Alternative Class Research Articles

Vedolizumab in Ulcerative Colitis and Crohn’s Disease-A Systematic Review

Background: Vedolizumab is a fully humanized monoclonal IgG-1 antibody that selectively inhibits the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). It prevents lymphocyte translocation from the blood into the inflamed gut tissue, resulting in a reduction in local inflammation. Ulcerative colitis (UC) and Crohn’s disease (CD) are inflammatory conditions of the bowel affecting approximately 1.4 million people in the US. The efficacy of the drug was studied. Methods: The outcome measures for Phase 3 and randomized clinical trials in ulcerative colitis and Crohn’s disease, was as per GEMINI 1, 2, and 3 for its efficacy. Results: A total of 309 out of 499 reported vedolizumab AEs. In comparison with all other drugs, 3PRR signals were detected including joint-related symptoms like arthralgia, upper respiratory tract infections like nasopharyngitis and sinusitis, and upper respiratory tract symptoms like oropharyngeal pain. Among the vedolizumab-associated reports with serious outcomes, the drug was used for CD in 52.5% and UC in 27.4% compared with 86.1% and 13.9% for the anti-TNFs-associated reports. Although safety data from both these studies suggest VDZ is safe, larger studies with longer follow-up will be necessary to determine the potential risk for the development of PML. Conclusion: There is limited information on other potential confounders, such as co-morbidities, duration, and severity of disease, disease phenotype, surgical history, smoking, and concurrent IBD treatment. The benefit and risk profile of combining Vedolizumab with anti-TNF-α agents in the treatment of IBD will need to be examined. Vedolizumab is revolutionary in the community of inflammatory bowel disease, especially with the potential advantage for VDZ’s selectivity to the gastrointestinal immune system. Vedolizumab provides an alternate class to biologic therapy with an encouraging response and safety profile.

Analyzing the Challenges of Implementing Online Classes in Developing Countries during COVID-19 Outbreak: A Perspective from Bangladesh

COVID-19 has posed a significant threat to the global education system. Rethinking alternative classes for continuing education is the central issue for coping with the new-normal system. The study aims to seek the preparedness and practicality of online education in developing countries from Bangladesh's perspective. The study examined primary data collected through a survey. In line with the descriptive analysis of the collected data, a logistic regression model has been applied to justify the hypotheses. Among sixteen variables, we have found seven variables that significantly impact the students’ opinion regarding conducting classes in online. The findings show a positive association of lack of high internet speed, frequent disconnection issues during class time, mental stress about COVID-19, lack of engaging course contents, and deteriorating family financial condition with students' unwillingness towards online class during COVID-19.The study also revealed that students who have technical expertise in online classes are more interested in this type of class format. In this changing circumstance, online class format is an alternative channel to maintain the continuity in higher studies in Bangladesh. Thus the educational institutions can arrange training programs for teachers to improve the course contents. The institutions can also support the students by providing financial assistance for purchasing devices, internet data packages, guidelines for joining in online class and consulting to relieve mental stress. The government can also play a significant role by ensuring nationwide high-speed internet service and subsidy to purchase internet data for the students. Journal of Business Studies, Vol. XLII, No. 1, April 2021 Page 133-150

P445 Does The Sequence Matter ? Comparative effectiveness of a second line biologic in patients with Ulcerative Colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab

Abstract Background Drug choice and order in Inflammatory Bowel Disease (IBD) is an important challenge and is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second line treatments in Ulcerative Colitis (UC). It is unclear if using anti-Tumour Necrosis Factor-a (anti-TNF) therapy following vedolizumab (VDZ) or VDZ after anti-TNF has a more favourable outcome in UC in a real-world outpatient setting. Methods Patients with UC who were exposed to first-line anti-TNF (adalimumab/ADA or infliximab/IFX) or VDZ who subsequently switched to the alternate class between May 2013-August 2020 were identified following a review of databases at 10 hospitals. 88 VDZ and 39 anti-TNF (12 ADA,27 IFX) second line patients were eligible. Data was collected retrospectively. Baseline demographics, disease activity indices, colectomy rates, treatment persistence and healthcare resource utilisation composite endpoint (HRUC) were examined over a 52 week period for the second line biologic. HRUC included unplanned emergency hospital attendance or hospital admission. The primary endpoints of 52 week treatment persistence, HRUC survival and colectomy free survival were analysed with Kaplan Meier method, statistical significance between the survival curves was assessed with Log Rank test. Propensity score matching (PSM) was applied to survival curves (tolerance level 0.1). For a subset where SCCAI scores available, week 52 corticosteroid free clinical response/remission rates were calculated (response: reduction of SCCAI ≥3 and remission: SCCAI ≤2).: Results The second line anti-TNF group had a significantly higher baseline endoscopic Mayo score (p=0.035) and lower concomitant immunomodulator use (p=0.001). Second line week 52 treatment persistence was higher in the VDZ group 71/80 (89%) vs. Anti-TNF 15/36 (42%) ,p<0.0001 (Figure 1). Second line week 52 HRUC survival was higher in the VDZ group 68/81 (84%) vs. anti-TNF 20/33 (61%), p=0.003 (Figure 2). Week 52 colectomy free survival VDZ 77/80 (96%) vs. anti-TNF 26/32 (81%), p= <0.011 (Figure 3). For treatment persistence and colectomy free survival statistical significance was maintained with PSM. Week 52 corticosteroid free clinical remission rates VDZ 22/32 (69%) vs. anti-TNF 5/19 (25%) p=0.004 (Figure 4). Conclusion The VDZ second line cohort had significantly higher 52-week treatment persistence, lower HRUC and lower colectomy rates and higher corticosteroid free clinical remission rates. This data suggests that VDZ is an effective biologic in UC in a second line therapy after anti-TNF exposure. It highlights the effect of biologic sequencing on clinically important outcomes in an outpatient setting. Larger prospective studies are required to confirm these findings.

Lung on a Chip Development from Off-Stoichiometry Thiol-Ene Polymer.

Current in vitro models have significant limitations for new respiratory disease research and rapid drug repurposing. Lung on a chip (LOAC) technology offers a potential solution to these problems. However, these devices typically are fabricated from polydimethylsiloxane (PDMS), which has small hydrophobic molecule absorption, which hinders the application of this technology in drug repurposing for respiratory diseases. Off-stoichiometry thiol–ene (OSTE) is a promising alternative material class to PDMS. Therefore, this study aimed to test OSTE as an alternative material for LOAC prototype development and compare it to PDMS. We tested OSTE material for light transmission, small molecule absorption, inhibition of enzymatic reactions, membrane particle, and fluorescent dye absorption. Next, we microfabricated LOAC devices from PDMS and OSTE, functionalized with human umbilical vein endothelial cell (HUVEC) and A549 cell lines, and analyzed them with immunofluorescence. We demonstrated that compared to PDMS, OSTE has similar absorption of membrane particles and effect on enzymatic reactions, significantly lower small molecule absorption, and lower light transmission. Consequently, the immunofluorescence of OSTE LOAC was significantly impaired by OSTE optical properties. In conclusion, OSTE is a promising material for LOAC, but optical issues should be addressed in future LOAC prototypes to benefit from the material properties.

A semi-classical model of regular inflationary cosmology

Quantum-effective gravity must lead to a regularized cosmology and thereby by itself source and regulate the high energy inflaton fields required for an appropriate inflationary beginning of the Universe. Pursuing this premise, we involve in the generic code of extended theories of gravity in conceiving semi-classical imprinting of quantum effects into gravitation. Hence, we prescribe a general semi-classical procedure of constructing the regular, quantum-effective form of the spatially flat FLRW cosmology whereby two alternative classes of the admissible dynamics are distinguished. In this paper, we explore only the particular class holding a minimally inflationary de Sitter UV-phase. Curiously, the low energy phase of the newly modeled Universe recovers the conventional dynamics of loop quantum cosmology. However, unlike the loop quantum cosmology, the high energy phase of the newly conceived cosmology has no bounce, instead, has a regular whimpering emergence of the Universe replacing the Big Bang. Our analysis manifests that without needing any non-standard equation of state, ordinary matter admits an inflationary beginning of the Universe.

The feasibility of heavy battery electric trucks

Summary Research on the decarbonization of transport often concludes that heavy battery electric trucks are infeasible due to the incompatibility of long driving distance with high energy use and low specific energy and high costs of batteries. However, emphasis is often placed on battery electric range matching that of diesel trucks, instead of overall competitiveness. We model battery electric trucks that use high-power fast charging, enabling smaller batteries and showing that the economics of battery electric trucks per ton-kilometer improves with greater weight, driven by increasing load capacity as well as increased energy savings as a function of weight. Furthermore, we show that previous findings that the competitiveness per kilometer is worse for heavy trucks than for lighter trucks are very sensitive to assumptions about the battery cost per kWh and lifetime of the battery pack. Given the rapid development of batteries, we conclude that the economic feasibility of heavy battery electric trucks might have been generally underestimated.

The Best Strategies for Inflationary Times

Over the past three decades, a sustained surge in inflation has been absent in developed markets. As a result, investors face the challenge of having limited experience and no recent data to guide the repositioning of their portfolios in the face of heighted inflation risk. We provide some insight by analyzing both passive and active strategies across a variety of asset classes for the U.S., U.K., and Japan over the past 95 years. Unexpected inflation is bad news for traditional assets, such as bonds and equities, with local inflation having the greatest effect. Commodities have positive returns during inflation surges but there is considerable variation within the commodity complex. Among the dynamic strategies, we find that trend-following provides the most reliable protection during important inflation shocks. Active equity factor strategies also provide some degree of hedging ability. We also provide analysis of alternative asset classes such as fine art and discuss the economic rationale for including cryptocurrencies as part of a strategy to protect against inflation.

Global risk factors of NYSE- and NASDAQ-listed shipping companies’ stock returns

PurposeThis paper aims to investigate the impact of global macro and other risk factors of the New York Stock Exchange (NYSE)- and National Association of Securities Dealers Automated Quotation (NASDAQ)-listed shipping companies’ stock returns from January 2001 to December 2019.Design/methodology/approachThe methodological design includes multi-factor regressions for individual companies, augmented versions of these regressions to examine the likely impact of additional factors and finally panel regressions to assess the impact risk factors on all companies simultaneously. Estimations are done via ordinary least squares and the generalized method of moments.FindingsMulti-factor model results showed that some of the US-specific and global macro risk factors surfaced as statistically significant for most of the companies and appeared to exhibit a consistent pattern in the way they affected shipping stocks. Thus, these companies’ exposures emanate mostly from the general US market’s movements and to a lesser extent from other firm-specific factors. Second, from the results of panel specifications, this study observes that domestic risk factors such as unemployment, inflation rates and industrial production growth emerged as significant for the NYSE-listed companies. As regard, the NASDAQ-listed ones, it was found that Libor and the G20 inflation rate were also affecting their stock returns.Research limitations/implicationsCompanies examined are listed only in the US’s NYSE and NASDAQ. Hence, companies listed elsewhere were excluded. It may be concluded that these US exchange-listed companies abide mostly by domestic fundamentals and to some extent to selected global factors.Practical implicationsThe significance of the findings in this study pertains to global investors and shipping companies’ managers alike. Specifically, given the differential sensitivities of the shipping companies to various risk factors (and the global business cycle, in general), it is possible to view the shipping companies’ stocks as a separate, alternate asset class in a global, well-diversified portfolio. Thus, such a broader portfolio would permit investors to earn positive returns and reduce overall risk. Managers of shipping companies would also benefit from the findings in this study in the sense that they should better understand the varying exposures of their companies to changing global and domestic macro conditions and successfully navigate their companies through business cycles.Originality/valueResearch on the global shipping industry has lagged behind and was mainly concentrated on the investigation of the sources of shipping finance and capital structure of shipping companies, investment and valuation, corporate governance and risk measurement and management. Empirical research on the potential micro and macro determinants of the stock returns of shipping companies, however, is scant. This paper fills the gap in the literature of identifying and evaluating the various macroeconomic, US and international risk, factors that affect shipping companies’ stock returns in a highly financially integrated world.

Occurrence of Beta-Lactamases Genes in Beta-Lactam Resistant Bacteria Isolated from Milk of Goats with Sub-Clinical Mastitis in Thika Sub-County, Kenya

For decades, beta-lactam antibiotics have played a critical role in the control of mastitis in animals. However, the emergence of beta-lactam-resistant bacteria poses a challenge to both human and veterinary medicine. In this regard, bacterial isolates from milk samples collected from dairy goats with sub-clinical mastitis from Thika Sub-county, Kenya, were used in the current study to interrogate the occurrence of beta-lactamases genes in bacterial isolates (Klebsiella pneumoniae, Staphylococcus aureus, and Acinetobacter spp., and Coagulase-negative Staphylococci) with known phenotypic resistance profiles to penicillin G, cephalexin, cefoxitin, and cefotaxime. Four target genes, blaTEM, blaSHV, blaCTX, blaOXA, and blaKPC were amplified using a polymerase chain reaction, and compared with Escherichia coli American Type Culture Collection 35218 and non-standard Klebsiella pneumonia positive controls. Out of the 46 samples, 44 samples (95.7%) harbored blaTEM with two samples of the 44 bacterial isolates, also possessing the blaSHV gene. Only one isolate of Klebsiella pneumonia and Acinetobacter spp had a combination of blaTEM and blaSHV. None of the bacteria had blaCTX, blaOXA, and blaKPC genes. The data indicated that sub-clinical mastitis in dairy goats in Thika Sub-county is associated with the bacteria carrying beta-lactamases genes, suggesting that the use of beta-lactam antibiotics for the treatment of sub-clinical mastitis may result in the treatment failure and potential transfer of the infectious bacteria to humans and other animals. The current study recommends the use of an alternative class of antibiotics for the management of beta-lactam-resistant bacteria.

A Review on Recent Progress of Glycan-Based Surfactant Micelles as Nanoreactor Systems for Chemical Synthesis Applications

The nanoreactor concept and its application as a modality to carry out chemical reactions in confined and compartmentalized structures continues to receive increasing attention. Micelle-based nanoreactors derived from various classes of surfactant demonstrate outstanding potential for chemical synthesis. Polysaccharide (glycan-based) surfactants are an emerging class of biodegradable, non-toxic, and sustainable alternatives over conventional surfactant systems. The unique structure of glycan-based surfactants and their micellar structures provide a nanoenvironment that differs from that of the bulk solution, and supported by chemical reactions with uniquely different reaction rates and mechanisms. In this review, the aggregation of glycan-based surfactants to afford micelles and their utility for the synthesis of selected classes of reactions by the nanoreactor technique is discussed. Glycan-based surfactants are ecofriendly and promising surfactants over conventional synthetic analogues. This contribution aims to highlight recent developments in the field of glycan-based surfactants that are relevant to nanoreactors, along with future opportunities for research. In turn, coverage of research for glycan-based surfactants in nanoreactor assemblies with tailored volume and functionality is anticipated to motivate advanced research for the synthesis of diverse chemical species.

CAS without SCF-Why to use CASCI and where to get the orbitals.

The complete active space self-consistent field (CASSCF) method has seen broad adoption due to its ability to describe the electronic structure of both the ground and excited states of molecules over a broader swath of the potential energy surface than is possible with the simpler Hartree-Fock approximation. However, it also has a reputation for being unwieldy, computationally costly, and un-black-box. Here, we discuss a class of alternatives, complete active space configuration interaction (CASCI) methods, paying particular attention to their application to electronic excited states. The goal of this Perspective is fourfold. First, we argue that CASCI is not merely an approximation to CASSCF, in that it can be designed to have important qualitative advantages over CASSCF. Second, we present several insights drawn from our experience experimenting with different schemes for computing orbitals to be employed in CASCI. Third, we argue that CASCI is well suited for application to nanomaterials. Finally, we reason that, with the rise in new low-scaling approaches for describing multireference systems, there is a greater need than ever to develop new methods for defining orbitals that provide an efficient and accurate description of both static correlation and electronic excitations in a limited active space.

Strategic Asset Allocation for Endowment Funds

An endowment fund serves as a permanent source of capital to support a specific mission. It has, in the case of a university, dual goals of providing current financial support to the university and preserving long-term purchasing power to ensure that support continues in perpetuity. This article explores a methodology for constructing strategic asset allocation for endowment funds in the context of these competing long-term investment goals. <b>TOPICS:</b>Foundations &amp; endowments, portfolio construction <b>Key Findings</b> ▪ In constructing a strategic asset allocation for an endowment, a traditional mean-variance optimization framework alone does not provide sufficient context to generate comprehensive forward-looking analysis. However, adding additional measures such as maximizing the probability of achieving investment goals or minimizing relevant downside distress measures over the long term can improve the analysis. ▪ A typical endowment’s asset allocation, with an equity orientation and tilt toward alternative asset classes, nearly maximizes the probability of achieving the dual long-term investment goals of meeting a spending rate target while preserving real capital, as well as minimizes endowment-specific downside risk measures. ▪ Optimal portfolio choices are dependent on underlying return expectations across asset classes. Although expected returns are typically the highest for private investments, there are limits to investing in private asset classes, including an endowment’s liquidity requirements and ability to access the best-performing managers.

Structurally photo-active metal–organic frameworks: Incorporation methods, response tuning, and potential applications

Metal–organic frameworks (MOFs) are an important family of materials due to the properties that make them well suited to a range of applications. This includes structurally photo-active MOFs, which have properties that can be efficiently modulated through controlled light irradiation, making them ideal due to the cost-effectiveness and noninvasive nature of this stimulus. The incorporation of structurally photo-active functional groups into MOFs has occurred through either guest inclusion, as pendant moieties, or as part of a ligand's backbone. While initial studies into the incorporation of these groups focused on prominent photo-switches such as azobenzenes, the literature has expanded to include other classes described in the wider photo-switch literature, most notably spiropyrans (SPs). The incorporation of alternative photo-switching classes has currently benefited the field through tuning the light responsive wavelength. Initial inquiries demonstrated suitable function in gas sorption applications where irradiation could be exploited for inducing adsorption or desorption. Furthermore, the potential applications explored in the literature have also recently expanded to include inquiries into other commercial functions, such as desalination [R. Ou et al., Nat. Sustain. 3, 1052–1058 (2020)], photo-lithography [H. A. Schwartz et al., Inorg. Chem. 56(21), 13100–13110 (2017)], and drug capture/release [X. Meng et al., Sci. Adv. 2(8), 2–8 (2016)].

Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex

Herpesviruses infect a majority of the human population, establishing lifelong latent infections for which there is no cure. Periodic viral reactivation spreads infection to new hosts while causing various disease states particularly detrimental in the immunocompromised. Efficient viral replication, and ultimately the spread of infection, is dependent on the nuclear egress complex (NEC), a conserved viral heterodimer that helps translocate viral capsids from the nucleus to the cytoplasm where they mature into infectious virions. Here, we have identified peptides, derived from the capsid protein UL25, that are capable of inhibiting the membrane-budding activity of the NEC from herpes simplex virus type 1 in vitro. We show that the inhibitory ability of the peptides depends on their length and the propensity to form an α-helix but not on the exact amino acid sequence. Current therapeutics that target viral DNA replication machinery are rendered ineffective by drug resistance due to viral mutations. Our results establish a basis for the development of an alternative class of inhibitors against nuclear egress, an essential step in herpesvirus replication, potentially expanding the current repertoire of available therapeutics.

Development of a CRISPR/Cpf1 system for targeted gene disruption in Aspergillus aculeatus TBRC 277

BackgroundCRISPR-Cas genome editing technologies have revolutionized biotechnological research particularly in functional genomics and synthetic biology. As an alternative to the most studied and well-developed CRISPR/Cas9, a new class 2 (type V) CRISPR-Cas system called Cpf1 has emerged as another versatile platform for precision genome modification in a wide range of organisms including filamentous fungi.ResultsIn this study, we developed AMA1-based single CRISPR/Cpf1 expression vector that targets pyrG gene in Aspergillus aculeatus TBRC 277, a wild type filamentous fungus and potential enzyme-producing cell factory. The results showed that the Cpf1 codon optimized from Francisella tularensis subsp. novicida U112, FnCpf1, works efficiently to facilitate RNA-guided site-specific DNA cleavage. Specifically, we set up three different guide crRNAs targeting pyrG gene and demonstrated that FnCpf1 was able to induce site-specific double-strand breaks (DSBs) followed by an endogenous non-homologous end-joining (NHEJ) DNA repair pathway which caused insertions or deletions (indels) at these site-specific loci.ConclusionsThe use of FnCpf1 as an alternative class II (type V) nuclease was reported for the first time in A. aculeatus TBRC 277 species. The CRISPR/Cpf1 system developed in this study highlights the feasibility of CRISPR/Cpf1 technology and could be envisioned to further increase the utility of the CRISPR/Cpf1 in facilitating strain improvements as well as functional genomics of filamentous fungi.

Benzothiazolyl and Benzoxazolyl Hydrazones Function as Zinc Metallochaperones to Reactivate Mutant p53.

We identified a set of thiosemicarbazone (TSC) metal ion chelators that reactivate specific zinc-deficient p53 mutants using a mechanism called zinc metallochaperones (ZMCs) that restore zinc binding by shuttling zinc into cells. We defined biophysical and cellular assays necessary for structure-activity relationship studies using this mechanism. We investigated an alternative class of zinc scaffolds that differ from TSCs by substitution of the thiocarbamoyl moiety with benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones. Members of this series bound zinc with similar affinity and functioned to reactivate mutant p53 comparable to the TSCs. Acute toxicity and efficacy assays in rodents demonstrated C1 to be significantly less toxic than the TSCs while demonstrating equivalent growth inhibition. We identified C85 as a ZMC with diminished copper binding that functions as a chemotherapy and radiation sensitizer. We conclude that the benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones can function as ZMCs to reactivate mutant p53 in vitro and in vivo.

