Development and Validation of a Clinical Nomogram for Predicting Complications From Pediatric Multiple Magnet Ingestion: A Large Retrospective Study.

INTRODUCTION: This study aimed to develop and validate a reliable nomogram based on clinical factors to predict complications associated with pediatric multiple magnet ingestion, addressing the urgency and controversy surrounding its management. METHODS: Patients aged 0-18 years with multiple magnet ingestion diagnosed at the Shenzhen Children's Hospital between January 2017 and December 2023 were enrolled. Clinical data were analyzed using least absolute shrinkage and selection operator regression and multifactor logistic regression analyses to screen for risk factors. A model was constructed, and a nomogram was plotted. Model performance was evaluated and internally validated using the area under the curve (AUC), Hosmer-Lemeshow test, calibration curve, decision curve analysis, and 1,000 bootstraps. We calculated the optimal cutoff value, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the prediction model. RESULTS: Of the 146 patients, 57 (39.0%) experienced complications. The nomogram included age, multiple ingestions, vomiting, abdominal pain, and abdominal tenderness. The AUC was 0.941, and the internally validated AUC was 0.930. The optimal cutoff value selected as a predictive value was 0.534, with a sensitivity of 82.5%, specificity of 93.3%, positive predictive value of 88.7%, negative predictive value of 89.3%, and accuracy of 89.0%. The Hosmer-Lemeshow test yielded a P value of 0.750. The calibration plot exhibited high consistency in prediction, and decision curve analysis showed excellent net benefits. DISCUSSION: Our nomogram demonstrates excellent discrimination, calibration, and clinical utility and may thus help clinicians accurately assess the risk of complications from pediatric multiple magnet ingestion.

Expanding the repertoire of Antibody Drug Conjugate (ADC) targets with improved tumor selectivity and range of potent payloads through in-silico analysis.

Antibody-Drug Conjugates (ADCs) have emerged as a promising class of targeted cancer therapeutics. Further refinements are essential to unlock their full potential, which is currently limited by a lack of validated targets and payloads. Essential aspects of developing effective ADCs involve the identification of surface antigens, ideally distinguishing target tumor cells from healthy types, uniformly expressed, accompanied by a high potency payload capable of selective targeting. In this study, we integrated transcriptomics, proteomics, immunohistochemistry and cell surface membrane datasets from Human Protein Atlas, Xenabrowser and Gene Expression Omnibus utilizing Lantern Pharma's proprietary AI platform Response Algorithm for Drug positioning and Rescue (RADR®). We used this in combination with evidence based filtering to identify ADC targets with improved tumor selectivity. Our analysis identified a set of 82 targets and a total of 290 target indication combinations for effective tumor targeting. We evaluated the impact of tumor mutations on target expression levels by querying 416 genes in the TCGA mutation database against 22 tumor subtypes. Additionally, we assembled a catalog of compounds to identify potential payloads using the NCI-Developmental Therapeutics Program. Our payload mining strategy classified 729 compounds into three subclasses based on GI50 values spanning from pM to 10 nM range, in combination with sensitivity patterns across 9 different cancer indications. Our results identified a diverse range of both targets and payloads, that can serve to facilitate multiple choices for precise ADC targeting. We propose an initial approach to identify suitable target-indication-payload combinations, serving as a valuable starting point for development of future ADC candidates.

Laccase-mimicking activity of octahedral Mn3O4 nanoparticles and fluorescence of carbon dots as dual-mode signals for the specific detection of arsenic(V) in environmental water samples.

