Restoring colistin sensitivity in colistin-resistant Salmonella and Escherichia coli: combinatorial use of berberine and EDTA with colistin.

The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the "last resort" for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR. We first demonstrated that the combination of berberine (BBR) and EDTA substantially restored COL sensitivity against COL-resistant Salmonella and Escherichia coli. Molecular docking indicated that BBR can interact with MCR-1 and the efflux pump system AcrAB-TolC, and BBR combined with EDTA downregulated the expression level of mcr-1 and tolC. Mechanically, BBR combined with EDTA could increase bacterial membrane damage, inhibit the function of multidrug efflux pump, and promote oxidative damage, thereby boosting the action of COL. In addition, transcriptome analysis found that the combination of BBR and EDTA can accelerate the tricarboxylic acid cycle, inhibit cationic antimicrobial peptide (CAMP) resistance, and attenuate Salmonella virulence. Notably, the combination of BBR and EDTA with COL significantly reduced the bacterial load in the liver and spleen of a mice model infected with Salmonella. Our findings revealed that BBR and EDTA can be used as adjuvants collectively with COL to synergistically reverse the COL resistance of bacteria. IMPORTANCE: Colistin is last-resort antibiotic used to treat serious clinical infections caused by MDR bacterial pathogens. The recent emergence of transferable plasmid-mediated COL resistance gene mcr-1 has raised the specter of a rapid worldwide spread of COL resistance. Coupled with the fact of barren antibiotic development pipeline nowadays, a critical approach is to revitalize existing antibiotics using antibiotic adjuvants. Our research showed that berberine combined with EDTA effectively reversed COL resistance both in vivo and in vitro through multiple modes of action. The discovery of berberine in combination with EDTA as a new and safe COL adjuvant provides a therapeutic regimen for combating Gram-negative bacteria infections. Our findings provide a potential therapeutic option using existing antibiotics in combination with antibiotic adjuvants and address the prevalent infections caused by MDR Gram-negative pathogens worldwide.

Highly efficient anion exchange membrane water electrolyzers via chromium-doped amorphous electrocatalysts.

In-depth comprehension and modulation of the electronic structure of the active metal sites is crucial to enhance their intrinsic activity of electrocatalytic oxygen evolution reaction (OER) toward anion exchange membrane water electrolyzers (AEMWEs). Here, we elaborate a series of amorphous metal oxide catalysts (FeCrOx, CoCrOx and NiCrOx) with high performance AEMWEs by high-valent chromium dopant. We discover that the positive effect of the transition from low to high valence of the Co site on the adsorption energy of the intermediate and the lower oxidation barrier is the key factor for its increased activity by synchrotron radiation in-situ techniques. Particularly, the CoCrOx anode catalyst achieves the high current density of 1.5 A cm-2 at 2.1 V and maintains for over 120 h with attenuation less than 4.9 mV h-1 in AEMWE testing. Such exceptional performance demonstrates a promising prospect for industrial application and providing general guidelines for the design of high-efficiency AEMWEs systems.

Symmetry Evolution Induced 2D Pt Single Atom Catalyst with High Density for Alkaline Hydrogen Oxidation.

The performance of single-atom catalysts is greatly influenced by the chemical environment surrounding the central atom. Here, a salt-assisted method is employed to transform the tetrahedral coordination structure of zeolitic imidazolate frameworks - 8 (ZIF-8) into a planar square coordination structure without altering the ligands. During the subsequent carbonization process, concurrent with the evaporation of zinc atoms, the structure of the nitrogen and carbon carriers (NC carriers) undergoes a transition from five-membered rings to six-membered rings to preserve the 2D structure. This transition results in the generation of additional defect sites on the 2D-NC substrates. Hence, the Pt single-atom catalysts with planar square coordination symmetries can be precisely prepared via electrodeposition (denoted as 2D-Pt SAC). The Pt loading of 2D-Pt SAC is 0.49 ± 0.03 µg cm-2, higher than that of 3D-Pt SAC (0.37 ± 0.04 µg cm-2). In the context of the hydrogen oxidation reaction electrocatalysis, under an overpotential of 50 mV, these single-atom catalysts with 2D coordination exhibit mass activities of 2396 A gPt -1 (32 times higher than commercial Pt/C catalyst, 2 times higher than 3D-PtNC).

