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Supplementary Table 1. Biochemical and biological features of anti-RON mAbs Zt/g4

Background: Aberrant expression of the MET receptor tyrosine kinase is an oncogenic determinant and a drug target for cancer therapy. Currently, antibody-based biotherapeutics targeting MET are under clinical trials. Objective: Here, we report the preclinical and therapeutic evaluation of a novel anti-MET antibody- drug conjugate PCMC1D3-duocarmycin SA (PCMC1D3-DCM) for targeted cancer therapy. Methods: The monoclonal antibody PCMC1D3 (IgG1a/κ), generated by a hybridoma technique and specific to one of the MET extracellular domains, was selected based on its high specificity to human MET with a binding affinity of 1.60 nM. PCMC1D3 was conjugated to DCM via a cleavable valine-citrulline dipeptide linker to form an antibody-drug conjugate with a drug-to-antibody ratio of 3.6:1. PCMC1D3-DCM in vitro rapidly induced MET internalization with an internalization efficacy ranging from 6.5 to 17.2h dependent on individual cell lines. Results: Studies using different types of cancer cell lines showed that PCMC1D3-DCM disrupted the cell cycle, reduced cell viability, and caused massive cell death within 96h after treatment initiation. The calculated IC50 values for cell viability reduction were 1.5 to 15.3 nM. Results from mouse xenograft tumor models demonstrated that PCMC1D3-DCM in a single dose injection at 10 mg/kg body weight effectively delayed xenograft tumor growth up to two weeks without signs of tumor regrowth. The calculated tumoristatic concentration, a minimal dose required to balance tumor growth and inhibition, was around 2 mg/kg body weight. Taken together, PCMC1D3-DCM was effective in targeting the inhibition of tumor growth in xenograft models. Conclusion: This work provides the basis for the development of humanized PCMC1D3-DCM for MET-targeted cancer therapy in the future.

Background and Aims. Elevated serum uric acid (SUA) is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD); however, whether this association is causal is undetermined. Methods. Each participant from the Dongfeng-Tongji cohort study based on 27,009 retirees was interviewed face-to-face following a clinical examination. Covariance, logistic regression analysis, and instrumental variables were used to assess associations between SUA and (severity of) NAFLD and the causal link. Results. Among 8,429 subjects free of NAFLD at baseline, 2,007 participants developed NAFLD after 5 years of follow-up. The multivariable-adjusted odds ratio (OR) for NAFLD for individuals in the fourth quartile of SUA level versus those in the first was 1.71 (95% CI: 1.45-2.01, P for trend P = 0.25 ) from what was expected (1.03, 95% CI: 1.03-1.03). Conclusions. SUA was positively associated with NAFLD incidence especially in female and normal-weight individuals and the suspected progression risk of newly developed NAFLD. However, the Mendelian randomization analyses lend no causal evidence, suggesting high SUA as a marker and not a cause of NAFLD.

Based on a close reading of 118 Tang epitaphs for those who died young, this paper explores how Tang parents remembered and recounted their children's lives as well as factors that contributed to the rise of intense expression of mourning. It finds that while descriptions in epitaphs for adults largely followed Confucian ideals of life course and gender roles, the epitaphs for the young are much less formulaic, allowing space and latitude for parents and families to impart anecdotes and emotions. More importantly, it argues that the rise of epitaphs for children (especially for daughters in the ninth century) reflected a strong influence of Buddhist perception of death and Buddhist mourning rituals. As a result, Tang parents ignored the restrictions and decorum stipulated in The Book of Rites and mourned their children with outward grief, regardless their age and gender.

In order to reuse the waste fabric and develop a novel textile-based adsorbent for heavy metal removal, the waste silk fabric was modified by tannic acid (TA) and the prepared adsorbents were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) analysis. The removal of Cd(II), Cu(II), and Ni(II) ions from aqueous solutions was investigated using the modified silk fabric (TA-SF) under various conditions and the adsorption behavior of heavy metal ions was compared with the original silk fabric. The results showed that the maximum metal adsorption amounts reached 100% in 10 min. The adsorption isotherm models were demonstrated using Langmuir, Freundlich, and Temkin isotherm models, and the adsorption of TA-SF to Cd(II), Cu(II), and Ni(II) were well fitted with Langmuir isotherm than Freundlich and Temkin isotherm model. Moreover, the adsorption kinetics was well fitted with to the pseudo-first-order and pseudo-second-order kinetic models, and adsorption kinetics indicated that the former model was better suited than the latter. For 60 mg/L initial concentrations of Cd(II), Cu(II), and Ni(II) at pH 9.0, the adsorbents' maximum adsorption capacity was 8.03 mg g−1, 7.42 mg g−1, and 7.47 mg g−1, respectively. Within 5 min, the absorbed metal ions on TA-SF could mostly be desorbed. Moreover, TA-SF can adsorb heavy metal ions from dyeing aqueous solution, showing its capability of simultaneous removal of heavy metal and waste dyes. The results suggest that the lower-cost TA-SF could be an effective adsorbent for removing heavy metals from industrial wastewater.

