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In 2017, four independent publications described the glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as receptor for the growth differentiation factor 15 (GDF15, also MIC-1, NAG-1) with an expression exclusively in the mice brainstem area postrema (AP) and nucleus tractus solitarii (NTS) where it mediates effects of GDF15 on reduction of food intake and body weight. GDF15 is a cell stress cytokine with a widespread expression and pleiotropic effects, which both seem to be in contrast to the reported highly specialized localization of its receptor. This discrepancy prompts us to re-evaluate the expression pattern of GFRAL in the brain and peripheral tissues of mice. In this detailed immunohistochemical study, we provide evidence for a more widespread distribution of this receptor. Apart from the AP/NTS region, GFRAL-immunoreactivity was found in the prefrontal cortex, hippocampus, nucleus arcuatus and peripheral tissues including liver, small intestine, fat, kidney and muscle tissues. This widespread receptor expression, not taken into consideration so far, may explain the multiple effects of GDF-15 that are not yet assigned to GFRAL. Furthermore, our results could be relevant for the development of novel pharmacological therapies for physical and mental disorders related to body image and food intake, such as eating disorders, cachexia and obesity.

Both mitochondrial dysfunction and neuroinflammation are implicated in neurodegeneration and neurodegenerative diseases. Accumulating evidence shows multiple links between mitochondrial dysfunction and neuroinflammation. Mitochondrial-derived damage-associated molecular patterns (DAMPs) are recognized by immune receptors of microglia and aggravate neuroinflammation. On the other hand, inflammatory factors released by activated glial cells trigger an intracellular cascade, which regulates mitochondrial metabolism and function. The crosstalk between mitochondrial dysfunction and neuroinflammatory activation is a complex and dynamic process. There is strong evidence that mitochondrial dysfunction precedes neuroinflammation during the progression of diseases. Thus, an in-depth understanding of the specific molecular mechanisms associated with mitochondrial dysfunction and the progression of neuroinflammation in neurodegenerative diseases may contribute to the identification of new targets for the treatment of diseases. In this review, we describe in detail the DAMPs that induce or aggravate neuroinflammation in neurodegenerative diseases including mtDNA, mitochondrial unfolded protein response (mtUPR), mitochondrial reactive oxygen species (mtROS), adenosine triphosphate (ATP), transcription factor A mitochondria (TFAM), cardiolipin, cytochrome c , mitochondrial Ca 2+ and iron.

Despite annual increases in the incidence and prevalence of neurodegenerative diseases, there is a lack of effective treatment strategies. An increasing number of E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) have been observed to participate in the pathogenesis mechanisms of neurodegenerative diseases, on the basis of which we conducted a systematic literature review of the studies. This review will help to explore promising therapeutic targets from highly dynamic ubiquitination modification processes.

Background NDR1/HIN1-like ( NHL ) genes play crucial roles in Psa resistance. Kiwifruit canker, caused by Pseudomonas syringae pv. Actinidiae (Psa) infection is one of the most serious diseases affecting the kiwifruit industry. However, the key NHL has not yet been identified in kiwifruit. Results In this study, we conducted a genome-wide identification of NHL family in kiwifruit ( Actinidia eriantha ). A total of 33 AeNHLs were divided into five domain-conserved subfamilies, which were mainly assigned into phytohormones and defense responses. The expression of AeNHL genes was analyzed to identify key genes in response to Psa, and we found AeNHL17 was highly expressed upon Psa inoculation. Transgenic tobacco overexpressing AeNHL17 presented higher resistance to Psa than wild-type (WT) tobacco, implying a key role for AeNHL17 in Psa resistance. Finally, we carried out a stable genetic transformation of kiwifruit ( A. chinensis ), which is sensitive to Psa, and found that the overexpression of AeNHL17 increased resistance to infection. AeNHL17 -silenced plants exhibited larger disease lesions than control plants. Conclusions Our findings revealed the function of AaNHL17 in Psa resistance, providing new data regarding the functional analysis of the NHL gene family in kiwifruit.

Kiwifruit bacterial canker, caused by the bacterial pathogen Pseudomonas syringae pv. actinidiae (Psa), is a destructive disease in the kiwifruit industry globally. Consequently, understanding the mechanism of defense against pathogens in kiwifruit could facilitate the development of effective novel protection strategies. The Non-expressor of Pathogenesis-Related genes 1 ( NPR1 ) is a critical component of the salicylic acid (SA)-dependent signaling pathway. Here, a novel kiwifruit NPR1 -like gene, designated AeNPR1a , was isolated by using PCR and rapid amplification of cDNA ends techniques. The full-length cDNA consisted of 1952 base pairs with a 1,746-bp open-reading frame encoding a 582 amino acid protein. Homology analysis showed that the AeNPR1a protein is significantly similar to the VvNPR1 of grape. A 2.0 Kb 5′-flanking region of AeNPR1a was isolated, and sequence identification revealed the presence of several putative cis-regulatory elements, including basic elements, defense and stress response elements, and binding sites for WRKY transcription factors. Real-time quantitative PCR results demonstrated that AeNPR1a had different expression patterns in various tissues, and its transcription could be induced by phytohormone treatment and Psa inoculation. The yeast two-hybrid assay revealed that AeNPR1a interacts with AeTGA2. Constitutive expression of AeNPR1a induced the expression of pathogenesis-related gene in transgenic tobacco plants and enhanced tolerance to bacterial pathogens. In addition, AeNPR1a expression could restore basal resistance to Pseudomonas syringae pv. tomato DC3000 (Pst) in Arabidopsis npr1-1 mutant. Our data suggest that AeNPR1a gene is likely to play a pivotal role in defense responses in kiwifruit.

infection represents a prevalent global health burden. Current eradication strategies are complicated by increasing antibiotic resistance and detrimental alterations to the gut microbiome. Jinghuaweikang capsule (JWC), a traditional Chinese medicine, has demonstrated efficacy against , yet its mechanisms involving microbiota-inflammation interactions remain incompletely elucidated. This study aimed to investigate the effects of the JWC on gastric mucosal inflammation and the expression of drug-resistance genes in -infected mice. Sixty Kunming mice were randomly allocated into six groups, including normal control group (Control), model group (Model), Western medicine triple group (AC), low-dose JWC group (JWCL), medium-dose JWC group (JWCM), and high-dose JWC group (JWCH). A mouse model of infection was established by intragastric administration of an SS1 solution for two weeks. The efficacy of this model was evaluated using rapid urease test (RUT) and Warthin-Starry (WS) silver stain. Subsequently, the experimental cohort of mice underwent pharmacological intervention. Hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess the impact of JWC on inflammation within the gastric mucosa of mice infected with . Metagenomic sequencing technology was used to identify alterations in the intestinal microbiota and antibiotic resistance genes in the murine models. Western blotting was used to assess the expression levels of proteins involved in the mitogen-activated protein kinase (MAPK) signaling pathway. JWC mitigated gastric mucosal inflammation induced by infection and reduced the concentrations of interleukin- (IL-) 6, IL-1β, and tumor necrosis factor-α (TNF-α) while inhibiting gene expression level. Metagenomic sequencing revealed that triple therapy in Western medicine markedly diminished the diversity of the intestinal microbiota while elevating the abundance of antibiotic-resistance genes, including , , , , and . The diversity and richness of the intestinal microbiota in the JWC group were comparable to those in the control group, with an increase in the abundance of beneficial bacteria such as . Furthermore, the expression levels of the antibiotic resistance genes , , , , were downregulated. Moreover, the activation of MAPK signaling pathway components phospho-ERK and phospho-p38 was inhibited. JWC preserves microbial diversity and promotes a beneficial compositional shift, mitigates the risk of antibiotic resistance, modulates the MAPK signaling pathway, and alleviates gastric mucosal inflammation in mice infected with .

The mitochondrial enzyme glutaminase (GLS) is frequently up-regulated during tumorigenesis and is being evaluated as a target for cancer therapy. GLS catalyzes the hydrolysis of glutamine to glutamate, which then supplies diverse metabolic pathways with carbon and/or nitrogen. Here, we report that SIRT5, a mitochondrial NAD⁺-dependent lysine deacylase, plays a key role in stabilizing GLS. In transformed cells, SIRT5 regulates glutamine metabolism by desuccinylating GLS and thereby protecting it from ubiquitin-mediated degradation. Moreover, we show that SIRT5 is up-regulated during cellular transformation and supports proliferation and tumorigenesis. Elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis. These findings reveal a mechanism for increasing GLS expression in cancer cells and establish a role for SIRT5 in metabolic reprogramming and mammary tumorigenesis.

In moiré crystals formed by stacking van der Waals materials, surprisingly diverse correlated electronic phases and optical properties can be realized by a subtle change in the twist angle. Here, we discover that phonon spectra are also renormalized in MoS 2 twisted bilayers, adding an insight to moiré physics. Over a range of small twist angles, the phonon spectra evolve rapidly owing to ultra-strong coupling between different phonon modes and atomic reconstructions of the moiré pattern. We develop a low-energy continuum model for phonons that overcomes the outstanding challenge of calculating the properties of large moiré supercells and successfully captures the essential experimental observations. Remarkably, simple optical spectroscopy experiments can provide information on strain and lattice distortions in moiré crystals with nanometre-size supercells. The model promotes a comprehensive and unified understanding of the structural, optical and electronic properties of moiré superlattices. Raman measurements of twisted bilayer MoS 2 as a function of twist angles, with theoretical support, reveal phonon renormalization in this moiré superlattice.

Lung cancer is one of the leading causes of cancer-related death worldwide. Various therapeutic failed in the effective treatment of the lung cancer due to their limited accumulation and exposure in tumors. In order to promote the chemotherapeutics delivery to lung tumor, we introduced chitosan oligosaccharide (CSO) modification on the liposomes. CSO conjugated Pluronic P123 polymers with different CSO grafting amounts, called as CP50 and CP20, were synthesized and used to prepare CSO modified liposomes (CP50-LSs and CP20-LSs). CP50-LSs and CP20-LSs displayed significantly enhanced cellular uptake in A549 cells in vitro as well as superior tumor accumulation in vivo compared with non-CSO modified liposomes (P-LSs). This phenomenon was related to the increased affinity between CSO modified liposomes and tumor cells following massive adsorption of collagen, which was highly expressed in lung tumors. In the A549 tumor-bearing mouse model, intravenous injection of paclitaxel (PTX)-loaded CP50-LSs every 3 days for 21 days resulted in optimal antitumor therapeutic performance with an inhibition rate of 86.4%. These results reveal that CSO modification provides promising applicability for nanomedicine design in the lung cancer treatment.

Improving the life service for the elderly is a topic of great concern to the government and society. This paper explores the influence of net attention on social work service satisfaction of the elderly. This paper studies and analyzes the current situation of the elderly’s net attention and social satisfaction, constructs the index system of social service satisfaction through the sample data of 17 districts and counties in A province, and establishes a multilayer linear model to analyze the influencing factors of social service satisfaction, and empirically analyzes the feasibility of the proposed model’s rationality and effectiveness. The structure shows that the scores of elderly people’s satisfaction with public services in all regions of A province are higher than 60 points, and the biggest difference of standard deviation of each region is 3.91 points. Public service expenditure has a negative effect on social service satisfaction, but population density, geographical location, and per capita GDP have no obvious effect. The regression coefficient of public service expenditure is -0.099134, which can reduce the score of social service satisfaction. Elderly participation in public welfare activities, elderly awareness of government, and elderly participation in government can improve the social service satisfaction score.