Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.

Promoting In Vivo NIR-II Fluorescent Imaging for Lipid in Lipid Metabolism Diseases Diagnosis.

Lipid metabolism diseases have become a tremendous risk worldwide, along with the development of productivity and particular attention to public health. It has been an urgent necessity to exploit reliable imaging strategies for lipids and thus to monitor fatty liver diseases. Herein, by converting the NIR-I signal to the NIR-II signal with IR1061 for the monitoring of lipid, the in vivo imaging of fatty liver disease was promoted on the contrast and visual effect. The main advantages of the imaging promotion in this work included a long emission wavelength, rapid response, and high signal-background-ratio (SBR) value. After promoting the NIR-I signal to NIR-II signal, IR1061 achieved higher SBR value and exhibited a dose-dependent fluorescence intensity at 1100 nm along with the increase of the EtOH proportion as well as steady and selective optical responses toward liposomes. IR1061 was further applied in the in vivo imaging of lipid in fatty liver diseases. In spite of the differences in body weight gain and TC level between healthy mice and fatty liver diseases two models, IR1061 achieved high-resolution imaging in the liver region to monitor the fatty liver disease status. This work might be informatic for the clinical diagnosis and therapeutical treatments of fatty liver diseases.

A human serum albumin-binding-based fluorescent probe for monitoring hydrogen sulfide and bioimaging.

In this work, a fluorescent probe, TPABF-HS, was developed for detecting hydrogen sulfide (H2S) using a human serum albumin (HSA)-binding-based approach for amplifying the fluorescence signal and extending the linear correlation range. Compared to the most recent probes for H2S, the most interesting feature of the detection system developed herein was the especially wide linear range (0-1000 µM (0-100 eq.)), which covered the physiological and pathological levels of H2S. TPABF-HS could be used in applications high sensitivity and selectivity with an LOD value of 0.42 µM. Further, site-competition experiments and molecular docking simulation experiments indicated that signal amplification was realized by the binding of the TPABF fluorophore to the naproxen-binding site of HSA. Moreover, the extension of the measurement span could allow for applications in living cells and Caenorhabditis elegans for imaging both exogenous and endogenous H2S. This work brings new information to the strategy of signal processing by exploiting fluorescent probes.

Ginseng-DF ameliorates intestinal mucosal barrier injury and enhances immunity in immunosuppressed mice by regulating MAPK/NF-κB signaling pathways.

PURPOSE: Dietary fiber (DF) has a good application prospect in effectively restoring the integrity of the intestinal mucosal barrier. Ginseng-DF has good physicochemical properties and physiological activity and shows positive effects in enhancing immunity. The aim of this study was to investigate the protective effect of Ginseng-DF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and its possible mechanism. METHODS: The effects of Gginseng-DF on immune function in mice were studied by delayed-type hypersensitivy, lymphocyte proliferation assay and NK cytotoxicity assay, the T lymphocyte differentiation and intestinal barrier integrity were analyzed by flow cytometry and western blot. RESULTS: Ginseng-DF (2.5% and 5%) could attenuate the inhibition of DTH response by CTX, promote the transformation and proliferation of lymphocytes, and stimulate NK effector cell activity. At the same time, Ginseng-DF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, improved spleen tissue damage, promoted the secretion of immunoglobulin IgG, and enhanced body immunity. More importantly, Ginseng-DF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1ß in serum and intestine of immunosuppressed mice to maintain the balance between Th1/Th2 cytokines, and improve the permeability of intestinal mucosal barrier. Meanwhile, Ginseng-DF could reduce intestinal epithelial cell apoptosis and improve intestinal adaptive immunity in CTX-induced immunosuppressed mice by regulating MAPK/NF-κB signaling pathway. CONCLUSION: Ginseng-DF can be used as a safe dietary supplement to enhance body immunity and reduce intestinal mucosal injury caused by CTX.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Performance of T2 mapping in the staging of Graves' ophthalmopathy based on different region of interest selection methods.

BACKGROUND: Discriminating the stage of Graves' ophthalmopathy (GO) is crucial for clinical decision. Application of conventional T2-weighted imaging in the staging is still limited. PURPOSE: To evaluate the performance of T2 mapping based on two different regions of interest (ROIs) for staging GO. MATERIAL AND METHODS: In total, 56 GO patients were retrospectively enrolled and divided into two groups according to the clinical activity score (CAS). T2 relaxation time (T2RT) of extraocular muscle (EOM) on T2 mapping based on two different ROIs (T2RTROI-1: ROIs were drawn separately in the four EOMs; T2RTROI-2: ROI was drawn in the most inflamed EOM) was measured and compared between active and inactive groups. RESULTS: Both T2RTROI-1 and T2RTROI-2 values in the active GO were significantly higher than those of inactive GO (P <0.001). T2RTROI-1 and T2RTROI-2 values were positively correlated with CAS (rs=0.73, 0.69; P <0.001). When the T2RTROI-1 value of 83.3 ms and T2RTROI-2 value of 106.3 ms were used as cutoff values for staging GO, respectively, the best results were obtained with areas under the curve (AUCs) of 0.822 and 0.827. There was no significant difference for AUCs between T2RTROI-1 and T2RTROI-2 (P = 0.751). Excellent and good inter-observer agreements were achieved in quantitative measurements for T2RTROI-1 and T2RTROI-2 values, respectively, with intraclass correlation coefficients of 0.954 and 0.882. CONCLUSION: The T2RT values derived from two different ROIs were useful for assessment of disease activity. Taking reproducibility and diagnostic performance into consideration, T2RTROI-1 would be an ideal image biomarker for staging GO compared to T2RTROI-2.

The energy metabolism of Balantidium polyvacuolum inhabiting the hindgut of Xenocypris davidi.

Anaerobic parasitic ciliates are a specialized group of ciliates that are adapted to anoxic and oxygen-depleted habitats. Among them, Balantidium polyvacuolum, which inhabits the hindgut of Xenocyprinae fishes, has received very limited scientific attention, so the molecular mechanism of its adaptation to the digestive tract microenvironment is still unclear. In this study, transmission electron microscopy (TEM) and single-cell transcriptome analysis were used to uncover the metabolism of B. polyvacuolum. Starch granules, endosymbiotic bacteria, and multiple specialized mitochondrion-related organelles (MROs) of various shapes were observed. The MROs may have completely lost the electron transport chain (ETC) complexes I, III, IV, and V and only retained succinate dehydrogenase subunit A (SDHA) of complex II. The tricarboxylic acid (TCA) cycle was also incomplete. It can be inferred that the hypoxic intestinal environment has led to the specialization of the mitochondria in B. polyvacuolum. Moreover, carbohydrate-active enzymes (CAZymes), including carbohydrate esterases, enzymes with a carbohydrate-binding module, glycoside hydrolases, and glycosyltransferases, were identified, which may constitute evidence that B. polyvacuolum is able to digest carbohydrates and starch. These findings can improve our knowledge of the energy metabolism and adaptive mechanisms of B. polyvacuolum.

Imaging Investigation of Hepatocellular Carcinoma Progress via Monitoring γ-Glutamyltranspeptidase Level with a Near-Infrared Fluorescence/Photoacoustic Bimodal Probe.

Hepatocellular carcinoma (HCC) is one of the main principal causes of cancer death, and the late definite diagnosis limits therapeutic approaches in time. The early diagnosis of HCC is essential, and the previous investigations on the biomarkers inferred that the γ-glutamyltranspeptidase (GGT) level could indicate the HCC process. Herein, a near-infrared fluorescence/photoacoustic (NIRF/PA) bimodal probe, CySO3-GGT, was developed for monitoring the GGT level and thus to image the HCC process. After the in-solution tests, the bimodal response was convinced. The various HCC processes were imaged by CySO3-GGT at the cellular level. Then, the CCl4-induced HCC (both induction and treatment) and the subcutaneous and orthotopic xenograft mice models were selected. All throughout the tests, CySO3-GGT achieved NIRF and PA bimodal imaging of the HCC process. In particular, CySO3-GGT could effectively realize 3D imaging of the HCC nodule by visualizing the boundary between the tumor and the normal tissue. The information here might offer significant guidance for the dynamic monitoring of HCC in the near future.

The Role of MR Assessments of Cardiac Morphology, Function, and Tissue Characteristics on Exercise Capacity in Well-Functioning Older Adults.

