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Cuproptosis is a novel type of copper-induced cell death that primarily occurs in cells that utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with the lipoylated proteins of the tricarboxylic acid cycle, leading to the disulfide-bond-dependent aggregation of these lipoylated proteins, destabilization of the iron-sulfur cluster proteins, and consequent proteotoxic stress. Cancer cells prefer glycolysis (Warburg effect) to oxidative phosphorylation for producing intermediate metabolites and energy, thereby achieving resistance to cuproptosis. Interestingly, the tumor suppressor p53 is a crucial metabolic regulator that inhibits glycolysis and drives a metabolic switch towards oxidative phosphorylation in cancer cells. Additionally, p53 regulates the biogenesis of iron-sulfur clusters and the copper chelator glutathione, which are two critical components of the cuproptotic pathway, suggesting that this tumor suppressor might play a role in cuproptosis. Furthermore, the possible roles of mutant p53 in regulating cuproptosis are discussed. In this essay, we review the recent progress in the understanding of the mechanism underlying cuproptosis, revisit the roles of p53 in metabolic regulation and iron-sulfur cluster and glutathione biosynthesis, and propose several potential mechanisms for wild-type and mutant p53-mediated cuproptosis regulation.

This review introduces low-density lipoprotein (LDL) delivery systems, summarizes the research status and progress in targeted diagnosis and therapy, and looks forward to the clinical application of LDL as an effective delivery vehicle.

Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular processes, including development and stress response. Many lincRNAs have been bioinformatically identified in plants, but their evolutionary dynamics and expression characteristics are still elusive. Here, we systematically identified thousands of lincRNAs in 26 plant species, including 6 non-flowering plants, investigated the conservation of the identified lincRNAs in different levels of plant lineages based on sequence and/or synteny homology and explored characteristics of the conserved lincRNAs during plant evolution and their co-expression relationship with protein-coding genes (PCGs). In addition to confirmation of the features well documented in literature for lincRNAs, such as species-specific, fewer exons, tissue-specific expression patterns and less abundantly expressed, we revealed that histone modification signals and/or binding sites of transcription factors were enriched in the conserved lincRNAs, implying their biological functionalities, as demonstrated by identifying conserved lincRNAs related to flower development in both the Brassicaceae and grass families and ancient lincRNAs potentially functioning in meristem development of non-flowering plants. Compared to PCGs, lincRNAs are more likely to be associated with transposable elements (TEs), but with different characteristics in different evolutionary lineages, for instance, the types of TEs and the variable level of association in lincRNAs with different conservativeness. Together, these results provide a comprehensive view on the evolutionary landscape of plant lincRNAs and shed new insights on the conservation and functionality of plant lincRNAs.

Post-operative bleeding after total knee arthroplasty (TKA) is a frequent cause of post-operative complications. This study compared blood loss and indicators of coagulation and fibrinolysis between TKA patients living at low or high altitudes.We retrospectively analyzed 120 patients at our institution who underwent primary TKA from May 2019 to March 2020, and we divided them into those living in areas about 500 m or 3000 m above sea level. We compared the primary outcome of total blood loss between them. We also compared them in terms of several secondary outcomes: coagulation and fibrinolysis parameters, platelet count, reduction in hemoglobin, hidden blood loss, intra-operative blood loss, transfusion rate, and incidence of thromboembolic events and other complications.Total blood loss was significantly higher in the high-altitude group than in the low-altitude group (mean, 748.2 mL [95% CI, 658.5-837.9] vs 556.6 mL [95% CI, 496.0-617.1]; p = 0.001). The high-altitude group also showed significantly longer activated partial thromboplastin time, prothrombin time, and thrombin time before surgery and on post-operative day one, as well as increased levels of fibrinogen/fibrin degradation product on post-operative days one and three. Ecchymosis was significantly more frequent in the high-altitude group (41.7 vs 21.7%; relative risk (RR) = 1.923 [95% CI, 1.091-3.389]; p = 0.019). The two groups showed similar transfusion rates, and none of the patients experienced venous thromboembolism, pulmonary embolism, or infection.High altitude may alter coagulation and fibrinolysis parameters in a way that increases risk of blood loss after TKA. Such patients may benefit from special management to avoid bleeding events.

High-fluoride (F) pollution is an environmental problem that severely affects the growth of human beings, animals and plants. High-fluoride groundwater severely harms the health of Shanxi residents and leads to frequent endemic diseases. This study aims to analyze the differences and possible health risks of fluoride among six basins in Shanxi Province, North China, using 338 groundwater samples collected from wells, infer the main sources of fluoride in the groundwater, and provide valuable suggestions for fluoride contamination in regional groundwater. The results revealed that F in the Yuncheng basin had the highest health risk. In addition to the Changzhi basin, the groundwater at the sampling points in other basins had adverse effects on human health. The main source of fluoride in groundwater is the dissolution of fluoride-containing minerals, which has little to do with human activities. The groundwater in Shanxi Province tends to be alkaline, and the fluorite saturation index is less than 0 in most circumstances, indicating that fluorite is in an unsaturated state, and fluoride will continue to dissolve into groundwater under suitable conditions. Clustering analysis shows that the high-fluoride areas are mainly distributed in the Yuncheng basin and the southern part of the Xinzhou basin. Fluoride-rich groundwater in a basin often exists only in a certain area, and the distribution of confined water and unconfined water in high-fluoride areas is different. Fluoride contamination in the Changzhi basin is not severe. For the high-fluoride areas in the Datong basin, Xinzhou basin, Taiyuan basin and Linfen basin, utilizing water from other areas or exploiting groundwater from other aquifers to diminish the harm of high-fluoride groundwater intake for a long period is suggested. For the Yuncheng basin, adopting membrane-based processes or variable temperature drop fluoride technology to make groundwater contaminated by excessive fluoride potable is recommended.

Abstract: The first complete chloroplast genome of rice (Oryza sativa) was published in 1989, ushering in a new era of studies of chloroplast genomics in Poaceae. Progresses in Next-Generation Sequencing (NGS) and Third-Generation Sequencing (TGS) technologiesand in the development of genome assembly software, have significantly advanced chloroplast genomics research. Poaceae is one of the most targeted families in chloroplast genome research because of its agricultural, ecological, and economic importance. Over the last 30 years, 2,050 complete chloroplast genome sequences from 40 tribes and 282 genera have been generated, most (97%) of them in the recent ten years. The wealth of data provides the groundwork for studies on species evolution, phylogeny, genetic transformation, and other aspects of Poaceae chloroplast genomes. As a result, we have gained a deeper understanding of the properties of Poaceae chloroplast genomes. Here, we summarize the achievements of the studies of the Poaceae chloroplast genomes and envision the challenges for moving the area ahead.

Xishuangbanna (XIS) cucumber (Cucumis sativus L. var. xishuangbannanesis) is a semiwild variety originated from low latitude tropic area, and therefore show extreme cold sensitivity and heat tolerance. Here, we mapped the quantitative trait loci (QTLs) that control cold-sensitivity and heat-tolerance of XIS cucumber seedlings. By bulked-segregant analysis (BSA), we identified three QTLs (HTT1.1, HTT3.1 and HTT3.2, in a total length of 11.98 Mb) for heat tolerance and two QTLs (LTT6.1 and LTT6.2, in a total length of 8.74 Mb) for cold sensitivity. The QTL LTT6.1 was then narrowed down to a length of 641 kb. Based on structural variants (SVs) and single nucleotide polymorphism (SNP), we found the LTT6.1 is covered by a high divergent region including a 50-kb deletion in XIS49 genome, which affect the gene structure of lipase ABHD6 (Csa_6G032560). Accordingly, there is a very big difference in lipid composition but not other osmoprotectants like free amino acids and fatty acids between XIS49 and cultivated cucumber CL. Moreover, we calculated the composite likelihood ratio (CLR) and identified selective sweeps from 115 resequencing data, and found that lipid- and fatty acid-related processes is a major aspect of the domestication of XIS group cucumber. LTT6.1 is such a special region positioned nearby lipid-related selective sweeps. These studies above suggested that lipids-related domestication of XIS cucumbers should account for their extreme cold sensitivity.

Forest cover significantly affects the global carbon cycle, biodiversity, and human welfare, but is seriously threatened by human activities. Here we found that anthropogenic forces did not necessarily lead to forest cover decline in the marginal agricultural region of northern China based on a quantitative reconstruction of 12,000-years forest cover changes using modern analog technique and random forest. The forest cover was strongly affected by human activities in the core agricultural region, as indicated by the high independent effects of archeological sites (38.3%) and burning area (42.3%). In contrast, climate impacted the forest cover in the marginal agricultural region, where the annual precipitation and summer mean temperature contributed 52.4% and 27.4%, respectively. Agricultural development in the marginal agricultural region likely occurred in the river valley or sunny slopes, not overlapping with zonal forests growing on shady slopes. This study implies much less afforestation potential than previously expected in the marginal agricultural region.

Wang et al suppl infor

Supplementary Table S2 shows antibodies used for Western blotting.

Supplementary Table S1 shows the sequences of siRNAs and the targeting sequences of high scored sgRNAs for CRISPR/Cas9.

Approximately 80% of human pancreatic ductal adenocarcinomas (PDAC) harbor TP53 mutations, among which, R273H is the most frequent. Although p53-R273H is known to possess gain-of-function properties, how it is regulated in PDAC has not been extensively explored. Here we identify valosin-containing protein (VCP) as a regulator of p53-R273H by conducting immunoprecipitation-tandem mass spectrometry analysis. VCP bound p53-R273H at its DNA binding domain. Ectopic or endogenous VCP stabilized p53-R273H by binding to MDM2 and disrupting its association with mutant p53. Inhibition of VCP either by genetic depletion or the pharmacologic inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. Consistently, ablation of VCP markedly retarded growth of cultured PDAC cells and xenograft PDAC tumors. Together, these results unveil VCP as a novel partner of p53-R273H in promoting PDAC growth and as a potential target for developing anti-PDAC therapy.Significance:These findings identify valosin-containing protein (VCP) as a novel regulator of p53-R273H stability and suggest VCP as a potential target for development of pancreatic cancer therapy.

Insertions and deletions (indels) are low-frequency deleterious genomic DNA alterations. Despite their rarity, indels are common, and insertions leading to long complementarity-determining region 3 (CDR3) are vital for antigen-binding functions in broadly neutralizing and polyreactive antibodies targeting viruses. Because of challenges in detecting indels, the mechanism that generates indels during immunoglobulin diversification processes remains poorly understood. We carried out ultra-deep profiling of indels and systematically dissected the underlying mechanisms using passenger-immunoglobulin mouse models. We found that activation-induced cytidine deaminase–dependent ±1–base pair (bp) indels are the most prevalent indel events, biasing deleterious outcomes, whereas longer in-frame indels, especially insertions that can extend the CDR3 length, are rare outcomes. The ±1-bp indels are channeled by base excision repair, but longer indels require additional DNA-processing factors. Ectopic expression of a DNA exonuclease or perturbation of the balance of DNA polymerases can increase the frequency of longer indels, thus paving the way for models that can generate antibodies with long CDR3. Our study reveals the mechanisms that generate beneficial and deleterious indels during the process of antibody somatic hypermutation and has implications in understanding the detrimental genomic alterations in various conditions, including tumorigenesis.

Supplementary Table S3 shows protein peptides identified by LC-MS/MS after IP.

Background Lung cancer is the leading cause of cancer-related death. Lysosomes are key degradative compartments that maintain protein homeostasis. In current study, we aimed to construct an lysosomes-related genes signature to predict the overall survival (OS) of patients with Lung Adenocarcinoma (LUAD). Results An eight prognostic genes (ACAP3, ATP8B3, BTK, CAV2, CDK5R1, GRIA1, PCSK9, and PLA2G3) signature was identified and divided patients into high-risk and low-risk groups. The prognostic signature was an independent prognostic factor for OS (HR > 1, p Conclusions LYSscore signature provide a new modality for the accurate diagnosis and targeted treatment of LUAD and will help expand researchers’ understanding of new prognostic models.

Pelvic organ prolapse (POP) markedly affects the quality of life of women, including significant financial burden. Different cell types and corresponding marker genes were identified in the vaginal wall of women with POP; however, no study has explored gene expression and cellular heterogeneity in the uterosacral ligament. Using single-cell RNA sequencing, we constructed a transcriptional profile of the uterosacral ligament and control samples, and identified 10 major cell types. We performed subpopulation analysis of POP primary cells, explored differentially expressed genes, and performed pseudo-time and transcription factor analyses. We verified previous cell clusters of human fibroblasts, neutrophils, and found new clusters of uterosacral ligaments. Additionally, we dissected pattern changes of cell–cell interaction between stromal and immune cells and transcription factors related to the extracellular matrix, development, and immunity in POP. Here we provide insight into the molecular mechanisms of POP and valuable information for future research directions.

Antibodies are important immune molecules that are elicited by B cells to protect our bodies during viral infections or vaccinations. In humans, the antibody repertoire is diversified by programmed DNA lesion processes to ensure specific and high affinity binding to various antigens. Broadly neutralizing antibodies (bnAbs) are antibodies that have strong neutralizing activities against different variants of a virus. bnAbs such as anti-HIV bnAbs often have special characteristics including insertions and deletions, long complementarity determining region 3 (CDR3), and high frequencies of mutations, often at improbable sites of the variable regions. These unique features are rare mutational outcomes that are acquired during antibody diversification processes. In this review, we will discuss possible mechanisms that generate these rare antibody mutational outcomes. The understanding of the mechanisms that generate these rare mutational outcomes during antibody diversification will have implications in vaccine design strategies to elicit bnAbs.

The deltex family protein DTX3 is believed to possess E3 ubiquitin ligase activity, as it contains a classic RING finger domain. However, its biological role and the underlying mechanism in cancer remain largely elusive. Here, we identified DTX3 as a novel mutant p53-interacting protein in ovarian carcinoma. Mechanistically, DTX3 mediated mutant p53 ubiquitination and stabilization by perturbing the MDM2-mutant p53 interaction, consequently leading to activation of diverse mutant p53 target genes. Importantly, a positive correlation between the expression of DTX3 and mutant p53 target genes was further validated in ovarian carcinomas. Ectopic DTX3 promoted, while depletion of DTX3 suppressed, ovarian cancer cell proliferation and invasion. Remarkably, the pro-tumorigenic effect of DTX3 is dependent on mutant p53, because ablation of mutant p53 significantly impaired DTX3-induced gene expression and ovarian cancer cell growth and propagation. Furthermore, DTX3 elevated the expression of mutant p53 target genes and boosted ovarian tumor growth in vivo. Finally, DTX3 was amplified and overexpressed in ovarian carcinomas, which is significantly associated with unfavorable prognosis. Altogether, our findings unveil the oncogenic role of DTX3 in ovarian cancer development by bolstering mutant p53 activity.

Publication of the complete genome sequence of Arabidopsis thaliana, the first plant reference genome, in December 2000 heralded the beginning of the plant genome era. Over the past 20 years reference genomes have been generated for hundreds of plant species, spanning non-vascular to flowering plants. Releasing these plant genomes has dramatically advanced studies in all disciplines of plant biology. Importantly, multiple reference-level genomes have been generated for the major crops and their progenitors, enabling the creation of pan-genomes and exploration of domestication history and natural variations that can be adopted by modern crop breeding. We summarize the progress of plant genome sequencing and the challenges of sequencing more complex plant genomes and generating pan-genomes.

Rye (Secale cereale) is an important crop with multiple uses and a valuable genetic resource for wheat breeding. However, due to its complex genome and outcrossing nature, the origin of cultivated rye remains elusive. The geneticist N.I. Vavilov proposed that cultivated rye had been domesticated from weedy rye, rather than directly from wild species like other crops. Unraveling the domestication history of rye will extend our understanding of crop evolution and upend our inherent understanding of agricultural weeds. To this end, in this study we generated the 8.5 Tb of whole-genome resequencing data from 116 worldwide accessions of wild, weedy, and cultivated rye, and demonstrated that cultivated rye was domesticated directly from weedy relatives with a similar but enhanced genomic selection by humans. We found that a repertoire of genes that experienced artificial selection is associated with important agronomic traits, including shattering, grain yield, and disease resistance. Furthermore, we identified a composite introgression in cultivated rye from the wild perennial Secale strictum and detected a 2-Mb introgressed fragment containing a candidate ammonium transporter gene with potential effect on the grain yield and plant growth of rye. Taken together, our findings unravel the domestication history of cultivated rye, suggest that interspecific introgression serves as one of the likely causes of obscure species taxonomy of the genus Secale, and provide an important resource for future rye and wheat breeding.

