CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease

Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg–Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease

The Internal and External Competition and System Changes Under the Background of Modern Chinese Party Politics

Since modern times, Chinese intellectual Liang Qichao and others have imitated the Western political system and vigorously advocated and implemented party politics in order to promote the historical process of political democratization and diplomacy in modern China. As China was in the current situation of internal and external troubles, various political parties have advocated national diplomacy, and have written national diplomacy policies into the party constitution or political program as a guideline for the fierce competition on the domestic and foreign affairs arena. Due to the frequent divisions and reorganizations between political parties, the political programs and political ideas of the political parties were confused with each other, and the responsibilities and obligations of party members were blurred, resulting in the increasingly complex internal and external competition of modern Chinese political parties, which reflected the modern Chinese political system Major changes

A 7.5-mV Input and 88%-Efficiency Single-Inductor Boost Converter with Self-Startup and MPPT for Thermoelectric Energy Harvesting

This paper presents a single-inductor boost converter for thermoelectric energy harvesting. A two-stages startup circuit with a three-phase operation is adopted to obtain self-startup with a single inductor. To extract the maximum energy, a coarse- and fine-tuning MPPT is proposed to adaptively and effectively track the internal source resistance. By designing a zero-current detector, the synchronization loss is reduced, which significantly improves the peak efficiency. The boost converter is implemented in a 0.18-μm standard CMOS process. Simulation results show that the converter self-starts the operation from a TEG voltage of 128 mV and achieves 88% peak efficiency, providing a maximum output power of 3.78 mW. The improved MPPT enables the converter to sustain the operation at an input voltage as low as 7.5 mV after self-startup

A high-accuracy indoor positioning system based on UWB

In this paper, a high-accuracy indoor positioning system based on the ultra-wideband (UWB) technique is proposed. The proposed system uses a simple ranging process to obtain the distance between the mobile node and the fixed base stations. Besides, an improved time of arrival (ToA) algorithm with Kalman filtering is proposed to improve the positioning accuracy. Measurements have been performed in the real indoor 13m*7.6m environment with many obstacles and the root-mean-square error (RMSE) is less than 0.3m. The proposed system offers a wide range of application in robotics, industrial automation, post-sorting system and so on

A 672-nW, 670-n<italic>Vrms</italic> ECG Acquisition AFE With Noise-Tolerant Heartbeat Detector

This paper presents an electrocardiogram acquisition analog front-end (AFE) with a noise tolerant heartbeat (HB) detector. Source degradation and transconductance bootstrap techniques are incorporated into the AFE to reduce the 1/f noise of the amplifier. Furthermore, the chopper modulation, DC-servo loop (DSL) and pre-charge technology are combined to reduce interference from the environment. A mixed-signal implementation of HB detector with the symmetric-comparison loop is proposed to reduce the power consumption and area, which also suppresses motion artifact interference by adaptive thresholds. Implemented in $0.18 ~\mu \text{m}$ CMOS process, the circuit only occupies an area of $0.122 mm^{2}$ and consumes $0.62 ~\mu \text{W}$ at a 1.2-V supply, of which AFE and HB detector consume 507 nW and 110 nW, respectively. Simulation results show that the gain and the CMRR of AFE range from 30&#x2013;45 dB and 65&#x2013;105 dB, respectively. The input-referred noise is 670 nVrms with a mid-band gain of 42 dB and a bandwidth ranging from 0.5 Hz to 1 kHz

Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder.

Alcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein. We studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples. Patients with AUD had significantly increased abundance of the genera , , , , and , and of the species and compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera , , , , , and the species and . This was mirrored by significantly higher specific anti- immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti- IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease. In conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of and , and lower serum anti- IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD

Engineered bacteria producing aryl‐hydrocarbon receptor agonists protect against ethanol‐induced liver disease in mice

International audienceBackground and Purpose Gut bacteria metabolize tryptophan into indoles. Intestinal levels of the tryptophan metabolite indole‐3‐acetic acid are reduced in patients with alcohol‐associated hepatitis. Supplementation of indole‐3‐acetic acid protects against ethanol‐induced liver disease in mice. The aim of this study was to evaluate the effect of engineered bacteria producing indoles as Aryl‐hydrocarbon receptor (Ahr) agonists. Methods C57BL/6 mice were subjected to chronic‐plus‐binge ethanol feeding and orally given PBS, control Escherichia coli Nissle 1917 (EcN) or engineered EcN‐Ahr. The effects of EcN and EcN‐Ahr were also examined in mice lacking Ahr in interleukin 22 (Il22)‐producing cells. ResultsThrough the deletion of endogenous genes trpR and tnaA , coupled with over expression of a feedback‐resistant tryptophan biosynthesis operon, EcN‐Ahr were engineered to overproduce tryptophan. Additional engineering allowed conversion of this tryptophan to indoles including indole‐3‐acetic acid and indole‐3‐lactic acid. EcN‐Ahr ameliorated ethanol‐induced liver disease in C57BL/6 mice. EcN‐Ahr upregulated intestinal gene expression of Cyp1a1 , Nrf2 , Il22 , Reg3b , and Reg3g , and increased Il22‐expressing type 3 innate lymphoid cells. In addition, EcN‐Ahr reduced translocation of bacteria to the liver. The beneficial effect of EcN‐Ahr was abrogated in mice lacking Ahr expression in Il22‐producing immune cells. ConclusionsOur findings indicate that tryptophan metabolites locally produced by engineered gut bacteria mitigate liver disease via Ahr‐mediated activation in intestinal immune cells

Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease

Alcohol-associated liver disease is accompanied by intestinal mycobiome dysbiosis, yet the impacts on liver disease are unclear. We demonstrate that Candida albicans-specific T helper 17 (Th17) cells are increased in circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration in mice causes migration of Candida albicans (C. albicans)-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin decreased C. albicans-specific Th17 cells in the liver and reduced ethanol-induced liver disease in mice. Transgenic mice expressing T cell receptors (TCRs) reactive to Candida antigens developed more severe ethanol-induced liver disease than transgene-negative littermates. Adoptively transferring Candida-specific TCR transgenic T cells or polyclonal C. albicans-primed T cells exacerbated ethanol-induced liver disease in wild-type mice. Interleukin-17 (IL-17) receptor A signaling in Kupffer cells was required for the effects of polyclonal C. albicans-primed T cells. Our findings indicate that ethanol increases C. albicans-specific Th17 cells, which contribute to alcohol-associated liver disease

Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease

Alcohol-associated liver disease is accompanied by intestinal mycobiome dysbiosis, yet the impacts on liver disease are unclear. We demonstrate that Candida albicans-specific T helper 17 (Th17) cells are increased in circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration in mice causes migration of Candida albicans (C. albicans)-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin decreased C. albicans-specific Th17 cells in the liver and reduced ethanol-induced liver disease in mice. Transgenic mice expressing T cell receptors (TCRs) reactive to Candida antigens developed more severe ethanol-induced liver disease than transgene-negative littermates. Adoptively transferring Candida-specific TCR transgenic T cells or polyclonal C. albicans-primed T cells exacerbated ethanol-induced liver disease in wild-type mice. Interleukin-17 (IL-17) receptor A signaling in Kupffer cells was required for the effects of polyclonal C. albicans-primed T cells. Our findings indicate that ethanol increases C. albicans-specific Th17 cells, which contribute to alcohol-associated liver disease