BACKGROUND: The relationship between resting cardiac indices and exercise capacity in older adults was still not well understood. New developments in cardiac magnetic resonance imaging (MRI) enable a much fuller assessment of cardiac characteristics. PURPOSE/HYPOTHESIS: To assess the association between exercise capacity and specific aspects of resting cardiac structure, function, and tissue. STUDY TYPE: Cross-sectional study. POPULATION: A total of 112 well-functioning older adults (mean age 69 years, 52 men). FIELD STRENGTH/SEQUENCE: All participants underwent 3.0 T MRI, using scan protocols including balanced steady-state free precession cine sequence, modified look-locker inversion recovery, and T2-prepared single-shot balanced steady-state free precession. ASSESSMENT: Demographic and geriatric characteristics were collected. Blood samples were assayed for lipid and glucose related biomarkers. All participants performed a symptom-limited cardiopulmonary exercise test to achieve peakVO2 . Cardiac MRI parameters were measured with semi-automatic software by S.Y., an 18-year experienced radiologist. STATISTICAL TESTS: Demographic, geriatric characteristics and MR measurements were compared among quartiles of peakVO2, with different methods according to the data type. Spearman's partial correlation and least absolute shrinkage selection operator regression were performed to select significant MR features associated with peakVO2 . Mediation effect analysis was conducted to test any indirect connection between age and peakVO2 . A two-sided P value of <0.05 was defined statistical significance. RESULTS: Epicardial fat volume, left atrial volume indexed to height, right ventricular end-systolic volume indexed to body surface area and global circumferential strain (GCS) were correlated with peakVO2 (regression coefficients were -0.040, -0.093, 0.127, and 0.408, respectively). Mediation analysis showed that the total effect of peakVO2 change was 43.6% from the change of age. The proportion of indirect effect from epicardial fat volume and GCS were 11.8% and 15.1% in total effect, respectively. DATA CONCLUSION: PeakVO2 was associated with epicardial fat volume, left atrial volume, right ventricular volume and GCS of left ventricle. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Real-time, in vivo skin cancer triage by laser-induced plasma spectroscopy combined with a deep learning-based diagnostic algorithm.

BACKGROUND: Although various skin cancer detection devices have been proposed, most of them are not used owing to their insufficient diagnostic accuracies. Laser-induced plasma spectroscopy (LIPS) can noninvasively extract biochemical information of skin lesions using an ultrashort pulsed laser. OBJECTIVE: To investigate the diagnostic accuracy and safety of real-time noninvasive in vivo skin cancer diagnostics utilizing nondiscrete molecular LIPS combined with a deep neural network (DNN)-based diagnostic algorithm. METHODS: In vivo LIPS spectra were acquired from 296 skin cancers (186 basal cell carcinomas, 96 squamous cell carcinomas, and 14 melanomas) and 316 benign lesions in a multisite clinical study. The diagnostic performance was validated using 10-fold cross-validations. RESULTS: The sensitivity and specificity for differentiating skin cancers from benign lesions using LIPS and the DNN-based algorithm were 94.6% (95% CI: 92.0%-97.2%) and 88.9% (95% CI: 85.5%-92.4%), respectively. No adverse events, including macroscopic or microscopic visible marks or pigmentation due to laser irradiation, were observed. LIMITATIONS: The diagnostic performance was evaluated using a limited data set. More extensive clinical studies are needed to validate these results. CONCLUSIONS: This LIPS system with a DNN-based diagnostic algorithm is a promising tool to distinguish skin cancers from benign lesions with high diagnostic accuracy in real clinical settings.

Performance of heart rate adjusted heart rate variability for risk stratification of sudden cardiac death.

PURPOSE: As a non-invasive tool for the assessment of cardiovascular autonomic function, the predictive value of heart rate variability (HRV) for sudden cardiac death (SCD) risk stratification remains unclear. In this study, we investigated the performance of the individualized heart rate (HR) adjusted HRV (HRVI) for SCD risk stratification in subjects with diverse risks. METHODS: A total of 11 commonly used HRV metrics were analyzed in 192 subjects, including 88 healthy controls (low risk group), 82 hypertrophic cardiomyopathy (HCM) patients (medium risk group), and 22 SCD victims (high risk group). The relationship between HRV metrics and HR was examined with long-term and short-term analysis. The performance HRVI was evaluated by area under the receiver operating characteristic curve (AUC) and covariance of variation (CV). RESULTS: Most of the HRV metrics were exponentially decayed with the increase of HR, while the exponential power coefficients were significantly different among groups. The HRVI metrics discriminated low, medium and high risk subjects with a median AUC of 0.72[0.11], which was considerably higher than that of the traditional long-term (0.63[0.04]) and short-term (0.58[0.05]) HRV without adjustment. The average CV of the HRVI metrics was also significantly lower than traditional short-term HRV metrics (0.09 ± 0.02 vs. 0.24 ± 0.13, p < 0.01). CONCLUSIONS: Subjects with diverse risks of SCD had similar exponential decay relationship between HRV metrics and HR, but with different decaying rates. HRVI provides reliable and robust estimation for risk stratification of SCD.

