bluuebunny/crossref_metadata_2025 huggingface dataset:
The quantity and quality of cardiovascular fat at mid‐life and future cognitive performance among women: The SWAN cardiovascular fat ancillary study
Authors: Qi Meiyuzhen , Janssen Imke , Barinas‐Mitchell Emma , Budoff Matthew , Brooks Maria M. , Karlamangla Arun S. , Derby Carol A. , Chang Chung‐Chou H. , Shields Kelly J. , El Khoudary Samar R.
Published: May 2023

INTRODUCTION

Cardiovascular fat is a novel risk factor that may link to dementia. Fat volume and radiodensity are measurements of fat quantity and quality, respectively. Importantly, high fat radiodensity could indicate healthy or adverse metabolic processes.

METHODS

The associations of cardiovascular fat (including epicardial, paracardial, and thoracic perivascular adipose tissue [PVAT]) quantity and quality assessed at mean age of 51 with subsequent cognitive performance measured repeatedly over 16 years of follow‐up were examined using mixed models among 531 women.

RESULTS

Higher thoracic PVAT volume was associated with a higher future episodic memory (β[standard error (SE)] = 0.08 [0.04], P = 0.033), while higher thoracic PVAT radiodensity with lower future episodic (β[SE] = −0.06 [0.03], P = 0.045) and working (β[SE] = −0.24 [0.08], P = 0.003) memories. The latter association is prominent at higher volume of thoracic PVAT.

DISCUSSION

Mid‐life thoracic PVAT may have a distinct contribution to future cognition possibly due to its distinct adipose tissue type (brown fat) and anatomical proximity to the brain circulation.

HIGHLIGHTS

Higher mid‐life thoracic perivascular adipose tissue (thoracic PVAT) volume is related to a better future episodic memory in women.

Higher mid‐life thoracic PVAT radiodensity is related to worse future working and episodic memories.

Negative association of high thoracic PVAT radiodensity with working memory is prominent at higher thoracic PVAT volume.

Mid‐life thoracic PVAT is linked to future memory loss, an early sign of Alzheimer's disease.

Mid‐life women's epicardial and paracardial fat are not related to future cognition.
Longitudinal changes in Alzheimer's‐related plasma biomarkers and brain amyloid
Authors: Bilgel Murat , An Yang , Walker Keenan A. , Moghekar Abhay R. , Ashton Nicholas J. , Kac Przemysław R. , Karikari Thomas K. , Blennow Kaj , Zetterberg Henrik , Jedynak Bruno M. , Thambisetty Madhav , Ferrucci Luigi , Resnick Susan M.
Published: May 2023

INTRODUCTION

Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer's progression assessment strategies.

METHODS

We examined the temporal order of changes in plasma amyloid‐β ratio (), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios (, ) relative to 11C‐Pittsburgh compound B (PiB) positron emission tomography (PET) cortical amyloid burden (PiB−/+). Participants (n = 199) were cognitively normal at index visit with a median 6.1‐year follow‐up.

RESULTS

PiB groups exhibited different rates of longitudinal change in . Change in brain amyloid correlated with change in GFAP (r = 0.5, 95% CI = [0.26, 0.68]). The greatest relative decline in (−1%/year) preceded brain amyloid positivity by 41 years (95% CI = [32, 53]).

DISCUSSION

Plasma may begin declining decades prior to brain amyloid accumulation, whereas p‐tau ratios, GFAP, and NfL increase closer in time.

HIGHLIGHTS

Plasma declines over time among PiB− but does not change among PiB+.

Phosphorylated‐tau to Aβ42 ratios increase over time among PiB+ but do not change among PiB−.

Rate of change in brain amyloid is correlated with change in GFAP and neurofilament light chain.

The greatest decline in may precede brain amyloid positivity by decades.
Chemical Modification of a Bacterial Siderophore by a Competitor in Dual‐Species Biofilms
Authors: Uzi‐Gavrilov Shaked , Tik Zohar , Sabti Omer , Meijler Michael M.
Published: May 2023

Chemical communication between competing bacteria in multi‐species environments often enables both species to adapt and survive, and perhaps even thrive. P. aeruginosa and S. aureus are two bacterial pathogens found in natural biofilms, especially in the lungs of cystic fibrosis (CF) patients, where recent studies showed that there is often cooperation between the two species, leading to increased disease severity and antibiotic resistance. However, the mechanisms behind this cooperation are poorly understood. In this study, we analyzed co‐cultured biofilms in various settings, and we applied untargeted mass spectrometry‐based metabolomics analyses, combined with synthetic validation of candidate compounds. We unexpectedly discovered that S. aureus can convert pyochelin into pyochelin methyl ester, an analogue of pyochelin with reduced affinity for iron (III). This conversion allows S. aureus to coexist more readily with P. aeruginosa and unveils a mechanism underlying the formation of robust dual‐species biofilms.
Highly Selective Catalytic Oxi‐upcycling of Polyethylene to Aliphatic Dicarboxylic Acid under a Mild Hydrogen‐Free Process
Authors: Wang Kaili , Jia Rongrong , Cheng Ping , Shi Liyi , Wang Xiang , Huang Lei
Published: May 2023

A low‐temperature hydrogen‐free process for upcycling polyethylene (PE) plastics into aliphatic dicarboxylic acid is developed using a heterogeneous catalyst Ru/TiO2. The low‐density PE (LDPE) conversion can reach 95 % in 24 h under a pressure of 1.5 MPa air at 160 °C with 85 % of the liquid product yield, which mainly is low molecular weight aliphatic dicarboxylic acid. Excellent performances can be also achieved for different PE feedstocks. This catalytic oxi‐upcycling process paving a new way of upcycling polyethylene waste.
Dynamic Axial‐to‐Helical Communication Mechanism in Poly[(allenylethynylenephenylene)acetylene]s under External Stimuli
Authors: Lago‐Silva María , Cid María Magdalena , Quiñoá Emilio , Freire Félix
Published: May 2023

Helix inversion in chiral dynamic helical polymers is usually achieved by conformational changes at the pendant groups induced through external stimuli. Herein, a different mechanism of helix inversion in poly(phenylacetylene)s (PPAs) is presented, based on the activation/deactivation of supramolecular interactions. We prepared poly[(allenylethynylenephenylene)acetylene]s (PAEPAs) in which the pendant groups are conformationally locked chiral allenes. Therefore, their substituents are placed in specific spatial orientations. As a result, the screw sense of a PAEPA is fixed by the allenyl substituent with the optimal size/distance relationship to the backbone. This helical sense command can be surpassed by supramolecular interactions between another substituent on the allene and appropriate external stimuli, such as amines. So, a helix inversion occurs through a novel axial‐to‐helical communication mechanism, opening a new scenario for taming the helices of chiral dynamic helical polymers.
Chemically Gradient Hydrogen‐Bonded Organic Framework Crystal Film
Authors: Mohammed Abdul Khayum , Raya Jésus , Pandikassala Ajmal , Addicoat Matthew A. , Gaber Safa , Aslam Mohamed , Ali Liaqat , Kurungot Sreekumar , Shetty Dinesh
Published: May 2023

Hydrogen‐bonded organic frameworks (HOFs) are ordered supramolecular solid structures, however, nothing much explored as centimetre‐scale self‐standing films. The fabrication of such crystals comprising self‐supported films is challenging due to the limited flexibility and interaction of the crystals, and therefore studies on two‐dimensional macrostructures of HOFs are limited to external supports. Herein, we introduce a novel chemical gradient strategy to fabricate a crystal‐deposited HOF film on an in situ‐formed covalent organic polymer film (Tam‐Bdca‐CGHOF). The fabricated film showed versatility in chemical bonding along its thickness from covalent to hydrogen‐bonded network. The kinetic‐controlled Tam‐Bdca‐CGHOF showed enhanced proton conductivity (8.3×10−5 S cm−1) compared to its rapid kinetic analogue, Tam‐Bdca‐COP (2.1×10−5 S cm−1), which signifies the advantage of bonding‐engineering in the same system.
Imaging the Footprint of Nanoscale Electrochemical Reactions for Assessing Synergistic Hydrogen Evolution
Authors: Godeffroy Louis , Ciocci Paolo , Ortiz Peña Nathaly , Alloyeau Damien , Noël Jean‐Marc , Lemineur Jean‐François , Kanoufi Frédéric
Published: May 2023

This work proposes a novel method for measuring the intrinsic activity of single metal‐based nanoparticles towards water reduction in neutral media at industrially relevant current densities. Instead of using gas nanobubbles as proxy, the method uses optical microscopy to track the local footprint of the reaction through the precipitation of metal hydroxide, which is associated to the local pH increase during electrocatalysis. The results show the electrocatalytic activities of different types of metal nanoparticles and bifunctionnal core‐shell nanostructures made of Ni and Pt, and demonstrate the importance of metal hydroxide nano‐shells in enhancing electrocatalysis. This method should be generalizable to any electrocatalytic reaction involving pH changes such as nitrate or CO2 reduction.
Profiling Phosphoproteome Landscape in Circulating Extracellular Vesicles from Microliters of Biofluids through Functionally Tunable Paramagnetic Separation
Authors: Sun Jie , Li Qing , Ding Yajie , Wei Dong , Hadisurya Marco , Luo Zhuojun , Gu Zhongze , Chen Bobin , Tao W. Andy
Published: May 2023

Many biological processes are regulated through dynamic protein phosphorylation. Monitoring disease‐relevant phosphorylation events in circulating biofluids is highly appealing but also technically challenging. We introduce here a functionally tunable material and a strategy, extracellular vesicles to phosphoproteins (EVTOP), which achieves one‐pot extracellular vesicles (EVs) isolation, extraction, and digestion of EV proteins, and enrichment of phosphopeptides, with only a trace amount of starting biofluids. EVs are efficiently isolated by magnetic beads functionalized with TiIV ions and a membrane‐penetrating peptide, octa‐arginine R8+, which also provides the hydrophilic surface to retain EV proteins during lysis. Subsequent on‐bead digestion concurrently converts EVTOP to TiIV ion‐only surface for efficient enrichment of phosphopeptides for phosphoproteomic analyses. The streamlined, ultra‐sensitive platform enabled us to quantify 500 unique EV phosphopeptides with only a few μL of plasma and over 1200 phosphopeptides with 100 μL of cerebrospinal fluid (CSF). We explored its clinical application of monitoring the outcome of chemotherapy of primary central nervous system lymphoma (PCNSL) patients with a small volume of CSF, presenting a powerful tool for broad clinical applications.
Surface‐Area Determination of Anisotropic Polymersomes by Amphiphilic Molecular Probe Loading
Authors: Li Wei , Zhang Shaohua , Rijpkema Sjoerd J. , Wilson Daniela A.
Published: May 2023

The surface area of anisotropic polymeric assemblies is a critical parameter concerning their properties. However, it is still a grand challenge for traditional techniques to determine the surface area. Here, a molecular probe loading (MPL) method is developed to measure the surface area of anisotropic polymersomes in the shape of tube, disc, and stomatocyte. This method uses an amphiphilic molecular probe, comprising hydrophobic pyrene as the anchor and hydrophilic tetraethylene glycol (EG4) as the float. The surface area of spherical polymersomes determined by dynamic light scattering is quantitatively correlated with the loading amount of probes, allowing the calculation of the average separation distance between the loaded probes. With the separation distance, we successfully determine the surface area of anisotropic polymersomes by measuring the loading amount. We envision that the MPL method will assist in the real‐time surface area characterization, enabling the customization of functions.
Enantioselective Synthesis of Biscyclopropanes Using Alkynes as Dicarbene Equivalents
Authors: Wang Chuntao , Wu Rui , Chen Kai , Zhu Shifa
Published: May 2023

Chiral biscyclopropanes are an important skeleton in many bioactive molecules. However, there are few routes to synthesize these molecules with high stereoselectivity due to the nature of multiple stereocenters. Herein, we report the first example of Rh2(II)‐catalyzed enantioselective synthesis of bicyclopropanes with alkynes as dicarbene equivalents. The bicyclopropanes with 4–5 vicinal stereocenters and 2–3 all‐carbon quaternary centers were constructed in excellent stereoselectivity. This protocol features high efficiency and excellent functional group tolerance. Moreover, the protocol was also extended to the cascaded cyclopropanation/cyclopropenation with excellent stereoselectivities. In these processes, both sp‐carbons of alkyne were converted into stereogenic sp3‐carbons. Experimental and density functional theory (DFT) calculations revealed that the cooperative weak hydrogen bonds between the substrates and the dirhodium catalyst may play key roles in this reaction.
Assembling a Heterobimetallic Actinide Metal‐Organic Framework by a Reaction‐Induced Preorganization Strategy
Authors: Mei Sen , Chen Lixi , Zhang Hailong , Li Zhiwei , Cheng Liwei , Lu Junhao , Li Xiaoqi , Yang Qian , Wang Yanlong , Liu Zhiyong , Chai Zhifang , Wang Shuao
Published: May 2023

Periodically arranging coordination‐distinct actinides into one crystalline architecture is intriguing but of great synthetic challenge. We report a rare example of a heterobimetallic actinide metal–organic framework (An‐MOF) by a unique reaction‐induced preorganization strategy. A thorium MOF (SCU‐16) with the largest unit cell among all Th‐MOFs was prepared as the precursor, then the uranyl was precisely embedded into the MOF precursor under oxidation condition. Single crystal of the resulting thorium‐uranium MOF (SCU‐16‐U) shows that a uranyl‐specific site was in situ induced by the formate‐to‐carbonate oxidation reaction. The heterobimetallic SCU‐16‐U exhibits multifunction catalysis properties derived from two distinct actinides. The strategy proposed here offers a new avenue to create mixed‐actinide functional material with unique architecture and versatile functionality.
Cu‐Bound Formates are Main Reaction Intermediates during CO2 Hydrogenation to Methanol over Cu/ZrO2
Authors: Meunier Frederic C. , Dansette Isaac , Paredes‐Nunez Anaelle , Schuurman Yves
Published: May 2023

Cu/ZrO2 is a promising catalyst for the hydrogenation of CO2 to methanol. Reaction pathways involving formates or hydroxycarbonyls have been proposed. We show here that three different types of formates can be observed under reaction conditions at 220 °C and 3 bar, one being located on metallic Cu and two others being bound to ZrO2. The surface concentrations of formates were determined through calibration curves and their reactivity measured during chemical transient experiments. The Cu‐bound formate represented only about 7 % of surface formates, but exhibited a higher reactivity and was found to be the only formate that could account for all the production of methanol. Copper is thus not there only to activate H2, but also bears other crucial intermediates. This work reemphasizes that fully quantitative IR analyses and transient methods are required to unravel the role of surface species.
Elucidating the Structures of Intermediate Fragments during Stepwise Dissociation of Monolayer‐Protected Silver Clusters
Authors: Chakraborty Papri , Malola Sami , Neumaier Marco , Weis Patrick , Häkkinen Hannu , Kappes Manfred M.
Published: May 2023

Fragmentation dynamics of ligated coinage metal clusters reflects their structural and bonding properties. So far methodological challenges limited probing structures of the fragments. Herein, we resolve the geometric structures of the primary fragments of [Ag29L12]3−, i.e. [Ag24L9]2−, [Ag19L6]− and [Ag5L3]− (L is 1,3‐benzene dithiolate). For this, we used trapped ion mobility mass spectrometry to determine collision cross sections of the fragments and compared them to structures calculated by density functional theory. We also report that following two sequential [Ag5L3]− elimination steps, further dissociation of [Ag19L6]− also involves a new channel of Ag2 loss and Ag−S and C−S bond cleavages. This reflects a competition between retaining the electronic stability of 8 e− superatom cluster cores and increasing steric strain of ligands and staples. These results are also of potential interest for future soft‐landing deposition studies aimed at probing catalytic behavior of Ag clusters on supports.
Transport properties investigations of nanocomposite membranes incorporating titanate nanowires for water desalination
Authors: de Resende Neuman Solange , Ohland Anderson Luis , Salim Vera M. M. , Borges Cristiano Piacsek
Published: May 2023