Investigation of Mold Flux Entrapment in Deep Oscillation Mark of Interstitial-Free Steel Shell Using Mold Simulator.

The slag entrapment defect has become a big issue for the IF steel casting process. In this study, the mechanism of mold flux entrapment in deep oscillation mark of an IF steel shell was studied by a high-temperature mold simulator. Results show that both temperature and heat flux in a copper mold become lower when mold flux B with lower melting and viscosity is used, compared with these when mold flux A with higher melting and viscosity is used. The average thickness of the slag film for mold fluxes A and B is 1.31 mm and 1.63 mm, and the consumption of them is 0.33 kg/m2 and 0.35 kg/m2, respectively. The shell for mold flux A exhibits sharper oscillation marks, while the shell for mold flux B has shallower oscillation marks. These deeper oscillation marks capture the mold flux by overflow of molten steel at the meniscus, which finally produces the slag entrapment defect in the shell.

Uncovering Structural Evolution during the Dealloying Process in Pt-Based Oxygen-Reduction Catalyst.

The comprehensive understanding toward the dealloying process is crucial for designing alloy catalysts employed in the oxygen reduction reaction (ORR). However, the specific leaching procedure and subsequent reconstruction of the dealloyed catalyst still remain unclear. Herein, we employ in situ X-ray absorption fine structure spectroscopy to monitor the dealloying process of a two-dimensional PtTe ordered alloy, known for its enhanced ORR activity. Our findings reveal the unsynchronous evolutions of Pt and Te sites, wherein the Pt component undergoes a structural transformation prior to the complete leaching of Te, leading to the formation of a defect-rich Pt catalyst. This dealloyed catalyst exhibits a significant enhancement in ORR activity, featuring a half-wave potential of 0.90 V versus the reversible hydrogen electrode and a mass activity of 0.62 A mgPt-1, outperforming the performance of commercial Pt/C counterpart. This in-depth understanding of the dealloying mechanism enriches our knowledge for the development of high-performance Pt-based alloy catalysts.

Self-Assembly Intermetallic PtCu3 Core with High-Index Faceted Pt Shell for High-Efficiency Oxygen Reduction.

Rational design of well-defined active sites is crucial for promoting sluggish oxygen reduction reactions. Herein, leveraging the surfactant-oriented and solvent-ligand effects, we develop a facile self-assembly strategy to construct a core-shell catalyst comprising a high-index Pt shell encapsulating a PtCu3 intermetallic core with efficient oxygen-reduction performance. Without undergoing a high-temperature route, the ordered PtCu3 is directly fabricated through the accelerated reduction of Cu2+, followed by the deposition of the remaining Pt precursor onto its surface, forming high-index steps oriented by the steric hindrance of surfactant. This approach results in a high half-wave potential of 0.911 V versus reversible hydrogen electrode, with negligible deactivation even after 15000-cycle operation. Operando spectroscopies identify that this core-shell catalyst facilitates the conversion of oxygen-involving intermediates and ensures antidissolution ability. Theoretical investigations rationalize that this improvement is attributed to reinforced electronic interactions around high-index Pt, stabilizing the binding strength of rate-determining OHads species.

