bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Cancer Immunotherapy through a Simvastatin‐Loaded Colloidal Dispersion System for the Generation of Sustained Antitumor Immunity
Authors: Kim Seong A , Nam Gi‐hoon , Bae Young Rang , Jha Saurav Kumar , Kim Seohyun , Choi Yoonjeong , Lee Yeji , Kwon Minsu , Jeong Cheolhyun , Byun Youngro , Park Jin Woo , Kim In‐San
Published: March 2021

Statins exhibit anticancer pleiotropic effects, such as the induction tumor‐specific apoptosis and the promotion antitumor immunity. However, due to low bioavailability, high doses are required to trigger such antitumor effects. In this study, an oral delivery system to improve bioavailability of simvastatin (SIMVA) is prepared and its application in combination with an oral anticancer formulation is investigated. A colloidal dispersion (CD) of SIMVA is prepared using Nα‐deoxycholyl‐l‐lysyl‐methylester (DL) to enhance a solubility and permeation (SIMVA/DL‐CD). Preparation of SIMVA/DL‐CD markedly increases the solubility and in vitro artificial membrane permeability of SIMVA by 291‐ and 4.68‐fold, respectively, compared to SIMVA in 5% dimethyl sulfoxide. The oral absorption of SIMVA/DL‐CD (20 mg kg−1 SIMVA) is significantly enhanced and its oral bioavailability is tenfold higher compared to that of free SIMVA. An in vivo study in CT26 tumor‐bearing mice receiving SIMVA/DL‐CD reveals substantial tumor growth suppression through upregulated anticancer immunity. In particular, the combination of oral SIMVA/DL‐CD and oxaliplatin powder formulation elicits considerable tumor‐suppressive effects and CD8+ T cell immunity. Furthermore, this combination therapy sensitizes antiprogramed cell death protein‐1 monoclonal antibody‐resistant tumors to checkpoint blockade. The current findings highlight the therapeutic potential of oral SIMVA/DL‐CD as an effective anticancer immunotherapy.
The Signature Features of COVID‐19 Pandemic in a Hybrid Mathematical Model—Implications for Optimal Work–School Lockdown Policy
Authors: Lazebnik Teddy , Bunimovich‐Mendrazitsky Svetlana
Published: March 2021

The new COVID‐19 pandemic has challenged policymakers on key issues. Most countries have adopted “lockdown” policies to reduce the spatial spread of COVID‐19, but they have damaged the economic and moral fabric of society. Mathematical modeling in non‐pharmaceutical intervention policy management has proven to be a major weapon in this fight due to the lack of an effective COVID‐19 vaccine. A new hybrid model for COVID‐19 dynamics using both an age‐structured mathematical model based on the SIRD model and spatio‐temporal model in silico is presented, analyzing the data of COVID‐19 in Israel. Using the hybrid model, a method for estimating the reproduction number of an epidemic in real‐time from the data of daily notification of cases is introduced. The results of the proposed model are confirmed by the Israeli Lockdown experience with a mean square error of 0.205 over 2 weeks. The use of mathematical models promises to reduce the uncertainty in the choice of “Lockdown” policies. The unique use of contact details from 2 classes (children and adults), the interaction of populations depending on the time of day, and several physical locations, allow a new look at the differential dynamics of the spread and control of infection.
How to Reduce Charge Recombination in Organic Solar Cells: There are Still Lessons to Learn from P3HT:PCBM
Authors: Wilken Sebastian , Scheunemann Dorothea , Dahlström Staffan , Nyman Mathias , Parisi Jürgen , Österbacka Ronald
Published: March 2021

Suppressing charge recombination is key for organic solar cells to become commercial reality. However, there is still no conclusive picture of how recombination losses are influenced by the complex nanoscale morphology. Here, new insight is provided by revisiting the P3HT:PCBM blend, which is still one of the best performers regarding reduced recombination. By changing small details in the annealing procedure, two model morphologies are prepared that vary in phase separation, molecular order, and phase purity, as revealed by electron tomography and optical spectroscopy. Both systems behave very similarly with respect to charge generation and transport, but differ significantly in bimolecular recombination. Only the system containing P3HT aggregates of high crystalline quality and purity is found to achieve exceptionally low recombination rates. The high‐quality aggregates support charge delocalization, which assists the re‐dissociation of interfacial charge‐transfer states formed upon the encounter of free carriers. For devices with the optimized morphology, an exceptional long hole diffusion length is found, which allows them to work as Shockley‐type solar cells even in thick junctions of 300 nm. In contrast, the encounter rate and the size of the phase‐separated domains appear to be less important.
Winter cover crop management in the production of organic flue‐cured tobacco
Authors: Hahn Samuel. L. , Woodley Alex. L. , Vann Matthew. C.
Published: March 2021