The detrimental growth of water pollutants such as heavy metals has become a life-threatening problem in the modern era. Challenges remain in the development of rapid and accurate methods for detecting pentavalent arsenic [As(V)] in environmental water. The octahedral Mn3O4 nanoparticles (NPs) did not display excellent laccase-mimicking catalytic activity, whereas the adsorbed As(V) on the surface significantly enhanced the catalytic activity. Meanwhile, the quinone imine generated from the substrates 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AAP) catalyzed by octahedral Mn3O4 NPs further quenched the carbon dots fluorescence. Thus, it is possible to establish a fast and accurate dual-mode sensor for detecting As(V). The developed dual-mode method of As(V) detection has good sensitivity and selectivity. The limit of detection for As(V) in colorimetric mode is 6.96 µg·L-1, whereas in the fluorescent mode, it is as low as 2.56 µg·L-1. Moreover, the detection data obtained by the dual-mode method can be validated by each other, thereby ensuring the dependability of the sensing system. The constructed dual-mode method with merits of sensitivity, speed and accuracy can offer a powerful tool for As(V) detection in environmental water. Furthermore, the application of laccase-mimicking activity in dual-mode detection provides new strategies for other environmental hazard detection.

Clinical research of fibroscan ‒ TE-CAP at noninvasive diagnosis of hepatic steatosis in children.

BACKGROUND & AIMS: The authors assess the diagnostic accuracy of the Transient Elastography-Controlled Attenuation Parameter (TE-CAP) in children of Southern China. METHODS: 105 obese or overweight children and adolescents were enrolled in the diagnostic test of TE-CAP assessment of hepatic steatosis using MRI-PDFF. Hepatic steatosis grades S0-S3 were classified. Statistical correlation, agreement and consistency between methods were evaluated. The diagnostic efficiency of TE-CAP was evaluated. The authors used the cutoff value of TE-CAP to detect hepatic steatosis in another 356 children. RESULTS: The Area Under Curve (AUC) of TE-CAP for grade ≥ S1, ≥ S2, and ≥ S3 steatosis were 0.975, 0.984, and 0.997, respectively. For detecting ≥ S1 steatosis, TE-CAP had a sensitivity of 96 % and a specificity of 97 %. For detecting ≥ S2 steatosis, TE-CAP had a sensitivity of 97 % and a specificity of 93 %. For detecting ≥ S3 steatosis, TE-CAP had a sensitivity of 1 and a specificity of 94 %. TE-CAP and MRI-PDFF had a linear correlation (r = 0. 0.87, p < 0.001). The hepatic steatosis was identified in 40.2 % (143/356) of children in which the obesity and overweight were 69.8 % (113/162) and 40.0 % (18/45). CONCLUSION: TE-CAP showed excellent diagnostic accuracy in pediatric hepatic steatosis.

Preliminary study on the ability of the machine learning models based on 18F-FDG PET/CT to differentiate between mass-forming pancreatic lymphoma and pancreatic carcinoma.

PURPOSE: The objective of this study was to preliminarily assess the ability of metabolic parameters and radiomics derived from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to distinguish mass-forming pancreatic lymphoma from pancreatic carcinoma using machine learning. METHODS: A total of 88 lesions from 86 patients diagnosed as mass-forming pancreatic lymphoma or pancreatic carcinoma were included and randomly divided into a training set and a validation set at a 4-to-1 ratio. The segmentation of regions of interest was performed using ITK-SNAP software, PET metabolic parameters and radiomics features were extracted using 3Dslicer and PYTHON. Following the selection of optimal metabolic parameters and radiomics features, Logistic regression (LR), support vector machine (SVM), and random forest (RF) models were constructed for PET metabolic parameters, CT radiomics, PET radiomics, and PET/CT radiomics. Model performance was assessed in terms of area under the curve (AUC), accuracy, sensitivity, and specificity in both the training and validation sets. RESULTS: Strong discriminative ability observed in all models, with AUC values ranging from 0.727 to 0.978. The highest performance exhibited by the combined PET and CT radiomics features. AUC values for PET/CT radiomics models in the training set were LR 0.994, SVM 0.994, RF 0.989. In the validation set, AUC values were LR 0.909, SVM 0.883, RF 0.844. CONCLUSION: Machine learning models utilizing the metabolic parameters and radiomics of 18F-FDG PET/CT show promise in distinguishing between pancreatic carcinoma and mass-forming pancreatic lymphoma. Further validation on a larger cohort is necessary before practical implementation in clinical settings.

