bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Peroxisome Proliferator–Activated Receptor (PPAR)δ Promotes Reversal of Multiple Metabolic Abnormalities, Reduces Oxidative Stress, and Increases Fatty Acid Oxidation in Moderately Obese Men
Authors: Risérus Ulf , Sprecher Dennis , Johnson Tony , Olson Eric , Hirschberg Sandra , Liu Aixue , Fang Zeke , Hegde Priti , Richards Duncan , Sarov-Blat Leli , Strum Jay C. , Basu Samar , Cheeseman Jane , Fielding Barbara A. , Humphreys Sandy M. , Danoff Theodore , Moore Niall R. , Murgatroyd Peter , O'Rahilly Stephen , Sutton Pauline , Willson Tim , Hassall David , Frayn Keith N. , Karpe Fredrik
Published: November 2007

OBJECTIVE— Pharmacological use of peroxisome proliferator–activated receptor (PPAR)δ agonists and transgenic overexpression of PPARδ in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans.

RESEARCH DESIGN AND METHODS— The PPARδ agonist (10 mg o.d. GW501516), a comparator PPARα agonist (20 μg o.d. GW590735), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress.

RESULTS— Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (−30%), apolipoprotein B (−26%), LDL cholesterol (−23%), and insulin (−11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (−30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO2 directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased.

CONCLUSIONS— The PPARδ agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.
Palilalia
Authors: BOLLER FRANCOIS , ALBERT MARTIN , DENES FRANCO
Published: November 2007

Palilalia, a disorder of speech characterised by compulsive repetition of a phrase or word, is not a rare phenomenon but is seldom mentioned in modern literature. This paper describes two patients, mother and son, affected by palilalia. Both patients had bilateral lesions affecting the basal ganglia and the grey matter of the hemispheres. In these cases as in others described in the literature, palilalia is felt to be due to bilateral lesions and to represent the speech counterpart of other motor phenomena such as festination or chorea.
Compensatory vowel articulation of the glossectomee: acoustic and videofluoroscopic evidence
Authors: Morrish Liz
Published: November 2007

An acoustic and articulatory study is made of the vowels of two highly intelligible total glossectomees. The subjects show a truncated acoustic vowel diagram; the frequency of F1 for the vowels /i, e, a, o, u/ corresponds to that of normal speakers, but the frequency range of F2 is much reduced. The male glossectomee's ability to vary the shape of the vocal tract is examined by means of videofluoroscopy. It is found that compensatory articulation for the total glossectomy is achieved by means of exaggerated use of articulators, e.g. jaw, pharynx and epiglottis, and by use of articulators not usually implicated in glossectomised speech, e.g. the grafted flap in the oral tract.
Reports of COVID-19 Vaccine Adverse Events in Predominantly Republican vs Democratic States
Authors: Asch David A. , Luo Chongliang , Chen Yong
Published: March 2024

Importance

Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored.

Objective

To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs.

Design, Setting, and Participants

This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican votes in the 2020 US presidential election.

Exposure

State-level percentage of Republican votes in the 2020 US presidential election.

Main Outcomes and Measures

Rates of any AE among COVID-19 vaccine recipients, rates of any severe AE among vaccine recipients, and the proportion of AEs reported as severe.

Results

A total of 620 456 AE reports (mean [SD] age of vaccine recipients, 51.8 [17.6] years; 435 797 reports from women [70.2%]; a vaccine recipient could potentially file more than 1 report, so reports are not necessarily from unique individuals) for COVID-19 vaccination were identified from the VAERS database. Significant associations between state political inclination and state AE reporting were observed for all 3 outcomes: a 10% increase in Republican voting was associated with increased odds of AE reports (odds ratio [OR], 1.05; 95% CI, 1.05-1.05; P < .001), severe AE reports (OR, 1.25; 95% CI, 1.24-1.26; P < .001), and the proportion of AEs reported as severe (OR, 1.21; 95% CI, 1.20-1.22; P < .001). These associations were seen across all age strata in stratified analyses and were more pronounced among older subpopulations.

Conclusions and Relevance

This cross-sectional study found that the more states were inclined to vote Republican, the more likely their vaccine recipients or their clinicians reported COVID-19 vaccine AEs. These results suggest that either the perception of vaccine AEs or the motivation to report them was associated with political inclination.
Magnetic Resonance Imaging, Clinical, and Biopsy Findings in Suspected Prostate Cancer
Authors: Haj-Mirzaian Arya , Burk Kristine S. , Lacson Ronilda , Glazer Daniel I. , Saini Sanjay , Kibel Adam S. , Khorasani Ramin
Published: March 2024

Importance

Multiple strategies integrating magnetic resonance imaging (MRI) and clinical data have been proposed to determine the need for a prostate biopsy in men with suspected clinically significant prostate cancer (csPCa) (Gleason score ≥3 + 4). However, inconsistencies across different strategies create challenges for drawing a definitive conclusion.

Objective

To determine the optimal prostate biopsy decision-making strategy for avoiding unnecessary biopsies and minimizing the risk of missing csPCa by combining MRI Prostate Imaging Reporting & Data System (PI-RADS) and clinical data.

Data Sources

PubMed, Ovid MEDLINE, Embase, Web of Science, and Cochrane Library from inception to July 1, 2022.

Study Selection

English-language studies that evaluated men with suspected but not confirmed csPCa who underwent MRI PI-RADS followed by prostate biopsy were included. Each study had proposed a biopsy plan by combining PI-RADS and clinical data.

