Far East and Vietnam, was shown to possess three different variants of rDNA sequences in earlier studies. The goal of the present study is to clarify the taxonomic status of genetically different trematodes, considered S. spasskii, in the Russian Far East and Vietnam by means of new morphological and molecular data. For this study, trematodes of the genus Skrjabinolecithum were collected from mugilid fish from estuaries of rivers of the south of the Russian Far East and the Cat Ba Island, Vietnam. Preliminary species identification and detailed morphometric analysis were carried out using high-resolution light microscopy. Molecular differentiation and phylogenetic analyses were carried out based on nuclear 28S rDNA and mitochondrial cox1 gene sequences. As a result, two morphotypes of S. spasskii were revealed, and two new species, S. kievkaense n. sp. and S. vietnamense n. sp., were validated. These species have no qualitative differences in body form and in organ structure and arrangements but have some differences in metric parameters. The validity of the new species was confirmed by phylogenetic analysis based on the mitochondrial cox1 gene sequence dataset.

The interaction between nuclear (nDNA) and mitochondrial DNA (mtDNA) methylation is not well known in the healthy population. The D-loop methylation level of the Olympic champions (N = 58) was significantly lower than that of non-champions (N = 32) (~ 36% unadjusted mean difference p = 0.016, sex and age adjusted p = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, p = 0.033). On the other hand, we cannot find relationships between the methylation levels of mtDNA and nuclear DNA, suggesting distinct regulation of the methylation/demethylation process of mtDNA and nuclear DNA. DNA methylation-based aging clocks showed a significant relationship with the levels of Klotho, irisin, and its receptor (irisin receptor integrin alpha-V), as well as with epigenetic regulators such as ten-eleven translocation enzyme 2, which were measured using enzyme-linked immunosorbent assay. Therefore, the data suggest a complex regulatory process of epigenetic aging and raise the possibility that D-loop methylation may have functional relevance in health, which remains to be explored.

Mitochondria regulate cellular activity in a tissue-selective manner. The role of mitochondria in corneal fibrosis is elusive. This study investigated changes in mitochondrial DNA (mtDNA) and mitochondrial transcription factor A (TFAM) in human corneal stromal fibroblasts (CSFs) and corneal myofibroblast (CMFs) and effects on corneal fibrosis in vitro and ex vivo. Healthy donor human corneas were used to generate CSFs and ex vivo culture. CMF formation was induced by transforming growth factor beta-1 (TGFβ1) in vitro and human cornea by nitrogen mustard (NM) ex vivo. mtTFA/TFAM CRISPR/Cas9 KO plasmid, Lipofectamine CRISPRMAX, and TrueCut Cas9 Protein v2 were used for gene editing. Long-range PCR and quantitative reverse-transcription PCR (qRT-PCR) measured mtDNA transcription, mtDNA quantity, and ratios of mtDNA to nuclear DNA (nDNA). Immunofluorescence and immunoblotting quantified protein expression. The MitoSOX assay was used to analyze mitochondrial reactive oxygen species (mtROS). Human CMFs showed significantly reduced mtDNA copies (P < 0.01) and mtDNA-to-nDNA ratios (P < 0.05) compared to CSFs. Significant time-dependent increases in mRNA levels of α-smooth muscle actin (αSMA) and nDNA-transcribed genes and decreases in TFAM and mtDNA-transcribed genes were noted during CSF transdifferentiation to CMFs (P < 0.05, P < 0.001, or P < 0.0001). Correspondingly, time-dependent decreases in TFAM and increases in Rieske iron-sulfur (Fe-S) and αSMA protein (P < 0.0001) and mtROS and ROS levels (P < 0.0001) were observed. TFAM silencing arrested fibrotic events and exhibited reduced αSMA and enhanced mtDNA (P < 0.001). The NM-induced fibrotic human cornea showed decreased TFAM and increased αSMA compared to naïve corneas (P < 0.01). We observed that mtDNA plays an important role in corneal fibroblast transdifferentiation to myofibroblast and that TFAM has the potential to modulate this process in an injured cornea. Additional studies are warranted.

We present a genome assembly from a female specimen of Zerynthia rumina (Spanish Festoon; Arthropoda; Insecta; Lepidoptera; Papilionidae). The assembly contains two haplotypes with total lengths of 852.84 megabases and 775.60 megabases. Most of haplotype 1 (99.64%) is scaffolded into 31 chromosomal pseudomolecules, including the W and Z sex chromosomes. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.26 kilobases. This work is part of Project Psyche, a collaborative programme generating genomes for European butterflies and moths.

We present a genome assembly from a male specimen of Setina aurita (Arthropoda; Insecta; Lepidoptera; Erebidae). The assembly contains two haplotypes with total lengths of 1 256.12 megabases and 1 211.86 megabases. Most of haplotype 1 (99.67%) is scaffolded into 32 chromosomal pseudomolecules, including the Z sex chromosome and a supernumerary B chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.44 kilobases. This work is part of Project Psyche, a collaborative programme generating genomes for European butterflies and moths.

