Effects of cadmium and zinc interactions on the physiological biochemistry and enrichment characteristics of Iris pseudacorus.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

Hydrolysis of Beef Sarcoplasmic Protein by Dry-Aged Beef-Isolated Penicillium oxalicum and Its Associated Metabolic Pathways.

Yanbian cattle have a unique meat flavor, and high-grade meat is in short supply. Therefore, in this study, we aimed to improve the added value of Yanbian cattle low-fat meat and provide a theoretical reference for the subsequent development of an excellent starter. Rump meat from Yanbian cattle was dry-aged and then screened for protease-producing fungi. Three protease-producing fungi (Yarrowia hollandica (D4 and D11), Penicillium oxalicum (D5), and Meesziomyces ophidis (D20)) were isolated from 40 d dry-aged beef samples, and their ability to hydrolyze proteins was determined using bovine sarcoplasmic protein extract. SDS-PAGE showed that the ability of Penicillium oxalicum (D5) to degrade proteins was stronger than the other two fungi. In addition, the volatile component content of sarcoplasmic proteins in the D5 group was the highest (45.47%) and comprised the most species (26 types). Metabolic pathway analysis of the fermentation broth showed that phenylalanine, tyrosine, and tryptophan biosynthesis was the most closely related metabolic pathway in sarcoplasmic protein fermentation by Penicillium oxalicum (D5). Dry-aged beef-isolated Penicillium oxalicum serves as a potential starter culture for the fermentation of meat products.

Monitoring and influencing factors of grassland livestock overload in Xinjiang from 1982 to 2020.

It is crucial to estimate the theoretical carrying capacity of grasslands in Xinjiang to attain a harmonious balance between grassland and livestock, thereby fostering sustainable development in the livestock industry. However, there has been a lack of quantitative assessments that consider long-term, multi-scale grass-livestock balance and its impacts in the region. This study utilized remote sensing and empirical models to assess the theoretical livestock carrying capacity of grasslands. The multi-scale spatiotemporal variations of the theoretical carrying capacity in Xinjiang from 1982 to 2020 were analyzed using the Sen and Mann-Kendall tests, as well as the Hurst index. The study also examined the county-level grass-livestock balance and inter-annual trends. Additionally, the study employed the geographic detector method to explore the influencing factors. The results showed that: (1) The overall theoretical livestock carrying capacity showed an upward trend from 1982 to 2020; The spatial distribution gradually decreased from north to south and from east to west. In seasonal scale from large to small is: growing season > summer > spring > autumn > winter; at the monthly scale, the strongest livestock carrying capacity is in July. The different grassland types from largest to smallest are: meadow > alpine subalpine meadow > plain steppe > desert steppe > alpine subalpine steppe. In the future, the theoretical livestock carrying capacity of grassland will decrease. (2) From 1988 to 2020, the average grass-livestock balance index in Xinjiang was 2.61%, showing an overall increase. At the county level, the number of overloaded counties showed an overall increasing trend, rising from 46 in 1988 to 58 in 2020. (3) Both single and interaction factors of geographic detectors showed that annual precipitation, altitude and soil organic matter were the main drivers of spatiotemporal dynamics of grassland load in Xinjiang. The results of this study can provide scientific guidance and decision-making basis for achieving coordinated and sustainable development of grassland resources and animal husbandry in the region.

Characterisation of a casein-/whey protein concentrate-Antarctic krill oil emulsion system and improvement of its storage stability.

AIMS: To develop Antarctic krill oil emulsions with casein and whey protein concentrate (WPC) and study their physicochemical properties and storage stability. METHODS: Emulsions were prepared by homogenisation and ultrasonication. The properties of the emulsions were investigated via ultraviolet ray spectroscopy, dynamic light scattering, confocal laser scanning microscope, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, Fourier transform infra-red spectrometer, and fluorescence spectrum. Shelf life was predicted by the Arrhenius model. RESULTS: Casein- and WPC-krill oil emulsions were well formed; the mean particle diameters were less than 128.19 ± 0.64 nm and 158 ± 1.56 nm, the polymer dispersity indices were less than 0.26 ± 0.01 and 0.27 ± 0.01, and the zeta potential were around -46.88 ± 5.02 mV and -33.51 ± 2.68 mV, respectively. Shelf life was predicted to be 32.67 ± 1.55 days and 29.62 ± 0.65 days (40 °C), 27.69 ± 1.15 days and 23.58 ± 0.14 days (50 °C), 24.02 ± 0.15 days and 20.1 ± 0.08 days (60 °C). CONCLUSION: The prepared krill oil emulsions have great potential to become a new krill oil supplement.

Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut-breast axis.

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.

Temperature fluctuation in soil alters the nanoplastic sensitivity in wheat.

Despite the wide acknowledgment that plastic pollution and global warming have become serious agricultural concerns, their combined impact on crop growth remains poorly understood. Given the unabated megatrend, a simulated soil warming (SWT, +4 °C) microcosm experiment was carried out to provide a better understanding of the effects of temperature fluctuations on wheat seedlings exposed to nanoplastics (NPs, 1 g L-1 61.71 ±â€¯0.31 nm polystyrene). It was documented that SWT induced oxidative stress in wheat seedlings grown in NPs-contaminated soil, with an 85.56 % increase in root activity, while decreasing plant height, fresh weight, and leaf area by 8.72 %, 47.68 %, and 15.04 % respectively. The SWT also resulted in reduced photosynthetic electron-transfer reaction and Calvin-Benson cycle in NPs-treated plants. Under NPs, SWT stimulated the tricarboxylic acid (TCA) metabolism and bio-oxidation process. The decrease in photosynthesis and the increase in respiration resulted in an 11.94 % decrease in net photosynthetic rate (Pn). These results indicated the complicated interplay between climate change and nanoplastic pollution in crop growth and underscored the potential risk of nanoplastic pollution on crop production in the future climate.

The efficient uptake of uranium by amine-functionalized ß-cyclodextrin supported fly ash composite from polluted water.

A novel polyethyleneimine/polydopamine-functionalized ß-cyclodextrin supported fly ash adsorbent (PEI/PDA/ß-CD/FA) had been synthesized to uptake uranium from polluted water. At pH = 5.0 and T = 298 K, the uranium uptake efficiency and capacity of PEI/PDA/ß-CD/FA reached to 98.7 % and 622.8 mg/g, respectively, which were much higher than those of FA (71.4 % and 206.7 mg/g).The excellent uranium uptake properties of PEI/PDA/ß-CD/FA could be explained by three points: (1) using ß-CD as a supporting material could effectively avoid the aggregation of FA and improve the hydrophily of FA; (2) the unique cavity structure of ß-CD could form chelates with uranyl ions; (3) the formation of PEI/PDA co-deposition coating on FA further enhanced the affinity of FA to UO22+. With the presence of interfering ions, the uptake efficiency of PEI/PDA/ß-CD/FA for uranium was still up to 94.5 % after five cycles, indicating the high selectively and recoverability of PEI/PDA/ß-CD/FA. In terms of the results of characterizations, uranium was captured by PEI/PDA/ß-CD/FA via electrostatic attraction, hydrogen bond, coordination and complexation. To sum up, PEI/PDA/ß-CD/FA was expected to be used for actual sewage treatment owing to its excellent uranium uptake efficiency/capacity, selectivity, cycle stability and feasibility of actual application.

Edible chitosan-based Pickering emulsion coatings: Preparation, characteristics, and application in strawberry preservation.

The long-term application of plant essential oils in food preservation coatings is limited by their poor water solubility and high volatility, despite their recognized synergistic antimicrobial effects in postharvest fruit preservation. To overcome these limitations, a Pickering emulsion loaded with thyme essential oil (TEO) was developed by utilizing hydrogen bonding and electrostatic interactions to induce cross-linking of chitosan particles. This novel emulsion was subsequently applied in the postharvest storage of strawberries. The shear-thinning behavior (flow index <1) and elastic gel-like characteristics of the emulsion made it highly suitable for spray application. Regarding TEO release, the headspace concentration of TEO increased from 0.21 g/L for pure TEO to 1.86 g/L after two instances of gas release due to the stabilizing effect of the chitosan particles at the oil-water interface. Notably, no phase separation was observed during the 10-day storage of the emulsion. Consequently, the emulsion was successfully employed for the postharvest storage of strawberries, effectively preventing undesirable phenomena such as weight loss, a decrease in firmness, an increase in pH, and microbial growth. In conclusion, the developed Pickering emulsion coating exhibits significant potential for fruit preservation applications, particularly for extending the shelf life of strawberries.

Carboxymethylcellulose-induced depletion attraction to stabilize high internal phase Pickering emulsions for the elderly: 3D printing and ß-carotene delivery.

In this study, a carboxymethylcellulose (CMC) induced depletion attraction was developed to stabilize high internal phase Pickering emulsions (HIPPEs) as age-friendly 3D printing inks. The results demonstrated that depletion force induced the adsorption of yolk particles at the droplet interface and the formation of osmotic droplet clusters, thereby increasing the stability of HIPPEs. In addition, the rheological properties and nutrient delivery properties of HIPPEs could be adjusted by the mass ratio of yolk/CMC. The HIPPEs stabilized at yolk/CMC mass ratio 20:7.5 showed optimal printability, viscoelastic, structural recovery, and swallowability. HIPPEs have been applied to 3D printing, International Dysphagia Dietary Standardization Initiative (IDDSI) test, and in vitro digestive simulation in the elderly, indicating their attractive appearance, safe swallowability, and enhanced bioaccessibility of ß-carotene. Our work provides new ideas for developing age-friendly foods with plasticity and nutrient delivery capacity by depletion attraction stabilizing HIPPEs.

ARPruning: An automatic channel pruning based on attention map ranking.

Structured pruning is a representative model compression technology for convolutional neural networks (CNNs), aiming to prune some less important filters or channels of CNNs. Most recent structured pruning methods have established some criteria to measure the importance of filters, which are mainly based on the magnitude of weights or other parameters in CNNs. However, these judgment criteria lack explainability, and it is insufficient to simply rely on the numerical values of the network parameters to assess the relationship between the channel and the model performance. Moreover, directly utilizing these pruning criteria for global pruning may lead to suboptimal solutions, therefore, it is necessary to complement search algorithms to determine the pruning ratio for each layer. To address these issues, we propose ARPruning (Attention-map-based Ranking Pruning), which reconstructs a new pruning criterion as the importance of the intra-layer channels and further develops a new local neighborhood search algorithm for determining the optimal inter-layer pruning ratio. To measure the relationship between the channel to be pruned and the model performance, we construct an intra-layer channel importance criterion by considering the attention map for each layer. Then, we propose an automatic pruning strategy searching method that can search for the optimal solution effectively and efficiently. By integrating the well-designed pruning criteria and search strategy, our ARPruning can not only maintain a high compression rate but also achieve outstanding accuracy. In our work, it is also experimentally concluded that compared with state-of-the-art pruning methods, our ARPruning method is capable of achieving better compression results. The code can be obtained at https://github.com/dozingLee/ARPruning.

Inducing spin polarization via Co doping in the BiVO4 cell to enhance the built-in electric field for promotion of photocatalytic CO2 reduction.

The efficiency of CO2 photocatalytic reduction is severely limited by inefficient separation and sluggish transfer. In this study, spin polarization was induced and built-in electric field was strengthened via Co doping in the BiVO4 cell to boost photocatalytic CO2 reduction. Results showed that owing to the generation of spin-polarized electrons upon Co doping, carrier separation and photocurrent production of the Co-doped BiVO4 were enhanced. CO production during CO2 photocatalytic reduction from the Co-BiVO4 was 61.6 times of the BiVO4. Notably, application of an external magnetic field (100 mT) further boosted photocatalytic CO2 reduction from the Co-BiVO4, with 68.25 folds improvement of CO production compared to pristine BiVO4. The existence of a built-in electric field (IEF) was demonstrated through density functional theory (DFT) simulations and kelvin probe force microscopy (KPFM). Mechanism insights could be elucidated as follows: doping of magnetic Co into the BiVO4 resulted in increased the number of spin-polarized photo-excited carriers, and application of a magnetic field led to an augmentation of intrinsic electric field due to a dipole shift, thereby extending carrier lifetime and suppressing charges recombination. Additionally, HCOO- was a crucial intermediate in the process of CO2RR, and possible pathways for CO2 reduction were proposed. This study highlights the significance of built-in electric fields and the important role of spin polarization for promotion of photocatalytic CO2 reduction.

Mortality in patients admitted to hospital with heart failure in China: a nationwide Cardiovascular Association Database-Heart Failure Centre Registry cohort study.

BACKGROUND: China has the largest burden of heart failure worldwide. However, large-scale studies on heart failure mortality are scarce. We aimed to investigate mortality and identify risk factors for mortality among patients with heart failure in China. METHODS: This prospective cohort study used data from the China Cardiovascular Association (CCA) Database-Heart Failure Centre Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. We included patients enrolled from Jan 1, 2017, to Dec 31, 2021, across 572 CCA Database-Heart Failure Centre certified hospitals in 31 provinces of mainland China. Eligible patients were aged 18 years or older (younger than 100 years) with a principal discharge diagnosis of heart failure based on Chinese heart failure guidelines. All-cause mortality at 30 days, 1 year, and 3 years for patients with heart failure were calculated and the causes of death were recorded. Multivariable analysis was used to analyse factors associated with all-cause mortality and cardiovascular mortality. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2200066305. FINDINGS: Of the 327 477 patients in the registry, 230 637 eligible adults with heart failure were included in our analyses. Participant mean age was 69·3 years (SD 13·2), 94 693 (41·1%) participants were female, and 135 944 (58·9%) were male. The median follow-up time was 531 days (IQR 251-883). Post-discharge all-cause mortality of patients with heart failure at 30 days was 2·4% (95% CI 2·3-2·5), at 1 year was 13·7% (13·5-13·9), and at 3 years was 28·2% (27·7-28·6). Cardiovascular death accounted for 32 906 (71·5%) of 46 006 all-cause deaths. Patients with heart failure with reduced ejection fraction had the highest all-cause mortality. A lower guideline adherence score was independently associated with the increase of all-cause and cardiovascular mortality. INTERPRETATION: In China, mortality for patients with heart failure is still high, especially in patients with reduced ejection fraction. Our findings suggest that guideline-directed medical therapy needs to be improved. FUNDING: National High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effect of different iron ratios on interaction and thermodynamic stability of bound whey protein isolate.

Whey protein isolates (WPI) are known to have mineral-binding capacity to promote iron absorption. The aim of this study was to investigate the effect of iron ratio on the conformational structure of iron-bound whey protein isolate (WPI-Fe) and its thermodynamic stability. It was shown that the iron to protein ratio affects both the iron binding capacity of WPI and the iron valence state on the surface of WPI-Fe complexes. As the iron content increases, aggregation between protein molecules occurs. In addition, WPI-Fe nanoparticles have thermodynamic stability and Fe2+ has a high affinity with WPI for spontaneous exothermic reactions. This study demonstrates that WPI-Fe complexes can be used to efficiently deliver high-quality iron source (Fe2+) for future iron supplements.

Leukotriene B4-induced neutrophil extracellular traps impede the clearance of Pneumocystis.

Pneumocystis pneumonia (PCP) is a fungal pulmonary disease with high mortality in immunocompromised patients. Neutrophils are essential in defending against fungal infections; however, their role in PCP is controversial. Here we aim to investigate the effects of neutrophil extracellular traps (NETs) on Pneumocystis clearance and lung injury using a mouse model of PCP. Intriguingly, although neutrophils play a fundamental role in defending against fungal infections, NETs failed to eliminate Pneumocystis, but instead impaired the killing of Pneumocystis. Mechanically, Pneumocystis triggered Leukotriene B4 (LTB4)-dependent neutrophil swarming, leading to agglutinative NET formation. Blocking Leukotriene B4 with its receptor antagonist Etalocib significantly reduced the accumulation and NET release of neutrophils in vitro and in vivo, enhanced the killing ability of neutrophils against Pneumocystis, and alleviated lung injury in PCP mice. This study identifies the deleterious role of agglutinative NETs in Pneumocystis infection and reveals a new way to prevent NET formation, which provides new insights into the pathogenesis of PCP.

Carbonic Anhydrase 3 is required for cardiac repair post myocardial infarction via Smad7-Smad2/3 signaling pathway.

Appropriate fibrosis is required to prevent subsequent adverse remodeling and heart failure post myocardial infarction (MI), and cardiac fibroblasts (CFs) play a critical role during the process. Carbonic anhydrase 3 (CAR3) is an important mediator in multiple biological processes besides its CO2 hydration activity; however, the role and underlying mechanism of CAR3 on cardiac repair post MI injury remains unknown. Here, we found that CAR3 expression was up-regulated in cardiac tissue in infarct area at the reparative phase of MI, with a peak at 7 days post MI. The upregulation was detected mainly on fibroblast instead of cardiomyocyte, and primary cardiac fibroblasts treated with TGF-ß1 recaptured our observation. While CAR3 deficiency leads to weakened collagen density, enlarged infarct size and aggravated cardiac dysfunction post-MI. In fibroblast, we observed that CAR3 deficiency restrains collagen synthesis, cell migration and gel contraction of cardiac fibroblasts, whereas overexpression of CAR3 in CFs improves wound healing and cardiac fibroblast activation. Mechanistically, CAR3 stabilizes Smad7 protein via modulating its acetylation, which dampens phosphorylation of Smad2 and Smad3, thus inhibiting fibroblast transformation. In contrast, inhibition of Smad7 acetylation with C646 blunts CAR3 deficiency induced suppression of fibroblast activation and impaired cardiac healing. Our data demonstrate a protective role of CAR3 in cardiac wound repair post MI via promoting fibroblasts activation through Smad7-TGF-ß/Smad2/3 signaling pathway.

Analytical evaluation of the automated genotyping system (GenPlex) compared to a traditional real-time PCR assay for the detection of high-risk human papillomaviruses.

The detection of high-risk human papillomaviruses (HPVs) is crucial for early screening and preventing cervical cancer. However, the substantial workload in high-level hospitals or the limited resources in primary-level hospitals hinder widespread testing. To address this issue, we explored a sample-to-answer genotyping system and assessed its performance by comparing it with the traditional real-time polymerase chain reaction (PCR) method conducted manually. Samples randomly selected from those undergoing routine real-time PCR detection were re-analyzed using the fully automatic GenPlex® system. This system identifies 24 types of HPV through a combination of ordinary PCR and microarray-based reverse hybridization. Inconsistent results were confirmed by repeated testing with both methods, and the κ concordance test was employed to evaluate differences between the two methods. A total of 365 samples were randomly selected from 7259 women. According to real-time PCR results, 76 were high-risk HPV negative, and 289 were positive. The GenPlex® system achieved a κ value greater than 0.9 (ranging from 0.920 to 1.000, p < 0.0001) for 14 types of high-risk HPV, except HPV 51 (κ = 0.697, p < 0.0001). However, the inconsistent results in high-risk HPV 51 were revealed to be false positive in real-time PCR by other method. When counting by samples without discriminating the high-risk HPV type, the results of both methods were entirely consistent (κ = 1.000, p < 0.0001). Notably, the GenPlex® system identified more positive cases, with 73 having an HPV type not covered by real-time PCR, and 20 potentially due to low DNA concentration undetectable by the latter. Compared with the routinely used real-time PCR assay, the GenPlex® system demonstrated high consistency. Importantly, the system's advantages in automatic operation and a sealed lab-on-chip format respectively reduce manual work and prevent aerosol pollution. For widespread use of GenPlex® system, formal clinical validation following international criteria should be warranted.

MCC950 Ameliorates Diabetic Muscle Atrophy in Mice by Inhibition of Pyroptosis and Its Synergistic Effect with Aerobic Exercise.

Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L-1 vs. 4.26 ± 0.6 mmol L-1, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min-1 vs. 34.75 ± 2.66 m min-1, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm2 vs. 2747.83 ± 406.44 µm2, p < 0.05). We found that both MCC950 (10 mg kg-1) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm2, p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm2, p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.

Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.