The predictive value of nontraditional lipid parameters for intracranial and extracranial atherosclerotic stenosis: a hospital-based observational study in China.

BACKGROUND: Ischemic strokes are primarily caused by intracranial and extracranial atherosclerotic stenosis. Nontraditional lipid parameters broaden traditional lipid profiles, better reflect the metabolism and interaction between different lipid components, and optimize the predictive ability of lipid profiles for atherosclerotic diseases. This research was carried out to investigate the predictive value of nontraditional lipid parameters for intracranial or extracranial atherosclerotic stenosis. METHODS: The investigation collected data from inpatients who underwent cervical vascular ultrasonography, carotid CTA, cerebral artery CTA or MRA, and brain MRI or CT from December 2014 to December 2021. The nontraditional lipid parameters were calculated by collecting traditional lipid parameters. To evaluate the predictive power of nontraditional lipid parameters, logistic regression and receiver operating characteristic curve (ROC) analyses were performed. RESULTS: Based on the inclusion and exclusion criteria, 545 patients were included. According to the imaging results, inpatients were divided into two groups, including no intracranial or extracranial atherosclerotic stenosis (n = 250) and intracranial or extracranial atherosclerotic stenosis (AS, n = 295). Among them, AS was further divided into three subgroups: intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and combined intracranial and extracranial atherosclerotic stenosis (IECAS). Logistic regression analysis showed that nontraditional lipid parameters, including the atherogenic index of plasma (AIP), TG/HDL-C, remnant cholesterol (RC), nonhigh-density lipoprotein cholesterol (non-HDL-C), lipoprotein combine index (LCI), atherogenic coefficient (AC), Castelli's index-I (CRI-I) and Castelli's index-II (CRI-II), were significantly correlated with intracranial or extracranial atherosclerotic stenosis (P < 0.05). Compared with other nontraditional lipid parameters, regardless of adjusting for potential confounding factors, AIP had a greater OR value in ICAS (OR = 4.226, 95% CI: 1.681-10.625), ECAS (OR = 2.993, 95% CI: 1.119-8.003) and IECAS (OR = 4.502, 95% CI: 1.613-12.561). ROC curve analysis revealed that nontraditional lipid parameters had good predictive power for intracranial or extracranial atherosclerotic stenosis. CONCLUSIONS: This Chinese hospital-based study demonstrates that nontraditional lipid parameters (AIP, LCI, RC, CRI-II, AC, CRI-I and non-HDL-C) are effective predictors of intracranial and extracranial atherosclerotic stenosis, of which AIP may be a significant risk factor for predicting atherosclerotic arterial stenosis in the intracranial or extracranial regions.

Comparative study on classifications of AJCC 8th and 7th in the patients with tongue squamous cell carcinoma.

OBJECTIVES: Depth of invasion (DOI) is the most important predictor for lymph node metastasis in early-stage oral cancer. This study aims to investigate the effects of the different classifications of AJCC 7th and 8th on predicting lymph node metastasis and the optimal cutoff point for DOI predicting the lymph node metastasis in patients with tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: We performed a retrospective study in 208 TSCC patients in early T stage without clinical or radiological signs of lymph node metastasis. Those patients were treated with elective neck dissection (END) between April 2019 and December 2020. And the relation between DOI and lymph node metastasis was analyzed. RESULTS: Metastases were found in 58 of 208 patients (27.88%). Of those 58 patients, the mean DOI was 8.311 mm compared to 5.425 mm in patients without metastases (p < 0.0001). The receiver operating characteristic curve (ROC curve) showed an area under the curve of 0.7066 with the most optimal cutoff point on a DOI of 4.050 mm (sensitivity 86.21%, specificity 52%). Linear regression analysis (1 mm ≤ DOI ≤6 mm) revealed that a DOI ≥ 3.211 mm predicated an incidence of occult lymph node metastasis greater than 20%. Regional metastases were found in 12.82% of patients with DOI ≤ 4.0 mm. Within the entire cohort, 60 cases (28.85%) got upgraded with respect to T stage. No tumor underwent downstaging. CONCLUSION: The 8th edition provides better lymph node metastasis prediction for TSCC than the 7th. And DOI is a poor predictor for regional metastasis in patients with early T stage clinically node-negative TSCC. END in patients with early-stage TSCC should be performed in patients with DOI ≥ 3.211 mm.

