Humic acids (HA) are a popular soil additive to reduce metal availability, but they have the drawbacks of reduced effectiveness over time and a significant reduction in soil pH. An alkaline humic ...acid fertilizer (AHAF) combining alkaline additives with HA was developed to overcome such drawbacks. A field experiment was conducted to investigate the effects of different AHAF application rates on the physicochemical properties, bioavailability, accumulation, and translocation of Cd and Zn heavy metals in Sauropus androgynus grown in acidic soil. Based on our results, the 100AF (100% AHAF) treatment significantly increased soil pH, cation exchange capacity (CEC), and organic matter content (OM) after one year of application. Compared with the control treatment (CK), the application of different rates of AHAF resulted in a 37.1-40.3% decrease in soil exchangeable Cd fractions (Exc-Cd) and an increase in the humic acid-bound Cd fractions (HA-Cd) Fe- and Mn-oxide-bound Cd fractions (OX-Cd), and organic matter-bound Cd fractions (OM-Cd) by 9.5-64.6%, 24.8-45.1%, and 158.8-191.2%, respectively (P < 0.05). The different AHAF treatments decreased the Res-Zn, Exc-Zn, and OM-Zn fractions by 69.6-73.0%, 7.4-23.9%, and 18.1-23.2%, respectively (P < 0.05), and increased the HA-Zn fraction by 8.4-28.1%. In the control treatment, the bioconcentration factors (BCFs) for Cd and Zn in different S. androgynus plant organs were in the following order: (Cd) Leaves > Stems > Branches > Roots > Edible branches; (Zn) Roots > Stems > Leaves > Branches > Edible branches. The transfer factors (TFs) of Cd and Zn in S. androgynus were classified as follows: TF2 > TF1 > TF3 > TF4. Thus, S. androgynus stems, and roots had a strong ability to transport Cd and Zn to the leaves. Compared with CK, the 100AF treatment significantly increased the BCFs for Zn in all plant parts (except BCFedible branches). In contrast, it significantly decreased all BCFs and TFs for Cd and the TF4 for Zn, effectively reducing Cd and Zn accumulation in the edible branches of S. androgynus. Soil pH, CEC, OM, and HA-M fraction were highly and significantly negatively correlated with Cd and Zn content in edible branches (P < 0.001). Stepwise multiple linear regression analysis revealed that the soil HA-M fraction was the key contributing factor for Zn accumulation and translocation in S. androgynus. Moreover, based on our findings, the absorption, uptake, and translocation of Cd and Zn were mainly determined by metal speciation and the pH in the soil. Moreover, the competitive antagonistic mechanisms between Zn and Cd absorption also affected their accumulation in S. androgynus. Thus, AHAF can be used as a soil amendment to sustainably improve acidic soils and effectively reduce Cd and Zn accumulation in edible branches of S. androgynus.
Peritoneal fibrosis (PF) is the main reason leading to declining efficiency and ultrafiltration failure of peritoneum, which restricts the application of peritoneal dialysis (PD). We aimed to ...investigate the effects and mechanisms of miR-122-5p on the PF. Sprague-Dawley (SD) rats were infused with glucose-based standard PD fluid to establish PF model. HE staining was performed to evaluate the extent of PF. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were performed to measure the expression level of miR-122-5p. Western blot was used to test the expression of transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-A, Fibronectin 1 (FN1), extracellular matrix protein 1 (ECM1), Smad5, α-smooth muscle actin (SMA), collagen type 1(COL-1), Vimentin, E-Cadherin, Wnt1, β-catenin, p-β-catenin, c-Myc, c-Jun, and Cyclin D1. Immunohistochemistry (IHC) staining was used to detect type I collagen alpha 1 (Col1α1), α-SMA, and E-Cadherin expression. We found PF was glucose concentration-dependently enhanced in peritoneum of PD rat. The PD rats showed increased miR-122-5p and decreased Smad5 expression. MiR-122-5p silencing improved PF and epithelial-mesenchymal transition (EMT) process in PD rats. MiR-122-5p silencing attenuated the activity of the Wnt/β-catenin signaling pathway. Importantly, dual-luciferase reporter assay showed Smad5 was a target gene of miR-122-5p. Smad5 overexpression significantly reversed the increases of PF and EMT progression induced by miR-122-5p overexpression. Moreover, miR-122-5p mimic activated Wnt/β-catenin activity, which was blocked by Smad5 overexpression. Overall, present results demonstrated that miR-122-5p overexpression showed a deterioration effect on PD-related PF by targeting Smad5 to activate Wnt/β-catenin pathway.
FT homologs are crucial for the flowering process, playing a vital role as ‘florigens’ in plants. In this study, we isolated and characterized an
FT
homolog,
FaFT1
, from cultivated strawberry. ...Nucleotide sequence analysis revealed a 531-bp open reading frame in
FaFT1
, encoding a putative protein with typical DPDxP and GxHR motifs belonging to the PEBP family proteins. For vegetative tissues or organs, qRT-PCR revealed that
FaFT1
was primarily expressed in leaves. Notably high expression levels were detected in flowers and fruits, including the pith and cortex of the receptacle. Analysis of potential putative
cis
-acting regulatory elements (
CREs
) in this gene promoter indicated that many of them are associated with plant hormonal responses and abiotic stress responses. Expression detection confirmed that GA
3
treatment enhanced the expression of
FaFT1
. When ectopically expressed in
Arabidopsis
,
FaFT1
could promote the flowering process under SD conditions. These results suggested the possible role of
FaFT1
in the regulation of reproductive development in cultivated strawberry.
Establishing diagnostic and prognostic biomarkers of primary central nervous system lymphoma (PCNSL) is a challenge. This study evaluated the value of dynamic interleukin (IL)-10 cerebrospinal fluid ...(CSF) concentrations for prognosis and relapse prediction in PCNSL.
Consecutive 40 patients newly diagnosed with PCNSL between April 2015 and April 2019 were recruited, and serial CSF specimens were collected by lumbar punctures (LP) or by Ommaya reservoir at diagnosis, treatment, and follow-up phase.
We confirmed that an elevated IL-10 cutoff value of 8.2 pg/mL for the diagnosis value of PCNSL showed a sensitivity of 85%. A persistent detectable CSF IL-10 level at the end of treatment was associated with poor progression-free survival (PFS) (836 vs. 481 days, p = 0.049). Within a median follow-up of 13.6 (2-55) months, 24 patients relapsed. IL-10 relapse was defined as a positive conversion in patients with undetectable IL-10 or an increased concentration compared to the last test in patients with sustained IL-10. IL-10 relapse was detected a median of 67 days (28-402 days) earlier than disease relapse in 10/16 patients.
This study highlights a new perspective that CSF IL-10 relapse could be a surrogate marker for disease relapse and detected earlier than conventional magnetic resonance imaging (MRI) scan. Further evaluation of IL-10 monitoring in PCNSL follow-up is warranted.
Nonalcoholic fatty liver disease (NAFLD) is a global health threat. Here, we presented the significant role of a novel signaling axis comprising long non-coding RNA maternally expressed gene 3 ...(MEG3), enhancer of zeste homolog 2 (EZH2), and sirtuin 6 (SIRT6) in controlling lipid accumulation, inflammation, and the progression of NAFLD. Mice fed with high-fat diet (HFD) were established as in vitro and in vivo NAFLD models, respectively. Lipid accumulation was measured by oil red O staining and assays for triglycerides or cholesterol. Inflammation was examined by ELISA for pro-inflammatory cytokines. Gene expressions were examined by RT-qPCR or Western blot. Interactions between key signaling molecules were examined by combining expressional analysis, RNA immunoprecipitation, cycloheximide stability assay, co-immunoprecipitation, and chromatin immunoprecipitation. MEG3 level was reduced in FFA-challenged hepatocytes or liver from HFD-fed mice, and the reduction paralleled the severity of NAFLD in clinic. Overexpressing MEG3 suppressed FFA-induced lipid accumulation or inflammation in hepatocytes. By promoting the ubiquitination and degradation of EZH2, MEG3 upregulated SIRT6, an EZH2 target. SIRT6 essentially mediated the protective effects of MEG3 in hepatocytes. Consistently, overexpressing MEG3 alleviated HFD-induced NAFLD in vivo. By controlling the expressions of genes involved in lipid metabolism and inflammation, the MEG3/EZH2/SIRT6 axis significantly suppressed lipid accumulation and inflammation in vitro, and NAFLD development in vivo. Therefore, boosting MEG3 level may benefit the treatment of NAFLD.
Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system lymphoma (PCNSL) that presents diagnostic challenges. Here, we focused on circulating cell-free DNA (cfDNA) ...and interleukin-10 (IL-10) isolated from cerebrospinal fluid. Twenty-three VRL patients (17 PVRL, 2 PCNSL/O, and 4 relapsed VRL, from 10/2018 to 12/2021) and 8 uveitis patients were included in this study. CSF samples from 19 vitreoretinal lymphoma patients had sufficient cfDNA for next-generation sequencing. Of these patients, 73.7% (14/19) had at least one meaningful non-Hodgkin lymphoma-related mutation. The characteristic
mutation was detected in the CSF of 12 VRL patients, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 63.2%, 100%, 100%, and 46.2%, respectively. No meaningful lymphoma related mutations were found in CSF samples from uveitis controls with typical intraocular lesions. Meanwhile, CSF IL-10 levels were elevated in 95.7% of the VRL patients, with a sensitivity, specificity, PPV, and NPV of 95.7%, 100%, 100% and 88.9%, respectively. Key somatic mutations like
and
detected from CSF cfDNA and elevated CSF IL-10 levels can be promising adjuncts for primary vitreoretinal lymphoma diagnosis.
The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome ...4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed—a member of the PDCD10-GCKIII kinase module we name PGCKA1. Genome-wide pooled overexpression screens using a barcoded library of human open reading frames identify chromosomal regions, including chr4p, that suppress proliferation when overexpressed in a context-dependent manner, implicating network interactions. Together, these results shed light on the early emergence of complex aneuploid karyotypes involving chr4p and adaptive landscapes shaping breast cancer genomes.
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•Chr4p loss evolves early in TNBC•Chr4p loss enhances growth•C4orf19 (PGCKA1) tumor suppressor
Kuzmin et al. report that chromosome 4p loss evolves early in triple-negative breast cancer (TNBC) and is associated with enhanced proliferation. C4orf19 (PGCKA1) is a tumor suppressor. Certain regions, including chr4p, suppress proliferation when overexpressed, differentially implicating network rewiring. This study illuminates the early emergence of complex aneuploid karyotypes in TNBC.
Peripheral T‐cell lymphoma (PTCL) is a heterogeneous disease with poor outcomes. We intend to explore the role of circulating PD‐1 (+) cells in tumor immune evasion in PTCL patients and the mechanism ...of chidamide as a regulator of immune‐associated medicine on PD‐1 (+) cells. Gene expression profiling (GEP) was performed on circulating PD‐1 (+) cells from 22 PTCL patients and 13 healthy subjects, and circulating PD‐1 (−) cells from 2 PTCL patients. PD‐1 (+) cells were treated with chidamide, and the production IFN‐γ and cytotoxicity were analyzed. GEP were performed on circulating PD‐1 (+) cells from 2 PTCL patients treated with chidamide combined with chemotherapy and 1 patient treated with traditional chemotherapy. GEP showed that genes associated with innate immune response were abnormally expressed in PD‐1 (+) cells of PTCL patients compared with healthy subjects, meanwhile the expression of CTLA‐4 was significantly higher in PD‐1 (+) cells than that of PD‐1 (−) cells. In vitro study revealed decreased level of IFN‐γ secretion and impaired cytotoxic activity of PD‐1 (+) cells compared with PD‐1 (−) cells, while chidamide could recover the deficiencies and upregulate adaptive immune‐associated genes in PD‐1 (+) cells of PTCL patients. Our research indicated that PD‐1 (+) cells might have deficiencies in innate and adaptive immune response and chidamide may reverse the defects.
These figures showed that the gene expression of PD‐1 (+) cells in peripheral blood of PTCL patients was different from that of healthy controls (Figures 1 and 2), and anti‐tumor effects of PD‐1 (+) cells were weaker than that of PD‐1 (‐) cells (Figures 3 and 4), while chidamide could normalize tumor immunity by regulating immune‐associated genes of PD‐1 (+) cells (Fig. 5).
Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system (CNS) lymphoma, for which currently there are no optimal treatment options. This prospective single-center ...study enrolled immunocompetent patients with newly diagnosed PVRL between August 2018 and January 2020. Patients received local and systemic therapies: intravitreal methotrexate (MTX, 400 μg, 0.1 mL) injections for 1 year (total 16 injections) and six cycles of the rituximab (375 mg/m
2
on day 1) and lenalidomide (25 mg on day 1–21; R2) regimen. Lenalidomide was maintained for 2 years in patients who had achieved a response. We enrolled 11 patients with a mean age of 58 (range, 48–70) years, of which 10 achieved complete remission at the first evaluation. The median follow-up period was 18.3 (range, 10.6–27.8) months, and the median progression-free survival was 12.7 months. Moreover, a total of eight patients relapsed. The most common adverse event (AE) was neutropenia, which occurred in seven patients (63.6%), followed by grade 3 ocular toxicities, including cataract formation, in six patients (54%). These findings suggest that the R2 regimen combined with intravitreal MTX, followed by lenalidomide maintenance, is a safe option for PVRL with moderate efficacy. This trial is registered with ClinicalTrials.gov (number NCT 03746223).
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