bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study of Dominant Vegetation Phenology in a Sphagnum Mountain Peatland Using In Situ and Sentinel‐2 Observations
Authors: Garisoain Raphael , Delire Christine , Decharme Bertrand , Ferrant Sylvain , Granouillac Franck , Payre‐Suc Virginie , Gandois Laure
Published: October 2023

Peatlands store more than a third of the global soil organic carbon stock. Bryophytes, more specifically Sphagnum mosses, play a major role in the carbon and water cycles of these ecosystems. There is a need to include Sphagnum mosses into Earth system models to better simulate the dynamics of peatlands in a changing environment. Leaf area index (LAI) is a key plant trait that characterizes the plant photosynthesizing capacity. Moreover, LAI is a variable calculated by land surface models used in climate models, allowing control of the exchange of matter and energy between vegetation and the environment. There is extremely little data on Sphagnum LAI and none on its seasonal change. We monitored Sphagnum mosses LAI phenology in a mountainous peatland site (altitude of 1,343 m) from June to December 2021 using two methods: 2D scans of monthly Sphagnum moss samples and analysis of Sentinel‐2 images. LAI derived from field campaigns and the remote sensing approach show a strong seasonality, with high peak values reaching 10 and 7 m2·m−2, respectively. The Sentinel‐2 images were also used to derive common vegetation indices. The moisture soil index effectively discriminates Sphagnum‐dominated areas in the peatland. Satellite‐derived LAI of Sphagnum mosses is directly correlated to gross primary production monitored by gas exchange measurements (R2 = 0.83) but also to physical drivers of the environment such as air temperature (R2 = 0.74) or water table depth (R2 = 0.61) over the 2017–2021 period. It is therefore highly suitable to investigate ecosystemic functions.
Assessing Impacts of Environmental Perturbations on Urban Biogenic Carbon Exchange in the Chicago Region
Authors: Li Peiyuan , Sharma Ashish , Wang Zhi‐Hua , Wuebbles Donald
Published: October 2023

Carbon dioxide (CO2) quantification is critical for assessing city‐level carbon emissions and sustainable urban development. While urban vegetation has the potential to provide environmental benefits, such as heat and carbon mitigation, the CO2 exchange from biogenic sectors and its impact from the environmental perturbations are often overlooked. It is also challenging to simulate the plant functions in the complex urban terrain. This study presents a processed‐based modeling approach to assess the biogenic carbon fluxes from the vegetated areas over the Chicago Metropolitan Area (CMA) using the Weather Research and Forecast—Urban Biogenic Carbon exchange model. We investigate the change of CO2 sink power in CMA under heatwaves and irrigation. The results indicate that the vegetation plays a significant role in the city's carbon portfolio and the landscaping management has the potential to reduce carbon emissions significantly. Furthermore, based on the competing mechanisms in the biogenic carbon balance identified in this study, we develop a novel Environmental Benefit Score metrics framework to identify the vulnerability and mitigation measures associated with nature‐based solutions (NbS) within CMA. By using the generalized portable framework and our science‐policy confluence analysis presented in this study, global cities can maximize the effectiveness of NbS and accelerate carbon neutrality.
Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer’s disease
Authors: Iyaswamy Ashok , Thakur Abhimanyu , Guan Xin-Jie , Krishnamoorthi Senthilkumar , Fung Tsz Yan , Lu Kejia , Gaurav Isha , Yang Zhijun , Su Cheng-Fu , Lau Kwok-Fai , Zhang Kui , Ng Roy Chun-Laam , Lian Qizhou , Cheung King-Ho , Ye Keqiang , Chen Huanhuan Joyce , Li Min
Published: October 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques, hyperphosphorylated tau protein, and neurofibrillary tangles in the brain. The overexpression of amyloid-β precursor protein (APP) in an AD brain results in the binding of APP intracellular domain (AICD) to Fe65 protein via the C-terminal Fe65-PTB2 interaction, which then triggers the secretion of amyloid-β and the consequent pathogenesis of AD. Apparently, targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD. Recently, exosome, a type of extracellular vesicle with diameter around 30–200 nm, has gained much attention as a potential delivery tool for brain diseases, including AD, due to their ability to cross the blood–brain barrier, their efficient uptake by autologous cells, and their ability to be surface-modified with target-specific receptor ligands. Here, the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65, enabled the development of a novel exosome-based targeted drug delivery system, which carried Corynoxine-B (Cory-B, an autophagy inducer) to the APP overexpressed-neuron cells in the brain of AD mice. The Fe65-engineered HT22 hippocampus neuron cell-derived exosomes (Fe65-EXO) loaded with Cory-B (Fe65-EXO-Cory-B) hijacked the signaling and blocked the natural interaction between Fe65 and APP, enabling APP-targeted delivery of Cory-B. Notably, Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells, leading to amelioration of the cognitive decline and pathogenesis in AD mice, demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.
Rapid growth rate responses of terrestrial bacteria to field warming on the Antarctic Peninsula
Authors: Purcell Alicia M , Dijkstra Paul , Hungate Bruce A , McMillen Kelly , Schwartz Egbert , van Gestel Natasja
Published: October 2023