Collision cross section (CCS) values generated from ion mobility mass spectrometry (IM-MS) have commonly been employed to facilitate lipid identification. However, this is hindered by the limited available lipid standards. Recently, CCS values were predicted by means of computational calculations, though the prediction precision was generally not good and the predicted CCS values of the lipid isomers were almost identical. To address this challenge, a least absolute shrinkage and selection operator (LASSO)-based prediction method was developed for the prediction of lipids' CCS values in this study. In this method, an array of molecular descriptors were screened and optimized to reflect the subtle differences in structures among the different lipid isomers. The use of molecular descriptors together with a wealth of standard CCS values for the lipids (365 in total) significantly improved the accuracy and precision of the LASSO model. Its accuracy was externally validated with median relative errors (MREs) of1.1% using an independent data set. This approach was demonstrated to allow differentiation of

A versatile organocatalytic atroposelective N-alkylation has been developed to access axially chiral sulfonamides bearing an allene and allyl entity, and biaryl amino phenols with high efficiency.

The graphical abstract of the study. Quercetin is present in a variety of common fruits and vegetables. And quercetin ameliorated the myocardial injury in diabetic mice.

Chun-Lian Wang,1 Yan Wang,2 Qi-Lan Jiang,3 Yang Zeng,4 Qing-Ping Yao,5 Xing Liu,6 Tao Li,7 Jun Jiang1 1Department of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Department of Clinical Nutrition, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 4Department of Orthodontics, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 5Institute of Mechanobiology & Medical Engineering, School of Life Science & Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 6Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 7Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Jun Jiang; Tao Li, Email jiangjun@swmu.edu.cn; leta49@swmu.edu.cnPurpose: Neutrophil extracellular traps (NETs) play an important role in ischemia-reperfusion injury (IRI) of the hindlimb. The aim of this study was to investigate the effect of recombinant DNase I and sivelestat in eliminating NETs and their effects on IRI limbs.Patients and Methods: An air pump was used to apply a pressure of 300 mmHg to the root of the right hindlimb of the rat for 2 h and then deflated to replicate the IRI model. The formation of NETs was determined by the detection of myeloperoxidase (MPO), neutrophil elastase (NE), and histone H3 in the skeletal muscles of the hindlimbs. Animals were administered 2.5 mg/kg bw/d DNase I, 15 or 60 mg/kg bw/d sivelestat by injection into the tail vein or intramuscularly into the ischemic area for 7d. Elimination of NETs, hindlimb perfusion, muscle fibrosis, angiogenesis and motor function were assessed.Results: DNase I reduced NETs, attenuated muscle fibrosis, promoted angiogenesis in IRI area and improved limb motor function. Local administration of DNase I improved hindlimb perfusion more than intravenous administration. Sivelestat at a dose of 15 mg/kg bw/d increased perfusion, counteracted skeletal muscle fibrosis, promoted angiogenesis and enhanced motor function. However, sivelestat at a dosage of 60 mg/kg bw/d had an adverse effect on tissue repair, especially when injected locally.Conclusion: Both DNase I and moderate doses of sivelestat can eliminate IRI-derived NETs. They improve hindlimb function by improving perfusion and angiogenesis, preventing muscle fibrosis. Appropriate administration mode and dosage is the key to prevent IRI by elimination of NETs. DNase I is more valid when administered topically and sivelestat is more effective when administered intravenously. These results will provide a better strategy for the treatment of IRI in clinical.Keywords: ischemia-reperfusion injury, IRI, neutrophil extracellular traps, NETs, DNase I, sivelestat, hindlimb

