bluuebunny/crossref_metadata_2025 huggingface dataset:
A qualitative exploration of the public perception of municipal drinking water
Authors: Jones Andria Q. , Dewey Catherine E. , Doré Kathryn , Majowicz Shannon E. , McEwen Scott A. , Waltner-Toews David , Henson Spencer J. , Mathews Eric
Published: May 2007

Surveys of water consumption patterns in Canada and the USA show a high frequency of alternative water use, including bottled water and water treatment devices. An in-depth understanding of the public perception of municipal water would enable public health and water utility professionals better to address the needs of residents in their jurisdictions. We explored these perceptions and the self-described behaviour and needs of participants served by municipal water systems in the City of Hamilton, Ontario (Canada). We conducted three focus groups; two with men and women aged between 36 and 65 years, and one with men and women aged between 20 and 35 years. In general, participants expressed negative views of the municipal water supplied to their homes. Concerns included unpleasant sensory qualities of the water, perceived poor source-water protection, a perceived insufficiency in water treatment and testing and potential contamination along the distribution system. Reasons for alternative water use included perceived improvements in quality and safety over regular tap water, although convenience also contributed to bottled water use. Participants wanted more information on water testing and suggested a variety of dissemination approaches. This study suggested important lines of inquiry and action regarding the perception of municipal drinking water in this population.
Subject Indexes to Poetry: Historical : (See Patriotism.)
Authors: Bell Hazel K.
Published: May 2007

This article considers various approaches to the indexing of poetry, and whether (serious) subject indexing of poetry is feasible, examining in particular The Pageant of English Poetry (1924).
When Knowing Grammar Depends on Knowing Vocabulary: Native-Speaker Grammaticality Judgements of Sentences with Real and Unreal Words
Authors: Barcroft Joe
Published: May 2007

Abstract:

This study examined how the presence of real versus unreal words in sentences affected the ability of native English speakers to make accurate grammaticality judgements and forced-choice decisions for sentences with violations in the use of dative alternation and comparatives. Sentences with dative alternation violations contained polysyllabic verbs (*John explained Mary the plan) that were real (e.g., explained), similar (e.g., explunned), and dissimilar (e.g., tidnopped) to real verbs. Sentences with comparative violations contained polysyllabic adjectives (*Robert is demandinger than Allen) that were real (e.g., demanding), similar (e.g., demunding), and dissimilar (e.g., natormunt) to real adjectives. Accuracy of grammaticality judgements was much lower for sentences with unreal words than real words. For sentences with comparatives, accuracy also was higher in sentences with similar words than with dissimilar words, demonstrating a graded effect for partial access. These findings provide support for theoretical accounts that associate knowledge of these structures with knowledge of real words and for instruction oriented toward the development of vocabulary knowledge.
Perceived Economic Burden, Mortality, and Health Status in Patients With Heart Failure
Authors: Yu Yuan , Liu Jiamin , Zhang Lihua , Ji Runqing , Su Xiaoming , Gao Zhiping , Xia Shuang , Li Jing , Li Liwen
Published: March 2024

Importance

In the face of an emerging heart failure (HF) epidemic, describing the association between perceived economic burden (PEB) and health care outcomes is an important step toward more equitable and achievable care.

Objectives

To examine the association between PEB and risk of 1-year clinical outcomes and HF–specific health status in patients with acute decompensated HF.

Design, Setting, and Participants

This prospective, multicenter, hospital-based cohort study prospectively enrolled adult patients hospitalized for acute decompensated HF at 52 hospitals in China from August 2016 to May 2018, with 1-year follow-up. Data were analyzed on June 17, 2022.

Exposure

Perceived economic burden, categorized as severe (cannot undertake expenses), moderate (can almost undertake expenses), or little (can easily undertake expenses).

Main Outcomes and Measures

The clinical outcomes of the study were 1-year all-cause death and rehospitalization for HF. Heart failure–specific health status was assessed by the 12-Item Kansas City Cardiomyopathy Questionnaire (KCCQ-12).

Results

Among 3386 patients, median age was 67 years (IQR, 58-75 years) and 2116 (62.5%) were men. Of these patients, 404 (11.9%) had severe PEB; 2021 (59.7%), moderate PEB; and 961 (28.4%), little PEB. Compared with patients with little PEB, those with severe PEB had increased risk of 1-year mortality (hazard ratio [HR], 1.61; 95% CI, 1.21-2.13; P < .001) but not 1-year HF rehospitalization (HR, 1.21; 95% CI, 0.98-1.49; P = .07). The mean (SD) adjusted KCCQ-12 score was lowest in patients with severe PEB and highest in patients with little PEB at baseline (40.0 [1.7] and 50.2 [1.0] points, respectively; P < .001) and at each visit (eg, 12 months: 61.5 [1.6] and 75.5 [0.9] points respectively; P < .001). Patients reporting severe PEB had a clinically significant lower 1-year KCCQ-12 score compared with those reporting little PEB (mean difference, −11.3 points; 95% CI, −14.9 to −7.6 points; P < .001).

