Enantioselective α-Boryl Carbene Transformations.

Carbenes, recognized as potent intermediates, enable unique chemical transformations, and organoborons are pivotal in diverse chemical applications. As a hybrid of carbene and the boryl group, α-boryl carbenes are promising intermediates for the construction of organoborons; unfortunately, such carbenes are hard to access and have low structural diversity with their asymmetric transformations largely uncharted. In this research, we utilized boryl cyclopropenes as precursors for the swift synthesis of α-boryl metal carbenes, a powerful category of intermediates for chiral organoboron synthesis. These α-boryl carbenes undergo a series of highly enantioselective transfer reactions, including B-H and Si-H insertion, cyclopropanation, and cyclopropanation/Cope rearrangement, catalyzed by a singular chiral copper complex. This approach opens paths to previously unattainable but easily transformable chiral organoborons, expanding both carbene and organoboron chemistry.

Iron-Catalyzed Allylic C(sp3)-H Silylation: Spin-Crossover-Efficiency-Determined Chemoselectivity.

The nuanced role of spin effects remains a critical gap in designing proficient open-shell catalysts. This study elucidates an iron-catalyzed allylic C(sp3)-H silylation/alkyne hydrosilylation reaction, in which the spin state of the open-shell iron catalyst dictates the reaction kinetics and pathway. Specifically, spin crossover led to alkyne hydrosilylation, whereas spin conservation resulted in a novel allylic C(sp3)-H silylation reaction. This chemoselectivity, governed by the spin-crossover efficiency, reveals an unexpected dimension in spin effects and a first in the realm of transition-metal-catalyzed in situ silylation of allylic C(sp3)-H bonds, which had been previously inhibited by the heightened reactivity of alkenes in hydrosilylation reactions. Furthermore, this spin crossover can either accelerate or hinder the reaction at different stages within a single catalytic reaction, a phenomenon scarcely documented. Moreover, we identify a substrate-assisted C-H activation mechanism, a departure from known ligand-assisted processes, offering a fresh perspective on C-H activation strategies.

C3: connect separate connected components to form a succinct disease module.

BACKGROUND: Precise disease module is conducive to understanding the molecular mechanism of disease causation and identifying drug targets. However, due to the fragmentization of disease module in incomplete human interactome, how to determine connectivity pattern and detect a complete neighbourhood of disease based on this is still an open question. RESULTS: In this paper, we perform exploratory analysis leading to an important observation that through a few intermediate nodes, most separate connected components formed by disease-associated proteins can be effectively connected and eventually form a complete disease module. And based on the topological properties of these intermediate nodes, we propose a connect separate connected components (C3) method to detect a succinct disease module by introducing a relatively small number of intermediate nodes, which allows us to obtain more pure disease module than other methods. Then we apply C3 across a large corpus of diseases to validate this connectivity pattern of disease module. Furthermore, the connectivity of the perturbed genes in multi-omics data such as The Cancer Genome Atlas also fits this pattern. CONCLUSIONS: C3 tool is not only useful in detecting a clearly-defined connected disease neighbourhood of 299 diseases and cancer with multi-omics data, but also helpful in better understanding the interconnection of phenotypically related genes in different omics data and studying complex pathological processes.

Correlated metals as transparent conductors.

The fundamental challenge for designing transparent conductors used in photovoltaics, displays and solid-state lighting is the ideal combination of high optical transparency and high electrical conductivity. Satisfying these competing demands is commonly achieved by increasing carrier concentration in a wide-bandgap semiconductor with low effective carrier mass through heavy doping, as in the case of tin-doped indium oxide (ITO). Here, an alternative design strategy for identifying high-conductivity, high-transparency metals is proposed, which relies on strong electron-electron interactions resulting in an enhancement in the carrier effective mass. This approach is experimentally verified using the correlated metals SrVO3 and CaVO3, which, despite their high carrier concentration (>2.2 × 10(22) cm(-3)), have low screened plasma energies (<1.33 eV), and demonstrate excellent performance when benchmarked against ITO. A method is outlined to rapidly identify other candidates among correlated metals, and strategies are proposed to further enhance their performance, thereby opening up new avenues to develop transparent conductors.