Improvement of membrane properties is an important issue to enhance the efficiency of water permeation processes. Nanocomposite membranes are gaining prominence in this field due to the particular properties of these materials. In the present study, incorporating titanate nanowires (TNW) into the cellulose acetate (CA) matrix allowed getting a nanocomposite membrane with modified characteristics. Morphologic and physical–chemical properties of the synthesized membranes were characterized by Fourier transform infrared spectrometry and scanning electron microscopy analysis, presenting a dense, uniform membrane formation with a highly dispersed inorganic phase when low amounts of particles were added. The membranes were tested by measuring water flux and salt rejection. The results showed that the incorporation of inorganic nanostructures into polymer membranes affects their transport properties. It was observed an increase of three times in water flux, reaching from 1.33 to 4.0 L/h m2, with NaCl rejection over 65%. Membranes with such characteristics could be specially designed for nanofiltration or forward osmosis processes as a promising application for water desalination or energy generation.
Biomarker‐based precision dose finding for immunotherapy combined with radiotherapy
Authors: Lin Li‐Hsiang , Han Yan , Zhang Rui , Guo Beibei
Published: May 2023

Recent success of sequential administration of immunotherapy following radiotherapy (RT), often referred to as immunoRT, has sparked the urgent need for novel clinical trial designs to accommodate the unique features of immunoRT. For this purpose, we propose a Bayesian phase I/II design for immunotherapy administered after standard‐dose RT to identify the optimal dose that is personalized for each patient according to his/her measurements of PD‐L1 expression at baseline and post‐RT. We model the immune response, toxicity, and efficacy as functions of dose and patient's baseline and post‐RT PD‐L1 expression profile. We quantify the desirability of the dose using a utility function and propose a two‐stage dose‐finding algorithm to find the personalized optimal dose. Simulation studies show that our proposed design has good operating characteristics, with a high probability of identifying the personalized optimal dose.
Manufacture of electrospun porous PLA fiber‐type film coated with CMC and its anti‐adhesion efficiency in white mice
Authors: Choi Sangmun , Chung Kyu Jin , Kim Youngjung , Kim Daeik , Hwang Sun Jin , Bae Su Ho , Ryoo Keon Sang
Published: May 2023

The electrospun polylactide (PLA) anti‐adhesion fiber‐type film coated with carboxymethylcellulose (CMC) was manufactured and evaluated for its usability through animal experiments. The PLA anti‐adhesion film developed in this study is an adhesion preventive film of a double composite structure with both hydrophobicity and hydrophilicity. This film has the anti‐adhesion effect due to hydrophobic PLA that do not melt easily in the body and at the same time is easily attached to the surgical site by hydrophilic CMC that reacts easily to body fluids and changes quickly to mucus. In this study, the diameter and the pore diameter of the PLA fiber and thickness of PLA film made by electrospinning was 0.2–0.4, 1–10, and 30–50 μm, respectively. Through observation of surface structure (×5000 magnification), the most suitable concentration of CMC to maintain pores on the PLA film as much as possible is 0.5% wt/vol. The CMC content in the PLA film coated with 0.5% wt/vol of CMC was measured to be 5.41% wt/wt and its tensile strength was about 2.92 times higher than that of the noncoated PLA film with CMC. The porosity of CMC‐coated PLA film (5.41% wt/wt) was found to be 76.4%. In the animal experiment, 20 white mice (10 as a control group and 10 as an experimental group) were used to determine the degree of adhesion prevention. As a result of observing adhesion and anti‐adhesion between the cecum and the peritoneum by performing U‐shaped laparotomy on white mice at the third week after surgery, the incidence of adhesion in the control group was 90%, whereas the experimental group was 20%.
Quantitative EEG as a diagnostic and prognostic tool in hemispheric stroke patients undergoing type A aortic dissection surgery
Authors: Wang Ya‐peng , Liu Wen‐xue , Jiang Yi , Lu Shan , Cheng Yong‐qing , Chen Yang , Wang Dong‐jin
Published: May 2023

Objective

The diagnostic and prognostic value of quantitative electroencephalogram (qEEG) parameters, specifically the symmetry of amplitude‐integrated electroencephalography (aEEG) and relative band power (RBP), in the postoperative stroke of the cerebral hemisphere following type A aortic dissection, remains an area of inquiry.

Methods

We analyzed and processed 56 patients with type A aortic dissection who underwent bedside qEEG monitoring and analyzed the qEEG indices, brain CT, and clinical data of these patients. qEEG (symmetry of aEEG and RBP, and affected/unaffected hemisphere) indices were analyzed at discharge and 60 days after discharge.

Results

A total of 56 patients were studied. The 60‐day mortality rate was 12.5%. The affected hemisphere's diagnosis and mortality after 1‐year follow‐up were evaluated, and RBP beta demonstrated the highest area under the curve values with 95% confidence intervals (CI) of .849 (95% CI: .771–.928) and .91 (95% CI: .834–.986), respectively. According to the results of the logistic regression analysis, we have identified the strongest predictors for cerebral hemisphere stroke and 1‐year mortality in stroke patients. Specifically, aEEGmin exhibited the highest predictive power with an odds ratio (OR) of .735 for cerebral hemisphere stroke, whereas DTABR was confirmed as one of the strongest predictors with an OR of 1.619 for 1‐year mortality in stroke patients, indicating a high level of reliability. Spearman correlation coefficients showed that aEEGmax and aEEGmin were positively correlated with Alberta Stroke Program Early CT Score (aEEGmax: rho = .50, p < .001; aEEGmin: rho = .44, p < .001).

