On-demand removable hydrogel film derived from gallic acid-phycocyanin and polyvinyl alcohol for fruit preservation.

Postharvest spoilage of fruits accounts for significant losses ranging between 20 %-30 %, leading to considerable resource wastage and economic downturns. The development of an effective fresh-keeping packaging material is of paramount importance. This study introduces an innovative on-demand removable active fruit fresh-keeping film (GPP), created by embedding a GP (gallic acid-phycocyanin) fiber mesh hydrogel with functional properties into a polyvinyl alcohol (PVA) matrix. The resultant GPP hydrogel-based film demonstrates outstanding UV and water vapor barrier capabilities, mechanical stability, resistance to external mechanical stress, universal surface adhesion, antibacterial efficacy, and on-demand removal attributes, while being devoid of potential toxicity hazards. Utilizing grapes and blueberries as representative fruits, it is shown that the GPP hydrogel film significantly preserves the fruits' hardness, pH, total soluble solids content (TSS), and minimizes the rate of weight loss, thereby prolonging the shelf life to 13 days for grapes and 20 days for blueberries at ambient temperature. These results underscore the potential of this hydrogel-based film as an invaluable material for fruit preservation within the food industry.

Analysis of electrode locations on limb condition effect for myoelectric pattern recognition.

BACKGROUND: Gesture recognition using surface electromyography (sEMG) has garnered significant attention due to its potential for intuitive and natural control in wearable human-machine interfaces. However, ensuring robustness remains essential and is currently the primary challenge for practical applications. METHODS: This study investigates the impact of limb conditions and analyzes the influence of electrode placement. Both static and dynamic limb conditions were examined using electrodes positioned on the wrist, elbow, and the midpoint between them. Initially, we compared classification performance across various training conditions at these three electrode locations. Subsequently, a feature space analysis was conducted to quantify the effects of limb conditions. Finally, strategies for group training and feature selection were explored to mitigate these effects. RESULTS: The results indicate that with the state-of-the-art method, classification performance at the wrist was comparable to that at the middle position, both of which outperformed the elbow, consistent with the findings from the feature space analysis. In inter-condition classification, training under dynamic limb conditions yielded better results than training under static conditions, especially at the positions covered by dynamic training. Additionally, fast and slow movement speeds produced similar performance outcomes. To mitigate the effects of limb conditions, adding more training conditions reduced classification errors; however, this reduction plateaued after four conditions, resulting in classification errors of 22.72%, 22.65%, and 26.58% for the wrist, middle, and elbow, respectively. Feature selection further improved classification performance, reducing errors to 19.98%, 19.75%, and 27.14% at the respective electrode locations, using three optimal features derived from single-condition training. CONCLUSIONS: The study demonstrated that the impact of limb conditions was mitigated when electrodes were placed near the wrist. Dynamic limb condition training, combined with feature optimization, proved to be an effective strategy for reducing this effect. This work contributes to enhancing the robustness of myoelectric-controlled interfaces, thereby advancing the development of wearable intelligent devices.

Higher risk of patients after stent(s) insertion with vessel bifurcation treated in the association between PM2.5 and cardiovascular hospital readmission.

Stent(s) insertion is a common form of surgery for patients with cardiovascular diseases, and is associated with a high rate of hospital readmission. This study aims to investigate the acute association between PM2.5 exposure and hospital readmission for patients with cardiovascular disease and a history of stent(s) insertion. The records of hospital admission were collected from the Beijing Municipal Commission of Health and Family Planning Information Center between 1st January 2013 and 31st December 2017. Subsequent hospital readmission records for patients with a history of stent(s) insertion or without any surgery were extracted. The conditional logistic regression model was applied to investigate the association between PM2.5 concentration and cardiovascular disease readmission in patients who had undergone stent(s) insertion or without any surgery. A total of 81,468 patients who had a history of stent(s) insertion were included in this study. Of these, 17,224 patients (21.1 % of the total number of patients) were readmitted 27,749 times due to cardiovascular disease. The median daily PM2.5 concentration was 62.8 µg/m3 with an interquartile range (IQR) of 71.5 µg/m3. The excess risk (ER) associated 10 µg/m3 increase in PM2.5 concentration for readmission due to cardiovascular disease was 0.48 % (95 % CI: 0.09 %, 0.87 %) in patients with a history of stent(s) insertion. Patients who had stent(s) insertion at the vessel bifurcation site showed the highest risk of readmission for cardiovascular disease when exposed to PM2.5; the ER was 4.12 % (95 % CI: 1.60 %, 6.70 %). PM2.5 was significantly associated with angina pectoris and readmission for chronic ischemic heart disease in patients with a history of stent(s) insertion. PM2.5 had a significant association with cardiovascular readmission among patients with a history of insertion of stent(s). Patients who had vessel bifurcation treated showed the highest risk of readmission.

Effects of 60Coγ-irradiation combined with sodium dehydrogenate on post-harvest preservation and physiological indices of Volvariella volvacea.

Volvariella volvacea is a mushroom known for its high palatability and nutritional value. However, it is susceptible to spoilage thus making it challenging to preserve and keep fresh after harvest, resulting in constraints in long-distance transportation and long-term storage. This study aimed to investigate the feasibility of using irradiation and sodium dehydrogenate (SD) as a preservative in the preservation process of V. volvacea. The effects of three treatments of 0.8 kGy 60Coγ irradiation (B), 0.04% SD (C), combined with 0.04% SD and 0.8 kGy 60Coγ irradiation (A) on the postharvest freshness of V. volvacea were investigated. The assessment indices for V. volvacea, including appearance, browning rate, weight loss, respiration rate, MDA content, antioxidant enzyme activities, vitamin C (Vc), and soluble protein content, were measured and compared. The three treatments were compared to determine the changes in storage time over 7 days post-harvest. The results demonstrated that the hardness of the fruiting body exhibited a significant increase of 81.19%, 97.96% and 168.81% in comparison to the control, B and C, respectively, following the application of the treatment A. Compared to the control group, the soluble protein content was significantly increased by 20.28%. Respiration intensity and browning rate were significantly lower in the control treatment, decreasing by 35.07% and 45.49% respectively. On the 6th day of storage, the activities of SOD and POD increased by 81.06% and 73.71%, respectively, compared to the control, which significantly delayed the senescence of the fruiting bodies. The Vc content was significantly increased by 50.27%, 133.90%, and 101.39% in treatment B, which received 0.8 kGy 60Coγ irradiation alone, compared to the control, treatment A, and treatment C, respectively. The treatment C alone significantly reduced respiratory intensity and MDA variables by 39.55% and 31.01%, respectively, compared to the control. The findings can provide theoretical references and technical support for extending the preservation period of V. volvacea after harvesting by using irradiation and sodium dehydrogenate as a preservative.

Effects of platelet-rich plasma injection on electrical activity and biomechanics of the erector spinae muscles in lumbar myofascial pain syndrome.

Low back pain (LBP) is a highly prevalent disease. Among the various causes of LBP, one of the most frequent is myofascial pain syndrome (MPS) which affects the spinal stabilizer muscles. The aims of this study were to compare the differences in muscular electrical activity and biomechanical properties between the painful and non-painful sides in patients with unilateral MPS and to verify the feasibility of surface electromyography (sEMG) and MyotonPRO for assisting in MPS assessment. Forty patients with unilateral lumbar MPS were recruited via the Department of Rehabilitation Medicine Center of West China Hospital Sichuan University from October 2022 to October 2023. The electrical properties of the bilateral erector spinae muscles were characterized by sEMG signals during a trunk extension task. The following four time-domain features of sEMG were extracted: root mean square (RMS), mean absolute value (MAV), integrated EMG (iEMG), and waveform length (WL). And two frequency domain features were extracted: the median frequency (MDF) and mean power frequency (MPF). The mechanical properties of the muscles were assessed by MyotonPRO at rest. The following biomechanical parameters were acquired: oscillation frequency [Hz], dynamic stiffness [N/m], logarithmic decrement, relaxation time [ms], and Creep. The visual analog scale (VAS) was used to evaluate the pain severity, and the Oswestry Disability Index (ODI) was used to evaluate the severity of disability and disruption to lifestyle activities caused by LBP pain. The outcome measures were obtained prior to the Platelet-rich plasma (PRP) treatment and repeated two weeks after treatment. (1) Prior to the PRP treatment, all sEMG time-domain features on the painful side were significantly higher than those on the non-painful side (RMS, p < 0.001; MAV, p < 0.001; iEMG, p < 0.001; WL, p = 0.001). However, there was no significant difference in the sEMG frequency-domain features (MPF, p = 0.478; MDF, p = 0.758). On the mechanical side, there were significant differences in oscillation frequency (p = 0.041) and logarithmic decrement (p = 0.022) between the painful side and non-painful side, but no significant differences in dynamic stiffness, relaxation time, and creep (both p > 0.05). (2) Two weeks after the PRP treatment, statistically significant decreases were observed in both post-treatment VAS (p < 0.001) and ODI scales (p < 0.001), indicating the PRP treatment clinically significantly reduced the level of. MPS. This change coincided with all sEMG time-domain features, in which the values at the painful side decreased significantly (RMS, p = 0.001; MAV, p = 0.001; iEMG, p = 0.001; WL, p = 0.001). However, no significant difference in the sEMG frequency-domain features (MPF, p = 0.620; MDF, p = 0.850) was found. On the mechanical side, only logarithmic decrement on the painful side increased significantly (p < 0.001). Our combined MyotonPRO and sEMG results indicated that MPS likely leads to increased muscle tone and decreased muscle elasticity, manifested by abnormal time-domain features of sEMG and biomechanical properties. The changes in these objective measurements were agreed with the changes in subjective outcome measures of pain and function currently assessed in the patients with MPS. A single PRP treatment may alleviate muscle dysfunction caused by MPS. These preliminary results demonstrated the potential feasibility of using sEMG and MyotonPRO as tools for assessing the neuromuscular function of MPS.

