18F-FDG PET/CT Radiomics-Based Multimodality Fusion Model for Preoperative Individualized Noninvasive Prediction of Peritoneal Metastasis in Advanced Gastric Cancer.

PURPOSE: This study was designed to develop and validate a machine learning-based, multimodality fusion (MMF) model using 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and kernelled support tensor machine (KSTM), integrated with clinical factors and nuclear medicine experts' diagnoses to individually predict peritoneal metastasis (PM) in advanced gastric cancer (AGC). METHODS: A total of 167 patients receiving preoperative PET/CT and subsequent surgery were included between November 2006 and September 2020 and were divided into a training and testing cohort. The PM status was confirmed via laparoscopic exploration and postoperative pathology. The PET/CT signatures were constructed by classic radiomic, handcrafted-feature-based model and KSTM self-learning-based model. The clinical nomogram was constructed by independent risk factors for PM. Lastly, the PET/CT signatures, clinical nomogram, and experts' diagnoses were fused using evidential reasoning to establish the MMF model. RESULTS: The MMF model showed excellent performance in both cohorts (area under the curve [AUC] 94.16% and 90.84% in training and testing), and demonstrated better prediction accuracy than clinical nomogram or experts' diagnoses (net reclassification improvement p < 0.05). The MMF model also had satisfactory generalization ability, even in mucinous adenocarcinoma and signet ring cell carcinoma which have poor uptake of 18F-FDG (AUC 97.98% and 89.71% in training and testing). CONCLUSIONS: The 18F-FDG PET/CT radiomics-based MMF model may have significant clinical implications in predicting PM in AGC, revealing that it is necessary to combine the information from different modalities for comprehensive prediction of PM.

Histone demethylase KDM4A mediating macrophage polarization: A potential mechanism of trichloroethylene induced liver injury.

Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the livers of TCE-drinking mice and found that the expression of KDM4A, M1-type polarization indicators, and related inflammatory factors in the livers of TCE-drinking mice. In the study, BALB/c mice were randomly divided into four groups: 2.5 mg/mL TCE dose group and 5.0 mg/mL TCE dose group, the vehicle control group, and the blank control group. We found that TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines. Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 and increased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to ß-catenin activation, a signal critical for the pro-inflammatory activation of macrophages. Furthermore, KDM4A inhibitor JIB-04 treatment resulted in a decrease in ß-catenin expression and prevented TCE-induced M1 polarization and the expression of the pro-inflammatory cytokines TNF-α and IL-1ß. These results suggest that the association of KDM4A and Wnt/ß-catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3/me2/me1. Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE.

Computed tomography and guidelines-based human-machine fusion model for predicting resectability of the pancreatic cancer.

BACKGROUND AND AIM: The study aims to develop a hybrid machine learning model for predicting resectability of the pancreatic cancer, which is based on computed tomography (CT) and National Comprehensive Cancer Network (NCCN) guidelines. METHOD: We retrospectively studied 349 patients. One hundred seventy-one cases from Center 1 and 92 cases from Center 2 were used as the primary training cohort, and 66 cases from Center 3 and 20 cases from Center 4 were used as the independent test dataset. Semi-automatic module of ITK-SNAP software was used to assist CT image segmentation to obtain three-dimensional (3D) imaging region of interest (ROI). There were 788 handcrafted features extracted for 3D ROI using PyRadiomics. The optimal feature subset consists of three features screened by three feature selection methods as the input of the SVM to construct the conventional radiomics-based predictive model (cRad). 3D ROI was used to unify the resolution by 3D spline interpolation method for constructing the 3D tumor imaging tensor. Using 3D tumor image tensor as input, 3D kernelled support tensor machine-based predictive model (KSTM), and 3D ResNet-based deep learning predictive model (ResNet) were constructed. Multi-classifier fusion ML model is constructed by fusing cRad, KSTM, and ResNet using multi-classifier fusion strategy. Two experts with more than 10 years of clinical experience were invited to reevaluate each patient based on their CECT following the NCCN guidelines to obtain resectable, unresectable, and borderline resectable diagnoses. The three results were converted into probability values of 0.25, 0.75, and 0.50, respectively, according to the traditional empirical method. Then it is used as an independent classifier and integrated with multi-classifier fusion machine learning (ML) model to obtain the human-machine fusion ML model (HMfML). RESULTS: Multi-classifier fusion ML model's area under receiver operating characteristic curve (AUC; 0.8610), predictive accuracy (ACC: 80.23%), sensitivity (SEN: 78.95%), and specificity (SPE: 80.60%) is better than cRad, KSTM, and ResNet-based single-classifier models and their two-classifier fusion models. This means that three different models have mined complementary CECT feature expression from different perspectives and can be integrated through CFS-ER, so that the fusion model has better performance. HMfML's AUC (0.8845), ACC (82.56%), SEN (84.21%), SPE (82.09%). This means that ML models might learn extra information from CECT that experts cannot distinguish, thus complementing expert experience and improving the performance of hybrid ML models. CONCLUSION: HMfML can predict PC resectability with high accuracy.

Enhanced Spatial Charge Separation in a Niobium and Tantalum Nitride Core-Shell Photoanode: In Situ Interface Bonding for Efficient Solar Water Splitting.

Tantalum nitride (Ta3 N5 ) has emerged as a promising photoanode material for photoelectrochemical (PEC) water splitting. However, the inefficient electron-hole separation remains a bottleneck that impedes its solar-to-hydrogen conversion efficiency. Herein, we demonstrate that a core-shell nanoarray photoanode of NbNx -nanorod@Ta3 N5 ultrathin layer enhances light harvesting and forms a spatial charge-transfer channel, which leads to the efficient generation and extraction of charge carriers. Consequently, an impressive photocurrent density of 7 mA cm-2 at 1.23 VRHE is obtained with an ultrathin Ta3 N5 shell thickness of less than 30 nm, accompanied by excellent stability and a low onset potential (0.46 VRHE ). Mechanistic studies reveal the enhanced performance is attributed to the high-conductivity NbNx core, high-crystalline Ta3 N5 mono-grain shell, and the intimate Ta-N-Nb interface bonds, which accelerate the charge-separation capability of the core-shell photoanode. This study demonstrates the key roles of nanostructure design in improving the efficiency of PEC devices.

Prenatal low-dose antibiotic exposure and children allergic diseases at 4 years of age: A prospective birth cohort study.

BACKGROUND: Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing. OBJECTIVES: This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age. METHODS: The current study including 2453 mother-child pairs was based on the Ma'anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children. RESULTS: The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-FDR=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-FDR=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-FDR=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children. CONCLUSIONS: Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.

Trichloroethylene Alters Th1/Th2/Th17/Treg Paradigm in Mice: A Novel Mechanism for Chemically Induced Autoimmunity.

The role of environmental factors in autoimmune diseases has been increasingly recognized. While major advance has been made in understanding biological pathogen-induced autoimmune diseases, chemically triggered autoimmunity is poorly understood. Trichloroethylene (TCE), a common environmental pollutant, has recently been shown to induce autoimmunity. This study explored whether TCE could cause imbalance of T helper (Th) cell subsets which would contribute to the pathogenesis of TCE-induced medicamentosa-like dermatitis. BALB/c mice were treated with TCE via drinking water at doses of 2.5 or 5.0 mg/mL for 2, 4, 8, 12, and 16 weeks. Trichloroethylene exposure caused time- and dose-dependent increase in Th1, Th2, and Th17 and decrease in regulatory cell (Treg) in the spleen at 2, 4, 8, 12, and 16 weeks, with greatest changes mainly at 4 weeks. These effects were mirrored by similar changes in the expression of their corresponding cytokines interferon-γ, interleukin 4 (IL-4), IL-17A, and IL-10. Mechanistically, these phenotypic changes were accounted for by alterations to their respective master transcription factors T-box expressed in T cells, GATA-binding protein 3, Retinoic acid-related orphan receptor ct (RORct), and forkhead box P3. Of interest, TCE treatment shifted the ratios of Th1/Th2 and Th17/Treg; specifically, TCE increased Th17/Treg. These findings provide the first evidence that TCE exposure significantly changes the Th1/Th2/Th17/Treg paradigm and their specific cytokines driven by altered master transcription factors. This may promote autoimmune reactions in the pathogenesis of TCE-induced skin sensitization and associated damage to other tissues.

Potential of transition metal atoms embedded in buckled monolayer g-C3N4 as single-atom catalysts.

We use first-principles calculations to systematically explore the potential of transition metal atoms (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Ru, Rh, Pd, Ag, Ir, Pt, and Au) embedded in buckled monolayer g-C3N4 as single-atom catalysts. We show that clustering of Sc and Ti on g-C3N4 is thermodynamically impeded and that V, Cr, Mn, and Cu are much less susceptible to clustering than the other TM atoms under investigation. Strong bonding of the transition metal atoms in the cavities of g-C3N4 and high diffusion barriers together are responsible for single-atom fixation. Analysis of the CO oxidation process indicates that embedding of Cr and Mn in g-C3N4 gives rise to promising single-atom catalysts at low temperature.

The association of mannose-binding lectin genetic polymorphisms with the risk of rheumatoid arthritis: a meta-analysis.

OBJECTIVE: To better understand the risks of rheumatoid arthritis (RA) and certain subsets conferred by mannose-binding lectin (MBL2) polymorphisms in different races. MATERIALS AND METHODS: Eighteen articles (4810 cases and 4585 controls) were identified from the latest literature search carried out in May 2014 using PubMed, Web of Science, Wanfang Database (Chinese) and Chinese National Knowledge Infrastructure. Three single nucleotide polymorphisms of codon 52, 54 and 57, exonic and extended genotypic variance in MBL2 were synthesized. RESULTS: Codon 54 mutation of MBL2 was unlikely to be a risk factor for RA in overall population, but turned out to be deleterious in East Asian (four studies with 523 cases and 647 controls, pooled OR:1.63, 95% CI: 1.23-2.17). Codon 54 mutation increased the risk of seropositive and erosive RA by 44% and 162%, respectively (three studies with 281 cases and 358 controls, 95% CI: 1.01-2.05; 3 studies with 180 cases and 499 controls, 95% CI: 1.77-3.88). Furthermore, those risks were relatively stronger when restricted in East Asian (two studies with 147 cases and 244 controls, pooled OR: 1.85, 95% CI: 1.19-2.87; 2 studies with 170 cases and 291 controls, pooled OR: 2.78, 95% CI: 1.85-4.20). No remarkable associations were detected regarding codon 52, 57, exon 1 and extended genotype of MBL2. CONCLUSIONS: Polymorphism of codon 54 in MBL2 may predispose to RA, especially seropositive or erosive RA, which East Asian appears to be more vulnerable.

An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization.

[Study on the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse].

OBJECTIVE: To study the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (ODMLT). METHODS: On the first days, intradermal injection by 50% TCE and the amount of FCA mixture 100 µl for initial sensitization; on 4, 7, 10 days, painted abdominal skin by 100 µl 50% TCE for three sensitization, on 17, 19 days, painted on the back skin by 100 µl 30% TCE for initial excitation and the last challenge; 24 h before each challenge, PKSI-527+TCE group received intraperitoneal injection by inhibitor PKSI-527 (50 mg/kg); solvent control group treat without TCE and sensitization and excitation reagent the same proportion of olive oil and acetone mixture, blank control group without any treatment. Before killing the mouse, renal weight and body weight were recorded. The renals and plasma were separated at 24 h, 48 h, 72 h and 7 d after the last challenge and observed pathological of the renals. Expression of B1R and B2R in renal were examined by immunofluorescence technique. Plasma were examined by ELISA for BK. RESULTS: The renal pathological examination revealed the apparent damage of TCE sensitized mice which compared to solvent control group showed obvious cellular infiltration, vacuolar degeneration of renal tubular epithelial cells. The renal damage of PKSI-527+TCE-sensitized groups which compared to the corresponding point of TCE-sensitized groups showed significantly reduced. The expression of BK in 24 h, 48 h and 72 h TCE-sensitized groups were significant higher than solvent control group and related TCE non-sensitized groups (P < 0.05) and 72 h point compared to the corresponding point of PKSI-527+TCE group was also increased, the difference was statistically significant (P < 0.05). The expression levels of B1R and B2R in the kidney in 24 h, 48 h, 72 h and 7 d TCE-sensitized groups were obviously higher than solvent control group and related TCE non-sensitized groups. The expression levels of B1R and B2R in the kidney in the four point of PKSI-527+TCE sensitized group were relatively lower than the corresponding point of TCE sensitized group. CONCLUSION: KKS activation may involved in the renal immune injury of trichloroethylene-sensitized mouse and the expression change of bradykinin and its receptors B1R and B2R which may play an important role in the process.

[Expression of C3aR and C5aR in trichloroethylene-sensitized mouse liver].

OBJECTIVE: To study the expression of C3aR and C5aR in trichloroethylene-sensitized mouse liver injury and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (DMLT). METHODS: 6∼8 w female BALB/c mouse were randomly divided into blank control group, solvent control group and TCE treatment group. TCE was given to the mouse for sensitization at 1th, 4th, 7th, 10th day and challenge at 17th day and 19th day. Before killing mouse, liver weight and body weight were recorded. The livers were separated at 24 h, 48 h, 72 h and 7 d after challenge. And the liver sections were used for immunofluorescence stain and RT-PCR to detect the expression levels of C3aR and C5aR. RESULTS: Microscopic examination showed no significant change in liver structure or organization in TCE non-sensitized group, while liver cell oedema, cell necrosis and inflammatory cell infiltration were clearly observed in TCE-sensitized groups. The expression levels of C3aR and C5aR in 24 h, 48 h, 72 h and 7 d TCE-sensitized groups were significant higher than blank control group, solvent control group and related TCE non-sensitized groups (P < 0.05). CONCLUSION: Complement activation was involved in TCE-induced liver injury and C3aR and C5aR might play essential role in the process.

[Levels of complement components C3a and C5a in renal injury among trichloroethylene-sensitized BALB/c mice].

OBJECTIVE: To determine the levels of complement components C3a and C5a in the kidneys of trichloroethylene (TCE)-sensitized BALB/c mice, and to investigate the role of complement components in TCE-induced renal injury among BALB/c mice. METHODS: Sixty-two female BALB/c mice were randomly divided into blank control group, vehicle control group, and TCE sensitization group. The mice in TCE sensitization group were sensitized by one intracutaneous injection and one abdominal smear of TCE. At 24 h, 48 h, 72 h, and 7 d after the second sensitization, mice were sacrificed, and the blood and kidneys were collected. An automatic biochemical analyzer was used in the determination of serum blood urea nitrogen (BUN) and creatinine (Cr). The levels of C3a and C5a in the kidneys were determined by immunohistochemistry. RESULTS: The sensitization rate of TCE sensitization group was 42.0%. Kidney coefficient and serum levels of BUN and Cr were significantly increased in the TCE sensitization group as compared with the vehicle control group at 48 h and 72 h after sensitization (P < 0.05). The kidney coefficients of the TCE sensitization group at 48 h and 72 h were significantly higher than those of the control groups (P < 0.05). In comparison with the vehicle control group, however, no significant change was found in kidney coefficient, serum BUN, or serum Cr at 7 d after TCE sensitization (P > 0.05). Levels of C3a and C5a at 48 h (3.80±0.84 and 4.00±1.00, respectively) and 72 h (4.40 ± 1.14 and 4.40 ± 1.14, respectively) after sensitization were all significantly higher than those of the vehicle control group (P < 0.05), but no significant difference was found in level of C3a (1.80±0.45) or C5a (2.00 ± 0.71) at 7 d (P > 0.05). CONCLUSION: TCE sensitization can induce renal injury in mice. Levels of complement components C3a and C5a are elevated in the kidneys of sensitized mice, indicating that C3a and C5a may be involved in the renal injury induced by TCE sensitization.

Ultra-thin nanosheets decorated in-situ S-doped 3D interconnected carbon network as interlayer modified Li-S batteries separator for accelerating adsorption-catalytic synergistic process of LiPSs.

The shuttle effect of soluble lithium polysulfides (LiPSs) is primarily responsible for the unstable performance of lithium-sulfur (Li-S) batteries, which has severely impeded their continued development. In order to solve this problem, a special strategy is proposed. Specifically, ultra-thin NiCo based layered double hydroxides (named LDH or NiCo-LDH) nanosheets are implanted into a pre-designed 3D interconnected carbon networks (SPC) to obtain porous composite materials (named SPC-LDH).During the operation of the battery, the 3D interconnected porous carbon mesh was the first to rapidly adsorb LiPSs, and then the LDH on the surface of the carbon mesh was used to realize the catalytic conversion of LiPSs. This facilitates the electrochemical conversion reaction between S substances while addressing the "shuttle effect". As a result, the battery maintains a discharge capacity of 1401.9, 1114.3, 975.5, 880.7, 760.4 and 679.6 mAh g-1 at the current densities of 0.1, 0.2, 0.5, 1, 2 and 3C, respectively. After 200 cycles at 2C, the battery's capacity stays at 732.9 mAh g-1, meaning that the average rate of capacity decay is only 0.007 % per cycle. Moreover, in-situ XRD demonstrates the critical function of PP/SPC-LDH separators in inhibiting LiPSs and encouraging Li2S transformation. The strong affinity of SPC-LDH for Li2S6 is also confirmed by density functional theory (DFT) calculation, offering more theoretical support for the synergistic adsorption process. This work offers a compelling method to develop modified separator materials that can counteract the "shuttle effect" in Li-S batteries.

