Mechanism of N-butanol extract of Pulsatilla decoction protected vaginal epithelial cells against Candida albicans infection by HIF-1α signaling and glucose metabolism revealed by transcriptomics and molecular docking.

Enhancing the acid tolerance of Lactiplantibacillus plantarum is essential for improving its fermentation performance and metabolic activity under acidic conditions, thereby strengthening its probiotic functionality. In this study, the glutamate decarboxylase gene (gadA) and the arginine decarboxylase gene (speA) from Alicyclobacillus acidoterrestris DSM 3922T were heterologously expressed in L. plantarum WCFS1 to enhance its acid resistance. Recombinant expression vectors pMG36e-gadA and pMG36e-speA were constructed and introduced into L. plantarum WCFS1 via electroporation. The acid tolerance, cell membrane integrity, intracellular pH, ATP content, gene expression profiles, and enzyme activities of the recombinant L. plantarum WCFS1-gadA and WCFS1-speA were systematically evaluated. The results demonstrate that both recombinant strains exhibited significantly higher acid tolerance than the control strains. Under acid stress, the expression of gadA and speA was up-regulated, accompanied by enhanced activities of glutamate and arginine decarboxylases. In addition, the recombinant strains maintained higher intracellular pH and ATP levels compared with the control strain. Furthermore, the fermentative activity results support their potential applicability in fruit juice fermentation. Collectively, the heterologous expression of gadA and speA effectively improved the acid tolerance of L. plantarum, providing both mechanistic insights into acid stress adaptation and a theoretical basis for developing industrially robust, acid-resistant probiotic strains.

Enhanced prevention of cell death by hypothermic storage with propyl gallate.

Developmental and metabolic toxicity of diphenyl phosphate: insights from an integrative mechanistic framework in zebrafish embryos.

Hepatic ischaemia-reperfusion (IR) injury is a serious clinical issue, especially in patients with type 2 diabetes mellitus (T2DM). As mitochondria play a critical role in the regulation of IR-induced liver damage, mitochondria-targeted treatment is of the utmost significance for improving outcomes. The present study explored the mitoprotective role of combined ginsenoside-MC1 (GMC1) and irisin administration in diabetic rats with hepatic IR injury. T2DM was induced in male Sprague-Dawley rats with a high-fat diet and a low-dose streptozotocin. Following the induction of diabetes, hepatic IR injury was induced. Rats were pretreated with GMC1 and/or irisin for 28days prior to IR injury. Liver function was evaluated by quantitation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Histopathological changes were observed with haematoxylin-eosin staining. Apoptotic markers (Bax, Bcl-2, cleaved caspase-3) and signalling proteins (AMP-activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK)) were examined by western blotting. Mitochondrial function was evaluated by measuring reactive oxygen species, membrane potential and ATP content. Oxidative stress markers, such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx), were also measured. Combined therapy lowered AST, ALT and LDH levels, and histopathological injury (P<0.05). It restored mitochondrial function; upregulated Bcl-2 and phosphorylated AMPK expression; downregulated Bax, cleaved caspase-3 and phosphorylated JNK expression; and reduced MDA levels, while elevating SOD and GPx activity (P<0.05). AMPK inhibition by compound C reversed these protective effects. GMC1-irisin combination therapy safeguarded diabetic rats against IR-caused liver damage through suppressing mitochondrial apoptosis by AMPK/JNK signalling, a hopeful therapeutic approach in diabetic patients.

PRDM14 promotes the bovine somatic stem cell reprogramming through enhancing oxidative phosphorylation at the initial stage.

Oula Tibetan sheep meat is rich in nutrients, but its tenderness is relatively poor. Therefore, exploring meat tenderization methods is crucial. Previous studies have indicated that reactive species generated by plasma promote mitochondrial dysfunction and induce apoptosis in tumor cells. However, the impacts of plasma treatment on mitochondrial pathway apoptosis and the tenderization of Oula Tibetan sheep meat have not been reported. This study aimed to explore the effects of cold atmospheric plasma (CAP) treatment on mitochondrial pathway apoptosis and meat tenderness of Tibetan sheep meat during postmortem aging. The results showed that after CAP treatment, reactive oxygen species (ROS) and nitric oxide (NO) content increased, pH value and ATP content decreased, resulting in an increase in mitochondrial permeability transition pore (MPTP) opening, a decrease in succinate dehydrogenase (SDH) activity,Cytochrome c (Cyt-c) reduction level and mitochondrial membrane potential (MMP), and an increase in Caspase-3/9 activity, promoting the occurrence of mitochondrial pathway apoptosis. Meanwhile, myofibril fragmentation index(MFI) increased, shear force value decreased and the mitochondrial structure was obviously damaged. The results of the correlation analysis showed that the degree of mitochondrial damage was significantly positively correlated with the tenderization of the meat during postmortem aging. Therefore, CAP treatment promoted mitochondrial pathway apoptosis and muscle tenderization during postmortem aging of Tibetan sheep meat by increasing the content of ROS and NO and altering the intracellular environment of muscle cells, thereby intensifying mitochondrial damage. The study can provide a theoretical basis for CAP treatment to improve the tenderness of Tibetan sheep meat. PRACTICAL APPLICATIONS: The results of this study indicate that CAP treatment can improve the tenderness of Tibetan sheep meat by promoting apoptosis in the mitochondrial pathway. Therefore, CAP treatment may be used as a nonthermal processing technology to effectively improve the tenderness of Tibetan sheep meat.

Multitarget mechanisms of Origanum vulgare L. essential oil against clinically isolated carbapenem-resistant Acinetobacter baumannii.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a ubiquitous organophosphate flame retardant posing potential threats to reproductive health. Given that TDCIPP toxicity is often linked to oxidative stress, pyrroloquinoline quinone (PQQ), a potent natural antioxidant and mitochondrial nutrient, was hypothesized to mitigate these adverse effects. This study investigated the impact of TDCIPP exposure on the in vitro maturation of mouse oocytes and evaluated the protective role of PQQ. Using an in vitro maturation model, we assessed the toxic effects of TDCIPP by examining the first polar body extrusion (PBE) rate and cumulus expansion, followed by analyses of oxidative stress (ROS and GSH), mitochondrial integrity (ATP content and distribution), and apoptosis-related markers through transcriptome sequencing (Smart RNA-seq), quantitative real-time PCR, and immunofluorescence. The results demonstrated that TDCIPP significantly suppressed cumulus expansion and reduced the PBE rate. Mechanistically, TDCIPP induced severe oxidative stress, disrupted mitochondrial function, and activated the apoptotic pathway. Furthermore, TDCIPP triggered early apoptotic signaling by downregulating Bcl-2 and upregulating Bax. Notably, supplementation with PQQ effectively reversed these detrimental effects by reducing intracellular ROS levels, maintaining GSH content, preserving mitochondrial density and ATP production, and inhibiting apoptosis. In conclusion, our findings provide new insights into the gamete toxicity of TDCIPP and suggest that PQQ may serve as a potential therapeutic agent to protect oocyte quality against environmental pollutant-induced damage.

Obesity is associated with numerous pathological processes in the body, including inflammation, oxidative stress, and consequently, mitochondrial dysfunction. In recent years, research in anti-obesity therapy has also focused on the function of adipocytes and the inhibition of adipogenesis. In this study, we investigated the effect of the well-known flavonoid quercetin on mitochondrial function, apoptosis and differentiation of human preadipocytes. The Chub-S7 cell line model was used in the in vitro studies. Mitochondrial function was measured by oxygen consumption rates, intracellular ATP content, mitochondrial membrane potential, apoptosis assay (Annexin-5, caspase-9 activity), and ROS generation. Chub-S7 cell differentiation was assessed by Oil Red O staining. The results showed that the quercetin inhibited differentiation of human Chub-S7 preadipocytes and reduced fat accumulation in lipid droplets. Additionally, quercetin influenced mitochondrial biogenesis and mitochondrial uncoupling by changes in mitochondrial respiratory states and also increased mitochondrial membrane potential. Quercetin decreased routine respiration, R/E and netROUTINE control ratio. Our results demonstrate that quercetin is a dietary component that may modulate mitochondrial bioenergetics and inhibit adipogenesis. If these results were confirmed in in vivo studies, quercetin could be considered a factor used to prevent obesity.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine Quinone (6PPDQ) not only causes acute mortality in salmon but also induces toxicities in other living organisms. The electrophilic quinone moiety in the 6PPDQ molecular structure can participate in binding to the cysteine residues that ubiquitously exist in protein nucleophiles, which are responsible for its toxicities. Out of the 82 6PPDQ-bonded proteins found in the human model cell line A549 on the sulfhydryl-reactive proteomics platform, which enables the precise identification of covalent binding protein targets of a pollutant, we discovered three 6PPDQ-bonded mitochondrial proteins─NDUS6, COX5B, and ATP5PB─that are involved in mitochondrial dysfunction for the first time. They impede the function of mitochondria, as witnessed by the decreased enzymatic activities of mitochondrial respiratory chain Complexes I (27.63%) and IV (23.11%), the decreased cellular ATP content (19.94%), and the reduced mitochondrial membrane potential (3.2-fold), as well as the elevated mitochondrial ROS level (2.2-fold) under the environmentally relevant 8.9 μg/L 6PPDQ exposure compared to the controls. Our findings provide experimental evidence for elucidating 6PPDQ's toxicities at the molecular level, and the knowledge learned will enhance the public's awareness of the adverse impacts of environmental pollution on health.