Legume cover crops are not traditionally used in tobacco (Nicotiana tabacumL.) production due to concerns related to unpredictability of N supply and extended mineralization affecting quality of cured tobacco leaf. This study was conducted to determine if cover cropping with legumes could mitigate organic N fertilizer investment in tobacco without compromising yield, value, or quality. In 2018 and 2019, three winter cover crops: hairy vetch (Vicia villosaRoth) (HV); Austrian winter pea (Pisum sativumvar.arvenseL.) (AWP); and crimson clover (Trifolium incarnatumL.) (CC), were compared to a no‐cover crop control with typical organic N management in Rocky Mount and Kinston, NC. This study found no significant negative effects (α = .05) from legume cover cropping on yield or value of tobacco. In addition, AWP and HV increased yields between 13 and 37% compared to the no‐cover control. Value (US$ ha−1) did not differ from the control in 2018 or 2019 at any location, except at Kinston, where HV increased value 44% in 2019. In‐season soil samples suggest that HV provided N to tobacco up to flowering, however this did not negatively impact quality, yield, or value. Our research did not support grower concerns of prolonged N availability and found evidence that legume cover crops may allow for partial reduction in applied N without compromising the value of the product.
Solvent‐Free Ruthenium‐Catalyzed Direct Coupling of Phosphines and Aryl Chlorides via C−H Activation: An Efficient and Straight Access to Aryl‐Substituted Biarylphosphines
Authors: Zhang Ni‐Juan , Ma Wen‐Tao , Li Jia‐Wei , Liu Yue‐Jin , Zeng Ming‐Hua
Published: March 2021

An efficient and straightforward synthesis of aryl‐substituted biarylphosphines via unprotected amino acid‐accelerated ruthenium‐catalyzed P‐directed ortho‐C−H arylation reaction is described. This protocol utilized commercial and inexpensive (hetero)aryl chlorides as efficient arylating reagents under solvent‐free reaction conditions. Notably, diverse aryl bromides were also effective for this transformation. With the protocol, a wide variety of mono‐arylated biarylphosphines were obtained in moderate to high yields and excellent selectivity. Moreover, the aryl‐substituted phosphine exhibited higher catalytic performance than its precursor and other substituted phosphines in palladium‐catalyzed Suzuki coupling.
Fluctuating asymmetry, a marker of poor growth quality, is associated with adult male metabolic rate
Authors: Longman Daniel P. , Oyama Sakura , Cracknell James , Thompson Nathan , Gordon Dan , Stock Jay T. , Wells Jonathan C. K.
Published: March 2021

Objectives

Life history theory, a branch of evolutionary theory, predicts the existence of trade‐offs in energetic allocation between competing physiological functions. The core metabolic cost of self‐maintenance, measured by resting metabolic rate (RMR), represents a large component of human daily energy expenditure. Despite strong selective pressures for energetic frugality and high observed interindividual variation in RMR, the link between RMR and energetic allocation to life‐history traits remains understudied in humans.

Materials

In a sample of 105 (m = 57, f = 48), we investigated the relationship between adult RMR and investment in growth quality, as measured by fluctuating asymmetry (FA).

Results

Measurement of RMR and FA in university rowers revealed a significant positive correlation amongst males (n= 57,r= 0.344,p= 0.005, 1‐tailed; standardized 95% CI, 0.090 to 0.598). Convincing evidence for a correlation among females was not found (n= 48,r= 0.142,p= 0.169, 1‐tailed, standardized 95% CI, −0.152 to 0.435).

Discussion

The data suggest that low‐quality asymmetrical growth is associated with later‐life metabolic inefficiencies in males. Energetic investment in processes (likely concerning the stress‐response) unrelated to growth during childhood may thereby trade‐off against adult metabolic efficiency. We suggest that the presence of a relationship between RMR and FA in males but not females may be explained by the additional metabolic strain associated with larger body size and increased male muscularity, which may amplify the inefficiencies arising from low‐quality growth.
Usefulness of intraoperative frozen section for diagnosing acute invasive fungal rhinosinusitis: A systematic review and meta‐analysis
Authors: Kim Do Hyun , Kim Sung Won , Hwang Se Hwan
Published: March 2021

Background

The accuracy of diagnoses of acute invasive fungal rhinosinusitis (AIFRS) based on frozen sections has been questioned.

Methods

PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, SCOPUS, and Google Scholar were used for data sources. True‐positive, true‐negative, false‐positive, and false‐negative data were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) Tool.

Results

Nine prospective and retrospective studies were included. The diagnostic odds ratio of intraoperative frozen section in AIFRS was 124.4717 (95% confidence interval [CI], 75.5168–205.1623). The area under the summary receiver operating characteristic curve was 0.906. The sensitivity, specificity, and positive predictive value were 0.8337 (95% CI, 0.7962–0.8655), 0.9858 (95% CI, 0.9330–0.9971), and 0.9822 (95% CI, 0.8905–0.9973), respectively. The correlation between sensitivity and the false‐positive rate was 0.437, indicating a lack of heterogeneity. In subgroup analysis, the “per patient” subgroup tended to show higher diagnostic accuracy than the “per specimen” subgroup. Regarding fungal species, the frozen biopsy of aspergillus showed higher sensitivity than that of mucor (0.8103 vs. 0.7544).

Conclusion

Positive frozen sections are reliable and facilitate early intervention in AIFRS. Collecting multiple specimens during surgery will decrease the rate of false‐negative results.
Photochemical Probe Identification of a Small‐Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT)**
Authors: Lanyon‐Hogg Thomas , Ritzefeld Markus , Zhang Leran , Andrei Sebastian A. , Pogranyi Balazs , Mondal Milon , Sefer Lea , Johnston Callum D. , Coupland Claire E. , Greenfield Jake L. , Newington Joshua , Fuchter Matthew J. , Magee Anthony I. , Siebold Christian , Tate Edward W.
Published: March 2021

