Metabolomic analysis of hydroxycinnamic acid inhibition on Saccharomyces cerevisiae.

Ferulic acid (FA) and p-coumaric acid (p-CA) are hydroxycinnamic acid inhibitors that are mainly produced during the pretreatment of lignocellulose. To date, the inhibitory mechanism of hydroxycinnamic acid compounds on Saccharomyces cerevisiae has not been fully elucidated. In this study, liquid chromatography-mass spectrometry (LC-MS) and scanning electron microscopy (SEM) were used to investigate the changes in S. cerevisiae cells treated with FA and p-CA. In this experiment, the control group was denoted as group CK, the FA-treated group was denoted as group F, and the p-CA-treated group was denoted as group P. One hundred different metabolites in group F and group CK and 92 different metabolites in group P and group CK were selected and introduced to metaboanalyst, respectively. A total of 38 metabolic pathways were enriched in S. cerevisiae under FA stress, and 27 metabolic pathways were enriched in S. cerevisiae under p-CA stress as identified through Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis. The differential metabolites involved included S-adenosine methionine, L-arginine, and cysteine, which were significantly downregulated, and acetyl-CoA, L-glutamic acid, and L-threonine, which were significantly upregulated. Analysis of differential metabolic pathways showed that the differentially expressed metabolites were mainly related to amino acid metabolism, nucleotide metabolism, fatty acid degradation, and the tricarboxylic acid cycle (TCA). Under the stress of FA and p-CA, the metabolism of some amino acids was blocked, which disturbed the redox balance in the cells and destroyed the synthesis of most proteins, which was the main reason for the inhibition of yeast cell growth. This study provided a strong scientific reference to improve the durability of S. cerevisiae against hydroxycinnamic acid inhibitors. KEY POINTS: • Morphological changes of S. cerevisiae cells under inhibitors stress were observed. • Changes of the metabolites in S. cerevisiae cells were explored by metabolomics. • One of the inhibitory effects on yeast is due to changes in the metabolic network.

Transcriptionally activates CCL28 expression to inhibit M2 polarization of macrophages and prevent immune escape in colorectal cancer cells.

OBJECTIVE: This study aimed to investigate the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and examine its impact on macrophage M2 polarization using the TCGA and GEO databases. METHODS: By combining TCGA and GEO databases, differential gene expression between CRC samples and standard tissue samples was analyzed to screen for immune-related genes (IRGs) associated with the prognosis of CRC patients. A predictive risk model was constructed based on 18 key IRGs, which were then validated using the GEO dataset. The relationship between transcription factors and IRGs was further explored to investigate their regulatory network in CRC. In vivo and in vitro experiments were carried out to validate these regulatory relationships and explore the function of SPDEF and CCL28 in CRC. RESULTS: Twelve key IRGs associated with clinical and pathological characteristics of CRC patients were identified. Among them, CCL28 significantly impacted macrophage infiltration in CRC cells and may be a critical factor in immune evasion. In both in vitro and in vivo experiments, overexpression of SPDEF upregulated CCL28 expression, thereby suppressing M2 polarization of macrophages and inhibiting CRC cell proliferation and tumor growth. Notably, interference with CCL28 could reverse the effect of SPDEF overexpression. CONCLUSION: SPDEF can suppress immune evasion of CRC cells by activating CCL28, which is achieved through the modulation of M2 polarization of macrophages. This provides a new research direction and potential therapeutic target for immunotherapy in CRC.

Analysis of Inhibitory Behaviour of Ferulic Acid and p-Coumaric Acid on Saccharomyces Cerevisiae Cells.

Metabolomics has been widely used to identify changes in relevant differential metabolites. The metabolites of Saccharomyces cerevisiae cells supplemented with ferulic acid and p-coumaric acid were prepared and extracted. Untargeted metabolomics analysis of saccharomyces cerevisiae metabolites was performed. In addition, GNPS, Respect and MassBank databases were used to search and compare the information in the whole database. It was found that 100 and 92 different metabolites were significantly changed (P value < 0.05,VIP value > 1,) in Saccharomyces cerevisiae cells treated with ferulic acid and p-coumaric acid respectively. Including isothiocyanate, L-threonine, adenosine, glycerin phospholipid choline, niacinamide and palmitic acid. These metabolites with significant differences were enriched by KEGG pathway using MetPA database.