Data Extraction and Synthesis

Studies were independently assessed for eligibility for inclusion. Quality of studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the Newcastle-Ottawa Scale. Mixed-effects meta-analyses and meta-regression models with multimodel inference were performed. Reporting of this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.

Main Outcomes and Measures

Independent risk factors of csPCa were determined by performing meta-regression between the rate of csPCa and PI-RADS and clinical parameters. Yields of different biopsy strategies were assessed by performing diagnostic meta-analysis.

Results

The analyses included 72 studies comprising 36 366 patients. Univariable meta-regression showed that PI-RADS 4 (β-coefficient [SE], 7.82 [3.85]; P = .045) and PI-RADS 5 (β-coefficient [SE], 23.18 [4.46]; P < .001) lesions, but not PI-RADS 3 lesions (β-coefficient [SE], −4.08 [3.06]; P = .19), were significantly associated with a higher risk of csPCa. When considered jointly in a multivariable model, prostate-specific antigen density (PSAD) was the only clinical variable significantly associated with csPCa (β-coefficient [SE], 15.50 [5.14]; P < .001) besides PI-RADS 5 (β-coefficient [SE], 9.19 [3.33]; P < .001). Avoiding biopsy in patients with lesions with PI-RADS category of 3 or less and PSAD less than 0.10 (vs <0.15) ng/mL2 resulted in reducing 30% (vs 48%) of unnecessary biopsies (compared with performing biopsy in all suspected patients), with an estimated sensitivity of 97% (vs 95%) and number needed to harm of 17 (vs 15).

Conclusions and Relevance

These findings suggest that in patients with suspected csPCa, patient-tailored prostate biopsy decisions based on PI-RADS and PSAD could prevent unnecessary procedures while maintaining high sensitivity.
Estimated Average-Risk Colorectal Cancer Screening–Eligible Population in the US
Authors: Ebner Derek W. , Kisiel John B. , Fendrick A. Mark , Estes Chris , Li Kevin , Vahdat Vahab , Limburg Paul J.
Published: March 2024

This cross-sectional study estimates the number of average-risk colorectal cancer screening–eligible individuals in the US since the US Preventive Services Task Force updated its recommendations in 2021.
Energy Management in Chemical Industry
Authors: Asprion Norbert , Giesa Sonja , Mairhofer Jonas , Poth Nikolaus , Reble Marcus , Rüther Joachim
Published: March 2024

The article contains sections titled:1Introduction2Sustainability and Energy Management2.1Feedstock and Energy Supply for the Chemical Industry2.1.1Current Feedstock Supply2.1.2Current Energy Supply2.1.3Alternative Feedstock Supply2.1.4Alternative Energy Supply2.2Regulatory Aspects2.3Process Design Objectives3Energy Management in Chemical Process Operations3.1Process Development3.1.1Process Synthesis3.1.2Development of New Processes3.1.3Reevaluation of Existing Processes3.2Plant Design3.2.1Exergy Analysis and Multicriteria Optimization3.2.2Process Operation Parameters3.2.3Pinch Technology3.3Equipment Design3.3.1Design of Distillation Columns3.3.2Heat Exchanger Design3.4Plant Operation3.4.1Control Design and Strategy3.4.2Plant Information Systems3.4.3Electrical Energy3.5Production Site Management4ConclusionList of AbbreviationsReferences
Self‐Signal‐Triggered Drug Delivery System for Tumor Therapy Using Cancer Cell Membrane‐Coated Biocompatible Mn3O4 Nanocomposites
Authors: Karthika Viswanathan , Jo Sung‐Han , Yadav Sonyabapu , Reddy Obireddy Sreekanth , Lim Hae Gyun , Lee Won‐Ki , Park Sang‐Hyug , Lim Kwon Taek
Published: March 2024

In anti‐cancer metastasis treatment, precise drug delivery to cancer cells remains a challenge. Innovative nanocomposites are developed to tackle these issues effectively. The approach involves the creation of manganese oxide (Mn3O4) nanoparticles (NPs) and their functionalization using trisodium citrate to yield functionalized Mn3O4 NPs (F‐Mn3O4 NPs), with enhanced water solubility, stability, and biocompatibility. Subsequently, the chemotherapeutic drug doxorubicin (DOX) is encapsulated with Mn3O4 NPs, resulting in DOX/Mn3O4 NPs. To achieve cell‐specific targeting, These NPs are coated with HeLa cell membranes (HCM), forming HCM/DOX/Mn3O4. For further refinement, a transferrin (Tf) receptor is integrated with cracked HCM to create Tf‐HCM/DOX/Mn3O4 nanocomposites (NC) with specific cell membrane targeting capabilities. The resulting Tf‐HCM/DOX/Mn3O4 NC exhibits excellent drug encapsulation efficiency (97.5%) and displays triggered drug release when exposed to NIR laser irradiation in the tumor's environment (pH 5.0 and 6.5). Furthermore, these nanocomposites show resistance to macrophage uptake and demonstrate homotypic cancer cell targeting specificity, even in the presence of other tumor cells. In vitro toxicity tests show that Tf‐HCM/DOX/Mn3O4 NC achieves significant anticancer activity against HeLa and BT20 cancer cells, with percentages of 76.46% and 71.36%, respectively. These results indicate the potential of Tf‐HCM/DOX/Mn3O4 NC as an effective nanoplatform for chemo‐photothermal therapy.
Label‐Free Visualization and Morphological Profiling of Neuronal Differentiation and Axonal Degeneration through Quantitative Phase Imaging
Authors: Kim Jeong Hee , Cetinkaya‐Fisgin Aysel , Zahn Noah , Sari Mehmet Can , Hoke Ahmet , Barman Ishan
Published: March 2024

