On optimal charging scheduling for electric vehicles with wind power generation.

We consider the scheduling of battery charging of electric vehicles (EVs) integrated with renewable power generation. The increasing adoption of EVs and the development of renewable energies contribute importance to this research. The optimization of charging scheduling is challenging because of the large action space, the multi-stage decision making, and the high uncertainty. To solve this problem is time-consuming when the scale of the system is large. It is urgent to develop a practical and efficient method to properly schedule the charging of EVs. The contribution of this work is threefold. First, we provide a sufficient condition on which the charging of EVs can be completely self-sustained by distributed generation. An algorithm is proposed to obtain the optimal charging policy when the sufficient condition holds. Second, the scenario when the supply of the renewable power generation is deficient is investigated. We prove that when the renewable generation is deterministic there exists an optimal policy which follows the modified least laxity and longer remaining processing time first (mLLLP) rule. Third, we provide an adaptive rule-based algorithm which obtains a near-optimal charging policy efficiently in general situations. We test the proposed algorithm by numerical experiments. The results show that it performs better than the other existing rule-based methods.

Nutrient vitamins enabled metabolic regulation of ferroptosis via reactive oxygen species biology.

Vitamins are dietary components necessary for cellular metabolic balance, especially redox homeostasis; deficient or excessive supply may give rise to symptoms of psychiatric disorders. Exploring the nutritional and metabolic pathways of vitamins could contribute to uncovering the underlying pathogenesis of ferroptosis-associated diseases. This mini-review aims to provide insights into vitamins closely linked to the regulation of ferroptosis from the perspective of cellular reactive oxygen species biology. The mainstream reprogramming mechanisms of ferroptosis are overviewed, focusing on unique biological processes of iron metabolism, lipid metabolism, and amino acid metabolism. Moreover, recent breakthroughs in therapeutic interventions targeting ferroptosis via fully utilizing vitamin-based pharmacological tools were overviewed, covering vitamins (B, C, E, and K). Finally, mechanism insight related to vitamin-associated nutrient signaling was provided, highlighting the pharmacological benefits of metabolically reprogramming ferroptosis-associated diseases.

An engineered self-biomineralized oncolytic adenovirus induces effective antitumor immunity and synergizes with immune checkpoint blockade.

Oncolytic adenoviruses (oADV) are promising cancer treatment agents. However, in vivo hepatic sequestration and the host immunological response against the agents limit the therapeutic potential of oADVs. Herein, we present a combined, rational design method for improving oADV infection efficiency, immunogenicity, and treatment efficacy by self-biomineralization. We integrated the biomimetic nucleopeptide W6p into the capsid of oADV using reverse genetics, allowing calcium phosphate mineralization to be biologically induced on the surface of oADV under physiological conditions, resulting in a mineral exterior. This self-biomineralized, modified oADV (oADV-W6-CaP) enhanced infection efficiency and therapeutic efficacy in coxsackie and adenovirus receptor (CAR)-negative cancer cells while protecting them against neutralization by pre-existing neutralizing antibodies. In subcutaneous mouse tumor models, systemic injection of oADV-W6-CaP demonstrated improved antitumor effectiveness, which was associated with increased T-cell infiltration and CD8+ T-cell activation. In addition, the anticancer immune response elicited by oADV-W6-CaP was dependent on CD8+ T cells, which mediated long-term immunological memory and systemic antitumor immunity against the same tumor. Finally, the addition of PD-1 or CD47 inhibition boosted the anticancer effects of oADV-W6-CaP and raised the rate of complete tumor clearance in tumor-bearing animals. The self-biomineralized oADV shifted the suppressive tumor microenvironment from a "cold" state to a "hot" state and synergized with immune checkpoint blockade to exert outstanding tumoricidal effects, demonstrating promising potential for cancer immunotherapy.

Dental Stem Cell-Derived Exosomes: A Review of Their Isolation, Classification, Functions, and Mechanisms.

