bluuebunny/crossref_metadata_2025 huggingface dataset:
An “All‐In‐One” Immunomodulator‐Engineered Clinical Translatable Immunotherapy of Advanced Hepatocellular Carcinoma
Authors: Xie Ting , Huang Cong , Wang Yuqing , Zhang Haitao , Guo Pei , Phann Thuy Thu , Cheng Yao , Lei Longtianyang , Tao Zhenghao , Gao Qing , Wei Hua , Yu Cui‐Yun
Published: March 2024

Clinical treatment of advanced hepatocellular carcinoma (HCC) remains a significant challenge. Utilizing 1‐bromoacetyl‐3,3‐dinitroazetidine (RRx‐001) to downregulate the expression of innate immune checkpoint molecule, cluster of differentiation 47 (CD47), provides a powerful means for treating advanced HCC containing abundant immunosuppressive macrophages. Herein engineering of a previously optimized Doxorubicin (DOX)‐delivery nanoplatform based on sodium alginate is reported to further co‐deliver RRx‐001 (biotinylated aldehyde alginate–doxorubicin micelle prodrug nanoplatform, BEA‐D@R) for efficient immunotherapy of advanced HCC. This groundbreaking  technique reveals the “all‐in‐one” immunotherapeutic functionalities of RRx‐001. Besides the previously demonstrated functions of downregulating CD47 expression and increasing reactive nitrogen species (RNS) generation, another key function of RRx‐001 for downregulating the expression of the adaptive immune checkpoint molecule programmed cell death 1 ligand 1 (PDL1) is first uncovered here. Combined with the reactive oxygen species (ROS) generation and an upregulated “eat me” signal level of DOX, BEA‐D@R collectively increases RNS generation, enhances T‐cell infiltration, and maximizes macrophage phagocytosis, leading to an average of 40% tumor elimination in a mice model bearing an initial tumor volume of ≈300 mm3 that mimics advanced HCC. Overall, the “all‐in‐one” immunotherapeutic functionalities of a clinical translatable nanoplatform are uncovered for enhanced immunotherapy of advanced HCC.
Human Cell‐Derived Matrix Composite Hydrogels with Diverse Composition for Use in Vasculature‐on‐chip Models
Authors: Doherty Elizabeth L. , Krohn Grace , Warren Emily C. , Patton Alexandra , Whitworth Chloe P. , Rathod Mitesh , Biehl Andreea , Aw Wen Yih , Freytes Donald O. , Polacheck William J.
Published: March 2024

Microphysiological and organ‐on‐chip platforms seek to address critical gaps in human disease models and drug development that underlie poor rates of clinical success for novel interventions. While the fabrication technology and model cells used to synthesize organs‐on‐chip have advanced considerably, most platforms rely on animal‐derived or synthetic extracellular matrix as a cell substrate, limiting mimicry of human physiology and precluding use in modeling diseases in which matrix dynamics play a role in pathogenesis. Here, the development of human cell‐derived matrix (hCDM) composite hydrogels for use in 3D microphysiologic models of the vasculature is reported. hCDM composite hydrogels are derived from human donor fibroblasts and maintain a complex milieu of basement membrane, proteoglycans, and nonfibrillar matrix components. The use of hCDM composite hydrogels as 2D and 3D cell culture substrates is demonstrated, and hCDM composite hydrogels are patterned to form engineered human microvessels. Interestingly, hCDM composite hydrogels are enriched in proteins associated with vascular morphogenesis as determined by mass spectrometry, and functional analysis demonstrates proangiogenic signatures in human endothelial cells cultured in these hydrogels. In conclusion, this study suggests that human donor‐derived hCDM composite hydrogels could address technical gaps in human organs‐on‐chip development and serve as substrates to promote vascularization.
Air‐Stable Perylene Diimide Trimer Material for N‐Type Organic Electrochemical Transistors
Authors: Nguyen‐Dang Tung , Bao Si Tong , Kaiyasuan Chokchai , Li Kunyu , Chae Sangmin , Yi Ahra , Joy Syed , Harrison Kelsey , Kim Jae Young , Pallini Francesca , Beverina Luca , Graham Kenneth R. , Nuckolls Colin , Nguyen Thuc‐Quyen
Published: March 2024

A new method is reported to make air‐stable n‐type organic mixed ionic‐electronic conductor (OMIEC) films for organic electrochemical transistors (OECTs) using a solution‐processable small molecule helical perylene diimide trimer, hPDI[3]‐C11. Alkyl side chains are attached to the conjugated core for processability and film making, which are then cleaved via thermal annealing. After the sidechains are removed, the hPDI[3] film becomes less hydrophobic, more ordered, and has a deeper lowest unoccupied molecular orbital (LUMO). These features provide improved ionic transport, greater electronic mobility, and increased stability in air and in aqueous solution. Subsequently, hPDI[3]‐H is used as the active material in OECTs and a device with a transconductance of 44 mS, volumetric capacitance of ≈250 F cm−3, µC* value of 1 F cm−1 V−1 s−1, and excellent stability (> 5 weeks) is demonstrated. As proof of their practical applications, a hPDI[3]‐H‐based OECTs as a glucose sensor and electrochemical inverter is utilized. The approach of side chain removal after film formation charts a path to a wide range of molecular semiconductors to be used as stable, mixed ionic‐electronic conductors.
Atomic‐Level Matching Metal‐Ion Organic Hybrid Interface to Enhance Energy Storage of Polymer‐Based Composite Dielectrics
Authors: Liu Xiaoxu , Chen Dongyang , Li Jialong , Zhong Shao‐Long , Feng Yu , Yue Dong , Sheng Dawei , Chen Haonan , Hao Xiaodong , Dang Zhi‐Min
Published: March 2024

