Identification and targeting of cancer-associated fibroblast signature genes for prognosis and therapy in Cutaneous melanoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play pivotal roles in tumor invasion and metastasis. However, studies on CAF biomarkers in Cutaneous Melanoma (CM) are still scarce. This study aimed to explore the potential CAF biomarkers in CM, propose the potential therapeutic targets, and provide new insights for targeted therapy of CAFs in CM. METHODS: We utilized weighted gene co-expression network analysis to identify CAF signature genes in CM, and conducted comprehensive bioinformatics analysis on the CAF risk score established by these genes. Moreover, single-cell sequencing analysis, spatial transcriptome analysis, and cell experiments were utilized for verifying the expression and distribution pattern of signature genes. Furthermore, molecular docking was employed to screen potential target drugs. RESULTS: FBLN1 and COL5A1, two crucial CAF signature genes, were screened to establish the CAF risk score. Subsequently, a comprehensive bioinformatic analysis of the CAF risk score revealed that high-risk score group was significantly enriched in pathways associated with tumor progression. Besides, CAF risk score was significantly negatively correlated with clinical prognosis, immunotherapy response, and tumor mutational burden in CM patients. In addition, FBLN1 and COL5A1 were further identified as CAF-specific biomarkers in CM by multi-omics analysis and experimental validation. Eventually, based on these two targets, Mifepristone and Dexamethasone were screened as potential anti-CAFs drugs. CONCLUSION: The findings indicated that FBLN1 and COL5A1 were the CAF signature genes in CM, which were associated with the progression, treatment, and prognosis of CM. The comprehensive exploration of CAF signature genes is expected to provide new insight for clinical CM therapy.

Identification of potential molecular mechanisms and therapeutic targets for recurrent pelvic organ prolapse.

Background: The pathogenesis of recurrent pelvic organ prolapse (POP) is currently unclear. Therefore, developing targeted preventive measures is difficult. This study identified potential key pathways, crucial genes, comorbidities, and therapeutic targets associated with the occurrence and development of recurrent POP. Methods: The original microarray data GSE28660, GSE53868, and GSE12852 were downloaded from the GEO database. Identification and validation of differentially expressed genes (DEGs) and hub genes associated with recurrent POP were performed using R software and cytoHubba of Cytoscape. Protein-protein interaction (PPI) networks were constructed using the STRING tool and visualized using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were effectively performed using DAVID platforms. In addition, the NetworkAnalyst platform was used to explore and visualize the miRNA-hub gene network, TF-hub gene network, hub gene-disease network, and hub gene-drug/chemical network. Results: A total of 110 DEGs and 6 hub genes (ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE) were identified in this study. These genes were primarily enriched in the PPAR, AMPK, and adipocytokine, non-alcoholic fatty liver disease, and signaling pathways related to glycerol metabolism. Moreover, 96 miRNAs and 97 TFs were identified to as being associated with recurrent POP. These genes were closely linked to adipocyte metabolism and distribution, energy metabolism, and the longevity regulatory pathway. In addition, 192 diseases or chronic complications were potentially related to the recurrence of POP, including diabetes, hypertension, obesity, inflammatory diseases, and chronic obstructive pulmonary disease. Furthermore, 954 drugs or compounds were shown to have therapeutic potential for recurrent POP, and the most critical target drugs were dexamethasone, bisphenol A, efavirenz, 1-methyl-3-isobutylxanthine, and estradiol. Conclusions: The results of this study revealed that ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE as potential hub genes associated with recurrent POP, and these hub genes may aid in the understanding of the mechanism underlying POP recurrence and the development of potential molecular drugs.

RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma.

The failure of melanoma immunotherapy can be mediated by immunosuppression in the tumor microenvironment (TME), and insufficient activation of effector T cells against the tumor. Here, we show that inhibition of galectin-3 (gal-3) enhances the infiltration of T cells in TME and improves the sensitivity of anti-PD-L1 therapy. We identify that RNF8 downregulated the expression of gal-3 by K48-polyubiquitination and promoted gal-3 degradation via the ubiquitin-proteasome system. RNF8 deficiency in the host but sufficiency in implanted melanoma results in immune exclusion and tumor progression due to the upregulation of gal-3. Upregulation of gal-3 decreased the immune cell infiltration by restricting IL-12 and IFN-γ. Inhibition of gal-3 reverses immunosuppression and induces immune cell infiltration in the tumor microenvironment. Moreover, gal-3 inhibitor treatment can increase the sensitivity of PD-L1 inhibitors via increasing immune cell infiltration and enhancing immune response in tumors. This study reveals a previously unrecognized immunoregulation function of RNF8 and provides a promising strategy for the therapy of "cold" tumors. Tremendous effects of melanoma treatment can be achieved by facilitating immune cell infiltration combined with anti-PD-L1 treatment.

