Optimizing graphene content in scaffolds for evenly distributed crumpled MoS2paper wads as anodes for high-performance Li-ion batteries.

Lithium-ion batteries (LIBs) have revolutionized portable electronics, yet their conventional graphite anodes face capacity limitations. Integrating graphene and 3D molybdenum disulfide (MoS2) offers a promising solution. Ensuring a uniform distribution of 3D MoS2nanostructures within a graphene matrix is crucial for optimizing battery performance and preventing issues like agglomeration and capacity degradation. This study focuses on synthesizing a uniformly distributed paper wad structure by optimizing a composite of reduced graphene oxide RGO@MoS2through structural and morphological analyses. Three composites with varying graphene content were synthesized, revealing that the optimized sample containing 30 mg RGO demonstrates beneficial synergy between MoS2and RGO. The interconnected RGO network enhances reactivity and conductivity, addressing MoS2aggregation. Experimental results exhibit an initially superior capacity of 911 mAh g-1, retained at 851 mAh g-1even after 100 cycles at 0.1 A g-1current density, showcasing improved rate efficiency and long-term stability. This research underscores the pivotal role of graphene content in customizing RGO@MoS2composites for enhanced LIB performance.

Milk replacer feeding once or twice a day did not change the ruminal metabolomic profile and the microbial diversity of dairy calves from birth to weaning.

In commercial dairy production systems, feeding calves once a day could be an alternative to reduce labor expenses. Several studies comparing once (OAD) versus twice (TAD) a day milk feeding systems have not evidenced differences in calf growth, rumen development, blood parameters or health scores, but impact on ruminal microbiota remains to be investigated. The objective of this study was to determine the effects of OAD or TAD on the establishment of the ruminal microbiota and its metabolic activity. Sixteen male calves (45.9 ± 5.7 kg at birth) were involved in the trial from birth to weaning (63 d). After the colostrum phase, 2 feeding programs based on a milk replacer were tested and calves were allocated to these programs on d 5. To study the establishment of the bacterial community, ruminal fluid was obtained from each calf one hour after the morning meal at 7 (d 7), 35 (d 35) and 63 (d 63) days of age. The ruminal metabolome was evaluated at a 7 d interval from d 1 to d 63. Ruminal microbiota and metabolite profiles were characterized by 16 S rRNA gene sequencing- and by H-NMR spectroscopy, respectively. Our results showed that feeding milk replacer once or twice a day did not change the ruminal microbiota and metabolites of dairy calves from birth to weaning. Microbial data showed that diversity and richness increased with age, suggesting a shift from an heterogeneous and less diverse community after birth (d 7) to a more diverse but homogeneous community at 35 and 63 d. These findings suggest that feeding milk once a day can be successfully applied to a calf feeding system without compromising microbial establishment and functions.

Stereodivergent, Kinetically Controlled Isomerization of Terminal Alkenes via Nickel Catalysis.

Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal-catalyzed olefin mono-transposition (i.e., positional isomerization) approaches have emerged to afford valuable E- or Z- internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel-catalyzed platform for the stereodivergent E/Z-selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one-carbon transposition of terminal alkenes to valuable E- or Z-internal alkenes via a Ni-H-mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with the Z-selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and the E-selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over-isomerization.

Single-Molecule DNA Methylation Reveals Unique Epigenetic Identity Profiles of T Helper Cells.

Both identity and plasticity of CD4 T helper (Th) cells are regulated in part by epigenetic mechanisms. However, a method that reliably and readily profiles DNA base modifications is still needed to finely study Th cell differentiation. Cytosine methylation in CpG context (5mCpG) and cytosine hydroxymethylation (5hmCpG) are DNA modifications that identify stable cell phenotypes, but their potential to characterize intermediate cell transitions has not yet been evaluated. To assess transition states in Th cells, we developed a method to profile Th cell identity using Cas9-targeted single-molecule nanopore sequencing. Targeting as few as 10 selected genomic loci, we were able to distinguish major in vitro polarized murine T cell subtypes, as well as intermediate phenotypes, by their native DNA 5mCpG patterns. Moreover, by using off-target sequences, we were able to infer transcription factor activities relevant to each cell subtype. Detection of 5mCpG and 5hmCpG was validated on intestinal Th17 cells escaping transforming growth factor ß control, using single-molecule adaptive sampling. A total of 21 differentially methylated regions mapping to the 10-gene panel were identified in pathogenic Th17 cells relative to their nonpathogenic counterpart. Hence, our data highlight the potential to exploit native DNA methylation profiling to study physiological and pathological transition states of Th cells.