The scientific field concerned with the study of regeneration has developed rapidly in recent years. Stem cell therapy is a highly promising therapeutic modality for repairing tissue defects; however, several limitations exist, such as cytotoxicity, potential immune rejection, and ethical issues. Exosomes secreted by stem cells are cell-specific secreted vesicles that play a regulatory role in many biological functions in the human body; they not only have a series of functional roles of stem cells and exert the expected therapeutic effects, but they can also overcome the mass limitations of stem cells and are thus considered in the research as an alternative treatment strategy for stem cells. Since dental stem cell-derived exosomes (DSC-Exos) are easy to acquire and present modulating effects in several fields, including neurovascular regeneration and craniofacial soft and hard tissue regeneration processes, they are served as an emerging cell-free therapeutic strategy in various systematic diseases. There is a growing body of research on various types of DSC-Exos; however, they lack systematic elaboration and tabular summarization. Therefore, this review presents the isolation, characterization, and phenotypes of DSC-Exos and focuses on their current status of functions and mechanisms, as well as the multiple challenges prior to clinical applications.

Post-transfer adaptation of HGT-acquired genes and contribution to guanine metabolic diversification in land plants.

Horizontal gene transfer (HGT) is a major driving force in the evolution of prokaryotic and eukaryotic genomes. Despite recent advances in distribution and ecological importance, the extensive pattern, especially in seed plants, and post-transfer adaptation of HGT-acquired genes in land plants remain elusive. We systematically identified 1150 foreign genes in 522 land plant genomes that were likely acquired via at least 322 distinct transfers from nonplant donors and confirmed that recent HGT events were unevenly distributed between seedless and seed plants. HGT-acquired genes evolved to be more similar to native genes in terms of average intron length due to intron gains, and HGT-acquired genes containing introns exhibited higher expression levels than those lacking introns, suggesting that intron gains may be involved in the post-transfer adaptation of HGT in land plants. Functional validation of bacteria-derived gene GuaD in mosses and gymnosperms revealed that the invasion of foreign genes introduced a novel bypass of guanine degradation and resulted in the loss of native pathway genes in some gymnosperms, eventually shaping three major types of guanine metabolism in land plants. We conclude that HGT has played a critical role in land plant evolution.

Ribosomal translation of fluorinated non-canonical amino acids for de novo biologically active fluorinated macrocyclic peptides.

Fluorination has emerged as a promising strategy in medicinal chemistry to improve the pharmacological profiles of drug candidates. Similarly, incorporating fluorinated non-canonical amino acids into macrocyclic peptides expands chemical diversity and enhances their pharmacological properties, from improved metabolic stability to enhanced cell permeability and target interactions. However, only a limited number of fluorinated non-canonical amino acids, which are canonical amino acid analogs, have been incorporated into macrocyclic peptides by ribosomes for de novo construction and target-based screening of fluorinated macrocyclic peptides. In this study, we report the ribosomal translation of a series of distinct fluorinated non-canonical amino acids, including mono-to tri-fluorinated variants, as well as fluorinated l-amino acids, d-amino acids, ß-amino acids, etc. This enabled the de novo discovery of fluorinated macrocyclic peptides with high affinity for EphA2, and particularly the identification of those exhibiting broad-spectrum activity against Gram-negative bacteria by targeting the BAM complex. This study not only expands the scope of ribosomally translatable fluorinated amino acids but also underscores the versatility of fluorinated macrocyclic peptides as potent therapeutic agents.

SomaSeg: a robust neuron identification framework for two-photon imaging video.

Objective.Accurate neuron identification is fundamental to the analysis of neuronal population dynamics and signal extraction in fluorescence videos. However, several factors such as severe imaging noise, out-of-focus neuropil contamination, and adjacent neuron overlap would impair the performance of neuron identification algorithms and lead to errors in neuron shape and calcium activity extraction, or ultimately compromise the reliability of analysis conclusions.Approach.To address these challenges, we developed a novel cascade framework named SomaSeg. This framework integrates Duffing denoising and neuropil contamination defogging for video enhancement, and an overlapping instance segmentation network for stacked neurons differentiating.Main results.Compared with the state-of-the-art neuron identification methods, both simulation and actual experimental results demonstrate that SomaSeg framework is robust to noise, insensitive to out-of-focus contamination and effective in dealing with overlapping neurons in actual complex imaging scenarios.Significance.The SomaSeg framework provides a widely applicable solution for two-photon video processing, which enhances the reliability of neuron identification and exhibits value in distinguishing visually confusing neurons.

m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3.

miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

Preparation empty peptide-receptive MHC class I complex for large-scale detection through photolabile peptide ligands.

Peptide-major histocompatibility complex (pMHC) multimers are wide recognized as the premier technique for detecting, characterizing, and isolating antigen-specific CD8+ T-cell subsets. These multimers are specifically useful in studying infections, autoimmune conditions, and cancer through single-cell analysis techniques such as flow cytometry and fluorescence microscopy. However, the development of high-throughput assays with commercially available pMHC tetramers can be expensive, while in-house production may pose challenges for most biology research laboratories. In this context, we introduce a cost-friendly and uncomplicated protocol to prepare empty MHC class I tetramers using disulfide-stabilized molecules and photolabile peptide ligands. Our method relies on disulfide bond-stabilized MHC-I molecules, which demonstrated stability when folded into stable monomers in the presence of a photolabile epitope. These monomers, upon ultraviolet irradiation and streptavidin binding, efficiently assemble into tetramers devoid of any peptide. Following a short incubation with the peptide of interest under gentle conditions, the resulting pMHC tetramer effectively detects patient-sourced, neoantigen-specific T cells. Our unique approach streamlines large-scale pMHC generation, thus paving the way for advancements in T cell-based diagnostics and personalized therapies.

A NIR-II absorbing conjugated polymer based on tetra-fused isoindigo with ultrahigh photothermal conversion efficiency for cancer therapy.

A conjugated polymer, P4TTD-DPP, based on tetra-fused isoindigo-alt-diketopyrrolopyrrole, has been synthesized as a photothermal therapeutic nanotransducer within the near-infrared-II (NIR-II) window. P4TTD-DPP exhibits a notable mass extinction coefficient of 62.8 L g-1 cm-1 at 1064 nm. Additionally, P4TTD-DPP nanoparticles demonstrate remarkable photothermal conversion efficiency of 91.5% at 1064 nm and exhibit excellent anticancer efficacy under photothermal conditions.

Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

Dietary Knowledge, Attitude, Practice Survey and Nutritional Knowledge-Based Intervention: A Cross-Sectional and Randomized Controlled Trial Study among College Undergraduates in China.

BACKGROUND: Understanding undergraduates' dietary literacy, including dietary knowledge, attitude and practice (KAP), is important for future health promotion policies. Therefore, this study aimed to investigate the current status and influencing factors of dietary literacy in Chinese college undergraduates and explore whether a nutritional lecture could improve their dietary literacy. METHODS: This study included two parts: a cross-sectional study (n = 1026) conducted by a dietary literacy questionnaire, and a randomized controlled trail (RCT) that enrolled 99 college undergraduates who were randomized to a control group or a nutritional lecture group. Data from the questionnaire and 72 h food records were obtained on day 0, day 3 and day 100 before and after intervention. RESULTS: This cross-sectional study showed that the mean scores of dietary KAP were respectively 100.0 (33.3), 59.1 (13.6) and 71.7 (11.7), with an excellent rate of 36.6%, 1.9% and 3.4%. Female upper-grade undergraduates and those with medicine-related majors illustrated higher dietary knowledge scores (p < 0.001). Dietary attitude rather than dietary knowledge had a significant impact on dietary practice (p < 0.001). This finding was in line with the results in the RCT study. Compared with the control group, dietary knowledge was significantly improved in the nutritional lecture group on both day 3 (p = 0.002) and day 100 (p = 0.023) after intervention. However, dietary behavior was improved only on day 3 post nutritional lecture (p = 0.029) but decreased to the original level 100 days later (p < 0.001). CONCLUSIONS: This study discovered the unsatisfying status and discrepancy between dietary literacy among college undergraduates of different sex, majors and college years. Dietary attitude instead of dietary knowledge was discovered as a determining role in dietary practice. One nutritional lecture could improve undergraduates' dietary literacy but the effect was not long-lasting. Further studies with more reinforced and durable interventions are warranted.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Phylogenetic indices and temporal and spatial scales shape the neighborhood effect on seedling survival in a mid-mountain moist evergreen broad-leaved forest, Gaoligong Mountains, Southwestern China.

Density dependence and habitat filtering have been proposed to aid in understanding community assembly and species coexistence. Phylogenetic relatedness between neighbors was used as a proxy for assessing the degree of ecological similarity among species. There are different conclusions regarding the neighborhood effect in previous studies with different phylogenetic indices or at different spatiotemporal scales. However, the effects of density dependence, neighbor phylogenetic relatedness, and habitat filtering on seedling survival with different phylogenetic indices or at different temporal and spatial scales are poorly understood. We monitored 916 seedlings representing 56 woody plant species within a 4-ha forest dynamics plot for 4 years (from 2020 to 2023) in a subtropical mid-mountain moist evergreen broad-leaved forest in the Gaoligong Mountains, Southwestern China. Using generalized linear mixed models, we tested whether and how four phylogenetic indices: total phylogenetic distance (TOTPd), average phylogenetic distance (AVEPd), relative average phylogenetic distance (APd'), and relative nearest taxon phylogenetic distance (NTPd'), three temporals (1, 2, and 3 years), and spatial scales (1, 2, and 4 ha) affect the effect of density dependence, phylogenetic density dependence, and habitat filtering on seedling survival. We found evidence of the effect of phylogenetic density dependence in the 4-ha forest dynamics plot. The effects of density dependence, phylogenetic density dependence, and habitat filtering on seedling survival were influenced by phylogenetic indices and temporal and spatial scales. The effects of phylogenetic density dependence and habitat filtering on seedling survival were more conspicuous only at 1-year intervals, compared with those at 2- and 3-year intervals. We did not detect any effects of neighborhood or habitat factors on seedling survival at small scales (1 and 2 ha), although these effects were more evident at the largest spatial scale (4 ha). These findings highlight that the effects of local neighborhoods and habitats on seedling survival are affected by phylogenetic indices as well as temporal and spatial scales. Our study suggested that phylogenetic index APd', shortest time scale (1 year), and largest spatial scales (4 ha) were suitable for neighborhood studies in a mid-mountain moist evergreen broad-leaved forest in Gaoligong Mountains. Phylogenetic indices and spatiotemporal scales have important impacts on the results of the neighborhood studies.

Unconventional Magnetic and Magneto-Transport Properties in Quasi-2D Ni0.28TaSeS Single Crystal.

Van der Waals (vdW) magnetic materials have broad application prospects in next-generation spintronics. Inserting magnetic elements into nonmagnetic vdW materials can introduce magnetism and enhance various transport properties. Herein, the unconventional magnetic and magneto-transport phenomena is reported in Ni0.28TaSeS crystal by intercalating Ni atoms into nonmagnetic 2H-TaSeS matrix. Magnetic characterization reveals a canted magnetic structure in Ni0.28TaSeS, which results in an antiferromagnetic (AFM) order along the c-axis and a ferromagnetic (FM) moment in the ab-plane. The presence of spin-flop (SF) behavior can also be attributed to the canted magnetic structure. Temperature-dependent resistivity exhibits a metallic behavior with an abrupt decrease corresponding to the magnetic transition. Magneto-transport measurements demonstrate a positive magnetoresistance (MR) with a plateau that is different from conventional magnetic materials. The field-dependent Hall signal exhibits nonlinear field dependence when the material is in magnetically ordered state. These unconventional magneto-transport behaviors are attributed to the field-induced formation of a complex spin texture in Ni0.28TaSeS. In addition, it further investigated the angle dependence of MR and observed an unusual fourfold anisotropic magnetoresistance (AMR) effect. This work inspires future research on spintronic devices utilizing magnetic atom-intercalated quasi-2D materials.

Continuous Theta-Burst Stimulation on the Left Posterior Inferior Frontal Gyrus Perturbs Complex Syntactic Processing Stability in Mandarin Chinese.

The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d' and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

Sirt3-Mediated Opa1 Deacetylation Protects Against Sepsis-Induced Acute Lung Injury by Inhibiting Alveolar Macrophage Pro-Inflammatory Polarization.

Aims: Mitochondrial dynamics in alveolar macrophages (AMs) are associated with sepsis-induced acute lung injury (ALI). In this study, we aimed to investigate whether changes in mitochondrial dynamics could alter the polarization of AMs in sepsis-induced ALI and to explore the regulatory mechanism of mitochondrial dynamics by focusing on sirtuin (SIRT)3-induced optic atrophy protein 1 (OPA1) deacetylation. Results: The AMs of sepsis-induced ALI showed imbalanced mitochondrial dynamics and polarization to the M1 macrophage phenotype. In sepsis, SIRT3 overexpression promotes mitochondrial dynamic equilibrium in AMs. However, 3-(1H-1, 2, 3-triazol-4-yl) pyridine (3TYP)-specific inhibition of SIRT3 increased the mitochondrial dynamic imbalance and pro-inflammatory polarization of AMs and further aggravated sepsis-induced ALI. OPA1 is directly bound to and deacetylated by SIRT3 in AMs. In AMs of sepsis-induced ALI, SIRT3 protein expression was decreased and OPA1 acetylation was increased. OPA1 acetylation at the lysine 792 amino acid residue (OPA1-K792) promotes self-cleavage and is associated with an imbalance in mitochondrial dynamics. However, decreased acetylation of OPA1-K792 reversed the pro-inflammatory polarization of AMs and protected the barrier function of alveolar epithelial cells in sepsis-induced ALI. Innovation: Our study revealed, for the first time, the regulation of mitochondrial dynamics and AM polarization by SIRT3-mediated deacetylation of OPA1 in sepsis-induced ALI, which may serve as an intervention target for precision therapy of the disease. Conclusions: Our data suggest that imbalanced mitochondrial dynamics promote pro-inflammatory polarization of AMs in sepsis-induced ALI and that deacetylation of OPA1 mediated by SIRT3 improves mitochondrial dynamic equilibrium, thereby ameliorating lung injury.

