p38-mediated FOXN3 phosphorylation modulates lung inflammation and injury through the NF-κB signaling pathway.

NF-κB activates the primary inflammatory response pathway responsible for methicillin-resistant Staphylococcus aureus (MRSA)-induced lung inflammation and injury. Here, we report that the Forkhead box transcription factor FOXN3 ameliorates MRSA-induced pulmonary inflammatory injury by inactivating NF-κB signaling. FOXN3 competes with IκBα for binding to heterogeneous ribonucleoprotein-U (hnRNPU), thereby blocking ß-TrCP-mediated IκBα degradation and leading to NF-κB inactivation. FOXN3 is directly phosphorylated by p38 at S83 and S85 residues, which induces its dissociation from hnRNPU, thus promoting NF-κB activation. After dissociation, the phosphorylated FOXN3 becomes unstable and undergoes proteasomal degradation. Additionally, hnRNPU is essential for p38-mediated FOXN3 phosphorylation and subsequent phosphorylation-dependent degradation. Functionally, genetic ablation of FOXN3 phosphorylation results in strong resistance to MRSA-induced pulmonary inflammatory injury. Importantly, FOXN3 phosphorylation is clinically positively correlated with pulmonary inflammatory disorders. This study uncovers a previously unknown regulatory mechanism underpinning the indispensable role of FOXN3 phosphorylation in the inflammatory response to pulmonary infection.

Enantioselective Construction of Quaternary Stereocenters via Cooperative Photoredox/Fe/Chiral Primary Amine Triple Catalysis.

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable and potentially versatile approach is the coupling of a C-C bond through an outer-sphere mechanism, accompanied by the realization of enantiocontrol through cooperative catalysis; however, examples of such processes are yet to be identified. Herein, we present such a method for creating different compounds with quaternary stereocenters by photoredox/Fe/chiral primary amine triple catalysis. This approach facilitates the connection of an unactivated alkyl source with a tertiary alkyl moiety, which is also rare. The scalable process exhibits mild conditions, does not necessitate the use of a base, and possesses a good functional-group tolerance. Preliminary investigations into the underlying mechanisms have provided valuable insights into the reaction pathway.

PHB2 inhibits WSSV replication by promoting the nuclear translocation of STAT.

Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses and cell proliferation. However, the function of the PHBs in immune regulation has largely not been determined. In the present study, we identified PHB2 in the red swamp crayfish Procambarus clarkii. PHB2 was found to be widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge. PHB2 significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. Here, we observed that PHB2 promotes the nuclear translocation of STAT by binding to STAT. After blocking PHB2 or STAT with antibodies or interfering with PHB2 or STAT, the expression levels of the antiviral genes ß-thymosin (PcThy-4) and crustin2 (Cru2) decreased. The gene sequence of PHB2 was analyzed and found to contain a nuclear introgression sequence (NIS). After in vivo injection of PHB2 with deletion of NIS (rΔNIS-PHB2), the nuclear translocation of STAT did not change significantly compared to that in the control group. These results suggest that PHB2 promoted the nuclear translocation of STAT through NIS and mediated the expression of antiviral proteins to inhibit WSSV infection.

Admission blood tests predicting survival of SARS-CoV-2 infected patients: a practical implementation of graph convolution network in imbalance dataset.

BACKGROUND: Predicting an individual's risk of death from COVID-19 is essential for planning and optimising resources. However, since the real-world mortality rate is relatively low, particularly in places like Hong Kong, this makes building an accurate prediction model difficult due to the imbalanced nature of the dataset. This study introduces an innovative application of graph convolutional networks (GCNs) to predict COVID-19 patient survival using a highly imbalanced dataset. Unlike traditional models, GCNs leverage structural relationships within the data, enhancing predictive accuracy and robustness. By integrating demographic and laboratory data into a GCN framework, our approach addresses class imbalance and demonstrates significant improvements in prediction accuracy. METHODS: The cohort included all consecutive positive COVID-19 patients fulfilling study criteria admitted to 42 public hospitals in Hong Kong between January 23 and December 31, 2020 (n = 7,606). We proposed the population-based graph convolutional neural network (GCN) model which took blood test results, age and sex as inputs to predict the survival outcomes. Furthermore, we compared our proposed model to the Cox Proportional Hazard (CPH) model, conventional machine learning models, and oversampling machine learning models. Additionally, a subgroup analysis was performed on the test set in order to acquire a deeper understanding of the relationship between each patient node and its neighbours, revealing possible underlying causes of the inaccurate predictions. RESULTS: The GCN model was the top-performing model, with an AUC of 0.944, considerably outperforming all other models (p < 0.05), including the oversampled CPH model (0.708), linear regression (0.877), Linear Discriminant Analysis (0.860), K-nearest neighbours (0.834), Gaussian predictor (0.745) and support vector machine (0.847). With Kaplan-Meier estimates, the GCN model demonstrated good discriminability between low- and high-risk individuals (p < 0.0001). Based on subanalysis using the weighted-in score, although the GCN model was able to discriminate well between different predicted groups, the separation was inadequate between false negative (FN) and true negative (TN) groups. CONCLUSION: The GCN model considerably outperformed all other machine learning methods and baseline CPH models. Thus, when applied to this imbalanced COVID survival dataset, adopting a population graph representation may be an approach to achieving good prediction.