Surface-displayed phenolic acid decarboxylase for increased vinylphenolic pyranoanthocyanins in blueberry wine.

During the fruit wine production, phenolic acid decarboxylase (PAD) converts free hydroxycinnamic acid into 4-vinyl derivatives that can then react spontaneously with anthocyanins, generating more stable pyranoanthocyanins that are responsible for the color stability of fruit wine. Nevertheless, the low PAD activity in yeast under the winemaking conditions has largely limited the generation of 4-vinyl derivatives. To bridge this gap, we expressed PAD from Bacillus amyloliquefaciens in Pichia pastoris and surface-displayed it on Saccharomyces cerevisiae. As a result, S. cerevisiae surface-displayed PAD (SDPAD) exhibited an enhanced thermal stability and tolerance to acidic conditions. Fermentation experiments showed that SDPAD can significantly increase the content of vinylphenolic pyranoanthocyanins and thus maintain the color stability of blueberry wine. Our study demonstrated the feasibility of surface display technology for color stability enhancement during the production of blueberry wine, providing a new and effective solution to increase the content of vinylphenolic pyranoanthocyanins in the fruit-based wines.

Isolation, identification, and optimization of conditions for the degradation of four sulfonamide antibiotics and their metabolic pathways in Pseudomonas stutzeri strain DLY-21.

Overuse of sulfonamides in aquaculture and agriculture leads to residual drugs that cause serious pollution of the environment. However, the residues of sulfonamides in the environment are not unique, and the existing microbial degradation technology has a relatively low degradation rate of sulfonamides. Therefore, in this study, a Pseudomonas stutzeri strain (DLY-21) with the ability to degrade four common SAs was screened and isolated from aerobic compost. Under optimal conditions, the DLY-21 strain degraded four sulfonamides simultaneously within 48 h, and the degradation rates were all over 90%, with the average degradation rates of SAs being sulfoxide (SDM) ≈ sulfachloropyridazine (SCP) > sulfa quinoxaline (SQ) > sulfadiazine (SQ). In addition, the main compounds of the strain DLY-21-degrading SAs were identified by LC-MS analysis. On this basis, four detailed reaction pathways for SA degradation were deduced. This is the first report of the use of a P. stutzeri strain to degrade four sulfonamide antibiotics (SQ, SDM, SCP, and SM1), which can improve the removal efficiency of sulfonamide antibiotic pollutants and thus ameliorate environmental pollution. The results showed that DLY-21 had a good degradation effect on four SAs (SQ, SDM, SCP, and SM1).

LP-184, a Novel Acylfulvene Molecule, Exhibits Anticancer Activity against Diverse Solid Tumors with Homologous Recombination Deficiency.

