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In this study, the toxigenic characteristics of 14 strains of Microcystis were analyzed, and single nucleotide polymorphism (SNP) and insertion/deletion (InDel) loci in microcystin synthetase (mcy) gene clusters were screened. Based on SNP and InDel loci associated with the toxigenic characteristics, primers and TaqMan or Cycling fluorescent probes were designed to develop duplex real-time fluorescent quantitative PCR (FQ-PCR) assays. After evaluating specificity and sensitivity, these assays were applied to detect the toxigenic Microcystis genotypes in a shrimp pond where Microcystis blooms occurred. The results showed a total of 2155 SNP loci and 66 InDel loci were obtained, of which 12 SNP loci and 5 InDel loci were associated with the toxigenic characteristics. Three duplex real-time FQ-PCR assays were developed, each of which could quantify two genotypes of toxigenic Microcystis. These FQ-PCR assays were highly specific, and two Cycling assays were more sensitive than TaqMan assay. In the shrimp pond, six genotypes of toxigenic Microcystis were detected using the developed FQ-PCR assays, indicating that above genotyping assays have the potential for quantitative analysis of the toxigenic Microcystis genotypes in natural water. [ABSTRACT FROM AUTHOR]

Solid-state infrared-to-visible photon up-conversion is important for spectral-tailoring applications. However, existing up-conversion systems not only suffer from low efficiencies and a need for high excitation intensity, but also exhibit a limited selection of materials and complex fabrication processes. Herein, we propose a sensitizer with a bulk-heterojunction structure, comprising both an energy donor and an energy acceptor, for triplet-triplet annihilation up-conversion devices. The up-conversion occurs through charge separation at the donor-acceptor interface, followed by the formation of charge transfer state between the energy donor and annihilator following the spin statistics. The bulk-heterojunction sensitizer ensures efficient charge generation and low charge recombination. Hence, we achieve a highly efficient solid-state up-conversion device with 2.20% efficiency and low excitation intensity (10 mW cm−2) through a one-step solution method. We also demonstrate bright up-conversion devices on highly-flexible large-area substrates. This study introduces a simple and scalable platform strategy for fabricating efficient up-conversion devices. Using donor-acceptor bulk heterojunction as sensitiser for efficient charge generation and low charge recombination in triplet-triplet annihilation upconversion, Bi et al report solid-state one-step printed device with upconversion efficiency of 2.2% and threshold excitation intensity of 10 mW cm−2. [ABSTRACT FROM AUTHOR]

This article proposes a parameter extraction method suitable for Si substrate based GaN HEMT small signal equivalent circuit models. The proposed method is based on a swarm intelligence optimization algorithm, which improves efficiency and accuracy by introducing a slope penalty factor (SPF) method for the objective function, rather than simply minimizing the error between simulation and measurement. By using PSO, WOA, and PNC-WOA for validation, we have demonstrated the advantages of the SPF method in extracting small signal parameters using swarm intelligence optimization algorithms. It is suitable for complex small-signal models that can describe the GaN HEMT-on-Si substrates, even if working up to 40 GHz. [ABSTRACT FROM AUTHOR]

TGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-β1 and TGF-βR1 and survivals. Patients with TGF-β1 rs1800470 CT or CC genotype had 30–35% risk reductions for OS, DSS, and DFS compared to patients with TT genotype among overall patients, ever smokers, and patients administered chemoradiation. Furthermore, patients with TGF-βR1 rs334348 GA or GG genotype had significant 50–60% risk reductions for OS, DSS, and DFS compared to patients with AA genotype among overall patients and patients administered chemoradiation; among ever smokers, the risk reductions even reached 60–70%. The TCGA dataset was used for validation. These findings suggest that TGF-β1 rs1800470 and TGF-βR1 rs334348 significantly affect survival outcomes in patients with smoking-related head and neck cancer, especially in the subgroups of ever smokers and patients treated with chemoradiation. These genetic variants may serve as prognostic indicators for patients with smoking-related head and neck cancer and could play a role in advancing the field of personalized chemoradiation, thereby improving patient survival and quality of life. [ABSTRACT FROM AUTHOR]

In this study, a bacterial strain Chryseobacterium bernardetii WK-3 was isolated from the rhizosphere soil of a uranium tailings in Southern China. It can efficiently adsorb hexavalent uranium with an adsorption ratio of 92.3%. The influence of different environmental conditions on the adsorption ratio of Chryseobacterium bernardetii strain WK-3 was investigated, and the adsorption mechanism was preliminarily discussed by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM–EDS). The results showed that the optimal adsorption conditions for U(VI) by Chryseobacterium bernardetii strain WK-3 were pH = 5, temperature 30 ℃, NaCl concentration 1%, and inoculation volume 10%. When the initial concentration of U was 50 ~ 150 mg/L, the adsorption capacity of Chryseobacterium bernardetii strain WK-3 to U(VI) reached the maximum and maintained the equilibrium at 44 h. SEM–EDS results showed that phosphorus in cells participates in the interaction of uranyl ions, which may indicate that phosphate was produced during cell metabolism and was further combined to form U(VI)-phosphate minerals. In summary, Chryseobacterium bernardetii strain WK-3 would be a promising alternative for environmental uranium contamination remediation. [ABSTRACT FROM AUTHOR]

A new species of the genus Lunovula Rosenberg, 1990, Lunovula supingae sp. nov. feeding on deep-sea hydroid Solanderia sp. (Solanderiidae, commonly known as tree hydroid) is described and illustrated from the East China Sea and South China Sea. It is most similar to Lunovula venusta Tsuchida & Kurozumi, 1999 in general shell shape but can be distinguished from the latter by having a more elevated funiculum with two large raised teeth, higher number of labial teeth, less protruding posterior extremity, and most notably, by having an outer lip that entirely thickens to the outside. This represents the first record of a pediculariid species feeding on a hydroid other than a hydrocoral. Phylogenetic analyses based on the COI and 16S rRNA genes using Bayesian inference and maximum likelihood showed that Lunovula supingae sp. nov. falls into the family Pediculariidae, supporting the systematic placement of Lunovula in the family. Furthermore, the phylogenetic analyses recovered the Ovulidae as polyphyletic, suggesting that this family needs a further taxonomic revision. [ABSTRACT FROM AUTHOR]

