Search Results (2,315)

Recent evolutionary genetics and molecular characterisation of Cryptolestes (Ganglbauer) stored grain pest beetle species revealed gaps in public DNA databases that resulted in molecular diagnostic inconsistencies in publicly available sequence databases. We report the characterisation of mitochondrial DNA cytochrome oxidase I (mtCOI) genes from specimens intercepted during Australia’s border biosecurity inspections, and surveys of public mtCOI gene sequences, for Cryptolestes species status re-assessment. We identified and characterised a new putative Cryptolestes species (C. sp. ‘WTT-2016’) and demonstrated the close evolutionary relationships between C. ferrugineus (Stephens)/C. pusilloides (Steel and Howe) and between C. pusillus (Schonherr) and the previously identified C. sp. ‘WTT-2013’ cryptic species. Confusion between C. ferrugineus, C. pusiolloides, C. pusillus, C. sp. ‘WTT-2013’, and C. sp. ‘WTT-2016’ highlighted a substantial and persistent taxonomic challenge within Cryptolestes, while low C. spartii (Curtis)/C. corticinus (Reitter) inter-specific genetic distances suggested they were the same species. Assembled and annotated mitochondrial DNA genomes (mitogenomes) of six Cryptolestes species identified assembly errors in published mitogenomes of C. ferrugineus and C. turcicus (Grouvelle) and misidentification of C. pusillus. Based on re-evaluation of genetic distances and phylogeny congruence, we proposed a Cryptolestes ‘operational species-level genetic gap’ at approximately 5% to help define Cryptolestes species boundaries, thereby contributing to improving agricultural biosecurity preparedness associated with this important stored grain beetle species. Our work also provides an evolutionary framework that will contribute to future understanding of ecological and environmental impact posed by this highly invasive cryptic beetle species complex. Full article

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, progressive β-cell dysfunction, and insulin resistance. While numerous chemically induced and transgenic rodent models exist, spontaneous models recapitulating natural type 2 diabetes mellitus (T2DM) progression remain scarce. Here, we characterize Myodes rufocanus as a novel spontaneous T2DM model through comprehensive assessments of 18-week-old male F6 voles, demonstrating hallmark diabetic features including weight gain, hyperphagia, polydipsia, hyperglycemia, insulin resistance, and dyslipidemia. Pancreatic transcriptomic profiling revealed pronounced COX14 (cytochrome c oxidase assembly factor 14) downregulation, as validated by qPCR and Western blotting in pancreatic tissue and MIN6 β-cells. MIN6 cells under chronic high-glucose conditions (30 mM) exhibited diminished mitochondrial membrane potential, impaired ATP biosynthesis, elevated reactive oxygen species, and attenuated glucose-stimulated insulin secretion, with consistent COX14 downregulation suggesting potential association with mitochondrial dysfunction. Additionally, suppressed Nrf2–HO-1 antioxidant signaling appeared to compound cellular injury, with intrinsic apoptotic pathway activation indicated by elevated Bax/Bcl-2 ratios and caspase-3 activity. These findings establish M. rufocanus as a valuable spontaneous T2DM model and implicate COX14 downregulation as a potential correlate of mitochondrial impairment and β-cell failure in diabetes pathogenesis. Full article

This paper reports the synthesis, structural characterization, and biological evaluation of a novel series of Cu^I and Cu^II complexes supported by an amantadine-functionalized bis(pyrazol-1-yl)acetate ligand (L^Ad) as potential anticancer agents for the treatment of glioblastoma (GBM). Comprehensive spectroscopic and structural investigations, including SR-XPS, XANES/EXAFS, and DFT modeling, confirmed the successful coordination of L^Ad to copper centers in both oxidation states, affording well-defined molecular architectures with distinct coordination geometries. Among the synthesized compounds, the Cu^I complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC₅₀ values lower than those of cisplatin. These complexes induced a pronounced redox imbalance through reactive oxygen species (ROS) overproduction and glutathione (GSH) depletion, leading to G2/M cell cycle arrest and cell death. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized Cu^I complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways. Full article

Petroleum contamination poses a serious threat to human health and ecosystems worldwide, and microbially driven natural attenuation is an effective approach for accelerating hydrocarbon removal. Species of the genus Rhodococcus are recognized for their ability to degrade long chain petroleum hydrocarbons. However, their physiological traits and degradation mechanisms under alkaline conditions remain insufficiently understood. In this study, soil samples were collected from the Dagang oilfield in Tianjin, China, and Rhodococcus sp. A17 was isolated as an active indigenous strain for genomic and physiological characterization under high pH petroleum degradation conditions. The results showed that strain A17 grew optimally at 30 °C, pH 9.0, and 2% salinity. Petroleum hydrocarbon degradation reached 67.8% within 72 h, with a degradation half life of 34.2 h. Genome sequencing identified 18 oxygenase related genes involved in alkane degradation, including alkB, cytochrome P450 monooxygenases, and the long chain alkane monooxygenase ladA, together with four antibiotic resistance genes. Metabolite analysis suggested that alkane degradation might proceed via terminal and subterminal oxidation pathways. Overall, these findings indicate that Rhodococcus sp. A17 exhibits multiple adaptive traits that support its potential application in the bioremediation of petroleum contaminated alkaline environments. Full article

Background/Objectives: The retromer protein complex is involved in various physiological processes, especially endosomal trafficking, and its dysregulation has been linked to Alzheimer’s disease and Parkinson’s disease, as well as VPS35 knockout (KO), causing early embryonic lethality. We aimed to investigate the cellular consequences of VPS35 deficiency. Methods: To investigate the effects of VPS35 loss, we used CRISPR/Cas9 to generate VPS35 KO human embryonic kidney 293 (HEK293) cells. We analyzed changes in retromer component expression, cell proliferation, apoptosis, and mitochondrial dynamics using Western blotting, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and confocal microscopy. Results: VPS35 KO led to a significant reduction in cell proliferation and decreased expression of VPS29 and VPS26, both essential for retromer complex assembly. Consequently, retromer formation was impaired. Compared to control cells, KO cells exhibited elevated levels of cleaved caspase-3, poly(ADP-ribose) polymerase, cytochrome C, and p21, while the expression of Ki-67, CDK4, and cyclin D was reduced. Additionally, VPS35 deletion also promoted mitochondrial fragmentation, associated with increased expression of mitochondrial fission-related proteins. Finally, the rescue experiment using the human VPS35 gene confirmed that the recovery of VPS35 not only led to the recovery of the essential elements constituting the retromer but also the recovery of molecules related to the cell cycle, restoring cell death to a normal level. Conclusions: These findings suggest that VPS35 plays a critical role in cell growth and survival by modulating apoptosis, mitochondrial dynamics, and cell cycle progression. Full article

Background/Objectives: Cariprazine (CAR), an atypical antipsychotic drug, exhibits potent anticancer activity; however, its mechanism of action remains unclear. Methods: We conducted a comparison of CAR-induced cell death mechanism in HeLa and HCT116 cancer cells and explored its potential role as a Qi-site inhibitor of cytochrome bc1 reductase (complex III). Results: CAR induced a dose-dependent cytotoxic effect and triggered apoptosis in both cell lines; however, the mitochondrial responses were distinctively different. HeLa cells exhibited significant mitochondrial membrane depolarization, significant cytochrome c release, a strong increase in the Bax/Bcl-2 ratio, elevated caspase-3 activation, and notable S phase arrest along with autophagy induction, indicating that mitochondria-driven apoptosis occurred rapidly. In contrast, HCT116 cells showed moderate mitochondrial dysfunction, moderate cytochrome c release, enhanced suppression of Akt signaling, and significant G0/G1 phase arrest, which are consistent with a slower and mixed apoptotic response. The findings from molecular docking studies predicted that CAR had stable binding at the Qi site and showed interactions at the Qi site that were comparable to those of antimycin A, thereby suggesting its possible inhibitory effect on complex III. Conclusions: The results from our study indicate the engagement of CAR-activated apoptotic pathways that are specific to different types of cancer cells, and hence suggest that CAR may act as a new anticancer drug by potentially directing its action towards the mitochondrial Qi-sites of complex III. Full article

Blossom-end rot (BER) in tomatoes is a physiological disorder primarily caused by the disruption of calcium absorption and transport. This study cultivated tomatoes using a trough-based vermiculite system. Two treatments were established: a calcium-deficient nutrient solution and a calcium-deficient nutrient solution supplemented with 0.1 mg/L BR (n = 40 plants per treatment). The activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), as well as the contents of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂), were measured in the leaves. Calcium ion content was also determined in various plant parts. Statistical analysis of differences was performed using Duncan’s multiple range test at a significance level of p < 0.01. Concurrently, transcriptome sequencing of root, stem, and leaf tissues was conducted via high-throughput sequencing technology. The results showed that foliar application of BR under calcium deficiency significantly reduced the incidence of BER (from 26.67% to 6.67%) and effectively increased calcium ion content in leaves, stems, and roots. At the physiological level, BR treatment markedly enhanced the activities of CAT, POD, and SOD in leaves (by 105.70%, 117.12%, and 82.77%, respectively), while reducing H₂O₂ and MDA contents (by 36.90% and 16.38%, respectively). This indicates that BR alleviates membrane lipid peroxidation damage by enhancing the antioxidant defense system. Gene Ontology (GO) enrichment analysis revealed that the differentially expressed genes (DEGs) were primarily involved in biological processes, such as secondary metabolic processes, response to oxygen-containing compounds, and cell wall organization. KEGG pathway analysis further indicated significant enrichment in pathways, including phenylpropanoid biosynthesis, plant hormone signal transduction, and plant–pathogen interaction. Additionally, key genes, such as the cytochrome c oxidase (COX) gene (Solyc03g013460.1), exhibited a gradient up-regulation pattern (root > stem > leaf) in the oxidative phosphorylation pathway. In conclusion, BR likely enhances tomato tolerance to calcium deficiency stress and effectively reduces BER incidence through multiple pathways: regulating calcium absorption and distribution, activating the antioxidant system, modulating hormone signaling pathways, and enhancing energy metabolism. These findings provide a theoretical basis for the application of BR in agricultural production. Full article

Natural products have emerged as promising multi-target agents for addressing the complex biology of gastric cancer, a malignancy characterized by marked molecular heterogeneity, late clinical presentation, and frequent resistance to systemic therapies. This narrative synthesis integrates primarily preclinical evidence, with emerging clinical data, on how naturally derived compounds modulate three central molecular processes that drive gastric tumor progression and therapeutic failure: evasion of programmed cell death, persistent tumor-promoting inflammation, and chemoresistance. Compounds such as curcumin, resveratrol, berberine, ginsenosides, quercetin, and epigallocatechin gallate restore apoptotic competence by shifting the balance between pro-survival and pro-death proteins, destabilizing mitochondrial membranes, promoting cytochrome c release, and activating caspase-dependent pathways. These agents also exert potent anti-inflammatory effects by inhibiting nuclear factor kappa B and signal transducer and activator of transcription signaling, suppressing pro-inflammatory cytokine production, reducing cyclooxygenase activity, and modulating the tumor microenvironment through changes in immune cell behavior. In parallel, multiple natural compounds function as chemo-sensitizers by inhibiting drug efflux transporters, reversing epithelial–mesenchymal transition, attenuating cancer stem cell-associated traits, and suppressing pro-survival signaling pathways that sustain resistance. Collectively, these mechanistic actions highlight the capacity of natural products to simultaneously target interconnected hallmarks of gastric cancer biology. Ongoing advances in formulation strategies may help overcome pharmacokinetic limitations; however, rigorous biomarker-guided studies and well-designed clinical trials remain essential to define the translational relevance of these compounds. Full article

Background/Objectives: Venlafaxine has been reported to exhibit significant interindividual pharmacokinetic heterogeneity across populations, which has been linked to cytochrome P450 polymorphisms and clinical factors. This study aimed to assess the impact of pharmacogenetic (PGx) and clinical determinants on the dose-normalized venlafaxine/O-desmethylvenlafaxine (ODV) metabolic ratios (MRs) in routine clinical settings in Spain. Methods: 29 adult patients receiving venlafaxine were prospectively recruited through the MedeA PGx Implementation Strategy into clinical practice (Extremadura, Spain). CYP2D6, CYP2C19, and CYP2C9 genotypes were determined using TaqMan^® assays, and CYP2D6 activity scores were assigned based on allele functionality. Steady-state trough plasma concentration of venlafaxine and ODV were measured using a validated high-performance liquid chromatography method. Dose-normalized venlafaxine/ODV MRs were compared across CYP2D6-, CYP2C19-, and CYP2C9-genotype-predicted metabolizer groups. The influence of demographic and clinical variables on dose-normalized venlafaxine/ODV MR was also assessed. Results: Significant variability in dose-normalized venlafaxine/ODV MRs was observed across CYP2D6 (p = 0.019) and CYP2C19 (p = 0.008) metabolizer groups. Among clinical variables, sex was significantly associated with differences in dose-normalized venlafaxine/ODV MR (p = 0.0006). Conclusions: CYP2D6 and CYP2C19 genotypes and sex significantly contribute to variability in venlafaxine metabolism in patients treated in routine clinical settings. These results highlight the value of combining PGx and clinical data with drug plasma concentration measurement to optimize venlafaxine therapy within PGx implementation programs. Full article

Drug- and alcohol-induced liver injury involves impaired bile acids or bilirubin secretion, but it is not known how senescence influences the secretion of hepatocytes exposed to drugs and alcohol. In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters and the secretion of bile acids and bilirubin were investigated in hydrogen peroxide-induced senescent HepG2 and doxorubicin-induced senescent primary human hepatocytes. In HepG2, intracellular conjugated bilirubin increased upon senescence and extracellular conjugated bilirubin in culture medium was decreased by ritonavir and lopinavir treatment. In the primary hepatocytes, intracellular bile acids or medium bilirubin were not significantly changed upon senescence. However, intracellular bile acids were increased, and medium conjugated bilirubin were decreased in senescent primary hepatocytes treated with alcohol and the two drugs. Transcriptional expressions of adenosine triphosphate (ATP)-binding cassette (ABC) transporters (ABCB4, ABCC6, ABCB11, and ABCD3) were decreased whereas UDP-glucuronosyltransferase (UGT1A1) was increased by ritonavir and lopinavir in senescent HepG2. In senescent primary hepatocytes, expressions of ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, and ABCC6 were apparently reduced whereas UGT1A1 and the cytochrome P450 enzyme CYP7A1 were markedly increased by alcohol combined with ritonavir and lopinavir. Selective ABCC6 knockdown in the primary hepatocytes altered expressions of two senescence markers, Lamin A/C and cyclin-dependent kinase inhibitor CKI (p21), increased expressions of CYP7A1 and hydroxy methyl glutaryl-CoA reductase (HMGCR), and increased intracellular bile acids. Further, anti-cholestasis agents, ursodeoxycholic acid and glycyrrhizin, significantly ameliorated the impaired secretions of bile acids and bilirubin as well as reducing intracellular lipid accumulation and cell death caused by ritonavir, lopinavir, and alcohol in the primary hepatocytes with ABCC6 knockdown. These results indicate that senescence moderately impairs the ABC transporters of hepatocytes and secretion of bile acids or bilirubin, which become worse in the presence of the drugs and alcohol but could be improved by anti-cholestasis agents. Full article

