Prevalence and genomic-based antimicrobial resistance analysis of Avibacterium paragallinarum isolates in Guangdong Province, China.

Infectious coryza (IC) is an acute infectious respiratory disease in chickens that is caused by Avibacterium paragallinarum (A. paragallinarum). A. paragallinarum poses a significant threat to poultry health due to its virulence and multidrug resistance. This study isolated and identified 21 A. paragallinarum isolates from Guangdong between 2022 and 2023. Biochemical tests showed that 100% of A. paragallinarum isolates fermented glucose but did not ferment alginate and galactose, and only YZ18 was nicotinamide adenine dinucleotide independent. To determine the genetic relatedness between these isolates and NCBI reference strains, whole-genome-based phylogenetic analysis was employed. In addition, analysis of the 2,000 bp-length hmtp210 gene showed that the hmtp210 gene was strongly associated with A. paragallinarum serotypes. Meanwhile, a PCR assay for serotyping A. paragallinarum was developed based on the hmtp210 gene, this assay has high sensitivity and specificity. The antimicrobial susceptibility of isolates was assessed using the disk diffusion method. The antibiotic resistance genes of isolates were analyzed using the genomic method. Phenotypic resistance to ampicillin (95.2%), streptomycin (95.2%), methotrexate-sulfamethoxazole (90.5%), and tetracycline (85.7%) was most frequent among the isolates. All of the isolates exhibited resistance to multiple drugs, and furthermore, the isolates possessed a collective total of 14 genes associated with antibiotic resistance. This study will contribute to advancing our knowledge of A. paragallinarum antibiotic resistance and provide a scientific basis for the prophylaxis and treatment of IC, and the subsequent rational design of potential clinical therapeutics.

Generation and characterization of a nanobody against the avian influenza virus H7 subtype.

Avian influenza virus (AIV) H7N9 diseases have been recently reported, raising concerns about a potential pandemic. Thus, there is an urgent need for effective therapeutics for AIV H7N9 infections. Herein, camelid immunization and yeast two-hybrid techniques were used to identify potent neutralizing nanobodies (Nbs) targeting the H7 subtype hemagglutinin. First, we evaluated the binding specificity and hemagglutination inhibition activity of the screened Nbs against the H7 subtype hemagglutinin. Nb-Z77, with high hemagglutination inhibition activity was selected from the screened Nbs to optimize the yeast expression conditions and construct oligomeric forms of Nb-Z77 using various ligation methods. The oligomers Nb-Z77-DiGS, Nb-Z77-TriGS, Nb-Z77-Fc and Nb-Z77-Foldon were successfully constructed and expressed. Nb-Z77-DiGS and Nb-Z77-Foldon exhibited considerably greater activity than did Nb-Z77 against H7 subtype hemagglutinin, with median effective concentrations of 384.7 and 27.33 pM and binding affinity values of 213 and 5.21 pM, respectively. Nb-Z77-DiGS and Nb-Z77-Foldon completely inhibited the hemagglutination activity of the inactivated virus H7-Re1 at the lowest concentration of 0.938 µg/mL. This study screened a strain of Nb with high hemagglutination inhibition activity and enhanced its antiviral activity through oligomerization, which may have great potential for developing effective agents for the prevention, diagnosis, and treatment of AIV H7 subtype infection.

On-column capillary suppressor for open tubular ion chromatography.

