Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway.

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation

Multi-Agent Reinforcement Learning Guided by Signal Temporal Logic Specifications

Reward design is a key component of deep reinforcement learning, yet some tasks and designer's objectives may be unnatural to define as a scalar cost function. Among the various techniques, formal methods integrated with DRL have garnered considerable attention due to their expressiveness and flexibility to define the reward and requirements for different states and actions of the agent. However, how to leverage Signal Temporal Logic (STL) to guide multi-agent reinforcement learning reward design remains unexplored. Complex interactions, heterogeneous goals and critical safety requirements in multi-agent systems make this problem even more challenging. In this paper, we propose a novel STL-guided multi-agent reinforcement learning framework. The STL requirements are designed to include both task specifications according to the objective of each agent and safety specifications, and the robustness values of the STL specifications are leveraged to generate rewards. We validate the advantages of our method through empirical studies. The experimental results demonstrate significant reward performance improvements compared to MARL without STL guidance, along with a remarkable increase in the overall safety rate of the multi-agent systems

Integrating Voice-Based Machine Learning Technology into Complex Home Environments

To demonstrate the value of machine learning based smart health technologies, researchers have to deploy their solutions into complex real-world environments with real participants. This gives rise to many, oftentimes unexpected, challenges for creating technology in a lab environment that will work when deployed in real home environments. In other words, like more mature disciplines, we need solutions for what can be done at development time to increase success at deployment time. To illustrate an approach and solutions, we use an example of an ongoing project that is a pipeline of voice based machine learning solutions that detects the anger and verbal conflicts of the participants. For anonymity, we call it the XYZ system. XYZ is a smart health technology because by notifying the participants of their anger, it encourages the participants to better manage their emotions. This is important because being able to recognize one's emotions is the first step to better managing one's anger. XYZ was deployed in 6 homes for 4 months each and monitors the emotion of the caregiver of a dementia patient. In this paper we demonstrate some of the necessary steps to be accomplished during the development stage to increase deployment time success, and show where continued work is still necessary. Note that the complex environments arise both from the physical world and from complex human behavior

Dichroism of x-­ray fluorescence under standing waves regime in magnetic periodic multilayers

We present the first test of the implementation of a characterization method whose aim is to study the interfaces of magnetic and periodic hetero-structures. The methodology relies on the combination of two techniques, generation of x-ray standing waves and dichroism in x-ray emission. The first one gives the depth selectivity since the maximum of the electric field can be put in specific locations of the stack, the centre of layers or their interfaces, while the second one enables being sensitive to the magnetic character of the atoms present within the stack. To concentrate on the methodology, the well-studied Mg/Co multilayer is analysed by using incident photon of monochromatic energies across the Co L2,3 absorption edge and measuring the intensity of the Co Lαβ emission. Despite large dispersive effects preventing the maxima of the electric field to reach the interfaces of the stack, it has been possible to observe the dichroic signal in the angular distribution of the Co emission intensity, i.e. in the so-called x-ray standing wave curve

Enhancing Vibrio vulnificus infection diagnosis for negative culture patients with metagenomic next-generation sequencing

ObjectiveTo evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in Vibrio vulnificus (V. vulnificus) infection.MethodsA retrospective analysis of patients with V. vulnificus infection at the Fifth Affiliated Hospital of Sun Yat-Sen University from January 1, 2020 to April 23, 2023 was conducted. 14 enrolled patients were diagnosed by culture or mNGS. The corresponding medical records were reviewed, and the clinical data analyzed included demographics, epidemiology laboratory findings, physical examination, symptoms at presentation, antibiotic and surgical treatment, and outcome.ResultsIn this study, 78.6% (11/14) patients had a history of marine trauma (including fish stab, shrimp stab, crab splints and fish hook wounds), 7.1% (1/14) had eaten seafood, and the remaining 14.3% (2/14) had no definite cause. Isolation of V. vulnificus from clinical samples including blood, tissue, fester and secreta. 9 cases were positive for culture, 5 cases were detected synchronously by mNGS and got positive for V. vulnificus. 85.7% (12/14) cases accepted surgical treatment, with 1 patient suffering finger amputated. 14 enrolled patients received appropriate antibiotic therapy, and all of them had recovered and discharged. 9 strains V. vulnificus isolated in this study were sensitive to most beta-lactam antibiotics, aminoglycosides, quinolones, etc.ConclusionVibrio vulnificus infection is a common water-exposed disease in Zhuhai, which requires identification of a number of pathogens. Of severe infections with unknown pathogen, mNGS can be used simultaneously, and the potential to detect multiple pathogens is of great help in guiding treatment

Molecular dynamics simulations of structural transformation of perfluorooctane sulfonate (PFOS) at water/rutile interfaces

Concentration and salinity conditions are the dominant environmental factors affecting the behavior of perfluorinated compounds (PFCs) on the surfaces of a variety of solid matrices (suspended particles, sediments, and natural minerals). However, the mechanism has not yet been examined at molecular scales. Here, the structural transformation of perfluorooctane sulfonate (PFOS) at water/rutile interfaces induced by changes of the concentration level of PFOS and salt condition was investigated using molecular dynamics (MD) simulations. At low and intermediate concentrations all PFOS molecules directly interacted with the rutile (110) surface mainly by the sulfonate headgroups through electrostatic attraction, yielding a typical monolayer structure. As the concentration of PFOS increased, the molecules aggregated in a complex multi-layered structure, where an irregular assembling configuration was adsorbed on the monolayer structure by the van der Waals interactions between the perfluoroalkyl chains. When adding CaCl2 to the system, the multi-layered structure changed to a monolayer again, indicating that the addition of CaCl2 enhanced the critical concentration value to yield PFOS multilayer assemblies. The divalent Ca2+ substituted for monovalent K+ as the bridging counterion in PFOS adsorption. MD simulation may trigger wide applications in study of perfluorinated compounds (PFCs) from atomic/molecular scale

MicroRNA-181a Functions as an Oncogene in Gastric Cancer by Targeting Caprin-1

MicroRNA-181a (miRNA-181a) is a multifaceted miRNA implicated in various cellular processes, particularly in cell fate determination and cellular invasion. It is frequently expressed aberrantly in human tumors and shows opposing functions in different types of cancers. In this study, we found that miRNA-181a is overexpressed in Gastric cancer (GC) tissues. Clinical and pathological analyses revealed that the expression of miRNA-181a is correlated with tumor size, lymph node metastasis, distant metastasis, and TNM stage. Kaplan-Meier analysis indicated that overexpression of miRNA-181a is associated with poor overall survival of patients with GC. Moreover, miRNA-181a is overexpressed in GC cells, and downregulation of miRNA-181a induced cell apoptosis and suppressed the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Target prediction and luciferase reporter assay showed that caprin-1 was a direct target of miRNA-181a. Downregulation of caprin-1 expression resulted in a converse change with miRNA-181a in GC. Spearman’s correlation test confirmed that the expression of miRNA-181a expression was inversely correlated with that of caprin-1 in GC cells. Furthermore, the expression of caprin-1 increased after downregulation of miRNA-181a in the GC cells. Caprin-1 siRNA can rescue the oncogenic effect of miRNA-181a on GC cell proliferation, apoptosis, migration, and invasion. These findings suggest that miRNA-181a directly inhibits caprin-1 and promotes GC development. miRNA-181a could be a target for anticancer drug development

Binding mechanism of arsenate on rutile (110) and (001) planes studied using grazing-incidence EXAFS measurement and DFT calculation

Characterization of contaminant molecules on different exposed crystal planes is required to conclusively describe its behavior on mineral surfaces. Here, the structural properties and relative stability of arsenate adsorbed on rutile TiO2 (110) and (001) surfaces were investigated using grazing-incidence extended X-ray absorption fine structure (GI-EXAFS) spectra and periodic density functional theory (DFT) calculation. The combined results indicated that arsenate mainly formed inner-sphere bidentate binuclear (BB) and monodentate mononuclear (MM) complexes on both surfaces, but the orientational polar angles of arsenate on the (110) surface were commonly smaller than that on the (001) surface for the two adsorption modes. The DFT calculation showed that the (110) plane had a higher affinity toward arsenate than the (001) plane, suggesting that, for a given adsorption mode (i.e., MM or BB structure), a small polar angle was more favorable for arsenate stabilized on the rutile surfaces

Structure and stability of arsenate adsorbed on α-Al2O3 single-crystal surfaces investigated using grazing-incidence EXAFS measurement and DFT calculation

Direct characterization of contaminants on single-crystal planes is required because the specific adsorption characteristics on different exposed crystal planes constitute their actual behavior at water–mineral interfaces in aquifers. Here, the structure and stability of arsenate on α-Al2O3 (0001) and (View the MathML source112¯0) surfaces were characterized by using a combination of grazing-incidence extended X-ray absorption fine structure (GI-EXAFS) spectra and periodic density functional theory (DFT) calculation. The combined results indicated that arsenate was mainly adsorbed as inner-sphere monodentate and bidentate complexes on both surfaces, but the orientational polar angles on the (0001) surface were commonly 10–20° greater than that on the (View the MathML source112¯0) surface. The DFT calculation showed that the large polar angle was more favorable for arsenate stabilized on the alumina surfaces. Based on the spectroscopic and computational data, the dominant bonding modes of arsenate on the two crystal planes of α-Al2O3 were identified as bidentate binuclear structures, and the (0001) surface displayed a stronger affinity toward arsenate