Understanding the intricate processes of neuronal growth, degeneration, and neurotoxicity is paramount for unraveling nervous system function and holds significant promise in improving patient outcomes, especially in the context of chemotherapy‐induced peripheral neuropathy (CIPN). These processes are influenced by a broad range of entwined events facilitated by chemical, electrical, and mechanical signals. The progress of each process is inherently linked to phenotypic changes in cells. Currently, the primary means of demonstrating morphological changes rely on measurements of neurite outgrowth and axon length. However, conventional techniques for monitoring these processes often require extensive preparation to enable manual or semi‐automated measurements. Here, a label‐free and non‐invasive approach is employed for monitoring neuronal differentiation and degeneration using quantitative phase imaging (QPI). Operating on unlabeled specimens and offering little to no phototoxicity and photobleaching, QPI delivers quantitative maps of optical path length delays that provide an objective measure of cellular morphology and dynamics. This approach enables the visualization and quantification of axon length and other physical properties of dorsal root ganglion (DRG) neuronal cells, allowing greater understanding of neuronal responses to stimuli simulating CIPN conditions. This research paves new avenues for the development of more effective strategies in the clinical management of neurotoxicity.
Microstructure Characterization and Mechanical Properties of the NiTif‐Reinforced Ti/Al‐Laminated Composites Using Vacuum Hot Pressing with Ultrasonic Consolidation Assisted
Authors: Guo Chunhuan , Shi Haocheng , Wang Shubang , Jiang Fengchun , Dong Tao , Jing Xuri
Published: March 2024

A novel method of preparing continuous NiTif‐reinforced Ti/Al‐laminated composites is proposed via ultrasonic consolidation (UC) and vacuum hot pressing. The microstructure of the composites is characterized by X‐ray diffraction, scanning electron microscopy, and electron backscattering diffraction. The tensile properties of the composites are measured by a universal testing machine. Results indicate that the composite exhibits multilayer structure consisting of residual NiTi fiber, intermetallic compounds (IMCs) layer, reaction layer, Ti layer, and Al layer. The intermetallic layer is composed of Al3Ti and Al3Ni, and some Ni‐rich precipitates are dispersed in the matrix. And with the introduction of UC assisted, grain refinement occurs at the IMC/Al interface, texture variation emerges at the NiTi fiber/IMCs interface, and a weakening of texture strength is observed at both interfaces. Compared to NiTif‐reinforced Ti/Al‐laminated composites without UC assisted, both the tensile strength (from 872.4 to 826.5 MPa) and failure strain (from 17.5% to 20.4%) of NiTif‐reinforced Ti/Al‐laminated composites with UC assisted increase due to the contribution of UC assisted. The reinforcing and fracture mechanisms of the UC assisted are also discussed.
Stretchable Multifunctional Polydimethylsiloxane Composites with Cage‐Like Conductive Architecture for Integrated Thermosensitive and Electromagnetic Interference Shielding Performance
Authors: Tian Ke , Qin Tian , Li Qianyang , Chen Chuanliang , Dai Zijian , Wei Xin , Fu Qiang , Deng Hua
Published: March 2024

High‐performance sensors with outstanding sensitivity, wide working range, and multifunctional properties are highly desirable in modern integrated smart wearable electronics. Herein, polydimethylsiloxane (PDMS)‐based stretchable pyroresistive sensors composed of tightly‐assembled silver nanowires (Ag NWs)‐encapsulated PDMS microspheres (PM) and expandable microspheres (EM) are fabricated. The synergistic cage‐like conductive network and EM endow the temperature sensor with tunable sensitivity (Max TCR: 27.4% °C−1), broad sensing range (25–85 °C), low perception limit (0.1 °C), and excellent anti‐interference ability. Interestingly, at elevated temperature field (> 90 °C), a remarkable conduction‐insulation transition is observed, which is employed to facilitate an early fire alarm system. In addition, the selectively distributed Ag NWs constructs segregated conductive pathways at an ultralow content (Pc = 0.014 vol%), leading to efficient electromagnetic interference shielding (40.0 dB). The underlying mechanism responsible for the observed superior thermosensation and EMI shielding performance is elucidated, and possible applications are demonstrated. Consequently, this work offers a novel strategy for the design of flexible, multifunctional pyroresistive sensors toward artificial intelligence and emerging wearable electronics.
Intensifying the Supported Ruthenium Metallic Bond to Boost the Interfacial Hydrogen Spillover Toward pH‐Universal Hydrogen Evolution Catalysis
Authors: Chen Ya , Liu Yaoda , Li Lei , Sakthivel Thangavel , Guo Zhixin , Dai Zhengfei
Published: March 2024

The effectuation of pH‐universal electrocatalysis is highly attractive but still challenging for the hydrogen evolution reaction (HER). It appeals for not only the facilitated electron transport but also the kinetical proton mass transfer. In this study, a via‐hole Ru/MoO2 confined heterostructure is profiled as a metal‐support platform for the electron/mass transfer‐boosted pH‐universal HER studies. It is indicated that the as‐formed Ru─O─Mo bridge can modulate the electronic transport at the interface, and the proton adsorption and transfer are kinetically derived by the intensified metallic Ru─Ru bond. Resultantly, the Ru/MoO2 heterostructure stably attains the Pt‐beyond HER activity with an ultralow overpotential of 9.2 mV at 10 mA cm−2 in 1 m KOH, and also achieves the competitive HER activity and stability in the acidic/neutral electrolytes. Both the experimental and computational results reveal the accelerated HER kinetics is attributable to the intensive mass transfer through the interfacial Ru→MoO2 hydrogen spillover effect. This work opens up the opportunities to rationalize the advanced metal‐support HER electrocatalysts through the interfacial hydrogen spillover effect and metallic bond engineering.
Deciphering UVA/Riboflavin Collagen Crosslinking: A Pathway to Improve Biomedical Materials
Authors: Fan Lu , Jung Ole , Herrmann Markus , Shirokikh Marina , Stojanovic Sanja , Najman Stevo , Körte Fabian , Xiong Xin , Schenke‐Layland Katja , Barbeck Mike
Published: March 2024

Collagen crosslinking employing ultraviolet A rays and riboflavin (UVA/R) has emerged as a pivotal technique in clinical therapies, especially in ophthalmology since the 1990s. Despite its clinical adoption, the lack of clarity of the detailed mechanism and the imperative for a refined manufacturing process necessitates further investigation. This study advances the understanding of UVA/R crosslinked collagen, concentrating on identifying the primary crosslinking sites using seven synthetic peptides and exploring the pathways of riboflavin‐mediated crosslinking. The results demonstrate that tyrosine residues are key crosslinking sites, and riboflavin plays a dual role as both a catalyst and a competitive inhibitor in the crosslinking process. Furthermore, the UVA/R crosslinked collagen matrix exhibits a more harmonious balance between stability and degradability compared with chemically crosslinked collagen matrices, coupled with superior mechanical properties and augmented biocompatibility. In vivo experiments further validate its excellent biocompatibility, reduced tissue inflammation, and promotion of tissue regeneration. The research provides crucial insights into collagen crosslinking mechanisms, paving the way for the development of sophisticated collagen‐based biomaterials tailored for biomedical applications.
Interfacial Dual‐Modulation via Cationic Electrostatic Shielding and Anionic Preferential Adsorption toward Planar and Reversible Zinc Electrodeposition
Authors: Tang Huan , Hu Nan , Ma Linxiang , Weng Haofan , Huang Dan , Zhu Jinliang , Yang Hao , Chen Zhengjun , Yin Xucai , Xu Jing , He Huibing
Published: March 2024

Rechargeable aqueous zinc‐ion batteries (ZIBs) with low cost and high safety arouse most promises as next‐generation energy storage configurations. Yet the heterogeneous electric field distributions and interfacial side reactions are considered stumbling roadblocks toward the commercialization of ZIBs. Here, these challenges via cationic electrostatic shielding and anionic preferential adsorption by sodium gluconate (SG) additive are addressed. The polar functional groups (─COO−) of SG anions preferentially anchor to the Zn anode, which can alter Zn2+ migration pathways and restrain side reactions. Moreover, as per the smaller effective reduction potential, the separated cations (Na+) from SG serve as a dynamic armor to provide strong electrostatic shielding effect for uniform Zn2+ deposition on the [002] crystal plane, radically eliminating Zn dendrite growth and promoting anti‐corrosion behaviors of Zn. Consequently, the Zn//Zn symmetric cell with modified electrolyte confers a lifespan of up to 600 h at a high 80% depth of discharge. Furthermore, even under a record‐low negative/positive ratio of 2.11 and lean electrolyte of 30 µL mAh−1, the Zn//VOX full cell remains enhanced capacity retention of 84.37% even after 800 cycles at 1 A g−1. This work develops an interfacial dual‐modulation strategy and provides unique insights to enlighten the practical application of ZIBs.
Tetrahedral DNA‐Based Functional MicroRNA‐21 Delivery System: Application to Corneal Epithelial Wound Healing
Authors: Li Yulin , Wang Shu , Dong Yueyan , Jin Xin , Wang Jingrao , Zhang Hong
Published: March 2024

Corneal injury occurs frequently which may lead to serious visual impairment. Rapid and efficient re‐epithelialization after corneal epithelial injury is the key issue for maintaining corneal homeostasis. Among various treatment strategies, microRNA (miR)‐based therapy shows great potential. However, structural limitations of miRNAs hinder its biomedical functionality. Nucleic acid nanotechnology is an appealing candidate for gene delivery because of its flexible modification and excellent biocompatibility. Herein, modified 3D tetrahedral framework nucleic acids (tFNAs) utilized as gene carriers for miR‐21 delivery are constructed. TFNAs‐miR‐21 (T‐21) shows great enzymatic resistance in extracellular environment and payload delivery into human corneal epithelial cells (HCECs) via clathrin‐mediated endocytosis. T‐21 facilitates proliferation and migration in HCECs via activating PI3K/AKT and ERK1/2 signaling pathways in vitro. In vivo studies, T‐21 can be internalized by corneal epithelium in mice. In the mice corneal scratch model, T‐21 ophthalmic solutions used as eye drops show no apparent side effects on the ocular surface histologically and exert great potential in accelerating corneal wound healing. These findings demonstrate that modified tFNAs are promising candidates for miRNA delivery for corneal wound healing. The convenient administration and great biocompatibility of tetrahedral DNA nanoparticles highlight its potential as gene transporter in solving ocular problems.
Biphase Pd Nanosheets with Atomic‐Hybrid RhOx/Pd Amorphous Skins Disentangle the Activity‐Stability Trade‐Off in Oxygen Reduction Reaction
Authors: Lyu Zixi , Cai Junlin , Zhang Xia‐Guang , Li Huiqi , Huang Hongpu , Wang Shupeng , Li Tianyu , Wang Qiuxiang , Xie Zhaoxiong , Xie Shuifen
Published: March 2024

