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Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma‐bearing mice. It could reduce the number of myeloid‐derived suppressor cells (MDSC), as well as the expression of MDSC‐related molecule Arg‐1 and cytokines IL‐10 and TGF‐β, so that CD8+ T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL‐6 and IL‐1β were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor‐bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma‐bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth. Astragalus polysaccharides (APS) inhibit melanoma growth in mouse models. APS attenuate the immunosuppressive activity of MDSC in melanoma mice. Remodeling of the gut microbiota and fecal metabolites by APS induce anti–tumor immunity.

This review highlights the critical role of software sensors in advancing biosystem monitoring and control by addressing the unique challenges biological systems pose. Biosystems—from cellular interactions to ecological dynamics—are characterized by intrinsic nonlinearity, temporal variability, and uncertainty, posing significant challenges for traditional monitoring approaches. A critical challenge highlighted is that what is typically measurable may not align with what needs to be monitored. Software sensors offer a transformative approach by integrating hardware sensor data with advanced computational models, enabling the indirect estimation of hard-to-measure variables, such as stress indicators, health metrics in animals and humans, and key soil properties. This article outlines advancements in sensor technologies and their integration into model-based monitoring and control systems, leveraging the capabilities of Internet of Things (IoT) devices, wearables, remote sensing, and smart sensors. It provides an overview of common methodologies for designing software sensors, focusing on the modelling process. The discussion contrasts hypothetico-deductive (mechanistic) models with inductive (data-driven) models, illustrating the trade-offs between model accuracy and interpretability. Specific case studies are presented, showcasing software sensor applications such as the use of a Kalman filter in greenhouse control, the remote detection of soil organic matter, and sound recognition algorithms for the early detection of respiratory infections in animals. Key challenges in designing software sensors, including the complexity of biological systems, inherent temporal and individual variabilities, and the trade-offs between model simplicity and predictive performance, are also discussed. This review emphasizes the potential of software sensors to enhance decision-making and promote sustainability in agriculture, healthcare, and environmental monitoring.

Background Deep learning has presented considerable potential and is gaining more importance in computer assisted diagnosis. As the gold standard for pathologically diagnosing cervical intraepithelial lesions and invasive cervical cancer, colposcopy-guided biopsy faces challenges in improving accuracy and efficiency worldwide, especially in developing countries. To ease the heavy burden of cervical cancer screening, it is urgent to establish a scientific, accurate and efficient method for assisting diagnosis and biopsy. Methods The data were collected to establish three deep-learning-based models. For every case, one saline image, one acetic image, one iodine image and the corresponding clinical information, including age, the results of human papillomavirus testing and cytology, type of transformation zone, and pathologic diagnosis, were collected. The dataset was proportionally divided into three subsets including the training set, the test set and the validation set, at a ratio of 8:1:1. The validation set was used to evaluate model performance. After model establishment, an independent dataset of high-definition images was collected to further evaluate the model performance. In addition, the comparison of diagnostic accuracy between colposcopists and models weas performed. Results The sensitivity, specificity and accuracy of the classification model to differentiate negative cases from positive cases were 85.38%, 82.62% and 84.10% respectively, with an AUC of 0.93. The recall and DICE of the segmentation model to segment suspicious lesions in acetic images were 84.73% and 61.64%, with an average accuracy of 95.59%. Furthermore, 84.67% of high-grade lesions were detected by the acetic detection model. Compared to colposcopists, the diagnostic system performed better in ordinary colposcopy images but slightly unsatisfactory in high-definition images. Implications The deep learning-based diagnostic system could help assist colposcopy diagnosis and biopsy for HSILs.

Nutritional supplementation, particularly creatine monohydrate, enhances strength and power output during high-intensity exercise. The synergistic effects of co-ingesting creatine, carbohydrates, and protein on repeated anaerobic efforts require clarification. This study evaluated the effects of combined creatine, carbohydrates, and protein supplementation on performance during consecutive Wingate Anaerobic Tests (WAnT). Sixty male participants (age 21 ± 2.8 years) were randomized into four groups: creatine alone (CR), creatine with carbohydrates (CRCHO), creatine with carbohydrates and protein (CRCPS), or placebo (PLA). Participants completed three consecutive 30-s WAnTs separated by 6-min recovery intervals at baseline and two days following a four-day supplementation protocol. Measured variables included absolute and relative mean power (AMP, RMP), peak power (APP, RPP), and blood lactate. Post-supplementation body mass increased in CR, CRCHO, and CRCPS groups ( p  < 0.05). CRCHO and CRCPS groups demonstrated higher AMP and RMP (increase of 5–10%) compared to baseline ( p  < 0.01). CR exhibited increased AMP across all three trials. PLA showed performance decrements in AMP during the second and third trials ( p  < 0.01). All supplementation groups improved APP and RPP across trials ( p  < 0.01). PLA improved APP and RPP only during the third trial. CRCPS yielded the highest post-exercise blood lactate concentrations. Combined supplementation may mitigate fatigue and enhance mean power output more effectively than placebo. These findings guide athletes in optimizing acute loading strategies for repeated high-intensity efforts.