Electrochemically Driven Nickel-Catalyzed Halogenation of Unsaturated Halide and Triflate Derivatives.

A robust electrochemically driven nickel-catalyzed halogen exchange of unsaturated halides and triflates (Br to Cl, I to Cl, I to Br, and OTf to Cl) is reported. A combination of NiCl2 ⋅ glyme as the precatalyst, 2,2'-bipyridine as a ligand, NMP as the solvent, and electrochemistry allowed the generation of a nickel species that promotes reductive elimination of the desired product. This paired electrochemical halogenation is compatible with a range of unsaturated halides and triflates, including heterocycles, dihaloarenes, and alkenes with good functional-group tolerance. Joint experimental and theoretical mechanistic investigations highlighted three catalytic events: i) oxidative addition of the aryl halide to a Ni(0) species to deliver a Ni(II) intermediate; ii) halide metathesis at Ni(II); iii) electrochemical oxidation of Ni(II) to Ni(III) to enable the formation of the desired aryl halide upon reductive elimination. This methodology allows the replacement of heavy halogens (I or Br) or polar atoms (O) with the corresponding lighter and more lipophilic Cl group to block undesired reactivity or modify the properties of drug and agrochemical candidates.

Electroreductive Synthesis of Nickel(0) Complexes.

Over the last fifty years, the use of nickel catalysts for facilitating organic transformations has skyrocketed. Nickel(0) sources act as useful precatalysts because they can enter a catalytic cycle through ligand exchange, without needing to undergo additional elementary steps. However, most Ni(0) precatalysts are synthesized with stoichiometric aluminum-hydride reductants, pyrophoric reagents that are not atom-economical and must be used at cryogenic temperatures. Here, we demonstrate that Ni(II) salts can be reduced on preparative scale using electrolysis to yield a variety of Ni(0) and Ni(II) complexes that are widely used as precatalysts in organic synthesis, including bis(1,5-cyclooctadiene)nickel(0) [Ni(COD)2 ]. This method overcomes the reproducibility issues of previously reported methods by standardizing the procedure, such that it can be performed anywhere in a robust manner. It can be transitioned to large scale through an electrochemical recirculating flow process and extended to an in situ reduction protocol to generate catalytic amounts of Ni(0) for organic transformations. We anticipate that this work will accelerate adoption of preparative electrochemistry for the synthesis of low-valent organometallic complexes in academia and industry.

Synthesis of Fluorinated Amines: A Personal Account.

This Account highlights the recent contributions made by our laboratory in the development of novel strategies to synthesize fluorinated amines. These strategies allow the practitioner to efficiently access carbamoyl fluorides, thiocarbamoyl fluorides as well as trifluoromethylamines using CO2 or CS2 as benign C1 sources. In addition, a novel N(SCF3)CF3 moiety was synthesized. Noteworthy, we demonstrated that this reagent could also be used in radical- or electrophilic-based trifluoromethylthiolation reactions.

Intrinsic factors and CD1d1 but not CD1d2 expression levels control invariant natural killer T cell subset differentiation.

Invariant natural killer T (NKT) cell subsets are defined based on their cytokine-production profiles and transcription factors. Their distribution is different in C57BL/6 (B6) and BALB/c mice, with a bias for NKT1 and NKT2/NKT17 subsets, respectively. Here, we show that the non-classical class I-like major histocompatibility complex CD1 molecules CD1d2, expressed in BALB/c and not in B6 mice, could not account for this difference. We find however that NKT cell subset distribution is intrinsic to bone marrow derived NKT cells, regardless of syngeneic CD1d-ligand recognition, and that multiple intrinsic factors are likely involved. Finally, we find that CD1d expression levels in combination with T cell antigen receptor signal strength could also influence NKT cell distribution and function. Overall, this study indicates that CD1d-mediated TCR signals and other intrinsic signals integrate to influence strain-specific NKT cell differentiation programs and subset distributions.

Epidemiology of Chronic Dermatologic Conditions in Skin of Color.