Study on the Mechanism of MC5R Participating in Energy Metabolism of Goose Liver.

Nutrition and energy levels have an important impact on animal growth, production performance, disease occurrence and health recovery. Previous studies indicate that melanocortin 5 receptor (MC5R) is mainly involved in the regulations of exocrine gland function, lipid metabolism and immune response in animals. However, it is not clear how MC5R participates in the nutrition and energy metabolism of animals. To address this, the widely used animal models, including the overfeeding model and the fasting/refeeding model, could provide an effective tool. In this study, the expression of MC5R in goose liver was first determined in these models. Goose primary hepatocytes were then treated with nutrition/energy metabolism-related factors (glucose, oleic acid and thyroxine), which is followed by determination of MC5R gene expression. Moreover, MC5R was overexpressed in goose primary hepatocytes, followed by identification of differentially expressed genes (DEGs) and pathways subjected to MC5R regulation by transcriptome analysis. At last, some of the genes potentially regulated by MC5R were also identified in the in vivo and in vitro models, and were used to predict possible regulatory networks with PPI (protein-protein interaction networks) program. The data showed that both overfeeding and refeeding inhibited the expression of MC5R in goose liver, while fasting induced the expression of MC5R. Glucose and oleic acid could induce the expression of MC5R in goose primary hepatocytes, whereas thyroxine could inhibit it. The overexpression of MC5R significantly affected the expression of 1381 genes, and the pathways enriched with the DEGs mainly include oxidative phosphorylation, focal adhesion, ECM-receptor interaction, glutathione metabolism and MAPK signaling pathway. Interestingly, some pathways are related to glycolipid metabolism, including oxidative phosphorylation, pyruvate metabolism, citrate cycle, etc. Using the in vivo and in vitro models, it was demonstrated that the expression of some DEGs, including ACSL1, PSPH, HMGCS1, CPT1A, PACSIN2, IGFBP3, NMRK1, GYS2, ECI2, NDRG1, CDK9, FBXO25, SLC25A25, USP25 and AHCY, was associated with the expression of MC5R, suggesting these genes may mediate the biological role of MC5R in these models. In addition, PPI analysis suggests that the selected downstream genes, including GYS2, ECI2, PSPH, CPT1A, ACSL1, HMGCS1, USP25 and NDRG1, participate in the protein-protein interaction network regulated by MC5R. In conclusion, MC5R may mediate the biological effects caused by changes in nutrition and energy levels in goose hepatocytes through multiple pathways, including glycolipid-metabolism-related pathways.

Picophotonic localization metrology beyond thermal fluctuations.

Despite recent tremendous progress in optical imaging and metrology1-6, there remains a substantial resolution gap between atomic-scale transmission electron microscopy and optical techniques. Is optical imaging and metrology of nanostructures exhibiting Brownian motion possible with such resolution, beyond thermal fluctuations? Here we report on an experiment in which the average position of a nanowire with a thermal oscillation amplitude of ∼150 pm is resolved in single-shot measurements with subatomic precision of 92 pm, using light at a wavelength of λ = 488 nm, providing an example of such sub-Brownian metrology with ∼λ/5,300 precision. To localize the nanowire, we employ a deep-learning analysis of the scattering of topologically structured light, which is highly sensitive to the nanowire's position. This non-invasive metrology with absolute errors down to a fraction of the typical size of an atom, opens a range of opportunities to study picometre-scale phenomena with light.

Extracellular Vesicles Derived from Adipose-Derived Stem Cells Facilitate Frostbite Wound Healing By Regulating SOCS3 Expression.

