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High-Mobility Group B (HMGB) proteins are conserved non-histone nuclear proteins involved in DNA replication, transcription, recombination, repair; plant growth and development; and stress responses. In this study, we identified nine ClHMGB genes in watermelon using genome-wide search. Phylogenetic and homology analyses classified them into four distinct classes. Synteny analysis revealed that ClHMGB genes share closer evolutionary relationships with dicots than with monocots. Tissue-specific expression profiling showed that eight ClHMGB members exhibit higher transcript levels in female and/or male flowers, suggesting that they play essential roles in floral organ development. Under drought, low-temperature, and salt stresses, ClHMGB members displayed distinct expression patterns. For instance, ClHMGB4 and ClHMGB8 were downregulated under drought and low-temperature stress but upregulated under salt stress, indicating potential functional specialization in response to different abiotic stresses. The highly virulent Fusarium oxysporum f. sp. niveum race 2 (Fon R2) induced the upregulation of more ClHMGB genes than the less virulent race 1 (Fon R1). Four members (ClHMGB1, 4, 6, and 7) were consistently upregulated by both races, suggesting that they may play fundamental roles in disease resistance. This study provides a foundation for further investigation into the roles of ClHMGB genes in growth, development, and stress responses of watermelon.

Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of bacteria to conventional antibiotics made it imperative to develop new liposome formulations for antibiotics, and investigate the fusion between liposome and bacterium. In this study, the factors involved in fluid liposome interaction with bacteria have been investigated. We also demonstrated a mechanism of fusion between liposomes (1,2-dipa lmitoyl-sn-glycero-3-phosphocholine [DPPC]/dimyristoylphosphatidylglycerol [DMPG] 9:1, mol/mol) in a fluid state, and intact bacterial cells, by lipid mixing assay. The observed fusion process is shown to be mainly dependent on several key factors. Perturbation of liposome fluidity by addition of cholesterol dramatically decreased the degree of fusion with P. aeruginosa from 44% to 5%. It was observed that fusion between fluid liposomes and bacteria and also the bactericidal activities were strongly dependent upon the properties of the bacteria themselves. The level of fusion detected when fluid liposomes were mixed with Escherichia coli (66%) or P. aeruginosa (44%) seems to be correlated to their outer membrane phosphatidylethanolamine (PE) phospholipids composition (91% and 71%, respectively). Divalent cations increased the degree of fusion in the sequence Fe(2+) > Mg(2+) > Ca(2+) > Ba(2+) whereas temperatures lower than the phase transition temperature of DPPC/DMPG (9:1) vesicles decreased their fusion capacity. Acidic as well as basic pHs conferred higher degrees of fusion (54% and 45%, respectively) when compared to neutral pH (35%). Based on the results of this study, a possible mechanism involving cationic bridging between bacterial negatively charged lipopolysaccharide and fluid liposomes DMPG phospholipids was outlined. Furthermore, the fluid liposomal-encapsulated tobramycin was prepared, and the in vitro bactericidal effects were also investigated.

During an ERCP procedure for bile duct stones, the patient experienced basket impaction during the operation. We successfully removed the impacted reticular basket without complications, utilizing a temporary salvage device modified with a lithotripter, thereby avoiding other future procedures such as ESWL or surgery.

Background Soil salinity is a major abiotic stress that severely restricts the growth, yield, and quality of melon ( Cucumis melo L.). The Salt Overly Sensitive (SOS) signaling pathway plays a crucial role in plant salt tolerance, in which SOS2 acts as a central kinase regulating ion homeostasis and stress responses. However, the SOS2 gene family in melon remains unclear. Results Here, we identified 20 SOS2 genes ( CmSOS2 ) in the melon genome, distributed unevenly across nine chromosomes. All CmSOS2 proteins contain conserved pkinase and NAF domains, essential for kinase activity and calcium sensor binding. Phylogenetic analysis classified the genes into seven clades, indicating evolutionary conservation across species. Promoter analysis revealed abundant cis -elements associated with light, hormone, and stress responses. Expression profiling under salt stress and hormone treatments showed significant upregulation of MELO3C010334 and MELO3C007208 , suggesting their pivotal roles in stress signaling. Further functional validation confirmed that overexpression of MELO3C010334 significantly enhanced salt tolerance in melon, promoted root growth, and improved Na + /K + homeostasis in roots. Conclusions This study represents the first systematic characterization of the genomic features and expression patterns of the SOS2 gene family in melon, and clarifies the positive regulatory role of MELO3C010334 under salt stress. It provides important genetic resources and a theoretical basis for further understanding the molecular mechanisms of salt tolerance and for genetic improvement of salt tolerance in melon.

Stroke is a major cause of morbidity and mortality worldwide. There is an urgent need for effective neuroprotective agents to reduce brain injury. SARM1 (sterile alpha and TIR motif-containing 1) has been identified as a key mediator of axonal degeneration. However, its role in stroke and the underlying mechanisms remain insufficiently understood. In the present study, a mouse model of stroke with focal infarction in the cortex was used to investigate the potential relation between SARM1 and post-stroke brain injury. We found that SARM1 expression increased in neurons of the peri-infarct cortex at an early stage after photothrombotic stroke induction (PTI) and was evenly distributed between excitatory and inhibitory neurons. Deficiency of SARM1 improved neurological performance, reduced the infarct volume and the inflammatory response including reactive gliosis and TNF-α level after PTI. Meanwhile, SARM1 deficiency promoted neuronal preservation in the peri-infarct cortex and mitigated axonal degeneration, possibly because of reduced NAD + consumption of neurons in the peri-infarct cortex. Additionally, we found that SARM1 deficiency inhibited glial scar formation and decreased activated microglia. FK866 and DSRM-3716, two recently reported pharmacological inhibitors of SARM1, failed to alleviate brain injury in mice with stroke. Our findings demonstrate that SARM1 deficiency attenuates ischemic neuronal injury and improves neurological performance post PTI, suggesting that the SARM1 signaling pathway could serve as a potential therapeutic target for stroke in the future.