We study the local quantum Fisher information (LQFI) in the mixed-spin Heisenberg XXZ chain. Both the maximal and minimal LQFI are studied and the former is essential to determine the accuracy of the quantum parameter estimation, the latter can be well used to characterize the discord-type quantum correlations. We investigate the effects of the temperature and the anisotropy parameter on the maximal LQFI and thus on the accuracy of the parameter estimation. Then we make use of the minimal LQFI to study the discord-type correlations of different site pairs. Different dimensions of the subsystems cause different values of the minimal LQFI which reflects the asymmetry of the discord-type correlation. In addition, the site pairs at different positions of the spin chains have different minimal LQFI, which reveals the influence of the surrounding spins on the bipartite quantum correlation. Our results show that the LQFI obtained through a simple calculation process provides a convenient way to investigate the discord-type correlation in high-dimensional systems. [ABSTRACT FROM AUTHOR]

In this study, the relationship between PM2.5 and ambient temperature, humidity, air pressure, wind speed and air indices was investigated by combining specific facilities at uranium mine with villages and cities. Humidity, atmospheric pressure and air quality index were positively correlated with PM2.5 concentration, whereas temperature and wind speed were negatively correlated, while altitude had no correlation with PM2.5 concentration. By constructing the corresponding PMF model data analysis, this study obtained six sources of eight metallic elements (U, Th, Al, Cu, Pb, Cd, Ti, Zn) in PM2.5 around a decommissioned uranium mine. [ABSTRACT FROM AUTHOR]

Optimizing collaborative behavior is crucial in educational activities, directly improving academic performance, social skills, and social-emotional learning for both teachers and students. In an effort to decipher the mechanisms underlying the effectiveness of collaborative learning, educators and neuroscientists have initiated the collection and analysis of learners' physiological parameters during such collaborative exercises. Considering both accuracy and portability, functional near-infrared spectroscopy (fNIRS) has emerged as a viable tool. The current study aims to understand its potential for studying neural mechanisms of collaboration. Sixty articles were reviewed from three databases to address three research questions: (1) What are the characteristics (i.e., number of publications per year and for different age groups of participants, sample size, and the usage of fNIRS devices) of fNIRS-based collaboration research? (2) What experimental designs are commonly employed in fNIRS-based collaboration research? (3) What is the relationship between neural activity and interactive behavioral performance? The results provide a comprehensive descriptive statistical analysis of the literature characteristics and offer a detailed summary of the research methods employed, including the experimental protocol, task, and duration. Importantly, these findings demonstrate compelling evidence of inter-brain synchrony (IBS), indicating synchronized cortical activities between interacting individuals, and it was observed in the prefrontal cortex or temporoparietal cortex during collaboration and interaction tasks, highlighting the crucial role of these brain regions in facilitating collaborative behavior. The finding of this review advanced our understanding of how fNIRS is ultilized in collaborative research and offer practical implications for designing educational interventions or programs aimd at enhancing collaborative behaviors and their associated benefits. [ABSTRACT FROM AUTHOR]

The limited surface coverage and activity of active hydrides on oxide surfaces pose challenges for efficient hydrogenation reactions. Herein, we quantitatively distinguish the long-puzzling homolytic dissociation of hydrogen from the heterolytic pathway on Ga2O3, that is useful for enhancing hydrogenation ability of oxides. By combining transient kinetic analysis with infrared and mass spectroscopies, we identify the catalytic role of coordinatively unsaturated Ga3+ in homolytic H2 dissociation, which is formed in-situ during the initial heterolytic dissociation. This site facilitates easy hydrogen dissociation at low temperatures, resulting in a high hydride coverage on Ga2O3 (H/surface Ga3+ ratio of 1.6 and H/OH ratio of 5.6). The effectiveness of homolytic dissociation is governed by the Ga-Ga distance, which is strongly influenced by the initial coordination of Ga3+. Consequently, by tuning the coordination of active Ga3+ species as well as the coverage and activity of hydrides, we achieve enhanced hydrogenation of CO2 to CO, methanol or light olefins by 4-6 times. Zhu et al. report a quantitative and time-resolved analysis of hydrogen activation on Ga2O3, specifically shedding light on the long-standing puzzle of homolytic dissociation as opposed to the heterolytic pathway on oxides. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQoL), which can be influenced by various aspects, especially socioeconomic status and lifestyle, has been identified as an important predictor of the prognosis of older adults. Dietary habit, a major part of lifestyle, can affect the nutritional status, which is closely correlated with the development of geriatric syndromes in the elderly. Aims: The aim of the study was to examine the association of HRQoL, socioeconomic status, and lifestyle with the risk and severity of sarcopenia, a geriatric syndrome characterized by progressive loss of skeletal muscle mass, strength and function. Methods: A cross-sectional retrospective study with 2877 participants aged ≥65 years was performed. HRQoL was assessed using EuroQoL Five Dimensions questionnaire. Socioeconomic status was assessed by the educational attainment, occupation, and household income. Lifestyle was assessed using 12 items closely related to Chinese living habits. The information of daily dietary habits including tea, alcohol, type of diet, and volume of drinking water were collected. The associations of HRQoL, socioeconomic status, and lifestyle with the risk of sarcopenia were examined by multivariate regression logistical analysis. The potential causal role of age, body mass index, and waist circumference in the effect of HRQoL on sarcopenia risk was analyzed by causal mediation analysis. Results: High HRQoL [adjusted odds ratio (OR) =0.85, 95% confidence interval (CI) =0.69–0.95, P=0.034] and household income levels (adjusted OR =0.74, 95% CI =0.57–0.95, P=0.019) were inversely associated with the risk of sarcopenia. Meanwhile, more consumption of spicy food (adjusted OR =1.34, 95% CI =1.09–1.81, P =0.037) and occasionally drinking (adjusted OR =1.46, 95% CI =1.07–2.00, P =0.016, as compared to those never drinking) were associated with higher risk of sarcopenia, while skipping breakfast occasionally (adjusted OR =0.37, 95% CI =0.21–0.64, P <0.001, as compared to those eating breakfast every day) and less consumption of salt (adjusted OR =0.71, 95% CI =0.52–0.96, P =0.026, as compared to those consuming high amount of salt) were associated with lower risk of sarcopenia. Further causal mediation analysis aimed to explore how much age, body mass index, and waist circumference might explain the effect of HRQoL on the risk of sarcopenia showed that the estimated proportion that mediated the effect of HRQoL on the risk of sarcopenia by age was 28.0%. Conclusions: In summary, our findings demonstrate that low levels of HRQoL and household income, more intake of salt and spicy food, and occasional intake of alcohol are correlated with higher risk of sarcopenia, while skipping breakfast occasionally is associated with lower risk of sarcopenia in a Chinese population of older adults. [ABSTRACT FROM AUTHOR]