Coupled Nonpolar-Polar Metal-Insulator Transition in 1∶1 SrCrO(3)/SrTiO(3) Superlattices: A First-Principles Study.

Using first-principles calculations, we determined the epitaxial-strain dependence of the ground state of the 1∶1 SrCrO(3)/SrTiO(3) superlattice. The superlattice layering leads to significant changes in the electronic states near the Fermi level, derived from Cr t(2g) orbitals. An insulating phase is found when the tensile strain is greater than 2.2% relative to unstrained cubic SrTiO(3). The insulating character is shown to arise from Cr t(2g) orbital ordering, which is produced by an in-plane polar distortion that couples to the superlattice d bands and is stabilized by epitaxial strain. This effect can be used to engineer the band structure near the Fermi level in transition metal oxide superlattices.

Association between haemoglobin-to-red blood cell distribution width ratio at admission and all-cause mortality in adult patients with sepsis in an intensive care unit: a secondary analysis of the MIMIC-IV database.

OBJECTIVE: The association between haemoglobin-to-red blood cell distribution width ratio (HRR) and all-cause mortality remains poorly understood. This study aimed to examine the influence of HRR at the time of admission mortality over 1 year and 30 days in patients with sepsis. DESIGN: This was a secondary analysis. SETTING: This study was conducted in intensive care units (ICUs). PARTICIPANTS: Adult patients with sepsis were identified and included from an intensive care database based on eligibility criteria. PRIMARY OUTCOME AND MEASURE: The primary outcome was the rate of death within 1 year. The secondary outcome was the death rate within 30 days. RESULTS: A total of 4233 patients with sepsis who met the inclusion criteria were analysed, excluding those ineligible. These participants were divided into quartiles based on their HRR at admission. The overall mortality rates at 1 year and 30 days were 42.9% and 25.5%, respectively. A significant inverse association was observed between HRR quartiles and all-cause mortality (p<0.001). Pairwise comparisons using Kaplan-Meier analysis showed significant differences in 1-year mortality rates across the quartiles. However, no significant difference was detected in 30-day mortality between the Q3 and Q4 groups (p=0.222). Multivariate Cox regression analysis demonstrated that a higher HRR at ICU admission was independently associated with reduced mortality at 1 year (HR, 0.935; 95% CI 0.913 to 0.958; p<0.001) and 30 days (HR, 0.969; 95% CI 0.939 to 0.999; p=0.043). Furthermore, restricted cubic spline models indicated a non-linear relationship between HRR and mortality at both 1 year and 30 days (p<0.001 for both). CONCLUSIONS: This retrospective analysis demonstrated that the HRR at the time of admission was a significant prognostic marker for long-term mortality in patients with sepsis.

Characterization of a Novel Thermostable 7α-Hydroxysteroid Dehydrogenase.

BACKGROUND: 7α-Hydroxysteroid dehydrogenase (7α-HSDH) plays a pivotal role in vivo in the biotransformation of secondary bile acids and has great potential in industrial biosynthesis due to its broad substrate specificity. In this study, we expressed and characterized a novel thermostable 7α-HSDH (named Sa 7α-HSDH). METHODS: The DNA sequence was derived from the black bear gut microbiome metagenomic sequencing data, and the coding sequence of Sa 7α-HSDH was chemically synthesized. The heterologous expression of the enzyme was carried out using the pGEX-6p-1 vector. Subsequently, the activity of the purified enzyme was studied by measuring the absorbance change at 340 nm. Finally, the three-dimensional structure was predicted with AlphaFold2. RESULTS: Coenzyme screening results confirmed it to be NAD(H) dependent. Substrate specificity test revealed that Sa 7α-HSDH could catalyze taurochenodeoxycholic acid (TCDCA) with catalytic efficiency (kcat/Km) 3.81 S-1 mM-1. The optimum temperature of Sa 7α-HSDH was measured to be 75°C, confirming that it belongs to thermophilic enzymes. Additionally, its thermostability was assessed using an accelerated stability test over 32 hours. The catalytic activity of Sa 7α-HSDH remained largely unchanged for the first 24 hours and retained over 90% of its functionality after 32 hours at 50°C. Sa 7α-HSDH exhibited maximal activity at pH 10. The effect of metal ions-K+, Na+, Mg2+ and Cu2+-on the enzymatic activity of Sa 7α-HSDH was investigated. Only Mg2+ was observed to enhance the enzyme's activity by 27% at a concentration of 300 mM. Neither K+ nor Na+ had a significant influence on activity. Only Cu2+ was found to reduce enzyme activity. CONCLUSION: We characterized the thermostable 7α-HSDH, which provides a promising biocatalyst for bioconversion of steroids at high reaction temperatures.

