Background/Objectives: Prostate cancer remains a major cause of cancer-related mortality in men. Arctigenin (ATG) and curcumin (CUR) exhibit anticancer activity; however, their combined effects on redox and metabolic stress remain incompletely understood. This study investigated the anticancer effects of combined ATG and CUR treatment in prostate cancer cells. Methods: PC-3 prostate cancer cells and normal human prostate epithelial (HPrEC) cells were treated with ATG and CUR alone or in combination. Cell viability, combination index, reactive oxygen species (ROS), GSH/GSSG ratio, ATP levels, AMPK phosphorylation, and apoptosis-related responses were evaluated. The contribution of oxidative stress was examined using N-acetyl-L-cysteine (NAC), and treatment effects were further assessed in three-dimensional (3D) spheroids. Results: Combined ATG and CUR treatment produced greater growth-inhibitory and apoptotic responses in PC-3 cells than in HPrEC cells and was synergistic under the tested condition in PC-3 cells. The combination increased ROS, reduced the GSH/GSSG ratio and ATP levels, increased AMPK phosphorylation, and enhanced apoptosis-related responses. NAC attenuated ROS accumulation, partially restored cell viability and ATP levels, and reduced caspase-3/7 activity in PC-3 cells. In 3D PC-3 spheroids, NAC also partially restored viability and ATP levels and attenuated increases in cleaved caspase-3 and cleaved PARP. Conclusions: Combined ATG and CUR treatment induces redox and metabolic stress and enhanced apoptotic responses in PC-3 cells, with weaker effects in HPrEC cells. NAC rescue supports a functional contribution of oxidative stress. These findings support an association between ROS-related metabolic stress, AMPK phosphorylation, and apoptotic signaling, while precise causal relationships require further investigation.

Red algae (Rhodophyta) are an ancient lineage of photosynthetic eukaryotes that play important roles in marine ecosystems. However, genomic information for many species within the order Rhodymeniales remains limited, particularly for mitochondrial genomes. In this study, we sequenced, assembled, and analyzed the complete mitochondrial genome (mitogenome) of Rhodymenia intricata to investigate its genome organization, gene content, and phylogenetic position within Rhodymeniales. The mitogenome of R. intricata is a circular DNA molecule of 26,213 bp containing 49 genes, including 25 protein-coding genes (PCGs), 21 tRNA genes, and 3 rRNA genes. The genome shows a strong A + T bias (70.9%) and positive AT and GC skews, typical of red algal mitogenomes. Comparative analysis with other Rhodymeniales mitogenomes revealed generally conserved gene content and organization, with several lineage-specific features such as the presence of the rpl20 gene, an additional open reading frame (orf148), and three rRNA genes (rnl, rns, and rns5). Codon usage analysis indicated a preference for leucine and isoleucine codons and dominant start and stop codons (ATG and TAA). Phylogenetic analysis based on a concatenated dataset of 23 mitochondrial PCGs strongly supported the monophyly of Rhodymeniales and confirmed the close relationship between R. intricata and R. pseudopalmata. Overall, this study presents the first complete mitogenome of R. intricata and expands mitogenomic resources for Rhodymeniales, providing new insights into mitogenome evolution and phylogenetic relationships in red algae.

The seedless trait in grapes primarily arises from pseudo-parthenocarpy, driven by early seed abortion involving programmed cell death (PCD) and autophagy. However, the specific regulatory networks governing these pathways remain poorly defined. To address this, we systematically characterized the PCD-related (vacuolar processing enzyme [VPE] and metacaspase [MC]) and autophagy-related (ATG) gene families in the seedless cultivar 'Jingkejing' utilizing comprehensive bioinformatic analyses, spatiotemporal transcriptomic profiling, and transient expression assays. We identified three VPE, six MC, and 33 ATG genes, whose promoters were significantly enriched in hormone-responsive and transcription factor (TF)-binding motifs. Transcriptomic profiling across critical seed abortion stages highlighted VvγVPE and VvMC9 as key differentially expressed genes. Furthermore, protein-protein interaction predictions indicated extensive crosstalk among PCD/ATG proteins, kinases, and ubiquitin system components. Notably, transient expression assays confirmed that two core transcription factors, VvWRKY46 and VvERF71, specifically regulate downstream PCD-related targets, supporting a proposed multi-hormonal and TF-mediated regulatory network during seed abortion. These findings elucidate the molecular mechanisms underlying pseudo-parthenocarpy, providing essential candidate gene resources for the marker-assisted breeding of seedless grapes.