Normobaric acute hypoxia models are widely applied to assess tolerance to acute hypoxic stress. Highland barley is a cereal crop originating from and traditionally cultivated in high-altitude regions; however, the dose-response relationship underlying its effects on hypoxia tolerance remains unclear. Male ICR mice were randomly allocated to five groups (n = 8 per group) and fed an AIN-93M basal diet or experimental diets supplemented with 20%, 40%, 60%, or 80% highland barley for 13 weeks. Hypoxia survival time was evaluated using a normobaric asphyxial hypoxia model, in which oxygen is progressively depleted in a sealed chamber by continuous respiration with carbon dioxide absorbed by soda lime. Hematological parameters, indices of oxidative stress and energy metabolism, and gut microbiota composition were also assessed. Compared with the control group, dietary supplementation with 20% highland barley was associated with a longer hypoxia survival time (mean difference: 9.49 min; 95% CI: -2.05 to 21.02), whereas the 80% group exhibited the shortest survival time (approximately 40.6 min). In the 20% group, red blood cell count and hemoglobin concentration increased by 41.6% and 42.1%, respectively. ATP content and superoxide dismutase activity in brain tissue increased by 33.2% and 28.4%, respectively, with similar trends observed in heart tissue. In addition, gut microbiota α-diversity was increased in the 20% highland barley group, and distinct separation of microbial community structures was observed among groups receiving different supplementation levels. Overall, the data suggest that moderate dietary supplementation with highland barley (20%) is associated with a favorable physiological and microbiota profile under normobaric asphyxial hypoxic challenge, suggesting the presence of a potentially effective intake range for highland barley-based nutritional intervention.

Thiocyanate (SCN-), a persistent inorganic contaminant widely present in industrial wastewater, poses severe risks to plant growth and photosynthesis. Hydrogen sulfide (H2S) is an emerging gaseous signaling molecule involved in the regulation of plant stress responses; however, its role in modulating Rubisco energy metabolism and activation under SCN- stress remains unclear. Here, we investigated the effects of exogenous H2S on magnesium homeostasis, ATP/NADPH metabolism, Rubisco activation, and photosynthetic performance in rice seedlings exposed to SCN- stress via physiological, biochemical, and transcriptional approaches. We found that exogenous H2S significantly increased Mg2+ accumulation, enhanced H+-ATPase and Mg2+-ATPase activities, and promoted Rubisco activase (RCA) abundance and activity. These changes were accompanied by reduced steady-state ATP and NADPH contents, indicating that increased energy consumption was driven by accelerated Calvin cycle turnover. At the transcriptional level, H2S regulated key genes involved in ATP hydrolysis, Mg2+ transport, Rubisco activation, and chlorophyll biosynthesis. Consequently, the chlorophyll content, stomatal conductance, and transpiration rate improved under SCN- stress. Collectively, our results demonstrate that exogenous H2S enhances photosynthetic efficiency and Rubisco carboxylation capacity by coordinating Rubisco energy metabolism and activation.

Seed aging is a complex biological process, the deterioration of oil crop seeds, in particular, has caused yield decline and economic loss to a large extent. However, research on the aging mechanism of oilseeds, such as cotton seeds, is still unclear. In this study, the physiological and biochemical changes in artificially aged cotton seeds were examined to further reveal the mechanism of seed aging and deterioration. Cotton seeds of “Xinluzao 74” were treated by artificial aging treatment method with high temperature (45°C) and high relative humidity (100%) for 1, 2, 3, 4, or 5 days, respectively, and untreated cotton seeds were used as control (CK). Our results showed that the germination rate, seed embryo viability, dehydrogenase activity, the activities of dehydrogenase antioxidant enzymes (SOD and POD), seed respiration rate, ATP content, ATP synthase activity and ATP synthase subunit mRNA integrity all showed a significant downward trend with the aging treatment time (P < 0.05), whereas the ROS generation (H2O2 content and ‧O2- production rate), relative conductivity, MDA content of seeds increased significantly, and the ultrastructure of cell membrane, mitochondria and chromatin of seed embryo was seriously damaged. Correlation analysis showed that there was a strong negative correlation between germination rate, SOD and POD activities, and respiration rate with H2O2 content (P < 0.05). This study reveals that excessive ROS, particularly H₂O₂, causes oxidative damage to ATP synthase subunit mRNAs, leading to impaired mitochondrial respiration and reduced seed vigor. These findings provide new molecular evidence linking oxidative RNA damage with seed aging, which could inform seed quality evaluation and storage strategies.