Knowledge mapping and visualization analysis of pelvic organ prolapse repair with mesh from 2001 to 2021.

Aims: In recent decades, extensive attention has been paid to the application of mesh to repair pelvic floor defects. However, a large body of related literature has not been system summarized. The purpose of this study is to summarize and visualize the literature on pelvic organ prolapse (POP) repair with mesh using bibliometrics. Methods: Medical literature regarding POP repair with mesh were searched and obtained in the Web of Science™ Core (WoSCC) database from 2001 to 2021. Microsoft Excel 2020, CiteSpace and VOSviewer were used to conduct the bibliometric and knowledge-map analysis. Results: In the past 20 years, a total of 2,550 articles and reviews have been published in 35 journals, and the published and cited results show a growing trend. Cosson M and International Urogynecology Journal were the authors and journals with the highest output, respectively. The United States, France and the United Kingdom are among the top three countries/organizations in relevant publications in worldwide. 584 key words in the literature are divided into 8 clusters, which are mainly related to prolapse type, risk factors, surgical methods, imaging, quality of life and bioengineering. Using clinical research and tissue engineering technology to reduce mesh complications is the current hot spot in this field. Conclusion: Reasonable application of mesh and avoiding mesh complications are still the most concerned topics in POP research. Although clinical research, surgical improvement, biological mesh and bioengineering technology have shown promising results, it is still urgent to carry out clinical transformation application research.

IGF-1-induced Muscle-Derived Stem Cells as a Potential Treatment of Stress Urinary Incontinence in Female Rats.

PURPOSE: Stress urinary incontinence (SUI) is prevalent among elderly women. This study aimed to discuss the potential of muscle-derived stem cells (MDSCs)-based therapy in treating SUI by exploring the effect of Insulin-like growth factor-1 (IGF-1) on transplanted MDSC and urethral sphincter function. MATERIALS AND METHODS: Bilaterally pudendal nerve-transected (PNT) female rats were divided into four groups: sham, PNT+ phosphate buffered solution (PBS) injection, PNT+IGF-1/MDSCs and PNT+ green fluorescent protein (GFP)/MDSCs. IGF-1 was expressed in MDSCs by lentiviral vector. Viable MDSCs were detected by laser scanning confocal microscopy (LSCM). The expression of Myosin heavy chain (MyHC), vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2), microvessel density (MID) and urethral resistance function were assessed. RESULTS: IGF-1 promoted the survival and differentiation of MDSCs. IGF-1-expressing MDSCs facilitated local angiogenesis and muscle fiber regeneration, and alleviated symptoms of SUI. CONCLUSIONS: IGF-1-expressing MDSCs may be used as a novel treatment for patients with SUI.

Identification of miRNAs and Target Genes at Key Stages of Sexual Differentiation in Androdioecious Osmanthus fragrans.

Androdioecy is the crucial transition state in the evolutionary direction of hermaphroditism to dioecy, however, the molecular mechanisms underlying the formation of this sex system remain unclear. While popular in China for its ornamental and cultural value, Osmanthus fragrans has an extremely rare androdioecy breeding system, meaning that there are both male and hermaphroditic plants in a population. To unravel the mechanisms underlying the formation of androdioecy, we performed small RNA sequencing studies on male and hermaphroditic O. fragrans. A total of 334 miRNAs were identified, of which 59 were differentially expressed. Functional categorization revealed that the target genes of differentially expressed miRNAs were mainly involved in the biological processes of reproductive development and the hormone signal transduction pathway. We speculated that the miRNA160, miRNA167, miRNA393 and miRNA396 families may influence the sex differentiation in O. fragrans. Overall, our study is the first exploration of miRNAs in the growth and development process of O. fragrans, and is also the first study of androdioecious plants from the miRNA sequencing perspective. The analysis of miRNAs and target genes that may be involved in the sex differentiation process lay a foundation for the ultimate discovery of the androdioecious molecular mechanism in O. fragrans.

