bluuebunny/crossref_metadata_2025 huggingface dataset:
Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder
Authors: He Xueqin , Xie Jiang , Zhang Jing , Wang Xiaorong , Jia Xufeng , Yin Heng , Qiu Zhongqing , Yang Zhihang , Chen Jiao , Ji Zhiliang , Yu Wenqi , Chen Meiwan , Xu Wenming , Gao Huile
Published: March 2022

The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain‐lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin‐triggered lipoxin A4 is a potent anti‐inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery system (Asp@TMNPs) is established, which can successively target the blood–brain barrier (BBB) and microglial cells and response to the acid microenvironment in lysosome. As a result, the mitochondrial oxidative stress, DNA damage, and inflammation of microglial cells are prominently alleviated. After the treatment of Asp@TMNPs, the social interaction, stereotype behavior, and anxious condition of ASD mice are notably improved and the activation of microglial cells is inhibited. Overall, this system successively penetrates the BBB and targets microglial cells, therefore, it significantly enhances the intracephalic drug accumulation and improves anti‐neuroinflammatory efficacy of aspirin, providing a promising strategy for ASD treatment.
High Energy and Power Density Peptidoglycan Muscles through Super‐Viscous Nanoconfined Water
Authors: Wang Haozhen , Liu Zhi‐Lun , Lao Jianpei , Zhang Sheng , Abzalimov Rinat , Wang Tong , Chen Xi
Published: March 2022

Water‐responsive (WR) materials that reversibly deform in response to humidity changes show great potential for developing muscle‐like actuators for miniature and biomimetic robotics. Here, it is presented that Bacillus (B.) subtilis’ peptidoglycan (PG) exhibits WR actuation energy and power densities reaching 72.6 MJ m−3 and 9.1 MW m−3, respectively, orders of magnitude higher than those of frequently used actuators, such as piezoelectric actuators and dielectric elastomers. PG can deform as much as 27.2% within 110 ms, and its actuation pressure reaches ≈354.6 MPa. Surprisingly, PG exhibits an energy conversion efficiency of ≈66.8%, which can be attributed to its super‐viscous nanoconfined water that efficiently translates the movement of water molecules to PG's mechanical deformation. Using PG, WR composites that can be integrated into a range of engineering structures are developed, including a robotic gripper and linear actuators, which illustrate the possibilities of using PG as building blocks for high‐efficiency WR actuators.
Ultralow‐Power Machine Vision with Self‐Powered Sensor Reservoir
Authors: Lao Jie , Yan Mengge , Tian Bobo , Jiang Chunli , Luo Chunhua , Xie Zhuozhuang , Zhu Qiuxiang , Bao Zhiqiang , Zhong Ni , Tang Xiaodong , Sun Linfeng , Wu Guangjian , Wang Jianlu , Peng Hui , Chu Junhao , Duan Chungang
Published: March 2022

A neuromorphic visual system integrating optoelectronic synapses to perform the in‐sensor computing is triggering a revolution due to the reduction of latency and energy consumption. Here it is demonstrated that the dwell time of photon‐generated carriers in the space‐charge region can be effectively extended by embedding a potential well on the shoulder of Schottky energy barrier. It permits the nonlinear interaction of photocurrents stimulated by spatiotemporal optical signals, which is necessary for in‐sensor reservoir computing (RC). The machine vision with the sensor reservoir constituted by designed self‐powered Au/P(VDF‐TrFE)/Cs2AgBiBr6/ITO devices is competent for both static and dynamic vision tasks. It shows an accuracy of 99.97% for face classification and 100% for dynamic vehicle flow recognition. The in‐sensor RC system takes advantage of near‐zero energy consumption in the reservoir, resulting in decades‐time lower training costs than a conventional neural network. This work paves the way for ultralow‐power machine vision using photonic devices.
XAI‐MEG: Combining symbolic AI and machine learning to generate first‐principles models and causal explanations
Authors: Sivaram Abhishek , Venkatasubramanian Venkat
Published: March 2022

Current 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

Mixed‐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

Objective

Although 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.

Methods

We 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.

Results

In 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.

Interpretation

The current study provides evidence that Sec31a plays a key role in inhibiting nerve regeneration in diabetic neuropathy. ANN NEUROL 2022;91:821–833
APOE Antibody Inhibits Aβ‐Associated Tau Seeding and Spreading in a Mouse Model
Authors: Gratuze Maud , Jiang Hong , Wang Chanung , Xiong Monica , Bao Xin , Holtzman David M.
Published: March 2022

APOE is the strongest genetic factor for late‐onset Alzheimer's disease (AD). A specific conformation of the ApoE protein is present in amyloid‐β (Aβ) containing plaques. Immunotherapy targeting ApoE in plaques reduces brain Aβ deposits in mice. Here, we evaluated the effects of the anti‐human APOE antibody HAE‐4 on amyloid plaques, Aβ‐mediated tau seeding and spreading, and neuritic dystrophy in the 5XFAD amyloid mice expressing human ApoE4. HAE‐4 reduced Aβ plaques as well as Aβ‐driven tau seeding/spreading and neuritic dystrophy. These results demonstrate that HAE‐4 may provide therapeutic effects on amyloid removal and Aβ driven downstream consequences such as tauopathy. ANN NEUROL 2022;91:847–852
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

Objective

The 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.

Methods

Cognitively 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.

Results

We 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.

Interpretation

These 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

The 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

The 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

We 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

N′‐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

Cadmium (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

Recent 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

Zika 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

Supernova 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

Rapp–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

The 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

A 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

IspG (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

Quantum 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.
Detection and remediation of chiral pharmaceuticals from wastewater: A review
Authors: Vashistha Vinod Kumar
Published: March 2022

Chiral organic pollutants including pharmaceuticals, pesticides, herbicides, flame retardants, and polycyclic musk cause significant risks to both the environment and human health. Chiral pharmaceuticals (CPs) are among the significant class of pseudo‐persistent substances that have been observed in the concentration level from nanomolar to micromolar quantities and cause bad impacts on nontargeted species and direct or indirect human health issues due to water and foodborne contamination. The CPs may contain one or more chiral centers in their structural framework and thus enantiomers of CPs often possess different distribution, fate, bioaccumulation potential, and toxicity. The enantioselective chromatographic techniques have been extensively applied to detect drug enantiomers during the last few years. Bioremediation techniques offer unique characteristics above conventional remediation procedures as these could be cost‐effective and accomplish total organic pollutant decomposition without causing collateral damage to the site material or native flora and fauna. This review describes the impacts of chiral pharmaceuticals on the environment; detection technologies (particularly liquid chromatography), and important remedial measures for safer disposal of such pollutants.
Panniculitis in dermatomyositis: Two cases with antitranscriptional intermediary factor‐1 antibody as myositis‐specific antibody and review of the literature
Authors: Takezawa Kaori , Ueda‐Hayakawa Ikuko , Tanaka Akihiro , Son Yonsu , Yamazaki Fumikazu , Kambe Naotomo , Okamoto Hiroyuki , Fujimoto Manabu
Published: March 2022

Dermatomyositis (DM) is a systemic disease characterized by chronic inflammation in the skin and muscle. A variety of myositis‐specific autoantibodies (MSAs) are detected in patients with DM. These antibodies are associated with unique clinical subsets in DM. Panniculitis is a rare cutaneous manifestation of DM that most commonly presents as tender, erythematous subcutaneous nodules on the thighs, arms, and buttocks. We herein describe the clinical features of two DM‐associated panniculitis patients with anti‐TIF1 antibodies. Both are female patients and showed characteristic cutaneous features, including heliotrope rashes and Gottron's signs with muscle involvement. While one patient had a posterior mediastinum tumor, another had no cancer. Furthermore, to elucidate the clinical significance of anti‐TIF1 antibodies in DM patients with panniculitis, we analyzed all cases with detailed information on the clinical features, including MSAs. A PubMed search of keywords “panniculitis” and “DM” was conducted. We found 23 cases with the detection of MSAs. A review of these cases and our two cases revealed a predominance of female gender (80%) with a median age of 48 years. Anti‐MDA5 antibodies were detected in 11 patients (11/23, 48%), and anti‐TIF1 antibodies were observed in four patients, including the current cases (4/23, 17%). Anti‐Mi‐2 antibodies were observed in four patients (4/23, 17%). Each patient had anti‐NXP‐2 antibodies or anti‐SAE antibodies (2/23; 9%). Although the pathogenesis of panniculitis in DM remains unknown, differences in pathogenesis of DM‐associated panniculitis according to MSAs may exist. Accumulation of additional cases is required to clarify the relationship between panniculitis and MSAs.
Toward a digital transformation of the theory of the firm: Emergence as framework for organizational sustainability
Authors: Valentinov Vladislav , Van Assche Kristof , Hermans Frans
Published: March 2022

Embracing methodological individualism, the mainstream economic theory of the firm has little to say about the precarious nature of the firm's embeddedness in encompassing socioecological systems. The digital transformation of the theory of the firm can address this gap by deconstructing the standpoint of methodological individualism. In transaction cost economics, this standpoint is manifest in two assumptions about human nature, namely bounded rationality and opportunism. Drawing on Chester Barnard's insights on the firm, the present paper seeks to construct a view of organizations as emergent systems irreducible to the activities of participating individuals. By inverting the assumptions of bounded rationality and opportunism, the paper differentiates between two varieties of the emergent nature of the firm, cognitive and moral. The ideas of the cognitive and moral emergence of the firm expand the pallet of options for the firm to adapt to socioecological systems and illuminate the notion of sustainability transitions. This way, the digitally enhanced understanding of the firm offers hope for a better dialogue between the economic theory of the firm, sustainability scholarship, and business ethics.
Joint influence of R&D strategy and environmental uncertainty on innovation performance: Insight from transaction cost economics
Authors: Lin Zhouyu , Jiang Marshall S. , Wang Xiaoting
Published: March 2022

This study aims to extend transaction cost economics (TCE) to explain the effects of the strategies of internal and external R&D on innovation performance under two types of environmental uncertainty, namely dynamism and complexity. As a departure from conventional TCE wisdom that internally focused R&D strategy is more efficient under environmental uncertainty, this study proposes that such a strategy can be less efficient under environmental dynamism, which is another important type of uncertainty. The results from a sample of manufacturing firms in China from 2002 to 2007 show that externally focused R&D strategy leads to better innovation performance under environmental dynamism, whereas internally focused R&D strategy results in better innovation performance under environmental complexity.
Synchronous tonsillar tumors with differing histopathology: A case report and review of the literature
Authors: Rossi Nicholas A. , Reddy Devin N. , Rawl Jordan W. , Dong Jianli , Qiu Suimin , Clement Cecilia G. , Resto Vicente A. , Joshi Rohan , McKinnon Brian , Coblens Orly
Published: March 2022

Background

Tonsillar squamous cell carcinoma (TSCC) due to human papillomavirus (HPV) infection has seen a dramatic increase in recent years. Bilateral tonsillar squamous cell carcinoma (biTSCC) has a much lower incidence than unilateral TSCC and three main hypotheses of biTSCC pathogenesis prevail: field carcinogenesis, single‐clone, and multiple HPV infections.

Case

A 49‐year‐old Male with a remote history of chewing tobacco presented with symptoms of spitting up tissue and occasional hemoptysis. Physical exam showed a sole left tonsillar mass which was confirmed to be TSCC on biopsy. The patient's computed tomographic (CT) scan was consistent with this finding; however, positron emission tomography (PET) scan indicated a second tumor in the contralateral right tonsil. Surgical resection of both masses and selective neck dissection was performed, and the specimens were sent for further pathological analysis. No complications of surgery were noted and the final diagnosis of synchronous biTSCC was made. The tumors were a T2N0M0 left poorly differentiated TSCC (p16+, EGFR+, bcl2+) with basaloid features, and a T1N0M0 right well to moderately differentiated TSCC (p16+, EGFR+, bcl2−).

Conclusion

Our present case was notable for differing tumor pathology and karyotype analysis between the right and left masses, directly supporting the multiple HPV infections hypothesis of biTSCC pathogenesis. Further genetic characterization of tonsillar tumors is needed to better characterize TSCC and best guide medical/surgical therapy.
A new ridge‐type estimator for the linear regression model with correlated regressors
Authors: Owolabi Abiola T. , Ayinde Kayode , Alabi Olusegun O.
Published: March 2022

The ridge‐type regression estimators are frequently being used to address multicollinearity in the linear regression model due to the inefficiency of the famous ordinary least squares estimator. The ridge‐type regression estimator can be in one or two‐parameter form. This paper proposes another ridge‐type estimator, a two‐parameter ridge‐type estimator, and establishes its statistical properties theoretically and through Monte Carlo simulation studies. Two different biasing parameters (k1d1 and k2d2) were considered for the proposed and compared with six other existing estimators. Results of Monte Carlo simulation studies show the dominance of the proposed method over some existing ones using the mean squared criterion. In addition, the proposed dominated the existing estimators when applied to real‐life datasets using mean squared error and cross‐validation as the criterion.
Dissociative Electron Attachment to Hexachlorobenzene
Authors: Goryunkov Alexey A. , Asfandiarov Nail L. , Rakhmeev Rustam G. , Markova Angelina V. , Pshenichnyuk Stanislav A. , Rybalchenko Alexey V. , Lukonina Natalia S. , Ioffe Ilya N.
Published: March 2022

Gas phase molecules of hexachlorobenzene (C6Cl6) were investigated by means of dissociative electron attachment spectroscopy (DEAS). Three channels of molecular negative ions decay have been identified: abstraction of Cl− and Cl2− as well as electron detachment (τa∼250 μs at 343 K). All three channels exhibit temperature dependence. The adiabatic electron affinity estimated using a simple but typically accurate Arrhenius model (EAa=1.6–1.9 eV) turns out to be much higher than the quantum‐chemical predictions (EAa=0.9–1.0 eV). We discuss the possible reasons behind the observed discrepancy.
Identification of Crucial Intermediates in the Formation of Humins from Cellulose‐Derived Platform Chemicals Under Brønsted Acid Catalyzed Reaction Conditions
Authors: Divya P. S. , Nair Swetha , Kunnikuruvan Sooraj
Published: March 2022

Humins are one of the undesirable products formed during the dehydration of sugars as well as the conversion of 5‐hydroxymethylfurfural (HMF) to value‐added products. Thus, reducing the formation of humins is an important strategy for improving the yield of the aforementioned reactions. Even after a plethora of studies, the mechanism of formation and the structure of humins are still elusive. In this regard, we have employed density functional theory‐based mechanistic studies and microkinetic analysis to identify crucial intermediates formed from glucose, fructose, and HMF that can initiate the polymerization reactions resulting in humins under Brønsted acid‐catalyzed reaction conditions. This study brings light into crucial elementary reaction steps that can be targeted for controlling humins formation. Moreover, this work provides a rationale for the experimentally observed aliphatic chains and HMF condensation products in the humins structure. Different possible polymerization routes that could contribute to the structure of humins are also suggested based on the results. Importantly, the findings of this work indicate that increasing the rate of isomerization of glucose to fructose and reducing the rate of reaction between HMF molecules could be an efficient strategy for reducing humins formation.
Design, Construction, and Implementation of a Magnetic Resonance Elastography Actuator for Research Purposes
Authors: Triolo Emily Rose , Khegai Oleksandr , Ozkaya Efe , Rossi Nicholas , Alipour Akbar , Fleysher Lazar , Balchandani Priti , Kurt Mehmet
Published: March 2022

Magnetic resonance elastography (MRE) is a technique for determining the mechanical response of soft materials using applied harmonic deformation of the material and a motion‐sensitive magnetic resonance imaging sequence. This technique can elucidate significant information about the health and development of human tissue such as liver and brain, and has been used on phantom models (e.g., agar, silicone) to determine their suitability for use as a mechanical surrogate for human tissues in experimental models. The applied harmonic deformation used in MRE is generated by an actuator, transmitted in bursts of a specified duration, and synchronized with the magnetic resonance signal excitation. These actuators are most often a pneumatic design (common for human tissues or phantoms) or a piezoelectric design (common for small animal tissues or phantoms). Here, we describe how to design and assemble both a pneumatic and a piezoelectric MRE actuator for research purposes. For each of these actuator types, we discuss displacement requirements, end‐effector options and challenges, electronics and electronic‐driving requirements and considerations, and full MRE implementation. We also discuss how to choose the actuator type, size, and power based on the intended material and use. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Design, construction, and implementation of a convertible pneumatic MRE actuator for use with tissues and phantom models

Basic Protocol 2: Design, construction, and implementation of a piezoelectric MRE actuator for localized excitation in phantom models
Toward Diiron Dithiolato Biomimetics with Rotated Conformation of the [FeFe]‐Hydrogenase Active Site: A DFT Case Study on Electron‐Rich, Isocyanide‐Based Scaffolds
Authors: Arrigoni Federica , Rizza Fabio , Bertini Luca , De Gioia Luca , Zampella Giuseppe
Published: March 2022

The electron rich Fe2(pdt)(RNC)6 1 (pdt=CH2(CH2S−)2) has been used as starting point for a DFT multi‐functional study to assess the feasibility of designing a stable inverted (or rotated) disposition of the two FeL3 pyramidal moieties in the dimetallic core, a key feature of [FeFe]‐hydrogenase cofactor. The choice of 1 was motivated by the presence of a rotated form in solution, slightly less stable than the unrotated stereoisomer. Aimed to find an upgraded version of 1, featuring the rotated isomer as ground state, various combinations of factors have been tested, for their effect on the relative stability of rotated vs unrotated isomers. The general result is that combining coordination asymmetry, electron donor presence and isocyanides R substituents able to establish intramolecular interactions is effective in stabilizing the rotated isomer. Our DFT study may inspire the design of synthetic biomimetics, with improved resemblance to the natural system.
Stereoselective Syntheses of Deuterated Pipecolic Acids as Tools to Investigate the Stereoselectivity of the Hydroxylase GetF
Authors: Neis Nadine , Xie Feng , Krug Daniel , Zhao Haowen , Siebert Andreas , Binz Tina M. , Fu Chengzhang , Müller Rolf , Kazmaier Uli
Published: March 2022

Members of the GE81112 family are interesting candidates for the development of antibiotics. The configuration of the OH group on the pipecolic acid moiety plays a pivotal role in antibiotic activity. To investigate the stereoselectivity of the corresponding hydroxylase GetF, involved in the biosynthetic pathway, we synthesized the two deuterium‐labeled pipecolic acid diastereomers in a highly stereoselective fashion via chelate‐enolate Claisen rearrangement. The stereochemical outcome of the enzymatic hydroxylation step could easily be determined by analysis of mass differences between the products.
Protein speciation is likely to increase the chance of proteins to be determined in 2‐DE/MS
Authors: Kwiatkowski Marcel , Hotze Madlen , Schumacher Julia , Asif Abdul R. , Pittol Jose Miguel Ramos , Brenig Bertram , Ramljak Sanja , Zischler Hans , Herlyn Holger
Published: March 2022

Multiple spotting due to protein speciation might increase a protein's chance of being captured in a random selection of 2‐DE spots. We tested this expectation in new (PXD015649) and previously published 2‐DE/MS data of porcine and human tissues. For comparison, we included bottom‐up proteomics studies (BU‐LC/MS) of corresponding biological materials. Analyses of altogether ten datasets proposed that amino acid modification fosters multispotting in 2‐DE. Thus, the number of 2‐DE spots containing a particular protein more tightly associated with a peptide diversity measure accounting for amino acid modification than with an alternative one disregarding it. Furthermore, every 11th amino acid was a post‐translational modification candidate site in 2‐DE/MS proteins, whereas in BU‐LC/MS proteins this was merely the case in every 21st amino acid. Alternative splicing might contribute to multispotting, since genes encoding 2‐DE/MS proteins were found to have on average about 0.3 more transcript variants than their counterparts from BU‐LC/MS studies. Correspondingly, resolution completeness as estimated from the representation of transcript variant‐rich genes was higher in 2‐DE/MS than BU‐LC/MS datasets. These findings suggest that the ability to resolve proteomes down to protein species can lead to enrichment of multispotting proteins in 2‐DE/MS. Low sensitivity of stains and MS instruments appears to enhance this effect.
Capillary electrophoresis‐acid barrage stacking online enrichment method for highly sensitive determination of four isoflavones
Authors: Zhang Yufei , Ma Haixia , Zhang Yuhui , Dong Yuming
Published: March 2022

A capillary electrophoresis‐acid barrage stacking online enrichment method has been established to detect the four isoflavones which are Daidzein, Genistein, Formononetin, and Biochanin A. The proposed method was optimized using a single factor alternative method, and the optimal conditions obtained from the optimization were: the BGE was 25 mM borax and 2 mM β‐cyclodextrin, the applied separation voltage was 20 kV, and the detection wavelength was 260 nm. The time ratio of the injection of sample and the injection of acid was 150 s:20 s, and the acid used was 250 mM acetic acid. The sample solvent used was 60% v/v acetonitrile. The established method had the enrichment factor of these four isoflavones at 24.5, 32.0, 29.2, and 33.7, respectively, LOD and LOQ are as low as nanograms per milliliter. Finally, the CE‐acid barrage stacking method was successfully applied to the determination of four isoflavones in rat plasma and red clover extract, verifying the applicability and feasibility of the method.