Ion entropy and accurate entropy-based FDR estimation in metabolomics.

Accurate metabolite annotation and false discovery rate (FDR) control remain challenging in large-scale metabolomics. Recent progress leveraging proteomics experiences and interdisciplinary inspirations has provided valuable insights. While target-decoy strategies have been introduced, generating reliable decoy libraries is difficult due to metabolite complexity. Moreover, continuous bioinformatics innovation is imperative to improve the utilization of expanding spectral resources while reducing false annotations. Here, we introduce the concept of ion entropy for metabolomics and propose two entropy-based decoy generation approaches. Assessment of public databases validates ion entropy as an effective metric to quantify ion information in massive metabolomics datasets. Our entropy-based decoy strategies outperform current representative methods in metabolomics and achieve superior FDR estimation accuracy. Analysis of 46 public datasets provides instructive recommendations for practical application.

How Much Storage Precision Can Be Lost: Guidance for Near-Lossless Compression of Untargeted Metabolomics Mass Spectrometry Data.

Several lossy compressors have achieved superior compression rates for mass spectrometry (MS) data at the cost of storage precision. Currently, the impacts of precision losses on MS data processing have not been thoroughly evaluated, which is critical for the future development of lossy compressors. We first evaluated different storage precision (32 bit and 64 bit) in lossless mzML files. We then applied 10 truncation transformations to generate precision-lossy files: five relative errors for intensities and five absolute errors for m/z values. MZmine3 and XCMS were used for feature detection and GNPS for compound annotation. Lastly, we compared Precision, Recall, F1 - score, and file sizes between lossy files and lossless files under different conditions. Overall, we revealed that the discrepancy between 32 and 64 bit precision was under 1%. We proposed an absolute m/z error of 10-4 and a relative intensity error of 2 × 10-2, adhering to a 5% error threshold (F1 - scores above 95%). For a stricter 1% error threshold (F1 - scores above 99%), an absolute m/z error of 2 × 10-5 and a relative intensity error of 2 × 10-3 were advised. This guidance aims to help researchers improve lossy compression algorithms and minimize the negative effects of precision losses on downstream data processing.

Impact of the timing of metformin administration on glycaemic and glucagon-like peptide-1 responses to intraduodenal glucose infusion in type 2 diabetes: a double-blind, randomised, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: Metformin lowers postprandial glycaemic excursions in individuals with type 2 diabetes by modulating gastrointestinal function, including the stimulation of glucagon-like peptide-1 (GLP-1). The impact of varying the timing of metformin administration on postprandial glucose metabolism is poorly defined. We evaluated the effects of metformin, administered at different intervals before an intraduodenal glucose infusion, on the subsequent glycaemic, insulinaemic and GLP-1 responses in metformin-treated type 2 diabetes. METHODS: Sixteen participants with type 2 diabetes that was relatively well-controlled by metformin monotherapy were studied on four separate days in a crossover design. On each day, participants were randomised to receive a bolus infusion of metformin (1000 mg in 50 ml 0.9% saline) via a nasoduodenal catheter at t = -60, -30 or 0 min (and saline at the other timepoints) or saline at all timepoints (control), followed by an intraduodenal glucose infusion of 12.56 kJ/min (3 kcal/min) at t = 0-60 min. The treatments were blinded to both participants and investigators involved in the study procedures. Plasma glucose, insulin and total GLP-1 levels were measured every 30 min between t = -60 min and t = 120 min. RESULTS: There was a treatment-by-time interaction for metformin in reducing plasma glucose levels and increasing plasma GLP-1 and insulin levels (p<0.05 for each). The reduction in plasma glucose levels was greater when metformin was administered at t = -60 or -30 min vs t = 0 min (p<0.05 for each), and the increases in plasma GLP-1 levels were evident only when metformin was administered at t = -60 or -30 min (p<0.05 for each). Although metformin did not influence insulin sensitivity, it enhanced glucose-induced insulin secretion (p<0.05), and the increases in plasma insulin levels were comparable on the 3 days when metformin was given. CONCLUSIONS/INTERPRETATION: In well-controlled metformin-treated type 2 diabetes, glucose-lowering by metformin is greater when it is given before, rather than with, enteral glucose, and this is associated with a greater GLP-1 response. These observations suggest that administration of metformin before meals may optimise its effect in improving postprandial glycaemic control. TRIAL REGISTRATION: www.anzctr.org.au ACTRN12621000878875 FUNDING: The study was not funded by a specific research grant.

