Ferroptosis-inducing photosensitizers alleviate hypoxia tumor microenvironment for enhanced fluorescence imaging-guided photodynamic therapy.

This study describes H2O2-activated photosensitizer nanoparticles (ICyHD NPs), which inhibit histone deacetylase via binding Zn2+ to induce ferroptosis and upregulate the intracellular O2, thus resulting in enhanced photodynamic therapeutic effect. ICyHD NPs exert strong antitumor effects on mice and have improved the therapeutic precision via observing the increase in cellular fluorescence.

Droplet digital molecular beacon-LAMP assay via pico-injection for ultrasensitive detection of pathogens.

A pico-injection-aided digital droplet detection platform is presented that integrates loop-mediated isothermal amplification (LAMP) with molecular beacons (MBs) for the ultrasensitive and quantitative identification of pathogens, leveraging the sequence-specific detection capabilities of MBs. The microfluidic device contained three distinct functional units including droplet generation, pico-injection, and droplet counting. Utilizing a pico-injector, MBs are introduced into each droplet to specifically identify LAMP amplification products, thereby overcoming issues related to temperature incompatibility. Our methodology has been validated through the quantitative detection of Escherichia coli, achieving a detection limit as low as 9 copies/µL in a model plasmid containing the malB gene and 3 CFU/µL in a spiked milk sample. The total analysis time was less than 1.5 h. The sensitivity and robustness of this platform further demonstrated the potential for rapid pathogen detection and diagnosis, particularly when integrated with cutting-edge microfluidic technologies.

One-Step Realization of Layered/Spinel Heterostructures and Na Doping by Sodium Dodecyl Sulfate-Assisted Sol-Gel Method for Li-Ion Batteries.

Li-rich layered oxide cathodes have attracted extensive attention due to their high energy density. However, due to the low initial Coulombic efficiency and the capacity fading and voltage fading during cycling, its practical application is still a great challenge. Here, we report the one-step realization of layered/spinel heterostructures and Na doping by the sodium dodecyl sulfate (SDS)-assisted sol-gel method. The spinel phase provides 3D diffusion channels for Li-ions, and sodium doping changes the layered lattice constant and expands the layer spacing. Therefore, the designed Li1.15Mn0.54Ni0.13Co0.13Na0.05O2 (SDS-2) cathode possesses excellent electrochemical performance such as higher initial Coulombic efficiency and rate capacity and also alleviates voltage decay. The initial discharge-specific capacity of SDS-2 is 298.8 mAh g-1 at 0.1 C, and the discharge-specific capacity can reach 111.7 mAh g-1 at 10 C. This strategy can provide new insights into the design and synthesis of high-performance Li-rich layered oxide cathode materials.

Ginseng extract improves pancreatic islet injury and promotes ß-cell regeneration in T2DM mice.

Introduction: Panax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting ß-cell regeneration. Methods: The T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet ß-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind ß-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses. Results and Discussion: The present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1ß decreased. Ginseng extract preserved normal islet morphology, increased nascent ß-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing ß-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to ß-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance ß-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

Evaluation of transport mechanisms of methotrexate in human choriocarcinoma cell lines by LC-MS/MS.