Homologous recombination (HR)-related gene alterations are present in a significant subset of prostate, breast, ovarian, pancreatic, lung, and colon cancers rendering these tumors as potential responders to specific DNA damaging agents. A small molecule acylfulvene prodrug, LP-184, metabolizes to an active compound by the oxidoreductase activity of enzyme prostaglandin reductase 1 (PTGR1), which is frequently elevated in multiple solid tumor types. Prior work demonstrated that cancer cell lines deficient in a spectrum of DNA damage repair (DDR) pathway genes show increased susceptibility to LP-184. Here, we investigated the potential of LP-184 in targeting multiple tumors with impaired HR function and its mechanism of action as a DNA damaging agent. LP-184 induced elevated DNA double-strand breaks in HR deficient (HRD) cancer cells. Depletion of key HR components BRCA2 or ataxia telangiectasia mutated (ATM) in cancer cells conferred up to 12-fold increased sensitivity to the LP-184. LP-184 showed nanomolar potency in a diverse range of HRD cancer models, including prostate cancer organoids, leiomyosarcoma cell lines, and patient-derived tumor graft models of lung, pancreatic, and prostate cancers. LP-184 demonstrated complete, durable tumor regression in 10 patient-derived xenograft (PDX) models of HRD triple-negative breast cancer (TNBC) including those resistant to PARP inhibitors (PARPi). LP-184 further displayed strong synergy with PARPi in ovarian and prostate cancer cell lines as well as in TNBC PDX models. These preclinical findings illustrate the potential of LP-184 as a pan-HRD cancer therapeutic. Taken together, our results support continued clinical evaluation of LP-184 in a large subset of HRD solid tumors. SIGNIFICANCE: New agents with activity against DDR-deficient solid tumors refractory to standard-of-care therapies are needed. We report multiple findings supporting the potential for LP-184, a novel alkylating agent with three FDA orphan drug designations, to fill this void clinically: strong nanomolar potency; sustained, durable regression of solid tumor xenografts; synthetic lethality with HR defects. LP-184 adult phase IA trial to assess safety in advanced solid tumors is ongoing.

18F-FDG PET/CT assists the diagnosis of primary pancreatic lymphoma: Two case reports and literature review.

Primary pancreatic lymphoma (PPL) is a rare malignancy, which is defined as a mass centered in pancreas with involvement of contiguous lymph nodes and distant spread may exist. Accurate diagnosis of PPL prior to pathological confirmation remains challenging, underscoring the critical significance of preoperative imaging assessments. This case report collected two instances of PPL that underwent initial evaluation via 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) between August 2021 and July 2022. Correspondingly, pertinent literature encompassing 18F-FDG PET/CT data related to PPL was meticulously reviewed. Including our aforementioned pair of cases, a cumulative total of 25 instances of PPL were assembled. The distinctive profile of 18F-FDG PET/CT images of PPL predominantly manifests as hypermetabolic lesions with diminished density. Primarily characterized by singular lesions and comparatively substantial volumetric dimensions, a total of eleven cases revealed contiguous lymph node engagement, with five instances displaying distant dissemination encompassing lymph nodes in multiple locations. Amongst these, ten patients underwent sequential 18F-FDG PET/CT follow-up post-intervention. In comparison to pancreatic carcinoma, PPL lesions exhibited heightened hypermetabolism, augmented volumetric proportions, and distinct patterns of distant metastasis. This study indicates that the pivotal role of 18F-FDG PET/CT in the diagnosis and assessment of therapeutic efficacy in PPL is unequivocal. Combined with the clinical attributes of patients, the integration of 18F-FDG PET/CT augments the differential diagnostic capacity differentiating PPL from pancreatic carcinoma.

Insight into the role of heterogeneous Fenton-like catalyst FeCo-γ-Al2O3 with dual electron-rich centers for Ni-EDTA removal.

To enhance the polarization distribution of electron cloud density on the catalyst surface, we have introduced a novel bimetallic-substituted dual-reaction center (DRC) catalyst (FeCo-γ-Al2O3) comprising iron (Fe) and cobalt (Co) for the decomplexation and mineralization of heavy metal complex Ni-EDTA in this study. Compared to the catalysts doped solely with Fe or Co, the bimetal-doped catalyst offered several advantages, including enhanced electron cloud polarization distribution, additional electron transfer pathway, and improved capacity of free radical generation. Through DFT calculations and EPR tests, we have elucidated the influences of the catalyst's adsorption toward Ni-EDTA and its decomplexation products on the electron transfer between the pollutant and the catalyst. The competition between the pollutants and H2O2 affects the generation of free radicals in both electron-rich Fe and Co centers as well as electron-deficient Al center. Building on these findings, we have proposed a plausible removal mechanism of Ni-EDTA using the heterogeneous Fenton-like catalyst FeCo-γ-Al2O3. This study sheds light on the potential of FeCo-γ-Al2O3 as a DRC catalyst and emphasizes the significance of pollutant characteristics in determining the catalyst's performance.