Objectives: To determine the predictive effect of Hounsfield unit (HU) values in the cervical vertebral body measured by computed tomography (CT) and T-scores measured by dual-energy X-ray absorptiometry (DXA) on Zero-P subsidence after anterior cervical discectomy and fusion (ACDF)with Zero-P. In addition, we evaluated the most reliable measurement of cervical HU values. Methods: We reviewed 76 patients who underwent single-level Zero-P fusion for cervical spondylosis. HU values were measured on CT images according to previous studies. Univariate analysis was used to screen the influencing factors of Zero-P subsidence, and then, logistic regression was used to determine the independent risk factors. The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability to predict Zero-P subsidence. Results: Twelve patients (15.8%) developed Zero-P subsidence. There were significant differences between subsidence group and non-subsidence group in terms of age, axial HU value, and HU value of midsagittal, midcoronal, and midaxial (MSCD), but there were no significant differences in lowest T-score and lowest BMD. The axial HU value (OR = 0.925) and HU value of MSCD (OR = 0.892) were independent risk factors for Zero-P subsidence, and the lowest T-score was not (OR = 1.186). The AUC of predicting Zero-P subsidence was 0.798 for axial HU value, 0.861 for HU value of MSCD, and 0.656 for T-score. Conclusions: Lower cervical HU value indicates a higher risk of subsidence in patients following Zero-P fusion for single-level cervical spondylosis. HU values were better predictors of Zero-P subsidence than DXA T-scores. In addition, the measurement of HU value in the midsagittal, midcoronal, and midaxial planes of the cervical vertebral body provides an effective method for predicting Zero-P subsidence. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of COVID-19 infection on pancreatic cancer. Methods: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. Results: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. Conclusion: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research. [ABSTRACT FROM AUTHOR]

Recent advances in immunotherapeutic approaches have the potential to bring new hope to the treatment of pancreatic cancer. The tumor microenvironment contributes significantly to tumor development and progression. In this study, miR-429 overexpression was found to inhibit proliferation, invasion, and clonogenicity while promoting apoptosis in HepG2 cells. Furthermore, co-culture of miR-429-overpressing or silenced HepG2 cells with PBMCs showed that miR-429 induced CD4+ and CD8+ T cell infiltration, decreased the numbers of Tregs, inhibited CD8+ T cell apoptosis and exhaustion, and enhanced CD8+ T cell functions in PBMCs. miR-429 was found to prevent an immunosuppressive HCC microenvironment by targeting and suppressing PD-L1. In a C57BL/6 mouse subcutaneous xenograft tumor model, overexpression of miR-429 reduced tumorigenesis and both tumor volumes and weights were decreased relative to controls. In addition, CD4+ and CD8+ T cells were increased, Tregs were reduced, and CD8+ T cell apoptosis and depletion were reduced in the tumor tissues induced by miR-429-overexpressing HepG2 cells. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common neurological disorders. The pro-epileptic and antiepileptic roles of microglia have recently garnered significant attention. Interleukin-1 receptor-associated kinase (IRAK)-M, an important kinase in the innate immune response, is mainly expressed in microglia and acts as a negative regulator of the TLR4 signaling pathway that mediates the anti-inflammatory effect. However, whether IRAK-M exerts a protective role in epileptogenesis as well as the molecular and cellular mechanisms underlying these processes are yet to be elucidated. An epilepsy mouse model induced by pilocarpine was used in this study. Real-time quantitative polymerase chain reaction and western blot analysis were used to analyze mRNA and protein expression levels, respectively. Whole-cell voltage-clamp recordings were employed to evaluate the glutamatergic synaptic transmission in hippocampal neurons. Immunofluorescence was utilized to show the glial cell activation and neuronal loss. Furthermore, the proportion of microglia was analyzed using flow cytometry. Seizure dynamics influenced the expression of IRAK-M. Its knockout dramatically exacerbated the seizures and the pathology in epilepsy and increased the N-methyl-d-aspartate receptor (NMDAR) expression, thereby enhancing glutamatergic synaptic transmission in hippocampal CA1 pyramidal neurons in mice. Furthermore, IRAK-M deficiency augmented hippocampal neuronal loss via a possible mechanism of NMDAR-mediated excitotoxicity. IRAK-M deletion promotes microglia toward the M1 phenotype, which resulted in high levels of proinflammatory cytokines and was accompanied by a visible increase in the expressions of key microglial polarization-related proteins, including p-STAT1, TRAF6, and SOCS1. The findings demonstrate that IRAK-M dysfunction contributes to the progression of epilepsy by increasing M1 microglial polarization and glutamatergic synaptic transmission. This is possibly related to NMDARs, particularly Grin2A and Grin2B, which suggests that IRAK-M could serve as a novel therapeutic target for the direct alleviation of epilepsy. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments. Chemodynamic therapy (CDT) uses Fenton chemistry to covert hydrogen peroxide in cancer cells to toxic hydroxyl radicals, but endogenous hydrogen peroxide is insufficient to drive sustainable CDT. Here, the authors report a water oxidation CoFe Prussian blue nanoframe to provide sustained, external energy free self-supply of hydroxyl radicals for CDT. [ABSTRACT FROM AUTHOR]