We present a genome assembly from a female specimen of Spatalia argentina (Argentine; Arthropoda; Insecta; Lepidoptera; Notodontidae). The assembly contains two haplotypes with total lengths of 324.98 megabases and 295.22 megabases. Most of haplotype 1 (99.89%) is scaffolded into 27 chromosomal pseudomolecules, including the W and Z sex chromosomes. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 16.64 kilobases. This work is part of Project Psyche, a collaborative programme generating genomes for European butterflies and moths.

We present a haploid genome assembly from an individual Lichina pygmaea (Black Lichen; Ascomycota; Lichinomycetes; Lichinales; Lichinaceae). The genome sequence has a total length of 32.42 megabases. The assembly is scaffolded into 7 chromosomal pseudomolecules. The mitochondrial genome has also been assembled, with a length of 47.95 kilobases. Gene annotation of this assembly on Ensembl identified 8 665 protein-coding genes. From the metagenome data, we recovered 9 bins, of which 4 were high-quality MAGs.

We present a genome assembly from a female specimen of Actinotia polyodon (Purple Cloud; Arthropoda; Insecta; Lepidoptera; Noctuidae). The assembly contains two haplotypes with total lengths of 686.76 megabases and 626.61 megabases. Most of haplotype 1 (99.78%) is scaffolded into 32 chromosomal pseudomolecules, including the W and Z sex chromosomes. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.36 kilobases. This work is part of Project Psyche, a collaborative programme generating genomes for European butterflies and moths.

We present a genome assembly from a male specimen of Shargacucullia scrophulariae (Water Betony; Arthropoda; Insecta; Lepidoptera; Noctuidae). The assembly contains two haplotypes with total lengths of 419.05 megabases and 419.35 megabases. Most of haplotype 1 (99.83%) is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.32 kilobases.

We present a genome assembly from a male specimen of Aplocera praeformata (Purple Treble-bar; Arthropoda; Insecta; Lepidoptera; Geometridae). The assembly contains two haplotypes with total lengths of 380.66 megabases and 380.72 megabases. Most of haplotype 1 (99.91%) is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 17.22 kilobases.

We present a genome assembly from a male specimen of Tomares ballus (Provence Hairstreak; Arthropoda; Insecta; Lepidoptera; Lycaenidae). The assembly contains two haplotypes with total lengths of 839.94 megabases and 831.10 megabases. Most of haplotype 1 (99.02%) is scaffolded into 23 chromosomal pseudomolecules, including the Z sex chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.43 kilobases. This work is part of Project Psyche, a collaborative programme generating genomes for European butterflies and moths.

We present a genome assembly from a female specimen of Siona lineata (Black-veined Moth; Arthropoda; Insecta; Lepidoptera; Geometridae). The assembly contains two haplotypes with total lengths of 390.00 megabases and 347.88 megabases. Most of haplotype 1 (99.09%) is scaffolded into 29 chromosomal pseudomolecules, including the W and Z sex chromosomes. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.62 kilobases. This work is part of Project Psyche, a collaborative programme generating genomes for European butterflies and moths.

Fish cell lines are indispensable tools for virology, biotechnology, and toxicology research. This study established a new marine fish cell line, designated EfE, from the eye tissue of the brown-marbled grouper (Epinephelus fuscoguttatus). The EfE cell line has been stably subcultured for over 70 passages in vitro for more than 300days. It proliferated optimally in Leibovitz's L-15 medium supplemented with 15% fetal bovine serum at 28°C. Species origin was confirmed by molecular analysis of the mitochondrial CO1 gene. Chromosome analysis revealed a diploid count of 48, which is consistent with the karyotype of E. fuscoguttatus. The cell line demonstrated high transfection efficiency (25.6%) with a pEGFP-N1 plasmid, indicating its potential for genetic manipulation. In virus susceptibility tests, EfE cells were highly permissive to red-spotted grouper nervous necrosis virus (RGNNV), developing severe cytopathic effects (CPE), including extensive vacuolation, cell rounding, and detachment. Viral replication was further confirmed by semi-quantitative RT-PCR and the observation of virus particles via transmission electron microscopy (TEM). In conclusion, the novel EfE cell line provides a valuable in vitro model for virus isolation, propagation, investigation of pathogenic mechanisms, and genetic studies.