Airborne microorganisms and key environmental factors shaping their community patterns in the core production area of the Maotai-flavor Baijiu.

Airborne microorganisms are important parts of the Moutai-flavor Baijiu brewing microbial community, which directly affects the quality of Baijiu. However, environmental factors usually shape airborne microbiomes in different distilleries, even in the different production areas of the same distillery. Unfortunately, current understanding of environmental factors shaping airborne microbiomes in distilleries is very limited. To bridge this gap, we compared airborne microbiomes in the Moutai-flavor Baijiu core production areas of different distilleries in the Chishui River Basin and systematically investigated the key environmental factors that shape the airborne microbiomes. The top abundant bacterial communities are mainly affiliated to the phyla Actinobacteriota, Firmicutes, and Proteobacteri, whereas Ascomycota and Basidiomycota are the predominant fungal communities. The Random Forest analysis indicated that the biomarkers in three distilleries are Saccharomonospora and Bacillus, Thermoactinomyces, Oceanobacillus, and Methylobacterium, which are the core functional flora contributing to the production of Daqu. The correlation and network analyses showed that the distillery age and environmental temperature have a strong regulatory effect on airborne microbiomes, suggesting that the fermentation environment has a domesticating effect on air microbiomes. Our findings will greatly help us understand the relationship between airborne microbiomes and environmental factors in distilleries and support the production of the high-quality Moutai-flavor Baijiu.

Enhancement of pyranoanthocyanin formation in blueberry wine with non-Saccharomyces yeasts.

The development of blueberry wine provides an alternative method for maintaining the nutritional value and extending the shelf life of blueberries. However, anthocyanin loss and off-flavor compound generation during fermentation impair blueberry wine color and quality. Hydroxycinnamate decarboxylase from yeast can catalyze the conversion of hydroxycinnamic acids to vinylphenols, which later may condense with anthocyanins to form more stable vinylphenolic pyranoanthocyanins. In this study, 10 non-Saccharomyces yeasts from Daqu that showed hydroxycinnamate decarboxylase activity were screened. Among the 10 strains, Wickerhamomyces anomalus Y5 showed the highest consumption (34.59%) of the total tested phenolic acids and almost no H2S production. Furthermore, Y5 seemed to produce four vinylphenol pyranoanthocyanins (cyanidin-3-O-galactoside/glucoside-4-vinylcatechol, cyanidin-3-O-galactoside/glucoside-4-vinylsyringol, malvidin-4-vinylguaiacol, and malvidin-4-vinylcatechol) during blueberry wine fermentation, which may improve the color stability of blueberry wine. These findings provide new insights for improving the quality of blueberry wine using non-Saccharomyces yeasts.

Association of Serum Concentrations of Copper, Selenium, and Zinc with Grip Strength Based on NHANES 2013-2014.

Increasing evidence has found metals to be strongly associated with muscle strength, but the correlations between serum copper (Cu), selenium (Se), and zinc (Zn) with grip strength in adult populations have not yet been established. We examined the linear and non-linear associations between these three metals and grip strength via multiple linear regression and restricted cubic spline (RCS) regression using data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. A higher concentration of serum Cu was monotonically linked with lower grip strength [ß = - 0.004 m2 (95% CI: - 0.005, - 0.002)], and serum Zn was positively associated with grip strength [ß = 0.004 m2 (95% CI: 0.002, 0.006)]. We observed a positive association between serum Se and grip strength in the unadjusted model but not in covariate-adjusted models. Interestingly, the results of RCS regression showed that serum Cu had an L-shaped non-linear association with grip strength in all participants and subgroups. We further found a linear-increased trend between serum Zn and the grip strength in all participants. There were also non-linear associations that varied across different subgroups. Taken together, serum Cu and Zn were significantly associated with grip strength, while Se was not. This study offers new evidence to help formulate a reference concentration range for serum Cu and Zn.

Clinical research of fibroscan ‒ TE-CAP at noninvasive diagnosis of hepatic steatosis in children

Abstract Background & aims The authors assess the diagnostic accuracy of the Transient Elastography-Controlled Attenuation Parameter (TE-CAP) in children of Southern China. Methods 105 obese or overweight children and adolescents were enrolled in the diagnostic test of TE-CAP assessment of hepatic steatosis using MRI-PDFF. Hepatic steatosis grades S0-S3 were classified. Statistical correlation, agreement and consistency between methods were evaluated. The diagnostic efficiency of TE-CAP was evaluated. The authors used the cutoff value of TE-CAP to detect hepatic steatosis in another 356 children. Results The Area Under Curve (AUC) of TE-CAP for grade ≥ S1, ≥ S2, and ≥ S3 steatosis were 0.975, 0.984, and 0.997, respectively. For detecting ≥ S1 steatosis, TE-CAP had a sensitivity of 96 % and a specificity of 97 %. For detecting ≥ S2 steatosis, TE-CAP had a sensitivity of 97 % and a specificity of 93 %. For detecting ≥ S3 steatosis, TE-CAP had a sensitivity of 1 and a specificity of 94 %. TE-CAP and MRI-PDFF had a linear correlation (r = 0. 0.87, p < 0.001). The hepatic steatosis was identified in 40.2 % (143/356) of children in which the obesity and overweight were 69.8 % (113/162) and 40.0 % (18/45). Conclusion TE-CAP showed excellent diagnostic accuracy in pediatric hepatic steatosis.

Associations of urinary caffeine and caffeine metabolites with metabolic syndrome in US adults.

Aims: The relationship between caffeine and metabolic syndrome (MetS) has only been evaluated from the perspective of caffeine consumption. The association between urinary caffeine and MetS is still unclear. This study examined the associations between urinary caffeine and its metabolites and MetS and its components among adults. Methods: Data from the United States (US) National Health and Nutrition Examination Survey (NHANES) 2011-2014 was analyzed. NHANES is a stratified, multi-stage survey of all non-institutionalized persons in the US. A total of 2,394 subjects aged ≥ 18 years without missing data were selected in this study. Urinary caffeine and caffeine metabolite levels were quantified using high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry (HPLC-ESI-MS/MS) with stable isotope-labeled internal standards. We performed principal components analysis (PCA) to investigate the underlying correlation structure of 15 features of urinary caffeine and its metabolites and then used these principal components (PCs) as independent variables to conduct logistic regression analysis with or without restricted cubic spline (RCS) terms to explore the associations between caffeine metabolites and MetS. Results: Two main PCs that were derived from the PCA explained 90.67% of the total variance of caffeine and its metabolites. The first PC (PC1, strongly correlated with 1-MU, 1,3-DMU, 1,7-DMU, 1,3,7-TMU, 1-MX, 1,3-DMX, 1,7-DMX, 1,3,7-TMX, and AAMU) was positively correlated with risk of MetS (OR = 1.27, p < 0.001) and all its components (all ORs > 1, all p-values < 0.001) in the unadjusted models, while in the adjusted models, it was positively correlated with MetS (OR = 1.16, p = 0.042) and central obesity (OR = 1.22, p < 0.001). In the unadjusted model, there were significant associations between the second PC (PC2, correlated with 3-MU, 7-MU, 3,7-DMU, 3-MX, 7-MX, and 3,7-DMX) and MetS (OR = 1.11, P = 0.030) and central obesity (OR = 1.16, P < 0.001), while in the adjusted models (adjustment variables include gender, age, race/ethnicity, education level and income-poverty ratio, smoking status, drinking, and physical activity), PC2 was positively associated with MetS (OR = 1.15, p = 0.035) and central obesity (OR = 1.15, p = 0.005) and negatively associated with raised triglycerides (TG) (OR = 0.84, p = 0.008). Moreover, we observed U-shaped associations between PC1 and the risk of raised TG both in unadjusted (Pnon-linear = 0.017) and adjusted (Pnon-linear = 0.014) models. Conclusion: Urinary caffeine metabolites were positively associated with the risk of MetS and its components through different linear or non-linear patterns.

