bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined docking and machine learning identify key molecular determinants of ligand pharmacological activity on β2 adrenoceptor
Authors: Jiménez‐Rosés Mireia , Morgan Bradley Angus , Jimenez Sigstad Maria , Tran Thuy Duong Zoe , Srivastava Rohini , Bunsuz Asuman , Borrega‐Román Leire , Hompluem Pattarin , Cullum Sean A. , Harwood Clare R. , Koers Eline J. , Sykes David A. , Styles Iain B. , Veprintsev Dmitry B. 
Published: August 2022

AbstractG protein‐coupled receptors (GPCRs) are valuable therapeutic targets for many diseases. A central question of GPCR drug discovery is to understand what determines the agonism or antagonism of ligands that bind them. Ligands exert their action via the interactions in the ligand binding pocket. We hypothesized that there is a common set of receptor interactions made by ligands of diverse structures that mediate their action and that among a large dataset of different ligands, the functionally important interactions will be over‐represented. We computationally docked ~2700 known β2AR ligands to multiple β2AR structures, generating ca 75 000 docking poses and predicted all atomic interactions between the receptor and the ligand. We used machine learning (ML) techniques to identify specific interactions that correlate with the agonist or antagonist activity of these ligands. We demonstrate with the application of ML methods that it is possible to identify the key interactions associated with agonism or antagonism of ligands. The most representative interactions for agonist ligands involve K972.68×67, F194ECL2, S2035.42×43, S2045.43×44, S2075.46×641, H2966.58×58, and K3057.32×31. Meanwhile, the antagonist ligands made interactions with W2866.48×48 and Y3167.43×42, both residues considered to be important in GPCR activation. The interpretation of ML analysis in human understandable form allowed us to construct an exquisitely detailed structure‐activity relationship that identifies small changes to the ligands that invert their pharmacological activity and thus helps to guide the drug discovery process. This approach can be readily applied to any drug target.
Fatty acid amide hydrolase inhibition and N‐arachidonoylethanolamine modulation by isoflavonoids: A novel target for upcoming antidepressants
Authors: Zada Wahid , VanRyzin Jonathan W. , Perez‐Pouchoulen Miguel , Baglot Samantha L. , Hill Matthew N. , Abbas Ghulam , Clark Sarah M. , Rashid Umer , McCarthy Margaret M. , Mannan Abdul 
Published: August 2022

AbstractModulation of the endocannabinoid system (ECS) is a novel putative target for therapeutic intervention in depressive disorders. Altering concentrations of one of the principal endocannabinoids, N‐arachidonoylethanolamine, also known as anandamide (AEA) can affect depressive‐like behaviors through several mechanisms including anti‐inflammatory, hormonal, and neural circuit alterations. Recently, isoflavonoids, a class of plant‐derived compounds, have been of therapeutic interest given their ability to modulate the metabolism of the endogenous ligands of the ECS. To determine the therapeutic potential of isoflavonoids, we screened several candidate compounds (Genistein, Biochanin‐A, and 7‐hydroxyflavone) in silico to determine their binding properties with fatty acid amide hydrolase (FAAH), the primary degrative enzyme for AEA. We further validated the ability of these compounds to inhibit FAAH and determined their effects on depressive‐like and locomotor behaviors in the forced swim test (FST) and open field test in male and female mice. We found that while genistein was the most potent FAAH inhibitor, 7‐hydroxyflavone was most effective at reducing immobility time in the forced swim test. Finally, we measured blood corticosterone and prefrontal cortex AEA concentrations following the forced swim test and found that all tested compounds decreased corticosterone and increased AEA, demonstrating that isoflavonoids are promising therapeutic targets as FAAH inhibitors.
Bombyx mori transcription factor, E74A, beneficially affects BmNPV infection through direct interaction
Authors: Wang Xin , Lv Jun‐li , Cheng Shuang , Su Zhi‐hao , Qin Sheng , Sun Xia , Tang Xu‐dong , Liu Qiu‐ning , Li Mu‐wang , Wang Xue‐yang 
Published: August 2022

AbstractBACKGROUNDNucleopolyhedrovirus (NPV), one of the baculoviruses, is a promising biopesticide for pest control. Lepidopteran account for 70% of pests, therefore investigation on highly conserved genes associated with viral infections in the lepidopteran model, the silkworm, will serve as a valuable reference for improving the effectiveness of pest management. BmE74A is a member of the erythroblast transformation‐specific (ETS) family of transcription factors in Bombyx mori, which we previously found to be highly conserved and closely associated with BmNPV. This study aimed to elucidate the role of BmE74A in viral infection.RESULTSA significantly high expression of BmE74A in eggs indicated its important role in embryonic development, as did relatively high expressions in the hemolymph and midgut. Significant differences in BmE74A expression in different resistant strains after BmNPV infection suggested its involvement as a response to viral infection. Moreover, RNA interference (RNAi) and overexpression experiments confirmed the important role of BmE74A in promoting viral infection. BmNPV infection was significantly suppressed and enhanced by BmE74A knockdown and overexpression, respectively. Besides, BmE74A was found to regulate the expression of BmMdm2 and Bmp53. Furthermore, the binding of ETS, the functional domain of BmE74A, to occlusion‐derived virus proteins was confirmed by far‐western blotting, and four viral proteins that may interact with ETS proteins were identified by mass spectrometry. Similarly, a homolog of BmE74A in Spodoptera litura was also found to be involved in larval susceptibility to BmNPV.CONCLUSIONBmE74A promotes BmNPV proliferation by directly interacting with the virus, which may be related to the suppression of the p53 pathway. © 2022 Society of Chemical Industry.
Synthesis, herbicidal activity and soil degradation of novel 5‐substituted sulfonylureas as AHAS inhibitors
Authors: Zhou Sha , Zhao Lv‐Ting , Meng Fan‐Fei , Hua Xue‐Wen , Li Yong‐Hong , Liu Bin , Chen Jie , Chen An‐Liang , Li Zheng‐Ming 
Published: August 2022

AbstractBACKGROUNDChlorsulfuron, metsulfuron‐methyl and ethametsulfuron can damage sensitive crops in rotation pattern as a result of their long persistence in soil. To explore novel sulfonylurea (SU) herbicides with favorable soil degradation rates, four series of SUs were synthesized through a structure‐based drug design (SBDD) strategy.RESULTSThe target compounds, especially Ia, Id and Ie, exhibited prospective herbicidal activity against dicotyledon oil seed rape (Brassica campestris), amaranth (Amaranthus retroflexus), monocotyledon barnyard grass (Echinochloa crusgalli) and crab grass (Digitaria sanguinalis) at a concentration of 15 a.i. g ha−1. Additionally, Ia, Id and Ig displayed excellent inhibitory effects against AtAHAS, with Kapp i values of 59.1, 34.5 and 71.8 μm, respectively, which were much lower than that of chlorsulfuron at 149.4 μm. The π‐π stack and H‐bonds between the Ia conformation and AtAHAS in the molecular docking results confirmed the series of compounds to be conventional AHAS inhibitors. In alkaline soil (pH = 8.46), compounds Ia–Ig revealed various degrees of acceleration in the degradation rate compared with chlorsulfuron. Besides, compound Ia showed considerable wheat and corn safety under postemergence at the concentration of 30, 60 and even 120 a.i. g ha−1.CONCLUSIONOverall, based on the synthetic procedure, herbicidal activity, soil degradation and crop safety, the Ia sulfonylureas series were chosen to be investigated as prospective AHAS inhibitors. The 5‐dimethylamino group on SUs accelerated the degradation rate at different levels in alkaline soils which seems to be controllable in conventional cropping systems in their further application. © 2022 Society of Chemical Industry.
Froude‐number‐based rainfall regimes over the Western Ghats mountains of India
Authors: Phadtare Jayesh A. , Fletcher Jennifer K. , Ross Andrew N. , Turner Andrew G. , Schiemann Reinhard K. H. 
Published: August 2022

