Feature Matching of Microsecond-Pulsed Magnetic Fields Combined with Fe3O4 Particles for Killing A375 Melanoma Cells.

The combination of magnetic fields and magnetic nanoparticles (MNPs) to kill cancer cells by magneto-mechanical force represents a novel therapy, offering advantages such as non-invasiveness, among others. Pulsed magnetic fields (PMFs) hold promise for application in this therapy due to advantages such as easily adjustable parameters; however, they suffer from the drawback of narrow pulse width. In order to fully exploit the potential of PMFs and MNPs in this therapy, while maximizing therapeutic efficacy within the constraints of the narrow pulse width, a feature-matching theory is proposed, encompassing the matching of three aspects: (1) MNP volume and critical volume of Brownian relaxation, (2) relaxation time and pulse width, and (3) MNP shape and the intermittence of PMF. In the theory, a microsecond-PMF generator was developed, and four kinds of MNPs were selected for in vitro cell experiments. The results demonstrate that the killing rate of the experimental group meeting the requirements of the theory is at least 18% higher than the control group. This validates the accuracy of our theory and provides valuable guidance for the further application of PMFs in this therapy.

The effect of ultrasonic power on the physicochemical properties and antioxidant activities of frosted figs pectin.

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.

Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification.

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

Amide proton transfer-weighted imaging and stretch-exponential model DWI based 18F-FDG PET/MRI for differentiation of benign and malignant solitary pulmonary lesions.

OBJECTIVES: To differentiate benign and malignant solitary pulmonary lesions (SPLs) by amide proton transfer-weighted imaging (APTWI), mono-exponential model DWI (MEM-DWI), stretched exponential model DWI (SEM-DWI), and 18F-FDG PET-derived parameters. METHODS: A total of 120 SPLs patients underwent chest 18F-FDG PET/MRI were enrolled, including 84 in the training set (28 benign and 56 malignant) and 36 in the test set (13 benign and 23 malignant). MTRasym(3.5 ppm), ADC, DDC, α, SUVmax, MTV, and TLG were compared. The area under receiver-operator characteristic curve (AUC) was used to assess diagnostic efficacy. The Logistic regression analysis was used to identify independent predictors and establish prediction model. RESULTS: SUVmax, MTV, TLG, α, and MTRasym(3.5 ppm) values were significantly lower and ADC, DDC values were significantly higher in benign SPLs than malignant SPLs (all P < 0.01). SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors. Within the training set, the prediction model based on these independent predictors demonstrated optimal diagnostic efficacy (AUC, 0.976; sensitivity, 94.64%; specificity, 92.86%), surpassing any single parameter with statistical significance. Similarly, within the test set, the prediction model exhibited optimal diagnostic efficacy. The calibration curves and DCA revealed that the prediction model not only had good consistency but was also able to provide a significant benefit to the related patients, both in the training and test sets. CONCLUSION: The SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors for differentiation of benign and malignant SPLs, and the prediction model based on them had an optimal diagnostic efficacy.

Characterization of oxylipins in Antarctic krill oil (Euphausia superba) during storage based on RPLC-MS/MS analysis.

Antarctic krill oil (AKO) is rich in polyunsaturated fatty acids (PUFAs), but is prone to oxidative degradation, resulting in the formation of oxylipins, which compromise AKO quality. Herein, we used reversed-phase-high performance liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) to perform qualitative and semi-quantitative analyses of oxylipins in AKO during storage. A total of 27 oxylipins were identified. A notable decrease in epoxy oxylipins (from 41.8 % to 26.9 % of the total oxylipins) was observed, whereas the content of dihydro oxylipins initially increased and then decreased with 48 h, as a pivotal point for AKO quality decline during storage. We suspected that the ratio of dihydroxyl and epoxy oxylipins could be a novel oxidative index to evaluate the oxidation of AKO. Statistical analysis allowed the identification of five oxylipins which showed unique correlations with various indexes. The findings discussed herein provide important new insights into mechanisms of oxidation occurring in AKO during storage.

