The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time ...assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of ß-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
The ability of severed rootstocks and shoots to re-establish vascular connections is used to generate grafted plants that combine desirable traits from both scions and rootstocks. Clarifying the ...mechanisms of graft healing is essential for its further application. We performed RNA sequencing of internodes near the cut position, making a distinction between separated or grafted tissues above and below the cut, in order to obtain a genetic description of graft union formation.
Using weighted gene co-expression analysis, variable transcripts were clustered into 10 distinct co-expression networks (modules) based on expression profiles, and genes with the most "hubness" ("hub" genes show the most connections in a network) within each module were predicted. A large proportion of modules were related to Position, and represent asymmetric expression networks from different pathways. Expression of genes involved in auxin and sugar transport and signaling, and brassinosteroid biosynthesis was increased above the cut, while stress response genes were up-regulated below the cut. Some modules were related to graft union formation, among which oxidative detoxification genes were co-expressed along with both wounding response and cell wall organization genes.
The present work provides a comprehensive understanding of graft healing-related gene networks in tomato. Also, the candidate pathways and hub genes identified here will be valuable for future studies of grafting in tomato.
Acquisition of external phosphorus (P) and optimisation of internal P are essential for plant growth and development, and insufficient availability of P in soils is a major challenge in agriculture. ...Members of the purple acid phosphatase (PAP) family of enzymes are candidates for increasing P use efficiency. Herein, we identified PAP homologs in the genomes of 10 vegetable species, along with Arabidopsis thaliana and Amborella trichopoda as references, to provide fundamental knowledge for this family.
Phylogenetic analysis of protein sequences revealed nine distinct clades, indicating that functional differentiation of extant PAPs was established prior to the emergence of early angiosperms, and conserved among homologs in each clade. Analysis of transcript abundance in different tissues (root, stem, leaf, flower, and fruit) and following phosphates (Pi) starvation treatments from published RNA-seq transcriptome datasets facilitated comprehensive evaluation of expression patterns, and some groups of tissue-specific and Pi starvation-induced PAPs were characterised. Conserved motifs identified from upstream sequences of homologs that are highly expressed in particular tissues or following starvation treatment suggests that divergence in PAP gene expression is associated with cis-acting elements in promoters.
The genome-wide analysis of PAP enzyme structure and transcriptional expression patterns advance our understanding of PAP family in vegetables genomes. Therefore, PAP homologs with known enzyme structures and expression profiles could serve as targets for plant breeding and/or genetic engineering programs to improve P acquisition and use.
The existing literature evaluating the association between neonatal morbidity and migrant status presents contradictory results. The purpose of this study was to compare the risk of preterm birth ...(PTB) and low birth weight (LBW) among newborns from local and migrant women in China's Pearl River Delta (PRD) region.
In this observational population-based study, we included all live singleton deliveries from PRD region local women and migrant women. Data were sourced from the Guangdong Medical Birth Registry Information System between Jan 1, 2014, and Dec 31, 2020. Women were categorized into three groups by maternal migrant status: local women from PRD region, migrant women from Guangdong province or from other provinces. The outcome variables that were examined included two adverse birth outcomes: PTB and LBW. The association between the risk of PTB and LBW and maternal migrant status was assessed using logistic regression.
During 2014-2020, 5,219,133 single live deliveries were recorded, corresponding 13.22% to local women and the rest to migrant women coming from Guangdong (53.51%) and other provinces (33.26%). PTB prevalence was highest among local women (5.79%), followed by migrant women from Guangdong (5.29%), and the lowest among migrants from other provinces (4.95%). This association did not change after including maternal age, infant sex, delivery mode, and birth season in the models. Compared to local women, migrant women from other provinces had a lower risk of LBW (4.00% vs. 4.98%, P < 0.001). The prevalence of PTB and LBW was higher among local women than migrants. The odds of delivery PTB and LBW were higher for women who were age ≥ 35. Among the three maternal migration groups, the age-LBW association displayed a typical U-shaped pattern, with those in the youngest (16-24 years) and oldest (≥ 35) age categories exhibiting the higher odds of delivering a LBW neonate. With respect to infant sex, the prevalence of PTB was significantly higher in males than females among the three maternal migration groups. An opposite trend was found for LBW, and the prevalence of LBW was higher in females among the three maternal migration groups.
The findings of this study contribute to the understanding of the epidemiology of PTB and LBW among migrant women. Our study suggests that it is the health and robust nature of migrant mothers that predisposes them to better birth outcomes. It is important to recognize that the results of this study, while supportive of the healthy migrant effect, cannot be considered definitive without some exploration of motivation for moving and changes in lifestyle postmigration.
•Gene co-expression networks during graft formation are stage-specific.•The asymmetric response phase (3−72 hours after grafting) is the critical period for graft formation.•Auxin and cytokinin ...respond to grafting, above and below the graft junction, respectively, to promote the graft formation.•The accumulation of auxin above the graft junction prepares cells for mitosis, which promotes cell division to form callus.•Exogenous application of certain concentrations of IAA and 6-BA will promote graft formation.
Grafting is widely used worldwide because of its obvious advantages, especially in solanaceous vegetable crops. However, the molecular mechanisms underlying graft formation are unknown. In this study, internode tissues from above and below the graft junction were harvested, and we performed weighted gene co-expression network analysis (WGCNA) to describe the temporal and spatial transcriptional dynamics that occur during graft formation in tomato. The wounding stress response involved in JA, ETH, and oxylipins mainly occurred at 1 h after grafting (HAG). From 3 to 12 HAG, the biological processes of snRNA and snoRNA modification and the gibberellin-mediated signaling pathway functioned both above and below the graft junction. However, auxin transport and signaling, DNA replication, and xylem and phloem pattern formation were restricted to the scion, whereas the cytokinin-activated signaling pathway and the cellular response to sucrose starvation was restricted to the rootstock. At 24−72 HAG, cell division occurred above the graft junction, and photosynthesis-related pathways were activated below the graft junction. The levels of auxin and cytokinin reached their maxima above and below the graft junction at 12 HAG, respectively. Exogenous application of certain concentrations of IAA and 6-BA will promote xylem and phloem transport capacity. The current work has analyzed the stage-specific events and hub genes during the developmental progression of tomato grafting. We found that auxin and cytokinin levels respond to grafting, above and below the graft junction, respectively, to promote the formation of xylem and phloem patterning. In addition, the accumulation of auxin above the graft junction induced cells to prepare for mitosis and promoted the formation of callus. In short, our work provides an important reference for theoretical research and production application of tomato grafting in the future.
Objective
In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and ...interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF–ISF exchange and interstitial solute clearance is impaired in the aging brain.
Methods
CSF–ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2–3 months), middle‐aged (10–12 months), and old (18–20 months) wild‐type mice. The relationship between age‐related changes in the expression of the astrocytic water channel aquaporin‐4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence.
Results
Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid‐β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF–ISF exchange.
Interpretation
We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. Ann Neurol 2014;76:845–861
The effects of two kinds of time-delayed feedbacks and non-Gaussian coloured noise on modulating bifurcations in a birhythmic model have been investigated. The non-Gaussian coloured noise is ...approximated as an Ornstein–Uhlenbeck process using the path integral approach. Subsequently, by the conjoint of the multiscale method and random average technique, the stationary probability density function (SPDF) of the amplitude is obtained. It is concluded that either in the condition of determinacy or randomness, time delays can effectively control birhythmicity. Especially considered the presence of noise, the varying displacement delay results in multiple bifurcation in the case of single delay, while the velocity delay triggers more complex bifurcation behaviour in the case of double delays. The strength and correlation time of noise present the opposite impacts on bifurcation, so do the two delayed coefficients. Bifurcation under different excitations is analysed theoretically, and the correctness is verified by numerical simulation. Many abundant bifurcations are available by adjusting the time-delayed feedbacks and noise intensity, which may be conductive to achieve the expected phenomenon in the enzymatic–substrate reactions.
Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of ...infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors.
A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population.
Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported.
While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials.
Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.
The glymphatic system is a fluid transport network of cerebrospinal fluid (CSF) entering the brain along arterial perivascular spaces, exchanging with interstitial fluid (ISF), ultimately ...establishing directional clearance of interstitial solutes. CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular endfeet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport. Yet, no studies have systematically examined how these abnormalities in structure and water transport correlate with glymphatic function. Here, we used high-resolution 3D magnetic resonance (MR) non-contrast cisternography, diffusion-weighted MR imaging (MR-DWI) along with intravoxel-incoherent motion (IVIM) DWI, while evaluating glymphatic function using a standard dynamic contrast-enhanced MR imaging to better understand how water transport and glymphatic function is disrupted after genetic deletion of AQP4. AQP4 KO mice had larger interstitial spaces and total brain volumes resulting in higher water content and reduced CSF space volumes, despite similar CSF production rates and vascular density compared to wildtype mice. The larger interstitial fluid volume likely resulted in increased slow but not fast MR diffusion measures and coincided with reduced glymphatic influx. This markedly altered brain fluid transport in AQP4 KO mice may result from a reduction in glymphatic clearance, leading to enlargement and stagnation of fluid in the interstitial space. Overall, diffusion MR is a useful tool to evaluate glymphatic function and may serve as valuable translational biomarker to study glymphatics in human disease.
Liver cancer is a very common and significant health problem. Therefore, powerful molecular targeting agents are urgently needed. Previously, we demonstrated that secalonic acid-F (SAF) suppresses ...the growth of hepatocellular carcinoma (HCC) cells (HepG2), but the other anticancer biological functions and the underlying mechanism of SAF on HCC are unknown. In this study, we found that SAF, which was isolated from a fungal strain in our lab identified as Aspergillus aculeatus, could inhibit the progression of hepatocellular carcinoma by targeting MARCH1, which regulates the PI3K/AKT/β-catenin and antiapoptotic Mcl-1/Bcl-2 signaling cascades. First, we confirmed that SAF reduced the proliferation and colony formation of HCC cell lines (HepG2 and Hep3B), promoted cell apoptosis, and inhibited the cell cycle in HepG2 and Hep3B cells in a dose-dependent manner. In addition, the migration and invasion of HepG2 and Hep3B cells treated with SAF were significantly suppressed. Western blot analysis showed that the level of MARCH1 was downregulated by pretreatment with SAF through the regulation of the PI3K/AKT/β-catenin signaling pathways. Moreover, knockdown of MARCH1 by small interfering RNAs (siRNAs) targeting MARCH1 also suppressed the proliferation, colony formation, migration, and invasion as well as increased the apoptotic rate of HepG2 and Hep3B cells. These data confirmed that the downregulation of MARCH1 could inhibit the progression of hepatocellular carcinoma and that the mechanism may be via PI3K/AKT/β-catenin inactivation as well as the downregulation of the antiapoptotic Mcl-1/Bcl-2. In vivo, the downregulation of MARCH1 by treatment with SAF markedly inhibited tumor growth, suggesting that SAF partly blocks MARCH1 and further regulates the PI3K/AKT/β-catenin and antiapoptosis Mcl-1/Bcl-2 signaling cascade in the HCC nude mouse model. Additionally, the apparent diffusion coefficient (ADC) values, derived from magnetic resonance imaging (MRI), were increased in tumors after SAF treatment in a mouse model. Taken together, our findings suggest that MARCH1 is a potential molecular target for HCC treatment and that SAF is a promising agent targeting MARCH1 to treat liver cancer patients.
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