Landscape quantifies the intermediate state and transition dynamics in ecological networks.

Understanding the ecological mechanisms associated with the collapse and restoration is especially critical in promoting harmonious coexistence between humans and nature. So far, it remains challenging to elucidate the mechanisms of stochastic dynamical transitions for ecological systems. Using an example of plant-pollinator network, we quantified the energy landscape of ecological system. The landscape displays multiple attractors characterizing the high, low and intermediate abundance stable states. Interestingly, we detected the intermediate states under pollinator decline, and demonstrated the indispensable role of the intermediate state in state transitions. From the landscape, we define the barrier height (BH) as a global quantity to evaluate the transition feasibility. We propose that the BH can serve as a new early-warning signal (EWS) for upcoming catastrophic breakdown, which provides an earlier and more accurate warning signal than traditional metrics based on time series. Our results promote developing better management strategies to achieve environmental sustainability.

Two distinct trajectories of clinical and neurodegeneration events in Parkinson's disease.

Increasing evidence suggests that Parkinson's disease (PD) exhibits disparate spatial and temporal patterns of progression. Here we used a machine-learning technique-Subtype and Stage Inference (SuStaIn) - to uncover PD subtypes with distinct trajectories of clinical and neurodegeneration events. We enrolled 228 PD patients and 119 healthy controls with comprehensive assessments of olfactory, autonomic, cognitive, sleep, and emotional function. The integrity of substantia nigra (SN), locus coeruleus (LC), amygdala, hippocampus, entorhinal cortex, and basal forebrain were assessed using diffusion and neuromelanin-sensitive MRI. SuStaIn model with above clinical and neuroimaging variables as input was conducted to identify PD subtypes. An independent dataset consisting of 153 PD patients and 67 healthy controls was utilized to validate our findings. We identified two distinct PD subtypes: subtype 1 with rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, and degeneration of the SN and LC as early manifestations, and cognitive impairment and limbic degeneration as advanced manifestations, while subtype 2 with hyposmia, cognitive impairment, and limbic degeneration as early manifestations, followed later by RBD and degeneration of the LC in advanced disease. Similar subtypes were shown in the validation dataset. Moreover, we found that subtype 1 had weaker levodopa response, more GBA mutations, and poorer prognosis than subtype 2. These findings provide new insights into the underlying disease biology and might be useful for personalized treatment for patients based on their subtype.

Genome-Wide Identification and Analysis of the MADS-Box Transcription Factor Genes in Blueberry (Vaccinium spp.) and Their Expression Pattern during Fruit Ripening.

MADS-box is a class of transcriptional regulators that are ubiquitous in plants and plays important roles in the process of plant growth and development. Identification and analysis of blueberry MADS-box genes can lay a foundation for their function investigations. In the present study, 249 putative MADS-box genes were identified in the blueberry genome. Those MADS-box genes were distributed on 47 out of 48 chromosomes. The phylogenetic and evolutionary analyses showed that blueberry MADS-box genes were divided into 131 type I members and 118 type II members. The type I genes contained an average of 1.89 exons and the type II genes contained an average of 7.83 exons. Motif analysis identified 15 conserved motifs, of which 4 were related to the MADS domain and 3 were related to the K-box domain. A variety of cis-acting elements were found in the promoter region of the blueberry MADS-box gene, indicating that the MADS-box gene responded to various hormones and environmental alterations. A total of 243 collinear gene pairs were identified, most of which had a Ka/Ks value of less than 1. Nine genes belonging to SEP, AP3/PI, and AGL6 subfamilies were screened based on transcriptomic data. The expression patterns of those nine genes were also verified using quantitative PCR, suggesting that VcMADS6, VcMADS35, VcMADS44, VcMADS58, VcMADS125, VcMADS188, and VcMADS212 had potential functions in blueberry fruit ripening. The results of this study provide references for an in-depth understanding of the biological function of the blueberry MADS-box genes and the mechanism of blueberry fruit ripening.

A simulated, randomized study on the safety and immunogenicity of three consecutive commercial-scale batches of the CTN-1V strain human rabies vaccine to verify the inter-batch consistency.

In this study, we sought to evaluate the inter-batch consistency and safety of the CTN-1 V human rabies vaccine (Vero cells). A total of 594 healthy participants aged 10-60 years were enrolled from Mianzhu, Sichuan Province, and randomized into three batch groups to receive vaccination via the Essen Regimen, that is, a single dose on days 0, 3, 7, 14, and 28 in the deltoid muscle of the upper arm. The serum antibody geometric mean concentration (GMC) and positive conversion rate of each group were determined using a rapid fluorescence focus inhibition test (RFFIT) before the first-dose immunization, 14 d after the first-dose immunization, and 14 d and 12 mo after full immunization. Adverse events (AEs) 30 min and 30 d after immunization were observed in each group. There were 322 cases of AEs during the observation period, with an overall incidence of 54.4%. The incidences of AEs in groups A, B, and C were 57.4%, 51.5%, and 54.3%, respectively. There were no significant differences among the groups (P > .05). Moreover, there were no significant differences (P > .05) in the serum GMC or antibody-positive conversion rate between any two groups at any time point. The bilateral 95% confidence interval of the GMC ratio between any two groups 14 d after the first-dose immunization was within the range of 0.67-1.50. This study shows that the CTN-1 V human rabies vaccine (Vero cells) has reliable safety and stable immunogenicity between batches.

This was a randomized, double-blind, equivalent clinical study on the inter-batch consistency of rabies vaccine. The rabies virus CTN strain adopted for the vaccine was isolated by China National Institute for Food and Drug Control. It has a gene sequence homology of 82.0%­93.0% with the representative strains of street virus isolated in China (i.e., CQ92, HN06, and J strains), higher than that of other vaccine strains (aG, PM, and PV strains). A total of 594 participants were enrolled in this study, and were randomized into three batch groups. Blood samples were collected from participants in each group before vaccination, at 14 days after the first dose of vaccination, and at 14 d and 12 mo after the fifth dose of vaccination, in order to detect antibody levels and observe adverse reactions. There was no significant difference in serum antibody levels and adverse reactions between any two of the three groups, indicating that different vaccine batches manufactured at the commercial scale can maintain stable immunogenicity and safety profiles.