In this work, a distinctive “metal‐ion organic hybrid interface” (MOHI) between polyimide (PI) and calcium niobate (CNO) nanosheets is designed. The metal ions in the MOHI can achieve atomic‐level matching not only with the inorganic CNO, but also with the PI chains, forming uniform and strong chemical bonds. These results are demonstrated by experiment and theory calculations. Significantly, the MOHI reduces the free volume and introduces deep traps across the filler‐matrix interfacial area, thus suppressing the electric field distortion in PI‐based composite dielectrics. Consequently, PI‐based dielectric containing the MOHI exhibits excellent energy storage performance. The energy storage densities (Ue) of the composite dielectric reach 9.42 J cm−3 and 4.75 J cm−3 with energy storage efficiency (η) of 90% at 25 °C and 150 °C respectively, which are 2.6 and 11.6 times higher than those of pure PI. This study provides new ideas for polymer‐based composite dielectrics in high energy storage.
Cationic [1,5]‐Aryl Migrations of Propargyl Benzyl Ethers – A Stereospecific Approach to E‐ and Z‐Tetrasubstituted Olefins
Authors: Sadhukhan Santu , Nair Sindoori R. , Baire Beeraiah
Published: March 2024

Herein we report the discovery and development of the first example of a cationic [1,5]‐aryl migration reaction, through an unprecedented phenonium ions. This reaction does not require any acid, base, transition metal‐based catalyst or promoter, instead promoted by the water activated NXS reagents. It provides a highly diastereoselective and rapid access to the medicinally and biologically important tetra‐substituted olefins (allyl alcohols). The involvement of an ipso‐carbon, as well as the phenonium ion during this novel, cationic [1,5]‐aryl migration was strongly supported by the isolation of 2‐oxaspiro[5.5]undecane‐9‐ones. This methodology is highly tolerable for a wide range of propargyl‐benzyl ethers, resulting in a selective construction of structurally divergent library of mono‐halo‐tricarbon‐substituted alkenes. Synthetic application has also been demonstrated by converting two isomeric‐iodo‐olefins to respective E‐ and Z‐isomers of tamoxifen in a stereospecific manner.
Mechanical Field Guiding Structure Design Strategy for Meta‐Fiber Reinforced Hydrogel Composites by Deep Learning
Authors: Liu Chuanzhi , Zhang Xingyu , Liu Xia , Yang Qingsheng
Published: March 2024

Fiber‐reinforced hydrogel composites are widely employed in many engineering applications, such as drug release, and flexible electronics, with more flexible mechanical properties than pure hydrogel materials. Comparing to the hydrogel strengthened by continuous fiber, the meta‐fiber reinforced hydrogel provides stronger individualized design ability of deformation patterns and tunable stiffness, especially for the elaborate applications in joint, cartilage, and organ. In this paper, a novel structure design strategy based on deep learning algorithm is proposed for hydrogel reinforced by meta‐fiber to achieve targeted mechanical properties, such as stress and displacement fields. A solid mechanic model for meta‐fiber reinforced hydrogel is first developed to construct the dataset of fiber distribution and the corresponding mechanical properties of the composite. Generative adversarial network (GAN) is then trained to characterize the relationship between stress or displacement field, and meta‐fiber distribution. The well‐trained GAN is implemented to design meta‐fiber reinforced hydrogel composite structure under specific operation conditions. The results show that the deep learning method may efficiently predict the structure of the hydrogel composite with satisfied confidence, and has great potential for applications in drug delivery and flexible electronics.
Biomimetic Anticoagulated Porous Particles with Self‐Reporting Structural Colors
Authors: Chen Hanxu , Bian Feika , Luo Zhiqiang , Zhao Yuanjin
Published: March 2024

Anticoagulation is vital to maintain blood fluidic status and physiological functions in the field of clinical blood‐related procedures. Here, novel biomimetic anticoagulated porous inverse opal hydrogel particles is presented as anticoagulant bearing dynamic screening capability. The inverse opal hydrogel particles possess abundant sulfonic and carboxyl groups, which serve as binding sites with multiple coagulation factors and inhibit the blood coagulation process. Owing to the variations of refractive index and pore sizes during the binding process, the particles appeared corresponding structure color variations, which can be adopted as sensory index of anticoagulation. Based on these features, a sensor containing these diverse structure color particle units is constructed for pattern recognition of coagulation factors level in clinical plasma samples. By analyzing the sensory information of the unit, the colorimetric “fingerprint” for each target can be obtained and summarized as a database. Besides, a portable test‐strip integrating sensory units is developed to distinguish the sample regarding abnormal coagulation factors‐derived diseases via multivariate data analysis. It is believed that such biomimetic anticoagulated structural color particles and their derived sensor will open new avenue for clinical detection and disease diagnosis.
Investigation of biofluorescence produced by the red king crab Paralithodes camtschaticus
Authors: Juhasz‐Dora Thomas , Thesslund Tina , Maguire Julie , Doyle Thomas K. , Lindberg Stein‐Kato
Published: March 2024

