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The aim of this study was to assess the effect of nitric oxide (NO)-mediated mitochondrial apoptosis on Tan sheep meat tenderness during postmortem aging. The hind leg muscle of Tan sheep was injected with 0.8% NaCl (control), 20 mmol/L aminoguanidine hydrochloride (AH) or 90 mmol/L L-arginine (L-Arg) and aged at 4 ℃ for 0, 6, 12, 24, 48, 96, and 192 h. NO and inducible nitric oxide synthase (iNOS) contents, cytochrome c (Cyt c) redox state, oxidative stress level, mitochondrial apoptotic pathways, and tenderness were measured during postmortem aging. The results indicated that at 12 and 24 h after slaughter, NO and iNOS levels were significantly higher, and ATP levels were significantly lower in the L-Arg group than in the control group (P < 0.05). At 24 and 48 h, Cyt c reduction levels and superoxide dismutase (SOD) activity were significantly higher, while the level of reactive oxygen species (ROS) was significantly lower in the AH group than in the control group (P < 0.05). From 12 to 96 h, ATP contents were significantly lower in the L-Arg group than in the control group (P < 0.05). In addition, at 24 h, Ca2+ concentration significantly increased in the L-Arg group compared with the control group (P < 0.05). At all time points except 24 h, the caspase-3 activity in the L-Arg group was significantly higher than that in the control group (P < 0.05). Moreover, it was found that the Bax/Bcl-2 ratio, pH, and myofibril fragmentation index (MFI) in the L-Arg group were significantly higher than those in the control group at all time points after slaughter (P < 0.05). Shear force was significantly lower in the L-Arg group but significantly higher in the AH group than in the control group (P < 0.05). In conclusion, NO exacerbates mitochondrial oxidative stress and directly upregulates ROS levels during the postmortem aging of Tan sheep meat, leading to a decrease in SOD activity, irreversible opening of mitochondrial permeability transition pore (MPTP), and ultimately mitochondrial damage. In addition, by controlling the redox state of Cyt c, NO indirectly activates caspase-3 activity to accelerate apoptotic energy metabolism, deplete ATP and consequently maintain myocyte homeostasis. Furthermore, NO affects the release of Ca2+, up-regulates the Bax/Bcl-2 ratio, and induces the occurrence of mitochondrial apoptotic cascade, ultimately resulting in an increase in MFI and a decrease in shear force and, consequently, improving the tenderness of Tan sheep meat.

In order to investigate the regulatory effect of B-cell lymphoma-2 (Bcl-2) on cell apoptosis and water retention in postmortem Qinchuan beef, the longissimus dorsi muscle of Qinchuan cattle was injected with either 200 μmol/L glycochenodeoxycholic acid (GCDA) or 10 μmol/L 2-ethyl-3-methylpentanamide (ABT-737) solution and aged at 4 ℃ postmortem. After 0, 6, 12, 24, 48, 72 and 120 h, the changes in Bcl-2 and Bcl-2-associated X protein (Bax) contents, the concentrations of endoplasmic reticulum and mitochondrial calcium ion, voltage-dependent anion channel protein 1 (VDAC1) expression, calpain content, the mitochondrial apoptosis pathway and water retention were determined. The results showed that at 6 h after slaughter, the Bcl-2 content of the GCDA-treated group was significantly higher than that of the control group (P < 0.01), the calcium ion concentration in the endoplasmic reticulum was significantly lower than that of the control group (P < 0.01), and cooking loss was significantly lower in both treatment groups than the control group (P < 0.05). At 12 and 24 h post-slaughter, the Bcl-2 content of the ABT-737-treated group was significantly lower than that of the control group (P < 0.01). At 12 and 120 h post-slaughter, the endoplasmic reticulum calcium ion, mitochondrial calcium ion and calpain levels in the ABT-737-treated group were significantly greater than those in the control group (P < 0.01). During 0–120 h post-slaughter, the total expression of VDAC1 in both treatment groups was lower than that in the control group. In summary, during the postmortem aging of Qinchuan beef, under the regulation of Bcl-2, calcium overload occurs through VDAC1-facilitated calcium transport, resulting in the activation of calpain, and the overloading of Ca2+ in mitochondria promotes the activation of caspase-9 and caspase-3, thus inducing cell apoptosis. The higher the degrees of cell apoptosis and caspase activation, the higher the degree of degradation of myofibrillar proteins, and the poorer the water-holding capacity of the meat.

Low triiodothyronine syndrome （LT3S） refers to the abnormal metabolism of thyroid hormones associated with critical illness， but without obvious symptoms of hypothyroidism. LT3S is closely associated with many critical diseases， such as severe burns， etc. During the occurrence and development of critical illness， many factors can induce LT3S by affecting the secretion， transfer and metabolism of thyroid hormones. LT3S is a risk factor for the development of critical illness and the occurrence of complications. It is a good indicator for evaluating the severity and prognosis of critical diseases. In this article， the pathogenesis， relationship with critical illness and treatment progress of LT3S were reviewed.

The water-gas relative permeability is an important parameter to characterize multiphase flow in sediments. To study the water-gas relative permeability of hydrate-bearing porous media, multiphase flow simulations were carried out at the pore scale using the lattice Boltzmann method. The effects of hydrate saturation and hydrate-growth habits on the water-gas relative permeability, which is scaled by the relative permeability considering the hydrate only, were evaluated in a two-dimensional porous medium. Results show that the increase of hydrate saturation causes the decrease of water-gas effective permeability as expected. However, the effect of hydrate saturation on the water-gas relative permeability is different from that of hydrate saturation on the water-gas effective permeability. The water-gas relative permeability increases with the increase of hydrate saturation in the pore-filling case. The water-gas relative permeability decreases with the increase of hydrate saturation in the grain-coating case. The wettability of solid phase has a different effect on the relative permeability of wetting phase and nonwetting phase. The Jamin effect (phase blocking) was observed and may exist in the production of gas from natural gas hydrate reservoirs. This seriously affects the multiphase flow characteristics. The changes of microscale fluid distribution effect the changes of water-gas relative permeability. The relationship between the water-gas relative permeability and the characterization parameters of microscale fluid distribution was analyzed.

Objective To explore the effect of E3 ligase neuregulin receptor degradation protein 1 (Nrdp1) regulating macrophage polarization on the function of fibroblasts. Methods Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) were combined to induce mouse primary peritoneal macrophages to M1 macrophages (M1), and IL-13 was used to induce macrophages to M2 macrophages (M2). Then flow cytometry and Western blotting were used to detect M1 surface marker protein CD11c and its specific secretion inducible nitric oxide synthase (iNOS), and M2 surface marker protein CD206 and the secretion arginase 1 (Arg1). After the mouse macrophages was transfected with siRNA-Nrdp1 transiently for 24 h, the expression of Nrdp1 was detected by Western blotting. A Transwell co-culture system was established for macrophages and fibroblasts, and was induced under different conditions. The co-cultured cells were divided into LPS group (co-induction of LPS and IFN-γ), LPS-NC group (co-induction and siRNA of irrelevant sequence), LPS-siRNA-Nrdp1 group (co-induction of LPS and siRNA-Nrdp1), IL-13 group, IL-13-NC group and IL-13-siRNA-Nrdp1 group. After co-culture for 8, 12 and 24 h, CCK-8 assay was employed to detect the proliferation of fibroblasts, and ELISA to measure the contents of transforming growth factor β1 (TGF-β1) and type Ⅰ procollagen. Analysis of variance of factorial designs and Bonferroni test were used for statistical analysis for the data. Results The proportion of CD11c positive cells was significantly higher in the LPS-induced macrophages than the non-induced cells (P < 0.05), and similar result was seen in the IL-13-induced macrophages for CD206 expression (P < 0.05). Western blot analysis indicated the levels of iNOS and Arg1 were obviously higher in the LPS- and IL-13-induced macrophages than the non-induced control cells, respectively (P < 0.01). Transient transfection of siRNA-Nrdp1 resulted in notably lower expression of Nrdp1 when compared with the blank control and negative control transfection (both P < 0.01). In the co-culture system for 24 h, CCK8 assay showed the count of fibroblasts was significantly lower in the IL-13-siRNA-Nrdp1 group than the IL-13 and IL-13-NC groups (P < 0.01), and ELISA indicated that the content of TGF-β1 was lower in the IL-13-siRNA-Nrdp1 group than the IL-13 and IL-13-NC groups (P < 0.01), and that of type Ⅰ procollagen was lower in the IL-13-siRNA-Nrdp1 group than the IL-13 groups (P < 0.01). Conclusion Interference of Nrdp1 synthesis by siRNA can affect the polarization of macrophages to M2 type, inhibit the proliferation of fibroblasts in the co-culture system of M2 type macrophages and fibroblasts, and reduce the TGF-β1 and type Ⅰ procollagen in the co-culture system.

Upconversion nanoparticles (UCNPs) have been used as a potential nanocarrier for photosensitizers (PSs), which have demonstrated a great deal of promise in achieving an effective photodynamic therapy (PDT) for deep-seated tumors. However, overcoming biological barriers to achieve mitochondria-targeted PDT remains a major challenge. Herein, CD44- and mitochondria-targeted photodynamic nanosystems were fabricated through the self-assembly of hyaluronic acid-conjugated-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-(chlorin e6-dihydrolipoic acid-(3-carboxypropyl)triphenylphosphine bromide) polymeric ligands (HA-c-mPEG-Deta-g-(Ce6-DHLA-TPP)) and NaErF4:Tm@NaYF4 core–shell UCNPs (termed CMPNs). The CMPNs presented ideal physiological stability, a good drug loading capacity and an improved capacity for the generation of singlet oxygen (1O2) based on the FRET mechanism. Significantly, confocal images revealed that CMPNs not only facilitated cellular uptake through CD44-receptor-targeted endocytosis, subsequently enabling rapid evasion from endo-lysosomal sequestration, but also specifically targeted mitochondria, ultimately inducing a profound disruption of mitochondrial membrane potential, which triggered apoptosis upon laser irradiation, thereby significantly enhancing the therapeutic effect. Furthermore, in vitro antitumor experiments further confirmed the substantial enhancement in cancer cell killing efficiency achieved by treating with CMPNs upon near-infrared (NIR) laser irradiation. This innovative approach holds promise for the development of NIR-laser-activated photodynamic nanoagents specifically designed for mitochondria-targeted PDT, thus addressing the limitations of the current PDT treatments. [ABSTRACT FROM AUTHOR]