bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering diaryl alcohol dehydrogenase KpADH reveals importance of retaining hydration shell in organic solvent tolerance
Authors: Zhang Lu , Dai Wei , Rong Shuo , Schwaneberg Ulrich , Xu Guochao , Ni Ye 
Published: March 2024

AbstractAlcohol dehydrogenases (ADHs) are synthetically important biocatalysts for the asymmetric synthesis of chiral alcohols. The catalytic performance of ADHs in the presence of organic solvents is often important since most prochiral ketones are highly hydrophobic. Here, the organic solvent tolerance of KpADH from Kluyveromyces polyspora was semi‐rationally evolved. Using tolerant variants obtained, meticulous experiments and computational studies were conducted to explore properties including stability, activity and kinetics in the presence of various organic solvents. Compared with WT, variant V231D exhibited 1.9‐fold improvement in ethanol tolerance, while S237G showed a 6‐fold increase in catalytic efficiency, a higher , as well as 15% higher tolerance in 7.5% (v/v) ethanol. Based on 3 × 100 ns MD simulations, the increased tolerance of V231D and S237G against ethanol may be ascribed to their enhanced ability in retaining water molecules and repelling ethanol molecules. Moreover, 6.3‐fold decreased KM value of V231D toward hydrophilic ketone substrate confirmed its capability of retaining hydration shell. Our results suggest that retaining hydration shell surrounding KpADH is critical for its tolerance to organic solvents, as well as catalytic performance. This study provides useful guidance for engineering organic solvent tolerance of KpADH and other ADHs.
Assessing the mechanism of fast‐cycling cancer‐associated mutations of Rac1 small Rho GTPase
Authors: Parise Angela , Magistrato Alessandra 
Published: March 2024

AbstractRho‐GTPases proteins function as molecular switches alternating from an active to an inactive state upon Guanosine triphosphate (GTP) binding and hydrolysis to Guanosine diphosphate (GDP). Among them, Rac subfamily regulates cell dynamics, being overexpressed in distinct cancer types. Notably, these proteins are object of frequent cancer‐associated mutations at Pro29 (P29S, P29L, and P29Q). To assess the impact of these mutations on Rac1 structure and function, we performed extensive all‐atom molecular dynamics simulations on wild‐type (wt) and oncogenic isoforms of this protein in GDP‐ and GTP‐bound states. Our results unprecedentedly elucidate that P29Q/S‐induced structural and dynamical perturbations of Rac1 core domain weaken the binding of the catalytic site Mg2+ ion, and reduce the GDP residence time within protein, enhancing the GDP/GTP exchange rate and Rac1 activity. This broadens our knowledge of the role of cancer‐associated mutations on small GTPases mechanism supplying valuable information for future drug discovery efforts targeting specific Rac1 isoforms.
Construction of a versatile fusion protein for targeted therapy and immunotherapy
Authors: Huang Xiu‐Song , Yang Li‐Ting , Yang Ke , Zhou Hang , Abudureheman Tuersunayi , Zheng Wei‐Wei , Chen Kai‐Ming , Duan Cai‐Wen 
Published: March 2024

AbstractAntibody (Ab)‐based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab‐based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag‐X (S‐X) to form the SpaCC‐S‐X complex, which binds non‐covalently to an Ab to form the Ab‐SpaCC‐S‐X protein complex. The “X” can be a variety of small molecules such as fluoresceins, cell‐penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab‐SpaCC‐S‐FITC(−TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab‐SpaCC‐SN3‐MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab‐DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab‐SpaCC‐SN3‐Ap boosted the tumor‐killing function of T‐cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy.
Structural dynamics and functional cooperativity of human NQO1 by ambient temperature serial crystallography and simulations
Authors: Grieco Alice , Boneta Sergio , Gavira José A. , Pey Angel L. , Basu Shibom , Orlans Julien , Sanctis Daniele de , Medina Milagros , Martin‐Garcia Jose Manuel 
Published: March 2024

