Gut microbiota-derived short-chain fatty acids regulate group 3 innate lymphoid cells in HCC.

BACKGROUND AND AIMS: Type 3 innate lymphoid cells (ILC3s) are essential for host defense against infection and tissue homeostasis. However, their role in the development of HCC has not been adequately confirmed. In this study, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) derived from intestinal microbiota in ILC3 regulation. APPROACH AND RESULTS: We report that Lactobacillus reuteri was markedly reduced in the gut microbiota of mice with HCC, accompanied by decreased SCFA levels, especially acetate. Additionally, transplantation of fecal bacteria from wild-type mice or L. reuteri could promote an anticancer effect, elevate acetate levels, and reduce IL-17A secretion in mice with HCC. Mechanistically, acetate reduced the production of IL-17A in hepatic ILC3s by inhibiting histone deacetylase activity, increasing the acetylation of SRY (sex-determining region Y)-box transcription factor 13 (Sox13) at site K30, and decreasing expression of Sox13. Moreover, the combination of acetate with programmed death 1/programmed death ligand 1 blockade significantly enhanced antitumor immunity. Consistently, tumor-infiltrating ILC3s correlated with negative prognosis in patients with HCC, which could be functionally mediated by acetate. CONCLUSIONS: These findings suggested that modifying bacteria, changing SCFAs, reducing IL-17A-producing ILC3 infiltration, and combining with immune checkpoint inhibitors will contribute to the clinical treatment of HCC.

Reduced Proliferative Capacity and Defense against Staphylococcus aureus in Human Nasal Mucosal Epithelium Lacking ZNF365.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nose characterized by barrier disruption and environmental susceptibility, and the deletion of ZNF365 may be a factor inducing these manifestations. However, there is no study on the mechanism of action between CRSwNP and ZNF365. Therefore, this study focuses on the effect of the zinc finger protein ZNF365 on the proliferation of nasal mucosal epithelial cells and their defense against Staphylococcus aureus (S. aureus). METHODS: Immunohistochemistry and Western blot were applied to verify the changes of ZNF365 expression in nasal polyp tissues and control tissues, as well as in primary epithelial cells. ZNF365 was knocked down in human nasal mucosa epithelial cell line (HNEpc), and the proliferation, migration, and transdifferentiation of epithelium were observed by immunofluorescence, QPCR, CCK8, and cell scratch assay. The changes of mesenchymal markers and TLR4-MAPK-NF-κB pathway were also observed after the addition of S. aureus. RESULTS: ZNF365 expression was reduced in NP tissues and primary nasal mucosal epithelial cells compared to controls. Knockdown of ZNF365 in HNEpc resulted in decreased proliferation and migration ability of epithelial cells and abnormal epithelial differentiation (decreased expression of tight junction proteins). S. aureus stimulation further inhibited epithelial cell proliferation and migration, while elevated markers of epithelial-mesenchymal transition and inflammatory responses occurred. CONCLUSION: ZNF365 is instrumental in maintaining the proliferative capacity of nasal mucosal epithelial cells and defending against the invasion of S. aureus. The findings suggest that ZNF365 may participate in the development of CRSwNP.

Highly Processable Covalent Organic Framework Gel Electrolyte Enabled by Side-Chain Engineering for Lithium-Ion Batteries.

Although covalent organic frameworks (COFs) with a graphene-like structure present unique chemical and physical properties, they are essentially insoluble and infusible crystalline powders with poor processability, hindering their further practical applications. How to improve the processability of COF materials is a major challenge in this field. In this contribution, we proposed a general side-chain engineering strategy to construct a gel-state COF with high processability. This method takes advantages of large and soft branched alkyl side chains as internal plasticizers to achieve the gelation of the COF. We systematically studied the influence of the length of the side chain on the COF gel formation. Benefitting from their machinability and flexibility, this novel COF gel can be easily processed into gel-type electrolytes with specific shape and thickness, which were further applied to assemble lithium-ion batteries that exhibited high cycling stability.

Perfluoroalkyl-Functionalized Covalent Organic Frameworks with Superhydrophobicity for Anhydrous Proton Conduction.

The development of anhydrous proton-conducting materials is critical for the fabrication of high-temperature (>100 °C) polymer electrolyte membrane fuel cells (HT-PEMFCs) and remains a significant challenge. Covalent organic frameworks (COFs) are an emerging class of porous crystalline materials with tailor-made nanochannels and hold great potential for ion and molecule transport, but their poor chemical stability poses great challenges in this respect. In this contribution, we present a bottom-up self-assembly strategy to construct perfluoroalkyl-functionalized hydrazone-linked 2D COFs and systematically investigate the effect of different lengths of fluorine chains on their acid stability and proton conductivity. Compared with their nonfluorous parent COFs, fluorinated COFs possess structural ultrastability toward strong acids as a result of enhanced hydrophobicity (water contact angle of 144°). Furthermore, the superhydrophobic 1D nanochannels can serve as robust hosts to accommodate large amounts of phosphonic acid for fast and long-term proton conduction under anhydrous conditions and a wide temperature range. The anhydrous proton conductivity of fluorinated COFs is 4.2 × 10-2 S cm-1 at 140 °C after H3PO4 doping, which is 4 orders of magnitude higher than their nonfluorous counterparts and among the highest values of doped porous organic frameworks so far. Solid-state NMR studies revealed that H3PO4 forms hydrogen-boding networks with the frameworks and perfluoroalkyl chains of COFs, and most of the H3PO4 molecules are highly dynamic and mobile while the frameworks are rigid, which affords rapid proton transport. This work paves the way for the realization of the target properties of COFs through predesign and functionalization of the pore surface and highlights the great potential of COF nanochannels as a rigid platform for fast ion transportation.

Dynamic Transformation between Covalent Organic Frameworks and Discrete Organic Cages.

We propose a dynamic covalent chemistry (DCC)-induced linker exchange strategy for the structural transformation between covalent organic frameworks (COFs) and cages for the first time. Studies have shown that the COF-to-cage and cage-to-COF transformations were realized by using borate bonds and imine bonds, respectively, as linkages. Self-sorting experiments suggested that borate cages and imine COFs are thermodynamic minimum compounds. This research builds a bridge between discrete and polymeric organic scaffolds and broadens the knowledge of chemistry and materials for porous materials science.

Composition Modulation and Structure Design of Inorganic-in-Polymer Composite Solid Electrolytes for Advanced Lithium Batteries.

Owing to their safety, high energy density, and long cycling life, all-solid-state lithium batteries (ASSLBs) have been identified as promising systems to power portable electronic devices and electric vehicles. Developing high-performance solid-state electrolytes is vital for the successful commercialization of ASSLBs. In particular, polymer-based composite solid electrolytes (PCSEs), derived from the incorporation of inorganic fillers into polymer solid electrolytes, have emerged as one of the most promising electrolyte candidates for ASSLBs because they can synergistically integrate many merits from their components. The development of PCSEs is summarized. Their major components, including typical polymer matrices and diverse inorganic fillers, are reviewed in detail. The effects of fillers on their ionic conductivity, mechanical strength, thermal/interfacial stability and possible Li+ -conductive mechanisms are discussed. Recent progress in a number of rationally constructed PCSEs by compositional and structural modulation based on different design concepts is introduced. Successful applications of PCSEs in various lithium-battery systems including lithium-sulfur and lithium-gas batteries are evaluated. Finally, the challenges and future perspectives for developing high-performance PCSEs are proposed.

ABCA1-Derived Nascent High-Density Lipoprotein-Apolipoprotein AI and Lipids Metabolically Segregate.