Methotrexate (MTX) is commonly prescribed as the initial treatment for gestational trophoblastic neoplasia (GTN), but MTX monotherapy may not be effective for high-risk GTN and choriocarcinoma. The cellular uptake of MTX is essential for its pharmacological activity. Thus, our study aimed to investigate the cellular pharmacokinetics and transport mechanisms of MTX in choriocarcinoma cells. For the quantification of MTX concentrations in cellular matrix, a liquid chromatography-tandem mass spectrometry method was created and confirmed initially. MTX accumulation in BeWo, JEG-3, and JAR cells was minimal. Additionally, the mRNA levels of folate receptor α (FRα) and breast cancer resistance protein (BCRP) were relatively high in the three choriocarcinoma cell lines, whereas proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and organic anion transporter (OAT) 4 were low. Furthermore, the expression of other transporters was either very low or undetectable. Notably, the application of inhibitors and small interfering RNAs (siRNAs) targeting FRα, RFC, and PCFT led to a notable decrease in the accumulation of MTX in BeWo cells. Conversely, the co-administration of multidrug resistance protein 1 (MDR1) and BCRP inhibitors increased MTX accumulation. In addition, inhibitors of OATs and organic-anion transporting polypeptides (OATPs) reduced MTX accumulation, while peptide transporter inhibitors had no effect. Results from siRNA knockdown experiments and transporter overexpression cell models indicated that MTX was not a substrate of nucleoside transporters. In conclusion, the results indicate that FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of MTX, whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells. These results have implications for predicting transporter-mediated drug interactions and offer potential directions for further research on enhancing MTX sensitivity.

FFT-Based Probability Density Imaging of Euler Solutions.

When using traditional Euler deconvolution optimization strategies, it is difficult to distinguish between anomalies and their corresponding Euler tails (those solutions are often distributed outside the anomaly source, forming "tail"-shaped spurious solutions, i.e., misplaced Euler solutions, which must be removed or marked) with only the structural index. The nonparametric estimation method based on the normalized B-spline probability density (BSS) is used to separate the Euler solution clusters and mark different anomaly sources according to the similarity and density characteristics of the Euler solutions. For display purposes, the BSS needs to map the samples onto the estimation grid at the points where density will be estimated in order to obtain the probability density distribution. However, if the size of the samples or the estimation grid is too large, this process can lead to high levels of memory consumption and excessive computation times. To address this issue, a fast linear binning approximation algorithm is introduced in the BSS to speed up the computation process and save time. Subsequently, the sample data are quickly projected onto the estimation grid to facilitate the discrete convolution between the grid and the density function using a fast Fourier transform. A method involving multivariate B-spline probability density estimation based on the FFT (BSSFFT), in conjunction with fast linear binning appropriation, is proposed in this paper. The results of two random normal distributions show the correctness of the BSS and BSSFFT algorithms, which is verified via a comparison with the true probability density function (pdf) and Gaussian kernel smoothing estimation algorithms. Then, the Euler solutions of the two synthetic models are analyzed using the BSS and BSSFFT algorithms. The results are consistent with their theoretical values, which verify their correctness regarding Euler solutions. Finally, the BSSFFT is applied to Bishop 5X data, and the numerical results show that the comprehensive analysis of the 3D probability density distributions using the BSSFFT algorithm, derived from the Euler solution subset of x0,y0,z0, can effectively separate and locate adjacent anomaly sources, demonstrating strong adaptability.

Comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers.

In recent years, attention has been directed towards cost-effective and compact freeform Schwarzschild imaging spectrometers with plane gratings. The utilization of tolerance analysis serves as a potent approach to facilitate the development of prototypes. Conventional tolerance analysis methods often rely solely on the modulation transfer function (MTF) criterion. However, for a spectrometer system, factors such as the keystone/smile distortion and spectral resolution performance also require consideration. In this study, a tailored comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers was developed, considering vital aspects such as the MTF, keystone/smile distortion, and spectral resolution. Through this approach, meticulous tolerance analysis was conducted for a freeform Schwarzschild imaging spectrometer, providing valuable insights for the prototype machining and assembly processes. Emphasis was placed on the necessity of precise control over the tilt and decenter between the first and third mirrors, whereas the other fabrication and assembly tolerances adhered to the standard requirements. Finally, an alignment computer-generated hologram (CGH) was employed for the preassembly of the first and third mirrors, enabling successful prototype development. The congruence observed between the measured results and tolerance analysis outcomes demonstrates the effectiveness of the proposed method.

Synthesis of polymerizable betulin maleic diester derivative for dental restorative resins with antibacterial activity.