The activity‐stability trade‐off relationship of oxygen reduction reaction (ORR) is a tricky issue that strikes the electrocatalyst population and hinders the widespread application of fuel cells. Here neoteric biphase Pd nanosheets that are structured with ultrathin two‐dimensional crystalline Pd inner cores and ≈1 nm thin atomic‐hybrid RhOx/Pd amorphous skins, named c/a‐Pd@PdRh NSs, for disentangling this trade‐off dilemma for alkaline ORR are developed. The superthin amorphous skins significantly amplify the quantity of flexibly low‐coordinated atoms for electrocatalysis. An in situ selected oxidation of the top‐surface Rh dopants creates atomically hybrid RhOx/Pd disorder surfaces. Detailed energy spectra and theoretical simulation confirm that these RhOx/Pd interfaces can arouse a surface charge redistribution, causing significant electron deficiency and lowered d‐band center for surface Pd. Meanwhile, anticorrosive Rh/RhOx species can thermodynamically passivate the neighboring Pd atoms from oxidative dissolution. Thanks to these amplified interfacial effects, the biphase c/a‐Pd@PdRh NSs simultaneously exhibit a superhigh ORR activity (5.92 A mg−1, 22.8 times that of Pt/C) and an outstanding long‐lasting stability after 100k cycles of accelerated durability test, showcasing unprecedented electrocatalysts for breaking the activity‐stability trade‐off relationship of ORR. This work paves a bran‐new strategy for designing high‐performance electrocatalysts through creating modulated amorphous skins on low‐dimensional nanomaterials.
An Encapsulation‐Free and Hierarchical Porous Triboelectric Scaffold with Dynamic Hydrophilicity for Efficient Cartilage Regeneration
Authors: Luo Bin , Wang Sinan , Song Xingqi , Chen Shuo , Qi Qiaoyu , Chen Wenyi , Deng Xiaoyuan , Ni Yufeng , Chu Chengzhen , Zhou Guangdong , Qin Xiaohong , Lei Dong , You Zhengwei
Published: March 2024

Tissue engineering and electrotherapy are two promising methods to promote tissue repair. However, their integration remains an underexplored area, because their requirements on devices are usually distinct. Triboelectric nanogenerators (TENGs) have shown great potential to develop self‐powered devices. However, due to their susceptibility to moisture, TENGs have to be encapsulated in vivo. Therefore, existing TENGs cannot be employed as tissue engineering scaffolds, which require direct interaction with surrounding cells. Here, the concept of triboelectric scaffolds (TESs) is proposed. Poly(glycerol sebacate), a biodegradable and relatively hydrophobic elastomer, is selected as the matrix of TESs. Each hydrophobic micropore in multi‐hierarchical porous TESs efficiently serves as a moisture‐resistant working unit of TENGs. Integration of tons of micropores ensures the electrotherapy ability of TESs in vivo without encapsulation. Originally hydrophobic TESs are degraded by surface erosion and transformed into hydrophilic surfaces, facilitating their role as tissue engineering scaffolds. Notably, TESs seeded with chondrocytes obtain dense and large matured cartilages after subcutaneous implantation in nude mice. Importantly, rabbits with osteochondral defects receiving TES implantation show favorable hyaline cartilage regeneration and complete cartilage healing. This work provides a promising electronic biomedical device and will inspire a series of new in vivo applications.
Narrow Bandgap Schottky Heterojunction Sonosensitizer with High Electron–Hole Separation Boosted Sonodynamic Therapy in Bladder Cancer
Authors: Li Guanlin , Wu Sicheng , Liu Jinggong , Wang Kaiyuan , Chen Xiaoyuan , Liu Hongxing
Published: March 2024

Sonodynamic therapy (SDT) is applied to bladder cancer (BC) given its advantages of high depth of tissue penetration and nontoxicity due to the unique anatomical location of the bladder near the abdominal surface. However, low electron–hole separation efficiency and wide bandgap of sonosensitizers limit the effectiveness of SDT. This study aims to develop a TiO2‐Ru‐PEG Schottky heterojunction sonosensitizer with high electron–hole separation and narrow bandgap for SDT in BC. Density functional theory (DFT) calculations and experiments collectively demonstrate that the bandgap of TiO2‐Ru‐PEG is reduced due to the Schottky heterojunction with the characteristic of crystalline‐amorphous interface formed by the deposition of ruthenium (Ru) within the shell layer of TiO2. Thanks to the enhancement of oxygen adsorption and the efficient separation of electron–hole pairs, TiO2‐Ru‐PEG promotes the generation of reactive oxygen species (ROS) under ultrasound (US) irradiation, resulting in cell cycle arrest and apoptosis of bladder tumor cells. The in vivo results prove that TiO2‐Ru‐PEG boosted the subcutaneous and orthotopic bladder tumor models while exhibiting good safety. This study adopts the ruthenium complex for optimizing sonosensitizers, contributing to the progress of SDT improvement strategies and presenting a paradigm for BC therapy.
Remote Control of Energy Transformation‐Based Cancer Imaging and Therapy
Authors: Xu Hai , Kim Dahee , Zhao Yuan‐Yuan , Kim Chowon , Song Guosheng , Hu Qiongzheng , Kang Heemin , Yoon Juyoung
Published: March 2024

Cancer treatment requires precise tumor‐specific targeting at specific sites that allows for high‐resolution diagnostic imaging and long‐term patient‐tailorable cancer therapy; while, minimizing side effects largely arising from non‐targetability. This can be realized by harnessing exogenous remote stimuli, such as tissue‐penetrative ultrasound, magnetic field, light, and radiation, that enable local activation for cancer imaging and therapy in deep tumors. A myriad of nanomedicines can be efficiently activated when the energy of such remote stimuli can be transformed into another type of energy. This review discusses the remote control of energy transformation for targetable, efficient, and long‐term cancer imaging and therapy. Such ultrasonic, magnetic, photonic, radiative, and radioactive energy can be transformed into mechanical, thermal, chemical, and radiative energy to enable a variety of cancer imaging and treatment modalities. The current review article describes multimodal energy transformation where a serial cascade or multiple types of energy transformation occur. This review includes not only mechanical, chemical, hyperthermia, and radiation therapy but also emerging thermoelectric, pyroelectric, and piezoelectric therapies for cancer treatment. It also illustrates ultrasound, magnetic resonance, fluorescence, computed tomography, photoluminescence, and photoacoustic imaging‐guided cancer therapies. It highlights afterglow imaging that can eliminate autofluorescence for sustained signal emission after the excitation.
Mendelian randomization analysis using GWAS and eQTL data to investigate the relationship between chronotype and neuropsychiatric disorders and their molecular basis
Authors: Crinion Shane , Wyse Cathy A. , Donohoe Gary , Lopez Lorna M. , Morris Derek W.
Published: March 2024

Chronotype is a proxy sleep measure that has been associated with neuropsychiatric disorders. By investigating how chronotype influences risk for neuropsychiatric disorders and vice versa, we may identify modifiable risk factors for each phenotype. Here we used Mendelian randomization (MR), to explore causal effects by (1) studying the causal relationships between neuropsychiatric disorders and chronotype and (2) characterizing the genetic components of these phenotypes. Firstly, we investigated if a causal role exists between five neuropsychiatric disorders and chronotype using the largest genome‐wide association studies (GWAS) available. Secondly, we integrated data from expression quantitative trait loci (eQTLs) to investigate the role of gene expression alterations on these phenotypes. Evening chronotype was causal for increased risk of schizophrenia and autism spectrum disorder and schizophrenia was causal for a tendency toward evening chronotype. We identified 12 eQTLs where gene expression changes in brain or blood were causal for one of the phenotypes, including two eQTLs for SNX19 in hippocampus and hypothalamus that were causal for schizophrenia. These findings provide important evidence for the complex, bidirectional relationship that exists between a sleep‐based phenotype and neuropsychiatric disorders, and use gene expression data to identify causal roles for genes at associated loci.
Theoretical Prediction Leads to Synthesize GDY Supported InOx Quantum Dots for CO2 Reduction
Authors: He Feng , Chen Xi , Xue Yurui , Li Yuliang
Published: March 2024

The preparation of formic acid by direct reduction of carbon dioxide is an important basis for the future chemical industry and is of great significance. Due to the serious shortage of highly active and selective electrocatalysts leading to the development of direct reduction of carbon dioxide is limited. Herein the target catalysts with high CO2RR activity and selectivity were identified by integrating DFT calculations and high‐throughput screening and by using graphdiyne (GDY) supported metal oxides quantum dots (QDs) as the ideal model. It is theoretically predicted that GDY supported indium oxide QDs (i.e., InOx/GDY) is a new heterostructure electrocatalyst candidate with optimal CO2RR performance. The interfacial electronic strong interactions effectively regulate the surface charge distribution of QDs and affect the adsorption/desorption behavior of HCOO* intermediate during CO2RR to achieve highly efficient CO2 conversion. Based on the predicted composition and structure, we synthesized the advanced catalytic system, and demonstrates superior CO2‐to‐HCOOH conversion performance. The study presents an effective strategy for rational design of highly efficient heterostructure electrocatalysts to promote green chemical production.
Lewis Säure‐Getriebene Inverse Hydrid‐Shuttle Katalyse
Authors: Jones Benjamin T. , Maulide Nuno
Published: March 2024

Inverse Hydrid‐Shuttle Katalyse bildet eine Plattform für die hocheffiziente und diastereoselektive Synthese von Alkaloidstrukturen durch Multikomponentenreaktionen. Mehrere Einschränkungen hindern jedoch die breite Anwendbarkeit dieses Ansatzes, darunter vor allem die Notwendigkeit nach besonders elektronenarmen Akzeptoren. Hier präsentieren wir einen allgemeinen, durch Lewis Säuren getriebenen Ansatz, um diese Einschränkung anzugehen, und haben zwei Strategien entwickelt, die die modulare Synthese komplexer azabicyclischer Systeme ermöglichen, die mit der früheren Methode unerreichbar waren. Die so gewonnene synthetische Flexibilität führt zu einer verbesserten asymmetrischen Cyclisierung, die eine kurze Totalsynthese des Alkaloids (−)‐Tashiromin ermöglicht hat.
Lewis Acid‐Driven Inverse Hydride Shuttle Catalysis
Authors: Jones Benjamin T. , Maulide Nuno
Published: March 2024