Across the board, common dermatologic conditions disproportionately affect patients of color. While the causes of these disparities have been tied to the environment, societal structure, access to care, health literacy, and biological factors, there is limited understanding of the extent and impact of dermatologic healthcare inequity. This study provides a resource on the epidemiology of common dermatologic diseases across racial lines and points out current lapses in scientific understanding of the disparate impact of certain conditions. This study will review epidemiological data on atopic dermatitis (AD), adult acne, pseudofolliculitis, dermatophytosis, psoriasis, vitiligo, melasma, hyperpigmentation, keloids, hidradenitis suppurativa (HS), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. J Drugs Dermatol. 2023;22(11):e21-e23    doi:10.36849/JDD.7131e.

Visualizing and Manipulating Olfactory Cilia Through Viral Delivery Coupled with En Face Imaging of Intact OE.

Olfactory cilia are the obligate transducers of the odorant signal, and thus their study has been a focus of investigation in the olfactory field. Various methodologies have been established to visualize the cilia of olfactory sensory neurons; however, these approaches are limited to static imaging and often lack the ability to resolve individual cilia projecting from solitary neurons in the postnatal mouse. Here we detail a procedure of the visualization of olfactory cilia by ectopic expression of fluorescently tagged proteins. The procedure can be used for the observation and manipulation of the olfactory cilia and ciliary proteins in both static and dynamic conditions.

An electroaffinity labelling platform for chemoproteomic-based target identification.

Target identification involves deconvoluting the protein target of a pharmacologically active, small-molecule ligand, a process that is critical for early drug discovery yet technically challenging. Photoaffinity labelling strategies have become the benchmark for small-molecule target deconvolution, but covalent protein capture requires the use of high-energy ultraviolet light, which can complicate downstream target identification. Thus, there is a strong demand for alternative technologies that allow for controlled activation of chemical probes to covalently label their protein target. Here we introduce an electroaffinity labelling platform that leverages the use of a small, redox-active diazetidinone functional group to enable chemoproteomic-based target identification of pharmacophores within live cell environments. The underlying discovery to enable this platform is that the diazetidinone can be electrochemically oxidized to reveal a reactive intermediate useful for covalent modification of proteins. This work demonstrates the electrochemical platform to be a functional tool for drug-target identification.

Spatial ecology to strengthen invasive snake management on islands.

Knowledge on the spatial ecology of invasive predators positively contributes to optimizing their management, especially when involving cryptic and secretive species, such as snakes. However, this information is lacking for most invasive snakes, particularly on islands, where they are known to cause severe ecological and socio-economic impacts. This research is focused on assessing the spatial ecology of the California kingsnake (Lampropeltis californiae) on Gran Canaria to strengthen management actions. We monitored 15 radio-tagged individuals once per day on 9-11 days per month from July 2020 to June 2021 to calculate the species' home range and describe annual activity patterns in the invaded range. To account for the species' diel activity during the emergence period, we additionally monitored snakes from January to May 2021 during three consecutive days per month in four different time intervals each day. We detected movement (consecutive detections at least 6 m apart) in 31.68% of the 1146 detections during the whole monitoring period. Movements most frequently detected were shorter than 100 m (82.24%), and among them the range 0-20 m was the most recurrent (27.03%). The mean distance of movement was 62.57 ± 62.62 m in 1-2 days. Average home range was 4.27 ± 5.35 ha-calculated with the Autocorrelated Kernel Density Estimator (AKDE) at 95%-and did not significantly vary with SVL nor sex. We detected an extremely low value of motion variance (0.76 ± 2.62 σ2m) compared to other studies, with a general inactivity period from November to February, January being the less active month of the year. Diel activity was higher during central and evening hours than during early morning and night. Our results should be useful to improve control programs for this invasive snake (e.g., trap placement and visual survey guidance) on Gran Canaria. Our research highlights the importance of gathering spatial information on invasive snakes to enhance control actions, which can contribute to the management of secretive invasive snakes worldwide.

Novel N(SCF3)(CF3)-amines: synthesis, scalability and stability.

We disclosed herein a straightforward strategy for the synthesis of unprecedented N-((trifluoromethyl)thio), N-(trifluoromethyl) amines using a combination of isothiocyanates with a fluoride source and an electrophilic trifluoromethylthiolation reagent. More interestingly, the scalability of the methodology has been demonstrated and the stability of the new motif has been studied.

Population Genetic Structure and Diversity of Cryptic Species of the Plant Genus Macrocarpaea (Gentianaceae) from the Tropical Andes.

The Pleistocene climatic oscillations (PCO) that provoked several cycles of glacial-interglacial periods are thought to have profoundly affected species distribution, richness and diversity around the world. While the effect of the PCO on population dynamics at temperate latitudes is well known, considerable questions remain about its impact on the biodiversity of neotropical mountains. Here, we use amplified fragment length polymorphism molecular markers (AFLPs) to investigate the phylogeography and genetic structure of 13 plant species belonging to the gentian genus Macrocarpaea (Gentianaceae) in the tropical Andes. These woody herbs, shrubs or small trees show complex and potentially reticulated relationships, including cryptic species. We show that populations of M. xerantifulva in the dry system of the Rio Marañón in northern Peru have lower levels of genetic diversity compared to other sampled species. We suggest that this is due to a recent demographic bottleneck resulting from the contraction of the montane wet forests into refugia because of the expansion of the dry system into the valley during the glacial cycles of the PCO. This may imply that the ecosystems of different valleys of the Andes might have responded differently to the PCO.

Developmental treatments with Δ9- tetrahydrocannabinol and the MAGL inhibitor JZL184 persistently alter adult cocaine conditioning in contrasting ways.

Using a songbird, zebra finches, as a developmental drug abuse model we found previously that cannabinoid agonists administered during the sensorimotor period of vocal learning (50-75 days of age) persistently alter song patterns and cocaine responsiveness in adulthood. However, these effects were not produced in adults exposed to similar treatment regimens. Currently, we have used the MAGL inhibitor, JZL184, to test whether enhanced endocannabinoid signaling may similarly alter cocaine responsiveness. We found that, as expected and consistent with prior results, repeated developmental (but not adult) treatments with Δ9-tetrahydrocannabinol (THC, 3 mg/kg QD IM) resulted in increased time spent in cocaine-paired chambers. Unexpectedly and in contrast, repeated developmental JZL184 (4 mg/kg QD IM) treatments decreased time spent in cocaine-conditioned chambers. That is, young finches repeatedly treated with JZL184 avoided cocaine-paired chambers later in adulthood, while similar development treatments with THC had the opposite effect. To begin to identify brain regions that may underly this differential responsiveness we used c-Fos expression as a marker of neuronal activity. Differences in c-Fos expression patterns following placement of cocaine-conditioned finches into vehicle- vs. cocaine-paired chambers suggest distinct involvement of circuits through striatal and amygdaloid regions in respective effects of THC and JZL184. Results demonstrate that, like exogenous cannabinoid exposure, inhibition of MAGL activity during late post-natal development persistently alters behavior in adulthood. Contrasting effects of THC vs. MAGL inhibition with JZL184 suggests the latter alters development of brain regions to favor promotion of aversive rather than appetitive cocaine responsiveness later in adulthood.

The role of a ciliary GTPase in the regulation of neuronal maturation of olfactory sensory neurons.

Olfactory sensory neurons (OSNs) form embryonically and mature perinatally, innervating glomeruli and extending dendrites with multiple cilia. This process and its timing are crucial for odor detection and perception and continues throughout life. In the olfactory epithelium (OE), differentiated OSNs proceed from an immature (iOSN) to a mature (mOSN) state through well-defined sequential morphological and molecular transitions, but the precise mechanisms controlling OSN maturation remain largely unknown. We have identified that a GTPase, ARL13B, has a transient and maturation state-dependent expression in OSNs marking the emergence of a primary cilium. Utilizing an iOSN-specific Arl13b-null murine model, we examined the role of ARL13B in the maturation of OSNs. The loss of Arl13b in iOSNs caused a profound dysregulation of the cellular homeostasis and development of the OE. Importantly, Arl13b null OSNs demonstrated a delay in the timing of their maturation. Finally, the loss of Arl13b resulted in severe deformation in the structure and innervation of glomeruli. Our findings demonstrate a previously unknown role of ARL13B in the maturation of OSNs and development of the OE.

LEF1 Drives a Central Memory Program and Supports Antitumor Activity of Natural Killer T Cells.