Mitochondrial dysfunction affects skeletal muscle (SkM) function and is critical in the etiology of age-related sarcopenia. The sirtuin 1-PGC1α pathway is a key regulator of mitochondrial mass, structure, and function. However, pathway activity decreases with aging. Cacao flavanols show promise in their ability to activate mitochondrial pathways. We evaluated the capacity of the flavanol (+)-epicatechin (+Epi) to stimulate such a pathway and favorably impact mitochondrial and oxidative stress (OS)-associated endpoints in aged SkM. Using 23-month-old male Sprague-Dawley rats, an 8-week oral administration of +Epi (1 mg/kg/day) was implemented, and results were compared versus vehicle-treated controls. Assessments included the nicotinamide adenine dinucleotide (NAD)/sirtuin 1/PGC1α pathway, acetylated proteins levels, mitochondrial function and biogenesis, as well as OS-related endpoints in SkM. +Epi increased the NAD/NADH ratio, activation of sirtuin 1, the deacetylation of nuclear protein content, including that of PGC1α. Also, +Epi induced increases of TFAM and NRF1 mRNA levels, deacetylation of mitochondrial complex I and V, increases in complex I activity, sirtuin 3, complexes I and V, mitofilin, and TFAM protein levels. SkM citrate synthase activity and ATP content increased with +Epi. OS markers in proteins and lipids were reduced, while buffering systems (superoxide dismutase 2 and catalase protein and activities) increased. In white blood cells, we documented serial reductions in mitochondrial DNA content and citrate synthase activity with aging, which were either fully or partially reversed with +Epi. Results demonstrate that +Epi treatment yields positive effects on mitochondrial biogenesis and function, leading to decreased OS and improved SkM bioenergetics in aged rats.

Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI). In this study, we demonstrated that the conditional knockout of eukaryotic initiation factor 2 (eIF2) subunits Eif2s1 and Eif2s2 in mouse oocytes caused oocyte apoptosis within the early growing follicles. Subsequent research indicated that the depletion of Eif2s2 in oocytes reduced the levels of mitochondrial fission-related proteins (p-DRP1, FIS1 and MFF) and increased the mRNA and protein levels of the integrated stress response (ISR)-related factors (ASNS, SLC7A1, GRB10 and PSAT1). Consistent with this, the depletion of Eif2s2 in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased mitochondrial membrane potential and ATP content, and excessive accumulation of reactive oxygen species (ROS). At the same time, the depletion of Eif2s2 in oocytes led to increased levels of DNA damage response proteins (γH2AX, p-CHK2 and p53) and proapoptotic proteins (BAX and PARP1), as well as decreased the levels of anti-apoptotic protein BCL-xL. Collectively, these findings indicate that the depletion of eIF2 subunits in mouse oocytes leads to oocyte apoptosis within the early growing follicles, attributed to the impaired translation of mitochondrial dynamics regulatory proteins and then the upregulated ROS levels and DNA damage. This study provides new insights into pathogenesis and genetic diagnosis for POI.

InDrosophila, Arginine kinase 1 (Argk1) is involved in maintaining ATP homeostasis during bursts of activity in tissues with high and variable rates of energy turnover such as muscle. However, its role beyond stress conditions is less understood. Here, we show thatArgk1maintains energy homeostasis during flight muscle development and is required for animal viability and proper muscle function. The knockdown of Argk1 causes defects in both early and late stages of myogenesis. In the proliferating myoblasts associated with the wing disc, Argk1 depletion results in a reduction in cell size without changes in cell cycle progression. Single cell RNA-sequencing revealed that the overall composition of differentiating and undifferentiating myoblasts is not altered. Nonetheless, Argk1 knockdown causes broad alterations in the expression of genes involved in various metabolic pathways. This correlates with low levels in both ATP content and NAD+/NADH ratio. Later in muscle development, Argk1-depleted muscles completely lack spontaneous muscle contractions that are essential in myofibrillogenesis. Accordingly, Argk1 knockdown results in severe defects in sarcomere structure, while the mitochondrial network is highly fragmented. Furthermore, muscle growth is severely reduced. Thus, our data reveal an essential role for Argk1 in maintaining energy homeostasis throughout muscle development, which is required to meet the demand to support myofibrillogenesis, muscle growth and proper muscle function.

SnRNA-seq reveals the ameliorative effects of optimized Xueyu Jingshen formula on high altitude cerebral edema by modulating energy metabolism, inflammation and BBB integrity.

Carbonyl sulfide exposure induces mitochondrial impairment by disrupting energy metabolism in Tribolium castaneum (Herbst).

Docosahexaenoic acid enhances porcine oocyte maturation via AMP-mediated improvement of mitochondrial function and energy metabolism.