Conclusions

QEEG has been proven to be a sensitive indicator for monitoring brain function and can be monitored continuously. It can help clinicians detect and treat these patients early and improve long‐term prognosis.
Sustainable sourcing strategy for mega construction projects: An empirical analysis
Authors: Bagul Avinash , Balon Virendra , Mathur Arpita
Published: May 2023

Time and cost overruns are the prominent issues faced by mega construction projects. To minimize cost overruns for the projects, a stepwise approach is suggested for the formulation of a sustainable sourcing strategy. Initially, weights are derived for the existing suppliers using the analytic hierarchy process to select the best set of suppliers. Multiple conflicting variables are considered for deriving the weights. Based on the derived weights, the supply network cost optimization model is developed for optimal order quantity allocation to the selected suppliers to maximize total purchasing value (TPV). A multi‐objective weighted goal programming model is used to minimize deviations in the TPV. Finally, the full factorial design of the experiment concept is employed to identify the significant factors impacting deviations in TPV. The methodology developed is verified using a case study approach. Mega‐construction project organization case was considered for analysis. Demand for the product, materials procurement cost, quality, and supplier lead time are found to be the significant factors impacting deviations in TPV. The developed approach can provide valuable insights to practitioners for the formulation of a sustainable sourcing strategy.
Characters of KRT80 and its roles in neoplasms diseases
Authors: Wei Xin‐Yuan , Zhao Jie , Tong Hao‐Bin , Cheng Shang‐Jie , He Na , Song Fei‐Xue
Published: May 2023

Background

KRT80 is a human epithelial intermediate filament type II gene; its expression product is a component of intracellular intermediate filaments (IFs) and is involved in the assembly of the cytoskeleton. There is evidence that IFs form a dense network mainly in the perinuclear area, but they can also reach the cortex. They are essential for mechanical cushioning of cells, organelle positioning, cell apoptosis, migration, adhesion, and interactions with other cytoskeletal components. Humans possess 54 functional keratin genes, and KRT80 is one of the more unique genes. It is widely expressed in almost all epithelial cells, although it is structurally more similar to type II hair keratins than to type II epithelial keratins.

Aim

In this review, we summarize the basic facts about the keratin family and KRT80, the essential role of KRT80 in neoplasms, and its potential as a therapeutic target. We hope that this review will inspire researchers to at least partially focus on this area.

Result

In many neoplastic diseases, the high expression status of KRT80 and its role in regulating the biological functions of cancer cells have been well established. KRT80 can effectively enhance the proliferation, invasiveness and migration of cancer cells. However, the effects of KRT80 on prognosis and clinically relevant indices in patients with various cancers have not been extensively studied, and even opposite conclusions have been reached in different studies of the same cancer. Based on this, we should add more clinically relevant studies to clarify the prospect of clinical application of KRT80. Many researchers have made great progress in studying the mechanism of action of KRT80. However, their studies should be extended to more cancers to find common regulators and signaling pathways of KRT80 in different cancers. KRT80 may have far‐reaching effects on the human body, and this marker may play a crucial role in the function of cancer cells and the prognosis of cancer patients, so it has a promising future in the field of neoplasms.

Conclusion

In neoplastic diseases, KRT80 is overexpressed in many cancers and plays an essential role in promoting proliferation, migration, invasiveness and poor prognosis. The mechanisms of KRT80 functions in cancer have been partially elucidated, suggesting that KRT80 is a potentially useful cancer therapeutic target. However, more systematic, in‐depth and comprehensive studies are still needed in this field.
Insulin‐like growth factor binding protein‐2 and glucose‐regulated protein 78 kDa: Potential biomarkers affect prognosis in IDH‐wildtype glioblastoma patients
Authors: Harland Abigail J. , Perks Claire M. , White Paul , Kurian Kathreena M. , Barber Hannah R.
Published: May 2023

Background

The overall survival of IDH‐wildtype glioblastoma patients is poor despite best available treatments. There is an urgent need for new biomarkers to inform more precise disease stratification. Previous studies have identified insulin‐like growth factor binding protein‐2 (IGFBP‐2) as a potential biomarker for glioblastoma diagnosis and therapeutic targeting. Other studies have indicated links between the insulin‐like growth factor (IGF) axis and tumorigenic functions of a molecular chaperone glucose related protein of 78 kDa (GRP78). We aimed to interrogate the oncogenic effects of IGFBP‐2 and GRP78 in our glioma stem cell (GSC) lines and clinical cohort.

Methods

Immunoblotting, reverse transcription quantitative real‐time PCR were used to quantify protein and mRNA levels derived from GSCs and non‐malignant neural stem cells (NSCs). Microarray analysis was used to compare the differences in IGFBP‐2 (IGFBP‐2) and GRP78 (HSPA5) transcript expression between NSCs, GSCs and adult human cortex samples. Immunohistochemistry was used to quantify IGFBP‐2 and GRP78 expression in IDH‐wildtype glioblastoma tissue sections (n = 92) and clinical implications assessed using survival analysis. Finally, the relationship between IGFBP‐2 and GRP78 was further explored molecularly using coimmunoprecipitation.

Results

Here, we demonstrate that IGFBP‐2 and HSPA5 mRNA is overexpressed in GSCs and NSCs in comparison to non‐malignant brain tissue. We also determined a relationship in which G144 and G26 GSCs expressed higher IGFBP‐2 protein and mRNA than GRP78, and this was reversed in mRNA isolated from adult human cortex samples. Clinical cohort analysis revealed that Glioblastomas with high IGFBP‐2 protein expression paired with low GRP78 protein expression were significantly associated with a much shorter survival time (Median = 4 months, p = 0.019) compared with 12‐14 months for any other combination of high/low protein expression.

Conclusions

Inverse levels of IGFBP‐2 and GRP78 may be adverse clinical prognostic markers in IDH‐wildtype glioblastoma. Further interrogation of the mechanistic link between IGFBP‐2 and GRP78 may be important for rationalisation of their potential as biomarkers and therapeutic targets.
Immunotherapy or antiangiogenic therapy plus chemotherapy as first‐line treatment of patients with PD‐L1(‐) advanced non‐squamous non‐small cell lung cancer in a Chinese cohort
Authors: Xia Ruolan , Li Yanying , Yang Ling , Huang Meijuan
Published: May 2023

Purpose

For patients with advanced nonsquamous non‐small cell lung cancer (NSCLC), immunotherapy or antiangiogenic therapy combined with pemetrexed and cisplatin/carboplatin have both shown significant efficacy at programmed cell death ligand 1 (PD‐L1) levels of <1%. Our study aimed to compare two first‐line regimens for patients with advanced nonsquamous NSCLC who were negative for PD‐L1.

Methods

A retrospective cohort study was conducted comparing the outcomes of patients with advanced PD‐L1(‐) nonsquamous NSCLC who were treated with antiangiogenic therapy plus chemotherapy (A Group) to those who were treated with anti‐PD‐L1 monoclonal antibodies plus chemotherapy (mAbs) (B Group). Both regimens were evaluated for progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and side effects.

Results

114 patients were enrolled in the study, 82 in Group A and 32 in Group B. Those in Group A had a longer median PFS (9.8 vs. 6.7 months, p = 0.025). The OS was also achieved (p = 0.058). No statistically significant difference was seen in ORR (52.4% vs. 50.0%, p = 0.815) or DCR (93.9% vs. 87.5%, p = 0.225) between the two groups. Patients in the A group who did not smoke and did not have specific metastases could benefit from survival. Adverse events (AEs) in both groups were tolerated.

Conclusion

Bevacizumab plus chemotherapy outperformed immunotherapy plus chemotherapy in terms of PFS.
Mycobacterium tuberculosis Rv1916 is an Acetyl‐CoA‐Binding Protein
Authors: Huang Evelyn Yu‐Wen , Kwai Brooke X. C. , Bhusal Ram Prasad , Bashiri Ghader , Leung Ivanhoe K. H.
Published: May 2023

Isocitrate lyase (ICL) isoform 2 is an essential enzyme for some clinical Mycobacterium tuberculosis (Mtb) strains during infection. In the laboratory Mtb strain H37Rv, the icl2 gene encodes two distinct gene products – Rv1915 and Rv1916 – due to a frameshift mutation. This study aims to characterise these two gene products to understand their structure and function. While we were unable to produce Rv1915 recombinantly, soluble Rv1916 was obtained with sufficient yield for characterisation. Kinetic studies using UV‐visible spectrophotometry and 1H‐NMR spectroscopy showed that recombinant Rv1916 does not possess isocitrate lyase activity, while waterLOGSY binding experiments demonstrated that it could bind acetyl‐CoA. Finally, X‐ray crystallography revealed structural similarities between Rv1916 and the C‐terminal domain of ICL2. Considering the probable differences between full‐length ICL2 and the gene products Rv1915 and Rv1916, care must be taken when using Mtb H37Rv as a model organism to study central carbon metabolism.
Chemoenzymatic Oxidation of Diols Catalyzed by Co‐Immobilized Flavins and Dehydrogenases**
Authors: Castillo Pacheco Sergio F. , Moran Maria Jesus , Santos José I. , Salassa Luca , López‐Gallego Fernando
Published: May 2023

Enzyme driven oxidations catalyzed by alcohol dehydrogenases rely on the in situ NAD(P)+ regeneration. A wide variety of chemoenzymatic and fully enzymatic methods have been reported over the last 30 years to integrate the cofactor regeneration in biocatalytic oxidations. However, the majority of examples are limited to homogeneous systems where the reuse of both enzymes and chemical catalysts are challenging. In this work, we co‐immobilize an alcohol dehydrogenase from Bacillus stearothermophilus with a flavin derivative (FMN), which performs as an organocatalyst that oxidizes NADH back to NAD+. This latter oxidized cofactor is sequentially utilized by the dehydrogenase to oxidize 1,ω‐diols. Remarkably, the immobilization chemistry of FMN determines its efficiency to oxidize NADH and, unlike in its free state, the immobilized FMN can recycle NAD+ in dark. This is possible because the support where both enzyme and FMN are immobilized also captures NADH, making the electron transfer from the substrates to the cofactors more efficient. This work illustrates how the co‐immobilization and confinement of bio and chemical catalysts on solid materials (heterogeneous phase) enable chemoenzymatic cascades that are precluded in solution (homogeneous phase).
Niobium‐doped Hematite Photoanodes Prepared through Low‐Cost Facile Methods for Photoelectrochemical Water Splitting
Authors: Melo Mauricio A. , Brito Igor M. , Mello João V. S. B. , Rocha Pamela S. M. , Bessa Isabela A. A. , Archanjo Braulio S. , Miranda Fabio S. , Cassella Ricardo J. , Ronconi Célia M.
Published: May 2023

Producing solar fuels through semiconductor‐based photocatalytic water splitting is one of the main options for worldwide employment of non‐fossil energy sources. Nonetheless, the relatively low efficiency of the known photocatalysts, the high prices of composing elements, and the costly preparation methods render expensive devices that would not be economically competitive with fossil energy sources. Herein, we present a facile method for the preparation of both round hematite (Fe2O3) nanoparticles, with average diameter of (56±7) nm, and of niobium‐doped hematite nanoparticles with similar size and morphology. Thin films of these nanoparticles were assembled through electrophoretic deposition, resulting in homogeneous photoanodes with nanometer thickness that can split water, under simulated solar irradiation, to produce oxygen in a photoelectrochemical cell. The optimization of the film composition and thickness resulted in the improvement of the photocurrent from 352.3 to 1,342.5 μA cm−2 at 1.23 V vs RHE for the pristine hematite and Nb‐doped hematite, respectively, both with thickness of (499±63) nm. This enhancement in the oxidation reaction yield is a clear consequence of the improvement of charge carriers transport along the nanoparticle structure due to niobium doping and adequate light absorption/charge transfer balance of the photoelectrode under operation.
From Terminal to Spiro‐Phosphonium Acceptors, Remarkable Moieties to Develop Polyaromatic NIR Dyes
Authors: Partanen Iida , Belyaev Andrey , Su Bo‐Kang , Liu Zong‐Ying , Saarinen Jarkko J. , Ibni Hashim Ishfaq , Steffen Andreas , Chou Pi‐Tai , Romero‐Nieto Carlos , Koshevoy Igor O.
Published: May 2023

Phosphonium‐based compounds gain attention as promising photofunctional materials. As a contribution to the emerging field, we present a series of donor‐acceptor ionic dyes, which were constructed by tailoring phosphonium (A) and extended π‐NR2 (D) fragments to an anthracene framework. The alteration of the π‐spacer of electron‐donating substituents in species with terminal −+PPh2Me groups exhibits a long absorption wavelength up to λabs=527 nm in dichloromethane and shifted the emission to the near‐infrared (NIR) region (λ=805 nm for thienyl aniline donor), although at low quantum yield (Φ<0.01). In turn, the introduction of a P‐heterocyclic acceptor substantially narrowed the optical bandgap and improved the efficiency of fluorescence. In particular, the phospha‐spiro moiety allowed to attain NIR emission (797 nm in dichloromethane) with fluorescence efficiency as high as Φ=0.12. The electron‐accepting property of the phospha‐spiro constituent outperformed that of the monocyclic and terminal phosphonium counterparts, illustrating a promising direction in the design of novel charge‐transfer chromophores.
RNA‐Catalyzed RNA Ligation within Prebiotically Plausible Model Protocells**
Authors: DasGupta Saurja , Zhang Stephanie J. , Smela Merrick P. , Szostak Jack W.
Published: May 2023

Demonstrating RNA catalysis within prebiotically relevant models of primordial cells (protocells) remains a challenge in origins of life research. Fatty acid vesicles encapsulating genomic and catalytic RNAs (ribozymes) are attractive models for protocells; however, RNA catalysis has largely been incompatible with fatty acid vesicles due to their instability in the presence of Mg2+ at the concentrations required for ribozyme function. Here, we report a ribozyme that catalyzes template‐directed RNA ligation at low Mg2+ concentrations and thus remains active within stable vesicles. Ribose and adenine, both prebiotically relevant molecules, were found to greatly reduce Mg2+‐induced RNA leakage from vesicles. When we co‐encapsulated the ribozyme, substrate, and template within fatty acid vesicles, we observed efficient RNA‐catalyzed RNA ligation upon subsequent addition of Mg2+. Our work shows that RNA‐catalyzed RNA assembly can occur efficiently within prebiotically plausible fatty acid vesicles and represents a step toward the replication of primordial genomes within self‐replicating protocells.
Symmetry‐Broken Charge‐Transfer Excited State in Homoleptic Zinc(II) Imidazo[1,2‐a]pyridine Complexes
Authors: Giuso Valerio , Jouaiti Elise , Cebrián Cristina , Parant‐Aury Sabrina , Kyritsakas Nathalie , Gourlaouen Christophe , Mauro Matteo
Published: May 2023

A series of four homoleptic cationic ZnII complexes (Zn1–Zn4) coordinated by two substituted bis‐imidazo[1,2‐a]pyridine (ImPy) ligands (L1–L4) is herein presented. The ligands are functionalized with either electron acceptor or donor functional groups at the C6 positions of the two ImPy moieties. In DMF solution, all of the complexes display intense near‐UV to blue emission (λem=379–450 nm) with high photoluminescence quantum yields (PLQY) up to 0.50 and short‐lived excited states. Additionally, complex Zn4, containing the ‐NPh2 functionalized ligand, displays an interesting solvatochromic behavior. The absorption spectrum is characterized by electronic transitions with mainly ligand‐centered (1LC) and intraligand charge‐transfer (1ILCT) character, which involves a symmetric electron density redistribution at Franck‐Condon (FC). In stark contrast, the subsequent excited‐state dynamics relaxes the molecular symmetry and allows symmetry‐breaking hole‐electron pair redistribution on the bichromophoric system. As a consequence, an efficient radiative de‐excitation process takes place that is ascribed to a singlet‐manifold excited state with symmetry‐broken charge transfer (1SBCT) character, as supported by an in‐depth photophysical, electrochemical and time‐dependent density functional theory (TD‐DFT) investigation. Remarkably, the 1SBCT nature provides structureless green photoluminescence in the solid state (λem up to 520 nm for Zn4), which is rather uncommon for ZnII complexes.
Dietary overlap and selectivity among mountain steppe river fish in the United States and Mongolia
Authors: Minder Mario , Arsenault Emily R. , Pyron Mark , Otgonganbat Amarbat , Mendsaikhan Bud
Published: May 2023