OBJECTIVE: Reverse cholesterol transport comprises cholesterol efflux from ABCA1-expressing macrophages to apolipoprotein (apo) AI, giving nascent high-density lipoprotein (nHDL), esterification of nHDL-free cholesterol (FC), selective hepatic extraction of HDL lipids, and hepatic conversion of HDL cholesterol to bile salts, which are excreted. We tested this model by identifying the fates of nHDL-[3H]FC, [14C] phospholipid (PL), and [125I]apo AI in serum in vitro and in vivo. APPROACH AND RESULTS: During in vitro incubation of human serum, nHDL-[3H]FC and [14C]PL rapidly transfer to HDL and low-density lipoproteins (t1/2=2-7 minutes), whereas nHDL-[125I]apo AI transfers solely to HDL (t1/2<10 minutes) and to the lipid-free form (t1/2>480 minutes). After injection into mice, nHDL-[3H]FC and [14C]PL rapidly transfer to liver (t1/2=≈2-3 minutes), whereas apo AI clears with t1/2=≈460 minutes. The plasma nHDL-[3H]FC esterification rate is slow (0.46%/h) compared with hepatic uptake. PL transfer protein enhances nHDL-[14C]PL but not nHDL-[3H]FC transfer to cultured Huh7 hepatocytes. CONCLUSIONS: nHDL-FC, PL, and apo AI enter different pathways in vivo. Most nHDL-[3H]FC and [14C]PL are rapidly extracted by the liver via SR-B1 (scavenger receptor class B member 1) and spontaneous transfer; hepatic PL uptake is promoted by PL transfer protein. nHDL-[125I]apo AI transfers to HDL and to the lipid-free form that can be recycled to nHDL formation. Cholesterol esterification by lecithin:cholesterol acyltransferase is a minor process in nHDL metabolism. These findings could guide the design of therapies that better mobilize peripheral tissue-FC to hepatic disposal.

Synergistic Coupling between Li6.75La3Zr1.75Ta0.25O12 and Poly(vinylidene fluoride) Induces High Ionic Conductivity, Mechanical Strength, and Thermal Stability of Solid Composite Electrolytes.

Easy processing and flexibility of polymer electrolytes make them very promising in developing all-solid-state lithium batteries. However, their low room-temperature conductivity and poor mechanical and thermal properties still hinder their applications. Here, we use Li6.75La3Zr1.75Ta0.25O12 (LLZTO) ceramics to trigger structural modification of poly(vinylidene fluoride) (PVDF) polymer electrolyte. By combining experiments and first-principle calculations, we find that La atom of LLZTO could complex with the N atom and C═O group of solvent molecules such as N,N-dimethylformamide along with electrons enriching at the N atom, which behaves like a Lewis base and induces the chemical dehydrofluorination of the PVDF skeleton. Partially modified PVDF chains activate the interactions between the PVDF matrix, lithium salt, and LLZTO fillers, hence leading to significantly improved performance of the flexible electrolyte membrane (e.g., a high ionic conductivity of about 5 × 10-4 S cm-1 at 25 °C, high mechanical strength, and good thermal stability). For further illustration, a solid-state lithium battery of LiCoO2|PVDF-based membrane|Li is fabricated and delivers satisfactory rate capability and cycling stability at room temperature. Our study indicates that the LLZTO modifying PVDF membrane is a promising electrolyte used for all-solid-state lithium batteries.

Mechanism of TiO2 nanoparticle-induced neurotoxicity in zebrafish (Danio rerio).

Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of environmental and aqueous toxicants, and there is an emerging literature reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos. Few researches, however, are focused on the neurotoxicity on adult zebrafish after subchronic exposure to TiO2 NPs. This study was designed to evaluate the morphological changes, alterations of neurochemical contents, and expressions of memory behavior-related genes in zebrafish brains caused by exposures to 5, 10, 20, and 40 µg/L TiO2 NPs for 45 consecutive days. Our data indicated that spatial recognition memory and levels of norepinephrine, dopamine, and 5-hydroxytryptamine were significantly decreased and NO levels were markedly elevated, and over proliferation of glial cells, neuron apoptosis, and TiO2 NP aggregation were observed after low dose exposures of TiO2 NPs. Furthermore, the low dose exposures of TiO2 NPs significantly activated expressions of C-fos, C-jun, and BDNF genes, and suppressed expressions of p38, NGF, CREB, NR1, NR2ab, and GluR2 genes. These findings imply that low dose exposures of TiO2 NPs may result in the brain damages in zebrafish, provide a developmental basis for evaluating the neurotoxicity of subchronic exposure, and raise the caution of aquatic application of TiO2 NPs.

