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1.
BMC Psychiatry ; 21(1): 483, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607594

RESUMO

BACKGROUND: Schizophrenia is a polygenic disease; however, the specific risk genetic variants of schizophrenia are still largely unknown. Single nucleotide polymorphism (SNP) is important genetic factor for the susceptibility of schizophrenia. Investigating individual candidate gene contributing to disease risk remains important. METHODS: In a case-control study, five SNPs located in 6p21.3-p23.1 including rs2021722 in human leukocyte antigen (HLA) locus and rs107822, rs383711, rs439205 and rs421446 within the upstream of microRNA-219a-1 were genotyped in 454 schizophrenia patients and 445 healthy controls to investigate the possible association between the loci and schizophrenia in a Han Chinese population. RESULTS: Our results showed significant associations between the rs2021722 and schizophrenia in allele (A vs. G: adjusted OR = 1.661, 95%CI = 1.196-2.308), co-dominant (AG vs. GG: OR = 1.760, 95%CI = 1.234-2.510) and dominant genetic model (AG + AA vs. GG: OR = 1.756, 95%CI = 1.237-2.492), respectively. Haplotype analysis showed that TGGT and CAAC were protective factor for schizophrenia compared with TAAC haplotype (OR = 0.324, 95% CI = 0.157-0.672; OR = 0.423, 95% CI = 0.199-0.900). CONCLUSIONS: These findings indicate that rs2021722 in HLA locus might be involved in pathogenesis of schizophrenia and that genotypes AG and allele A of the locus are risk factors for schizophrenia in the Han Chinese population, confirming the association between immune system and schizophrenia.

2.
Biometals ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599706

RESUMO

Selenium is an essential trace element that can regulate the function of immnue cells via selenoproteins. However, the effects of selenium on human dendritic cell (DCs) remain unclear. Thus, selenoprotein levels in monocytes, immature DCs (imDCs) and mature DCs (mDCs) treated with or without Na2SeO3 were evaluated using RT-PCR, and then the immune function of imDCs and mDCs was detected by flow cytometry, cell counting and the CCK8 assay. In addition, the effects of Se on cytokine and surface marker expression were investigated by RT-PCR. The results revealed different expression levels of selenoprotein in monocytes, imDCs and mDCs, and selenoproeins could be regulated by Se. Moreover, it was indicated that anti-phagocytic activity was improved by 0.1 µM Se, whereas it was suppressed by 0.2 µM Se in imDCs; The migration of imDCs and mDCs was improved by 0.1 µM Se, whereas their migration was inhibited by treatment with 0.05 or 0.2 µM Se; The mixed lymphocyte reaction of mDCs was improved by 0.1 µM Se, and it was inhibited by 0.05 and 0.2 µM Se. In addition, 0.1 µM Se improved the immune function of DCs through the regulation of CD80, CD86, IL12-p35 and IL12-p40. Wheres 0.05 and 0.2 µM Se impaired immune function of DCs by up-regulation of interleukin (IL-10) in imDCs and down-regulation of CD80, CD86, IL12-p35 and IL12-p40 in mDCs. In conclusion, 0.1 µM Se might improve the immune function of human DCs through selenoproteins.

