Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced ...by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.
A digital phase-locked loop (DPLL) using the feedforward phase-error cancellation (FPC) is presented. The phase error of this DPLL using a digitally controlled ring oscillator is quickly canceled by ...a digitally controlled delay line (DCDL), which improves the phase noise performance. The loop gain of this FPC DPLL is also calibrated. In addition, a dead-zone-free (DZF) bang-bang phase-frequency detector (BBPFD) is presented to enhance the resolution of the time-to-digital converter (TDC). This proposed DPLL is fabricated in a 40-nm CMOS process which occupies 0.05 mm<inline-formula> <tex-math notation="LaTeX">^{2}</tex-math> </inline-formula>. The measured rms jitter integrated from 1 kHz to 100 MHz is 788 fs at 1.6 GHz. The measured reference spur is <inline-formula> <tex-math notation="LaTeX">-</tex-math> </inline-formula>57.84 dBc for a 50 MHz reference frequency. Its power consumption is 5 mW for a 1.1-V supply voltage.
Interleukin-6 is an inflammatory cytokine with wide-ranging biological effects. It has been widely demonstrated that neuroinflammation plays a critical role in the development of pathological pain. ...Recently, various pathological pain models have shown elevated expression levels of interleukin-6 and its receptor in the spinal cord and dorsal root ganglia. Additionally, the administration of interleukin-6 could cause mechanical allodynia and thermal hyperalgesia, and an intrathecal injection of anti-interleukin-6 neutralizing antibody alleviated these pain-related behaviors. These studies indicated a pivotal role of interleukin-6 in pathological pain. In this review, we summarize the recent progress in understanding the roles and mechanisms of interleukin-6 in mediating pathological pain associated with bone cancer, peripheral nerve injury, spinal cord injury, chemotherapy-induced peripheral neuropathy, complete Freund's adjuvant injection, and carrageenan injection. Understanding and regulating interleukin-6 could be an interesting lead to novel therapeutic strategies for pathological pain.
Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts （CAFs） in tumor stroma play an important role. Prostaglandin E2 （PGE2） and interleukin （IL）-6 signal ...pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates this crosstalk remains unclear. Here, we show that microRNA （miR）-149 links PGE2 and IL-6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer （GC）. miR-149 inhibited fibroblast activation by targeting IL-6 and miR-149 expression was substantially suppressed in the CAFs of GC. miR-149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo. CAFs enhanced epithelial-to-mesenchymal transition （EMT） and the stem-like properties of GC cells in a miR-149-1L-6-dependent manner. In addition to IL-6, PGE2 receptor 2 （PTGER2/EP2） was revealed as another potential target of miR-149 in fibroblasts. Furthermore, H. pylori infection, a leading cause of human GC, was able to induce cyclooxygenase-2 （COX-2）/PGE2 signaling and to enhance PGE2 production, resulting in the hypermethylation of miR-149 in CAFs and increased IL-6 secretion. Our findings indicate that miR-149 mediates the crosstalk between tumor cells and CAFs in GC and highlight the potential of interfering miRNAs in stromal cells to improve cancer therapy.
Mendelian randomization (MR) analysis was used to determine the causal relationship between Type 2 diabetes (T2D) and osteomyelitis (OM). We performed MR analysis using pooled data from different ...large-scale genome-wide association studies (GWAS). Instrumental variables were selected based on genome-wide significance, instrumental strength was assessed using F-values, and thresholds for the number of exposed phenotypes were further adjusted by Bonferroni correction. univariable and multivariable MR analyses were performed to assess causal effects and proportions mediated by T2D. IVW (inverse variance weighting) showed a significant genetic effect of osteomyelitis on the following: After correction by Bonferroni, univariable analyses showed that childhood body mass index (BMI) was not significantly associated with genetic susceptibility to OM odds ratio (OR), 1.26; 95% confidence interval (CI), 1.02, 1.55; P = .030, not significantly associated with adulthood BMI (OR, 1.28; 95% CI, 1.02, 1.61; P = .034), significantly associated with waist circumference (OR, 1.84; 95% CI, 1.51, 2.24; P < .001), and significantly associated with hip circumference (OR, 1.52; 95% CI, 1.31, 1.76; P < .001). Meanwhile, multivariable analyses showed no significant effect of childhood BMI on OM (OR, 1.16; 95% CI, 0.84, 1.62; P = .370), no significant effect of adulthood BMI on OM (OR, 0.42; 95% CI, 0.21, 0.84; P = .015), a significant association between waist circumference and OM (OR, 4.30; 95% CI, 1.89, 9.82; P = .001), T2D mediated 10% (95% CI, 0.02, 0.14), and no significant association between hip circumference and OM (OR, 1.01; 95% CI, 0.54, 1.90; P = .968). Our study provides evidence for a genetically predicted causal relationship among obesity, T2D, and OM. We demonstrate that increased waist circumference is positively associated with an increased risk of OM and that T2D mediates this relationship. Clinicians should be more cautious in the perioperative management of osteomyelitis surgery in obese patients with T2D. In addition, waist circumference may be a more important criterion to emphasize and strictly control than other measures of obesity.
Reliable power transmission requires the safe operation of high‐voltage cable. A number of high‐voltage cable failures caused by aluminium sheath corrosion has been reported these years. However, ...neither discussion on factors influencing corrosion rate nor specification describing corrosion inhibiting method has been presented. Thus, it is crucial to address the research gap in evaluating corrosion rate of aluminium sheath in various corrosive environments. Here, the effect of chlorides on aluminium sheath corrosion is analyzed. Using scanning electron microscopy (SEM) and energy dispersive spectrometer (EDS), the corroded surface is investigated. Titration experiment is performed to quantify the chlorides content in buffer layer of cable. Polarization curves are employed to analyze the corrosion rate of aluminium sheath in different chlorides content environment. Surface analysis result shows that chlorine‐rich phase can be observed on the corroded surface. Titration experiment result reveals that buffer layer used in high voltage cable is one of the sources of chlorides content which varies from 0.7 to 4.2 wt%. Finally, polarization curve shows that when chloride content increases from 0.6 to 1.8 wt%, the pitting potential left shifts from −0.689 to −0.742 V. The corrosion resistance of aluminium sheath deteriorates significantly with the increase of chlorides content.
Pathological brain detection is an automated computer-aided diagnosis for brain images. This study provides a novel method to achieve this goal.We first used synthetic minority oversampling to ...balance the dataset. Then, our system was based on three components: wavelet packet Tsallis entropy, extreme learning machine, and Jaya algorithm. The 10 repetitions of K-fold cross validation showed our method achieved perfect classification on two small datasets, and achieved a sensitivity of 99.64 ± 0.52%, a specificity of 99.14 ± 1.93%, and an accuracy of 99.57 ± 0.57% over a 255-image dataset. Our method performs better than six state-of-the-art approaches. Besides, Jaya algorithm performs better than genetic algorithm, particle swarm optimization, and bat algorithm as ELM training method.
Background:
Major orthopedic surgery, including hip and knee replacement and lower extremity trauma fractures surgery, is associated with a high risk of venous thromboembolism (VTE), especially ...proximal deep vein thrombosis (DVT), and pulmonary embolism (PE), and is linked with high morbidity and mortality rates. Chemical anticoagulation is routinely used to prevent VTE, with previous meta-analyses reporting on the efficacy and safety of aspirin and other anticoagulants, however, opinions are divided. In the past 2 years, several large randomized controlled trials have been published, therefore, we reanalyzed aspirin efficacy and safety when compared with other anticoagulants in preventing VTE in major orthopedic surgery.
Methods:
Using PubMed, The Cochrane Library, Embase, and Web of Science databases, we conducted a RCT search in August 2023. The main outcomes included VTE, proximal DVT or PE. Additional outcomes included bleeding events, wound complications, wound infections, blood transfusions, and death events.
Results:
In total, 17 eligible articles, involving 29,522 patients (15,253 aspirin vs 14,269 other anticoagulant cases), were included. Primary outcomes showed that VTE incidence was more high in the aspirin group when compared with other anticoagulants (risk ratio RR = 1.45, 95% confidence interval CI = 1.18–1.77,
P
= .0004) and proximal in the aspirin group the DVT and/or PE incidence was significantly higher in the aspirin group when compared with other anticoagulants (RR = 1.19, 95% CI = 1.02–1.39,
P
= .03). No significant secondary outcome differences were identified in the aspirin group when compared with other anticoagulants (bleeding events RR = 0.83, 95% CI = 0.63–1.10,
P
= .20); wound complications (RR = 0.45, 95% CI = 0.20–1.04,
P
= .06); wound infection (RR = 1.08, 95% CI = 0.85–1.38,
P
= .53); blood transfusion events (RR = 1.00, 95% CI = 0.84–1.19,
P
= 1.00) and death events (RR = 1.11, 95% CI = 0.78–1.57,
P
= .55).
Conclusions:
Our updated meta-analysis showed that aspirin was inferior to when compared with other anticoagulants in VTE-related orthopedic major surgery, including proximal DVT and/or PE, and was more likely to form VTE. No differences between groups were identified for bleeding, wound complications, wound infections, transfusion, or death events.
Distinct regio- and enantioselectivity control in copper-catalyzed vinylogous and bisvinylogous propargylic substitution has been accomplished by using a novel chiral N,N,P ligand. The developed ...method provides an efficient and selective approach to an array of highly enantioenriched alkynyl unsaturated carbonyl compounds. Salient features include excellent functional group tolerance and broad substrate scope. The synthetic utility of the developed method is further demonstrated by a gram-scale synthesis and by application to a range of transformations including enantioselective synthesis of unique challenging compounds.
The intervertebral disc is the largest avascular organ of the body. Vascularization of the disc has been typically regarded as a pathological feature of intervertebral disc degeneration (IDD). ...However, the underlying mechanism of vascularization in IDD is still unclear. The current study aimed to investigate the role of AF cell derived exosome (AF-exo) in the interaction with human umbilical vein endothelial cells (HUVECs) and its potential role in the regulation of vascularization in IDD.
Human AF tissues were obtained from patients with IDD and idiopathic scoliosis. The AF-exo were isolated and identified by transmission electron microscopy (TEM), nanoparticle trafficking analysis (NTA) and Western blotting. Then, the AF-exo were used for HUVECs cultures. The migration of HUVECs was observed in 2D and 3D cultures. The inflammatory phenotype of HUVECs was examined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA). Additionally, apoptosis of HUVECs were analyzed by flow cytometry.
Here, we for the first time found that AF cells could secrete AF-exo and that the AF-exo could be phagocytosed by HUVECs. Additionally, we found that degenerated AF-exo exerted pro-vascularization effect on HUVECs by promoting cell migration (in 2D and 3D cultures) and inflammatory factor expression including IL-6, TNF-α, MMP-3, MMP-13 and VEGF, whereas the application of non-degenerated AF-exo demonstrated inverse effects.
These results showed that AF-exo is an essential regulator mediating intercellular communication between AF cells and HUVECs, suggesting its important role in vascularization in the intervertebral disc.
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