New species of Diaporthe (Diaporthaceae, Diaporthales) from Bauhiniavariegata in China.

Diaporthe species are known as endophytes, saprobes and pathogens infecting a wide range of plants and resulting in important crop diseases. In the present study, four strains of Diaporthe were obtained from diseased leaves of Bauhiniavariegata in Guangdong Province, China. Phylogenetic analyses were conducted to identify these strains using five gene regions: internal transcribed spacer (ITS), calmodulin (cal), histone H3 (his3), translation elongation factor 1-α (tef1) and ß-tubulin (tub2). The results combined with morphology revealed two new species of Diaporthe named D.bauhiniicola in D.arecae species complex and D.guangzhouensis in D.sojae species complex.

Two new species of Dendrostoma (Erythrogloeaceae, Diaporthales) associated with Castaneamollissima canker disease in China.

The genus Dendrostoma is known to inhabit tree barks associated with branch canker diseases in China and several countries of Europe. Previous studies indicated that species of Dendrostoma prefer inhabiting fagaceous hosts, especially species of Castanea. In the present study, we obtained four isolates from cankered branches of Chinese chestnut (C.mollissima) in Rizhao City, Shandong Province, China. Morphological comparisons and phylogenetical analyses of a combined ITS-tef1-rpb2 sequence matrix were conducted, which revealed two new species named Dendrostomarizhaoense sp. nov. and D.tianii sp. nov. The new taxa are compared with other Dendrostoma species and comprehensive descriptions and illustrations are provided herein.

Dual-layer probiotic encapsulation using metal phenolic network with gellan gum-tamarind gum coating for colitis treatment.

Probiotic oral therapy has been recognised as an effective treatment for inflammatory bowel disease (IBD). However, the efficacy of probiotics is often diminished due to their limited resistance to harsh gastrointestinal conditions. Therefore, the importance of designing innovative strategies for oral probiotic delivery for the effective treatment of IBD is increasingly recognised. In this study, we present a novel encapsulation strategy of Lactobacillus plantarum (L.P) using the dual-layer system consisting of a tannic acid­calcium network and polysaccharide coating (gellan gum-tamarind gum) named L.P-C/T-G/T. This double-layer encapsulation system not only does not affect the normal proliferation of probiotics and provide protection, but also endows probiotics with more functions. More specifically, the acid resistance ability of the encapsulated probiotics is increased by 10 times, the free radical scavenging rate is enhanced by 5 times, and the intestinal retention time can be prolonged by 6-12 h. In the DSS-induced murine colitis model, it significantly alleviated colon shortening, inhibited ROS overexpression, and promoted the repair and regeneration of the mucus layer. This dual-layer encapsulation approach for a single probiotic demonstrates a significant advancement in probiotic delivery technology, offering hope for a comprehensive approach to the treatment of colitis and potentially other gastrointestinal disorders.

Genetic microevolution of clinical Candida auris with reduced Amphotericin B sensitivity in China.

The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB1) or ≥ 2 µg/mL (AmB2). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB1 C. auris. Additionally, AmB2 C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB1 group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB2 group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the "super fungus", C. auris.

DeepPBI-KG: a deep learning method for the prediction of phage-bacteria interactions based on key genes.