The role of dynamic, static, and delayed total-body PET imaging in the detection and differential diagnosis of oncological lesions.

OBJECTIVES: Commercialized total-body PET scanners can provide high-quality images due to its ultra-high sensitivity. We compared the dynamic, regular static, and delayed 18F-fluorodeoxyglucose (FDG) scans to detect lesions in oncologic patients on a total-body PET/CT scanner. MATERIALS & METHODS: In all, 45 patients were scanned continuously for the first 60 min, followed by a delayed acquisition. FDG metabolic rate was calculated from dynamic data using full compartmental modeling, whereas regular static and delayed SUV images were obtained approximately 60- and 145-min post-injection, respectively. The retention index was computed from static and delayed measures for all lesions. Pearson's correlation and Kruskal-Wallis tests were used to compare parameters. RESULTS: The number of lesions was largely identical between the three protocols, except MRFDG and delayed images on total-body PET only detected 4 and 2 more lesions, respectively (85 total). FDG metabolic rate (MRFDG) image-derived contrast-to-noise ratio and target-to-background ratio were significantly higher than those from static standardized uptake value (SUV) images (P < 0.01), but this is not the case for the delayed images (P > 0.05). Dynamic protocol did not significantly differentiate between benign and malignant lesions just like regular SUV, delayed SUV, and retention index. CONCLUSION: The potential quantitative advantages of dynamic imaging may not improve lesion detection and differential diagnosis significantly on a total-body PET/CT scanner. The same conclusion applied to delayed imaging. This suggested the added benefits of complex imaging protocols must be weighed against the complex implementation in the future. CLINICAL RELEVANCE: Total-body PET/CT was known to significantly improve the PET image quality due to its ultra-high sensitivity. However, whether the dynamic and delay imaging on total-body scanner could show additional clinical benefits is largely unknown. Head-to-head comparison between two protocols is relevant to oncological management.

Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study. AIM OF THE STUDY: To investigate F.S in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action. RESULTS: In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment. CONCLUSION: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway.

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin ß3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention.

DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3K-Akt-NF-κB pathway.

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.

An [18F]FDG PET/3D-ultrashort echo time MRI-based radiomics model established by machine learning facilitates preoperative assessment of lymph node status in non-small cell lung cancer.

OBJECTIVES: To develop an [18F]FDG PET/3D-UTE model based on clinical factors, three-dimensional ultrashort echo time (3D-UTE), and PET radiomics features via machine learning for the assessment of lymph node (LN) status in non-small cell lung cancer (NSCLC). METHODS: A total of 145 NSCLC patients (training, 101 cases; test, 44 cases) underwent whole-body [18F]FDG PET/CT and chest [18F]FDG PET/MRI were enrolled. Preoperative clinical factors and 3D-UTE, CT, and PET radiomics features were analyzed. The Mann-Whitney U test, LASSO regression, and SelectKBest were used for feature extraction. Five machine learning algorithms were used to establish prediction models, which were evaluated by the area under receiver-operator characteristic (ROC), DeLong test, calibration curves, and decision curve analysis (DCA). RESULTS: A prediction model based on random forest, consisting of four clinical factors, six 3D-UTE, and six PET radiomics features, was used as the final model for PET/3D-UTE. The AUCs of this model were 0.912 and 0.791 in the training and test sets, respectively, which not only showed different degrees of improvement over individual models such as clinical, 3D-UTE, and PET (AUC-training = 0.838, 0.834, and 0.828, AUC-test = 0.756, 0.745, and 0.768, respectively) but also achieved the similar diagnostic efficacy as the optimal PET/CT model (AUC-training = 0.890, AUC-test = 0.793). The calibration curves and DCA indicated good consistency (C-index, 0.912) and clinical utility of this model, respectively. CONCLUSION: The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using machine learning methods could noninvasively assess the LN status of NSCLC. CLINICAL RELEVANCE STATEMENT: A machine learning model of 18F-fluorodeoxyglucose positron emission tomography/ three-dimensional ultrashort echo time could noninvasively assess the lymph node status of non-small cell lung cancer, which provides a novel method with less radiation burden for clinical practice. KEY POINTS: • The 3D-UTE radiomics model using the PLS-DA classifier was significantly associated with LN status in NSCLC and has similar diagnostic performance as the clinical, CT, and PET models. • The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using the RF classifier could noninvasively assess the LN status of NSCLC and showed improved diagnostic performance compared to the clinical, 3D-UTE, and PET models. • In the assessment of LN status in NSCLC, the [18F]FDG PET/3D-UTE model has similar diagnostic efficacy as the [18F]FDG PET/CT model that incorporates clinical factors and CT and PET radiomics features.

Value evaluation of serum (sdLDLc*HCYc)/HDLc ratio in the stability of intracranial arterial plaques in patients with acute cerebral infarction.

BACKGROUND: We aimed to analyze the value of serum (sdLDLc*HCYc)/HDLc ratio in the stability of intracranial arterial plaques among patients with acute cerebral infarction. METHODS: A retrospective analysis was conducted on 140 patients with acute cerebral infarction admitted to the neurology department and 101 healthy individuals for regular examinations in our hospital from 2013 to 2019, who were respectively allocated into the study group and the control group. Participants in both groups were measured for serum sdLDLc, HDLc, and HCYc using peroxidase method, enzyme-linked immunosorbent assay, and enzyme method, respectively. The laboratory indexes of the two groups were compared. The multivariate logistic regression analysis was done to analyze the influencing factors of the stability of intracranial artery plaque in patients with acute cerebral infarction. The value of high-density lipoprotein cholesterol (HDL-C), homocysteine, sdLDLc, (sdLDLc*HCYc)/HDLc in diagnosing the stability of intracranial artery plaque was also evaluated in patients with acute cerebral infarction. RESULTS: There was no distinct difference in height, hypertension, diabetes, coronary heart disease, smoking history and drinking history between the two groups (P>0.05). The study group showed statistically significant differences in age, gender, weight, and BMI (P<0.05). The current study demonstrated no statistical difference in the levels of TG, low-density lipoprotein cholesterol (LDL-C), α-lipoprotein, and HCYc between the two groups (P>0.05). However, the levels of TC, HDL-C, sdLDLc, (sdLDLc*HCYc)/HDLc in the study group were significantly different when comparing with the control group (P<0.05). No statistically significant difference was found in the levels of TG, triglycerides, LDL-C, α-lipoprotein, and HCYc among patients with different degrees of stenosis in the study group (P>0.05). The level of HDL-C was significantly lower in cases of severe stenosis compared to no stenosis, mild stenosis and moderate stenosis, with severe stenosis showing the lowest levels; mild stenosis had lower levels than no stenosis, while moderate stenosis had lower levels than both no stenosis and mild stenosis (P<0.05). The levels of sdLDLc, (sdLDLc*HCYc)/HDLc exhibited a significant increase in cases of severe stenosis as compared tono stenosis, mild stenosis, and moderate stenosis. Furthermore, the levels of sdLDLc, (sdLDLc*HCYc)/HDLc were found to be higher in moderate stenosis as compared to no stenosis and mild stenosis. Similarly, the levels of sdLDLc, (sdLDLc*HCYc)/HDLc were observed to be higher in mild stenosis than no stenosis (P<0.05).The independent variables were set as the indicators with difference in single factor comparison, including age, gender, BMI, TC, LDL-C, HDL-C, HCYc, sdLDLc, (sdLDLc*HCYc)/HDLc. The dependent variable was the stability of intracranial artery plaque in patients with acute cerebral infarction. After variable selection, the results showed that the factors influencing the stability of intracranial artery plaque in patients with acute cerebral infarction were age, BMI, (sdLDLc*HCYc)/HDLc. The degree of plaque enhancement was used as a criterion to reflect the stability of plaque. ROC curve analysis showed that (sdLDLc*HCYc)/HDLc had a higher evaluation value for the stability of intracranial artery plaque than HDL-C, homocysteine, and sdLDLc in patients with acute cerebral infarction. CONCLUSION: The serum (sdLDLc*HCYc)/HDLc ratio was found to have potential in evaluating the stability of intracranial arterial plaques in patients with acute cerebral infarction.

[Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice].

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-ß1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-ß1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-ß1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Identification of Crucial Genes and Signaling Pathways in Alectinib-Resistant Lung Adenocarcinoma Using Bioinformatic Analysis.

Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, has been shown to be effective for patients with ALK-positive non-small cell lung cancer (NSCLC). However, alectinib resistance is a serious problem worldwide. To the best of our knowledge, little information is available on its molecular mechanisms using the Gene Expression Omnibus (GEO) database. In this study, the differentially expressed genes (DEGs) were selected from the gene expression profile GSE73167 between parental and alectinib-resistant human lung adenocarcinoma (LUAD) cell samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation enrichment analyses were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). The construction of protein-protein interaction (PPI) network was performed to visualize DEGs. The hub genes were extracted based on the analysis of the PPI network using plug-in cytoHubba of Cytoscape software. The functional roles of the key genes were investigated using Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer (UALCAN), Gene Set Enrichment Analysis (GSEA), and Tumor Immune Estimation Resource (TIMER) analysis. The networks of kinase, miRNA, and transcription-factor targets of SFTPD were explored using LinkedOmics. The drug sensitivity analysis of SFTPD was analyzed using the RNAactDrug database. Results showed a total of 144 DEGs were identified. Five hub genes were extracted, including mucin 5B (MUC5B), surfactant protein D (SFTPD), deleted in malignant brain tumors 1 (DMBT1), surfactant protein A2 (SFTPA2), and trefoil factor 3 (TFF3). The survival analysis using GEPIA displayed that low expression of SFTPD had a significantly negative effect on the prognosis of patients with LUAD. GSEA revealed that low expression of SFTPD was positively correlated with the pathways associated with drug resistance, such as DNA replication, cell cycle, drug metabolism, and DNA damage repair, including mismatch repair (MMR), base excision repair (BER), homologous recombination (HR), and nucleotide excision repair (NER). The SFTPD expression was negatively correlated with the drug sensitivity of alectinib according to RNAactDrug database. The expression of SFTPD was further validated in parental H3122 cells and alectinib-resistant H3122 cells by quantitative reverse transcription PCR (RT-qPCR). In conclusion, our study found that the five hub genes, especially low expression of SFTPD, are closely related to alectinib resistance in patients with LUAD.

P-coumaric acid ameliorates Aß25-35-induced brain damage in mice by modulating gut microbiota and serum metabolites.

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aß25-35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aß25-35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aß25-35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aß25-35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aß25-35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

Amide Proton Transfer-Weighted Imaging and Multiple Models Intravoxel Incoherent Motion-Based 18 F-FDG PET/MRI for Predicting Progression-Free Survival in Non-Small Cell Lung Cancer.

BACKGROUND: Amide proton transfer-weighted imaging (APTWI) and multiple models intravoxel incoherent motion (IVIM) based 18 F-FDG PET/MR could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non-small cell lung cancer (NSCLC) still needs to be further explored. PURPOSE: To determine whether pretreatment APTWI, mono-, bi-, and stretched-exponential model IVIM, and 18 F-FDG PET-derived parameters of the primary lesion may be associated with progression-free survival (PFS) in NSCLC. STUDY TYPE: Prospective. POPULATION: Seventy-seven patients (mean age, 62 years, range, 20-81 years) with 37 men and 40 women were included. FIELD STRENGTH/SEQUENCE: 3.0 T 18 F-FDG PET/MRI, single shot echo planar imaging sequences for IVIM and fast spin-echo sequences with magnetization transfer pulses for APTWI. ASSESSMENT: Patient clinical characteristics (age, sex, smoke, subtype, TNM stage, and surgery), PFS (chest CT every 3 months, median follow-up was 18 months, range, 4-27 months), and APTWI (MTRasym(3.5 ppm)), IVIM (ADCstand , D, D*, f, DDC, and α), and 18 F-FDG PET (SUVmax , MTV, and TLG) parameters were recorded. STATISTICAL TESTS: Proportional hazards model, concordance index, calibration curve, decision curve analysis (DCA), and Log-rank test. A P value <0.05 was considered statistically significant. RESULTS: Histological subtype, TNM stage, MTV, D*, and MTRasym(3.5 ppm) were all independent predictors of PFS. A prediction model based on these predictors was developed with a C-index of 0.895 (95% CI: 0.839-0.951), which was significantly superior to each of the above predictors alone (C-index = 0.629, 0.707, 0.692, 0.678, and 0.558, respectively). The calibration curve and DCA indicated good consistency and clinical utility of the prediction model, respectively. Log-rank test results showed a significant difference in PFS between the high- and low-risk groups. DATA CONCLUSION: APTWI and multiple models IVIM based 18 F-FDG PET/MRI can be used for PFS assessment in NSCLC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

[Effect of aqueous extract of Corni Fructus on Aß_(25-35)-induced brain injury and neuroinflammation in mice with Alzheimer's disease].

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on ß-amyloid protein 25-35(Aß_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aß_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of ß-amyloid protein 1-42(Aß_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aß_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol with ß-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aß_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aß_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aß_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aß_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aß_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

[Platycladi Semen oil ameliorates Aß_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota].

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aß_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aß_(25-35), 200 µmol·L~(-1), 0.15 µL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aß_(1-42)/Aß_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aß_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aß_(1-42)/Aß_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aß_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1ß-exposed chondrocytes via suppressing GRP78 expression.

BACKGROUND: Osteoarthritis (OA) is a frequently encountered debilitating joint disorder. Whether plexin C1 (PLXNC1) is implicated in OA is far from being investigated despite its well-documented pro-inflammatory property in human diseases. The goal of this study is to expound the specific role of PLXNC1 in OA and elaborate the probable action mechanism. METHODS: Firstly, PLXNC1 expression in the cartilage tissues of patients with OA was examined with GEO database. In interleukin-1beta (IL-1ß)-induced OA cell model, RT-qPCR and western blotting tested the expression of PLXNC1, glucose-regulating protein 78 (GRP78) and extracellular matrix (ECM) degradation-related factors. Cell viability and inflammation were respectively judged by CCK-8 assay and RT-qPCR. TUNEL and western blotting estimated cell apoptosis. The potential binding between PLXNC1 and GRP78 was corroborated by Co-IP assay. Western blotting also tested the expression of endoplasmic reticulum stress (ERS)-associated proteins. RESULTS: As it turned out, PLXNC1 expression was elevated in the cartilage tissues of patients with OA and IL-1ß-treated chondrocytes. When PLXNC1 was depleted, the viability injury, inflammation, apoptosis and ECM degradation of chondrocytes exposed to IL-1ß were obstructed. Besides, GRP78 bond to PLXNC1 in IL-1ß-treated chondrocytes. The ascending GRP78 expression in the chondrocytes exposed to IL-1ß was depleted after PLXNC1 was silenced. Meanwhile, the impacts of PLXNC1 deficiency on the viability, inflammatory response, apoptosis, ECM degradation as well as ERS in IL-1ß-exposed chondrocytes were abolished by GRP78 up-regulation. CONCLUSION: In summary, PLXNC1 silencing might interact with and down-regulate GRP78 to mitigate the apoptosis, inflammation, and ECM degradation of IL-1ß-insulted chondrocytes in OA.

Quantitative parameters of static imaging and fast kinetics imaging in 18F-FDG total-body PET/CT for the assessment of histological feature of pulmonary lesions.

Background: To investigate the value of quantitative parameters related to static imaging and fast kinetics imaging of total-body (TB) 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in differentiating benign from malignant pulmonary lesions and squamous cell carcinoma (SCC) from adenocarcinoma (AC) and to analyze the correlation of each parameter with the Ki-67 index. Methods: A total of 108 patients with pulmonary lesions from July 2021 to May 2022 in the Henan Provincial People's Hospital, China, were consecutively recruited for TB 18F-FDG PET/CT in this prospective study. Static imaging parameters maximum standardized uptake value (SUVmax) and fast kinetics imaging parameters transport constant (K1), rate constants (k2), time delay (td), and fractional blood volume (vb) were calculated and compared. The area under the receiver operating characteristic (ROC) curve (AUC), Delong test, Logistic regression analyses, and Pearson correlation were used to assess diagnostic efficacy, find independent predictors and analyse correlations respectively. Results: Malignant lesions had higher SUVmax and K1 and lower vb than benign lesions, and SCC had higher SUVmax and K1 and lower td and vb than AC (all P<0.05). For the differentiation of benign and malignant lesions, SUVmax, K1, and vb were independent predictors, and AUC (SUVmax + K1+ vb) =0.909 (95% CI: 0.839-0.956), AUC (SUVmax) =0.883 (95% CI: 0.807-0.937), AUC (K1) =0.810 (95% CI: 0.723-0.879), and AUC (vb) =0.746 (95% CI: 0.653-0.825), where AUC (SUVmax + K1+ vb) was significantly different from AUC (K1), AUC (vb) (Z=3.006, 3.965, all P<0.05). For the differentiation of SCC and AC, SUVmax, K1, td, and vb were independent predictors, and AUC (SUVmax + K1+ td + vb) =0.946 (95% CI: 0.840-0.991), AUC (SUVmax) =0.818 (95% CI: 0.680-0.914), AUC (K1) =0.770 (95% CI: 0.626-0.879), AUC (vb) =0.737 (95% CI: 0.590-0.853), and AUC (td) =0.669 (95% CI: 0.510-0.791), where AUC (SUVmax + K1+ td + vb) was significantly different from AUC (SUVmax), AUC (K1), AUC (vb), and AUC (td) (Z=2.269, 2.821, 2.848, and 3.276, all P<0.05). SUVmax and K1 were moderately and mildly positively correlated with the Ki-67 index (r=0.541, 0.452, all P<0.05), respectively. Conclusions: Quantitative parameters of static imaging and fast kinetics imaging in 18F-FDG total-body PET/CT can be used to differentiate benign from malignant pulmonary lesions and SCC from AC and to assess Ki-67 expression.

Colon Metastasis from Pancreatic Cancer: A Case Report.

Pancreatic cancer commonly metastasizes to the liver, lung or adrenal glands, but rarely spreads to the colon. We describe a case of a 65-year-old man with operation history of endoscopic submucosal dissection for rectal adenoma, who visited our department with a lesion in the sigmoid colon. A biopsy of the sigmoid pathologic lesion found heterologous cells in the muscularis mucosa, which indicated that this lesion did not originate in the colon. Abdominal enhanced CT results revealed a soft tissue mass in pancreatic tail and several masses in the liver and rectovesical pouch. 18-FDG PET-scan results showed pancreatic neoplastic mass. Biopsy result of pancreatic pathologic area was positive for ductal pancreatic adenocarcinoma. Immunohistochemical staining confirmed that the sigmoid lesion was a metastasis from a primary pancreatic adenocarcinoma-an unusual pattern of spread. The patient accepted chemotherapy after an oncologic evaluation. To our knowledge, there were only nine reported cases of metastatic pancreatic cancer spreading to the colon. This was a rare route of metastasis for pancreatic cancer. It is important to keep this possibility in mind when patients present with a colon lesion. Furthermore, our case highlights the importance of considering metastases when a colon mass is found in patients with a history of colon cancer, although primary colon cancer is still more likely.