bluuebunny/crossref_metadata_2025 huggingface dataset:
A Radio‐Pharmaceutical Fluorescent Probe for Synergistic Cancer Radiotherapy and Ratiometric Imaging of Tumor Reactive Oxygen Species
Authors: Ge Xiaoguang , Su Lichao , Chen Zhongxiang , Zhu Kang , Zhang Xuan , Wu Ying , Song Jibin
Published: May 2023

Radiotherapy (RT) is an effective and widely applied cancer treatment strategy in clinic. However, it usually suffers from radioresistance of tumor cells and severs side effects of excessive radiation dose. Therefore, it is highly significant to improve radiotherapeutic performance and monitor real‐time tumor response, achieving precise and safe RT. Herein, an X‐ray responsive radio‐pharmaceutical molecule containing chemical radiosensitizers of diselenide and nitroimidazole (BBT‐IR/Se‐MN) is reported. BBT‐IR/Se‐MN exhibits enhanced radiotherapeutic effect via a multifaceted mechanisms and self‐monitoring ROS levels in tumors during RT. Under X‐ray irradiation, the diselenide produces high levels of ROS, leading to enhanced DNA damage of cancer cell. Afterwards, the nitroimidazole in the molecule inhibits the damaged DNA repair, offering a synergetic radiosensitization effect of cancer. Moreover, the probe shows low and high NIR‐II fluorescence ratios in the absence and presence of ROS, which is suitable for precise and quantitative monitoring of ROS during sensitized RT. The integrated system is successfully applied for radiosensitization and the early prediction of in vitro and in vivo RT efficacy.
Efficient Selective Oxidation of Aromatic Alkanes by Double Cobalt Active Sites over Oxygen Vacancy‐rich Mesoporous Co3O4
Authors: Liu Yali , Zheng Yuenan , Feng Danyang , Zhang Liangliang , Zhang Ling , Song Xiaowei , Qiao Zhen‐An
Published: May 2023

The development of efficient catalyst for selective oxidation of hydrocarbon to functional compounds remains a challenge. Herein, mesoporous Co3O4 (mCo3O4‐350) showed excellent catalytic activity for selective oxidation of aromatic‐alkanes, especially for oxidation of ethylbenzene with a conversion of 42 % and selectivity of 90 % for acetophenone at 120 °C. Notably, mCo3O4 presented a unique catalytic path of direct oxidation of aromatic‐alkanes to aromatic ketones rather than the conventional stepwise oxidation to alcohols and then to ketones. Density functional theory calculations revealed that oxygen vacancies in mCo3O4 activate around Co atoms, causing electronic state change from Co3+(Oh)→Co2+(Oh). Co2+(Oh) has great attraction to ethylbenzene, and weak interaction with O2, which provide insufficient O2 for gradual oxidation of phenylethanol to acetophenone. Combined with high energy barrier for forming phenylethanol, the direct oxidation path from ethylbenzene to acetophenone is kinetically favorable on mCo3O4, sharply contrasted to non‐selective oxidation of ethylbenzene on commercial Co3O4.
An exploratory study on the effect of mechanical stress on particle formation in monoclonal antibody infusions
Authors: Abdel‐Tawab Mona , Banerjee Srijib , Kirchner Roland , Wellenhofer Thomas , Hahn Lukas , Meinel Lorenz , Holzgrabe Ulrike , Schubert‐Zsilavecz Manfred , Seidl Andreas , Stadler Franz
Published: May 2023

Monoclonal antibody infusions (mAb‐i) are administered for the treatment of various diseases. They are often transported over long distances from the compounding site to the site of administration. However, transport studies are typically carried out with the original drug product but not with compounded mAb‐i. To address this gap, the impact of mechanical stress on the formation of subvisible/nanoparticles in mAb‐i was investigated by dynamic light scattering and flow imaging microscopy. Different mAb‐i concentrations were subjected to vibrational orbital shaking and stored at 2–8°C up to 35 days. The screening revealed that pembrolizumab and bevacizumab infusions show the highest propensity for particle formation. Especially bevacizumab at low concentrations exhibited an increase in particle formation. Because of the unknown health risks associated with the long‐term application of subvisible particles (SVPs)/nanoparticles in infusion bags, stability studies carried out in the frame of licensing application procedures should also focus on SVP formation in mAb‐i. In general, pharmacists should minimize the time of storage and mechanical stress during transport, especially in the case of low‐concentrated mAb‐i. Moreover, if siliconized syringes are used, they should be washed once with saline solution to minimize particle entry.
Existence and stability of impulsive stochastic coupled systems in infinite dimensions
Authors: Yang Ni , Zhang Shuo , Su Huan
Published: May 2023

This paper considers the exponential stability of a class of infinite‐dimensional impulsive stochastic coupled systems. With the help of generalized Itô's formula for the mild solution of infinite‐dimensional systems, we avoid limiting the domain of the mild solution. Then we use the combination of the Lyapunov function and graph theory to construct the Lyapunov function of the systems; the criteria of
‐th moment exponential stability are obtained, which is related to the average impulsive interval
and the connectivity of impulsive stochastic systems. In addition, noting that the existence may be affected by impulsive effects and stochastic perturbations, using the graph theory and the principle of contraction mapping, we get the condition that guarantees the existence and uniqueness, which is also related to the structure of the networks. Finally, we consider the stability of impulsive stochastic coupled heat equations and neural networks with reaction diffusion and give some numerical simulations to verify the theoretical results.
Combined experimental/computational aspects for the molecular interaction of empagliflozin with bovine serum albumin: Quantification and application to human plasma
Authors: Hosny Noha M. , GadAllah Mohamed I. , Qayed Wesam S.
Published: May 2023