In this study, three distinct hydrolysates, which are designated Dur-I, Dur-II, and Dur-III, were generated from extrusion-pretreated Durvillaea antarctica biomass by applying viscozyme, cellulase, and α-amylase, respectively. Chemical analyses demonstrated distinct compositional differences among the extracts, whereas FTIR spectra verified the presence of fucose-containing sulfated polysaccharides. Furthermore, NMR analyses revealed pronounced structural variations among the extracts. To investigate neuroprotective properties of Dur-I, Dur-II, and Dur-III, rotenone (Rot) was added to SH-SY5Y cells that had been pretreated with Dur-I/II/III. Here, flow cytometry was employed to assess changes in mitochondrial membrane potential (MMP), Bcl-2 expression, cytochrome c release, caspase-9, -8, and -3 activation, as well as DNA fragmentation. The protective effect of Dur-I/II/III pretreatment of SH-SY5Y cells on the Rot-induced death process was further investigated using cell cycle and annexin V-fluorescein isothiocyanate (FITC)/PI (propidium iodide) double staining analyses. The results reveal that the Rot-induced apoptotic factors were all recovered by the pretreatment of Dur-I/II/III. Moreover, cell cycle and annexin V-FITC/PI double staining analyses also indicated that Dur-I/II/III were capable of protecting SH-SY5Y cells from Rot-induced cytotoxicity. Therefore, these Dur extracts are considered as good candidates for the prevention and treatment of neurodegeneration induced by oxidative stress. Full article

Acne vulgaris is a chronic inflammatory dermatosis where conventional therapies often face limitations in efficacy and safety, necessitating the development of microbiome-targeted interventions. This study investigated the immunomodulatory potential of microbiome-derived tryptophan metabolites as a novel therapeutic strategy for Cutibacterium acnes (C. acnes)-induced inflammation, focusing on the aryl hydrocarbon receptor (AHR) pathway. We evaluated indole-3-lactic acid (ILA), indole-3-acrylic acid (IAA), and indole-3-propionic acid (IPA) in comparison to tapinarof, utilizing C. acnes-stimulated human epidermal keratinocytes and a C. acnes-induced acne mouse model. In vitro, ILA and IPA significantly suppressed C. acnes-driven inflammatory mediators, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, and Cyclooxygenase-2 (COX2), whereas IAA demonstrated limited efficacy. In vivo, ILA treatment exhibited superior therapeutic activity, markedly reducing inflammatory cell infiltration, epidermal hyperplasia, and IL-1β expression. Transcriptomic analysis confirmed that ILA attenuates inflammatory signaling (e.g., IL-17 and TNF pathways) while upregulating AHR-responsive genes such as Cytochrome (CYP) 1A1 and CYP1B1. Collectively, these findings establish ILA as a potent postbiotic that mitigates cutaneous inflammation through selective activation of the AHR. Future studies should prioritize the clinical translation of ILA-based topical formulations, with rigorous evaluation of their efficacy and safety in well-designed human trials, to support their development as a non-antibiotic therapeutic alternative for acne management. Full article

Limpets are marine gastropod molluscs well adapted to intertidal rocky environments, yet their taxonomic resolution remains challenging due to extensive morphological convergence and the presence of cryptic species. In this study, we applied an integrative taxonomic framework combining multi-locus DNA barcoding and fine-scale morphological characterization to clarify species boundaries within three families of limpets—Nacellidae, Lottiidae, and Siphonariidae. A total of 132 individuals collected from six coastal sites in Shenzhen and adjacent areas of southern China were analyzed using four markers Cytochrome c oxidase subunit I (COI), 16S ribosomal RNA (16S rRNA), Cytochrome b (Cytb) and 28S ribosomal RNA (28S rRNA), together with scanning electron microscopy (SEM) observations of radular morphology. Molecular analyses identified nine distinct species across five genera. Kimura two-parameter distance analyses revealed clear barcode gaps in 16S rRNA, Cytb, and 28S rRNA genes, particularly among Cellana and Nipponacmea, whereas COI exhibited stronger discriminatory power within Siphonaria. Moreover, our study provides newly 16S, 28S references for Nipponacmea formosa and Cytb references for Nipponacmea formosa, Lottia luchuana, Siphonaria atra, Siphonaria sirius, Siphonaria sp. and Siphonaria sirius, enriching the public references and explaining the lack of corresponding records in previous BLAST searches. In addition, we identified misannotated COI references in NCBI which were labelled as Nipponacema schrenckii but belong to Cellana toreuma, highlighting inconsistencies in existing reference data rather than issues with our samples. SEM-based radular features displayed consistent interspecific variation that corroborated molecularly defined clades, offering comprehensive search of the NCBI reliable morphological evidence for species delimitation. Collectively, our findings highlight the value of integrating lineage-specific molecular markers with detailed morphological analyses to resolve taxonomic ambiguities in morphologically conservative marine gastropods. Furthermore, this approach strengthens molecular reference resources essential for future biodiversity and evolutionary research on intertidal limpets. Full article

Mactra antiquata sensu lato, a commercially important clam species in China, exhibits remarkable morphological and molecular diversity, which has led to the proposal of cryptic species within this complex. In the present study, specimens of M. antiquata sensu lato were collected from four coastal provinces (Shandong, Guangdong, Guangxi, and Hainan) of China, and an integrated comparative analysis was performed based on morphological traits and partial sequences of two mitochondrial genes (cytochrome c oxidase subunit I, COI; and 16S rRNA). Our results revealed that M. antiquata sensu lato could be clearly delineated into two distinct clades: the N-group (comprising specimens collected from Shandong in this study) and the S-group (including specimens collected from Guangdong, Guangxi, and Hainan), with significant intergroup differences. Morphologically, S-group individuals possessed relatively narrower shells (mean shell width-to-length ratio = 0.465) and shorter shells (mean shell height-to-length ratio = 0.781) compared to N-group conspecifics. Additionally, the pallial sinus of S-group clams extended directly toward the anterior adductor muscle, whereas that of N-group clams pointed to the region below the anterior adductor muscle. Furthermore, the escutcheon of N-group individuals was considerably more slender than that of the S-group. Phylogenetic trees and haplotype networks constructed based on both partial COI and 16S rRNA sequences further confirmed a deep genetic divergence between the two groups, with Kimura 2-parameter distances of 0.158 for COI and 0.084 for 16S rRNA. Collectively, these morphological and molecular lines of evidence strongly support the existence of cryptic species within M. antiquata sensu lato. By comparing the morphological characteristics of specimens in this study with the original description of M. antiquata, we herein propose that the S-group represents a new species, which we named M. haiboensis sp. nov. Our findings provide a scientific basis for the targeted conservation and further research of both M. antiquata and M. haiboensis sp. nov. Full article

Thrips are cosmopolitan agricultural pests and important vectors of plant viruses, and the increasing coexistence of multiple morphologically similar species has intensified the demand for species-specific molecular identification. However, traditional morphological identification and PCR assays using universal primers are often inadequate for mixed-species samples and field-adaptable application. In this study, we developed a species-specific molecular identification framework targeting a polymorphism-rich region of the mitochondrial cytochrome c oxidase subunit I (COI) gene, which is more time-efficient than sequencing-based COI DNA barcoding, for four economically important thrips species in southern China, including the globally invasive Frankliniella occidentalis. By aligning COI sequences, polymorphism-rich regions were identified and used to design four species-specific primer pairs, each containing a diagnostic 3′-terminal nucleotide. These primers were combined with a PBS-based DNA extraction workflow optimized for single-insect samples that minimizes dependence on column-based purification. The assay achieved a practical detection limit of 1 ng per reaction, demonstrated species-specific amplification, and maintained reproducible amplification at DNA inputs of ≥1 ng per reaction. Notably, PCR inhibition caused by crude extracts was effectively alleviated by fivefold dilution. Although the chemical identities of the inhibitors remain unknown, interspecific variation in inhibition strength was observed, with T. hawaiiensis exhibiting the strongest suppression, possibly due to differences in lysate composition. This integrated framework balances target specificity, operational simplicity, and dilution-mitigated inhibition, providing a field-adaptable tool for thrips species identification and invasive species monitoring. Moreover, it provides a species-specific molecular foundation for downstream integration with visual nucleic acid detection platforms, such as the CRISPR/Cas12a system, thereby facilitating the future development of portable molecular identification workflows for small agricultural pests. Full article