BACKGROUND: Suppressors with different dead volumes are required to match different suppressed ion chromatography systems. Especially for suppressed open tubular ion chromatography (SOTIC), the dead volume is a critical parameter. Both connection tubes between open tubular (OT) columns and suppressors and the dead volumes of the suppressors should be as short/small as possible to minimize peak dispersion. Suppressors with different dead volumes are required to match the various suppressed ion chromatography systems that operate at low flow rates 20-200 nL/min. RESULTS: We describe three designs of on-column capillary suppressors for SOTIC: (A) on-column electrodialytic suppressor prepared by making small cracks on the cycloolefin polymer (COP) capillary at targeted locations, (B) on-column electrodialytic suppressor built on a polyether ether ketone (PEEK) capillary by removing the wall materials at target locations, (C) on-column chemical suppressor based on a single cut on a PEEK capillary at a targeted location a single cut on a PEEK capillary at a targeted location. The on-column electrodialytic suppressors work in two different modes with suppression voltage applied in co-current and counter-current direction to the eluent flow. Because of very narrow column inner diameter (i.d.), up to several hundred volts were required to suppress the hydroxide eluent, but it was found the there was a >90% loss of analytes in the suppressor accompanied with a high noise level after on-column electrodialytic suppression. Theoretical analysis reveals that high suppression voltage significantly affects the retention of specific analytes by electromigration. Further analysis indicated that the electrodialytic on-column suppressor in co-current mode would behave totally different from traditional suppressors. The on-column chemical suppression, with minimum dead volume of 0.27 nL, provides fairly well suppression of low hydroxide eluent without analyte loss in the suppressor. In design C, an efficiency of 47000 ± 1800 plates/m for Cl-, corresponding to a peak volume of 17.9 ± 0.7 nL, was obtained when separating five anion mixture (0.5 mM each) in the 25 µm i.d. AS18 latex coated PEEK OT column with an injection of 7.3 nL. Theoretical calculation revealed that a column efficiency loss of ≤3% would result in a cylindrical chemical suppression channel and thus it is taken as the acceptable dispersion contribution originating from the on-column chemical suppressor. SIGNIFICANCE: Different on-column suppressors have been designed on OT columns with i.d.s less than 30 µm. Two electrodialytic on-column suppressor designs with eluent flow parallel to the direction of electric field were proposed and tested. The eluent flow rate, analytes' retention behavior, resistance of suppression channel, current-voltage relationship, and working principles in both co-current and counter-current were experimentally investigated and comprehensively discussed. It was found that although the on-column electrodialytic suppressions (Design A and B) are not feasible in practice, the electrodialytic on-column suppressor on co-current mode has a potential of being used as an enriching capillary column for analyte ions. Design C provides fairly well chemical suppression. Theoretical calculation indicates that the loss of column efficiency can be controlled within 3%.

Anharmonic strong-coupling effects at the origin of the charge density wave in CsV3Sb5.

The formation of charge density waves is a long-standing open problem, particularly in dimensions higher than one. Various observations in the vanadium antimonides discovered recently further underpin this notion. Here, we study the Kagome metal CsV3Sb5 using polarized inelastic light scattering and density functional theory calculations. We observe a significant gap anisotropy with 2 Δ max / k B T CDW ≈ 20 , far beyond the prediction of mean-field theory. The analysis of the A1g and E2g phonons, including those emerging below TCDW, indicates strong phonon-phonon coupling, presumably mediated by a strong electron-phonon interaction. Similarly, the asymmetric Fano-type lineshape of the A1g amplitude mode suggests strong electron-phonon coupling below TCDW. The large electronic gap, the enhanced anharmonic phonon-phonon coupling, and the Fano shape of the amplitude mode combined are more supportive of a strong-coupling phonon-driven charge density wave transition than of a Fermi surface instability or an exotic mechanism in CsV3Sb5.

Computational fluid dynamics-based design and in vitro characterization of a novel pediatric pump-lung.