Background The use of cervical strain elastography for nulliparous women during late-term pregnancy remains unclear. This study assesses the predictive value of late-term cervical strain elastography for successful induction of labor (IOL) in nulliparous women. Methods This single-centered, prospective study included 86 patients undergoing IOL between January 2020 and March 2022. Univariate and multivariate analyses were conducted to identify predictive factors for successful IOL. The predictive values were assessed using the area under receiver operating characteristic (ROC) curves. Results IOL was successful in 58 patients. The hardness ratio and cervical length were significantly associated with successful late-term IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone. Conclusions The hardness ratio and cervical length assessed by cervical strain elastography during late-term pregnancy are predictors of the success of IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused a global outbreak of coronavirus disease 2019 (COVID-19) pandemic. To elucidate the mechanism of SARS-CoV-2 replication and immunogenicity, we performed a comparative transcriptome profile of mRNA and long non-coding RNAs (lncRNAs) in human lung epithelial cells infected with the SARS-CoV-2 wild-type strain (8X) and the variant with a 12-bp deletion in the E gene (F8). In total, 3,966 differentially expressed genes (DEGs) and 110 differentially expressed lncRNA (DE-lncRNA) candidates were identified. Of these, 94 DEGs and 32 DE-lncRNAs were found between samples infected with F8 and 8X. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzes revealed that pathways such as the TNF signaling pathway and viral protein interaction with cytokine and cytokine receptor were involved. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to the immune response, which might explain the different replication and immunogenicity properties of the 8X and F8 strains. These results provide a useful resource for studying the pathogenesis of SARS-CoV-2 variants.

Background Proper nutritional management was demonstrated to reduce complications and related to better clinical outcomes. However, inaccurate nutritional screening and assessment, inappropriate nutrition support, and contrary to the suggested guidelines were observed in clinical. Methods A self-designed questionnaire was used to conduct a cross-sectional survey in a tertiary-level general hospital. Nutritional Risk Screening 2002 was used for nutrition screening. A total of 620 patients with neurological diseases were enrolled in this study. Results All patients were conducted with nutritional screening, and among them, 24.4% had nutritional risk on admission and 22.7% in the final assessment. However, there were no statistically significant differences in nutritional status between the first and final assessments, except for the serum albumin concentration. 118 patients (19.0%) received pharmaceutical nutrition therapy and complications occurred in 35(45.5%) patients treated with EN and 29 (30.5%) patients treated with PN. In our study, not all nursing measures for tube feeding apart from confirming catheter position and raising the head of the bed were carried out in every patient receiving tube feeding in our research. Conclusions The incidence of nutritional risk of inpatients with neurological diseases enrolled in this research was relatively lower. However, nutritional treatment in this study was not standardized enough and the medical staff was suggested to accept relevant professional training to perform better in nutrition support.

Like the twisting control in magic angle twisted bilayer graphenes, the stacking control is another mechanical approach to manipulate the fundamental properties of solids, especially the van der Waals materials. We explore the stacking-induced magnetic frustration and the spiral spin liquid on a multilayer triangular lattice antiferromagnet where the system is built from ABC stacking with competing intralayer and interlayers couplings. By combining the nematic bond theory and the self-consistent Gaussian approximation, we establish the phase diagram for this ABC-stacked multilayer magnet. It is shown that, the system supports a wide regime of spiral spin liquid with multiple degenerate spiral lines in the reciprocal space, separating the low-temperature spiral order and the high-temperature featureless paramagnet. The transition to the spiral order from the spiral spin liquid regime is first order. We further show that the spiral-spin-liquid behavior persists even with small perturbations such as further neighbor intralayer exchanges. The connection to the ABC-stacked magnets, the effects of Ising or planar spin anisotropy, and the outlook on the stacking-engineered quantum magnets are discussed., Comment: main text: 7 pages + 4 figures; supplemental materials: 15 pages + 5 figures. update: added discussions on the few-layer case

This study proposed and evaluated, for the first time, a novel membrane-photo-electrochemical oxidation (MPEO) process combining electrochemical oxidation, UV irradiation, and ceramic microfiltration for the advanced treatment of coal processing wastewater. The MPEO process could achieve 600 h of sustainable and continuous operation with excellent color (∼90%) and turbidity (>90%) removal. Without electrochemical oxidation and UV irradiation, severe membrane fouling was observed during direct microfiltration due to the accumulation of high content of polysaccharides, proteins and humic-like substances contained in the feedwater on the membrane. On the other hand, in the MPEO system, these macro-organic molecules were effectively degraded into small molecules by the highly reactive hydroxyl free radical (∙OH) produced from electrochemical oxidation and UV irradiation. FT-ICR-MS analysis confirmed these results and showed a significant increase in the number of small organic molecules after MPEO treatment. The MPEO system in this study could potentially be an efficient and sustainable treatment process for treating chemical industrial wastewater containing refractory organics.

Study ObjectivesTo investigate the relationship between sleep transition dynamics and stage-specific functional connectivity (FC) of the anterior cingulate cortex (ACC) in patients with insomnia disorder (ID).MethodsSimultaneous electroencephalography–functional magnetic resonance imaging (EEG–fMRI) data from 37 patients with ID and 30 well-matched healthy controls (HCs) were recorded during wakefulness and different sleep stages and subsequently analyzed. A Markov chain model was used to estimate the transition probability between each stage. The FC between the ACC (set as the seed) and voxels across the whole brain was calculated. A linear mixed effect model was used to determine the group-by-stage interaction of the seed-based connectivity. The correlation between the sleep-stage transition probability and the ACC-based connectivity was explored.ResultsPatients with ID exhibited a higher likelihood of transitioning from N2 to wakefulness than HCs. A significant group-by-stage interaction of connectivity with the bilateral ACC was observed in the cerebellar, subcortical, and cortical regions. Moreover, a significant positive correlation was found in patients with ID between the transition probability from N2 to wakefulness and the FC of the ACC with the anterior cerebellum in N2 (r = 0.48).ConclusionsThis exploratory analysis indicates that enhanced FC between the ACC and cerebellum represents a potential neural pathway underlying the greater likelihood of patients with ID waking during N2 sleep. These findings contribute to an emerging framework that reveals the link between sleep maintenance difficulty and ACC function, further highlighting the possibility that N2 sleep is a therapeutic target for meaningfully reducing sleep disruption.

Cold metal transfer (CMT) additive manufacturing (AM) is widely used for its efficiency and low cost, in order to improve the efficiency the manufacturing,this study carried out CMT arc modes and i...

Optical carrier power fading is a severe problem in radio-over-few-mode-fiber (RoFMF) direct-detection system. We propose a novel method to mitigate the issue of carrier power fading. By analyzing the property of mode coupling in a few-mode fiber, our method is to utilize the linear mode coupling. The method successfully reduces the interference among optical carriers without increasing complexity, achieving the estimated throughput of 114.71 Gbps in the RoFMF system with 1.7-m FMF and 3-m wireless transmission.

Whether the definition of hypertension according to 2017 AHA/ACC guidelines and blood pressure (BP) changes was related to the increased risk of chronic kidney disease (CKD) remained debated. This prospective cohort study aimed to investigate the association of BP and long‐term BP change with CKD risk with different glucose metabolism according to the new hypertension guidelines. This study examined 12 951 participants and 11 183 participants derived from the older people cohort study, respectively. Participants were divided into three groups based on blood glucose and the risks were assessmented by the logistic regression model. During a 10 years of follow‐up period, 2727 individuals developed CKD (21.1%). Compared with those with BP

Con el rapido desarrollo del transporte en China y la mejora del nivel de vida de la poblacion, las carreteras chinas han entrado en el periodo de maximo mantenimiento. De acuerdo con las antiguas condiciones de las carreteras y las condiciones financieras, como elegir la tecnologia de mantenimiento adecuada para cumplir con los requisitos tecnicos y economicos de los proyectos de mantenimiento y construccion de carreteras se ha convertido en un problema dificil al que se enfrentan los departamentos de gestion de mantenimiento de carreteras. Por lo tanto, basandose en el principio de la seleccion de indices, este estudio considera de forma exhaustiva el impacto de varios factores en la toma de decisiones sobre el mantenimiento, determina cuatro indices de evaluacion y estudia sistematicamente el sistema de toma de decisiones integral del mantenimiento del reciclado del pavimento asfaltico. Basandose en la vinculacion subjetiva-objetiva y en el metodo estadistico de la probabilidad, el valor propio de la aplicabilidad del modo de reciclaje se transformo en la misma escala de 0 a 100, y se propuso el intervalo de puntuacion difusa de las cuatro ofertas. Se aclaro el metodo de calculo del indice de recuperacion de la calidad del pavimento (PQRI) y la base de analisis de los beneficios economicos. Por ultimo, se calculo el peso de cada indice mediante el proceso jerarquico analitico, y se construyo el metodo de toma de decisiones integral multiindice de mantenimiento de pavimentos, que se utilizo para verificar y guiar teoricamente la seccion real de la carretera. Los resultados demuestran que el PQRI propuesto puede realizar la operatividad de la cuantificacion de la operacion posterior del pavimento. El peso de cada indice de grande a pequeno es PQRI > beneficio economico > aplicabilidad del modo de reciclaje. Los indices de recuperacion de la calidad del pavimento reciclado y la aplicabilidad de los cuatro modos de reciclaje tienen pequenas diferencias, y el intervalo de cuatro ofertas propuesto hace que el proceso de evaluacion de la decision sea mas sencillo y explicito. Los resultados de la evaluacion de la decision de un tramo de carretera real verifican la racionalidad y la viabilidad del metodo de decision. Las conclusiones son importantes para el mantenimiento y la gestion de la tecnologia de reciclaje del pavimento asfaltico. Palabras clave: ingenieria de carreteras, mantenimiento del reciclado, toma de decisiones inteligente, evaluacion difusa RESUMEN

It is difficult for WTO member countries to raise tariffs unilaterally under current WTO regulations. Therefore, given a constant tariff rate, we examine the impacts of two commodity taxes, an ad valorem tax and a specific tax, on the rent-extracting effect regarding the foreign firm and on the protection effect regarding the domestic firm. We obtain two main results. First, the government can extract more profits from the foreign firm by imposing an ad valorem (a specific) tax, when the tariff rate is low (high); and second, when the tariff rate is low, an ad valorem tax is welfare superior to a specific tax while the reverse may occur when the tariff rate is high. This demonstrates that the magnitude of the tariff rate is crucial when the government chooses the commodity tax scheme.

Sleep spindles have been implicated in sleep protection, depression and anxiety. However, spindle-related brain imaging mechanism underpinning the deficient sleep protection and emotional regulation in insomnia disorder (ID) remains elusive. The aim of the current study is to investigate the relationship between spindle-related brain activations and sleep quality, symptoms of depression and anxiety in patients with ID. Participants (n = 46, 28 females, 18–60 years) were recruited through advertisements including 16 with ID, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and 30 matched controls. Group differences in spindle-related brain activations were analyzed using multimodality data acquired with simultaneous electroencephalography and functional magnetic resonance imaging during sleep. Compared with controls, patients with ID showed significantly decreased bilateral spindle-related brain activations in the cingulate gyrus (familywise error corrected p ˂ 0.05, cluster size 4401 mm3). Activations in the cingulate gyrus were negatively correlated with Pittsburgh Sleep Quality Index scores (r = -0.404, p = 0.005) and Self-Rating Anxiety Scale scores (r = -0.364, p = 0.013), in the pooled sample. These findings underscore the key role of spindle-related brain activations in the cingulate gyrus in subjective sleep quality and emotional regulation in ID.

Quantum spin liquid (QSL) is a disordered state of quantum-mechanically entangled spins commonly arising from frustrated magnetic dipolar interactions. However, QSL in some pyrochlore magnets can also come from frustrated magnetic octupolar interactions. Although the key signature for both dipolar and octupolar interaction-driven QSL is the presence of a spin excitation continuum (spinons) arising from the spin quantum number fractionalization, an external magnetic field-induced ferromagnetic order will transform the spinons into conventional spin waves in a dipolar QSL. By contrast, in an octupole QSL, the spin waves carry octupole moments that do not couple, in the leading order, to the external magnetic field or to neutron moments but will contribute to the field dependence of the heat capacity. Here we use neutron scattering to show that the application of a large external magnetic field to Ce2Zr2O7, an octupolar QSL candidate, induces an Anderson-Higgs transition by condensing the spinons into a static ferromagnetic ordered state with octupolar spin waves invisible to neutrons but contributing to the heat capacity. Our theoretical calculations also provide a microscopic, qualitative understanding for the presence of octupole scattering at large wavevectors in Ce2Sn2O7 pyrochlore, and its absence in Ce2Zr2O7. Therefore, our results identify Ce2Zr2O7 as a strong candidate for an octupolar U (1) QSL, establishing that frustrated magnetic octupolar interactions are responsible for QSL properties in Ce-based pyrochlore magnets.