Biofluorescence is widely documented in marine organisms, yet few studies exist for decapods. After observing the king crab Paralithodes camtschaticus biofluoresces, we carried out studies on two separately maintained groups of male crabs under controlled conditions. Hyperspectral imaging on Group 1 (n = 18) examined the exoskeleton, whereas fluorospectrometry examined the hemolymph of Group 2 animals (n = 19). Both groups were investigated for fluorescence signals before and after exposure to a live shipping transportation simulation. The spines, chelae, eyestalks and cervical grooves of the cardiac region of P. camtschaticus fluoresce in the green spectra (∼500 nm), while the arthrodial membranes of the joints fluoresce in the red spectrum (∼680 nm). After the shipping simulation, we observed a significant decrease in fluorescence in the eyestalks (p = 0.009), while the cervical grooves showed a less significant change (p = 0.01). The hemolymph examined with 21 excitation wavelengths (250–350 nm) emitted fluorescence in ∼400–550 nm spectrum. We found a significant increase (p < 0.05) in fluorescence for 16 excitation wavelengths after transport simulation. The results presented in this study indicate that king crab fluorescence changes due to external stimuli. Fluorospectroscopy or hyperspectral imaging technology may serve as an effective early indicator of preclinical stress in these commercially important decapods.
Overexpression of circular RNA hsa_circ_0008621 facilitates colorectal cancer progression and predicts poor prognosis
Authors: Zhou Xiaohu , Wu Lei , Tian Chunyan
Published: March 2024

Aim

To evaluate the potential role of serum and tissue hsa_circ_0008621 as a prognostic biomarker for CRC patients. Focused on the functional role of hsa_circ_0008621 in colorectal cancer (CRC).

Methods

Serum and tissue hsa_circ_0008621 expression were quantified by qRT‐PCR in 157 CRC patients, as well as 100 serums from healthy controls. Serum and tissue hsa_circ_0008621 expression was evaluated for their prognostic role in CRC patients using Kaplan–Meier curves and Multivariate Cox proportional hazards analysis. To further characterize the biological role of hsa_circ_0008621 expression in CRC, in vitro hsa_circ_0008621 inhibition was performed and the effects on cellular growth, migration, invasion, apoptosis, and glycolysis were explored. Next, the downstream molecules for hsa_circ_0008621 were predicted.

Results

Hsa_circ_0008621 expression was significantly upregulated in CRC tissues and serums. Serum hsa_circ_0008621 levels were significantly up‐regulated in advanced‐staged samples. High serum hsa_circ_0008621 expression was associated with shorter overall survival and recurrence‐free survival in CRC patients. Multivariate Cox regression analysis identified a high level of serum hsa_circ_0008621 expression as an independent prognostic factor with respect to overall survival and recurrence‐free survival. Loss of function assays for hsa_circ_0008621 in vitro led to a significant decrease in cell proliferation, migration, invasion, and glycolysis, but an increase in cell apoptosis. Hsa_circ_0008621 can sponge miR‐532‐5p, which targets SLC16A3.

Conclusion

High level of serum hsa_circ_0008621 is associated with poor survival in CRC and promotes CRC progression, suggesting it to be a promising non‐invasive prognostic biomarker and novel therapeutic target in CRC patients.
Pro‐Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property
Authors: Ishiyama Hiroyuki , Kim Hyunjin , Saito Satoshi , Takeda Soichi , Takegami Misa , Yamamoto Yumi , Abe Soichiro , Nakazawa Shinsaku , Tanaka Tomotaka , Washida Kazuo , Morita Yoshiaki , Oh Seung‐Taek , Jung Hee‐Jae , Choi Jay Chol , Nakaoku Yuriko , Nakahara Jin , Koga Masatoshi , Toyoda Kazunori , Amemiya Kisaki , Ikeda Yoshihiko , Hatakeyama Kinta , Mizuta Ikuko , Mizuno Toshiki , Kim Kwang‐Kuk , Ihara Masafumi
Published: March 2024

Objectives

Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian‐specific NOTCH3 p.R75P mutation.

Methods

This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi‐Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations.

Results

Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45–37.31), multiple CMB (3.00, 1.34–6.71), and absence of temporopolar lesions (4.91, 2.29–10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83–35.89), multiple CMB (1.90, 1.01–3.56), and absence of temporopolar lesions (2.32, 1.08–4.97). Structural analysis revealed solvent‐exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations.