Phages, the natural predators of bacteria, were discovered more than 100 years ago. However, increasing antimicrobial resistance rates have revitalized phage research. Methods that are more time-consuming and efficient than wet-laboratory experiments are needed to help screen phages quickly for therapeutic use. Traditional computational methods usually ignore the fact that phage-bacteria interactions are achieved by key genes and proteins. Methods for intraspecific prediction are rare since almost all existing methods consider only interactions at the species and genus levels. Moreover, most strains in existing databases contain only partial genome information because whole-genome information for species is difficult to obtain. Here, we propose a new approach for interaction prediction by constructing new features from key genes and proteins via the application of K-means sampling to select high-quality negative samples for prediction. Finally, we develop DeepPBI-KG, a corresponding prediction tool based on feature selection and a deep neural network. The results show that the average area under the curve for prediction reached 0.93 for each strain, and the overall AUC and area under the precision-recall curve reached 0.89 and 0.92, respectively, on the independent test set; these values are greater than those of other existing prediction tools. The forward and reverse validation results indicate that key genes and key proteins regulate and influence the interaction, which supports the reliability of the model. In addition, intraspecific prediction experiments based on Klebsiella pneumoniae data demonstrate the potential applicability of DeepPBI-KG for intraspecific prediction. In summary, the feature engineering and interaction prediction approaches proposed in this study can effectively improve the robustness and stability of interaction prediction, can achieve high generalizability, and may provide new directions and insights for rapid phage screening for therapy.

Orally Deliverable Microalgal-Based Carrier with Selenium Nanozymes for Alleviation of Inflammatory Bowel Disease.

Excessive reactive oxygen species (ROS) is a hallmark of both the onset and progression of inflammatory bowel disease (IBD), where a continuous cycle of ROS and inflammation drives the progression of diseases. The design of oral antioxidant nanoenzymes for scavenging ROS has emerged as a promising strategy to intervene in IBD. However, the practical application of these nanoenzymes is limited due to their single catalytical property and significantly impacted by substantial leakage in the upper gastrointestinal tract. This study introduces a novel oral delivery system, SP@CS-SeNPs, combining natural microalgae Spirulina platensis (SP), which possesses superoxide dismutase (SOD)-like activity, with chitosan-functionalized selenium nanoparticles (CS-SeNPs) that exhibit catalase-like activity. The SP@CS-SeNPs system leverages the dual catalytic capabilities of these components to initiate a cascade reaction that first converts superoxide anion radicals (O2•-) into hydrogen peroxide (H2O2), and then catalyzes the decomposition of H2O2 into water and oxygen. This system not only utilizes the resistance of the microalgae carrier to gastric acid and its efficient capture by intestinal villi, thereby enhancing intestinal distribution and retention but also demonstrates significant anti-inflammatory effects and effective repair of the damaged intestinal barrier in a colitis mice model. These results demonstrate that this oral delivery system successfully combines the features of microalgae and nanozymes, exhibits excellent biocompatibility, and offers a novel approach for antioxidant nanozyme intervention in IBD.

Novel Arf1 Inhibitors Drive Cancer Stem Cell Aging and Potentiate Anti-Tumor Immunity.

The small G protein Arf1 has been identified as playing a selective role in supporting cancer stem cells (CSCs), making it an attractive target for cancer therapy. However, the current Arf1 inhibitors have limited translational potential due to their high toxicity and low specificity. In this study, two new potent small-molecule inhibitors of Arf1, identified as DU101 and DU102, for cancer therapy are introduced. Preclinical tumor models demonstrate that these inhibitors triggered a cascade of aging in CSCs and enhance anti-tumor immunity in mouse cancer and PDX models. Through single-cell sequencing, the remodeling of the tumor immune microenvironment induced by these new Arf1 inhibitors is analyzed and an increase in tumor-associated CD8+ CD4+ double-positive T (DPT) cells is identified. These DPT cells exhibit superior features of active CD8 single-positive T cells and a higher percentage of TCF1+PD-1+, characteristic of stem-like T cells. The frequency of tumor-infiltrating stem-like DPT cells correlates with better disease-free survival (DFS) in cancer patients, indicating that these inhibitors may offer a novel cancer immunotherapy strategy by converting the cold tumor immune microenvironment into a hot one, thus expanding the potential for immunotherapy in cancer patients.

