The gasdermin (GSDM) protein family plays a pivotal role in pyroptosis, a process critical to the body's immune response, particularly in combatting bacterial infections, impeding tumor invasion, and ...contributing to the pathogenesis of various inflammatory diseases. These proteins are adept at activating inflammasome signaling pathways, recruiting immune effector cells, creating an inflammatory immune microenvironment, and initiating pyroptosis. This article serves as an introduction to the GSDM protein-mediated pyroptosis signaling pathways, providing an overview of GSDMs' involvement in tumor immunity. Additionally, we explore the potential applications of GSDMs in both innovative and established antitumor strategies.
Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify ...effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.
Whether and how the uncertainty about a public health crisis should be communicated to the general public have been important and yet unanswered questions arising over the past few years. As the most ...threatening contemporary public health crisis, the COVID-19 pandemic has renewed interest in these unresolved issues by both academic scholars and public health practitioners.
The aim of this study was to investigate the impact of communicating uncertainty about COVID-19-related threats and solutions on individuals' risk perceptions and misinformation vulnerability, as well as the sequential impact of these effects on health information processing and preventative behavioral intentions.
A 2×2 (threat uncertainty presence vs absence×solution uncertainty presence vs absence) full-fractional between-subjects online experiment was conducted with 371 Chinese adults. Focusing on the discussion of whether the asymptomatic cases detected during the COVID-19 pandemic would further lead to an uncontrolled pandemic, news articles were manipulated in terms of whether the infectiousness of asymptomatic cases and the means to control the transmission are presented in terms of their certainty or uncertainty. Participants were randomly assigned to one of the four experimental conditions, being instructed to read one news article. After reading the news article assigned, participants were asked to respond to a series of questions to assess their cognitive and behavioral responses.
Individuals were more susceptible to believing false COVID-19-related information when a certain threat and uncertain solution were framed in the news article. Moreover, individuals' perceptions of crisis severity increased when exposed to news information containing uncertain solutions. Both misinformation vulnerability and perceived severity were positively associated with information processing. Information seeking was positively associated with protective behavioral intention, whereas information avoidance was negatively associated with protective behavioral intention.
Our findings imply that uncertainty, depending on its aspect, can be effectively communicated to the public during an emerging public health crisis. These results have theoretical and practical implications for health communicators and journalists. Given its limited influence on individuals' cognitive and behavioral responses, uncertainty related to a health threat should be disseminated to meet the public's expectation of information transparency. However, caution is advised when communicating uncertainty related to potential solutions, as this factor exhibited a mixed impact on individual responses during a crisis.
Alzheimer's disease (AD), as one of most common dementia, mainly affects older people from the worldwide. In this study, we intended to explore the possible mechanism of improving cognitive function ...and protecting the neuron effect by electroacupuncture.
We applied senescence-accelerated mouse prone 8 (SAMP8) mice as AD animal model, used Morris water maze, HE staining, 16S rDNA amplicon sequencing of gut microbiota and ELISA to demonstrate our hypothesis.
electroacupuncture improved the learning and memory abilities in SAMP8 mice (P<0.05) and could protect the frontal lobe cortex and hippocampus of SAMP8 mice; electroacupuncture significantly decreased the expression of IL-1β (P<0.01), IL-6 (P<0.01) and TNF-α (P<0.01 in hippocampus, P<0.05 in serum) in serum and hippocampus; electroacupuncture balanced the quantity and composition of gut microbiome, especially of the relative abundance in Delta-proteobacteria (P<0.05) and Epsilon-proteobacteria (P<0.05).
electroacupuncture treatment could inhibit the peripheral and central nerve system inflammatory response by balancing the gut microbiota.
Hippo signaling is a tumor-suppressor pathway involved in organ size control and tumorigenesis through the inhibition of YAP and TAZ. Here, we show that energy stress induces YAP cytoplasmic ...retention and S127 phosphorylation and inhibits YAP transcriptional activity and YAP-dependent transformation. These effects require the central metabolic sensor AMP-activated protein kinase (AMPK) and the upstream Hippo pathway components Lats1/Lats2 and angiomotin-like 1 (AMOTL1). Furthermore, we show that AMPK directly phosphorylates S793 of AMOTL1. AMPK activation stabilizes and increases AMOTL1 steady-state protein levels, contributing to YAP inhibition. The phosphorylation-deficient S793Ala mutant of AMOTL1 showed a shorter half-life and conferred resistance to energy-stress-induced YAP inhibition. Our findings link energy sensing to the Hippo-YAP pathway and suggest that YAP may integrate spatial (contact inhibition), mechanical, and metabolic signals to control cellular proliferation and survival.
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•Energy stress inhibits YAP•AMPK is required to mediate the effects•AMPK directly phosphorylates AMOTL1, an upstream inhibitor of YAP, at S793•AMOTL1 S793 phosphorylation affects its stability
DeRan et al. discovered that cellular energy level is an upstream regulator of Hippo-YAP pathway. Energy stress, such as inhibition of glucose metabolism and ATP production, could inhibit YAP activity. This process requires the central metabolic sensor AMPK, which directly phosphorylates and stabilizes AMOTL1, an upstream regulator of YAP.
DNA replication-coupled nucleosome assembly is essential to maintain genome integrity and retain epigenetic information. Multiple involved histone chaperones have been identified, but how nucleosome ...assembly is coupled to DNA replication remains elusive. Here we show that replication protein A (RPA), an essential replisome component that binds single-stranded DNA, has a role in replication-coupled nucleosome assembly. RPA directly binds free H3-H4. Assays using a synthetic sequence that mimics freshly unwound single-stranded DNA at replication fork showed that RPA promotes DNA-(H3-H4) complex formation immediately adjacent to double-stranded DNA. Further, an RPA mutant defective in H3-H4 binding exhibited attenuated nucleosome assembly on nascent chromatin. Thus, we propose that RPA functions as a platform for targeting histone deposition to replication fork, through which RPA couples nucleosome assembly with ongoing DNA replication.
Nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) gene variants are associated with a range of phenotypes, including epilepsy, intellectual disability, cerebellar ataxia, Parkinson's disease, ...dystonia, and congenital disorders of glycosylation. Additionally, cases describing genotypes and clinical features are rare.
Herein, we report the case of a 23-year-old Chinese female patient who presented with tremors, intellectual disability, and epilepsy. A history of carbon monoxide exposure, brain trauma, or encephalitis was not present in this case. Trio whole-exome sequencing analysis revealed a
pathogenic variant of c.750del in exon 4, leading to p.Leu251* amino acid substitution. Genetic analysis failed to identify the identical mutations in the remaining family members who underwent screening. The patient was diagnosed with a rare congenital disease, "congenital glycosylation disorder, type 1aa, autosomal dominant, type 55, with seizures (MRD-55)."
We provide further evidence for the role of variants in
in the development of tremors, epilepsy, and intellectual disabilities. These findings expand our understanding of the clinical phenotypes of
variants.
High-proportion pellet smelting is the direction of optimization of blast furnace burden structures in the future. In this paper, the effect of SiO2 content on the softening and dropping properties ...of magnesia flux pellets was studied. And the influence of SiO2 content on the mineralogical composition and microstructure of magnesia flux pellets was analyzed, which clarified the reason for the air permeability of the middle and lower columns of magnesia flux pellets becoming poor during smelting. The results show that with increasing SiO2 content, the T10 (softening start temperature) and TS (melting start temperature) of the column gradually decrease, and the melting range increases; in particular, T10 and Ts decrease dramatically when the SiO2 content exceeds 6%. The maximum pressure difference increases from 15.0 kPa to 20.7 kPa, and the characteristic value increases from 644.8 kPa·°C to 1334.8 kPa·°C when the SiO2 content of magnesia flux pellets increases from 6% to 8%. The mineralogical composition difference between low-silica magnesia flux pellets (SiO2=3.5%) and high-silica magnesia flux pellets (SiO2=7.0%) at different temperatures is caused by a large amount of unreacted SiO2 in high-silica magnesia flux pellets. SiO2 and silicate produce a large amount of liquid phase at low temperature, which reduces TS. In addition, the dropping temperature of high-silica magnesia flux pellets is higher than that of low-silica magnesia flux pellets. It’s due to the existence of particulate SiO2 in the primary slag, which causes the slag to become sticky and makes it difficult to separate the slag from iron.
The measurement of pressure is one of the most important functions of the artificial skin. In general, most of the pressure is not only coupled with the vertical normal interfacial stress ...(Z-direction) but also the parallel shear interfacial stress (Xand V-direction). It is very important to develop a sensor to measure the 3-D interfacial stress. This paper presents a 3-D interfacial stress sensor based on graphene foams and superelastic materials. A data-fitted measurement model is constructed to calculate the 3-D interfacial stress. The sensor is measured by utilizing a resistive measurement circuit, and experiments are performed with a 3-D stress simulation system. Results show that the fabricated sensor is capable of measuring the normal stress at a range of 0-50 kPa with a sensitivity of 0.0270 kPa -1 and the shear stress at a range of 0-25 kPa with a sensitivity of 0.0169 kPa -1 . The response time of the sensor is 80 ms, which is less than the human response time. By taking advantage of the graphene foam, our sensor has a high sensitivity, good stability, and has potential application in the fields of artificial skin, intelligent robot, wearable electronics, and prosthetics.
Transforming growth factor-beta (TGF-beta) functions as a tumor suppressor of the prostate through mechanisms that remain unresolved. Although TGF-beta receptors directly activate both Smads 2 and 3, ...to date, Smad3 has been shown to be the essential mediator of most Smad-dependent TGF-beta responses, including control of gene expression, cell growth, apoptosis, and tumor suppression. Using a robust lentiviral short hairpin RNA system to silence Smads 2 and/or 3 in the NRP-152 nontumorigenic rat prostate basal epithelial cell line, we provide the first evidence for Smad2 as a critical mediator of TGF-beta-induced apoptosis and gene expression. Parallel analyses revealed that Smad3 is the major mediator of TGF-beta-induced transcriptional and apoptotic responses in the NRP-154 rat prostate carcinoma cell line. Remarkably, silencing Smad2 alone caused malignant transformation of NRP-152 cells, as assayed by s.c. tumor growth in athymic mice, whereas silencing Smad3 alone did not induce tumors. Nevertheless, tumors induced by silencing both Smads 2 and 3 were larger than those from silencing Smad2 alone. Given previous reports that NRP-152 cells have a stem cell phenotype, we speculate a critical role for Smad2 as a tumor suppressor in the basal epithelial or stem cell compartment of the prostate.
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