NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations.

Aging in mammals is accompanied by an imbalance of intestinal homeostasis and accumulation of mitochondrial DNA (mtDNA) mutations. However, little is known about how accumulated mtDNA mutations modulate intestinal homeostasis. We observe the accumulation of mtDNA mutations in the small intestine of aged male mice, suggesting an association with physiological intestinal aging. Using polymerase gamma (POLG) mutator mice and wild-type mice, we generate male mice with progressive mtDNA mutation burdens. Investigation utilizing organoid technology and in vivo intestinal stem cell labeling reveals decreased colony formation efficiency of intestinal crypts and LGR5-expressing intestinal stem cells in response to a threshold mtDNA mutation burden. Mechanistically, increased mtDNA mutation burden exacerbates the aging phenotype of the small intestine through ATF5 dependent mitochondrial unfolded protein response (UPRmt) activation. This aging phenotype is reversed by supplementation with the NAD+ precursor, NMN. Thus, we uncover a NAD+ dependent UPRmt triggered by mtDNA mutations that regulates the intestinal aging.

Breviscapine protects against pathological cardiac hypertrophy by targeting FOXO3a-mitofusin-1 mediated mitochondrial fusion.

Forkhead box O3a (FOXO3a)-mediated mitochondrial dysfunction plays a pivotal effect on cardiac hypertrophy and heart failure (HF). However, the role and underlying mechanisms of FOXO3a, regulated by breviscapine (BRE), on mitochondrial function in HF therapy remain unclear. This study reveals that BRE-induced nuclear translocation of FOXO3a facilitates mitofusin-1 (MFN-1)-dependent mitochondrial fusion in cardiac hypertrophy and HF. BRE effectively promotes cardiac function and ameliorates cardiac remodeling in pressure overload-induced mice. In addition, BRE mitigates phenylephrine (PE)-induced cardiac hypertrophy in cardiomyocytes and fibrosis remodeling in fibroblasts by inhibiting ROS production and promoting mitochondrial fusion, respectively. Transcriptomics analysis underscores the close association between the FOXO pathway and the protective effect of BRE against HF, with FOXO3a emerging as a potential target of BRE. BRE potentiates the nuclear translocation of FOXO3a by attenuating its phosphorylation, other than its acetylation in cardiac hypertrophy. Mechanistically, over-expression of FOXO3a significantly inhibits cardiac hypertrophy and mitochondrial injury by promoting MFN-1-mediated mitochondrial fusion. Furthermore, BRE demonstrates its ability to substantially curb cardiac hypertrophy, reduce mitochondrial ROS production, and enhance MFN-1-mediated mitochondrial fusion through a FOXO3a-dependent mechanism. In conclusion, nuclear FOXO3a translocation induced by BRE presents a successful therapeutic avenue for addressing cardiac hypertrophy and HF through promoting MFN-1-dependent mitochondrial fusion.

The role of T cells and shared genes in psoriasis and inflammatory bowel disease based on single-cell RNA and comprehensive analysis.

Psoriasis and inflammatory bowel disease (IBD) have a similar etiology, including abnormal activation of T cells. Differentially expressed genes (DEGs) analysis was used to search for shared genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis were then performed. Secondly, single-cell RNA analysis (scRNA-seq) and immune infiltration were employed to explore the immune imbalance of the diseases. By weighted gene co expression network analysis (WGCNA), we obtained hub shared genes. Furthermore, we analyzed the diagnostic performance and immune association with the hub genes. Finally, functional enrichment of miRNAs related to hub shared genes was carried out. Single-cell analysis showed a high proportion of T cells among infiltrated immune cells and immune infiltration showed CD4+ T and γδ T cells were significantly elevated in diseases. Hub shared genes, LCN2, CXCL1 and PI3 had excellent diagnostic properties and were positively correlated with neutrophils, CD4+ T and γδ T cells. IL17 and TNF signaling pathway were the common pathway. In conclusion, CD4+ and γδ T cells and hub shared genes may play a crucial part in common mechanism between psoriasis and IBD. Moreover, hub shared genes may be potential diagnostic markers.

[Characteristics of Cadmium Concentration and Transport of Pueraria thornsonii in Farmland with Different Cadmium Pollution Degrees].