Comparative analysis of the complete plastid genomes in Prunus subgenus Cerasus (Rosaceae): Molecular structures and phylogenetic relationships.

Prunus subgenus Cerasus (cherry) is an economically important group that distributed in temperate regions of the northern hemisphere. However, shared interspecific morphological traits and variability across taxa of Cerasus are among the impediments to taxonomic efforts to correctly delimit taxa. This is further complicated by a lack of genetic information on these taxa, with no focused genomic or phylogenetic studies being done on Cerasus. In this study, we conducted comparative analysis on the complete plastid genomes (plastomes) of 20 Cerasus species to gain a greater understanding of the attributes of the plastome of these taxa while helping resolve their phylogenetic placement in Prunus sensu lato and interspecific relationships within the subgenus. Our results displayed that (1) the plastomes of the 20 Cerasus species studied exhibited a typical quadripartite structure with conversed genome arrangement, structure, and moderate divergence. (2) The average size of complete plastomes for the Cerasus taxa studied was 157,861 bp, ranging from 157,458 to 158,024 bp. A total of 134 genes were annotated, including 86 protein-coding genes, 40 tRNAs, and 8 rRNAs across all species. In simple sequence repeat analysis, we found Cerasus had a comparable number of dispersed and tandem repeats to those identified in other angiosperm taxa, with only P. pseudocerasus found to contain trinucleotide repeats. Nucleotide diversity analysis revealed that the trnG-GCC gene and rpl32-trnL region had the highest Pi value showing potential as phylogenetic markers. (3) Two phylogenetic trees of the plastomes verified the monophyletic relationship of Cerasus and provided a more resolved species-level phylogeny. Our study provides detailed plastome information for exploring the phylogeny of subg. Cerasus taxa. We identified various types of repeats and nucleotide diversity hotspots, which can be a reference for species identification and reconstruction of phylogenetic relationships.

Acute and long-term effects of VX in rat brain cell aggregate culture.

The contact poison VX (O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate) is a chemical warfare agent that is one of the most toxic organophosphorus compounds known. Its primary mechanism of toxic action is through the inhibition of acetylcholinesterase and resultant respiratory paralysis. The majority of work on VX has thus concentrated on its potent anticholinesterase activity and acute toxicity, with few studies investigating potential long-term effects. In this report we describe the effects of VX in aggregating rat brain cell cultures out to 28 days post-exposure. Cholinesterase activity was rapidly inhibited (60 min IC50 = 0.73 +/- 0.27 nM), but recovered towards baseline values over the next four weeks. Apoptotic cell death, as measured using caspase-3 activity was evident only at 100 µM concentrations. Cell type specific enzymatic markers (glutamine synthase, choline acetyltransferase and 2',3'-cyclic nucleotide 3'-phosphodiesterase) showed no significant changes. Total Akt levels were unchanged, while an increased phosphorylation of this protein was noted only at the highest VX concentration on the first day post-exposure. In contrast, significant and delayed (28 days post-exposure) decreases were noted in vascular endothelial growth factor (VEGF) levels, a protein whose reduced levels are known to contribute to neurodegenerative disorders. These observations may indicate that the long-term effects noted in some survivors of nerve agent intoxication may be due to VX-induced declines in brain VEGF levels.

Characterization of the complete chloroplast genome of Prunus clarofolia C.K. Schneid (Rosaceae).

Prunus clarofolia is an endemic species that widely distributed in subtropical regions of China. Here we present its complete plastome. The plastome of P. clarofolia is successfully assembled from raw reads sequenced by Illumina Hiseq 2500 platform system. The complete chloroplast of this species is 158,053 bp in length with 36.7% overall GC content, including a pair of invert repeat regions (IR) (26,393bp) that is divided by a large single copy region (LSC) (86,088bp) and a small single copy region (SSC) (19,179bp). The plastid genome contained a total of 130 genes, including 85 coding genes, 8 rRNA genes, and 37 tRNA genes. Each of rps16, atpF, rpoC1, clpP, petB, petD, rpl16, rpl2, ndhB, and ndhA contains one intron, rps12 and ycf3 contains two introns. Phylogenetic analysis indicates that P. clarofolia has a closer relationship with P. avium.

The complete plastid genome of cherry plants Prunus sargentii (Rosaceae) and its phylogenetic implication.

Prunus sargentii is an ornamental flowering cherry species, spread in Japan, Korea, Russia, and Northeast China. Little information is available regarding its genomic, with limited phylogenetic relationship study performed on P. sargentii until now. In this research, we reported the complete plastid genome of P. sargentii. The complete chloroplast of this species is 158,138 bp in length, including a pair of invert repeat regions (IR) (26,463bp) that is divided by a large single-copy region (LSC) (85,959bp) and a small single-copy region (SSC) (19,253bp). The plastid genome contained a total of 128 genes, including 84 coding genes, eight rRNA genes, and 36 tRNA genes. Phylogenetic analysis indicates that P. sargentii has a closer relationship with P. kumanoensis.

Sulphur mustard induces progressive toxicity and demyelination in brain cell aggregate culture.

Sulphur mustard (H; bis(2-chloroethyl) sulphide) is a vesicant chemical warfare (CW) agent that has been well documented as causing acute injury to the skin, eyes and respiratory system. Although a great deal of research effort has been expended to understand how H exerts these effects, its mechanism of action is still poorly understood. At high exposures, H also causes systemic toxicity with chronic and long-term effects to the immune, cardiovascular and central nervous systems, and these aspects of H poisoning are much less studied and comprehended. Rat aggregate cultures comprised of multiple brain cell types were exposed to H and followed for four weeks post-exposure to assess neurotoxicity. Toxicity (LDH, caspase-3 and aggregate diameter) was progressive with time post-exposure. In addition, statistically significant changes in neurofilament heavy chain (NFH), glial fibrillary acidic protein (GFAP), Akt phosphorylation, IL-6, GRO-KC and TNF-α were noted that were time- and concentration-dependent. Myelin basic protein, CNPase and vascular endothelial growth factor (VEGF) were found to be especially sensitive to H exposure in a time- and concentration-dependent fashion, with levels falling to ∼50 % of control values at ∼10 µM H by 8 days post-exposure. Demyelination and VEGF inhibition may be causal in the long-term neuropsychological illnesses that have been documented in casualties exposed to high concentrations of H, and may also play a role in the peripheral neuropathy that has been observed in some of these individuals.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse.

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER: NCT03620565, https://register.clinicaltrials.gov.

DNA Damage and Activation of cGAS/STING Pathway Induce Tumor Microenvironment Remodeling.

DNA damage occurs throughout tumorigenesis and development. The immunogenicity of DNA makes it an immune stimulatory molecule that initiates strong inflammatory responses. The cGAS/STING pathway has been investigated as a critical receptor in both exogenous and endogenous DNA sensing to activate the innate immune response. Growing lines of evidence have indicated that activation of the cGAS/STING pathway is critical in antitumor immunity. Recent studies have demonstrated the outstanding advancement of this pathway in tumor-combined immunotherapy; accordingly, increased studies focus on exploration of STING pathway agonists and analogues. However, current studies propose the potential use of the cGAS/STING pathway in tumor initiation and metastasis. Here, we review the molecular mechanisms and activation of the cGAS/STING pathway, and the relationship between DNA damage and this pathway, particularly highlighting the remodeling of immune contexture in tumor environment (TME) triggered by cascade inflammatory signals. A detailed understanding of TME reprogramming initiated by this pathway may pave the way for the development of new therapeutic strategies and rational clinical application.

Roles of galectin­3 in the tumor microenvironment and tumor metabolism (Review).

Galectin­3 is expressed in various tissues and plays an important role in the tumor microenvironment (TME). Galectin­3 has been found to be overexpressed in a variety of cancers and is associated with tumor progression and metastasis. Over the past decades, emerging evidence has suggested that the TME may induce galectin­3 expression to maintain cellular homeostasis and promote cell survival. Furthermore, galectin­3 regulates immune cell function to promote tumor­driven immunosuppression through several mechanisms. In the TME, intracellular and extracellular galectin­3 has different functions. In addition, it has been reported that galectin­3 is associated with glycolysis and mitochondrial metabolism in tumors, and it is involved in the regulation of relevant signaling pathways, thus promoting cancer cell survival via adapting to the TME. The aim of the present review was to summarize the current knowledge on galectin­3 production and its function in the TME, its effect on TME immunosuppression, its association with tumor metabolism and relevant signaling pathways, and to report common types of cancer in which galectin­3 is highly expressed, in order to ensure a comprehensive understanding of the critical effects of galectin­3 on tumor progression and metastasis.

Uncovering the Potential Differentially Expressed miRNAs and mRNAs in Ischemic Stroke Based on Integrated Analysis in the Gene Expression Omnibus Database.

INTRODUCTION: Ischemic stroke is the third leading cause of death. There is no known treatment or cure for the disease. Moreover, the pathological mechanism of ischemic stroke remains unclear. OBJECTIVE: We aimed to identify potential microRNAs (miRNAs) and mRNAs, contributing to understanding the pathology of ischemic stroke. METHODS: First, the data of miRNA and mRNA were downloaded for differential expression analysis. Then, the regulatory network between miRNA and mRNAs was constructed. Third, top 100 differentially expressed mRNAs were used to construct a protein-protein interaction network followed by the function annotation of mRNAs. In addition, in vitro experiment was used to validate the expression of mRNAs. Last, receiver operating characteristic diagnostic analysis of differentially methylated genes was performed. RESULTS: Totally, up to 26 differentially expressed miRNAs and 1,345 differentially expressed mRNAs were identified. Several regulatory interaction pairs between miRNA and mRNAs were identified, such as hsa-miR-206-HMGCR/PICALM, hsa-miR-4491-TMEM97, hsa-miR-3622b-5p/hsa-miR-548k-KLF12, and hsa-miR-302a-3p/hsa-miR-3145-3p-CTSS. MAPK signaling pathway (involved DUSP1) and the Notch signaling pathway (involved NUMB and CREBBP) were identified. The expression validation of KLF12, ARG1, ITGAM, SIRT4, SERPINH1, and DUSP1 was consistent with the bioinformatics analysis. Interestingly, hsa-miR-206, hsa-miR-4491, hsa-miR-3622b-5p, hsa-miR-548k, hsa-miR-302a-3p, hsa-miR-3145-3p, KLF12, and ID3 had the potential diagnostic value of ischemic stroke. CONCLUSIONS: The identified differentially expressed miRNAs and mRNAs may be associated with the development of ischemic stroke.

Loss of RAD6B induces degeneration of the cochlea in mice.

Presbycusis is a form of age-related hearing loss (AHL). Many studies have shown that the degeneration of various structures in the cochlea of the inner ear is related to AHL, and DNA damage is an important factor leading to the above process. As an E2 ubiquitin-conjugated enzyme, RAD6B plays an important role in DNA damage repair (DDR) through histone ubiquitination. However, the molecular mechanism is still unclear. In this study, we investigated the role of RAD6B in the morphological changes and DDR mechanisms in aging-related degeneration of the cochlea of mice. We observed that the hair cells, stria vascularis and spiral ganglion in the cochlea of the RAD6B knockout mice showed significant degenerative changes and abnormal expression of proteins associated with DDR mechanisms compared with those of the littermate wild-type mice. In conclusion, our results suggest that the deletion of RAD6B may lead to abnormalities in DDR, thereby accelerating the degeneration of various structures in the cochlea and senescence and apoptosis of cochlea cells.

A Hypothesis Generating the Mechanical Systems Underlying Posterior Vaginal Prolapse Based on Observed Displacements by Dynamic Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to analyze quantified displacements of the posterior vaginal wall (PVW) on dynamic magnetic resonance imaging (MRI), which may generate hypotheses for the detailed mechanisms that underlie the development of posterior vaginal prolapse. METHODS: Pelvic dynamic MRI scans were obtained for 12 women with normal vaginal structure (stage 0) and 62 women with 4 consecutive stages (1-4) of posterior vaginal prolapse. Structural locations (apex vagina, distal vagina, and mid-perineal body [PB]) and equidistant points along the PVW (points 4-6 were considered as midvagina) were identified, and PVW length, straight distance of PVW, levator ani parameters (levator hiatus length [LHL], levator hiatus width [LHW], levator plate angle, anorectal angle, and M line [ML]), urogenital hiatus, and prolapse diameter were measured at rest and maximal Valsalva, respectively. The displacement of these measurements was obtained. RESULTS: From stage 0 to 2, the variables LHL, LHW, levator plate angle, anorectal angle, and ML increased gradually, but midvagina, distal vagina, and mid-PB were the opposite. From stage 2 to 3, apex vagina, midvagina, distal vaginal, mid-PB, LHL, LHW, and ML raised rapidly and peaked at stage 3, then declined at stage 4. In addition, the correlation coefficients between each measurement from stage 2 to 3 were statistically higher than those from stage 0 to 2. CONCLUSIONS: Quantified displacements of the PVW and its supporting structure were shown on dynamic MRI, and the mechanical mechanisms were hypothesized regarding the interaction between pressure and the support force contributing to the deformation of the PVW and the supporting structures.

RAD6B Plays a Critical Role in Neuronal DNA Damage Response to Resist Neurodegeneration.

RAD6 participates in DNA double-strand breaks (DSBs) repair by ubiquitinating histone H2B in mitotic cells. In terminally differentiated cells, however, the mechanisms of DNA damage repair are less well known. In this study, we investigate whether RAD6B is involved in DSBs repair in neurons and effects of RAD6B deficiency on neuronal survival. We compared neurons of RAD6B-deficient mice with those of littermate wild type (WT) mice and induced DNA damage by X-ray irradiation. We provide evidence that RAD6B is essential for neural DDR and RAD6B deficiency results in increased genomic instability and neurodegeneration. Moreover, higher levels of p53 and p21 are present in the brains of RAD6B-deficient mice, which may be responsible for neuronal senescence, and degeneration. In addition, behavioral experiments show that RAD6B-deficient mice exhibit marked learning and memory deficits. In conclusion, these findings suggest that RAD6B is critical for neural integrity and that the absence of RAD6B accelerates neurodegeneration in mice.

Ex vivo detection of cadmium-induced renal damage by using confocal Raman spectroscopy.

Cadmium (Cd) is a toxic heavy metal which is harmful to environment and organisms. The reabsorption of Cd in kidney leads it to be the main damaged organ in animals under the Cd exposure. In this work, we applied confocal Raman spectroscopy to map the pathological changes in situ in normal and Cd-exposed mice kidney. The renal tissue from Cd-exposed group displayed a remarkable decreasing in the intensity of typical peaks related to mitochondria, DNA, proteins and lipids. On the contrary, the peaks of collagen in Cd-exposed group elevated significantly. The components in each tissue were identified and distinguished by principal component analysis. Furthermore, all the biological investigations in this study were consistent with the Raman spectrum detection, which revealed the progression and degree of lesion induced by Cd. The confocal Raman spectroscopy provides a new perspective for in situ monitoring of substances changes in tissues, which exhibits more comprehensive understanding of the pathogenic mechanisms of heavy metals in molecular toxicology.

Biochar can mitigate methane emissions by improving methanotrophs for prolonged period in fertilized paddy soils.

Biochar application to fertilized paddy soils has been recommended as an effective countermeasure to mitigate methane (CH4) emissions, but its mechanism and effective duration has not yet been adequately elucidated. A laboratory incubation experiment was performed to gain insight into the combined effects of fresh and six-year aged biochar on potential methane oxidation (PMO) in paddy soils with ammonium or nitrate-amendment. Results showed that both ammonium and nitrate were essential for CH4 oxidation though high ammonium (4 mM) inhibited PMO as compared to low ammonium (1 mM and 2 mM), and that nitrate was better in promoting PMO than ammonium. Moreover, ammonium-amendment promoted type I pmoA, and nitrate-amendment enhanced type II pmoA abundance. Both fresh and aged biochar increased PMO as well as nitrification by enhancing the total, type I and type II methanotrophs as compared to the control. Increased soil PMO with mineral N input in both six-year aged biochar and fresh biochar amendment, indicating that biochar mitigated CH4 by promoting PMO for prolonged period in fertilized paddy soils.