Electrifying Energy and Chemical Transformations with Single-Atom Alloy Nanoparticle Catalysts.

Single-atom alloys (SAAs) have attracted considerable attention as promising electrocatalysts in reactions central to energy conversion and chemical transformation. In contrast to monometallic nanocrystals and metal alloys, SAAs possess unique and intriguing physicochemical properties, positioning them as ideal model systems for studying structure-property relationships. However, the field is still in its early stages. In this Perspective, we first review and summarize rational synthesis methods and advanced characterization techniques for SAA nanoparticle catalysts. We then emphasize the extensive applications of SAAs in a range of electrocatalytic reactions, including fuel cell reactions, water splitting, and carbon dioxide and nitrate reductions. Finally, we provide insights into existing challenges and prospects associated with the controlled synthesis, characterization, and design of SAA catalysts.

Combination of Contrast-enhanced FlAIR and Contrast-enhanced T1WI: A Quick and Efficient Method in Detecting Brain Metastases of Lung Cancers.

BACKGROUND: Some patients with suspected brain metastases (BM) could not tolerate longer scanning examinations according to the standardized MRI protocol. OBJECTIVE: The purpose of this study was to evaluate the clinical value of contrast-enhanced fast fluid-attenuated inversion recovery (CE FLAIR) imaging in combination with contrast-enhanced T1 weighted imaging (CE T1WI) in detecting BM of lung cancer and explore a quick and effective MRI protocol. MATERIAL AND METHODS: In 201 patients with lung cancers and suspected BM, T1WI and FLAIR were performed before and after administration of gadopentetate dimeglumine. Two radiologists reviewed pre- and post-contrast images to determine the presence of abnormal contrast enhancement or signal intensity and decided whether it was metastatic or not on CE T1WI (Group 1) and CE FLAIR (Group 2). The number, locations and features of abnormal findings in two groups were recorded. Receiver Operating Characteristic (ROC) analyses were conducted in three groups: Group 1, 2 and 3(combination of CE FLAIR and CE T1WI). RESULTS: A total of 714 abnormal findings were revealed, of which 672 were considered as BM and 42 nonmetastatic. Superficial and small metastases(≤10mm) in parenchyma and ependyma, leptomeningeal and non-expansive skull metastases were typically better seen on CE FLAIR. The areas under ROC in the three groups were 0.720,0.887 and 0.973, respectively. Group 3 was significantly better in diagnostic efficiency of BMs than Group 1 (p<0.0001) or Group 2 (p=0.0006). CONCLUSION: The combination of CE T1WI and CE FLAIR promotes diagnostic performance and results in better observation and characterization of BM in patients with lung cancers. It provides a quick and efficient way of detecting BM.

Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism.

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

Fusobacterium nucleatum promotes tumor progression in KRAS p.G12D-mutant colorectal cancer by binding to DHX15.

Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/KrasG12D+/- mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/KrasG12D+/- mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment.

Atomic Layers of B2 CuPd on Cu Nanocubes as Catalysts for Selective Hydrogenation.

The search for highly active and selective catalysts with high precious metal atom utilization efficiency has attracted increasing interest in both the fundamental synthesis of materials and important industrial reactions. Here, we report the synthesis of Pd-Cu nanocubes with a Cu core and an ordered B2 intermetallic CuPd shell with controllable atomic layers on the surface (denoted as Cu/B2 CuPd), which can efficiently and robustly catalyze the selective hydrogenation of acetylene (C2H2) to ethylene (C2H4) under mild conditions. The optimized Cu/B2 CuPd with a Pd loading of 9.5 at. % exhibited outstanding performance in the C2H2 semi-hydrogenation with 100% C2H2 conversion and 95.2% C2H4 selectivity at 90 °C. We attributed this outstanding performance to the core/shell structure with a high surface density of active Pd sites isolated by Cu in the B2 intermetallic matrix, representing a structural motif of single-atom alloys (SAAs) on the surface. The combined experimental and computational studies further revealed that the electronic states of Pd and Cu are modulated by SAAs from the synergistic effect between Pd and Cu, leading to enhanced performance compared with pristine Pd and Cu catalysts. This study provides a new synthetic methodology for making single-atom catalysts with high precious metal atom utilization efficiency, enabling simultaneous tuning of both geometric and electronic structures of Pd active sites for enhanced catalysis.

Lung adenocarcinoma associated with cystic airspaces: Predictive value of CT features in assessing pathologic invasiveness.

OBJECTIVES: Lung adenocarcinoma associated with cystic airspaces (LACA) is a unique entity with limited understanding. Our aim was to evaluate the radiological characteristics of LACA and to study which criteria were predictive of invasiveness. METHODS: A retrospective monocentric analysis of consecutive patients with pathologically confirmed LACA was performed. The diagnosed adenocarcinomas were classified into preinvasive (atypical adenomatous hyperplasia, adenocarcinoma in situ, or minimally invasive adenocarcinoma) and invasive adenocarcinomas. Eight clinical features and twelve CT features were evaluated. Univariable and multivariable analyses were performed to analyse the correlation between invasiveness, and CT and clinical features. The inter-observer agreement was evaluated using κ statistics and intraclass correlation coefficients. The predictive performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 252 patients with 265 lesions (128 men and 124 women; mean age, 58.0 ± 11.1 years) were enrolled. Multivariable logistic regression indicated that multiple cystic airspaces (OR, 5.599; 95 % CI, 1.865-16.802), irregular shape of cystic airspace (OR, 3.236; 95 % CI, 1.073-9.761), entire tumour size (OR, 1.281; 95 % CI, 1.075-1.526), and attenuation (OR, 1.007; 95 % CI, 1.005-1.010) were independent risk factors for invasive LACA. The AUC of the logistic regression model was 0.964 (95 % CI, 0.944-0.985). CONCLUSION: Multiple cystic airspaces, irregular shape of cystic airspace, entire tumour size, and attenuation were identified as independent risk factors for invasive LACA. The prediction model gives a good predictive performance, providing additional diagnostic information.

RIG-I contributes to keratinocyte proliferation and wound repair by inducing TIMP-1 expression through NF-κB signaling pathway.

Epithelial keratinocyte proliferation is an essential element of wound repair, and chronic wound conditions, such as diabetic foot, are characterized by aberrant re-epithelialization. In this study, we examined the functional role of retinoic acid inducible-gene I (RIG-I), a key regulator of epidermal keratinocyte proliferation, in promoting TIMP-1 expression. We found that RIG-I is overexpressed in keratinocytes of skin injury and underexpressed in skin wound sites of diabetic foot and streptozotocin-induced diabetic mice. Moreover, mice lacking RIG-I developed an aggravated phenotype when subjected to skin injury. Mechanistically, RIG-I promoted keratinocyte proliferation and wound repair by inducing TIMP-1 via the NF-κB signaling pathway. Indeed, recombinant TIMP-1 directly accelerated HaCaT cell proliferation in vitro and promoted wound healing in Ddx58-/- and diabetic mice in vivo. In summary, we demonstrated that RIG-I is a crucial factor that mediates epidermal keratinocyte proliferation and may be a potential biomarker for skin injury severity, thus making it an attractive locally therapeutic target for the treatment of chronic wounds such as diabetic foot.

Mast cells inhibit colorectal cancer development by inducing ER stress through secreting Cystatin C.

Mast cells (MCs) are abundantly distributed in the human intestinal mucosa and submucosa. However, their roles and mechanisms in the development of colorectal cancer (CRC) are still unclear. In the present research, we found that the infiltration density of MCs in CRC tissues was positively correlated with improved patients' prognoses. Moreover, MCs suppressed the growth and induced the apoptosis of CRC cells in vitro and in vivo but had no effect on normal colonic epithelial cells. The present study revealed that MCs specifically induced endoplasmic reticulum stress (ERS) and activated the unfolded protein response (UPR) in CRC cells but not in normal cells, which led to the suppression of CRC development in vivo. Furthermore, we found that the secreted Cystatin C protein was the key factor for the MC-induced ERS in CRC cells. This work is of significance for uncovering the antitumor function of MCs in CRC progression and identifying the potential of CRC to respond to MC-targeted immunotherapy.

Revealing the Regulatory Mechanism of lncRNA-LMEP on Melanin Deposition Based on High-Throughput Sequencing in Xichuan Chicken Skin.

The therapeutic, medicinal, and nourishing properties of black-bone chickens are highly regarded by consumers in China. However, some birds may have yellow skin (YS) or light skin rather than black skin (BS), which causes economic losses every year. Long noncoding RNAs (lncRNAs) are widely present in living organisms, and they perform various biological functions. Many genes associated with BS pigmentation have been discovered, but the lncRNAs involved and their detailed mechanisms have remained untested. We detected 56 differentially expressed lncRNAs from the RNA-seq of dorsal skin (BS versus YS) and found that TCONS_00054154 plays a vital role in melanogenesis by the combined analysis of lncRNAs and mRNAs. We found that the full length of the TCONS_00054154 sequence was 3093 bp by RACE PCR, and we named it LMEP. Moreover, a subcellular localization analysis identified that LMEP is mainly present in the cytoplasm. After the overexpression and the interference with LMEP, the tyrosinase content significantly increased and decreased, respectively (p < 0.05). In summary, we identified the important lncRNAs of chicken skin pigmentation and initially determined the effect of LMEP on melanin deposition.

Metal-Metal Oxide Catalytic Interface Formation and Structural Evolution: A Discovery of Strong Metal-Support Bonding, Ordered Intermetallics, and Single Atoms.

In-depth investigation of metal-metal oxide interactions and their corresponding evolution is of paramount importance to heterogeneous catalysis as it allows the understanding and maneuvering of the structure of catalytic motifs. Herein, using a series of core/shell metal/iron oxide (M/FeOx, M = Pd, Pt, Au) nanoparticles and through a combination of in situ and ex situ electron and X-ray investigations, we revealed anomalous and dissimilar M-FeOx interactions among different systems under reducing conditions. Pd interacts strongly with FeOx after high-temperature reductive treatment, featured by the formation of Pd single atoms in the FeOx matrix and increased Pd-Fe bonding, while Pt transforms into ordered PtFe intermetallics and Pt single atoms immediately upon the coating of FeOx. In contrast, Au does not manifest strong bonding with FeOx. As a proof of concept of tailoring metal-metal oxide interactions for catalysis, optimized Pd/FeOx demonstrates 100% conversion and 86.5% selectivity at 60 °C for acetylene semihydrogenation.

Value of transbronchial needle aspiration combined with a rapid on-site evaluation of cytology in the diagnosis of pulmonary lesions.

Background: The diagnostic value of rapid on-site evaluation (ROSE) of cytology during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains controversial. The purpose of this study was to validate the value of ROSE during the EUBS-TBNA procedure in the diagnosis of pulmonary lesions (PLs). Methods: Enrolled in this study were 260 patients with nodules, masses, cavities, or inflammatory lesions on pulmonary CT images. They were assigned to undergo EBUS-TBNA with ROSE (n = 134) or without ROSE (n = 126). The diagnostic results of ROSE during EBUS-TBNA and the final pathologic reports were analyzed and compared by utilizing SPSS21.0 software to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we further explored whether the ROSE method during EBUS-TBNA would improve the diagnostic yield and reduce the incidence of complications. Results: The overall diagnostic yield of EBUS-TBNA for malignant diseases in the ROSE and the non-ROSE group were 29.9 and 11.1%, respectively. The sensitivity, specificity, PPV and NPV of the ROSE method during EBUS-TBNA were 97.4, 96.9, 92.5, and 98.90%, respectively. The result of the chi-square test effectively proved that ROSE operation during EBUS-TBNA contributes to the diagnosis of malignancy compared with the non-ROSE group (χ2 = 13.858, P < 0.001). The number of punctures in the ROSE group was significantly lower than that in the non-ROSE group (P < 0.001). Conclusion: ROSE examination during EBUS-TBNA could effectively improve the diagnostic yield of malignant diseases compared with the non-ROSE group and reduce the number of intraoperative punctures, which is a clinical application worth popularizing.

Breaking adsorption-energy scaling limitations of electrocatalytic nitrate reduction on intermetallic CuPd nanocubes by machine-learned insights.