Discovery of coumaric acid derivatives hinted by coastal marine source to seek for uric acid lowering agents.

In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 µM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 µM in the hyperuricemic model mice (723.0 µM), comparable with Allopurinol (325.8 µM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health.

Development of Combretastatin A-4 Analogues as Potential Anticancer Agents with Improved Aqueous Solubility.

Combretastatin A-4 (CA-4) is a potent tubulin polymerisation inhibitor. However, the clinical application of CA-4 is limited owing to its low aqueous solubility and the easy conversion of the olefin double bond from the more active cis- to the less active trans-configuration. Several structural modifications were investigated to improve the solubility of CA-4 derivatives. Among the compounds we synthesized, the kinetic solubility assay revealed that the solubility of compounds containing a piperazine ring increased the most, and the solubility of compounds 12a1, 12a2, 15 and 18 was increased 230-2494 times compared with that of the control compound (Z)-3-(4-aminophenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (9a). In addition, these synthesised stilbene nitriles had high anticancer cell (AGS, BEL-7402, MCF-7, and HCT-116) selectivity over L-02 and MCF-10A normal cells while maintaining micromolar activity against cancer cells. The most cytotoxic compound is 9a, and the IC50 value is 20 nM against HCT-116 cancer cells. Preliminary studies indicated that compound 12a1 had excellent plasma stability and moderate binding to rat plasma proteins, suggesting it is a promising lead compound for the development of an anticancer agent.

Fabrication of biologically inspired electrospun collagen/silk fibroin/bioactive glass composited nanofibrous to accelerate the treatment efficiency of wound repair.

A triple-layer matrix Collagen/Silk fibroin/Bioactive glass composited Nanofibrous was fabricated by linking electrospinning and freeze-drying systems, this typical three layered composite with a nanofibrous fragment as the key (top) layer, middle portion as inferior, and a spongy porous fragment as the third (bottom) deposit to develop the synergistic effect of composite materials resultant to physical and biological performances. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy were used to assess the final material's physicochemical properties (SEM). The triple-layer matrix had a nanofibrous and porous structure, which has qualities including high porosity, swelling, and stability, which are important in soft-tissue engineering. NIH 3 T3 fibroblast and humanoid keratinocyte (HaCaT) cell lines were also used to investigate the matrix's in vitro biological and fluorescent capabilities, which showed excellent cell adherence and proliferation across the composite layers. The synergistic arrangement of nanofibrous substantial deposition onto collagenous with silk fibroin candidates has therefore proven effective in the construction of a tri-layer matrix for skin-tissue-engineering applications.

Multifunctional Fluorescent Probe for Simultaneously Detecting Microviscosity, Micropolarity, and Carboxylesterases and Its Application in Bioimaging.

Based on OR logic gate, we proposed a smart near-infrared (NIR) fluorescent probe, named VPCPP, for simultaneously monitoring local microviscosity, micropolarity, and carboxylesterases (CEs) in living cells through blue and red channels. This proposed probe was capable of distinguishing cancer cells from normal cells and had good potential for identifying living liver cell lines. Furthermore, the fluctuations of the three analytes of interest in different cell status was successfully explored. Particularly, facilitated with high-content analysis (HCA) and VPCPP, a simple and efficient high-throughput screening (HTS) platform was first constructed for screening antitumor drugs and studying their effect on the analytes. For the first time, we found that sorafenib-induced ferroptosis led to an increase in the microviscosity and up-regulation of CEs at the same time. Additionally, the procedure that aristolochic acid (AA) induced the overexpression of CEs was verified. Besides, VPCPP was utilized for imaging the variations of the two microenvironment parameters and CEs in the inflammation model. Finally, VPCPP was able to image the tumor ex vivo and in vivo through two channels and one channel separately, as well as to visualize the kidneys and liver ex vivo with dual emissions, which indicated that the probe had great potential for imaging applications such as medical diagnosis, preclinical research, and imaging-guided surgery.