OBJECTIVE: Bisphenol A glycidyl methacrylate (Bis-GMA) is of great importance for dental materials as the preferred monomer. However, the presence of bisphenol-A (BPA) core in Bis-GMA structure causes potential concerns since it is associated with endocrine diseases, developmental abnormalities, and cancer lesions. Therefore, it is desirable to develop an alternative replacement for Bis-GMA and explore the intrinsic relationship between monomer structure and resin properties. METHODS: Here, the betulin maleic diester derivative (MABet) was synthesized by a facile esterification reaction using plant-derived betulin and maleic anhydride as raw materials. Its chemical structure was confirmed by 1H and 13C NMR spectra, FT-IR spectra, and HR-MS, respectively. The as-synthesized MABet was then used as polymerizable comonomer to partially or completely substitute Bis-GMA in a 50:50 Bis-GMA: TEGDMA resin (5B5T) to formulate dental restorative resins. These were then determined for the viscosity behavior, light transmittance, real-time degree of conversion, residual monomers, mechanical performance, cytotoxicity, and antibacterial activity against Streptococcus mutans (S. mutans) in detail. RESULTS: Among all experimental resins, increasing the MABet concentration to 50 wt% made the resultant 5MABet5T resin have a maximum in viscosity and appear dark yellowish after polymerization. In contrast, the 1MABet4B5T resin with 10 wt% MABet possessed comparable shear viscosity and polymerization conversion (46.6 ± 1.0% in 60 s), higher flexural and compressive strength (89.7 ± 7.8 MPa; 345.5 ± 14.4 MPa) to those of the 5B5T control (48.5 ± 0.6%; 65.7 ± 6.7 MPa; 223.8 ± 57.1 MPa). This optimal resin also had significantly lower S. mutans colony counts (0.35 ×108 CFU/mL) than 5B5T (7.6 ×108 CFU/mL) without affecting cytocompatibility. SIGNIFICANCE: Introducing plant-derived polymerizable MABet monomer into dental restorative resins is an effective strategy for producing antibacterial dental materials with superior physicochemical property.

Theoretical exploration of the phenolic compounds' inhibition mechanism of heterocyclic aromatic amines in roasted beef patties by density functional theory.

The ability of spices (bay leaf, star anise, and red pepper) and their characteristic phenolic compounds (quercetin, kaempferol, and capsaicin) to inhibit Heterocyclic aromatic amines (HAAs) in roasted beef patties were compared. Density functional theory (DFT) was used to reveal phenolic compounds interacting with HAAs-related intermediates and free radicals to explore possible inhibitory mechanisms for HAAs. 3 % red chili and 0.03 % capsaicin reduced the total HAAs content by 57.09 % and 68.79 %, respectively. DFT demonstrated that this was due to the stronger interaction between capsaicin and the ß-carboline HAAs intermediate (Ebind = -32.95 kcal/mol). The interaction between quercetin and phenylacetaldehyde was found to be the strongest (Ebind = -17.47 kcal/mol). Additionally, DFT indicated that capsaicin reduced the carbonyl content by transferring hydrogen atoms (HAT) to eliminate HO·, HOO·, and carbon-centered alkyl radicals. This study provided a reference for the development of DFT in the control of HAAs.

Non-chest pain symptoms and likelihood of coronary occlusion in emergency department patients with ST segment elevation undergoing emergent coronary angiography.

