Type IV pili are involved in phenotypes associated with Clostridioides difficile pathogenesis.

Clostridioides difficile is a Gram-positive, spore-forming, rod-shaped, obligate anaerobe that is the leading cause of antibiotic-associated diarrhea. Type IV pili (T4P) are elongated appendages on the surface of C. difficile that are polymerized from many pilin proteins. T4P play an important role in C. difficile adherence and particularly in its persistence in the host intestine. Recent studies have shown that T4P promote C. difficile aggregation, surface motility, and biofilm formation, which may enhance its pathogenicity. Additionally, the second messenger cyclic diguanylate increases pilA1 transcript abundance, indirectly promoting T4P-mediated aggregation, surface motility, and biofilm formation of C. difficile. This review summarizes recent advances in C. difficile T4P research and the physiological activities of T4P in the context of C. difficile pathogenesis.

Recycling Bonded Nd-Fe-B Magnet Wastes by Chemical Reaction and Its Mechanism.

The difficulty of short-process bonded Nd-Fe-B magnet waste recycling lies in the effective removal of the cured polymer matrix while protecting the magnetic powder. In this study, the polymer matrix in bonded Nd-Fe-B magnet waste was destroyed using sodium hydroxide ethanol solution, and the effect of the recycling process on the magnetic powders was studied. The nonmagnetic polymer matrix was removed, while the magnetic phase was not destroyed. The carbon and oxygen contents of the recycled magnetic powders decreased by 92.96 and 89.30%, respectively, while the MS (saturation magnetization), Mr (remanence), and Hcj (coercivity) values of the recycled magnetic powders were 99.8, 98.5, and 95.9% of the original magnetic powders, respectively. The curing and decomposition processes of the polymer matrix were also analyzed. During the curing process, dicyandiamide and bisphenol A epoxy resin acted as bridges and skeletons, respectively, finally forming a thermosetting three-dimensional network structure. In the alkaline alcohol solution, the bridges and skeletons were destroyed by the free hydroxyl groups and free hydrogen radicals in ethanol, and small molecular products were dissolved in the solution.

Combined effects of quercetin and sodium chloride concentrations on wheat gliadin structure and physicochemical properties.

BACKGROUND: Polyphenols may interact with protein via covalent bonds and non-covalent interactions, improving the structures and functional properties of the protein. The cross-linking between the polyphenol and protein is susceptible to salt (sodium chloride, NaCl) concentrations. Our study investigated the combined effects of quercetin (Q) and NaCl concentrations on wheat gliadin (G) structure and physicochemical properties. RESULTS: Q and NaCl addition resulted in a more compact protein microstructure. The improved foaming and emulsifying properties indicated that the modified G might be potent as a novel surface-active agent. Differential scanning calorimetry analysis indicated that Q protected the thermal stability from destruction at 50 and 200 mmol L-1 NaCl concentrations, with narrower protein denaturation peaks. Fourier transform infrared and the Raman spectral analyses showed the secondary structural and microenvironmental changes of G. NaCl addition imparted a rearrangement of hydrogen bonds in the polypeptide chain and the disorder of protein structure, whereas Q enhanced the transition from ß-sheets and random coils to α-helices and ß-turns, forming a more ordered structure. Moreover, the interaction between G and Q resulted in significant disulfide bridges conformational rearrangements in the protein. CONCLUSION: The results showed the benefits of natural food additives in food processing, which might have potential in improving the structure and physicochemical properties of protein-based foods. © 2020 Society of Chemical Industry.

Distinct DNA binding sites contribute to the TCF transcriptional switch in C. elegans and Drosophila.

Regulation of gene expression by signaling pathways often occurs through a transcriptional switch, where the transcription factor responsible for signal-dependent gene activation represses the same targets in the absence of signaling. T-cell factors (TCFs) are transcription factors in the Wnt/ß-catenin pathway, which control numerous cell fate specification events in metazoans. The TCF transcriptional switch is mediated by many co-regulators that contribute to repression or activation of Wnt target genes. It is typically assumed that DNA recognition by TCFs is important for target gene location, but plays no role in the actual switch. TCF/Pangolin (the fly TCF) and some vertebrate TCF isoforms bind DNA through two distinct domains, a High Mobility Group (HMG) domain and a C-clamp, which recognize DNA motifs known as HMG and Helper sites, respectively. Here, we demonstrate that POP-1 (the C. elegans TCF) also activates target genes through HMG and Helper site interactions. Helper sites enhanced the ability of a synthetic enhancer to detect Wnt/ß-catenin signaling in several tissues and revealed an unsuspected role for POP-1 in regulating the C. elegans defecation cycle. Searching for HMG-Helper site clusters allowed the identification of a new POP-1 target gene active in the head muscles and gut. While Helper sites and the C-clamp are essential for activation of worm and fly Wnt targets, they are dispensable for TCF-dependent repression of targets in the absence of Wnt signaling. These data suggest that a fundamental change in TCF-DNA binding contributes to the transcriptional switch that occurs upon Wnt stimulation.

Deep Learning for Nasopharyngeal Carcinoma Segmentation in Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis.

Nasopharyngeal carcinoma is a significant health challenge that is particularly prevalent in Southeast Asia and North Africa. MRI is the preferred diagnostic tool for NPC due to its superior soft tissue contrast. The accurate segmentation of NPC in MRI is crucial for effective treatment planning and prognosis. We conducted a search across PubMed, Embase, and Web of Science from inception up to 20 March 2024, adhering to the PRISMA 2020 guidelines. Eligibility criteria focused on studies utilizing DL for NPC segmentation in adults via MRI. Data extraction and meta-analysis were conducted to evaluate the performance of DL models, primarily measured by Dice scores. We assessed methodological quality using the CLAIM and QUADAS-2 tools, and statistical analysis was performed using random effects models. The analysis incorporated 17 studies, demonstrating a pooled Dice score of 78% for DL models (95% confidence interval: 74% to 83%), indicating a moderate to high segmentation accuracy by DL models. Significant heterogeneity and publication bias were observed among the included studies. Our findings reveal that DL models, particularly convolutional neural networks, offer moderately accurate NPC segmentation in MRI. This advancement holds the potential for enhancing NPC management, necessitating further research toward integration into clinical practice.

An "all-in-one" treatment and imaging nanoplatform for breast cancer with photothermal nanoparticles.

Drug delivery systems based on nanoparticles still face challenges of low efficacy and an inability to track treatment effects in tumor therapy due to biological barriers. This limitation hinders clinicians' ability to determine treatment effects and proper drug dosages, thus, ultimately impeding the further application and transformation of nanoplatforms. To address this challenge, an all-in-one nanoplatform for therapy and imaging is proposed. The nanoplatform is constructed by using nanoparticles through the co-encapsulation of the photothermal therapeutic agent IR780, the passively targeted drug OA@Fe3O4, and the chemotherapeutic drug paclitaxel. Under the guidance of magnetic navigation, the nanoparticles can enhance local enrichment of the drug, while the luminescence properties of IR780 enable drug tracking at the same time. Remarkably, the nanoparticles exhibit improved photothermal-chemotherapy synergy under magnetic targeting guidance, demonstrating antitumor effects in both in vitro and in vivo experiments. It is demonstrated that the use of these polymeric nanoparticles has significant potential for future biomedical applications and clinical decisions.

Precision targeting of CuET overload to disrupt mitochondrial unfolded protein response by integrated liposome.

Mitochondria in breast cancer play a critical role in survival and adaptation to dynamic environments. Thus, targeting mitochondria emerges as a promising therapeutic strategy for breast cancer. However, the adaptive unfolded protein response in mitochondria (UPRmt) due to mitochondrial unspecific distribution might contribute to diminished therapeutic outcomes. Herein, mitochondrial targeting liposome agents (CTPP-Lipid) are constructed and adopted for delivering the copper ion (CuET-DSF), which is especially sensitive for mitochondria-abundant breast tumors. In brief, the CTPP-Lipid@CuET achieves the goal of Cu2+ overloading by mitochondria targeting delivery. This rapidly increases ROS production, disrupts mitochondrial structure, and avoids the adaptive UPRmt formation, finally leading to apoptosis of breast cancer cells. In general, the Cu2+ overloading at mitochondria by CTPP-Lipid@CuET is a potential strategy for antitumor therapy, providing new insights into breast tumor therapy.

A gain-of-function mutation in the ROC1 gene alters plant architecture in Arabidopsis.

Plant architecture is an important agronomic trait and is useful for identification of plant species. The molecular basis of plant architecture, however, is largely unknown. Forward genetics was used to identify an Arabidopsis mutant with altered plant architecture. Using genetic and molecular approaches, we analyzed the roles of a mutated cyclophilin in the control of plant architecture. The Arabidopsis mutant roc1 has reduced stem elongation and increased shoot branching, and the mutant phenotypes are strongly affected by temperature and photoperiod. Map-based cloning and transgenic experiments demonstrated that the roc1 mutant phenotypes are caused by a gain-of-function mutation in a cyclophilin gene, ROC1. Besides, application of the plant hormone gibberellic acid (GA) further suppresses stem elongation in the mutant. GA treatment enhances the accumulation of mutated but not of wildtype (WT) ROC1 proteins. The roc1 mutation does not seem to interfere with GA biosynthesis or signaling. GA signaling, however, antagonizes the effect of the roc1 mutation on stem elongation. The altered plant architecture may result from the activation of an R gene by the roc1 protein. We also present a working model for the interaction between the roc1 mutation and GA signaling in regulating stem elongation.

Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner.

Metastasis leads to the vast majority of breast cancer mortality. Increasing evidence has shown that N6-methyladenosine (m6A) modification and its associated regulators play a pivotal role in breast cancer metastasis. Here, we showed that overexpression of the m6A reader IGF2BP1 was clinically correlated with metastasis in breast cancer patients. Moreover, IGF2BP1 promoted distant metastasis in vitro and in vivo. Mechanistically, we first identified USP10 as the IGF2BP1 deubiquitinase. USP10 can bind to, deubiquitinate, and stabilize IGF2BP1, resulting in its higher expression level in breast cancer. Furthermore, by MeRIP-seq and experimental verification, we found that IGF2BP1 directly recognized and bound to the m6A sites on CPT1A mRNA and enhanced its stability, which ultimately mediated IGF2BP1-induced breast cancer metastasis. In clinical samples, USP10 levels correlated with IGF2BP1 and CPT1A levels, and breast cancer patients with high levels of USP10, IGF2BP1, and CPT1A had the worst outcome. Therefore, these findings suggest that the USP10/IGF2BP1/CPT1A axis facilitates breast cancer metastasis, and this axis may be a promising prognostic biomarker and therapeutic target for breast cancer.

Epithelial-to-mesenchymal transition proceeds through directional destabilization of multidimensional attractor.

How a cell changes from one stable phenotype to another one is a fundamental problem in developmental and cell biology. Mathematically, a stable phenotype corresponds to a stable attractor in a generally multi-dimensional state space, which needs to be destabilized so the cell relaxes to a new attractor. Two basic mechanisms for destabilizing a stable fixed point, pitchfork and saddle-node bifurcations, have been extensively studied theoretically; however, direct experimental investigation at the single-cell level remains scarce. Here, we performed live cell imaging studies and analyses in the framework of dynamical systems theories on epithelial-to-mesenchymal transition (EMT). While some mechanistic details remain controversial, EMT is a cell phenotypic transition (CPT) process central to development and pathology. Through time-lapse imaging we recorded single cell trajectories of human A549/Vim-RFP cells undergoing EMT induced by different concentrations of exogenous TGF-ß in a multi-dimensional cell feature space. The trajectories clustered into two distinct groups, indicating that the transition dynamics proceeds through parallel paths. We then reconstructed the reaction coordinates and the corresponding quasi-potentials from the trajectories. The potentials revealed a plausible mechanism for the emergence of the two paths where the original stable epithelial attractor collides with two saddle points sequentially with increased TGF-ß concentration, and relaxes to a new one. Functionally, the directional saddle-node bifurcation ensures a CPT proceeds towards a specific cell type, as a mechanistic realization of the canalization idea proposed by Waddington.