Effects of a bitter substance, denatonium benzoate, on pancreatic hormone secretion.

There is increasing evidence linking bitter taste receptor (BTR) signaling to gut hormone secretion and glucose homeostasis. However, its effect on islet hormone secretion has been poorly characterized. This study investigated the effect of the bitter substance, denatonium benzoate (DB), on hormone secretion from mouse pancreatic islets and INS-1 832/13 cells. DB (0.5-1 mM) augmented insulin secretion at both 2.8 mM and 16.7 mM glucose. This effect was no longer present at 5 mM DB likely due to the greater levels of cellular apoptosis. DB-stimulated insulin secretion involved closure of the KATP channel, activation of T2R signaling in beta-cells, and intraislet glucagon-like peptide-1 (GLP-1) release. DB also enhanced glucagon and somatostatin secretion, but the underlying mechanism was less clear. Together, this study demonstrates that the bitter substance, DB, is a strong potentiator of islet hormone secretion independent of glucose. This observation highlights the potential for widespread off-target effects associated with the clinical use of bitter-tasting substances.NEW & NOTEWORTHY We show that the bitter substance, denatonium benzoate (DB), stimulates insulin, glucagon, somatostatin, and GLP-1 secretion from pancreatic islets, independent of glucose, and that DB augments insulin release via the KATP channel, bitter taste receptor signaling, and intraislet GLP-1 secretion. Exposure to a high dose of DB (5 mM) induces cellular apoptosis in pancreatic islets. Therefore, clinical use of bitter substances to improve glucose homeostasis may have unintended negative impacts beyond the gut.

Highly Bright and Stable CsPbX3@Cs4PbX6 Hexagonal Nanoarchitectonics Created by Controlling Dissolution-Recrystallization of CsPbX3 Nanomaterials.

CsPbBr3@Cs4PbBr6 hexagonal NCs with a bright photoluminescence (PL) peak of 456 nm are created through the dissolution-recrystallization of CsPbBr3 nanoplatelets. Small CsPbBr3 nanocrystals are encapsulated in hexagonal Cs4PbBr6 during recrystallization to form a core-shell structure and keep high brightness and stability. The recrystallization kinetics is systematically investigated to explore the roles of methyl acetate, oleylamine, and n-hexane. Result further indicates that core/shell NCs remained high PL under a variety of harsh conditions (e.g., light irradiation and heat treatment) because of Cs4PbX6 shell and the controlling of recrystallization. Their initial PL intensity is remained after 4 months of storage under ambient conditions and continuous exposure to UV lamp for 180 min. The bright PL is also maintained even treatment at 120 °C. To indicate the universality of this synthesis method, CsPbX3@Cs4PbX6 hexagonal NCs with different emission colors are fabricated by changing temperature, solvent viscosity, and precursors (e,g, oleylamine and halogens). These core-shell samples reveal bright and stable green, orange, and red PL. Because of its high stability, the core/shell NCs are dispersed in flexible films to create diverse patterns. The films also exhibit high brightness and excellent stability. This strategy opens a novel avenue for the application of perovskite nanomaterials in the display field.

Imaging performance prediction of a hypersonic target in a geosynchronous orbit based on multi-dimensional information correlation of radiation, multi-spectral, and polarization.