Gut microbiota in children with split-dose bowel preparations revealed by metagenomics.

Objective: Split-dose polyethylene glycol (PEG) is routinely used for bowel preparation before colonoscopy. This study aimed to investigate the composition of gut microbiota and its functions in pediatric patients undergoing split-dose PEG bowel preparation for colonoscopy to understand the stability and resilience of gut microbiota. Material and methods: From September to December 2021, 19 pediatric patients were enrolled at Shenzhen Children's Hospital and 76 samples (4 time points) were analyzed using metagenomics. Time points included Time_1 (one day before bowel preparation), Time_2 (one day after colonoscopy), Time_3 (two weeks after bowel preparation), and Time_4 (four weeks after bowel preparation). Result: Alpha diversity comparison at both the species and gene levels showed a decrease in community richness after colonoscopy, with little statistical significance. However, the Shannon diversity index significantly decreased (P<0.05) and gradually returned to pre-preparation levels at two weeks after bowel preparation. The genus level analysis showed six genera (Eubacterium, Escherichia, Intertinibacter, Veillonella, Ruminococcaceae unclassified, and Coprobacillus) significantly different across the four time periods. Additionally, at the species level, the abundance of Escherichia coli, Bacteroides fragilis, and Veillonella parvula significantly increased at one day after colonoscopy before gradually decreasing at two weeks after bowel preparation. In contrast, the abundance of Intertinibacter bartlettii decreased at one day after colonoscopy but then recovered at two weeks after bowel preparation, reaching the preoperative level at four weeks after bowel preparation. Furthermore, five functional pathways (base excision repair, biosynthesis of ansamycins, biosynthesis of siderophore group nonribosomal peptide, flavonoid biosynthesis, and biosynthesis of type II polyketide products) were significantly different across the four time periods, with recovery at two weeks after bowel preparation and reaching preoperative levels at four weeks after bowel preparation. Conclusions: Gut microbiota at the genus level, species level, and functional pathways are impacted in pediatric patients undergoing split-dose PEG bowel preparation and colonoscopy, with recovery two weeks following bowel preparation. However, the phylum level was not impacted. Modifications in gut microbiota composition and function may be investigated in future studies of bowel preparation. This study highlights the stability and resilience of gut microbiota among pediatric patients during bowel preparation.

Intrinsic auxeticity and mechanical anisotropy of Si9C15 siligraphene.

Graphene-like two-dimensional (2D) silicon carbide or siligraphene has attracted remarkable attention, owing to its fascinating physical properties. Nevertheless, the first high-quality siligraphene, i.e. monolayer Si9C15, was synthesised very recently, which exhibits an excellent semiconducting behaviour. In this work, we investigate the mechanical properties of Si9C15 siligraphene by using atomistic simulations including density functional theory (DFT) calculations and molecular dynamics (MD) simulations. Both methods confirm the existence of intrinsic negative Poisson's ratios in Si9C15 siligraphene, which, as illustrated by MD simulations, is attributed to the tension-induced de-wrinkling behaviours of its intrinsic rippled configuration. Different de-wrinkling behaviours are observed in different directions of Si9C15 siligraphene, which result in the anisotropy of its auxetic properties. The fracture properties of Si9C15 siligraphene are similarly anisotropic, but relatively large fracture strains are observed in different orientations, indicating the stretchability of Si9C15 siligraphene. The stretchability together with the strain-sensitive bandgap of Si9C15 siligraphene observed in DFT calculations indicates the effectiveness of strain engineering in modulating its electronic properties. The combination of unique auxetic properties, excellent mechanical properties and tunable electronic properties may make Si9C15 siligraphene a novel 2D material with multifunctional applications.

