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Two-dimensional honeycomb antiferromagnets are promising materials class for realizing Kitaev quantum spin liquids. The signature of these materials includes anisotropic bond-dependent magnetic responses and persistent fluctuations in paramagnetic regime. Here, we propose Cu 3 Co 2 SbO 6 heterostructures as an intriguing candidate, wherein bond-dependent and frustrated spins interact with optical excitons. First-principles spin Hamiltonian calculations and in-plane anisotropic critical fields suggest strong frustration and dominant Kitaev exchange interactions. Optical spectroscopy reveals exciton coupled to frustrated magnetism, enabling optical detection of spin states. Spin-exciton coupling displays anisotropic responses to light polarization along the bond-parallel and the bond-perpendicular directions, highlighting Kitaev interactions and persistent short-range spin correlations above twice the Néel temperatures. The robustness of short-range spin fluctuations under magnetic fields underscores the stability of the spin-fluctuation region. Our results establish Cu 3 Co 2 SbO 6 as an attractive candidate for exploring quantum spin liquid, where the spin Hamiltonian and quasiparticle excitations can be probed and potentially controlled by light., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Protein inhibition via the traditional drug-designing approach has been shown to be an effective method for developing numerous small-molecule-based therapeutics. In the last decade, small inhibitors-guided protein degradation has arisen as an alternative method with the potential to fulfill the drug requirement for undruggable targets. Focal adhesion kinase (FAK) is a crucial modulator of the growth and spread of tumors, apart from it also acts as a scaffold for signaling of other proteins. FAK inhibitors have thus far had unsatisfactory results in clinical trials for cancer applications. Unlike prior attempts to control FAK expression, which were restricted to kinase domain inhibition with limited success in clinical research, protein degradation has the potential to concurrently disrupt FAK's kinase and scaffolding function. Recently, several FAK degraders were reported based on FAK Type I inhibitors using complex chemical synthesis approaches. Interestingly, recently a ternary complex was published revealing the binding mode of the FAK-PROTAC-E3 complex. This complex opens an avenue for the development of rational PROTAC design against FAK protein. Therefore, in the present study, we selected the most active Type I FAK inhibitor GSK2256098. The binding mode of the inhibitor prompted us to identify the most suitable analog for PROTAC design. We have identified a high-affinity analog that is suitable for PTOTAC design through the application of molecular docking (MD) and molecular dynamics simulations (MDS). Further based on the ternary FAK-PROTAC-E3 complex we build a binary complex FAK-Hit-E3-VHL between both proteins. Using the structure-based approach ten different potential FAK PROTACs candidates were designed. The stability of the complexes was analyzed using MDS and binding free energies were used to predict the binding affinity. Finally, based on desirable intermolecular interactions with the target and E3 ligase ProTAC4 was selected as the best candidate when compared with known FAK PROTAC GSK215., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Vibrio parahaemolyticus strain causing acute hepatopancreatic necrosis disease (AHPND) in shrimp secretes toxins A and B (PirA Vp /PirB Vp ). These toxins have been implicated in pathogenesis and are targets for developing anti-AHPND therapeutics or prophylactics that include passive immunization. We have previously reported that Ccombodies (recombinant hagfish variable lymphocyte receptor B antibodies; VLRB) targeting PirB Vp conferred protection against V. parahaemolyticus in shrimp when administered as a feed supplement. In this study, we screened a phage-displayed library of engineered VLRBs for PirA Vp -targeting Ccombodies that were mass-produced in a bacterial expression system. We then introduced these Ccombodies into the diet of Pacific white shrimp (Penaeus vannamei) over a seven-day period. Subsequently, the shrimp were exposed to a challenge with V. parahaemolyticus. Mortality rates were then observed and recorded over the following seven days. Administering shrimp feed supplemented with Ccombodies at a high dose (100 mg per 100 g feed) reduced mortality in recipient animals (2.96-5.19 %) statistically similar to mock-challenged control (1.48 %), but significantly different from the Ccombody-deficient control (74.81 %). This suggests that the Ccombodies provided strong protection against the bacterium. Feeding shrimp with a median dose (10 mg/100 g feed) gave statistically comparable low mortality (5.93-6.67 %) as the high dose. Reducing the Ccombody dose to 1 mg/100 g feed showed variable effects. Ccombody A2 showed mortality (11.85 %) significantly lower than that of the Ccombody-deficient group (74.81 %), suggesting that it can effectively protect against the bacterial challenge at a low dose. Our results demonstrate the ability of the phage-displayed VLRB library to generate antigen-specific Ccombodies rapidly and simply, with the expression of high protein levels in bacteria. The protective effect provided by these Ccombodies aligns with our earlier results, strongly supporting the use of VLRB antibodies as a substitute for IgY in passive immunoprophylaxis against AHPND in shrimp., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Wolverines are facultative scavengers that feed near the top of terrestrial food chains. We characterized concentrations of mercury and other trace elements in tissues of wolverine from a broad geographic area, representing much of their contemporary distribution in northwestern North America. We obtained tissues from 504 wolverines, from which mercury was measured on muscle (n = 448), kidney (n = 222), liver (n = 148), hair (n = 130), and brain (n = 52). In addition, methylmercury, seven trace elements (arsenic, cadmium, chromium, cobalt, lead, nickel, selenium), and arsenic compounds were measured on a subset of samples. Concentrations of mercury and other trace elements varied between tissues and were generally highest in kidney compared to brain, liver and muscle. Mercury was predominately as methylmercury in brain and muscle, but largely as inorganic mercury in liver and kidney. Mercury concentrations of hair were moderately correlated with those of internal tissues (Pearson r = 0.51-0.75, p ≤ 0.004), making hair a good non-lethal indicator of broad spatial or temporal differences in mercury exposure to wolverine. Arsenobetaine was the dominant arsenic compound identified in tissues, and arsenite, arsenocholine and dimethylarsinic acid were also detected. A preliminary risk assessment suggested the cadmium, lead, mercury, and selenium concentrations in our sample of wolverines were not likely to pose a risk of overt toxicological effects. This study generated a comprehensive dataset on mercury and other trace elements in wolverine, which will support future contaminants study of this northern terrestrial carnivore., (© 2024. Crown.)

Context: Cyclin-dependent kinase 9 (CDK9) plays a significant role in gene regulation and RNA polymerase II transcription under basal and stimulated conditions. The upregulation of transcriptional homeostasis by CDK9 leads to various malignant tumors and therefore acts as a valuable drug target in addressing cancer incidences. Ongoing drug development endeavors targeting CDK9 have yielded numerous clinical candidate molecules currently undergoing investigation as potential CDK9 modulators, though none have yet received Food and Drug Administration (FDA) approval., Methods: In this study, we employ in silico approaches including the molecular docking and molecular dynamics simulations for the virtual screening over the natural compounds library to identify novel promising selective CDK9 inhibitors. The compounds derived from the initial virtual screening were subsequently employed for molecular dynamics simulations and binding free energy calculations to study the compound's stability under virtual physiological conditions. The first-generation CDK inhibitor Flavopiridol was used as a reference to compare with our novel hit compound as a CDK9 antagonist. The 500-ns molecular dynamics simulation and binding free energy calculation showed that two natural compounds showed better binding affinity and interaction mode with CDK9 receptors over the reference Flavopiridol. They also showed reasonable figures in the predicted absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculations as well as in computational cytotoxicity predictions. Therefore, we anticipate that the proposed scaffolds could contribute to developing potential and selective CDK9 inhibitors subjected to further validations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Head and neck cancer ranks as the sixth-most common malignancy worldwide, characterized by high mortality and recurrence rates. Research studies indicate that molecular diagnostics play a crucial role in the early detection and prognostic evaluation of these diseases. This study aimed to identify potential biomarkers for head and neck cancer and elucidate their interactions with miRNAs and possible therapeutic drugs. Four drivers, namely, FN1 , IL1A , COL1A1 , and MMP9 , were identified using network biology and machine learning approaches. Gene set variation analysis (GSVA) showed that these genes were significantly involved in different biological processes and pathways, including coagulation, UV-response-down, apoptosis, NOTCH signaling, Wnt-beta catenin, and other signal pathways. The diagnostic value of these hub genes was validated using receiver operating characteristic (ROC) curves. The top interactive miRNAs, including miR-128-3p , miR-218-5p , miR-214-3p , miR-124-3p , miR-129-2-3p , and miR-1-3p , targeted the key genes. Furthermore, the interaction between the key genes and drugs was also identified. In summary, the key genes and miRNAs or drugs reported in this study might provide valuable information for potential biomarkers to increase the prognosis and diagnosis of head and neck cancer.

The jawless vertebrates (agnathans/cyclostomes) are ancestral animals comprising lampreys and hagfishes as the only extant representatives. They possess an alternative adaptive immune system (AIS) that uses leucine-rich repeats (LRR)-based variable lymphocyte receptors (VLRs) instead of the immunoglobulin (Ig)-based antigen receptors of jawed vertebrates (gnathostomes). The different VLR types are expressed on agnathan lymphocytes and functionally resemble gnathostome antigen receptors. In particular, VLRB is functionally similar to the B cell receptor and is expressed and secreted by B-like lymphocytes as VLRB antibodies that bind antigens with high affinity and specificity. The potential repertoire scale of VLR-based antigen receptors is believed to be at least comparable to that of Ig-based systems. VLR proteins inherently possess characteristics that render them excellent candidates for biotechnological development, including tractability to recombinant approaches. In recent years, scientists have explored the biotechnological development and utility of VLRB proteins as alternatives to conventional mammalian antibodies. The VLRB antibody platform represents a non-traditional approach to generating a highly diverse repertoire of unique antibodies. In this review, we first describe some aspects of the biology of the AIS of the jawless vertebrates, which recognizes antigens by means of unique receptors. We then summarize reports on the development of VLRB-based antibodies and their applications, particularly those from the inshore hagfish (Eptatretus burgeri) and their potential uses to address microbial diseases in aquaculture. Hagfish VLRB antibodies (we call Ccombodies) are being developed and improved, while obstacles to the advancement of the VLRB platform are being addressed to utilize VLRBs effectively as tools in immunology. VLRB antibodies for novel antigen targets are expected to emerge to provide new opportunities to tackle various scientific questions. We anticipate a greater interest in the agnathan AIS in general and particularly in the hagfish AIS for greater elucidation of the evolution of adaptive immunity and its applications to address microbial pathogens in farmed aquatic animals and beyond., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Frog virus 3 (FV3) in the genus Ranavirus of the family Iridoviridae causes mass mortality in both anurans and urodeles worldwide; however, the phylogenetic origin of FV3-like ranaviruses is not well established. In Asia, three FV3-like ranaviruses have been reported in farmed populations of amphibians and reptiles. Here, we report the first case of endemic FV3-like ranavirus infections in the Korean clawed salamander Onychodactylus koreanus , caught in wild mountain streams in the Republic of Korea (ROK), through whole-genome sequencing and phylogenetic analysis. Two isolated FV3-like ranaviruses ( Onychodactylus koreanus ranavirus, OKRV1 and 2) showed high similarity with the Rana grylio virus (RGV, 91.5%) and Rana nigromaculata ranavirus (RNRV, 92.2%) but relatively low similarity with the soft-shelled turtle iridovirus (STIV, 84.2%) in open reading frame (ORF) comparisons. OKRV1 and 2 formed a monophyletic clade with previously known Asian FV3-like ranaviruses, a sister group of the New World FV3-like ranavirus clade. Our results suggest that OKRV1 and 2 are FV3-like ranaviruses endemic to the ROK, and RGV and RNRV might also be endemic strains in China, unlike previous speculation. Our data have great implications for the study of the phylogeny and spreading routes of FV3-like ranaviruses and suggest the need for additional detection and analysis of FV3-like ranaviruses in wild populations in Asian countries.

Climate change may affect the ability of hunters to harvest wildlife and, hence, threaten food security of local people. However, few studies have investigated the relative influence of environmental conditions on wildlife harvest rates. We harnessed a 24-year dataset of harvest dates for a boreal ungulate in a region where climate change is having pronounced impacts on snow depth, precipitation, and temperatures to investigate the effect of weather on harvest rates. We used generalized linear models and a model selection framework to examine the influence of weather covariates (snow depth, mean daily temperature, precipitation) and socio-economic factors (gasoline and red meat prices, employment rates, and moose [Alces americanus] harvest) on harvest rates of bison (Bison bison) in Yukon, Canada, at two temporal scales: annual and daily. At an annual scale, snow depth was the only covariate that was important in explaining bison harvest. No socioeconomic variables improved our model beyond the null. At the daily scale, snow depth and mean daily temperature influenced bison harvest rates, with a 1 SD increase resulting in a 14 % and 9 % increase in daily harvest rates, respectively. Increased snow depth facilitates ease of travel in remote, roadless areas by snowmobile to locate bison and truncates movements of bison, resulting in increased harvest rates. Decreased snow depth due to climate change will impact hunter access to boreal ungulates and food security for northern people. More broadly, our data suggests that in some socioecological systems, environmental covariates have a greater influence on wildlife harvest rates than socioeconomic factors and need to be considered in future studies to better understand and predict harvest rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Jung reports financial support was provided by Government of Yukon. Thomas Jung reports financial support was provided by Government of Canada. Michael J.L. Peers reports financial support was provided by Weston Family Foundation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fish diseases caused by viruses are a major threat to aquaculture. Development of disease protection strategies for sustainable fish aquaculture requires a better understanding of the immune mechanisms involved in antiviral defence. The innate and adaptive arms of the vertebrate immune system collaborate to mount an effective defence against viral pathogens. The T lymphocyte components of the adaptive immune system, comprising two major classes (helper T, Th or CD4 + and cytotoxic T lymphocytes, CTLs or CD8 + T cells), are responsible for cell-mediated immune responses. In particular, CD4 + T cells and their different subsets orchestrate the actions of various other immune cells during immune responses, making CD4 + T cells central drivers of responses to pathogens and vaccines. CD4 + T cells are also present in teleost fish. Here we review the literature that reported the use of antibodies against CD4 in a few teleost fish species and transcription profiling of Th cell-relevant genes in the context of viral infections and virus-relevant immunomodulation. Studies reveal massive CD4 + T cell proliferation and expression of key cytokines, transcription factors, and effector molecules that evoke mammalian Th cell responses. We also discuss gaps in the current understanding and evaluation of teleost CD4 + T cell responses and how development and application of novel tools and approaches to interrogate such responses could bridge these gaps. A greater understanding of fish Th cell responses will further illuminate the evolution of vertebrate adaptive immunity, inform strategies to address viral infections in aquaculture, and could further foster fish as model organisms., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In May 2015, a high mortality event in farmed rainbow trout occurred in Jeollabuk-do province in Korea. Histopathological analysis revealed necrosis in the kidney, liver, branchial arch, and gills of moribund fish, and infectious hematopoietic necrosis virus (IHNV) was detected in the lesions by immunohistochemistry. Cytopathic effects were observed in EPC, FHM, and RTG-2 cell lines after inoculation with kidney and spleen tissues and IHNV was detected by reverse transcription polymerase chain reaction (PCR). The amplified PCR product was sequenced, and phylogenetic analysis placed IHNV in the JRt Nagano group. Both in vivo and in vitro trials were performed to compare the virulence properties between RtWanju15 isolate, which causes 100% mortality in imported fry, and a previous isolate RtWanju09 of the JRt Shizuoka group isolated from eggs of healthy broodfish. In vivo challenge with high dose on specific pathogen free (SPF) rainbow trout fry performed in Denmark with isolates RtWanju09, RtWanju15 and DF04/99 isolates showed a survival rates of 60%, 37.5% and 52.5% (average), respectively without statistical difference. The replication efficiency of the two isolates in the in vitro challenge was similar., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Coronavirus disease 2019 (COVID-19) is a recent pandemic that caused serious global emergency. To identify new and effective therapeutics, we employed a drug repurposing approach. The poly (ADP ribose) polymerase inhibitors were used for this purpose and were repurposed against the main protease (Mpro) target of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The results from these studies were used to design compounds using the 'Grow Scaffold' modules available on Discovery Studio v2018. The three designed compounds, olaparib 1826 and olaparib 1885, and rucaparib 184 demonstrated better CDOCKER docking scores for Mpro than their parent compounds. Moreover, the compounds adhered to Lipinski's rule of five and demonstrated a synthetic accessibility score of 3.55, 3.63, and 4.30 for olaparib 1826, olaparib 1885, and rucaparib 184, respectively. The short-range Coulombic and Lennard-Jones potentials also support the potential binding of the modified compounds to Mpro. Therefore, we propose these three compounds as novel SARS-CoV-2 inhibitors., (© 2023. The Author(s).)

The assumption that activity and foraging are risky for prey underlies many predator-prey theories and has led to the use of predator-prey activity overlap as a proxy of predation risk. However, the simultaneous measures of prey and predator activity along with timing of predation required to test this assumption have not been available. Here, we used accelerometry data on snowshoe hares ( Lepus americanus ) and Canada lynx ( Lynx canadensis ) to determine activity patterns of prey and predators and match these to precise timing of predation. Surprisingly we found that lynx kills of hares were as likely to occur during the day when hares were inactive as at night when hares were active. We also found that activity rates of hares were not related to the chance of predation at daily and weekly scales, whereas lynx activity rates positively affected the diel pattern of lynx predation on hares and their weekly kill rates of hares. Our findings suggest that predator-prey diel activity overlap may not always be a good proxy of predation risk, and highlight a need for examining the link between predation and spatio-temporal behaviour of predator and prey to improve our understanding of how predator-prey behavioural interactions drive predation risk.

Limited information exists on mercury concentrations and environmental drivers of mercury bioaccumulation in high latitude terrestrial carnivores. Spatial patterns of mercury concentrations in wolverine (Gulo gulo, n = 419) were assessed across a 1,600,000 km2 study area in relation to landscape, climate, diet and biological factors in Arctic and boreal biomes of western Canada. Hydrogen stable isotope ratios were measured in wolverine hair from a subset of 80 animals to assess the spatial scale for characterizing environmental conditions of their habitat. Habitat characteristics were determined using GIS methods and raster datasets at two scales, the collection location point and a 150 km radius buffer, which was selected based on results of a correlation analysis between hydrogen stable isotopes in precipitation and wolverine hair. Total mercury concentrations in wolverine muscle ranged >2 orders of magnitude from 0.01 to 5.72 μg/g dry weight and varied geographically, with the highest concentrations in the Northwest Territories followed by Nunavut and Yukon. Regression models at both spatial scales indicated diet (based on nitrogen stable isotope ratios) was the strongest explanatory variable of mercury concentrations in wolverine, with smaller though statistically significant contributions from landscape variables (soil organic carbon, percent cover of wet area, percent cover of perennial snow-ice) and distance to the Arctic Ocean coast. The carbon and nitrogen stable isotope ratios of wolverine muscle suggested greater mercury bioaccumulation could be associated with feeding on marine biota in coastal habitats. Landscape variables identified in the modelling may reflect habitat conditions which support enhanced methylmercury transfer to terrestrial biota. Spatially-explicit estimates of wet atmospheric deposition were positively correlated with wolverine mercury concentrations but this variable was not selected in the final regression models. These landscape patterns provide a basis for further research on underlying processes enhancing methylmercury uptake in high latitude terrestrial food webs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Peraza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Time reversal symmetry (TRS) breaking often generates exotic quantum phases in condensed matter. In superconductors, TRS breaking by an external magnetic field not only suppresses superconductivity but also leads to a novel quantum state called the gapless superconducting state. Here we show that magneto-terahertz spectroscopy provides us with a rare opportunity to access and explore the gapless superconducting state of Nb thin films. We present the complete functional form of the superconducting order parameter for an arbitrary magnetic field, for which a fully self-consistent theory is, surprisingly, yet unavailable. We observe a Lifshitz topological phase transition with a vanishing quasiparticle gap everywhere on the Fermi surface, whereas the superconducting order parameter smoothly crosses over from the gapped to the gapless regime. Our observation of the magnetic pair-breaking effects in Nb challenges traditional perturbative theories and opens a pathway to further exploring and manipulating the exotic state of gapless superconductivity., (© 2023. The Author(s).)

Some mammal species inhabiting high-latitude biomes have evolved a seasonal moulting pattern that improves camouflage via white coats in winter and brown coats in summer. In many high-latitude and high-altitude areas, the duration and depth of snow cover has been substantially reduced in the last five decades. This reduction in depth and duration of snow cover may create a mismatch between coat colour and colour of the background environment, and potentially reduce the survival rate of species that depend on crypsis. We used long-term (1977-2020) field data and capture-mark-recapture models to test the hypothesis that whiteness of the coat influences winter apparent survival in a cyclic population of snowshoe hares ( Lepus americanus ) at Kluane, Yukon, Canada. Whiteness of the snowshoe hare coat in autumn declined during this study, and snowshoe hares with a greater proportion of whiteness in their coats in autumn survived better during winter. However, whiteness of the coat in spring did not affect subsequent summer survival. These results are consistent with the hypothesis that the timing of coat colour change in autumn can reduce overwinter survival. Because declines in cyclic snowshoe hare populations are strongly affected by low winter survival, the timing of coat colour change may adversely affect snowshoe hare population dynamics as climate change continues.

We have conducted a terahertz spectroscopic study and a density functional theory analysis of the phonon dynamics of the layered van der Waals semiconductors Nb 3 Cl 8 and Nb 3 I 8 . Several infrared-active phonon modes were observed in the terahertz region, and their frequencies were found to be in excellent agreement with our first-principles lattice dynamics calculations. For Nb 3 Cl 8 , the observed phonon spectra are consistent with a structural transition at 90 K from the high-temperature P 3̅ m 1 phase to the low-temperature R 3̅ m phase. Also, our study confirmed that the structural and magnetic transitions were coupled in Nb 3 Cl 8 . For Nb 3 I 8 , which is nonmagnetic at and below room temperature, no significant temperature or magnetic field dependence was observed in the phonon spectra. Our study provides an intriguing connection between the structural properties and the paramagnetic-nonmagnetic transitions in Nb 3 Cl 8 and Nb 3 I 8 ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Climate warming is causing asynchronies between animal phenology and environments. Mismatched traits, such as coat color change mismatched with snow, can decrease survival. However, coat change does not serve a singular adaptive benefit of camouflage, and alternate coat change functions may confer advantages that supersede mismatch costs. We found that mismatch reduced, rather than increased, autumn mortality risk of snowshoe hares in Yukon by 86.5% when mismatch occurred. We suggest that the increased coat insulation and lower metabolic rates of winter-acclimatized hares confer energetic advantages to white mismatched hares that reduce their mortality risk. We found that white mismatched hares forage 17-77 min less per day than matched brown hares between 0°C and -10°C, thus lowering their predation risk and increasing survival. We found no effect of mismatch on spring mortality risk, during which mismatch occurred at warmer temperatures, suggesting a potential temperature limit at which the costs of conspicuousness outweigh energetic benefits., (© 2022 The Ecological Society of America.)

Tuberculosis (TB) in one of the dreadful diseases present globally. This is caused by Mycobacterium tuberculosis . Mycobacterium tuberculosis dethiobiotin synthetase ( Mt DTBS) is an essential enzyme in biotin biosynthesis and is an ideal target to design and develop novel inhibitors. In order to effectively combat this disease six natural compound (butein) analogues were subjected to molecular docking to determine their binding mode and the binding affinities. The resultant complex structures were subjected to 500 ns simulation run to estimate their binding stabilities using GROMACS. The molecular dynamics simulation studies provided essential evidence that the systems were stable during the progression of 500 ns simulation run. The root mean square deviation (RMSD) of all the systems was found to be below 0.3 nm stating that the systems are well converged. The radius of gyration (Rg) profiles indicated that the systems were highly compact without any major fluctuations. The principle component analysis (PCA) and Gibbs energy landscape studies have revealed that the comp3, comp5 and comp11 systems navigated marginally through the PC2. The intermolecular interactions have further demonstrated that all the compounds have displayed key residue interactions, firmly holding the ligands at the binding pocket. The residue Lys37 was found consistently to interact with all the ligands highlighting its potential role in inhibiting the Mt DTBS. Our investigation further put forth two novel compounds (comp10 and comp11) as putative antituberculosis agents. Collectively, we propose six compounds has plausible inhibitors to curtail TB and further can act as scaffolds in designing new compounds., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Abnormal foot posture and poor muscle performance are potential causes of plantar fasciitis (PF). However, no study has compared the differences between lower extremity muscle performance and foot pressure in patients who have PF with and without abnormal foot postures. This study aimed to compare the differences in lower extremity muscle performance, such as in the hip, quadriceps, hamstring, and plantar flexor, and foot pressure in patients who have PF with and without flat foot postures. Seventy patients with plantar heel pain were enrolled (37 flat feet and 33 without flat feet). The hip muscle strength was measured using a handheld digital dynamometer. The strength and reaction time of the quadriceps, hamstring, and plantar flexor muscles were evaluated using an isokinetic device. Foot pressure parameters were assessed using pedobarography. The strength of the plantar flexor muscles was significantly lower ( p = 0.008), while the reaction time of the plantar flexor muscles was significantly faster ( p = 0.007) for the involved feet of PF patients with flat feet than in those without flat feet. This study confirmed the differences in muscle performance between patients who have PF with different foot postures. Therefore, clinicians and therapists should plan treatment considering the differences in these characteristics for the management of these patients.

Cysteine-cysteine chemokine receptor 5 (CCR5) has been discovered as a co-receptor for cellular entry of human immunodeficiency virus (HIV). Moreover, the role of CCR5 in a variety of cancers and various inflammatory responses was also discovered. Despite the fact that several CCR5 antagonists have been investigated in clinical trials, only Maraviroc has been licensed for use in the treatment of HIV patients. This indicates that there is a need for novel CCR5 antagonists. Keeping this in mind, the present study was designed. The active CCR5 inhibitors with known IC 50 value were selected from the literature and utilized to develop a ligand-based common feature pharmacophore model. The validated pharmacophore model was further used for virtual screening of drug-like databases obtained from the Asinex, Specs, InterBioScreen, and Eximed chemical libraries. Utilizing computational methods such as molecular docking studies, molecular dynamics simulations, and binding free energy calculation, the binding mechanism of selected inhibitors was established. The identified Hits not only showed better binding energy when compared to Maraviroc, but also formed stable interactions with the key residues and showed stable behavior throughout the 100 ns MD simulation. Our findings suggest that Hit1 and Hit2 may be potential candidates for CCR5 inhibition, and, therefore, can be considered for further CCR5 inhibition programs.

Chiral fermions (CFs) in condensed matters, distinguished by right (+) or left (-) handedness, hold a promise for emergent quantum devices. Although a chiral anomaly induced current, J chiral = J (+) - J (-), occurs in Weyl semimetals due to the charge imbalance of the CFs, monitoring spatial flow and temporal dynamics of J chiral has not been demonstrated yet. Here, we report real-space imaging and control of J chiral on the topological Dirac semimetal KZnBi at room temperature (RT) by near-field terahertz (THz) spectroscopy, establishing a relation for an electromagnetic control of J chiral . In THz electric and external magnetic fields, we visualize a spatial flow of coherent J chiral in macroscopic length scale and monitor its temporal dynamics in picosecond time scale, revealing its ultralong transport length around 100 micrometers. Such coherent J chiral is further found to be controlled according to field directions, suggesting the feasibility of information science with topological Dirac semimetals at RT.

Listeria monocytogenes is a foodborne pathogen that can cause a potentially life-threatening infection, and almost all cases of human listeriosis are caused by L. monocytogenes isolates in serotypes 1/2a, 1/2b, 1/2c, and 4b. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid, accurate, and high-throughput tool for clinical diagnosis and microbiological research. In the current study, we examined the potential of MALDI-TOF MS for rapid identification of the foodborne pathogen L. monocytogenes and to identify high-risk serotypes. To achieve this, MALDI-TOF MS was applied to 50 L monocytogenes strains. All strains were identified as L. monocytogenes species based on pattern matching against reference spectra for the species. Importantly, 83 specific mass ions were consistently and uniquely found in high-risk L. monocytogenes serotypes 1/2a, 1/2b, 1/2c, and 4b. These 83 mass ions were also unique to specific combinations of these serotypes, which enabled specific identification of these four serotypes using MALDI Biotyper analysis. Hence, this method shows potential for using MALDI-TOF MS for the rapid identification of L. monocytogenes species and to discriminate high-risk L. monocytogenes serotypes through specific serotype-specific biomarker ions., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Reduced food availability is implicated in declines in avian aerial insectivores, but the effect of nutritional stress on mammalian aerial insectivores is unclear. Unlike birds, insectivorous bats provision their young through lactation, which might protect nursing juveniles when prey availability is low but could increase the energetic burden on lactating females. We analyzed a 15-year capture-mark-recapture data set from 5312 individual little brown myotis (Myotis lucifugus) captured at 11 maternity colonies in northwestern Canada, to test the hypothesis that nutritional stress is impacting these mammalian aerial insectivores. We used long-bone (forearm [FA]) length as a proxy for relative access to nutrition during development, and body mass as a proxy for access to nutrition prior to capture. Average FA length and body mass both decreased significantly over the study period in adult females and juveniles, suggesting decreased access to nutrition. Effect sizes were very small, similar to those reported for declining body size in avian aerial insectivores. Declines in juvenile body mass were only observed in individuals captured in late summer when they were foraging independently, supporting our hypothesis that lactation provides some protection to nursing young during periods of nutritional stress. Potential drivers of the decline in bat size include one or both of (1) declining insect (prey) abundance, and (2) declining prey availability. Echolocating insectivorous bats cannot forage effectively during rainfall, which is increasing in our study area. The body mass of captured adult females and juveniles in our study was lower, on average, after periods of high rainfall, and higher after warmer-than-average periods. Finally, survival models revealed a positive association between FA length and survival, suggesting a fitness consequence to declines in body size. Our study area has not yet been impacted by bat white-nose syndrome (WNS), but research elsewhere has suggested that fatter bats are more likely to survive infection. We found evidence for WNS-independent shifts in the body size of little brown myotis, which can inform studies investigating population responses to WNS. More broadly, the cumulative effects of multiple stressors (e.g., disease, nutritional stress, climate change, and other pressures) on mammalian aerial insectivores require urgent attention., (© 2022 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Spleen tyrosine kinase (SYK) is an essential mediator of immune cell signaling and has been anticipated as a therapeutic target for autoimmune diseases, notably rheumatoid arthritis, allergic rhinitis, asthma, and cancers. Significant attempts have been undertaken in recent years to develop SYK inhibitors; however, limited success has been achieved due to poor pharmacokinetics and adverse effects of inhibitors. The primary goal of this research was to identify potential inhibitors having high affinity, selectivity based on key molecular interactions, and good drug-like properties than the available inhibitor, fostamatinib. In this study, a 3D-QSAR model was built for SYK based on known inhibitor IC 50 values. The best pharmacophore model was then used as a 3D query to screen a drug-like database to retrieve hits with novel chemical scaffolds. The obtained compounds were subjected to binding affinity prediction using the molecular docking approach, and the results were subsequently validated using molecular dynamics (MD) simulations. The simulated compounds were ranked according to binding free energy (ΔG), and the binding affinity was compared with fostamatinib. The binding mode analysis of selected compounds revealed that the hit compounds form hydrogen bond interactions with hinge region residue Ala451, glycine-rich loop residue Lys375, Ser379, and DFG motif Asp512. Identified hits were also observed to form a desirable interaction with Pro455 and Asn457, the rare feature observed in SYK inhibitors. Therefore, we argue that identified hit compounds ZINC98363745, ZINC98365358, ZINC98364133, and ZINC08789982 may help in drug design against SYK., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumar, Parate, Danishuddin, Zeb, Singh, Lee, Jung, Lee and Ha.)

Lead (Pb) is a toxic element which is released as a result of anthropogenic activities, and Pb stable isotope ratios provide a means to distinguish sources and transport pathways in receiving environments. In this study, isotopes of bioaccumulated Pb ( 204 Pb, 206 Pb, 207 Pb, 208 Pb) were examined for diverse terrestrial and aquatic biota from three areas in western Canada: (a) otter, marten, gulls, terns, and wood frogs in the Alberta Oil Sands Region (AOSR), (b) fish, plankton, and gulls of Great Slave Lake (Yellowknife, Northwest Territories), and (c) wolverine from the Yukon. Aquatic and terrestrial biota from different habitats and a broad geographic area showed a remarkable similarity in their Pb isotope composition (grand mean ± 1 standard deviation: 206 Pb/ 207 Pb = 1.189 ± 0.007, 208 Pb/ 207 Pb = 2.435 ± 0.009, n = 116). Comparisons with Pb isotope ratios of local sources and environmental receptors showed that values in biota were most similar to those of atmospheric Pb, either measured in local aerosols influenced by industrial activities in the AOSR or in lichens (an aerosol proxy) near Yellowknife and in the Yukon. Biotic Pb isotope ratios were different from those of local geogenic Pb. Although the Pb isotope measurements could not unambiguously identify the specific anthropogenic sources of atmospheric Pb in biota, initial evidence points to the importance of fossil fuels currently used in transportation and power generation. Further research should characterize bioavailable chemical species of Pb in aerosols and important emission sources in western Canada., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Aim: Bacteria naturally produce membrane vesicles (MVs), which have been shown to contribute to the spread of multi-drug resistant bacteria (MDR) by delivering antibiotic-resistant substances to antibiotic-susceptible bacteria. Here, we aim to show that MVs from Gram-positive bacteria are capable of transferring β-lactam antibiotic-resistant substances to antibiotic-sensitive Gram-negative bacteria., Materials and Methods: MVs were collected from a methicillin-resistant strain of Staphylococcus aureus (MRSA) and vesicle-mediated fusion with antimicrobial-sensitive Escherichia coli (RC85). It was performed by exposing the bacteria to the MVs to develop antimicrobial-resistant E. coli (RC85-T)., Results: The RC85-T exhibited a higher resistance to β-lactam antibiotics compared to the parent strain. Although the secretion rates of the MVs from RC85-T and the parent strain were nearly equal, the β-lactamase activity of the MVs from RC85-T was 12-times higher than that of MVs from the parent strain, based on equivalent protein concentrations. Moreover, MVs secreted by RC85-T were able to protect β-lactam-susceptible E. coli from β-lactam antibiotic-induced growth inhibition in a dose-dependent manner., Conclusion: MVs play a role in transferring substances from Gram-positive to Gram-negative bacteria, shown by the release of MVs from RC85-T that were able to protect β-lactam-susceptible bacteria from β-lactam antibiotics., Significance and Impact of Study: MVs are involved in the emergence of antibiotic-resistant strains in a mixed bacterial culture, helping us to understand how the spread of multidrug-resistant bacteria could be reduced., (© 2022 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

Diarrheal diseases due to foodborne Escherichia coli are the leading cause of illness in humans. Here, we performed pathogenic typing, molecular typing, and antimicrobial susceptibility tests on seventy-five isolates of E. coli isolated from stool samples of patients suffering from foodborne diseases in Busan, South Korea. All the isolates were identified as E. coli by both biochemical analysis (API 20E system) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The bacteria displayed entero-pathogenic E. coli (EPEC) (47.0%), entero-aggregative E. coli (EAEC) (33.3%), entero-toxigenic E. coli (ETEC) (6.6%), ETEC and EPEC (6.6%), EPEC and EAEC (4%), and ETEC and EAEC (2.7%) characteristics. The E. coli isolates were highly resistant to nalidixic acid (44.0%), tetracycline (41.3%), ampicillin (40%), ticarcillin (38.7%), and trimethoprim/sulfamethoxazole (34.7%); however, they were highly susceptible to imipenem (98.6%), cefotetan (98.6%), cefepime (94.6%), and chloramphenicol (94.6%). Although 52 strains (69.3%) showed resistance against at least 1 of the 16 antibiotics tested, 23 strains (30.7%) were susceptible to all the antibiotics. Nine different serotypes (O166, O8, O20, O25, O119, O159, O28ac, O127a, and O18), five genotypes (I to V, random-amplified polymorphic DNA), and four phenotypes (A to D, MALDI-TOF MS) were identified, showing the high level of heterogeneity between the E. coli isolates recovered from diarrheal patients in South Korea.

The emergence of antimicrobial-resistant Staphylococcus aureus has become a grave concern worldwide. In this study, 95 strains of S. aureus isolated from stool samples were collected from Busan, South Korea to characterize their antimicrobial susceptibility, enterotoxin genes, and molecular typing using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and random amplification of polymorphic DNA (RAPD) assay. Only two strains showed no drug resistance, whereas resistance to three or more antibiotics was observed in 87.4% of strains. Ampicillin resistance was the most common at 90% and all strains were susceptible to vancomycin. The distribution of enterotoxin genes encoded in isolates was sea (32.6%), sec (11.6%), seg (19%), sea & sec (2.1%), and sec & seg (34.7%). Molecular typing using both MALDI-TOF MS and RAPD indicated that S. aureus exhibited diverse clonal lineages and no correlations were observed among the profiling of enterotoxin, MALDI-TOF MS, and RAPD. This investigation provides useful information on foodborne pathogenic S. aureus that has a significant public health impact in South Korea.

Throughout the ages, hair has had psychological and sociological importance in framing the personality and general appearance of an individual. Despite efforts to solve this problem, no groundbreaking measures have been proposed. Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Three fractions (F1, F2 and F3) were obtained after separation and purification of GAGs from ascidian tunics. F1 was observed to contain a small amount of amino sugar while high contents of galactose and N-acetylglucosamine were noted in F2 and F3. 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (∆Di-6S) and 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (∆Di-4S) were the main disaccharide components. F3 exhibited the highest proliferation activity on human follicle dermal papilla (HFDP) cells. In addition, mixed samples (FFM) of F2 and F3 at different concentrations showed peak activities for five days. After cell culture at a concentration of 10 mg/mL and dihydrotestosterone (DHT), the inhibition effect was higher than that for Minoxidil. Application of 10 mg of FFM to the hair of mice for 28 days resulted in a hair growth effect similar to that of Minoxidil, a positive control.

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha (IL2Rα) has been shown to influence immune responses. In the present research, using in silico techniques, we have demonstrated the potential IL2Rα binding properties of three polyphenol stilbenes (desoxyrhaponticin, rhaponticin, rhapontigenin) from fenugreek. As the first step, molecular docking was performed to assess the binding potential of the fenugreek phytochemicals with IL2Rα. All three phytochemicals demonstrated interactions with active site residues. To confirm the reliability of our molecular docking results, 100 ns molecular dynamics simulations studies were undertaken. As discerned by the RMSD and RMSF analyses, IL2Rα in complex with the desoxyrhaponticin, rhaponticin, and rhapontigenin indicated stability. The RMSD analysis of the phytochemicals alone also demonstrated no significant structural changes. Based on the stable molecular interactions and comparatively slightly better MM/PBSA binding free energy, rhaponticin seems promising. Additionally, ADMET analysis performed for the stilbenes indicated that all of them obey the ADMET rules. Our computational study thus supports further in vitro IL2Rα binding studies on these stilbenes, especially rhaponticin.

We aimed to analyze the differences in static (including conventional and modified [single-leg heel-raise balance]) and dynamic postural stability and muscle endurance between patients with chronic ankle instability (CAI) and healthy controls, and to determine the reliability and usefulness of the single-leg heel-raise balance test in patients with CAI. In total, 26 patients with CAI and 26 healthy controls were enrolled. Postural stability was assessed using a postural stabilometry system. Muscle endurance was measured in dorsiflexion and plantarflexion using an isokinetic device. Modified static postural stability (P < 0.001) and dynamic postural stability (P < 0.001) were significantly poorer in the affected ankles of patients with CAI than in the controls. Plantarflexion endurance was significantly lower in the affected ankles of the patients with CAI than in the controls (P = 0.023). Modified static postural stability significantly correlated with plantarflexion endurance in both groups (CAI group: r = - 0.470, P = 0.015; healthy controls group: r = - 0.413, P = 0.036). Plantarflexion endurance was a significant risk factor for modified static postural stability in both the CAI group (R 2  = 0.221, P = 0.015) and healthy controls (R 2  = 0.170, P = 0.036). Given the reliability of the modified static postural stability test, clinicians and therapists should consider using it to assess improvements in postural stability and muscle endurance in patients with CAI before and after rehabilitation., (© 2021. The Author(s).)

Chemokines are a superfamily of chemotactic cytokines that regulate the migration and immune responses of leukocytes. Depending on the arrangement of the first two cysteine residues, chemokines are divided into four groups: CXC (α), CC (β), C (γ), and CX3C (δ). Chemokine C-C motif ligand 34 (CCL34) is a member of the CC chemokine family and is known as a fish-specific CC chemokine. In this experiment, we analyzed the molecular cloning and characterization of the PoCCL34 gene in olive flounder (Paralichthys olivaceus), including CCL34a.3 (PoCCL34a.3) and CCL34b.3 (PoCCL34b.3). The amino acid sequence of PoCCL34 has four highly conserved cysteine residues and it has a C-C motif. Phylogenetic analysis revealed that PoCCL34 was phylogenetically clustered in the fish CCL34 subcluster. Recombinant PoCCL34 induced chemotaxis of head kidney leukocytes in a dose-dependent manner. Head kidney leukocytes stimulated with PoCCL34 also exhibited significant respiratory burst activity and increased expression of pro-inflammatory cytokines (IL-1β, IL-6, and CXCL8), but the overall expression of interferon-related genes (IFN-α/β, IFN-γ, Mx, and ISG15) did not increase. Olive flounder injected with recombinant PoCCL34 demonstrated increased expression of pro-inflammatory cytokines (IL-1β and IL-6) in the head kidney. However, there was no increase in the expression of interferon-related genes (IFN-α/β, IFN-γ, Mx, and ISG15). Additionally, recombinant PoCCL34 induced high lysozyme activity in the serum of the flounder. These results indicate that although PoCCL34 is not involved in the antiviral response, it may play a significant role in the overall immune response of the flounder, particularly in mediating the inflammatory response., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Realizing a state of matter in two dimensions has repeatedly proven a novel route of discovering new physical phenomena. Van der Waals (vdW) materials have been at the center of these now extensive research activities. They offer a natural way of producing a monolayer of matter simply by mechanical exfoliation. This work demonstrates that the possible multiferroic state with coexisting antiferromagnetic and ferroelectric orders persists down to the bilayer flake of NiI 2 . By exploiting the optical second-harmonic generation technique, both magnitude and direction of the ferroelectric order, arising from the cycloidal spin order, are successfully traced. The possible multiferroic state's transition temperature decreases from 58 K for the bulk to about 20 K for the bilayer. Our observation will spur extensive efforts to demonstrate multifunctionality in vdW materials, which have been tried mostly by using heterostructures of singly ferroic ones until now.

Terahertz spectroscopy can be utilized as an effective nondestructive identification tool for the study of artist's pigments. Consequently, extensive measurements have been conducted on representative pigment species, and a few terahertz spectral databases have been constructed. However, the reported spectra were often acquired from pigment samples mixed with polyethylene at room temperature with low resolution, which often led to low-quality spectra with unresolved overlapping lines further broadened due to thermal effects. Here, we present our study of vermilion (HgS, mercury sulfide) as an illustration of how we can overcome such difficulties by studying free-standing oil-paint samples at room temperature and then by performing low-temperature measurements on polyethylene-mixed samples to minimize line broadening due to thermal effects. Our results identify clearly resolved absorption peaks due to lattice vibrations of vermilion at 40.4, 44.5, and 89.9 cm -1 at 2 K. The temperature dependence of the peak shift and line broadening reveals anharmonic characteristics of these lattice vibrational modes. Our approach will definitely suggest new ways to improve and enhance existing terahertz spectral databases of ancient and modern pigments toward actual analysis, diagnosis, and conservation of heritage artworks., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Owing to their remarkable spin-charge conversion (SCC) efficiency, topological insulators (TIs) are the most attractive candidates for spin-orbit torque generators. The simple method of enhancing SCC efficiency is to reduce the thickness of TI films to minimize the trivial bulk contribution. However, when the thickness reaches the ultrathin regime, the SCC efficiency decreases owing to intersurface hybridization. To overcome these contrary effects, we induced dehybridization of the ultrathin TI film by breaking the inversion symmetry between surfaces. For the TI film grown on an oxygen-deficient transition-metal oxide, the unbonded transition-metal d-orbitals affected only the bottom surface, resulting in asymmetric surface band structures. Spintronic terahertz emission spectroscopy, an emerging tool for investigating the SCC characteristics, revealed that the resulting SCC efficiency in symmetry-broken ultrathin Bi 2 Se 3 was enhanced by up to ∼2.4 times.

Viral hemorrhagic septicemia (VHS), caused by viral hemorrhagic septicemia virus (VHSV), is a viral disease affecting teleosts, and is the major cause of virus-related deaths in olive flounder ( Paralichthys olivaceus ). Research has focused on ways to control VHS, and recently, the use of polyinosinic-polycytidylic acid poly (I:C)-potentiated vaccination has been investigated, whereby fish are injected with poly (I:C) and then with live pathogenic virus, resulting in a significant decrease in VHSV-related mortality. T cell responses were investigated in the present study after vaccinating olive flounder with poly (I:C)-potentiated vaccination to understand the ability of poly (I:C) to induce T cell immunity. Stimulation of T cell responses with the poly (I:C)-potentiated vaccination was confirmed by examining levels of CD3 + T cells, CD4-1 + T cells and CD4-2 + T cells. Higher levels of CD4-2 + T cells were found in vaccinated fish than CD4-1 + T cells, believed to result from a synergistic effect between poly (I:C) administration and pathogenic VHSV immunization. More importantly, the role of CD4-2 + T cells in the antiviral response was clearly evident. The results of this study suggest that the outstanding protection obtained with the poly (I:C)-potentiated vaccination is due to the robust immune response initiated by the CD4-2 + T cells.

Background: Species of Trichinella are globally important foodborne parasites infecting a number of domestic and wild vertebrates, including humans. Free-ranging carnivores can act as sentinel species for detection of Trichinella spp. Knowledge of the epidemiology of these parasites may help prevent Trichinella spp. infections in northern Canadian animals and people. Previous research on Trichinella spp. in wildlife from Yukon did not identify risk factors associated with infection, or the diversity and identity of species of Trichinella in regional circulation, based on geographically extensive sampling with large sample sizes., Methods: In a cross-sectional study, we determined the prevalence, infection intensity, risk factors, and species or genotypes of Trichinella in wolverine (Gulo gulo) in two regions of Yukon, Canada, from 2013-2017. A double separatory funnel digestion method followed by mutiplex PCR and PCR-RFLP were used to recover and identify species of Trichinella, respectively., Results: We found larvae of Trichinella in the tongues of 78% (95% CI 73-82) of 338 wolverine sampled. The odds of adult (≥ 2 years) and yearling (1 year) wolverine being Trichinella spp.-positive were four and two times higher, respectively, compared to juveniles (<1 year). The odds of Trichinella spp. presence were three times higher in wolverine from southeast than northwest Yukon. The mean intensity of infection was 22.6 ± 39 (SD, range 0.1-295) larvae per gram. Trichinella T6 was the predominant genotype (76%), followed by T. nativa (8%); mixed infections with Trichinella T6 and T. nativa (12%) were observed. In addition, T. spiralis was detected in one wolverine. Out of 22 isolates initially identified as T. nativa in multiplex PCR, 14 were analyzed by PCR-RFLP to distinguish them from T. chanchalensis, a recently discovered cryptic species, which cannot be distinguished from the T. nativa on multiplex PCR. Ten isolates were identified either as T. chanchalensis alone (n = 7), or mixed infection with T. chanchalensis and T. nativa (n = 2) or T. chanchalensis and Trichinella T6 (n = 1)]., Conclusions: Wolverine hosted high prevalence, high larval intensity, and multiple species of Trichinella, likely due to their scavenging habits, apex position in the food chain, and wide home range. Wolverine (especially adult males) should be considered as a sentinel species for surveys for Trichinella spp. across their distributional range.