Hypersonic target detection based on infrared intensity characteristics is easily disturbed by sea surface and cloud flares when detected by space-based optical systems, which results in a low detection rate, high false alarm, and difficulty in stable detection. This paper explores a method to improve target detection performance based on the correlation of infrared radiation, multi-spectral and polarization. Firstly, the comprehensive factors that influence complex ambient illumination, atmospheric transmission, and clutter background on spectral-polarization characteristics of hypersonic targets are analyzed. Based on the global radiation scattering theory, the temperature distribution model of the hypersonic target is established by using FLUENT. The polarization emission and pBRDF model of the target is established, and the radiation polarization transfer model is generated. Secondly, the sea surface temperature distribution is obtained by inversion of Landsat8 remote sensing data. The radiation polarization transfer model of the sea surface is established based on the Cox-Munk model combined with pBRDF and the polarization emission model. Thirdly, the polarization scattering effect of atmospheric particles on the upward radiation of the interaction of the target with the sunlight is considered comprehensively, and the 6SV radiative transfer model is used to calculate the polarization effect of atmospheric particles on the upward radiation transmission of the target and the background. Then, combined with the point diffusion of the optical system and the photoelectric conversion of the detector, the multi-dimensional full-chain imaging prediction model of the hypersonic target-sea background-ambient atmosphere-optical system-detector is established. The imaging characteristics and detection performance of the target in different imaging dimensions are simulated and analyzed with the signal-to-clutter ratio (SCR). The research shows that in the direction of reflected sunlight from the sea surface, the sea surface glare is suppressed and the target is highlighted through a target detection method of multi-dimensional information. This method has better detection results than the infrared multi-spectral detection method.

The Progress of Poststroke Seizures.

A stroke is one of the most common fatal diseases of the nervous system, and the number of strokes per year has increased substantially in recent years. Epilepsy is a poststroke complication that greatly affects the prognosis of patients and reduces their quality of survival. Effective avoidance of causative factors can reduce the risk of a poststroke seizure. However, while many studies have been devoted to elucidating the pathogenesis of poststroke seizures, the literature lacks a comprehensive understanding of the pathogenic mechanism. This article briefly presents the current definition, risk factors, pathogenesis, and prognosis of poststroke seizures based on reported studies and literature reviews, aiming to enrich the available knowledge of this disease.

Gastric emptying in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes and the impact of 4-week insulin pump therapy.

AIM: To evaluate gastric emptying (GE) and the glycaemic response to a 75-g oral glucose load in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12-15 months after insulin pump therapy. MATERIALS AND METHODS: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75-g glucose drink containing 150 mg 13C-acetate, to determine the gastric half-emptying time, and underwent assessment of plasma glucose and serum insulin, C-peptide and glucagon-like peptide-1 (GLP-1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re-assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12-15 months, GE was re-measured in 14 of the T2D participants. RESULTS: At baseline, participants with T2D exhibited substantially augmented fasting and post-glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP-1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP-1 secretion was attenuated, fasting and post-glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12-15 months of follow-up. CONCLUSIONS: In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short-term insulin pump therapy. The effect on GE is maintained for at least 12 months.

Gastric emptying is slower in women than men with type 2 diabetes and impacts on postprandial glycaemia.

AIM: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). METHODS: In cohort 1, 70 newly diagnosed, treatment-naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75-g glucose drink containing 150 mg 13C-acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi-solid mashed potato meal, labelled with 100 µl 13C-octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). RESULTS: Gastric emptying was slower in female than male subjects in both cohorts (both p < .01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p < .05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p < .001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p < .05). CONCLUSIONS: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume-adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D.

Randomised comparison of intravenous and subcutaneous routes of glucagon-like peptide-1 administration for lowering plasma glucose in hyperglycaemic subjects with type 2 diabetes.