AbstractThe human NQO1 (hNQO1) is a flavin adenine nucleotide (FAD)‐dependent oxidoreductase that catalyzes the two‐electron reduction of quinones to hydroquinones, being essential for the antioxidant defense system, stabilization of tumor suppressors, and activation of quinone‐based chemotherapeutics. Moreover, it is overexpressed in several tumors, which makes it an attractive cancer drug target. To decipher new structural insights into the flavin reductive half‐reaction of the catalytic mechanism of hNQO1, we have carried serial crystallography experiments at new ID29 beamline of the ESRF to determine, to the best of our knowledge, the first structure of the hNQO1 in complex with NADH. We have also performed molecular dynamics simulations of free hNQO1 and in complex with NADH. This is the first structural evidence that the hNQO1 functional cooperativity is driven by structural communication between the active sites through long‐range propagation of cooperative effects across the hNQO1 structure. Both structural results and MD simulations have supported that the binding of NADH significantly decreases protein dynamics and stabilizes hNQO1 especially at the dimer core and interface. Altogether, these results pave the way for future time‐resolved studies, both at x‐ray free‐electron lasers and synchrotrons, of the dynamics of hNQO1 upon binding to NADH as well as during the FAD cofactor reductive half‐reaction. This knowledge will allow us to reveal unprecedented structural information of the relevance of the dynamics during the catalytic function of hNQO1.
Reengineering of a flavin‐binding fluorescent protein using ProteinMPNN
Authors: Nikolaev Andrey , Kuzmin Alexander , Markeeva Elena , Kuznetsova Elizaveta , Ryzhykau Yury L. , Semenov Oleg , Anuchina Arina , Remeeva Alina , Gushchin Ivan 
Published: March 2024

AbstractRecent advances in machine learning techniques have led to development of a number of protein design and engineering approaches. One of them, ProteinMPNN, predicts an amino acid sequence that would fold and match user‐defined backbone structure. Its performance was previously tested for proteins composed of standard amino acids, as well as for peptide‐ and protein‐binding proteins. In this short report, we test whether ProteinMPNN can be used to reengineer a non‐proteinaceous ligand‐binding protein, flavin‐based fluorescent protein CagFbFP. We fixed the native backbone conformation and the identity of 20 amino acids interacting with the chromophore (flavin mononucleotide, FMN) while letting ProteinMPNN predict the rest of the sequence. The software package suggested replacing 36–48 out of the remaining 86 amino acids so that the resulting sequences are 55%–66% identical to the original one. The three designs that we tested experimentally displayed different expression levels, yet all were able to bind FMN and displayed fluorescence, thermal stability, and other properties similar to those of CagFbFP. Our results demonstrate that ProteinMPNN can be used to generate diverging unnatural variants of fluorescent proteins, and, more generally, to reengineer proteins without losing their ligand‐binding capabilities.
Meat consumption and obesity: A climate‐friendly way to reduce health inequalities
Authors: Sares‐Jäske Laura , Tapanainen Heli , Valsta Liisa , Haario Peppi , Männistö Satu , Vaalavuo Maria 
Published: March 2024

AbstractBackgroundClimate change, health inequalities and obesity are considerable public health challenges of the 21st century. Red and processed meat (RPM) consumption is associated with an increased risk of obesity and with higher climate impact. At the same time, educational inequalities exist not only in RPM consumption and obesity but also in other health behaviours. Thus, we investigated whether educational inequalities exist in the association between RPM consumption and obesity, while also considering health behaviours (physical activity, vegetable, legume and fruit consumption, alcohol consumption and smoking) as potential confounding and effect modifying factors.MethodsThe FinHealth 2017 Study data, including 4494 participants aged 18–74 years, were used. A validated food frequency questionnaire was employed to determine dietary intake. Height and weight were measured by trained study nurses. Linear and logistic regression models were used.ResultsOdds of obesity increased along with RPM consumption in women (p < 0.001) and men (p < 0.001) and in each educational group regardless of other unfavourable health behaviours. Only in men with basic education were the differences between RPM consumption categories not statistically significant. Compared to those with high education and the lowest RPM consumption, those with basic education and the highest RPM consumption had multiple odds of obesity (odds ratio (95% confidence interval) among women: 7.5 (2.7–20.4); among men: 5.3 (2.5–11.1)).ConclusionHigh RPM consumption appears to be associated with obesity independently of other unfavourable health behaviours or education, yet the odds are higher with basic education. Targeting unhealthy dietary patterns with heavy ecological burden could help reduce both health inequalities and mitigate climate change.
Indirect effects of latent heat of condensation on the simulation of the 2021 catastrophic Henan rainfall event in central China
Authors: Xu Hongxiong , Zhao Dajun , Gao Wenhua , Duan Yihong , Yin Jinfang , Li Ying , Zhou Lingli 
Published: March 2024