The Solid Volume Ratio is Better Than the Consolidation Tumor Ratio in Predicting the Malignant Pathological Features of cT1 Lung Adenocarcinoma.

BACKGROUND: More effective methods are urgently needed for predicting the pathological grade and lymph node metastasis of cT1-stage lung adenocarcinoma. METHODS: We analyzed the relationships between CT quantitative parameters (including three-dimensional parameters) and pathological grade and lymph node metastasis in cT1-stage lung adenocarcinoma patients of our center between January 2015 and December 2023. RESULTS: A total of 343 patients were included, of which there were 233 males and 110 females, aged 61.8 ± 9.4 (30-82) years. The area under the receiver operating characteristic (ROC) curve for predicting the pathological grade of lung adenocarcinoma using the consolidation-tumor ratio (CTR) and the solid volume ratio (SVR) were 0.761 and 0.777, respectively. The areas under the ROC curves (AUCs) for predicting lymph node metastasis were 0.804 and 0.873, respectively. Multivariate logistic regression analysis suggested that the SVR was an independent predictor of highly malignant lung adenocarcinoma pathology, while the SVR and pathological grade were independent predictors of lymph node metastasis. The sensitivity of predicting the pathological grading of lung adenocarcinoma based on SVR >5% was 97.2%, with a negative predictive value of 96%. The sensitivity of predicting lymph node metastasis based on SVR >47.1% was 97.3%, and the negative predictive value was 99.5%. CONCLUSION: The SVR has greater diagnostic value than the CTR in the preoperative prediction of pathologic grade and lymph node metastasis in stage cT1-stage lung adenocarcinoma patients, and the SVR may replace the diameter and CTR as better criteria for guiding surgical implementation.

Plasmodium berghei TatD-like DNase hijacks host innate immunity by inhibiting the TLR9-NF-κB pathway.

Neutrophils and macrophages confine pathogens by entrapping them in extracellular traps (ETs) through activating TLR9 function. However, plasmodial parasites secreted TatD-like DNases (TatD) to counteract ETs-mediated immune clearance. We found that TLR9 mutant mice increased susceptibility to rodent malaria, suggesting TLR9 is a key protein for host defense. We found that the proportion of neutrophils and macrophages in response to plasmodial parasite infection in the TLR9 mutant mice was significantly reduced compared to that of the WT mice. Importantly, PbTatD can directly bind to the surface TLR9 (sTLR9) on macrophages, which blocking the phosphorylation of mitogen-activated protein kinase and nuclear factor-κB, negatively regulated the signaling of ETs formation by both macrophages and neutrophils. Such, P. berghei TatD is a parasite virulence factor that can inhibit the proliferation of macrophages and neutrophils through directly binding to TLR9 receptors on the cell surface, thereby blocking the activation of the downstream MyD88-NF-kB pathways.

Calcium-binding protein TgpCaBP regulates calcium storage of the zoonotic parasite Toxoplasma gondii.

Toxoplasma gondii, the causative parasite of toxoplasmosis, is an apicomplexan parasite that infects warm-blooded mammals. The ability of the calcium-binding proteins (CBPs) to transport large amounts of Ca2+ appears to be critical for the biological activity of T. gondii. However, the functions of some members of the CBP family have not yet been deciphered. Here, we characterized a putative CBP of T. gondii, TgpCaBP (TGME49_229480), which is composed of four EF-hand motifs with Ca2+-binding capability. TgpCaBP was localized in the cytosol and ER of T. gondii, and parasites lacking the TgpCaBP gene exhibited diminished abilities in cell invasion, intracellular growth, egress, and motility. These phenomena were due to the abnormalities in intracellular Ca2+ efflux and ER Ca2+ storage, and the reduction in motility was associated with a decrease in the discharge of secretory proteins. Therefore, we propose that TgpCaBP is a Ca2+ transporter and signaling molecule involved in Ca2+ regulation and parasitization in the hosts.IMPORTANCECa2+ signaling is essential in the development of T. gondii. In this study, we identified a calcium-binding protein in T. gondii, named TgpCaBP, which actively regulates intracellular Ca2+ levels in the parasite. Deletion of the gene coding for TgpCaBP caused serious deficits in the parasite's ability to maintain a stable intracellular calcium environment, which also impaired the secretory protein discharged from the parasite, and its capacity of gliding motility, cell invasion, intracellular growth, and egress from host cells. In summary, we have identified a novel calcium-binding protein, TgpCaBP, in the zoonotic parasite T. gondii, which is a potential therapeutic target for toxoplasmosis.

TYROBP serve as potential immune-related signature genes in the acute phase of intracerebral hemorrhage.

The development of intracerebral hemorrhage (ICH) is a dynamic process and intervention during the acute phase of ICH is critical for subsequent recovery. Therefore, it is crucial to screen potential signature genes and therapeutic target genes in the acute phase of ICH. In this study, based on the results of mRNA sequencing in mouse ICH and mRNA sequencing of human ICH from online databases, top five potential signature genes after ICH, Tyrobp, Itgb2, Tlr2, Ptprc and Itgam, were screened. Quantitative PCR results showed higher mRNA expression of Tyrobp, Itgb2, Tlr2, Ptprc, and Itgam in the 1-, 3- and 5-day mouse ICH groups compared to the sham-operated group. Immune infiltration correlation analysis shows that the top-ranked signature gene, Tyrobp, is negatively correlated with M2 macrophages and plasma cells, and Western blot analysis shows higher expression of the Tyrobp protein in the 1-, 3-, and 5-day mouse ICH groups compared to the sham-operated group. Furthermore, immunohistochemistry revealed that TYROBP protein expression was significantly higher in human ICH tissues than in normal brain tissues. Our results suggest that Tyrobp is a signature gene in the acute phase of ICH and may be a potential target for the treatment of the acute phase of ICH.

Supplementation of coated sodium butyrate relieved weaning stress and reshaped microbial flora in weaned lambs.

Weaning is an important period in the growth and development of lambs. Thus, effectively reducing the occurrence of weaning stress is critical for maintaining lamb production. Coated sodium butyrate has been shown to reduce inflammation, promote intestinal health, and maintain homeostasis. However, the application and potential mechanism of coated sodium butyrate in alleviating weaning stress in lambs are still unclear. To evaluate the effects of coated sodium butyrate on the growth performance, antioxidant capacity, and gut microbiota of weaned lambs, 10 weaned lambs of 21-day-old were randomly divided into two groups: the CON group (basal diet) and the NaB group (basal diet +3 g/kg of coated sodium butyrate). The trial lasted 21 days. The experimental results showed that compared to the CON group, coated sodium butyrate supplementation in the diet significantly increased the average daily weight gain and daily feed intake of lambs (p < 0.05). In addition, compared to the CON group, the addition of coated sodium butyrate also significantly decreased the serum MDA level of lambs (p < 0.05). Notably, the addition of coated sodium butyrate did not have a significant effect on the cecal microbiota, while increasing the diversity of colonic microbiota and promoting the abundance of Lachnospiraceae, Verrucomicrobiota, Akkermansia, Roseburia, and Sinobacteraceae, which are associated with the nutrient absorption of lambs (p < 0.05). These results indicate that dietary supplementation with coated sodium butyrate could promote the growth and antioxidant capacity of weaned lambs and alleviate weaning stress.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Target deubiquitinase OTUB1 as a therapeatic strategy for BLCA via ß-catenin/necroptosis signal pathway.

Ubiquitination, a prevalent and highly dynamic reversible post-translational modification, is tightly regulated by the deubiquitinating enzymes (DUBs) superfamily. Among them, OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 1 (OTUB1) stands out as a critical member of the OTU deubiquitinating family, playing a pivotal role as a tumor regulator across various cancers. However, its specific involvement in BLCA (BLCA) and its clinical significance have remained ambiguous. This study aimed to elucidate the biofunctions of OTUB1 in BLCA and its implications for clinical prognosis. Our investigation revealed heightened OTUB1 expression in BLCA, correlating with unfavorable clinical outcomes. Through in vivo and in vitro experiments, we demonstrated that increased OTUB1 levels promote BLCA tumorigenesis and progression, along with conferring resistance to cisplatin treatment. Notably, we established a comprehensive network involving OTUB1, ß-catenin, necroptosis, and BLCA, delineating their regulatory interplay. Mechanistically, we uncovered that OTUB1 exerts its influence by deubiquitinating and stabilizing ß-catenin, leading to its nuclear translocation. Subsequently, nuclear ß-catenin enhances the transcriptional activity of c-myc and cyclin D1 while suppressing the expression of RIPK3 and MLKL, thereby fostering BLCA progression and cisplatin resistance. Importantly, our clinical data suggest that the OTUB1/ß-catenin/RIPK3/MLKL axis holds promise as a potential biomarker for BLCA.