AIM: To perform a direct, double-blind, randomised, crossover comparison of subcutaneous and intravenous glucagon-like peptide-1 (GLP-1) in hyperglycaemic subjects with type 2 diabetes naïve to GLP-1-based therapy. MATERIALS AND METHODS: Ten fasted, hyperglycaemic subjects (1 female, age 63 ± 10 years [mean ± SD], glycated haemoglobin 73.5 ± 22.0 mmol/mol [8.9% ± 2.0%], both mean ± SD) received subcutaneous GLP-1 and intravenous saline, or intravenous GLP-1 and subcutaneous saline. Infusion rates were doubled every 120 min (1.2, 2.4, 4.8 and 9.6 pmol·kg-1·min-1 for subcutaneous, and 0.3, 0.6, 1.2 and 2.4 pmol·kg-1·min-1 for intravenous). Plasma glucose, total and intact GLP-1, insulin, C-peptide, glucagon and gastrointestinal symptoms were evaluated over 8 h. The results are presented as mean ± SEM. RESULTS: Plasma glucose decreased more with intravenous (by ~8.0 mmol/L [144 mg/dL]) than subcutaneous GLP-1 (by ~5.6 mmol/L [100 mg/dL]; p < 0.001). Plasma GLP-1 increased dose-dependently, but more with intravenous than subcutaneous for both total (∆max 154.2 ± 3.9 pmol/L vs. 85.1 ± 3.8 pmol/L; p < 0.001), and intact GLP-1 (∆max 44.2 ± 2.2 pmol/L vs. 12.8 ± 2.2 pmol/L; p < 0.001). Total and intact GLP-1 clearance was higher for subcutaneous than intravenous GLP-1 (p < 0.001 and p = 0.002, respectively). The increase in insulin secretion was greater, and glucagon was suppressed more with intravenous GLP-1 (p < 0.05 each). Gastrointestinal symptoms did not differ (p > 0.05 each). CONCLUSIONS: Subcutaneous GLP-1 administration is much less efficient than intravenous GLP-1 in lowering fasting plasma glucose, with less stimulation of insulin and suppression of glucagon, and much less bioavailability, even at fourfold higher infusion rates.

MMP-2-mediated Scube2 degradation promotes blood-brain barrier disruption by blocking the interaction between astrocytes and endothelial cells via inhibiting Sonic hedgehog pathway during early cerebral ischemia.

We have previously demonstrated a rapid secretion of matrix metalloproteinase-2 (MMP-2) in the ischemic brain. Since Scube2 can interact with Sonic hedgehog (Shh) to maintain blood-brain barrier (BBB) integrity via regulating the interaction between brain capillary endothelial cells (ECs) and perivascular astrocytes, and it is also a substrate of MMP-2, we hypothesized that the secreted MMP-2 could degrade Scube2 and contribute to ischemic BBB disruption. Using an in vitro ischemic model of 90-min oxygen-glucose deprivation/3-h reoxygenation (OGD/R) and an in vivo mouse stroke model of 90-min middle cerebral artery occlusion (MCAO) with 3-h reperfusion, we established an important role of MMP-2-mediated Scube2 degradation in early ischemic BBB disruption. Exposure of C8-D1A cells and bEnd.3 cells to OGD/R increased MMP secretion in both cells, and C8-D1A cells appeared to secrete more MMPs than bEnd.3 cells. Co-IP and double-immunostaining revealed that Scube2 co-localized well with MMP-2 in C8-D1A cells and could be pulled down by MMP-2 antibodies. In MCAO mice, Scube2 protein showed a drastic reduction in ischemic brain tissue, which was accompanied by suppressed expression of Shh and its downstream molecules. Of note, specific knockdown of astrocytic Scube2 with AAV-shScube2 augmented MCAO-induced Shh suppression and exacerbated BBB leakage and inflammatory reactions in the ischemic brain. Last, incubation of bEnd.3 cells with conditioned medium derived from OGD-treated C8-D1A cells led to a significant inhibition of the Shh pathway in bEnd.3 cells and degradation of VE-cadherin and ZO-1. Inhibition of MMP-2 with SB-3CT or over-expression of Scube2 with plasmids in C8-D1A cells alleviated the above effect of C8-D1A cells-derived conditioned medium. Taken together, our data indicate that ischemia-induced secretion of MMP-2 may contribute to early BBB disruption in ischemic stroke via interrupting the shared Scube2-Shh pathway between brain capillary ECs and perivascular astrocytes.