The mammalian membrane‐bound O‐acyltransferase (MBOAT) superfamily is involved in biological processes including growth, development and appetite sensing. MBOATs are attractive drug targets in cancer and obesity; however, information on the binding site and molecular mechanisms underlying small‐molecule inhibition is elusive. This study reports rational development of a photochemical probe to interrogate a novel small‐molecule inhibitor binding site in the human MBOAT Hedgehog acyltransferase (HHAT). Structure‐activity relationship investigation identified single enantiomer IMP‐1575, the most potent HHAT inhibitor reported to‐date, and guided design of photocrosslinking probes that maintained HHAT‐inhibitory potency. Photocrosslinking and proteomic sequencing of HHAT delivered identification of the first small‐molecule binding site in a mammalian MBOAT. Topology and homology data suggested a potential mechanism for HHAT inhibition which was confirmed by kinetic analysis. Our results provide an optimal HHAT tool inhibitor IMP‐1575 (Ki=38 nM) and a strategy for mapping small molecule interaction sites in MBOATs.
A Cavity‐Tailored Metal‐Organic Cage Entraps Gases Selectively in Solution and the Amorphous Solid State
Authors: Zhu Jun‐Long , Zhang Dawei , Ronson Tanya K. , Wang Wenjing , Xu Lin , Yang Hai‐Bo , Nitschke Jonathan R.
Published: March 2021

Here we report the subcomponent self‐assembly of a truxene‐faced Zn4L4tetrahedron, which is capable of binding the smallest hydrocarbons in solution. By deliberately incorporating inward‐facing ethyl groups on the truxene faces, the resulting partially‐filled cage cavity was tailored to encapsulate methane, ethane, and ethene via van der Waals interactions at atmospheric pressure in acetonitrile, and also in the amorphous solid state. Interestingly, gas capture showed divergent selectivities in solution and the amorphous solid state. The selective binding may prove useful in designing new processes for the purification of methane and ethane as feedstocks for chemical synthesis.
Biosynthesis and Mechanism of Action of the Cell Wall Targeting Antibiotic Hypeptin
Authors: Wirtz Daniel A. , Ludwig Kevin C. , Arts Melina , Marx Carina E. , Krannich Sebastian , Barac Paul , Kehraus Stefan , Josten Michaele , Henrichfreise Beate , Müller Anna , König Gabriele M. , Peoples Aaron J. , Nitti Anthony , Spoering Amy L. , Ling Losee L. , Lewis Kim , Crüsemann Max , Schneider Tanja
Published: March 2021

Hypeptin is a cyclodepsipeptide antibiotic produced by Lysobacter sp. K5869, isolated from an environmental sample by the iChip technology, dedicated to the cultivation of previously uncultured microorganisms. Hypeptin shares structural features with teixobactin and exhibits potent activity against a broad spectrum of gram‐positive pathogens. Using comprehensive in vivo and in vitro analyses, we show that hypeptin blocks bacterial cell wall biosynthesis by binding to multiple undecaprenyl pyrophosphate‐containing biosynthesis intermediates, forming a stoichiometric 2:1 complex. Resistance to hypeptin did not readily develop in vitro. Analysis of the hypeptin biosynthetic gene cluster (BGC) supported a model for the synthesis of the octapeptide. Within the BGC, two hydroxylases were identified and characterized, responsible for the stereoselective β‐hydroxylation of four building blocks when bound to peptidyl carrier proteins. In vitro hydroxylation assays corroborate the biosynthetic hypothesis and lead to the proposal of a refined structure for hypeptin.
Asymmetric Core–Shell Gold Nanoparticles and Controllable Assemblies for SERS Ratiometric Detection of MicroRNA
Authors: Zhu Rong , Feng Hongjuan , Li Qingqing , Su Lichao , Fu Qinrui , Li Juan , Song Jibin , Yang Huanghao
Published: March 2021

Janus nanogap gold nanoparticles (JAuNNPs) with varying proportions of Au shell coverage of (ca. 100/75/50/25 %) are presented. The internal nanogap between the partial Au shell and core caused asymmetric optical behavior; tunability depends on the degree of Au shell coverage and structural asymmetry. The shell‐to‐shell or core‐to‐core JAuNNDs(50 %) were self‐assembled from amphiphilic JAuNNPs(50 %) by tuning the hydrophilic and hydrophobic polymer brushes on the Au core or shell. The positions of electromagnetic field enhancement of JAuNNDs varied with geometrical configurations because of hybridized plasmonic coupling effects. Furthermore, DNA linkers were utilized to form JAuNND12(50 %). By combining with Raman molecules, ratiometric SERS signals could be generated, enabling JAuNND12(50 %) to image the distribution of miR‐21 in living cells and tumors. Asymmetric JAuNNPs allowed facile conjugation of various linkage molecules to fabricate dimeric nanostructures.
Rekombinante Spinnenseidengele aus wässrig‐organischen Mischphasen als Wirkstoffdepots
Authors: Neubauer Vanessa J. , Trossmann Vanessa T. , Jacobi Sofia , Döbl Annika , Scheibel Thomas
Published: March 2021

Hydrogele finden weitreichend Anwendung in der Biomedizin, wo sie nicht nur als Material in der Biofabrikation, sondern u. a. auch als Wirkstoffdepots verwendet werden. Die Möglichkeiten, wasserunlösliche Wirkstoffe in Hydrogelen zu formulieren, sind jedoch begrenzt. In dieser Studie konnten rekombinante Spinnenseidenproteine durch ein neuartiges Herstellungsverfahren in wässrig‐organischen Mischphasen zu Gelen selbstassemblieren. Deren Eigenschaften konnten dabei durch die Wahl der Lösungsmittel kontrolliert werden. Die Gegenwart einer organischen Phase erlaubte das Einbringen hydrophober Wirkstoffe, was exemplarisch anhand von 6‐Mercaptopurin gezeigt wurde. Die entwickelten Gele zeigten scherverdünnende Eigenschaften und konnten injiziert (zum Beispiel für Anwendungen als Wirkstoffdepot) und sogar 3D‐verdruckt werden, um Gerüste für die Geweberegeneration herzustellen. Mithilfe dieser neuen Herstellungsroute können nun wasserunlösliche Wirkstoffe in Spinnenseidendepots formuliert und damit gängige pharmazeutische Löslichkeitsgrenzen überwunden werden.
Ligand Controls the Activity of Light‐Driven Water Oxidation Catalyzed by Nickel(II) Porphyrin Complexes in Neutral Homogeneous Aqueous Solutions
Authors: Liu Chengyu , van den Bos Daan , den Hartog Barthold , van der Meij Dennis , Ramakrishnan Ashok , Bonnet Sylvestre
Published: March 2021