Vα24-invariant natural killer T cells (NKT) possess innate antitumor properties that can be exploited for cancer immunotherapy. We have shown previously that the CD62L+ central memory-like subset of these cells drives the in vivo antitumor activity of NKTs, but molecular mediators of NKT central memory differentiation remain unknown. Here, we demonstrate that relative to CD62L- cells, CD62L+ NKTs express a higher level of the gene encoding the Wnt/ß-catenin transcription factor lymphoid enhancer binding factor 1 (LEF1) and maintain active Wnt/ß-catenin signaling. CRISPR/Cas9-mediated LEF1 knockout reduced CD62L+ frequency after antigenic stimulation, whereas Wnt/ß-catenin activator Wnt3a ligand increased CD62L+ frequency. LEF1 overexpression promoted NKT expansion and limited exhaustion following serial tumor challenge and was sufficient to induce a central memory-like transcriptional program in NKTs. In mice, NKTs expressing a GD2-specific chimeric-antigen receptor (CAR) with LEF1 demonstrated superior control of neuroblastoma xenograft tumors compared with control CAR-NKTs. These results identify LEF1 as a transcriptional activator of the NKT central memory program and advance development of NKT cell-based immunotherapy. See related Spotlight by Van Kaer, p. 144.

Coupling phenotypic changes to extinction and survival in an endemic prey community threatened by an invasive snake.

When facing novel invasive predators, native prey can either go extinct or survive through exaptation or phenotypic shifts (either plastic or adaptive). Native prey can also reflect stress-mediated responses against invasive predators, affecting their body condition. Although multiple native prey are likely to present both types of responses against a single invader, community-level studies are infrequent. The invasive California kingsnake (Lampropeltis californiae) a good example to explore invasive predators' effects on morphology and body condition at a community level, as this invader is known to locally extinct the Gran Canaria giant lizard (Gallotia stehlini) and to notably reduce the numbers of the Gran Canaria skink (Chalcides sexlineatus) and the Boettger's gecko (Tarentola boettgeri). By comparing a set of morphological traits and body condition (i.e. body index and ectoparasite load) between invaded and uninvaded areas for the three squamates, we found clear evidence of a link between a lack of phenotypic change and extinction, as G. stehlini was the single native prey that did not show morphological shifts. On the other side, surviving C. sexlineatus and T. boettgeri exhibited phenotypic differences in several morphological traits that could reflect plastic responses that contribute to their capacity to cope with the snake. Body condition responses varied among species, indicating the potential existence of simultaneous consumptive and non-consumptive effects at a community level. Our study further highlights the importance addressing the impact of invasive predators from a community perspective in order to gain a deeper understanding of their effect in native ecosystems.

Novel antigen-presenting cell imparts Treg-dependent tolerance to gut microbiota.

Establishing and maintaining tolerance to self-antigens or innocuous foreign antigens is vital for the preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (AIRE) have a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (Treg) cell development1-4. Within weeks of birth, a separate wave of Treg cell differentiation occurs in the periphery upon exposure to antigens derived from the diet and commensal microbiota5-8, yet the cell types responsible for the generation of peripheral Treg (pTreg) cells have not been identified. Here we describe the identification of a class of RORγt+ antigen-presenting cells called Thetis cells, with transcriptional features of both mTECs and dendritic cells, comprising four major sub-groups (TC I-TC IV). We uncover a developmental wave of Thetis cells within intestinal lymph nodes during a critical window in early life, coinciding with the wave of pTreg cell differentiation. Whereas TC I and TC III expressed the signature mTEC nuclear factor AIRE, TC IV lacked AIRE expression and was enriched for molecules required for pTreg generation, including the TGF-ß-activating integrin αvß8. Loss of either major histocompatibility complex class II (MHCII) or ITGB8 by Thetis cells led to a profound impairment in intestinal pTreg differentiation, with ensuing colitis. By contrast, MHCII expression by RORγt+ group 3 innate lymphoid cells (ILC3) and classical dendritic cells was neither sufficient nor required for pTreg generation, further implicating TC IV as the tolerogenic RORγt+ antigen-presenting cell with an essential function in early life. Our studies reveal parallel pathways for the establishment of tolerance to self and foreign antigens in the thymus and periphery, respectively, marked by the involvement of shared cellular and transcriptional programmes.