Activation of Swell1 in microglia suppresses neuroinflammation and reduces brain damage in ischemic stroke.

Cl- movement and Cl--sensitive signal pathways contributes to the survival and switch of inflammatory phenotype of microglia and are believed to play a key role in the inflammatory brain injury after ischemic stroke. Here, we demonstrated an important role of Cl- transmembrane transporter Swell1, in the survival and M2-like polarization of microglia in ischemic stroke. Knockdown or overexpression of Swell1 in cultured microglia inhibited or increased hypotonic-activated Cl- currents, respectively, and these changes were completely blocked by the volume-regulated anion channels (VRACs) inhibitor DCPIB. Swell1 conditional knock-in mice promoted microglia survival in ischemic brain region and resulted in significant reductions in neural cell death, infarction volume and neurological deficits following transient middle cerebral artery occlusion (tMCAO). Using gene manipulating technique and pharmacological inhibitors, we further revealed that Swell1 opening led to SGK1 (a Cl--sensitive kinase)-mediated activation of FOXO3a/CREB as well as WNK1 (another Cl--sensitive kinase)-mediated SPAK/OSR1-CCCs activation, which promoted microglia survival and M2-like polarization, thereby attenuating neuroinflammation and ischemic brain injury. Taken together, our results demonstrated that Swell1 is an essential component of microglia VRACs and its activation protects against ischemic brain injury through promoting microglia survival and M2-like polarization.

Synthesis-Kinetics of Violet- and Blue-Emitting Perovskite Nanocrystals with High Brightness and Superior Stability toward Flexible Conversion Layer.

The low photoluminescence (PL) efficiency and unstable features of small blue-emitting CsPbX3 nanocrystals (NCs) greatly limit their applications in optoelectronics field. Herein, the synergistic and post-treatment kinetics are studied to create highly bright and anomalous stable violet (peak position of ≈408 nm) and blue (peak position of ∼ 466 nm) emitting perovskite NCs. Ligand and ion exchange mechanism are systematic studied by the evolution of absorption, PL, and fluorescence lifetime to evaluate ligand bonding, defect engineering, and non-radiative recombination. Didodecyl dimethyl mmonium chloride (DDAC) and CuX2 post-synergistic treatment created DDAC-CsPbCl3 -CuCl2 and DDAC-CsPbCl3 -CuBr2 NCs that remained the phase composition, morphology, and size of CsPbCl3 NCs. The PL efficiencies are drastically increased to 42 and 85% for violet- and blue-emitting NCs, respectively. The stability test indicated that the NCs enable against various harsh conditions (e.g., ultraviolet light irradiation and heat-treatment). The NCs retained their initial PL efficiency after 2 months under ambient conditions and UV light irradiation. These NCs also exhibited high stability after heat-treatment at 120 °C. The emitting NCs embedded in flexible films still revealed bright PL and high stability, suggesting current results provide a new avenue for the application in the field of optoelectronics.

MetaPro: a web-based metabolomics application for LC-MS data batch inspection and library curation.