Conclusions and Relevance

In this cohort study of patients with acute decompensated HF, greater PEB was associated with higher risk of mortality and poorer health status but not with risk of HF rehospitalization. The findings suggest that PEB may serve as a convenient tool for risk estimation and as a potential target for quality-improvement interventions for patients with HF.
Neoadjuvant Chemoimmunotherapy for NSCLC
Authors: Sorin Mark , Prosty Connor , Ghaleb Louis , Nie Kathy , Katergi Khaled , Shahzad Muhammad H. , Dubé Laurie-Rose , Atallah Aline , Swaby Anikka , Dankner Matthew , Crump Trafford , Walsh Logan A. , Fiset Pierre O. , Sepesi Boris , Forde Patrick M. , Cascone Tina , Provencio Mariano , Spicer Jonathan D.
Published: March 2024

Importance

To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non–small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.

Objective

To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.

Data Sources

MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients.

Study Selection

Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded.

Main Outcomes and Measures

Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis.

Results

Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%).

Conclusion and Relevance

This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.
Multifocal Unilateral Orange Fundus Tumors in a Young Man
Authors: Poudel Bibhav , Vempuluru Vijitha S. , Shields Carol L.
Published: March 2024

A 38-year-old man had an asymptomatic, orange, macular choroidal mass with macular choroidal folds and a retinal pigment epithelial detachment in the right eye and a second orange mass nasal to the optic disc also in the right eye. What would you do next?
Clinical Features and Treatment Outcomes of Carbapenem-Resistant Pseudomonas aeruginosa Keratitis
Authors: Tribin Felipe Echeverri , Lieux Caroline , Maestre-Mesa Jorge , Durkee Heather , Krishna Katherine , Chou Brandon , Neag Emily , Tóthová Jana D’Amato , Martinez Jaime D. , Flynn Harry W. , Parel Jean Marie , Miller Darlene , Amescua Guillermo
Published: March 2024

Importance

Evaluation of the microbiological diagnostic profile of multidrug-resistant Pseudomonas aeruginosa keratitis and potential management with rose bengal–photodynamic antimicrobial therapy (RB-PDAT) is important.

Objective

To document the disease progression of carbapenemase-resistant P aeruginosa keratitis after an artificial tear contamination outbreak.

Design, Setting, and Participants

This retrospective observation case series included 9 patients 40 years or older who presented at Bascom Palmer Eye Institute and had positive test results for multidrug-resistant P aeruginosa keratitis between January 1, 2022, and October 31, 2023.

Main Outcomes and Measures

Evaluation of type III secretion phenotype, carbapenemase-resistance genes blaGES and blaVIM susceptibility to antibiotics, and in vitro and in vivo outcomes of RB-PDAT against multidrug-resistant P aeruginosa keratitis.

Results

Among the 9 patients included in the analysis (5 women and 4 men; mean [SD] age, 73.4 [14.0] years), all samples tested positive for exoU and carbapenemase-resistant blaVIM and blaGES genes. Additionally, isolates were resistant to carbapenems as indicated by minimum inhibitory concentration testing. In vitro efficacy of RB-PDAT indicated its potential application for treating recalcitrant cases. These cases highlight the rapid progression and challenging management of multidrug-resistant P aeruginosa. Two patients were treated with RB-PDAT as an adjuvant to antibiotic therapy and had improved visual outcomes.

Conclusions and Relevance

This case series highlights the concerning progression in resistance and virulence of P aeruginosa and emphasizes the need to explore alternative therapies like RB-PDAT that have broad coverage and no known antibiotic resistance. The findings support further investigation into the potential effects of RB-PDAT for other multidrug-resistant microbes.
Binary observation‐based identification for finite impulse response systems under denial of service attacks
Authors: Wei Jingliang , Jia Ruizhe , Jing Fengwei , Guo Jin
Published: March 2024

This article considers the parameter identification problem for the finite impulse response system based on binary observations under denial of service attacks. First, in addition to designing the identification algorithm for the unknown parameter, and its convergence is verified, simultaneously obtaining the asymptotic normality. Then, based on the convergence speed of the identification algorithm and the covariance matrix of the estimation error, the optimal attack strategy problem is transformed into an optimization problem with constraints, then the optimal solution is given. Furthermore, a defense strategy with dual time‐scale input design method is proposed and its effectiveness is demonstrated. Finally, numerical simulations are applied to evidence the correctness of the raised method.
Self‐Carrier Nanoparticles for Delivery of Paclitaxel and IDO Inhibitor to Boost Antitumor Chemo‐Immunotherapy
Authors: Li Zixuan , Pei Qing , Zhao Min , Xie Zhigang , Zheng Min
Published: March 2024

The combination of chemotherapy and immunotherapy holds great potential in clinical treatment of advanced cancers. Whereas, the therapeutic outcome of chemotherapeutic and immune regulator is suboptimal due to their poor tumor availability and severe off‐target toxicity. Herein, self‐carrier nanoparticles (PSMT NPs) integrating a paclitaxel (PTX) prodrug and indoleamine 2,3‐dioxygenase 1 (IDO) inhibitor (1‐methyl‐tryptophan, 1MT) for tumor‐specific chemo‐immunotherapy is constructed. After internalization by cancer cells, PSMT NPs can respond to endogenous redox stimulus, and release PTX and 1MT. The released PTX can not only promote cell apoptosis via the intervention of cell mitosis but also initiate immunogenic cell death to facilitate the recruitment and activation of tumor‐infiltrating cytotoxic T lymphocytes. The concomitant 1MT can inhibit the IDO activity to exhaust regulatory T cells, thereby synergistically activating cytotoxic T lymphocytes. PSMT NPs exhibit potentiated antitumor output toward triple‐negative breast cancer and negligible systemic toxicity. This facile and versatile nanoplatform provides a promising strategy to cooperatively activate antitumor immunity for potentiated chemo‐immunotherapy.
Robust Thiazole‐Linked Covalent Organic Frameworks with Post‐Modified Azobenzene Groups: Photo‐Regulated Dye Adsorption and Separation
Authors: Zhao Yanli , Tao Xinfeng , Xu Binbin , Liu Wenbin , Lin Shaoliang
Published: March 2024