Preclinical Efficacy of LP-184, a Tumor Site Activated Synthetic Lethal Therapeutic, in Glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most common brain malignancy with median survival <2 years. Standard-of-care temozolomide has marginal efficacy in approximately 70% of patients due to MGMT expression. LP-184 is an acylfulvene-derived prodrug activated by the oxidoreductase PTGR1 that alkylates at N3-adenine, not reported to be repaired by MGMT. This article examines LP-184 efficacy against preclinical GBM models and identifies molecular predictors of LP-184 efficacy in clinical GBM. EXPERIMENTAL DESIGN: LP-184 effects on GBM cell viability and DNA damage were determined using cell lines, primary PDX-derived cells and patient-derived neurospheres. GBM cell sensitivities to LP-184 relative to temozolomide and MGMT expression were examined. Pharmacokinetics and CNS bioavailability were evaluated in mice with GBM xenografts. LP-184 effects on GBM xenograft growth and animal survival were determined. Machine learning, bioinformatic tools, and clinical databases identified molecular predictors of GBM cells and tumors to LP-184 responsiveness. RESULTS: LP-184 inhibited viability of multiple GBM cell isolates including temozolomide-resistant and MGMT-expressing cells at IC50 = approximately 22-310 nmol/L. Pharmacokinetics showed favorable AUCbrain/plasma and AUCtumor/plasma ratios of 0.11 (brain Cmax = 839 nmol/L) and 0.2 (tumor Cmax = 2,530 nmol/L), respectively. LP-184 induced regression of GBM xenografts and prolonged survival of mice bearing orthotopic xenografts. Bioinformatic analyses identified PTGR1 elevation in clinical GBM subtypes and associated LP-184 sensitivity with EGFR signaling, low nucleotide excision repair (NER), and low ERCC3 expression. Spironolactone, which induces ERCC3 degradation, decreased LP-184 IC50 3 to 6 fold and enhanced GBM xenograft antitumor responses. CONCLUSIONS: These results establish LP-184 as a promising chemotherapeutic for GBM with enhanced efficacy in intrinsic or spironolactone-induced TC-NER-deficient tumors.

Smartphone-assisted colorimetric aptasensor for rapid detection of carbendazim residue in agriculture products based on the oxidase-mimicking activity of octahedral Ag2O nanoparticles.

Carbendazim (CBZ) is a widely used pesticides, and its excessive intake is serious damage to humans and animals. Herein, a stable and sensitive colorimetric aptasensor for rapid detection of CBZ residue has been established based on the enhancement of CBZ-specific aptamer (CZ-13) on oxidase-mimicking activity of octahedral Ag2O nanoparticles (NPs). The CZ-13 aptamer can significantly increase the catalytic activity by promoting the production of superoxide anion (·O2-) on the surface of Ag2O NPs and enhancing the affinity of octahedral Ag2O NPs to 3,3',5,5'-tetramethylbenzidine (TMB) molecules. In the presence of CBZ, the quantity of CZ-13 aptamer will be exhausted due to the specific binding to CBZ pesticide. Thus, the rest CZ-13 aptamer no longer enhanced the catalytic activity of octahedral Ag2O NPs, which leads to the change in color of sensing solution. The color change of sensing solution can be easily converted to the corresponding RGB value by a smartphone for quantitative and rapid detection of CBZ. The designed aptasensor has excellent sensitivity and specificity, and the limit of detection was determined as low as 7.35 µg L-1 for CBZ assay. Besides, the aptasensor exhibited good recoveries in the spiked cabbage, apple and cucumber, showing that it may have broad application prospects for detecting CBZ residues in agriculture products.