Intrinsic skeletal muscle function and contraction-stimulated glucose uptake do not vary by time-of-day in mice.

A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from female mice at four times-of-day (Zeitgeber Times 1, 7, 13, 19). Significantly, while both muscles demonstrated circadian-related changes in gene expression, intrinsic contractile function, endurance, and contraction-stimulated glucose uptake were not different between the four time points. Overall, these results demonstrate that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake. Impact statement: Ex vivo testing demonstrates that there is no time-of-day variation in the intrinsic contractile properties of skeletal muscle (including no effect on force production or endurance) or contraction-stimulated glucose uptake.

An evidence based conceptual framework for the multifactorial understanding of proximal junctional kyphosis.

Introduction: Adult spinal deformity (ASD) is a debilitating pathology that arises from a variety of etiologies. Spinal fusion surgery is the mainstay of treatment for those who do not achieve symptom relief with conservative interventions. Fusion surgery can be complicated by a secondary deformity termed proximal junctional kyphosis (PJK). Research question: This scoping review evaluates the modern body of literature analyzing risk factors for PJK development and organizes these factors according to a multifactorial framework based on mechanical, tissue or demographic components. Materials and methods: An extensive search of the literature was performed in PubMed and Embase back to the year 2010. Articles were assessed for quality. All risk factors that were evaluated and those that significantly predicted the development of PJK were compiled. The frequency that a risk factor was predictive compared to the number of times it was evaluated was calculated. Results: 150 articles were reviewed. 57.3% of papers were of low quality. 76% of risk factors analyzed were focusing on the mechanical contribution to development of PJK versus only 5% were focusing on the tissue-based contribution. Risk factors that were most frequently predictive compared to how often they were analyzed were Hounsfield Units of vertebrae, UIV disc degeneration, paraspinal muscle cross sectional area and fatty infiltration, ligament augmentation, instrument characteristics, postoperative hip and lower extremity radiographic metrics, and postoperative teriparatide supplementation. Discussion and conclusion: This review finds a multifactorial framework accounting for mechanical, patient and tissue-based risk factors will improve the understanding of PJK development.

Cold temperatures drive the latitudinal range limits and inhibit overwintering survival of the redbanded stink bug (Hemiptera: Pentatomidae).

For non-native insects that are economically damaging, understanding the drivers of range expansions and contractions is important for forecasting pest pressure. The invasion of the redbanded stink bug, Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae), reached Louisiana, United States, in 2000, after which the northern range limits of this species have fluctuated annually. Low winter temperatures have been implicated as a major driver of this pattern, but the importance of cold temperatures-or other abiotic factors-for the persistence of this pest over large geographic scales are incompletely understood. We coupled occurrence data of P. guildinii with climatic data to investigate trends in P. guildinii presence in relation to winter temperatures and develop species distribution models, forecasting habitat suitability based on current and future climatic scenarios. Our results show that (i) some P. guildinii persisted in locations where ambient temperatures reached -12°C, (ii) overwintering temperatures drive P. guildinii range dynamics, and (iii) with intermediate projections of climatic warming, northward expansion by P. guildinii in North America is likely to be minimal. While the northern extent of P. guildinii's range may now be largely realized in North America, our results suggest that increased frequency of mild winters could reduce interannual fluctuations of P. guildinii and enable it to become a more consistent economic concern for soybean growers throughout the Midsouth region of the United States.

Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training.

Exercise-induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise-induced phenotypes. Using this network, we formulated a logic-based ordinary differential equation model predicting time-dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training showed that, in the model, exercise regulates cell growth and protein synthesis primarily by signalling via mechanistic target of rapamycin, which is activated by Akt and inhibited in endurance exercise by AMP-activated protein kinase. Endurance exercise preferentially activates inflammation via reactive oxygen species and nuclear factor κB signalling. Furthermore, the expected preferential activation of mitochondrial biogenesis by endurance exercise was counterbalanced in the model by protein kinase C in response to resistance training. This model provides a new tool for investigating cross-talk between skeletal muscle signalling pathways activated by endurance and resistance exercise, and the mechanisms of interactions such as the interference effects of endurance training on resistance exercise outcomes.

Dispase/collagenase cocktail allows for coisolation of satellite cells and fibroadipogenic progenitors from human skeletal muscle.

Satellite cells (SCs) and fibroadipogenic progenitors (FAPs) are progenitor populations found in muscle that form new myofibers postinjury. Muscle development, regeneration, and tissue-engineering experiments require robust progenitor populations, yet their isolation and expansion are difficult given their scarcity in muscle, limited muscle biopsy sizes in humans, and lack of methodological detail in the literature. Here, we investigated whether a dispase and collagenase type 1 and 2 cocktail could allow dual isolation of SCs and FAPs, enabling significantly increased yield from human skeletal muscle. Postdissociation, we found that single cells could be sorted into CD56 + CD31-CD45- (SC) and CD56-CD31-CD45- (FAP) cell populations, expanded in culture, and characterized for lineage-specific marker expression and differentiation capacity; we obtained ∼10% SCs and ∼40% FAPs, with yields twofold better than what is reported in current literature. SCs were PAX7+ and retained CD56 expression and myogenic fusion potential after multiple passages, expanding up to 1012 cells. Conversely, FAPs expressed CD140a and differentiated into either fibroblasts or adipocytes upon induction. This study demonstrates robust isolation of both SCs and FAPs from the same muscle sample with SC recovery more than two times higher than previously reported, which could enable translational studies for muscle injuries.NEW & NOTEWORTHY We demonstrated that a dispase/collagenase cocktail allows for simultaneous isolation of SCs and FAPs with 2× higher SC yield compared with other studies. We provide a thorough characterization of SC and FAP in vitro expansion that other studies have not reported. Following our dissociation, SCs and FAPs were able to expand by up to 1012 cells before reaching senescence and maintained differentiation capacity in vitro demonstrating their efficacy for clinical translation for muscle injury.

Overwintering site selection and associated microclimates for the redbanded stink bug (Hemiptera: Pentatomidae), a non-native pest of soybean.

Cold winter temperatures govern the distribution and abundance of many insect species, but refugia that provide microclimates can moderate temperature-driven mortality. Winter temperatures have been implicated in limiting the survival and range of Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae; redbanded stink bug), an economically damaging invasive pest in the southeastern United States, but the role of refugia in overwintering survival of this pest is poorly understood. We conducted 2 studies in successive years to evaluate how leaf litter from hardwoods, pines, and soybeans modulate overwintering site selection and survival of P. guildinii. In the second-year study, we also quantified the buffering effect of the 3 leaf litter types compared to ambient conditions and assessed diapause. In the first-year study, we found that stink bugs preferentially dispersed into leaf litter compared with remaining unsheltered on bare soil; no clear preference among leaf litter types was found. In the second year, however, no clear differences were found among leaf litter types and bare soil. Means of daily minimum temperatures under leaf litter were at least 3.0 ±â€…0.9 °C (SE) warmer and generally less variable than ambient conditions. While high mortality in both studies illustrates that more work must be done to fully understand overwintering survival, limited survival through potentially lethal conditions in the first-year study nonetheless emphasizes the possibility of populations persisting and rebounding in the following spring. Furthermore, our study highlights the potential for stink bugs to persist in areas with lethal ambient temperatures by dispersing into widely available substrates.

Scaling relationships between human leg muscle architectural properties and body size.

A skeletal muscle's peak force production and excursion are based on its architectural properties that are, in turn, determined by its mass, muscle fiber length and physiological cross-sectional area (PCSA). In the classic interspecific study of mammalian muscle scaling, it was demonstrated that muscle mass scales positively allometrically with body mass whereas fiber length scales isometrically with body mass, indicating that larger mammals have stronger leg muscles than they would if they were geometrically similar to smaller ones. Although this relationship is highly significant across species, there has never been a detailed intraspecific architectural scaling study. We have thus created a large dataset of 896 muscles across 34 human lower extremities (18 females and 16 males) with a size range including approximately 90% and 70% of the United States population height and mass, respectively, across the range 36-103 years. Our purpose was to quantify the scaling relationships between human muscle architectural properties and body size. We found that human muscles depart greatly from isometric scaling because muscle mass scales with body mass1.3 (larger exponent than isometric scaling of 1.0) and muscle fiber length scales with negative allometry with body mass0.1 (smaller exponent than isometric scaling of 0.33). Based on the known relationship between architecture and function, these results suggest that human muscles place a premium on muscle force production (mass and PCSA) at the expense of muscle excursion (fiber length) with increasing body size, which has implications for understanding human muscle design as well as biomechanical modeling.

The effect of tenotomy, neurotomy, and dual injury on mouse rotator cuff muscles: Consequences for the mouse as a preclinical model.

A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post-RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time-series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration-regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically.

Paraspinal muscles in individuals undergoing surgery for lumbar spine pathology lack a myogenic response to an acute bout of resistance exercise.

Background: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine-based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non-exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub-cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. Results: The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non-exercised cohort, with similar patterns in the matched sub-analysis. There were no clinical phenotypes significantly associated with gene expression profiles. Conclusion: An acute bout of moderate-high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis.

The effect of fatty infiltration, revision surgery, and sex on lumbar multifidus passive mechanical properties.

Purpose: Previous research has demonstrated increased stiffness in the multifidus muscle compared to other paraspinal muscles at the fiber bundle level. We aimed to compare single fiber and fiber bundle passive mechanical properties of multifidus muscle: (1) in 40 patients undergoing primary versus revision surgery and (2) in muscle with mild versus severe fatty infiltration. Methods: The degree of muscle fatty infiltration was graded using the patients' spine magnetic resonance images. Average single fiber and fiber bundle passive mechanical properties across three tests were compared between primary (N = 30) and revision (N = 10) surgery status, between mild and severe fatty infiltration levels, between sexes, and with age from passive stress-strain tests of excised multifidus muscle intraoperative biopsies. Results: At the single fiber level, elastic modulus was unaffected by degree of fatty infiltration or surgery status. Female sex (p = 0.001) and younger age (p = 0.04) were associated with lower multifidus fiber elastic modulus. At the fiber bundle level, which includes connective tissue around fibers, severe fatty infiltration (p = 0.01) and younger age (p = 0.06) were associated with lower elastic modulus. Primary surgery also demonstrated a moderate, but non-significant effect for lower elastic modulus (p = 0.10). Conclusions: Our results demonstrate that female sex is the primary driver for reduced single fiber elastic modulus of the multifidus, while severity of fatty infiltration is the primary driver for reduced elastic modulus at the level of the fiber bundle in individuals with lumbar spine pathology.

A Simple and Versatile Test for Elbow Posterolateral Rotatory Instability.

BACKGROUND: Posterolateral rotatory instability (PLRI) results from lateral ulnar collateral ligament (LCL) deficiency. The lateral pivot shift test is used to diagnose PLRI but can be difficult to perform and is poorly tolerated. We present a new maneuver, the Posterior Radiocapitellar Subluxation Test (PRST), that we believe is easier to perform. The purpose of this study was to compare the efficacy and reproducibility of the PRST with the lateral pivot shift test. METHODS: We obtained 10 cadaveric upper extremity specimens, performed a Kocher approach on each, released the LCL origin in 5, then closed. The specimens were randomized, and 3 attending orthopedic surgeons and 1 resident blindly performed the PRST then the lateral pivot shift test after re-randomization and assessed presence or absence of PLRI. This process was repeated the following day. The data for each test were analyzed for sensitivity, specificity, and accuracy. RESULTS: For the blinded testing when comparing PRST with the pivot shift test, overall accuracy was 77.5%, compared with 67.5% (P = .03), sensitivity was 75.0%, compared with 50.0% (P = .003), and specificity was 80.0%, compared with 85.0% (P = .55). Conclusions: The PRST appears to be at least as accurate as the lateral pivot shift test, with comparable intraobserver and interobserver reliability.

Warm temperatures and host tree abundance explain variation in directional spread by laurel wilt.

The rate at which invading organisms disperse into novel habitats is fundamental to their distribution and abundance. Forecasts of spread often assume that invasion speed is constant through time and among directions but, depending on the extent to which this assumption is violated, the efficacy of delimitation surveys and eradication programs could suffer. Knowledge of the mechanisms underlying spatiotemporal variation in spread could help refine forecasts and guide management, particularly in the early stages of invasions. We investigated rates of spread by laurel wilt, one of the most damaging non-native forest pests in North America, using three standard approaches (effective range radius, distance regression, and boundary displacement) and evaluated the strength and drivers of variation in directional spread (i.e., anisotropy). Estimates of mean annual spread varied from 24 to 40 km/yr, but spread was highly anisotropic with invasion speeds reaching approximately 100 km/yr south, 80 km/yr west, and 50 km/yr north, a pattern that we attribute to the abundance of host redbay trees and warmer temperatures fostering rapid southern and western spread. This pattern-quicker spread of laurel wilt from the point of introduction into areas forecasted as highly suitable for its persistence-suggests that establishment location might have a major influence on rates of anisotropy. Our findings underscore the utility of habitat suitability modeling-in which host availability and suitable climate are widely used to forecast establishment risk-for identifying areas into which spread will proceed most rapidly following establishment of a new invader and/or a satellite population via a long-distance dispersal event. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-023-03069-5.

Transcriptional time course after rotator cuff repair in 6 month old female rabbits.

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae. Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways. Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks post-repair.

Photochemical and Single Electron Transfer Generation of 2'-Deoxycytidin-N4-yl Radical from Oxime Esters.

A 2'-deoxycytidin-N4-yl radical (dC·), a strong oxidant that also abstracts hydrogen atoms from carbon-hydrogen bonds, is produced in a variety of DNA damaging processes. We describe here the independent generation of dC· from oxime esters under UV-irradiation or single electron transfer conditions. Support for this σ-type iminyl radical generation is provided by product studies carried out under aerobic and anaerobic conditions, as well as electron spin resonance (ESR) characterization of dC· in a homogeneous glassy solution at low temperature. Density functional theory (DFT) calculations also support fragmentation of the corresponding radical anions of oxime esters 2d and 2e to dC· and subsequent hydrogen atom abstraction from organic solvents. The corresponding 2'-deoxynucleotide triphosphate (dNTP) of isopropyl oxime ester 2c (5) is incorporated opposite 2'-deoxyadenosine and 2'-deoxyguanosine by a DNA polymerase with approximately equal efficiency. Photolysis experiments of DNA containing 2c support dC· generation and indicate that the radical produces tandem lesions when flanked on the 5'-side by 5'-d(GGT). These experiments suggest that oxime esters are reliable sources of nitrogen radicals in nucleic acids that will be useful mechanistic tools and possibly radiosensitizing agents when incorporated in DNA.

Pathways of the Dissociative Electron Attachment Observed in 5- and 6-Azidomethyluracil Nucleosides: Nitrogen (N2) Elimination vs Azide Anion (N3-) Elimination.

5-Azidomethyl-2'-deoxyuridine (5-AmdU, 1) has been successfully employed for the metabolic labeling of DNA and fluorescent imaging of live cells. 5-AmdU also demonstrated significant radiosensitization in breast cancer cells via site-specific nitrogen-centered radical (π-aminyl (U-5-CH2-NH•), 2, and σ-iminyl (U-5-CH═N•), 3) formation. This work shows that these nitrogen-centered radicals are not formed via the reduction of the azido group in 6-azidomethyluridine (6-AmU, 4). Radical assignments were performed using electron spin resonance (ESR) in supercooled solutions, pulse radiolysis in aqueous solutions, and theoretical (DFT) calculations. Radiation-produced electron addition to 4 leads to the facile N3- loss, forming a stable neutral C-centered allylic radical (U-6-CH2•, 5) through dissociative electron attachment (DEA) via the transient negative ion, TNI (U-6-CH2-N3•-), in agreement with DFT calculations. In contrast, TNI (U-5-CH2-N3•-) of 1, via facile N2 loss (DEA) and protonation from the surrounding water, forms radical 2. Subsequently, 2 undergoes rapid H-atom abstraction from 1 and produces the metastable intermediate α-azidoalkyl radical (U-5-CH•-N3). U-5-CH•-N3 converts facilely to radical 3. N3- loss from U-6-CH2-N3•- is thermodynamically controlled, whereas N2 loss from U-5-CH2-N3•- is dictated by protonation from the surrounding waters and resonance conjugation of the azidomethyl side chain at C5 with the pyrimidine ring.

Paraspinal muscle gene expression across different aetiologies in individuals undergoing surgery for lumbar spine pathology.

PURPOSE: The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis. METHODS: Multifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini-Hochberg) and for between-group post hoc comparisons (Sidak) were applied. RESULTS: Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p < 0.001 and p = 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (p = 0.012). CONCLUSION: Individuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences.

Drivers of invasion by laurel wilt of redbay and sassafras in the southeastern US.

Context: Timely responses to mitigate economic and environmental impacts from invading species are facilitated by knowledge of the speed and drivers of invasions. Objective: Quantify changes in invasion patterns through time and factors that governed time-to-invasion by laurel wilt, one of the most damaging, non-native disturbance agents invading forests of the United States. Methods: We analyzed county-level occurrence data (2004-2021) for laurel wilt across the southeastern United States. A Cox proportional hazards modeling framework was used to elucidate drivers of invasion. Results: As of 2021, laurel wilt had been detected in 275 counties and made 72 discrete jumps (averaging 164 km ± 16 SE) into counties that did not share a border with a previously invaded county. Spread decelerated from 40 km/yr to 24 km/yr after 5 years, with a marked decline in the number of counties invaded in 2021 (16) compared with 2020 (33). The Cox proportional hazards model indicated that proxies for anthropogenic movement and habitat invasibility increased invasion risk. Conclusion: The recent decline in number of counties invaded could be due to disruptions to travel and/or surveys from the coronavirus pandemic, but exhaustion of the most suitable habitat, such as counties in the southeastern US with warm annual temperatures and high densities of host trees, could have also contributed to this trend. This work suggests that without a shift in spread driven by additional insect vectors, that rates of range expansion by laurel wilt might have peaked in 2020 and could continue decelerating. Supplementary Information: The online version contains supplementary material available at 10.1007/s10980-022-01560-3.

A novel approach for the prevention of ionizing radiation-induced bone loss using a designer multifunctional cerium oxide nanozyme.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

3D printing a biocompatible elastomer for modeling muscle regeneration after volumetric muscle loss.

Volumetric muscle loss (VML) injuries due to trauma, tumor ablation, or other degenerative muscle diseases are debilitating and currently have limited options for self-repair. Advancements in 3D printing allow for the rapid fabrication of biocompatible scaffolds with designer patterns. However, the materials chosen are often stiff or brittle, which is not optimal for muscle tissue engineering. This study utilized a photopolymerizable biocompatible elastomer - poly (glycerol sebacate) acrylate (PGSA) - to develop an in vitro model of muscle regeneration and proliferation into an acellular scaffold after VML injury. Mechanical properties of the scaffold were tuned by controlling light intensity during the 3D printing process to match the specific tension of skeletal muscle. The effect of both geometric (channel sizes between 300 and 600 µm) and biologic (decellularized muscle extracellular matrix (dECM)) cues on muscle progenitor cell infiltration, proliferation, organization, and maturation was evaluated in vitro using a near-infrared fluorescent protein (iRFP) transfected cell line to assess cells in the 3D scaffold. Larger channel sizes and dECM coating were found to enhance cell proliferation and maturation, while no discernable effect on cell alignment was observed. In addition, a pilot experiment was carried out to evaluate the regenerative capacity of this scaffold in vivo after a VML injury. Overall, this platform demonstrates a simple model to study muscle progenitor recruitment and differentiation into acellular scaffolds after VML repair.