Wiley最新文献

Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions.

Background: In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed "Shrunken pore syndrome." Numerous studies have thereafter found an association between this syndrome (defined by a low eGFR_{cystatin C} to eGFR_creatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFR_{cystatin C} and eGFR_creatinine to describe a similar disorder, and this investigation compares the two measures.

Methods: Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFR_difference and the eGFR_ratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated.

Results: Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 "healthy" individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria.

Conclusion: The eGFR_difference is not superior to the eGFR_ratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.

Transition metal π-arene complexes enable the dearomatization of benzene rings to access diversified unsaturated carbocycles through multistep synthetic procedures involving sequential addition of nucleophiles and electrophiles. This work details a single-step dearomatization process by reaction of Ru(η6-arene) complexes with enolates derived from α-halo or α-(tosyloxy)esters to directly transform π-coordinated arenes to ring-expanded cycloheptatrienes.

Methanolation of olefins is introduced as a new low-pressure synthetic pathway to C1 elongated alcohols. Formally, H3COH is added to the C=C bond in a 100% atom efficient manner. Mechanistically, the overall transformation occurs as a tandem reaction sequence by combining the dehydrogenation of methanol to syngas at a CO:H2 ratio of 1:2 with subsequent hydroformylation to the corresponding aldehyde and its final hydrogenation to the alcohol. The dehydrogenation and hydrogenation steps are catalysed by a Mn/pincer complex, while the hydroformylation is accomplished by a Rh/phosphine catalyst. Using 1-octene as prototypical substrate, a yield of 80% nonanol was achieved with a ratio of 93:7 of linear to branched alcohols and turnover numbers (TONRh) of more than 17 000 could be obtained in relation to the precious metal Rhodium. The integrated catalytic system provides direct access to alcohols from olefins and "green" methanol, avoiding the handling of pressurized CO and H2 and the use of specialized high-pressure equipment as the process conditions do not exceed 10 bar with partial pressures of syngas in the range of only 1-2 bar.

Although geoscience of natural hydrogen (H₂), hydrogen-producing soil bacteria, and especially plant-based H₂, has been observed, it is not clear whether or how above H₂ resources influence root gravitropic responses. Here, pharmacological, genetic, molecular, and cell biological tools were applied to investigate how plant-based H₂ coordinates gravity responses in Arabidopsis roots. Since roots show higher H₂ production than shoots, exogenous H₂ supply was used to mimic this function. After H₂ supplementation, the asymmetric expression of the auxin-response reporter DR5 driven by auxin influx and efflux carriers, and thereafter positive root gravitropism were observed. These positive responses in root gravitropism were sensitive to auxin polar transport inhibitors, and importantly, the defective phenotypes observed in aux1-7, pin1, and pin2 mutants were not significantly altered by exogenous H₂. The observed starch accumulation was matched with the reprogramming gene expression linked to starch synthesis and degradation. Transgenic plants expressing hydrogenase1 (CrHYD1) from Chlamydomonas reinhardtii not only displayed higher endogenous H₂ concentrations, the inducible AUX1 gene expression and starch accumulation, but also showed pronounced root gravitropism. Collectively, above evidence preliminarily provides a framework for understanding the molecular basis of the possible functions of both plant/soil-based and nature H₂ in root architecture.

Si-based anodes can increase specific energy and energy density of Li ion batteries. However, the volume-induced material stress and capacity loss necessitates only a partial Si utilization within composite anodes, typically with state-of-the-art graphite, so called Si/Gr composites. In this work, various Si nanowires (SiNWs), a promising Si architecture for these composites, are investigated and modified via pre-lithiation. Though, charged pre-lithiated anodes show potentials below 0 V vs. Li|Li+ in the initial cycles, they do not show indications for metallic Li, which is likely a hint for a triggered surface Li depletion in course of a continuous "transfer-lithiation" from lithiated Gr to Si, which is indicated by decreasing LiC6 and increasing LixSiy signals via nuclear magnetic resonance (NMR), X-ray diffraction (XRD) as well as shifts in capacities of respective voltage plateaus during discharge after storage. A relevant contribution of self-discharge is unlikely as shown by a stable open-circuit-voltage during storage in charged state and similar subsequent discharge capacities, being consequently also a hint for an intra-electrode capacity shift. The process of transfer lithiation is finally validated via solid-state 7Li NMR for varied Si morphology, i.e., amorphous and crystalline, as well as during pre-lithiation with passivated lithium metal powder (PLMP).

Impaired endometrial function and reduced receptivity remain significant causes of female infertility. Here, a sprayable hydrogel combined with human endometrial organoid extracellular vesicles (HEO-EVs) is developed to enhance uterine function preservation and fertility restoration. The peptide amphiphile hydrogel (labeled CPA) is engineered by conjugating a collagen-binding peptide with glutathione to impart its biocompatible adhesive and antioxidant properties. The therapeutic EVs are isolated and purified from human endometrial organoids that have been stably passaged long-term using a bioreactor-culture system. The resulting HEO-EVs-loaded CPA (CPA@HEO-EVs) rapid gelation, triggered by salt-ion interactions, occurs when the fluid is sprayed onto the uterine lining. The ex vivo studies demonstrate that CPA@HEO-EVs promote cell proliferation, scavenges free radicals, and increases tube formation in human umbilical vein endothelial cells. In vivo experiments further validate that in situ spraying with the CPA@HEO-EVs can promote neovascularization, prevent localized endometrial fibrosis, and effectively enhance fertility in a mouse model of endometrial injury. These findings highlight the promising clinical application of in situ sprayed CPA@HEO-EVs hydrogel for targeted endometrial therapy.

Intratumour heterogeneity significantly hinders the efficacy of anticancer therapies. Compared with drug perturbation experiments, which yield pharmacological data at the bulk cell level, single-cell RNA sequencing (scRNA-seq) technology provides a means to capture molecular heterogeneity at single-cell resolution. Here, scPharm is introduced, a computational framework that integrates pharmacological profiles with scRNA-seq data to identify pharmacological subpopulations of cells within a tumour and prioritize tailored drugs. scPharm uses the normalized enrichment scores (NESs) determined from gene set enrichment analysis to assess the distribution of cell identity genes in drug response-determined gene lists. Based on the strong correlation between the NES and drug response at single-cell resolution, scPharm successfully identified the sensitive subpopulations in ER-positive and HER2-positive human breast cancer tissues, revealed dynamic changes in the resistant subpopulation of human PC9 cells treated with erlotinib, and expanded its ability to a mouse model. Its superior performance and computational efficiency are confirmed through comparative evaluations with other single-cell prediction tools. Additionally, scPharm predicted combination drug strategies by gauging compensation or booster effects between drugs and evaluated drug toxicity in healthy cells in the tumour microenvironment. Overall, scPharm provides a novel approach for precision medicine in cancers by revealing therapeutic heterogeneity at single-cell resolution.