Due to the intrinsic porosity and photo‐regulated pore environment, azobenzene (Azo) functionalized covalent organic frameworks (COFs) show great potential for contaminant removal. However, the stability and degree of functionality of the COFs greatly affect the porosity and subsequent adsorption capacity and selectivity. Herein, a highly stable thiazole‐linked COF containing phenolic hydroxyl groups (OH‐COF) is constructed by using 4,4′,4′‐(1,3,5‐triazine‐2,4,6‐triyl)trianiline and 2,5‐dihydroxyterephthalaldehyde in the presence of sulfur, which shows high crystallinity and specific surface. Azo‐functionalized COFs ((Azo)x‐COFs) are prepared by grafting different amounts azobenzene groups onto OH‐COF through post‐modification, whose aperture is conveniently tuned by the grafted azobenzene amount. The pore size of (Azo)x‐COFs also can be reversibly adjusted under UV and visible light irradiation without affecting the crystallinity. Appropriate amount of Azo‐grafted (Azo)0.1‐COF possessed a high adsorption capacity (1216.93 mg g−1) to Congo red (CR). While the adsorption capacity of (Azo)1.0‐COF to CR significantly increased 2.9 times to reach 1489.96 mg g−1 after UV irradiation. (Azo)1.0‐COF also can selectively separate dye molecules with different sizes based on photo‐regulated pore size, showing excellent reversibility and reusability. As such, the ability to photo‐regulate the adsorption and interception of (Azo)x‐COFs highlights their significance in functioning as smart porous nanomaterials for pollutant removal and water purification.
Low‐Dose and Stable X‐Ray Imaging Enabled by Low‐Dimensional Dion‐Jacobson Perovskites
Authors: Xin Deyu , Zhang Min , Fan Zhenghui , Yang Yujie , Dong Siyin , Lei Lin , Zhao Wei , Lin Qianqian , Zheng Xiaojia
Published: March 2024

Metal halide perovskites have emerged as highly promising candidates for next‐generation X‐ray detectors due to their facile and low‐cost processability, high attenuation coefficient, and tunable optoelectrical properties. In this work, quasi‐2D Dion‐Jacobson (DJ) perovskites are introduced in a flat panel X‐ray imager (FPXI) for X‐ray imaging. This study demonstrates that the diammonium interlayers in DJ perovskites play a key role in enhancing structural stability, suppressing ion migration, and improving charge transport. As a result, DJ perovskite‐based X‐ray FPXIs achieve a sensitivity of 18000 µC Gyair−1 cm−2, a low detection limit of 5.7 nGyair s−1, representing performance comparable to that of state‐of‐the‐art 3D perovskite FPXIs. Thanks to the decrease in the signal crosstalk effect of the FPXIs, a high spatial resolution of 0.54 line‐pair‐per‐pixel is achieved, which is higher than that of 3D perovskite FPXIs. Remarkably, high‐quality X‐ray imaging is achieved at a total dose of 20 µGyair, which is only 1/5 of the dose typically used in commercial equipment. This work not only provides valuable insights and guidance for the fabrication of 2D DJ perovskite X‐ray detectors but also lays the groundwork for the adoption of high‐performance, stable DJ perovskite imagers as novel flat‐panel X‐ray detectors.
One‐Pot Synthesis of Luminescent and Photothermal Carbon Boron‐Nitride Quantum Dots Exhibiting Cell Damage Protective Effects
Authors: Consoli Grazia M. L. , Maugeri Ludovica , Musso Nicolò , Gulino Antonino , D'Urso Luisa , Bonacci Paolo , Buscarino Gianpiero , Forte Giuseppe , Petralia Salvatore
Published: March 2024

Zero‐dimensional boron nitride quantum dots (BNQDs) are arousing interest for their versatile optical, chemical, and biochemical properties. Introducing carbon contents in BNQDs nanostructures is a great challenge to modulate their physicochemical properties. Among the carbon moieties, phenolic groups have attracted attention for their biochemical properties and phenol‐containing nanomaterials are showing great promise for biomedical applications. Herein, the first example of direct synthesis of water dispersible BNQDs exposing phenolic and carboxylic groups is presented. The carbon‐BNQDs are prepared in a single‐step by solvent‐assisted reaction of urea with boronic reagents and are characterized by optical absorption, luminescence, Raman, Fourier transform infrared and NMR spectroscopy, X‐ray photoelectron spectroscopy, dynamic light scattering, and atomic force microscopy. The carbon‐BNQDs exhibit nanodimension, stability, high photothermal conversion efficiency, pH‐responsive luminescence and Z‐potential. The potential of the carbon‐BNQDs to provide photothermal materials in solid by embedding in agarose substrate is successfully investigated. The carbon‐BNQDs exhibit biocompatibility on colorectal adenocarcinoma cells (Caco‐2) and protective effects from chemical and oxidative stress on Caco‐2, osteosarcoma (MG‐63), and microglial (HMC‐3) cells. Amplicon mRNA‐seq analyses for the expression of 56 genes involve in oxidative‐stress and inflammation are performed to evaluate the molecular events responsible for the cell protective effects of the carbon‐BNQDs.
Ultrasound‐Activated Piezoelectric Nanoparticles Trigger Microglia Activity Against Glioblastoma Cells
Authors: Montorsi Margherita , Pucci Carlotta , De Pasquale Daniele , Marino Attilio , Ceccarelli Maria Cristina , Mazzuferi Martina , Bartolucci Martina , Petretto Andrea , Prato Mirko , Debellis Doriana , De Simoni Giorgio , Pugliese Giammarino , Labardi Massimiliano , Ciofani Gianni
Published: March 2024