Interpretation

NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040–1054
Hydrogen‐Bond‐Network Breakdown Boosts Selective CO2 Photoreduction by Suppressing H2 Evolution
Authors: Cong Die , Sun Jikai , Pan Yuwei , Fang Xu , Yang Li , Zhou Wei , Yu Tie , Li Zhen , Liu Chengcheng , Deng Wei‐Qiao
Published: March 2024

Conventional strategies for highly efficient and selective CO2 photoreduction focus on the design of catalysts and cocatalysts. In this study, we discover that hydrogen bond network breakdown in reaction system can suppress H2 evolution, thereby improving CO2 photoreduction performance. Photosensitive poly(ionic liquid)s are designed as photocatalysts owing to their strong hydrogen bonding with solvents. The hydrogen bond strength is tuned by solvent composition, thereby effectively regulating H2 evolution (from 0 to 12.6 mmol g−1 h−1). No H2 is detected after hydrogen bond network breakdown with trichloromethane or tetrachloromethane as additives. CO production rate and selectivity increase to 35.4 mmol g−1 h−1 and 98.9 % with trichloromethane, compared with 0.6 mmol g−1 h−1 and 26.2 %, respectively, without trichloromethane. Raman spectroscopy and theoretical calculations confirm that trichloromethane broke the systemic hydrogen bond network and subsequently suppressed H2 evolution. This hydrogen bond network breakdown strategy may be extended to other catalytic reactions involving H2 evolution.
Reduced Volume Expansion of Micron‐Sized SiOx via Closed‐Nanopore Structure Constructed by Mg‐Induced Elemental Segregation
Authors: Xu Di‐Xin , Zhao Yu‐Ming , Chen Han‐Xian , Lu Zhuo‐Ya , Tian Yi‐Fan , Xin Sen , Li Ge , Guo Yu‐Guo
Published: March 2024

The inherently huge volume expansion during Li uptake has hindered the use of Si‐based anodes in high‐energy lithium‐ion batteries. While some pore‐forming and nano‐architecting strategies show promises to effectively buffer the volume change, other parameters essential for practical electrode fabrication, such as compaction density, are often compromised. Here we propose a new in situ Mg doping strategy to form closed‐nanopore structure into a micron‐sized SiOx particle at a high bulk density. The doped Mg atoms promote the segregation of O, so that high‐density magnesium silicates form to generate closed nanopores. By altering the mass content of Mg dopant, the average radii (ranged from 5.4 to 9.7 nm) and porosities (ranged from 1.4 % to 15.9 %) of the closed pores are precisely adjustable, which accounts for volume expansion of SiOx from 77.8 % to 22.2 % at the minimum. Benefited from the small volume variation, the Mg‐doped micron‐SiOx anode demonstrates improved Li storage performance towards realization of a 700‐(dis)charge‐cycle, 11‐Ah‐pouch‐type cell at a capacity retention of >80 %. This work offers insights into reasonable design of the internal structure of micron‐sized SiOx and other materials that undergo conversion or alloying reactions with drastic volume change, to enable high‐energy batteries with stable electrochemistry.
Correlation between materials and band‐selective detection in organic photodetectors based on bulk heterojunction
Authors: Eynaud Quentin , Khodr Anass , Kramdi Mohamed El Amine , Quéléver Gilles , Margeat Olivier , Ackermann Jörg , Videlot‐Ackermann Christine
Published: March 2024

For wavelength‐selective photodetection or color discrimination, organic photodetectors (OPDs) can provide significant advantages as solution processability, chemical versatility and functionality. To eliminate the need for commonly used filters, the development of a narrowing approach that simultaneously achieves a selective detection range of less than 50 nm bandwidth and a spectral response of ~20% as efficiency at a required wavelength, remains a real challenge. Herein, different donor polymers and small acceptor molecules have been involved in bulk heterojunctions (BHJs) at 1:1 weight ratio as photoactive layers in specific OPDs. Indeed, the mechanism of charge collection in these OPDs is based on the charge collection narrowing (CCN) principle. In this approach, the detection window can be selected to match the absorption onset of the junction materials used in the BHJ layer. Although essentially based on very thick layers, we are focusing here on OPDs with layer thicknesses of less than 2 μm and post‐deposition annealing temperatures not in excess of 100°C.
Giving a voice to our silent teachers: Whole body donation from the donor perspective at one donation program in the United States
Authors: Bagian Lauren K. , Davis Danielle C. , Parker Ryan C. , Mosley Claudia F. , Balta Joy Y.
Published: March 2024

Human body donors play a crucial role in anatomical education, research, and clinical skills training, and those interested in anatomical donation may bequeath their bodies to body donation programs (BDPs). The purpose of this study was to evaluate the perspective of body donors on the donation process in order to make recommendations for improvement that align with donor values. A survey was administered via email to 2145 individuals that had enrolled in The Ohio State University's BDP and yielded a 40% response rate. Results showed that a majority of registered donors do not place high importance on detailed consent options during the enrollment process, but do value BDP oversight, such as through the use of an oversight committee to supervise the program. Only 9.1% of donors felt that their loved ones should be permitted to make changes to their consent forms after they have passed. Although 96.2% of participants would allow photos/videos to be taken of their donated bodies, females were significantly less likely to consent to this than males (p = 0.001), as well as less likely to allow their donations to be utilized for anatomy outreach (p = 0.023). Racial minorities were significantly less trusting of the university to treat their donation with dignity and respect compared to White registrants (p = 0.034). Suggestions for improving BDP protocols include the implementation of an annual newsletter for registrants, improving methods to spread awareness about donation, increasing transparency during the consent process, and creating resources for donors' families.
Environmental values and sustainable consumption
Authors: Perera Chamila R. , Kalantari Hassan D. , Johnson Lester W.
Published: March 2024

This special issue of the Journal of Consumer Behaviour engages in a scholarly debate on the association between environmental values and sustainable consumption using 16 studies that examine a range of exciting phenomena relevant to the debate. The special issue provides insights into three key areas of scholarly conversations in the field of study. First, it provides recent accounts of the literature on the role of environmental values in sustainable consumption. Given that the association between the two areas has been widely debated for decades, adding novel insights into the phenomenon in the context of recent environmental issues significantly contributes to the field of study. It should be noted that the novel insights cover several mediating and moderating factors of the association, which add new research directions to the field of study. Second, the special issue examines the recent discourse on environmental values considering the more specific behaviours (collaborative consumption, disposal behaviour, consumer engagement in circular economy) that are related to sustainable consumption. This discourse provides insight into environmentally conscious marketing practitioners. Third, the special issue highlights diverse consumer perspectives on sustainable consumption, especially those from diverse consumer generations, both local and international consumers. They inform global initiatives such as the UN sustainable development goals. Overall, engaging in a collective dialogue to understand recent developments in the field of study, the special issue informs environmental policies and fosters sustainable consumption and marketing practices that tackle climate change‐related environmental and social issues.
Coronary microvascular dysfunction assessment: A comparative analysis of procedural aspects
Authors: Merdler Ilan , Wallace Ryan , Banerjee Avantika , Medranda Giorgio A. , Reddy Pavan , Cellamare Matteo , Zhang Cheng , Ozturk Sevket Tolga , Sawant Vaishnavi , Lopez Kassandra , Ben‐Dor Itsik , Waksman Ron , Case Brian C. , Hashim Hayder D.
Published: March 2024

Background

Full adoption of coronary microvascular dysfunction (CMD) assessment faces challenges due to its invasive nature and concerns about prolonged procedure time and increased contrast and/or radiation exposure. We compared procedural aspects of CMD invasive assessment to diagnostic left heart catheterization (DLHC) in patients with chest pain who were not found to have obstructive coronary artery disease.

Methods

A total of 227 patients in the Coronary Microvascular Disease Registry were compared to 1592 patients who underwent DLHC from August 2021 to November 2023. The two cohorts were compared using propensity‐score matching; primary outcomes were fluoroscopy time and total contrast use.

Results

The participants' mean age was 64.1 ± 12.6 years. CMD‐assessed patients were more likely to be female (66.5% vs. 45.2%, p < 0.001) and have hypertension (80.2% vs. 44.5%, p < 0.001), history of stroke (11.9% vs. 6.3%, p = 0.002), and history of myocardial infarction (20.3% vs. 7.7%, p < 0.001). CMD assessment was safe, without any reported adverse outcomes. A propensity‐matched analysis showed that patients who underwent CMD assessment had slightly higher median contrast exposure (50 vs. 40 mL, p < 0.001), and slightly longer fluoroscopy time (6.9 vs. 4.7 min, p < 0.001). However, there was no difference in radiation dose (209.3 vs. 219 mGy, p = 0.58) and overall procedure time (31 vs. 29 min, p = 0.37).

Conclusion

Compared to DLHC, CMD assessment is safe and requires only slightly additional contrast use (10 mL) and slightly longer fluoroscopy time (2 min) without clinical implications. These findings emphasize the favorable safety and feasibility of invasive CMD assessment.
Astropharmazie und ‐toxikologie in der Raumfahrt
Authors: Strey Karsten
Published: March 2024

Die Geschichte der Raumfahrt ist bisher kürzer als eine durchschnittliche Lebensspanne. Seit 1961 sind erst etwa 600 Menschen jemals im Orbit gewesen. Die extremen Verhältnisse des Weltalls erweitern alle uns auf der Erde bekannten Wissenschaften um eine neue astronomische Dimension und erfordern für einen dauernden Aufenthalt viele Schutzmaßnahmen und Anpassungen. Es ist absehbar, dass die Fortschritte der bemannten Raumfahrt, insbesondere künftige neue Mondmissionen oder gar Flüge zum Mars in den nächsten Jahrzehnten große Impulse auf dem Gebiet der Astropharmazie und Astrotoxikologie bringen werden.
Dynamically Securing the Data by 1O2 Sensitization of Fluorescent Composites with a High Latency and Uncrackable Features
Authors: Chen Yuanyuan , Chen Jiamao , Wu Huacan , Liu Yifan , Wang Donghui , Huang Weiguo
Published: March 2024

