bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antimicrobial, Hemostatic, and Anti‐Adhesion Effects of a Peptide Hydrogel Constructed by the All‐d‐Enantiomer of Antimicrobial Peptide Jelleine‐1
Authors: Zhang Hanru , Wu Zhiyu , Zhou Jingjing , Wang Zhaopeng , Yang Changyan , Wang Panpan , Fareed Muhammad Subaan , He Yuhang , Su Jie , Cha Ruitao , Wang Kairong
Published: August 2023

Peptide hydrogels are believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and 3D printability. Most of the previously reported polypeptide hydrogels are composed of l‐peptides, while the hydrogels formed by self‐assembly of d‐peptides are rarely reported. Herein, a peptide hydrogel constructed by D‐J‐1, which is the all‐d‐enantiomer of antimicrobial peptide Jelleine‐1 (J‐1) is reported. Field emission scanning electron microscope (FE‐SEM) and rheologic study are performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti‐adhesion studies are carried out to evaluate its biofunction. The results show that D‐J‐1 hydrogel is formed by self‐assembly and cross‐linking driven by hydrogen bonding, hydrophobic interaction, and π–π stacking force of aromatic ring in the structure of D‐J‐1. It exhibits promising antimicrobial activity, hemostatic activity, and anti‐adhesion efficiency in a rat sidewall defect‐cecum abrasion model. In addition, it also exhibits good biocompatibility. Notably, D‐J‐1 hydrogel shows improved in vitro and in vivo stability when compared with its l‐enantiomer J‐1 hydrogel. Therefore, the present study will provide new insight into the application of d‐peptide hydrogel, and provides a new peptide hydrogel with antibacterial, hemostatic, and anti‐adhesion efficacy for clinical use.
Structural‐Activity Relationship‐Inspired the Discovery of Saturated Fatty Acids as Novel Colistin Enhancers
Authors: Cai Jinju , Shi Jingru , Chen Chen , He Mengping , Wang Zhiqiang , Liu Yuan
Published: August 2023

The emergence and prevalence of mobile colistin resistance gene mcr have dramatically compromised the clinical efficacy of colistin, a cyclopeptide antibiotic considered to be the last option for treating different‐to‐treat infections. The combination strategy provides a productive and cost‐effective strategy to expand the lifespan of existing antibiotics. Structural‐activity relationship analysis of polymyxins indicates that the fatty acyl chain plays an indispensable role in their antibacterial activity. Herein, it is revealed that three saturated fatty acids (SFAs), especially sodium caprate (SC), substantially potentiate the antibacterial activity of colistin against mcr‐positive bacteria. The combination of SFAs and colistin effectively inhibits biofilm formation and eliminates matured biofilms, and is capable of preventing the emergence and spread of mobile colistin resistance. Mechanistically, the addition of SFAs reduces lipopolysaccharide (LPS) modification by simultaneously promoting LPS biosynthesis and inhibiting the activity of MCR enzyme, enhance bacterial membrane damage, and impair the proton motive force‐dependent efflux pump, thereby boosting the action of colistin. In three animal models of infection by mcr‐positive pathogens, SC combined with colistin exhibit an excellent therapeutic effect. These findings indicate the therapeutic potential of SFAs as novel antibiotic adjuvants for the treatment of infections caused by multidrug‐resistant bacteria in combination with colistin.
Efficient N‐Type Organic Electrochemical Transistors and Field‐Effect Transistors Based on PNDI‐Copolymers Bearing Fluorinated Selenophene‐Vinylene‐Selenophenes
Authors: Kim Jongho , Ren Xinglong , Zhang Youcheng , Fazzi Daniele , Manikandan Suraj , Andreasen Jens Wenzel , Sun Xiuming , Ursel Sarah , Un Hio‐Ieng , Peralta Sébastien , Xiao Mingfei , Town James , Marathianos Arkadios , Roesner Stefan , Bui Thanh‐Tuan , Ludwigs Sabine , Sirringhaus Henning , Wang Suhao
Published: August 2023

n‐Type organic electrochemical transistors (OECTs) and organic field‐effect transistors (OFETs) are less developed than their p‐type counterparts. Herein, polynaphthalenediimide (PNDI)‐based copolymers bearing novel fluorinated selenophene‐vinylene‐selenophene (FSVS) units as efficient materials for both n‐type OECTs and n‐type OFETs are reported. The PNDI polymers with oligo(ethylene glycol) (EG7) side chains P(NDIEG7‐FSVS), affords a high µC* of > 0.2 F cm−1 V−1 s−1, outperforming the benchmark n‐type Pg4NDI‐T2 and Pg4NDI‐gT2 by two orders of magnitude. The deep‐lying LUMO of −4.63 eV endows P(NDIEG7‐FSVS) with an ultra‐low threshold voltage of 0.16 V. Moreover, the conjugated polymer with octyldodecyl (OD) side chains P(NDIOD‐FSVS) exhibits a surprisingly low energetic disorder with an Urbach energy of 36 meV and an ultra‐low activation energy of 39 meV, resulting in high electron mobility of up to 0.32 cm2 V−1 s−1 in n‐type OFETs. These results demonstrate the great potential for simultaneously achieving a lower LUMO and a tighter intermolecular packing for the next‐generation efficient n‐type organic electronics.
Progress in Manipulating Dynamic Surface Reconstruction via Anion Modulation for Electrocatalytic Water Oxidation
Authors: He Zexing , Ajmal Muhammad , Zhang Minghui , Liu Xiaokang , Huang Zhen‐Feng , Shi Chengxiang , Gao Ruijie , Pan Lun , Zhang Xiangwen , Zou Ji‐Jun
Published: August 2023

The development of efficient and economical electrocatalysts for oxygen evolution reaction (OER) is of paramount importance for the sustainable production of renewable fuels and energy storage systems; however, the sluggish OER kinetics involving multistep four proton‐coupled electron transfer hampers progress in these systems. Fortunately, surface reconstruction offers promising potential to improve OER catalyst design. Anion modulation plays a crucial role in controlling the extent of surface reconstruction and positively persuading the reconstructed species' performances. This review starts by providing a general explanation of how various types of anions can trigger dynamic surface reconstruction and create different combinations with pre‐catalysts. Next, the influences of anion modulation on manipulating the surface dynamic reconstruction process are discussed based on the in situ advanced characterization techniques. Furthermore, various effects of survived anionic groups in reconstructed species on water oxidation activity are further discussed. Finally, the challenges and prospects for the future development directions of anion modulation for redirecting dynamic surface reconstruction to construct highly efficient and practical catalysts for water oxidation are proposed.
Variation in ripe fruit volatiles across the tomato clade: An evolutionary framework for studying fruit scent diversity in a crop wild relative
Authors: Barnett Jacob R. , Tieman Denise M. , Caicedo Ana L.
Published: August 2023

Premise

The scents of volatile organic compounds (VOCs) are an important component of ripe fleshy fruit attractiveness, yet their variation across closely related wild species is poorly understood. Phylogenetic patterns in these compounds and their biosynthetic pathways offer insight into the evolutionary drivers of fruit diversity, including whether scent can communicate an honest signal of nutrient content to animal dispersers. We assessed ripe fruit VOC content across the tomato clade (Solanum sect. Lycopersicon), with implications for crop improvement since these compounds are key components of tomato flavor.

Methods

We analyzed ripe fruit volatiles from 13 species of wild tomato grown in a common garden. Interspecific variations in 66 compounds and their biosynthetic pathways were assessed in 32 accessions, and an accession‐level phylogeny was constructed to account for relatedness.

Results

Wild tomato species can be differentiated by their VOCs, with Solanum pennellii notably distinct. Phylogenetic conservatism exists to a limited extent. Major cladewide patterns corresponded to divergence of the five brightly colored‐fruited species from the nine green‐fruited species, particularly for nitrogen‐containing compounds (higher in colored‐fruited) and esters (higher in green‐fruited), the latter appearing to signal a sugar reward.

Conclusions

We established a framework for fruit scent evolution studies in a crop wild relative system, showing that each species in the tomato clade has a unique VOC profile. Differences between color groups align with fruit syndromes that could be driven by selection from frugivores. The evolution of colored fruits was accompanied by changes in biosynthetic pathways for esters and nitrogen‐containing compounds, volatiles important to tomato flavor.
Pregnancy‐related thromboembolism in women with sickle cell disease: An analysis of National Medicaid Data
Authors: Agarwal Shreya , Stanek Joseph R. , Vesely Sara K. , Creary Susan E. , Cronin Robert M. , Roe Andrea H. , O'Brien Sarah H.
Published: August 2023

Pregnancy and sickle cell disease (SCD) both individually carry a risk of thromboembolism (TE). Pregnancy in people with SCD may further enhance the prothrombotic effect of the underlying disease. The objectives of this study were to determine the rate and risk factors for arterial and venous thrombosis in pregnant people with SCD. Administrative claims data from the United States Centers for Medicare and Medicaid Service Analytic eXtract from 2006 to 2018 were used. The study population included people with SCD from the start of their first identified pregnancy until 1 year postpartum and a control cohort of pregnant people without SCD of similar age and race. Outcomes of interest were identified with ICD‐9 or 10 codes. Logistic regression analyses were used to analyze risk factors. We identified infant deliveries in 6388 unique people with SCD and 17 110 controls. A total of 720 venous thromboembolism (11.3%) and 335 arterial TE (5.2%) were observed in people with SCD compared to 202 (1.2%) and 95 (0.6%) in controls. People with SCD had an 8–11 times higher odds of TE compared to controls (p < .001). Within the SCD cohort, age, hemoglobin SS (HbSS) genotype, hypertension, and history of thrombosis were identified as independent risk factors for pregnancy‐related TE. Pregnancy‐specific factors (pre‐eclampsia, eclampsia, multigestational pregnancy) were not associated with TE. In conclusion, the risk of pregnancy‐related TE is considerably higher in people with SCD compared with controls without SCD. Hence, people with SCD, particularly those with multiple risk factors may be candidates for thromboprophylaxis during pregnancy and the postpartum period.
Migration and biological continuity in central Mexico during the Classic‐Epiclassic transition
Authors: Pacheco‐Fores Sofía I. , Stojanowski Christopher M. , Morehart Christopher T.
Published: August 2023

Objectives

The role of migration in the cultural development of central Mexico has long been debated. Archaeological models suggest that central Mexico likely experienced increased migration during the Epiclassic period (600–900 CE) and that migrants may have originated in northwestern Mexico. While previous biodistance analyses of Classic and Postclassic populations have come to similar conclusions, none have incorporated Epiclassic skeletal populations. This study uses multi‐scalar biodistance analyses to directly evaluate archaeological Epiclassic migration models within central Mexico.