BACKGROUND: Though adipose-derived stem cells (ADSCs) have potential applications for the repair and regeneration of damaged tissues, limited studies have defined the function of ADSCs on dermal fibroblasts. Our RNA-seq sequencing identified differentially expressed SOCS3 in frostbite injury. OBJECTIVE: In the current study, we aim to examine the hypothesis that extracellular vesicles derived from adipose-derived mesenchymal stem cells (ADSCs-EVs) may modulate SOCS3/TGF-ß1 signaling in wound healing of frostbite injury. METHODS: sh-SOCS3 and sh-TGF-ß1 were introduced to explore the biological role of SOCS3 in frostbite injury by detecting the proliferation and migration of human skin fibroblast (HSF) cells and the wound healing in mice. Furthermore, the extracted ADSCs-EVs were interfered with HSF cells in vitro or injected into the frostbitten mouse model in vivo. RESULTS: Upregulation of SOCS3 occurred in the skin tissues of frostbitten mice. Compared to sh-NC, the wound healing rate of sh-SOCS3 presented higher on day 7(31.34±4.35 vs 41.83±3.74, p < 0.05) and day 14 (63.42±6.01 vs 88.99±5.12, p < 0.05) after injury. Silencing SOCS3 can promote frostbite wound healing. Moreover, SOCS3 downregulated TGF-ß1 to suppress the proliferation and migration of HSF cells, thus impeding the skin wound healing. Additionally, ADSCs-EVs could enhance the proliferation and migration of HSF cells according to the results of CCK-8 assay (p < 0.05), scratch test (17.82±4.25 vs 49.78±2.54, p < 0.05) and Transwell assay (42.33±6.81 vs 91.33±7.02, p < 0.05), and regulate the expression of SOCS3/TGF-ß1. The role of ADSCs-EVs in frostbite wound healing was also confirmed in vivo. ADSCs-EVs could promote frostbite wound healing by downregulating the expression of SOCS3 and upregulating the expression of TGF-ß1 and collagen I. CONCLUSION: Collectively, ADSCs-EVs inhibit SOCS3 and facilitate the expression of TGF-ß1, which promotes the proliferation and migration of HSF cells and subsequently enhances wound healing of frostbite injury.

A prognostic signature based on cuprotosis-related long non-coding RNAs predicts the prognosis and sensitivity to chemotherapy in patients with colorectal cancer.

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.

Witnessing multi-observer steering on both sides simultaneously via weak measurements.

The quantum steering as an intermediate form of quantum correlations, has various peculiarities differing from the Bell nonlocality and the quantum entanglement. In a specific scenario, each side of the observer shares one of the two entangled qubits, steering can be witnessed simultaneously between any two observers from different sides by performing weak or projective measurements successively, with independently chosen and unbiased inputs. Here, we demonstrate this steering scenario experimentally to simultaneously witness quartic Einstein-Podolsky-Rosen steerings of two successive observers between each side with the entangled pair with a state fidelity of 97.6% compared with a maximally-entangled one.

Porous fibrous bacterial cellulose/La(OH)3 membrane for superior phosphate removal from water.

Lanthanum (La)-based nanoparticles (NPs) are promising candidates for phosphate removal owing to their inherently high affinity towards phosphate. However, significant challenges remain to be addressed before their practical deployment, especially the problems associated with their aggregation. Herein, we fabricated a high-efficient sorbent for phosphate removal through in-situ synthesizing La(OH)3 NPs on a natural support, bacterial cellulose (BC), which is pre-modified with polyethyleneimine. The resultant La(OH)3 NPs-immobilized BC with different La contents (BPLa-X) exhibited a highly fibrous porous structure, in which BPLa-3 was selected for further phosphate adsorption studies. BPLa-3 demonstrated a high adsorption capacity of 125.5 mg P g-1, and high adsorption selectivity due to the large surface area and abundant exposed active adsorption sites for phosphate. Additionally, BPLa-3 also displayed high reusability and still possessed high adsorption capacity after four consecutive cycles of adsorption-desorption. Therefore, the present adsorbent is believed to be a promising candidate for practical phosphate removal.

Targeting cancer stem cells with polymer nanoparticles for gastrointestinal cancer treatment.

Nanomaterials are developing rapidly in the medical field, bringing new hope for treating various refractory diseases. Among them, polymer nanomaterials, with their excellent properties, have been used to treat various diseases, such as malignant tumors, diabetes, and nervous system diseases. Gastrointestinal cancer is among the cancers with the highest morbidity and mortality worldwide. Cancer stem cells are believed to play an important role in the occurrence and development of tumors. This article summarizes the characteristics of gastrointestinal cancer stem cells and reviews the latest research progress in treating gastrointestinal malignant tumors using polymer nanoparticles to target cancer stem cells. In addition, the review article highlights the potential of polymer nanoparticles in targeting gastrointestinal cancer stem cells.

Co-delivery of sorafenib and metformin from amphiphilic polypeptide-based micelles for colon cancer treatment.

Colorectal cancer (CRC) is a common clinical disease with a poor prognosis and a high recurrence rate. Chemotherapy is important to inhibit the post-surgical recurrence of CRC patients. But many limitations restrict the further application of chemotherapy. In this study, sorafenib (Sor) and metformin (Met) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) [mPEG-b-P(Glu-co-Phe)] micelles were developed. The characterizations, drug release, in vivo biodistribution, and pharmacokinetics of the micelles were analyzed. The treatment efficacy of the dual-drug loaded micelles was evaluated in a subcutaneous colon cancer mice model. Sor is a common molecular target agent that can inhibit the mitogen-activated protein kinase (MAPK) pathway to treat solid tumors. Met can also regulate the MAPK pathway and inhibit the expression of the phosphorylated extracellular signal-regulated kinase (p-ERK). Moreover, both Sor and Met play important roles in cell cycle arrest. The integration of these two drugs aims to achieve synergistic effects against colon cancer. The micelles can be targeted to cancer cells and possess longer blood circulation time. The two agents can be released rapidly in the tumor sites. The in vivo study showed that the micelles can prevent tumor progression by inhibiting the expressions of p-ERK and cyclin D1. This study indicated that the Sor/Met-loaded micelles are suitable for CRC treatment.

Protective effects of silibinin on LPS-induced inflammation in human periodontal ligament cells.

Clinically, periodontitis is a chronic nonspecific inflammation that leads to damaged teeth and their supporting gum tissues. Although many studies on periodontitis have been conducted, therapy with natural products is still rare. Silibinin has been proven to have anti-inflammatory and antioxidant activities. However, the effects of silibinin on lipopolyssacharide (LPS)-induced inflammation in periodontal ligaments (PDLs) have not yet been investigated. In this study, the PDLs were treated with silibinin (10, 20, and 40 µM) in the presence of LPS. The results showed that silibinin treatment reduced the levels of NO, PGE2, IL-6, TNF-α, MMP-1, and MMP-3 and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH). Moreover, silibinin treatment downregulated RANKL levels and upregulated OPG and ALP levels. In summary, silibinin protected PDLs against LPS-induced inflammation, oxidative stress, and osteogenic differentiation.

Bioinformatics-Based Analysis: Noncoding RNA-Mediated COL10A1 Is Associated with Poor Prognosis and Immune Cell Infiltration in Pancreatic Cancer.