3.
Circ Arrhythm Electrophysiol ; : CIRCEP121010082, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34587755

RESUMO

BACKGROUND: The cellular mechanism of focal, idiopathic right ventricular outflow tract (RVOT) tachycardia is thought to be due to cAMP-mediated triggered activity. A potential molecular mechanism has not yet been determined. We identified and characterized a novel missense somatic mutation in the gene (GNAS) encoding the Gsα (stimulatory G protein alpha-subunit) from a patient with RVOT tachycardia that is proposed to be the etiology of the clinical tachycardia. METHODS: Percutaneous endomyocardial biopsies were obtained from multiple sites in a patient with nonexertional, repetitive monomorphic RVOT tachycardia. Sequencing of extracted genomic DNA identified a Gsα W234R variant only at the site of tachycardia origin. Functional studies using in vitro transfection with S49 cyc- murine lymphoma cells and measurement of cyclic AMP levels were performed. A trypsin protection assay assessed GTP binding kinetics and structural modeling predicted the impact of the mutation on protein-protein interactions. Whole-cell patch clamp experiments of transfected CHO cells assessed the downstream effects of the mutation. RESULTS: In vitro studies of the GNAS mutation (W234R) demonstrated basal levels of cAMP ≈16-fold higher than wild-type cells, consistent with constitutive stimulation of Gsα. Mutant Gsα was partially protected from proteolysis after incubation with GTP, indicating diminished GTPase activity and reduced GTP hydrolysis as the mechanism for increased basal intracellular cAMP levels. Transfected mutant CHO cells increased unstimulated mean peak L-type calcium channel current density by ≈50% and in silico modeling demonstrated spontaneous delayed afterdepolarizations and triggered activity. CONCLUSIONS: We identified a novel somatic mutation in GNAS associated with RVOT tachycardia. The mutation results in constitutive activation of Gsα, impairs GTP hydrolysis, and elevates basal cAMP levels, leading to enhanced L-type calcium current and triggered activity. These findings confirm that RVOT tachycardia can be caused by somatic mutations in signal transduction proteins that regulate intracellular cAMP and its downstream effectors.

4.
Bioengineered ; 12(1): 5830-5838, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34488538

RESUMO

MicroRNAs (miRNAs) have been proved to be involved in many biological processes during tumorigenesis and progression, including cell proliferation and cell cycle progression. However, the potential role of miR-26b-5p in tongue squamous cell carcinoma (TSCC) remains unclear. In the present study, we demonstrated that miR-26b-5p was decreased in TSCC tissues in both TCGA-TSCC subset and eight paired samples from TSCC patients, while Proline Rich 11 (PRR11) was obviously increased. Transfection of miR-26b-5p mimics inhibited CALL7 cell proliferation by arresting the cells at the S/G2 transition. Meanwhile, miR-26b-5p inhibitor had the opposite biological functions. The results of luciferase activity and RNA-pulldown assays indicated that miR-26b-5p directly targeted the PRR11 3' -untranslated region in CAL27 cells. Furthermore, the effects of miR-26b-5p on cell cycle regulation were reversed after treatment with siRNA against PRR11. In summary, our findings indicate that miR-26b-5p induce cell cycle arrest in TSCC by targeting PRR11. Hence, targeting miR-26b-5p could be a promising therapeutic strategy for the treatment of TSCC.

5.
J Invest Dermatol ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34571002

RESUMO

STING agonists are a new class of drugs for cancer immunotherapy that activate both innate and adaptive antitumor immunity. Recently, multiple clinical trials of STING agonists have been conducted in hematological malignancies and solid tumors. However, STING is commonly suppressed in melanoma via mechanisms that remain unclear. We found that STING expression was epigenetically suppressed by H3K27me3 in melanoma, and EZH2 inhibitor could induce an H3K27 shift from trimethylation to acetylation, resulting in increased expression of STING. Furthermore, a combination of STING agonist and EZH2 inhibitor upregulated major histocompatibility complex (MHC) class I expression and chemokines production. Whole-transcriptome analysis showed that type I interferon-related genes were significantly upregulated in the combination treatment group. In addition, the combination treatment synergistically reduced tumor growth and increased CD8+ T cell infiltration in a poorly immunogenic melanoma mouse model B16-F10. These results demonstrated a novel mechanism underlying the epigenetic regulation of STING expression in melanoma; combination of STING agonists and EZH2 inhibitors can boost the antitumor immune response and would be a promising treatment option for melanoma patients refractory to current immunotherapies.

6.
Eur J Cancer ; 156: 83-92, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34425407

RESUMO

PURPOSE: The combination of vascular endothelial growth factor receptor (VEGFR) inhibitor and programmed cell death-1 (PD-1) blockade provides promising therapeutic opportunities for advanced mucosal melanoma in early phase trials. The aim of this retrospective study was to evaluate the efficacy and safety of the combination regimen for advanced mucosal melanoma in the real world. METHODS: Patients with advanced mucosal melanoma received an anti-PD-1 antibody plus the VEGFR inhibitor axitinib until confirmed disease progression or unacceptable toxicity. In addition, those with liver metastasis were allowed to take hepatic transcatheter arterial chemoembolisation (TACE). The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), time to treatment failure (TTF), duration of response (DOR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: Eighty-one and sixty-six patients received axitinib plus immunotherapy as first-line and salvage therapy, respectively. Overall, ORR was 24.5% (95% CI, 17.3-31.6), DCR was 72.7% (95% CI, 65.3-80.1). Median TTF, DOR and OS were 5.2 months (95% CI, 3.7-6.6), 9.2 months (95% CI, 7.2-11.2) and 11.1 months (95% CI, 7.2-15.0). ORR was 30.0% (95% CI, 19.7-40.3) and 17.5% (95% CI, 7.8-27.1) as first-line and salvage therapy, respectively. No statistical difference among the primary sites was noted for ORR. The ORR of patients with liver metastasis with or without hepatic TACE was 26.1% (95% CI, 6.7-45.5) and 15.0% (95% CI, 2.1-32.1), respectively (P = 0.467). Elevated LDH and poor ECOG status are negative predictive factors. CONCLUSION: This is the largest analysis of anti-PD-1 plus VEGFR inhibitor therapy for mucosal melanoma to date. Immunotherapy plus anti-angiogenesis is applicable for advanced mucosal melanoma, especially as front-line. Hepatic TACE might act synergistically with systemic immunotherapy and anti-angiogenesis.

7.
Inorg Chem ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351141

RESUMO

Despite the numerous titanium-oxo clusters (TOCs) which have been reported, the nature of small clusters (nuclearity < 10) as model compounds showed large deviation from that of nanoscale TiO materials. Therefore, theoretical and experimental studies for large TOCs merit more attention. We recently prepared and crystallographically characterized a series of large TOCs: Ti11O15(OiPr)16(Cophen) (1), Ti11O15(OiPr)16(Mnphen) (2), Ti10O14(OEt)16(Mnphen)2 (3), and Ti10O14(OEt)16(Mnphphen)2 (4) (phen = 1,10-phenanthroline, phphen = 4,7-biphenyl-phen). These compounds are derivatives of a Ti12 parent cluster by replacing one or two of the five-coordinated titanium atoms of the Ti12 cluster with a transition metal M, Co(II) and Mn(II), that is chelated by a phen group. The effects of mono- and bis-substituted Mphen on the charge and structure of the clusters are discussed. Theoretical evaluation of the frontier orbitals of the clusters is carried out on the basis of the precisely defined crystal structures. Different from the dye molecule to TiO core charge transfer for the dye-modified TOCs, charge transfer in these clusters is from TiO/TiOM to phen/Mphen. The effects of different metal ions and the number of substituted Mphen moieties on the photocurrent properties are evaluated. The results will be of interest to research on cluster chemistry, especially on the TOC chemistry.

8.
Ann Thorac Surg ; 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34343475

RESUMO

BACKGROUND: Pulmonary aspergilloma is chronic and invasive, potentially leading to life-threatening massive hemoptysis. The role of surgery for treating pulmonary aspergilloma and its effect on long-term survival need more study. METHODS: We reviewed 166 patients with aspergillomas treated at Shanghai Pulmonary Hospital from 2004 to 2017. Surgery indications included destroyed lung parenchyma, recurrent hemoptysis despite appropriate medical treatment and isolated pulmonary nodules suspected to be aspergilloma. Pulmonary aspergillomas are classified as simple (in an isolated thin-walled cavity, ≤3 mm) or complex (a thick-walled cyst, >3 mm) based on CT scan findings. RESULTS: Aspergilloma was complex in 100 (60.2%) patients and simple in 66 (39.8%) patients. The median size of complex aspergillomas (2.5 [0.3-8.0] cm) was larger than that (2.0 [0.2-6.0] cm) of simple types (p<0.001). Hemoptysis occurred in 72 (72%) patients with complex disease and 35 (53%) with simple disease (p=0.014). Video-assisted thoracoscopic surgeries were performed in 42 (63.6%) simple aspergillomas, while 75 (75%) of complex aspergillomas patients underwent thoracotomy. Prolonged air leakage (>7d) was the most (17, [10.2%]) common postoperative complication. One (0.6%) patient had postoperative bronchopleural fistula. One (0.6%) patient died within 30 days postoperatively due to respiratory failure. Two (1.2%) patients experienced recurrence during follow-up. The overall 10-year survival rates of complex and simple aspergillomas were 87.7% and 94.97% (p=0.478). Diabetes (12, [7.2%], HR [95% CI] = 13.15(1.12-154.46)) was associated with a worse prognosis. CONCLUSIONS: The perioperative morbidity and mortality of pulmonary aspergillomas are acceptable. Overall survival rates of simple and complex types are comparable.

9.
Ann Thorac Surg ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34428431

RESUMO

BACKGROUND: This study aims to investigate the oncological outcomes of video-assisted thoracoscopic (VATS) left upper tri-segmentectomy (LTS) versus left upper lobectomy (LUL) for patients presenting with stage I non-small-cell lung cancer (NSCLC). METHODS: A retrospective analysis identified 1543 consecutive patients presenting to Shanghai Pulmonary Hospital with NSCLC for VATS-LTS or LUL from 2013-2017. After propensity-score matching for patient demographics and tumor characteristics, 273 pairs were identified. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the Log-rank test. RESULTS: The median follow-up time was 51.5 months. There were no significant differences in operative duration (2.11±0.64 versus 2.49±5.96 h, p=0.30), total blood loss (106.19±170.83 versus 97.07±149.34 mL, p=0.51) and operation complications (10% versus 8%, p=0.37) between LUL and LTS. Patients undergoing LUL had longer postoperative hospital stay (5.55±3.00 versus 4.87±2.33 days, p=0.003), greater tumor margin distance (3.3±1.2 versus 3.1±0.9 cm, p<.001) and greater number of lymph nodes harvested (8.0±3.2 versus 6.8±3.3, p<.001) than LTS, but the margin/tumor ratio was not statistically different (2.5±1.6 versus 2.3±1.1, p=0.11). Median DFS (49.5 versus 54.3 months, p=0.77) and OS (49.5 versus 55.0 months, p=0.88) were not significantly different between patients undergoing LTS and LUL, and similar outcomes were noted across subgroups of patients stratified by tumor stages, pathological type, and radiographic manifestations. CONCLUSIONS: VATS-LTS and LUL had comparable oncological outcomes for stage I NSCLC, regardless of tumor pathological types and radiological findings, as long as negative margins were confirmed.

10.
Plant J ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252236

RESUMO

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: "missing a small part" in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis-like cell death were detected in qk1 endosperm. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.

11.
Ying Yong Sheng Tai Xue Bao ; 32(6): 1935-1942, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34212597

RESUMO

To clarify the changes of water sources for Caragana intermedia plantations at different ages (4, 9, 17 and 31 years) in response to rainfall in the Gonghe Basin of Qinghai Province, China, we used the stable isotope technique to identify δ2H and δ18O compositions of soil water, xylem water, groundwater, and rain water before and after rainfalls. The proportions of different water sources were calculated by the Iso-Source model. The results showed that the δ2H and δ18O compositions of the shallow soil layer (0-40 cm) of all plantations responded significantly to the precipitation. The isotopic values of plant xylem water, soil water, and groundwater of each plantation were spotted on the lower right of the local meteoric water line (LMWL) either before or after rainfall, with lower intercepts and slopes than LMWL and the global meteoric water line (GMWL). The isotopic compositions of xylem water and soil water of C. intermedia plantations were closer to LMWL after rainfall. The 4- and 9-year-old C. intermedia plantations mainly used shallow soil water, the 17-year-old plantation mainly used middle layer soil water (40-90 cm), and the 31-year-old plantation primarily use deep soil water before rainfall. After rainfall, the shallow soil layer became sources of water absorption for all plantations. The utilization proportions of groundwater for all plantations were only 1.8%-11.9%. In general, water sources of different aged C. intermedia plantations showed similar responses to rainfall, by primarily absorbing the shallow soil water supplied by rainfall and reducing the use of groundwater.


Assuntos
Caragana , China , Chuva , Areia , Solo , Água
12.
ACS Nano ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269058

RESUMO

Spatially controlled preparation of heterostructures composed of layered materials is important in achieving interesting properties. Although vapor-phased deposition methods can prepare vertical and lateral heterostructures, liquid-phased methods, which can enable scalable production and further solution processes, have shown limited controllability. Herein, we demonstrate by using wet chemical methods that metallic Sn0.5Mo0.5S2 nanosheets can be deposited epitaxially on the edges of semiconducting SnS2 nanoplates to form SnS2/Sn0.5Mo0.5S2 lateral heterostructures or coated on both the edges and basal surfaces of SnS2 to give SnS2@Sn0.5Mo0.5S2 core@shell heterostructures. They also showed good light-to-heat conversion ability due to the metallic property of Sn0.5Mo0.5S2. In particular, the core@shell heterostructure showed a higher photothermal conversion efficiency than the lateral counterpart, largely due to its randomly oriented and polycrystalline Sn0.5Mo0.5S2 layers with larger interfacing area for multiple internal light scattering.

13.
Lung Cancer ; 159: 111-116, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34325317

RESUMO

OBJECTIVE: The association between the morphological characteristics and survival outcome of lung cancer associated with cystic airspaces (LCCAs) is unclear due to rarity of this disease. The current study attempted to compare the survival outcome between LCCAs and non-LCCAs and investigate the correlation between imaging features and prognosis of LCCA. METHOD: Of 10,835 patients diagnosed with non-small cell lung carcinoma (NSCLC) between January 2015 and December 2016, 123 patients with LCCA were included. The non-LCCA group comprised 3136 patients with primary solitary adenocarcinoma or squamous cell lung cancer. Propensity score matching (PSM) was performed for age, sex, tumor size, tumor stage, and lymph node involvement in a 1:1 ratio between the LCCAs and non-LCCAs, and the correlation between radiological features and recurrence-free survival (RFS) was analyzed. RESULT: The computed tomography (CT) lesion size was found to be higher in all LCCA subtypes, particularly in Type III (a cystic airspace with a mural nodule) and Type IV (mixed) LCCAs (3.09 and 3.65 cm, respectively), than in non-LCCAs (2 cm) after PSM. Three-year RFS in the LCCA group was higher than in the non-LCCA group (Type I- IV LCCAs: 100%, 84%, 77% and 83%, respectively vs. non-LCCAs: 77%). However, statistically significant difference was only found in comparison between LCCA Type I (thin-walled) and non-LCCA groups (P = 0.026). Type III lung cancer exhibited the worst survival among all four LCCA subtypes. CONCLUSIONS: The CT lesion size and pathologic tumor size varied significantly across LCCAs. Type I LCCAs exhibited better survival than non-LCCAs, whereas Type III LCCAs exhibited the worst survival rate among the four LCCA subtypes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos
14.
Inorg Chem ; 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34081433

RESUMO

Two dimensional (2D) hybrid perovskites have attracted a great deal of interest because of their appropriate photovoltaic efficiency and environmental stability. Although some 2D hybrid perovskites with sulfur-containing amines have been reported, the cation having the mercaptan group has not been well explored yet. In this work, cysteamine (Cya, HS(CH2)2NH2), a mercaptan-containing amine, was introduced into 2D hybrid perovskite. Two 2D lead iodides with different structures, (HCya)2PbI4 (1) and (HCya)7Pb4I15 (2), were isolated as a red low-temperature phase and a yellow high-temperature phase, respectively. X-ray single-crystal structural analysis showed that the red phase 1 is a single layered corner-shared perovskite and that the yellow phase 2 is a corner/edge-shared quasi-2D perovskite. A thermo-induced reversible 1 to 2 phase transition was found in this synthetic system. The configuration of HCya cation greatly influences the crystallization equilibrium, generating different structures of the lead halides. The single-crystal structure of 1 is discussed in comparison with that of (HAE)2PbI4 (AE = HO(CH2)2NH2), an analogue of 1. The different effects of OH and SH groups on the 2D frameworks are studied based on their hydrogen bonding properties. More remarkably, although the two perovskites have similar structures, the (HCya)2PbI4 (1) has an intrinsic water stability that is much more stable than (HAE)2PbI4, which should be attributed to the affinity of the SH group with lead on the surface of the lead halide.

15.
Inorg Chem ; 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34139843

RESUMO

Titanium oxides and bismuth halides or oxyhalides have been known to be excellent semiconductors with both excellent photocatalytic and photoelectric properties. The design of supersalts assembled by titanium-oxo clusters (TOCs) and bismuth iodide clusters is a hopeful strategy for exploring the chemistry and application of new titanium-oxo clusters. We report herein a series of unusual ionic TOCs with Ti12 oxo cluster cations and bismuth iodide anions, [Ti12O15(OiPr)17]3[Bi3I12] (Bi3), [Ti12O14(OiPr)18][Bi4I14(THF)2] (Bi4), and [Ti12O14(OiPr)18][Ti11BiO14(OiPr)17][Bi6I22] (Bi6). Single-crystal X-ray analysis revealed that the type and charge of the Ti12 clusters varied with the charges of different bismuth iodide clusters. Taking advantage of the easy hydrolysis of the TOCs and BiI clusters in water, we used these supersalt crystals as single-source precursors to prepare a p-n-type BiOI-TiO photocatalyst. The heterojunction materials were carefully characterized by powder X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, etc. The synergistic effect of the two components of BiOI and TiO on the photocatalytic degradation of RhB in water is demonstrated. This is a very convenient method for obtaining a p-n-type BiOI-TiO heterojuction photocatalyst by just placing the ground TOC crystals into water.

16.
Plant Cell Physiol ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34185870

RESUMO

Previous studies had demonstrated that in Arabidopsis, IDM3 is involved in ROS1-mediated DNA demethylation pathway, and SUVH-SDJ complex functions as a DNA methylation reader complex for enhancing gene transcription, which presumably recruits ROS1 to the promoters of target genes for DNA demethylation. Here, our analyses, however, showed that the IDM3 and SDJ1/2/3, the components of the SUVH-SDJ complex, are implicated in establishing and/or maintaining DNA methylation as well through DDR complex. idm3-3 or sdj1/2/3 mutations led to genome-wide DNA hypomethylation, and both mutants shared a large number of common hypo-DMRs with rdm1-4 and dms3-4, suggesting that IDM3 and SDJ1/2/3 help establish and/or maintain DNA methylation, mediated by RdDM pathway, at a subset of genomic regions largely through DDR complex. IDM3 is able to strongly interact with RDM1 and DMS3, but weakly with SDJ1 and SDJ3; SDJ1 and SDJ3 is capable of interacting separately with RDM1 and DMS3. Furthermore, comparisons of DNA methylation features in idm3-3 and sdj1/2/3 indicated that idm3-3 and sdj1/2/3 mutations make differential impacts on DNA methylation levels and patterns on a genome-wide scale, indicating that they are targeted to quite distinct genomic regions for aiding in DNA methylation. Further analyses on ChIP-seq data demonstrated that RDM1, DMS3 and NRPE1 are enriched in IDM3- and SDJ1/2/3-targted regions. Altogether, our results provide clear demonstration that IDM3 and SDJ1/2/3 play a part in establishing and/or maintaining DNA methylation of a group of genomic regions, through the DDR complex.

17.
Dalton Trans ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34021298

RESUMO

Introducing electronically active organic components into lower dimensional metal halide compounds is an effective strategy to improve the electronic properties of hybrid metal halide materials. We have previously used this strategy to explore hybrid halides with tetrathiafulvalenes (TTFs) and a series of lead iodides and bismuth halides were isolated. The electronic properties were improved notably using this modification. In this work, we expand the study of TTF based main-group metal halides to double metal halides with mixed lead and copper transition metals. Two hybrid TTF-lead-cuprous iodides, formulated as [TTF]5[Pb2Cu2I10]·H2O (1) and [TTF]2[PbCu2I6] (2), and two monometal analogues of [TTF]2[Cu4I6]·H2O (3) and [TTF]2[Ag4I6] (4) were crystallographically characterized. The anion of 1 is a 0D cluster, while that of the others is a 1D chain structure. The anion structures of 1-4 are novel and are reported for the first time. The TTF moieties are stacked to form a 2D framework in 1 and 1D columns in 2-4. We found that the semiconductor properties of the hybrids are related to electron donation from an anion to a cation. The electronic state of the TTF cations is another significant factor that affects the electronic properties of the materials. More notably, this work proved that the conductivity and photoconductivity of the mixed metal iodides are superior to those of the monometal iodides.

18.
Chem Commun (Camb) ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33970181

RESUMO

SnS2 nanoplates are used as sacrificial templates to facilitate the in situ growth of intermetallic compound Pt3Sn nanoparticles. The Pt3Sn/SnS2 heterostructures show promise for selective NO2 sensing due to the favored gas adsorption and gas-solid charge transfer on Pt3Sn, combined with the optimized film conductance and formation of ohmic-type Pt3Sn/SnS2 heterointerfaces.

19.
Eur J Cancer ; 148: 297-306, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33770575

RESUMO

BACKGROUND: Genetic aberrations in the cyclin-dependent kinase (CDK)4 pathway occur in 82% of patients with acral melanoma (AM), which is the predominant subtype of melanoma in China. We aimed to evaluate the anti-tumour activity of palbociclib, a selective CDK4/6 inhibitor, in patients with advanced AM with CDK4 pathway gene aberrations. METHODS: In this phase II trial, patients with advanced AM with CDK4 or/and CCND1 gain or/and CDKN2A loss were treated with oral palbociclib (125 mg) on days 1-21 of a 28-day cycle. The primary end-point was overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Whole-exome sequencing and multiplex immunohistochemistry of the available formalin-fixed, paraffin-embedded samples of nine patients were analysed to explore the predictive biomarkers of palbociclib response. RESULTS: Fifteen patients were enrolled. Three (20.0%) patients achieved tumour shrinkage at 8 weeks, including one with confirmed partial response. At data cut-off date, treatment was ongoing for one patient. The median PFS was 2.2 mo (range: 1.5-13.3 mo; 95% confidence interval [CI]: 1.9-2.5), and the median OS was 9.5 mo (range: 2.6-14.1 mo, 95% CI: 5.7-13.4). Eight patients died due to disease progression. The most common TRAEs were leukopenia (87%; Grade III/IV, 27%), neutropenia (80%; grade III/IV, 27%), and fatigue (53%; grade III/IV, 7%). Significant JAK2 deletions and SH2B3 amplifications were observed in patients who did not achieve any clinical benefit (CB) with palbociclib treatment. MCM7 amplification or protein expression level was found to be associated with CB. CONCLUSIONS: Palbociclib monotherapy demonstrated preliminary efficacy and an acceptable safety profile in advanced AM patients with CDK4 pathway aberrations. Patients with amplification or high protein levels of MCM7 were more prone to benefit from palbociclib. The JAK-STAT pathway might play a role in the mechanism of action of palbociclib in AM. TRIAL REGISTRATION NUMBER: NCT03454919. THE DATE OF REGISTRATION: March 6, 2018.

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