In Parkinson's disease and dementia with Lewy bodies, aggregated and phosphorylated α-synuclein appears in select neurons throughout cortical and subcortical regions, but little is currently known about why certain populations are selectively vulnerable. Here, using imaging spatial transcriptomics (IST) coupled with downstream immunofluorescence for α-synuclein phosphorylated at Ser129 (pSyn) in the same tissue sections, we identified neuronal subtypes in the cortex and hippocampus of transgenic human α-synuclein-overexpressing mice that preferentially developed pSyn accumulation. Additionally, we investigated the transcriptional underpinnings of this vulnerability, pointing to expression of Plk2, which phosphorylates α-synuclein at Ser129, and human SNCA (hSNCA), as key to pSyn development. Finally, we performed differential expression analysis, revealing gene expression changes broadly downstream of hSNCA overexpression, as well as pSyn-dependent alterations in mitochondrial and endolysosomal genes. Overall, this study yields new insights into the formation of phospho-α-synuclein and its downstream effects in a synucleinopathy mouse model.

Mitochondria, which evolved from symbiotic bacteria, possess their own genomes (mtDNA) and support independent transcription and translation within the organelle. Given the essential role of mtDNA in energy production, metabolism, as well as cellular homeostasis, and the high density of confirmed pathogenic mutations that map to mtDNA, there is a pressing need for versatile methods to study and manipulate this genome. Although CRISPR technology has revolutionized the editing of nuclear genomes, it has not been successfully extended to mtDNA, primarily due to the challenge of delivering single guide RNAs (sgRNAs) across both outer and inner mitochondrial membranes. Here we develop a survival-based reporter in Saccharomyces cerevisiae to screen for potential RNA import motifs. We identify a 40-nucleotide aptamer (IM83) that facilitates sgRNA entry into the mitochondrial matrix, enabling CRISPR editing by a mitochondrially-localized adenine base editor. We show that mitochondrial import of IM83 is ATP-dependent and enhanced by the tRNA synthetase Msk1. Further investigations identify barriers to efficient CRISPR editing of mtDNA, including loss of membrane potential associated with mitochondrial targeting of the base editor. These insights lay the groundwork for future improvements in CRISPR-based editing of mtDNA in eukaryotes.

The dung beetle family Geotrupidae (Scarabaeoidea) plays a vital ecological role in nutrient cycling and soil health, yet the scarcity of complete mitochondrial genome (mitogenome) data has hindered phylogenetic and comparative studies within this family. Here, we sequenced, assembled, and annotated the first complete mitogenomes of Geotrupes stercorarius and Phelotrupes auratus, collected from the Qinghai–Tibetan Plateau. Comparative analysis of these two novel mitogenomes with eight existing mitogenomes revealed conserved architectural features across Geotrupidae, such as gene arrangement, tRNA secondary structures, and small intergenic spacers. Nucleotide composition was largely conserved, though marked divergence occurred at the third codon positions. Substantial structural variation was observed in non-coding regions, particularly in the control region and the nad2-trnW spacer. Evolutionary analyses indicated strong purifying selection across all protein-coding genes, with no evidence of widespread positive selection linked to high-altitude adaptation. Phylogenetic reconstruction consistently recovered the relationships (Bolboceratinae, (Lethrinae, Geotrupinae)), with Anoplotrupes and Geotrupes forming sister genera within Geotrupinae. This study provides additional mitogenomic resources and a well-supported phylogenetic framework for Geotrupidae, resolving key taxonomic uncertainties and establishing a basis for future evolutionary and ecological research.

Ischemic heart disease is a leading cause of death worldwide, and heart failure after myocardial infarction (MI) is a growing issue in an ageing society. Macrophages play a central role in left ventricular (LV) remodeling after MI. Mitochondria consistently change their morphology, including fission and fusion; however, the role of these morphological changes, particularly in macrophages, remains unknown. This study investigated the role of dynamin-related protein 1 (Drp1), a key mediator of mitochondrial fission, in macrophages and its involvement in the mechanisms of left ventricular remodeling after myocardial infarction (MI). This study utilized genetically altered mice lacking Drp1 in Lysozyme M-positive cells (Drp1-KO) to elucidate the specific role of macrophage Drp1 in post-infarct LV remodeling. Deletion of Drp1 in macrophages exacerbated LV remodeling, underpinned by reduced ejection fraction and increased LV diameter, which resulted in a poor prognosis after MI. Histological analysis indicated increased fibrosis and sustained macrophage accumulation in the infarcted hearts of Drp1-KO mice. Blockade of Drp1 in macrophages decreased mitochondrial fission and impaired mitophagy, leading to the subsequent release of mitochondrial DNA (mtDNA) into the cytosol and the induction of inflammatory cytokines. This induction was abrogated by the autophagy inducer Tat-beclin1 or siRNA-mediated knockdown of Z-DNA Binding Protein 1 (ZBP1). Deletion of ZBP1 in bone marrow-derived cells abrogated LV remodeling induced by the Drp1 inhibitor Mdivi-1. Macrophage Drp1 plays a critical role in the pathobiology of post-infarct LV remodeling, particularly in mitochondrial quality control mechanisms. Macrophage Drp1 could be a novel therapeutic molecule to mitigate the progression of LV remodeling and consequent heart failure after MI.