Empagliflozin (EMP) is an oral antihyperglycemic agent for type 2 diabetic patients. The molecular binding of EMP to bovine serum albumin (BSA) was elucidated by a combined experimental/computational approach to fulfil the pharmacokinetics and pharmacodynamics gaps of the cited drug for further development. Fluorescence, synchronous, and three‐dimensional fluorescence spectroscopy verified that EMP quenched BSA native fluorescence through a dual static/dynamic mechanism that was further supported by Fӧrster resonance energy transfer and ultraviolet absorption spectroscopy. Fourier transform infrared spectroscopy revealed the conformational variations in BSA secondary structure induced by EMP. Thermodynamic properties of the BSA–EMP complex were also investigated, and the hydrophobic interactions' role in the binding process was demonstrated by the computed enthalpy (ΔH = 6.558 kJ mol−1) and entropy (ΔS = 69.333 J mol−1 K−1). Gibbs free energy (ΔG) values were negative at three distinct temperatures, illuminating the spontaneity of this interaction. In addition, molecular docking studies depicted the optimal fitting of EMP to BSA on Site I (sub‐domain IIA) through three hydrogen bonds. Additionally, and based on the quenching effect of EMP on BSA fluorescence, this study suggests a simple validated spectrofluorometric method for the quantitation of the studied drug in bulk form and human plasma samples with reasonable recoveries (96.99–103.10%).
Development of porous calcite structure from industrial waste for efficient adsorbent for protein
Authors: Khalid Zubair , Oh Jae‐Min
Published: May 2023

Porous adsorbent (PA) with high specific surface area and calcite surface was prepared from an industrial waste, electric arc furnace oxidizing slag (EOS). As the EOS is composed of silica and metal oxide nanoparticle like CaO, MgO, and so on, the metal oxide parts were selectively dissolved by acid treatment. The remained silica part exhibited porous structure due to the assembly of nanoparticles. Then, calcite was developed on the silica surface by simply titrating the silica framework with carbonate under basic condition. According to the x‐ray diffraction pattern and scanning electron microscopy, we could hypothesize that the EOS had dense texture of amorphous nanoparticles. On the other hand, the PA had well‐crystallized calcite particles with sufficient interparticle pores. The zeta potential of EOS shifted to positive region upon transformation to PA, possibly due to the change in surface‐exposed moiety from silica to calcite. The albumin adsorption profiled exhibited that the PA had very high protein adsorption capacity up to 3.33 mg‐protein/mg‐adsorbent at 5 mg/L of protein concentration, while the EOS itself did not show meaningful adsorption.
Use of single analytic tool to quantify both absolute N‐glycosylation and glycan distribution in monoclonal antibodies
Authors: Mao Leran , Schneider James W. , Robinson Anne S.
Published: May 2023

Recombinant proteins represent almost half of the top selling therapeutics—with over a hundred billion dollars in global sales—and their efficacy and safety strongly depend on glycosylation. In this study, we showcase a simple method to simultaneously analyze N‐glycan micro‐ and macroheterogeneity of an immunoglobulin G (IgG) by quantifying glycan occupancy and distribution. Our approach is linear over a wide range of glycan and glycoprotein concentrations down to 25 ng/mL. Additionally, we present a case study demonstrating the effect of small molecule metabolic regulators on glycan heterogeneity using this approach. In particular, sodium oxamate (SOD) decreased Chinese hamster ovary (CHO) glucose metabolism and reduced IgG glycosylation by 40% through upregulating reactive oxygen species (ROS) and reducing the UDP‐GlcNAc pool, while maintaining a similar glycan profile to control cultures. Here, we suggest glycan macroheterogeneity as an attribute should be included in bioprocess screening to identify process parameters that optimize culture performance without compromising antibody quality.
Support for religious minorities' rights among (non)religious national majority group members: A motivational approach to worldviews
Authors: Renvik Tuuli Anna , Eskelinen Viivi , Kunst Jonas , Jetten Jolanda , van der Noll Jolanda , Rohmann Anette , Jasinskaja‐Lahti Inga
Published: May 2023

Increasing religious diversity caused by immigration is often perceived as a threat to national majority members' (non)religious worldviews. However, defensive reactions to diversity are not inevitable. Building on the social identity approach and motivated identity construction theory, we argue that (non)religious worldviews that satisfy motivational needs may promote support for religious minorities' rights. We tested this hypothesis in a sample of 1,499 national majority group members in four countries with Christian traditions (Australia, Finland, Germany, and Norway). Participants reported their adherence to a (non)religious worldview in terms of their (dis)belief in God, and also the extent to which their worldview satisfied their needs for belonging, continuity, and meaning in life. The more religious worldview was perceived to satisfy these motives, the more religious majority group members supported religious minorities' rights. Worldview motive satisfaction was not associated with support for religious minorities' rights among the non‐religious. In addition, perceived diversity threat was associated with weaker support for minority rights, but again, this negative effect of threat was less evident among religious participants whose religious worldview satisfied their needs for belonging, continuity, and meaning. We conclude that communities based on a shared (religious) worldview should invest in fulfilling the motivational needs of their members, to foster interreligious solidarity. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.
Emotionally intelligent virtual tour guide in handling group conflicts: Effect on user outcomes
Authors: Li Qing , Liu Tingting , Liu Zhen , Chai Yanjie
Published: May 2023