BACKGROUND: Although extracorporeal membrane oxygenation (ECMO) has been used to provide temporary support for pediatric patients suffering severe respiratory or cardiac failure since 1970, ECMO systems specifically designed for pediatric patients, particularly for long-term use, remain an unmet clinical need. We sought to develop a new pediatric ECMO system, that is, pediatric pump-lung (PPL), consisting of a unique cylinder oxygenator with an outside-in radial flow path and a centrifugal pump. METHODS: Computational fluid dynamics was used to analyze the blood fluid field for optimized biocompatible and gas exchange performances in terms of flow characteristics, hemolysis, and gas transfer efficiency. Ovine blood was used for in vitro hemolysis and gas transfer testing. RESULTS: Both the computational and experimental data showed that the pressure drop through the PPL's oxygenator is significantly low, even at a flow rate of more than 3.5 L/min. The PPL showed better hemolysis performance than a commercial ECMO circuit consisting of the Quadrox-iD pediatric oxygenator and the Rotaflow pump at a 3.5 L/min flow rate and 250 mm Hg afterload pressure. The oxygen transfer rate of the PPL can reach over 200 mL/min at a flow rate of 3.5 L/min. CONCLUSIONS: The PPL has the potential to provide adequate blood pumping and excellent respiratory support with minimal risk of hemolysis for a wide range of pediatric patients.

GRP/GRPR signaling pathway aggravates hyperuricemia-induced renal inflammation and fibrosis via ABCG2-dependent mechanisms.

The gastrin-releasing peptide receptor (GRPR) binds to ligands such as gastrin-releasing peptide (GRP) and plays a variety of biological roles. In this study, we investigated the therapeutic effect of a novel gastrin-releasing peptide receptor antagonist RH-1402 in hyperuricemia-induced kidney fibrosis and its underlying mechanisms. We conducted enzyme linked immunosorbent assay (ELISA) and immunohistochemical analyses and found that proGRP and GRPR expression levels were significantly increased in patients with hyperuricemic nephropathy (HN) and HN mice. GRPR knockdown significantly attenuated inflammatory and fibrotic responses in adenosine-treated human proximal tubule epithelial cells. GRPR knockout or GRPR conditional knockout in renal tubular epithelial cells significantly alleviated the decline in renal function and fibrosis in HN mice in vivo. RNA-seq and String database analysis revealed that GRP/GRPR promoted HN by suppressing the ABCG2/PDZK1 and increasing TGF-ß/Smad3 levels by activating the NF-κB pathway. Overexpression of GRPR increased TGF-ß/Smad3 levels, where as it reduced ABCG2/PDZK1 levels in adenosine-treated HK2 cells, which was reversed by the NF-κB inhibitor. Furthermore, we evaluated the therapeutic effects of the novel GRPR inhibitor RH-1402 on hyperuricaemia-induced renal injury and evaluated the inflammatory and fibrosis responses in vivo and in vitro. Pre-treatment with RH-1402 attenuated hyperuricaemia-induced renal injury, restored renal function, and suppressed renal inflammation and fibrosis. Taken together, GRPR enhances hyperuricaemia-induced tubular injury, inflammation, and renal fibrosis via ABCG2-dependent mechanisms and may serve as a promising therapeutic target for HN treatment.

Plasma-Promoted Ammonia Decomposition over Supported Ruthenium Catalysts for COx -Free H2 Production.

The efficient decomposition of ammonia to produce COx -free hydrogen at low temperatures has been extensively investigated as a potential method for supplying hydrogen to mobile devices based on fuel cells. In this study, we employed dielectric barrier discharge (DBD) plasma, a non-thermal plasma, to enhance the catalytic ammonia decomposition over supported Ru catalysts (Ru/Y2 O3 , Ru/La2 O3 , Ru/CeO2 and Ru/SiO2 ). The plasma-catalytic reactivity of Ru/La2 O3 was found to be superior to that of the other three catalysts. It was observed that both the physicochemical properties of the catalyst (such as support acidity) and the plasma discharge behaviours exerted significant influence on plasma-catalytic reactivity. Combining plasma with a Ru catalyst significantly enhanced ammonia conversion at low temperatures, achieving near complete NH3 conversion over the 1.5 %-Ru/La2 O3 catalyst at temperatures as low as 380 °C. Under a weight gas hourly space velocity of 2400 mL gcat -1 h-1 and an AC supply power of 20 W, the H2 formation rate and energy efficiency achieved were 10.7 mol gRu -1 h-1 and 535 mol gRu -1 (kWh)-1 , respectively, using a 1.5 %-Ru/La2 O3 catalyst.

Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis.

Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor [GRPR]) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.

DKADE: a novel framework based on deep learning and knowledge graph for identifying adverse drug events and related medications.

Adverse drug events (ADEs) are common in clinical practice and can cause significant harm to patients and increase resource use. Natural language processing (NLP) has been applied to automate ADE detection, but NLP systems become less adaptable when drug entities are missing or multiple medications are specified in clinical narratives. Additionally, no Chinese-language NLP system has been developed for ADE detection due to the complexity of Chinese semantics, despite ˃10 million cases of drug-related adverse events occurring annually in China. To address these challenges, we propose DKADE, a deep learning and knowledge graph-based framework for identifying ADEs. DKADE infers missing drug entities and evaluates their correlations with ADEs by combining medication orders and existing drug knowledge. Moreover, DKADE can automatically screen for new adverse drug reactions. Experimental results show that DKADE achieves an overall F1-score value of 91.13%. Furthermore, the adaptability of DKADE is validated using real-world external clinical data. In summary, DKADE is a powerful tool for studying drug safety and automating adverse event monitoring.

Novel insight on GRP/GRPR axis in diseases.

The gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptors (GPCRs), binds to ligands such as gastrin-releasing peptide (GRP) and plays a variety of biological roles. GRP/GRPR signalling is involved in the pathophysiological processes of many diseases, including inflammatory diseases, cardiovascular diseases, neurological diseases, and various cancers. In the immune system, the unique function of GRP/GRPR in neutrophil chemotaxis suggests that GRPR can be directly stimulated through GRP-mediated neutrophils to activate selective signalling pathways, such as PI3K, PKC, and MAPK, and participate in the occurrence and development of inflammation-related diseases. In the cardiovascular system, GRP increases intercellular adhesion molecule 1 (ICAM-1) and induces vascular cell adhesion molecule-1 (VCAM-1). GRP activates ERK1/2, MAPK, and AKT, leading to cardiovascular diseases, including myocardial infarction. Central nervous system signal transduction mediated by the GRP/GRPR axis plays a vital role in emotional responses, social interaction, and memory. The GRP/GRPR axis is elevated in various cancers, including lung, cervical, colorectal, renal cell, and head and neck squamous cell carcinomas. GRP is a mitogen in a variety of tumour cell lines. Its precursor, pro-gastrin-releasing peptide (ProGRP), may play an important role as an emerging tumour marker in early tumour diagnosis. GPCRs serve as therapeutic targets for drug development, but their function in each disease remains unclear, and their involvement in disease progression has not been well explored or summarised. This review lays out the above mentioned pathophysiological processes based on previous research conclusions. The GRP/GRPR axis may be a potential target for treating multiple diseases, and the study of this signalling axis is particularly important.

A transversely isotropic viscohyperelastic-damage model for the brain tissue with strain rate sensitivity.

Understanding the mechanical behaviors and properties of brain tissue are crucial to study the mechanisms of traumatic brain injury (TBI). Such injury may be associated with high rate loading conditions and the large deformation of brain tissue. Thus, constitutive models that consider the rate dependent large deformation of brain tissue and its possible damage initiation and evolution may help uncover the related mechanisms of TBI. Motivated from this, in this paper we present a fully three-dimensional large strain viscohyperelastic-damage model with the purpose of reproducing the experimentally observed rate sensitive elastic and damage-induced stress softening behaviors of brain tissue. The parameters of the proposed model can be identified using the experimental data from simple monotonic tests such as uniaxial tension, compression and simple shear. The proposed model is validated by comparing its prediction with experimental data. Good agreement between predictive results and experimental data is achieved indicating the potential of the proposed model in characterizing the mechanical behaviors of brain tissue considering rate dependence and damage effect.