INTRODUCTION: Metabolomics analysis based on liquid chromatography-mass spectrometry (LC-MS) has been a prevalent method in the metabolic field. However, accurately quantifying all the metabolites in large metabolomics sample cohorts is challenging. The analysis efficiency is restricted by the abilities of software in many labs, and the lack of spectra for some metabolites also hinders metabolite identification. OBJECTIVES: Develop software that performs semi-targeted metabolomics analysis with an optimized workflow to improve quantification accuracy. The software also supports web-based technologies and increases laboratory analysis efficiency. A spectral curation function is provided to promote the prosperity of homemade MS/MS spectral libraries in the metabolomics community. METHODS: MetaPro is developed based on an industrial-grade web framework and a computation-oriented MS data format to improve analysis efficiency. Algorithms from mainstream metabolomics software are integrated and optimized for more accurate quantification results. A semi-targeted analysis workflow is designed based on the concept of combining artificial judgment and algorithm inference. RESULTS: MetaPro supports semi-targeted analysis workflow and functions for fast QC inspection and self-made spectral library curation with easy-to-use interfaces. With curated authentic or high-quality spectra, it can improve identification accuracy using different peak identification strategies. It demonstrates practical value in analyzing large amounts of metabolomics samples. CONCLUSION: We offer MetaPro as a web-based application characterized by fast batch QC inspection and credible spectral curation towards high-throughput metabolomics data. It aims to resolve the analysis difficulty in semi-targeted metabolomics.

Prediction of H3K27M Alteration Status in Brainstem Glioma Using Multi-Shell Diffusion MRI Metrics.

BACKGROUND: Multi-shell diffusion characteristics may help characterize brainstem gliomas (BSGs) and predict H3K27M status. PURPOSE: To identify the diffusion characteristics of BSG patients and investigate the predictive values of various diffusion metrics for H3K27M status in BSG. STUDY TYPE: Prospective. POPULATION: Eighty-four BSG patients (median age 10.5 years [IQR 6.8-30.0 years]) were included, of whom 56 were pediatric and 28 were adult patients. FIELD STRENGTH/SEQUENCE: 3 T, multi-shell diffusion imaging. ASSESSMENT: Diffusion kurtosis imaging and neurite orientation dispersion and density imaging analyses were performed. Age, gender, and diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis, intracellular volume fraction (ICVF), orientation dispersion index, and isotropic volume fraction (ISOVF), were compared between H3K27M-altered and wildtype BSG patients. STATISTICAL TESTS: Chi-square test, Mann-Whitney U test, multivariate analysis of variance (MANOVA), step-wise multivariable logistic regression. P-values <0.05 were considered significant. RESULTS: 82.4% pediatric and 57.1% adult patients carried H3K27M alteration. In the whole group, the H3K27M-altered BSGs demonstrated higher FA, AK and lower RD, ISOVF. The combination of age and median ISOVF showed fair performance for H3K27M prediction (AUC = 0.78). In the pediatric group, H3K27M-altered BSGs showed higher FA, AK, MK, ICVF and lower RD, MD, ISOVF. The combinations of median ISOVF, 5th percentile of FA, median MK and median MD showed excellent predictive power (AUC = 0.91). In the adult group, H3K27M-altered BSGs showed higher ICVF and lower RD, MD. The 75th percentile of RD demonstrated fair performance for H3K27M status prediction (AUC = 0.75). DATA CONCLUSION: Different alteration patterns of diffusion measures were identified between H3K27M-altered and wildtype BSGs, which collectively had fair to excellent predictive value for H3K27M alteration status, especially in pediatric patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Potassium-Derived Charge Channels in Boron-Doped g-C3N4 Nanosheets for Photocatalytic NO Oxidation and Hydrogen Evolution.

The application of graphitic carbon nitride (g-C3N4) in photocatalytic NO oxidation was limited due to severe recombination of photogenerated carriers and low concentration of oxidizing species. In this work, K and B were introduced into the interlayer and in-plane framework of g-C3N4 to address this challenge through the thermal polymerization process. The synthesized K-doped B-g-C3N4 nanosheets exhibited expanded light absorption and low charge recombination efficiency. In addition, the doping of K and B reduced the band gap of g-C3N4, which corresponded to enhanced light absorption. B was introduced into the in-plane structure by replacing C atoms, which adjusted the in-plane electron distribution. K was inserted into the interlayer by binding to the N and C atoms of adjacent layers. K-derived electron transfer channels were constructed, which increased electron delocalization and expanded the π-conjugate system. More electrons were transferred through the interlayer channels and were involved in the reaction process. The severe carrier recombination and weak transfer were improved due to the synergistic effect of K and B doping. K-doped B-g-C3N4 nanosheets exhibited enhanced generation of superoxide radicals and hydroxyl radicals, which played a key role during NO oxidation. The photocatalytic NO oxidation efficiency of codoped g-C3N4 nanosheets reached 61%, which was 2.1 and 1.2 times of that of pristine g-C3N4 and B-doped g-C3N4, respectively. The codoped g-C3N4 sample still exhibited stable photocatalytic NO oxidation efficiency after five cycles. This result provided a potential idea for improving the charge distribution and transfer of layered materials by codoping metallic and nonmetallic elements and for photocatalytic NO oxidation.