Cells with the same genetic code can take on many different formss, or phenotypes, which have distinct roles and appearances. Sometimes cells switch from one phenotype to another as part of healthy growth or during disease. One such change is the epithelial-to-mesenchymal transition (EMT), which is involved in fetal development, wound healing and the spread of cancer cells. During EMT, closely connected epithelial cells detach from one another and change into mesenchymal cells that are able to migrate. Cells undergo a number of changes during this transition; however, the path they take to reach their new form is not entirely clear. For instance, do all cells follow the same route, or are there multiple ways that cells can shift from one state to the next? To address this question, Wang et al. studied individual lung cancer cells that had been treated with a protein that drives EMT. The cells were then imaged at regular intervals over the course of two to three days to see how they changed in response to different concentrations of protein. Using a mathematical analysis designed to study chemical reactions, Wang et al. showed that the cells transform into the mesenchymal phenotype through two main routes. This result suggests that attempts to prevent EMT, in cancer treatment for instance, would require blocking both paths taken by the cells. This information could be useful for biomedical researchers trying to regulate the EMT process. The quantitative approach of this study could also help physicists and mathematicians study other types of transition that occur in biology.

Interactions and structural properties of zein/ferulic acid: The effect of calcium chloride.

Zein is potential in encapsulating and delivering polyphenols in food industry. Our study investigated the interaction mechanisms and structural changes of the interaction between ferulic acid (FA) and zein under different CaCl2 concentrations. Addition of CaCl2 resulted in amino acids micro-environment and structural changes of zein and zein/FA complex, which was dependent on different CaCl2 concentrations. At 0.5 mol/L CaCl2 concentration, zein/FA exhibited spherical particles with rough surfaces. Fourier transform infrared analysis showed the decrease of α-helix and ß-sheets contents accompanied by the increase of ß-turns and unordered coil contents. Molecular dynamics simulation demonstrated FA interacted with zein mainly through hydrogen bonds and hydrophobic force. These observations might contribute to the decreased surface hydrophobicity and digestibility of zein. Results provided a better understanding of the interaction between zein and other molecules, which might be helpful for the development of zein particles as functional materials to encapsulate and deliver bioactive compounds.

Artificial Intelligence for Early Detection of Chest Nodules in X-ray Images.

Early detection increases overall survival among patients with lung cancer. This study formulated a machine learning method that processes chest X-rays (CXRs) to detect lung cancer early. After we preprocessed our dataset using monochrome and brightness correction, we used different kinds of preprocessing methods to enhance image contrast and then used U-net to perform lung segmentation. We used 559 CXRs with a single lung nodule labeled by experts to train a You Only Look Once version 4 (YOLOv4) deep-learning architecture to detect lung nodules. In a testing dataset of 100 CXRs from patients at Taipei Veterans General Hospital and 154 CXRs from the Japanese Society of Radiological Technology dataset, the sensitivity of the AI model using a combination of different preprocessing methods performed the best at 79%, with 3.04 false positives per image. We then tested the AI by using 383 sets of CXRs obtained in the past 5 years prior to lung cancer diagnoses. The median time from detection to diagnosis for radiologists assisted with AI was 46 (3-523) days, longer than that for radiologists (8 (0-263) days). The AI model can assist radiologists in the early detection of lung nodules.

Interaction between wheat gliadin and quercetin under different pH conditions analyzed by multi-spectroscopy methods.

Polyphenols have been known to have significant binding affinity for proteins, and the specific condition (such as pH) could affect the degree of binding, the formation of covalent bond, and non-covalent interaction. In this study, characteristics of binding quercetin (Q) to wheat gliadin (G) which is a strong food allergen, were studied from pH 2.0 to pH 9.0. The results showed that Q quenched the fluorescence intensity of G by dynamic and static quenching modes and the stoichiometry of binding was close to 1. Intermolecular binding distances were smaller than 8 nm. Thermodynamic parameters suggested that hydrophobic force took charge of the formation of complexes at pH 2.0-4.0, whereas hydrogen bonds and van der Waals forces at pH 5.0-9.0. Analyses of the Fourier transform infrared and the Raman spectra along with synchronous fluorescence spectra revealed secondary and tertiary structural alterations and microenvironmental changed around protein fluorophores upon complexation with Q. The gauche-gauche-trans conformation increased at the expenses of the gauche-gauche-gauche conformation and the transition from ß-turn and random coil to α-helix and ß-sheet at pH 5.0 might decrease the allergenicity of G. These results provided new insights into G/Q interactions at different pH values, which may have potentials in decreasing allergen immunoreactivity.