OBJECTIVES: Patients presenting with suspected ST segment elevation myocardial infarction frequently have symptoms in addition to chest pain, including dyspnea, nausea or vomiting, diaphoresis, and lightheadedness or syncope. These symptoms are often regarded as supporting the diagnosis of infarction. We sought to determine the prevalence of the non-chest pain symptoms among patients who were confirmed as having a critically diseased coronary vessel as opposed to those with no angiographic culprit lesion. METHODS: Data from 1393 consecutive patients with ST segment elevation who underwent emergent coronary angiography were analyzed. Records were reviewed in detail for symptoms, ECG findings, prior history, angiographic findings, and in-hospital outcomes. RESULTS: Dyspnea was present in 50.8% of patients, nausea or vomiting in 36.5%, diaphoresis in 51.2%, and lightheadedness/syncope in 16.8%. On angiography, 1239 (88.9%) patients had a culprit lesion and 154 (11.1%) were found not to have a culprit. Only diaphoresis had a higher prevalence among the patients with, as compared with those without a culprit, with an odds ratio of 2.64 (P < 0.001). The highest occurrence of diaphoresis was among patients with a totally occluded artery, with an intermediate frequency among patients with a subtotal stenosis, and the lowest prevalence among those with no culprit. These findings were consistent regardless of ECG infarct location, affected vessel, patient age, or sex. Among the subset of patients who presented without chest discomfort, none of the symptoms were associated with the presence of a culprit. CONCLUSION: The presence of diaphoresis, but not dyspnea, nausea, or lightheadedness is associated with an increased likelihood that patients presenting with ST elevation will prove to have a culprit lesion. In patients who present with ST elevation but without chest discomfort, these symptoms should not be regarded as 'chest pain equivalents'. Further objective data among patients with angiographic confirmation of culprit lesion status is warranted.

The enhanced affinity of moderately hydrolyzed whey protein to EGCG promotes the isoelectric separation and unlocks the protective effects on polyphenols.

The instability and discoloration of (-)-epigallocatechin-3-gallate (EGCG) constrain its application in functional dairy products. Concurrently, challenges persist in the separation and utilization of whey in the dairy industry. By harnessing the interactions between polyphenols and whey proteins or their hydrolysates, this study proposed a method that involved limited enzymatic hydrolysis followed by the addition of EGCG and pH adjustment around the isoelectric point to obtain whey protein hydrolysates (WPH)-EGCG. Over 92 % of protein-EGCG complexes recovered from whey while ensuring the preservation of α-lactalbumin. The combination between EGCG and WPH depended on hydrogen bonding and hydrophobic interactions, significantly enhanced the thermal stability and storage stability of EGCG. Besides, the intestinal phase retention rate of EGCG in WPH-EGCG complex was significantly increased by 23.67 % compared to free EGCG. This work represents an exploratory endeavor in the improvement of EGCG stability and expanding the utilization approaches of whey.

Warming Leads to Changes in Soil Organic Carbon Molecules Due to Decreased Mineral Protection.

Climate change affects the content and composition of soil organic carbon (SOC). However, warming-induced changes in the SOC compounds remain unknown. Using nuclear magnetic resonance spectroscopy, molecular mixing models, and Fourier transform ion cyclotron resonance mass spectrometry, we analyzed the variations and relationships in molecular compounds in Mollisol with 10-56 g C kg-1 soil-1 by translocating soils under six climate regimes. We found that increased temperature and precipitation were negatively correlated with carbohydrate versus lipid and lignin versus protein. The former was consistent across soils with varying SOC contents, but the latter decreased as the SOC content increased. The carbohydrate-lipid correlations were related to dithionite-citrate-extractable Fe, while the lignin-protein correlations were linked to changes in moisture and pyrophosphate-extractable Fe/Al. Our findings indicate that the reduction in the mineral protection of SOC is associated with molecular alterations in SOC under warming conditions.

Application of PLSR in correlating sensory and chemical properties of middle flue-cured tobacco leaves with honey-sweet and burnt flavour.