Inverse hydride shuttle catalysis provides a multicomponent platform for the highly efficient synthesis of alkaloid frameworks with exquisite diastereoselectivity. However, a number of limitations hinder this method, primarily the strict requirement for highly electron‐deficient acceptors. Herein, we present a general Lewis acid‐driven approach to address this constraint, and have developed two broad strategies enabling the modular synthesis of complex azabicycles that were entirely unattainable using the previous method. The enhanced synthetic flexibility facilitates a streamlined asymmetric cyclization, leading to a concise total synthesis of the alkaloid (−)‐tashiromine.
Production of Aromatic Hydrocarbons from Co‐Hydropyrolysis of Biomass Components and HDPE with Application of Modified HZSM‐5 Catalyst
Authors: Ren Long , Xu Yupu , Chen Wenjun , Zhang Changsen
Published: March 2024

Experiments were conducted in this study on the co‐hydropyrolysis of three components of biomass (cellulose, hemicellulose, and lignin) and HDPE by using SR‐Pd/Trap‐HZ‐5 as catalyst. To control the variable, we use the same experiment conditions in co‐hydropyrolysis: Si/Al ratio of 50, Pd load 1 %, catalyst to reactant ratio of 1 : 10, 1 MPa, 400 °C, reaction time 1 h. Use XRD, TEM, BET, and NH3‐TPD to confirm catalyst successful synthesis; use pine sawdust (PW) co‐hydropyrolysis with HDPE to analyse catalytic activity; and use GC/MS to characterize the chemical composition of the bio‐oil from the co‐hydropyrolysis of biomass components and HDPE. The results show that cellulose has a significant synergistic effect with aromatic hydrocarbon production, whose selectivity was 93.3 %; hemicellulose has a synergistic effect; aromatic selectivity can reach 75.1 %; and a negative synergistic effect between lignin and HDPE was shown as the selectivity of aromatic hydrocarbons decreased from 62.1 % to 15.6 %.
Peptide‐conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications
Authors: Ilieş Bogdan Dragoş , Yildiz Ibrahim , Abbas Manzar
Published: March 2024

Peptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide‐modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, and stimuli responsive behavior. Targeting peptides can direct the nanoparticles into specific tissues for targeted drug and gene delivery and imaging applications due to their specificity towards certain receptors. Furthermore, due to their stimuli‐responsive features, they can offer controlled release of therapeutics into desired sites of disease. In addition, peptide‐based biosensors and imaging agents can provide non‐invasive detection and monitoring of diseases including cancer, infectious diseases, and neurological disorders. In this review, we covered the design and formulation of recent peptide‐based NP platforms, as well as their utilization in in vitro and in vivo applications such as targeted drug and gene delivery, targeting, sensing, and imaging applications. In the end, we provided the future outlook to design new peptide conjugated nanomaterials for biomedical applications.
A Family of Hexacopper Phenylsilsesquioxane/Acetate Complexes: Synthesis, Solvent‐Controlled Cage Structures, and Catalytic Activity
Authors: Zueva Anna Y. , Bilyachenko Alexey N. , Arteev Ivan S. , Khrustalev Victor N. , Dorovatovskii Pavel V. , Shul'pina Lidia S. , Ikonnikov Nikolay S. , Gutsul Evgenii I. , Rahimov Karim G. , Shubina Elena S. , Reis Conceição Nuno , Mahmudov Kamran T. , Guedes da Silva M. Fátima C. , Pombeiro Armando J. L.
Published: March 2024

Convenient self‐assembly synthesis of copper(II) complexes via double (phenylsilsesquioxane and acetate) ligation allows to isolate a family of impressive sandwich‐like cage compounds. An intriguing feature of these complexes is the difference in the structure of a pair of silsesquioxane ligands despite identical (Cu6) nuclearity and number (four) of acetate fragments. Formation of particular combination of silsesquioxane ligands (cyclic/cyclic vs condensed/condensed vs cyclic/condensed) was found to be dependent on the synthesis/crystallization media. A combination of Si4‐cyclic and Si6‐condensed silsesquioxane ligands is a brand new feature of cage metallasilsesquioxanes. A representative Cu6‐complex (4) (with cyclic silsesquioxanes) exhibited high catalytic activity in the oxidation of alkanes and alcohols with peroxides. Maximum yield of the products of cyclohexane oxidation attained 30 %. The compound 4 was also tested as catalyst in the Baeyer‐Villiger oxidation of cyclohexanone by m‐chloroperoxybenzoic acid: maximum yields of 88 % and 100 % of ϵ‐caprolactone were achieved upon conventional heating at 50 °C for 4 h and MW irradiation at 70 or 80 °C during 30 min, respectively. It was also possible to obtain the lactone (up to 16 % yield) directly from the cyclohexane via a tandem oxidation/Baeyer‐Villiger oxidation reaction using the same oxidant.
A computational method for predicting color palette discriminability
Authors: Westland Stephen , Finlayson Graham , Lai Peihua , Pan Qianqian , Yang Jie , Chen Yun
Published: March 2024

Automatic analysis of images is increasingly being used to generate color insights and this has led to various methods for generating palettes. Several studies have recently been published that explore methods to predict the visual similarity between pairs of palettes and these methods are often used to evaluate different generative methods. This work is concerned with being able to predict visual similarity between color palettes. Three data sets (two of which were previously published) are used to evaluate two methods for predicting visual similarity between palettes. A novel palette‐difference metric (based on the Hungarian algorithm) is compared to the previously published minimum color difference model (MICD) and was found to agree better with the visual data for two of the three data sets. Agreement between models and visual data was also better for CIEDE2000 (1, 2) than for CIELAB metrics.
Continuous‐Flow Catalysis Using Phosphine‐Metal Complexes on Porous Polymers: Designing Ligands, Pores, and Reactors
Authors: Matsumoto Hikaru , Iwai Tomohiro , Sawamura Masaya , Miura Yoshiko
Published: March 2024

Continuous‐flow syntheses using immobilized catalysts can offer efficient chemical processes with easy separation and purification. Porous polymers have gained significant interests for their applications to catalytic systems in the field of organic chemistry. The porous polymers are recognized for their large surface area, high chemical stability, facile modulation of surface chemistry, and cost‐effectiveness. It is crucial to immobilize transition‐metal catalysts due to their difficult separation and high toxicity. Supported phosphine ligands represent a noteworthy system for the effective immobilization of metal catalysts and modulation of catalytic properties. Researchers have been actively pursuing strategies involving phosphine‐metal complexes supported on porous polymers, aiming for high activities, durabilities, selectivities, and applicability to continuous‐flow systems. This review provides a concise overview of phosphine‐metal complexes supported on porous polymers for continuous‐flow catalytic reactions. Polymer catalysts are categorized based on pore sizes, including micro‐, meso‐, and macroporous polymers. The characteristics of these porous polymers are explored concerning their efficiency in immobilized catalysis and continuous‐flow systems.
Oral SSTR5 Antagonist SCO‐240 for Growth Hormone Stimulation: A Phase I Single‐Dose Study in Healthy Individuals
Authors: Nishizaki Harunobu , Kagawa Tomoya , Sugama Jun , Kobayashi Akihiro , Moritoh Yusuke , Watanabe Masanori
Published: March 2024

Somatostatin inhibits endocrine and exocrine secretion in various tissues by acting on five somatostatin receptor subtypes (SSTR1–5). The clinical effects of SSTR5 antagonism remain unknown. Herein, we evaluated the effects of SCO‐240, an oral SSTR5 antagonist, in healthy individuals. This randomized, single‐center, double‐blind, placebo‐controlled, phase I study included healthy Japanese and White individuals. The effects of ascending single oral doses of SCO‐240 were evaluated in healthy individuals. The main outcome measures were safety, tolerability, pharmacokinetics, and pharmacodynamics (gallbladder contractions and levels of serum insulin and plasma glucagon‐like peptide‐1 (GLP‐1)). The levels of pituitary hormones were evaluated in our exploratory analysis. The results indicated that SCO‐240 was safe and well‐tolerated at all tested doses. Oral SCO‐240 was readily absorbed, with its systemic exposure increasing in a dose‐dependent manner. The median time to maximum concentration and mean terminal half‐life of SCO‐240 were 3–4 and 10.2–12.6 hours, respectively, in the ascending dose section. No clinically meaningful changes in SCO‐240 pharmacokinetic profiles were observed between fed and fasted or between Japanese and White individuals. No increase in gallbladder contractions or levels of insulin and GLP‐1 were detected. SCO‐240 induced robust growth hormone (GH) secretion without altering the levels of other pituitary hormones. In conclusion, the study is the first to demonstrate that SSTR5 antagonism stimulates GH secretion in humans. SCO‐240 was safe and well‐tolerated and exhibited once‐daily oral dosing potential. The robust effects of SCO‐240 on GH secretion suggest that it may be a treatment option for GH‐related disorders.
Adherence to GLP1‐RA and SGLT2‐I affects clinical outcomes and costs in patients with type 2 diabetes
Authors: Ciardullo Stefano , Savaré Laura , Rea Federico , Perseghin Gianluca , Corrao Giovanni
Published: March 2024

Aims

To evaluate the impact of adherence to glucagon like peptide‐1 receptor agonists (GLP1‐RA) and sodium‐glucose transporter two inhibitors (SGLT2‐I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM).

Materials and Methods

The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007–2015 were followed to identify those who started therapy with GLP1‐RA or SGLT2‐I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non‐adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro‐ and macrovascular complications and all‐cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system.

Results

After matching, 1182 pairs of adherent and non‐adherent GLP1‐RA users and 1126 pairs of adherent and non‐adherent SGLT2‐I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72–0.98 for GLP1‐RA and HR: 0.69, 95% CI 0.55–0.87 for SGLT2‐I). A significant reduction in hospitalizations was found for adherent patients in the GLP1‐RA group but not for the SGLT2‐I group. Results were consistent when analyses were stratified by age and sex. While higher drug‐related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2‐I treated patients, this was not the case for GLP1‐RA.

Conclusions

Higher adherence to drug treatment with GLP1‐RA and SGLT2‐I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real‐world setting.
N‐Directed defluorinative γ‐C(sp3)−H allylation of sulfamate esters for synthesis of gem‐difluoroalkenes via photoredox catalysis
Authors: Yang Jia‐Wen , Li Meng , Tan Guang‐Qiang , Liu Feng , Qin Hai‐Tao
Published: March 2024

gem‐Difluoroalkenes are unique structural motifs with important applications ranging from drugs to materials. Herein, we report a novel radical‐mediated defluorinative allylation of sulfamate esters with through distal C(sp3)−H functionalization under photoredox conditions. The reaction could readily incorporate various gem‐difluoroalkene motifs into previously unfunctionalized sp3 carbon centers. The transformation allows directly dual activation of N−H and C(sp3)−H bonds via a photocatalytic and redox‐neutral process, as well as using water as environmentally friendly co‐solvent. The reaction could provide a general and operationally simple method to access gem‐difluoroalkene compounds with high diversity.