Investigation into intratumoral heterogeneity (ITH) of the epigenome is in a formative stage. The patterns of tumor evolution inferred from epigenetic ITH and genetic ITH are remarkably similar, ...suggesting widespread co-dependency of these disparate mechanisms. The biological and clinical relevance of epigenetic ITH are becoming more apparent. Rare tumor cells with unique and reversible epigenetic states may drive drug resistance, and the degree of epigenetic ITH at diagnosis may predict patient outcome. This perspective presents these current concepts and clinical implications of epigenetic ITH, and the experimental and computational techniques at the forefront of ITH exploration.
Investigation into intratumoral heterogeneity (ITH) of the epigenome is in a formative stage. The patterns of tumor evolution inferred from epigenetic ITH and genetic ITH are remarkably similar, suggesting widespread co-dependency of these disparate mechanisms. The biological and clinical relevance of epigenetic ITH are becoming more apparent. Rare tumor cells with unique and reversible epigenetic states may drive drug resistance, and the degree of epigenetic ITH at diagnosis may predict patient outcome. This perspective presents these current concepts and clinical implications of epigenetic ITH, and the experimental and computational techniques at the forefront of ITH exploration.
A surface coating of SiO2 is applied to a Ni rich LiNi0.6Co0.2Mn0.2O2 cathode material in a bid to improve its electrochemical and thermal properties. A uniform coating is achieved through a wet ...process using nano-sized SiO2 powder, and though the coated electrode is found to exhibit a reduced rate capability, its cycle performance at a high temperature of 60 °C is greatly enhanced. The effect of this SiO2 coating is further investigated by electrochemical impedance spectroscopy, which confirms that it suppresses the growth of interfacial impedance during progressive cycles. The SiO2 coating also demonstrates good HF scavenging ability, producing a subsequent reduction in the degradation of the active core material. The thermal properties of LiNi0.6Co0.2Mn0.2O2 are also improved by the SiO2 coating due to a reduction in the direct contact between the electrode and electrolyte. On the basis of these results, SiO2 coating is considered a viable surface modification method for improving the electrochemical and thermal properties of LiNi0.6Co0.2Mn0.2O2.
•Nano-sized SiO2 was uniformly coated on the surface of LiNi0.6Co0.2Mn0.2O2 cathode.•Thermal stability and cycle performance are improved by SiO2 coating.•EIS results suggest that side reaction on interface is suppressed by SiO2 coating.•SiO2 coating shows significant HF scavenging effect.
In this study, we propose a modified particle swarm optimization (PSO) algorithm, which is an improved version of the conventional PSO algorithm. To improve the performance of the conventional PSO, a ...novel method is applied to intelligently control the number of particles. The novel method compares the cost value of the global best (gbest) in the current iteration to that of the gbest in the previous iteration. If there is a difference between the two cost values, the proposed algorithm operates in the exploration stage, maintaining the number of particles. However, when the difference in the cost values is smaller than the tolerance values assigned by the user, the proposed algorithm operates in the exploitation stage, reducing the number of particles. In addition, the algorithm eliminates the particle that is nearest to the best particle to ensure its randomness in terms of the Euclidean distance. The proposed algorithm is validated using five numerical test functions, whose number of function calls is reduced to some extent in comparison to conventional PSO. After the algorithm is validated, it is applied to the optimal design of an interior permanent magnet synchronous motor (IPMSM), aiming at minimizing the total harmonic distortion (THD) of the back electromotive force (back EMF). Considering the performance constraint, an optimal design is attained, which reduces back EMF THD and satisfies the back EMF amplitude. Finally, we build and test an experimental model. To validate the performance of the optimal design and optimization algorithm, a no-load test is conducted. Based on the experimental result, the effectiveness of the proposed algorithm on optimal design of an electric machine is validated.
A new SHG material, namely, Pb2(BO3)(NO3), which contains parallel π‐conjugated nitrate and borate anions, was obtained through a facile hydrothermal reaction by using Pb(NO3)2 and Mg(BO2)2⋅H2O as ...starting materials. Its structure contains honeycomb Pb2(BO3)∞ layers with noncoordination NO3− anions located at the interlayer space. Pb2(BO3)(NO3) shows a remarkable strong SHG response of approximately 9.0 times that of potassium dihydrogen phosphate (KDP) and the material is also phase‐matchable. The large SHG coefficient of Pb2(BO3)(NO3) arises from the synergistic effect of the stereoactive lone pairs on Pb2+ cations and parallel alignment of π‐conjugated BO3 and NO3 units. Based on its unique properties, Pb2(BO3)(NO3) may have great potential as a high performance NLO material in photonic applications.
Pb2(BO3)(NO3) is a new second‐harmonic generation (SHG) material that contains parallel π‐conjugated nitrate and borate anions. It was obtained through a facile hydrothermal reaction, shows a remarkable strong SHG response of about 9.0 times that of potassium dihydrogen phosphate (KDP), and is phase‐matchable.
The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or ...described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.
What is known and objective
B vitamin therapy is a common treatment for diabetic pain and neuropathy, yet its use remains controversial in patients lacking B vitamin deficiencies. The aim of this ...review was to summarize the current evidence for the efficacy of B vitamin therapy in diabetic patients with neuropathy.
Comment
We screened the English literature for clinical studies evaluating B vitamins as a therapy for pain and neuropathy in diabetic patients. We selected 43 relevant studies for qualitative analysis based on our selection criteria. Our survey of the literature revealed substantive heterogeneity with respect to efficacies of reported outcomes, as well as study design. Most beneficial outcomes were reported against baseline measures, with few positive comparisons against placebo. This highlights the need for larger, placebo‐controlled studies.
What is new and conclusion
B vitamins should be considered a plausible therapy for diabetic neuropathy, but its overall efficacy remains uncertain and requires further study.
This article summarizes evidence for use of B vitamins to treat diabetic neuropathy. We report that the evidence supporting such use of B vitamins is mixed, and more high quality studies are needed to confirm efficacy of this treatment.
Materials and fabrication procedures are described for bioresorbable transistors and simple integrated circuits, in which the key processing steps occur on silicon wafer substrates, in schemes ...compatible with methods used in conventional microelectronics. The approach relies on an unusual type of silicon on insulator wafer to yield devices that exploit ultrathin sheets of monocrystalline silicon for the semiconductor, thin films of magnesium for the electrodes and interconnects, silicon dioxide and magnesium oxide for the dielectrics, and silk for the substrates. A range of component examples with detailed measurements of their electrical characteristics and dissolution properties illustrate the capabilities. In vivo toxicity tests demonstrate biocompatibility in sub‐dermal implants. The results have significance for broad classes of water‐soluble, “transient” electronic devices.
Materials, designs, and integration techniques are presented for a class of water‐soluble electronics capable of fabrication using wafer‐based processes. The active components exploit biocompatible and bioresorbable materials that are capable of dissolution in biofluids. Characterization of the electronic properties of the devices, their kinetics for dissolution, and preliminary evaluations in animal models highlight key aspects of the materials and concepts.
Grain weight is one of the most important components of grain yield and is controlled by quantitative trait loci (QTLs) derived from natural variations in crops. However, the molecular roles of QTLs ...in the regulation of grain weight have not been fully elucidated. Here, we report the cloning and characterization of GW2, a new QTL that controls rice grain width and weight. Our data show that GW2 encodes a previously unknown RING-type protein with E3 ubiquitin ligase activity, which is known to function in the degradation by the ubiquitin-proteasome pathway. Loss of GW2 function increased cell numbers, resulting in a larger (wider) spikelet hull, and it accelerated the grain milk filling rate, resulting in enhanced grain width, weight and yield. Our results suggest that GW2 negatively regulates cell division by targeting its substrate(s) to proteasomes for regulated proteolysis. The functional characterization of GW2 provides insight into the mechanism of seed development and is a potential tool for improving grain yield in crops.
Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in ...biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.
Inhibition and eradication of Staphylococcus aureus biofilms with conventional antibiotic is difficult, and the treatment is further complicated by the rise of antibiotic resistance among ...staphylococci. Consequently, there is a need for novel antimicrobials that can treat biofilm-related infections and decrease antibiotics burden. Natural compounds such as eugenol with anti-microbial properties are attractive agents that could reduce the use of conventional antibiotics. In this study we evaluated the effect of eugenol on MRSA and MSSA biofilms in vitro and bacterial colonization in vivo.
Effect of eugenol on in vitro biofilm and in vivo colonization were studied using microtiter plate assay and otitis media-rat model respectively. The architecture of in vitro biofilms and in vivo colonization of bacteria was viewed with SEM. Real-time RT-PCR was used to study gene expression. Check board method was used to study the synergistic effects of eugenol and carvacrol on established biofilms. Eugenol significantly inhibited biofilms growth of MRSA and MSSA in vitro in a concentration-dependent manner. Eugenol at MIC or 2×MIC effectively eradicated the pre-established biofilms of MRSA and MSSA clinical strains. In vivo, sub-MIC of eugenol significantly decreased 88% S. aureus colonization in rat middle ear. Eugenol was observed to damage the cell-membrane and cause a leakage of the cell contents. At sub-inhibitory concentration, it decreases the expression of biofilm-and enterotoxin-related genes. Eugenol showed a synergistic effect with carvacrol on the eradication of pre-established biofilms.
This study demonstrated that eugenol exhibits notable activity against MRSA and MSSA clinical strains biofilms. Eugenol inhibited biofilm formation, disrupted the cell-to-cell connections, detached the existing biofilms, and killed the bacteria in biofilms of both MRSA and MSSA with equal effectiveness. Therefore, eugenol may be used to control or eradicate S. aureus biofilm-related infections.
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