An effective virtual agent can serve humans complete task‐based work efficaciously and manage interpersonal relationships with humans judiciously. This article investigates the effectiveness of emotional intelligence (EI) of a virtual agent taking over the role of a virtual tour guide (VTGuide) in a desktop application when witnessing a personal conflict between a human user and two virtual agents participating in the tour (the human user was ignored by the agents). A within‐subject experiment is conducted to verify the validity of EI. Participants rate VTGuides (with or without EI) on conflict handling and report their feelings during the interaction. In addition, objective behavioral data of users are recorded, including facial expressions and textual sentiment, to assess the perception of rapport. The results show that an emotionally intelligent VTGuide performs an agreeable behavior system (e.g., nodding, eye contact, friendly facial expressions), comforting verbal strategy (e.g., distracting attention, mediating between conflicting parties), and positive paralinguistic cues (e.g., smiling textual emojis). It can effectively mitigate intra‐group conflicts and maintain interpersonal relationships. Thus, demonstrating a stronger sense of EI can better transmit engagement, interest, understanding, and emotional feedback in complex relationships.
In Vitro, In Silico, ADME and Theoretical Analysis of Mn(II) and Co(II) Complexes Derived from Methyl‐(Z)‐N′‐Carbamothioylcarbamohydrazonate Schiff Base Ligand
Authors: Alka  , Vishvakarma Vijay K. , Yadav Sandeep , Singh Prashant , Jain Pallavi
Published: May 2023

Mn(II) and Co(II) complexes of methyl‐(Z)−N′‐carbamothioylcarbamohydrazonate Schiff base ligand were synthesized. The ligand and metal salts were taken in 2 : 1 stoichiometric ratio. All the synthesized complexes were characterized using elemental analysis, molar conductance, magnetic moment and various spectroscopic techniques (FT‐IR, UV/VIS, EPR) techniques. Elemental and spectroscopic results verified bidentate donor nature of the ligand and octahedral geometry of all the complexes. The non‐electrolytic nature of Mn(II) and Co(II) complexes were suggested by conductivity data analysis. In vitro antibacterial (E. coli and S. aureus) and antifungal (C. albicans and C. tropicalis) screening were achieved by employing agar well diffusion method which revealed better antimicrobial activity of Co(II) complexes than Mn(II) complexes. In silico SwissADME study predicted the drug‐likeness probability of ligand and complexes. The interaction of two bacterial proteins (E. coli and S. aureus) with compounds was also analyzed using molecular docking study, which corroborate the in vitro analysis.
Comparative Study on Phenolic Profile and Biological Activities of the Aerial Parts of Sinapis pubescens L. subsp. pubescens (Brassicaceae) Wild from Sicily (Italy)
Authors: Arena Paola , Miceli Natalizia , Marino Andreana , Davì Federica , Cavò Emilia , Spadaro Vivienne , Raimondo Francesco Maria , Cacciola Francesco , Laganà Vinci Roberto , Mondello Luigi , Taviano Maria Fernanda
Published: May 2023

This work aimed to investigate Sinapis pubescens subsp. pubescens spontaneously grown in Sicily (Italy) as new potential source of active metabolites; specifically, a comparative study on leaf, flower, and stem hydroalcoholic extracts was performed. Polyphenols were quantitatively determined by spectrophotometric methods and characterized by HPLC‐PDA/ESI‐MS; a total of 55 polyphenolic compounds were identified, highlighting considerably different qualitative‐quantitative profiles. The extracts showed antioxidant activity, evaluated by in vitro assays; particularly, the leaf extract displayed the best radical scavenging activity (DPPH test) and reducing power, while the flower extract showed the greatest chelating activity. The antimicrobial properties of the extracts were investigated against bacteria and yeasts by standard methods; no antimicrobial activity was found against the strains tested. The extracts resulted to be non‐toxic after preliminary toxicity evaluation by the Artemia salina lethality bioassay. The aerial parts of S. pubescens subsp. pubescens proved to be valuable sources of antioxidants for pharmaceutical and nutraceutical applications.
Percutaneous treatment of left circumflex coronary artery injury related to mitral valve surgery: Case series and systematic review of the literature
Authors: Benedetti Alice , Castaldi Gianluca , Poletti Enrico , Moroni Alice , Scott Benjamin , Convens Carl , Verheye Stefan , Vermeersch Paul , Agostoni Pierfrancesco , Zivelonghi Carlo
Published: May 2023

Left circumflex coronary artery (LCx) injury related to mitral valve surgery is a rare complication. The best treatment option is not defined, and percutaneous coronary intervention (PCI) may represent an effective treatment to avoid prolonged myocardial ischemia. To evaluate feasibility and efficacy of PCI treatment, all records of LCx injury related to mitral valve surgery and treated with PCI were included after a systematic PubMed searching. Moreover, we retrospectively analyzed our single‐center PCI database and patients fulfilling the inclusion criteria were included. Patients undergoing transcatheter mitral valve intervention, non‐mitral valve surgery, conservatively or surgically treated after LCx injury were excluded. Data about patient characteristics, procedural details, PCI success, and in‐hospital mortality were collected. Fifty‐six patients were included, 58.9% were male (n = 33) and the median age was 60.5 years (IQR = 21.75). The majority had left dominant or codominant coronary system (62.2%,n = 28 and 15.6%,n = 7, respectively). Clinical manifestations ranged from hemodynamic stability (21.1%,n = 8) to hemodynamic instability (42.1%,n = 16) and cardiac arrest (18.4%,n = 7). On ECG, 23.5% of patients (n = 12) presented ST‐segment depression, 58.8% (n = 30) ST‐segment elevation, 7.8% (n = 4) atrioventricular block, and 29.4% (n = 15) ventricular arrhythmias. Left ventricle dysfunction was present in 52.3% (n = 22) of patients and wall motion abnormalities in 71.4% (n = 30). PCI success rate was 82.1% (n = 46) and in‐hospital mortality 4.5% (n = 2). LCx injury related to mitral surgery is a rare complication characterized by an increased risk of mortality. PCI seems a feasible treatment option, still burdened by suboptimal results, probably related to the technical challenges posed by the surgical failure.
Implant rehabilitation of a posterior maxilla with 4‐mm long implants splinted to a 10‐mm long implant in a patient with osteopenia taking antiresorptive drugs: A 5‐year follow‐up case report
Authors: Povšič Katja , Oblak Čedomir , Dard Michel , Gašperšič Rok
Published: May 2023

The report describes the rehabilitation of a maxillary arch with limited bone volume in a 67‐year‐old female taking antiresorptives due to osteopenia. One 10‐mm and two extra‐short 4‐mm implants were inserted, and implant‐supported splinted crowns were fabricated. The 5‐year follow‐up showed stable bone levels, despite poor initial stability (ISQ: 14–51).
A rare case of bilateral renal angiomyolipoma: Radiological findings of tuberous sclerosis complex
Authors: Ali Sajjad , Lalani Ali Salim , Mukherjee Deblina , Hashmi Kayhan Nasir
Published: May 2023

Key Clinical Message

Renal angiomyolipoma is a type of benign hamartoma that may occur sporadically or be associated with tuberous sclerosis complex. Due to their distinct appearance, CT, MRI, or sonography are typically used to diagnose AMLs.

The uncommon benign hamartoma known as renal angiomyolipoma (AML) linked with tuberous sclerosis has a poor prognosis and potentially fatal side effects. Due of their distinct appearance, computed tomography (CT), magnetic resonance imaging (MRI), or sonography are typically used to diagnose AMLs.
A case report of an extremely rare association of ankylosing spondylitis with pachydermoperiostosis
Authors: Gorial Faiq I. , Awadh Nabaa Ihsan , Hamzah Maryam A.
Published: May 2023

Key Clinical Message

We describe a case of a young man with features of pachydermoperiostosis and spondyloarthropathy. By describing this rarity, we aim to help build a database for future studies and construct a management plan that rheumatologists and clinicians can use.

This is the first case report in Iraq describing the combination of pachydermoperiostosis and ankylosing spondylitis. We report this interesting association in a 23‐year‐old male who presented with inflammatory back pain, coarse facial features, clubbing, signs of enthesitis, limitation of spine movement, and clinical and radiographic signs of sacroiliitis.
Synthesis of Bisubstrate Analogues for RNA Methylation Studies using two Transition‐Metal‐Catalyzed Reactions
Authors: Coelho Dylan , Le Corre Laurent , Bartosik Karolina , Iannazzo Laura , Braud Emmanuelle , Ethève‐Quelquejeu Mélanie
Published: May 2023

RNA methyltransferases (RNA MTases) are a family of enzymes that catalyze the methylation of RNA using the cofactor S‐adenosyl‐L‐methionine. While RNA MTases are promising drug targets, new molecules are needed to fully understand their roles in disease and to develop effective drugs that can modulate their activity. Since RNA MTases are suitable for bisubstrate binding, we report an original strategy for the synthesis of a new family of m6A MTases bisubstrate analogues. Six compounds containing a S‐adenosyl‐L‐methionine (SAM) analogue unit covalently tethered by a triazole ring to the N‐6 position of an adenosine were synthesized. A procedure using two transition‐metal‐catalyzed reactions was used to introduce the α‐amino acid motif mimicking the methionine chain of the cofactor SAM. First, a copper(I)‐catalyzed alkyne‐azide iodo‐cycloaddition (iCuAAC) reaction afforded the 5‐iodo‐1,4‐disubstituted‐1,2,3‐triazole which was functionalized by palladium‐catalyzed cross‐coupling to connect the α‐amino acid substituent. Docking studies of our molecules in the active site of the m6A ribosomal MTase RlmJ show that the use of triazole as a linker provides additional interactions and the presence of the α‐amino acid chain stabilizes the bisubstrate. The synthetic method developed here enhances the structural diversity of bisubstrate analogues to explore the active site of RNA modification enzymes and to develop new inhibitors.
Organic Afterglow Nanoparticles in Bioapplications
Authors: Shen Hengxin , Liao Shiyi , Li Zhe , Wang Youjuan , Huan Shuangyan , Zhang Xiao‐Bing , Song Guosheng
Published: May 2023

Organic afterglow nanoparticles are unique optical materials that emit light long after cessation of excitation. Due to their advantages of no need for real‐time light excitation, avoiding autofluorescence, low imaging background, high signal‐to‐background ratio, deep tissue penetration, and high sensitivity, afterglow imaging technology has been widely used in cell tracking, biosensing, cancer diagnosis, and cancer therapy, which provides an effective technical method for the acquisition of molecular information with high sensitivity, specificity and real‐time at the cellular and living level. In this review, we summarize and illustrate the recent progress of organic afterglow imaging, focusing on the mechanism of organic afterglow materials and their biological application. Furthermore, we also discuss the potential challenges and the further directions of this field.
Enantioselective binding of carvedilol to human serum albumin and alpha‐1‐acid glycoprotein
Authors: Toma Camelia‐Maria , Imre Silvia , Farczadi Lenard , Ion Valentin , Marc Gabriel
Published: May 2023

Carvedilol, a highly protein‐bound beta‐blocker, is used in therapy as a racemic mixture of its two enantiomers that exhibit different pharmacological activity. The aim of this study was to evaluate the stereoselective nature of its binding to the two major plasma proteins: albumin and alpha‐1‐acid glycoprotein. The determination of the plasma protein‐binding degree for carvedilol and its enantiomers was achieved using ultrafiltration for the separation of the free fraction, followed by LC‐MS/MS quantification, using two different developed and validated methods in terms of stationary phase: achiral C18 type and chiral ovomucoid type. Furthermore, molecular docking methods were applied in order to investigate and to better understand the mechanism of protein‐binding for S‐(−)‐ and R‐(+)‐carvedilol. A difference in the binding behavior of the two enantiomers to the plasma proteins was observed when taken individually, with R‐(+)‐carvedilol having a higher affinity for albumin and S‐(−)‐carvedilol for alpha‐1‐acid glycoprotein. However, in the case of the racemic mixture, the binding of the S enantiomer to alpha‐1‐acid glycoprotein seemed to be influenced by the presence of its antipode, although no such influence was observed in the case of albumin. The results raise the question of a binding competition between the two enantiomers for alpha‐1‐acid glycoprotein.
Rational Design and Cellular Synthesis of Proteins with Unconventional Chemical Topology
Authors: Li Tianzuo , Zhang Fan , Fang Jing , Liu Yajie , Zhang Wen‐Bin
Published: May 2023

Comprehensive Summary

Chemical topology refers to the three‐dimensional arrangement (i.e., connectivity and spatial relationship) of a molecule's constituent atoms and bonds. The molecular mechanism for translation defines the linear configuration of all nascent proteins. Nontrivial protein topology arises only upon post‐translational processing events and often imparts functional benefits such as enhanced stability, making topology a unique dimension for protein engineering. Utilizing the assembly‐reaction synergy, our group has developed several methods for the effective and convenient cellular synthesis of a variety of topological proteins, such as lasso proteins, protein rotaxanes, and protein catenanes. The work opens the access to new protein classes and paves the road toward illustrating the topological effects on structure‐function relationship of proteins, which lays solid foundation for exploring topological proteins’ practical application.

What is the most favorite and original chemistry developed in your research group?

Cellular synthesis of artificial topological proteins using genetically programmed post‐translational cascade events.

How do you get into this specific field?

I was trained as a polymer chemist and always dream of accomplishing full control over macromolecules’ length, sequence, stereochemistry, and topology. I got to learn about how nature uses polymer chemistry during my postdoc study at Caltech and was amazed by the delicate cellular machinery for making biopolymers. However, the rigorous template polymerization mechanism also defines the linear configuration of DNA, RNA, and protein. Inspired by my experience in supramolecular chemistry and genetically encoded click chemistry, I proposed the use of “assembly‐reaction” synergy to make nonlinear proteins. By pre‐programming information regarding assembly and reaction into the precursor protein's gene, the nascent linear protein knows what to do and undergoes a series of cascade events to transform into various chemical topologies. I enjoy this interdisciplinary approach in tackling a long‐standing challenge.

How do you supervise your students?

Recognize that students are different. Start from a small project and finish it. Be rigorous on science, but flexible on routines. Give them sufficient freedom to explore, yet not too much to get lost. Open to debate and cultivate critical thinking. Always ready to help. Try to be a role model by acts, not words.

What is the most important personality for scientific research?

Curiosity, courage, persistence, and optimism.

What are your hobbies?

Reading and hiking.

If you have anything else to tell our readers, please feel free to do so.

There is no real boundary between scientific disciplines. They are often set by our training and mindsets. It often requires tremendous efforts to break such boundaries in order to advance science.
Subnanomolar Cathepsin S Inhibitors with High Selectivity: Optimizing Covalent Reversible α‐Fluorovinylsulfones and α‐Sulfonates as Potential Immunomodulators in Cancer
Authors: Fuchs Natalie , Meta Mergim , Lantzberg Bellinda , Bros Matthias , Ling Kuan Seah , Weil Tanja , Schirmeister Tanja
Published: May 2023