Among the eight types of aroma and flavour characteristics of Chinese flue-cured tobacco (FCT), tobacco grown in Shandong is classified as having a honey-sweet and burnt aroma. To elucidate the key chemical components that determine the characteristics of the honey-sweet and burnt aroma styles of Shandong FCT, we qualitatively and quantitatively evaluated the smoke flavour quality and five categories of flavour-related chemical components (routine components, water-soluble sugars, free amino acids, Amadori compounds and key aroma-active compounds) in Shandong middle FCT leaves using sensory analysis and modern instrumental analysis techniques. The association between the chemical components and sensory quality was analysed. Our results showed that the total sugars, reducing sugars (fructose, glucose, and psicose), total sugar-nicotine ratio, proline-total amino acid ratio, sulphur-containing amino acid-total amino acid ratio and fructosyl-proline (Fru-Pro) were high in premium FCT leaves. The aroma-active compounds associated with the honey-sweet burnt flavour style of the Shandong Middle FCT included sweet-scented 2,3-pentanedione, 2,3-butanedione, butyrolactone, 2-furanmethanol, roasted-like 2-pentylfura, and green-like 1-penten-3-one. Partial least squares regression (PLSR) analysis revealed that 29 aroma precursors were positively correlated with the sensory quality characteristics of Shandong FCT. The results of our study can provide guidance for the targeted improvement and precise regulation of the flavour-style characteristics of Shandong FCT.

Effects of dietary forage neutral detergent fiber and rumen degradable starch ratios on chewing activity, ruminal fermentation, ruminal microbes and nutrient digestibility of Hu sheep fed a pelleted total mixed ration.

Pelleted total mixed ration (P-TMR) feeding, which has become a common practice in providing nutrition for fattening sheep, requires careful consideration of the balance between forage neutral detergent fiber (FNDF) and rumen degradable starch (RDS) to maintain proper rumen functions. The present study aimed to investigate the effects of the dietary FNDF/RDS ratio (FRR) on chewing activity, ruminal fermentation, ruminal microbes, and nutrient digestibility in Hu sheep fed a P-TMR diet. This study utilized eight ruminally cannulated male Hu sheep, following a 4 × 4 Latin square design with 31 d each period. Diets consisted of four FRR levels: 1.0 (high FNDF/RDS ratio, HFRR), 0.8 (middle high FNDF/RDS ratio, MHFRR), 0.6 (middle low FNDF/RDS ratio, MLFRR), and 0.4 (low FNDF/RDS ratio, LFRR). Reducing the dietary FRR levels resulted in a linear decrease in ruminal minimum pH and mean pH, while linearly increasing the duration and area of pH below 5.8 and 5.6, as well as the acidosis index. Sheep in the HFRR and MHFRR groups did not experience subacute ruminal acidosis (SARA), whereas sheep in another two groups did. The concentration of total volatile fatty acid and the molar ratios of propionate and valerate, as well as the concentrate of lactate in the rumen linearly increased with reducing dietary FRR, while the molar ratio of acetate and acetate to propionate ratio linearly decreased. The degradability of NDF and ADF for alfalfa hay has a quadratic response with reducing the dietary FRR. The apparent digestibility of dry matter, organic matter, neutral detergent fiber, and acid detergent fiber linearly decreased when the dietary FRR was reduced. In addition, reducing the dietary FRR caused a linear decrease in OTUs, Chao1, and Ace index of ruminal microflora. Reducing FRR in the diet increased the percentage of reads assigned as Firmicutes, but it decreased the percentage of reads assigned as Bacteroidetes in the rumen. At genus level, the percentage of reads assigned as Prevotella, Ruminococcus, Succinivibrio, and Butyrivibrio linearly decreased when the dietary FRR was reduced. The results of this study demonstrate that the dietary FRR of 0.8 is crucial in preventing the onset of SARA and promotes an enhanced richness of ruminal microbes and also improves fiber digestibility, which is a recommended dietary FRR reference when formulating P-TMR diets for sheep.

Forage neutral detergent fiber (FNDF) and rumen degradable starch (RDS) are key components of carbohydrates in the diet for ruminants, which would reflect saliva secretion and the acid production potential of feed. However, appropriate FNDF to RDS ratios (FRR) applicable to ruminants under the condition of pelleted total mixed ration (P-TMR) feeding have not been reported. In this study, we investigated the effects of the dietary FRR on chewing activity, ruminal fermentation, ruminal microbial communities, and nutrient digestibility of Hu sheep under P-TMR feeding. The results indicate that reducing dietary FRR levels would induce acidosis in sheep, which negatively affected fiber utilization and ruminal bacterial communities. The FRR of 0.8 was a recommended dietary FRR when formulating a P-TMR diet for fattening sheep, as indicated by decreased ruminal acidosis risk and increased richness of ruminal microbes in the rumen as well as nutrient digestibility.