Finding photostable, first‐row transition metal‐based molecular systems for photocatalytic water oxidation is a step towards sustainable solar fuel production. Herein, we discovered that nickel(II) hydrophilic porphyrins are molecular catalysts for photocatalytic water oxidation in neutral to acidic aqueous solutions using [Ru(bpy)3]2+ as photosensitizer and [S2O8]2− as sacrificial electron acceptor. Electron‐poorer Ni‐porphyrins bearing 8 fluorine or 4 methylpyridinium substituents as electron‐poorer porphyrins afforded 6‐fold higher turnover frequencies (TOFs; ca. 0.65 min−1) than electron‐richer analogues. However, the electron‐poorest Ni‐porphyrin bearing 16 fluorine substituents was photocatalytically inactive under such conditions, because the potential at which catalytic O2 evolution starts was too high (+1.23 V vs. NHE) to be driven by the photochemically generated [Ru(bpy)3]3+. Critically, these Ni‐porphyrin catalysts showed excellent stability in photocatalytic conditions, as a second photocatalytic run replenished with a new dose of photosensitizer, afforded only 1–3 % less O2 than during the first photocatalytic run.
Covalent Bisfunctionalization of Two‐Dimensional Molybdenum Disulfide
Authors: Chen Xin , Bartlam Cian , Lloret Vicent , Moses Badlyan Narine , Wolff Stefan , Gillen Roland , Stimpel‐Lindner Tanja , Maultzsch Janina , Duesberg Georg S. , Knirsch Kathrin C. , Hirsch Andreas
Published: March 2021

Covalent functionalization of two‐dimensional molybdenum disulfide (2D MoS2) holds great promise in developing robust organic‐MoS2 hybrid structures. Herein, for the first time, we demonstrate an approach to building up a bisfunctionalized MoS2 hybrid structure through successively reacting activated MoS2 with alkyl iodide and aryl diazonium salts. This approach can be utilized to modify both colloidal and substrate supported MoS2 nanosheets. We have discovered that compared to the adducts formed through the reactions of MoS2 with diazonium salts, those formed through the reactions of MoS2 with alkyl iodides display higher reactivity towards further reactions with electrophiles. We are convinced that our systematic study on the formation and reactivity of covalently functionalized MoS2 hybrids will provide some practical guidance on multi‐angle tailoring of the properties of 2D MoS2 for various potential applications.
Versatile Direct Cyclization Constructs Spiro‐acridan Derivatives for Highly Efficient TADF emitters
Authors: Liu He , Liu Zhiwen , Li Ganggang , Huang Huaina , Zhou Changjiang , Wang Zhiming , Yang Chuluo
Published: March 2021

Spiro‐acridan (SpA) derivatives possess a great potential in preparing efficient thermally activated delayed fluorescent (TADF) emitters. However, the conventional synthetic routes are cost‐expensive and time‐consuming. The development of a simple procedure to synthesize SpAs is still in urgent pursuing appreciated by academic and industrial communities. In this contribution, we present a feasible acid‐catalyzed solvent‐free metal‐free cyclization between diarylamines and ketones to construct SpAs. The as‐constructed moieties provide a wide possibility to assemble efficient TADF emitters. As an example, D2T‐TR with high photoluminescent quantum yield and proper TADF character is applied in organic light emitting diodes (OLEDs) which achieves a maximum external quantum efficiency (EQE) of 27.1 %. This work shows us a bright inspiration on developing excellent organic optoelectronic materials and an effective tool to realize it.
Self‐doped sulfonated polyaniline ultrafiltration membranes with enhanced chlorine resistance and antifouling properties
Authors: Alhweij Hassan , Amura Ida , Wenk Jannis , Emanuelsson Emma Anna Carolina , Shahid Salman
Published: March 2021

Membranes heavily rely on chlorination to diminish (bio)fouling, but chlorination can also lead to membrane degradation. We developed sulfonated polyaniline (S‐PANI) ultrafiltration (UF) membranes with improved chlorine resistance and intrinsic antifouling properties. The S‐PANI membranes were synthesized through Non‐solvent Induced Phase Separation (NIPS). Membrane performance was evaluated under harsh chlorine conditions (250 ppm sodium hypochlorite for 3 days under different pH conditions). The S‐PANI membranes showed improved chlorine resistance including a stable performance without changes in model foulant BSA rejection. In contrast, PANI membranes suffered critical structural damage with complete leakage and commercial PES membranes showed a 76% increase in pure water flux and a noticeable change in BSA rejection. Small changes in S‐PANI membrane performance could be linked to membrane structural changes with pH, as confirmed by SEM, IR spectroscopy, and contact angle measurements. Additionally, the S‐PANI membranes showed better antifouling properties with a high flux recovery ratio in comparison to PANI membranes using alginic acid, humic acid, and BSA model foulants. Chemical cleaning by sodium hypochlorite re‐instated the transport properties to its initial condition. Overall, the developed S‐PANI membranes have a high chlorine tolerance and enhanced antifouling properties making them promising for a range of UF membrane applications.
Photoactive mussels inspired polymer coatings: Preparation and antibacterial activity
Authors: Bryaskova Rayna , Philipova Nikoleta , Georgiev Nikolay , Lalov Ivo , Bojinov Vladimir , Detrembleur Christophe
Published: March 2021

In this article we report on the facile preparation of photoactive antibacterial mussel inspired polymer coatings deposited on a stainless steel (SS) substrate from water based precursors. The coating is prepared by the sequential deposition of aqueous based solutions of an anchoring layer based on bio‐inspired glue, a cationic polymer bearing pendent catechols, a nanogel decorated by ortho‐quinones and a photosensitizer of the aminoacridine type. This latter is grafted to the coating by reaction of its amino group with the o‐quinone of the deposited nanogel. The deposition of all layers is followed in‐line by Quartz crystal microbalance coupled with dissipation (QCM‐D) and AFM shows that the thin polymer film repeated the roughness of the SS substrate. The prepared coatings show good mechanical properties applying nanoindentation techniques. The established antibacterial activity of the prepared photoactive polymer coatings on SS against Gram‐negative E. coli strain demonstrate their potential as a power tool for medical applications.
Harnessing the potential for otolith microchemistry to foster the conservation of Amazonian fishes
Authors: Hermann Theodore W. , Duponchelle Fabrice , Castello Leandro , Limburg Karin E. , Pereira Luciana A. , Hauser Marília
Published: March 2021

Freshwater environments host roughly half of the world’s fish diversity, much of which is concentrated in large, tropical river systems such as the Amazon. Fishes are critical to ecosystem functioning in the Amazon River basin but face increasing human threats. The basic biology of these species, and particularly migratory behaviour, remains poorly studied, in part owing to the difficulty associated with conducting tagging studies in remote tropical regions.

Otolith microchemistry can circumvent logistical issues and is an increasingly important tool for studying fish life histories. However, this approach is still new in the Amazon, and its potential and limitations to inform fish conservation strategies remain unclear.

Here, otolith microchemistry studies in the Amazon are reviewed, highlighting current possibilities, and several key factors that limit its use as a conservation tool in the Amazon are discussed. These include the dearth of spatiotemporal elemental data, poor understanding of environment–fish–otolith pathways, and insufficient funding, facilities, and equipment.

A research initiative is proposed to harness the potential of this technique to support conservation in the Amazon. Key aspects of the proposal include recommendations for internal and external funding, which are critical to acquiring and maintaining technical staff, cutting‐edge equipment, and facilities, as well as fostering regular scientific meetings and working groups. Meetings can facilitate a systematic approach to investigating environment–otolith pathways, broadening the chemical baseline for most Amazonian tributaries, and exploring potential valuable elements.

These outcomes are urgently needed to conserve biodiversity and ecosystem functioning in the Amazon, especially given threats such as widespread hydroelectric damming. The initiative proposed here could make otolith microchemistry an important, cost‐effective tool to inform and foster conservation in the Amazon, and act as a template for other imperilled tropical river basins, such as the Mekong and the Congo.
Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer
Authors: Hu Qingjiang , Nonaka Kentaro , Wakiyama Hiroaki , Miyashita Yu , Fujimoto Yoshiaki , Jogo Tomoko , Hokonohara Kentaro , Nakanishi Ryota , Hisamatsu Yuichi , Ando Koji , Kimura Yasue , Masuda Takaaki , Oki Eiji , Mimori Koshi , Oda Yoshinao , Mori Masaki
Published: March 2021

Background

A simple measure of immune cytolytic activity (CYT) base on mRNA expression levels of two genes, GZMA and PRF1, was recently reported. Here, we aimed to evaluate the CYT score's potential as a measure of antitumor immunity and predictor of clinical outcome in gastric cancer (GC) patients.

Materials and Methods

We evaluated the correlations between tumor‐infiltrating immune cells and the CYT score in 238 GC samples from The Cancer Genome Atlas (TCGA). Next, we investigated CYT score associations with molecular subtypes, somatic mutation load, and immune checkpoint molecules in GC samples from TCGA and Asian Cancer Research Group (ACRG). Moreover, we evaluated the clinical significance of the CYT score calculated by reverse transcription (RT)‐quantitative PCR (qPCR) data in 123 GC samples and the association of the CYT score with the response to anti‐PD‐1 therapy in 7 GC samples from Kyushu University Hospital.

Results

The CYT score positively correlated with the proportions of tumor‐infiltrating CD8+ T cells and macrophages and negatively correlated with the proportion of regulatory T cells in GC tissues. A high CYT score was associated with common immune checkpoint molecules, a high mutation, the Epstein–Barr virus subtype, and the microsatellite instability subtype in GC. Moreover, a low CYT score was a poor prognosis factor in patients with GC. Finally, the CYT score was higher in a responder to anti‐PD‐1 therapy compared to nonresponders.

Conclusion

The CYT score reflects antitumor immunity and predicts clinical outcome in GC patients.
When the context rows against. Voicing parents of transgender children and teenagers in Italy: A qualitative study
Authors: Lorusso Maric , Albanesi Cinzia
Published: March 2021

Having a supportive family with a non‐binary vision of gender differences is a protective factor for transgender and gender‐variant (TGV) children and teenagers; however, the parents of TGV children find themselves alone when dealing with doubts and challenges, and this may hamper their capacity to provide support to their children. This study aimed to map/describe the needs of the parents of TGV children in Italy, their relationship with the health care and educational systems, and how they cope with the challenges of the context they live in. We used a qualitative approach based on thematic interviews with respondent validation, involving 13 parents of TGV children and teenagers. Our participants reported difficulties in accessing information, obstacles in finding adequate support from mental health professionals and in interactions with educational professionals, recognizing that these challenges are strongly embedded in the Italian socio‐cultural context and its widespread homobitransphobic culture. Nevertheless, they are personally committed to changing this situation through advocacy and affirmative action for their children, engaged in knowledge production on gender variance, and with parent support groups. Please refer to the Supplementary Material section to find this article'sCommunity and Social Impact Statement.
Beyond the Active Site. Cp*ZrMe3/Sulfated Alumina‐Catalyzed Olefin Polymerization Tacticity via Catalyst⋅⋅⋅Surface Ion‐Pairing
Authors: Zhang Jialong , Mason Alexander H. , Wang Yang , Motta Alessandro , Kobayashi Takeshi , Pruski Marek , Gao Yanshan , Marks Tobin J.
Published: March 2021

Surface‐bound organometallic molecules have recently enabled the development of single‐site heterogeneous catalysts, advancing the atomic scale understanding and diversity of heterogeneous catalysis. Here we report that supporting Cp*ZrMe3 (Cat1) on acidic sulfated‐alumina (AlS) affords the surface catalyst Cat1/AlS, which was characterized by multi‐dimensional solid‐state NMR spectroscopies, and is active in ethylene homo‐ and copolymerizations, as well as propylene and 1‐hexene homopolymerizations. In contrast to propylene (or 1‐hexene) polymerization by homogeneous Cp*ZrMe2+ B(C6F5)4− which yields atactic polyolefins, Cat1/AlS promotes remarkable isotacticity with mmmm >95 %. Complementary DFT analysis argues that the restrictive local Cat1/AlS C1‐symmetry favors activation and enchainment at the propylene re enantioface, promoting isotactic polymerization via a “back‐skip‐like” mechanism.
Double‐Network Heparin Dynamic Hydrogels: Dynagels as Anti‐bacterial 3D Cell Culture Scaffolds
Authors: Cui Han , Wang Qimeng , Zhang Ye , Barboiu Mihail , Zhang Yan , Chen Jinghua
Published: March 2021

Double cross‐linked dynamic hydrogels, dynagels, have been prepared through reversible imine bonds and supramolecular interactions, which showed good pH responsiveness, injectability, self‐healing property and biocompatibility. With the further encapsulation of heparin, the obtained hydrogels exhibited good anti‐bacterial activity and promotion effects for 3D cell culture.
Mapping C−H⋅⋅⋅M Interactions in Confined Spaces: (α‐ICyDMe)Au, Ag, Cu Complexes Reveal “Contra‐electrostatic H Bonds” Masquerading as Anagostic Interactions**
Authors: dos Passos Gomes Gabriel , Xu Guangcan , Zhu Xiaolei , Chamoreau Lise‐Marie , Zhang Yongmin , Bistri‐Aslanoff Olivia , Roland Sylvain , Alabugin Igor V. , Sollogoub Matthieu
Published: March 2021

What happens when a C−H bond is forced to interact with unpaired pairs of electrons at a positively charged metal? Such interactions can be considered as “contra‐electrostatic” H‐bonds, which combine the familiar orbital interaction pattern characteristic for the covalent contribution to the conventional H‐bonding with an unusual contra‐electrostatic component. While electrostatics is strongly stabilizing component in the conventional C−H⋅⋅⋅X bonds where X is an electronegative main group element, it is destabilizing in the C−H⋅⋅⋅M contacts when M is Au(I), Ag(I), or Cu(I) of NHC−M−Cl systems. Such remarkable C−H⋅⋅⋅M interaction became experimentally accessible within (α‐ICyDMe)MCl, NHC‐Metal complexes embedded into cyclodextrins. Computational analysis of the model systems suggests that the overall interaction energies are relatively insensitive to moderate variations in the directionality of interaction between a C−H bond and the metal center, indicating stereoelectronic promiscuity of fully filled set of d‐orbitals. A combination of experimental and computational data demonstrates that metal encapsulation inside the cyclodextrin cavity forces the C−H bond to point toward the metal, and reveals a still attractive “contra‐electrostatic” H‐bonding interaction.
Acetylenic Replacement of Albicidin's Methacrylamide Residue Circumvents Detrimental E/Z Photoisomerization and Preserves Antibacterial Activity
Authors: Behroz Iraj , Kleebauer Leonardo , Hommernick Kay , Seidel Maria , Grätz Stefan , Mainz Andi , Weston John B. , Süssmuth Roderich D.
Published: March 2021

The natural product albicidin is a highly potent inhibitor of bacterial DNA gyrase. Its outstanding activity, particularly against Gram‐negative pathogens, qualifies it as a promising lead structure in the search for new antibacterial drugs. However, as we show here, the N‐terminal cinnamoyl moiety of albicidin is susceptible to photochemical E/Z isomerization. Moreover, the newly formed Z isomer exhibits significantly reduced antibacterial activity, which hampers the development and biological evaluation of albicidin and potent derivatives thereof. Hence, we synthesized 13 different variants of albicidin in which the vulnerable para‐coumaric acid moiety was replaced; this yielded photostable analogues. Biological activity assays revealed that diaryl alkyne analogues exhibited virtually undiminished antibacterial efficacy. This promising scaffold will therefore serve as a blueprint for the design of a potent albicidin‐based drug.
Acetophenyl‐thienyl‐aniline‐Linked Nucleotide for Construction of Solvatochromic Fluorescence Light‐Up DNA Probes Sensing Protein‐DNA Interactions
Authors: Güixens‐Gallardo Pedro , Hocek Michal
Published: March 2021

The synthesis of 2′‐deoxycytidine and its 5′‐O‐triphosphate bearing solvatochromic acetophenyl‐thienyl‐aniline fluorophore was developed using the Sonogashira cross‐coupling reaction as the key step. The triphosphate was used for polymerase synthesis of labelled DNA. The labelled nucleotide or DNA exerted weak red fluorescence when excited at 405 nm, but a significant colour change (to yellow or green) and light‐up (up to 20 times) was observed when the DNA probes interacted with proteins or lipids.
Chalcogen Bonding Ion‐Pair Cryptand Host Discrimination of Potassium Halide Salts
Authors: Docker Andrew , Bunchuay Thanthapatra , Ahrens Michael , Martinez‐Martinez Antonio J. , Beer Paul D.
Published: March 2021

A series of chalcogen, halogen and hydrogen bonding heteroditopic macrobicyclic cryptands are reported and their potassium halide ion‐pair recognition properties investigated. Saliently, the co‐bound potassium cation was determined to be crucial in switching on the bromide and iodide recognition properties of the respective cryptand receptor. Importantly, the nature of the sigma‐hole mediated interaction employed in the anion recognition component is demonstrated to significantly augment the ion‐pair binding behaviour, markedly so for the halogen bonding analogue. Most notably the incorporation of a chelating chalcogen bonding donor motif significantly improves the selectivity towards KBr over KI, relative to halogen and hydrogen bonding analogues.
Catalytic Reductive Cross‐Coupling between Aromatic Aldehydes and Arylnitriles
Authors: Mitsui Atsuhisa , Nagao Kazunori , Ohmiya Hirohisa
Published: March 2021

A reductive cross‐coupling reaction between aromatic aldehydes and arylnitriles using a copper catalyst and a silylboronate as a reductant is reported. This protocol represents an unprecedented approach to the chemoselective synthesis of α‐hydroxy ketones by electrophile–electrophile cross‐coupling.
Covalent 2D Patterning, Local Electronic Structure and Polarization Switching of Graphene at the Nanometer Level
Authors: Bao Lipiao , Zhao Baolin , Assebban Mhamed , Halik Marcus , Hauke Frank , Hirsch Andreas
Published: March 2021

A very facile and efficient protocol for the covalent patterning and properties tuning of graphene is reported. Highly reactive fluorine radicals were added to confined regions of graphene directed by laser writing on graphene coated with 1‐fluoro‐3,3‐dimethylbenziodoxole. This process allows for the realization of exquisite patterns on graphene with resolutions down to 200 nm. The degree of functionalization, ranging from the unfunctionalized graphene to extremely high functionalized graphene, can be precisely tuned by controlling the laser irradiation time. Subsequent substitution of the initially patterned fluorine atoms afforded an unprecedented graphene nanostructure bearing thiophene groups. This substitution led to a complete switch of both the electronic structure and the polarization within the patterned graphene regions. This approach paves the way towards the precise modulation of the structure and properties of nanostructured graphene.
High throughput can produce better decisions than high accuracy when phenotyping plant populations
Authors: Lane Holly M. , Murray Seth C.
Published: March 2021

Studies assessing phenotypes of plant populations traditionally place their primary focus on increasing measurement precision and improving accuracy. Phenotyping methods that use imaging, remote sensing, and spectroscopy, continue to increase throughput capacity, but information has been unavailable to assess the tradeoffs between increased throughput and any potential decreases in measurement accuracy. In this simulation study, we compare four levels of measurement accuracy across varying levels of throughput, and discuss how an increased error rate can be compensated for via increased throughput, if experimental resources are allocated appropriately. Under the tested scenarios of increased throughput, the correct values of genotypes were best estimated by increasing the number of environments. Genetic mapping studies should increase population size as well to see improvements over more accurate measurement methods. This simplistic simulation mimics many empirical findings and will be of interest to any researcher interested in assessing how high‐throughput phenotyping methods affect decision‐making in crop research programs.
Higher‐order inertial Alfvén wave dressed solitons, quasiperiodic structures, and chaos in plasmas
Authors: Mahmood Shahzad , Ur‐Rehman Hafeez , Ali Munazza Zulfiqar , Basit Abdul
Published: March 2021

The higher‐order, low‐amplitude inertial Alfvén wave (IAW) dressed soliton and chaos are investigated in a magnetized plasma. In the linear limit, the dispersion relation for propagation of IAWs in plasmas is also obtained in the presence of electron thermal effects and illustrated numerically. It is found that the electron inertial length plays an important role for wave dispersion effects and its phase speed is increased on including the electron temperature in the model. The reductive perturbation method is employed to obtain the first‐order IAW Korteweg–de Vries (KdV) soliton and second‐order dressed soliton solutions analytically, which gives electron density dip (or rarefactive) structure and moves with super Alfvénic speed in plasmas. The numerical illustrations of the KdV and dressed IAW solitons are also presented by using the laboratory and space plasma parameters given in the literature. Furthermore, a numerical study of quasi‐periodicity and chaotic behaviour of IAWs in the presence of external periodic force is also discussed in detail. The effects of plasma beta (which depends on plasma density, electron temperature, and magnetic field intensity) and obliqueness of the wave propagation on the formation of nonlinear Alfvénic wave structures have also been presented.
Traits explain invasion of alien plants into tropical rainforests
Authors: Junaedi Decky I. , Guillera‐Arroita Gurutzeta , Vesk Peter A. , McCarthy Michael A. , Burgman Mark A. , Catford Jane A.
Published: March 2021

1. The establishment of new botanic gardens in tropical regions highlights a need for weed risk assessment tools suitable for tropical ecosystems. The relevance of plant traits for invasion into tropical rainforests has not been well studied.