Comprehensive Summary

Dynamic fluorescent materials play a crucial role in secure inks for data encryption; however, they are still plagued by issues such as photodegradation, poor latency, and susceptibility to unauthorized access. Herein, we propose a photochemically modulated dynamic fluorescent encryption system based on 1O2 sensitization of fluorescent composites, comprising a 1O2‐sensitive fluorophore (F2) and non‐emissive polymers. After UV irradiation, in‐situ generated 1O2 from the polymer effectively binds with F2 to form endoperoxides (F2EPO), resulting in a significant redshift in emission, up to 150 nm. The 1O2 concentration is closely related to the irradiation time, rendering different fluorescent colors in a time‐gated fashion. Moreover, the emission of F2EPO can be regulated by polymer chemical structure, molecular weight, and crosslinking density. Relying on these merits, we develop a dynamic data encryption method with various non‐emissive polymers as the data storage media, UV light irradiation as the data encoder, and F2 as the data decoder. UV light irradiation of diverse polymer solutions generates 1O2 at different concentrations, effectively encoding the data, which remains invisible under both UV and natural lights. The addition of F2 to these irradiated polymer solutions produces different redshifted fluorescence, enabling secure data decryption. Attributing to the non‐emissive nature of the polymers, time‐gated readout fashion, excellent latency of 1O2, and subtle interactions between 1O2 and F2, this data encryption is nearly undecipherable. This work offers an advantage data encryption approach beyond the reach of conventional fluorophores.
Vanadyl Sulfate Based Hole‐Transporting Layer Enables Efficient Organic Solar Cells
Authors: Li Mengdi , Sun Yuqing , Cheng Yang , Zhao Chaowei , Zhang Jicai , Li Weiwei
Published: March 2024

Comprehensive Summary

It remains an urgent task to develop alternative hole‐transporting layer (HTL) materials beyond commonly used PEDOT:PSS to increase the shelf‐life of organic solar cells (OSCs). Inorganic metal oxide type materials, such as NiOx, CoOx and VOx, with suitable work functions have attracted numerous research attention recently. In this work, more abundant and easily accessible oxygenated salt, vanadyl sulfate (VOSO4) has been demonstrated to be excellent choice as HTL for OSCs. The VOSO4‐based HTL can be readily processed by spin‐coating from the precursor solution with subsequent thermal annealing and UVO treatment. As a consequence, a high power conversion efficiency (PCE) of 18.72% can be achieved for PM8:L8‐BO based OSCs with the VOSO4‐based HTL. High transmittance, smooth film surface, suitable energy level and high conductivity were revealed to contribute to the high OSC performance. More importantly, compared to device with PEDOT:PSS, VOSO4‐based OSCs exhibit improved stability when stored in the N2 filled glove box. After being stored for 600 h, VOSO4‐based device can retain 89% of its initial efficiency. Notably, VOSO4 can be used as general HTL in PM6:BTP‐BO‐4Cl and PM6:IT‐4F based OSCs, yielding high PCEs of 17.87% and 13.85%, respectively.
Epidermal growth factor receptor inhibition potentiates chemotherapeutics‐mediated sensitization of metastatic breast cancer stem cells
Authors: Kar Trisha , Dugam Prachi , Shivhare Surbhi , Shetty Swathi R. , Choudhury Subholakshmi , Sen Debanjan , Deb Barnali , Majumdar Swapan , Debnath Sudhan , Das Amitava
Published: March 2024

Background

Metastasis has been a cause of the poor prognosis and cancer relapse of triple‐negative breast cancer (TNBC) patients. The metastatic nature of TNBC is contributed by the breast cancer stem cells (CSCs) which have been implicated in tumorigenesis. Higher expression of epidermal growth factor receptor (EGFR) in breast CSCs has been used as a molecular target for breast cancer therapeutics. Thus, it necessitates the design and generation of efficacious EGFR inhibitors to target the downstream signaling associated with the cellular proliferation and tumorigenesis of breast cancer.

Aim

To generate efficacious EGFR inhibitors that can potentiate the chemotherapeutic‐mediated mitigation of breast cancer tumorigenesis.

Methods and Results

We identified small molecule EGFR inhibitors using molecular docking studies. In‐vitro screening of the compounds was undertaken to identify the cytotoxicity profile of the small‐molecule EGFR inhibitors followed by evaluation of the non‐cytotoxic compounds in modulating the doxorubicin‐induced migration, in‐vitro tumorigenesis potential, and their effect on the pro‐apoptotic genes' and protein markers' expression in TNBC cells. Compound 1e potentiated the doxorubicin‐mediated inhibitory effect on proliferation, migration, in‐vitro tumorigenesis capacity, and induction of apoptosis in MDA‐MB‐231 cells, and in the sorted CD24+‐breast cancer cells and CD24−/CD44+‐breast CSC populations. Orthotopic xenotransplantation of the breast CSCs‐induced tumors in C57BL/6J mice was significantly inhibited by the low dose of Doxorubicin in the presence of compound 1e as depicted by molecular and immunohistochemical analysis.

Conclusion

Thus, the study suggests that EGFR inhibition‐mediated sensitization of the aggressive and metastatic breast CSCs in TNBCs toward chemotherapeutics may reduce the relapse of the disease.
Population Pharmacokinetics of Cabotegravir Following Oral Administration and Long‐Acting Intramuscular Injection in Real‐World People with HIV
Authors: Thoueille Paul , Saldanha Susana Alves , Schaller Fabian , Choong Eva , Veuve François , Munting Aline , Cavassini Matthias , Braun Dominique , Günthard Huldrych F. , Duran Ramirez Jessy J. , Surial Bernard , Furrer Hansjakob , Rauch Andri , Ustero Pilar , Calmy Alexandra , Stöckle Marcel , Di Benedetto Caroline , Bernasconi Enos , Schmid Patrick , Marzolini Catia , Girardin François R. , Buclin Thierry , Decosterd Laurent A. , Guidi Monia ,   the Swiss HIV Cohort Study
Published: March 2024

Long‐acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real‐world reference percentile curves of cabotegravir concentrations, accounting for patient‐related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one‐compartment model with distinct first order‐absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady‐state of 8 months and an elimination half‐life of 4.6 weeks for long‐acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model‐based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4‐fold protein‐adjusted 90% inhibitory target concentration.
Effect of a quasi‐aperiodic substrate on diffusion in a strongly coupled quasi‐one‐dimensional system
Authors: Bekda Ahmed , Djebli Mourad
Published: March 2024

This study investigates the diffusion of charged particles interacting through a Yukawa potential. Confined by a parabolic potential along the y‐axis, the particles experience an aperiodic substrate potential along the x‐axis. To analyze their diffusion behavior, we employ molecular dynamics simulations based on the Langevin equation. We primarily focus on the influence of particle density, system temperature, particle charge, and the aperiodicity parameter () of the quasi‐aperiodic substrate on the system's diffusion characteristics. By adjusting for various system parameters, we can manipulate diffusion and observe diverse diffusion modes. Our findings reveal that the aperiodicity's effect becomes pronounced at lower densities and smaller values, leading to faster diffusion compared with the periodic case. However, over longer timescales, the system transitions to normal diffusion regardless of the specific parameters.
Cytomorphology of monomorphic spindle epithelial tumor with thymus‐like elements: A case with local recurrence after subtotal resection
Authors: Arshia Asma , Balikani Lame , Booth Christine N.
Published: March 2024

Spindle epithelial tumor with thymus‐like elements (SETTLE) is a rare biphasic thyroid tumor with low malignant potential that has a distinct morphology. Despite fine needle aspiration (FNA) being a common method for evaluating thyroid nodules and lymph nodes, there are limited cytologic descriptions of SETTLE in the literature due to its rarity. As a result, SETTLE is frequently underdiagnosed or misdiagnosed as medullary carcinoma, thymoma, teratoma, synovial sarcoma, or solitary fibrous tumor, among others. We present a case of a 28‐year‐old man with a history of a hemithyroidectomy diagnosed as SETTLE found to have a neck nodule along the strap muscle suspicious for recurrence 5 years post‐surgery. The ultrasound‐guided FNA cytology specimen of the neck nodule showed loosely cohesive, monomorphous ovoid to spindled cells with scant cytoplasm and nuclei with fine to granular chromatin. In addition, there were occasional clusters of cells with a papillary configuration. The tumor cells were associated with magenta, amorphous extracellular material. Immunocytochemical staining of the cell block material revealed that tumor cells were positive for p63, cytokeratin AE1/3, and CK8/18 and negative for TTF‐1 and thyroglobulin. Overall, the morphological and immunocytochemical findings were consistent with a local recurrence of SETTLE. The subsequent left anterior strap mass excision revealed a 4 cm encapsulated tumor consistent with SETTLE. Because ofits rarity and low level of awareness, SETTLE poses a diagnostic and therapeutic challenge. We herein present the cytologic findings of monomorphic SETTLE and highlight the potential cytomorphologic and immunophenotypic pitfalls. We also highlight how tumors with high‐risk features can be a therapeutic challenge.
Fractional excretion of urea nitrogen can identify true worsening renal function in patients with heart failure
Authors: Watanabe Yukihiro , Kubota Yoshiaki , Nishino Takuya , Tara Shuhei , Kato Katsuhito , Hayashi Daisuke , Matsuda Junya , Miyachi Hideki , Tokita Yukichi , Iwasaki Yu‐ki , Asai Kuniya
Published: March 2024

Aims

Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF).

Methods and results

Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut‐off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow‐up, 170 HF readmissions occurred. Kaplan–Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log‐rank test, P < 0.001). Additionally, among patients with WRF, HF readmission rates were lowest in those with medium FEUN values, followed by those with low FEUN values and those with high FEUN values. On multivariable analysis, the presence of WRF with low or high FEUN values was independently associated with increased HF readmission, as compared with the absence of WRF with medium FEUN values. Notably, no association was noted between WRF with medium FEUN values and HF readmission.

