bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrin‐specific poly(N‐isopropylacrylamide) nanogels for targeted delivery of tissue‐type plasminogen activator to treat thrombotic complications are well tolerated in vivo
Authors: Mihalko Emily P. , Nellenbach Kimberly , Krishnakumar Manasi , Moiseiwitsch Nina , Sollinger Jennifer , Cooley Brian C. , Brown Ashley C. 
Published: December 2021

AbstractTargeted drug delivery for maintaining blood fluidity can reduce the risks associated with systemic anticoagulants that can lead to off‐target bleeding. Recently, there has been much interest in targeted delivery of tissue‐type plasminogen activator (tPA) for treating thrombotic complications. The work presented here characterizes a fibrin‐specific nanogel (FSN) design for targeted delivery of tPA to treat thrombotic complications. Fibrin binding and clot degradation were characterized in vitro, and animal models of thrombosis were used to examine nanogel effects on coagulation parameters. In vitro assays showed tPA‐FSNs attach to fibrin in a dose‐dependent manner independent of tPA loading. In animal models of thrombosis, including an electrolytic injury to monitor clot properties in real time, and a lipopolysaccharide‐induced disseminated intravascular coagulation (DIC) animal model, tPA‐FSNs modulated fibrin/fibrinogen and platelet incorporation into clots and at optimized dosing could recover consumptive coagulopathy in DIC. Distribution of unloaded and tPA‐loaded FSNs showed potential clearance of tPA‐FSNs after 24 h, although unloaded FSNs may be retained at sites of fibrin deposits. Maximum tolerated dose studies showed tPA‐FSNs have minimal toxicity up to 20 times the optimized therapeutic dose. Overall, these studies demonstrate the therapeutic efficacy of targeted fibrinolysis for systemic microthrombi and begin to evaluate key translational parameters for tPA‐FSN therapeutics, including optimal tPA‐FSN dosage in a DIC rodent model and safety of intravenous tPA‐FSN therapeutics.
Vibsane‐Type Diterpenoids: Structures, Derivatives, Bioactivities, and Synthesis
Authors: Li Meng , Zhou Zhi‐Ping , Yuan Zai‐Feng , Zhao Qin‐Shi 
Published: December 2021

AbstractVibsane‐type diterpenoids isolated from the genus Viburnum, are rare 6–11 membered ring polysubstituted macrocyclic diterpenoids. Since the first report of vibsane‐type diterpenoids from V. odoratissimum in 1980, they have attracted the attention of scientists due to their complex structures, excellent biological activities, and great synthetic challenges. Recently, there are some notable research achievements on the discovery, synthesis, structural modification, and pharmacological mechanism of vibsane‐type diterpenoids. Therefore, we will focus on these aspects to review important achievements of vibsane diterpenoids between 1980–2021.
Synthesis of Chiral Amines via a Bi‐Enzymatic Cascade Using an Ene‐Reductase and Amine Dehydrogenase
Authors: Jongkind Ewald P. J. , Fossey‐Jouenne Aurélie , Mayol Ombeline , Zaparucha Anne , Vergne‐Vaxelaire Carine , Paul Caroline E. 
Published: December 2021

AbstractAccess to chiral amines with more than one stereocentre remains challenging, although an increasing number of methods are emerging. Here we developed a proof‐of‐concept bi‐enzymatic cascade, consisting of an ene reductase and amine dehydrogenase (AmDH), to afford chiral diastereomerically enriched amines in one pot. The asymmetric reduction of unsaturated ketones and aldehydes by ene reductases from the Old Yellow Enzyme family (OYE) was adapted to reaction conditions for the reductive amination by amine dehydrogenases. By studying the substrate profiles of both reported biocatalysts, thirteen unsaturated carbonyl substrates were assayed against the best duo OYE/AmDH. Low (5 %) to high (97 %) conversion rates were obtained with enantiomeric and diastereomeric excess of up to 99 %. We expect our established bi‐enzymatic cascade to allow access to chiral amines with both high enantiomeric and diastereomeric excess from varying alkene substrates depending on the combination of enzymes.
Co‐Feeding of Ethene, Propene, and 1‐Butene to Co‐Mn‐Catalyzed Fischer‐Tropsch Synthesis
Authors: Reul Andreas , Thiessen Johannes , Jess Andreas , Scholz Judith , Heykamp Angela 
Published: December 2021