Development and validation of a federated learning framework for detection of subphenotypes of multisystem inflammatory syndrome in children.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection. The highly diverse clinical features of MIS-C necessities characterizing its features by subphenotypes for improved recognition and treatment. However, jointly identifying subphenotypes in multi-site settings can be challenging. We propose a distributed multi-site latent class analysis (dMLCA) approach to jointly learn MIS-C subphenotypes using data across multiple institutions. Methods: We used data from the electronic health records (EHR) systems across nine U.S. children's hospitals. Among the 3,549,894 patients, we extracted 864 patients < 21 years of age who had received a diagnosis of MIS-C during an inpatient stay or up to one day before admission. Using MIS-C conditions, laboratory results, and procedure information as input features for the patients, we applied our dMLCA algorithm and identified three MIS-C subphenotypes. As validation, we characterized and compared more granular features across subphenotypes. To evaluate the specificity of the identified subphenotypes, we further compared them with the general subphenotypes identified in the COVID-19 infected patients. Findings: Subphenotype 1 (46.1%) represents patients with a mild manifestation of MIS-C not requiring intensive care, with minimal cardiac involvement. Subphenotype 2 (25.3%) is associated with a high risk of shock, cardiac and renal involvement, and an intermediate risk of respiratory symptoms. Subphenotype 3 (28.6%) represents patients requiring intensive care, with a high risk of shock and cardiac involvement, accompanied by a high risk of >4 organ system being impacted. Importantly, for hospital-specific clinical decision-making, our algorithm also revealed a substantial heterogeneity in relative proportions of these three subtypes across hospitals. Properly accounting for such heterogeneity can lead to accurate characterization of the subphenotypes at the patient-level. Interpretation: Our identified three MIS-C subphenotypes have profound implications for personalized treatment strategies, potentially influencing clinical outcomes. Further, the proposed algorithm facilitates federated subphenotyping while accounting for the heterogeneity across hospitals.

Alleviating OH Blockage on the Catalyst Surface by the Puncture Effect of Single-Atom Sites to Boost Alkaline Water Electrolysis.

Nonprecious transition metal catalysts have emerged as the preferred choice for industrial alkaline water electrolysis due to their cost-effectiveness. However, their overstrong binding energy to adsorbed OH often results in the blockage of active sites, particularly in the cathodic hydrogen evolution reaction. Herein, we found that single-atom sites exhibit a puncture effect to effectively alleviate OH blockades, thereby significantly enhancing the alkaline hydrogen evolution reaction (HER) performance. Typically, after anchoring single Ru atoms onto tungsten carbides, the overpotential at 10 mA·cm-2 is reduced by more than 130 mV (159 vs 21 mV). Also, the mass activity is increased 16-fold over commercial Pt/C (MA100 = 17.3 A·mgRu-1 vs 1.1 A·mgPt-1, Pt/C). More importantly, such electrocatalyst-based alkaline anion-exchange membrane water electrolyzers can exhibit an ultralow potential (1.79 Vcell) and high stability at an industrial current density of 1.0 A·cm-2. Density functional theory (DFT) calculations reveal that the isolated Ru sites could weaken the surrounding local OH binding energy, thus puncturing OH blockage and constructing bifunctional interfaces between Ru atoms and the support to accelerate water dissociation. Our findings exhibit generality to other transition metal catalysts (such as Mo) and contribute to the advancement of industrial-scale alkaline water electrolysis.

Landslide susceptibility zonation using the analytical hierarchy process (AHP) in the Great Xi'an Region, China.

This study aims to delineate landslide susceptibility maps using the Analytical Hierarchy Process (AHP) method for the Great Xi'an Region, China, which is a key planning project for urban construction in Shaanxi Province, China from 2021 to 2035. Multiple data as elevation, slope, aspect, curvature, river density, soil, lithology, and land use have been considered for delineating the landslide susceptibility maps. Spatially thematic layers and distributed maps of all the aforementioned parameters were created in a GIS environment. Determine the relative importance of these thematic layers in the occurrence of landslides in the study area concerning historical landslide data to assign appropriate weights. Landslide sensitivity maps were generated by a weighted combination in a GIS environment after being analyzed by the AHP method. The sensitivity maps were categorized as "very high (11.06%), high (19.41%), moderate (23.03%), low (28.70%), and very low (17.80%)". Overlay analysis of the test data with the LSM showed that the moderate to very high landslide susceptibility zones were able to contain 82.58% of the historic landslides. The results of the study help determine the landslide-prone areas in the area and provide a reference for subsequent construction. In addition, the analysis of landslide susceptibility in the area contributes to the study of landslides in similar loess sites.