Extracellular vesicle-transmitted miR-671-5p alleviates lung inflammation and injury by regulating the AAK1/NF-κB axis.

Mesenchymal stem cells regulate remote intercellular signaling communication via their secreted extracellular vesicles. Here, we report that menstrual blood-derived stem cells alleviate acute lung inflammation and injury via their extracellular vesicle-transmitted miR-671-5p. Disruption of this abundantly expressed miR-671-5p dramatically reduced the ameliorative effect of extracellular vesicles released by menstrual blood-derived stem cells on lipopolysaccharide (LPS)-induced pulmonary inflammatory injury. Mechanistically, miR-671-5p directly targets the kinase AAK1 for post-transcriptional degradation. AAK1 is found to positively regulate the activation of nuclear factor κB (NF-κB) signaling by controlling the stability of the inhibitory protein IκBα. This study identifies a potential molecular basis of how extracellular vesicles derived from mesenchymal stem cells improve pulmonary inflammatory injury and highlights the functional importance of the miR-671-5p/AAK1 axis in the progression of pulmonary inflammatory diseases. More importantly, this study provides a promising cell-based approach for the treatment of pulmonary inflammatory disorders through an extracellular vesicle-dependent pathway.

Modeling Structured Dependency Tree with Graph Convolutional Networks for Aspect-Level Sentiment Classification.

Aspect-based sentiment analysis is a fine-grained task where the key goal is to predict sentiment polarities of one or more aspects in a given sentence. Currently, graph neural network models built upon dependency trees are widely employed for aspect-based sentiment analysis tasks. However, most existing models still contain a large amount of noisy nodes that cannot precisely capture the contextual relationships between specific aspects. Meanwhile, most studies do not consider the connections between nodes without direct dependency edges but play critical roles in determining the sentiment polarity of an aspect. To address the aforementioned limitations, we propose a Structured Dependency Tree-based Graph Convolutional Network (SDTGCN) model. Specifically, we explore construction of a structured syntactic dependency graph by incorporating positional information, sentiment commonsense knowledge, part-of-speech tags, syntactic dependency distances, etc., to assign arbitrary edge weights between nodes. This enhances the connections between aspect nodes and pivotal words while weakening irrelevant node links, enabling the model to sufficiently express sentiment dependencies between specific aspects and contextual information. We utilize part-of-speech tags and dependency distances to discover relationships between pivotal nodes without direct dependencies. Finally, we aggregate node information by fully considering their importance to obtain precise aspect representations. Experimental results on five publicly available datasets demonstrate the superiority of our proposed model over state-of-the-art approaches; furthermore, the accuracy and F1-score show a significant improvement on the majority of datasets, with increases of 0.74, 0.37, 0.65, and 0.79, 0.75, 1.17, respectively. This series of enhancements highlights the effective progress made by the STDGCN model in enhancing sentiment classification performance.

Characteristics and source apportionment of ambient volatile organic compounds and ozone generation sensitivity in urban Jiaozuo, China.

