Currently, the main drivers for developing Li-ion batteries for efficient enery applications include energy density, cost, calendar life, and safety. The high energy/capacity anodes and cathodes needed for these applications is hindered by challengers like: 1) aging and degradation; 2) improved safety; 3) material costs, and 4) recyclability. The present begins by summarising the progress made from early Li-metal anode-based batteries to current commercial Li-ion batteries. Then discusses the recent progress made in studying and developing various types of materials for both anode and cathode electrodes, as well the various types of electrolytes and separator materials developed specifically for Li-ion battery operation. Battery management, handling and safety are also discussed at length. Also, as a consequence of the exponentially growth in the production of Li-ion batteries over the last ten years, the review identifies the challenge of dealing with the ever-increasing quantities of spent batteries. The review identifies the economic value of metals like Co and Ni contained with batteries and the extremely large numbers of batteries produced to date and the extremely large numbers that are expected to be manufactured in the next ten years. Thus, highlighting the need to develop effective recycling strategies to reduce the levels of mining for raw materials and prevents harmful products from entering the environment through landfill disposal.
L-Hexoses are key components of many biologically relevant natural products and pharmaceuticals. As rare sugars, L-hexoses are not readily obtained from natural sources. Access to L-hexose building blocks from commercially available and inexpensive D-sugars is highly desirable from the viewpoints of organic synthesis and drug discovery. As demonstrated by the convenient preparation of L-glucosyl, L-galactosyl, and L-mannosyl fluorides from readily available β-D-C-glucosyl, β-D-C-mannosyl, and β-D-C-galactosyl derivatives, we describe a novel and efficient approach to the demanding L-glycosyl fluorides. The transformation features the installation of anomeric hydroxymethyl group under mild conditions and head-to-tail inversion of sugar rings through radical decarboxylative fluorination of uronic acids. The power of this protocol is highlighted by the first assembly of a pentasaccharide repeating unit of Pseudomonas ATCC 31554 extracellular polysaccharide (S-88). This synthesis relies on the efficient extension of sugar chain at the sterically hindered hydroxy group and the facile introduction of L-mannosyl unit using L-mannosyl fluoride as glycosylating agent. The methods developed in this work would provide new tools to the arsenal of synthesis of L-sugar building blocks and of assembly of glycans containing L-sugar moieties.
On the basis of the mechanisms of action and characteristics of immune effects, immunity is generally divided into innate and adaptive immunity. Adaptive immunity is associated with the response to non-self entities and is characterized by high specificity and memory. In contrast, innate immunity is believed to lack memory. However, an increasing number of studies have sought to challenge this traditional immunological dogma and have shown that innate immune cells respond to secondary stimulation more strongly and rapidly than to the primary triggers, thus providing evidence of the immune memory in innate immunity. Macrophages, which are among the most important innate immune cells, can also acquire memory that facilitates the mediation of recall responses. Macrophage memory is a relatively new concept that is revolutionizing our understanding of macrophage biology and immunological memory and could lead to a new class of vaccines and immunotherapies. In this review, we describe the characteristics and mechanisms of macrophage memory, as well as its key roles in various diseases.
Laccases have shown to be efficient biocatalysts for the removal of recalcitrant pollutants from wastewater. Thus, they catalyse the oxidation of a wide variety of organic compounds by reducing molecular oxygen to water. However, the use of free laccases holds several drawbacks such as poor reusability, high cost, low stability and sensibility to different denaturing agents that may occur in wastewater. Such drawbacks can be circumvented by immobilising laccase enzymes in/on solid carriers. Hence, during the last decades different approaches considering various techniques and solid carriers to immobilise laccase enzymes have been developed and tested for the removal of pollutants from wastewater. To scale up wastewater treatment bioprocesses, the immobilised laccases are placed in different reactor configurations.
VO2(B) is considered as a promising anode material for the next-generation sodium-ion batteries (SIBs) due to its accessible raw materials and considerable theoretical capacity. However, the VO2(B) electrode has inherent defects such as low conductivity and serious volume expansion, which hinder their practical application. Herein, a flower-like VO2(B)/V2CTx (VO@VC) heterojunction was prepared by a simple hydrothermal synthesis method with in situ growth. The flower-like structure composed of thin nanosheets alleviates the volume expansion, as well as the rapid Na+ transport pathways are built by the heterojunction structure, resulting in long-term cycling stability and superior rate performance. At a current density of 100 mA g-1, VO@VC anode can maintain a specific capacity of 276 mAh g-1 with an average coulombic efficiency of 98.7% after 100 cycles. Additionally, even at a current density of 2 A g-1, the VO@VC anode still exhibited a capacity of 132.9 mAh g-1 for 1000 cycles. The enhanced reaction kinetics can be attribute to the fast Na+ adsorption and storage at interfaces, which has been confirmed by the experimental and theoretical methods. These results demonstrate that the tailored nanoarchitecture design and additional surface engineering are effective strategies for optimizing vanadium-based anode.
Transition from secukinumab to adalimumab in COVID-19-Induced psoriasis flare-up treatment: a case reportAbstract: Coronavirus disease 2019 (COVID-19) is known to trigger systemic inflammation and elicit immune responses, which may disrupt the delicate balance of cytokines involved in psoriatic regulation. Compared to other therapies in dermatology, biologics used for immune-mediated dermatological diseases have been more extensively studied during the COVID-19 pandemic. Herein, we report a case of flare-up of previously well-controlled psoriasis shortly after infection with COVID-19, with treatment transition from secukinumab to adalimumab.Keywords: COVID-19; psoriasis; flare-up; adalimumab; secukinumab
For decades, molecular biologists have been uncovering the mechanics of biological systems. Efforts to bring their findings together have led to the development of multiple databases and information systems that capture and present pathway information in a computable network format. Concurrently, the advent of modern omics technologies has empowered researchers to systematically profile cellular processes across different modalities. Numerous algorithms, methodologies, and tools have been developed to use prior knowledge networks in the analysis of omics datasets. Interestingly, it has been repeatedly demonstrated that the source of prior knowledge can greatly impact the results of a given analysis. For these methods to be successful it is paramount that their selection of prior knowledge networks is amenable to the data type and the computational task they aim to accomplish. Here we present a five-level framework that broadly describes network models in terms of their scope, level of detail, and ability to inform causal predictions. To contextualize this framework, we review a handful of network-based omics analysis methods at each level, while also describing the computational tasks they aim to accomplish.
The nests of ground-nesting birds rely heavily on camouflage for their survival, and predation pressures, often linked to human activity, are a major source of mortality. Numerous ground-nesting bird populations are in decline, so understanding the effects of camouflage on their nesting behaviour is of relevance to their conservation concern. Habitat three-dimensional (3D) geometry together with predator visual abilities, viewing distance, and viewing angle determine whether a nest is either visible, occluded or too far away to detect. While this link is intuitive, few studies have investigated how fine-scale geometry is likely to help defend nests from different predator guilds. We quantified nest visibility based on 3D occlusion, camouflage, and predator visual modelling in northern lapwing, Vanellus Vanellus, on different land management regimes. Lapwings selected local backgrounds that had a higher 3D complexity at a spatial scale greater than their entire clutches compared to nearby control sites. Importantly, our findings show that habitat geometry – rather than predator visual acuity restricts nest visibility to terrestrial predators, and that an open field would actually be perceived as a closed habitat to a terrestrial predator searching for nests on the ground. Taken together with lapwings’ careful nest site selection, our findings highlight the importance of considering habitat geometry for understanding the evolutionary ecology and management of conservation sites for ground-nesting birds.
Histopathology for tumor margin assessment is time-consuming and expensive. High-resolution full-field optical coherence tomography (FF-OCT) images fresh tissues rapidly at cellular resolution, facilitating evaluation. We imaged fresh ex vivo skin tissues (normal and neoplastic) from Mohs surgery. FF-OCT features were defined and diagnostic accuracy for malignancies was performed by the two experts OCT readers via a blinded analysis. A convolutional neural network was built to distinguish and outline normal structures and tumors. Of the 113 tissues imaged, 95 (84%) had a tumor (75 BCCs and 17 SCCs). The average reader diagnostic accuracy was 88.1%, a sensitivity of 93.7%, and a specificity of 58.3%. The AI model achieved a diagnostic accuracy of 87.6%±5.9%, sensitivity of 93.2%±2.1%, and specificity of 81.2%±9.2%. A mean intersection-over-union of 60.3%±10.1% was achieved delineating nodular BCC from normal. We envision FF-OCT for rapid evaluation of surgical margins and AI tumor detection leading to widespread technique integration.
The Astyanax mexicanus complex include two different morphs, a surface and a cave adapted ecotype, found at three mountain ranges in Northeastern Mexico: Sierra de El Abra, Sierra de Guatemala, and Sierra de la Colmena (Micos). Since their discovery, multiple studies have attempted to characterize the timing and the number of events that gave rise to the evolution of these cave-adapted ecotypes. Here, using RAD-seq and genome-wide sequencing, we assessed the phylogenetic relationships, genetic structure, and gene flow events between the cave and surface Astyanax mexicanus populations, to estimate the time and mode of evolution of the cave-adapted ecotypes. We also evaluated the body shape evolution across different cave lineages using geometric morphometrics to examine the role of phylogenetic signal vs. environmental pressures. We found strong evidence of parallel evolution of cave-adapted ecotypes derived from two separate lineages of surface fish and hypothesize that there may be up to four independent invasions of caves from surface fish. Moreover, a strong congruence between the genetic structure and geographic distribution was observed across the cave populations, with the Sierra de Guatemala the region exhibiting most genetic drift among the cave populations analyzed. Interestingly, we found no evidence of phylogenetic signal in body shape evolution, but we found support for parallel evolution in body shape across independent cave lineages, with cavefish from the Sierra de El Abra reflected the most divergent morphology relative to surface and other cavefish populations.
Introduction:Pericardial syndromes are not uncommon manifestations in clinical practice . About 5% of all patients admitted to the emergency department with the chief complaint of chest pain, are diagnosed with acute pericarditis . Cardiac involvement is a common presentation of different autoimmune rheumatic diseases. Systemic lupus erythematous (SLE) is a chronic autoimmune rheumatic disease with multiorgan involvement. Cardiac involvement has been reported in about 50% of SLE patients; in some cases, as their first presentation of SLE . The most common type of cardiac involvement in SLE patients is pericarditis . While it is classically known that SLE like most of other autoimmune diseases are more prevalent in women, cardiac involvement as pericarditis in SLE is more prevalent in male patients . Although being a common manifestation of SLE, it is uncommon for acute fibrinous pericarditis with constrictive features to be the first presentation of SLE in patients with severe manifestations and in need for hospital admission .
Dehydration of serine/threonine residues necessitates the activity of a dehydratase enzyme (domain) during the biosynthesis of ribosomally synthesized and post-translationally modified peptide (RiPP). Recently, it was reported that the dehydration process in thioviridamide relies on a distinct dehydratase complex which showcases the activities of a phosphotransferase TvaC for serine/threonine phosphorylation and a lyase TvaD for subsequent phosphate elimination. Herein, we report that the dehydration process of lantibiotic cacaoidin involves a similar dehydratase complex, CaoK/CaoY. Remarkably, this dehydratase complex exhibits flexible enzymatic activity and tolerates significant variations in its substrate peptide sequence. By binding with the leader peptide (LP) sequence of precursor peptide CaoA, the dehydration reactions proceed directionality from the C-terminus of the core peptide (CP) to its N-terminus, and C-terminally truncated variants of CP are acceptable. We show that fusing CaoK to CaoY in a 1:1 molar ratio enables the resulting enzyme CaoYK to exert enhanced dehydration activity. CaoK binds with the LP to improve its own solubility and to ensure the phosphate transfer activity, while CaoY functions independently of the LP. This work advances our understanding of the dehydration process of cacaoidin, and provides valuable enzymes and methods for the studies of the rapidly emerging RiPPs.
IntroductionCoronavirus belongs to RNA viruses that cause respiratory, neurologic, enteric, and hepatic diseases distributed among mammals, including humans and birds (1). A novel coronavirus discovered in late 2019 in China caused Coronavirus Disease 2019 (COVID-19). It is associated with complications like severe viral pneumonia, ARDS, AKI, cardiac injury, liver dysfunction, spontaneous pneumothorax, lung cavitation, pleural effusion, pericardial effusion, along with other minor ailments like fever, loss of smell, myalgia, dry cough, lymphadenopathy (2) (3).Pneumothorax due to COVID-19 pneumonia is very rare, and few cases are reported with bronchopleural fistula-associated persistent pneumothorax while recovering from COVID-19 pneumonia (4) (5) (6).
Electrocatalytic reduction of CO2 to fuels and chemicals possesses huge potential to alleviate current environmental crisis. Heteroatom doping in metal-nitrogen-carbon (M-N-C) single-atom catalysts (SACs) has been found capable to promote the electrocatalytic CO2 reduc-tion reaction (CO2RR). However, the origin of the enhanced activity is still elusive. Here, we report that sulfur-doped cobalt-nitrogen-carbon single-atom catalyst (Co1-SNC) exhibits superior CO2RR performance compared to sulfur-free counterpart (Co1-NC). On the basis of in situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), kinetic isotope effect (KIE) and theoretical calculation, it is demonstrated that sulfur doping can promote water activation, elevate the d-band center of Co active site, and reduce the free energy of *COOH intermediate formation. This work deepens the understanding of the CO2RR chemistry over heteroatom-doped SACs for designing efficient CO2RR processes.
Early Childhood Atopic Phenotypes and the Development of Allergic Respiratory DiseaseTo the Editor,Pediatric atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disorder that affects up to 20% of children worldwide1. Often the earliest sign of atopy, AD has been recognized as the start of the “atopic march”, described as the progression of AD to allergic respiratory diseases (ARD) including asthma and allergic rhinitis2. Although these atopic conditions often share a common T2 enriched pathway influenced by both genetic and environmental factors, not all children with AD have subsequent risk of ARD. Additionally, recent investigations dispute the theory that the temporal progression of the atopic march occurs in a sequential pattern3. Early AD can facilitate allergen sensitization due to a dysfunctional skin barrier4. Both aeroallergen and food sensitization has been associated with risk of ARD5, but it is less clear whether AD may partially mediate that risk. Additionally, food allergy has been recognized to be part of the atopic march, however its role in the march to ARD is less well identified. It is also unclear how these risks may appear in ethnically diverse populations. Distinct atopic phenotypes may better predict risk of ARD. Our objective was to identify whether associations between early food sensitization, aeroallergen sensitization, or food allergy (FA) and the subsequent risk of ARD by age 10 was modified by the development of early AD by age 2 years.We analyzed data from our racially and socioeconomically diverse birth cohort, Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) that enrolled pregnant women 21–45 years of age and their offspring. Recruitment period was from September 2003–December 2007. Eligibility and recruitment are described in previous publications 6 and all study protocols were approved by the Henry Ford Health System Institutional Review Board.Offspring sensitization to aeroallergens (Alternaria, cat, cockroach, dog, Dermatophagoides farina, ragweed, timothy grass), milk, egg, or peanut was determined at 2 years of age by sIgE≥0.35 IU/mL and skin prick testing (SPT; wheal size ≥3 mm larger than the saline control defined a positive test). As sensitization does not always translate to clinical allergy, we also formed an algorithm to determine those most likely to have true IgE-mediated food allergy7. Two allergists reviewed subjects with at least one of the following criteria: (1) at least one food (milk, egg or peanut) with sIgE ≥0.35 IU/mL; (2) a positive SPT; or (3) parental report of infant symptoms potentially related to food allergy plus at least one sIgE >0.10 IU/mL. To standardize classifying infants to the presence of IgE-mediated food allergy (IgE-FA), physicians were asked to combine professional experience with investigator-developed protocols based on the Guidelines for the Diagnosis and Management of Food Allergy in the United States8. A third allergist independently reviewed and ruled on discordant decisions. Data on asthma and AR by age 10 diagnosed by the study physician was collected using clinical history, physical exam, spirometry, and methacholine test.Adjusted relative risk (aRR) was calculated using Poisson regression with robust error variance and following adjustment for sex, child’s race, parental history of asthma, parental history of AR, BMI z-score at age 2, delivery mode, 1-month breastfeeding status, prenatal indoor dog exposure, prenatal indoor cat exposure, and 1-month daycare status.Of the 1258 mother-child pairs enrolled in WHEALS, 347 had sufficient data for analyses (Supplemental Figure 1). Demographics are shown in Table 1. The overall rate of early AD by age 2 years was 25.4% (88 out of 347 subjects). Supplemental Table 1 shows the overall rates of asthma and allergic rhinitis by age 10 by 2-year AD status. AD by age 2 years significantly modified the association between FA at 3-5 years and the risk of ever having asthma by age 10 (p=0.027) (Figure 1). In the absence of AD, FA to milk, egg, or peanut was associated with an increased risk of ever having asthma (aRR 3.36(1.71, 6.58), p<0.001), while no difference was observed in the presence of AD (aRR 1.24(0.57, 2.68), p=0.99). Food sensitization in the absence of AD was associated with increased risk of ever asthma (aRR 2.04(1.03, 4.05), p=0.038), but was not associated with ever AR (aRR 1.10(0.81, 1.48), p=0.97). Food sensitization in the presence of AD was not associated with ever asthma (aRR 0.89(0.45,1.78), p=0.99) or ever allergic rhinitis (aRR 1.45(0.97-2.16), p=0.078).In terms of aeroallergen sensitization, AD by age 2 did not significantly modify the association between aeroallergen sensitization at age 2 and the risk of ARD by age 10. This was true for aeroallergen sensitization overall and when sub-analyzed by seasonal versus perennial (Table 2, Figure 1). However, among those without AD by age 2, perennial aeroallergen sensitization was associated with an increased risk of ever having asthma by age 10 (aRR 2.15 (1.06, 4.36), p=0.031). This association was not significant for those with AD by age 2 (aRR 1.68 (0.78, 3.63), p=0.26).Our findings among a racially and socioeconomically diverse birth cohort suggest that early AD modifies the relationship between FA and the risk of ever having asthma by age 10. However, the association between FA and increased risk of ever having asthma was only seen among those without AD by age 2, which does not support the previously reported atopic progression of disease as described by the atopic march. This held true after correcting for several environmental and parental factors that may increase risk of ARD in our cohort. Our findings may represent a distinct atopic phenotype more characteristic among non-White subgroups, as our cohort is 67% self-identified Black. Previous reports have highlighted the differences in AD phenotypes among ethnically diverse subgroups9. Additionally, recent reports highlight atopic trajectories differ among White and Black children, with Black children more likely to have asthma without FA, AR, or allergen sensitization10. Due to sample size, we were unable to assess the differing trajectories in whites versus blacks. However, because our cohort is composed of 64.8% black children, we believe that black race may be contributing to the outcomes of our study as previous studies have reported atopic trajectories that are different in Black children10. Future studies investigating these endotypes that differ by ethnicity would be beneficial to identify potential immunological markers that would guide therapies for ethnically diverse populations and allow appropriate anticipatory guidance.Keywords : Atopic march, atopic dermatitis, food allergy, food sensitization, aeroallergen sensitization, asthma, allergic rhinitisKey message: Identifying early atopic phenotypes may help identify later ARD risk. This study reiterates that the “march” is not always a chronological process, but rather a complex relationship between heterogenous allergic phenotypes.
The cellular uptake of drug carriers to the cytosol of a specific cell remains challenging, and a non-classical supramolecular strategy is motivated. Here, we select a model host-guest complex in which a diamino-viologen (VG) fluorescent tag was engulfed by cucurbituril (CB8) and covalently linked to alginate polysaccharides (ALG) as the modified drug vehicle. When adsorbed on the ALG surface, the encapsulation of VG was first confirmed utilizing FTIR and NMR spectroscopic methods. Solid optical measurements (DRS, PL, and TRPL) revealed emissive materials at around 650 nm and that CB8 enhanced the rigidity of the modified hydrogel. The molar composition of 2 to 1 for the complexation of VG to CB8 on the alginate surface and the thermal stabilities were also confirmed using TGA and DSC techniques. CB8 induced a dramatic decrease in the average size of the VGALG polysaccharides from 485 to 165 nm and a turnover in their charge from -19.8 to +14.4 mV. Flow cytometry with inhibitors of various endocytosis pathways was employed to track the cellular uptake across different blood cell types: human T-cell leukemia 1301 and peripheral blood mononuclear cells. Noticeably, complexation of VG to CB8 host on top of the sugar platform dramatically enhanced the internalization to 1301 cells (viz. from 1 to 99%) at a concentration of 1.8 mg/mL via caveolae-mediated endocytosis (CvME) because of the size reduction, turnover in the charge from negative to positive, and rigidity induction. These observations reveal a more profound understanding of the macrocyclic effects on drug delivery