Amide proton transfer-weighted imaging and derived radiomics in the classification of adult-type diffuse gliomas.

OBJECTIVES: To evaluate the utility of amide proton transfer-weighted (APTw) MRI imaging and its derived radiomics in classifying adult-type diffuse glioma. MATERIALS AND METHODS: In this prospective study, APTw imaging was performed on 129 patients with adult-type diffuse gliomas. The mean APTw-related metrics (chemical exchange saturation transfer ratio (CESTR), CESTR normalized with the reference value (CESTRnr), and relaxation-compensated inverse magnetization transfer ratio (MTRRex)) and radiomic features within 3D tumor masks were extracted. APTw-radiomics models were developed using a support vector machine (SVM) classifier. Sensitivity analysis with tumor area of interest, different histogram cutoff values, and other classifiers were conducted. RESULTS: CESTR, CESTRnr, and MTRRex in glioblastomas were all significantly higher (p < 0.0003) than those of oligodendrogliomas and astrocytomas, with no significant difference between oligodendrogliomas and astrocytomas. The APTw-related metrics for IDH-wildtype and high-grade gliomas were significantly higher (p < 0.001) than those for the IDH-mutant and low-grade gliomas, with area under the curve (AUCs) of 0.88 for CESTR. The CESTR-radiomics models demonstrated accuracies of 84% (AUC 0.87), 83% (AUC 0.83), 90% (AUC 0.95), and 84% (AUC 0.86) in predicting the IDH mutation status, differentiating glioblastomas from astrocytomas, distinguishing glioblastomas from oligodendrogliomas, and determining high/low grade prediction, respectively, but showed poor performance in distinguishing oligodendrogliomas from astrocytomas (accuracy 63%, AUC 0.63). The sensitivity analysis affirmed the robustness of the APTw signal and APTw-derived radiomics prediction models. CONCLUSION: APTw imaging, along with its derived radiomics, presents a promising quantitative approach for prediction IDH mutation and grading adult-type diffuse glioma. CLINICAL RELEVANCE STATEMENT: Amide proton transfer-weighted imaging, a quantitative imaging biomarker, coupled with its derived radiomics, offers a promising non-invasive approach for predicting IDH mutation status and grading adult-type diffuse gliomas, thereby informing individualized clinical diagnostics and treatment strategies. KEY POINTS: • This study evaluates the differences of different amide proton transfer-weighted metrics across three molecular subtypes and their efficacy in classifying adult-type diffuse glioma. • Chemical exchange saturation transfer ratio normalized with the reference value and relaxation-compensated inverse magnetization transfer ratio effectively predicts IDH mutation/grading, notably the first one. • Amide proton transfer-weighted imaging and its derived radiomics holds potential to be used as a diagnostic tool in routine clinical characterizing adult-type diffuse glioma.

Composite nanoarchitectonics with TiO2 nanocrystals and superior thin Ti3C2Tx nanosheets towards efficient NO removal.