Boosting Electrocatalytic Ammonia Synthesis via Synergistic Effect of Iron-Based Single Atoms and Clusters.

Electrocatalytic reduction of nitrate to ammonia (NO3RR) is gaining attention for low carbon emissions and environmental protection. However, low ammonia production rate and poor selectivity have remained major challenges in this multi-proton coupling process. Herein, we report a facile strategy toward a novel Fe-based hybrid structure composed of Fe single atoms and Fe3C atomic clusters that demonstrates outstanding performance for synergistic electrocatalytic NO3RR. By operando synchrotron Fourier transform infrared spectroscopy and theoretical computation, we clarify that Fe single atoms serve as the active site for NO3RR, while Fe3C clusters facilitate H2O dissociation to provide protons (*H) for continued hydrogenation reactions. As a result, the Fe-based electrocatalyst exhibits ammonia Faradaic efficiency of nearly 100%, with a corresponding production rate of 24768 µg h-1 cm-2 at -0.4 V vs RHE, exceeding most reported metal-based catalysts. This research provides valuable guidance toward multi-step reactions.

Durable CO2 conversion in the proton-exchange membrane system.

Electrolysis that reduces carbon dioxide (CO2) to useful chemicals can, in principle, contribute to a more sustainable and carbon-neutral future1-6. However, it remains challenging to develop this into a robust process because efficient conversion typically requires alkaline conditions in which CO2 precipitates as carbonate, and this limits carbon utilization and the stability of the system7-12. Strategies such as physical washing, pulsed operation and the use of dipolar membranes can partially alleviate these problems but do not fully resolve them11,13-15. CO2 electrolysis in acid electrolyte, where carbonate does not form, has therefore been explored as an ultimately more workable solution16-18. Herein we develop a proton-exchange membrane system that reduces CO2 to formic acid at a catalyst that is derived from waste lead-acid batteries and in which a lattice carbon activation mechanism contributes. When coupling CO2 reduction with hydrogen oxidation, formic acid is produced with over 93% Faradaic efficiency. The system is compatible with start-up/shut-down processes, achieves nearly 91% single-pass conversion efficiency for CO2 at a current density of 600 mA cm-2 and cell voltage of 2.2 V and is shown to operate continuously for more than 5,200 h. We expect that this exceptional performance, enabled by the use of a robust and efficient catalyst, stable three-phase interface and durable membrane, will help advance the development of carbon-neutral technologies.

Highly dispersed ultrafine PtCo alloy nanoparticles on unique composite carbon supports for proton exchange membrane fuel cells.

The design of highly efficient and robust platinum-based electrocatalysts is pivotal for proton exchange membrane fuel cells (PEMFC). One of the long-standing issues for PEMFC is the rapid deactivation of the catalyst under working conditions. Here, we report a simple synthesis strategy for ultrafine PtCo alloy nanoparticles loaded on a unique carbon support derived from a zeolitic imidazolate framework-67 (ZIF-67) and Ketjen Black (KB) composite, exhibiting a remarkable catalytic performance toward the oxygen reduction reaction (ORR) and PEMFC. Benefitting from the N-doping and wide pore size distribution of the composite carbon supports, the growth of PtCo nanoparticles can be evenly restricted, leading to a uniform distribution. The Pt-integrated catalyst delivers an outstanding electrochemical performance with a mass activity that is 8.6 times higher than that of the commercial Pt/C catalyst. Impressively, the accelerated durability test (ADT) demonstrates that the hybrid carbon support can significantly enhance the durability. Theoretical simulations highlight the synergistic contribution between the supports and the PtCo nanoparticles. Moreover, hydrogen-oxygen fuel cells assembled with the catalyst exhibited a high power density of 1.83 W cm-2 at 4 A cm-2. These results provide a new opportunity to design advanced catalysts for PEMFC.