Enhanced red blood cell distribution width to platelet ratio is a predictor of mortality in patients with sepsis: a propensity score matching analysis based on the MIMIC-IV database.

OBJECTIVE: To explore the association between dynamic changes in red blood cell distribution width to platelet count ratio (RPR) during hospitalisation and short-term mortality in patients with sepsis. DESIGN: A retrospective cohort study using propensity score matching. SETTING: Intensive care units (ICUs) of Beth Israel Deaconess Medical Center. PARTICIPANTS: A total of 8731 adult patients with sepsis were included in the study. The patients were identified from the ICU of the Medical Information Mart for Intensive Care database. The observed group included patients who experienced an increase in RPR of more than 30% during the first week of ICU admission, whereas the control group included the rest. MAIN OUTCOME AND MEASURE: Using propensity score matching, a matched control group was created. The primary outcome was 28-day mortality, and the length of hospital stay and in-hospital mortality were the secondary outcomes. RESULTS: The difference was evident in 28-day mortality between the two groups (85.8% vs 74.5%, p<0.001, Kaplan-Meier analysis, and HR=1.896, 95% CI=1.659 to 2.168, p<0.001, Cox regression). In the secondary outcomes, there was a significant difference in in-hospital mortality (p<0.001). In addition, the study discovered that the observed groups had a significantly longer hospital stay (p<0.001). Meanwhile, the results of subgroup analyses were consistent with those of the primary analyses. CONCLUSIONS: In patients with sepsis, a significantly increased RPR is positively associated with the short-term death rate. Continuous RPR monitoring could be a valuable measure for predicting short-term mortality in patients with sepsis.

In-situ liquid cell transmission electron microscopy investigation on oriented attachment of gold nanoparticles.

Inside a liquid solution, oriented attachment (OA) is now recognized to be as important a pathway to crystal growth as other, more conventional growth mechanisms. However, the driving force that controls the occurrence of OA is still poorly understood. Here, using in-situ liquid cell transmission electron microscopy, we demonstrate the ligand-controlled OA of citrate-stabilized gold nanoparticles at atomic resolution. Our data reveal that particle pairs rotate randomly at a separation distance greater than twice the layer thickness of adsorbed ligands. In contrast, when the particles get closer, their ligands overlap and guide the rotation into a directional mode until they share a common {111} orientation, when a sudden contact occurs accompanied by the simultaneous expulsion of the ligands on this surface. First-principle calculations confirm that the lower ligand binding energy on {111} surfaces is the intrinsic reason for the preferential attachment at this facet, rather than on other low-index facets.

Ultrastructural observations of human epidermal melanocytes cultured on polyethylene terephthalate film.

OBJECTIVE: To assess the application of polyethylene terephthalate film as a supporting material of cultured human epidermal melanocytes and to observe the ultrastructure of human epidermal melanocytes in vitro. METHODS: Human epidermal melanocytes were isolated from 7- to 14-years old children foreskins and were cultured in M254 culture medium containing human melanocyte growth supplement. Cultured melanocytes were purified via a differential trypsinization method. Purified melanocytes were cultured on a film and prepared for transmission electron microscopy. RESULTS: In comparing with the cellular supporting materials polyvinylidene chloride and cellophane, human epidermal melanocytes only attached and grew on polyethylene terephthalate film. Melanocytes grown on polyethylene terephthalate film maintained an intact shape, and retained special ultrastructures characteristic of melanocytes such as dendrites. CONCLUSIONS: Polyethylene terephthalate film proved to be an ideal cellular supporting material for the cultivation of human epidermal melanocytes. Ultrastructure of melanocytes showed melanosomes are transferred both from the tip and middle section of dendrites.