bluuebunny/crossref_metadata_2025_split huggingface dataset:
XAI‐MEG: Combining symbolic AI and machine learning to generate first‐principles models and causal explanations
Authors: Sivaram Abhishek , Venkatasubramanian Venkat 
Published: March 2022

AbstractCurrent machine learning methods generally do not reveal any mechanistic insights or provide causal explanations for their decisions. While this may not be a big concern in typical computer vision, game playing, and recommendation systems, this is important for many problems in chemical engineering such as fault diagnosis, process control, and process safety analysis. To address these drawbacks, one needs to go beyond purely data‐driven machine learning techniques and incorporate the lessons learned from the expert systems era of artificial intelligence (AI), in the 1970s and 1980s. In this article, we present such a hybrid‐AI framework that demonstrates how symbolic AI techniques can be integrated with numeric AI‐based machine learning methods.
UTSA‐280 metal–organic framework incorporated 6FDA‐polyimide mixed‐matrix membranes for ethylene/ethane separation
Authors: Chen Xi , Chen Guining , Liu Guozhen , Liu Gongping , Jin Wanqin 
Published: March 2022

AbstractMixed‐matrix membranes (MMMs), judiciously combining processability of polymer and remarkable separation performance of nanofillers, have been extensive pursuits for molecular separation process. Permeability matching between filler and polymer is one of the necessary requisites to desirable mixed‐matrix effect. Considering the superior molecular sieving effect of UTSA‐280 metal‐organic frameworks on C2H4 and C2H6, here, we report two types of UTSA‐280/6FDA‐polyimide MMMs toward C2H4/C2H6 separation. The molecular sieving effect of UTSA‐280 endowed 6FDA‐DAM:DABA(3:2) membrane with simultaneous improvements in C2H4 permeability and C2H4/C2H6 selectivity. Optimally, when the filler reached 21.80 wt%, C2H4 permeability and C2H4/C2H6 selectivity was increased to 6.49 Barrer (by 15%) and 4.94 (by 32%), respectively. On the contrary, UTSA‐280/6FDA‐DAM MMMs showed undesirable mixed‐matrix effect that C2H4 permeability decreased meanwhile C2H4/C2H6 selectivity nearly kept at polymeric pristine membrane level. It was found that permeability matching between two phases was responsible to these opposite mixed‐matrix effects. More specifically, UTSA‐280 had a relatively low gas permeability so that it required a less permeable polymeric matrix like 6FDA‐DAM:DABA(3:2) to exert its molecular sieving effect. Furthermore, the optimal‐matching 6FDA‐matrix in permeability with UTSA‐280 fillers was predicted by theoretical model. This work not only reports improving C2H4/C2H6 separation performance via mixed‐matrix formulation, but also emphasizes the importance of permeability matching between polymer and filler to realize the mixed‐matrix effect.
Nonpermissive Skin Environment Impairs Nerve Regeneration in Diabetes via Sec31a
Authors: Kan Hung‐Wei , Hsieh Jung‐Hsien , Wang Shih‐Wei , Yeh Ti‐Yen , Chang Ming‐Fong , Tang Tsz‐Yi , Chao Chi‐Chao , Feng Fang‐Ping , Hsieh Sung‐Tsang 
Published: March 2022