Tandem Addition/Cyclization/Halogenation Reaction of Difluoromethylated N-Acylhydrazones with Allyltrimethylsilanes.

As novel difluoromethyl building blocks, difluoromethylated N-acylhydrazones react with allyltrimethylsilanes and the halogen source via a tandem addition/cyclization/halogenation strategy, which produces various difluoromethylpyrazoline compounds in good yields. The method features mild reaction conditions, broad substrate scopes, and a transition metal-free process with easy operation. It also proves that difluoromethylated N-acylhydrazones are useful difluoromethyl building blocks for the construction of difluoromethylated nitrogen heterocycles.

Spectrum of severity of multisystem inflammatory syndrome in children: an EHR-based cohort study from the RECOVER program.

Multi-system inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection in children, and there is a critical need to unfold its highly heterogeneous disease patterns. Our objective was to characterize the illness spectrum of MIS-C for improved recognition and management. We conducted a retrospective cohort study using data from March 1, 2020-September 30, 2022, in 8 pediatric medical centers from PEDSnet. We included 1139 children hospitalized with MIS-C and used their demographics, symptoms, conditions, laboratory values, and medications for analyses. We applied heterogeneity-adaptive latent class analyses and identified three latent classes. We further characterized the sociodemographic and clinical characteristics of the latent classes and evaluated their temporal patterns. Class 1 (47.9%) represented children with the most severe presentation, with more admission to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 (23.3%) represented a moderate presentation, with 4-6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 (28.8%) represented a mild presentation. Our results indicated that MIS-C has a spectrum of clinical severity ranging from mild to severe and the proportion of severe or critical MIS-C decreased over time.

Chemical composition analysis of Angelica sinensis (Oliv.) Diels and its four processed products by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics.

Angelica sinensis (Oliv.) Diels. has been used for women to enrich the blood, prevent and treat blood deficiency syndrome in Traditional Chinese Medicine for thousands of years. Wine-processed Angelica sinensis, soil-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis are the most significant four processed products used in Chinese clinic. However, there have been few studies aimed at comparing their chemical differences. Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics was applied to investigate the diversity of processed products of Angelica sinensis. A total of 74 compounds with the variable importance in the projection value more than 1.5 and P less than 0.05 in ANOVA were highlighted as the compounds that contribute most to the discrimination of Angelica sinensis and four processed products. The results showed the metabolic changes between Angelica sinensis and its four processed products, there were 19 metabolites, 3 metabolites, 6 metabolites, and 45 metabolites were tentatively assigned in soil-processed Angelica sinensis, wine-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis, respectively. These results suggested that the proposed metabolomics approach was useful for the quality evaluation and control of processed products of Angelica sinensis.

Automatic identification and morphological comparison of bivalve and brachiopod fossils based on deep learning.

Fossil identification is an essential and fundamental task for conducting palaeontological research. Because the manual identification of fossils requires extensive experience and is time-consuming, automatic identification methods are proposed. However, these studies are limited to a few or dozens of species, which is hardly adequate for the needs of research. This study enabled the automatic identification of hundreds of species based on a newly established fossil dataset. An available "bivalve and brachiopod fossil image dataset" (BBFID, containing >16,000 "image-label" data pairs, taxonomic determination completed) was created. The bivalves and brachiopods contained in BBFID are closely related in morphology, ecology and evolution that have long attracted the interest of researchers. We achieved >80% identification accuracy at 22 genera and ∼64% accuracy at 343 species using EfficientNetV2s architecture. The intermediate output of the model was extracted and downscaled to obtain the morphological feature space of fossils using t-distributed stochastic neighbor embedding (t-SNE). We found a distinctive boundary between the morphological feature points of bivalves and brachiopods in fossil morphological feature distribution maps. This study provides a possible method for studying the morphological evolution of fossil clades using computer vision in the future.

