Esophageal cancer (EC) is a type of aggressive cancer without clinically relevant molecular subtypes, hindering the development of effective strategies for treatment. To define molecular subtypes of ...EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling of EC tumors and adjacent non-tumor tissues, revealing a catalog of proteins and phosphosites that are dysregulated in ECs. The EC cohort is stratified into two molecular subtypes-S1 and S2-based on proteomic analysis, with the S2 subtype characterized by the upregulation of spliceosomal and ribosomal proteins, and being more aggressive. Moreover, we identify a subtype signature composed of ELOA and SCAF4, and construct a subtype diagnostic and prognostic model. Potential drugs are predicted for treating patients of S2 subtype, and three candidate drugs are validated to inhibit EC. Taken together, our proteomic analysis define molecular subtypes of EC, thus providing a potential therapeutic outlook for improving disease outcomes in patients with EC.
Ni-rich cathode materials always suffer from surface lithium residues mainly caused by the reduction of Ni3+ to Ni2+ when exposing to moisture, and severe side reactions between organic electrolyte ...and highly active Ni4+ when fully charged. An appropriate amount of NH4H2PO4 is firstly coated on the hydroxide precursor Ni0.815Co0.15Al0.035(OH)2 before mixing with Li2CO3. The NH4H2PO4 can react with the lithium residues and form a uniform Li3PO4 coating layer. X-ray diffraction, scanning electron microscopy, field emission transmission electron microscopy and element mapping are employed to investigate the Li3PO4 coating layer. Electrochemical measurements results show that the cycle stability of the synthesized LiNi0.815Co0.15Al0.035O2 both at room temperature and 55 °C has been significantly improved. Its thermal stability has also been greatly enhanced.
•NH4H2PO4 can remove lithium residues and form a uniform Li3PO4 coating layer.•Porous Li3PO4 coating layer suppresses side reactions.•The thermal stability of Ni-rich cathode materials can be significantly enhanced.
Highly twisted electron donor (D)–electron acceptor (A)-type thermally activated delayed fluorescence (TADF) emitters can achieve high efficiency while suffering from serious structural relaxations ...and broad emissions. Multiple resonance (MR)-type TADF emitters can realize narrow emission. However, until now, only a few efficient MR-emitting cores are reported and custom tunning of their emission color remains a major challenge in their wider applications. In this work, by combining the conventional TADF and MR-TADF designs, we demonstrate that color tuning and narrowing the spectral width of conventional TADF emission can be easily achieved simultaneously. We select a prototypical carbonyl (CO)/N-based MR core as a backbone and attach it with D segments of different electron-donating abilities and numbers to obtain three different TADF emitters with emissions from sky blue to green and orange-red while maintaining the narrow emission of the original MR core. The corresponding sky blue, green, and orange-red organic light-emitting diodes achieve maximum external quantum efficiencies of 20.3, 27.3, and 26.3%, respectively, and narrow full widths at half-maximum all below 0.28 eV. These results provide a new molecular design strategy for developing narrowband TADF emitters with easily tunable emissions covering the full visible range.
Practicing mindfulness, focusing attention on the internal and external experiences occurring in the present moment with open and nonjudgement stance, can lead to the development of emotional ...regulation skills. Yet, the effective connectivity of brain regions during mindfulness has been largely unexplored. Studies have shown that mindfulness practice promotes functional connectivity in practitioners, potentially due to improved emotional regulation abilities and increased connectivity in the lateral prefrontal areas. To examine the changes in effective connectivity due to mindfulness training, we analyzed electroencephalogram (EEG) signals taken before and after mindfulness training, focusing on training‐related effective connectivity changes in the frontal area. The mindfulness training group participated in an 8‐week mindfulness‐based stress reduction (MBSR) program. The control group did not take part. Regardless of the specific mindfulness practice used, low‐gamma band effective connectivity increased globally after the mindfulness training. High‐beta band effective connectivity increased globally only during Breathing. Moreover, relatively higher outgoing effective connectivity strength was seen during Resting and Breathing and Body‐scan. By analyzing the changes in outgoing and incoming connectivity edges, both F7 and F8 exhibited strong parietal connectivity during Resting and Breathing. Multiple regression analysis revealed that the changes in effective connectivity of the right lateral prefrontal area predicted mindfulness and emotional regulation abilities. These results partially support the theory that the lateral prefrontal areas have top‐down modulatory control, as these areas have high outflow effective connectivity, implying that mindfulness training cultivates better emotional regulation.
This study illustrated the relationship between the effective connectivity of neurophysiological signal and emotional regulation in mindfulness practitioners. The top‐down theory may address the neural network mechanism of mindfulness‐enhanced emotional regulation. The EEG effective connectivity strength indicated in this study may serve as objective indicators for evaluating mindfulness practices.
This brief proposes an antislip balancing controller for wheel inverted pendulum (WIP) vehicles to deal with various traction environments. The controller is designed based on a general plant model ...which not only characterizes the dynamics of the pendulum body and the wheels but also the slip effect. As the general model can be decomposed into a convex combination of four linear subsystems with time-varying coefficients, the proposed controller also consists of a convex combination of four linear, full-state feedback controllers. It is proven that if the full-state feedback controllers satisfy a set of linear matrix inequalities, the WIP vehicle can maintain its stability regardless of the change of traction environments during operation. The convex coefficients in the control law are related to the traction force ratios which are identified via a two-step process. The validity of the antislip balancing controller is verified by both numerical simulations and experiments on a prototype WIP vehicle.
Cognitive impairment and change are a focus of research into late-life depression. The aims of this 5-year prospective study were (1) to observe cognitive status change; (2) to investigate the rate ...and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5 years among a clinical cohort with remitted major depressive disorder (MDD).
The study cohort included 130 elderly persons with late-life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow-up visit at the 5-year point. In total, 98 cases and 55 normal controls completed the 5-year follow-up assessment.
Of the study cohort with late-life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5 years. Patients with late-life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information-processing speed (p = 0.009) and memory (p = 0.041) could predict subsequent progression to dementia within 5 years among patients with MDD.
This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5 years. Further, we found that in depressed patients, deficits in information-processing speed and memory domains were highly suggestive of progression to dementia within 5 years.
Pulsed radiofrequency (PRF) works by delivering short bursts of radiofrequency to a target nerve, thereby affecting nerve signal transduction to reduce pain. Although preliminary clinical ...investigations have shown that PRF treatment can be used safely as an alternative interventional treatment in patients with refractory pain conditions, unexpected damage to a normal nerve/ganglion is still one of the possible complications of using the PRF strategy. Noxious pain may also be triggered if PRF treatment accidentally damages an intact nerve. However, few studies in the literature have described the intracellular modifications that occur in neuronal cells after PRF stimulation. Therefore, in this study, we evaluated the effects of PRF on unimpaired nerve function and investigated the potential mechanisms of PRF-induced pain. Wistar rats were stimulated with 30-60 V of PRF for 6 min, and mechanical allodynia, cold hypersensitivity, cytokine and matrix metalloproteinase (MMP) production, and mitogen-activated protein kinase activity (p38 MAPK, ERK1/2, JNK/SAPK) were analyzed. The results indicated that PRF stimulation induced a significant algesic effect and nociceptive response. In addition, the protein array and Western blotting analyses showed that the clinical application of 60 V of PRF can induce the activation of MAPKs and the production of inflammatory cytokines and MMPs in the lumbar dorsal horn, which is necessary for nerve inflammation, and it can be suppressed by MAPK antagonist treatment. These results indicate that PRF stimulation may induce inflammation of the intact nerve, which in turn causes inflammatory pain. This conclusion can also serve as a reminder for PRF treatment of refractory pain.
Abstract
Background
Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen HBsAg seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) ...treatment are incompletely understood.
Methods
This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.
Results
The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%–2.88%) and an annual rate of 0.22% (.17%–.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 95% confidence interval, 1.80–5.49), elevated serum alanine aminotransferase >200 U/L (3.68 2.07–6.53), serum bilirubin (1.11 per mg/dL; 1.06–1.17 mg/dL), and fatty liver (1.84 1.03–3.29).
Conclusion
HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.
Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.
Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in ...Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug–drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement.
Astrocytes activation in response to stroke results in altered mitochondrial exchange with neurons. Ginsenoside Rb1is a major ginsenoside of Panax ginseng particularly known for its neuroprotective ...potential. This work aimed to investigate if Rb1 could rescue neurons from ischemic insult via astrocyte inactivation and mitochondrial transfer. We prepared conditioned astrocytes-derived medium for co-culture with neurons and examined the role of Rb1 in mitochondrial transfer from astrocytes to neurons. The neuroprotective potential of Rb1 was further confirmed in vivo using a mouse model of brain ischemia. In response to oxygen-glucose deprivation and reperfusion (OGD/R), astrocytes were reactivated and produced reactive oxygen species (ROS), an action that was blocked by Rb1. Mechanistically, Rb1 inhibited NADH dehydrogenase in mitochondrial complex I to block reverse electron transport-derived ROS production from complex I, and thus inactivated astrocytes to protect the mitochondria. Mitochondrial signal, mitochondrial membrane potential and ATP production detected in conditioned astrocyte-derived medium indicated that Rb1 protected functional mitochondria and facilitated their transfer. When neurons were injured by OGD/R insult, co-culturing with conditioned medium increased mitochondrial membrane potential and oxygen consumption rate within the neurons, indicating the protection conferred on them by Rb1 via mitochondrial transfer from astrocytes. Using the ischemic mouse brain model, CD38 knockdown in the cerebral ventricles diminished the neuroprotective effects of Rb1, providing evidence in support of the role of astrocyte mitochondrial transfer. Transient inhibition of mitochondrial complex I by Rb1 reduced mitochondrial ROS production and consequently avoided astrocyte activation. Astrocyte mitochondrial transfer therefore seemed a means by which Rb1 could promote neuronal survival and function. Different from the neurocentric view, these findings suggest the astrocytes may be a promising target for pharmacological interventions in ischemic brain injury.
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