AbstractCloud‐related latent heat is critical to the development and maintenance of atmospheric circulation. However, it is unclear how sensitive the key large‐scale weather systems of an extreme rainfall event could be to the variation in cloud‐related latent heat. In a companion study, by investigating the indirect effects of different microphysics schemes, we hypothesized that the latent heat of condensation (CT) would play a role in the ability to simulate the extreme rainfall event that took place in Henan Province, central China, on July 19–21, 2021. To examine the proposed hypothesis, the impacts of varying the CT and the collection of cloud water by rainwater (ACW) in the Thompson, WDM6, and Morrison microphysics schemes on the simulation of the southerly flow and its indirect effect on this extreme rainfall case were studied using the Advanced Research Weather Research and Forecasting (ARW‐WRF) model. It was found that directly changing the CT and ACW had significant effects on the southerly flow and precipitation. An increase in CT generally led to a reduced temperature gradient, a smaller pressure gradient, a stronger southerly flow, and a precipitation surge of 32%–50%. Similar outcomes resulted from increasing ACW in the WDM6 scheme, which effectively diminished the cloud mixing ratio, generated higher CT, and consequently intensified the southerly flow and precipitation by 31%. This study confirmed that the accurate simulation of microphysical processes, along with latent heating, is desirable for more realistically reproducing the key weather systems in the simulation of extreme rainfall.
Photonic Non‐Markovianity Identification by Quantum Process Capabilities of Non‐CP Processes
Authors: Hsu Chan , Kao Yu‐Chien , Chen Hong‐Bin , Chen Shih‐Hsuan , Li Che‐Ming 
Published: March 2024

AbstractA Markovian quantum process can be arbitrarily divided into two or more legitimate completely‐positive (CP) subprocesses. When at least one non‐CP process exists among the divided processes, the dynamics is considered non‐Markovian. However, how to utilize minimum experimental efforts, without examining all process input states and using entanglement resources, to identify or measure non‐Markovianity is still being determined. Herein, a method is proposed to quantify non‐CP processes for identifying and measuring non‐Markovianity without the burden of state optimization and entanglement. This relies on the non‐CP processes as new quantum process capabilities and can be systematically implemented by quantum process tomography. Additionally, an approach for witnessing non‐Markovianity by analyzing at least four system states without process tomography is provided. It is faithfully demonstrated that this method can be explicitly implemented using all‐optical setups and applied to identify the non‐Markovianity of single‐photon and two‐photon dynamics in birefringent crystals. The results also can be used to explore non‐Markovianity in other dynamical systems where process or state tomography is implementable.
Bevacizumab‐induced pulmonary cystic disease
Authors: McNierney Dakota , Owda Fahed , Salim Hamza A. , Mallah Shatha M. A. , Azar Jehad 
Published: March 2024

AbstractThe use of Bevacizumab has significantly advanced the treatment of various malignancies. Bevacizumab's inhibition of angiogenesis is a known mechanism that impedes tumour growth and facilitates chemotherapy delivery; however, its association with the development of cystic lung disease is not fully understood. We report a unique case of a 73‐year‐old woman with a past medical history of metastatic endometrial adenocarcinoma status post‐chemotherapy with bevacizumab that presented with worsening respiratory symptoms. A follow‐up chest CT scan post chemotherapy showed the transformation of the metastatic lesions into cystic formations. After further extensive evaluation, she was diagnosed with pulmonary cystic disease secondary to bevacizumab. This case illustrates a rare presentation of secondary pulmonary cystic disease following Bevacizumab therapy in a patient with metastatic endometrial adenocarcinoma. It highlights the importance of recognizing uncommon side effects of targeted immunotherapy and underscores the need for ongoing research to understand the underlying mechanisms and manage such complications effectively.
Ferritin: Significance in viral infections
Authors: Zhao Xia , Zhou Yuntao , Zhang Yong , Zhang Yan 
Published: March 2024

AbstractAs an indispensable trace element, iron is essential for many biological processes. Increasing evidence has shown that virus infection can perturb iron metabolism and play a role in the occurrence and development of viral infection‐related diseases. Ferritin plays a crucial role in maintaining the body's iron homoeostasis. It is an important protein to stabilise the iron balance in cells. Ferritin is a 24‐mer hollow iron storage protein composed of two subunits: ferritin heavy chain and ferritin light chain. It was reported that ferritin is not only an intra‐cellular iron storage protein, but also a pathogenic mediator that enhances the inflammatory process and stimulates the further inflammatory pathway, which is a key member of the vicious pathogenic cycle to perpetuate. Ferritin exerts immuno‐suppressive and pro‐inflammatory functions during viral infection. In this review, we describe in detail the basic information of ferritin in the first section, including its structural features, the regulation of ferritin. In the second part, we focus on the role of ferritin in viral infection‐related diseases and the molecular mechanisms by which viral infection regulates ferritin. The last section briefly outlines the potential of ferritin in antiviral therapy. Given the importance of iron and viral infection, understanding the role of ferritin during viral infection helps us understand the relationship between iron metabolic dysfunction and viral infection, which provides a new direction for the development of antiviral therapeutic drugs.
Analyzing natural bed‐level dynamics to mitigate the morphological impact of river interventions
Authors: van Denderen R. Pepijn , Schielen Ralph M. J. , Paarlberg Andries J. , Reneerkens Michiel , Augustijn Denie C. M. 
Published: March 2024

AbstractLocal river interventions, such as channel narrowing or side channels, are often necessary to maintain safety, ecology, or navigation. Such interventions have different effects on the river's bed morphology during periods of high‐ and low‐discharge events. Mapping the bed‐level variations for different discharge levels and understanding these effects can provide new opportunities for the design of interventions in multifunctional rivers. At any moment, the local bed level in a river is composed of bed‐level changes that occur at various spatial and temporal scales. These changes consist of bed aggradation/degradation trends on a large scale, on an intermediate scale bed‐level variations as a result of discharge fluctuations, and on small‐scale moving river bed forms like dunes. Using the river Waal in the Netherlands as a case study, we analyze the intermediate‐term bed‐level changes resulting from discharge fluctuations (dynamic component) and propose adaptations to the design of floodplain interventions such that possible negative impact on the local bed‐level changes is minimized. Time series of bed levels along two 10 km stretches of the case study are considered for a period of 16 years (2005–2020). Using a wavelet transform, we isolate bed‐level variations resulting from discharge events. These bed‐level variations are presented based on the magnitude of the discharge event and are compiled in an interactive atlas of river morphodynamics, allowing us to mitigate the impact of interventions. This will help river managers in the design of interventions and lead to improved management, operation, and maintenance of multifunctional rivers.
Advancement in Sustainable Wastewater Treatment: A Multifaceted Approach to Textile Dye Removal through Physical, Biological and Chemical Techniques
Authors: N Lotha Tsenbeni , Sorhie Viphrezolie , Bharali Pranjal , Jamir Latonglila 
Published: March 2024

AbstractThe global manufacturing sector heavily relies on the textile industry, yet the widespread utilization of synthetic dyes within this sector has raised serious environmental apprehensions, notably regarding wastewater contamination. The release of untreated wastewater containing residual dyes poses a significant risk to both aquatic ecosystems and human well‐being. In reaction to this issue, considerable efforts have been made to develop efficient and sustainable methods for the removal of textile dyes from wastewater. This comprehensive review paper furnishes in‐depth literature information covering various aspects of dyes, including their classification, toxicity effects, and evaluation of recent advancements in dye removal technology, emphasizing their advantages, limitations, and future potential. Various strategies are covered, including physical, chemical, and biological methods. Physical techniques like adsorption, filtration, and membrane technologies are contrasted with chemical approaches such as coagulation, precipitation, and advanced oxidation processes. Biological methods include the utilization of micro‐organisms, fungi, and enzymes to break down or metabolize dye compounds. Key considerations in the critical analysis include the efficiency, cost‐effectiveness, and scalability of each method. This review focuses on enzyme breakdown (biological) and adsorption (physical) color removal procedures, which are currently considered the most effective. It also proposes the utilization of a composite adsorbent, anticipating enhanced efficiency and faster removal of dyes through this technique.
Preparation of Metal‐Containing Zwitterionic Fe3O4@SiO2−βPDMA Composite Systems and Catalytic Activity Studies
Authors: Tuncer Cansel , Yurdakul Cagdas 
Published: March 2024

AbstractIn response to the current challenges in the field, this study will contribute to the development of a highly versatile magnetic core/shell nanocomposite by addressing issues in the synthesis and functionalization of Fe3O4 nanoparticles through the presentation of innovative solutions. Firstly, Fe3O4 nanoparticles were synthesized. Tetraethyl orthosilicate was used as a silicon source and Fe3O4@SiO2 magnetic nanoparticles were synthesized. The outer surface of Fe3O4@SiO2 nanoparticles were modified and converted into Fe3O4@SiO2−NH2 structure. These modified particles were then functionalized with alkyl bromide to be used as an ATRP initiator and Fe3O4@SiO2−Br structure was obtained. The polymerization of 2‐(dimethylamino)ethyl methacrylate (DMA) monomer on the particle surface was achieved by the SI‐ATRP method. In the last step, betainization of Fe3O4@SiO2−PDMA composite was worked, and the salts of gold and silver were added to composite systems. The dispersions of the metal loaded Fe3O4@SiO2−βPDMA composite was obtained and used as catalysts in the reduction reaction of p‐nitrophenol to p‐aminophenol. Consequently, Fe3O4@SiO2−βPDMA composite system with magnetic properties in the range of 145–160 nm was prepared. The structure of synthesized magnetic nanoparticle was characterized by PXRD, TEM, TG‐DTA and the catalyst activity in the reduction reaction of p‐nitrophenol to p‐aminophenol was examined by UV‐vis spectrophotometer.
Precise Control of Metal Active Sites of Metal–Organic Framework Nanozymes for Achieving Excellent Enzyme‐Like Activity and Efficient Pancreatitis Therapy
Authors: Zhang Jie , Guo Meilin , He Qikuan , Zhang Zhisen , Wu Boda , Wu Hongji , Li Rizhao , Zhang Qiyu , Tang Yonghua , Lin Youhui , Jin Yuepeng 
Published: March 2024

AbstractAcute pancreatitis (AP) is a potentially life‐threatening inflammatory disease that can lead to the development of systemic inflammatory response syndrome and its progression to severe acute pancreatitis. Hence, there is an urgent need for the rational design of highly efficient antioxidants to treat AP. Herein, an optimized Cu‐based metal–organic framework (MOF) nanozyme with exceptional antioxidant activity is introduced, designed to effectively alleviate AP, by engineering the metal coordination centers in MN2Cl2 (M = Co, Ni, Cu). Specifically, the Cu MOF, which benefits from a Cu active center similar to that of natural superoxide dismutase (SOD), exhibited at least four times higher SOD‐like activity than the Ni/Co MOF. Theoretical analyses further demonstrate that the CuN2Cl2 site not only has a moderate adsorption effect on the substrate molecule •OOH but also reduces the dissociation energy of the product H2O2. Additionally, the Cu MOF nanozyme possesses the excellent catalase‐like activity and •OH removal ability. Consequently, the Cu MOF with broad‐spectrum antioxidant activity can efficiently scavenge reactive oxygen species to alleviate arginine‐induced AP. More importantly, it can also mitigate apoptosis and necrosis of acinar cells by activating the PINK1/PARK2‐mediated mitophagy pathway. This study highlights the distinctive functions of tunable MOF nanozymes and their potential bio‐applications.