Circular RNA (circRNAs) is a covalently closed circular non-coding RNA formed by reverse back-splicing from precursor messenger RNA. It is found widely in eukaryotic cells and can be released to the surrounding environment and captured by other cell types. This, circRNAs serve as connections between different cell types for the mediation of multiple signaling pathways. CircRNAs reshape the tumor microenvironment (TME), a key factor involved in all stages of cancer development, by regulating epithelial-stromal transformation, tumor vascularization, immune cell function, and inflammatory responses. Immune cells are the most abundant cellular TME components, and they have profound toxicity to cancer cells. This review summarizes circRNA regulation of immune cells, including T cells, natural killer cells, and macrophages; highlights the impact of circRNAs on tumor progression, treatment, and prognosis; and indicates new targets for tumor immunotherapy.

Background Alzheimer’s disease (AD), a type of neurodegeneration disease, is characterized by Aβ deposition and tangles of nerve fibers. Schisandrin is one of the main components of Fructus Schisandrae Chinensis. Researches showed that schisandrin can improve the cognitive impairment and memory of AD mice, but the specific mechanism has not been fully elucidated. Purpose The purpose of this study is to investigate the possible mechanism of schisandrin in improving AD pathology. Methods The Morris water maze test was executed to detect spatial learning and memory. Ultra performance liquid chromatography-Triple time of flight mass spectrometry (UPLC-Triple-TOF/MS)-based plasma lipidomics was used to study the changes of plasma lipids. Moreover, we measured the levels of protein and mRNA expression of APOE and ABCA1 in the rat brains and in BV2 microglia. Results Our study found that schisandrin could improve learning and memory, and reduce Aβ deposition in AD rats. Furthermore, we found that schisandrin can improve plasma lipid metabolism disorders. Therefore, we hypothesized schisandrin might act via LXR and the docking results showed that schisandrin interacts with LXRβ. Further, we found schisandrin increased the protein and mRNA expression of LXR target genes APOE and ABCA1 in the brain of AD rats and in BV2 microglia. Conclusion Our study reveals the neuroprotective effect and mechanism of schisandrin improves AD pathology by activating LXR to produce APOE and ABCA1.

IntroductionVerticillium wilt (VW) caused by Verticillium dahliae is a soil-borne vascular fungal disease that severely affects cotton yield and fiber quality. Sugar metabolism plays an important role in the growth and pathogenicity of V. dahliae. However, limited information is known about the sugar transporter genes and their roles in the growth and pathogenicity of V. dahliae.MethodIn this study, genome-wide identification of sugar transporter genes in V. dahliae was conducted and the expression profiles of these genes in response to root exudates from cotton varieties susceptible or resistant to V. dahliae were investigated based on RNA-seq data. Tobacco Rattle Virus-based host-induced gene silencing (TRV-based HIGS) and artificial small interfering RNAs (asiRNAs) were applied to investigate the function of candidate genes involved in the growth and pathogenic process of V. dahliae.ResultsA total of 65 putative sugar transporter genes were identified and clustered into 8 Clades. Of the 65 sugar transporter genes, 9 were found to be induced only by root exudates from the susceptible variety, including VdST3 and VdST12 that were selected for further functional study. Silencing of VdST3 or VdST12 in host plants by TRV-based HIGS reduced fungal biomass and enhanced cotton resistance against V. dahliae. Additionally, silencing of VdST12 and VdST3 by feeding asiRNAs targeting VdST12 (asiR815 or asiR1436) and VdST3 (asiR201 or asiR1238) inhibited fungal growth, exhibiting significant reduction in hyphae and colony diameter, with a more significant effect observed for the asiRNAs targeting VdST12. The inhibitory effect of asiRNAs on the growth of V. dahliae was enhanced with the increasing concentration of asiRNAs. Silencing of VdST12 by feeding asiR815+asiR1436 significantly decreased the pathogenicity of V. dahliae.DiscussionThe results suggest that VdST3 and VdST12 are sugar transporter genes required for growth and pathogenicity of V. dahliae and that asiRNA is a valuable tool for functional characterization of V. dahliae genes.

Background and Purpose：Alzheimer’s disease (AD) is a neurodegenerative disease whose main clinical symptoms are cognitive impairment. Synaptic dysfunction is currently a widely accepted pathogenic factor for AD, and this process is closely related to abnormalities in the glutamate receptor /cyclic adenosine monophosphate response element binding protein (NMDAR/CREB) signaling pathway is closely related. The purpose of this study was to identify a new drug for AD treatment. Experimental Approach: PC12 cells, primary neuron model and APPswe/PSEN1dE9(APP/PS1) transgenic mouse model were studied using Aβ1-42 oligomer intervention. Combined with the treatment of AS-IV and NMDAR inhibitors, RT-qPCR, Western-blotting, immunofluorescence and behavioral analysis were performed to explore the pharmacological action and possible mechanism of AS-IV. Key Results: AS-IV significantly improved synaptic damage in AD models and up-regulated the expression of NMDAR (NR1, NR2A, NR2B), CaMKs (CaMKII, CaMKIV), CREB and BDNF. Ultimately, learning, memory, and cognitive impairments in APP/PS1 mice were improved. Inhibition of NMDAR expression significantly attenuated the related protective function of AS-IV. Conclusion and Implications: AS-IV effectively exerts its anti-AD function by activating the NMDAR /CREB signaling pathway. This could help in the development of drugs to treat AD.

Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C>T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677 C>T), is linked to an increased risk of IS in different age groups and ancestry groups.Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations.Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C>T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33–1.61; p < 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36–1.71; p < 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24–1.48; p < 0.001), homozygous model (OR = 1.82; 95%CI = 1.58–2.11; p < 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27–1.48; p < 0.001)]. Further subgroup analyses indicated that the MTHFR rs1801133 (677C>T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations (p < 0.001).Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C>T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.

ObjectiveThis study aimed to investigate the application value of multi-parametric magnetic resonance imaging (MRI) in the diagnosis of iron deposition in the substantia nigra dense zone in Parkinson's disease (PD) and to evaluate the diagnostic value of the correlation among multi-parametric imaging indicators, clinical stage, and disease duration.Materials and methodsThirty-six patients with clinically confirmed PD and 36 healthy controls were enrolled. The disease course was recorded, and PD severity was graded using the Hoehn–Yahr (H–Y) scale. All subjects underwent magnetic sensitivity weighted imaging (SWI), neuromelanin magnetic resonance imaging (NM-MRI), and a T2*mapping sequence. Based on the fusion of the NM-MRI and SWI amplitude maps, phase maps, and T2*MAPPING value maps, NM-MRI was used to delineate the dense zone of the substantia nigra, which was divided into three sub-regions: upper, middle, and lower. In this way, the amplitude, phase, and R2* values of each sub-region and the average value of the sum of the three sub-regions were obtained simultaneously in the SWI amplitude, phase, and T2*MAPPING maps. The multi-parameter imaging indices were compared between the two groups, and the correlation between them and clinical indices was evaluated in the PD group.ResultsThe upper (amplitude, phase value, R2* value), middle, and lower (amplitude) right substantia nigra compact zones were significantly different between the PD and control groups. The upper (phase value, R2* value) and middle (amplitude) areas of the left substantia nigra compact zone were also significantly different between the two groups (all P < 0.05). The mean values (amplitude, phase value, R2* value) of the right substantia nigra densification zone and the mean values (phase value) of the left substantia nigra densification zone were also significantly different (all P < 0.05). Amplitudes in the middle and lower parts of the right substantia nigra dense zone were negatively correlated with the H–Y grade (middle: r = −0.475, P = 0.003; lower: r = −0.331, P = 0.049). Amplitudes of the middle and lower parts of the dense zone of the left substantia nigra were negatively correlated with the H–Y grade (middle: r = −0.342, P = 0.041; lower: r = −0.399, P = 0.016). The average amplitude of the right substantia nigra compact zone was negatively correlated with the H–Y grade (r = −0.367, P = 0.027). The average R2* value of the compact zone of the left substantia nigra was positively correlated with the H–Y grade (r = 0.345, P = 0.040).ConclusionMultiparametric MRI sequence examination has application value in the evaluation of iron deposition in the dense zone of the substantia nigra in PD. Combined with NM-MRI, fusion analysis is beneficial for accurately locating the substantia nigra compact zone and quantitatively analyzing the iron deposition in different sub-regions. Quantitative iron deposition in the middle and lower parts of the substantia nigra dense zone may become an imaging biological indicator for early diagnosis, severity evaluation, and follow-up evaluation of PD and is thus conducive for clinical diagnosis and treatment evaluation.

The tumor-suppressive activity of p53 is largely attributed to its ability to induce cell death, including apoptosis, through transcription-dependent and transcription-independent mechanisms. On the one hand, nuclear p53 transcriptionally activates the expression of a myriad of pro-apoptotic BCL-2 family genes, such as NOXA, PUMA, BID, BAD, BIK, BAX, etc., whereas it inactivates the expression of anti-apoptotic BCL-2, BCL-XL, and MCL1, leading to mitochondrial apoptosis. On the other hand, cytoplasmic p53 also promotes mitochondrial apoptosis by directly associating with multiple BCL-2 family proteins in the mitochondria. Apoptosis-related protein in TGF-β signaling pathway (ARTS), a mitochondria-localized pro-apoptotic protein encoded by an alternative spliced variant of the SEPT4 gene, triggers apoptosis by facilitating proteasomal degradation of BCL-2 and XIAP upon pro-apoptotic stimuli. We recently identified SEPT4/ARTS as a new p53 target gene in response to genotoxic stress. ARTS in turn binds to p53, drives its mitochondrial localization, and enhances the interaction between p53 and BCL-XL, thereby promoting mitochondrial apoptosis. This review will illustrate the mechanisms of p53-induced mitochondrial apoptosis, offer some recently discovered new insights into the functions of ARTS in regulating mitochondrial cell death, and discuss the clinical significance of ARTS in cancer and non-cancer diseases.

Phytolith carbon (C) sequestration plays a key role in mitigating global climate change at a centennial to millennial time scale. However, previous estimates of phytolith-occluded carbon (PhytOC) storage and potential in China's grasslands have large uncertainties mainly due to multiple data sources. This contributes to the uncertainty in predicting long-term C sequestration in terrestrial ecosystems using Earth System Models. In this study, we carried out an intensive field investigation (79 sites, 237 soil profiles [0–100 cm], and 61 vegetation assessments) to quantify PhytOC storage in China's grasslands and to better explore the biogeographical patterns and influencing factors. Generally, PhytOC production flux and soil PhytOC density in both the Tibetan Plateau and the Inner Mongolian Plateau had a decreasing trend from the Northeast to the Southwest. The aboveground PhytOC production rate in China's grassland was 0.48 × 106 t CO2 a–1, and the soil PhytOC storage was 383 × 106 t CO2. About 45% of soil PhytOC was stored in the deep soil layers (50–100 cm), highlighting the importance of deep soil layers for C stock assessments. Importantly, the Tibetan Plateau had the greatest contribution (more than 70%) to the PhytOC storage in China's grasslands. The results of multiple regression analysis indicated that altitude and soil texture significantly influenced the spatial distribution of soil PhytOC, explaining 78.1% of the total variation. Soil phytolith turnover time in China's grasslands was mainly controlled by climatic conditions, with the turnover time on the Tibetan Plateau being significantly longer than that on the Inner Mongolian Plateau. Our results offer more accurate estimates of the potential for phytolith C sequestration from ecological restoration projects in degraded grassland ecosystems. These estimates are essential to parameterizing and validating global C models.