Selective degradation of hyperphosphorylated tau by proteolysis-targeting chimeras ameliorates cognitive function in Alzheimer's disease model mice.

Alzheimer's disease (AD) is one of the most common chronic neurodegenerative diseases. Hyperphosphorylated tau plays an indispensable role in neuronal dysfunction and synaptic damage in AD. Proteolysis-targeting chimeras (PROTACs) are a novel type of chimeric molecule that can degrade target proteins by inducing their polyubiquitination. This approach has shown promise for reducing tau protein levels, which is a potential therapeutic target for AD. Compared with traditional drug therapies, the use of PROTACs to reduce tau levels may offer a more specific and efficient strategy for treating AD, with fewer side effects. In the present study, we designed and synthesized a series of small-molecule PROTACs to knock down tau protein. Of these, compound C8 was able to lower both total and phosphorylated tau levels in HEK293 cells with stable expression of wild-type full-length human tau (termed HEK293-htau) and htau-overexpressed mice. Western blot findings indicated that C8 degraded tau protein through the ubiquitin-proteasome system in a time-dependent manner. In htau-overexpressed mice, the results of both the novel object recognition and Morris water maze tests revealed that C8 markedly improved cognitive function. Together, our findings suggest that the use of the small-molecule PROTAC C8 to degrade phosphorylated tau may be a promising therapeutic strategy for AD.

Magnolia Officinalis Alcohol Extract Alleviates the Intestinal Injury Induced by Polygala Tenuifolia Through Regulating the PI3K/AKT/NF-κB Signaling Pathway and Intestinal Flora.

Purpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer's disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT. Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques. Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas). Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.

Mitogenomic phylogeny, biogeography, and cryptic divergence of the genus Silurus (Siluriformes: Siluridae).

The genus Silurus, an important group of catfish, exhibits heterogeneous distribution in Eurasian freshwater systems. This group includes economically important and endangered species, thereby attracting considerable scientific interest. Despite this interest, the lack of a comprehensive phylogenetic framework impedes our understanding of the mechanisms underlying the extensive diversity found within this genus. Herein, we analyzed 89 newly sequenced and 20 previously published mitochondrial genomes (mitogenomes) from 13 morphological species to reconstruct the phylogenetic relationships, biogeographic history, and species diversity of Silurus. Our phylogenetic reconstructions identified eight clades, supported by both maximum-likelihood and Bayesian inference. Sequence-based species delimitation analyses yielded multiple molecular operational taxonomic units (MOTUs) in several taxa, including the Silurus asotus complex (four MOTUs) and Silurus microdorsalis (two MOTUs), suggesting that species diversity is underestimated in the genus. A reconstructed time-calibrated tree of Silurus species provided an age estimate of the most recent common ancestor of approximately 37.61 million years ago (Ma), with divergences among clades within the genus occurring between 11.56 Ma and 29.44 Ma, and divergences among MOTUs within species occurring between 3.71 Ma and 11.56 Ma. Biogeographic reconstructions suggested that the ancestral area for the genus likely encompassed China and the Korean Peninsula, with multiple inferred dispersal events to Europe and Central and Western Asia between 21.78 Ma and 26.67 Ma and to Japan between 2.51 Ma and 18.42 Ma. Key factors such as the Eocene-Oligocene extinction event, onset and intensification of the monsoon system, and glacial cycles associated with sea-level fluctuations have likely played significant roles in shaping the evolutionary history of the genus Silurus.