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug‐resistant progression. GBM “builds” around its primary core a genetically heterogeneous tumor‐microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma‐associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti‐inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth. Conversely, “classically activated” M1 microglia could provide proinflammatory and antitumorigenic activity, expected to exert a beneficial effect in defeating glioblastoma. In this work, an immunotherapy approach based on proinflammatory modulation of the GAM phenotype is proposed, through a controlled and localized electrical stimulation. The developed strategy relies on the wireless ultrasonic excitation of polymeric piezoelectric nanoparticles coated with GBM cell membrane extracts, to exploit homotypic targeting in antiglioma applications. Such camouflaged nanotransducers locally generate electrical cues on GAM membranes, activating their M1 phenotype and ultimately triggering a promising anticancer activity. Collected findings open new perspectives in the modulation of immune cell activities through “smart” nanomaterials and, more specifically, provide an innovative auspicious tool in glioma immunotherapy.
In Vivo Microrheology Reveals Local Elastic and Plastic Responses Inside 3D Bacterial Biofilms
Authors: Ohmura Takuya , Skinner Dominic J. , Neuhaus Konstantin , Choi Gary P. T. , Dunkel Jörn , Drescher Knut
Published: March 2024

Bacterial biofilms are highly abundant 3D living materials capable of performing complex biomechanical and biochemical functions, including programmable growth, self‐repair, filtration, and bioproduction. Methods to measure internal mechanical properties of biofilms in vivo with spatial resolution on the cellular scale have been lacking. Here, thousands of cells are tracked inside living 3D biofilms of the bacterium Vibrio cholerae during and after the application of shear stress, for a wide range of stress amplitudes, periods, and biofilm sizes, which revealed anisotropic elastic and plastic responses of both cell displacements and cell reorientations. Using cellular tracking to infer parameters of a general mechanical model, spatially‐resolved measurements of the elastic modulus inside the biofilm are obtained, which correlate with the spatial distribution of the polysaccharides within the biofilm matrix. The noninvasive microrheology and force‐inference approach introduced here provides a general framework for studying mechanical properties with high spatial resolution in living materials.
Toward the High‐Voltage Stability of Layered Oxide Cathodes for Sodium‐Ion Batteries: Challenges, Progress, and Perspectives
Authors: Chen Zhigao , Deng Yuyu , Kong Ji , Fu Weibin , Liu Chenyang , Jin Ting , Jiao Lifang
Published: March 2024

Sodium‐ion batteries (SIBs) have garnered significant attention as ideal candidates for large‐scale energy storage due to their notable advantages in terms of resource availability and cost‐effectiveness. However, there remains a substantial energy density gap between SIBs and commercially available lithium‐ion batteries (LIBs), posing challenges to meeting the requirements of practical applications. The fabrication of high‐energy cathodes has emerged as an efficient approach to enhancing the energy density of SIBs, which commonly requires cathodes operating in high‐voltage regions. Layered oxide cathodes (LOCs), with low cost, facile synthesis, and high theoretical specific capacity, have emerged as one of the most promising candidates for commercial applications. However, LOCs encounter significant challenges when operated in high‐voltage regions such as irreversible phase transitions, migration and dissolution of metal cations, loss of reactive oxygen, and the occurrence of serious interfacial parasitic reactions. These issues ultimately result in severe degradation in battery performance. This review aims to shed light on the key challenges and failure mechanisms encountered by LOCs when operated in high‐voltage regions. Additionally, the corresponding strategies for improving the high‐voltage stability of LOCs are comprehensively summarized. By providing fundamental insights and valuable perspectives, this review aims to contribute to the advancement of high‐energy SIBs.
Customized Enhancement of Thermal Sensitivity of Tumors at Different Subcutaneous Depths by Multichannel Lanthanide Nanocomposites
Authors: Liu Yuxin , Wei Zheng , Zhang Jieying , Xu Yang , Zhou Jing , Ma Zhanfang , Mutti Francesco G. , Zhang Hong , Zhu Xingjun , Loeffler Felix F.
Published: March 2024

The photothermal therapeutic effect on tumors located at different subcutaneous depths varies due to the attenuation of light by tissue. Here, based on the wavelength‐dependent optical attenuation properties of tissues, the tumor depth is assessed using a multichannel lanthanide nanocomposite. A zeolitic imidazolate framework (ZIF‐8)‐coated nanocomposite is able to deliver high amounts of the hydrophilic heat shock protein 90 inhibitor epigallocatechin gallate through a hydrogen‐bonding network formed by the encapsulated highly polarized polyoxometalate guest. It is superior to both bare and PEGylated ZIF‐8 for drug delivery. With the assessment of tumor depth and accumulated amount of nanocomposite by fluorescence, an irradiation prescription can be customized to release sufficient HSP90 inhibitor and generate heat for sensitized photothermal treatment of tumors, which not only ensured therapeutic efficacy but also minimized damage to the surrounding tissues.
Electrocorticogram (ECoG): Engineering Approaches and Clinical Challenges for Translational Medicine
Authors: Moon Hyunmin , Kwon Jii , Eun Jonghee , Chung Chun Kee , Kim June Sic , Chou Namsun , Kim Sohee
Published: March 2024