Antioxidant and Antiproliferative Activities of Modified Polysaccharides Originally Isolated from Morchella Angusticepes Peck.

Polysaccharides extracted from Morchella angusticepes Peck (PMEP) were chemically modified to obtain sulfated, carboxymethylated, and acetyled derivatives. Results showed that the acetyled derivatives with the degree of substitution (0.40 ± 0.07) exerted higher antioxidant ability than native polysaccharides, demonstrating inhibitory effects on growth of human hepatoma cells (EC50  = 0.710 ± 0.002 mg/mL) and human colon cancer cells (EC50  =  1.229 ± 0.008 mg/mL). It indicated that the acetylation was a favorable way to enhance the bioactivities of PMEP. PRACTICAL APPLICATION: Polysaccharides extracted from Morchella angusticepes Peck (PMEP) have many health-promoting properties. Chemical modifications could improve the bioactivities of polysaccharides. We demonstrated that acetylation enhanced the cellular antioxidant and antiproliferative activities of PMEP. The results support further research that explores clinical utility, and may justify ex vivo and in vivo designs toward that end.

Acetylation of polysaccharide from Morchella angusticeps peck enhances its immune activation and anti-inflammatory activities in macrophage RAW264.7 cells.

Morchella angusticeps Peck has been recognized as a resource of nutraceuticals and drug discovery. Three acetylated polysaccharides (Ac-PMEP1-3) with appropriate degree of substitution were obtained from Morchella angusticeps Peck, chemically characterized, and cultured with macrophage RAW264.7 cells to evaluate their immune activation and anti-inflammatory activities. Results of ultraviolet-visible spectroscopy and fourier-transform infrared showed these modifications were successful. Compared with the control group, PMEP and Ac-PMEP1-3 enhanced cell proliferation and the production of nitric oxide and tumor necrosis factor-α of RAW264.7 macrophages (cultured without lipopolysaccharide). Compared with PMEP, Ac-PMEP3 enhanced cell viability and NO production by inducing the degradation of cytoplasmic IκBα and nuclear translocation of NF-κB subunit p65 as well as the expression of iNOS and phosphorylated-p38. Moreover, in lipopolysaccharide-stimulated RAW264.7 macrophages, Ac-PMEP3 showed a stronger ability to suppress the overproduction of nitric oxide and tumor necrosis factor-α by down-regulating the level of nuclear NF-κB p65, iNOS, and phosphorylated-p38 and inhibiting the degradation of cytoplasmic IκBα. Therefore, Ac-PMEP enhanced immune activation and anti-inflammatory activities via nuclear factor κB and p38/mitogen-activated protein kinase signaling pathways.

Protective effects of Coreopsis tinctoria flowers phenolic extract against D-galactosamine/lipopolysaccharide -induced acute liver injury by up-regulation of Nrf2, PPARα, and PPARγ.

Coreopsis tinctoria flowers, a well-known medicinal and edible plant, have been reported to possess antioxidant and anti-inflammatory activities. However, its protective effects and underlying mechanisms on liver injury remain unclear. The aim of this study was to investigate the underlying mechanisms by which Coreopsis tinctoria flowers phenolic extract (CTP) alleviated D-galactosamine and lipopolysaccharide (D-GalN/LPS) induced acute liver injury in mice. Our results showed that pretreatment with CTP improved liver histology while decreased levels of serum aminotransferase and malondialdehyde. CTP also increased levels of glutathione in D-GalN/LPS -induced acute liver injury mice by up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor alpha (PPARα), and peroxisome proliferator-activated receptor gamma (PPARγ). In conclusion, results suggested that CTP protected against D-GalN/LPS -induced acute liver injury by up-regulation of Nrf2, PPARα, and PPARγ.