Lotic systems in mountain regions have historically provided secure habitat for native fish populations because of their relative isolation from human settlement and lack of upstream disturbances. However, rivers of mountain ecoregions are currently experiencing heightened levels of disturbance due to the introduction of nonnative species impacting endemic fishes in these areas. We compared the fish assemblages and diets of mountain steppe fishes of the stocked rivers in Wyoming with rivers in northern Mongolia where stocking is absent. Using gut content analysis, we quantified the selectivity and diets of fishes collected in these systems. Nonnative species had more generalist diets with lower levels of selectivity than most native species and native species had high levels of dietary specificity and selectivity. High abundances of nonnative species and high levels of dietary overlaps in our Wyoming sites is a cause of concern for native Cutthroat Trout and overall system stability. In contrast, fish assemblages characterizing Mongolia mountain steppe rivers were composed of only native species with diverse diets and higher selectivity values, suggesting low probability for interspecific competition.
Electronic nudges to increase influenza vaccination uptake among patients with heart failure: A pre‐specified analysis of the NUDGE‐FLU trial
Authors: Johansen Niklas Dyrby , Vaduganathan Muthiah , Bhatt Ankeet S. , Lee Simin Gharib , Modin Daniel , Claggett Brian L. , Dueger Erica L. , Samson Sandrine , Loiacono Matthew M. , Harris Rebecca C. , Køber Lars , Solomon Scott D. , Sivapalan Pradeesh , Jensen Jens Ulrik Stæhr , Martel Cyril Jean‐Marie , Valentiner‐Branth Palle , Krause Tyra Grove , Biering‐Sørensen Tor
Published: May 2023

Aims

Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE‐FLU trial recently found two electronic behavioural nudging letter strategies – a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 –effective in increasing influenza vaccination in Denmark. The aims of this pre‐specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off‐target effects on guideline‐directed medical therapy (GDMT) use.

Methods and results

The nationwide NUDGE‐FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022–2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE‐FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain‐framed letter: pinteraction = 0.37; repeated letter: pinteraction = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (pinteraction = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain‐framed letter (pinteraction = 0.07). The letters had no impact on longitudinal GDMT use.

Conclusions

Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain‐framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed.

Clinical Trial Registration: ClinicalTrials.gov NCT05542004.
Experimental Investigation of Pure Spinel Mn3O4 Properties Synthesized through Chemical Spray Pyrolysis for Future Gas Sensor Application
Authors: Doubi Youssef , Hartiti Bouchaib , Siadat Maryam , Labrim Hicham , Fadili Salah , Tahri Mounia , Stitou Mohamed , Thevenin Philippe , Losson Etienne
Published: May 2023

The semiconductor realization is a very significant stage in gas sensor application. Herein, the Mn3O4 semiconductor was deposited using chemical spray pyrolysis. The effect of deposition temperature on structural, vibrational optical and electrical Mn3O4 thin layers properties were investigated through: X‐ray diffraction, Raman spectroscopy, UV‐visible spectrophotometer, and two points electrometers respectively. The X‐ray diffraction showed the appearance of spinel phase of tetragonal Mn3O4 with strong formation direction along (101) plan and without any secondary phase indicating the formation of pure Mn3O4. The Raman spectroscopy confirmed the results obtained in XRD and certified the high‐quality formation of Mn3O4. In addition, the crystallinity improvement (the increase of crystallite size and the decrease of dislocation density) was caused by the increasing of deposition temperature from 350 °C to 450 °C. Optical properties such as transmittance, absorbance and band gap energy were extracted by UV‐Visible spectrophotometer. Thus, low transmittance, high absorbance and small band gap energy were observed at the highest substrate temperature (450 °C). The electrical conductivity showed good values between 4.83 and 13.89 mS.cm−1. These properties make Mn3O4 an appropriate material to be used as a sensitive layer in gas sensors applications.
Formal Addition of β‐Acylalkenyl Anions to Ketones Utilizing [1,2]‐Phospha‐Brook Rearrangement under Brønsted Base Catalysis
Authors: Kondoh Azusa , Takada Sena , Aita Kohei , Terada Masahiro
Published: May 2023

A methodology for the formal addition of β‐acylalkenyl anions was developed by utilizing the [1,2]‐phospha‐Brook rearrangement under Brønsted base catalysis. The two‐step reaction involves the catalytic addition of α‐oxygenated propargyl anions generated via [1,2]‐phospha‐Brook rearrangement to electron‐deficient ketones and subsequent alcoholysis to afford tertiary alcohols having an enone moiety. This is a rare example of a catalytic carbon‐carbon bond forming reaction of β‐acylalkenyl anion equivalents, providing synthetic building blocks that are otherwise difficult to access.