Modeling the damage-induced softening behavior of brain white matter using a coupled hyperelasticty-damage model.

White matter in the brain is structurally anisotropic consisting of large bundle of aligned axonal fibers. Hyperelastic, transversely isotropic constitutive models are typically used in the modeling and simulation of such tissues. However, most studies constrain the material models to describe the mechanical behavior of white matter in the limit of small deformation, without considering the experimentally observed damage initiation and damage-induced material softening in large strain regime. In this study, we extend a previously developed transversely isotropic hyperelasticity model for white matter by coupling it with damage equations within the framework of thermodynamics and using continuum damage mechanics method. Two homogeneous deformation cases are used to demonstrate the proposed model's capability in capturing the damage-induced softening behaviors of white matter under uniaxial loading and simple shear, along with the investigation of fiber orientation effect on such behaviors and material stiffness. As a demonstration case of inhomogeneous deformation, the proposed model is also implemented into finite element codes to reproduce the experimental data (nonlinear material behavior and damage initiation) from an indentation configuration of porcine white matter. Good agreement between numerical results and experimental data is achieved indicating the potential of the proposed model in characterizing the mechanical behaviors of white matter considering damage at large strain.

Steric effects of CN vacancies for boosting CO2 electroreduction to CO with ultrahigh selectivity.

In the electrochemical reduction of CO2 to CO, controlling the binding of the *COOH intermediate is key to adjusting the selectivity and catalytic activity of the CO product. Herein, we report that CN vacancies were used to control the binding of the *COOH intermediate on a Co PBA-VCN catalyst treated by H2 cold plasma bombardment to improve the CO2RR into CO. The CN vacancies can tune the local electronic structure and coordination environment of CoIII-CN-CoII (Co-PBA-VCN) with a high CO faradaic efficiency close to 100% with remarkable durability (>87 h), and a low onset overpotential of 0.17 V in CO2RR. The steric effects of the VCN can decrease the free energy barrier of the rate limiting step for the formation of *COOH which can further crack into *CO on the active site of the Co near the VCN. This work provides a new strategy to tune the binding of the *COOH intermediate on the catalyst surface by new vacancies of VCN to enhance the CO2RR into a single product.

Identification of PI3K/HDAC Dual-targeted inhibitors with subtype selectivity as potential therapeutic agents against solid Tumors: Building HDAC6 potency in a Quinazolinone-based PI3Kδ-selective template.

Pharmacological inhibition of PI3Kδ for battling solid tumors is relatively unexplored. Given the potential synergism of concurrent PI3Kδ/HDAC6 inhibition, and the drawbacks of pioneering PI3K/HDAC dual inhibitors, we discovered a novel series of dual-targeted inhibitors via building HDAC6 potency in a PI3Kδ-selective template. SAR study culminated in the discovery of compound 59, which exhibited remarkable inhibitory activity against both PI3Kδ (IC50 = 2.3 nM) and HDAC6 (IC50 = 13 nM), along with acceptable subtype specificity. In addition to the attractive anti-proliferative activities, especially against T47D cell line (IC50 = 0.042 µM), 59 treatment dramatically ablated the tumor immune escape-related STAT3 signaling and lowered PD-L1 expression at two-digit nanomolar level, reflecting the immunomodulatory properties. Due to its subtype selectivity, it demonstrated low cytotoxicity against normal cells. This research validated the therapeutic potential of PI3Kδ/HDAC6 dual inhibitors against solid tumors, attributed to their dual roles in anti-proliferation and anticancer immunomodulation.

Computational fluid dynamics analysis and experimental hemolytic performance of three clinical centrifugal blood pumps: Revolution, Rotaflow and CentriMag.