Materials and Methods

This study uses finite mixture and relationship (R) matrix analyses of cervicometric tooth dimensions to reconstruct patterns of biological affinity among Classic and Epiclassic Mesoamerican populations (n = 333), including at the central Mexican Epiclassic shrine site of Non‐Grid 4 where the remains of at least 180 individuals were interred.

Results

Estimated inter‐site phenotypic distances demonstrate support for some degree of both biological continuity and extra‐local gene flow within central Mexican populations during the Classic‐Epiclassic transition. Furthermore, estimated phenotypic distances and finite mixture posterior probabilities indicate central Mexican Epiclassic populations were biologically diverse, originating from various source populations throughout Mesoamerica, including the Bajío region, the Malpaso Valley, and the Oaxaca Valley.

Discussion

Results suggest that emphasizing both local and extra‐local gene flow rather than population replacement may be more appropriate to understand central Mexican population structure during the Classic‐Epiclassic transition. Moreover, analyses support previous archaeological migration models positing that Epiclassic migrants into central Mexico originated in northwestern Mexico, but also find evidence of Epiclassic migrants originating from previously unanticipated locales like southern Mexico.
Coordination Tuning of Metal Porphyrins for Improved Oxygen Evolution Reaction
Authors: Lv Haoyuan , Zhang Xue‐Peng , Guo Kai , Han Jinxiu , Guo Hongbo , Lei Haitao , Li Xialiang , Zhang Wei , Apfel Ulf‐Peter , Cao Rui
Published: August 2023

The nucleophilic attack of water or hydroxide on metal‐oxo units forms an O−O bond in the oxygen evolution reaction (OER). Coordination tuning to improve this attack is intriguing but has been rarely realized. We herein report on improved OER catalysis by metal porphyrin 1‐M (M=Co, Fe) with a coordinatively unsaturated metal ion. We designed and synthesized 1‐M by sterically blocking one porphyrin side with a tethered tetraazacyclododecane unit. With this protection, the metal‐oxo species generated in OER can maintain an unoccupied trans axial site. Importantly, 1‐M displays a higher OER activity in alkaline solutions than analogues lacking such an axial protection by decreasing up to 150‐mV overpotential to achieve 10 mA/cm2 current density. Theoretical studies suggest that with an unoccupied trans axial site, the metal‐oxo unit becomes more positively charged and thus is more favoured for the hydroxide nucleophilic attack as compared to metal‐oxo units bearing trans axial ligands.
The Power of Action Plots: Unveiling Reaction Selectivity of Light‐Stabilized Dynamic Covalent Chemistry
Authors: Gauci Steven C. , Du Prez Filip E. , Holloway Joshua O. , Houck Hannes A. , Barner‐Kowollik Christopher
Published: August 2023

Exploiting the optimum wavelength of reactivity for efficient photochemical reactions has been well‐established based on the development of photochemical action plots. We herein demonstrate the power of such action plots by a remarkable example of the wavelength‐resolved photochemistry of two triazolinedione (TAD) substrates, i.e., aliphatic and aromatic substituted, that exhibit near identical absorption spectra yet possess vastly disparate photoreactivity. We present our findings in carefully recorded action plots, from which reaction selectivity is identified. The profound difference in photoreactivity is exploited by designing a ‘hybrid’ bisfunctional TAD molecule, enabling the formation of a dual‐gated reaction manifold that demonstrates the exceptional and site‐selective (photo)chemical behavior of both TAD substrates within a single small molecule.
Link marine restoration to marine spatial planning through ecosystem‐based management to maximize ocean regeneration
Authors: Manea Elisabetta , Agardy Tundi , Bongiorni Lucia
Published: August 2023

The speed at which marine and coastal ecosystems are being degraded due to cumulative impacts limits the effectiveness of conservation strategies. To abate ocean degradation and allow ocean regeneration, conservation planning needs to be improved and ecological restoration will be needed.

This study explores the potential of incorporating restoration into marine spatial planning (MSP) anchored to ecosystem‐based management (EBM), termed EB‐MSP, for maximizing ocean regeneration. This perspective explicitly brings both passive and active restorations into EB‐MSP in a broad and holistic framework for achieving the recovery of ocean ecosystems, their functions and their valuable services.

By proposing a restoration‐focused EB‐MSP framework, we highlight the co‐benefits of interlinking MSP and marine restoration through the EBM core principles. Such benefits include a scaling‐up of restoration effectiveness, a greater guarantee that sustainability and conservation goals will be met and improvements in MSP as an integrated planning tool with the potential to address climate change. Together, this will promote ocean regeneration alongside management for sustainable use to prevent further degradation and to allow much‐needed ecological recovery.
The design, synthesis, biological evaluation, and molecular docking of new 5‐aminosalicylamide‐4‐thiazolinone hybrids as anticancer agents
Authors: Othman Shimaa A. , Abou‐Ghadir Ola F. , Ramadan Wafaa S. , Mostafa Yaser A. , El‐Awady Raafat , Abdu‐Allah Hajjaj H. M.
Published: August 2023

New 5‐aminosalicylamide‐4‐thiazolinone hybrids (27) were efficiently synthesized, characterized, and evaluated to explore their structure–activity relationship as anticancer agents. The antiproliferative activities of the new hybrids were evaluated against eight cancer cell lines using the sulforhodamine B assay. The most potent compound (24b) possessed high selectivity on the tested cell lines in the low micromolar range, with much lower effects on normal fibroblast cells (IC50 > 50 µM). The cell lines derived from leukemia (Jurkat), cervix (HeLa), and colon (HCT116) cancers appeared to be the most sensitive, with IC50 of 2 µM. 24b is the N‐ethylamide derivative with p‐dimethylaminobenzylidene at position 5 of the 4‐thiazolinone moiety. Other N‐substituents or arylidene derivatives showed lower activity. Hybrids with salicylamides showed lower activity than with methyl salicylate. The results clearly show that the modifications of the carboxy group and arylidene moiety greatly affect the activity. Investigating the possible molecular mechanisms of these hybrids revealed that they act through cell‐cycle arrest and induction of apoptosis and epidermal growth factor receptor (EGFR) inhibition. Molecular docking studies rationalize the molecular interactions of 24b with EGFR. This work expands our knowledge of the structural requirements to improve the anticancer activity of 5‐aminosalicylic‐thiazolinone hybrids and pave the way toward multitarget anticancer salicylates.
Investigating the relationship between research income and research excellence in education: Evidence from the REF2021‐UoA23 data
Authors: Boeren Ellen
Published: August 2023

This paper presents and discusses the relationship between the generation of research income and the REF2021 results for universities who submitted a return to Unit of Assessment 23—Education. Research Excellence Framework exercises tend to be time intensive and come with income streams of Government Quality Research funding as well as reputational gains and risks. Based on REF2021 research environment research income data, freely available on the REF2021 website, analyses have been undertaken to investigate the strength of relationships between different types of fundings streams and grade point averages. The results demonstrate strong variation in funding capture across the different universities with Russell Group members tending to generate more income from prestigious funders such as UK Research and Innovation. However, several post‐1992 universities managed to capture significant income from funders like UK and EU governments, without this necessarily translating into higher grade point averages or 4* scores. While generating research income is perceived as an important part of academic life, the paper concludes that achieving research excellence seems more complicated than just following the money.
Dominant negative variants and cotranslational assembly of macromolecular complexes
Authors: Veitia Reiner A.
Published: August 2023

Pathogenic variants occurring in protein‐coding regions underlie human genetic disease through various mechanisms. They can lead to a loss of function (LOF) such as in recessive conditions or in dominant conditions due to haploinsufficiency. Dominant‐negative (DN) effects, counteracting the activity of the normal gene‐product, and gain of function (GOF) are also mechanisms driving dominance. Here, I discuss a few papers on these specific mechanisms. In short, there is accumulating evidence pointing to differences between LOF versus non‐LOF variants (DN and GOF). The latter are thought to have milder effects on protein structure and, as expected, DN variants are enriched at protein interfaces. This tendency to cluster in 3D space can help improve the ability of computational tools to predict the pathogenicity of DN variants, which is currently a challenging issue. More recent results support the hypothesis whereby cotranslational assembly of macromolecular complexes can buffer deleterious consequences of variants that would otherwise lead to DN effects (DNEs). Indeed, subunits the variants of which are responsible for DNEs tend to elude cotranslational assembly, thus poisoning complexes involving wild‐type subunits. The constraints explaining why the buffering of DNEs is not universal require further investigation.
Unbiased and efficient estimation of causal treatment effects in crossover trials
Authors: Madsen Jeppe Ekstrand Halkjær , Scheike Thomas , Pipper Christian
Published: August 2023

We introduce causal inference reasoning to crossover trials, with a focus on thorough QT (TQT) studies. For such trials, we propose different sets of assumptions and consider their impact on the modeling strategy and estimation procedure. We show that unbiased estimates of a causal treatment effect are obtained by a g‐computation approach in combination with weighted least squares predictions from a working regression model. Only a few natural requirements on the working regression and weighting matrix are needed for the result to hold. It follows that a large class of Gaussian linear mixed working models lead to unbiased estimates of a causal treatment effect, even if they do not capture the true data‐generating mechanism. We compare a range of working regression models in a simulation study where data are simulated from a complex data‐generating mechanism with input parameters estimated on a real TQT data set. In this setting, we find that for all practical purposes working models adjusting for baseline QTc measurements have comparable performance. Specifically, this is observed for working models that are by default too simplistic to capture the true data‐generating mechanism. Crossover trials and particularly TQT studies can be analyzed efficiently using simple working regression models without biasing the estimates for the causal parameters of interest.
Combination of MAR and intron increase transgene expression of episomal vectors in CHO cells
Authors: Wang Xiao‐yin , Zhang Wei‐li , Zhang Xi , Fu Yu‐shun , Wang Hao‐min , Sun Qiu‐li , Li Qin , Jia Yan‐long , Zhang Jun‐he , Wang Tian‐yun
Published: August 2023

Previous work has shown that the EF‐1α promoter of episomal vectors maintains high‐level transgene expression in stably transfected Chinese hamster ovary (CHO) cells. However, the transgene expression levels need to be further increased. Here, we first incorporated matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE), stabilizing anti repressor elements 40 (STAR 40) elements into episomal vector at different sites and orientations, and systemically assessed their effects on transgene expression in transfected CHO‐K1 cells. Results showed that enhanced green fluorescent protein (eGFP) expression levels increased remarkably when MAR X‐29 was inserted upstream of the promoter, followed by the insertion of MAR1 downstream of the poly A, and the orientation had no significant effect. Moreover, MAR X‐29 combined with human cytomegalovirus intron (hCMVI) yielded the highest transgene expression levels (4.52‐fold). Transgene expression levels were not exclusively dependent on transgene copy numbers and were not related to the mRNA expression level. In addition, vector with MAR X‐29+hCMVI can induce herpes simplex virus thymidine kinase (HSV‐TK) protein expression, and the HSV‐TK protein showed a cell‐killing effect and an obvious bystander effect on HCT116 cells. In conclusion, the combination of MAR X‐29 and hCMV intron can achieve high efficiency transgene expression mediated by episomal vectors in CHO‐K1 cells.
Giving information strategically and transparently: A pilot trial of the Oncolo‐GIST intervention to promote patients' prognostic understanding
Authors: Prigerson Holly G. , Russell David , Kakarala Sophia E. , Derry‐Vick Heather M. , Shah Manish A. , Saxena Ashish , Reyna Valerie F. , Ocean Allyson , Scheff Ronald , Maciejewski Paul K. , Epstein Andrew S.
Published: August 2023