Accordion-like Ti3C2Tx MXene supplied a possibility to construct two-dimensional composites with novel performance. In this paper, few-layered Ti3C2Tx MXene was created via a chemical etching strategy. The oxidation in-situ using a powerful alkaline solution resulted successfully in TiO2 nanocrystals grown on Ti3C2Tx nanosheets. The alkaline treatment adjusted terminations of the Ti3C2Tx MXene and controlled the oxidation degree by changing temperature. The ratio of Ti3C2Tx and TiO2 was finally optimized. Because of Ti3C2Tx nanosheets with well conductivity and excellent light absorption as well as TiO2 nanocrystal arrays on Ti3C2Tx nanosheets with a high specific surface area and more active sites, TiO2/Ti3C2Tx composites revealed excellent photocatalystic activity, especially for NO removal. The improvement of separation and transfer efficiency of phootogenerated carriers is ascribed to the microstructure of TiO2/Ti3C2Tx composites. The composite sample synthesized at 75 °C revealed the best NO removal efficiency, in which 70% of NO was removed at a concentration of 600 ppb. This study offers a new thought for preparing high performance MXene-based photocatalysts.

Experimental and computational models to investigate intestinal drug permeability and metabolism.

Oral administration is the preferred route for drug administration that leads to better therapy compliance. The intestine plays a key role in the absorption and metabolism of oral drugs, therefore, new intestinal models are being continuously proposed, which contribute to the study of intestinal physiology, drug screening, drug side effects, and drug-drug interactions.Advances in pharmaceutical processes have produced more drug formulations, causing challenges for intestinal models. To adapt to the rapid evolution of pharmaceuticals, more intestinal models have been created. However, because of the complexity of the intestine, few models can take all aspects of the intestine into account, and some functions must be sacrificed to investigate other areas. Therefore, investigators need to choose appropriate models according to the experimental stage and other requirements to obtain the desired results.To help researchers achieve this goal, this review summarised the advantages and disadvantages of current commonly used intestinal models and discusses possible future directions, providing a better understanding of intestinal models.

Pulmonary fibrosis model of mice induced by different administration methods of bleomycin.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease of the lung. How to build a typical human mimicking animal model has been a challenge. Thus, to reveal the mechanism and to make it useful for IPF clinical treatment, a different type of mice model and inspection methods are used to evaluate which one is applicable for the study of IPF. METHOD: 69 Twelve-weeks-old C57BL/6 mice were divided into 3 type groups (n = 7 for each control group, n = 8 for each BLM-induced pulmonary fibrosis groups), as intraperitoneal injection, intratracheal administration, and intravenous administration of bleomycin (BLM) to initiate lung fibrosis. Changes of the lung function measured through mice Pulmonary function test (PFT). Morphological changes in mice were observed by PET/CT, Masson and Picro-Sirius staining, Transmission electron microscopy (TEM). Biochemical changes were tested by Enzyme-linked immunosorbent assay (Elisa). RESULTS: PET/CT of BLM-receiving mice showed an increase in fibrotic consolidations and an increase in non-aerated lung area in BLM-treated mice compared with that in controls. TGF-b1, TNF-a, IL-6, GM-CSF in BALF and serum. PAI-1, HYP in the lung tissue of mice were significantly different in each BLM groups than those in the controls. The results of Masson staining in mice indicate that the lung tissues of all BLM received groups, the intratracheal groups, the intravenous groups, and the intraperitoneal groups have a higher degree of pulmonary septal thickening and collagen fiber consolidation compare to saline control. Picro-Sirius staining results are consistent with the results of Masson staining. Compared with the saline control group, the ratio of Col 1/Col 3 was significantly increased in each BLM group. TEM results found that in BLM group, type I alveolar epithelial cells were degenerated. Exfoliated endothelial cells were swelling, and type II alveolar epithelial cells were proliferated, the shape of the nucleus was irregular, and some tooth-like protrusions were seen. CONCLUSIONS: With three different methods of animal model construction, high dose of each show more compliable, and BLM can successfully induce animal models of pulmonary fibrosis, however, certain differences in the fibrosis formation sites of them three, and tail vein injection of BLM induced PF model is closer to the idiopathic pulmonary interstitial fibrosis.