Background: Collagen type X alpha 1 (COL10A1) is a structural component of the extracellular matrix that is aberrantly expressed in a variety of cancer tissues. However, its role in pancreatic cancer progression is not well understood. Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Gene Expression Profiling Interaction Analysis (GEPIA) data were employed to explore the expression of COL10A1 in normal and tumor tissues and its prognostic value in pancreatic adenocarcinoma. The clinical data of pancreatic cancer in TCGA were used to explore the relationship between COL10A1 and clinical features. Genes coexpressed with COL10A1 were explored using multiple databases and analyzed for functional enrichment. In addition, the lncRNA/miRNA/COL10A1 axis that may be involved in COL10A1 regulation in pancreatic cancer was explored by constructing a competitive endogenous RNA (ceRNA) regulatory axis. Finally, COL10A1 was analyzed for correlation with immune cell infiltration and various immune checkpoint molecules in pancreatic cancer. Results: It was found that the expression of COL10A1 was significantly increased in pancreatic cancer tissues. High expression of COL10A1 was related to the clinicopathological characteristics and the worse prognosis of pancreatic cancer patients. The TUG1/miR-144-3p/COL10A1 axis was identified as the most likely upstream noncoding RNA pathway for COL10A1 in pancreatic cancer. Besides, in pancreatic adenocarcinoma, the expression level of COL10A1 showed a significant positive correlation with tumor immune cell infiltration, biomarkers of immune cells, and expression of immune checkpoint molecules. Conclusion: COL10A1 is an early diagnostic marker, and its high expression correlates with immune infiltration in pancreatic cancer. The TUG1/miR-144-3p/COL10A1 axis was identified as the most likely upstream noncoding RNA pathway for COL10A1 in pancreatic cancer.

Perineural invasion-associated biomarkers for tumor development.

Perineural invasion (PNI) is the process of neoplastic invasion of peripheral nerves and is considered to be the fifth mode of cancer metastasis. PNI has been detected in head and neck tumors and pancreatic, prostate, bile duct, gastric, and colorectal cancers. It leads to poor prognostic outcomes and high local recurrence rates. Despite the increasing number of studies on PNI, targeted therapeutic modalities have not been proposed. The identification of PNI-related biomarkers would facilitate the non-invasive and early diagnosis of cancers, the establishment of prognostic panels, and the development of targeted therapeutic approaches. In this review, we compile information on the molecular mediators involved in PNI-associated cancers. The expression and prognostic significance of molecular mediators and their receptors in PNI-associated cancers are analyzed, and the possible mechanisms of action of these mediators in PNI are explored, as well as the association of cells in the microenvironment where PNI occurs.

Two giant connected retroperitoneal schwannomas: a rare case report.

Schwannoma is a type of tumor originating from Schwann cells of peripheral nerves. In this study, we report a rare case of two giant connected retroperitoneal schwannomas. The patient presented to our department with a 1-day history of abdominal pain and without other symptoms. There were no abnormalities in the patient's tumor markers. Abdominal plain computed tomography (CT) revealed two (combined) retroperitoneal masses appearing as soft tissue-density shadows with uneven internal density, cystic low-density shadows, and patchy calcification shadows. The larger mass measured approximately 12.0 cm × 12.3 cm in size. The tumors were completely excised by a reasonable surgical approach while the surrounding organs closely related to the tumor were preserved. Postoperative pathology confirmed that the tumors were benign schwannomas. In the 18-month follow-up, the patient had no recurrences and was asymptomatic. We summarize the diagnosis and treatment of two rare combined giant retroperitoneal schwannomas in a single patient. Laparotomy for the management of retroperitoneal giant schwannomas may be safe and effective.

Ballistic dynamics of flexural thermal movements in a nanomembrane revealed with subatomic resolution.

Flexural oscillations of freestanding films, nanomembranes, and nanowires are attracting growing attention for their importance to the fundamental physical and optical properties and device applications of two-dimensional and nanostructured (meta)materials. Here, we report on the observation of short-time scale ballistic motion in the flexural mode of a nanomembrane cantilever, driven by thermal fluctuation of flexural phonons, including measurements of ballistic velocities and displacements performed with subatomic resolution, using a free electron edge-scattering technique. Within intervals <10 µs, the membrane moves ballistically at a constant velocity, typically ~300 µm/s, while Brownian-like dynamics emerge for longer observation periods. Access to the ballistic regime provides verification of the equipartition theorem and Maxwell-Boltzmann statistics for flexural modes and can be used in fast thermometry and mass sensing during atomic absorption/desorption processes on the membrane.

Carbon dots with intrinsic theranostic properties for photodynamic therapy of oral squamous cell carcinoma.