Centrifugal blood pumps have become popular for adult extracorporeal membrane oxygenation (ECMO) due to their superior blood handling and reduced thrombosis risk featured by their secondary flow paths that avoid stagnant areas. However, the high rotational speed within a centrifugal blood pump can introduce high shear stress, causing a significant shear-induced hemolysis rate. The Revolution pump, the Rotaflow pump, and the CentriMag pump are three of the leading centrifugal blood pumps on the market. Although many experimental and computational studies have focused on evaluating the hydraulic and hemolytic performances of the Rotaflow and CentriMag pumps, there are few on the Revolution pump. Furthermore, a thorough direct comparison of these three pumps' flow characteristics and hemolysis is not available. In this study, we conducted a computational and experimental analysis to compare the hemolytic performances of the Revolution, Rotaflow, and CentriMag pumps operating under a clinically relevant condition, i.e., the blood flow rate of 5 L/min and pump pressure head of 350 mmHg, for adult ECMO support. In silico simulations were used to characterize the shear stress distributions and predict the hemolysis index, while in vitro blood loop studies experimentally determined hemolysis performance. Comparative simulation results and experimental data demonstrated that the CentriMag pump caused the lowest hemolysis while the Revolution pump generated the highest hemolysis.

Discovery of selective HDAC6 inhibitors capped by flavonoid or flavonoid-analogous moieties as anti-cancer therapeutics simultaneously harboring anti-proliferative and immunomodulatory activities.

Specific HDAC6 inhibitors (HDAC6is) simultaneously harboring anti-proliferative and immunomodulatory properties may prohibit tumor progression via intrinsic and immune driven effects. Herein, built upon the structurally novel lead TFH-7, structure-activity relationship study culminated in the identification of azaflavone-capped compound 20, which exhibited comparable HDAC6 inhibitory activity (IC50 = 8.5 nM) to that of Tubastatin A, a highly selective HDAC6i, as well as favorable subtype specificity. Importantly, concurrent with its impressive anti-proliferative efficacy against several solid tumor cell lines, 20 remarkably alleviated the transduction of immune-related STAT3 signaling and attenuated the expression of immunosuppressive checkpoint PD-L1 at submicromolar concentration, highlighting the immunomodulatory properties. Moreover, consistent with its favorable subtype selectivity, 20 displayed low cytotoxicity against normal human umbilical vein endothelial cells, revealing a promising safety profile. Following the intravenous administration, it demonstrated acceptable elimination half-life and exposure in Sprague-Dawley rats. Hence, the extensive functional investigation or structural modification of 20 is valuable.

SAR study culminates in a series of HDAC6 selective inhibitors featuring Schisandrin C-analogous Cap as potential immunomodulatory agents for cancer therapy.

HDAC6 inhibitors (HDAC6is) represent an emerging therapeutic option for triggering anti-cancer immune response. In this work, a novel series of HDAC6is, derived from an in-house analog of the traditional Chinese medicine monomer Schisandrin C, were designed and synthesized for SAR study. Throughout the 29 target compounds, 24a, 24b and 24h exerted single-digit nanomolar enzymatic activity and remarkably elevated subtype selectivity compared to the clinically investigated HDAC6i Ricolinostat (Selectivity index = 3.3). In A549 tumor cells, 24h, as the representative in this series (IC50 = 7.7 nM; selectivity index = 31.4), was capable of reversing IL-6-mediated PD-L1 upregulation, highlighting its immunomodulatory capability. Importantly, unlike numerous other hydroxamate-based HDACis, 24h displayed an acceptable oral bioavailability in Sprague-Dawley rats, along with high plasma exposure, long elimination half-life and slow clearance. With the aforementioned attractive performance, 24h deserves further in vivo investigation as an immunomodulatory therapeutic agent for batting human malignance.

Polymyxin B-Associated Nephrotoxicity and Its Predictors: A Retrospective Study in Carbapenem-Resistant Gram-Negative Bacterial Infections.