In recent years, many cities have taken measures to reduce volatile organic compounds (VOCs), an important precursor of ozone (O3), to alleviate O3 pollution in China. 116 VOC species were measured by online and offline methods in the urban area of Jiaozuo from May to October in 2021 to analyze the compositional characteristics. VOC sources were analyzed by a positive matrix factorization (PMF) model, and the sensitivity of ozone generation was determined by ozone isopleth plotting research (OZIPR) simulation. The results showed that the average volume concentration of total VOCs was 30.54 ppbv and showed a bimodal feature due to the rush-hour traffic in the morning and at nightfall. The most dominant VOC groups were oxygenated VOCs (OVOCs, 29.3%) and alkanes (26.7%), and the most abundant VOC species were acetone and acetylene. However, based on the maximum incremental reactivity (MIR) method, the major VOC groups in terms of ozone formation potential (OFP) contribution were OVOCs (68.09 µg/m3, 31.5%), aromatics (62.90 µg/m3, 29.1%) and alkene/alkynes (54.90 µg/m3, 25.4%). This indicates that the control of OVOCs, aromatics and alkene/alkynes should take priority. Five sources of VOCs were quantified by PMF, including fixed sources of fossil fuel combustion (27.8%), industrial processes (25.9%), vehicle exhaust (19.7%), natural and secondary formation (13.9%) and solvent usage (12.7%). The empirical kinetic modeling approach (EKMA) curve obtained by OZIPR on O3 exceedance days indicated that the O3 sensitivity varied in different months. The results provide theoretical support for O3 pollution prevention and control in Jiaozuo.

Bibliometric analysis and mini-review of global research on pyroptosis in the field of cancer.

Pyroptosis is one of the mechanisms of programmed cell death (PCD) activated by inflammasomes and involved by the caspase family and the gasdermin family. During the oncogenesis and progression of tumors, pyroptosis is crucial, and complex withal. Currently, pyroptosis is the focus topic in the research field of oncology, but there is no single bibliometric analysis systematically studying 'pyroptosis and cancer'. Our study aimed to visualize the research status of pyroptosis in oncology and excavate the hotspots and prospects in this field. Furthermore, in consideration of the professional direction of researchers, we particularly emphasized articles on pyroptosis in gynecology and formed a mini systematic review. This bibliometric work integrated and analyzed all articles from ISI Web of Science: Science Citation Index Expanded (SCI-Expanded) (dated April 25th, 2022), based on quantitative and visual mapping approaches. Systematically reviewing articles on pyroptosis in gynecology helped us complement our analysis of research advancements in this field. Including 634 articles, our study found that the number of articles on pyroptosis in cancer increased exponentially in recent years. These publications came from 45 countries and regions headed by China and the US mainly aiming at the mechanism of pyroptosis in cell biology and biochemistry molecular biology, as well as the role of pyroptosis in the development and therapeutic application of various cancers. The top 20 most cited studies on this topic mostly came from the US, followed by China and England, and half of the articles cited more than 100 times in total were published in Nature. Moreover, as for gynecologic cancer, in vitro and bioinformatics analysis were the main methodology conducting to explore roles of pyroptosis-related genes (PRGs) and formation of inflammasomes in cancer progression and prognosis. Pyroptosis has evolved into a burgeoning research field in oncology. The cellular and molecular pathway mechanism of pyroptosis, as well as the effect of pyroptosis in oncogenesis, progression, and treatment have been the hot topic of the current study and provided us the future direction as the potential opportunities and challenges. We advocate more active cooperation to improve therapeutic strategies for cancer.

Resveratrol reduces ROS-induced ferroptosis by activating SIRT3 and compensating the GSH/GPX4 pathway.

BACKGROUND: Intestinal ischemia-reperfusion injury occurs in acute intestinal obstruction, intussusception, acute mesenteric artery embolism, and other diseases and can lead to local intestinal necrosis, distant organ involvement, or systemic reactions, with high morbidity and mortality. Ferroptosis plays a crucial role in intestinal ischemia-reperfusion injury, and inhibition of ferroptosis may provide new approaches for treating the disease. SIRT3 protects cells from oxidative stress and may be involved in the process of ferroptosis. We hypothesized that resveratrol, an agonist of SIRT3, could ameliorate intestinal ischemia-reperfusion injury by compensating the GSH/GPX4 pathway. METHODS: Intestinal ischemia-reperfusion (I/R) and Caco-2 hypoxia-reoxygenation models were established. Transmission electron microscopy was used to assess mitochondrial function; the Chiu's score was used to evaluate the degree of intestinal mucosal injury based on HE staining; and Western blot was used to detect the SIRT3/FoxO3a pathway, tight junction proteins and ferroptosis-related protein expression. Sirt3-/- C57, shSIRT3-Caco-2 cells and siFoxO3a-Caco-2 cells were established. C11-BODIPY was used to detect lipid peroxide in cells; FD4 and IFABP were used to detect intestinal permeability; MitoSOX was used to detect ROS levels; and MitoTracker and immunofluorescence colocalization were used to detect SIRT3 levels. RESULTS: In the intestinal I/R model, I/R injury occurs mainly during the reperfusion period and leads to ferroptosis through the GSH/GPX4 pathway. Resveratrol could reduce ferroptosis and ameliorate I/R injury by activating SIRT3. In Sirt3-/- mice, more intestinal mucosal cells underwent ferroptosis, I/R injury was more severe, and resveratrol lost the ability to ameliorate I/R injury. In addition, hypoxia-reoxygenation increased RSL3-induced ferroptosis sensitivity in Caco-2 cells in vitro. In the presence of shSIRT3 or RSL3 alone, resveratrol could ameliorate Caco-2 ferroptosis, but not RSL3-induced shSIRT3-Caco-2 ferroptosis. Furthermore, resveratrol might activate the SIRT3/FoxO3a pathway, increase the expression of SOD2 and catalase, and inhibit ROS generation, thus reducing lipid peroxidation and ferroptosis. CONCLUSION: To date, this is the first study to show that resveratrol ameliorates intestinal ischemia-reperfusion injury by activating SIRT3 and reducing ferroptosis. Resveratrol can reduce intestinal ischemia-reperfusion injury by activating the SIRT3/FoxO3a pathway, increasing the expression of SOD2 and catalase, reducing ROS and LPO production, compensating for the GSH/GPX4 pathway and inhibiting ferroptosis. Resveratrol increases the expression of SOD2 and catalase, reduces the production of ROS and LPO, compensates for the GSH/GPX4 pathway and inhibits ferroptosis by activating the SIRT3/FoxO3a pathway.

Time-reversal waveform design for underwater wireless optical communication systems.

Underwater wireless optical communications (UWOC) is a promising technology to construct underwater Internet of Things. In spite of the great progress in high-speed communication having been realized, scattering, absorption, and turbulence result in an unreliable underwater channel for reliable data transmissions. In this paper, we propose a time-reversal (TR) waveform design technique in UWOC systems for intersymbol interference (ISI) reduction. Due to the optical scattering properties in the ocean, the dispersive channel impulse response (CIR) of UWOC is caused by the multi-path effects of numerous scattered and delayed photons. Based on the analysis and simulation results shown in this paper, the TR waveform is well-suited for UWOC systems. After transmitting the TR waveform, the equivalent channel becomes symmetric, which is easily equalized to mitigate the ISI. Since only the intensity modulation and direct detection can be used for UWOC systems, we derive the UWOC channel as a combination of an exponential bias with the random scattering effects. From the numerical results shown in this work, a phenomenon called the squeezing effect is found, which explains the influence of non-negative channels for the TR waveform design in the UWOC system. Due to the squeezing effect, an equalizer is necessarily applied. With the help of TR waveforms, the bit error rate in the tested environment is greatly better than the case of not using the TR waveform.

Fusobacterium nucleatum-derived small extracellular vesicles facilitate tumor growth and metastasis via TLR4 in breast cancer.

BACKGROUND: The contributive role of the microbiome in tumor progression has been reported in multiple studies, such as the Fusobacterium nucleatum (F. nucleatum) in breast cancer (BC). This study aimed to explore the role of F. nucleatum-derived small extracellular vesicles (Fn-EVs) in BC and preliminarily uncover the mechanism. METHODS: Ten normal and 20 cancerous breast tissues were harvested to investigate the gDNA expression of F. nucleatum and its relation with the clinical characteristics of BC patients. After isolating Fn-EVs by ultracentrifugation from F. nucleatum (ATCC 25,586), both MDA-MB-231 and MCF-7 cells were treated with PBS, Fn, or Fn-EVs, followed by being subjected to CCK-8, Edu staining, wound healing, and Transwell assays to detect their cell viability, proliferation, migration, and invasion. TLR4 expression in BC cells with diverse treatments was assessed by western blot. In vivo experiments were performed to verify its role in tumor growth and liver metastasis. RESULTS: The F. nucleatum gDNA levels of breast tissues in BC patients were significantly higher than those in normal subjects, and positively associated with tumor size and metastasis. Fn-EVs administration significantly enhanced the cell viability, proliferation, migration, and invasion of BC cells, while knocking down TLR4 in BC cells could block these effects. Furthermore, in vivo study verified the contributive role of Fn-EVs in tumor growth and metastasis of BC, which might rely on its regulation of TLR4. CONCLUSIONS: Collectively, our results suggest that F. nucleatum plays an important role in BC tumor growth and metastasis by regulating TLR4 through Fn-EVs. Thus, a better understanding of this process may aid in the development of novel therapeutic agents.

PcTrim prevents early infection with white spot syndrome virus by inhibiting AP1-induced endocytosis.

Viruses have evolved various strategies to achieve early infection by initiating transcription of their own early genes via host transcription factors, such as NF-κb, STAT, and AP1. How the host copes with this immune escape has been a topic of interest. Tripartite motif (TRIM) family proteins with RING-type domains have E3 ubiquitin ligase activity and are known as host restriction factors. Trim has been reported to be associated with phagocytosis and is also believed to be involved in the activation of autophagy. Preventing the virus from entering the host cell may be the most economical way for the host to resist virus infection. The role of TRIM in the early stage of virus infection in host cells remains to be further interpreted. In the current study, a crayfish TRIM with a RING-type domain, designated as PcTrim, was significantly upregulated under white spot syndrome virus (WSSV) infection in the red swamp crayfish (Procambarus clarkii). Recombinant PcTrim significantly inhibited WSSV replication in crayfish. RNAi targeting PcTrim or blocking PcTrim with an antibody promoted WSSV replication in crayfish. Pulldown and co-IP assays showed that PcTrim can interact with the virus protein VP26. PcTrim restricts the expression level of dynamin, which is involved in the regulation of phagocytosis, by inhibiting AP1 entry into the nucleus. AP1-RNAi effectively reduced the expression levels of dynamin and inhibited host cell endocytosis of WSSV in vivo. Our study demonstrated that PcTrim might reduce early WSSV infection by binding to VP26 and then inhibiting AP1 activation, resulting in reduced endocytosis of WSSV in crayfish hemocytes. Video Abstract.

Characterization of immune landscape and development of a novel N7-methylguanine-related gene signature to aid therapy in recurrent aphthous stomatitis.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is the most common inflammatory disease of the oral mucosa resulting in an impaired life quality and even leading to tumors in susceptible populations. N7-Methylguanine (m7G) plays a vital role in various cellular activities but has not yet been investigated in RAS. We aimed at picturing the immune landscape and constructing an m7G-related gene signature, and investigating candidate drugs and gene-disease association to aid therapy for RAS. METHODS: For our study, m7G-related differentially expressed genes (DEGs) were screened. We outlined the immune microenvironment and studied the correlations between the m7G-related DEGs and immune cells/pathways. We performed functional enrichment analyses and constructed the protein-protein interaction (PPI) and multifactor regulatory network in RAS. The m7G-related hub genes were extracted to formulate the corresponding m7G predictive signature. RESULTS: We obtained 11 m7G-related DEGs and studied a comprehensive immune infiltration landscape, which indicated several immune markers as possible immunotherapeutic targets. The PPI and multifactor regulatory network was constructed and 4 hub genes (DDX58, IFI27, IFIT5, and PML) were identified, followed by validation of the corresponding m7G predictive signature for RAS. GO and KEGG analyses revealed the participation of JAK-STAT and several immune-related pathways. Finally, we suggested candidate drugs and gene-disease associations for potential RAS medical interventions. CONCLUSIONS: The present study pictured a comprehensive immune infiltration landscape and suggested that m7G played a vital role in RAS through immune-related pathways. This study provided new insight for the future investigation of the mechanisms and therapeutic strategies for RAS.

Amplified Single-Atom U-O Interfacial Effect Originated from U 5f-O 2p Hybridization over UOx/GO for Enhanced Nitrogen Reduction Reaction.

Uranium-based catalysts have been regarded as promising candidates for N2 fixation owing to the low-valent uranium metal active sites possessing the ability to enhance the electron back-donating to the π* antibonding orbitals of N2 for N≡N dissociation. Herein, we report a directional half-wave rectified alternating current electrochemical method to confine oxygen-rich uranium precursors over ultrathin 2D GO nanosheets. The as-prepared uranium catalysts exhibit a considerable Faradaic efficiency of 12.7% for NH3 and the NH3 yield rate of 18.7 µg h-1 mg-1 for N2 electroreduction. Operando XAS and isotope-labeling FTIR further unravel the preferred nitrogen adsorption reaction intermediate N-(2Oax-1 U-4Oeq) and confirm the key *N2Hy intermediate species derived from the fed N2 gas. Theoretical simulations demonstrate that the U-O atomic interface originated from U 5f-O 2p orbital hybridization can accumulate partial charge from GO, which can facilitate the N≡N dissociation and lower the thermodynamic energy barrier of the first hydrogenation step.

Unveiling the Critical Role of Surface Hydroxyl Groups for Electro-Assisted Uranium Extraction from Wastewater.

The electro-driven extraction of uranium from fluorine-containing uranium wastewater is anticipated to address the challenge of separating fluoro-uranium complexes in conventional technologies. Herein, we developed hydroxy-rich cobalt-based oxides (CoOx) for electro-assisted uranium extraction from fluorine-containing wastewater. Relying on theoretical calculations and other spectral measurements, the hydroxy-rich CoOx nanosheets can enhance the affinity for uranium due to the existence of a substantial quantity of hydroxyl groups. Accordingly, the CoOx nanosheets exhibit outstanding U(VI) removal efficiency in the presence of fluorine ions. Through the utilization of X-ray absorption fine structure (XAFS), we confirm that hydroxy-rich CoOx nanosheets capture free uranyl ions to form a sturdy 2Oax-1U-3Oeq configuration, which can be achieved through electro-driven fluorine-uranium separation. Notably, for the first time, the whole reaction process of uranium species on the CoOx surface from the initial uranium single atom growth to uranium oxide nanosheets is monitored by aberration-corrected transmission electron microscopes (AC-TEM). This work provides a paradigm for the advancement of novel functional materials as electrocatalysts for uranium extraction, as well as a new approach for studying the evolution mechanism of uranium species.

Recent Advances in Corrosion Science Applicable To Disposal of High-Level Nuclear Waste.

High-level radioactive waste is accumulating at temporary storage locations around the world and will eventually be placed in deep geological repositories. The waste forms and containers will be constructed from glass, crystalline ceramic, and metallic materials, which will eventually come into contact with water, considering that the period of performance required to allow sufficient decay of dangerous radionuclides is on the order of 105-106 years. Corrosion of the containers and waste forms in the aqueous repository environment is therefore a concern. This Review describes the recent advances of the field of materials corrosion that are relevant to fundamental materials science issues associated with the long-term performance assessment and the design of materials with improved performance, where performance is defined as resistance to aqueous corrosion. Glass, crystalline ceramics, and metals are discussed separately, and the near-field interactions of these different material classes are also briefly addressed. Finally, recommendations for future directions of study are provided.

Anatomical location, risk factors, and outcomes of lower gastrointestinal bleeding in colorectal cancer patients: a national inpatient sample analysis (2009-2019).

PURPOSE: This study aimed to investigate the incidence, predictors, and impact of lower gastrointestinal bleeding (LGIB) on inpatient mortality among colorectal cancer patients, due to its clinical significance and potential influence on patient outcomes. METHODS: We conducted a retrospective analysis of data from the National Inpatient Sample database between 2009 and 2019, including 2,598,326 colorectal cancer patients with and without LGIB. Univariate and multivariate logistic regression analyses were performed to determine predictors of LGIB and its association with inpatient outcomes. RESULTS: The highest incidence of LGIB was observed in rectal cancer patients (3.8%), followed by distal colon cancer patients (1.4%) and proximal colon cancer patients (1.2%). Several factors were significantly associated with LGIB, including older age; male sex; certain racial such as Black, Hispanic, and Asia/Pacific Islander patients; or lower socioeconomic status. Multivariate analysis identified independent predictors of LGIB, such as severe sepsis, use of anticoagulants, long-term use of aspirin or antiplatelet drugs, palliative care, malnutrition, cachexia, chemotherapy or immunotherapy, metastasis, alcohol abuse, hypertension, obesity, and family history of digestive cancer. No significant difference in inpatient mortality was observed between patients with and without LGIB. CONCLUSION: Our study underscores the importance of considering colorectal cancer location and identified risk factors for LGIB assessment. Clinicians should address modifiable risk factors and healthcare disparities. Future research should explore underlying mechanisms, targeted interventions, and long-term outcomes beyond inpatient mortality.

Reliability and validity of the Chinese version of chronic liver disease questionnaire-nonalcoholic fatty liver disease in patients with nonalcoholic fatty liver disease: a multicenter cross-sectional survey in China.

PURPOSE: The Chronic Liver Disease Questionnaire (CLDQ)-Nonalcoholic Fatty Liver Disease (NAFLD) is a disease-specific instrument to assess the health-related quality of life (HRQL) of patients with NAFLD. In order to provide further evidence for the cross-cultural utility of this instrument in the Chinese population, we translated the CLDQ-NAFLD into Chinese and examined its reliability and validity. METHODS: Patients with NAFLD in 90 hospitals across China were enrolled in this multicenter cross-sectional survey. Eligible patients completed the Chinese version of CLDQ-NAFLD at enrollment to assess HRQL. Internal consistency of the questionnaire was assessed using Cronbach's alpha coefficient and split-half reliability. Convergent and discriminant validity were assessed using Spearman correlation coefficient. Factor analysis was used to test the construct validity. RESULTS: Between March and August 2019, 5181 patients with a mean age of 43.8 ± 13.3 years were enrolled. All domains exhibited good internal consistency, with Cronbach's alpha and split-half reliability greater than 0.70. The scaling success rate of all domains was 100% for convergent validity and 99.4% (179/180) for discriminant validity. The inter-scale correlations indicated a significant correlation between all CLDQ-NAFLD domains (r = 0.608 to 0.832, all p < 0.001). Factor analysis of 36 items extracted 6 factors, which explained 69.14% of the total variance. CONCLUSION: The Chinese version of CLDQ-NAFLD is a reliable and valid instrument for assessing the HRQL of Chinese patients with NAFLD.

First-principles molten salt phase diagrams through thermodynamic integration.

Precise prediction of phase diagrams in molecular dynamics simulations is challenging due to the simultaneous need for long time and large length scales and accurate interatomic potentials. We show that thermodynamic integration from low-cost force fields to neural network potentials trained using density-functional theory (DFT) enables rapid first-principles prediction of the solid-liquid phase boundary in the model salt NaCl. We use this technique to compare the accuracy of several DFT exchange-correlation functionals for predicting the NaCl phase boundary and find that the inclusion of dispersion interactions is critical to obtain good agreement with experiment. Importantly, our approach introduces a method to predict solid-liquid phase boundaries for any material at an ab initio level of accuracy, with the majority of the computational cost at the level of classical potentials.

Dynamic contrast-enhanced MRI perfusion parameters are imaging biomarkers for angiogenesis in lung cancer.

BACKGROUND: Quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may have the potential to reflect angiogenesis and proliferation of pulmonary neoplasms. PURPOSE: To verify whether DCE-MRI can identify pulmonary neoplasm property and evaluate the correlation of DCE-MRI perfusion parameters with microvessel density (MVD) and Ki-67 in lung cancer. MATERIAL AND METHODS: This study enrolled 65 patients with one pulmonary neoplasm who underwent computed tomography-guided percutaneous lung biopsy with pathological diagnosis (43 malignant, 22 benign; mean age = 59.71 ± 11.72 years). All patients did DCE-MRI before biopsy. Quantitative MRI parameters including endothelial transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space (EES) volume (Ve) were calculated by extended Tofts linear model. MVD was evaluated by CD34-expressing tumor vessels. Proliferation was assessed by Ki-67 staining. The correlations of parameters with MVD and Ki-67 expression were analyzed. RESULTS: Ktrans and Kep values were significantly increased in malignant lesions compared to benign lesions (P = 0.001 and 0.022, respectively), whereas no statistical difference in Ve was found. The CD34 expression was positively correlated to Ktrans (r = 0.608; P = 0.004) and Kep (r = 0.556; P = 0.001). Subsequent subtype analyses also showed positive correlations of Ktrans and Kep with MVD in adenocarcinoma group (r = 0.550 and 0.563; P = 0.012 and 0.015, respectively). No significant correlation was found between these parameters and Ki-67. CONCLUSION: Ktrans and Kep may distinguish benign and malignant pulmonary neoplasm. Ktrans and Kep, with their positive correlation to MVD, can be used as non-invasive parameters reflecting lung cancer angiogenesis.