TiO2 nanoparticle-induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice.

Titanium dioxide nanoparticles (TiO2 NPs) have been used in environmental management, food, medicine, and industry. But TiO2 NPs have been demonstrated to cross the blood-brain barrier and store up in the brain organization, leading to glutamate-mediated neurotoxicity. However, the neurotoxicity in the brain is not well understood. In this study, mice were exposed to 1.25, 2.5, or 5 mg/kg body weight TiO2 NPs for 9 months, and the glutamate-glutamine cyclic pathway and expressions of glutamate receptors associated with the hippocampal neurotoxicity were investigated. Our findings showed elevations of glutamate release and phosphate-activated glutaminase activity, and reductions in glutamine and glutamine synthetase in the hippocampus following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly inhibited the expression of N-methyl-d-aspartate receptor subunits (including NR1, NR2A, and NR2B) and metabotropic glutamate receptor 2 in mouse hippocampus. These findings suggest that the imbalance of glutamate metabolism triggered inhibitions of glutamate receptor expression in the TiO2 NP-exposed hippocampus. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 655-662, 2016.

One-Pot Synthesis of Pyrrolo[3,2,1-kl]phenothiazines through Copper-Catalyzed Tandem Coupling/Double Cyclization Reaction.

A novel and efficient synthesis of pyrrolo[3,2,1-kl]phenothiazines has been developed through a Cu(I)-catalyzed tandem C-S coupling/double cyclization process. Using 2-alkynyl-6-iodoanilines and o-bromobenzenethiols as the starting materials, a wide range of pyrrolo[3,2,1-kl]phenothiazine derivatives were facilely and efficiently generated in one pot under Cu(I) catalysis.

Nanoparticulate TiO2 protection of midgut damage in the silkworm (Bombyx mori) following phoxim exposure.

Bombyx mori (B. mori) is often subjected to phoxim poisoning in China due to phoxim exposure, which leads to a decrease in silk production. Nanoparticulate (NP) titanium dioxide (nano-TiO2) has been shown to attenuate damages in B. mori caused by phoxim exposure. However, little is known about the molecular mechanisms of midgut injury due to organophosphorus insecticide exposure and its repair by nano-TiO2 pretreatment. In this study, phoxim exposure for 36 h led to significant decreases in body weight and survival and increased oxidative stress and midgut injury. Pretreatment with nano-TiO2 attenuated the phoxim-induced midgut injury, increased body weight and survival, and decreased oxidative stress in the midgut of B. mori. Digital gene-expression data showed that exposure to phoxim results in significant changes in the expression of 254 genes in the phoxim-exposed midgut and 303 genes in phoxim + nano-TiO2-exposed midgut. Specifically, phoxim exposure led to upregulation of Tpx, α-amylase, trypsin, and glycoside hydrolase genes involved in digestion and absorption. Phoxim exposure also led to the downregulation of Cyp450 and Cyp4C1 genes involved in an antioxidant capacity. In contrast, a combination of both phoxim and nano-TiO2 treatment significantly decreased the change in α-amylase, trypsin, and glycoside hydrolases (GHs), which are involved in digestion and absorption. These results indicated that Tpx, α-amylase, trypsin, GHs, Cyp450, and Cyp4C1 may be potential biomarkers of midgut toxicity caused by phoxim exposure and the attenuation of these toxic impacts by nano-TiO2.

Serum iron level is independently associated with sarcopenia: a retrospective study.

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.

[Bacteriological analysis of nasal secretions in patients with nasal lymphoma].

Objective:To investigate the etiological characteristics of nasal bacterial infection in patients with nasal lymphoma. Methods:The results of bacterial culture of nasal secretions from 39 healthy people and 86 patients with nasal lymphoma in the Affiliated Hospital of Qingdao University from January 2019 to June 2022 were retrospectively analyzed, and the differences in nasal bacteria distribution between nasal lymphoma and healthy people were analyzed and compared. Results:Corynebacterium（38.90%） was the most common bacteria in the nasal cavity of healthy people, followed by coagulase-negative Staphylococcus（31.95%）, Staphylococcus epidermidis（15.28%） and Staphylococcus aureus（6.95%）. The most common bacteria in nasal lymphoma patients was Staphylococcus aureus（30.37%）, followed by Corynebacterium（9.63%）, Staphylococcus epidermidis（7.41%） and coagulase negative Staphylococcus（6.67%）. A total of 81 nasal lymphoma patients were detected with bacteria, positive rate is as high as 94.19%（81/86）. Conclusion:Staphylococcus aureus is the main pathogenic bacteria in nasal secretion of patients with nasal lymphoma, which provides guiding significance for the clinical prevention and treatment of nasal lymphoma complicated with infection or not.

Bioinformatics analysis of CUL2/4A/9 and its function in head and neck squamous cell carcinoma.

INTRODUCTION: Several previous studies have shown that differential expression of cullin (CUL) family proteins may be involved in mediation of the signal transduction pathways associated with cancer. However, the function of CULs is still unclear in head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: We used The Cancer Genome Atlas (TCGA) database, cBioPortal, Metascape, STRING, Cytoscape, Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter, and Tumor Immune System Interaction Database (TISIDB) to access the expression of CULs and the possible correlation with the tumourigenesis, development, prognosis, immunity, and transcriptional level of CULs in HNSCC. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect messenger ribonucleid acid (mRNA) levels in HNSCC tissues and cell samples. We also explored the cell proliferation and migration separately by CCK8 assay and wound healing assay. RESULTS: The results showed that the expressions of CUL2/4A were upregulated and CUL9 was downregulated in HNSCC patients as compared with normal patients. CUL2/4A/9 were also linked to the clinicopathological features and overall survival of HNSCC in bioinformatics analysis. Moreover, we noticed that CUL2/4A/9 may take part in tumour-specific immune response by modulating the tumour-infiltrating lymphocytes (TILs) and immunomodulators. Lastly, we found that CUL2/4A/9 could promote cellular proliferation and migration. CONCLUSION: These results suggest that the transcriptional levels of CUL2/4A/9 were upregulated and these genes could affect proliferation and migration of HNSCC cells. Therefore, CUL2/4A/9 could potentially function as novel independent biomarkers in HNSCC patients.

In vitro exposure to environmentally relevant concentrations of norgestrel affects sperm physiology and reproductive success of the Pacific oyster Crassostrea gigas.

Progestins in aquatic environments are of increasing concern, as shown by the results of toxicological studies on adult invertebrates with external fertilization. However, their potential effects on the gametes and reproductive success of such animals remain largely unknown. Thus, the current study assessed the effect of in vitro exposure of environmentally relevant concentrations (10 ng/L and 1000 ng/L) of norgestrel (NGT) on the sperm of Pacific oyster Crassostrea gigas, analyzing sperm motility, ultrastructure, mitochondrial function, ATP status, characteristic enzyme activities, and DNA integrity underlying fertilization and hatching success. The results showed that NGT increased the percentage of motile sperm by elevating intracellular Ca2+ levels, Ca2+-ATPase activity, creatine kinase activity, and ATP content. Although superoxide dismutase activity was enhanced to eliminate reactive oxygen species generated by NGT, oxidative stress occurred, as indicated by the increase in malonaldehyde content and damage to plasma membranes and DNA. As a consequence, fertilization rates decreased. However, hatching rates did not alter significantly, possibly as a result of DNA repair processes. This study demonstrates oyster sperm as a useful, sensitive tool for toxicological research of progestins and provides ecologically relevant information on reproductive disturbance in oysters resulting from exposure to NGT.

JLP/Foxk1/N-cadherin axis fosters a partial epithelial-mesenchymal transition state in epithelial tubular cells.

Renal tubular epithelial cells (TECs) undergoing partial epithelial-mesenchymal transition (pEMT) during renal fibrosis has been recognized as a featuring and detrimental event. However, the mechanism for redirecting the cell fate of pEMT remains unclear. Here we mapped the temporal expression trajectories of a series of EMT-related molecules in renal fibrosis. It revealed a unique expression profile of N-cadherin of initial rising and late dropdown, which is distinct from that of other mesenchymal markers. The transcription factor Foxk1, which serves as a negative regulator of the N-cadherin gene, was induced by TGF-ß1 but was tightly regulated in the presence of JNK-associated leucine zipper protein (JLP). The loss of JLP resulted in Foxk1 induction, leading to N-cadherin downregulation and compromised cell viability. We propose a novel axis consisting of JLP/Foxk1/N-cadherin in shaping the EMT program and suggest JLP as the checkpoint of the EMT continuum during renal fibrosis progression.

The association of lipid metabolism and sarcopenia among older patients: a cross-sectional study.

Sarcopenia has become a heavy disease burden among the elderly. Lipid metabolism was reported to be involved in many degenerative diseases. This study aims to investigate the association between dysregulated lipid metabolism and sarcopenia in geriatric inpatients. This cross-sectional study included 303 patients aged ≥ 60, of which 151 were diagnosed with sarcopenia. The level of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine (HCY), BMI, and fat percentage, were compared between sarcopenia and non-sarcopenia patients. The Spearman correlation coefficient was used to estimate the association between sarcopenia and the level of lipid metabolism. To determine risk factors related to sarcopenia, a multivariate logistic regression analysis was carried out. Risk prediction models were constructed based on all possible data through principal component analysis (PCA), Logistic Regression (LR), Support Vector Machine (SVM), k-Nearest Neighbor (KNN), and eXtreme Gradient Boosting (XGboost). We observed rising prevalence of sarcopenia with increasing age, decreasing BMI, and fat percentage (p < 0.001, Cochran Armitage test). Multivariate logistic regression analysis revealed sarcopenia's risk factors, including older age, male sex, lower levels of BMI, TC, and TG, and higher levels of LDL and HCY (p < 0.05). The sarcopenia risk prediction model showed the risk prediction value of sarcopenia, with the highest area under the receiver operating curve (AUC) of 0.775. Our study provided thorough insight into the risk factors associated with sarcopenia. It demonstrated that an increase in lipid metabolism-related parameters (BMI, TG, TC), within normal reference ranges, may be protective against sarcopenia. The present study can illuminate the direction and significance of lipid metabolism-related factors in preventing sarcopenia.

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma.

SLC2A3 is an important member of the glucose transporter superfamily. It has been recently suggested that upregulation of SLC2A3 is associated with poor survival and acts as a prognostic marker in a variety of tumors. Unfortunately, the prognostic role of SLC2A3 in head and neck squamous cell carcinoma (HNSC) is less known. In the present study, we analyzed SLC2A3 expression in HNSC and its correlation with prognosis using TCGA and GEO databases. The results showed that SLC2A3 mRNA expression was higher in HNSC compared with adjacent normal tissues, which was validated with our 9 pairs of HNSC specimens. Moreover, high SLC2A3 expression predicted poor prognosis in HNSC patients. Mechanistically, GSEA revealed that high expression of SLC2A3 was enriched in epithelial-mesenchymal transition (EMT) and NF-κB signaling. In HNSC cell lines, SLC2A3 knockdown inhibited cell proliferation and migration. In addition, NF-κB P65 and EMT-related gene expression was suppressed upon SLC2A3 knockdown, indicating that SLC2A3 may play a preeminent role in the progression of HNSC through the NF-κB/EMT axis. Meanwhile, the expression of SLC2A3 was negatively correlated with immune cells, suggesting that SLC2A3 may be involved in the immune response in HNSC. The correlation between SLC2A3 expression and drug sensitivity was further assessed. In conclusion, our study demonstrated that SLC2A3 could predict the prognosis of HNSC patients and mediate the progression of HNSC via the NF-κB/EMT axis and immune responses.

Identifying FGA peptides as nasopharyngeal carcinoma-associated biomarkers by magnetic beads.

Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis™ and ClinProt™ bioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC.