Pediatric Patient With Neurofibromatosis I Presenting With Perceptual Disturbances and a Suicide Attempt.

This is a case of a pediatric patient with a history of neurofibromatosis I (NFI) presenting to the emergency department secondary to a suicide attempt via self-strangulation after being verbally and physically bullied at school. Upon hospital admission, the 10-year-old patient was found to have significant auditory and visual perceptual hallucinations in addition to suicidal ideations, for which psychiatry was consulted. The patient underwent magnetic resonance imaging (MRI) of the brain to evaluate for intracranial neurofibromas as a potential etiology of his behavior. There is evidence that the growth of neurofibromas in the brain can be associated with psychosis. His brain MRI was significant for multiple foci of non-enhancing lesions seen in the cerebellum, white matter, supratentorial white matter, and bilateral hippocampi that can be seen in NFI, highlighting a medical etiology for the patient's auditory and visual perceptual disturbances. The objective of this case report is to explore medical causes of psychosis including metabolic disorders, neurodegenerative diseases, metabolic disturbances, parathyroid diseases, genetic disorders (Fragile X, Prader-Willi, etc.), autoimmune disorders, multiple sclerosis, temporal lobe epilepsy, infections, and brain tumors.

Next-gen regional fire risk mapping: Integrating hyperspectral imagery and National Forest Inventory data to identify hot-spot wildland-urban interfaces.

The increasing threat of high-severity wildfires in Mediterranean Wildland-Urban Interface (WUI) areas demands to develop effective fire risk assessment and management strategies. Simultaneously, the newfound accessibility of spaceborne hyperspectral data represents a significant potential for generating fire severity assessments, whereas National Forest Inventories (NFI) offer a vast dataset related to vegetation and fuel loads, which is essential for shaping the planning and strategies of forest services. This research work aims to advance the state-of-the-art in WUI fire risk mapping in the western Mediterranean Basin by combining PRISMA spaceborne hyperspectral data and Spanish NFI data. The proposed methodology had three main stages: (i) fire severity assessment at local scale (a wildfire) by using PRISMA hyperspectral data and Multi-Endmember Spectral Mixture Analysis (MESMA) leveraging field-based measurements of the Composite Burn Index (70 plots); (ii) development of a high fire severity probability map at regional scale from the extrapolation of a Random Forest predictive model calibrated from fire severity estimates, NFI data and topo-climatic variables at local scale (overall accuracy = 92 %; Kappa = 0.8); and (iii) identification and characterization of zones that concentrate WUIs with high probability of high fire severity if a fire event occurs (hot-spot WUIs) by crossing the information from the previous regional high fire severity probability map and a WUI cartography developed at regional scale. Study area was Castilla y León Autonomous Region (larger Spanish region, 94,226 km2), where the second-largest extreme Spanish wildfire event (28,000 ha) occurred. We identified hot-spot WUIs so that stakeholders and decision-makers could (i) prioritize resources and interventions for effective fire management and mitigation, (ii) allocate resources for prevention, and (iii) plan evacuation measures to safeguard lives and property. This study contributes to the development of next-generation fire risk assessment methods that combine remote sensing technologies with comprehensive ground-level datasets.

Knockdown of NFIC Promotes Bovine Myoblast Proliferation through the CENPF/CDK1 Axis.

As cellular transcription factors and DNA replicators, nuclear factor I (NFI) family members play an important role in mammalian development. However, there is still a lack of research on the muscle regeneration of NFI family members in cattle. In this study, the analysis of NFI family factors was conducted on their characterization, phylogenetics, and functional domains. We found that NFI family members were relatively conserved among different species, but there was heterogeneity in amino acid sequences, DNA coding sequences, and functional domain among members. Furthermore, among NFI family factors, we observed that NFIC exhibited highly expression in bovine muscle tissues, particularly influencing the expression of proliferation marker genes in myoblasts. To investigate the influence of NFIC on myoblast proliferation, we knocked down NFIC (si-NFIC) and found that the proliferation of myoblasts was significantly promoted. In terms of regulation mechanism, we identified that si-NFIC could counteract the inhibitory effect of the cell cycle inhibitor RO-3306. Interestingly, CENPF, as the downstream target gene of NFIC, could affect the expression of CDK1, CCNB1, and actively regulate the cell cycle pathway and cell proliferation. In addition, when CENPF was knocked down, the phosphorylation of p53 and the expression of Bax were increased, but the expression of Bcl2 was inhibited. Our findings mainly highlight the mechanism by which NFIC acts on the CENPF/CDK1 axis to regulate the proliferation of bovine myoblasts.

Epigenetic Mechanisms in Vascular Inflammation: Modulation of Endothelial Adhesion Molecules and Endothelium-Leukocyte Adhesion.

The endothelium, an essential component of the vascular system, plays a critical role in the inflammatory response. Under pro-inflammatory stimuli, endothelial cells undergo activation and dysfunction, leading to the release of inflammatory mediators and upregulation of cell adhesion molecules. These changes facilitate the adhesion, rolling, and transmigration of leukocytes into the subendothelial space. Emerging evidence suggests that epigenetic mechanisms, including nucleic acid methylation, post-translational histone modifications, and non-coding RNA, contribute significantly to the regulation of vascular inflammation and expression of cell adhesion molecules. Understanding the epigenetic molecular signatures that govern these processes may provide new insights into the development of therapeutic strategies to combat vascular inflammation and associated diseases. This review aims to summarize the current knowledge on the epigenetic mechanisms involved in modulating the intricate processes underlying vascular inflammation, with a specific focus on the expression of endothelial adhesion molecules and endothelium-leukocyte adhesion.

Noninvasive identification of probable fibrotic nonalcoholic steatohepatitis across the spectrum of glucose tolerance in the United States.

AIM: Identifying patients with fibrotic nonalcoholic steatohepatitis (NASH) is crucial in order to refer them to specialist care as fibrotic NASH represents one of the major inclusion criteria for clinical trials. The aim of this study is to report the prevalence of fibrotic NASH in the general US population across the spectrum of glucose tolerance and evaluate the performance of the recently proposed Fibrotic NASH Index (FNI). METHODS: This is a cross-sectional study of US adults participating in the 2017-2020 cycles of the National Health and Nutrition Examination Survey. Participants with available data to calculate FNI (which is based on AST, HbA1c and HDL-cholesterol) and with a reliable vibration controlled transient elastography examination were included. We excluded participants with chronic viral hepatitis, significant alcohol consumption or other forms of liver disease. Probable fibrotic NASH was defined as a Fibroscan-AST (FAST) score ≥ 0.35. RESULTS: We included a total of 6268 participants. The overall prevalence of probable fibrotic NASH was 5.9 % (95 % CI 5.2-6.7) and it increased progressively from participants with normal glucose tolerance (3.7 %, 95 % CI 2-9-4.7) to those with diabetes (14.7 %, 95 % CI 12.1-17.8). The performance of FNI for probable fibrotic NASH was satisfactory in the overall population (area under the receiver operating characteristic curve (AUROC): 0.93, 95 % CI 0.92-0.94) and it maintained a good accuracy also in participants with diabetes (n = 1113, AUROC 0.89, 95 % CI 0.86-0.92). In all groups it outperformed Fibrosis-4. CONCLUSIONS: FNI is an easy and reliable test to screen for NASH and its performance is maintained in patients with diabetes, a condition that was shown to negatively influence the performance of several non-invasive scores.

Forest disturbance and recovery in Peruvian Amazonia.

Amazonian forests function as biomass and biodiversity reservoirs, contributing to climate change mitigation. While they continuously experience disturbance, the effect that disturbances have on biomass and biodiversity over time has not yet been assessed at a large scale. Here, we evaluate the degree of recent forest disturbance in Peruvian Amazonia and the effects that disturbance, environmental conditions and human use have on biomass and biodiversity in disturbed forests. We integrate tree-level data on aboveground biomass (AGB) and species richness from 1840 forest plots from Peru's National Forest Inventory with remotely sensed monitoring of forest change dynamics, based on disturbances detected from Landsat-derived Normalized Difference Moisture Index time series. Our results show a clear negative effect of disturbance intensity tree species richness. This effect was also observed on AGB and species richness recovery values towards undisturbed levels, as well as on the recovery of species composition towards undisturbed levels. Time since disturbance had a larger effect on AGB than on species richness. While time since disturbance has a positive effect on AGB, unexpectedly we found a small negative effect of time since disturbance on species richness. We estimate that roughly 15% of Peruvian Amazonian forests have experienced disturbance at least once since 1984, and that, following disturbance, have been increasing in AGB at a rate of 4.7 Mg ha-1 year-1 during the first 20 years. Furthermore, the positive effect of surrounding forest cover was evident for both AGB and its recovery towards undisturbed levels, as well as for species richness. There was a negative effect of forest accessibility on the recovery of species composition towards undisturbed levels. Moving forward, we recommend that forest-based climate change mitigation endeavours consider forest disturbance through the integration of forest inventory data with remote sensing methods.

Los bosques amazónicos son reservorios y sumideros de carbono, contribuyendo a la mitigación del cambio climático. Si bien experimentan perturbaciones, el efecto de estas en la biomasa y biodiversidad a través del tiempo no ha sido evaluado a gran escala. En este estudio, evaluamos el grado de perturbación forestal reciente en la Amazonía peruana y los efectos de las perturbaciones, condiciones ambientales y actividad antrópica sobre la biomasa y la biodiversidad en bosques perturbados. Los datos de biomasa aérea y riqueza de especies forestales provenientes de 1,840 subparcelas del Inventario Nacional Forestal y de Fauna Silvestre (INFFS) se analizaron en conjunto con la información de detección de cambios de cobertura forestal derivadas de perturbaciones detectadas a partir de series de tiempo de índices de diferencia de humedad normalizados (NDMI) a partir de imágenes Landsat. Nuestros resultados muestran un claro efecto negativo de la intensidad de las perturbaciones sobre la riqueza de especies arbóreas. Este efecto también fue observado en los valores de recuperación de biomasa aérea y riqueza de especies arbóreas hacia niveles no perturbados, así como en la recuperación de la composición florística. El tiempo transcurrido desde la perturbación tuvo un efecto mayor sobre la biomasa aérea que sobre la riqueza de especies. Mientras el tiempo desde una perturbación forestal tuvo un efecto positivo sobre la biomasa área, se observó un pequeño efecto negativo sobre la riqueza de especies. Estimamos que aproximadamente el 15% de los bosques en la Amazonía peruana han experimentado una perturbación al menos una vez desde 1984, y que, tras esta, han aumentado en biomasa aérea en una tasa de 4.7 Mg ha−1 año−1 durante los primeros 20 años posteriores al evento de perturbación. Además, el efecto positivo de la cubierta forestal circundante fue evidente tanto para la biomasa aérea como para su recuperación hacia niveles no perturbados, así como para los valores de riqueza de especies. La accesibilidad a bosques tuvo un efecto negativo en la recuperación de la composición de especies hacia niveles no perturbados. Recomendamos que los esfuerzos de mitigación de cambio climático basados en bosques tengan en cuenta las perturbaciones forestales mediante el análisis integrado de información de inventarios forestales con métodos de teledetección.

Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization.

The majority of pathogenic mutations in the neurofibromatosis type I (NF1) gene reduce total neurofibromin protein expression through premature truncation or microdeletion, but it is less well understood how loss-of-function missense variants drive NF1 disease. We have found that patient variants in codons 844 to 848, which correlate with a severe phenotype, cause protein instability and exert an additional dominant-negative action whereby wild-type neurofibromin also becomes destabilized through protein dimerization. We have used our neurofibromin cryogenic electron microscopy structure to predict and validate other patient variants that act through a similar mechanism. This provides a foundation for understanding genotype-phenotype correlations and has important implications for patient counseling, disease management, and therapeutics.

A highly efficient needle-free-injection delivery system for mRNA-LNP vaccination against SARS-CoV-2.

Despite the various vaccines that have been developed to combat the coronavirus disease 2019 (COVID-19) pandemic, the persistent and unpredictable mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require innovative and unremitting solutions to cope with the resultant immune evasion and establish a sustainable immune barrier. Here we introduce a vaccine-delivery system with a combination of a needle-free injection (NFI) device and a SARS-CoV-2-Spike-specific mRNA-Lipid Nanoparticle (LNP) vaccine. The benefits are duller pain and a significant increase of immunogenicity compared to the canonical needle injection (NI). From physicochemical and bioactivity analyses, the structure of the mRNA-LNP maintains stability upon NFI, contradictory to the belief that LNPs are inclined towards destruction under the high-pressure conditions of NFI. Moreover, mRNA-LNP vaccine delivered by NFI induces significantly more binding and neutralizing antibodies against SARS-CoV-2 variants than the same vaccine delivered by NI. Heterogeneous vaccination of BA.5-LNP vaccine with NFI enhanced the generation of neutralizing antibodies against Omicron BA.5 variants in rabbits previously vaccinated with non-BA.5-specific mRNA-LNP or other COVID-19 vaccines. NFI parameters can be adjusted to deliver mRNA-LNP subcutaneously or intramuscularly. Taken together, our results suggest that NFI-based mRNA-LNP vaccination is an effective substitute for the traditional NI-based mRNA-LNP vaccination.

Exploring characteristics of national forest inventories for integration with global space-based forest biomass data.

National forest inventories (NFIs) are a reliable source for national forest measurements. However, they are usually not developed for linking with remotely sensed (RS) biomass information. There are increasing needs and opportunities to facilitate this link towards better global and national biomass estimation. Thus, it is important to study and understand NFI characteristics relating to their integration with space-based products; in particular for the tropics where NFIs are quite recent, less frequent, and partially incomplete in several countries. Here, we (1) assessed NFIs in terms of their availability, temporal distribution, and extent in 236 countries from FAO's Global Forest Resources Assessment (FRA) 2020; (2) compared national forest biomass estimates in 2018 from FRA and global space-based Climate Change Initiative (CCI) product in 182 countries considering NFI availability and temporality; and (3) analyzed the latest NFI design characteristics in 46 tropical countries relating to their integration with space-based biomass datasets. We observed significant NFI availability globally and multiple NFIs were mostly found in temperate and boreal countries while most of the single NFI countries (94 %) were in the tropics. The latest NFIs were more recent in the tropics and many countries (35) implemented NFIs from 2016 onwards. The increasing availability and update of NFIs create new opportunities for integration with space-based data at the national level. This is supported by the agreement we found between country biomass estimates for 2018 from FRA and CCI product, with a significantly higher correlation in countries with recent NFIs. We observed that NFI designs varied greatly in tropical countries. For example, the size of the plots ranged from 0.01 to 1 ha and more than three-quarters of the countries had smaller plots of ≤0.25 ha. The existing NFI designs could pose specific challenges for statistical integration with RS data in the tropics. Future NFI and space-based efforts should aim towards a more integrated approach taking advantage of both data streams to improve national estimates and help future data harmonization efforts. Regular NFI efforts can be expanded with the inclusion of some super-site plots to enhance data integration with currently available space-based applications. Issues related to cost implications versus improvements in the accuracy, timeliness, and sustainability of national forest biomass estimation should be further explored.

NBCe1 Regulates Odontogenic Differentiation of Human Dental Pulp Stem Cells via NF-κB.

Background and Objectives: Dental pulp stem cells (DPSCs) play an important role in the repair of tooth injuries. Electrogenic sodium bicarbonate cotransporter 1 (NBCe1) is a Na＋-coupled HCO3- transporter encoded by the solute carrier 4A4 (SLC4A4) gene and plays a crucial role in maintaining the pH of DPSCs. Our previous research confirmed that NBCe1 is highly expressed in odontoblasts during the development of the tooth germ. Therefore, in this study, we aimed to investigate the effect of NBCe1 on odontogenic differentiation of DPSCs and further clarify the underlying mechanisms. Methods and Results: DPSCs were isolated and identified, and the selective NBCe1 inhibitor S0859 was used to treat DPSCs. We used a cell counting Kit-8 assay to detect cell proliferative ability, and intracellular pH was assessed using confocal microscopy. Odontogenic differentiation of DPSCs was analyzed using real-time PCR and Alizarin Red S staining, and the NF-κB pathway was assessed using western blotting. Our results indicated that 10 µM S0859 was the optimal concentration for DPSC induction. Intracellular pH was decreased upon treatment with S0859. The mRNA expressions of DSPP, DMP1, RUNX2, OCN, and OPN were upregulated in the NBCe1 inhibited group compared to the controls. Moreover, NBCe1 inhibition significantly activated the NF-κB pathway, and a NF-κB inhibitor reduced the effect of NBCe1 on DPSC differentiation. Conclusions: NBCe1 inhibition significantly promotes odontogenic differentiation of DPSCs, and this process may be regulated by activating the NF-κB signaling pathway.

Increase in dead wood, large living trees and tree diversity, yet decrease in understory vegetation cover: The effect of three decades of biodiversity-oriented forest policy in Swedish forests.

In Sweden, the majority of forest area has been altered by industrial forestry over the decades. Almost 30 years ago, a shift towards biodiversity-oriented forest management practices occurred. Here we took advantage of long-term data collected by the Swedish National Forest Inventory to track developmental changes in forest structural components over this time. We assessed changes in structural components that play an important role in biodiversity (dead wood, large living trees, tree species composition, and understory vegetation) in four forest types with descending tiers of biodiversity protection: protected areas, woodland key habitats, low-productivity forests and production forests. Overall, we found a positive trend in the volumes of dead wood and large living trees, as well as in tree species diversity, while there was a general decline in understory vegetation coverage. Most observed changes were consistent with the intended outcomes of the current forest policy, adapted in the early 1990s. The implementation of retention forestry is likely driving some of the observed changes in forest structural components in the south. In contrast, we observed no changes in any of the focal structural components in the north, which could be attributed to the ongoing clear-cutting of forests previously managed less intensively. Dead wood and large living trees increased not only in managed, but also in unmanaged forests, likely reflecting historical management. The increased tree species diversity can be explained through current forest management practices that encourages maintenance of additional tree species. Decreasing understory vegetation coverage in both dense managed and unmanaged forests suggests that factors other than forestry contribute to the ongoing changes in understory vegetation in Swedish forests. Overall, the observed increase in structural components has not yet been reflected in documented improvements for red-listed forest species, which may be due to delays in species responses to small improvements, as well as a lack of detailed monitoring. Similarly, the increased availability of forest structural components might still be insufficient to meet the specific habitat requirements of red-listed species.

Transcription Factors with Targeting Potential in Gliomas.

Gliomas portray a large and heterogeneous group of CNS tumors, encompassing a wide range of low- to high-grade tumors, as defined by histological and molecular characteristics. The identification of signature mutations and other molecular abnormalities has largely impacted tumor classification, diagnosis, and therapy. Transcription factors (TFs) are master regulators of gene expression programs, which ultimately shape cell fate and homeostasis. A variety of TFs have been detected to be aberrantly expressed in brain tumors, being highly implicated in critical pathological aspects and progression of gliomas. Herein, we describe a selection of oncogenic (GLI-1/2/3, E2F1-8, STAT3, and HIF-1/2) and tumor suppressor (NFI-A/B, TBXT, MYT1, and MYT1L) TFs that are deregulated in gliomas and are subsequently associated with tumor development, progression, and migratory potential. We further discuss the current targeting options against these TFs, including chemical (Bortezomib) and natural (Plumbagin) compounds, small molecules, and inhibitors, and address their potential implications in glioma therapy.

Deletion of NFIX results in defective progression through meiosis within the mouse testis†.

Members of the nuclear factor I (NFI) family are key regulators of stem cell biology during development, with well-documented roles for NFIA, NFIB, and NFIX in a variety of developing tissues, including brain, muscle, and lung. Given the central role these factors play in stem cell biology, we posited that they may be pivotal for spermatogonial stem cells or further developing spermatogonia during testicular development. Surprisingly, in stark contrast to other developing organ systems where NFI members are co-expressed, these NFI family members show discrete patterns of expression within the seminiferous tubules. Sertoli cells (spermatogenic supporting cells) express NFIA, spermatocytes express NFIX, round spermatids express NFIB, and peritubular myoid cells express each of these three family members. Further analysis of NFIX expression during the cycle of the seminiferous epithelium revealed expression not in spermatogonia, as we anticipated, but in spermatocytes. These data suggested a potential role for NFIX in spermatogenesis. To investigate, we analyzed mice with constitutive deletion of Nfix (Nfix-null). Assessment of germ cells in the postnatal day 20 (P20) testes of Nfix-null mice revealed that spermatocytes initiate meiosis, but zygotene stage spermatocytes display structural defects in the synaptonemal complex, and increased instances of unrepaired DNA double-strand breaks. Many developing spermatocytes in the Nfix-null testis exhibited multinucleation. As a result of these defects, spermatogenesis is blocked at early diplotene and very few round spermatids are produced. Collectively, these novel data establish the global requirement for NFIX in correct meiotic progression during the first wave of spermatogenesis.

NFI transcriptionally represses CDON and is required for SH-SY5Y cell survival.

Nuclear Factor One (NFI) family of transcription factors regulate proliferation and multiple aspects of differentiation, playing analogous roles in embryonic development and various types of cancer. While all NFI family members are expressed in the developing brain and are involved in progression of brain cancers, their role in neuroblastoma has not been studied. Here we show that NFIB is required for the survival and proliferation of SH-SY5Y neuroblastoma cells, assessed by viability and colony formation assays. Cdon, an Ig superfamily member, is a SHH dependence receptor that acts as a tumor suppressor in neuroblastoma. In the absence of NFI, Cdon is upregulated in the developing mouse brain, however the mechanisms by which its transcription is regulated remains unknown. We report CDON as a downstream target of NFIs in SH-SY5Y cells. There are three putative NFI binding sites within the one kb CDON promoter, two of which are occupied by NFIs in SH-SY5Y cells and human neural stem cells. In dual-luciferase assays, Nfib directly represses CDON proximal promoter activity. Moreover, silencing NFIB leads to upregulation of CDON in SH-SY5Y cells, however, decreased cell proliferation in NFIB silenced cells could not be rescued by concomitantly silencing CDON, suggesting other molecular players are involved. For instance, p21, an NFI target in glioblastoma and breast cancer cells, is also upregulated upon NFIB knock-down. We propose that NFIB is indispensable for SH-SY5Y cells which may involve regulation of apoptosis inducer proteins CDON and p21.

Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina.

Gene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis and cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA and single-cell ATAC sequencing (scATAC-seq) analysis in developing mouse and human retina to identify multiple interconnected, evolutionarily conserved GRNs composed of cell-type-specific transcription factors that both activate genes within their own network and inhibit genes in other networks. These GRNs control temporal patterning in primary progenitors, regulate transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirm that NFI transcription factors selectively activate expression of genes promoting late-stage temporal identity in primary retinal progenitors and identify other transcription factors that regulate rod photoreceptor specification in postnatal retina. This study inventories cis- and trans-acting factors that control retinal development and can guide cell-based therapies aimed at replacing retinal neurons lost to disease.

Neutrophil extracellular trap formation index predicts occurrences of deep surgical site infection after laparotomy.

BACKGROUND: Deep surgical site infections (DSSIs) are serious complications after laparotomy. Neutrophil extracellular traps (NETs) play a vital role in the development of DSSI. Here, we focused on a new approach to predicting the occurrence of DSSI through the detection of the NET formation index (NFI), and compared its prediction ability with other clinical infection indicators. METHODS: Patients who received laparotomy were prospectively enrolled in this study. General information, APACHE II score, SOFA score, and serum infection indicators were recorded. The postoperative abdominal drainage fluid was collected within 3 days after the operation for quantification of the NFI. RESULTS: A total of 92 consecutive patients were included, with 22 patients were diagnosed with DSSI. The NFI in the DSSI group was 32.70%±19.33% while the corresponding index was 10.70%±8.25% in the non-DSSI group (P<0.01). The mean APACHE II and SOFA score had significant differences between the two groups. The NFI was positively correlated with the APACHE II score (P<0.01, r=0.269) and SOFA score (P=0.013, r=0.258). Patients with a high NFI (NFI >13.86%) had a higher risk of developing DSSI. According to the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC) of the NFI, C-reactive protein (CRP) and procalcitonin (PCT) were 0.912, 0.748 and 0.731, respectively. CONCLUSIONS: In this cohort of surgical patients, the quantification of the NFI had a considerable predictive value for early identification of DSSI. The NFI in drainage fluid turned out to be a more sensitive and specific predictor of DSSI than serum infection indicators including CRP and PCT.

Two large-scale forest scenario modelling approaches for reporting CO2 removal: a comparison for the Romanian forests.

BACKGROUND: Forest carbon models are recognized as suitable tools for the reporting and verification of forest carbon stock and stock change, as well as for evaluating the forest management options to enhance the carbon sink provided by sustainable forestry. However, given their increased complexity and data availability, different models may simulate different estimates. Here, we compare carbon estimates for Romanian forests as simulated by two models (CBM and EFISCEN) that are often used for evaluating the mitigation options given the forest-management choices. RESULTS: The models, calibrated and parameterized with identical or harmonized data, derived from two successive national forest inventories, produced similar estimates of carbon accumulation in tree biomass. According to CBM simulations of carbon stocks in Romanian forests, by 2060, the merchantable standing stock volume will reach an average of 377 m3 ha-1, while the carbon stock in tree biomass will reach 76.5 tC ha-1. The EFISCEN simulations produced estimates that are about 5% and 10%, respectively, lower. In addition, 10% stronger biomass sink was simulated by CBM, whereby the difference reduced over time, amounting to only 3% toward 2060. CONCLUSIONS: This model comparison provided valuable insights on both the conceptual and modelling algorithms, as well as how the quality of the input data may affect calibration and projections of the stock and stock change in the living biomass pool. In our judgement, both models performed well, providing internally consistent results. Therefore, we underline the importance of the input data quality and the need for further data sampling and model improvements, while the preference for one model or the other should be based on the availability and suitability of the required data, on preferred output variables and ease of use.

Downregulation of miR-184 facilitates osseous differentiation in periodontal ligament stem cells by modulating nuclear factor I-C.

BACKGROUND/PURPOSE: PDLSCs (periodontal ligament stem cells), derived from dental tissues, are candidate cells for regeneration of dental tissues. MiRNAs could regulate osteogenic differentiation and the transformation into osteoblasts. This study was conducted to figure out how miR-184 regulates osteoblastic differentiation in PDLSCs. MATERIALS AND METHODS: PDLSCs were isolated from premolars, and the osteoblastic differentiation was validated via Alizarin red staining and determination of ALP (alkaline phosphatase) activity. Expression of osteogenic specific genes were evaluated by western blot, and the expression pattern of miR-184 was determined by qRT-PCR. Target gene of miR-184 was then verified by dual luciferase reporter assay. RESULTS: Osteogenic-induced PDLSCs were successfully established with increased mineral deposition, ALP activity and protein expression of RUNX2 (runt-related transcription factor 2), osterix and BSP (bone sialoprotein). MiR-184 was reduced during osteoblastic differentiation of PDLSCs, and over-expression of miR-184 suppressed osteoblastic differentiation, as evidenced by reduction in mineral deposition, ALP activity and protein expression of RUNX2, osterix and BSP. MiR-184 could target NFI-C (nuclear factor I-C), and inhibit NFI-C expression in PDLSCs. NFI-C was enhanced during osteoblastic differentiation of PDLSCs, suggesting negative correlation with miR-184. Forced NFI-C expression promoted osteoblastic differentiation, and counteracted with the suppressive effects of miR-184 on osteoblastic differentiation. CONCLUSION: Downregulation of miR-184 facilitates osteoblastic differentiation in PDLSCs by modulating NFI-C, providing novel therapeutic strategy for regeneration of dental tissues.

The physical and mental health of the medical staff in Wuhan Huoshenshan Hospital during COVID-19 epidemic: A Structural Equation Modeling approach.

INTRODUCTION: Early in the epidemic of coronavirus disease 2019, the Chinese government recruited a proportion of healthcare workers to support the designated hospital (Huoshenshan Hospital) in Wuhan, China. The majority of front-line medical staff suffered from adverse effects, but their real health status during COVID-19 epidemic was still unknown. The aim of the study was to explore the latent relationship of the physical and mental health of front-line medical staff during this special period. METHODS: A total of 115 military medical staff were recruited between February 17th and February 29th, 2020 and asked to complete questionnaires assessing socio-demographic and clinical characteristics, self-reported sleep status, fatigue, resilience and anxiety. RESULTS: 55 medical staff worked within Intensive Care and 60 worked in Non-intensive Care, the two groups were significantly different in reported general fatigue, physical fatigue and tenacity (P<0.05). Gender, duration working in Wuhan, current perceived stress level and health status were associated with significant differences in fatigue scores (P<0.05), the current perceived health status (P<0.05) and impacted on the resilience and anxiety of participants. The structural equation modeling analysis revealed resilience was negatively associated with fatigue (ß=-0.52, P<0.01) and anxiety (ß=-0.24, P<0.01), and fatigue had a direct association with the physical burden (ß=0.65, P<0.01); Fatigue mediated the relationship between resilience and anxiety (ß=-0.305, P=0.039) as well as resilience and physical burden (ß=-0.276, P=0.02). CONCLUSION: During an explosive pandemic situation, motivating the effect of protective resilience and taking tailored interventions against fatigue are promising ways to protect the physical and mental health of the front-line medical staff.