Depression mediated the relationships between precentral-subcortical causal links and motor recovery in spinal cord injury patients.

Depression after brain damage may impede the motivation and consequently influence the motor recovery after spinal cord injury (SCI); however, the neural mechanism underlying the psychological effects remains unclear. This study aimed to examine the casual connectivity changes of the emotion-motivation-motor circuit and the potential mediating effects of depression on motor recovery after SCI. Using the resting-state functional magnetic resonance imaging data of 35 SCI patients (24 good recoverers, GR and 11 poor recoverers, PR) and 32 healthy controls (HC), the results from the conditional Granger causality (GC) analysis demonstrated that the GR group exhibited sparser emotion-motivation-motor GC network compared with the HC and PR groups, though the in-/out-degrees of the emotion subnetwork and the motor subnetwork were relatively balanced in the HC and GR group. The PR group showed significantly inhibitory causal links from amygdala to supplementary motor area and from precentral gyrus to nucleus accumbens compared with GR group. Further mediation analysis revealed the indirect effect of the 2 causal connections on motor function recovery via depression severity. Our findings provide further evidence of abnormal causal connectivity in emotion-motivation-motor circuit in SCI patients and highlight the importance of emotion intervention for motor function recovery after SCI.

Neural efficiency and proficiency adaptation of effective connectivity corresponding to early and advanced skill levels in athletes of racket sports.

This study explored how the neural efficiency and proficiency worked in athletes with different skill levels from the perspective of effective connectivity brain network in resting state. The deconvolved conditioned Granger causality (GC) analysis was applied to functional magnetic resonance imaging (fMRI) data of 35 elite athletes (EAs) and 42 student-athletes (SAs) of racket sports as well as 39 normal controls (NCs), to obtain the voxel-wised hemodynamic response function (HRF) parameters representing the functional segregation and effective connectivity representing the functional integration. The results showed decreased time-to-peak of HRF in the visual attention brain regions in the two athlete groups compared with NC and decreased response height in the advanced motor control brain regions in EA comparing to the nonelite groups, suggesting the neural efficiency represented by the regional HRF was different in early and advanced skill levels. GC analysis demonstrated that the GC values within the middle occipital gyrus had a linear trend from negative to positive, suggesting a stepwise "neural proficiency" of the effective connectivity from NC to SA then to EA. The GC values of the inter-lobe circuits in EA had the trend to regress to NC levels, in agreement with the neural efficiency of these circuits in EA. Further feature selection approach suggested the important role of the cerebral-brainstem GC circuit for discriminating EA. Our findings gave new insight into the complementary neural mechanisms in brain functional segregation and integration, which was associated with early and advanced skill levels in athletes of racket sports.

Detection of DNA copy number alterations by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of single nucleotide polymorphisms.

OBJECTIVES: Copy number alterations (CNAs) are frequently found in malignant tissues. Different approaches have been used for CNA detection. However, it is not easy to detect a large panel of CNA targets in heterogenous tumors. METHODS: We have developed a CNAs detection approach through quantitatively analyzed allelic imbalance by allelotyping single nucleotide polymorphisms (SNPs) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, the copy number changes were quantified by real-competitive PCR (rcPCR) to distinguish loss of heterozygosity (LOH) and genomic amplification. The approach was used to validate the CNA regions detected by next generation sequencing (NGS) in early-stage lung carcinoma. RESULTS: CNAs were detected in heterogeneous DNA samples where tumor DNA is present at only 10% through the SNP based allelotyping. In addition, two different types of CNAs (loss of heterozygosity and chromosome amplification) were able to be distinguished quantitatively by rcPCR. Validation on a total of 41 SNPs from the selected CNA regions showed that copy number changes did occur, and the tissues from early-stage lung carcinoma were distinguished from normal. CONCLUSIONS: CNA detection by MALDI-TOF MS can be used for validating potentially interesting genomic regions identified from next generation sequencing, and for detecting CNAs in tumor tissues consisting of a mixture of neoplastic and normal cells.

A reachable probability approach for the analysis of spatio-temporal dynamics in the human functional network.

The dynamic architecture of the human brain has been consistently observed. However, there is still limited modeling work to elucidate how neuronal circuits are hierarchically and flexibly organized in functional systems. Here we proposed a reachable probability approach based on non-homogeneous Markov chains, to characterize all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level. We proved at the theoretical level the convergence of the functional brain network system, and demonstrated that this approach is able to detect network steady states across connectivity structure, particularly in areas of the default mode network. We further explored the dynamically hierarchical functional organization centered at the primary sensory cortices. We observed smaller optimal reachable steps to their local functional regions, and differentiated patterns in larger optimal reachable steps for primary perceptual modalities. The reachable paths with the largest and second largest transition probabilities between primary sensory seeds via multisensory integration regions were also tracked to explore the flexibility and plasticity of the multisensory integration. The present work provides a novel approach to depict both the stable and flexible hierarchical connectivity organization of the human brain.

Genome-wide identification of Rosa roxburghii CML family genes identifies an RrCML13-RrGGP2 interaction involved in calcium-mediated regulation of ascorbate biosynthesis.

Calmodulin-like proteins (CMLs) are an essential family of calcium sensors involved in multiple Ca2+-mediated cellular processes in plants. Rosa roxburghii Tratt, known for the abundance of L-ascorbic acid (AsA) in its fruits, is widely distributed in calcium-rich soil of the karst region in southwestern China. The aim of this study was to identify key CMLs that respond to exogenous Ca2+ levels and regulate AsA biosynthesis in R. roxburghii. A genome-wide scan revealed the presence of 41 RrCML genes with 1-4 EF-hand motif (s) unevenly distributed across the 7 chromosomes of R. roxburghii. qRT-PCR analysis revealed that RrCML13, RrCML10, and RrCML36 responded significantly to exogenous Ca2+ treatment, and RrCML13 was positively correlated with GDP-L-galactose phosphorylase encoding gene (RrGGP2) expression and AsA content in the developing fruit. Overexpression of RrCML13 in fruits and roots significantly promoted the transcription of RrGGP2 and the accumulation of AsA, while virus-induced silencing of RrCML13 reduced the transcription of RrGGP2 and the content of AsA. Furthermore, Moreover, the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) analysis confirmed the interaction between RrCML13 and RrGGP2 proteins, indicating that RrCML13 plays a regulatory role in calcium-mediated AsA biosynthesis. This study enhances our understanding of R. roxburghii CMLs and sheds light on the calcium-mediated regulation of AsA biosynthesis.

Magnetic-navigable silk fibroin microneedles for oral drug delivery: Ensuring long-lasting helicobacter pylori eradication and rapid hemostasis in the stomach.

The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.

Natural killer cells in sepsis: Friends or foes?

Sepsis is one of the major causes of death in the hospital worldwide. The pathology of sepsis is tightly associated with dysregulation of innate immune responses. The contribution of macrophages, neutrophils, and dendritic cells to sepsis is well documented, whereas the role of natural killer (NK) cells, which are critical innate lymphoid lineage cells, remains unclear. In some studies, the activation of NK cells has been reported as a risk factor leading to severe organ damage or death. In sharp contrast, some other studies revealed that triggering NK cell activity contributes to alleviating sepsis. In all, although there are several reports on NK cells in sepsis, whether they exert detrimental or protective effects remains unclear. Here, we will review the available experimental and clinical studies about the opposing roles of NK cells in sepsis, and we will discuss the prospects for NK cell-based immunotherapeutic strategies for sepsis.

Label-Free Analysis of Exosomes with Hairpin Structure-Mediated Multiple Signal Amplification Strategy.

Considering the crucial role of exosomes in various biological processes and disease diagnosis, development of label-free and sensitive exosome detection methods is in urgent demand. Herein, we develop an exponential amplification-based method pining the hope on sensitive exosomes detection in a label-free manner. In this method, a designed SMB (Streptavidin magnetic bead)-capture probe is utilized to specially recognize CD63 protein on the surface of exosome. The recognition of CD63 protein by SMB-capture probe induces the subsequent hairpin structure probe-mediated multiple signal amplifications. Eventually, the proposed approach can detect exosomes at a concentration as low as 1.2 × 102 particles/µl and can be potentially applied for clinical practices.

Dynamic alterations of amplitude of low-frequency fluctuations in patients with chronic neck pain.

Background: The pathogenesis of neck pain in the brain, which is the fourth most common cause of disability, remains unclear. Furthermore, little is known about the characteristics of dynamic local functional brain activity in cervical pain. Objective: The present study aimed to investigate the changes of local brain activity caused by chronic neck pain and the factors leading to neck pain. Methods: Using the amplitude of low-frequency fluctuations (ALFF) method combined with sliding window approach, we compared local brain activity that was measured by the functional magnetic resonance imaging (fMRI) of 107 patients with chronic neck pain (CNP) with that of 57 healthy control participants. Five pathogenic factors were selected for correlation analysis. Results: The group comparison results of dynamic amplitude of low-frequency fluctuation (dALFF) variability showed that patients with CNP exhibited decreased dALFF variability in the left inferior temporal gyrus, the middle temporal gyrus, the angular gyrus, the inferior parietal marginal angular gyrus, and the middle occipital gyrus. The abnormal dALFF variability of the left inferior temporal gyrus was negatively correlated with the average daily working hours of patients with neck pain. Conclusions: The findings indicated that the brain regions of patients with CNP responsible for audition, vision, memory, and emotion were subjected to temporal variability of abnormal regional brain activity. Moreover, the dALFF variability in the left inferior temporal gyrus might be a risk factor for neck pain.This study revealed the brain dysfunction of patients with CNP from the perspective of dynamic local brain activity, and highlighted the important role of dALFF variability in understanding the neural mechanism of CNP.

Pacific freshening drives Pliocene cooling and Asian monsoon intensification.

The monsoon is a fundamental component of Earth's climate. The Pliocene warm period is characterized by long-term global cooling yet concurrent monsoon dynamics are poorly known. Here we present the first fully quantified and calibrated reconstructions of separate Pliocene air temperature and East Asian summer monsoon precipitation histories on the Chinese Loess Plateau through joint analysis of loess/red clay magnetic parameters with different sensitivities to air temperature and precipitation. East Asian summer monsoon precipitation shows an intensified trend, paradoxically at the same time that climate cooled. We propose a hitherto unrecognized feedback where persistently intensified East Asian summer monsoon during the late Pliocene, triggered by the gradual closure of the Panama Seaway, reinforced late Pliocene Pacific freshening, sea-ice development and ice volume increase, culminating in initiation of the extensive Northern Hemisphere glaciations of the Quaternary Ice Age. This feedback mechanism represents a fundamental reinterpretation of the origin of the Quaternary glaciations and the impact of the monsoon.