Polymyxin B (PMB), a kind of polymyxin, was widely used in carbapenem-resistant Gram-negative bacterial (CR-GNB) infections. However, adverse reactions such as nephrotoxicity and neurotoxicity limit its use in clinical practice. The aim of this study was to explore PMB associated with nephrotoxicity and its predictors. Patients who received PMB intravenous drip for more than 72 h were eligible for the study. Characteristics of patients, concomitant nephrotoxic agents, underlying disease, and antimicrobial susceptibility were submitted for descriptive analysis. Univariate analysis and binary logistic regression were used to assess the factors leading to acute kidney injury (AKI). AKI was assessed with serum creatinine variations according to the classification of risk (stage R), injury (stage I), failure (stage F), loss, and end-stage of kidney disease. Among 234 patients with CR-GNB infections who used PMB in our study, 67 (28.63%) patients developed AKI, including 31 (14.25%) patients in stage R, 15 (6.41%) patients in stage I, and 21 (8.97%) patients in stage F. The incident rate of PMB-related nephrotoxicity in patients with normal renal function was 32.82% (43/131). The higher risk factors of AKI include males [odds ratio (OR) = 3.237; 95% confidence interval (95%CI) = 1.426-7.350], digestive system diseases [OR = 2.481 (1.127-5.463)], using furosemide (>20 mg/day) [OR = 2.473 (1.102-5.551)], and baseline serum creatinine [OR = 0.994 (0.990-0.999)]. Nonparametric tests of K-independent samples showed that baseline serum creatinine and the PMB maintenance dose were associated with the severity of nephrotoxicity (both p < 0.05). Male, digestive system diseases, using furosemide (>20 mg/day), and high baseline serum creatinine were the independent risk factors of PMB-associated AKI development. The maintenance dose of PMB may be related to the severity of AKI. These risk factors should be taken into consideration when initiating PMB-based therapy. The serum creatinine value should be closely monitored when using PMB.

Scaling of the strange-metal scattering in unconventional superconductors.

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.

Ni@CNTs/Al2O3 Ceramic Composites with Interfacial Solder Strengthen the Segregated Network for High Toughness and Excellent Electromagnetic Interference Shielding.

Ingenious microstructure design and appropriate multicomponent strategies are still challenging for advanced electromagnetic interference (EMI) shielding materials with excellent shielding effectiveness (SE) and reliable mechanical properties in harsh environments and low filling levels. In this study, nickel@multiwalled carbon nanotubes/alumina (Ni@CNTs/Al2O3) ceramic composites with segregated structures and electric/magnetic-coupling networks anchored by CNTs and magnetic Ni nanofillers were prepared by hot-press sintering. CNTs/Al2O3 ceramic composites exhibit a percolation threshold of only about 0.32013 vol %, which is lower than those of other reported CNTs/Al2O3 composites with segregated or uniformly dispersed structures. The electrical conductivity and EMI SE of 9CNTs/Al2O3 ceramic composites with 9 vol % (4.76 wt %) CNT content were 103.1 S/m and 33.6 dB, respectively. In addition, EMI SE and toughness were both enhanced by the synergistic effect of Ni nanoparticles and CNTs. In the unit of a segregated structure, a three-dimensional (3D) electric/magnetic-coupling network effectively captures and attenuates electromagnetic wave energy by electrical conduction, dielectric loss, and magnetic loss. On the other hand, the pull-out of CNTs and deflection of cracks distributed along the segregated structures synergistically enhance the fracture toughness of Ni@CNTs/Al2O3 ceramic composites. High-performance 3Ni@5CNTs/Al2O3 ceramic composites with 5 vol % (2.64 wt %) and 3 vol % (0.76 wt %) CNT contents have been achieved, whose EMI SE is 41.8 dB, density is 90.99%, flexural strength is 197.83 ± 18.62 MPa, and fracture toughness is 6.03 ± 0.23 MPa·m1/2. This efficient method provides a promising way to fabricate EMI shielding ceramic composites with high mechanical properties.