AbstractIn Fischer‐Tropsch synthesis (FTS), a variety of hydrocarbons with different chain lengths are formed. The selectivities depend on the catalyst and the reaction conditions. Co‐feeding olefins allows changing the selectivity even outside the rules of the Anderson‐Schulz‐Flory distribution. In this work, ethene, propene, and 1‐butene were co‐fed to Co‐Mn‐catalyzed FTS to increase the olefin selectivity in the C3‐ to C8‐fraction. An increase of the CO reaction rate and oxygenate selectivity indicates that besides FTS also hydroformylation takes place. While the predominant reaction is the unwanted hydrogenation of the co‐fed olefins, this could in case of ethene be reduced by lowering the H2 pressure.
On properties of EFA plots
Authors: Neymeyr Klaus , Beese Martina , Sawall Mathias 
Published: December 2021

AbstractThe evolving factor analysis (EFA) facilitates the detection of the emergence or loss of chemical species during a chemical reaction, a chromatographic process, a spectroelectrochemical analysis, and other experiments. To this end, EFA monitors the singular values of sequences of spectral data matrices with increasing dimensions. This paper studies the growth behavior of these singular values. It investigates properties of the EFA techniques, analyzes the general shape of the singular value curves, and gives practical remarks for an improved extraction of chemical information from EFA plots.
CO2‐Philic Mixed‐Matrix Membranes Based on Ultra‐Stable Porous‐Framework Zirconium Phosphate
Authors: Ji Taotao , Liu Liangliang , Wang Lingyi , Li Yanshuo , Liu Yi 
Published: December 2021

AbstractThe practical application of membrane separation, such as CO2 recovery from flue gas, is usually accompanied by harsh operating conditions of high temperature and pressure as well as acidic and humid feed properties, which poses a great challenge to the stability of membrane materials. In this work, zirconium phosphate material with highly stable porous‐framework structure was synthesized by ionothermal method, and then, its incorporation into the polymer matrix to prepare ZrPOF‐Pebax mixed‐matrix membranes (MMMs) was pioneered. Benefiting from their 4.0 × 3.0 Å 7‐ring windows and CO2‐philic framework, the optimal MMMs with a 5 wt % ZrPOF content exhibited enhanced CO2/N2 selectivity of 29.6, with a decent CO2 permeability of 286.3 Barrer, which raised by 79.4 and 67.5% compared to the neat Pebax 2533 membranes, respectively. Furthermore, owing to their excellent thermal, water, and chemical stability, obtained MMMs maintained excellent performances under harsh operating conditions.
Recent Advances of Monolithic All‐Perovskite Tandem Solar Cells: From Materials to Devices
Authors: Jiang Shan , Bai Yiming , Ma Zongwen , Jin Shengli , Zou Chao , Tan Zhao'ao 
Published: December 2021

Comprehensive SummaryOrganic–inorganic metal‐halide perovskite solar cells (PerSCs) have achieved significant progresses due to their outstanding optoelectronic characteristics, and the power conversion efficiency (PCE) of single‐junction PerSCs has been boosted from 3.8% to a certified 25.2%. However, the efficiency of single‐junction cells is governed by the Shockley–Queisser (S–Q) radiative limit, and fabricating all‐perovskite tandem solar cells is a particularly attractive method to break the S–Q limit. Since the bandgap of lead (Pb)–based mixed halide perovskite can be tuned from 1.55 eV to 2.3 eV, and the mixed tin (Sn)–Pb perovskites have bandgap of ~1.2 eV, these perovskites become the best candidates for the front and rear subcells of all‐perovskite tandem device, respectively. In this review, we firstly summarize the current development progresses of two‐terminal (2‐T) all‐perovskite tandem solar cells. For further optimizing the device performance, the wide bandgap mixed halide perovskites for front subcell, mixed Sn–Pb narrow bandgap perovskites for rear subcell, and the interconnection layer (ICL) of 2‐T tandem device are then discussed. This review aims to open a pathway to realize highly efficient all‐perovskite tandem solar cells.
Revealing the Solution Structure of Pd(OAc)2 with Halide Additives
Authors: Wang Liwei , Yang Dali , Alhumade Hesham , Yi Hong , Qi Xiaotian , Lei Aiwen 
Published: December 2021

Comprehensive SummaryMechanistic studies of the palladium catalyst activation with halide additives are of great importance to palladium catalysis. In this work, XAFS spectroscopy and cyclic voltammetry were utilized to study real structures of Pd(OAc)2 in solution with different inorganic halogen additives. XAFS results demonstrate that Pd maintained +2 in the presence of excessive LiCl, LiBr, ZnCl2, ZnBr2, and NaI. Fitting results of EXAFS spectra revealed that the Pd's first shell is replaced by halogen partially or completely depending on the halogen species. DFT calculations were conducted to identify the most reliable solvated structures. The combined experimental and computational studies elucidate the critical role of inorganic halide additives in Pd chemistry.
Development, validation, and visualization of a web‐based nomogram for predicting the incidence of leiomyosarcoma patients with distant metastasis
Authors: Li Zhehong , Wei Junqiang , Cao Haiying , Song Mingze , Zhang Yafang , Jin Yu 
Published: December 2021

AbstractBackgroundLeiomyosarcoma (LMS) is one of the most common soft tissue sarcomas. LMS is prone to distant metastasis (DM), and patients with DM have a poor prognosis.AimIn this study, we investigated the risk factors of DM in LMS patients and the prognostic factors of LMS patients with DM.Methods and resultsLMS patients diagnosed between 2010 and 2016 were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. Patients were randomly divided into the training set and validation set. Univariate and multivariate logistic regression analyses were performed, and a nomogram was established. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. Based on the nomogram, a web‐based nomogram is established. The univariate and multivariate Cox regression analyses were used to assess the prognostic risk factors of LMS patients with DM. Eventually, 2184 patients diagnosed with LMS were enrolled, randomly divided into the training set (n = 1532, 70.14%) and validation set (n = 652, 29.86%). Race, primary site, grade, T stage, and tumor size were correlated with DM incidence in LMS patients. The AUC of the nomogram is 0.715 in training and 0.713 in the validation set. The calibration curve and DCA results showed that the nomogram performed well in predicting the DM risk. A web‐based nomogram was established to predict DM's risk in LMS patients (https://wenn23.shinyapps.io/riskoflmsdm/). Epithelioid LMS, in uterus, older age, giant tumor, multiple organ metastasis, without surgery, and chemotherapy had a poor prognosis.ConclusionsThe established web‐based nomogram (https://wenn23.shinyapps.io/riskoflmsdm/) is an accurate and personalized tool to predict the risks of LMS developing DM. Advanced age, larger tumor, multiple organ metastasis, epithelioid type, uterine LMS, no surgery, and no chemotherapy were associated with poor prognosis in LMS patients with DM.
Safety, Pharmacokinetics, and Pharmacodynamics of the ADAMTS‐5 Inhibitor GLPG1972/S201086 in Healthy Volunteers and Participants With Osteoarthritis of the Knee or Hip
Authors: van der Aar Ellen , Deckx Henri , Dupont Sonia , Fieuw Ann , Delage Stephane , Larsson Staffan , Struglics André , Lohmander L. Stefan , Lalande Agnes , Leroux Emilie , Amantini David , Passier Paul 
Published: December 2021

AbstractGLPG1972/S201086 is a disintegrin and metalloproteinase with thrombospondin motif‐5 (ADAMTS‐5) inhibitor in development as an osteoarthritis disease‐modifying therapy. We report the safety, tolerability, pharmacokinetics, and pharmacodynamics (turnover of plasma/serum ARGS‐aggrecan neoepitope fragments [ARGS]) of GLPG1972 in 3 randomized, double‐blind, placebo‐controlled phase 1 trials. Study A, a first‐in‐human trial of single (≤2100 mg [fasted] and 300 mg [fed]) and multiple (≤1050 mg once daily [fed]; 14 days) ascending oral (solution) doses, investigated GLPG1972 in healthy men (N = 41; NCT02612246). Study B investigated multiple ascending oral (tablet) doses of GLPG1972 (≤300 mg once daily [fed]; 4 weeks) in male and female participants with osteoarthritis (N = 30; NCT03311009). Study C investigated single (Japanese: ≤1500 mg; White: 300 mg [fasted]) and multiple (Japanese, ≤1050 mg once daily; White, 300 mg once daily [fed]; 14 days) ascending oral (tablet) doses of GLPG1972 in healthy Japanese and White men (N = 88). The pharmacokinetic profile of GLPG1972 was similar between healthy participants and participants with osteoarthritis, with low to moderate interindividual variability. GLPG1972 was rapidly absorbed (median time to maximum concentration, 4 hours), and eliminated with a mean apparent terminal elimination half‐life of ≈10 hours. Steady state was achieved within 2 days of dosing, with minimal accumulation. Steady‐state plasma exposure after 300 mg of GLPG1972 showed no or minor differences between populations. Area under the plasma concentration–time curve (56.8‐67.6 μg · h/mL) and time to maximum concentration (4 hours) were similar between studies. Urinary excretion of GLPG1972 (24 hours) was low (<11%). Multiple dosing significantly reduced ARGS levels vs baseline at all time points for all doses vs placebo. GLPG1972 was generally well tolerated at all doses.
A Rhenium Single‐Atom Catalyst for the Electrocatalytic Oxygen Reduction Reaction
Authors: Zhang Xiaohan , Shang Lu , Yang Zhaojun , Zhang Tierui 
Published: December 2021

AbstractSingle atom catalysts (SACs) have received a great deal of attention due to their extremely high active site utilization and superior activities. The exploration of metal SACs has been carried out by screening the elemental periodic table from first‐row to second‐row, and even third‐row transition metals. However, Re SACs have not been reported, even if Re metal sites also play essential roles in catalyzing many important reactions. The construction of Re SACs may maximize Re catalytic sites and provide new Re active sites for higher activity. Herein, we used 1,10‐phenanthroline to complex Re cations on carbon black, followed by heat treatment to obtain Re SAC. The Re SAC exhibited an oxygen reduction reaction (ORR) half‐wave potential of 0.72 V versus reversible hydrogen electrode (RHE) in 0.1 M KOH, superior to Re nanoparticles catalyst (0.67 V vs. RHE). Re SAC exhibited better stability at 0.5 V vs. RHE than Pt/C, showing potential as a new electrocatalyst for ORR.
Bidentate Pyridyl‐NHC Ligands: Synthesis, Ground and Excited State Properties of Their Iron(II) Complexes and the Role of the fac/mer Isomerism
Authors: Magra Kévin , Francés‐Monerris Antonio , Cebrián Cristina , Monari Antonio , Haacke Stefan , Gros Philippe C. 
Published: December 2021

AbstractIron complexes are promising candidates for the development of sustainable molecular photoactive materials as an alternative to those based on precious metals such as Ir, Pt or Ru. These compounds possess metal‐ligand charge transfer (MLCT) transitions potentially of high interest for energy conversion or photocatalysis applications if the ultrafast deactivation via lower‐lying metal‐centred (MC) states can be impeded. Following an introduction describing the main design strategies used so far to increase the MLCT lifetimes, we review some of our latest contributions to the field regarding bidentate Fe(II) complexes comprising N‐heterocyclic carbene ligands. The discussion covers all aspects from their synthesis to their characterization via photophysical, electrochemical and computational techniques. The impact of bidentate coordination together with the configuration (facial and meridional isomers) is analysed, finally highlighting the current challenges in this promising area.
Construction of Tetracyclic Core Skeleton of Cephalotaxus Diterpenoids through Diastereoselective Pauson‐Khand Reaction
Authors: Chen Chong‐Chong , Ren Zhiqiang , Sun Zhongliu , Sun Zezhong , Shu Xin , Wang Yunxia , Hu Xiangdong 
Published: December 2021

AbstractCephalotaxus diterpenoids represent a class of attractive natural products with diverse chemical structures and valuable biological activities. The Construction of tetracyclic core skeleton plays an important role in synthesizing these compounds. We report here the development of diastereoselective Pauson‐Khand reactions as an effective strategy to the core structure, which enabled the total synthesis of (+)‐3‐deoxyfortalpinoid F, (+)‐fortalpinoid A, and (+)‐cephinoid H.
Cyber‐physical network architecture for data stream provisioning in complex ecosystems
Authors: Okafor Kennedy Chinedu , Ndinechi Michael Chukwudi , Misra Sanjay 
Published: December 2021

AbstractIntelligent fog cyber‐physical social systems (iFog CPSS) is a novel smart city project that uses intrinsic processes to automate microservices such as edge‐to‐fog or fog‐to‐cloud monitoring of complex real‐time activities. This article presents a dynamic cyber‐physical architecture that leverages iFog layers to map location‐based services (LBS) on a spine‐leaf datacenter clos topology. Individual edge clusters are connected to the edge‐fog layer, which communicates with iFog gateways for processing streams' requests. Use‐case application of artificial intelligence (AI) in vehicular ad‐hoc networks (VANETs) is introduced for data stream provisioning. In the validation study, a secure docker‐based iFog CPS experiment is carried out using traffic trace files from C++ modeller. iFog spine‐leaf architecture for fog‐computing and cloud‐computing are compared using two key metrics. For traffic workload utilization, the results show that 83.33% of the traffic workload is utilized at the Fog layer while 16.67% is consumed in the cloud layer. For latency profile, the results indicate that Fog and cloud streams had 20.31% and 77.69%, respectively. In terms of iFog VANET spine‐leaf congestion control, three distinct algorithms are studied, namely the proposed linear routing algorithm (LRA), LEACH, and collection tree protocol (CTP). In each case, the resource utilization for VANET gave 34.45%, 32.18%, and 33.37%, respectively. Latency response gave 11.76%, 82.35%, and 5.89%, respectively. Also, the throughput scenario offered 19.61%, 39.22%, and 41.17%, respectively. Consequently, the iFog scenario offers satisfactory LBS provisioning for VANETs clusters.
The use of nondirected donor organs in living donor liver transplantation: Perspectives and guidance
Authors: Fox Alyson N. , Liapakis AnnMarie , Batra Ramesh , Bittermann Therese , Emamaullee Juliet , Emre Sukru , Genyk Yuri , Han Hyosun , Jackson Whitney , Pomfret Elizabeth , Raza Muhammad , Rodriguez‐Davalos Manuel , Rubman Gold Susan , Samstein Benjamin , Shenoy Akhil , Taner Timucin , Roberts John P. ,   The North American Living Liver Donor Innovations Group (NALLDIG)
Published: December 2021

Abstract
Interest in anonymous nondirected living organ donation is increasing in the United States and a small number of transplantation centers are accumulating an experience regarding nondirected donation in living donor liver transplantation. Herein, we review current transplant policy, discuss emerging data, draw parallels from nondirected kidney donation, and examine relevant considerations in nondirected living liver donation. We aim to provide a consensus guidance to ensure safe evaluation and selection of nondirected living liver donors and a schema for just allocation of nondirected grafts.
Enhancing the therapeutic efficacy of programmed death ligand 1 antibody for metastasized liver cancer by overcoming hepatic immunotolerance in mice
Authors: Xin Bing , Yang Meixiang , Wu Panyisha , Du Li , Deng Xingyu , Hui Enfu , Feng Gen‐Sheng 
Published: December 2021

Abstract

Background and Aims
Immunotherapy with programmed cell death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) blockade has shown low response rates in liver cancer patients, with the underlying mechanisms unclear. To decipher a specific impact of the liver microenvironment, we compared the effects of anti‐PD‐L1 antibody (αPD‐L1) blockade on the same tumor grown s.c. or in the liver.

Approach and Results
We generated s.c. tumors in mice by inoculating MC38 colorectal cancer (CRC) cells under the skin and metastatic liver tumors by portal vein or splenic injection of CRC cells. Tumor‐bearing mice were treated by i.p. injection of αPD‐L1, polyinosinic:polycytidylic acid (poly[I:C]), or both. αPD‐L1 monotherapy significantly suppressed s.c. tumor growth, but showed no effect on metastatic liver tumors. However, the combination of αPD‐L1 with poly(I:C), an innate immunity‐stimulating reagent, robustly inhibited tumor progression in liver. The combination therapy effectively down‐regulated myeloid‐derived suppressor cells (MDSCs), but up‐regulated ratios of M1/M2 macrophages, CD8/CD4, and CD8/regulatory T (Treg) cells infiltrated into liver tumors and whole liver. A group of long‐lasting T‐bet+Eomes−PD‐1− cytotoxic T cells was maintained in the combo‐treated liver, leading to resistance to tumor recurrence. Depleting macrophages or blocking type Ⅰ interferon signaling abrogated the synergistic antitumor effect of αPD‐L1 and poly(I:C), indicating a requirement of boosting innate immunity for optimized activation of cytotoxic T cells by PD‐1/PD‐L1 blockade.

Conclusions
The poor response of liver cancers to αPD‐L1 therapy is largely attributable to a unique hepatic immunotolerant microenvironment, independent of tumor origins or types. The success of a combinatorial immunotherapy relies on coordinated inhibition or activation of various innate and adaptive immune cell activities.
Sensitized Lanthanide Photoluminescence Based Sensors–a Review
Authors: Afzal Saima , Maitra Uday 
Published: December 2021

AbstractPhotoluminescent supramolecular systems such as hydrogels and metal‐organic frameworks (MOFs) can be useful for applications in many areas. In aqueous media, lanthanides exhibit luminescence by sensitization through covalently linked chromophores (antenna effect), making them valuable for sensing and imaging applications. Fluorescent sensing by sensitized lanthanide emission in gels and MOFs provides a simple and rapid detection of analytes with high sensitivity and selectivity. This review presents the gradual evolution and the intriguing conceptualization of sensitized luminescence of lanthanides spanning the sensing of biomolecules, drugs, small organic molecules and enzymes employing hydrogels or MOFs as the sensing platform.