Conclusions

The prognostic impact of WRF was significantly mediated by the FEUN values and was associated with worse outcomes only when the FEUN values were either low or high. Our study suggests that FEUN can identify prognostically relevant WRF in patients with AHF.
Synthesis of a Bicyclo[1.1.1]pentane‐Containing Aromatic Lipoxin B4 Analogue and Heteroaromatic Congeners
Authors: Owen Benjamin , Guiry Patrick J.
Published: March 2024

Lipoxins are pro‐resolving mediators that play an important role in the resolution phase of the innate inflammatory response. However, because of their chemical and metabolic instability, the design of more stable synthetic analogues of lipoxin A4 and lipoxin B4 is an ongoing area of study. Herein we report the asymmetric synthesis of an aromatic lipoxin B4 analogue containing a conformationally rigid and potentially more metabolically resistant bicyclo[1.1.1]pentane (BCP) ring incorporated into the upper alkyl chain. This was achieved by the development of a 9‐step chiral‐pool synthesis of a novel BCP‐containing boronic ester coupling partner which could serve as a common precursor to the target analogue as well as other analogues with further modifications to the aromatic core.
A Simple Preparation Method of Reduced Graphene Oxide‐Incorporated BiVO4 Loaded with CoOx Composites and Application to Z‐Schematic Water Splitting under Visible Light Irradiation
Authors: Moriya Misa , Ng Yun Hau , Iwase Akihide
Published: March 2024

The construction of Z‐scheme systems is an efficient strategy to realize water splitting under visible light irradiation. In particular, various photocatalysts can be employed for Z‐scheme systems when a reduced graphene oxide (RGO) is used as an electron mediator. Herein, a simple 1‐step process for the preparation of RGO‐(CoOx/BiVO4) composites is developed. In the developed preparation method, Co ions are oxidized to CoOx by photogenerated holes in BiVO4 accompanied by simultaneous reduction of GO to RGO by photoexcited electrons. The developed preparation method is simpler than a conventional method that contains loading with CoOx by impregnation and subsequent incorporation of RGO by photocatalytic reduction. Z‐schematic water splitting under visible light irradiation proceeds when RGO‐(CoOx/BiVO4) prepared by the 1‐step process is combined with Pt/(CuGa)0.5ZnS2. Moreover, the developed method is also able to be applied to the preparation of RGO‐(FeOx/BiVO4) composites.
Incorporation of spray‐dried encapsulated bioactive peptides from coconut (Cocos nucifera L.) meal by‐product in bread formulation
Authors: Sarabandi Khashayar , Dashipour Alireaza , Akbarbaglu Zahra , Peighambardoust Seyed Hadi , Ayaseh Ali , Kafil Hossein Samadi , Jafari Seid Mahdi , Mousavi Khaneghah Amin
Published: March 2024

This study aimed to stabilize and mask the bitterness of peptides obtained from the enzymatic hydrolysis of coconut‐meal protein with maltodextrin (MD) and maltodextrin‐pectin (MD‐P) as carriers via spray‐drying. Essential (~35%), hydrophobic (~32%), antioxidant (~15%), and bitter (~45%) amino acids comprised a significant fraction of the peptide composition (with a degree of hydrolysis of 33%). The results indicated that the peptide's production efficiency, physical and functional properties, and hygroscopicity improved after spray‐drying. Morphological features of free peptides (fragile and porous structures), spray‐dried with MD (wrinkled with indented structures), and MD‐P combination (relatively spherical particles with smooth surfaces) were influenced by the process type and feed composition. Adding free and microencapsulated peptides to the bread formula (2% W/W) caused changes in moisture content (35%–43%), water activity (0.89–0.94), textural properties (1–1.6 N), specific volume (5.5–6 cm3/g), porosity (18%–27%), and color indices of the fortified product. MD‐P encapsulated peptides in bread fortification resulted in thermal stability and increased antioxidant activity (DPPH and ABTS+ radical scavenging: 4.5%–39.4% and 31.6%–46.8%, respectively). MD‐P (as a carrier) could maintain sensory characteristics and mask the bitterness of peptides in the fortified bread. The results of this research can be used to produce functional food and diet formulations.
Brain reserve affects the expression of cognitive reserve networks
Authors: Coors Annabell , Lee Seonjoo , Gazes Yunglin , Gacheru Margaret , Habeck Christian , Stern Yaakov
Published: March 2024

Cognitive reserve (CR) explains differential susceptibility of cognitive performance to neuropathology. However, as brain pathologies progress, cognitive decline occurs even in individuals with initially high CR. The interplay between the structural brain health (= level of brain reserve) and CR‐related brain networks therefore requires further research. Our sample included 142 individuals aged 60–70 years. National Adult Reading Test intelligence quotient (NART‐IQ) was our CR proxy. On an in‐scanner Letter Sternberg task, we used ordinal trend (OrT) analysis to extract a task‐related brain activation pattern (OrT slope) for each participant that captures increased expression with task load (one, three, and six letters). We assessed whether OrT slope represents a neural mechanism underlying CR by associating it with task performance and NART‐IQ. Additionally, we investigated how the following brain reserve measures affect the association between NART‐IQ and OrT slope: mean cortical thickness, total gray matter volume, and brain volumes proximal to the areas contained in the OrT patterns. We found that higher OrT slope was associated with better task performance and higher NART‐IQ. Further, the brain reserve measures were not directly associated with OrT slope, but they affected the relationship between NART‐IQ and OrT slope: NART‐IQ was associated with OrT slope only in individuals with high brain reserve. The degree of brain reserve has an impact on how (and perhaps whether) CR can be implemented in brain networks in older individuals.