Electrocorticogram (ECoG) is an electrophysiological signal that results from the summation of neuronal activity near the cortical surface. To record ECoG signals, the scalp and skull are surgically opened and electrodes are placed on the cortical surface, either epidurally or subdurally. Owing to its improved spatiotemporal resolution and signal quality compared with electroencephalography, it is widely used to diagnose and treat neurological disorders in clinical settings for several decades, despite the invasiveness of ECoG. Recently, ECoG is applied in research to explore brain functions and connectivity, brain‐computer interfaces, and brain‐machine interfaces. In addition to the need for ECoG in neuroscience research, ECoG devices have advanced in terms of materials, fabrication, and function to overcome the limitations of commercially available ECoG arrays. Here, the conventional use of ECoG in clinical medicine, the new applications of ECoG in basic neuroscience research, and the future challenges in translating recent developments in ECoG devices for clinical use are described.
Hypoxic Exosomal circPLEKHM1‐Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis
Authors: Wang Dongliang , Wang Shuoer , Jin Mingming , Zuo Yan , Wang Jianpeng , Niu Ya , Zhou Qian , Chen Jiwei , Tang Xinru , Tang Wenxuan , Liu Xiyu , Yu Hang , Yan Wangjun , Wei Huan‐Huan , Huang Gang , Song Shaoli , Tang Shuang
Published: March 2024

Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell‐derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non‐small cell lung cancer (NSCLC) cells, a hypoxia‐induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1‐eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1‐targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA‐mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.
A High‐Density Hydrogen Bond Locking Strategy for Constructing Anisotropic High‐Strength Hydrogel‐Based Meniscus Substitute
Authors: Zhang Qian , Yang Xuxuan , Wang Kuan , Xu Ziyang , Liu Wenguang
Published: March 2024

Mimicking anisotropic features is crucial for developing artificial load‐bearing soft tissues such as menisci). Here, a high‐density hydrogen bond locking (HDHBL) strategy, involving preloading a poly(N‐acryloylsemicarbazide) (PNASC) hydrogel with an aqueous solution containing a hydrogen bond breaking agent, followed by water exchange, to fabricate anisotropic high‐strength hydrogels are proposed. During this process, multiple high‐density hydrogen bonds of the PNASC network are re‐established, firmly freezing oriented molecular chains, and creating a network with an anisotropic microstructure. The resulting anisotropic hydrogels exhibit superior mechanical properties: tensile strength over 9 MPa, Young's modulus exceeding 120 MPa along the orientation direction, and fatigue thresholds exceeding 1900 J m−2. These properties meet the mechanical demands for load‐bearing tissue substitutes compared to other reported anti‐fatigue hydrogels. This strategy enables the construction of an anisotropic meniscal scaffold composed of circumferentially oriented microfibers by preloading a digital light processing‐3D printed PNASC hydrogel‐based wedge‐shaped construct with a resilient poly(N‐acryloyl glycinamide) hydrogel. The 12‐week implantation of a meniscus scaffold in rabbit knee joints after meniscectomy demonstrates a chondroprotective effect on the femoral condyle and tibial plateau, substantially ameliorating the progression of osteoarthritis. The HDHBL strategy enables the fabrication of various anisotropic polymer hydrogels, broadening their scope of application.
Undiagnosed Disease Network collaborative approach in diagnosing rare disease in a patient with a mosaic CACNA1D variant
Authors: Ezell Kimberly M. , Tinker Rory J. , Furuta Yutaka , Gulsevin Alican , Bastarache Lisa , Hamid Rizwan , Cogan Joy D. , Rives Lynette , Neumann Serena , Corner Brian , Kozuria Mary , Phillips John A. ,   the Undiagnosed Diseases Network
Published: March 2024

The Undiagnosed Disease Network (UDN) is comprised of clinical and research experts collaborating to diagnose rare disease. The UDN is funded by the National Institutes of Health and includes 12 different clinical sites (About Us, 2022). Here we highlight the success of collaborative efforts within the UDN Clinical Site at Vanderbilt University Medical Center (VUMC) in utilizing a cohort of experts in bioinformatics, structural biology, and genetics specialists in diagnosing rare disease. Our UDN team identified a de novo mosaic CACNA1D variant c.2299T>C in a 5‐year‐old female with a history of global developmental delay, dystonia, dyskinesis, and seizures. Using a collaborative multidisciplinary approach, our VUMC UDN team diagnosed the participant with Primary Aldosteronism, Seizures, and Neurologic abnormalities (PASNA) OMIM: 615474 due to a rare mosaic CACNA1D variant (O'Neill, 2013). Interestingly, this patient was mosaic, a phenotypic trait previously unreported in PASNA cases. This report highlights the importance of a multidisciplinary approach in diagnosing rare disease.
Copper(I)‐Catalyzed Enantioselective Synthesis of Chiral Cyclohexenylallenes and Transfer of Axial to Center Chirality by Ytterbium (III) Catalyzed [4+2] Cycloaddition
Authors: Satyanarayana Iddum , Mohan Lakavathu , Periasamy Mariappan
Published: March 2024