Background Grafting with dwarf rootstock is an efficient method to control plant height in fruit production. However, the molecular mechanism remains unclear. Our previous study showed that plants with Prunus mume (mume) rootstock exhibited a considerable reduction in plant height, internode length, and number of nodes compared with Prunus persica (peach) rootstock. The present study aimed to investigate the mechanism behind the regulation of plant height by mume rootstocks through transcriptomic and metabolomic analyses with two grafting combinations, ‘Longyan/Mume’ and ‘Longyan/Peach’. Results There was a significant decrease in brassinolide levels in plants that were grafted onto mume rootstocks. Plant hormone signal transduction and brassinolide production metabolism gene expression also changed significantly. Flavonoid levels, amino acid and fatty acid metabolites, and energy metabolism in dwarf plants decreased. There was a notable upregulation of PmLBD3 gene expression in plant specimens that were subjected to grafting onto mume rootstocks. Auxin signalling cues promoted PmARF3 transcription, which directly controlled this upregulation. Through its binding to PmBAS1 and PmSAUR36a gene promoters, PmLBD3 promoted endogenous brassinolide inactivation and inhibited cell proliferation. Conclusions Auxin signalling and brassinolide levels are linked by PmLBD3 . Our findings showed that PmLBD3 is a key transcription factor that regulates the balance of hormones through the auxin and brassinolide signalling pathways and causes dwarf plants in stone fruits.

Ischemic stroke, an intractable neurovascular disease with high lethality, disability and recurrence rates, poses a serious challenge to human health. The only effective treatment for acute stroke is reperfusion therapy. However, the inflammatory response caused by reperfusion therapy often aggravates secondary brain tissue damage, which greatly affects the treatment effect. Currently, therapeutic options for reperfusion injury remain unsatisfactory, and neuroprotective options are lacking. The inhibition of microglia polarization and promotion of neovascular maturation are essential for reestablishing the integrity of the BBB. Specifically, McM/RNPs effectively inhibited the secretion of pro-inflammatory factors such as tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and promoted the release of anti-inflammatory and neuroprotective factors such as interleukin-10 (IL-10), vascular endothelial growth factor-A (VEGF-A), and brain-derived neurotrophic factor (BDNF). This effect not only alleviated the inflammatory response but also promoted the expression of endothelial tight junction proteins (such as ZO-1 and Claudin 5), thereby enhancing the integrity of the BBB. Furthermore, McM/RNPs exerted multiple effects, such as promoting neuronal survival, regulating pericyte function, and accelerating the maturation of the neovasculature, which are essential for repairing the damaged BBB. Through the multi-functional effects of anti-inflammation, anti-apoptosis and pericyte regulation, the McM/RNPs nanosystem successfully maintained the stability of the intracerebral environment, providing novel ideas and strategies for the clinical treatment of reperfusion injury in ischemic stroke. Graphical Abstract

Triple-negative breast cancer (TNBC) possesses high malignant and metastatic rates among all subtypes. Chemotherapy is a standard of care for TNBC but only a small moiety of patients achieved complete relief (CR) after chemotherapy. The recent concept of tumor ecosystem has provided new insights into solutions from an approach of enhancing anti-tumoral immunity of macrophages. We hereby observed a positive correlation of YTHDC2 abundance with anti-tumoral gene markers of macrophages. YTHDC2 -high macrophages also exerted interactions with other immune cells such as T helper cells, cytotoxic T cells, and NK cells. Further investigation on the transcriptional regulatory network identified six transcriptional factors upregulated by YTHDC2, and they together influenced the expressions of TWISTNB and the oncogene MYC . Additionally, our survival analysis prompted that YTHDC2 is prognostic of higher chemo-therapeutic efficacy and better survival outcomes. We demonstrated that ample macrophage YTHDC2 indicates anti-tumoral phenotype polarization and propitious survival outcome in post-treatment TNBC patients (Clinical trial registry name: Chinese Clinical Trial Registry, Registration No.: ChiCTR2400084513, Registration Date: 2024-05-20).

Prunus mume originated from China and is highly valued for its remarkable combination of ornamental blossoms and high economic value. Previously published P . mume genomes contain unanchored genetic regions and excessive gaps. Here, we report the P . mume f. viridicalyx gap-free telomere-to-telomere (T2T) haplotype genome. The LE_hap1 and LE_hap2 genomes were 229.29 and 228.36 Mb in length, respectively, with an N50 length of the contig between 27.65 and 27.79 Mb and 24,318 and 24,316 protein-coding genes, respectively. The completeness, continuity, and accuracy of the P . mume f. viridicalyx genome was significantly improved over the previous P . mume genomes. The key mutated genes during P . mume f. viridicalyx cultivar domestication were identified by comparative genomic, population evolution, and selective sweep analyses to be significantly enriched in the anthocyanin metabolism process, glutathione metabolism process, and carotenoid biosynthesis. Further analysis revealed that early codon termination of the PmGSTF2 gene, which is the key gene for the characteristic production of P . mume f. viridicalyx, reduced anthocyanin accumulation. We assembled a complete T2T gap-free haplotype P . mume genome, which provides a reference for gene mining and genome evolution of the anthocyanin deficiency phenotype in P . mume .

Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG), 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS), 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA), nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections.