Purpose
Patients with anaplastic thyroid cancer (ATC) have a very poor prognosis. Immunotherapy is a potential treatment, while the current outcome is limited which may be due to the complicated ...tumor microenvironment (TME). Tumor associated macrophages (TAMs) is the most abundant cell in the TME of ATC. We aimed to clarify the novel indicators based on TAM in ATC.
Methods
Transcriptome files were downloaded from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis, cox regression, support vector machine, and random forest were utilized to identify TAM-related prognostic genes. Consensus clustering and principal component analysis were performed for integrated analysis. Moreover, external validation (Fudan University Shanghai Cancer Center cohort) was conducted in 23 ATC samples via immunohistochemistry.
Results
ATC patients with an abundance of TAMs had a poorer prognosis. Four TAM related genes (FZD6, RBBP8, PREX1, HSD3B7) were identified and a TAM-related prognostic index (TAMRPI) was constructed with high area under the curve (AUC). Next, high TAMRPI was related to the higher level of TAM infiltration and upregulation of several pathways, such as E2F targets, IL6-JAK-STAT3, and G2M checkpoint. Immune checkpoint TIM-3 and CSF1R were positively associated with TAMRPI, and dysfunction of T cells was increased in high TAMRPI subset. Moreover, in the external validation of protein level, strong expression of TAM related genes was related to poorer prognosis, which was further supported by time-dependent AUC analysis.
Conclusion
TAM is negatively correlated to the prognosis of ATC. FZD6, RBBP8, PREX1, and HSD3B7 are potential biomarkers of ATC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
MicroRNAs (miRNAs) play crucial roles in regulating plant development and stress responses. However, the functions and mechanism of intronic miRNAs in plants are poorly understood. This study reports ...a stress-responsive RNA splicing mechanism for intronic miR400 production, whereby miR400 modulates reactive oxygen species (ROS) accumulation and improves plant tolerance by downregulating its target expression. To monitor the intron splicing events, we used an intronic miR400 splicing-dependent luciferase transgenic line. Luciferase activity was observed to decrease after high cadmium concentration treatment due to the retention of the miR400-containing intron, which inhibited the production of mature miR400. Furthermore, we demonstrated that under Cd treatments, Pentatricopeptide Repeat Protein 1 (PPR1), the target of miR400, acts as a positive regulator by inducing ROS accumulation. Ppr1 mutation affected the Complex III activity in the electron transport chain and RNA editing of the mitochondrial gene ccmB. This study illustrates intron splicing as a key step in intronic miR400 production and highlights the function of intronic miRNAs as a 'signal transducer' in enhancing plant stress tolerance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Four coordination polymers (CPs) Mn-TMPP (
1
), Zn-TMPP (
2
), Mn-THPP (
3
), and Zn-THPP (
4
) have been synthesized and characterized (H
2
TMPP =
meso
-tetrakis (6-methylpyridin-3-yl) porphyrin; H
...2
THPP =
meso
-tetrakis (6-(hydroxymethyl) pyridin-3-yl) porphyrin). The one-dimensional (1D) chain compound
1
is formed
via
a head-to-tail connection of the Mn-TMPP unit, wherein the central Mn
2+
features a square pyramidal geometry coordinated by four N atoms from the porphyrin skeleton and one additional N atom from an adjacent Mn-TMPP unit. Compound
2
features an octahedral Zn
2+
center associated with four N atoms from the porphyrin skeleton to define the equatorial plane and two additional N donors at the axial positions to give a two-dimensional (2D) CP. The 1D chain of
1
and the 2D layer of
2
possess distinctive molecular structures but nearly identical molecular arrangements in their unit cells viewed along all three crystallographic axes. By contrast, Mn- and Zn-based CPs
3
and
4
supported by the THPP ligand share both identical molecular connectivities and crystal packing. In
3
/
4
, each Mn/Zn center is chelated by four N donors of the porphyrin interior to define the equatorial plane of an octahedron, whose axial sites are occupied by two alcoholic OH groups from a pair of
trans
-located pyridinemethanol moieties. The third-order nonlinear optical properties of
1-4
investigated using the
Z
-scan technique at 532 nm revealed reverse saturable absorption and self-focusing effects for all four CPs, with hyperpolarizability values (
γ
) in the range 1.42 × 10
−28
esu to 7.64 × 10
−28
esu. These high
γ
values are comparable to the best porphyrin-based molecular assemblies, demonstrating potential for these materials in optical limiting applications.
Pyridine- and pyridinemethanol-based coordination polymers of Mn(
ii
) and Zn(
ii
) with porphyrinic ligand skeleton demonstrate rich similarities and differences in terms of solution and solid-state properties.
Plants have evolved interconnected regulatory pathways which enable them to respond and adapt to their environments. In plants, stress memory enhances stress tolerance through the molecular retention ...of prior stressful experiences, fostering rapid and robust responses to subsequent challenges. Mounting evidence suggests a close link between the formation of stress memories and effective future stress responses. However, the mechanism by which environmental stressors trigger stress memory formation is poorly understood. Here, we review the current state of knowledge regarding the RNA-based regulation on stress memory formation in plants and discuss research challenges and future directions. Specifically, we focus on the involvement of microRNAs (miRNAs), small interfering RNAs (siRNAs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) in stress memory formation. miRNAs regulate target genes via post-transcriptional silencing, while siRNAs trigger stress memory formation through RNA-directed DNA methylation (RdDM). lncRNAs guide protein complexes for epigenetic regulation, and AS of pre-mRNAs is crucial to plant stress memory. Unraveling the mechanisms underpinning RNA-mediated stress memory formation not only advances our knowledge of plant biology but also aids in the development of improved stress tolerance in crops, enhancing crop performance and global food security.
A heterometallic metal-organic framework (MOF) of Cd
Ca
(BTB)
(HCOO)
(DEF)
(H
O)
∙DEF∙
Sol (
, H
BTB = benzene-1,3,5-tribenzoic acid; DEF =
,
'-diethylformamide;
Sol. = undefined solvates within the ...pore) was prepared by solvothermal reaction of Cd(NO
)
·4H
O, CaO and H
BTB in a mixed solvent of DEF/H
O/HNO
. The compatibility of these two divalent cations from different blocks of the periodic table results in a solid-state structure consisting of an unusual combination of a discrete V-shaped heptanuclear cluster of Cd
Ca
Ca' and an infinite one-dimensional (1D) chain of Cd
CaCa'
that are orthogonally linked via a corner-shared Ca
ion (denoted as Ca'), giving rise to an unprecedented branched-chain secondary building unit (SBU). These SBUs propagate via tridentate BTB to yield a three-dimensional (3D) structure featuring a corner-truncated
4
helix in MOF
. This outcome highlights the unique topologies possible via the combination of carefully chosen s- and d-block metal ions with polydentate ligands.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The head and neck squamous cell carcinomas (HNSCC) is one of the most frequent cancers in the world, with an unfavorable prognosis. Cancer stem cells (CSCs) have been found to be responsible for ...HNSCC recurrence and therapeutic resistance.
The stemness of HNSCC was measured using a stemness index based on mRNA expression (mRNAsi). Stemness-related genes were discovered using weighted gene co-expression network analysis, least absolute shrinkage and selection operator analysis, and Cox regression, and a stemness-related prognostic index (SPI) was constructed. This research was based on TCGA and GSE65858.
Stemness was found upregulated in HNSCC compared with normal tissues. The risk score model including five stemness-related genes exhibited a good accuracy in predicting outcomes. High SPI predicted a shorter overall survival (OS) in HNSCC patients, in the meantime, also demonstrated a lower CD8
T cell infiltration and a higher enrichment of macrophages and fibroblasts than the low-SPI group, focusing on several up-regulated pathways such as epithelial mesenchymal transition (EMT), MYC targets v1, E2F targets, mTORC1 signaling, hypoxia, MYC targets v2, angiogenesis, G2M checkpoint, and glycolysis.
The SPI signature, which includes five stemness-related genes, could be utilized as a prognostic biomarker for HNSCC, implying that stemness may impact HNSCC immunologic profiles and be a feasible therapeutic target.
The delivery of biocompatible reagents into cancer cells can elicit an anticancer effect by taking advantage of the unique characteristics of the tumor microenvironment (TME). In this work, we report ...that nanoscale two-dimensional FeII- and CoII-based metal–organic frameworks (NMOFs) of porphyrin ligand meso-tetrakis (6-(hydroxymethyl) pyridin-3-yl) porphyrin (THPP) can catalyze the generation of hydroxyl radicals (•OH) and O2 in the presence of H2O2 that is overexpressed in the TME. Photodynamic therapy consumes the generated O2 to produce a singlet oxygen (1O2). Both •OH and 1O2 are reactive oxygen species (ROS) that inhibit cancer cell proliferation. The FeII- and CoII-based NMOFs were non-toxic in the dark but cytotoxic when irradiated with 660 nm light. This preliminary work points to the potential of porphyrin-based ligands of transition metals as anticancer drugs by synergizing different therapeutic modalities.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Patients with advanced thyroid carcinoma (TC), such as anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), and locally advanced papillary thyroid carcinoma (PTC), have ...poor prognoses and require novel treatments. Immune checkpoint (ICP) inhibitors have demonstrated encouraging and good results; nevertheless, their effect in advanced TCs remains largely unclear. Thus, we demonstrated ICP profiles and investigated their potential clinical significance.
A total of 234 TC patients were involved, with 22 ATCs, 44 PDTCs, and 168 PTCs, including 58 advanced PTCs. Immunohistochemistry was performed to evaluate nine ICPs programmed cell death ligand 1 (PDL1), Programmed cell death 1 (PD1), cytotoxic T lymphocyte-associated protein 4 (CTLA4), B and T lymphocyte attenuator (BTLA), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), lymphocyte activation gene 3 (LAG3), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B7 homolog 3 (B7-H3), and T-cell immunoglobulin and mucin domain- 3 protein (TIM3) expression
tissue microarrays (TMAs), and clinical correlations were analyzed simultaneously.
ATC had the highest positive rate of ICPs among the three pathological types, as well as relatively high ICP co-expression. ATC with high expression of PDL1 positivity had a poor prognosis. Shorter survival was associated with VISTA, B7H3, TIM3, and TIGIT expression in PDTC. The greater the co-expression of these four ICPs, the poorer the prognosis in PDTC patients. VISTA and B7H3 were the two most commonly expressed ICPs in advanced PTC, both of which were linked to a poor prognosis.
PDL1 is linked to the overall survival (OS) of ATC. A subset of PDTC is likely immunogenic with poor prognosis and co-expression of VISTA, B7H3, TIM3, and TIGIT. Furthermore, VISTA and B7H3 are prognostic biomarkers in advanced PTC. Single or combined blockade targeting these ICPs might be effective for advanced TCs in the future.
A series of conjugated polymers based on PFS derivatives with n-conjugated 5-（9H-fluoren-2-yl）-2,2＇-bithiophene （fluorene-alt-bithiophene） backbones, namely PFS-3C, PFS-4C and PFS-6C, were ...synthesized for their use as the anode interfacial layers （AILs） in the efficient fullerene-free polymer solar ceils （PSCs）. Alkyl sulfonate pendants with different lengths of alkyl side chains were introduced in the three polymers in order to investigate the effect of the alkyl chain length on the anode modification. The obtained three polymers exhibited similar absorption bands and energy levels, indicating that changing the length of the alkyl side chains did not affect the optoelectronic properties of the conjugated polymers. Based on the PBDB-T：ITIC active layer, we fabricated the fullerene-free PSCs using the three polymers as the AILs. The superior performance of the fullerene-free PSC device was achieved when PFS-4C was used as the AIL, showing a power conversion efficiency （PCE） of 10.54%. The high performance of the PFS-4C-modified device could be ascribed to the high transmittance, suitable work-function （WF） and smooth surface of PFS-4C. To the best of our knowledge, the PCE obtained in the PFS-4C-modified device is among the highest PCE values in the fullerene-free PSCs at present. These results demonstrate that the PFS derivatives are promising candidates in serving as the AIL materials for high-performance fullerene-free PSCs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A new analysis method based on serial sectioning and three-dimensional (3D) reconstruction was developed to characterize the mineral microstructure of iron ore sinter. Through the 3D reconstruction ...of two types of iron ore sinters, the morphology and distribution of minerals in three-dimensional space were analyzed, and the volume fraction of minerals in a 3D image was calculated based on their pixel points. In addition, the microhardness of minerals was measured with a Vickers hardness tester. Notably, different mineral compositions and distributions are obtained in these two sinters. The calcium ferrite in Sinter 1 is dendritic with many interconnected pores, and these grains are crisscrossed and interwoven; the calcium ferrite in Sinter 2 is strip shaped and interweaves with magnetite, silicate and columnar pores. The calculated mineral contents based on a two-dimensional region are clearly different among various layers. Quantitative analysis shows that Sinter 1 contains a greater amount of calcium ferrite and hematite, whereas Sinter 2 contains more magnetite and silicate. The microhardness of minerals from highest to lowest is hematite, calcium ferrite, magnetite and silicate. Thus, Sinter 1 has a greater tumbler strength than Sinter 2.
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