Pancreatic adenocarcinoma (PDA) is one of the most lethal human malignancies and unresponsive to current chemotherapies. Here we investigate the therapeutic potential of phycocyanin as an anti-PDA agent in vivo and in vitro . Phycocyanin, a natural product purified from Spirulina, effectively inhibits the pancreatic cancer cell proliferation in vitro and xenograft tumor growth in vivo . Phycocyanin induces G2/M cell cycle arrest, apoptotic and autophagic cell death in PANC-1 cells. Inhibition of autophagy by targeting Beclin 1 using siRNA significantly suppresses cell growth inhibition and death induced by phycocyanin, whereas inhibition of both autophagy and apoptosis rescues phycocyanin-mediated cell death. Mechanistically, cell death induced by phycocyanin is the result of cross-talk among the MAPK, Akt/mTOR/p70S6K and NF-κB pathways. Phycocyanin is able to induce apoptosis of PANC-1 cell by activating p38 and JNK signaling pathways while inhibiting Erk pathway. On the other hand, phycocyanin promotes autophagic cell death by inhibiting PI3/Akt/mTOR signaling pathways. Furthermore, phycocyanin promotes the activation and nuclear translocation of NF-κB, which plays an important role in balancing phycocyanin-mediated apoptosis and autosis. In conclusion, our studies demonstrate that phycocyanin exerts anti-pancreatic cancer activity by inducing apoptotic and autophagic cell death, thereby identifying phycocyanin as a promising anti-pancreatic cancer agent.

Background Emerging evidence has shown that circular RNAs (circRNAs) play essential roles in cancer biology and are potential biomarkers and targets for cancer therapy. However, the expression and function of circRNAs in ovarian carcinogenesis and its progression remain elusive. Methods RNA sequencing was performed to reveal circRNA expression profiles in ovarian cancerous and normal tissues. Single-molecule RNA in-situ hybridization was used to quantify circPLEKHM3 expression in tumor tissues. Cell-based in-vitro and in-vivo assays were subsequently conducted to support the clinical findings. Results CircPLEKHM3 was identified as one of the most significantly down-regulated circRNAs in ovarian cancer tissues compared with normal tissues. Its expression was further decreased in peritoneal metastatic ovarian carcinomas compared to primary ovarian carcinomas. Patients with lower circPLEKHM3 tend to have a worse prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial–mesenchymal transition, whereas its knockdown exerted an opposite role. Further analyses showed that circPLEKHM3 sponged miR-9 to regulate the endogenous expression of BRCA1, DNAJB6 and KLF4, and consequently inactivate AKT1 signaling. In addition, AKT inhibitor MK-2206 could block the tumor-promoting effect of circPLEKHM3 depletion, and potentiate Taxol-induced growth inhibition of ovarian cancer cells. Conclusions Our findings demonstrated that circPLEKHM3 functions as a tumor suppressor in ovarian cancer cells by targeting the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis and may be used as a prognostic indicator and therapeutic target in ovarian cancer patients. The new strategy for treating ovarian cancer by a combination therapy of Taxol with MK-2206 is worth further investigation, especially in ovarian cancer patients with loss of circPLEKHM3 expression.