High catalytic activity and abundant active sites in M2C12 monolayer for nitrogen reduction reaction.

Developing highly efficient single-atom catalysts (SACs) for the nitrogen reduction reaction (NRR) to ammonia production has garnered significant attention in the scientific community. However, achieving high activity and selectivity remains challenging due to the lack of innate activity in most existing catalysts or insufficient active site density. This study delves into the potential of M2C12 materials (M = Cr, Ir, Mn, Mo, Os, Re, Rh, Ru, W, Fe, Cu, and Ti) with high transition metal coverage as SACs for NRR using first-principles calculations. Among these materials, Os2C12 exhibited superior catalytic activity for NRR, with a low overpotential of 0.39 V and an Os coverage of up to 72.53 wt%. To further boost its catalytic activity, a nonmetal (NM) atom doping (NM = B, N, O, and S) and C vacancy modification were explored in Os2C12. It is found that the introduction of O enables exceptional catalytic activity, selectivity, and stability, with an even lower overpotential of 0.07 V. Incorporating the O atom disrupted the charge balance of its coordinating C atoms, effectively increasing the positive charge density of the Os-d-orbit-related electronic structure. This promoted strong d-π* coupling between Os and N2H, enhancing N2H adsorption and facilitating NRR processes. This comprehensive study provides valuable insights into NRR catalyst design for sustainable ammonia production and offers a reference for exploring alternative materials in other catalytic reactions.

Multiscale and multiperception feature learning for pancreatic lesion detection based on noncontrast CT.

Background. Pancreatic cancer is one of the most malignant tumours, demonstrating a poor prognosis and nearly identically high mortality and morbidity, mainly because of the difficulty of early diagnosis and timely treatment for localized stages.Objective. To develop a noncontrast CT (NCCT)-based pancreatic lesion detection model that could serve as an intelligent tool for diagnosing pancreatic cancer early, overcoming the challenges associated with low contrast intensities and complex anatomical structures present in NCCT images.Approach.We design a multiscale and multiperception (MSMP) feature learning network with ResNet50 coupled with a feature pyramid network as the backbone for strengthening feature expressions. We added multiscale atrous convolutions to expand different receptive fields, contextual attention to perceive contextual information, and channel and spatial attention to focus on important channels and spatial regions, respectively. The MSMP network then acts as a feature extractor for proposing an NCCT-based pancreatic lesion detection model with image patches covering the pancreas as its input; Faster R-CNN is employed as the detection method for accurately detecting pancreatic lesions.Main results. By using the new MSMP network as a feature extractor, our model outperforms the conventional object detection algorithms in terms of the recall (75.40% and 90.95%), precision (40.84% and 68.21%), F1 score (52.98% and 77.96%), F2 score (64.48% and 85.26%) and Ap50 metrics (53.53% and 70.14%) at the image and patient levels, respectively.Significance.The good performance of our new model implies that MSMP can mine NCCT imaging features for detecting pancreatic lesions from complex backgrounds well. The proposed detection model is expected to be further developed as an intelligent method for the early detection of pancreatic cancer.

Regulating the thickness of the carbon coating layer in iron/carbon heterostructures to enhance the catalytic performance for oxygen evolution reaction.

The exploration of high-performance electrocatalysts for the oxygen evolution reaction (OER) is crucial and urgent for the fast development of green and renewable hydrogen energy. Herein, an ultra-fast and energy-efficient preparation strategy (microwave-assisted rapid in-situ pyrolysis of organometallic compounds induced by carbon nanotube (CNT)) is developed to obtain iron/carbon (Fe/C) heterogeneous materials (Fe/Fe3C particles wrapped by carbon coating layer). The thickness of the carbon coating layer can be adjusted by changing the content and form of carbon in the metal sources during the fast preparation process. Fe/Fe3C-A@CNT using iron acetylacetonate as metal sources possesses unique Fe/C heterogeneous, small Fe/Fe3C particles encapsulated by the thin carbon coating layer (1.77 nm), and obtains the optimal electron penetration effect. The electron penetration effect derives from the redistribution of charge between the surface carbon coating layer and inner Fe/Fe3C nanoparticles efficiently improving both catalytic activity and stability. Therefore, Fe/Fe3C-A@CNT shows efficient OER catalytic activity, just needing a low overpotential of 292 mV to reach a current density of 10 mA cm-2, and long-lasting stability. More importantly, the unique control strategy for carbon thickness in this work provides more opportunity and perspective to prepare robust metal/carbon-based catalytic materials at the nanoscale.

Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer.

BACKGROUND: Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2 (HER2)-positive gastric cancer. However, the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit, and there is currently no effective reversal measure. Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves, while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking. This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients. METHODS: Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing. Bioinformatics were used to analyze cell subtypes, metabolic pathways, and molecular signaling pathways. Changes in microenvironmental indicators (such as macrophage, angiogenesis, and metabolism) were verified by immunofluorescence (IF) and immunohistochemical (IHC) analyses. Finally, a multi-scale agent-based model (ABM) was constructed. The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM. RESULTS: Based on transcriptome sequencing, molecular biology, and in vivo experiments, we found that the level of glutamine metabolism in trastuzumab-resistant HER2-positive cells was increased, and glutaminase 1 (GLS1) was significantly overexpressed. Meanwhile, tumor-derived GLS1 microvesicles drove M2 macrophage polarization. Furthermore, angiogenesis promoted trastuzumab resistance. IHC showed high glutamine metabolism, M2 macrophage polarization, and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nude mice. Mechanistically, the cell division cycle 42 (CDC42) promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B (NF-κB) p65 and drove GLS1 microvesicle secretion through IQ motif-containing GTPase-activating protein 1 (IQGAP1). Based on the ABM and in vivo experiments, we confirmed that the combination of anti-glutamine metabolism, anti-angiogenesis, and pro-M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2-positive gastric cancer. CONCLUSIONS: This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism, M2 macrophage polarization, and pro-angiogenic function of macrophages, leading to acquired trastuzumab resistance in HER2-positive gastric cancer. A combination of anti-glutamine metabolism, anti-angiogenesis, and pro-M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.

A multimodal model fusing multiphase contrast-enhanced CT and clinical characteristics for predicting lymph node metastases of pancreatic cancer.

Objective.To develop a multimodal model that combines multiphase contrast-enhanced computed tomography (CECT) imaging and clinical characteristics, including experts' experience, to preoperatively predict lymph node metastasis (LNM) in pancreatic cancer patients.Methods.We proposed a new classifier fusion strategy (CFS) based on a new evidential reasoning (ER) rule (CFS-nER) by combining nomogram weights into a previous ER rule-based CFS. Three kernelled support tensor machine-based classifiers with plain, arterial, and venous phases of CECT as the inputs, respectively, were constructed. They were then fused based on the CFS-nER to construct a fusion model of multiphase CECT. The clinical characteristics were analyzed by univariate and multivariable logistic regression to screen risk factors, which were used to construct correspondent risk factor-based classifiers. Finally, the fusion model of the three phases of CECT and each risk factor-based classifier were fused further to construct the multimodal model based on our CFS-nER, named MMM-nER. This study consisted of 186 patients diagnosed with pancreatic cancer from four clinical centers in China, 88 (47.31%) of whom had LNM.Results.The fusion model of the three phases of CECT performed better overall than single and two-phase fusion models; this implies that the three considered phases of CECT were supplementary and complemented one another. The MMM-nER further improved the predictive performance, which implies that our MMM-nER can complement the supplementary information between CECT and clinical characteristics. The MMM-nER had better predictive performance than based on previous classifier fusion strategies, which presents the advantage of our CFS-nER.Conclusion.We proposed a new CFS-nER, based on which the fusion model of the three phases of CECT and MMM-nER were constructed and performed better than all compared methods. MMM-nER achieved an encouraging performance, implying that it can assist clinicians in noninvasively and preoperatively evaluating the lymph node status of pancreatic cancer.