The primary motor cortex (M1) is often abnormally recruited in stroke patients with motor disabilities. However, little is known about the alterations in the causal connectivity of M1 following ...stroke. The purpose of the present study was to investigate whether the effective connectivity of the ipsilesional M1 is disturbed in stroke patients who show different outcomes in hand motor function. 23 patients with left-hemisphere subcortical stroke were selected and divided into two subgroups: partially paralyzed hands (PPH) and completely paralyzed hands (CPH). Further, 24 matched healthy controls (HCs) were recruited. A voxel-wise Granger causality analysis (GCA) on the resting-state fMRI data between the ipsilesional M1 and the whole brain was performed to explore differences between the three groups. Our results showed that the influence from the frontoparietal cortices to ipsilesional M1 was diminished in both stroke subgroups and the influence from ipsilesional M1 to the sensorimotor cortices decreased greater in the CPH group than in the PPH group. Moreover, compared with the PPH group, the decreased influence from ipsilesional M1 to the contralesional cerebellum and from the contralesional superior parietal lobe to ipsilesional M1 were observed in the CPH group, and their GCA values were positively correlated with the FMA scores; Conversely, the increased influence from ipsilesional M1 to the ipsilesional middle frontal gyrus and middle temporal gyrus were observed, whose GCA values were negatively correlated with the FMA scores. This study suggests that the abnormalities of casual flow in the ipsilesional M1 are related to the severity of stroke-hand dysfunction, providing valuable information to understand the deficits in resting-state effective connectivity of motor execution and the frontoparietal motor control network during brain plasticity following stroke.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The activated c-Jun N-terminal kinase (JNK) specifically combined with SH3 domain-binding protein 5 (Sab) may mediate damage to the mitochondrial respiratory chain. Whether mitochondrial dysfunction ...induced by the JNK/Sab signaling pathway plays a pivotal role in the lipotoxic injury of nonalcoholic steatohepatitis (NASH) remains a lack of evidence. Scoparone, a natural compound from Traditional Chinese Medicine herbs, has the potential for liver protection and lipid metabolism regulation. However, the effect of scoparone on NASH induced by a high-fat diet (HFD) as well as its underlying mechanism remains to be elucidated. The HepG2 and Huh7 cells with/without Sab-knockdown induced by palmitic acid (PA) were used to determine the role of JNK/Sab signaling in mitochondrial dysfunction and cellular lipotoxic injury. To observe the effect of scoparone on the lipotoxic injured hepatocytes, different dose of scoparone together with PA was mixed into the culture medium of HepG2 and AML12 cells to incubate for 24 h. In addition, male C57BL/6J mice were fed with an HFD for 22 weeks to induce the NASH model and were treated with scoparone for another 8 weeks to investigate its effect on NASH. Molecules related to JNK/Sab signaling, mitochondrial function, and lipotoxic injury were detected in
and/or
experiments. The results showed that PA-induced activation of JNK/Sab signaling was blocked by Sab knockdown in hepatocytes, which improved mitochondrial damage, oxidative stress, hepatosteatosis, cell viability, and apoptosis. Scoparone demonstrated a similar effect on the PA-induced hepatocytes as Sab knockdown. For the NASH mice, treatment with scoparone also downregulated the activation of JNK/Sab signaling, improved histopathological changes of liver tissues including mitochondrial number and morphology, lipid peroxide content, hepatosteatosis and inflammation obviously, as well as decreased the serum level of lipid and transaminases. Taken together, this study confirms that activation of the JNK/Sab signaling pathway-induced mitochondrial dysfunction plays a crucial role in the development of NASH. Scoparone can improve the lipotoxic liver injury partially by suppressing this signaling pathway, making it a potential therapeutic compound for NASH.
Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that ...the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of T04C9.1, the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in Caenorhabditis elegans (C. elegans), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of let-363 suppresses the age-related alternations, impaired motility, and shortened lifespan of C. elegans, which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its C. elegans homologue T04C9.1 decrease with age and reveals that a lack of T04C9.1 bridges autophagy decline and ageing in C. elegans.
White adipose tissue (WAT) development and adult homeostasis rely on distinct adipocyte progenitor cells (APCs). While adult APCs are defined early during embryogenesis and generate adipocytes after ...WAT organogenesis, the mechanisms underlying adult adipose lineage determination and preservation remain undefined. Here, we uncover a critical role for platelet-derived growth factor receptor beta (Pdgfrβ) in identifying the adult APC lineage. Without Pdgfrβ, APCs lose their adipogenic competency to incite fibrotic tissue replacement and inflammation. Through lineage tracing analysis, we reveal that the adult APC lineage is lost and develops into macrophages when Pdgfrβ is deleted embryonically. Moreover, to maintain the APC lineage, Pdgfrβ activation stimulates p38/MAPK phosphorylation to promote APC proliferation and maintains the APC state by phosphorylating peroxisome proliferator activated receptor gamma (Pparγ) at serine 112. Together, our findings identify a role for Pdgfrβ acting as a rheostat for adult adipose lineage confinement to prevent unintended lineage switches.
Display omitted
•Pdgfrβ deletion results in adult-onset white adipose tissue dysfunction•Pdgfrβ is required for adult adipose lineage confinement and adult adipogenesis•Embryonic deletion of Pdgfrβ results in adipocyte-to-macrophage lineage conversion•Pdgfrβ signaling upholds the APC state but halts adipogenesis by PparγSer112
Molecular biology; Cell biology; Embryology
Organ development is directed by selector gene networks. Eye development in the fruit fly Drosophila melanogaster is driven by the highly conserved selector gene network referred to as the "retinal ...determination gene network," composed of approximately 20 factors, whose core comprises twin of eyeless (toy), eyeless (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development, and sufficient to direct ectopic eye development when misexpressed. While it is well documented that the downstream genes so, eya, and dac are necessary not only during early growth and determination stages but also during the differentiation phase of retinal development, it remains unknown how the retinal determination gene network terminates its functions in determination and begins to promote differentiation. Here, we identify a switch in the regulation of ey by the downstream retinal determination genes, which is essential for the transition from determination to differentiation. We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so. Our results suggest a model in which the retinal determination gene network is rewired to end the growth and determination stage of eye development and trigger terminal differentiation. We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This research examines when and why a threat to self-image influences saving intentions. Data from a set of seven studies, comprising a large-scale survey and 6 experiments, show that when ...individuals experience a self-image threat, they generate negative expectations about their future. Consequently, these individuals show a greater propensity to save money compared with nonthreatened individuals. We demonstrate that this effect diverges from the effects of environmental threats (e.g., resource scarcity) on saving, and find that it is more likely to occur among individuals with strong rather than weak beliefs in the instrumentality of money. Finally, we observe that the relationship between self-image threat and saving intentions is attenuated under the following conditions: (a) when individuals are induced to adopt positive future expectations; (b) when individuals perceive themselves as having abundant social connections, a perception that buffers their anxiety about the future; or (c) when individuals' attention is directed, through self-affirmation, to important aspects of their lives that are irrelevant to the threat.
Objective:
This study aimed to compare the potential of monoexponential model (MEM), intravoxel incoherent motion (IVIM) model, kurtosis model, and IVIM–kurtosis model in the diagnosis and ...aggressiveness assessment of prostate cancer (PCa).
Materials and Methods:
Thirty-six patients were recruited. Diffusion-weighted images were acquired on a 3.0-T magnetic resonance imaging (MRI) system using 0
b
values up to 2,000 s/mm
2
and analyzed using four models: MEM (ADC
MEM
), IVIM (
D
IVIM
,
D
*
IVIM
,
f
IVIM
), kurtosis (
D
kurtosis
,
K
kurtosis
), and IVIM–kurtosis (
D
IVIM−kurtosis
,
D
*
IVIM−kurtosis
,
f
IVIM−kurtosis
,
D
IVIM−kurtosis
) models. The values of these parameters were calculated and compared between PCa, benign prostatic hyperplasia (BPH), and prostatitis. Correlations between these parameters and the Gleason score (GS) of PCa were evaluated using the Pearson test.
Results:
Forty-five lesions were studied, including 18 PCa, 12 prostatitis, and 15 BPH lesions. The ADC
MEM
,
D
IVIM
,
f
IVIM
,
D
kurtosis
, and
D
IVIM−kurtosis
values were significantly lower and
K
kurtosis
and
K
IVIM−kurtosis
values were significantly higher in PCa compared with prostatitis and BPH. The area under the curve (AUC) of ADC
MEM
showed significantly higher values than that of
f
IVIM
and
K
IVIM−kurtosis
, but no statistical differences were found between the other parameters. The
D
*
IVIM−kurtosis
value correlated negatively and
f
IVIM−kurtosis
and
K
IVIM−kurtosis
values correlated positively with the GS.
Conclusion:
The MEM, IVIM, kurtosis, and IVIM–kurtosis models were all useful for the diagnosis of PCa, and the diagnostic efficacy seemed to be similar. The IVIM–kurtosis model may be superior to the MEM, IVIM, and kurtosis models in the grading of PCa.
Although amphiphilic chitosan has been widely studied as a drug carrier for drug delivery, fewer studies have been conducted on the antimicrobial activity of amphiphilic chitosan. In this study, we ...successfully synthesized deoxycholic acid-modified chitosan (CS-DA) by grafting deoxycholic acid (DA) onto chitosan C
-NH
, followed by grafting succinic anhydride, to prepare a novel amphiphilic chitosan (CS-DA-SA). The substitution degree was 23.93% for deoxycholic acid and 29.25% for succinic anhydride. Both CS-DA and CS-DA-SA showed good blood compatibility. Notably, the synthesized CS-DA-SA can self-assemble to form nanomicelles at low concentrations in an aqueous environment. The results of CS, CS-DA, and CS-DA-SA against
and
showed that CS-DA and CS-DA-SA exhibited stronger antimicrobial effects than CS. CS-DA-SA may exert its antimicrobial effect by disrupting cell membranes or forming a membrane on the cell surface. Overall, the novel CS-DA-SA biomaterials have a promising future in antibacterial therapy.
Rich chemical properties and a well-developed pore structure are the key factors of porous materials for gas storage. Herein, rich heteroatom-doped porous carbon nanofibers (U1K2-X) with a large ...surface area were prepared by electrospinning followed by potassium hydroxide (KOH) activation. Low-cost urea was chosen as the nitrogen source and structural guiding agent. U1K2-X have a high specific surface area (628–2688 m2 g–1), excellent pore volume (0.468–1.571 cm3 g–1), and abundant nitrogen (2.5–12.8 atom %) and oxygen (4.5–12.5 atom %) contents. Acetone and carbon dioxide were used as target adsorbents to evaluate the adsorption properties of U1K2-X by experiments. These U1K2-X exhibit excellent adsorption performance (260.03–955.74 mg g–1, 25 °C, 18 kPa) and multilayer adsorption (the adsorption layer number n > 2) for acetone, which is mainly attributed to the large specific surface area and pore volume. Besides this, the carbon dioxide uptake reached 2.73–3.34 mmol g–1 at 25 °C. This was attributed to the combination of high nitrogen–oxygen contents and microporous structure. Furthermore, U1K2-X show the desirable repeatability. This study provides a new direction for the preparation of heteroatom-doped porous carbon nanofibers, which will be a promising material for gas adsorption.
Creation of bio-multifunctional wound dressings with potent hemostatic, antibacterial, anti-inflammatory, and angiogenesis features for bolstering the healing of full-thickness wounds is sought after ...for clinical applications. We created bio-multifunctional composite sponges by coupling alginate and chitosan with
polysaccharides through electrostatic interactions, calcium ion (Ca
) crosslinking, and lyophilization. Alginate/chitosan (AC) sponges with different concentrations of
polysaccharides were obtained and termed AC, ACS-1%, ACS-2.5%, and ACS-5%. ACS-1% and ACS-2.5% sponges exhibited uniform porosity, high water vapor transmission rate, high water absorption, as well as good hemostatic and antibacterial abilities. ACS-2.5% sponges facilitated wound closure and promoted angiogenesis and re-epithelialization in the dermis. These data suggest that ACS sponges containing a certain amount of
polysaccharides could be employed for treatment of full-thickness skin wounds.
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