2. Working in and around four botanic gardens in Indonesia where 590 alien species have been planted, we estimated the effect of four plant traits, plus time since species introduction, on: (a) the naturalization probability and (b) abundance (density) of naturalized species in adjacent native tropical rainforests; and (c) the distance that naturalized alien plants have spread from the botanic gardens.

3. We found that specific leaf area (SLA) strongly differentiated 23 naturalized from 78 non‐naturalized alien species (randomly selected from 577 non‐naturalized species) in our study. These trends may indicate that aliens with high SLA, which had a higher probability of naturalization, benefit from at least two factors when establishing in tropical forests: high growth rates and occupation of forest gaps. Naturalized aliens had high SLA and tended to be short. However, plant height was not significantly related to species' naturalization probability when considered alongside other traits.

4. Alien species that were present in the gardens for over 30 years and those with small seeds also had higher probabilities of becoming naturalized, indicating that garden plants can invade the understorey of closed canopy tropical rainforests, especially when invading species are shade tolerant and have sufficient time to establish.

5. On average, alien species that werenotanimal dispersed spread 78 m further into the forests and were more likely to naturalize than animal‐dispersed species. We did not detect relationships between the measured traits and estimated density of naturalized aliens in the adjacent forests.

6.Synthesis: Traits were able to differentiate alien species from botanic gardens that naturalized in native forest from those that did not; this is promising for developing trait‐based risk assessment in the tropics. To limit the risk of invasion and spread into adjacent native forests, we suggest tropical botanic gardens avoid planting alien species with fast carbon capture strategies and those that are shade tolerant.
Gut microbial ecology of the Critically Endangered Fijian crested iguana (Brachylophus vitiensis): Effects of captivity status and host reintroduction on endogenous microbiomes
Authors: Eliades Samuel J. , Brown Joseph C. , Colston Timothy J. , Fisher Robert N. , Niukula Jone B. , Gray Kim , Vadada Jhabar , Rasalato Sia , Siler Cameron D.
Published: March 2021

Animals often exhibit distinct microbial communities when maintained in captivity as compared to when in the wild. Such differentiation may be significant in headstart and reintroduction programs where individuals spend some time in captivity before release into native habitats. Using 16S rRNA gene sequencing, we (i) assessed differences in gut microbial communities between captive and wild Fijian crested iguanas (Brachylophus vitiensis) and (ii) resampled gut microbiota in captive iguanas released onto a native island to monitor microbiome restructuring in the wild. We used both cloacal swabs and fecal samples to further increase our understanding of gut microbial ecology in this IUCN Critically Endangered species. We found significant differentiation in gut microbial community composition and structure between captive and wild iguanas in both sampling schemes. Approximately two months postrelease, microbial communities in cloacal samples from formerly captive iguanas closely resembled wild counterparts. Interestingly, microbial communities in fecal samples from these individuals remained significantly distinct from wild conspecifics. Our results indicate that captive upbringings can lead to differences in microbial assemblages in headstart iguanas as compared to wild individuals even after host reintroduction into native conditions. This investigation highlights the necessity of continuous monitoring of reintroduced animals in the wild to ensure successful acclimatization and release.
Mutualism promotes site selection in a large marine planktivore
Authors: Armstrong Asia O. , Armstrong Amelia J. , Bennett Michael B. , Richardson Anthony J. , Townsend Kathy A. , Everett Jason D. , Hays Graeme C. , Pederson Hugh , Dudgeon Christine L.
Published: March 2021

Mutualism is a form of symbiosis whereby both parties benefit from the relationship. An example is cleaning symbiosis, which has been observed in terrestrial and marine environments. The most recognized form of marine cleaning symbiosis is that of cleaner fishes and their clients.

Cleaner species set up cleaning stations on the reef, and other species seek out their services. However, it is not well understood how the presence of cleaning stations influence movements of large highly mobile species. We examined the role of cleaning stations as a driver of movement and habitat use in a mobile client species.

Here, we used a combination of passive acoustic telemetry and in‐water surveys to investigate cleaning station attendance by the reef manta ray Mobula alfredi. We employed a novel approach in the form of a fine‐scale acoustic receiver array set up around a known cleaning area and tagged 42 rays. Within the array, we mapped structural features, surveyed the distribution of cleaner wrasse, and observed the habitat use of the rays.

We found manta ray space use was significantly associated with blue‐streak cleaner wrasse Labroides dimidiatus distribution and hard coral substrate. Cleaning interactions dominated their habitat use at this site, taking precedence over other life history traits such as feeding and courtship.

This study has demonstrated that cleaning symbiosis is a driver for highly mobile, and otherwise pelagic, species to visit inshore reef environments. We suggest that targeted and long‐term use of specific cleaning stations reflects manta rays having a long‐term memory and cognitive map of some shallow reef environments where quality cleaning is provided. We hypothesize that animals prefer cleaning sites in proximity to productive foraging regions.