Ice-free terrestrial environments of the western Antarctic Peninsula are expanding and subject to colonization by new microorganisms and plants, which control biogeochemical cycling. Measuring growth rates of microbial populations and ecosystem carbon flux is critical for understanding how terrestrial ecosystems in Antarctica will respond to future warming. We implemented a field warming experiment in early (bare soil; +2 °C) and late (peat moss-dominated; +1.2 °C) successional glacier forefield sites on the western Antarctica Peninsula. We used quantitative stable isotope probing with H218O using intact cores in situ to determine growth rate responses of bacterial taxa to short-term (1 month) warming. Warming increased the growth rates of bacterial communities at both sites, even doubling the number of taxa exhibiting significant growth at the early site. Growth responses varied among taxa. Despite that warming induced a similar response for bacterial relative growth rates overall, the warming effect on ecosystem carbon fluxes was stronger at the early successional site—likely driven by increased activity of autotrophs which switched the ecosystem from a carbon source to a carbon sink. At the late-successional site, warming caused a significant increase in growth rate of many Alphaproteobacteria, but a weaker and opposite gross ecosystem productivity response that decreased the carbon sink—indicating that the carbon flux rates were driven more strongly by the plant communities. Such changes to bacterial growth and ecosystem carbon cycling suggest that the terrestrial Antarctic Peninsula can respond fast to increases in temperature, which can have repercussions for long-term elemental cycling and carbon storage.
HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation
Authors: Li Yuheng , Sun Weijia , Li Jianwei , Du Ruikai , Xing Wenjuan , Yuan Xinxin , Zhong Guohui , Zhao Dingsheng , Liu Zizhong , Jin Xiaoyan , Pan Junjie , Li Youyou , Li Qi , Kan Guanghan , Han Xuan , Ling Shukuan , Sun Xiqing , Li Yingxian
Published: October 2023

Bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoblast function play critical roles in bone formation, which is a highly regulated process. Long noncoding RNAs (lncRNAs) perform diverse functions in a variety of biological processes, including BMSC osteogenic differentiation. Although several studies have reported that HOX transcript antisense RNA (HOTAIR) is involved in BMSC osteogenic differentiation, its effect on bone formation in vivo remains unclear. Here, by constructing transgenic mice with BMSC (Prx1-HOTAIR)- and osteoblast (Bglap-HOTAIR)-specific overexpression of HOTAIR, we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo. Specifically, Prx1-HOTAIR mice showed delayed bone formation, while Bglap-HOTAIR mice showed increased bone formation. HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro. Furthermore, we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts. HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation. We first identified that the RNA-binding protein human antigen R (HuR) is responsible for HOTAIR nucleocytoplasmic translocation. HOTAIR is essential for osteoblast function, and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function. Bglap-HOTAIR mice, but not Prx1-HOTAIR mice, showed alleviation of bone loss induced by unloading. This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation, which provides new insights into precise regulation as a target for bone loss.
Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms
Authors: Morken Siren , Langer Seppo W. , Sundlöv Anna , Vestermark Lene Weber , Ladekarl Morten , Hjortland Geir Olav , Svensson Johanna B. , Tabaksblat Elizaveta Mitkina , Haslerud Torjan Magne , Assmus Jörg , Detlefsen Sönke , Couvelard Anne , Perren Aurel , Sorbye Halfdan
Published: October 2023

Background

The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients.

Methods

Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed.

Results

For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2 months and the median overall survival (OS) 26.4 months. Considering 26 NET G3 patients, 6 months DCR was 77% vs. 22% among nine NEC patients (p = 0.006). PFS was superior for NET G3 vs. NEC (12.6 months vs. 3.4 months, Log-rank-test: p = 0.133, Breslow-test: p < 0.001). OS was significantly better for NET G3 (31.4 months vs. 7.8 months, p = 0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment.

Conclusion

Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL.

Clinical trial registration

ClinicalTrials.gov (NTC02248012).
Potent Rifampicin derivatives can clear MRSA infections at single low doses when concomitantly dosed with Vancomycin
Authors: Nittoli Thomas , Zumsteg Anna Brotcke , Bandyopadhyay Abira , Federici Stephanie , Coppi Alida , Jorgenson Susan , Choi Seung-Yong , Saha Mrinmoy , Wertz Benjamin , Trivedi Priyanka , Korgaonkar Chandrashekhar , Chin Harvey , Luong Onson , Kyratsous Christos , Olson William
Published: October 2023

For a number of years, antimicrobial resistance (AMR) has been a critical issue for humanity. Drug discovery efforts have been very limited and the spread of bacterial pathogens has over-run our traditional arsenal of antibiotics. Bacteria can involve to evade compounds that can halt their rapid growth. The authors have discovered a potent macrocycle derivative that when dosed concomitantly with the standard of care (SOC) antibiotic vancomycin, can clear methicillin resistant Staphylococcus aureus (MRSA) infections. In addition, we have probed the lead compounds in Salmonella typhimurium bacterial strains. In vitro, in vivo, and ADME data have been included to stress the virtues of this new antibiotic.
Blood pressure in atrial fibrillation and in sinus rhythm during ambulatory blood pressure monitoring: data from the TEMPLAR project
Authors: Lundwall Kristina , Kahan Thomas , Omboni Stefano
Published: October 2023

The coexistence of hypertension and atrial fibrillation (AF) is common and accounts for a worse prognosis. Uncertainties exist regarding blood pressure (BP) measurements in AF patients by automated oscillometric devices. The Microlife WatchBP 03 AFIB ambulatory BP monitoring (ABPM) device including an AF algorithm with each measurement was used in 430 subjects aged >65 years referred for ABPM and with assumed paroxysmal AF to perform intra-individual comparisons of BP during both AF-indicated and sinus rhythm. Only subjects with >30% of measurements indicating AF and episodes >30 min for assumed AF and for sinus rhythm were included. Mean age was 78 ± 7 years, 43% were male, 77% hypertensive, and 72% were treated. Compared to sinus rhythm, 24-h mean arterial pressure was similar (87.2 ± 9.5 vs 87.5 ± 10.6 mm Hg, p = 0.47), whereas 24-h systolic BP tended to be lower (123.6 ± 13.9 vs 124.7 ± 16.1 mm Hg, p = 0.05) and night-time diastolic BP higher (64.6 ± 10.9 vs 63.3 ± 10.4 mm Hg, p = 0.01) in assumed AF. Diastolic (not systolic) BP variability was higher in AF (p < 0.001). Results were similar with heart rates <90 and ≥90 bpm. In conclusion, this is the first study to use intra-individual comparisons of averaged BP during an ABPM in assumed paroxysmal AF and sinus rhythm. Our results imply that ABPM is feasible and informative also in patients with AF. We also suggest that an AF detection algorithm offers a new approach to evaluate the reliability of averaged BP values in AF compared to SR during an ABPM.
Parametric simulation of electron backscatter diffraction patterns through generative models
Authors: Ding Zihao , De Graef Marc
Published: October 2023

Recently, discriminative machine learning models have been widely used to predict various attributes from Electron Backscatter Diffraction (EBSD) patterns. However, there has never been any generative model developed for EBSD pattern simulation. On one hand, the training of generative models is much harder than that of discriminative ones; On the other hand, numerous variables affecting EBSD pattern formation make the input space high-dimensional and its relationship with the distribution of backscattered electrons complicated. In this study, we propose a framework (EBSD-CVAE/GAN) with great flexibility and scalability to realize parametric simulation of EBSD patterns. Compared with the frequently used forward model, EBSD-CVAE/GAN can take variables more than just orientation and generate corresponding EBSD patterns in a single run. The accuracy and quality of generated patterns are systematically evaluated. The model does not only summarize a distribution of backscattered electrons at a higher level, but also mitigates data scarcity in this field.
Self-healable stretchable printed electronic cryogels for in-vivo plant monitoring
Authors: Bihar Eloïse , Strand Elliot J. , Crichton Catherine A. , Renny Megan N. , Bonter Ignacy , Tran Tai , Atreya Madhur , Gestos Adrian , Haseloff Jim , McLeod Robert R. , Whiting Gregory L.
Published: October 2023

A key challenge in bioelectronics is to establish and improve the interface between electronic devices and living tissues, enabling a direct assessment of biological systems. Sensors integrated with plant tissue can provide valuable information about the plant itself as well as the surrounding environment, including air and soil quality. An obstacle in developing interfaces to plant tissue is mitigating the formation of fibrotic tissues, which can hinder continuous and accurate sensor operation over extended timeframes. Electronic systems that utilize suitable biocompatible materials alongside appropriate fabrication techniques to establish plant-electronic interfaces could provide for enhanced environmental understanding and ecosystem management capabilities. To meet these demands, this study introduces an approach for integrating printed electronic materials with biocompatible cryogels, resulting in stable implantable hydrogel-based bioelectronic devices capable of long-term operation within plant tissue. These inkjet-printed cryogels can be customized to provide various electronic functionalities, including electrodes and organic electrochemical transistors (OECTs), that exhibit high electrical conductivity for embedded conducting polymer traces (up to 350 S/cm), transconductance for OECTs in the mS range, a capacitance of up to 4.2 mF g−1 in suitable structures, high stretchability (up to 330% strain), and self-healing properties. The biocompatible functionalized cryogel-based electrodes and transistors were successfully implanted in plant tissue, and ionic activity in tomato plant stems was collected for over two months with minimal scar tissue formation, making these cryogel-based printed electronic devices excellent candidates for continuous, in-situ monitoring of plant and environmental status and health.
CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial
Authors: Mackensen Andreas , Haanen John B.A.G. , Koenecke Christian , Alsdorf Winfried , Wagner-Drouet Eva , Borchmann Peter , Heudobler Daniel , Ferstl Barbara , Klobuch Sebastian , Bokemeyer Carsten , Desuki Alexander , Lüke Florian , Kutsch Nadine , Müller Fabian , Smit Eveline , Hillemanns Peter , Karagiannis Panagiotis , Wiegert Erol , He Ying , Ho Thang , Kang-Fortner Qing , Schlitter Anna Melissa , Schulz-Eying Catrine , Finlayson Andrew , Flemmig Carina , Kühlcke Klaus , Preußner Liane , Rengstl Benjamin , Türeci Özlem , Şahin Uğur
Published: October 2023

The oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) at two dose levels (DLs) in relapsed/refractory CLDN6-positive solid tumors. The primary endpoints were safety and tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary endpoints included objective response rate (ORR) and disease control rate. We observed manageable toxicity, with 10 out of 22 patients (46%) experiencing cytokine release syndrome including one grade 3 event and 1 out of 22 (5%) with grade 1 immune effector cell-associated neurotoxicity syndrome. Dose-limiting toxicities occurred in two patients at the higher DL, resolving without sequelae. CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR in 21 evaluable patients was 33% (7 of 21), including one complete response. The disease control rate was 67% (14 of 21), with stable disease in seven patients. Patients with germ cell tumors treated at the higher DL exhibited the highest response rate (ORR 57% (4 of 7)). The maximum tolerated dose and RP2D were not established as the trial has been amended to utilize an automated manufacturing process. A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278.
Targeted depletion of TRBV9+ T cells as immunotherapy in a patient with ankylosing spondylitis
Authors: Britanova Olga V. , Lupyr Kseniia R. , Staroverov Dmitry B. , Shagina Irina A. , Aleksandrov Alexey A. , Ustyugov Yakov Y. , Somov Dmitry V. , Klimenko Alesia , Shostak Nadejda A. , Zvyagin Ivan V. , Stepanov Alexey V. , Merzlyak Ekaterina M. , Davydov Alexey N. , Izraelson Mark , Egorov Evgeniy S. , Bogdanova Ekaterina A. , Vladimirova Anna K. , Iakovlev Pavel A. , Fedorenko Denis A. , Ivanov Roman A. , Skvortsova Veronika I. , Lukyanov Sergey , Chudakov Dmitry M.
Published: October 2023

Autoimmunity is intrinsically driven by memory T and B cell clones inappropriately targeted at self-antigens. Selective depletion or suppression of self-reactive T cells remains a holy grail of autoimmune therapy, but disease-associated T cell receptors (TCRs) and cognate antigenic epitopes remained elusive. A TRBV9-containing CD8+ TCR motif was recently associated with the pathogenesis of ankylosing spondylitis, psoriatic arthritis and acute anterior uveitis, and cognate HLA-B*27-presented epitopes were identified. Following successful testing in nonhuman primate models, here we report human TRBV9+ T cell elimination in ankylosing spondylitis. The patient achieved remission within 3 months and ceased anti-TNF therapy after 5 years of continuous use. Complete remission has now persisted for 4 years, with three doses of anti-TRBV9 administered per year. We also observed a profound improvement in spinal mobility metrics and the Bath Ankylosing Spondylitis Metrology Index (BASMI). This represents a possibly curative therapy of an autoimmune disease via selective depletion of a TRBV-defined group of T cells. The anti-TRBV9 therapy could potentially be applicable to other HLA-B*27-associated spondyloarthropathies. Such targeted elimination of the underlying cause of the disease without systemic immunosuppression could offer a new generation of safe and efficient therapies for autoimmunity.
Study on creep characteristics and component model of saline soil in hexi corridor
Authors: Yu Yun-yan , Luo Chong-liang , Cui Wen-hao , Tao Jing-yan , Zhang Ting-hua
Published: October 2023

Accurate mastery of the creep characteristics of unsaturated saline soil is extremely important for the long-term stability and safe operation of all types of buildings. In this paper, the research object focused on the saline soil of the Zhangye area, Hexi corridor. The indoor triaxial CU creep test was carried out by means of graded loading to study the creep characteristics of saline soil under different salt content and loading stress. The Merchant and Burgers models were used to predict the creep behavior of the saline soils, and the predicted results were compared with the experimental values. The results showed that the triaxial creep curve of saline soil developed in stage III. Namely, transient creep stage, deceleration creep stage and steady-state creep stage. The creep deformation increases with the increase of salt content and loading stress. The stress–strain isochronous curve has non-linear growth, and the cluster of curves develops from dense to sparse after increasing to long-term strength (100∼150 kPa). The parameters of the Merchant and Burgers model vary with salt content and loading stress, and the creep curve predicted by the Burgers model is closer to the test value.
Effects of vitamins C and E in tris citric acid glucose extender on chilled semen quality of Kail ram during different storage times
Authors: Akhter Shereen , Zubair Muhammad , Mahmood Majid , Andrabi Syed Murtaza Hassan , Hameed Nasir , Ahmad Ejaz , Saleemi Muhammad Kashif
Published: October 2023

Mammalian sperm cells are highly vulnerable to lipid peroxidation by free radicals. Antioxidants such as vitamin E, and vitamin C neutralize the activity of free radicals and protect the sperm from reactive oxygen species. The present study was conducted to investigate the effects of vitamin C, vitamin E, and their combination in a Tris-based extender on the semen quality of Kail Ram. Semen samples from five mature Kail rams were collected in this study. The semen samples were diluted by Tris-glucose-egg yolk. Diluted semen samples were divided into four parts. The first part was added with 1 mg/ml of vitamin C, the second part was added with 1 mg/ml of vitamin E and the third part was added with both vitamin C and E, in combination with a dose of 1 mg/ml. The fourth part was considered as control without any addition. The diluted semen samples were cooled gradually and preserved at 5˚C for three days. Sperms in chilled diluted semen samples were examined for motility, viability, and plasma membrane integrity every 24 h for three days (72 h). Present study results showed significant (P < 0.05) effects of vitamins C, E, and their combination on some parameters such as motility, straightness of average special path, linearity of the curvilinear trajectory, and beat-cross frequency. However, there was no significant (P < 0.05) effect of storage duration and antioxidants (vitamin C, E, and their combination) on viability, sperm plasma membrane integrity, and some CASA parameters. From the present study, it could be concluded that the supplementation of vitamins C, and E, and their combination do not enhance the life span and quality of semen in Kail ram during liquid storage at 5 °C.
Targeting allosteric binding site in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to identify natural product inhibitors via structure-based computational approach
Authors: Rana Nisarg , Patel Dhaval , Parmar Meet , Mukherjee Nandini , Jha Prakash C. , Manhas Anu
Published: October 2023

Cancer has been viewed as one of the deadliest diseases worldwide. Among various types of cancer, breast cancer is the most common type of cancer in women. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a promising druggable target and is overexpressed in cancerous cells, like, breast cancer. We conducted structure-based modeling on the allosteric site of the enzyme. Targeting the allosteric site avoids the problem of drug resistance. Pharmacophore modeling, molecular docking, HYDE assessment, drug-likeness, ADMET predictions, simulations, and free-energy calculations were performed. The RMSD, RMSF, RoG, SASA, and Hydrogen-bonding studies showed that seven candidates displayed stable behaviour. As per the literature, average superimposed simulated structures revealed a similar protein conformational change in the αEʹ-βfʹ loop, causing its displacement away from the allosteric site. The MM-PBSA showed tight binding of six compounds with the allosteric pocket. The effect of inhibitors interacting in the allosteric site causes a decrease in the binding energy of J49 (active-site inhibitor), suggesting the effect of allosteric binding. The PCA and FEL analysis revealed the significance of the docked compounds in the stable behaviour of the complexes. The outcome can contribute to the development of potential natural products with drug-like properties that can inhibit the MTHFD2 enzyme.
Computational prognostic evaluation of Alzheimer’s drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches
Authors: Hassan Mubashir , Shahzadi Saba , Yasir Muhammad , Chun Wanjoo , Kloczkowski Andrzej
Published: October 2023

Drug designing is high-priced and time taking process with low success rate. To overcome this obligation, computational drug repositioning technique is being promptly used to predict the possible therapeutic effects of FDA approved drugs against multiple diseases. In this computational study, protein modeling, shape-based screening, molecular docking, pharmacogenomics, and molecular dynamic simulation approaches have been utilized to retrieve the FDA approved drugs against AD. The predicted MADD protein structure was designed by homology modeling and characterized through different computational resources. Donepezil and galantamine were implanted as standard drugs and drugs were screened out based on structural similarities. Furthermore, these drugs were evaluated and based on binding energy (Kcal/mol) profiles against MADD through PyRx tool. Moreover, pharmacogenomics analysis showed good possible associations with AD mediated genes and confirmed through detail literature survey. The best 6 drug (darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar) further docked and analyzed their interaction behavior through hydrogen binding. Finally, MD simulation study were carried out on these drugs and evaluated their stability behavior by generating root mean square deviation and fluctuations (RMSD/F), radius of gyration (Rg) and soluble accessible surface area (SASA) graphs. Taken together, darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar displayed good lead like profile as compared with standard and can be used as possible therapeutic agent in the treatment of AD after in-vitro and in-vivo assessment.
Uncovering the global ranking of greenhouse gases intensity, efficiency and structural transformation
Authors: Saleem Muhammad , Aslam Muhammad , Janjua Azhar Ali
Published: October 2023

This study incorporated the index decomposition analysis to drive the GHGs emissions intensity and separate the impact into true efficiency and structural transformation of economic activities on GHGs emissions. The global perspective is investigated in three aspects; (i) global groups of countries regarding income level, (ii) global countries bifurcated into geo-political regions and, (iii) hundred countries are taken to perform individual country level analysis, by taking 20 years (2000–2019) data. The hundred countries are ranked regarding GHGs intensity, efficiency and economic activities with respect to (i) for the latest year performance, (ii) twenty years average performance and, (iii) annual average reduction of GHGs emissions, comparable with base year 2000. Income-based countries groups explicate the improvement of GHGs intensity for HIC only and the economic transformation contributed to it. Efficiency index for all income groups while economic activities of LMIC, MIC and UMIC deteriorated the GHGs emissions. Global geo-political regions explicate the mixed pattern of GHGs intensity. Efficiency index is best for Azerbaijan and least for Uzbekistan. While ranking average GHGs emission reduction countries; Zimbabwe is the best and Qatar is the last country in the intensity list.
Biomechanical explanation of W-plasty effectiveness using a finite element method approach
Authors: Papadakis Marios , Manios Georgios , Zacharopoulos Georgios , Koumaki Dimitra , Manios Andreas
Published: October 2023

The finite element method has often been used to assist analyzing local flaps in terms of deformation and stress measurements as it takes into account complex skin properties. We, herein, present an isotropic two-dimensional finite element skin model applied to the W-plasty method to demonstrate that the good outcomes of W-plasty should be attributed to the geometry itself, as it generates lower stresses. The skin was modeled as a two-dimensional (2D) planar geometry. The model was created and solved as a plane stress problem. The model was based on simulation of the loading and stitching of W-plasties of various angles. Each central triangular flap was segmented in nine triangular elements. The stitching was modeled with one suture at the top of each triangular flap with the center of the opposite corner. X- and Y-axis stresses and shearing stresses Txy in the elements involved in the broken stitching line, show lower stresses than the elements behind the stitching line. Interestingly, in the triangular flaps, the stresses were clearly lower than those of their neighboring areas. The maximum compressive stresses in the 2D model we used, correspond to the dog ears. We conclude that the effectiveness of W-plasty should be attributed not only to the scar orientation in relation to the relaxed tension skin lines but also to the special design of the triangular flaps used. This finding assists the general understanding of the method and should be taken into account by the clinician during flap designing.
The cancer inflammation prognostic index is a valuable biomarker for predicting the survival of patients with stage I–III colorectal cancer
Authors: Xie Hailun , Wei Lishuang , Liu Mingxiang , Liang Yanren , Wang Qiwen , Tang Shuangyi , Gan Jialiang
Published: October 2023

This study aimed to assess the relationship between the Cancer-Inflammation Prognostic Index (CIPI) and disease-free survival (DFS) and overall survival (OS) in patients with stage I–III colorectal cancer (CRC). The relationship between the CIPI and survival was evaluated using restricted cubic splines. Survival curves were established using the Kaplan–Meier method and the log-rank test. Cox proportional hazards models were used to explore independent prognostic factors for CRC. Meaningful variables from the multivariate analysis were used to construct prognostic nomograms. The relationship between the CIPI values on a continuous scale and the risk of DFS/OS mortality was an inverted L-shape. Patients with a high CIPI had significantly lower DFS (53.0% vs. 68.5%, p < 0.001) and OS (55.5% vs. 71.7%, p < 0.001) than those with a low CIPI. The CIPI can also serve as an effective auxiliary tool to further distinguish the prognosis of patients with CRC at the same pathological stage, especially for stages II and III. After multivariate adjustment, a high CIPI was found to be an independent risk factor for DFS (HR 1.443, 95% CI 1.203–1.730, p < 0.001) and OS (HR 1.442, 95% CI 1.189–1.749, p < 0.001) in CRC patients. These nomograms have the advantage of integrating individual profiles, tumour characteristics, and serum inflammatory markers, providing favourable discrimination and calibration values. Compared with traditional TNM staging, nomograms have a better predictive performance. The CIPI is an effective and easy-to-use clinical tool for predicting the recurrence and overall mortality of patients with stage I–III CRC.
A data-driven network decomposition of the temporal, spatial, and spectral dynamics underpinning visual-verbal working memory processes
Authors: Rossi Chiara , Vidaurre Diego , Costers Lars , Akbarian Fahimeh , Woolrich Mark , Nagels Guy , Van Schependom Jeroen
Published: October 2023

The brain dynamics underlying working memory (WM) unroll via transient frequency-specific large-scale brain networks. This multidimensionality (time, space, and frequency) challenges traditional analyses. Through an unsupervised technique, the time delay embedded-hidden Markov model (TDE-HMM), we pursue a functional network analysis of magnetoencephalographic data from 38 healthy subjects acquired during an n-back task. Here we show that this model inferred task-specific networks with unique temporal (activation), spectral (phase-coupling connections), and spatial (power spectral density distribution) profiles. A theta frontoparietal network exerts attentional control and encodes the stimulus, an alpha temporo-occipital network rehearses the verbal information, and a broad-band frontoparietal network with a P300-like temporal profile leads the retrieval process and motor response. Therefore, this work provides a unified and integrated description of the multidimensional working memory dynamics that can be interpreted within the neuropsychological multi-component model of WM, improving the overall neurophysiological and neuropsychological comprehension of WM functioning.
Neural scaling of deep chemical models
Authors: Frey Nathan C. , Soklaski Ryan , Axelrod Simon , Samsi Siddharth , Gómez-Bombarelli Rafael , Coley Connor W. , Gadepally Vijay
Published: October 2023

Massive scale, in terms of both data availability and computation, enables important breakthroughs in key application areas of deep learning such as natural language processing and computer vision. There is emerging evidence that scale may be a key ingredient in scientific deep learning, but the importance of physical priors in scientific domains makes the strategies and benefits of scaling uncertain. Here we investigate neural-scaling behaviour in large chemical models by varying model and dataset sizes over many orders of magnitude, studying models with over one billion parameters, pre-trained on datasets of up to ten million datapoints. We consider large language models for generative chemistry and graph neural networks for machine-learned interatomic potentials. We investigate the interplay between physical priors and scale and discover empirical neural-scaling relations for language models in chemistry with a scaling exponent of 0.17 for the largest dataset size considered, and a scaling exponent of 0.26 for equivariant graph neural network interatomic potentials.
Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia
Authors: Knorr Katherine , Rahman Jahan , Erickson Caroline , Wang Eric , Monetti Mara , Li Zhuoning , Ortiz-Pacheco Juliana , Jones Andrew , Lu Sydney X. , Stanley Robert F. , Baez Maria , Fox Nina , Castro Cynthia , Marino Alessandra E. , Jiang Caroline , Penson Alex , Hogg Simon J. , Mi Xiaoli , Nakajima Hideaki , Kunimoto Hiroyoshi , Nishimura Koutarou , Inoue Daichi , Greenbaum Benjamin , Knorr David , Ravetch Jeffrey , Abdel-Wahab Omar
Published: October 2023

Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes. Anti-U5 snRNP200 antibodies engaging activating Fcγ receptors were efficacious across immunocompetent AML models and were augmented by combination with azacitidine. These data provide a roadmap of AML-associated antigens with Fc receptor distribution in AML and highlight the potential for targeting the AML cell surface using Fc-optimized therapeutics.
Nitrite anodic oxidation at Ni(ii)/Ni(iii)-decorated mesoporous SnO2 and its analytical applications
Authors: Mihai Marius Alexandru , Spataru Tanta , Somacescu Simona , Moga Olivia Georgeta , Preda Loredana , Florea Mihaela , Kuncser Andrei , Spataru Nicolae
Published: October 2023

Mesoporous Ni/SnO2 was hydrothermally obtained and, mixed with a small amount of Black Pearls, exhibited excellent analytical figures of merit for nitrite voltammetric determination.
Small molecule modulators of immune pattern recognition receptors
Authors: Tsukidate Taku , Hespen Charles W. , Hang Howard C.
Published: October 2023

In this review article, we summarize exciting developments in discovery and characterization of small molecule PRR modulators and highlight opportunities for chemical biology and therapeutic discovery.
Graphdiyne chelated AuNPs for ultrasensitive electrochemical detection of tyrosine
Authors: Shi Zhuanzhuan , Li Yunpeng , Wu Xiaoshuai , Zhang Kaiwen , Gu Jiatao , Sun Wei , Li Chang Ming , Guo Chun Xian
Published: October 2023

A unique material of GDY@AuNPs is developed for electrochemical tyrosine (Tyr) sensor. Its excellent sensing performance is mainly due to the alkyne of GDY strongly chelate with AuNPs and promote the absorption of Tyr via π–π interaction.
Cu doping in FeP enabling efficient electrochemical nitrate reduction to ammonia in neutral media
Authors: Li Bo , Xue Pengfei , Qiao Man , Tang Yujia , Zhu Dongdong
Published: October 2023

It is demonstrated that Cu doping can boost the electrochemical nitrate reduction performance of FeP towards NH3 production.
Amine-modified polyionic liquid supports enhance the efficacy of PdNPs for the catalytic hydrogenation of CO2 to formate
Authors: Paterson Reece , Fahy Luke E. , Arca Elisabetta , Dixon Casey , Wills Corinne Y. , Yan Han , Griffiths Anthony , Collins Sean M. , Wu Kejun , Bourne Richard A. , Chamberlain Thomas W. , Knight Julian G. , Doherty Simon
Published: October 2023

Highly efficient hydrogenation of CO2 to formate catalysed by palladium nanoparticles stabilised by aniline modified polymer immobilised ionic liquid.
Differential supercapacitor and Schottky diode behaviours in two new isostructural coordination polymers based on redox active metal ions
Authors: Das Chhatan , Debnath Subhrajyoti , Patel Vishwas D. , Gupta Dhritiman , Banerjee Anjan , Mahata Partha
Published: October 2023

Two isostructural 2D coordination polymers utilizing redox-active metal ions, Fe(ii) and Mn(ii), were synthesized. The Mn-based compound showed higher capacitance values and ten times higher conductivity compared to the Fe-based compound.
Synthesis and characterization of two metallo-hydrogen-bonded organic frameworks with diverse structures and properties
Authors: Zhou Mi , Wang Yujiang , Yuan Guoyuan , Ju Zhanfeng , Yuan Daqiang
Published: October 2023

With phosphate participating in H-bond linkage or not, two MHOFs with different structures were synthesized based on a phosphate complex.
Benchmarks for transition metal spin-state energetics: why and how to employ experimental reference data?
Authors: Radoń Mariusz
Published: October 2023

Experimental data provide reliable benchmarks for computed spin-state energetics.
N-type silver ammonia-polyethyleneimine/single-walled carbon nanotube composite films with enhanced thermoelectric properties
Authors: Li Zan , Jiang Duo , Gong Jiayan , Li Yi , Fu Ping , Zhang Yunfei , Du Feipeng
Published: October 2023

Carbon nanotubes and their composite thermoelectric (TE) materials have significant advantages in supplying power to flexible electronics due to their high electrical conductivity, excellent flexibility, and facile preparation technology.
Weyl semimetal mediated epsilon-near-zero hybrid polaritons and the induced nonreciprocal radiation
Authors: Xu Sicheng , Qian Liming , Sun Mengran , Zheng Gaige
Published: October 2023

Schematic of the proposed structure, the obvious anti-crossing of resonances and the impact of azimuthal angle φ on nonreciprocity, which is symmetric along φ = 180°.
Few-layer MoS2 nanosheets vertically supported on Ti3C2-MXene sheets promoting lithium storage performance
Authors: Tan Hankun , Zhang Lei , Gao Kaiyue , Sun Li , Zhang Yihe , Xie Feng
Published: October 2023

Few-layer MoS2 nanosheets vertically anchored on CTAB-treated MXene sheets exhibit excellent cycling performance and rate performance.
A simple hydrothermal synthesis of an oxygen vacancy-rich MnMoO4 rod-like material and its highly efficient electrocatalytic nitrogen reduction
Authors: Yin Huhu , Xing Xiujing , Zhang Wei , Li Jin , Xiong Wei , Li Hao
Published: October 2023

A simple hydrothermal synthesis method was developed to prepare bimetallic oxide MnMoO4 rod-like materials. The typical sample exhibits excellent electrocatalytic NRR performance.
Correction: Long-chain polyunsaturated fatty acids and extensively hydrolyzed casein-induced browning in a Ucp-1 reporter mouse model of obesity
Authors: Mao Liufeng , Lei Jiwen , Schoemaker Marieke H. , Ma Bingxiu , Zhong Yan , Lambers Tim T. , Van Tol Eric A. F. , Zhou Yulai , Nie Tao , Wu Donghai
Published: October 2023

Correction for ‘Long-chain polyunsaturated fatty acids and extensively hydrolyzed casein-induced browning in a Ucp-1 reporter mouse model of obesity’ by Liufeng Mao et al., Food Funct., 2018, 9, 2362–2373, https://doi.org/10.1039/C7FO01835E.
Synthesis of functionalized sulfilimines via iron-catalyzed sulfur alkylation of sulfenamides with diazo compounds
Authors: Wu Xianda , Chen Minghong , He Fu-Sheng , Wu Jie
Published: October 2023

An efficient iron-catalyzed sulfur alkylation of sulfenamides with diazo compounds for the synthesis of functionalized sulfilimines is developed under air conditions.
Continuous-flow electrorotation (cROT): improved throughput characterization for dielectric properties of cancer cells
Authors: Yoda Kazuma , Ichikawa Yoshiyasu , Motosuke Masahiro
Published: October 2023

A continuous-flow electrorotation (cROT) device for improved throughput characterization of dielectric properties of cells has been developed.
Microfluidic device-fabricated spiky nano-burflower shape gold nanomaterials facilitate large biomolecule delivery into cells using infrared light pulses
Authors: Illath Kavitha , Kar Srabani , Shinde Ashwini , Ojha Rajdeep , Iyer Dhanya R. , Mahapatra Nitish R. , Nagai Moeto , Santra Tuhin Subhra
Published: October 2023

Microfluidics-synthesised spiky burflower gold nanoparticles-sensitised photoporation for highly efficient and uniform intracellular delivery of biomolecules.
Graphene-based chemiresistive gas sensors
Authors: Recum Patrick , Hirsch Thomas
Published: October 2023

This review describes critical aspects and perspectives in data-analysis when using graphene-composite nanomaterials as substrates for chemiresistive gas sensors.
Engineering GaN/AuNC core–shell nanowire heterojunctions by gold nanoclusters with excitation-dependent behavior for enhancing the responsivity and stability of self-driven photodetectors
Authors: Huang Yuanyuan , Zhang Jianya , Zhou Min , Pei Renjun , Zhao Yukun
Published: October 2023

It is novel to demonstrate a self-driven ultraviolet-visible photodetector based on the gallium nitride/gold nanocluster (GaN/AuNC) core–shell nanowire heterojunctions fabricated by introducing the AuNCs onto the GaN NW surfaces.
LIS-doped thin-film nanocomposite membrane adsorbent with low shielding effect for effective lithium recovery from geothermal water
Authors: Miao Ju , Guo Feng , Xu Lina , Deng Tianlong
Published: October 2023

A LIS-doped thin-film nanocomposite (TFN) membrane adsorbent was constructed by an interfacial polymerization technique, showing a comparable Li+ adsorption capacity of 23.94 mg g−1 and a shorter adsorption time of 35 minutes than powdery LIS.
Synthesis of small-crystal Y zeolites via regulating Na2O/Al2O3 and superior catalytic performance of corresponding NiWS-supported catalysts for hydrocracking of naphthalene
Authors: Dai Xiaojun , Cheng Yan , Liu Tingting , Mao Lingjuan , Kang Ruihua , Wei Qiang , Zhou Yasong
Published: October 2023

In the process of petroleum refining, realizing the production and utilization of chemical raw materials is the common goal pursued by the petrochemical industry at present.
MOF-derived Fe–N–C electrocatalyst via a dual ligand strategy for efficient oxygen reduction in acidic media
Authors: Sheng Yi , Zheng Hongmei , Hou Jingting , Zhang Wanying , Chen Hong , Nie Luanjie , Zheng Jing , Lai Qingxue
Published: October 2023

A metal–organic-framework based dual ligand strategy is proposed to develop high-performance acid ORR Fe–N–C electrocatalyst via the synergistic effect between in situ Zn evaporation and ligand-manipulated pyrolysis.
CeO2-supported multi-nuclear NbxSy clusters for hydrogen evolution reaction
Authors: Liu Hongxian , Zhao Chencheng , Li Hong , Li Xuelan , Mu Xianfeng , Hong Dunhua , Zhong Furu , Fang Zhenxing , Zhang Yanning
Published: October 2023

The CeO2 supported multi-nuclear NbxSy clusters may be very promising HER catalysts.
Stimuli responsive gelation of tert-butylacetic acid based LMOGs – applications in remediation of marine oil spills, dye removal and heavy metal sensing
Authors: Bhardwaj Varsha , Patel Ajaykumar M. , Ballabh Amar
Published: October 2023

Tert-butylacetic acid based amides containing a structural backbone, a hydrogen bonding linker and a bulky end group have been synthesized (TBA1–TBA6) and explored for gelation of fuel oils and organic solvents.