ObjectiveAlthough the microenvironment for peripheral nerve regeneration is permissive, such a mechanism is defective in diabetes, and the molecular mediators remain elusive. [Correction added on May 11, 2022, after first online publication: In the preceding sentence, “is ok” was changed to “is defective”.] This study aimed to (1) investigate the relationship between skin innervation and collagen pathology in diabetic neuropathy and to (2) clarify the molecular alterations that occur in response to hyperglycemia and their effects on axon regeneration.MethodsWe addressed this issue using two complementary systems: (1) human skin from patients with diabetic neuropathy and to (2) a coculture model of human dermal fibroblasts (HDFs) with rat dorsal root ganglia neurons in the context of intrinsic neuronal factor and extrinsic microenvironmental collagen and its biosynthetic pathways.ResultsIn diabetic neuropathy, the skin innervation of intraepidermal nerve fiber density (IENFd), a measure of sensory nerve degeneration, was reduced with similar expression of a growth associated protein 43, a marker of nerve regeneration. In contrast, the content and packing of collagen in the diabetic skin became more rigid than the control skin. Sec31a, a protein that regulates the collagen biosynthetic pathway, was upregulated and inversely correlated with IENFd. In the cell model, activated HDFs exposed to high‐glucose medium enhanced the expression of Sec31a and collagen I through the activation of transforming growth factor β, a profibrotic molecule. Sec31a upregulation impaired neurite outgrowth. This effect was reversed by silencing Sec31a expression and neurite outgrowth was resumed.InterpretationThe current study provides evidence that Sec31a plays a key role in inhibiting nerve regeneration in diabetic neuropathy. ANN NEUROL 2022;91:821–833
Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease
Authors: Benitez Andreana , Jensen Jens H. , Thorn Kathryn , Dhiman Siddhartha , Fountain‐Zaragoza Stephanie , Rieter William J. , Spampinato Maria Vittoria , Hamlett Eric D. , Nietert Paul J. , Falangola Maria de Fatima , Helpern Joseph A. 
Published: March 2022

ObjectiveThe Alzheimer's continuum is biologically defined by beta‐amyloid deposition, which at the earliest stages is superimposed upon white matter degeneration in aging. However, the extent to which these co‐occurring changes is characterized is relatively underexplored. The goal of this study was to use diffusional kurtosis imaging (DKI) and biophysical modeling to detect and describe amyloid‐related white matter changes in preclinical Alzheimer disease.MethodsCognitively unimpaired participants ages 45 to 85 years completed brain magnetic resonance imaging, amyloid positron emission tomography (florbetapir), neuropsychological testing, and other clinical measures at baseline in a cohort study. We tested whether beta‐amyloid‐negative (AB−) and ‐positive (AB+) participants differed on DKI‐based conventional (ie, fractional anisotropy [FA], mean diffusivity [MD], mean kurtosis) and modeling (ie, axonal water fraction [AWF], extra‐axonal radial diffusivity [De,⊥]) metrics, and whether these metrics were associated with other biomarkers.ResultsWe found significantly greater diffusion restriction (higher FA/AWF, lower MD/De,⊥) in white matter in AB+ than AB− (partial η2 =0.08–0.19), more notably in the extra‐axonal space within primarily late myelinating tracts. Diffusion metrics predicted amyloid status incrementally over age (area under the curve = 0.84) with modest yet selective associations, where AWF (a marker of axonal density) correlated with speed/executive functions and neurodegeneration, whereas De,⊥ (a marker of gliosis/myelin repair) correlated with amyloid deposition and white matter hyperintensity volume.InterpretationThese results support prior evidence of a nonmonotonic change in diffusion behavior, where an early increase in diffusion restriction is hypothesized to reflect inflammation and myelin repair prior to an ensuing decrease in diffusion restriction, indicating glial and neuronal degeneration. ANN NEUROL 2022;91:864–877
Catalytic Desymmetric Dicarbofunctionalization of Unactivated Alkenes
Authors: Wu Xianqing , Luan Baixue , Zhao Wenyu , He Feng , Wu Xin‐Yan , Qu Jingping , Chen Yifeng 
Published: March 2022

AbstractThe construction of multi‐stereocenters by a transition metal‐catalyzed cross‐coupling reaction is a major challenge. The catalytic desymmetric functionalization of unactivated alkenes remains largely unexplored. Herein, we disclose ‐a desymmetric dicarbofunctionalization of 1,6‐dienes via a nickel‐catalyzed reductive cross‐coupling reaction. The leverage of the underdeveloped chiral 8‐Quinox enables the Ni‐catalyzed desymmetric carbamoylalkylation of both unactivated mono‐ and disubstituted alkenes to form pyrrolidinone bearing two nonadjacent stereogenic centers in high enantio‐ and stereoselectivitives with broad functional‐group tolerance. The synthetic application of pyrrolidinones allows the rapid access to complex chiral fused‐heterocycles.
Direct Asymmetric Reductive Amination of Alkyl (Hetero)Aryl Ketones by an Engineered Amine Dehydrogenase
Authors: Kong Weixi , Liu Yunting , Huang Chen , Zhou Liya , Gao Jing , Turner Nicholas J. , Jiang Yanjun 
Published: March 2022

AbstractThe direct asymmetric reductive amination of heteroaryl ketones has been a long‐standing synthetic challenge. Here we report the engineering of an amine dehydrogenase (AmDH) from Jeotgalicoccus aerolatus for the asymmetric synthesis of chiral α‐(hetero)aryl primary amines in excellent conversions (up to 99 %) and enantioselectivities (up to 99 % ee). The best AmDH variant (Ja‐AmDH‐M33) exhibited high activity and specificity toward alkyl (hetero)aryl ketones, even for those bearing a bulky alkyl chain. An efficient directed evolution approach based on molecular docking was implemented to enlarge the active pocket with a more hydrophobic entrance, which is responsible for the high activity. The Ja‐AmDH‐M33 was also used for preparative‐scale synthesis of pharmaceutically relevant amines and a key intermediate of chiral pincer ligands, which highlighted its practical application in synthetic chemistry.
Synthesis of FeIII and FeIV Cyanide Complexes Using Hypervalent Iodine Reagents as Cyano‐Transfer One‐Electron Oxidants
Authors: Souilah Charafa , Jannuzzi Sergio A. V. , Demirbas Derya , Ivlev Sergei , Swart Marcel , DeBeer Serena , Casitas Alicia 
Published: March 2022

AbstractWe disclose a new reactivity mode for electrophilic cyano λ3‐iodanes as group transfer one‐electron oxidants to synthesize FeIII and FeIV cyanide complexes. The inherent thermal instability of high‐valent FeIV compounds without π‐donor ligands (such as oxido (O2−), imido (RN2−) or nitrido (N3−)) makes their isolation and structural characterization a very challenging task. We report the synthesis of an FeIV cyanide complex [(N3N′)FeCN] (4) by two consecutive single electron transfer (SET) processes from FeII precursor [(N3N′)FeLi(THF)] (1) with cyanobenziodoxolone (CBX). The FeIV complex can also be prepared by reaction of [(N3N′)FeIII] (3) with CBX. In contrast, the oxidation of FeII with 1‐cyano‐3,3‐dimethyl‐3‐(1H)‐1,2‐benziodoxole (CDBX) enables the preparation of FeIII cyanide complex [(N3N′)FeIII(CN)(Li)(THF)3] (2‐LiTHF). Complexes 4 and 2‐LiTHF have been structurally characterized by single crystal X‐ray diffraction and their electronic structure has been examined by Mössbauer, EPR spectroscopy, and computational analyses.
Lipase‐catalyzed hydrazine insertion for the synthesis of N′‐alkyl benzohydrazides
Authors: Yu Yue , Li Fengxi , Li Jiapeng , Zheng Xin , Tian Haochen , Mahmut Zulpiya , Du Yanan , Dai Yuyin , Wang Lei 
Published: March 2022

AbstractN′‐alkyl benzohydrazides are classic organic compounds that have been widely utilized in organic chemistry. In this study, an efficient method was developed for the synthesis of N′‐alkyl benzohydrazides by hydrazine insertion catalyzed by lipase. Under the optimal conditions (Morita–Baylis–Hillman ketone [1 mmol], phenylhydrazine [1.3 mmol], N,N‐dimethylformamide [2 ml], lipase [20 mg], room temperature, 12 h), satisfactory yields (71–97%) and substrate tolerance were obtained when porcine pancreatic lipase was used as biocatalyst. These findings imply the great potential for the lipase‐catalyzed synthesis of N′‐alkyl benzohydrazides and extend the utilization of lipase in organic chemistry.
Autophagy flux inhibition mediated by lysosomal dysfunction participates in the cadmium exposure‐induced cardiotoxicity in swine
Authors: Zhao Xia , Shi Xu , Yao Yujie , Li Xiaojing , Xu Shiwen 
Published: March 2022

AbstractCadmium (Cd), a common toxic heavy metal, is believed as a risk factor for the induction and progression of cardiovascular disease. Autophagy is a highly ordered intracellular lysosomal‐mediated degradation pathway that is crucial for protein and organelle quality control. Autophagy dysfunction could develop exacerbated cardiac dysfunction. However, the role of autophagy in Cd exposure‐induced cardiotoxicity remains largely unknown. In this study, the Cd‐induced swine cardiotoxicity model was established by feeding with a CdCl2 suppled diet (20 mg Cd/kg diet). The results showed that Cd exposure increased the expression of endoplasmic reticulum stress‐related genes (GRP78, GRP94, IRE1, XBP1, PERK, ATF4, and ATF6), increased the expression of Ca2+ release channels IP3R and RYR1 and decreased the expression of Ca2+ uptake pump SERCA1. Cd exposure upregulated the expression of autophagy‐related genes (CAMKKII, AMPK, ATG5, ATG7, ATG12, Beclin1, LC3‐II, and P62) and downregulated mTOR expression. Cd exposure inhibited the expression of V‐ATPase and cathepsins (CTSB and CTSD), and increased the expression of cathepsins in cytoplasm. Cd exposure decreased the colocalization of autophagosome and lysosome. This study revealed that autophagy flux inhibition caused by lysosomal dysfunction participates in the cardiotoxicity induced by Cd exposure in swine.
Identification of tumor antigens and immune subtypes of glioma for mRNA vaccine development
Authors: Chen Zhuohui , Wang Xiang , Yan Zhouyi , Zhang Mengqi 
Published: March 2022

AbstractRecent evidence suggested that the mRNA vaccine has been effective for many tumors, but its progress in gliomas was slow. In this study, we screened potential tumor antigens and suitable populations for mRNA vaccine to develop mRNA vaccine for glioma. We integrated the normalized RNA sequencing expression data and somatic mutation data from TCGA‐GBM, TCGA‐LGG, and CGGA datasets. Putative antigens in glioma were identified by selecting highly mutated genes with intimate correlation with clinical survival and immune infiltration. An unsupervised partition around medoids algorithm was utilized to stably cluster the patients into five different immune subtypes. Among them, IS1/2 was cold tumor with low tumor mutation burden (TMB), immunogenic cell death (ICDs), and immune checkpoints (ICPs), and IS4/5 was hot tumor with high TMB, ICDs, and ICPs. Monocle3 package was used to evaluate the immune status similarity and evolution in glioma, which identified cluster IS2A/2B within IS2 subtype to be more suitable vaccination receivers. Weighted gene co‐expression network analysis identified five hub immune genes as the biomarkers of patients' immune status in glioma. In conclusion, NAT1, FRRS1, GTF2H2C, BRCA2, GRAP, NR5A2, ABCB4, ZNF90, ERCC6L, and ZNF813 are potential antigens suitable for glioma mRNA vaccine. IS1/2A/2B are suitable for mRNA vaccination.
Anti‐Zika Virus Activity of Plant Extracts Containing Polyphenols and Triterpenes on Vero CCL‐81 and Human Neuroblastoma SH‐SY5Y Cells
Authors: Santos Pereira Rosângela , Vasconcelos Costa Vivian , Luiz Menezes Gomes Gabriel , Rodrigues Valadares Campana Priscilla , Maia de Pádua Rodrigo , Barbosa Milton , Oki Yumi , Heiden Gustavo , Fernandes Geraldo Wilson , Menezes de Oliveira Djalma , Souza Daniele G. , Martins Teixeira Mauro , Castro Braga Fernão 
Published: March 2022

AbstractZika virus (ZIKV) infection is a global threat associated to neurological disorders in adults and microcephaly in children born to infected mothers. No vaccine or drug is available against ZIKV. We herein report the anti‐ZIKV activity of 36 plant extracts containing polyphenols and/or triterpenes. ZIKV‐infected Vero CCL‐81 cells were treated with samples at non‐cytotoxic concentrations, determined by MTT and LDH assays. One third of the extracts elicited concentration‐dependent anti‐ZIKV effect, with viral loads reduction from 0.4 to 3.8 log units. The 12 active extracts were tested on ZIKV‐infected SH‐SY5Y cells and significant reductions of viral loads (in log units) were induced by Maytenus ilicifolia (4.5 log), Terminalia phaeocarpa (3.7 log), Maytenus rigida (1.7 log) and Echinodorus grandiflorus (1.7 log) extracts. Median cytotoxic concentration (CC50) of these extracts in Vero cells were higher than in SH‐SY5Y lineage. M. ilicifolia (IC50=16.8±10.3 μg/mL, SI=3.4) and T. phaeocarpa (IC50=22.0±6.8 μg/mL, SI=4.8) were the most active extracts. UPLC‐ESI‐MS/MS analysis of M. ilicifolia extract led to the identification of 7 triterpenes, of which lupeol and a mixture of friedelin/friedelinol showed no activity against ZIKV. The composition of T. phaeocarpa extract comprises phenolic acids, ellagitannins and flavonoids, as recently reported by us. In conclusion, the anti‐ZIKV activity of 12 plant extracts is here described for the first time and polyphenols and triterpenes were identified as the probable bioactive constituents of T. phaeocarpa and M. ilicifolia, respectively.
Optimizing the Chemiluminescence of a Light‐Producing Deoxyribozyme
Authors: Jakubec Martin , Pšenáková Karolína , Svehlova Katerina , Curtis Edward A. 
Published: March 2022

AbstractSupernova is a chemiluminescent deoxyribozyme recently discovered in our group. It transfers the phosphate group from the 1,2‐dioxetane substrate CDP‐Star to its 5′ hydroxyl group, which triggers a decomposition reaction and the production of light. Here we investigated the effects of reaction conditions on the ability of Supernova to generate a chemiluminescent signal (using a plate reader assay) and to phosphorylate itself (using a ligation assay). Our experiments indicate that multiple zinc ions are required for catalytic function, suggesting links between Supernova and protein enzymes that catalyze similar reactions. They also show how factors such as pH, potassium concentration, CDP‐Star concentration, and DNA concentration affect the reaction. By combining information from different experiments, the rate enhancement of light production was increased by more than 1000‐fold. These results should be useful for applications in which Supernova is used as a sensor.
Palmoplantar keratoderma: An unusual manifestation of hypohydrotic ectodermic dysplasia
Authors: Abdelli Wissal , Souissi Asmahen , Alaoui Fatima , Sassi Wiem , Chelly Ines , Haouat Slim , Mokni Mourad 
Published: March 2022

AbstractRapp–Hodgkin syndrome (RHS) is a rare condition that is characterized by ectodermal dysplasia and palatal abnormalities. Palmoplantar keratoderma (PPK) is an unusual manifestation of hidrotic ED. Ulcerations on the palms are also not common in RHS. We describe a 15‐year‐old boy who has RHS associated with PPK.
A robust functional partial least squares for scalar‐on‐multiple‐function regression
Authors: Beyaztas Ufuk , Lin Shang Han 
Published: March 2022

AbstractThe scalar‐on‐function regression model has become a popular analysis tool to explore the relationship between a scalar response and multiple functional predictors. Most of the existing approaches to estimate this model are based on the least‐squares estimator, which can be seriously affected by outliers in empirical datasets. When outliers are present in the data, it is known that the least‐squares‐based estimates may not be reliable. This paper proposes a robust functional partial least squares method, allowing a robust estimate of the regression coefficients in a scalar‐on‐multiple‐function regression model. In our method, the functional partial least squares components are computed via the partial robust M‐regression. The predictive performance of the proposed method is evaluated using several Monte Carlo experiments and two chemometric datasets: glucose concentration spectrometric data and sugar process data. The results produced by the proposed method are compared favorably with some of the classical functional or multivariate partial least squares and functional principal component analysis methods.
An Allyl Uranium(IV) Sandwich Complex: Are ϕ Bonding Interactions Possible?
Authors: Popov Ivan A. , Billow Brennan S. , Carpenter Stephanie H. , Batista Enrique R. , Boncella James M. , Tondreau Aaron M. , Yang Ping 
Published: March 2022

AbstractA method to explore head‐to‐head ϕ back‐bonding from uranium f‐orbitals into allyl π* orbitals has been pursued. Anionic allyl groups were coordinated to uranium with tethered anilide ligands, then the products were investigated by using NMR spectroscopy, single‐crystal XRD, and theoretical methods. The (allyl)silylanilide ligand, N‐((dimethyl)prop‐2‐enylsilyl)‐2,6‐diisopropylaniline (LH), was used as either the fully protonated, singly deprotonated, or doubly deprotonated form, thereby highlighting the stability and versatility of the silylanilide motif. A free, neutral allyl group was observed in UI2(L1)2 (1), which was synthesized by using the mono‐deprotonated ligand [K][N‐((dimethyl)prop‐2‐enyl)silyl)‐2,6‐diisopropylanilide] (L1). The desired homoleptic sandwich complex U[L2]2 (2) was prepared from all three ligand precursors, but the most consistent results came from using the dipotassium salt of the doubly deprotonated ligand [K]2[N‐((dimethyl)propenidesilyl)‐2,6‐diisopropylanilide] (L2). This allyl‐based sandwich complex was studied by using theoretical techniques with supporting experimental spectroscopy to investigate the potential for phi (ϕ) back‐bonding. The bonding between UIV and the allyl fragments is best described as ligand‐to‐metal electron donation from a two carbon fragment‐localized electron density into empty f‐orbitals.
Irreversible Inhibition of IspG, a Target for the Development of New Antimicrobials, by a 2‐Vinyl Analogue of its MEcPP Substrate
Authors: Herrscher Vivien , Witjaksono Clea , Buchotte Marie , Ferret Claire , Massicot Fabien , Vasse Jean‐Luc , Borel Franck , Behr Jean‐Bernard , Seemann Myriam 
Published: March 2022

AbstractIspG (also called GcpE) is an oxygen‐sensitive [4Fe‐4S] enzyme catalyzing the penultimate step of the methylerythritol phosphate (MEP) pathway, a validated target for drug development. It converts 2‐C‐methyl‐d‐erythritol‐2,4‐cyclo‐diphosphate (MEcPP) into (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl‐1‐diphosphate (HMBPP). The reaction, assimilated to a reductive dehydration, involves redox partners responsible for the formal transfer of two electrons to substrate MEcPP. The 2‐vinyl analogue of MEcPP was designed to generate conjugated species during enzyme catalysis, with the aim of providing new reactive centers to be covalently trapped by neighboring amino acid residues. The synthesized substrate analogue displayed irreversible inhibition towards IspG. Furthermore, we have shown that electron transfer occurs prior to inhibition; this might designate conjugated intermediates as probable affinity tags through covalent interaction at the catalytic site. This is the first report of an irreversible inhibitor of the IspG metalloenzyme.
High‐Pressure Reaction Profiles and Activation Volumes of 1,3‐Cyclohexadiene Dimerizations Computed by the Extreme Pressure‐Polarizable Continuum Model (XP‐PCM)
Authors: Chen Bo , Houk K. N. , Cammi Roberto 
Published: March 2022

AbstractQuantum chemical calculations are reported for the thermal dimerizations of 1,3‐cyclohexadiene at 1 atm and high pressures up to the GPa range. Computed activation enthalpies of plausible dimerization pathways at 1 atm agree well with the experiment activation energies and the values from previous calculations. High‐pressure reaction profiles, computed by the recently developed extreme pressure‐polarizable continuum model (XP‐PCM), show that the reduction of reaction barrier is more profound in concerted reactions than in stepwise reactions, which is rationalized on the basis of the volume profiles of different mechanisms. A clear shift of the transition state towards the reactant under pressure is revealed for the [6+4]‐ene reaction by the calculations. The computed activation volumes by XP‐PCM agree excellently with the experimental values, confirming the existence of competing mechanisms in the thermal dimerization of 1,3‐cyclohexadiene.