Time-Resolved SAXS Study of Polarity- and Surfactant-Controlled Superlattice Transformations of Oleate-Capped Nanocubes During Solvent Removal.

Structural transformations and lattice expansion of oleate-capped iron oxide nanocube superlattices are studied by time-resolved small-angle X-ray scattering (SAXS) during solvent removal. The combination of conductor-like screening model for real solvents (COSMO-RS) theory with computational fluid dynamics (CFD) modeling provides information on the solvent composition and polarity during droplet evaporation. Evaporation-driven poor-solvent enrichment in the presence of free oleic acid results in the formation of superlattices with a tilted face-centered cubic (fcc) structure when the polarity reaches its maximum. The tilted fcc lattice expands subsequently during the removal of the poor solvent and eventually transforms to a regular simple cubic (sc) lattice during the final evaporation stage when only free oleic acid remains. Comparative studies show that both the increase in polarity as the poor solvent is enriched and the presence of a sufficient amount of added oleic acid is required to promote the formation of structurally diverse superlattices with large domain sizes.

The gibberellic acid derived from the plastidial MEP pathway is involved in the accumulation of Bamboo mosaic virus.

A gene upregulated in Nicotiana benthamiana after Bamboo mosaic virus (BaMV) infection was revealed as 1-deoxy-d-xylulose-5-phosphate reductoisomerase (NbDXR). DXR is the key enzyme in the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway that catalyzes the conversion of 1-deoxy-d-xylulose 5-phosphate to 2-C-methyl-d-erythritol-4-phosphate. Knockdown and overexpression of NbDXR followed by BaMV inoculation revealed that NbDXR is involved in BaMV accumulation. Treating leaves with fosmidomycin, an inhibitor of DXR function, reduced BaMV accumulation. Subcellular localization confirmed that DXR is a chloroplast-localized protein by confocal microscopy. Furthermore, knockdown of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase, one of the enzymes in the MEP pathway, also reduced BaMV accumulation. The accumulation of BaMV increased significantly in protoplasts treated with isopentenyl pyrophosphate. Thus, the metabolites of the MEP pathway could be involved in BaMV infection. To identify the critical components involved in BaMV accumulation, we knocked down the crucial enzyme of isoprenoid synthesis, NbGGPPS11 or NbGGPPS2. Only NbGGPPS2 was involved in BaMV infection. The geranylgeranyl pyrophosphate (GGPP) synthesized by NbGGPPS2 is known for gibberellin synthesis. We confirmed this result by supplying gibberellic acid exogenously on leaves, which increased BaMV accumulation. The de novo synthesis of gibberellic acid could assist BaMV accumulation.

Formononetin inhibits inflammation and promotes gastric mucosal angiogenesis in gastric ulcer rats through regulating NF-κB signaling pathway.

To investigate the effects of formononetin on rats with gastric ulcer and further to explore its possible mechanism. Rats were randomly divided into sham operation group (Sham), model group (Model), omeprazole control group (Omeprazole) and formononetin in different dose groups (FOR-L, FOR-M, FOR-H). Rats model with gastric ulcer were established by 100% glacial acetic acid. Hematoxylin-eosin (H&E) staining was used to observe the pathological morphology of gastric mucosa. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to detect the level of inflammatory and angiogenesis related factors. The expressions of nuclear factor kappa-B (NF-κB) signaling pathway-related proteins were detected by western blot. Formononetin and omeprazole could ameliorate the pathological morphology of gastric mucosa in gastric ulcer rats. Compared with Model group, the levels of tumor necrosis factor (TNF)-α, Interleukin (IL)-1ß, IL-6, myeloperoxidase (MPO), human endothelin (ET)-1 and p-P65 protein in formononetin treatment and omeprazole groups were significantly decreased (p < 0.05). Moreover, formononetin could increase the content of vascular endothelial growth factor (VEGF), nitric oxide (NO) and the levels of CD34, tight junction proteins (ZO-1 and occludin) and p-IκBα in a dose-dependent manner. Formononetin can ameliorate gastric ulcer in rats by inhibiting inflammation and promoting gastric mucosal angiogenesis, and its mechanism maybe related to NF-κB signaling pathway.