Safe sodium‐ion battery using hybrid electrolytes of organic solvent/pyrrolidinium ionic liquid

AbstractIonic liquids (ILs) have been considered as an alternative class of electrolytes compared to conventional carbonate solvents in rechargeable lithium/sodium batteries. However, the drawbacks of ILs are their reducing ionic conductivity and their large viscosity. Therefore, mixtures of alkyl carbonate solvents with an IL and a sodium bis(trifluoromethane sulfonyl)imide (NaTFSI) have been investigated to develop new electrolytes for sodium‐ion batteries. In this work, N‐Butyl‐N‐methylpyrrolidinium bis(trifluoro‐methanesulfonyl) imide (Py14TFSI) was used as co‐solvent mixing with commercial electrolytes based on the carbonate, i.e. EC‐PC (1:1), EC‐DMC (1:1), and EC‐PC‐DMC (3:1:1). The addition of ionic liquid in the carbonate‐based electrolyte solution results in (i) enhancing ionic conductivity to be comparable with a solvent‐free IL‐based electrolyte, (ii) maintaining the electrochemical stability window, and (iii) IL acted as a retardant rather than a flame‐inhibitor based on the self‐extinguish time (SET) of the mixed electrolyte mixture when exposed to a free flame. All mixed electrolyte systems have been tested in sodium‐coin cells versus Na0.44MnO2 (NMO) and hard carbon (HC) electrodes. The cells show good performances in charge/discharge cycling with a retention &gt; 96 % after 30 cycles (∼90 mAh.g‐1 for NMO and 180 mAh.g‐1 for HC, respectively) demonstrating good interfacial stability and highly stable discharge capacities.

In vitro cytocompatibility of a Zr-based metallic glass modified by laser surface texturing for potential implant applications

Existing studies have shown the benefit of laser surface texturing (LST) in promoting the cytocompatibility of traditional metallic biomaterials. Researchers have also reported the potential of bulk metallic glasses (BMGs) as an alternative class of material for biomedical applications. However, investigations specifically focussed on studying the cytocompatibility of BMG surfaces processed with LST are still lacking. The present work demonstrated the feasibility of nanosecond LST as a method to modify the cytocompatibility of a Zr-based BMG material known as Vitreloy 105. Two different types of laser-induced surface patterns, namely grooves and dimples, were considered. Their respective influence on the resulting cell viability, attachment and morphology was studied and compared against the cytocompatibility of the original BMG surface. It was found that MG63 osteoblast-like cells on the groove-textured surface exhibited higher viability and better adhesion compared to those on the original and dimple-textured surfaces. Possible underlying mechanisms associated with LST, which can affect the in vitro cytocompatibility of Vitreloy 105 were discussed based on the induced changes to surface chemistry, wettability and roughness. It is suggested that the higher surface roughness, increased presence of metallic oxides and enhanced hydrophilicity of the groove-textured sample were the main contributors to its improved cytocompatibility.

An Amorphous Spirobifluorene‐Phosphine‐Oxide Compound as the Balanced n‐Type Host in Bright and Efficient Light‐Emitting Electrochemical Cells with Improved Stability

AbstractA rational host–guest concept design for the attainment of high efficiency at strong luminance from light‐emitting electrochemical cells (LECs) by suppression of exciton‐polaron quenching [Tang et al., Nature Communications 2017, 8, 1190] has been reported. However, a practical drawback with the presented host–guest LEC devices was that the operational stability is insufficient for many applications. Here, a systematic study is performed, revealing that a major culprit for the limited operational stability is that the employed n‐type host, 1,3‐bis[2‐(4‐tert‐butylphenyl)‐1,3,4‐oxadiazo‐5‐yl]benzene (OXD‐7), has a strong propensity for crystallization and that this crystallization results in a detrimental phase separation of the constituents in the active material during device operation. The authors, therefore, identify an alternative class of concept‐functional n‐type hosts in the form of spirobifluorene‐phosphine‐oxide compounds, and report that the replacement of OXD‐7 with amorphous 2,7‐bis(diphenylphosphoryl)‐9,9′‐spirobifluorene results in a much improved operational lifetime of 700 h at &gt;100 cd m−2 during constant‐bias driving at an essentially retained high current efficacy of 37.9 cd A−1 and a strong luminance of 2940 cd m−2.

Chemically modified and conjugated antimicrobial peptides against superbugs.

Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied.