Ferroptosis, a novel form of regulated cell death, is different from other types of cell death in morphology, genetics and biochemistry. Increasing evidence indicates that ferroptosis has significant ...implications on cell death linked to cardiomyopathy, tumorigenesis, and cerebral hemorrhage to name a few. Here we summarize current literature on ferroptosis, including organelle dysfunction, signaling transduction pathways, metabolic reprogramming and epigenetic regulators in cancer progression. With regard to organelles, mitochondria-induced cysteine starvation, endoplasmic reticulum-related oxidative stress, lysosome dysfunction and golgi stress-related lipid peroxidation all contribute to induction of ferroptosis. Understanding the underlying mechanism in ferroptosis could provide insight into the treatment of various intractable diseases including cancers.
In China, despite the traumatic collective memory relating to militaristic Japan during World War II, an increasing number of Chinese young adults have developed an obsession with Japanese culture, ...due to its export of anime, movies, pop music, and other popular culture. Based on interviews with 40 Chinese and Japanese young adults, this work examines how contemporary pop culture and historical war memories related to Japan influenced Chinese young adults, who had to reconcile their contradictory sentiments toward the Japanese government, people, and culture. The success of Japanese pop culture in China also shows how the allegedly apolitical, virtual sphere of entertainment has helped build Japan's soft power through shaping a cool image of Japan in Asia and worldwide.
Abstract
WEGO (Web Gene Ontology Annotation Plot), created in 2006, is a simple but useful tool for visualizing, comparing and plotting GO (Gene Ontology) annotation results. Owing largely to the ...rapid development of high-throughput sequencing and the increasing acceptance of GO, WEGO has benefitted from outstanding performance regarding the number of users and citations in recent years, which motivated us to update to version 2.0. WEGO uses the GO annotation results as input. Based on GO's standardized DAG (Directed Acyclic Graph) structured vocabulary system, the number of genes corresponding to each GO ID is calculated and shown in a graphical format. WEGO 2.0 updates have targeted four aspects, aiming to provide a more efficient and up-to-date approach for comparative genomic analyses. First, the number of input files, previously limited to three, is now unlimited, allowing WEGO to analyze multiple datasets. Also added in this version are the reference datasets of nine model species that can be adopted as baselines in genomic comparative analyses. Furthermore, in the analyzing processes each Chi-square test is carried out for multiple datasets instead of every two samples. At last, WEGO 2.0 provides an additional output graph along with the traditional WEGO histogram, displaying the sorted P-values of GO terms and indicating their significant differences. At the same time, WEGO 2.0 features an entirely new user interface. WEGO is available for free at http://wego.genomics.org.cn.
Cloud properties over the Tibetan Plateau (TP) and their underlying dynamics play a crucial role in the energy balance and regional water cycle of the climate system. In this review, we assess the ...progress in observational methods and model simulations of cloud macro- and micro-physical properties over the TP since the 1960s. We summarize the spatiotemporal patterns of cloud distribution and the main drivers, discussing the difficulties posed by cloud dynamics and their feedback into climate change on the TP. In short, we found that while the TP is warming and wetting, total cloud cover has decreased over the TP from 1960 to 2021 and from the southeast to the northwest, which typically exhibits the largest proportion of high cloud cover (HCC) and mid-high cloud cover. Meteorological elements (such as air temperature, precipitation), topography, and atmospheric circulation are the main factors influencing cloud formation. During the warm season (May–October), the intensification and northward shift of the South–Asian High and the South Asian monsoon lead to an uneven distribution of precipitation over the TP, while the Indian monsoon promotes the formation of low cloud cover. During the cold season (November–April), the northward expansion of the Hadley circulation inhibits the formation of HCC and middle cloud cover. The amount of cloud cover also affects climatic warming on the TP by radiative forcing. We end the review with a discussion of future research challenges, and propose to focus on improving the accuracy of model parameterizations to facilitate a deeper understanding of the effects of climate change on the TP and the associated water cycle processes.
•Corrosion behavior of tin under UV illumination was investigated for the first time.•Photo-inhibition of corrosion was observed on tin, while photo-enhanced pitting corrosion was found on ...copper.•The structure and stability of the oxide film appeared to be crucial in the corrosion of metals under irradiation.•Photostability of the oxide film was found to decrease in the presence of chloride anions.
Corrosion behaviors of copper and tin in chloride-containing borate buffer solutions (pH 8.4) were investigated through electrochemical and spectroscopic techniques in the presence and absence of UV illumination. Concerning effects of UV light on the corrosion processes, in a borate buffer solution containing 0.025 M NaCl, photo-enhanced pitting corrosion was observed on copper while photo-induced passivation was found on tin. The effect of UV illumination on corrosion was dependent on the interaction between the photo-generated carriers and the metal oxides, as well as the photostability of the oxide film. Chloride anions can decrease the photostability of the oxide film.
The NLRP3 inflammasome is critical for EAE pathogenesis; however, the role of gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome, in EAE has not been well ...defined. Here, we observed that the levels of GSDMD protein were greatly enhanced in the CNS of EAE mice, especially near the areas surrounding blood vessels. GSDMD was required for the pathogenesis of EAE, and GSDMD deficiency in peripheral myeloid cells impaired the infiltration of immune cells into the CNS, leading to the suppression of neuroinflammation and demyelination. Furthermore, the loss of GSDMD reduced the activation and differentiation of T cell in the secondary lymphoid organs and prevented T cell infiltration into CNS of EAE. The administration of inflammasome-related cytokines partially rescued the impairment of pathogenesis of EAE in GSDMD KO mice. Collectively, these findings provide the first demonstration of GSDMD in peripheral myeloid cells driving neuroinflammation during EAE pathogenesis.
The role of the PYHIN family member absent in melanoma 2 (AIM2), another important inflammasome sensor, in EAE remains unclear. In this study, we found that AIM2 negatively regulates the pathogenesis ...of EAE independent of inflammasome activation. AIM2 deficiency enhanced microglia activation and infiltration of peripheral immune cells into the CNS, thereby promoting neuroinflammation and demyelination during EAE. Mechanistically, AIM2 negatively regulates the DNA-PK-AKT3 in microglia to control neuroinflammation synergistically induced by cGAS and DNA-PK. Administration of a DNA-PK inhibitor reduced the severity of the EAE. Collectively, these findings identify a new role for AIM2 in controlling the onset of EAE. Furthermore, delineation of the underlying inflammasome-independent mechanism highlights cGAS and DNA-PK signaling as potential targets for the treatment of heterogeneous MS.
Synthetic framework materials have been cherished as appealing candidates for separation membranes in daily life and industry, while the challenges still remain in precise control of aperture ...distribution and separation threshold, mild processing methods, and extensive application aspects. Here, we show a two-dimensional (2D) processible supramolecular framework (SF) by integrating directional organic host-guest motifs and inorganic functional polyanionic clusters. The thickness and flexibility of the obtained 2D SFs are tuned by the solvent modulation to the interlayer interactions, and the optimized SFs with limited layers but micron-sized areas are used to fabricate the sustainable membranes. The uniform nanopores allow the membrane composed of layered SF to exhibit strict size retention for substrates with the rejection value of 3.8 nm, and the separation accuracy within 5 kDa for proteins. Furthermore, the membrane performs high charge selectivity for charged organics, nanoparticles, and proteins, due to the insertion of polyanionic clusters in the framework skeletons. This work displays the extensional separation potentials of self-assembled framework membranes comprising of small-molecules and provides a platform for the preparation of multifunctional framework materials due to the conveniently ionic exchange of the counterions of the polyanionic clusters.
We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending ...the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high‐fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high‐fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n‐6/n‐3 ratio but significantly increased the n‐3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF‐κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.
This study investigates the effects and mechanisms of a high dose of epigallocatechin gallate (EGCG) in extending the lifespan of obese rats. We find that EGCG improved serum glucose, lipids, inflammation, oxidative stress associated with ageing in obese rats induced by a high‐fat diet, total free fatty acids (FFAs), transcriptome, and proteome. The results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.
Although pain is a prevalent nonmotor symptom in Parkinson’s disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ...ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that the STN might play a critical role in parkinsonian pain hypersensitivity. To test this hypothesis, we established a unilateral parkinsonian mouse model with moderate lesions of dopaminergic neurons in the substantia nigra. The mice displayed pain hypersensitivity and neuronal hyperactivity in the ipsilesional STN and in central pain-processing nuclei. Optogenetic inhibition of STN neurons reversed pain hypersensitivity phenotypes in parkinsonian mice, while hyperactivity in the STN was sufficient to induce pain hypersensitivity in control mice. We further demonstrated that the STN differentially regulates thermal and mechanical pain thresholds through its projections to the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi)/ventral pallidum (VP), respectively. Interestingly, optogenetic inhibition of STN-GPi/STN-VP and STN-SNr projections differentially elevated mechanical and thermal pain thresholds in parkinsonian mice. In summary, our results support the hypothesis that the STN and its divergent projections play critical roles in modulating pain processing under both physiological and parkinsonian conditions, and suggest that inhibition of individual STN projections may be a therapeutic strategy to relieve distinct pain phenotypes in PD.
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