Purpose

Most patients with cancer lack the prognostic understanding necessary to make informed decisions. We tested the feasibility and acceptability of the Oncolo‐GIST (“Giving Information Strategically and Transparently, GIST”) intervention and explored its associations with patients' improved prognostic understanding.

Methods

The Oncolo‐GIST intervention distills prognostic discussions into easy‐to‐understand talking points. Patients with metastatic cancers that progressed on ≥1 line of chemotherapy and not expected to survive 12 months (n = 31) were recruited from October 2020 through November 2022. We compared patients who discussed their progressive scans with an oncologist trained in the GIST technique or not (i.e., usual care). A primary outcome was prognostic understanding (e.g., patients reporting a life‐expectancy of months) assessed within a week of the scan discussion visit.

Results

Oncologists (n = 4) appeared receptive to the Oncolo‐GIST intervention and scored nearly perfectly on post‐training tests of material mastery after a < 2‐h tutorial. Post‐scan discussion visit, 100% of patients who met with an Oncolo‐GIST‐trained clinician understood that their cancer was considered incurable (a 31% improvement from pre‐visit) compared with 91% of patients meeting with usual care oncologists (an 18% improvement); 33% of patients who met with an Oncolo‐GIST‐trained oncologist understood that they likely had months, not years, compared to 18% in the usual care group. No statistically significant differences emerged for these changes, nor for therapeutic alliance, anxiety, or depression scores between groups.

Conclusion

Oncolo‐GIST appears to be an easily learned approach to improve prognostic understanding that neither undermines therapeutic alliances nor increases patients' anxiety or depressive symptoms. Efficacy testing in a larger trial is warranted.
Dehydration of Amides by Redox‐Active Phenalenyl Based Mn‐Catalyst
Authors: Chakraborty Soumi , Biswas Amit , Mandal Swadhin K.
Published: August 2023

A redox‐active phenalenyl ligand coordinated Mn(III)‐complex can be reduced chemically to generate an active catalyst containing a ligand‐centered radical. This chemically reduced Mn‐catalyst shows excellent catalytic reactivity for silylative dehydration of a wide range of primary amides (including late‐stage diversification of various bio‐active molecules) to synthesize nitriles using an inert and inexpensive silane, polymethylhydrosiloxane (PMHS), under mild conditions. Control experiments suggest a radical pathway for the present catalytic reaction, initiated by the ligand‐centered radical.
Highly Efficient Base Catalyzed N‐alkylation of Amines with Alcohols and β‐Alkylation of Secondary Alcohols with Primary Alcohols
Authors: Garg Nitish K. , Tan Mattias , Johnson Magnus T. , Wendt Ola F.
Published: August 2023

Borrowing hydrogen (BH) reactions are very useful for the sustainable synthesis of C−C and C−N bonds. They generally operate with transition metal‐based catalysts along with stoichiometric/catalytic amounts of added base. Here we report that two catalytic transformations, generally carried out with the BH methodology, i. e. N‐alkylation of amines with alcohols and β‐alkylation of secondary alcohols with primary alcohols, can be performed very effectively with just catalytic amounts of base under air without using any transition metal‐based catalyst. The mechanism is proposed to be based on air oxidation of the alcohol to aldehyde followed by condensation to an unsaturated intermediate which undergoes transfer hydrogenation with alcohol to the product.
Thermodynamics of Textile Dyes Partitioning in Alcohol‐Based Aqueous Two‐Phase Systems
Authors: Silva Santos Beatriz , de Carvalho Batista Muniz Izabella , Santos Sampaio Vanessa , Reinert Ramos Gandolfi Olga , Martins Veloso Cristiane , da Costa Ilhéu Fontan Rafael , Ferreira Bonomo Renata Cristina
Published: August 2023

The aim of this work was a complete thermodynamic study on the partitioning of Remazol Yellow l, Remazol Brilliant Blue, and Remazol Red dyes in isopropyl alcohol + sodium phosphate + water aqueous two‐phase systems at different temperatures. The free energy change of transfer, enthalpy change of transfer, and entropy change of transfer were evaluated. The effects of the structure of the dye, tie line length, and temperature on the partitioning were studied. The results indicate that these aqueous two‐phase systems have high capacity to extract the dyes from aqueous matrices to the organic phase of these systems and are an interesting alternative to effluent treatment process.
Pd‐Catalyzed Tandem Pathway for Stereoselective Synthesis of (E)‐1,3‐Enyne from β‐Nitroalkenes by Using a Sacrificial Directing Group
Authors: Mondal Subal , Midya Siba P. , Das Suman , Mondal Soumya , Islam Abu S. M. , Ghosh Pradyut
Published: August 2023

The involvement of nitroalkenes instead of minimal one alkyne motif for (E)‐1,3‐enynes synthesis through a palladium catalyzed stereoselective bond forming pathway at room temperature is presented. Implication of nitro group as a sacrificial directing group, formation of magical alkyne on a newly developed Csp3‐Csp3 bond with initial palladium‐MBH adduct make this methodology distinctive. This protocol features an unprecedented sequential acetate addition, carbon‐carbon bond formation, isomerization of double bond and nitromethane degradation in a tandem catalytic walk via dancing hybridization. Mechanistic understanding through identification of intermediates and computational calculations furnishes complete insight into the tandem catalytic pathway. Broad substrates scope and functional groups tolerance make this synthetic methodology magnificent and dynamic. This represents the first example of stereoselective 1,3‐enyne synthesis exclusively from alkene substrates by introducing the concept of sacrificial directing group.
Chiral Dual Core Chromophores Based on Binaphthyl Acrylonitrile Motif with Tunable Dual Emission Bands and Anti‐counterfeiting
Authors: Qu Jun , Zhang Qing , Liao Xiaoming , Song Cunyu , Meng Xin , He Yuanchun , Li Zan , Zhang Xiaoxiang , Cao Ziping
Published: August 2023

Small organic molecules which can emit fluorescence with tunable dual emission bands are significant for fundamental research and broad applications. In this work, two binaphthyl based arylacrylonitrile derivatives with pyrene and triphenylamine unit (BiNp‐Py and BiNp‐TPA) were designed and synthesized, respectively, featuring chiral backbone and dual AIE‐active cyanostyrene‐linked chromophores. Excellent fluorescence emissions in a range of solution and solid states were observed with high quantum yields, indicative of the solvatochromism and mechanochromism. More interestingly, dual emission bands were found and tunable by the water fraction in THF, and speculatively attributed to the balancing of intramolecular charge transfer (ICT) and locally excited (LE) emission in solution and aggregate states. Furthermore, the potential application in anti‐counterfeiting ink was also explored, indicating the very low concentration (5 ppm) for sufficient distinguishable vision and small colour migration (28 nm) for printing on the filter. The present work provides a new strategy to design organic luminescent structure having widely fluorescent emissions in dual states and a valuable reference for the study of chiral optical materials.
Computer aided analysis of biomechanical performance of schanz screw with different additive manufacturing materials used in pertrochanteric fixator on an intertrochanteric femoral fracture (corrosion resistance approach)
Authors: Gok Arif , Urtekin Levent , Gok Kadir , Ada H. Deniz , Nalbant Asrin
Published: August 2023

This study examines the use of computer‐aided analysis to evaluate the biomechanical performance of Schanz screws made from different additive manufacturing materials (Ti6Al4V, 316 L, Inconel 625, and Inconel 718) in a pertrochanteric fixator for the treatment of intertrochanteric femoral fractures. Intertrochanteric fractures (ITFs) are severe traumas often seen in the elderly population and can lead to serious consequences. The primary objective of ITF surgery is to provide stability and allow for early ambulation and rehabilitation. The Pertrochanteric Fixator is a surgical implant used to treat hip fractures near the greater trochanter, and is attached to the femur with screws. The procedure is performed under general anesthesia and typically takes 1–2 h. Possible complications include infection, nerve injury, and hardware failure. The aim of this study is to evaluate the biomechanical performance of Schanz screw using computer‐aided analysis, comparing the effects of various additive manufacturing materials including Ti6Al4V, 316 L, Inconel 625 and Inconel 718 in a pertrochanteric fixator for intertrochanteric femoral fractures. Additionally, this study will also consider the corrosion resistance of these materials to ensure long‐term durability and effectiveness in a clinical setting. The stress values mentioned for the implant materials are as follows. Ti6Al4V: 153.33 MPa, 316 L: 180.98 MPa, Inconel 625: 158.94 MPa, Inconel 718: 148.91 MPa. Higher stress values indicate a greater load transfer to the bone, which can potentially lead to stress shielding. Stress shielding occurs when an implant bears a significant portion of the load that should be transferred to the bone. This reduced stress at the fracture site can prevent the healing process, as bones require adequate stress levels for optimal remodeling and regeneration.
SURF: A Screening Tool (for Sponsors) to Evaluate Whether Using Real‐World Data to Support an Effectiveness Claim in an FDA Application Has Regulatory Feasibility
Authors: Campbell Ulka B. , Honig Nicholaas , Gatto Nicolle M.
Published: August 2023

Based on recent guidance and publicly available approvals, the US Food and Drug Administration (FDA) has demonstrated its openness to considering evidence of effectiveness from real‐world data (RWD) and nonrandomized studies (or “real‐world evidence (RWE)”) in its decision making. Through analysis of the FDA approvals, several authors have identified methodologic issues commonly discussed by FDA reviewers. However, in our analysis of FDA guidance and use cases, acceptability of RWE also critically depends on whether the characteristics of the clinical development program align with circumstances in which the FDA may have flexibility in considering evidence from real‐world study designs relative to more robust designs. Successful use of RWD requires advance planning to allocate the necessary resources and time to undertake principled epidemiology approaches to study design, data selection, and implementation of analyses as well as address regulatory feedback. Thus, sponsors benefit from early identification of programs in which successful RWD use is more likely, to ensure efficient use of resources required for the next steps of scientific feasibility assessment. We developed SURF, a screening tool intended to help a sponsor decide whether to prioritize resources for further exploring the feasibility of using an RWD approach to meet the FDA's effectiveness evidentiary standards for a particular clinical development program. Here, we provide an analysis of FDA guidance, highlighting the circumstances in which RWD approaches may be most acceptable, and demonstrate the use of this screening tool, including the rationale for its construction, types of evidence needed, and application to publicly available approvals as support of concept.
Performance analysis of intelligent reflecting surface‐assisted mobile wireless networks subjected to generalized Gaussian noise
Authors: Ashraf Umer , Rasool Begh Gh.
Published: August 2023

Different from the prior works, this paper presents the performance analysis of an intelligent reflecting surface (IRS)‐assisted communication link in a static and mobile scenario impaired by Rayleigh fading and additive white generalized Gaussian noise (AWGGN). Precisely, the IRS is configured as an intelligent access point, and the mobile behavior of the nodes is characterized by the random waypoint (RWP) model. To this end, closed‐form expressions of average bit error rate (BER), average channel capacity (ACC), and outage probability (OP) in both static and mobile scenarios are obtained. To gain further insight into the system performance at high signal‐to‐noise ratio (SNR), asymptotic expressions are obtained. Moreover, the effect of the number of reflective elements (
) and the shaping parameter (
) on the system performance is thoroughly studied. The results indicate that introduction of IRS leads to significant improvement in the overall system performance. The derived results are corroborated with Monte Carlo simulations.
Population size affected by environmental variability impacts genetics, traits, and plant performance in Trifolium montanum L.
Authors: Karbstein Kevin , Römermann Christine , Hellwig Frank , Prinz Kathleen
Published: August 2023

Population size, genetic diversity, and performance have fundamental importance for ecology, evolution, and nature conservation of plant species. Despite well‐studied relationships among environmental, genetic, and intraspecific trait variation (ITV), the influence of population size on these aspects is less understood. To assess the sources of population size variation, but also its impact on genetic, functional trait, and performance aspects, we conducted detailed population size estimations, assessed 23 abiotic and biotic environmental habitat factors, performed population genetic analyses using nine microsatellite markers, and recorded nine functional traits based on 260 Trifolium montanum individuals from 13 semi‐dry grassland locations of Central Europe. Modern statistical analyses based on a multivariate framework (path analysis) with preselected linear regression models revealed that the variation of abiotic factors (in contrast to factors per se) almost completely, significantly explained fluctuations in population size (R2 = .93). In general, abiotic habitat variation (heterogeneity) was not affected by habitat area. Population size significantly explained genetic diversity (NA: R2 = .42, Ho: R2 = .67, He: R2 = .43, and I: R2 = .59), inbreeding (FIS: R2 = .35), and differentiation (GST: R2 = .20). We also found that iFDCV (ITV) was significantly explained by abiotic habitat heterogeneity, and to a lesser extent by genetic diversity He (R2 = .81). Nevertheless, habitat heterogeneity did not statistically affect genetic diversity. This may be due to the use of selectively neutral microsatellite markers, and possibly by insufficient abiotic selective pressures on habitats examined. Small T. montanum populations in nonoptimal habitats were characterized by reduced genetic and functional trait diversity, and elevated genetic inbreeding and differentiation. This indicates reduced adaptability to current and future environmental changes. The long‐term survival of small populations with reduced genetic diversity and beginning inbreeding will be highly dependent on habitat protection and adequate land‐use actions.
Variable rates of hybridization among contact zones between a pair of topminnow species, Fundulus notatus and F. olivaceus
Authors: Duvernell David D. , Remex Naznin S. , Miller Jeffrey T. , Schaefer Jacob F.
Published: August 2023

Pairs of species that exhibit broadly overlapping distributions, and multiple geographically isolated contact zones, provide opportunities to investigate the mechanisms of reproductive isolation. Such naturally replicated systems have demonstrated that hybridization rates can vary substantially among populations, raising important questions about the genetic basis of reproductive isolation. The topminnows, Fundulus notatus and F. olivaceus, are reciprocally monophyletic, and co‐occur in drainages throughout much of the central and southern United States. Hybridization rates vary substantially among populations in isolated drainage systems. We employed genome‐wide sampling to investigate geographic variation in hybridization, and to assess the possible importance of chromosome fusions to reproductive isolation among nine separate contact zones. The species differ by chromosomal rearrangements resulting from Robertsonian (Rb) fusions, so we hypothesized that Rb fusion chromosomes would serve as reproductive barriers, exhibiting steeper genomic clines than the rest of the genome. We observed variation in hybridization dynamics among drainages that ranged from nearly random mating to complete absence of hybridization. Contrary to predictions, our use of genomic cline analyses on mapped species‐diagnostic SNP markers did not indicate consistent patterns of variable introgression across linkage groups, or an association between Rb fusions and genomic clines that would be indicative of reproductive isolation. We did observe a relationship between hybridization rates and population phylogeography, with the lowest rates of hybridization tending to be found in populations inferred to have had the longest histories of drainage sympatry. Our results, combined with previous studies of contact zones between the species, support population history as an important factor in explaining variation in hybridization rates.
Past energy allocation overwhelms current energy stresses in determining energy allocation trade‐offs
Authors: Griffen Blaine D. , Bolander Mikayla , Blakeslee April , Crane Laura C. , Repetto Michele F. , Tepolt Carolyn K. , Toscano Benjamin J.
Published: August 2023

Regeneration of lost appendages is a gradual process in many species, spreading energetic costs of regeneration through time. Energy allocated to the regeneration of lost appendages cannot be used for other purposes and, therefore, commonly elicits energetic trade‐offs in biological processes. We used limb loss in the Asian shore crab Hemigrapsus sanguineus to compare the strength of energetic trade‐offs resulting from historic limb losses that have been partially regenerated versus current injuries that have not yet been repaired. Consistent with previous studies, we show that limb loss and regeneration results in trade‐offs that reduce reproduction, energy storage, and growth. As may be expected, we show that trade‐offs in these metrics from historic limb losses far outweigh trade‐offs from current limb losses, and correlate directly with the degree of historic limb loss that has been regenerated. As regenerating limbs get closer to their normal size, these historical injuries get harder to detect, despite the continued allocation of additional resources to limb development. Our results demonstrate the importance of and a method for identifying historic appendage losses and of quantifying the amount of regeneration that has already occurred, as opposed to assessing only current injury, to accurately assess the strength of energetic trade‐offs in animals recovering from nonlethal injury.
Temporal trends in evidence supporting therapeutic interventions in heart failure and other European Society of Cardiology guidelines
Authors: Canepa Marco , De Marzo Vincenzo , Ameri Pietro , Ferrari Roberto , Tavazzi Luigi , Rapezzi Claudio , Porto Italo , Maggioni Aldo Pietro
Published: August 2023

Aims

This study aimed to determine whether any change occurred over time in level of evidence (LoE) of therapeutic interventions supporting heart failure (HF) and other European Society of Cardiology guideline recommendations.

Methods and results

We selected topics with at least three documents released between 2008 and April 2022. Classes of recommendations (CoR) and supporting LoE related to therapeutic interventions within each document were collected and compared over time. A total of 1822 recommendations from 18 documents on 6 topics [median number per document = 112, 867 (48%) CoR I] were included in the analysis. There was a trend towards a reduction over time in the percentage of CoR I in HF (46–36–34%), non‐ST elevation myocardial infarction (NSTEMI; 78–58–54%), and pulmonary embolism (PE; 65–50–39%) guidelines, with a decrease in the total number of recommendations for HF only. Percentage of CoR I was stable over time around 40% for valvular heart disease (VHD) and atrial fibrillation (AF), and around 60% for cardiovascular prevention (CVP), with an increase in the total number of recommendations for VHD and CVP and a decrease for AF. Among CoR I, 319 (37%) were supported by LoE A, with a decrease over time for HF (56–46–42%), an increase for NSTEMI (29–38–48%) and AF (28–31–36%), a bimodal distribution for PE and CVP, and a lack for VHD.

Conclusions

LoE supporting therapeutic recommendations in contemporary European guidelines is generally low. Physicians should be aware of these limitations, and scientific societies promote a greater understanding of their significance and drive future research directions.
Propofol synergizes with circAPBB2 to protect against hypoxia/reoxygenation‐induced oxidative stress, inflammation, and apoptosis of human cardiomyocytes
Authors: Jin Chenghao , Yuan Shunnv , Piao Longyi , Ren Mingcheng , Liu Qiang
Published: August 2023

Background

Myocardial injury is the main manifestation of cardiovascular diseases, and previous studies have shown that propofol (PPF) regulates myocardial injury. However, the mechanism of PPF in regulating myocardial injury remains to be further explored. This work aims to analyze the effects of PPF on human cardiomyocyte injury and the underlying mechanism.

Methods

The regulatory and functional role of PPF and circAPBB2 in human cardiomyocyte injury were analyzed using an in vitro hypoxia/reoxygenation (H/R) cell model, which was established by treating human cardiomyocytes (AC16 cells) with H/R. The study evaluated AC16 cell injury by analyzing cytotoxicity, oxidative stress, inflammation and apoptosis of H/R‐induced AC16 cells. Quantitative real‐time polymerase chain reaction was performed to detect circAPBB2, miR‐18a‐5p and dual specificity phosphatase 14 (DUSP14) expression. Protein expression was analyzed by Western blot analysis assay. Dual‐luciferase reporter assay, RNA pull‐down assay and RNA immunoprecipitation assay were performed to identify the associations among circAPBB2, miR‐18a‐5p and DUSP14. Cytotoxicity was investigated by cell counting kit‐8 assay and lactate dehydrogenase activity detection kit. Oxidative stress was evaluated by cellular reactive oxygen species assay kit and superoxide dismutase activity assay kit. The production of tumor necrosis factor‐α and interleukin‐1β was evaluated by enzyme‐linked immunosorbent assays.

Results

The expression of circAPBB2 and DUSP14 was significantly decreased, while miR‐18a‐5p was increased in H/R‐induced AC16 cells when compared with controls. H/R treatment‐induced cytotoxicity, oxidative stress, inflammation and cell apoptosis were attenuated after circAPBB2 overexpression or PPF treatment, whereas these effects were restored by increasing miR‐18a‐5p expression. PPF treatment improved the inhibitory effect of ectopic circAPBB2 expression on H/R‐induced cell injury. MiR‐18a‐5p silencing ameliorated H/R‐induced AC16 damage by interacting with DUSP14. Mechanically, circAPBB2 acted as a miR‐18a‐5p sponge, and miR‐18a‐5p targeted DUSP14 in AC16 cells.

Conclusion

PPF synergized with circAPBB2 to protect AC16 cells against H/R‐induced oxidative stress, inflammation and apoptosis through the miR‐18a‐5p/DUSP14 pathway.