Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy

Diabetic cardiomyopathy (DCM), one of the most serious complications of diabetes mellitus, has become recognized as a cardiometabolic disease. In normoxic conditions, the majority of the ATP production (>95%) required for heart beating comes from mitochondrial oxidative phosphorylation of fatty acids (FAs) and glucose, with the remaining portion coming from a variety of sources, including fructose, lactate, ketone bodies (KB) and branched chain amino acids (BCAA). Increased FA intake and decreased utilization of glucose and lactic acid were observed in the diabetic hearts of animal models and diabetic patients. Moreover, the polyol pathway is activated, and fructose metabolism is enhanced. The use of ketones as energy sources in human diabetic hearts also increases significantly. Furthermore, elevated BCAA levels and impaired BCAA metabolism were observed in the hearts of diabetic mice and patients. The shift in energy substrate preference in diabetic hearts results in increased oxygen consumption and impaired oxidative phosphorylation, leading to diabetic cardiomyopathy. However, the precise mechanisms by which impaired myocardial metabolic alterations result in diabetes mellitus cardiac disease are not fully understood. Therefore, this review focuses on the molecular mechanisms involved in alterations of myocardial energy metabolism. It not only adds more molecular targets for the diagnosis and treatment, but also provides an experimental foundation for screening novel therapeutic agents for diabetic cardiomyopathy

Perturbation estimation based nonlinear adaptive control of VSC flexible excitation system

A new type of flexible excitation system (FES) is proposed by using fully-controlled power electronic devices such as IGBTs to replace the half controlled devices in the conventional static excitation system, which has the merit of independent control of rotor angle and terminal voltage of the synchronous generator. This paper proposes nonlinear adaptive control (NAC) strategies for synchronous generator with FES in a single machine infinite bus system. External disturbances and the uncertainties of all parameters as well as modelling are defined as lumped perturbation terms and estimated by perturbation observers or state and perturbation observer. The estimated perturbation terms are used to compensate the real perturbations and achieve a model-independent and robust NAC. Merits of the FES against the conventional static excitation system and effectiveness of the proposed NAC scheme against the accurate model based multi-variable feedback linearisation control are verified via small-signal stability analysis and simulation studies. The simulation results have shown that the proposed NAC can achieve superior control performance with less states feedback during a three-phase short circuit and better robustness against parameter uncertainties, compared with linear control and multi-variable feedback linearisation control

Involvement of potential pathways in malignant transformation from Oral Leukoplakia to Oral Squamous Cell Carcinoma revealed by proteomic analysis

<p>Abstract</p> <p>Background</p> <p>Oral squamous cell carcinoma (OSCC) is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it from cancer lesions, there is an urgent need to elucidate the molecular determinants and critical signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target.</p> <p>Results</p> <p>We have utilized two dimensional electrophoresis (2-DE) followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair was collected from a single patient. Approximately 85 differentially and constantly expressed proteins (> two-fold change, P < 0.05) were identified, including 52 up-regulated and 33 down-regulated. Gene ontological methods were employed to identify the biological processes that were over-represented in this carcinogenic stage. Biological networks were also constructed to reveal the potential links between those protein candidates. Among them, three homologs of proteosome activator PA28 a, b and g were shown to have up-regulated mRNA levels in OSCC cells relative to oral keratinocytes.</p> <p>Conclusion</p> <p>Varying levels of differentially expressed proteins were possibly involved in the malignant transformation of oral leukoplakia. Their expression levels, bioprocess, and interaction networks were analyzed using a bioinformatics approach. This study shows that the three homologs of PA28 may play an important role in malignant transformation and is an example of a systematic biology study, in which functional proteomics were constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results provide new insights into the pathogenesis of oral cancer. These differentially expressed proteins may have utility as useful candidate markers of OSCC.</p

ESMC: Entire Space Multi-Task Model for Post-Click Conversion Rate via Parameter Constraint