Development and Validation of a Predictive Model to Evaluate the Risk of Dysphagia Following Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the potential risk factors of dysphagia after anterior cervical discectomy and fusion (ACDF) and to establish and validate a prediction model. METHODS: The clinical data of 252 patients who underwent anterior cervical discectomy and fusion in our hospital from January 2018 to October 2020 were retrospectively analyzed and divided into the dysphagia group and the non-dysphagia group according to whether dysphagia occurred after surgery. Age, gender, body mass index, smoking and drinking history, hypertension history, diabetes history, disease duration, placement of Hemovac negative pressure drain, number of segments involved in surgery, whether C4-5/C5-6 segment surgery, incision length, incision position, level of preoperative EAT-10 score, whether preoperative tracheal exercise, and changes in cervical curvature before and after surgery were recorded in both groups. Risk factors for postoperative dysphagia were identified and nomogram prediction models were developed. RESULTS: A total of 252 patients were included in the study, 115 of whom presented with dysphagia within 1 week after anterior cervical fusion. The results of multivariate logistic regression analysis indicated that male gender (OR = .045, 95% CI .223-.889) and whether preoperative tracheal exercise (OR = .260, 95% CI .107-.633) were independent risk factors associated with reduced incidence of postoperative dysphagia. CONCLUSION: The incidence of dysphagia symptoms after anterior cervical decompression and fusion gradually decreased with the extension of follow-up time, and preoperative tracheal exercise and shortening the operation time may help to reduce the occurrence of postoperative dysphagia.

Contribution of microbial necromass to soil organic carbon formation during litter decomposition under incubation conditions.

We conducted a 512-day incubation experiment to study the dynamics of microbial necromass and soil carbon fraction in the 'litter-soil' transformation interface soil layer (TIS) during litter decomposition, using a perennial C3 herb, Stipa bungeana, in the loess hills. The results showed that soil microbial necromass was dominated by fungi in the early and middle stages, and by bacteria in the late stage. The contribution of fungal necromass C to mineral-associated organic C (MAOC) was significantly higher (38.7%-75.8%) than that of bacteria (9.2%-22.5%) and 2-3 times more than the contribution rate of bacterial necromass. Soil organic C (SOC) content was decreasing during litter decomposition. The input of plant C resources stimulated microbial utilization of soil C fractions. The continuous decrease in particulate organic C during the early and late stages of decomposition was directly responsible for the decrease in SOC content. In contrast, the fluctuating changes in microbial necromass C and MAOC played an indirect role in the reduction of SOC. The increase in soil microbial necromass C caused by a single exogenous addition of litter did not directly contribute to SOC accumulation.

Progress in Manipulating Dynamic Surface Reconstruction via Anion Modulation for Electrocatalytic Water Oxidation.

The development of efficient and economical electrocatalysts for oxygen evolution reaction (OER) is of paramount importance for the sustainable production of renewable fuels and energy storage systems; however, the sluggish OER kinetics involving multistep four proton-coupled electron transfer hampers progress in these systems. Fortunately, surface reconstruction offers promising potential to improve OER catalyst design. Anion modulation plays a crucial role in controlling the extent of surface reconstruction and positively persuading the reconstructed species' performances. This review starts by providing a general explanation of how various types of anions can trigger dynamic surface reconstruction and create different combinations with pre-catalysts. Next, the influences of anion modulation on manipulating the surface dynamic reconstruction process are discussed based on the in situ advanced characterization techniques. Furthermore, various effects of survived anionic groups in reconstructed species on water oxidation activity are further discussed. Finally, the challenges and prospects for the future development directions of anion modulation for redirecting dynamic surface reconstruction to construct highly efficient and practical catalysts for water oxidation are proposed.