Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes ...reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Using anterograde and retrograde tracings, we confirmed that a subgroup of ACC neurons projected to the nucleus accumbens (NAc) and ventral tegmental area (VTA), which are two crucial nodes of the mesolimbic dopamine system. Combining electrophysiology in juvenile rats 7 days post-CCI, we found that the NAc/VTA-projecting neurons were hyperexcitable after CCI. Chemogenetic inhibition of these projections induced conditioned place preference in young adult rats 10–14 days post-CCI, without modulating the evoked pain threshold, whereas activation of these projections in sham rats mimicked aversive behavior. Furthermore, the function of the ACC projections was probably mediated by NAc D2-type medium spiny neurons and VTA GABAergic neurons. Taken together, our findings suggest that projections from the ACC to the NAc and VTA mediate neuropathic pain-related aversive behavior.
•ACC output neurons project directly to NAc and VTA.•The ACC-NAc/VTA projection mediates aversion of chronic pain.•ACC activates NAc D2-type medium spiny neurons during chronic pain.•ACC inhibits the VTA by activating GABAergic neurons after CCI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In selecting logistics service providers, the evaluation criteria can be easily prioritized and possibly interrelated with each other, and the assessment of alternatives under qualitative criteria is ...usually accomplished by more than one decision maker. A novel multicriteria decision‐making approach with multihesitant fuzzy linguistic term elements (MHFLTEs) based on the Heronian mean (HM) and prioritized average operators can effectively deal with the problems inherent in such a scenario. Multihesitant fuzzy linguistic term sets (MHFLTSs) were proposed on the basis of multihesitant fuzzy sets (MHFSs) and hesitant fuzzy linguistic sets (HFLSs), where each MHFLTE can contain nonconsecutive and repeated linguistic terms. Using MHFLTEs, one decision maker can provide one or several consecutive linguistic terms in evaluating an alternative under one specific criterion, different decision makers’ evaluation values can be collected, and the frequency of a linguistic term in the evaluation information can accord with reality. This paper revises the basic operations and comparison method for MHFLTEs on the basis of the originals and defines some multihesitant fuzzy linguistic HM operators for MHFLTEs to deal with problems in which weight information cannot be accurately established for criteria, but their priorities can be provided in groups or without groups. Finally, the validity and effectiveness of the proposed approach are demonstrated through an illustration of a logistics outsourcing problem and a comparison analysis.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper deals with the dynamic modelling and pure delayed
control for a deepwater drilling riser system in the presence of the friction force of seawater and drilling discharge mud. First, by ...simplifying a drilling riser system as a spring-mass-damping unit with three degrees of freedom, an increment equation of the riser system subject to friction force of seawater and drilling discharge mud is established. Then, by artificially introducing a time-varying delay with given lower and upper bounds into the control channel, a pure delayed
control scheme is presented to restrain the recoil responses of the riser system. Based on the Lyapunov-Krasovskii functional approach, several new sufficient conditions are derived to design the pure delayed
controller. Finally, comparative simulation results are given to show the effectiveness and merits of the proposed control scheme. It is demonstrated that to mitigate recoil response of the deepwater riser in the event of emergency disconnection, the proposed pure delayed
controllers are more economic than the delay-free
controller.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Background and Objectives
This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients.
...Methods
Eighty‐five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis.
Results
The response rate to neoadjuvant imatinib was 65.9%. After the IPTW‐adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence‐free survival (DRFS) and disease‐specific survival (DSS) compared with those who underwent upfront surgery (5‐year DRFS 97.8 vs. 71.9%, hazard ratio HR, 0.15; 95% CI, 0.03–0.87; p = 0.03; 5‐year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01–0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5‐year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03–1.15).
Conclusions
In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor‐related deaths when compared to upfront surgery and adjuvant imatinib alone.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The rapid development of society has resulted in great competitive pressures, leading to the increase in suicide rates as well as incidence and recurrence of depression in recent years. Proprietary ...Chinese medicines containing
DC. (Chaihu) are widely used in clinical practice. This study aimed at evaluating the efficacy and safety of oral proprietary Chinese medicines containing Chaihu for treating depression by network meta-analysis (NMA) and exploring the potential pharmacological mechanisms of the optimal drugs obtained based on NMA.
This study searched for clinical randomized controlled trial studies (RCTs) about Chaihu-containing products alone or in combination with selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and cyclic antidepressants (CAS) for depression in eight databases. The search deadline is from data inception to April 2021. For efficacy assessment, the clinical response rate, the Hamilton Depression Scale-17 (HAMD-17), and adverse reactions were calculated. The methodological quality of the included studies was assessed for risk of bias following the
of
, and the data were subjected to NMA via the Stata version 16.0 software. Subsequently, the optimal drug obtained from the NMA results, Danzhi Xiaoyao pill (DZXY), was used to conduct network pharmacology analysis. We searched databases to acquire bioactive and potential targets of DZXY and depression-related targets. The protein-protein interaction (PPI) network, component-target network, the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by the STRING database, Cytoscape 3.9.0 software, and R version 4.1.2, respectively.
Thirty-seven RCTs, with a total of 3,263 patients, involving seven oral proprietary Chinese medicines containing Chaihu, were finally included. The results of the NMA demonstrated that the top four interventions with the best efficiency were Jiawei Xiaoyao + SSRI, DZXY + SNRI, Xiaoyao pill + SSRI, and Jieyu pill + SNRI; the top four interventions reducing HAMD score were DZXY + SNRI, Jiawei Xiaoyao, Jieyu pill, and Puyu pill + SNRI; the top four interventions with the least adverse effects were Jieyu pill, Anle pill + SSRI, DZXY + SNRI, and Puyu pill + SNRI. In the aspects above, DZXY + SNRI performed better than other treatments. After network meta-analysis, we conducted a network pharmacology-based strategy on the optimal drugs, DZXY, to provide the pharmacological basis for a conclusion. A total of 147 active compounds and 248 targets in DZXY were identified, of which 175 overlapping targets related to depression. Bioinformatics analysis revealed that MAPK3, JUN, MAPK14, MYC, MAPK1, etc. could become potential therapeutic targets. The MAPK signaling pathway might play an essential role in DZXY against depression.
This is the very first systematic review and network meta-analysis evaluating different oral proprietary Chinese medicines containing Chaihu in depressive disorder. This study suggested that the combination of proprietary Chinese medicines containing Chaihu with antidepressants was generally better than antidepressant treatment. The incidence of adverse reactions with antidepressants alone was higher than that with proprietary Chinese medicines containing Chaihu alone or in combination with antidepressants. DZXY + SNRI showed significantly better results in efficacy, HAMD scores, and safety. The antidepressant effect of DZXY may be related to its regulation of neuroinflammation and apoptosis.
Marine structures are inevitably influenced by parametric perturbations as well as multiple external loadings. Among these loadings, earthquake is generally more destructive and unpredictable than ...others. It is significant to develop effective active control schemes to guarantee the safety, stability, and integrity of marine structures subject to earthquakes and parametric perturbations. In this paper, the problem of networked
H
∞
robust damping control is addressed to stabilize a marine structure subject to earthquakes. First, in consideration of perturbations of the structure parameters, an uncertain model of the networked marine structure under earthquakes is presented. Second, a robust networked
H
∞
control scheme is presented to suppress seismic responses of the structure. By using stability theory of time-delay systems, several sufficient conditions on robust stability of the networked marine structure system are obtained, and the linear matrix inequality methods are utilized to solve the gain matrix of the controller. Finally, simulation indicates that compared with the traditional robust
H
∞
control and the proposed networked
H
∞
control, the seismic responses amplitudes of the marine structure under the two controllers are almost the same, while the latter is more economic than the former.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
In deepwater-drilling engineering, it is necessary to disconnect the bottom equipment of the lower marine-riser package from the blowout preventer when encountering multi-hazard environmental ...factors. In order to reduce the impact of recoil on the drilling platform after the sudden disconnection of the riser, in this paper, an optimal guaranteed cost H∞ recoil control problem is considered for the drilling riser. First, a three-element mass-damper-spring deepwater-drilling riser model subject to fluid discharge and heave motion of offshore platform is given. Then, an optimal guaranteed cost H∞ controller (OGCHC) is designed to suppress the recoil response of the drilling riser, and the sufficient conditions for the asymptotic stability of the closed-loop system are derived. Third, it is found through simulation results that the designed OGCHC can reduce the recoil response effectively. In order to further analyze the advantages of the OGCHC, the performance indices of the riser without active-recoil control and with optimal control (OC) and OGCHC are compared. It is shown that the average response amplitudes of three mass blocks of the riser are almost the same, while the control cost by the OGCHC is less than that by the OC. Further, under the designed recoil control, no riser compression occurs, thereby ensuring the safety of the riser system.
The performance degradation of gate-recessed metal–oxide–semiconductor high electron mobility transistor (MOS-HEMT) is compared with that of conventional high electron mobility transistor (HEMT) ...under direct current (DC) stress, and the degradation mechanism is studied. Under the channel hot electron injection stress, the degradation of gate-recessed MOS-HEMT is more serious than that of conventional HEMT devices due to the combined effect of traps in the barrier layer, and that under the gate dielectric of the device. The threshold voltage of conventional HEMT shows a reduction under the gate electron injection stress, which is caused by the barrier layer traps trapping the injected electrons and releasing them into the channel. However, because of defects under gate dielectrics which can trap the electrons injected from gate and deplete part of the channel, the threshold voltage of gate-recessed MOS-HEMT first increases and then decreases as the conventional HEMT. The saturation phenomenon of threshold voltage degradation under high field stress verifies the existence of threshold voltage reduction effect caused by gate electron injection.
BACKGROUND AND AIMS: Root growth and development are closely dependent upon nitrate supply in the growth medium. To unravel the mechanism underlying dependence of root growth on nitrate, an ...examination was made of whether endogenous nitric oxide (NO) is involved in nitrate-dependent growth of primary roots in maize. METHODS: Maize seedlings grown in varying concentrations of nitrate for 7 d were used to evaluate the effects on root elongation of a nitric oxide (NO) donor (sodium nitroprusside, SNP), a NO scavenger (methylene blue, MB), a nitric oxide synthase inhibitor (Nω-nitro-L-arginine, L-NNA), H₂O₂, indole-3-acetic acid (IAA) and a nitric reducatse inhibitor (tungstate). The effects of these treatments on endogenous NO levels in maize root apical cells were investigated using a NO-specific fluorescent probe, 4, 5-diaminofluorescein diacetate (DAF-2DA) in association with a confocal microscopy. KEY RESULTS: Elongation of primary roots was negatively dependent on external concentrations of nitrate, and inhibition by high external nitrate was diminished when roots were treated with SNP and IAA. MB and L-NNA inhibited root elongation of plants grown in low-nitrate solution, but they had no effect on elongation of roots grown in high-nitrate solution. Tungstate inhibited root elongation grown in both low- and high-nitrate solutions. Endogenous NO levels in root apices grown in high-nitrate solution were lower than those grown in low-nitrate solution. IAA and SNP markedly enhanced endogenous NO levels in root apices grown in high nitrate, but they had no effect on endogenous NO levels in root apical cells grown in low-nitrate solution. Tungstate induced a greater increase in the endogenous NO levels in root apical cells grown in low-nitrate solution than those grown in high-nitrate solution. CONCLUSIONS: Inhibition of root elongation in maize by high external nitrate is likely to result from a reduction of nitric oxide synthase-dependent endogenous NO levels in maize root apical cells.
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BFBNIB, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
As an important member of the chemokines, CCL14 plays a vital role in cancer progression. However, the role of CCL14 in THCA has not been investigated. This study aimed to reveal the clinical ...significance of CCL14 in THCA.
This study evaluated the expression and prognostic value of CCL14 in THCA. Also, the correlation between CCL14 and immune infiltrates was assessed. Enrichment analysis was finally performed to predict CCL14-associated pathways involved in THCA.
The mRNA and protein expressions of CCL14 in THCA tissues were down-regulated compared with normal tissues. CCL14 high expression predicted favorable DFI and PFI but did not influence the DSS and OS. Further, CCL14 showed a good prediction performance on the PFI of patients. Enrichment analysis found that CCL14 was negatively correlated with migration-related pathways such as Notch signaling, ECM-receptor interaction, and cell adhesion molecules. Further, we found that CCL14 was negatively related to immune infiltrates and their gene markers. A negative relationship was also observed between CCL14 and immune checkpoint genes. These results implied the potential effect of CCL14 on the immune response and immune therapy in THCA.
CCL14 high expression prolonged the DFI and PFI of THCA patients. It was negatively correlated with the migration-related pathways, suggesting that CCL14 might participate in the recurrence of THCA. Further, CCL14 was also shown to be important in immune response and immune therapy in THCA.
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