While functional MRI (fMRI) studies have mainly focused on gray matter, recent studies have consistently found that blood-oxygenation-level-dependent (BOLD) signals can be reliably detected in white matter, and functional connectivity (FC) has been organized into distributed networks in white matter. Nevertheless, it remains unclear whether this white matter FC reflects underlying electrophysiological synchronization. To address this question, we employ intracranial stereotactic-electroencephalography (SEEG) and resting-state fMRI data from a group of 16 patients with drug-resistant epilepsy. We find that BOLD FC is correlated with SEEG FC in white matter, and this result is consistent across a wide range of frequency bands for each participant. By including diffusion spectrum imaging data, we also find that white matter FC from both SEEG and fMRI are correlated with white matter structural connectivity, suggesting that anatomical fiber tracts underlie the functional synchronization in white matter. These results provide evidence for the electrophysiological and structural basis of white matter BOLD FC, which could be a potential biomarker for psychiatric and neurological disorders. Whether connectivity in white matter detected by functional MRI relates to underlying electrophysiological synchronization is unclear. Here, the authors show that blood-oxygenation-level-dependent (BOLD) functional connectivity and intracranial stereotactic-electroencephalography (SEEG) connectivity are correlated across a wide range of frequency bands. [ABSTRACT FROM AUTHOR]

Cadmium (Cd), a common heavy metal in the environment, is associated with cognitive impairment. In the present study, we carried out a preliminary inquiry to explore whether Cd causes neurotoxicity by regulating the JAK2/STAT3 signaling pathway and affecting the expression of klotho genes in vivo and in vitro, providing clues for the mechanism of Cd-induced cognitive dysfunction. The rat samples were injected with Cd chloride solution for 14 weeks, and the memory function of the rats was detected. Different concentrations of Cd and JAK2/STAT3 signaling pathway inhibitors were used to treat PC12 cells and thus detect the apoptosis rate. The protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3, and klotho in rat and PC12 cell were detected by ELISA and Western blot, respectively. With the increase in exposure dose, the memory function of rats was severely impaired. The expression of p-JAK2 and p-STAT3 proteins was significantly up-regulated, whereas that of klotho was significantly down-regulated both in vivo and in vitro (p < 0.05). In comparison with the high-dose Cd exposure group, after adding tyrphostin AG490 (AG490), the apoptosis rate of PC12 cells increased, whereas the phosphorylation levels of JAK2 and STAT3 in the cells decreased significantly (p < 0.05). Cd exposure may cause neurotoxicity by regulating the JAK2/STAT3 signaling pathway and down-regulating klotho protein expression, leading to cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Timely formation of collagen-rich-scar is of importance to prevent ventricular rupture after myocardial infarction (MI). Chil1 (Chitinase 3-like 1) is a secreted protein associated with tissue remodeling response. However, its function in MI progression remains elusive. Chil1 was downregulated in the injured area overall post-MI. Overexpression of Chil1 markedly reduced cardiac rupture, increased wall thickness, and improved cardiac function post-MI due to collagen-rich-scar formation and extracellular matrix remodeling. In vitro, Chil1 induced the transformation of fibroblasts to myofibroblasts. Mechanistically, a phosphoproteomics study revealed that Chil1 binded to the EGFR enhancing RAF/MEK1/ERK signaling pathway to exert cardiac protection function. The effects of Chil1 on fibroblasts transformation and cardiac protections after MI were partially abolished by co-treated with RAF inhibitor. Together, our findings identify Chil1 as a protection factor in MI progression through binding to EGFR which further activates RAF/MEK1/ERK signaling pathway. [ABSTRACT FROM AUTHOR]

Ultra-high molecular weight polyethylene (UHMWPE) has extremely outstanding mechanical properties and wear resistance, but its melt flowability is too poor, resulting in poor processability. In this work, high-density polyethylene (HDPE) was melt-blended with UHMWPE to promote the flowability of UHMWPE melt. We investigated the effects of UHMWPE and HDPE contents on the rheological behavior, crystallization behavior, mechanical properties, and wear resistance of UHMWPE/HDPE blends. The results show that when the content ratio of UHMWPE and HDPE is 50:50, the UHMWPE/HDPE blend exhibits the best mechanical properties and wear resistance, as well as good processability. The tensile strength and elongation at break of 50UHMWPE/50HDPE are as high as 52.12 MPa and 700%, respectively, and the mass loss after erosion is only 0.04 g, which is far lower than the mass loss of pure HDPE (0.267g). Therefore, UHMWPE/HDPE blends with outstanding wear resistance and mechanical properties are expected to achieve large-scale industrial applications. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (PD-1 inhibitors) have shown clinical activity in Richter transformation-diffuse large B-cell lymphoma variant (RT-DLBCL), thus providing for a novel therapeutic approach. The study group consists of 64 patients with RT-DLBCL. Expression of PD-1, PD-L1, CD30, and microsatellite instability (MSI) status (hMLH1, hMSH2, hMSH6, PMS1) was assessed using immunohistochemistry. EBV-encoded RNA (EBER) was evaluated using colorimetric in situ hybridization. PD-1 and PD-L1 expression levels were categorized on the basis of tumor cell expression as follows: negative (< 5%), positive to low-positive (5–50%), or high-positive (> 50%). An "immune evasion phenotype" (IEP) was defined as RT-DLBCL cases having high-positive expression of PD-1 and/or PD-L1 on tumor cells. The level of PD1-positive tumor-infiltrating lymphocytes (TILs) was estimated as a fraction of total lymphocytes and categorized as negative/low vs. brisk (> 20%). 28/64 (43.7%) patients were characterized as IEP+ RT-DLBCL. A brisk level of PD1+ TILs was significantly more common in IEP1+ compared with IEP- tumors (17/28, 60.7% vs. 5/34, 14.7%; p = 0.001). In addition, CD30 expression was significantly more common in IEP+ compared with IEP- RT-DLBCL (6/20, 30% vs. 1/27, 3.7%; p = 0.0320). Two (2/36; 5.5%) cases were positive for EBER, both IEP+. There was no significant difference between the two groups in terms of age, sex, or time to transformation. Assessment of mismatch repair proteins demonstrated absence of microsatellite instability (MSI) in all cases (18/18; 100%). Notably, patients with brisk PD1+ TILs had a significantly better OS compared to those with a negative/low infiltrate (p = 0.0285). [ABSTRACT FROM AUTHOR]