Ultrasensitive Electrochemical Immunosensor for Multiplex Sandwich Bioassaying Based on the Functional Antibodies.

In vitro diagnostics (IVDs) based on electrochemical immunosensors are crucial for disease screening, diagnosis, prognosis, and treatment monitoring. However, label-free electrochemical immunosensors commonly suffer from poor specificity, leading to false positives. To address this issue, we propose a highly sensitive and precise electrochemical immunosensor for protein marker detection. This approach involves directly labeling the detection antibodies (Ab2) with thionine (Thi). The Ab2 labeled by Thi exhibits a distinct redox peak upon targeted voltage stimulation, enabling accurate quantification of protein biomarkers. Thi-modified antibodies provide significant advantages over traditional antibody modification methods, such as enhanced detection sensitivity, improved accuracy, and specificity in protein marker identification. The method is straightforward and efficient, ensuring specific analyte detection while minimizing interference from other substances in the sample. Additionally, a multielectrode detection method was employed, achieving remarkably low limits of detection (LoDs) for tumor necrosis factor-alpha (TNF-alpha), cardiac troponin I (cTnI), and interleukin-6 (IL-6), with LoDs of 9.38 fg/mL, 1.70 fg/mL, and 8.14 fg/mL, respectively. The proposed electrochemical immunosensor also exhibited high selectivity and repeatability, with relative standard deviations (RSD) of 6.39% for TNF-alpha, 2.42% for cTnI, and 2.72% for IL-6 (n = 5). Moreover, it demonstrated high sensitivity and was evaluated for serum detection using the standard addition method. The results highlight the great potential of the proposed electrochemical immunosensor for clinical applications, offering a novel approach for future utilization in clinical settings.

Dynamical modulation of hypersynchronous seizure onset with transcranial magneto-acoustic stimulation in a hippocampal computational model.

Hypersynchronous (HYP) seizure onset is one of the frequently observed seizure-onset patterns in temporal lobe epileptic animals and patients, often accompanied by hippocampal sclerosis. However, the exact mechanisms and ion dynamics of the transition to HYP seizures remain unclear. Transcranial magneto-acoustic stimulation (TMAS) has recently been proposed as a novel non-invasive brain therapy method to modulate neurological disorders. Therefore, we propose a biophysical computational hippocampal network model to explore the evolution of HYP seizure caused by changes in crucial physiological parameters and design an effective TMAS strategy to modulate HYP seizure onset. We find that the cooperative effects of abnormal glial uptake strength of potassium and excessive bath potassium concentration could produce multiple discharge patterns and result in transitions from the normal state to the HYP seizure state and ultimately to the depolarization block state. Moreover, we find that the pyramidal neuron and the PV+ interneuron in HYP seizure-onset state exhibit saddle-node-on-invariant-circle/saddle homoclinic (SH) and saddle-node/SH at onset/offset bifurcation pairs, respectively. Furthermore, the response of neuronal activities to TMAS of different ultrasonic waveforms revealed that lower sine wave stimulation can increase the latency of HYP seizures and even completely suppress seizures. More importantly, we propose an ultrasonic parameter area that not only effectively regulates epileptic rhythms but also is within the safety limits of ultrasound neuromodulation therapy. Our results may offer a more comprehensive understanding of the mechanisms of HYP seizure and provide a theoretical basis for the application of TMAS in treating specific types of seizures.

Effect of partial substitution of complex phosphates with sodium bicarbonate on aggregation, conformation and gel properties of beef-pork-chicken complex myofibrillar proteins.

BACKGROUND: Complex phosphates (CP) can improve the physicochemical properties and gelation properties of myofibrillar fibrous protein (MP) in mixed meat products, but an excessive intake of phosphates over a long period of time is harmful to health. The present study investigated the effects of partial or complete substitution of CP with sodium bicarbonate (SB) on the physicochemical properties and gel properties of beef-pork-chicken mixed myofibrillar protein (BPC-MP), aiming to evaluate the feasibility of this method in reducing the amount of phosphate in mixed meat products. RESULTS: Under the optimal substitution conditions, the turbidity of BPC-MP was reduced by 37.8%, the net negative potential was increased by 28.9% and the modulus of elasticity (G') was increased. The tertiary structure indexes of protein (including fluorescence intensity, surface hydrophobicity and active thiol content) were significantly changed, whereas the α-helix and ß-turn angle contents in the secondary structure of protein were significantly increased. In addition, the water retention ability and strength of gel were also improved, which were increased by 20.7% and 42.6%, respectively. The results of scanning electron microscopy showed that the SB substitution group had a more compact and ordered microstructure. CONCLUSION: The results showed that partial substitution of CP with SB reduced the amount of phosphate added to BPC-MP and had a positive effect on the physicochemical and gel properties of BPC-MP. © 2024 Society of Chemical Industry.

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/ß-catenin signaling.

Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.

Improving feed intake and rumen fermentation in lambs using mixed-dimensional attapulgite clay to adsorb naturally occurring mycotoxins.

This experiment was conducted to evaluate the effects of including a mixed-dimensional attapulgite clay (MDA) into a naturally moldly diet for Hu lambs. Fifty male Hu lambs with similar initial body weight (28.24 ±â€…1.80 kg) were randomly allocated into five dietary treatments: a basal diet containing naturally occurring mycotoxins with 0, 0.5, 1.0, and 2.0 kg/t MDA, and basal diet with a commercial mycotoxin adsorbent Solis with montmorillonite as the major component at 1 kg/t. Both MDA and Solis increased average daily gain (ADG) and dry matter intake (DMI; P ≤ 0.004), and there was no difference in growth performance between MDA and Solis (P ≥ 0.26). The final body weight, DMI, and ADG were linearly increased with increasing MDA supplementation (P < 0.01). Lambs treated with both MDA and Solis demonstrated greater apparent digestibility of dry matter (DM), organic matter (OM), and energy compared with the control group (P ≤ 0.03), and there were no differences in nutrient digestibilities between MDA and Solis (P ≥ 0.38). Digestibility of CP was linearly increased with the increasing MDA supplementation (P = 0.01). Neither MDA nor Solis affected rumen total volatile fatty acid (TVFA) concentration (P ≥ 0.39), but decreased the acetate-to-propionate ratio and molar proportion of n-butyrate (P ≤ 0.01), and MDA also increased the concentration of ammonia (P = 0.003). Besides, increasing MDA supplementation linearly reduced the acetate-to-propionate ratio and molar proportion of n-butyrate (P = 0.01), but linearly and quadratically increased the concentration of ammonia (P ≥ 0.003). These results showed that the incorporation of MDA into a naturally moldy diet of Hu lambs yielded comparable results to the Solis product, with higher growth performance and nutrient digestibility but lower acetate-to-propionate ratio observed. In conclusion, including ≥ 1 kg/t of MDA in high mycotoxin risk diets for growing lambs improves feed intake and rumen fermentation.

The issue of mycotoxin-contaminated animal feed has consistently presented a significant challenge in relation to animal health and production. The mixed-dimensional attapulgite clay (MDA) has been proven effective in binding polar mycotoxins such as aflatoxin, while also effectively adsorbing hydrophobic or weakly polar mycotoxins such as zearalenone (ZEN) and ochratoxin. Therefore, this study was undertaken to assess the impact of MDA inclusion in mycotoxin-contaminated diets on performance and rumen fermentation variables in lambs. The results indicated that MDA not only significantly improved the growth performance and nutrient digestibility of Hu lambs but also enhanced the molar proportion of propionate and ammonia concentration, and reduced the acetate to propionate ratio and the molar proportion of n-butyrate.