Large-scale online recommender system spreads all over the Internet being in charge of two basic tasks: Click-Through Rate (CTR) and Post-Click Conversion Rate (CVR) estimations. However, traditional CVR estimators suffer from well-known Sample Selection Bias and Data Sparsity issues. Entire space models were proposed to address the two issues via tracing the decision-making path of "exposure_click_purchase". Further, some researchers observed that there are purchase-related behaviors between click and purchase, which can better draw the user's decision-making intention and improve the recommendation performance. Thus, the decision-making path has been extended to "exposure_click_in-shop action_purchase" and can be modeled with conditional probability approach. Nevertheless, we observe that the chain rule of conditional probability does not always hold. We report Probability Space Confusion (PSC) issue and give a derivation of difference between ground-truth and estimation mathematically. We propose a novel Entire Space Multi-Task Model for Post-Click Conversion Rate via Parameter Constraint (ESMC) and two alternatives: Entire Space Multi-Task Model with Siamese Network (ESMS) and Entire Space Multi-Task Model in Global Domain (ESMG) to address the PSC issue. Specifically, we handle "exposure_click_in-shop action" and "in-shop action_purchase" separately in the light of characteristics of in-shop action. The first path is still treated with conditional probability while the second one is treated with parameter constraint strategy. Experiments on both offline and online environments in a large-scale recommendation system illustrate the superiority of our proposed methods over state-of-the-art models. The real-world datasets will be released

Highly selective recognition of Al3+ and I- ions using a bifunctional fluorescent probe

A tripodal fluorescent probe L1 armed with rhodamine B and 1-naphthaleneisothiocyanates was prepared in high yield. A study of the recognition properties revealed that probe L1 exhibited high sensitivity and selectivity towards Al3⁺ through a “FRET” fluorescence response and colorimetric response with low detection limits of the order of 10-8 M. Meanwhile, probe L1 also possessed high recognition capability for I⁻ through fluorescent decay, which given there are comparatively few selective fluorescent probes for I⁻, is significant. Furthermore, the complexation mechanisms were fully investigated by spectral titrations, 1H NMR spectroscopic titrations and mass spectrometry. The utility of probe L1 as a biosensor in living cells (PC3 cells) towards Al3⁺ ions has also been demonstrated

Quantum interface between frequency-uncorrelated down-converted entanglement and atomic-ensemble quantum memory

Photonic entanglement source and quantum memory are two basic building blocks of linear-optical quantum computation and long-distance quantum communication. In the past decades, intensive researches have been carried out, and remarkable progress, particularly based on the spontaneous parametric down-converted (SPDC) entanglement source and atomic ensembles, has been achieved. Currently, an important task towards scalable quantum information processing (QIP) is to efficiently write and read entanglement generated from a SPDC source into and out of an atomic quantum memory. Here we report the first experimental realization of a quantum interface by building a 5 MHz frequency-uncorrelated SPDC source and reversibly mapping the generated entangled photons into and out of a remote optically thick cold atomic memory using electromagnetically induced transparency. The frequency correlation between the entangled photons is almost fully eliminated with a suitable pump pulse. The storage of a triggered single photon with arbitrary polarization is shown to reach an average fidelity of 92% for 200 ns storage time. Moreover, polarization-entangled photon pairs are prepared, and one of photons is stored in the atomic memory while the other keeps flying. The CHSH Bell's inequality is measured and violation is clearly observed for storage time up to 1 microsecond. This demonstrates the entanglement is stored and survives during the storage. Our work establishes a crucial element to implement scalable all-optical QIP, and thus presents a substantial progress in quantum information science.Comment: 28 pages, 4 figures, 1 tabl

Transport evidence of superlattice Dirac cones in graphene monolayer on twisted boron nitride substrate

Strong band engineering in two-dimensional (2D) materials can be achieved by introducing moir\'e superlattices, leading to the emergence of various novel quantum phases with promising potential for future applications. Presented works to create moir\'e patterns have been focused on a twist embedded inside channel materials or between channel and substrate. However, the effects of a twist inside the substrate materials on the unaligned channel materials are much less explored. In this work, we report the realization of superlattice multi-Dirac cones with the coexistence of the main Dirac cone in a monolayer graphene (MLG) on a ~0.14{\deg} twisted double-layer boron nitride (tBN) substrate. Transport measurements reveal the emergence of three pairs of superlattice Dirac points around the pristine Dirac cone, featuring multiple metallic or insulating states surrounding the charge neutrality point (CNP). Displacement field tunable and electron-hole asymmetric Fermi velocities are indicated from temperature dependent measurements, along with the gapless dispersion of superlattice Dirac cones. The experimental observation of multiple Dirac cones in MLG/tBN heterostructure is supported by band structure calculations employing periodic moir\'e potential. Our results unveil the potential of using twisted substrate as a universal band engineering technique for 2D materials regardless of lattice matching and crystal orientations, which might pave the way for a new branch of twistronics.Comment: 13 pages, 4 figure

MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains

Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence among adult humans, chimpanzees, and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using a combination of high-throughput sequencing, miRNA microarrays, and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2%–4% of mRNA and 4%–6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA–driven regulation on the human evolutionary lineage, was further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions