Hepatic mitochondrial NAD + transporter SLC25A47 activates AMPKα mediating lipid metabolism and tumorigenesis.

BACKGROUND AIMS: SLC25A47 was initially identified as a mitochondrial HCC-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism. APPROACH RESULTS: In the treatment of hepatocytes with metformin, we found that metformin can transcriptionally activate the expression of Slc25a47 , which is required for AMP-activated protein kinase α (AMPKα) phosphorylation. Slc25a47 -deficient mice had increased hepatic lipid content, triglycerides, and cholesterol levels, and we found that Slc25a47 deficiency suppressed AMPKα phosphorylation and led to an increased accumulation of nuclear SREBPs, with elevated fatty acid and cholesterol biosynthetic activities. Conversely, when Slc25a47 was overexpressed in mouse liver, AMPKα was activated and resulted in the inhibition of lipogenesis. Moreover, using a diethylnitrosamine-induced mouse HCC model, we found that the deletion of Slc25a47 promoted HCC tumorigenesis and development through the activated mammalian target of rapamycin cascade. Employing homology modeling of SLC25A47 and virtual screening of the human metabolome database, we demonstrated that NAD + was an endogenous substrate for SLC25A47, and the activity of NAD + -dependent sirtuin 3 declined in Slc25a47 -deficient mice, followed by inactivation of AMPKα. CONCLUSIONS: Our findings reveal that SLC25A47, a hepatocyte-specific mitochondrial NAD + transporter, is one of the pharmacological targets of metformin and regulates lipid homeostasis through AMPKα, and may serve as a potential drug target for treating NAFLD and HCC.

Association of Cardiovascular Health With Risk of Incident Depression and Anxiety.

OBJECTIVE: To investigate the association between cardiovascular health (CVH), defined by the American Heart Association's Life's Essential 8 (LE8) score, and incident depression and anxiety. DESIGN: A prospective cohort study using data from UK Biobank. SETTING: Participants were enrolled from March 2006 to October 2010. PARTICIPANTS: Participants without cardiovascular diseases and common mental disorders at baseline and having complete data on metrics of LE8 were included. MEASUREMENTS: CVH was assessed by LE8 score including eight components. The overall CVH was categorized as low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80). RESULTS: We included 115,855 participants (mean age: 55.7 years; female: 52.6%). During a median follow-up of 12.4 years, 3,194 (2.8%) and 4,005 (3.5%) participants had incident depression and anxiety, respectively. Compared with participants having low CVH, those having moderate and high CVH had 37% (HR = 0.63, 95% CI: 0.57-0.70) and 52% (HR = 0.48, 95% CI: 0.41-0.55) lower risk of incident depression. Similarly, moderate and high CVH were related to a lower risk of incident anxiety (HR = 0.81, 95% CI: 0.73-0.89 and HR = 0.68, 95% CI: 0.60-0.78). Restricted cubic spline showed that LE8 score was inversely related to incident depression and anxiety in a linear manner, and the risk of incident depression and anxiety decreased by 17% (HR = 0.83, 95% CI: 0.80-0.85) and 10% (HR = 0.90, 95% CI: 0.88-0.92) for 10-point increment in LE8 score, respectively. CONCLUSIONS: Higher CVH, evaluated by LE8 score, is strongly associated with a lower risk of incident depression and anxiety, suggesting the significance of optimizing CVH by adopting LE8.

Novel multi-target angiogenesis inhibitors as potential anticancer agents: Design, synthesis and preliminary activity evaluation.

Based on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cellswere 0.078 µmol/L and 0.068 µmol/L, respectively. The cytotoxicity evaluation indicated that TC9, TA11, TM4, and TH3 displayed good safety against HEK293T cells. TH2 and TH3 could induce apoptosis of MCF-7 cells. Molecular modeling and ADMET prediction results indicated that most of target compounds showed promising medicinal properties, which was consistent with the experimental results. Our findings provided new lead compounds for the structural optimization of multi-target angiogenesis inhibitors.

Molecular mechanisms underlying human spatial cognitive ability revealed with neurotransmitter and transcriptomic mapping.

Mental rotation, one of the cores of spatial cognitive abilities, is closely associated with spatial processing and general intelligence. Although the brain underpinnings of mental rotation have been reported, the cellular and molecular mechanisms remain unexplored. Here, we used magnetic resonance imaging, a whole-brain spatial distribution atlas of 19 neurotransmitter receptors, transcriptomic data from Allen Human Brain Atlas, and mental rotation performances of 356 healthy individuals to identify the genetic/molecular foundation of mental rotation. We found significant associations of mental rotation performance with gray matter volume and fractional amplitude of low-frequency fluctuations in primary visual cortex, fusiform gyrus, primary sensory-motor cortex, and default mode network. Gray matter volume and fractional amplitude of low-frequency fluctuations in these brain areas also exhibited significant sex differences. Importantly, spatial correlation analyses were conducted between the spatial patterns of gray matter volume or fractional amplitude of low-frequency fluctuations with mental rotation and the spatial distribution patterns of neurotransmitter receptors and transcriptomic data, and identified the related genes and neurotransmitter receptors associated with mental rotation. These identified genes are localized on the X chromosome and are mainly involved in trans-synaptic signaling, transmembrane transport, and hormone response. Our findings provide initial evidence for the neural and molecular mechanisms underlying spatial cognitive ability.

Role of reactive oxygen species in myelodysplastic syndromes.

Reactive oxygen species (ROS) serve as typical metabolic byproducts of aerobic life and play a pivotal role in redox reactions and signal transduction pathways. Contingent upon their concentration, ROS production not only initiates or stimulates tumorigenesis but also causes oxidative stress (OS) and triggers cellular apoptosis. Mounting literature supports the view that ROS are closely interwoven with the pathogenesis of a cluster of diseases, particularly those involving cell proliferation and differentiation, such as myelodysplastic syndromes (MDS) and chronic/acute myeloid leukemia (CML/AML). OS caused by excessive ROS at physiological levels is likely to affect the functions of hematopoietic stem cells, such as cell growth and self-renewal, which may contribute to defective hematopoiesis. We review herein the eminent role of ROS in the hematological niche and their profound influence on the progress of MDS. We also highlight that targeting ROS is a practical and reliable tactic for MDS therapy.

Observing the Evolution of Metal Oxides in Liquids.

Metal oxides with diverse compositions and structures have garnered considerable interest from researchers in various reactions, which benefits from transmission electron microscopy (TEM) in determining their morphologies, phase, structural and chemical information. Recent breakthroughs have made liquid-phase TEM a promising imaging platform for tracking the dynamic structure, morphology, and composition evolution of metal oxides in solution under work conditions. Herein, this review introduces the recent advances in liquid cells, especially closed liquid cell chips. Subsequently, the recent progress including particle growth, phase transformation, self-assembly, core-shell nanostructure growth, and chemical etching are introduced. With the late technical advances in TEM and liquid cells, liquid-phase TEM is used to characterize many fundamental processes of metal oxides for CO2 reduction and water-splitting reactions. Finally, the outlook and challenges in this research field are discussed. It is believed this compilation inspires and stimulates more efforts in developing and utilizing in situ liquid-phase TEM for metal oxides at the atomic scale for different applications.

Multi-objective genetic algorithm for synchrotron radiation beamline optimization.

In beamline design, there are many floating parameters that need to be tuned; manual optimization is time-consuming and laborious work, and it is also difficult to obtain well optimized results. Moreover, there are always several objectives that need to be considered and optimized at the same time, making the problem more complicated. For example, asking for both the flux and energy to be as large as possible is a usual requirement, but the changing trends of these two variables are often contradictory. In this study, a novel optimization method based on a multi-objective genetic algorithm is introduced, the first attempt to optimize a beamline with multiple objectives. In order to verify this method, beamline ID17 of the European Synchrotron Radiation Facility (ESRF) is taken as an example for simulation, with energy and dose rate as objectives. The result shows that this method can be effective for beamline optimization, and an optimal solution set can be obtained within 30 generations. For the solutions whose objectives are both improved compared with those of ESRF beamline ID17, the maximums of energy and dose rate increase by around 7% and 20%, respectively.

Targeting SMYD2 inhibits prostate cancer cell growth by regulating c-Myc signaling.

SMYD2 is a lysine histone methyl transferase involved in various cancers epigenetically via methylating histone H3K4, and H3K36. c-Myc is one of the major drivers of prostate cancer (PCa) initiation and progression. The roles of SMYD2 in PCa and the regulators of c-Myc activity in PCa are still under-researched. SMYD2 expression and survival outcomes in PCa cohorts were analyzed by bioinformatics analysis. SMYD2 protein levels were detected in PCa tissues by immunohistochemistry. SMYD2 knockdown cells were established to identify the effects of SMYD2 on cell growth in vitro and in vivo. GSEA and RNA sequencing were adopted to reconnoiter the signaling regulated by SMYD2 in PCa. The relationship between SMYD2 and c-Myc was examined by western blot analysis, qPCR, and immunohistochemistry. SMYD2 specific inhibitor-AZ505 was used to pharmacologically inhibit SMYD2 function in vitro and in vivo. SMYD2 expression increased in PCa tissues compared with benign prostate tissues and higher SMYD2 expression was associated with a higher risk of biochemical relapse after radical prostatectomy. SMYD2 knockdown inhibited the growth of PCa cells both in vitro and in vivo. Furthermore, high SMYD2 levels conduced to activated c-Myc signaling in PCa cells. Importantly, the pharmacological intervention of SMYD2 by AZ505 significantly repressed PCa cell growth both in vitro and in vivo. Our findings indicate that SMYD2 inhibition restrains PCa cell proliferation by regulating c-Myc signaling and provide evidence for the potential practice of SMYD2 targeting in the treatment of PCa.

Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers.

Serpin family A member 1 (SERPINA1) encodes a protease inhibitor participating in many human diseases, but its value in immunoregulation and prognosis of human cancers remains unclear. In this study, through comprehensive analysis of data from The Cancer Genome Atlas (TCGA) datasets, we found that SERPINA1 was dysregulated in many cancers compared with normal tissues. SERPINA1 expression was significantly associated with prognosis, immune subtype, molecular subtype, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), and the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) score. There was a strong connection between SERPINA1 expression and tumor-infiltrating lymphocytes, and SERPINA1 showed significant relation to gene markers of immune cells in digestive tumors. Fluorescence-based multiplex immunohistochemistry confirmed that SERPINA1 protein expression was related to clinicopathologic features and immune infiltrates in hepatic cancer. This study suggests that SERPINA can potentially serve as a novel biomarker for cancer prognosis and immunotherapy.

Localized Ligands Assist Ultrafast Multivalent-Cation Intercalation Pseudocapacitance.

Rechargeable batteries based on multivalent cation (Mvn+ , n>1) carriers are considered potentially low-cost alternatives to lithium-ion batteries. However, the high charge-density Mvn+ carriers generally lead to sluggish kinetics and poor structural stability in cathode materials. Herein, we report an Mvn+ storage via intercalation pseudocapacitance mechanism in a 2D bivalve-like organic framework featured with localized ligands. By switching from conventional intercalation to localized ligand-assisted-intercalation pseudocapacitance, the organic cathode exhibits unprecedented fast kinetics with little structural change upon intercalation. It thus enables an excellent power density of 57 kW kg-1 over 20000 cycles for Ca2+ storage and a power density of 14 kW kg-1 with a long cycling life over 45000 cycles for Zn2+ storage. This work may provide a largely unexploited route toward constructing a local dynamic coordination microstructure for ultrafast Mvn+ storage.

Extracellular vesicle-derived long non-coding RNA as circulating biomarkers for endometriosis.

RESEARCH QUESTION: Could extracellular vesicle-derived long non-coding RNA (lncRNA) serve as promising circulating biomarkers for endometriosis? DESIGN: To obtain novel diagnostic markers, 85 patients with endometriosis were enrolled as the endometriosis group and 86 unaffected participants as the control group. RNA sequencing was performed to identify extracellular vesicle-derived lncRNA that were differentially expressed between women with endometriosis (n = 5) and unaffected participants (n = 6). Messenger RNA and lncRNA sequences of the plasma extracellular vesicles were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. lncRNA expression levels were further validated using quantitative reverse transcriptase polymerase chain reaction. Moreover, receiver operating characteristic curve analysis was performed to determine the diagnostic value of candidate lncRNA. Clinical features were correlated to the expression levels of candidate lncRNA. RESULTS: It was found that 210 lncRNA were significantly dysregulated; among these, expression of LINC01569, RP3-399L15.2, FAM138B and CH507-513H4.6 was significantly decreased, whereas expression of RP11-326N17.2, KLHL7-AS1 and MIR548XHG was increased, in the plasma of patients with endometriosis. Combined expression level of RP3-399L15.2 and CH507-513H4.6 was used to distinguish patients with endometriosis from control participants; the results revealed a sensitivity of 80.00% and specificity of 85.45% at the cut-off point, and an area under the ROC curve of 0.9045. The findings demonstrated the potential of these two lncRNA as diagnostic biomarkers for endometriosis. Moreover, CH507-513H4.6 alone may be useful in detecting early-stage endometriosis lesions. CONCLUSIONS: The combination of RP3-399L15.2 and CH507-513H4.6 may be a potential candidate for endometriosis biomarkers.

Presence of CD133-positive circulating tumor cells predicts worse progression-free survival in patients with metastatic castration-sensitive prostate cancer.

OBJECTIVE: To investigate the clinical significance of the expression of the stemness marker CD133 in circulating tumor cells of newly diagnosed metastatic castration-sensitive prostate cancer patients. METHODS: For this study, 104 metastatic castration-sensitive prostate cancer patients treated at the Fudan University Shanghai Cancer Center from September 2015 to February 2017 were considered. After enrollment, the patients received androgen deprivation therapy (bicalutamide + goserelin). Circulating tumor cells were isolated and identified using the CanPatrol system, which can identify not only traditional epithelial markers but also mesenchymal markers in cells that have undergone epithelial mesenchymal transition. CD133 was used to characterize the circulating tumor cells. The primary endpoint of this research was to evaluate progression to castration resistance. RESULTS: Among the 104 patients enrolled, 89 patients were circulating tumor cell positive at baseline, and the median circulating tumor cell count was four. The median follow-up was 24 months, and at the end of follow-up, the proportion of patients who progressed to castration-resistant prostate cancer in the CTC+CD133+ group was 93.3%, which was significantly higher than that of the circulating tumor cell negative group (73.3%) and the CTC+CD133- group (75.0%), with P = 0.043. After follow-up, progression-free survival for CTC+CD133+, CTC+CD133-, and circulating tumor cell patients was 10.0, 13.0, and 14.0 months, respectively, with P = 0.022. Univariate and multivariate analyses also confirmed that the characterization of circulating tumor cells using CD133 can independently predict progression-free survival in metastatic castration-sensitive prostate cancer patients after receiving androgen deprivation therapy (P = 0.042; hazard ratio 1.396). CONCLUSION: Baseline CTC+CD133+ was a poor independent prognostic factor for metastatic castration-sensitive prostate cancer patients to progress to castration-resistant prostate cancer after receiving androgen deprivation therapy.

Comprehensive preimplantation genetic testing by massively parallel sequencing.

STUDY QUESTION: Can whole genome sequencing (WGS) offer a relatively cost-effective approach for embryonic genome-wide haplotyping and preimplantation genetic testing (PGT) for monogenic disorders (PGT-M), aneuploidy (PGT-A) and structural rearrangements (PGT-SR)? SUMMARY ANSWER: Reliable genome-wide haplotyping, PGT-M, PGT-A and PGT-SR could be performed by WGS with 10× depth of parental and 4× depth of embryonic sequencing data. WHAT IS KNOWN ALREADY: Reduced representation genome sequencing with a genome-wide next-generation sequencing haplarithmisis-based solution has been verified as a generic approach for automated haplotyping and comprehensive PGT. Several low-depth massively parallel sequencing (MPS)-based methods for haplotyping and comprehensive PGT have been developed. However, an additional family member, such as a sibling, or a proband, is required for PGT-M haplotyping using low-depth MPS methods. STUDY DESIGN, SIZE, DURATION: In this study, 10 families that had undergone traditional IVF-PGT and 53 embryos, including 13 embryos from two PGT-SR families and 40 embryos from eight PGT-M families, were included to evaluate a WGS-based method. There were 24 blastomeres and 29 blastocysts in total. All embryos were used for PGT-A. Karyomapping validated the WGS results. Clinical outcomes of the 10 families were evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS: A blastomere or a few trophectoderm cells from the blastocyst were biopsied, and multiple displacement amplification (MDA) was performed. MDA DNA and bulk DNA of family members were used for library construction. Libraries were sequenced, and data analysis, including haplotype inheritance deduction for PGT-M and PGT-SR and read-count analysis for PGT-A, was performed using an in-house pipeline. Haplotyping with a proband and parent-only haplotyping without additional family members were performed to assess the WGS methodology. Concordance analysis between the WGS results and traditional PGT methods was performed. MAIN RESULTS AND THE ROLE OF CHANCE: For the 40 PGT-M and 53 PGT-A embryos, 100% concordance between the WGS and single-nucleotide polymorphism (SNP)-array results was observed, regardless of whether additional family members or a proband was included for PGT-M haplotyping. For the 13 embryos from the two PGT-SR families, the embryonic balanced translocation was detected and 100% concordance between WGS and MicroSeq with PCR-seq was demonstrated. LIMITATIONS, REASONS FOR CAUTION: The number of samples in this study was limited. In some cases, the reference embryo for PGT-M or PGT-SR parent-only haplotyping was not available owing to failed direct genotyping. WIDER IMPLICATIONS OF THE FINDINGS: WGS-based PGT-A, PGT-M and PGT-SR offered a comprehensive PGT approach for haplotyping without the requirement for additional family members. It provided an improved complementary method to PGT methodologies, such as low-depth MPS- and SNP array-based methods. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the research grant from the National Key R&D Program of China (2018YFC0910201 and 2018YFC1004900), the Guangdong province science and technology project of China (2019B020226001), the Shenzhen Birth Defect Screening Project Lab (JZF No. [2016] 750) and the Shenzhen Municipal Government of China (JCYJ20170412152854656). This work was also supported by the National Natural Science Foundation of China (81771638, 81901495 and 81971344), the National Key R&D Program of China (2018YFC1004901 and 2016YFC0905103), the Shanghai Sailing Program (18YF1424800), the Shanghai Municipal Commission of Science and Technology Program (15411964000) and the Shanghai 'Rising Stars of Medical Talent' Youth Development Program Clinical Laboratory Practitioners Program (201972). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Universality of mesoporous coal gasification slag for reinforcement and deodorization in four common polymers.

Mesoporous adsorbents and polymer deodorants are difficult to implement on a large scale because of their complicated preparation methods. Herein, a mesoporous adsorbent (CGSA) with a specific surface area of 564 m2g-1and a pore volume of 0.807 cm3g-1was prepared from solid waste coal gasification slag using a simple acid leaching process. The adsorption thermodynamics and adsorption kinetics results verified that the adsorption mechanism of propane on CGSA was mainly physisorption. Then the universality of CGSA in different polymers was investigated by introducing CGSA and its commercialized counterparts (CaCO3, and zeolite) into four common polymers. When the filler content was 30 wt%, the average reinforcement effect of CGSA on the tensile, flexural, and impact strengths of the four polymers was 46.68%, 83.62%, and 211.90% higher than that of CaCO3, respectively. Gas chromatography results also showed that CGSA significantly decreased total volatile organic compound emissions from the composites, and its optimal deodorization performance reached 69.58%, 81.33%, and 91.09% for different polymers, respectively, far exceeding that of zeolite. Therefore, this study showed that low-cost, high-performance, and multifunctional mesoporous polymer fillers with excellent universality can be manufactured from solid contaminants.

Dynamic content changes of cordycepin and adenosine and transcriptome in Cordyceps kyushuensis Kob at different fermentation stages.

20% (w/w) Astragali radix was added to the rice medium to cultivate C. kyushuensis Kob. The fermentation product was collected at mycelium stage, coloring stage, stromata-forming initial stage and fruiting body stage of C. kyushuensis Kob. The dynamic content changes of cordycepin and adenosine were detected at different fermentation stages. In the rice medium with Astragalus radix, both cordycepin and adenosine reached the highest content value on the 30th day of fermentation, 17.31 mg/g and 0.94 mg/g, respectively, which were 8.6 times and 2.0 times of that in rice medium at the same stage. At the same time, transcriptomics technology was used to analyze C. kyushuensis Kob during these four periods.

[Prenatal diagnosis of spinal muscular atrophy using multiple ligation-dependent probe amplification].

OBJECTIVE: To carry out prenatal diagnosis for families with high risk for spinal muscular atrophy (SMA) by using multiplex ligation-dependent probe amplification (MLPA). METHODS: Twenty-one families were enrolled. MLPA was used to detect copy numbers of SMN1 and SMN2 genes. Maternal contamination was excluded by using a short tandem repeat method. RESULTS: For 23 fetuses from the 21 families, 14 were identified as carriers, 1 as SMA patient, and 8 as normal. By linkage analysis of parental samples, three individuals were determined as silent (2+0) carriers. CONCLUSION: MLPA can determine the carrier status of SMA. The identification of three silent (2+0) carriers among the 44 parental samples indicated a risk for such families, for which genetic counseling and reproduction guidance should be provided.

The effect of blastomere loss during frozen embryo transfer on the transcriptome of offspring's umbilical cord blood.

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.

Removal of Zn(II), Mn(II) and Cu(II) by adsorption onto banana stalk biochar: adsorption process and mechanisms.

Low-cost banana stalk (Musa nana Lour.) biochar was prepared using oxygen-limited pyrolysis (at 500 °C and used), to remove heavy metal ions (including Zn(II), Mn(II) and Cu(II)) from aqueous solution. Adsorption experiments showed that the initial solution pH affected the ability of the biochar to adsorb heavy metal ions in single- and polymetal systems. Compared to Mn(II) and Zn(II), the biochar exhibited highly selective Cu(II) adsorption. The adsorption kinetics of all three metal ions followed the pseudo-second-order kinetic equation. The isotherm data demonstrated the Langmuir model fit for Zn(II), Mn(II) and Cu(II). The results showed that the chemical adsorption of single molecules was the main heavy metal removal mechanism. The maximum adsorption capacities (mg·g-1) were ranked as Cu(II) (134.88) > Mn(II) (109.10) > Zn(II) (108.10)) by the single-metal adsorption isotherms at 298 K. Moreover, characterization analysis was performed using Fourier transform infrared spectroscopy, the Brunauer-Emmett-Teller method, scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The results revealed that ion exchange was likely crucial in Mn(II) and Zn(II) removal, while C-O, O-H and C = O possibly were key to Cu(II) removal by complexing or other reactions.

Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology.

The eutopic endometrium has been suggested to play a crucial role in the pathogenesis of adenomyosis. However, the specific genes in eutopic endometrium responsible for the pathogenesis of adenomyosis still remain to be elucidated. We aim to identify differentially expressed genes (DEGs) and molecular pathways/networks in eutopic endometrium from adenomyosis patients and provide a new insight into disease mechanisms at transcriptome level. RNA sequencing (RNA-Seq) was performed with 12 eutopic endometrium from adenomyosis and control groups. Differentially expressed genes in adenomyosis were validated by quantitative real-time PCR (qPCR) and immunochemistry. Functional annotations of the DEGs were analysed with Ingenuity Pathway Analysis (IPA). Quantitative DNA methylation analysis of CEBPB was performed with MassArray system. A total of 373 differentially expressed genes were identified in the adenomyosis eutopic endometrium compared to matched controls. Bioinformatic analysis predicted that IL-6 signalling and ERK/MAPK signalling were activated in adenomyosis endometrium. We also found that the increased expression and DNA hypomethylation of CEBPB were associated with adenomyosis. Our results revealed key pathways and networks in eutopic endometrium of adenomyosis. The study is the first to propose the association between C/EBPß and adenomyosis and can improve the understanding of the pathogenesis of adenomyosis.

CD19+ tumor-infiltrating B-cells prime CD4+ T-cell immunity and predict platinum-based chemotherapy efficacy in muscle-invasive bladder cancer.

PURPOSE: CD19+ tumor-infiltrating B-cells (CD19+ TIB) play a crucial role in tumorigenesis, but their clinical relevance in muscle-invasive bladder cancer (MIBC) remains unknown. This study aimed to investigate the prognostic value of CD19+ TIB for post-surgery survival and adjuvant chemotherapy response in MIBC. EXPERIMENTAL DESIGN: We assessed TIB by immunohistochemical staining of CD19 in 246 MIBC patients from Zhongshan Hospital and Shanghai Cancer Center. We evaluated the survival benefit of platinum-based chemotherapy according to CD19+ TIB. The mechanism underlying CD19+ TIB antitumor immunity was explored through the Cancer Genome Atlas (TCGA) dataset analysis and an in vitro Ag presentation assay. RESULTS: CD19+ TIB extensively infiltrated into the tumor stroma of MIBC. Adjuvant chemotherapy (ACT) led to a significantly increased benefit in the high CD19+ TIB MIBC patients (P = 0.003). In multivariate analysis, high CD19+ TIB MIBC patients had significantly longer OS with ACT in the discovery set (HR = 0.487, P = 0.038). TCGA gene expression analyses showed enrichment of adaptive immunity, T-cell-mediated immunity, and antigen-presentation signaling pathways in high CD19+ TIB MIBC patients. Moreover, CD19+ TIB co-localized with activated CD4+ TIT and expressed surface markers characteristic of antigen-presenting cells. Finally, an antigen-presentation assay demonstrated the antigen-presentation function of CD19+ TIB. CONCLUSION: CD19+ TIB was identified as an independent prognostic factor, which could predict for post-surgery survival and platinum-based ACT benefits in MIBC. CD19+ TIB serve as antigen-presenting cells (APCs) to activate CD4+ TIT in the tumor environment of MIBC.