The electrochemical nitrate reduction reaction (NO3RR) to ammonia is an essential step toward restoring the globally disrupted nitrogen cycle. In search of highly efficient electrocatalysts, tailoring catalytic sites with ligand and strain effects in random alloys is a common approach but remains limited due to the ubiquitous energy-scaling relations. With interpretable machine learning, we unravel a mechanism of breaking adsorption-energy scaling relations through the site-specific Pauli repulsion interactions of the metal d-states with adsorbate frontier orbitals. The non-scaling behavior can be realized on (100)-type sites of ordered B2 intermetallics, in which the orbital overlap between the hollow *N and subsurface metal atoms is significant while the bridge-bidentate *NO3 is not directly affected. Among those intermetallics predicted, we synthesize monodisperse ordered B2 CuPd nanocubes that demonstrate high performance for NO3RR to ammonia with a Faradaic efficiency of 92.5% at -0.5 VRHE and a yield rate of 6.25 mol h-1 g-1 at -0.6 VRHE. This study provides machine-learned design rules besides the d-band center metrics, paving the path toward data-driven discovery of catalytic materials beyond linear scaling limitations.

Heterostructured Bi-Cu2S nanocrystals for efficient CO2 electroreduction to formate.

The electrochemical CO2 reduction reaction (ECO2RR) driven by renewable electricity holds promise to store intermittent energy in chemical bonds, while producing value-added chemicals and fuels sustainably. Unfortunately, it remains a grand challenge to simultaneously achieve a high faradaic efficiency (FE), a low overpotential, and a high current density of the ECO2RR. Herein, we report the synthesis of heterostructured Bi-Cu2S nanocrystals via a one-pot solution-phase method. The epitaxial growth of Cu2S on Bi leads to abundant interfacial sites and the resultant heterostructured Bi-Cu2S nanocrystals enable highly efficient ECO2RR with a largely reduced overpotential (240 mV lower than that of Bi), a near-unity FE (>98%) for formate production, and a high partial current density (2.4- and 5.2-fold higher JHCOO- than Cu2S and Bi at -1.0 V vs. reversible hydrogen electrode, RHE). Density functional theory (DFT) calculations show that the electron transfer from Bi to Cu2S at the interface leads to the preferential stabilization of the formate-evolution intermediate (*OCHO).

Accurate prediction of epidermal growth factor receptor mutation status in early-stage lung adenocarcinoma, using radiomics and clinical features.

OBJECTIVES: To develop a nomogram based on CT radiomics and clinical features to predict the epidermal growth factor receptor (EGFR) mutations in early-stage lung adenocarcinomas. METHODS: A retrospective analysis of postoperative patients with pathologically confirmed lung adenocarcinoma, which had been tested for EGFR mutations was performed from January 2015 to December 2015. Patients were randomly assigned to training and validation cohorts. A total of 1,078 radiomics features were extracted. least absolute shrinkage and selection operator (LASSO) regression analysis was applied to select clinical and radiomics features, and to establish predictive models. The radiomics score (rad-score) of each patient was calculated. The discrimination of the model was evaluated with area under the curve. RESULTS: 1092 patients (444 men and 648 women; mean age: 59.59±9.6) were enrolled. The radiomics signature consisted of 28 radiomics features and emphysema. The mean validation cohort result of the rad-score for patients with EGFR mutations (0.814±0.988) was significantly higher than those with EGFR wild-type (0.315±1.237; p = 0.001). When combined with clinical features, LASSO regression analysis revealed four radiomics features, emphysema, and three clinical features including sex, age, and histologic subtype as associated with to EGFR mutation status. The nomogram that combined radiomics and clinical features significantly improved the predictive discrimination (AUC: 0.723), which is better than that of the radiomics signature alone (AUC: 0.646). CONCLUSION: A relationship between selected radiomics features and EGFR mutant lung adenocarcinomas is demonstrated. A nomogram, combining radiomics features and clinical features for EGFR prediction in early-stage lung adenocarcinomas, has shown a moderate discriminatory efficiency and high sensitivity, providing additional information for clinicians.

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations.

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.

Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer.

Given that only a subset of patients with colorectal cancer (CRC) benefit from immune checkpoint therapy, efforts are ongoing to identify markers that predict immunotherapeutic response. Increasing evidence suggests that microbes influence the efficacy of cancer therapies. Fusobacterium nucleatum induces different immune responses in CRC with different microsatellite-instability (MSI) statuses. Here, we investigated the effect of F. nucleatum on anti-PD-L1 therapy in CRC. We found that high F. nucleatum levels correlate with improved therapeutic responses to PD-1 blockade in patients with CRC. Additionally, F. nucleatum enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged survival. Combining F. nucleatum supplementation with immunotherapy rescued the therapeutic effects of PD-L1 blockade. Furthermore, F. nucleatum induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma (IFN-γ)+ CD8+ tumor-infiltrating lymphocytes (TILs) during treatment with PD-L1 blockade, thereby augmenting tumor sensitivity to PD-L1 blockade. Finally, patient-derived organoid models demonstrated that increased F. nucleatum levels correlated with an improved therapeutic response to PD-L1 blockade. These findings suggest that F. nucleatum may modulate immune checkpoint therapy for CRC.

Fusobacterium Nucleatum Promotes the Development of Colorectal Cancer by Activating a Cytochrome P450/Epoxyoctadecenoic Acid Axis via TLR4/Keap1/NRF2 Signaling.

Emerging research has revealed regulation of colorectal cancer metabolism by bacteria. Fusobacterium nucleatum (Fn) plays a crucial role in the development of colorectal cancer, however, whether Fn infection modifies metabolism in patients with colorectal cancer remains unknown. Here, LC-MS/MS-based lipidomics identified the upregulation of cytochrome P450 monooxygenases, primarily CYP2J2, and their mediated product 12,13-EpOME in patients with colorectal cancer tumors and mouse models, which increased the invasive and migratory ability of colorectal cancer cells in vivo and in vitro by regulating the epithelial-mesenchymal transition (EMT). Metagenomic sequencing indicated a positive correlation between increased levels of fecal Fn and serum 12,13-EpOME in patients with colorectal cancer. High levels of CYP2J2 in tumor tissues also correlated with high Fn levels and worse overall survival in patients with stage III/IV colorectal cancer. Moreover, Fn was found to activate TLR4/AKT signaling, downregulating Keap1 and increasing NRF2 to promote transcription of CYP2J2. Collectively, these data identify that Fn promotes EMT and metastasis in colorectal cancer by activating a TLR4/Keap1/NRF2 axis to increase CYP2J2 and 12,13-EpOME, which could serve as clinical biomarkers and therapeutic targets for Fn-infected patients with colorectal cancer. SIGNIFICANCE: This study uncovers a mechanism by which Fusobacterium nucleatum regulates colorectal cancer metabolism to drive metastasis, suggesting the potential biomarker and therapeutic utility of the CYP2J2/12,13-EpOME axis in Fn-infected patients.

Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma: an exploratory study.

BACKGROUND: Previous studies have shown that macrophage migration inhibitory factor (MIF) is involved in the pathogenesis of asthma. This study aimed to investigate whether serum MIF reflects a therapeutic response in allergic asthma. METHODS: We enrolled 30 asthmatic patients with mild-to-moderate exacerbations and 20 healthy controls, analyzing the parameter levels of serum MIF, serum total immunoglobulin E (tIgE), peripheral blood eosinophil percentage (EOS%), and fractional exhaled nitric oxide (FeNO). Lung function indices were used to identify disease severity and therapeutic response. RESULTS: Our study showed that all measured parameters in patients were at higher levels than those of controls. After one week of treatment, most parameter levels decreased significantly except for serum tIgE. Furthermore, we found that serum MIF positively correlated with EOS% as well as FeNO, but negatively correlated with lung function indices. Receiver operator characteristic (ROC) curve analysis indicated that among the parameters, serum MIF exhibited a higher capacity to evaluate therapeutic response. The area under the curve (AUC) of MIF was 0.931, with a sensitivity of 0.967 and a specificity of 0.800. CONCLUSIONS: Our results suggested that serum MIF may serve as a potential biomarker for evaluating therapeutic response in allergic asthma with mild-to-moderate exacerbations.