Carbon dots (CDs) are one of the carbon-based materials with remarkable optical properties, good water dispersibility and high biocompatibility. However, few studies have emphasized the intrinsic photodynamic and anticancer properties of CDs. Herein, we used CDs as photosensitizers to explore their photodynamic therapy (PDT) effect on oral squamous cell carcinoma (OSCC) cells. The obtained CDs had an effective cellular internalization capacity and possessed good biocompatibility in both CAL-27 and UM1 cells. After irradiation, the CDs showed obvious photodynamic effects on the test cells, which were confirmed by apoptosis analysis. In addition, the CDs exhibited excellent intracellular ROS generation under irradiation, and the subsequent induced cell death may be related to a lysosome-associated pathway.

Dedifferentiated liposarcoma (DDLPS) in the rectum: A case report.

Dedifferentiated liposarcoma (DDLPS) is a rare subtype of liposarcoma with a poor prognosis. This current case report describes a rectal DDLPS in a 68-year-old Chinese male that presented with lower abdominal pain and weight loss. Computed tomography and magnetic resonance imaging were undertaken to evaluate the tumour. The patient underwent radical resection of the rectal tumour, sigmoid colostomy and partial ureterectomy. The tumour was positive for mouse double minute 2 by immunohistochemistry. The patient healed well but refused chemotherapy postoperatively for economic reasons. The tumour recurred and metastasized 4 weeks after the operation. After relevant treatment, the patient's condition deteriorated and he died of shock, metabolic acidosis, hyperlactataemia and acute renal failure. The case report also reviews the literature in terms of the clinical diagnosis, treatment and pathological characteristics of rectal DDLPS with the aim of improving the level of diagnosis and treatment.

Development of artificial intelligence technology in diagnosis, treatment, and prognosis of colorectal cancer.

Artificial intelligence (AI) technology has made leaps and bounds since its invention. AI technology can be subdivided into many technologies such as machine learning and deep learning. The application scope and prospect of different technologies are also totally different. Currently, AI technologies play a pivotal role in the highly complex and wide-ranging medical field, such as medical image recognition, biotechnology, auxiliary diagnosis, drug research and development, and nutrition. Colorectal cancer (CRC) is a common gastrointestinal cancer that has a high mortality, posing a serious threat to human health. Many CRCs are caused by the malignant transformation of colorectal polyps. Therefore, early diagnosis and treatment are crucial to CRC prognosis. The methods of diagnosing CRC are divided into imaging diagnosis, endoscopy, and pathology diagnosis. Treatment methods are divided into endoscopic treatment, surgical treatment, and drug treatment. AI technology is in the weak era and does not have communication capabilities. Therefore, the current AI technology is mainly used for image recognition and auxiliary analysis without in-depth communication with patients. This article reviews the application of AI in the diagnosis, treatment, and prognosis of CRC and provides the prospects for the broader application of AI in CRC.

Polymer nanotherapeutics to correct autoimmunity.

The immune system maintains homeostasis and protects the body from pathogens, mutated cells, and other harmful substances. When immune homeostasis is disrupted, excessive autoimmunity will lead to diseases. To inhibit the unexpected immune responses and reduce the impact of treatment on immunoprotective functions, polymer nanotherapeutics, such as nanomedicines, nanovaccines, and nanodecoys, were developed as part of an advanced strategy for precise immunomodulation. Nanomedicines transport cytotoxic drugs to target sites to reduce the occurrence of side effects and increase the stability and bioactivity of various immunomodulating agents, especially nucleic acids and cytokines. In addition, polymer nanomaterials carrying autoantigens used as nanovaccines can induce antigen-specific immune tolerance without interfering with protective immune responses. The precise immunomodulatory function of nanovaccines has broad prospects for the treatment of immune related-diseases. Besides, nanodecoys, which are designed to protect the body from various pathogenic substances by intravenous administration, are simple and relatively noninvasive treatments. Herein, we have discussed and predicted the application of polymer nanotherapeutics in the correction of autoimmunity, including treating autoimmune diseases, controlling hypersensitivity, and avoiding transplant rejection.