The cysteine protease cathepsin S (CatS) is overexpressed in many tumors. It is known to be involved in tumor progression as well as antigen processing in antigen‐presenting cells (APC). Recent evidence suggests that silencing CatS improves the anti‐tumor immune response in several cancers. Therefore, CatS is an interesting target to modulate the immune response in these diseases. Here, we present a series of covalent‐reversible CatS inhibitors based on the α‐fluorovinylsulfone and ‐sulfonate warheads. We optimized two lead structures by molecular docking approaches, resulting in 22 final compounds which were evaluated in fluorometric enzyme assays for CatS inhibition and for selectivity towards the off‐targets CatB and CatL. The most potent inhibitor in the series has subnanomolar affinity (Ki=0.08 nM) and more than 100,000‐fold selectivity towards cathepsins B and L. These new reversible and non‐cytotoxic inhibitors could serve as interesting leads to develop new immunomodulators in cancer therapy.
Modifiable risk‐attributable and age‐related burden of lung cancer in China, 1990–2019
Authors: Wang Chenran , Chang Yuting , Ren Jingyu , Wu Zheng , Zheng Yadi , Luo Zilin , Qin Chao , Cao Wei , Wang Fei , Xu Yongjie , Zhao Liang , Dong Xuesi , Xia Changfa , Li Jiang , Ren Jiansong , Shi Jufang , Li Jibin , Zou Kaiyong , Chen Wanqing , Tan Fengwei , Li Ni , He Jie
Published: May 2023

Background

There were limited studies on the quantification of the modifiable and nonmodifiable lung cancer burden over time in China. Furthermore, the potential effect of risk factor reduction for lung cancer on gains in life expectancy (LE) remains unknown.

Methods

This study explored temporal trends in lung cancer deaths and disability‐adjusted life years (DALY) attributable to modifiable risk factors from 1990 to 2019, based on the 2019 Global Burden of Disease Study. The abridged period life table method was used to quantify the effect of risk factors on LE. The authors used the decomposition approach to estimate contributions of aging metrics to change in the lung cancer burden.

Results

Nationally, the majority of lung cancer deaths and DALYs were attributable to behavioral and environmental risk clusters. Potential gains in life expectancy (PGLE) at birth would be 0.78 years for males and 0.35 years for females if the exposure to risk factors was mitigated to the theoretical minimum level. Tobacco use had the most robust impact on LE for both sexes (PGLE: 0.71 years for males and 0.19 years for females). From 1990 to 2019, risk‐attributable age‐standardized death and DALY rates of lung cancer showed an increasing trend in both sexes; adult population growth imposed 245.9 thousand deaths and 6.2 million DALYs for lung cancer.

Conclusions

The modifiable risk‐attributable lung cancer burden remains high in China. Effective tobacco control is the critical step toward addressing the lung cancer burden. Adult population growth was the foremost driver of transition in the age‐related lung cancer burden.

Plain Language Summary

We estimate the lung cancer burden attributable to modifiable and nonmodifiable contributors and the effect of risk factor reduction for lung cancer on the life expectancy in China.

The findings suggest that the majority of lung cancer deaths and disability‐adjusted life years were attributable to behavioral risk clusters, and the risk‐attributable lung cancer burden increased nationally from 1990 to 2019.

The average gains in life expectancy would be 0.78 years for males and 0.35 years for females if the exposure to risk factors for lung cancer was reduced to the theoretical minimum risk exposure level.

Adult population growth was identified as the foremost driver of variation in the aging lung cancer burden.
Stereotactic ablative radiotherapy before resection to avoid delay for early‐stage lung cancer or oligometastases during the COVID‐19 pandemic: Pathologic outcomes from the SABR‐BRIDGE protocol
Authors: Kidane Biniam , Gerard Ian J. , Spicer Jonathan , Kim Julian O. , Fiset Pierre O. , Wawryko Paul , Cecchini Matthew J. , Inculet Richard , Abdulkarim Bassam , Fortin Dalilah , Qiabi Mehdi , Qing Gefei , Enns Stephanie , Bashir Bashir , Tankel James , Wakeam Elliot , Warner Andrew , Kopek Neil , Yaremko Brian P. , Rodrigues George B. , Laba Joanna M. , Qu Melody , Malthaner Richard A. , Palma David A.
Published: May 2023

Background

During coronavirus disease 2019 (COVID‐19)–related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR‐BRIDGE. This study presents the preliminary surgical and pathological results.

Methods

Eligible participants from four institutions (three in Canada and one in the United States) had early‐stage presumed or biopsy‐proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue.

Results

Seventy‐two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3–4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well‐tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID‐19) and five grade 2–3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time‐to‐surgery was 4.5 months post‐SABR (range, 2–17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3–6 months, and 33% if ≥6 months; p = .069). In the exploratory best‐case scenario analysis, pCR rate does not exceed 82%.

Conclusions

The SABR‐BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well‐tolerated. Even in the best‐case scenario, pCR rate does not exceed 82%.
Acrylic colors for peace: Non‐invasive study of an outdoor mural painting
Authors: Cano Nathael , de Lucio Oscar G. , Pérez Miguel , Mitrani Alejandro , Nagaya Alan , Sil José Luis Ruvalcaba , Medina Ricardo
Published: May 2023

In 1952, contemporary artist Federico Silva (Mexico City, 1923–2022) carried out the first outdoor mural painting: The technique at the service of peace. At the end of 2021, the project for the study and conservation of this mural began with a diagnosis of its conservation, which was done through a multi‐technique study based on the experience acquired in research projects from other contemporary mural paintings. This included the proposal of an adequate conservation strategy to resolve the stability of the painting, since the behavior of the synthetic paints exposed to the different effects of the outdoor environment has altered the perception, form and meaning of the mural. Main results from this approach by documentation and global examination with Visible Imaging and Digital Microscopy, allowed us to describe the color palette and its alterations. Additional examination of cross sections acquired from this mural, allowed a material characterization by means of optical microscopy (OM), micro‐hyperspectral imaging, Fourier transformed infrared spectroscopy and X‐ray fluorescence spectroscopies.
Spectral reflectance estimation from non‐raw color images with nonlinearity correction
Authors: Xu Peng , Hosseinkhani Jila , Rajan Sreeraman , Wang Hangjun , Yang Jie
Published: May 2023

The spectral reflectance is recognized as the fingerprint of an object surface and has been used to achieve accurate color measurement in textile and other fields. Spectral reflectance can be recovered from color images to preserve high spectral and spatial resolutions simultaneously. However, a color camera commonly supplies a non‐raw color image, which is non‐linear with respect to the scene radiance, and is inappropriate for quantitative analysis. In this study, for non‐raw color images, different nonlinearity correction models are designed and evaluated with respect to different spectral estimation algorithms. The colorimetric and spectral accuracy of spectral estimation after the nonlinearity correction is assessed through both simulation and practical experiments. In the simulation, a large number of spectral images from several datasets are employed to directly verify the effectiveness of the nonlinearity correction. In the practical experiments, the spectral estimation accuracy following the nonlinearity correction is verified directly and indirectly based on actual color images. The resulting linear color image data after the nonlinearity correction can provide better spectral estimation accuracy especially for the PI algorithm with one power‐function based model. Besides, the combination of the simple PI algorithm with the power‐function based model can exceed other combinations comprising complex algorithms and models in both accuracy and efficiency. For the linear color image data, the PI algorithm even surpasses the deep learning‐based methods in certain metric, thus indicating a shallow relationship exists between the linear color image data and the spectral reflectance.
Effect of Food on the Pharmacokinetics of Limertinib (ASK120067) and its Main Metabolite in Healthy Chinese Volunteers
Authors: Yang Dandan , Chen Wenjun , Ruan Zourong , Guo Haifang , Jiang Qianqian , Lou Honggang , Jiang Bo
Published: May 2023

Limertinib (ASK120067) is a newly developed third‐generation epidermal growth factor receptor tyrosine kinase inhibitor. This phase I, open‐label, 2‐period crossover study was conducted to evaluate the effect of food on the pharmacokinetics (PK) of limertinib and its active metabolite CCB4580030 in Chinese healthy volunteers (HVs). HVs were randomly assigned (1:1) to receive a single dose of limertinib (160 mg) under the fasted state in period 1 and fed condition in period 2, or vice versa. Twenty‐four HVs were enrolled, and 20 HVs completed both study periods. PK were assessed before dosing and ≤72 hours after dosing. PK parameters were analyzed by a noncompartmental method. Limertinib was absorbed faster in the fasted state compared with the fed state. The geometric mean ratios (fed/fast) of maximum concentration, area under the plasma concentration–time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration–time curve from time 0 to infinity for ASK120067 were 145.5%, 145.4%, and 141.9%, respectively. Geometric mean ratios of the PK parameters of CCB4580030 were >125.00% and 90% confidence intervals were outside the preset bioequivalent range. Safety profiles were similar in both prandial states, and limertinib was well tolerated. Food reduced the rate and increased the extent of limertinib absorption following oral administration. Whether limertinib can be administered regardless of prandial state in patients warrants further investigation of efficacy and safety.
Reverse Dual‐Ion Battery Enabled by Reversing the Cation/Anion Storage Mechanism in an Aqueous ZnCl2 Water‐in‐Salt Electrolyte
Authors: Sethi Asis , Kumar U. Anil , Dhavale Vishal M.
Published: May 2023

Dual ion batteries (DIBs) have garnered significant attention from researchers due to their unique ability to store charges using electrolyte‐born ions, making them promising candidates for grid storage applications. However, despite extensive efforts to explore DIBs with various electrolytes, such as organic, aqueous, gel polymer etc., challenges such as electrolyte decomposition and poor stability of anode materials in aqueous electrolytes remain unresolved. To address these issues, we report a novel approach utilizing a flip‐cum‐reverse sequence of anion/cation storage chemistry in a ZnCl2 water‐in‐salt electrolyte (ZnCl2‐WiSE)‐based reverse dual ion battery (RDIB), employing Zn‐based Prussian blue analogue i. e., Zn3[Fe(CN)6]2 and ferrocene‐carbon composite (FcC) as cathode and anode electrodes, respectively. The RDIB operates in the opposite direction compared to conventional DIBs, offering a fresh perspective. Through our investigations, we discovered that increasing the concentration of ZnCl2‐WiSE [ZnCl2‐WiSE] resulted in a positive shift of 270 mV in the redox potential for cation/anion (de)insertion at the cathode, and a negative shift of 70 mV at the anode, indicating enhanced performance. Remarkably, the RDIB operate in 10 m ZnCl2‐WiSE exhibited an impressive energy density of 23 Wh kg−1, showcasing the potential of this approach for high‐performance energy storage.
Fractional‐order LC filter modeling, implementation, and analysis for distributed power generation system
Authors: Govind D. , Suryawanshi H. M. , Nachankar P. P. , Narayana Chintalpudi L. , Singhal Ankit
Published: May 2023

This paper proposes a comprehensive mathematical modeling and analysis considering fractional‐order LC filters (FOLCF) in the utility grid‐connected mode (UGCM) and the standalone mode (SM) of operation for the distributed power generation system. The fractional‐order behavior of LC filter elements helps to more properly depict a practical inductor or capacitor than the integer‐order LC filters (IOLCF) in the distributed power generation system. The fractional‐order model of UGCM and SM is obtained in the synchronously rotating reference frame using coordinate transformation. A detailed stability and time domain analysis is performed on the developed FO UGCM and SM mathematical models. The stability of fractional‐order LC filters increases for orders
less than 1, based on the performance evaluation of the FO and IO mathematical models for UGCM and SM with the corresponding designed controller gains. The FOLCFs are approximated using the constant phase element method, which gives a compact and exact approximation of the fractional‐order inductor and capacitor elements. The implementation of FOLCF with UGCM and SM operations verifies the effectiveness of the proposed model in real‐time simulation. The results show the FOLCF model provides better dynamic tracking and disturbance rejection response than the IOLCF model. Hence, the FOLCF model imparts immunity against local load disturbances to regulate the point of common coupling voltage and frequency in standalone mode. Furthermore, a significant improvement in % total harmonic distortion is also observed in grid current and load voltage.
The effect of sleep disorders on dementia risk in patients with traumatic brain injury: A large‐scale cohort study
Authors: Mollayeva Tatyana , Tran Andrew , Hurst Mackenzie , Escobar Michael , Colantonio Angela
Published: May 2023

Introduction

We investigated the association between sleep disorders (SDs) and incident dementia in adults with traumatic brain injury (TBI).

Methods

Adults with a TBI between 2003 and 2013 were followed until incident dementia. Sleep disorders at TBI were predictors in Cox regression models, controlling for other dementia risks.

Results

Over 52 months, 4.6% of the 712,708 adults (59% male, median age 44, <1% with SD) developed dementia. An SD was associated with a 26% and a 23% of increased risk of dementia in male and female participants (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.11–1.42 and HR 1.23, 95% CI 1.09–1.40, respectively). In male participants, SD was associated with a 93% increased risk of early‐onset dementia (HR 1.93, 95% CI 1.29–2.87); this did not hold in female participants (HR 1.38, 95% CI 0.78–2.44).

Discussion

In a province‐wide cohort, SDs at TBI were independently associated with incident dementia. Clinical trials testing sex‐specific SD care after TBI for dementia prevention are timely.

Highlights

TBI and sleep disorders are linked to each other, and to dementia.

It is unclear if sleep disorders pose a sex‐specific dementia risk in brain injury.

In this study, presence of a sleep disorder increased dementia risk in both sexes.

The risk differed by type of sleep disorder, which differed between the sexes.

Sleep disorder awareness and care in persons with brain injury is vital for dementia prevention.
Micro‐ to macro‐scaling analysis of PM2.5 in sensitive environment of Himalaya, India
Authors: Kimothi Sanjeev , Chilkoti Sumit , Rawat Vikash , Thapliyal Asha , Gautam Alok Sagar , Gautam Sneha
Published: May 2023

Fine particulate matter (PM) in the atmosphere has become a significant air contaminant with substantial health consequences. Although airborne remote sensing and ground sensor monitoring can offer air quality datasets containing PM2.5, there are limitations to effectively analysing large long‐term datasets. The research aims to evaluate air quality over the Himalayan region using the multifractal approach for the PM2.5 data time series. Fractal dimension (FD), Hurtz exponent (H), and predictability (PI) are estimated using the rescaled range. PM2.5 is found to have high concentration and frequency throughout the day. The same is found in the night hours during peak tourism months. The hourly PM2.5 time series datasets have shown multifractality. The primary reason for this is emissions produced by vehicles and anthropocentric activities in the region. The H is used to assess the dynamic features of the PM2.5 time series in terms of persistence and self‐correlation. In the context of climate change studies, it is crucial to monitor the spatial distribution and dynamic behaviour of PM2.5 in the Himalayan foothills. This study aims to provide prediction analyses and air quality index (AQI) estimates and demonstrate how PM2.5 concentrations alter the sensitive environment throughout the micro to macro scale. This will help us to build a long‐term strategy for reducing the harmful effect of increasing pollution levels on the ecosystem and human health.
Application of artificial intelligence in geotechnical and geohazard investigations
Authors: Zhang Wengang , Pradhan Biswajeet , Stuyts Bruno , Xu Chong
Published: May 2023

The application of artificial intelligence (AI) and big data in geohazard investigations has gained popularity due to the development of machine learning algorithms and data collection methods. Previous studies have compared and applied various machine learning‐based methods, such as conventional machine learning, deep learning, and transfer learning in different areas. This special issue provides state‐of‐the‐art information on the use of AI in geotechnical research, particularly in the Three Gorges Reservoir (TGR) area and adjoining regions. The aim of this volume is to serve as a reference for future researchers interested in exploring the potential of AI in geohazard investigations. It is hoped that this special issue will contribute to the development of guidelines for enhancing the application of AI and big data in geotechnical research, thereby improving our understanding of geological terrains and their associated hazards.