Background and Clinical Significance: Carbimazole is a widely used medication to treat Graves' disease, although it can rarely cause acquired aplastic anemia, a complication that happens in less than 0.01% of people. Case Presentation: We report a 36-year-old woman treated with supratherapeutic dose carbimazole who, after approximately six months of treatment, developed high grade fever, severe menorrhagia, spontaneous epistaxis, and pancytopenia. Her bone marrow biopsy showed severe bone marrow failure with only 5% cellularity and trilineage hypoplasia. Other potential causes were ruled out. Immediate discontinuation of carbimazole was done, and supportive care, including blood transfusions, broad-spectrum antibiotics, G-CSF, and eltrombopag, was started. The patient deteriorated during her hospital stay, developed neutropenic sepsis and acute respiratory failure from diffuse alveolar hemorrhage, which required intubation and pulse steroid therapy. She was stabilized and discharged, with a referral to a tertiary medical center for starting antithymocyte globulin (ATG) immunosuppressive therapy, which she subsequently completed; two months after discharge she was transfusion independent with near-normalization of her blood counts. Conclusions: This case serves as a stark reminder of how lethal thionamide-induced bone marrow failure can be, highlighting the vital need for immediate drug cessation, swift intensive care, and thorough patient education on early warning signs.

Background: Oxidative stress, neuroinflammation, impaired autophagy, and mitochondrial dysfunction are major contributors to ageing and neurodegenerative diseases. This study investigated whether AgeViva could counteract these processes by modulating redox balance, inflammation, autophagy, and mitochondrial function. Methods: The effects of AgeViva were evaluated using two complementary experimental models: lipopolysaccharide (LPS)-stimulated BV2 microglial cells and Caenorhabditis elegans (C. elegans) nematodes. In BV2 cells, the expression of inflammatory, autophagy-related, and antioxidant response genes, including NRF2, SOD, and GPX, was evaluated by RT-qPCR, while cell viability was assessed by Trypan Blue exclusion assay. In C. elegans, lifespan, healthspan parameters, ROS accumulation, mitochondrial integrity, membrane potential, and the expression of stress-response, longevity, and autophagy-related genes were analyzed following AgeViva supplementation. Results: In LPS-stimulated BV2 cells, AgeViva significantly reduced the expression of mRNA the pro-inflammatory cytokines Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor alpha (TNF-α) while increasing Interleukin-10 (IL-10) levels, AgeViva also induced changes in autophagy-related transcripts, such as modulation of microtubule-associated protein 1a/1b-Light Chain (LC3) and Sequestosome 1 (p62) expression, activated antioxidant-related gene expression, increasing the expression of Superoxide Dismutase 1(SOD1) and Glutathione Peroxidase (GPX). In C. elegans, AgeViva supplementation extended lifespan and improved healthspan parameters, including locomotor activity and pharyngeal pumping. Treated nematodes showed reduced cytosolic and mitochondrial ROS accumulation, preservation of mitochondrial network integrity, and maintenance of mitochondrial-associated fluorescence, reflecting mitochondrial content and/or membrane potential during ageing. Molecular analyses revealed modulation of key pathways involved in stress resistance and longevity, including Insulin-like Growth Factor 1 (Insulin/IGF-1) signaling Dauer Formation-2 and 16 (DAF-2/DAF-16), Skinhead-1 (SKN-1/Nrf2) signaling, and autophagy-related genes, like Ligating (lgg-1), Autophagy-Related-7 (atg-7), Autophagy Related-18 (atg-18), uncoordinated-51 (unc-51), and ectopic p-granules autophagy protein 5 (epg-5). Conclusions: AgeViva promotes healthy ageing by modulating oxidative stress, inflammation, autophagy, and mitochondrial homeostasis.