A crystal structure of a complex between the DNA methyltransferase regulatory factor Dnmt3L and the catalytic domain of Dnmt3a leads to a model being proposed for the preferential methylation of DNA on maternally imprinted genes. Genetic imprinting, found in flowering plants and placental mammals, uses DNA methylation to yield gene expression that is dependent on the parent of origin 1 . DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA methylation of imprinted genes in mammalian germ cells. Dnmt3L interacts specifically with unmethylated lysine 4 of histone H3 through its amino-terminal PHD (plant homeodomain)-like domain 2 . Here we show, with the use of crystallography, that the carboxy-terminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and activating DNA methyltransferase. The complexed C-terminal domains of Dnmt3a and Dnmt3L showed further dimerization through Dnmt3a–Dnmt3a interaction, forming a tetrameric complex with two active sites. Substitution of key non-catalytic residues at the Dnmt3a–Dnmt3L interface or the Dnmt3a–Dnmt3a interface eliminated enzymatic activity. Molecular modelling of a DNA–Dnmt3a dimer indicated that the two active sites are separated by about one DNA helical turn. The C-terminal domain of Dnmt3a oligomerizes on DNA to form a nucleoprotein filament. A periodicity in the activity of Dnmt3a on long DNA revealed a correlation of methylated CpG sites at distances of eight to ten base pairs, indicating that oligomerization leads Dnmt3a to methylate DNA in a periodic pattern. A similar periodicity is observed for the frequency of CpG sites in the differentially methylated regions of 12 maternally imprinted mouse genes. These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing.

Acinetobacter baumannii resistance to carbapenem antibiotics is a serious clinical challenge. As a newly developed technology, silver nanoparticles (AgNPs) show some excellent characteristics compared to older treatments, and are a candidate for combating A. baumannii infection. However, its mechanism of action remains unclear. In this study, we combined AgNPs with antibiotics to treat carbapenem-resistant A. baumannii (aba1604). Our results showed that single AgNPs completely inhibited A. baumannii growth at 2.5 μg/mL. AgNP treatment also showed synergistic effects with the antibiotics polymixin B and rifampicin, and an additive effect with tigecyline. In vivo, we found that AgNPs-antibiotic combinations led to better survival ratios in A. baumannii-infected mouse peritonitis models than that by single drug treatment. Finally, we employed different antisense RNA-targeted Escherichia coli strains to elucidate the synergistic mechanism involved in bacterial responses to AgNPs and antibiotics.

This study aimed to investigate the effects of Tai Chi Softball (TCSB) training on the physical health of older men, with a focus on improvements in muscle strength, flexibility, balance, and blood lipid profiles. A 12-week randomized controlled trial was conducted, recruiting 140 men aged 55–65 years. Participants were randomly assigned to either a Tai Chi Softball group (TCSBG, N = 70) or a control group (CG, N = 70). The TCSBG engaged in TCSB training sessions 4 to 5 times per week, with each session lasting 70 to 90 min, while the CG maintained their usual daily routines without any additional interventions. Measurements were taken before and after the intervention and included waist-to-hip ratio (WHR), handgrip strength (HS), sit-and-reach (SAR), single-leg stance (SLS), vital capacity (VC), heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol. The results revealed that after 12 weeks of TCSB training, participants in the TCSBG showed significant improvements (p < .05) in HS, SAR, and SLS, indicating enhanced muscle strength, flexibility, and balance, respectively. The VC also increased significantly, while both SBP and DBP decreased notably (p < .05). Moreover, significant reductions were observed in TC, TG, and LDL-C levels p < .05). In conclusion, TCSB training demonstrated efficacy in improving muscle strength, flexibility, balance, cardiorespiratory fitness, and blood lipid profiles in older men. These findings suggest that TCSB training can mitigate age-related declines in physical function and reduce cardiovascular risk in older men.

The application of PARP inhibitors has revolutionized cancer treatment and has achieved significant advancements, particularly with regard to tumors with defects in genes involved in homologous recombination repair (HRR) processes, such as BRCA1 and BRCA2. Despite the promising outcomes of PARP inhibitors, certain limitations and challenges still exist, including acquired drug resistance, severe side effects, and limited therapeutic benefits for patients without homologous recombination deficiency (HRD). Various combinations involving PARP inhibitors have been developed to overcome these limitations. Among these, combinations with immune checkpoint inhibitors, antiangiogenic agents, and various small-molecule inhibitors are well-studied strategies that show great potential for optimizing the efficacy of PARP inhibitors, overcoming resistance mechanisms, and expanding target populations. However, the efficiency and overlapping toxicity of these combination strategies for cancers vary among studies, thereby limiting their use. In this review, we describe the mechanisms and limitations of PARP inhibitors to better understand the mechanisms of combination treatments. Furthermore, we have summarized recent studies on the combination of PARP inhibitors with a range of medications and discussed their clinical efficacy. The objective of this review is to enhance the comprehensiveness of information pertaining to this topic.