Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.

The hepatic acute-phase response is characterized by a massive upregulation of serum proteins, such as haptoglobin and serum amyloid A, at the expense of liver homeostatic functions. Although the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A) has a well-established role in safeguarding liver function and its cistrome spans around 50% of liver-specific genes, its role in the acute-phase response has received little attention so far. We demonstrate that HNF4A binds to and represses acute-phase genes under basal conditions. The reprogramming of hepatic transcription during inflammation necessitates loss of HNF4A function to allow expression of acute-phase genes while liver homeostatic genes are repressed. In a pre-clinical liver organoid model overexpression of HNF4A maintained liver functionality in spite of inflammation-induced cell damage. Conversely, HNF4A overexpression potently impaired the acute-phase response by retaining chromatin at regulatory regions of acute-phase genes inaccessible to transcription. Taken together, our data extend the understanding of dual HNF4A action as transcriptional activator and repressor, establishing HNF4A as gatekeeper for the hepatic acute-phase response.

Preparation and thermal responsiveness of microencapsulated fluorinated liquids for automatic fire extinguishing.

Most early-stage fires originating in small confined spaces may not be effectively mitigated by automatic fire-extinguishing systems. Leveraging the unique controlled release capability and barrier properties of microcapsules presents a promising avenue for developing multifunctional and intelligent fire-extinguishing agents tailored for early-stage fire suppression. This paper introduces two types of microcapsules that integrate automatic detection and fire extinguishing functions, utilizing fluorinated liquids specifically perfluoro(2-methyl-3-pentanone) and 1,1,1,2,2,3,4,5,5,5 decafluoro-3-methoxy-4(trifluoromethyl)-pentane as core materials. The preparation process was optimized, and the thermal response of the microcapsules was evaluated by directly incorporating them into combustible materials. The results indicated a correlation between the preparation method, coating efficiency, and thermal stability of microcapsules with the core-wall materials. When the fluoride solution in the core material reaches the thermal response threshold temperature, the gas pressure generated during vaporization and phase change can break through the shell, enabling early active fire protection. Beyond a specific threshold of additive microcapsules in the material, the material exhibits self-extinguishing potential during combustion. In cases where the additive amount falls short of achieving self-extinguishing, the fire-resistant performance of materials can be enhanced through various measures. For instance, reducing the amount of fire-extinguishing agents, delaying the ignition time of fuel, and lowering the heat release rate during combustion are effective strategies. Moreover, the degree of improvement is related to the additional amount and the type of core-wall materials. The thermal-response mechanism of microcapsules constitutes a comprehensive mechanism with physical and chemical effects. The finding of this research offer a new technical approach for microencapsulating high-boiling-point gas extinguishing agents, facilitating intelligent and precise prevention of early fires resulting from combustible materials.

Inducing Directional Charge Delocalization in 3D-Printable Micro-Supercapacitors Based on Strongly Coupled Black Phosphorus and ReS2 Nanocomposites.

The growing interest in so-called interface coupling strategies arises from their potential to enhance the performance of active electrode materials. Nevertheless, designing a robust coupled interface in nanocomposites for stable electrochemical processes remains a challenge. In this study, an epitaxial growth strategy is proposed by synthesizing sulfide rhenium (ReS2 ) on exfoliated black phosphorus (E-BP) nanosheets, creating an abundance of robust interfacial linkages. Through spectroscopic analysis using X-ray photoelectron spectroscopy and X-ray absorption spectroscopy, the authors investigate the interfacial environment. The well-developed coupled interface and structural stability contribute to the impressive performance of the 3D-printed E-BP@ReS2 -based micro-supercapacitor, achieving a specific capacitance of 47.3 mF cm-2 at 0.1 mA cm-2 and demonstrating excellent long-term cyclability (89.2% over 2000 cycles). Furthermore, density functional theory calculations unveil the positive impact of the strongly coupled interface in the E-BP@ReS2 nanocomposite on the adsorption of H+ ions, showcasing a significantly reduced adsorption energy of -2.17 eV. The strong coupling effect facilitates directional charge delocalization at the interface, enhancing the electrochemical performance of electrodes and resulting in the successful construction of advanced micro-supercapacitors.

Single-cell RNA sequencing reveals the dynamics and heterogeneity of lymph node immune cells during acute and chronic viral infections.

Introduction: The host immune response determines the differential outcome of acute or chronic viral infections. The comprehensive comparison of lymphoid tissue immune cells at the single-cell level between acute and chronic viral infections is largely insufficient. Methods: To explore the landscape of immune responses to acute and chronic viral infections, single-cell RNA sequencing(scRNA-seq), scTCR-seq and scBCR-seq were utilized to evaluate the longitudinal dynamics and heterogeneity of lymph node CD45+ immune cells in mouse models of acute (LCMV Armstrong) and chronic (LCMV clone 13) viral infections. Results: In contrast with acute viral infection, chronic viral infection distinctly induced more robust NK cells and plasma cells at the early stage (Day 4 post-infection) and acute stage (Day 8 post-infection), respectively. Moreover, chronic viral infection exerted decreased but aberrantly activated plasmacytoid dendritic cells (pDCs) at the acute phase. Simultaneously, there were significantly increased IgA+ plasma cells (MALT B cells) but differential usage of B-cell receptors in chronic infection. In terms of T-cell responses, Gzma-high effector-like CD8+ T cells were significantly induced at the early stage in chronic infection, which showed temporally reversed gene expression throughout viral infection and the differential usage of the most dominant TCR clonotype. Chronic infection also induced more robust CD4+ T cell responses, including follicular helper T cells (Tfh) and regulatory T cells (Treg). In addition, chronic infection compromised the TCR diversity in both CD8+ and CD4+ T cells. Discussion: In conclusion, gene expression and TCR/BCR immune repertoire profiling at the single-cell level in this study provide new insights into the dynamic and differential immune responses to acute and chronic viral infections.

Histone Deacetylase Inhibitor (SAHA) Reduces Mortality in an Endotoxemia Mouse Model by Suppressing Glycolysis.

Sepsis is a life-threatening medical emergency triggered by excessive inflammation in response to an infection. High mortality rates and limited therapeutic options pose significant challenges in sepsis treatment. Histone deacetylase inhibitors (HDACi), such as suberoylanilide hydroxamic acid (SAHA), have been proposed as potent anti-inflammatory agents for treating inflammatory diseases. However, the underlying mechanisms of sepsis treatment remain poorly understood. In this study, we investigated the effects of SAHA treatment in the lipopolysaccharide (LPS)-induced endotoxemia mouse model as it closely mimics the early stages of the systemic inflammation of sepsis. Our results demonstrate a reduced inflammatory mediator secretion and improved survival rates in mice. Using quantitative acetylomics, we found that SAHA administration increases the acetylation of lactate dehydrogenase (LDHA), and consequently inhibits LDHA activity. Notably, the reduced enzyme activity of LDHA results in a reduced rate of glycolysis. Furthermore, our experiments with bone marrow-derived macrophages (BMDMs) show that SAHA administration reduced oxidative stress and extracellular ATP concentrations, ultimately blunting inflammasome activation. Overall, our study provides insights into the mechanism underlying SAHA's therapeutic effects in sepsis treatment and highlights LDHA as a potential target for developing novel sepsis treatment.

Glaesserella australis sp. nov., isolated from the lungs of pigs.

Twenty-nine isolates of an unknown haemophilic organism were isolated from the lungs of pigs from 14 farms in Australia. Phylogenetic analyses based on the 16S rRNA gene, recN and rpoA showed a monophyletic group that was most closely related to Glaesserella parasuis and [Actinobacillus] indolicus. Whole genome sequence analysis indicated that the Glaesserella parasuis and this group, using the type strain HS4635T for comparison, showed a similarity of 30.9 % DNA-DNA renaturation. The isolates were Gram-stain-negative, NAD-dependent, CAMP-negative and were oxidase-positive, catalase-negative and produced indole but not urease. The isolates could be separated from all currently recognized haemophilic and non-haemophilic members of the family Pastuerellaceae. Key phenotypic properties were the production of indole, the lack of urease activity, production of ß-galactosidase but not α-fucosidase, acid formation from (-)-d-arabinose, (+)-d-galactose, maltose and trehalose and a failure to produce acid from (-)-d-mannitol. Taken together, these data indicate that the isolates belong to a novel species for which the name Glaesserella australis sp. nov. is proposed. The type strain is HS4635T (=CCUG 71931T and LMG 30645T).

Deciphering Electron-Shuttling Characteristics of Neurotransmitters to Stimulate Bioelectricity-Generating Capabilities in Microbial Fuel Cells.

This first-attempt study used electrochemical methods to quantitatively assess electron-shuttling capabilities of different neurotransmitters crucial to catecholamine biosynthesis in human brain. As prior studies mentioned, aromatics bearing ortho- or para-dihydroxybenzenes could reveal promising electroactivities to stimulate bioenergy generation in microbial fuel cells (MFCs). This feasibility study extended to investigate the electrochemical characteristics of catecholamines and trace amines (e.g., 14 model compounds selected from neurotransmitters) synthesized by human brain via cyclic voltammetry methods (CVs) and MFCs. Dopamine (DA), levodopa (L-DOPA), epinephrine (EP), norepinephrine (NP), and 3,4-dihydroxyphenylacetic acid (DOPAC) would perform the electron-shuttling characteristics, and the rest would not. In particular, DA formed by decarboxylation of L-DOPA could exhibit relatively higher electrochemical activities than their precursors. In addition, carboxylic acids formed by deamination and carboxylation of trace monoamines would reveal more significant reductive potential (Epc); however, their oxidative electric currents seemed to be reduced. That is, chemical structure significantly influenced whether the electrochemical characteristics could be effectively expressed. This work also clearly revealed that neurotransmitters with ortho-dihydroxybenzenes exhibited promising stimulation to bioelectricity-generating capabilities of MFCs in the ranking of DA ~ EP > NP > L-DOPA > DOPAC. This was consistent with ES behaviors as CV analyses indicated.

Variation of rhizosphere bacterial community in watermelon continuous mono-cropping soil by long-term application of a novel bioorganic fertilizer.

The application method for a novel bioorganic fertilizer (BIO) was developed to improve its biocontrol efficacy of Fusarium wilt (Ling et al. 2010). However, its efficacy on controlling Fusarium wilt and the variations of microbial community after long-term application for watermelon production had not been elucidated. To clarify, a 4-years pot experiment of mono-cropping watermelon was conducted. The results revealed that though the disease incidences were increased in all treatments with the increase of continuous cropping years, the treatment of BIO application both in nursery and pot soil always maintained the lowest disease incidence. The real-time PCR results showed that the population of Paenibacillus polymyxa was decreased with continuous cropping years, but in all seasons, the treatment with BIO application both in nursery and pot soil had a highest population of P. polymyxa than the other treatments. On the other hand, the abundance of the pathogen FON was increased with the increase of continuous cropping years and the lowest rate of increase was found by BIO application in both nursery and pot soil. DGGE patterns showed that the bacterial diversity was weakened after mono-cropping of watermelon for 4 years, but the consecutive applications of BIO at nursery and transplanting stage resulted in the minimal change of bacterial diversity. More detailed differences on bacterial diversity between control and double application of BIO treatment after 4-years monoculture were analyzed by 454 pyrosequencing, which showed the dominant phyla found in both samples were Firmicutes, Proteobacteria and Actinobacteria, and the consecutive applications of BIO recruited more beneficial bacteria than control, such as Bacillus, Paenibacillus, Haliangium, Streptomyces. Overall, these results, to a certain extent, approved that the consecutive applications of BIO at nursery and transplanting stage could effectively suppress watermelon Fusarium wilt by regulating the rhizosphere bacterial diversity. These results could give some clues that how to regulate the soil microbial community to an appropriate level which can keep the plant healthy and thus control the soil-borne diseases.

A novel tunable green- to yellow-emitting ß-YFS:Ce³+ phosphor for solid-state lighting.

A Ce(3+)-activated fluorosulfide phosphor (ß-YFS:Ce(3+)) was synthesized by solid-state reaction in a sealed tube. The crystal structure has been refined from the XRD profiles and there are two different crystallographic rare earth sites, namely, Y(1) and Y(2), where the Ce(3+) ions occupied. The emission band with a maximum at 495 nm of ß-Y(0.99)Ce(0.01)FS phosphor was characterized by the 4f-5d transitions of Ce(3+) ion. With increasing Ce(3+) concentration, the emission variations were observed from 495 to 547 nm. When ß-YFS:Ce(3+) phosphors were utilized to incorporate with n-UV/blue chip, greenish-white light with color rendering index of 65-77 were obtained. The results indicate that the tunable green- to yellow-emitting ß-YFS:Ce(3+) can serve as a potential phosphor for incorporation in fabrication for solid-state lighting. The preparation, spectroscopic characterization, quantum efficiency, thermal-quenching behavior, and related LED device data are also presented.