Early Regeneration Research Articles

Evenly Distributed Microporous Structure and E7 Peptide Functionalization Synergistically Accelerate Osteogenesis and Angiogenesis in Engineered Periosteum.

Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance. The E7 peptide (EPLQLKM), which exhibits a specific affinity for mesenchymal stem cells (MSCs), is beneficial for modulating cellular functions. In this study, a unique microporous structured carboxymethyl chitosan/sodium alginate membrane with a proper mass ratio is developed by the addition of Poloxam 407 （P407）, which is then functionalized with the E7 affinitive peptide. This membrane, characterized by its microporous structure and E7 peptide functionalization (CSSA/P/E), not only demonstrated favorable mechanical properties, enhanced hydrophilicity, satisfactory biodegradation profile, and excellent biocompatibility, but also synergistically enhanced MSCs recruitment. It is found to promote the proliferation, spreading, and osteogenic differentiation of MSCs in vitro and to accelerate early periosteal regeneration, bone matrix deposition, and vascularization in vivo, leading to effective regeneration of critical-sized bone defects. Overall, this study presents a robust, cell and growth factor-free strategy for bioengineering periosteum, offering a potential solution for the challenging large size bone defects.

The role of the cyclooxygenase-2 pathway in tissue ischemia and revascularization following skeletal muscle injury induced by bothropic snake venom

Bothrops asper venom (Bav) contains metalloproteinases that disrupt the microvascular system, impairing muscle tissue regeneration after injury. This study investigated the impact of the cyclooxygenase-2 (COX-2) pathway on vascular injury and revascularization in muscle injuries induced by Bav. Mice were injected with Bav into the gastrocnemius muscle and treated with lumiracoxib, a selective COX-2 inhibitor, 30 min, 2 days, and 6 days post-Bav injection. Muscle tissue was analyzed at 24 h, 7 days, and 21 days post-injection. A decrease in COX-2 expression at 24 h post-Bav injection indicated significant necrosis and tissue loss. Both Bav injection and lumiracoxib treatment influenced the decrease of prostaglandin (PG)D2 and PGE2 production. Seven and 21 days post-Bav injections, COX-2 expression increased, along with PGDs levels unaffected by lumiracoxib, indicating that the other isoform COX-1 pathway could contribute to the release of PGs. Bav/lumiracoxib treated animals presented exacerbated limb ischemia, implying that COX-2-derived prostaglandins preserve vessel integrity. CD31, an angiogenesis marker, initially (24 h) decreased post-Bav injection but increased at 7 and 21 days in Bav/lumiracoxib mice, suggesting a down-modulatory role for COX-2-derived prostaglandins in early angiogenesis and tissue regeneration. Vascular endothelial growth factor (VEGF) production rose 7 days post-Bav injection, supporting its role in angiogenesis. Previous treatment with lumiracoxib promoted release of VEGF levels 21 days post-Bav injury showing that the inhibition of COX-2 pathway in the early stage of revascularization stimulates the neovascularization regulated by elevated release of VEGF. Similarly, metalloproteinases (MMPs), such as MMP-9, MMP-10, and MMP-13, crucial for vascular remodeling, were elevated 21 days after Bav/lumiracoxib treatment. In conclusion, the COX-2 pathway is essential to decrease the high grade of ischemia caused by acute injury induced by Bav. However, the decrease of activity in the COX-2 pathway in the first stages of revascularization contributes to the elevated production of key pro-angiogenic mediators that up-regulate the restoration of microvasculature and blood flow in muscle tissue injured by botropic venoms.

Enhancing Bone Regeneration and Osteogenic Quality by n-HA Internalized Osteoblasts Synergized with ON Protein: Mechanistic Insights.

Bone scaffolds offer hope for oral jawbone repair, yet improving their osteogenic performance remains a clinical challenge. This study investigates a novel approach to enhance early bone formation and osteogenic quality by coloading hydroxyapatite (HA)─internalized osteoblasts (OHA) and osteonectin (ON) onto various scaffolds. Our findings demonstrated that the OHA could effectively facilitate the early bone regeneration by providing rapid calcium and phosphorus ion release via lysosome-mediated HA degradation, while the ON protein helps in ion deposition, cell proliferation, and matrix mineralization. When the PHA (PCL+HA) scaffold was incorporated with both the OHA and ON, the scaffold exhibited superior pro-osteogenic performance, driven by synergistic effects of rapid ion release from the OHA, slow ion release from the PHA, and upregulation of osteogenesis-related genes. The analyses of mechanisms revealed that the OHA activated MAPK and PI3K-Akt pathways, while ON stimulated calcium and Wnt signaling, collectively promoting the osteogenic potential. The strategy presented in this study paves a promising way for the development of advanced bone scaffolds to improve the bone regeneration quality.

Molecular Dynamics and Spatial Response of Proliferation and Apoptosis in Wound Healing and Early Intestinal Regeneration of sea cucumber Apostichopus japonicus

The sea cucumber, Apostichopus japonicus, exhibits significant regenerative capabilities. To ensure survival and reduce metabolic costs under adverse conditions, A. japonicus can expel intestine, respiratory trees and other internal organs. It takes only 14 days to regenerate a fully connected, lumen-containing intestine. Despite numerous reports characterizing the cellular events in intestinal regeneration, limited investigation has been conducted on the molecular events that occur during wound healing and the initial stages of regeneration after evisceration. Here, we identified differentially expressed genes (DEGs) during wound healing (6 hours post-evisceration, Aj6hpe) and early intestinal regeneration (Aj1dpe, Aj3dpe, Aj7dpe). Cell proliferation and apoptosis were detected by EdU and TUNEL assays, respectively. Results demonstrated that calcium ion and neuroactive ligand-receptor interaction were involved in the transmission of injury signals from evisceration to Aj1dpe. The main events occurring in the wound healing and early regeneration process were autophagy, apoptosis, dedifferentiation, migration and shutdown of feeding. Cell proliferation was primarily observed during the lumen formation stage. Maximal number of apoptotic cells were found during wound healing stage (6 hpe - 1 dpe). Consequently, the immune response is mainly mobilized by neural regulation after evisceration. Our findings bridge the gap between evisceration and regeneration, illuminating the molecular events that mediate damage response and initiate regeneration. This study significantly advances our understanding of the mechanisms underlying intestinal regeneration.

Cytokine expression and cytokine‐mediated cell–cell communication during skeletal muscle regeneration revealed by integrative analysis of single‐cell RNA sequencing data

AbstractSkeletal muscles undergo self‐repair upon injury, owing to the resident muscle stem cells and their extensive communication with the microenvironment of injured muscles. Cytokines play a critical role in orchestrating intercell communication to ensure successful regeneration. Immune cells as well as other types of cells in the injury site, including muscle stem cells, are known to secret cytokines. However, the extent to which various cell types express distinct cytokines and how the secreted cytokines are involved in intercell communication during regeneration are largely unknown. Here we integrated 15 publicly available single‐cell RNA‐sequencing (scRNA‐seq) datasets of mouse skeletal muscles at early regeneration timepoints (0, 2, 5, and 7 days after injury). The resulting dataset was analyzed for the expression of 393 annotated mouse cytokines. We found widespread and dynamic cytokine expression by all cell types in the regenerating muscle. Interrogating the integrated dataset using CellChat revealed extensive, bidirectional cell–cell communications during regeneration. Our findings provide a comprehensive view of cytokine signaling in the regenerating muscle, which can guide future studies of ligand‐receptor signaling and cell–cell interaction to achieve new mechanistic insights into the regulation of muscle regeneration.

Neural Crest-Derived Mesenchymal Cells Support Thymic Reconstitution After Lethal Irradiation.

Reconstitution of the thymus is essential for assessing thymic function following injury. However, the currently employed cytoreductive regimes unvaryingly affect the thymic microenvironment, thereby impeding the recovery of T lymphopoiesis. The thymic stroma is composed of epithelial and mesenchymal cells. Thymic mesenchymal cells originate from the Neural crest (NC) and mesoderm and contribute to thymus organogenesis, yet their role in thymic regeneration is unclear. In this study, using transgenic mice expressing NC-specific Cre and Cre-driven DT receptors, we investigated the role of NC-derived mesenchymal cells in thymic regeneration following total body irradiation. We revealed that NC-derived mesenchymal cells have reduced susceptibility to irradiation and induce the upregulation of hematopoietic factors that promote thymus regeneration after irradiation. Additionally, using adult thymic organ culture and renal capsule transplantation, depletion of NC-derived mesenchymal cells resulted in a reduction of DN1-like early T-cell progenitors (ETP) and impaired thymic regeneration. Furthermore, among the numerous factors upregulated by NC-derived mesenchymal cells, Periostin and Flt3L were markedly increased after irradiation and promoted abundance of DN1-like ETPs during thymic reconstitution. Collectively, these findings highlight the importance of NC-derived mesenchymal cells in thymic regeneration.

Role of Steatosis in Preventing Post-hepatectomy Liver Failure After Major Resection: Findings From an Animal Study

Post-hepatectomy liver failure (PHLF) and hepatic steatosis are evident shortly after extensive partial hepatectomy (PH) in rodents. This study aimed to extrapolate the protein expression and biological pathways involved in recovering PHLF (rPHLF) and non-recovering PHLF (nrPHLF). Rats were randomly assigned to 90% PH or sham surgery. rPHLF was distinguished from nrPHLF using a quantitative scoring system. The sham (n= 6), rPHLF (n= 8), and nrPHLF (n= 13) groups were compared 24h post-PH. Proteomics was used to assess protein variations and to investigate differentially regulated biological pathways. Stereological methods were used to quantify hepatic lipid content. The plasma triglyceride levels were measured. rPHLF demonstrated substantial downregulation of proteins involved in lipid metabolism compared to nrPHLF (P < 0.001). Several proteins associated with lipogenesis, beta-oxidation, lipolysis, membrane trafficking, and inhibition of cell proliferationwere markedly downregulated in rPHLF.The hepatic lipid proportion was significantly higher for rPHLF (61% of hepatocyte volume, 95% confidence interval [CI]: 48%-82%) than for nrPHLF (32% of hepatocyte volume, 95% CI: 22%-39%). The median lipid volume per hepatocyte in rPHLF was 2815μm3 (95% CI: 2208-3774μm3)and 1759μm3 in nrPHLF (95% CI: 1188-2134μm3). Lipid droplets were not detected in the sham-operated rats. No significant differences in plasma triglyceride levels were found between the groups (P > 0.08). The degree of hepatic steatosis is a promising prognostic indicator for early liver regeneration and nrPHLF onset immediately following extensive PH. Intrahepatic lipid accumulation appears to be linked to the coordinated downregulation of proteins integral to lipid metabolism and cellular transport.

Three-Dimensional Semiconductor Network as Regulators of Energy Metabolism Drives Angiogenesis in Bone Regeneration.

Insufficient vascularization is a primary cause of bone implantation failure. The management of energy metabolism is crucial for the achievement of vascularized osseointegration. In light of the bone semiconductor property and the electric property of semiconductor heterojunctions, a three-dimensional semiconductor heterojunction network (3D-NTBH) implant has been devised with the objective of regulating cellular energy metabolism, thereby driving angiogenesis for bone regeneration. The three-dimensional heterojunction interfaces facilitate electron transfer and establish internal electric fields at the nanoscale interfaces. The 3D-NTBH was found to noticeably accelerate glycolysis in endothelial cells, thereby rapidly providing energy to support cellular metabolic activities and ultimately driving angiogenesis within the bone tissue. Molecular dynamic simulations have demonstrated that the 3D-NTBH facilitates the exposure of fibronectin's Arg-Gly-Asp peptide binding site, thereby regulating the glycolysis of endothelial cells. Further evidence suggests that 3D-NTBH promotes early vascular network reconstruction and bone regeneration in vivo. The findings of this research offer a promising research perspective for the design of vascularizing implants.

Myeloid derived suppressor cells mediate hepatocyte proliferation and immune suppression during liver regeneration following resection.

Liver regeneration following resection is a complex process relying on coordinated pathways and cell types in the remnant organ. Myeloid-Derived Suppressor Cells (MDSCs) have a role in liver regeneration-related angiogenesis but other roles they may play in this process remain to be elucidated. In this study, we sought to examine the effect of G-MDSCs on hepatocytes proliferation and immune modulation during liver regeneration. Global gene expression profiling of regenerating hepatocytes in mice with CD11b+Ly6G+ MDSCs (G-MDSCs) depletion revealed disrupted transcriptional progression from day one to day two after major liver resection. Key genes and pathways related to hepatocyte proliferation and immune response were differentially expressed upon MDSC depletion. Hepatocytes cellularity increased when co-cultured with G-MDSCs, or treated with amphiregulin, which G-MDSCs upregulate during regeneration. Cytometry by time-of-flight (CyTOF) analysis of the intra-liver immune milieu upon MDSC depletion during regeneration demonstrated increased natural killer cell proportions, alongside changes in other immune cell populations. Taken together, these results provide evidence that MDSCs contribute to early liver regeneration by promoting hepatocyte proliferation and modulating the intra-liver immune response, and illuminate the multifaceted role of MDSCs in liver regeneration.

Influencing factors and repair advancements in rodent models of peripheral nerve regeneration.

Peripheral nerve injuries lead to severe functional impairments, with rodent models essential for studying regeneration. This review examines key factors affecting outcomes. Age-related declines, like reduced nerve fiber density and impaired axonal transport of vesicles, hinder recovery. Hormonal differences influence regeneration, with BDNF/trkB critical for testosterone and nerve growth factor for estrogen signaling pathways. Species and strain selection impact outcomes, with C57BL/6 mice and Sprague-Dawley rats exhibiting varying regenerative capacities. Injury models - crush for early regeneration, chronic constriction for neuropathic pain, stretch for traumatic elongation and transection for severe lacerations - provide insights into clinically relevant scenarios. Repair techniques, such as nerve grafts and conduits, show that autografts are the gold standard for gaps over 3cm, with success influenced by graft type and diameter. Time course analysis highlights crucial early degeneration and regeneration phases within the first month, with functional recovery stabilizing by three to six months. Early intervention optimizes regeneration by reducing scar tissue formation, while later interventions focus on remyelination. Understanding these factors is vital for designing robust preclinical studies and translating research into effective clinical treatments for peripheral nerve injuries.

MXene-montmorillonite nanocomposites-based scaffold sensors for early pancreatic cancer diagnosis

Pancreatic cancer is increasingly prevalent and characterized by a high mortality rate. Due to the limitations of current diagnostic methods, early-stage detection remains elusive, contributing to persistently low survival rates among affected individuals. Nanomaterials have garnered significant attention in cancer research for their potential diagnostic applications. Among these, MXenes &amp;ndash; a novel family of two-dimensional nanomaterials composed of transition metal carbides, nitrides, and carbonitrides &amp;ndash; are of particular interest due to their unique properties. These include high electrical conductivity, hydrophilicity, thermal stability, large interlayer spacing, tunable structure, and high surface area. These characteristics make MXenes highly effective for detecting trace amounts of various analytes. In addition, their tunable structure enables precise manipulation of their properties, allowing for optimized sensing responses. Montmorillonite nanoclay (MMT), a member of the smectite group of natural clay minerals, is known for its ability to promote bone development and influence cell behavior. When combined with MXenes, MMT forms promising nanocomposites for early pancreatic cancer detection through sensing applications. The Ti3C2 MXene-MMT nanocomposites exhibit potential as scaffold sensors capable of distinguishing cancerous from non-cancerous samples by observing the distinctive patterns in resistance changes. In addition, MXenes possess excellent selectivity, allowing for the reliable identification of targeted analytes from a complex mixture of chemical and biological analytes. Due to the advanced sensing capabilities of MXene-MMT composite scaffold sensors, they hold great promise for early cancer diagnosis and tissue regeneration, providing a novel therapeutic approach to improving patient outcomes.

URBAN REGENERATION AND PUBLIC SPACE: LESSONS ON EARLY INTERVENTION OF COMMUNITY-BASED MICRO-PLANNING

Documenting lessons learned from revitalization projects through community-based micro-planning is crucial in developing countries, as it lacks mainstream urban regeneration recognition. This research aimed to evaluate the early intervention of community gardening or urban farming initiatives under an urban regeneration project: the Special Area Action Plan Section 13, Petaling Jaya City, Malaysia. This single case study was investigated using the mixed-methods approach. In the quantitative approach, 200 samples were collected via questionnaires and analyzed using descriptive statistics. In the qualitative approach, eight interviews were conducted and analyzed via thematic analysis. The findings show that the respondents are sceptical about the awareness, safety infrastructure and support services, caretaker, and land ownership concerns surrounding the proposal for community gardening at the Sungai Penchala monsoon drain area. When revitalizing left-over urban public spaces, authorities are recommended to plan more awareness intervention campaigns, enhance safety infrastructure designs, provide policy support in appointing caretakers, and resolve land acquisition matters to realize and sustain the regeneration projects in the public interest. This study contributes lessons learned by auditing the early intervention urban regeneration initiatives in development plans, particularly in fourth-tier-community-based micro-planning in a developing country.

Endothelial Foxo1 Phosphorylation Inhibition via Aptamer-Liposome Alleviates OPN-Induced Pathological Vascular Remodeling Following Spinal Cord Injury.

Reconstruction of the neurovascular unit is essential for the repair of spinal cord injury (SCI). Nonetheless, detailed documentation of specific vascular changes following SCI and targeted interventions for vascular treatment remains limited. This study demonstrates that traumatic pathological vascular remodeling occurs during the chronic phase of injury, characterized by enlarged vessel diameter, disruption of blood-spinal cord barrier, endothelial-to-mesenchymal transition (EndoMT), and heightened extracellular matrix deposition. After SCI, osteopontin (OPN), a critical factor secreted by immune cells, is indispensable for early vascular regeneration but also contributes to traumatic pathological vascular remodeling. This work further elucidates the mechanism by which OPN influences spinal cord microvascular endothelial cells, involving Akt-mediated Foxo1 phosphorylation. This process facilitates the extranuclear transport of Foxo1 and decreases Smad7 expression, leading to excessive activation of the TGF-β signaling pathway, which ultimately results in EndoMT and fibrosis. Targeted inhibition of Foxo1 phosphorylation through an endothelium-specific aptamer-liposome small molecule delivery system significantly mitigates vascular remodeling, thereby enhancing axon regeneration and neurological function recovery following SCI. The findings offer a novel perspective for drug therapies aimed at specifically targeting pathological vasculature after SCI.

Factors affecting early red oak (Quercus rubra L.) regeneration near its northern distribution limit in Quebec

Red oak is an important species within the North American landscape, with climate change projections indicating a potential northward shift in its distribution. However, understanding the factors influencing its regeneration success at the northern limit remains limited. Site conditions and seed provenance adaptability may play critical roles. To bridge this knowledge gap, we conducted a seed transfer study in two northern red oak stands in Quebec. We firstly investigated stand regeneration history through dendrochronological characterization. Then, we monitored the survival and growth of saplings for four red oak provenances across a south-to-north gradient in field and greenhouse settings, with varying soil nutrient levels due to fertilization, and with or without protection from large herbivores. Results indicated that stands have similar age structures with red oak establishment coinciding with the last major fire disturbance in the early 1920s. However, tree species composition and density differed, suggesting differences in fire disturbance regime or ecological succession status prior to fire. Site had the largest influence on red oak regeneration, with the highest tree density and soil water availability site exhibiting a 29% higher survival rate. Protection against large herbivores also significantly impacted red oak seedling performance, leading to a 16% higher survival rate. Germination, survival and growth also significantly differed between provenances. The local (northernmost) provenance exhibited the poorest overall performance with 28 to 42% lower germination, survival and growth rates, while the two southernmost provenances exhibited superior germination and sprout survival. An increase in soil nutrient availability was beneficial to red oak in the greenhouse, but only marginally benefited survival and growth in the field, suggesting that this factor is of less importance than other factors (e.g., water and light availability) for red oak early regeneration. The findings of this study suggest that silvicultural efforts to favor red oak should focus on site and provenance selection, and that water availability is currently limiting red oak regeneration success at acorn and early seedling life stages (i.e., 1 year old seedlings) near its northern distribution limit.

Galectin-8 Contributes to Human Trophoblast Cell Invasion.

Galectins are a class of lectins that are extensively expressed in all organisms. Galectins are involved in a range of functions, including early development, tissue regeneration, cancer and inflammation. It has been shown that galectin-8 is expressed in the villous and extravillous trophoblast (EVT) cells of the human placenta; however, its physiological role in pregnancy establishment has not been elucidated. Taking these factors into account, we investigated the functional role of galectin-8 in HTR-8/SVneo cells-a human EVT cell line-and human primary cytotrophoblast cells isolated from a first-trimester placenta. We analyzed the effects of recombinant human galectin-8 (rh galectin-8) on the adhesion, migration and invasion of HTR-8/SVneo cells. We used qPCR, cell-based ELISA (cELISA) and gelatin zymography to study the effects of galectin-8 on mediators of these processes, such as integrin subunits alpha-1 and beta-1 and matrix metalloproteinases (MMPs)-2 and -9, on the mRNA and protein levels. Further, we studied the effects of galectin-8 on primary cytotrophoblast cells' invasion. Galectin-8 stimulated the adhesion, migration and invasion of HTR-8/SVneo cells, as well as the invasion of primary cytotrophoblasts. In addition, the MMP-2 and -9 levels were increased, while the expression of integrins alpha-1 and beta-1 was not affected. Galectin-8 has the ability to positively affect EVTs' invasion, so it can be considered a significant factor in the trophoblast cell invasion process.

"Mitotic" kinesin-5 is a dynamic brake for axonal growth.

During neuronal development, neurons undergo significant microtubule reorganization to shape axons and dendrites, establishing the framework for efficient wiring of the nervous system. Previous studies from our laboratory demonstrated the key role of kinesin-1 in driving microtubule-microtubule sliding, which provides the mechanical forces necessary for early axon outgrowth and regeneration in Drosophila melanogaster. In this study, we reveal the critical role of kinesin-5, a mitotic motor, in modulating the development of postmitotic neurons. Kinesin-5, a conserved homotetrameric motor, typically functions in mitosis by sliding antiparallel microtubules apart in the spindle. Here, we demonstrate that the Drosophila kinesin-5 homolog, Klp61F, is expressed in larval brain neurons, with high levels in ventral nerve cord (VNC) neurons. Knockdown of Klp61F using a pan-neuronal driver leads to severe locomotion defects and complete lethality in adult flies, mainly due to the absence of kinesin-5 in VNC motor neurons during early larval development. Klp61F depletion results in significant axon growth defects, both in cultured and in vivo neurons. By imaging individual microtubules, we observe a significant increase in microtubule motility, and excessive penetration of microtubules into the axon growth cone in Klp61F-depleted neurons. Adult lethality and axon growth defects are fully rescued by a chimeric human-Drosophila kinesin-5 motor, which accumulates at the axon tips, suggesting a conserved role of kinesin-5 in neuronal development. Altogether, our findings show that at the growth cone, kinesin-5 acts as a brake on kinesin-1-driven microtubule sliding, preventing premature microtubule entry into the growth cone. This regulatory role of kinesin-5 is essential for precise axon pathfinding during nervous system development.

Competition between resprouting chaparral and the recruits of a serotinous conifer following stand-replacing fire

In western North America, fire regimes are shifting towards more frequent, larger, and more severe wildfire. There is concern that this will shift the vegetation type in many areas, especially on the lower, drier slopes. In northern California, mature serotinous conifers and resprouting shrub species easily regenerate in severe patches of any size. There is no consensus, however, regarding the effects of shrub competition on conifer recruitment; conifer response to shade varies with shade tolerance and abiotic factors. Many conifers and almost all chaparral shrubs are shade intolerant, and we expect shading to be the main driver of the inter-species competition between these taxa on dry low-elevation, slopes We chose to examine early post-fire regeneration of knobcone pine (Pinus attenuata), a shade intolerant serotinous conifer, because (a) as a serotinous species we could be assured of a high initial density of recruits, and (b) it is mainly found on lower-elevation slopes in a matrix of chaparral. We examined the competitive interactions of the pine and shrubs within the 2018 Carr and Delta fires at the third and fourth post-fire years, as well as at the 2008 Motion Fire at the 14th post-fire year, focusing on two measurements of shrub shading: inter-shrub porosity (% shrub cover) and intra-shrub porosity (species-specific ground-level light availability). Our response variables included recruitment success (recruits per ovulate cone) and growth (height). We only chose stands where knobcone pine was a minor pre-fire component to ensure a high density of vigorously resprouting shrubs. We found (1) there were significantly fewer pine recruits under shrubs, with the bulk of the shrub-induced mortality of knobcone pine occurring before the third growing season; (2) knobcone pine averaged about six established recruits per burned parent tree by the third year following fire; and (3), extrapolating from height reconstruction of post-fire knobcone pine regeneration from the 2008 Motion Fire, the remaining tree recruits are expected to persist and dominate the stand within a decade of the fire. We conclude that competition with shrubs on low elevation sites in northern California does have a negative effect on knobcone pine density but is insufficient to seriously impede a dramatic post-fire increase in conifer density when conifer regeneration arrives promptly following fire.

On-demand Opto-Laser activatable nanoSilver ThermoGel for treatment of full-thickness diabetic wound in a mouse model

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models. The characterization findings confirmed the formation of spherical-shaped nanometric Opto-Laser activatable nanoSilver (30.75 ± 2.7 nm; ∆T: 37 ± 0.2 °C → 66.2 ± 0.1 °C; at 1.8 W/cm2 NIR laser density). The findings indicated acceptable in vitro cytocompatibility and significant keratinocyte migration (95.04 ± 0.07 %) activity of OL→nSil towards HaCaT cells. The rheological data of OL→nSil hybridized in situ thermoresponsive gel (OL→nSil-ThermoGel) showed the gelling temperature at 32 ± 2 °C. In vivo studies on full-thickness diabetic wounds in a Mouse model showed OL→nSil-ThermoGel accelerated wound closure (94.42 ± 1.03 %) and increased collagen synthesis, angiogenesis, and decreased inflammatory markers. Similarly, immunohistochemistry study showed significant angiogenesis and faster phenotypic switching of fibroblasts to myofibroblasts in OL→nSil-ThermoGel treated diabetic wounds. Histological evaluation revealed a marked rise in keratinocyte migration, organized collagen deposition, and early regeneration of the epithelial layer compared to the diabetic wound control. In conclusion, the OL→nSil-ThermoGel modulates the cytokines, re-epithelialization, protein expression, and growth factors, thereby improving the repair and regeneration of diabetic wounds in mice.

Salvage logging and subsequent post‐windthrow management diminish forest bird communities for two decades

Abstract Post‐disturbance forest management is known to impair biodiversity, including bird communities, but most studies focus on short‐term effects of salvage logging, without recognition of the cumulative, lasting impact of collective post‐disturbance silvicultural practices. We tracked bird community succession in a temperate pine forest from 5 to 19 years after wind disturbance in managed and unmanaged windthrow areas, covering the period from gap creation to early canopy regeneration and comparing it to nearby production forest unaffected by wind disturbance. Bird communities of unmanaged windthrow were consistently the richest in terms of bird abundance and richness. They hosted comparable forest bird diversity to unaffected production stands throughout the study period, as well as a substantial diversity of farmland birds. Managed and unmanaged windthrows followed two distinct successional pathways and did not converge. Despite the bird communities in both windthrows gradually resembling those found in undisturbed forests as the canopy regenerated, each type of windthrow and the unaffected production forest maintained distinct communities until the end of the study. Synthesis and applications. Restraining from any active post‐windthrow management sets bird succession on a distinct pathway, leading to unique and diverse bird communities. We advocate viewing natural disturbances as cost‐effective ecosystem restoration tools, provided no active management is implemented. Furthermore, we advise against using the term ‘salvage logging’ to refer to collective post‐disturbance silvicultural practices, as its varying interpretation may lead to growing confusion as the number of long‐term studies increase.

Photodynamic Therapy under Diagnostic Control of Wounds with Antibiotic-Resistant Microflora

Background: Difficulties in the treatment of purulent wounds are caused by bacterial biofilms, which results in decontamination limitations. Infected wounds are not sufficiently susceptible to existing antibiotics, necessitating the search for alternative approaches to reduce the concentration of pathogenic microflora. Methods: This study describes an approach to the effective treatment of wounds by photodynamic inactivation or therapy (PDI/PDT) of antibiotic-resistant microflora under fluorescence control. For this purpose, laser and LED light (660–680 nm) and different groups of photosensitizers (PS) (1% solutions of methylene blue, aluminum phthalocyanine, chlorine e6 and nanocomposites containing these groups of PS) were used. The study included 90 patients with various wounds. Some patients were subjected to fluorescence diagnosis by laser spectral analysis before the PDT. Results: Positive results were achieved in 76 patients (84%, p &lt; 0.05). After the first PDT session, a decrease in the concentration of microflora was noticeable. By the third and seventh days, a significant to complete inactivation of bacteria was obtained. In all patients who were photo-diagnosed before PDT, a significant PS concentration decrease of more than 75% after PDT was obtained. Conclusion: PDT is an effective method for the inactivation of antibiotic-resistant pathogens, including in long non-healing wounds, contributing also to early tissue regeneration.