Since wireless sensor network have a finite amount of energy, lowering network energy consumption and prolonging the life of the network are essential considerations for WSN applications. A novel multi-hop clustering routing algorithm based on particle swarm optimization was suggested to address the problem of existing routing algorithms' short network life. Formerly, the most suitable cluster head was chosen by taking into account the energy of sensor nodes, the distance between nodes in the cluster, the distance between cluster head and BS, and other factors during the cluster head selection stage. Second, a relay node selection mechanism is proposed during the data transmission stage. Finally, to decrease energy usage, the energy threshold re-clustering scheme is employed. In comparison to POFCA, LEACH, and EEUC, simulation experiments show that the EBPSO algorithm enhances network lifetime by 1.7 percent, 24.7 percent, and 9.2 percent, respectively. [ABSTRACT FROM AUTHOR]

Background: We evaluated the relevance of PD-1+CD8+ T-cells in gastric cancer (GC) including prognostic significance, association with chemotherapy and immunotherapy sensitivity and correlations with the tumor microenvironment (TME). Methods: Discovery cohort: GC samples were evaluated for AE1/3, CD8, PD-1, Ki-67 and Granzyme-B expression with fluorescence-based multiplex immunohistochemistry (mIHC). Validation cohorts: we analyzed bulk RNAseq GC datasets from TCGA, the "3G" chemotherapy trial and an immunotherapy phase 2 trial. The cox proportional hazards model was used to identify factors that influenced overall survival (OS). To study the TME, we analyzed single-cell RNAseq performed on GCs. Results: In the discovery cohort of 350 GCs, increased PD-1 expression of CD8 T-cells was prognostic for OS (HR 0.822, p = 0.042). PD-1 expression in CD8 T-cells highly correlated with cytolytic [Granzyme-B+] (r = 0.714, p < 0.001) and proliferative [Ki-67+] (r = 0.798, p < 0.001) activity. Analysis of bulk RNAseq datasets showed tumors with high PD-1 and CD8A expression levels had improved OS when treated with immunotherapy (HR 0.117, p = 0.036) and chemotherapy (HR 0.475, p = 0.017). Analysis of an scRNAseq dataset of 152,423 cells from 40 GCs revealed that T-cell and NK-cell proportions were higher (24% vs 18% and 19% vs 15%, p < 0.0001), while macrophage proportions were lower (7% vs 11%, p < 0.0001) in CD8PD-1high compared to CD8PD-1low tumors. Conclusion: This is one of the largest GC cohorts of mIHC combined with analysis of multiple datasets providing orthogonal validation of the clinical relevance of PD-1+CD8+ T-cells being associated with improved OS. CD8PD-1high tumors have distinct features of an immunologically active, T-cell inflamed TME. [ABSTRACT FROM AUTHOR]

Background: Phosphatase of regenerating liver-3 (PRL-3) is involved in cellular processes driving metastasis, cell proliferation, invasion, motility and survival. It has been shown to be upregulated and overexpressed in cancer tissue, in contrast to low or no expression in most normal tissue. PRL3-zumab is a first-in-class humanized antibody that specifically binds to PRL-3 oncotarget with high affinity and has been shown to reduce tumor growth and increase survival. Objective: In the study, we aimed to determine the safety and efficacy of PRL3-zumab in patients with advanced solid tumors and hematological malignancies. Methods: We conducted a phase I, first-in-human study in advanced solid tumors and hematological malignancies to investigate the safety, tolerability and efficacy of PRL3-zumab. Response rates were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) for solid tumors. For acute myeloid leukemia (AML) patients, bone marrow response criteria based on the European Leukaemia Network (ELN) 2017 guidelines for AML were used. We also explored the pharmacokinetics and pharmacodynamic relationships of PRL3-zumab in patients. This study was registered with ClinicalTrials.gov: NCT03191682. Results: In the dose-escalation cohort, 11 patients with advanced solid tumors were enrolled into the study. An additional 12 patients with solid tumors and four patients with AML were enrolled in the dose-expansion cohort. Maximum tolerability was not achieved in this study, as there were no dose-limiting toxicities. Potential treatment-emergent adverse events were grade 1 increased stoma output and fatigue and grade 2 vomiting. Best response observed was stable disease in three solid-tumor patients (11.1%). The pharmacokinetics of PRL3-zumab were dose proportional, consistent with an IgG type monoclonal antibody. Conclusions: PRL3-zumab, a first-in-class humanized antibody, was safe and tolerable in solid tumors and hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil–lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population. Methods: We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020. Results: The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96–1.70); RMH score 2, HR 2.27 (95% CI: 1.62–3.17); RMH score 3, HR 4.14 (95% CI: 2.62–6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24–2.04), P < 0.001) and primary tumour site (GI vs. breast cancer: HR = 3.06, 95% CI = 2.16–4.35, P < 0.001) were prognostic. Conclusions: We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65–0.76]), and validated the RMH model in the largest Asian study to date. [ABSTRACT FROM AUTHOR]

Characterization of filamentous fungal regulatory elements remains challenging because of time-consuming transformation technologies and limited quantitative methods. Here we established a method for quantitative assessment of filamentous fungal promoters based on flow cytometry detection of the superfolder green fluorescent protein at single-cell resolution. Using this quantitative method, we acquired a library of 93 native promoter elements from Aspergillus nidulans in a high-throughput format. The strengths of identified promoters covered a 37-fold range by flow cytometry. PzipA and PsltA were identified as the strongest promoters, which were 2.9- and 1.5-fold higher than that of the commonly used constitutive promoter PgpdA. Thus, we applied PzipA and PsltA to activate the silent nonribosomal peptide synthetase gene Afpes1 from Aspergillus fumigatus in its native host and the heterologous host A. nidulans. The metabolic products of Afpes1 were identified as new cyclic tetrapeptide derivatives, namely, fumiganins A and B. Our method provides an innovative strategy for natural product discovery in fungi. [ABSTRACT FROM AUTHOR]

An extremely heavy rainfall event occurred in Zhengzhou, China, on 20 July 2021 and produced an hourly rainfall rate of 201.9 mm, which broke the station record for mainland China. Based on radar observations and a convection-permitting simulation using the WRF-ARW model, this paper investigates the multiscale processes, especially those at the mesoscale, that support the extreme observed hourly rainfall. Results show that the extreme rainfall occurred in an environment characteristic of warm-sector heavy rainfall, with abundant warm moist air transported from the ocean by an abnormally northward-displaced western Pacific subtropical high and Typhoon In-Fa (2021). However, rather than through back building and echo training of convective cells often found in warm-sector heavy rainfall events, this extreme hourly rainfall event was caused by a single, quasi-stationary storm in Zhengzhou. Scale separation analysis reveals that the extreme-rain-producing storm was supported and maintained by the dynamic lifting of low-level converging flows from the north, south, and east of the storm. The low-level northerly flow originated from a mesoscale barrier jet on the eastern slope of the Taihang Mountain due to terrain blocking of large-scale easterly flows, which reached an overall balance with the southerly winds in association with a low-level meso-β-scale vortex located to the west of Zhengzhou. The large-scale easterly inflows that fed the deep convection via transport of thermodynamically unstable air into the storm prevented the eastward propagation of the weak, shallow cold pool. As a result, the convective storm was nearly stationary over Zhengzhou, resulting in record-breaking hourly precipitation. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), which mainly comprises ulcerative colitis (UC) and Crohn's disease (CD), is a common chronic intestinal inflammatory disease that affects the ileum, rectum, and colon. Currently, the diagnosis of IBD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in amino acid metabolites in IBD serum and to identify potential predictive biomarkers of IBD diagnosis and progression. Serum samples were collected from 158 UC patients, 130 CD patients and 138 healthy controls (HCs). The 37 amino acids in serum were determined by ultra-high-pressure liquid chromatography coupled to a mass spectrometer. A panel of three-amino-acid metabolites (taurine, homocitrulline and kynurenine) was identified as a specific biomarker panel of IBD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 88.4% with a specificity of 84.6% for discriminating CD patients from UC patients. The biomarkers identified are increased in CD compared to UC. Our approach demonstrated a strong relationship between serum amino acid levels and IBD. We successfully identified serum amino acid biomarkers associated with CD and UC. The biomarker panel has potential in clinical practice for IBD diagnosis and will provide new insights into IBD pathogenesis. [ABSTRACT FROM AUTHOR]

To introduce a new knotting technique for vascular anastomosis, which was different from the conventional knotting methods, is the aim of this study. A microsurgeon learned this technique and practiced on gauze, and then he used this new technique to perform vascular anastomosis. The times that he spent with this new technique and conventional method were recorded and compared. After this new technique was applied, the speed of vascular anastomosis was reduced compared with conventional method, and the difference showed statistical significance. This new knotting technique can avoid the adherence of the suture to the soft tissue during knotting and can be knotted rapidly and continuously. In particular, the surgeon can perform this technique without the help of an assistant. [ABSTRACT FROM AUTHOR]

Modified polyimides (MPIs) show great potential towards 5G communication applications, due to its excellent thermal stability, mechanical property and chemical stability as compared to most of polymers. Introducing fluoride groups or porous structure is favorable to ultra-low dielectric constant (Dk) and dielectric loss (Df). However, the cost of the fluorinated MPIs is high and their synthetic processes are complicated, and porous MPIs suffer poor mechanical properties. Also, increasing the fraction of free volume is a very effective way to lower Dk through introducing more ultra-low-Dk air component. However, most of this kind of MPIs lag far behind the fluorinated MPIs and the porous MPIs in terms of ultra-low Df, hindering the application of MPIs in high-speed communication devices. Thus, it is highly desirable to develop intrinsic ultra-low-Dk/Df MPIs at high frequency with less fluoric groups and nonporous structure. Herein, we introduce a facile and effective strategy to lower Dk and Df through introducing rigid and large sterically hindered aromatic groups into MPIs. On the one hand, their large steric hindrance effect leads to low Dk by increasing intrinsic free volume. On the other hand, the resulting highly stiff polymer chain and strong intermolecular interaction are favorable to reduce Df by inhibiting dipole orientations. Based on this strategy, the spirobifluorene groups are preferred. The as-prepared MPIs show excellent dielectric performance with low Dk of 2.74–2.76 and low Df of 0.00599 at 10 GHz, to some extent, exceeding the multiple fluorinated MPI with Dk/Df of 2.67/0.00663 at 10 GHz. [ABSTRACT FROM AUTHOR]

Based on the water quality test data of 257 groups of phreatic groundwater and 165 groups of confined groundwater in the Nanchang area and the redox conditions, acid–base conditions and the organic matter content in groundwater, we identified hydrochemical characteristics and genesis of groundwater with high Fe and Mn contents in Nanchang. The results showed that Fe and Mn exceeded the standard in both phreatic and confined groundwater. The over-standard rates of Fe and Mn in groundwater were 8.56–11.52% and 33.07–36.36%, respectively. The degree of pollution Fe and Mn in the confined groundwater is higher than that in the phreatic groundwater, and the degree of pollution caused by Mn is higher than that caused by Fe. The high Fe and Mn contents in groundwater were caused by the release of Fe and Mn minerals from the native environment due to changes in the groundwater environment of the study area. A mild redox environment (Eh < 100) and low pH value are favorable for Fe and Mn enrichment in groundwater. The presence of organic matter accelerates microbial activity and promotes the release of Fe and Mn from aquifer sediments. Therefore, the change in the native environment played an important role in the increase in Fe and Mn content in the study area. [ABSTRACT FROM AUTHOR]

Composite polymer electrolyte (CPE) with ceramic fillers has gained great attention for lithium batteries with high energy density and safety. However, the agglomeration of ceramic fillers and weak polymer-ceramic interaction induces limited ionic conductivity and hinders its implementation. Here, hollow multishelled structure (HoMS) ZnO with a size range of 700 ~ 900 nm is designed as fillers for polyethylene oxide (PEO)-based CPE. Strong chemical and mechanical interaction between PEO and ZnO HoMS enable a high ionic conductivity and good electrochemical and mechanical stability. Wherein, double-shelled ZnO HoMS exhibits a good ionic conductivity of 1.04 × 10−4 S∙cm−1 and 1.2 × 10−3 S∙cm−1 at 30 ℃ and 60 ℃. Additionally, all-solid-state LiFePO4/Li full cell adopted with ZnO HoMS filled CPE exhibits a high initial specific capacity of 169 mAh∙g−1 and good cycling stability and withstands abuse test. The enhanced performance is due to that HoMS provides PEO with faster ion transport channels, more effective Lewis acid-based interaction sites, suppressed PEO crystallinity, and improved ionic conductivity. [ABSTRACT FROM AUTHOR]

Phytoremediation, as a green and safe bioremediation technology, has attracted much attention to researchers. The rhizosphere effect caused by plant–microbe-soil interaction, which makes plant roots adapt to the external environment, plays an important role in phytoremediation. Therefore, we summarized the membrane transport, morphological transformation, migration and distribution mechanism of uranium in plants under rhizosphere effect, and the molecular mechanism of microbial-mediated uranium-contaminated soil remediate; the influencing factors and regulatory measures of rhizosphere remediate. Finally, we conclude some promising research challenges regarding the rhizosphere effect of phytoremediation in uranium-contaminated soil, in order to provide a useful reference for future research. [ABSTRACT FROM AUTHOR]

Objectives: To integrate the glucose metabolism measured using [18F]FDG PET/CT and anatomical features measured using MRI to forecast the post-surgical seizure outcomes of intractable temporal lobe epilepsy. Methods: This retrospective study enrolled 63 patients with drug-resistant temporal lobe epilepsy. Z-transform of the patients' PET images based on comparison with a database of healthy controls, cortical thickness, and quantitative anisotropy (QA) of the diffusion spectrum imaging concordant/non-concordant with cortical resection was adopted to quantify their predictive values for the post-surgical seizure outcomes. Results: The PET hypometabolism region was concordant with the surgical field in 47 of the 63 patients. Forty-two patients were seizure-free post-surgery. The sensitivity and specificity of PET in predicting seizure freedom were 89.4% and 68.8%, respectively. Complete resection of foci with overlapped PET, cortical thickness, and QA abnormalities resulted in Engel I in 27 patients, which was a good predictor of seizure freedom with an odds ratio (OR) of 19.57 (95% CI 2.38–161.25, p = 0.006). Hypometabolism involved in multiple lobes (OR = 7.18, 95% CI 1.02–50.75, p = 0.048) and foci of hypometabolism with QA/cortical thickness abnormalities outside surgical field (OR = 14.72, 95% CI 2.13–101.56, p = 0.006) were two major predictors of Engel III/IV outcomes. ORs of QA to predict Engel I and seizure recurrence were 14.64 (95% CI 2.90–73.80, p = 0.001) and 12.01 (95% CI 2.91–49.65, p = 0.001), respectively. Conclusion: Combined PET and structural pattern is helpful to predict the post-surgical seizure outcomes and worse outcomes of Engel III/IV. This might decrease unnecessary surgical injuries to patients who are potentially not amenable to surgery. Key Points: • A combined metabolic and structural pattern is helpful to predict the post-surgical seizure outcomes. • Favorable post-surgical seizure outcome was most likely reached in patients whose hypometabolism overlapped with the structural changes. • Hypometabolism in multiple lobes and QA or cortical thickness abnormalities outside the surgical field were predictors of worse seizure outcomes of Engel III/IV. [ABSTRACT FROM AUTHOR]

To assess the cortical activity in people with Parkinson's disease (PwP) with different motor phenotype (tremor-dominant—TD and postural instability and gait difficulty—PIGD) and to compare with controls. Twenty-four PwP (during OFF and ON medication) and twelve age-/sex-/handedness-matched healthy controls underwent electrophysiological assessment of spectral ratio analysis through electroencephalography (EEG) at resting state and during the hand movement. We performed a machine learning method with 35 attributes extracted from EEG. To verify the efficiency of the proposed phenotype-based EEG classification the random forest and random tree were tested (performed 30 times, using a tenfolds cross validation in Weka environment). The analyses based on phenotypes indicated a slowing down of cortical activity during OFF medication state in PwP. PD with TD phenotype presented this characteristic at resting and the individuals with PIGD presented during the hand movement. During the ON state, there is no difference between phenotypes at resting nor during the hand movement. PD phenotypes may influence spectral activity measured by EEG. Random forest machine learning provides a slightly more accurate, sensible and specific approach to distinguish different PD phenotypes. The phenotype of PD might be a clinical characteristic that could influence cortical activity. [ABSTRACT FROM AUTHOR]

In this paper, a novel crack and void identification method is proposed based on the scaled boundary finite element method (SBFEM) with the pixel-based quadtree mesh and the parameter level set method (PLSM), in which the particle swarm optimization method (PSO) is applied to optimize the objective function. It fully exploits the advantages of fast image-based quadtree mesh generation and efficient assembly of global stiffness matrix to accomplish a fast analysis of the forward problem and accelerate the efficiency of the inversion. Furthermore, multiple level set functions are introduced to represent cracks and voids simultaneously. The application of PSO dexterously avoids the difficulty of solving sensitivity. Numerical examples show that the proposed method can identify the position and shape of cracks and voids accurately by discussing different influencing factors. In addition, the method has shown certain anti-noise performance. [ABSTRACT FROM AUTHOR]

Fundamental technology of Computer Aided Design, free-form surface flattening is important for both practical and scientific point of view in mechanical engineering. This paper proposed a flattening algorithm by using a local rigid registration and a global energy optimization. Firstly, each 3D element is aligned to the plane by minimizing the distance between the original 3D element and its corresponding planar element. Then, a global optimization operator is used to stitch and optimize these best-aligned local elements by iteratively minimizing a quadratic energy function composed of linear elastic energy, which makes the internal force of the nodes reach the equilibrium state. The experimental results show that this method is stable and reliable, and can obtain good surface flattening effect under free boundary conditions. [ABSTRACT FROM AUTHOR]