Allogeneic hematopoietic stem cell transplantation (HCT) is a curative treatment for acquired aplastic anemia (AA). More than 1,000 cases of transplants for AA are performed annually in China, and transplant protocols have been continuously refined over recent years. To characterize contemporary transplant practices in China and provide useful insights for global professionals, this study analyzed the 2024 Chinese National Registry data. In 2024, 1,919 transplants were reported among 1,893 patients by 158 centers. Haploidentical donor (HID) was the leading donor source (57.22%). Matched sibling donor (MSD) and unrelated donor (URD) were used in 19.23% and 17.87% of cases, respectively. The G-CSF/ATG-based platform (84.42%) was the predominant transplant modality, followed by the ATG/ATLG+PTCY platform (14.17%). Low-dose busulfan was frequently used in conditioning regimens for both platforms. Due to the dominant use of HID and peripheral blood stem cell grafts, novel graft-versus-host disease (GVHD) prophylactic strategies have been explored. Based on a representative contemporary cohort of 226 patients, we report a favorable 1-year survival rate of 92.0% and a GVHD-/failure-free survival rate of 77.8%, which are comparable to reports from the EBMT and CIBMTR. Moreover, modern HCT practice supports broader consideration of transplantation for older patients, especially those aged 40-50 years. In conclusion, our report offers a comprehensive overview of the current HCT landscape in China and serves as a valuable resource for global practice.

Prior to this study, the mitogenomic characterization, genetic diversity, and phylogenetic placement of the Tinfoil Barb Barbonymus schwanefeldii remained largely unexplored, despite its notable ecological and economic importance. Hence, this study aimed to provide the first in-depth insight into the mitogenomic features of this species from its native range in Sumatra, Indonesia. The generated mitogenome is 16,578 bp in length and contains 37 genes along with a control region (CR). The genome also exhibited a 57.03% A + T bias and all protein-coding genes (PCGs) initiated with the ATG codon, except COI (GTG). The codon usage was dominated by arginine, leucine, and serine, whereas methionine and tryptophan were rare. The pairwise nonsynonymous-to-synonymous substitution ratios demonstrated strong purifying selection across all Barbonymus species. This pattern was further supported by complementary codon-based approaches, which showed that the 13 PCGs were predominantly subject to strong evolutionary constraints, with evidence of positive selection confined to a small number of sites in a limited subset of genes. Most transfer RNA genes of B. schwanefeldii maintained the canonical cloverleaf secondary structure, except tRNA-Ser1, which lacked the dihydrouridine stem. The comparative profiling of conserved sequence blocks within the CR among Barbonymus taxa highlighted variation in length and nucleotide composition, with tandem repeats exclusively detected in B. gonionotus. A mitogenome-wide assessment of B. schwanefeldii revealed considerable intra-specific genetic divergence (0%-3.932%) and notable haplotypic diversity across Southeast Asian islands and mainland populations. This population genetic structure likely reflects historical connectivity during the Pleistocene via ancient drainage systems of the Malacca Strait or North Sunda, followed by subsequent isolation after post-glacial eustatic sea-level rise. The phylogenetic inference robustly corroborated a sister-species relationship between B. schwanefeldii and Barbonymus altus within the clade 'Poropuntiinae'. Collectively, these findings elucidate the phylogeographic patterns and evolutionary history of this Southeast Asian endemic cyprinid fish within the Sundaland biodiversity hotspot.

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes. The increasing use of post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG) has expanded beyond haploidentical transplantation to matched related (MRD) and unrelated donor (MUD) settings, although real-world GVHD incidence in this context is not well characterized. We performed a nationwide retrospective study including 1544 alloHSCTs conducted in Spain between 2018 and 2020. PTCy-based prophylaxis was used in 65.6% of transplants, being almost universal in haploidentical procedures (96.9%) and predominant in mismatched donors (72.4%), with notable use in MRD (43.5%) and MUD (56.8%). The cumulative incidence of grade II-IV acute GVHD at day +100 and 1 year was 28.4% and 30.7%, respectively, while grade III-IV occurred in 6.9% and 8.0%. Despite the prevalent use of peripheral blood stem cells, chronic GVHD at 2 years was 36.7%, with 23.5% moderate-to-severe. Acute GVHD was strongly associated with inferior survival (HR 2.40; P < 0.001), particularly grade III-IV disease (HR 4.34; P < 0.001). This large nationwide real-world study highlights the shift in GVHD prophylaxis in modern alloHSCT and underscores the need to define new studies based on this evolving landscape.