This study aimed to elucidate the cadmium (Cd) concentration and transport characteristics of Pueraria thornsonii in farmland with different Cd pollution degrees, so as to provide a reference basis for phytoremediation of Cd-contaminated farmland. The multi-point experiments in farmland with different Cd pollution degrees[ω(Cd) 0.32-38.08 mg·kg-1] were conducted, and the biomass (dry weight), Cd content, accumulation, concentration, and transport of Cd in P. thornsonii tissues under the main growing period were assessed. According to the results, for P. thornsonii, the tuber dry weight ranged from 5.04 to 11.98 t·hm-2, biomass ranged from 13.21 to 29.07 t·hm-2, and Cd accumulation ranged from 15.74 to 106.03 g·hm-2in the study area. The pattern of Cd uptake by P. thornsonii showed that the main vine>leaf>lateral branches>basal part of sti>tuber. The Cd content in P. thornsonii tissues considerably increased with soil Cd content (P<0.05), whereas the biomass decreased significantly (P<0.05). The Cd concentration and transport factor of aboveground parts in P. thornsonii showed a trend of initially falling, then increasing and decreasing again, whereas the Cd enrichment and transport coefficient of tubers gradually decreased. Correlation analysis revealed that the amount of Cd in the soil was a major predictor of Cd accumulation in P. thornsonii. Under light to moderate Cd contamination, the commercial portion of P. thornsonii (arrowroot)[ω(Cd) 0.03-0.22 mg·kg-1] was less than the standard limit for medicinal plants (≤ 0.30 mg·kg-1). In P. thornsonii from moderately contaminated areas, the Cd concentration and transport factor of aboveground parts were 2.43-7.97 and 3.02-9.81, respectively. This indicates that P. thornsonii is a prospective plant ideal for remediating Cd-contaminated soil because of its high capacity to transfer and enrich Cd.

Identification of prognostic genes for breast cancer related to systemic lupus erythematosus by integrated analysis and machine learning.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multi-organ involvement, and some studies have found that SLE has a reduced risk of breast cancer (BRCA). So, we tried to find prognostic genes for BRCA related to SLE by integrated analysis and machine learning. METHOD: First, we downloaded 2 SLE datasets from Gene Expression Omnibus (GEO) and BRCA data from the Cancer Genome Atlas (TCGA). Subsequently, we performed differentially expressed genes (DEGs) and functional enrichment analysis by Metascape in SLE. Genes that were differentially expressed in both datasets were the validated DEGs. And after constructing PPI network, genes with nodes >30 were intersected with survival genes in BRCA to obtain candidate genes. Then, the candidate genes were validated by lasso regression in both training and validation sets to obtain prognostic genes. Afterwards, we investigated the diagnostic potential of prognostic genes for SLE and the predictive efficacy for BRCA prognosis. Moreover, GSEA analysis and immune infiltration were performed for SLE and BRCA. Finally, we constructed a prognostic gene-miRNAs network and did functional enrichment of the shared genes. RESULT: DEGs for SLE were mainly enriched with neutrophil degranulation and IFN pathways. After the lasso model of BRCA was established, IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE and had good predictive ability for the prognosis of BRCA. Prognostic genes had excellent diagnostic potential for SLE, with IFI35 and EIF2AK2 positively associated with SLE activity and IRF7 positively associated with IFI35. GSEA showed that both SLE and BRCA were associated with ubiquitinated degradation. Immune infiltrates suggest that plasma cells, dendritic cells (DC), neutrophils and monocyte were elevated in SLE. DC, NK and CD8+ T cells were elevated in the BRCA low-risk group. Finally, 5 shared miRNAs were confirmed, which were mainly enriched in the IFN pathway. CONCLUSION: IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE. IFN pathway played an important role in the etiology of SLE and the prognosis of BRCA.

Scientometric analysis of lipid metabolism in breast neoplasm: 2012-2021.

Introduction: In recent years, more and more studies have proved that lipid metabolism plays an essential role in breast cancer's proliferation and metastasisand also has a specific significance in predicting survival. Methods: This paper collected data from 725 publications related to lipid metabolism in breast neoplasm from 2012 to 2021 through the Web of Science Core Collection database. Bibliometrix, VOSviewer, and CiteSpace were used for the scientometrics analysis of countries, institutions, journals, authors, keywords, etc. Results: The number of documents published showed an increasing trend, with an average annual growth rate of 14.49%. The United States was the most productive country (n = 223, 30.76%). The journals with the largest number of publications are mostly from developed countries. Except for the retrieved topics, "lipid metabolism" (n = 272) and "breast cancer" (n = 175), the keywords that appeared most frequently were "expression" (n = 151), "fatty-acid synthase" (n = 78), "growth" (n = 72), "metabolism" (n = 67) and "cells" (n = 66). Discussion: These findings and summaries help reveal the current research status and clarify the hot spots in this field.

Genes associated with cellular senescence favor melanoma prognosis by stimulating immune responses in tumor microenvironment.

PURPOSE: Skin cutaneous melanoma (SKCM), a malignant tumor from melanocytes, is the fifth most prevalent tumor. Immune checkpoint inhibitor (ICI) immunotherapy improves prognosis of SKCM, but immune response varies for different populations. Cellular senescence in the tumor microenvironment (TME) promotes antitumor immunity, mediated by dendritic cells (DC) and CD8+ T cells. Therefore, we sought to explore the role of cellular senescence in the TME of SKCM through bioinformatics and machine learning. METHODS: First, we obtained 93 cellular senescence-prognosis genes (CSPGs) by univariate survival analysis. Thereafter, 23 optimal CSPGs were obtained by least absolute shrinkage and selection operator (lasso) analysis. Based on the riskscore obtained by lasso analysis and clinical information from multivariate cox, we obtained the nomogram of SKCM, which was validated in the validation cohort. Based on the riskscore, the patients were split into low- and high-risk groups. Functional differences between the two groups were analyzed using Metascape and GSEA, and immune infiltration differences were achieved by multiple algorithms. We obtained a risk prediction nomogram for the validated SKCM based on the lasso model by univariate and multivariate cox regression analysis. RESULTS: In the low-risk group, immune responses were in an active state. NK, CD8+ T, DC, macrophages, and neutrophils were significantly upregulated, and ICI-relevant genes were notably upregulated. With the differentially expressed genes (DEGs) and optimal CSPGs, we obtained the hub genes: NOX4, NTN4, PROX1, and TRPM8. The hub genes were mainly expressed by cancer-associated fibroblasts (CAFs) and endothelial cells by single cell analysis, which were mainly associated with angiogenesis. CONCLUSION: Genes associated with cellular senescence favor SKCM prognosis by stimulating immune responses in TME. Patients with high expression of cellular senescence associated genes in the TME might have better benefit from ICI immunotherapy. Cellular senescence functions as a pro-tumor agent in mesenchymal cells and needs further study.

Integrated analysis and clinical correlation analysis of hub genes, immune infiltration, and potential therapeutic agents related to lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). This study aimed to explore biomarkers, mechanisms, and potential novel agents regarding LN through bioinformatic analysis. METHOD: Four expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were acquired. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses of DEGs were performed using the R software. The protein-protein interaction (PPI) network was developed using the STRING database. Additionally, five algorithms were used to screen out the hub genes. Expression of the hub genes were validated using Nephroseq v5. CIBERSORT was used to evaluate the infiltration of immune cells. Finally, The Drug-Gene Interaction Database was used to predict potential targeted drugs. RESULT: FOS and IGF1 were identified as hub genes, with excellent specificity and sensitivity diagnosis of LN. FOS was also related to renal injury. LN patients had lower activated and resting dendritic cells (DCs) and higher M1 macrophages and activated NK cells than healthy control (HC). FOS had a positive correlation with activated mast cells and a negative correlation with resting mast cells. IGF1 had a positive correlation with activated DCs and a negative correlation with monocytes. The targeted drugs were dusigitumab and xentuzumab target for IGF1. CONCLUSION: We analyzed the transcriptomic signature of LN along with the landscape of the immune cell. FOS and IGF1 are promising biomarkers for diagnosing and evaluating the progression of LN. The drug-gene interaction analyses provide a list of candidate drugs for the precise treatment of LN.

Exploration of the molecular mechanisms, shared gene signatures, and MicroRNAs between systemic lupus erythematosus and diffuse large B cell lymphoma by bioinformatics analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex heterogeneous systemic autoimmune disease. Previous studies have shown that SLE may be related to diffuse large B cell lymphoma (DLBCL), but the mechanism of their relationship is still unclear. The present study aimed to explore the common genetic molecular mechanisms, core shared genes, and miRNAs between SLE and DLBCL as well as to investigate the diagnostic markers of DLBCL. METHODS: The SLE and DLBCL microarray data were downloaded from the comprehensive Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules. Four core shared genes were screened out by various algorithms and validated in other cohorts. Finally, we constructed a common core gene-miRNA network using the human microRNA disease database (HMDD) and TarBase. RESULTS: Using WGCNA, four modules were identified as important modules for SLE and DLBCL. Enrichment analysis of the shared genes showed that the highly activated NF-κB pathway was a common feature of the pathophysiology. Four core shared genes, namely, PSMB10, PSMB4, TAF10, and NFΚBIA, were screened out. These core shared genes were significantly upregulated in both diseases, and they may be potential diagnostic markers of DLBCL. The core gene-miRNA network showed that miR-155-5p, regulating the shared NF-κB pathway, may play an important role in the susceptibility of SLE patients to DLBCL. CONCLUSION: The present study revealed that NF-κB pathway in SLE may be a crucial susceptible factor for DLBCL. In addition, we identified PSMB10, PSMB4, TAF10, NFΚBIA and miR-155 involved in the common pathogenesis as potential biomarkers and therapeutic targets for DLBCL.

Frutescone O from Baeckea frutescens Blocked TLR4-Mediated Myd88/NF-κB and MAPK Signaling Pathways in LPS Induced RAW264.7 Macrophages.

Frutescone O was isolated from the aerial parts of Baeckea frutescens L., which was commonly used as a folk medicinal material for treating anti-inflammatory disease in South East Asia. This study aimed to investigate the anti-inflammatory activity and related signaling cascade of Frutescone O (Fru) in LPS induced RAW264.7 cells. The anti-inflammation activity of Frutescone O was determined according to the inhibitory effects on the secretion of nitric oxide (NO), expression of inducible NO synthase, and pro-inflammatory cytokines. The regulation of Myeloid differentiation factor 88 (Myd88), inhibition of NF-κB, and MAPK pathways were further investigated for molecular mechanisms. Fru significantly decreased the expression of iNOS and the production of NO in LPS-stimulated RAW264.7 cells. It also dose-dependently suppressed LPS induced expression of IL-1ß, IL-6, and TNF-α. Furthermore, Fru remarkably inhibited the upregulation of NF-κB (p50) expression in the nucleus and the phosphorylation ratio of p38, JNK, ERK, and Myd88 signaling protein. The molecular docking and cellular thermal shift assay (CETSA) results indicated that Fru participated in a robust and stable interaction with the active site of TLR4-MD2. Thus, Fru suppressed the LPS induced inflammation in RAW264.7 cells by blocking the TLR4 mediated signal transduction through the NF-κB and MAPK signaling pathways and inhibiting the Myd88 and iNOS expression.

Baeckein E suppressed NLRP3 inflammasome activation through inhibiting both the priming and assembly procedure: Implications for gout therapy.

BACKGROUND: Baeckein E (BF-2) was isolated from the aerial parts of Baeckea frutescens L., which has a long history of use in traditional medicine in Southeast Asia to treat inflammatory disease. PURPOSE: BF-2 was identified to have inhibitory activity on nucleotide oligomerization domain (NOD)-like receptor protein-3 inflammasome (NLRP3) activation. This study aimed to investigate the related signaling cascade of BF-2 in both lipopolysaccharides (LPS)/ATP induced pyroptosis in J774A.1 macrophages and its application in a mouse model of gout induced by monosodium urate crystal (MSU). METHODS: The effect of BF-2 on NLRP3 inflammasome activation and gouty arthritis was studied in J774A.1 macrophages and male C57BL/6 mice. The J774A.1 macrophages were primed with LPS and stained by propidium iodide (PI) for cell pyroptosis detection. A gout mouse model was established by subcutaneous injection of MSU crystals into the hind paw of C57BL/6 mice. Mice were then randomly divided into different groups. The concentrations of IL-1ß and IL-18 in both J774A.1 macrophage and gout mouse model were analyzed by ELISA. The NLRP3 inflammasome related protein expression was detected by western blot analysis. The inhibitory effects of BF-2 on NLRP3 inflammasome assembly were analyzed by immunoprecipitation assay. The roles of BF-2 in mitochondrial damage were imaged by Mito Tracker Green and Mito Tracker Red probes. The inhibitory effects of BF-2 on ROS production were imaged by DCF (2',7'-dichlorofluorescein diacetate) probe. RESULTS: The results demonstrated BF-2 could significantly suppress the cell pyroptosis and IL-1ß secretion in macrophages. Furthermore, BF-2 significantly inhibited NLRP3 inflammasome activation and reduced ankle swelling in the gout mouse model. In detail, it alleviated mitochondrial damage mediated oxidative stress and inhibited the assembly of NLRP3 inflammasome by affecting the binding of pro-Caspase 1 and ASC. Moreover, BF-2 blocked NLRP3 activation by inhibiting the MAPK/NF-κB signaling pathways. CONCLUSIONS: Results demonstrated BF-2 inhibited NLRP3 inflammasome activation in both LPS primed macrophages and mouse model of gout through blocking MAPK/NF-κB signaling pathway and mitochondrial damage mediated oxidative stress. This study strongly suggests BF-2 could be a promising drug candidate against inflammatory diseases associated with NLRP3 inflammasome activation.

Ainsliaea fragrans champ. Extract prevents cervicitis in BALB/c mice and regulates MyD88-NF-κB signaling pathway in MALP-2-stimulated RAW264.7 cells.

Ethnopharmacological relevance Ainsliaea fragrans Champ. (A. fragrans) is used to treat infection of the lower genital tract in gynecology, such as cervicitis and pelvic inflammatory disease. This study analyzed the therapeutic efficiency of A. fragrans on cervicitis and the inhibition mechanism of AF-p2 in MALP-2-stimulated RAW264.7 cells. Materials and methods The anti- Ureaplasma urealyticum (Uu) activity of A. fragrans and AF-p2 were determined by antimicrobial susceptibility testing. The activity of A. fragrans extracts (AFext) was evaluated in female BALB/c mice with cervicitis induced by Uu. Furthermore, the therapeutic mechanism of AFext and AF-p2 on myeloid differentiation factor 88 (MyD88) pathway were studied in macrophage activating lipopeptide-2 (MALP-2) irritated RAW264.7 cells. Results AFext could suppress the proliferation of Uu in vitro, including the azithromycin resistant strains. Meanwhile, AFext prevented cervicitis caused by Uu infection in BALB/c mice. Moreover, both AFext and AF-p2 could significantly suppress the nitric oxide (NO) production as well as other proinflammatory cytokines (IL-1ß,IL-6,TNF-α) in MALP-2 stimulated RAW264.7 cells. Moreover, AF-p2 also down-regulated iNOS, p65, Iκ-Bα, MyD88 and cyclooxygenase-2 (COX-2) levels in RAW264.7 cells. Conclusion This study indicated that AFext had a therapeutic effect in cervicitis induced by Uu infection. Furthermore, the lead compound AF-p2 showed an anti-infectious effect in MALP-2 irritated RAW264.7 cells through downregulating MyD88-NF-κB signaling pathway.

Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD+ redox.

Mammals' aging is correlated with the accumulation of somatic heteroplasmic mitochondrial DNA (mtDNA) mutations. Whether and how aging accumulated mtDNA mutations modulate fertility remains unknown. Here, we analyzed oocyte quality of young (≤30 years old) and elder (≥38 years old) female patients and show the elder group had lower blastocyst formation rate and more mtDNA point mutations in oocytes. To test the causal role of mtDNA point mutations on infertility, we used polymerase gamma (POLG) mutator mice. We show that mtDNA mutation levels inversely correlate with fertility, interestingly mainly affecting not male but female fertility. mtDNA mutations decrease female mice's fertility by reducing ovarian primordial and mature follicles. Mechanistically, accumulation of mtDNA mutations decreases fertility by impairing oocyte's NADH/NAD+ redox state, which could be rescued by nicotinamide mononucleotide treatment. For the first time, we answer the fundamental question of the causal effect of age-accumulated mtDNA mutations on fertility and its sex dependence, and show its distinct metabolic controlling mechanism.

[Soil fertility characteristics and their influencing factors in tea plantations of Jiangxi Pro-vince, China]. / æ±Ÿè¥¿çœèŒ¶å›­åœŸå£¤è‚¥åŠ›ç‰¹å¾åŠå ¶å½±å“å› å­.

To investigate soil fertility status and characteristics of typical tea plantations, we selec-ted 372 typical tea plantations of 21 areas across Jiangxi Province and analyzed the soil nutrient, spatial data, and their correlations with topography, soil type, elevation and plantation age. The results showed that soil pH, organic matter, alkaline nitrogen, available phosphorus, available potassium, total nitrogen, total phosphorus and total potassium of tea plantation in Jiangxi reached 53.9%, 60.1%, 56.1%, 22.9%, 38.5%, 43.7%, 11.1% and 95.5% of indices of high fertility, high efficiency and high yield tea plantation, respectively, with the available phosphorus showing a strong variation. Soil available copper, zinc, iron, manganese and boron reached 76.3%, 74.2%, 96.8%, 73.1% and 0.0% of the first-class standards for soil trace elements, respectively. Tea plantations with highest soil fertility located in central Jiangxi, followed by northeastern and northwestern Jiangxi, and lowest in southern Jiangxi. Soil pH was significantly positively correlated with organic matter, alkaline nitrogen, available phosphorus, available potassium, total nitrogen and total phosphorus but not for total potassium. For different topography, soil fertility was highest in the flat land, followed by the high mountains, and lowest in the mountains and hills. Across different soil types, soil fertility was higher in paddy soil, sandy soil and mountain yellow brown soil, followed by yellow soil, red-yellow soil and purple soil, and lowest in red soil. Soil pH, organic matter and total potassium increased while available phosphorus decreased with altitude. The organic matter, alkaline nitrogen, available phosphorus, total nitrogen and total phosphorus increased, but soil pH decreased with time. In summary, soil fertility of tea plantations in Jiangxi Province was generally good, with high organic matter, total potassium, available copper, zinc, iron and manganese. However, soil was acidic, available phosphorus and total phosphorus content was low, available boron was seriously limited. We suggest increase soil pH and potassium supply in central Jiangxi, increase potassium and nitrogen fertilizer supply in northeastern Jiangxi, increase organic matter and phosphorus fertilizer supply in northwestern Jiangxi, and increase nitrogen, phosphorus and potassium supply combined with organic fertilizers in southern Jiangxi. High mountain tea plantations should enhance available phosphorus and potassium supply. Mountain tea plantations should enhance nitrogen and phosphate supply. Tea plantations with red and yellow soil should increase pH and total potassium supply. Tea plantations with red soil should apply nitrogen, phosphorus and potassium fertilizers combined with organic fertilizers. Tea plantations with yellow soil and mountain yellow brown soil required additional phosphorus supply, and tea plantations with purple soil should increase soil organic matter supply. Tea plantations need to increase dolomite powder, physiological alkaline fertilizers and organic fertilizers to prevent soil acidification.

OPA1-Exon4b Binds to mtDNA D-Loop for Transcriptional and Metabolic Modulation, Independent of Mitochondrial Fusion.

Optic Atrophy 1 (OPA1) has well-established roles in both mitochondrial fusion and apoptotic crista remodeling and is required for the maintenance and distribution of mitochondrial DNA (mtDNA), which are essential for energy metabolism. However, the relationship between OPA1 and mitochondrial metabolism and the underlying mechanisms remain unclear. Here, we show that OPA1-Exon4b modulates mitochondrial respiration and rescues inner mitochondrial membrane potential (Δψm), independent of mitochondrial fusion. OPA1-Exon4b is required for the maintenance of normal TFAM distribution and enhances mtDNA transcription by binding the D-loop of mtDNA. Finally, we show that mRNA levels of OPA1 isoforms containing Exon4b are specifically downregulated in hepatocellular carcinoma (HCC), leading to a reduction in Δψm. Thus, our study demonstrates a novel mitochondrial functional self-recovery pathway involving enhanced mtDNA transcription-mediated recovery of mitochondrial respiratory chain proteins. This mitochondrial fusion-independent pathway may contribute to mitochondrial multi-functional switches in tumorigenesis.

[Remediation of Cadmium Contaminated Paddy Fields Using Soil Conditioners].

Four soil conditioners, SAMMNS, CCT01, Mineral, and Tebeigai were selected for this study. The effects of the four conditioners on soil pH, bulk density, organic matter, available nutrients, texture, microaggregates, Cd available in soil, and Cd content in brown rice were investigated using field-controlled cadmium tests conducted in cadmium-contaminated paddy fields in Pingxiang. The results showed that compared to the control, soil conditioners could increase pH, bulk density, and cation exchange capacity in soil. SAMMNS and CCT01 soil conditioners increased the amount of silt and clay, but that of sand decreased, whereas the Mineral and Tebeigai soil conditioners decreased silt and clay, and sand increased. In addition to the CCT01 soil conditioner, the application of soil conditioners increased large-scale agglomerates and reduced small-scale microaggregates. The effects of soil conditioners on soil physical and chemical properties promoted the conversion of Cd from contaminated soil from high activity to low activity, which reduced available Cd content in soil (5.21%-34.78%) and Cd content in brown rice (51.39%-68.06%). Correlation analysis showed that Cd content in brown rice was significantly positively correlated with available Cd and available phosphorus in soil, whereas it was negatively correlated with pH and bulk density in soil. Considering the effects of soil and brown rice on cadmium reduction and physicochemical properties, Tebeigai soil conditioner exhibited the best repair effects, followed by SENMES and Mineral soil conditioner.

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta-analysis.

BACKGROUND: The present study focused on understanding the prognostic value of the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms rs1801133 (C667T) and rs1801131 (A1298C) in patients with colorectal cancer (CRC). METHODS: A systematic literature search was conducted in March 2016. Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC. Data regarding overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were collected and analysed. RESULTS: Twenty-four studies with 5423 patients with CRC were included. Significant differences in OS, PFS and DFS were not observed among the different comparisons of patients carrying different alleles of the MTHFR rs1801133 polymorphism (including TT versus CC, TT versus CT + CC, CT + TT versus CC and CT versus CC). Compared with patients with the rs1801131 CA + AA genotypes, patients with the CC genotype had a shorter OS (hazard ratio = 1.85; 95% confidence interval = 1.30-2.65) and DFS (hazard ratio = 2.16; 95% confidence interval= 1.19-3.93). Significant differences in OS, PFS and DFS were not observed among the other patient groups (including CC versus AA, CC + CA versus AA and CA versus AA). Subgroup analysis of rs1801133 and rs1801131 showed that patients with CRC from Asian regions and Western regions demonstrated similar results. CONCLUSIONS: The MTHFR rs1801133 polymorphism was not associated with the prognosis of patients with CRC; however, rs1801131 may be associated with the prognosis of patients with CRC. Well-designed prospective studies are necessary to obtain a better understanding of the prognostic value of rs1801133 and rs1801131.

Short-Term Mitochondrial Permeability Transition Pore Opening Modulates Histone Lysine Methylation at the Early Phase of Somatic Cell Reprogramming.

Reprogramming of somatic cells to induced pluripotent stem cells reconfigures chromatin modifications. Whether and how this process is regulated by signals originating in the mitochondria remain unknown. Here we show that the mitochondrial permeability transition pore (mPTP), a key regulator of mitochondrial homeostasis, undergoes short-term opening during the early phase of reprogramming and that this transient activation enhances reprogramming. In mouse embryonic fibroblasts, greater mPTP opening correlates with higher reprogramming efficiency. The reprogramming-promoting function of mPTP opening is mediated by plant homeodomain finger protein 8 (PHF8) demethylation of H3K9me2 and H3K27me3, leading to reduction in their occupancies at the promoter regions of pluripotency genes. mPTP opening increases PHF8 protein levels downstream of mitochondrial reactive oxygen species production and miR-101c and simultaneously elevates levels of PHF8's cofactor, α-ketoglutarate. Our findings represent a novel mitochondria-to-nucleus pathway in cell fate determination by mPTP-mediated epigenetic regulation.

[Accumulation of Heavy Metals in Different Rice Varieties].

Field experiments were conducted on the heavy metal contents (Cd, Pb, Cr, inorganic As, and total Hg) of the 129 main cultivated rice varieties in southern China. We analyzed the effects of different varieties and types of rice on the absorption capacities of these heavy metals. The results showed that the Cd content in 35 brown rice of early rice was 0.35-0.60 mg·kg-1, exceeding the standard rate of 100%. The Pb content in brown rice was 0.08-0.30 mg·kg-1, exceeding the rate of 14.29%. The Cd content in 54 brown rice of medium rice was 0.03-0.45 mg·kg-1, exceeding the rate of 33.33%. The Cd content in 40 brown rice of late rice was 0.08-0.20 mg·kg-1, which did not exceed the national standard. Early, middle, and late rice all showed that the Cd content of three-line hybrid rice was higher than that of two-line hybrid rice, but the difference was not obvious. The contents of Cr and total Hg in brown rice of three-line hybrid rice in early rice were significantly higher than that of two-line hybrid rice. There was a significant positive correlation between Cd content in brown rice and Pb and total Hg content in medium rice, and there was a significant negative correlation between inorganic Cd content and inorganic As content, whereas there was no significant correlation between Cd and Cr content. In short, rice's absorption and accumulation of heavy metals is greatly affected by genetic background, species types, and heavy metal interactions.