Robust ionic sensing materials that are both fatigue-resistant and self-healable like human skin are essential for soft electronics and robotics with extended service life. However, most existing self-healable artificial ionic skins produced on the basis of network reconfiguration suffer from a low fatigue threshold due to the easy fracture of low-energy amorphous polymer chains with susceptible crack propagation. Here we engineer a fatigue-free yet fully healable hybrid ionic skin toughened by a high-energy, self-healable elastic nanomesh, resembling the repairable nanofibrous interwoven structure of human skin. Such a design affords a superhigh fatigue threshold of 2950 J m−2 while maintaining skin-like compliance, stretchability, and strain-adaptive stiffening response. Moreover, nanofiber tension-induced moisture breathing of ionic matrix leads to a record-high strain-sensing gauge factor of 66.8, far exceeding previous intrinsically stretchable ionic conductors. This concept creates opportunities for designing durable ion-conducting materials that replicate the unparalleled combinatory properties of natural skins more precisely. Developing robust skin-like sensing materials is essential for soft electronics and robotics with extended service life. Here, inspired by the repairable nanofibrous structure of human skin, the authors engineer a fatigue-resistant artificial ionic skin toughened by self-healable elastic nanomesh. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICI) are now standard-of-care treatment for patients with metastatic gastric cancer (GC). To guide patient selection for ICI therapy, programmed death ligand-1 (PD-L1) biomarker expression is routinely assessed via immunohistochemistry (IHC). However, with an increasing number of approved ICIs, each paired with a different PD-L1 antibody IHC assay used in their respective landmark trials, there is an unmet clinical and logistical need for harmonization. We investigated the interchangeability between the Dako 22C3, Dako 28–8 and Ventana SP-142 assays in GC PD-L1 IHC. Methods: In this cross-sectional study, we scored 362 GC samples for PD-L1 combined positive score (CPS), tumor proportion score (TPS) and immune cells (IC) using a multiplex immunohistochemistry/immunofluorescence technique. Samples were obtained via biopsy or resection of gastric cancer. Results: The percentage of PD-L1-positive samples at clinically relevant CPS ≥ 1, ≥ 5 and ≥ 10 cut-offs for the 28–8 assay were approximately two-fold higher than that of the 22C3 (CPS ≥ 1: 70.3 vs 49.4%, p < 0.001; CPS ≥ 5: 29.1 vs 13.4%, p < 0.001; CPS ≥ 10: 13.7 vs 7.0%, p = 0.004). The mean CPS score on 28–8 assay was nearly double that of the 22C3 (6.39 ± 14.5 vs 3.46 ± 8.98, p < 0.001). At the clinically important CPS ≥ 5 cut-off, there was only moderate concordance between the 22C3 and 28–8 assays. Conclusion: Our findings suggest that scoring PD-L1 CPS with the 28–8 assay may result in higher PD-L1 scores and higher proportion of PD-L1 positivity compared to 22C3 and other assays. Until stronger evidence of inter-assay concordance is found, we urge caution in treating the assays as equivalent. [ABSTRACT FROM AUTHOR]

The metal-support interfaces between metals and oxide supports have long been studied in catalytic applications, thanks to their significance in structural stability and efficient catalytic activity. The metal-rare earth oxide interface is particularly interesting because these early transition cations have high electrophilicity, and therefore good binding strength with Lewis basic molecules, such as H2O. Based on this feature, here we design a highly efficient composite Ni-Y2O3 catalyst, which forms abundant active Ni-NiOx-Y2O3 interfaces under the water-gas shift (WGS) reaction condition, achieving 140.6 μmolCO gcat−1 s−1 rate at 300 °C, which is the highest activity for Ni-based catalysts. A combination of theory and ex/in situ experimental study suggests that Y2O3 helps H2O dissociation at the Ni-NiOx-Y2O3 interfaces, promoting this rate limiting step in the WGS reaction. Construction of such new interfacial structure for molecules activation holds great promise in many catalytic systems. Developing effective and stable catalytic interfaces in the medium temperature region is a practical route to replace the existing water gas shift (WGS) process. Here the authors designed a composite Ni-Y2O3 catalyst achieving the highest WGS activity for Ni based catalysts. [ABSTRACT FROM AUTHOR]

Background: Varlitinib is a highly potent, small-molecule, pan-HER inhibitor targeting HER1, HER2, and HER4. It has demonstrated activity in gastric, biliary tract, and breast cancers. Objective: We conducted a phase Ib dose confirmation study to determine safety and early efficacy signals of varlitinib in combination with chemotherapy (paclitaxel ± carboplatin) ± subcutaneous trastuzumab. Methods: Eligible patients had advanced or metastatic solid tumors. A 3+3 dose de-escalation study design was used and pharmacokinetic analyses of varlitinib and paclitaxel were performed. Results: Thirty-seven patients were enrolled into eight cohorts with median 4 (0–14) prior lines of palliative systemic therapies. Carboplatin area under the curve 1.5 and paclitaxel 80 mg/m2 weekly with varlitinib 500 mg twice daily continuously was de-escalated over four dose levels to 300 mg twice daily intermittently (4 days on, 3 days off) due to dose-limiting toxicities, most commonly neutropenia, febrile neutropenia, and electrolyte disturbances, with the triplet combination deemed intolerable and unable to be developed further. Varlitinib was then combined with paclitaxel alone; the recommended phase II dose of varlitinib was 300 mg twice daily intermittently. The addition of subcutaneous trastuzumab 600 mg was safe with no dose-limiting toxicities. Thirty-one patients were evaluable for response: 35.5% partial response, 41.9% stable disease. Twenty patients had HER2+ metastatic breast cancer with a median of 4 (0–14) treatment lines, 8/20 continued on single-agent varlitinib after completing chemotherapy for a median of 5.1 (range 2.0–13.3) months. A pharmacokinetic analysis showed that plasma exposure of varlitinib was dose dependent. Varlitinib administration did not significantly affect the maximum concentration or area under the curve of paclitaxel. Conclusions: The recommended phase II dose of varlitinib with paclitaxel is 300 mg twice daily intermittently dosed. This is active in HER2+ metastatic breast cancer. Subcutaneous trastuzumab can be added safely to varlitinib and paclitaxel. This combination is currently being evaluated as neoadjuvant therapy in HER2+ breast cancer (NCT02396108). Clinical Trial Registration: NCT02396108, date of registration: 25 March, 2015. [ABSTRACT FROM AUTHOR]