Chiral cyclohexenylallenes are readily accessed from 1‐enynes, aldehydes and chiral secondary amines in good yields (up to 79 % yield) with excellent enantioselectivities (up to 99 % ee), through CuI catalyzed the formation of chiral propargylamine intermediates. Subsequent Yb(OTf)3 catalyzed [4+2] cycloaddition reaction of cyclohexylallenes with the dienophiles tetracyanoethylene and diethyl acetylenedicarboxylate afforded the corresponding bicyclic products in 69–75 % yield and 84–90 % ee.
Visible‐Light Activation of Diorganyl Bis(pyridylimino) Isoindolide Aluminum(III) Complexes and Their Organometallic Radical Reactivity
Authors: Wenzel Jonas O. , Werner Johannes , Allgaier Alexander , van Slageren Joris , Fernández Israel , Unterreiner Andreas‐Neil , Breher Frank
Published: March 2024

We report on the synthesis and characterization of a series of (mostly) air‐stable diorganyl bis(pyridylimino) isoindolide (BPI) aluminum complexes and their chemistry upon visible‐light excitation. The redox non‐innocent BPI pincer ligand allows for efficient charge transfer homolytic processes of the title compounds. This makes them a universal platform for the generation of carbon‐centered radicals. The photo‐induced homolytic cleavage of the Al−C bonds was investigated by means of stationary and transient UV/Vis spectroscopy, spin trapping experiments, as well as EPR and NMR spectroscopy. The experimental findings were supported by quantum chemical calculations. Reactivity studies enabled the utilization of the aluminum complexes as reactants in tin‐free Giese‐type reactions and carbonyl alkylations under ambient conditions, which both indicated radical‐polar crossover behavior. A deeper understanding of the physical fundamentals and photochemical process was provided, furnishing in turn a new strategy to control the reactivity of bench‐stable aluminum organometallics.
Hydrogen Evolution in Neutral Media by Differential Intermediate Binding at Charge‐Modulated Sites of a Bimetallic Alloy Electrocatalyst
Authors: Maji Mamoni , Dutta Supriti , Jena Rohan , Dey Anupam , Maji Tapas Kumar , Pati Swapan K. , Bhattacharyya Sayan
Published: March 2024

The energy barrier to dissociate neutral water has been lowered by the differential intermediate binding on the charge‐modulated metal centers of Co85Mo15 sheets supported on Ni‐foam (NF), where the overpotential for hydrogen evolution reaction (HER) in 1 M phosphate buffer solution (PBS) is only 50±9 mV at −10 mA cm−2. It has a turnover frequency (TOF) of 0.18 s−1, mass activity of 13.2 A g−1 at −200 mV vs. reversible hydrogen electrode (RHE), and produces 16 ml H2 h−1 at −300 mV vs. RHE, more than double that of 20 % Pt/C. The Moδ+ and Coδ− sites adsorb OH*, and H*, respectively, and the electron injection from Co to H−O−H cleaves the O−H bond to form the Mo−OH* intermediate. Operando spectral analyses indicate a weak H‐bonded network for facilitating the H2O*/OH* transport, and a potential‐induced reversal of the charge density from Co to the more electronegative Mo, because of the electron withdrawing Co−H* and Mo−OH* species. Co85Mo15/NF can also drive the complete electrolysis of neutral water at only 1.73 V (10 mA cm−2). In alkaline, and acidic media, it demonstrates a Pt‐like HER activity, accomplishing −1000 mA cm−2 at overpotentials of 161±7, and 175±22 mV, respectively.
In‐depth investigation and industry plan for enhancing surface finishing of 3D printed polymer composite components: A critical review
Authors: Karimi Naeim , Bozorgnia Tabary Seyed Amir Ali , Fayazfar Haniyeh (Ramano)
Published: March 2024

Additive manufacturing (AM) is pivotal in modern manufacturing, allowing diverse materials to create functional parts. Polymer composites, with superior properties like enhanced mechanics and conductivity, are highly regarded. Fused deposition modeling (FDM) is a favored, cost‐effective AM technique. Despite popularity, FDM struggles with poor surface quality, impacting final part properties. This challenge affects composite part performance, prompting a need for surface quality enhancements in AM processes, like FDM. The review explores essential post‐treatments required to optimize composite parts for various applications. It examines surface finishing techniques for FDM 3D printed polymeric composites, categorizing them into chemical, thermal, and physical methods. Recent research is extensively analyzed, offering a comprehensive guide for academia and industry. The review covers diverse aspects, including properties, surface morphology, electrical conductivity, and mechanical properties pre‐ and post‐finishing methods. Additionally, it summarizes leading companies worldwide providing surface finishing services for 3D printed polymer parts. Discussions on future trends, challenges, and research gaps in this field are included, emphasizing its significance in refining surface finishing methods for FDM 3D‐printed polymeric composites and encouraging broader industrial adoption of AM. This overview serves as a crucial roadmap for engineers, scientists, customers, and companies interested in surface finishing services.
Ligand‐free MnBr2‐Catalyzed Chemo‐ and Stereoselective Hydroboration of Terminal Alkynes
Authors: Pawar Rameshwar B. , Karmur Mital H. , Punji Benudhar
Published: March 2024

Developing simple and benign protocols for synthesizing alkenylboronates is crucial as they are synthetically valuable compounds in various organic transformations. In this work, we report a straightforward ligand‐free protocol for synthesizing alkenylboronates via atom‐economical hydroboration of alkynes with HBpin catalyzed by a manganese salt. The reaction shows a high level of chemo and regioselectivity for the terminal alkynes and exclusively produces E‐selective alkenylboronates. The hydroboration scope is vast, with the resilience of a range of synthetically beneficial functionalities, such as halides, ether, alkenyl, silyl and thiophenyl groups. This reaction proceeds through the involvement of a metal‐hydride intermediate. The developed alkenylboronate can be smoothly converted to useful C‐C, C‐N and C‐I bond‐forming reactions.
Sequential extraction of hesperidin, pectin, lignin, and cellulose from orange peels: towards valorization of agro‐waste
Authors: de Castro Symone C. , Stanisic Danijela , Tasic Ljubica
Published: March 2024

To maximize the reuse of citrus fruit processing waste, which is generated in large amounts due to juice production, this work shows the results of a new renewable approach for the extraction of high‐added‐value compounds present in orange biomass, specifically in orange peels (OP). The method is based on the use of diluted Ca2+, acid, and base solutions for the extraction of hesperidin (HSD), pectin, lignin, and cellulose sequentially, without generating any organic solid waste at the end, and without the need for air drying the starting biomass. Good yields of hesperidin were recovered (~1.56%), with excellent purity (up to 95%), as well as lignin (yield ~2.2%) and cellulose (yield ~12%). Pectin obtained by this process showed a high amount of galacturonic acid (~88%) and a low degree of methylation (~16%). All products were thoroughly characterized by applying Fourier transform infrared (FTIR) spectroscopy and solid‐state cross‐polarization/magic angle spinning carbon‐13 nuclear magnetic resonance spectroscopy (CP/MAS 13C‐NMR). The products recovered from OP can be applied in a wide array of fields, such as food, medicine, and pharmaceuticals, among others.
Unique biomedical application of fluorescence derivatization based on palladium‐catalyzed coupling reactions for HPLC analysis of pharmaceuticals and biomolecules
Authors: El‐Maghrabey Mahmoud , Kishikawa Naoya , Kuroda Naotaka
Published: March 2024

Palladium‐catalyzed coupling reactions are versatile and powerful tools for the construction of carbon–carbon bonds in organic synthesis. Although these reactions have favorable features that proceed selectively in mild reaction conditions using aqueous organic solvents, no attention has been given to their application in the field of biomedical analysis. Therefore, we focused on these reactions and evaluated the scope and limitations of their analytical performance. In this review, we describe the pros and cons and future trends of fluorescence derivatization of pharmaceuticals and biomolecules based on palladium‐catalyzed coupling reactions such as Suzuki–Miyaura coupling, Mizoroki–Heck coupling, and Sonogashira coupling reactions for HPLC analysis.
Enhanced Ceftriaxone Determination using a Glassy Carbon Electrode Modified with a Cr‐Based Metal‐Organic Framework Film Stabilized by β‐Cyclodextrin Polymer
Authors: Bougna Honorine Hortense Tchoumi , Dongmo Liliane Medonbou , Jiokeng Sherman Lesly Zambou , Ntep Tobie Matemb Ma , Mbokou Serge Foukmeniok , Janiak Christoph , Djouaka Rousseau , Tonle Ignas Kenfack
Published: March 2024

A selective amperometric sensor was developed to detect the antibiotic ceftriaxone (CEF) using a composite film of poly(β‐cyclodextrin) and a metal‐organic framework (MOF). The sensor was obtained by electro‐polymerizing β‐cyclodextrin (β‐CD) onto a glassy carbon electrode (GCE) previously coated with a MIL‐101(Cr) MOF film. This design prevents MOF particles’ loss during extended electrode use. The MOF was structurally characterized using scanning electron microscopy, X‐ray diffraction, N2 adsorption‐desorption isotherms (BET method) and FTIR spectroscopy. Electrochemical impedance spectroscopy and cyclic voltammetry were used to assess the GCE/MIL‐101(Cr)‐pβ‐CD sensor, revealing reduced charge transfer resistance and enhanced sensitivity to CEF. Differential pulse voltammetry was then employed for CEF determination. Under optimized conditions, the sensor exhibited high sensitivity, a broad linear working range of 0.5 to 6 μM (R2=0.991), and a low detection limit of 0.34±0.02 μM (0.19±0.01 mg L−1). The selectivity of the sensor was evaluated in the presence of potential interferences such as organic acids, antibiotics and selected ions expected to affect the CEF signal. In an application to quantify a pharmaceutical formulation, the sensor displayed an impressive recovery rate of 98.3 % compared to results obtained using high‐performance liquid chromatography.
Biopolymers‐Based Proton Exchange Membranes For Fuel Cell Applications: A Comprehensive Review
Authors: Abouricha Souhaib , Aziam Hasna , Noukrati Hassan , Sel Ozlem , Saadoune Ismael , Lahcini Mohammed , Youcef Hicham Ben
Published: March 2024

Nafion has been dominating the proton exchange membrane (PEM) market because of its adequacy for the proton exchange operation. However, because of its high cost, low performance at low relative humidity, and finally environmental unfriendliness, researchers have been developing and working on Nafion alternatives. In this review, we assess how biopolymers present an opportunity as an eco‐friendly material able to replace the conventional Nafion membrane in proton exchange membrane fuel cells (PEMFC). Chitosan and cellulose were the most studied in literature owing to their abundance in nature, low cost, and high affinity for water, which are sought‐after properties for PEM. In addition to that, their ease of modification through their hydroxyl or amine groups represents an opportunity to further enhance their characteristics and thus meet the criteria of diverse applications. The use of biopolymers as an adequate PEM is facing many challenges. Having a practical proton conductivity and securing the physicochemical stability of the biopolymers in fuel cell operating conditions are two of the most important challenges to overcome. Promising strategies to simultaneously address these challenges such as crosslinking, making interpenetrated networks, and making blends and composites are reported.
Pressure‐Induced Structural, Optical and Magnetic Modifications in Lanthanide Single‐Molecule Magnets
Authors: Pointillart Fabrice , Le Guennic Boris , Cador Olivier
Published: March 2024

Lanthanide Single‐Molecule Magnets are fascinating objects that break magnetic performance records with observable magnetic bistability at the boiling temperature of liquid nitrogen, paving the way for potential applications in high‐density data storage. The switching of lanthanide SMM has been successfully achieved using several external stimuli such as redox reaction, pH titration, light irradiation or solvation/desolvation thanks to the high sensitivity of the magnetic anisotropy to any structural change in the lanthanide surrounding. Nevertheless, the use of applied high pressure as an external stimulus is largely underused, especially considering that it can be combined with high pressure X‐ray diffraction to establish a complementary structure‐property relationship. This Concept article summarizes the few relevant examples of investigations of lanthanide SMMs under applied high pressure, provides conclusions on the effect of such stimulus on molecular structures and magnetic anisotropy, and finally draws perspective on the future development of magnetic measurements under applied pressure.
Optimized Recombinant Expression and Purification of the SARS‐CoV‐2 Polymerase Complex
Authors: Podadera Ana , Campo Lucas , Rehman Fasih , Kolobaric Nikola , Zutic Adriana , Ng Kenneth K‐S.
Published: March 2024

An optimized protocol has been developed to express and purify the core RNA‐dependent RNA polymerase (RdRP) complex from the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). The expression and purification of active core SARS‐CoV‐2 RdRp complex is challenging due to the complex multidomain fold of nsp12, and the assembly of the multimeric complex involving nsp7, nsp8, and nsp12. Our approach adapts a previously published method to express the core SARS‐CoV‐2 RdRP complex in Escherichia coli and combines it with a procedure to express the nsp12 fusion with maltose‐binding protein in insect cells to promote the efficient assembly and purification of an enzymatically active core polymerase complex. The resulting method provides a reliable platform to produce milligram amounts of the polymerase complex with the expected 1:2:1 stoichiometry for nsp7, nsp8, and nsp12, respectively, following the removal of all affinity tags. This approach addresses some of the limitations of previously reported methods to provide a reliable source of the active polymerase complex for structure, function, and inhibition studies of the SARS‐CoV‐2 RdRP complex using recombinant plasmid constructs that have been deposited in the widely accessible Addgene repository. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Expression and production of SARS‐CoV‐2 nsp7, nsp8, and nsp12 in E. coli cells

Support Protocol: Establishment and maintenance of insect cell cultures

Basic Protocol 2: Generation of recombinant baculovirus in Sf9 cells and production of nsp12 fusion protein in T. ni cells

Basic Protocol 3: Purification of the SARS‐CoV‐2 core polymerase complex
A Step‐by‐Step Guide for the Production of Recombinant Fluorescent TAT‐HA‐Tagged Proteins and their Transduction into Mammalian Cells
Authors: Anny Christer Abou , Nouaille Sébastien , Fauré Régis , Schulz Céline , Spriet Corentin , Huvent Isabelle , Biot Christophe , Lefebvre Tony
Published: March 2024

Investigating the function of target proteins for functional prospection or therapeutic applications typically requires the production and purification of recombinant proteins. The fusion of these proteins with tag peptides and fluorescently derived proteins allows the monitoring of candidate proteins using SDS‐PAGE coupled with western blotting and fluorescent microscopy, respectively. However, protein engineering poses a significant challenge for many researchers. In this protocol, we describe step‐by‐step the engineering of a recombinant protein with various tags: TAT‐HA (trans‐activator of transduction‐hemagglutinin), 6×His and EGFP (enhanced green fluorescent protein) or mCherry. Fusion proteins are produced in E. coli BL21(DE3) cells and purified by immobilized metal affinity chromatography (IMAC) using a Ni‐nitrilotriacetic acid (NTA) column. Then, tagged recombinant proteins are introduced into cultured animal cells by using the penetrating peptide TAT‐HA. Here, we present a thorough protocol providing a detailed guide encompassing every critical step from plasmid DNA molecular assembly to protein expression and subsequent purification and outlines the conditions necessary for protein transduction technology into animal cells in a comprehensive manner. We believe that this protocol will be a valuable resource for researchers seeking an exhaustive, step‐by‐step guide for the successful production and purification of recombinant proteins and their entry by transduction within living cells. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: DNA cloning, molecular assembly strategies, and protein production

Basic Protocol 2: Protein purification

Basic Protocol 3: Protein transduction in mammalian cells