AbstractVariations in the character of monsoonal rainfall over the Western Ghats region on the west coast of India are studied using radiosondes, satellite observations, and reanalysis products. Summer monsoon rainfall over this region occurs in alternate offshore and onshore phases. It is shown that these phases are controlled primarily by the strength of the low‐level westerly jet. Thus, a classification based on the Froude number, , of the onshore flow is proposed, where, is the mountain height, is the mean wind speed, and is the mean Brunt–Väisäla frequency over depth . At low (< 0.5), onshore winds are weak and the diurnal thermal fluctuation over the orography is strong; the land–sea and mountain–valley circulations are enhanced, leading to a stronger diurnal control over the rainfall. A nocturnal offshore propagation of rainfall from the west coast is seen during this phase. Rainfall over the rainshadow region to the east of the Western Ghats also increases, due to a weaker lee effect, while it decreases over the Western Ghats, due to a greater blocking effect. At high (> 1), orographic blocking of the low‐level winds is weak. Thus, rainfall is enhanced over the Western Ghats and reduced over the rainshadow region due to a stronger lee effect. In this phase, the diurnal thermal fluctuation over the orography is weak. The bulk Richardson number is less than 1, suggesting a dominance of vertical wind shear over the buoyancy forces. The level of free convection and convective inhibition over the west coast are also very low. Hence, at high , rainfall over the west coast results mainly from mechanical uplifting of the westerly winds by the Western Ghats, with no preference for a particular time of day. These findings will help in improving the representation of orographic effects and the diurnal cycle of rainfall in numerical models.
Si6C18: A bispentalene derivative with two planar tetracoordinate carbons
Authors: Inostroza Diego , Leyva‐Parra Luis , Yañez Osvaldo , Cruz J. César , Garza Jorge , García Víctor , Thimmakondu Venkatesan S. , Ceron Maria L. , Tiznado William 
Published: August 2022

AbstractHere we show that substituting the ten protons in the dianion of a bispentalene derivative (C18H102−) by six Si2+ dications produces a minimum energy structure with two planar tetracoordinate carbons (ptC). In Si6C18, the ptCs are embedded in the terminal C5 pentagonal rings and participate in a three‐center, two‐electron (3c‐2e) Si‐ptC‐Si σ‐bond. Our exploration of the potential energy surface identifies a triphenylene derivative as the putative global minimum. Nevertheless, robustness to Born–Oppenheimer molecular dynamics (BOMD) simulations at 900 and 1500 K supports bispentalene derivative kinetic stability. Chemical bonding analysis reveals ten delocalized π‐bonds, which, according to Hückel's 4n + 2 π‐electron rule, would classify it as an aromatic system. Magnetically induced current density analysis reveals the presence of intense local paratropic currents and a weakly global diatropic current, the latter agreeing with the possible global aromatic character of this specie.
A new method for phosphate purification for oxygen isotope ratio analysis in freshwater and soil extracts using solid‐phase extraction with zirconium‐loaded resin
Authors: Ishida Takuya , Kamiya Hiroshi , Uehara Yoshitoshi , Kato Toshikuni , Sugahara Shogo , Onodera Shin‐ichi , Ban Syuhei , Paytan Adina , Tayasu Ichiro , Okuda Noboru 
Published: August 2022

RationalePhosphate (PO4) oxygen isotope (δ18OPO4) analysis is increasingly applied to elucidate phosphorus cycling. Due to its usefulness, analytical methods continue to be developed and improved to increase processing efficiency and applicability to various sample types. A new pretreatment procedure to obtain clean Ag3PO4 using solid‐phase extraction (SPE) with zirconium‐loaded resin (ZrME), which can selectively adsorb PO4, is presented and evaluated here.MethodsOur method comprises (1) PO4 concentration, (2) PO4 separation by SPE, (3) cation removal, (4) Cl− removal, and (5) formation of Ag3PO4. The method was tested by comparing the resulting δ18OPO4 of KH2PO4 reagent, soil extracts (NaHCO3, NaOH, and HCl), freshwater, and seawater with data obtained using a conventional pretreatment method.ResultsPO4 recovery of our method ranged from 79.2% to 97.8% for KH2PO4, soil extracts, and freshwater. Although the recovery rate indicated incomplete desorption of PO4 from the ZrME columns, our method produced high‐purity Ag3PO4 and accurate δ18OPO4 values (i.e., consistent with those obtained using conventional pretreatment methods). However, for seawater, the PO4 recovery was low (1.1%), probably due to the high concentrations of F− and SO42− which interfere with PO4 adsorption on the columns. Experiments indicate that the ZrME columns could be regenerated and used repeatedly at least three times.ConclusionsWe demonstrated the utility of ZrME for purification of PO4 from freshwater and soil extracts for δ18OPO4 analysis. Multiple samples could be processed in three days using this method, increasing sample throughput and potentially facilitating more widespread use of δ18OPO4 analysis to deepen our understanding of phosphorus cycling in natural environments.
Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review
Authors: Rezaei Tolzali Mohammad Mahdi , Noori Maryam , Shokri Pourya , Rahmani Shayan , Khanzadeh Shokoufeh , Nejadghaderi Seyed Aria , Fazlollahi Asra , Sullman Mark J. M. , Singh Kuljit , Kolahi Ali‐Asghar , Arshi Shahnam , Safiri Saeid 
Published: August 2022

AbstractTocilizumab is an interleukin (IL)‐6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID‐19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID‐19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: ‘SARS‐CoV‐2’, ‘COVID‐19’, ‘tocilizumab’, ‘RHPM‐1’, ‘systematic review’, and ‘meta‐analysis’. Studies were included if they were systematic reviews (with or without meta‐analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID‐19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61–0.93), deaths (RR 0.78; 95%CI, 0.71–0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64–0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43–0.63). In addition, tocilizumab substantially increased the number of ventilator‐free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51–6.25). Furthermore, lymphocyte count (WMD 0.26 × 109/L; 95%CI, 0.14–0.37), IL‐6 (WMD 176.99 pg/mL; 95%CI, 76.34–277.64) and D‐dimer (WMD 741.08 ng/mL; 95%CI, 109.42–1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD −30.88 U/L; 95%CI, −51.52, −10.24) and C‐reactive protein (CRP) (WMD ‐104.83 mg/L; 95%CI, −133.21, −76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID‐19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID‐19.
Prognostic value of novel serum biomarkers, including C‐reactive protein to albumin ratio and fibrinogen to albumin ratio, in COVID‐19 disease: A meta‐analysis
Authors: Rathore Sawai Singh , Oberoi Sharvi , Iqbal Kinza , Bhattar Keshav , Benítez‐López Guadalupe Abigail , Nieto‐Salazar María Alejandra , Velasquez‐Botero Felipe , Moreno Cortes Guillermo Andrés , Hilliard Jonathan , Madekwe Chinelo Chioma , Madekwe Chika Chizitelu , Flowers Thomas C. , Khalil Khalil 
Published: August 2022

AbstractWith COVID‐19 still hovering around and threatening the lives of many at‐risk patients, an effective, quick, and inexpensive prognostic method is required. Few studies have shown fibrinogen to albumin ratio (FAR) and C‐reactive protein to albumin ratio (CAR) to be promising as prognostic markers for COVID‐19 disease. However, their implications remain unclear. This meta‐analysis aimed to elucidate the prognostic role of FAR and CAR in COVID‐19 disease. A systematic literature search was undertaken using PubMed and Embase till April 2022. Inverse variance standardised mean difference (SMD) was calculated to report the overall effect size using random effect models. The generic inverse variance random‐effects method was used to pool the area under the curve (AUC) values. All statistical analyses were performed on Revman and MedCalc Software. A total of 23 studies were included. COVID‐19 non‐survivors had a higher CAR on admission compared with survivors (SMD = 1.79 [1.04, 2.55]; p < 0.00001; I2 = 97%) and patients with a severe COVID‐19 infection had a higher CAR on admission than non‐severe patients (SMD = 1.21 [0.54, 1.89]; p = 0.0004; I2 = 97%). Similarly, higher mean FAR values on admission were significantly associated with COVID‐19 mortality (SMD = 0.55 [0.32, 0.78]; p < 0.00001; I2 = 82%). However, no significant association was found between mean FAR on admission and COVID‐19 severity (SMD = 0.54 [−0.09, 1.18]; p = 0.09; I2 = 91%). The pooled AUC values found that CAR had a good discriminatory‐power to predict COVID‐19 severity (AUC = 0.81 [0.75, 0.86]; p < 0.00001; I2 = 80%) and mortality (AUC = 0.81 [0.74, 0.87]; p < 0.00001; I2 = 86%). FAR had a fair discriminatory‐power to predict COVID‐19 severity (AUC = 0.73 [0.64, 0.82]; p < 0.00001; I2 = 89%). Overall, CAR was a good predictor of both severity and mortality associated with COVID‐19 infection. Similarly, FAR was a satisfactory predictor of COVID‐19 mortality but not severity.
Spring peak flows control abundance of Cladophora in a Hydropower‐Impacted River
Authors: Eilers Joseph M. , Davis Clinton J. , Vander Meer Dennis , Vache Kellie 
Published: August 2022

AbstractThe lower Deschutes River represents the 161‐km reach downstream of three hydroelectric dams flowing to its confluence at the Columbia River. We examined hydrology and nutrient chemistry from 2015–2017 to 2019 to determine factors affecting periphyton community composition and abundance following a change in the outlet structure and depth of release waters from the major upstream impoundment. The periphyton community composition was abundant and diverse in 2015 and 2016 and lower in 2017 and 2019. Filamentous chlorophytes were dominant in the first 2 years but were sparse in the subsequent years. Cyanophytes were dominant in 2017 and 2019. The expectation entering the study was that altered nutrient chemistry associated with the change in operations resulted in conditions more favorable for periphyton growth. Concentrations of total and soluble phosphorous are independent of reservoir operations, being high in all years because of natural weathering of P‐rich volcanic rocks in the basin. Concentrations of TN and DIN were low all study years, resulting in a system that was N‐limited, but with similar chemistry among the study years. The hydrology during 2015 and 2016, with abundant chlorophytes, exhibited low flow in the spring, whereas high spring flows were observed in the latter years. We conclude that high spring flows were far more influential in affecting the periphyton community composition in the lower Deschutes River compared to nutrient chemistry.
The number of bounded‐degree spanning trees
Authors: Yuster Raphael 
Published: August 2022

AbstractFor a graph , let be the number of spanning trees of with maximum degree at most . For , it is proved that every connected ‐vertex ‐regular graph with satisfies
where approaches 1 extremely fast (e.g., ). The minimum degree requirement is essentially tight as for every there are connected ‐vertex ‐regular graphs with for which . Regularity may be relaxed, replacing with the geometric mean of the degree sequence and replacing with that also approaches 1, as long as the maximum degree is at most . The same holds with no restriction on the maximum degree as long as the minimum degree is at least .
Soil‐test biological activity associates with soil aggregation characteristics under different land uses in North Carolina
Authors: Franzluebbers Alan J. 
Published: August 2022

AbstractSoil erosion is a major constraint to agricultural sustainability. Land management that protects soil from water erosion can be assessed from the fraction of aggregates stable upon water immersion. Conservation management with minimal soil disturbance is known to enhance water‐stable aggregation, but how annual vs. perennial vegetative cover affects soil biological activity and aggregation from soils varying in texture remains relatively unexplored. This study assessed the effects of long‐term conventional‐till and no‐till cropland, grassland, and woodland on dry‐stable and water‐stable mean‐weight diameter (MWD) from 25 research stations across North Carolina. Soil clay concentration varied from 36 to 279 g kg–1 and sand concentration varied from 392 to 904 g kg–1 (5–95% distribution). Across locations, water‐stable MWD followed the order: conventional‐till cropland (0.64 mm) < no‐till cropland (0.87 mm) < woodland (1.12 mm) = grassland (1.15 mm). Soil stability index (i.e., water‐stable MWD/dry‐stable MWD) followed a similar order: conventional‐till cropland (0.59 mm mm–1) < no‐till cropland (0.76 mm mm–1) < grassland (0.92 mm mm–1) = woodland (0.96 mm mm–1). Although water‐stable MWD was positively associated with clay concentration (r = .50, p < .001, n = 310), soil‐test biological activity had the strongest association with water‐stable MWD (r = .80). Soil‐test biological activity reflected biological manipulation of surface‐concentrated organic matter, as mediated by conservation land uses. This study revealed the large impact of surface organic C and N resources on water‐stable aggregation through soil biological manipulations interacting across a textural gradient.