Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson’s disease in rats

Neural progenitor cells(NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox(VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR(0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition(5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6(Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs(ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease.

Legacy effects of historical woodland changes on contemporary plant functional composition

Considering the legacy of plant functional composition can help assess ecosystem functions and ecosystem services across different spatial scales under land cover changes.Woody plants likely respond to natural and anthropogenic perturbations due to historical events(e.g.,agricultural development),thus contemporary plant functional composition may be explained by historical woodland change,a type of land cover change.We propose that historical woodland changes may have legacy effects on contemporary plant functional composition.Here,we used partial least squares regression and linear mixed model analyses to test this assumption by coupling data on community weighted means(CWM)and community weighted variance(CWV)of vegetation plots and calculating the time of woodland existence across different periods from AD 0 to 2017.We found that the legacy effects of historical land cover changes on CWM and CWV during the existence time of woodland,particularly from AD 0 to 900,were drivers of contemporary plant functional composition at large spatial scales.Furthermore,historical woodland changes can affect contemporary plant functional composition,depending on the biome type.Particularly,the CWM of plant height,seed mass,and seed length showed the strongest correlations with woodland changes from AD 1910 to 2010 in tropics with year-round rain,and the CWM of leaf traits correlated with woodland changes from AD 0 to 1700 in tropics with summer rain.Our study provides the effective evidence on the legacy of historical woodland changes and the effects on contemporary plant functional composition,which is crucial with respect to effective management of plant diversity and assessing ecosystem functions and services from local to global scales over time.

Determinants of species assemblages of insect pests in alpine forest ecosystems of western China

Background:Insect pests are a significant threat to natural resources and social development.Modeling species assemblages of insect pests can predict spatiotemporal pest dynamics.However,research gaps remain regarding the mechanism for determining species assemblages of insect pests in alpine forest ecosystems.Here,we explored these determinants using a field investigation conducted for insect pests in a region of the Qinghai-Tibet Plateau.We assessed the species assemblages of insect pests in alpine forest ecosystems based on species co-occurrence patterns and species diversity(i.e.,observed diversity,dark diversity,community completeness,and species pool).A probabilistic model was used to test for statistically significant pairwise patterns of species co-occurrence using the presence-absence matrix of pest species based on species interactions.We used ordinary least squares regression modeling to explore relationships between abiotic factors(i.e.,climate factors and human influence)and species diversity.Results:Positive pest species interactions and many association links can occur widely across different investigation sites and parts of plant hosts in alpine forest ecosystems.We detected high dark diversity and low community completeness of insect pests in alpine forest ecosystems.High temperature and precipitation could promote pest species diversity,particularly dark diversity and species pools.Human influence could drive high levels of pest species diversity and lead to dark diversity and species pools.Community completeness could be an effective indicator for insect pest risk assessment.Conclusions:Our study provides new evidence for the determinants of insect pest species assemblages in alpine forest ecosystems from the perspectives of pest species interactions and abiotic factors.The findings of our study could reveal the mechanism for shaping species assemblages and support the prevention and control of insect pests in alpine forest ecosystems.