Herein, a giant Sb‐rich polyoxometalate (POM) {Sb21Tb7W56} is reported, which contains the largest number of Sb atoms in a POM so far. The Sb‐rich POM has many interesting structural features and is ...a rare example of a soluble and water‐stable giant POM. Biomedical studies indicate that the Sb‐rich POM exhibits broad‐spectrum antitumor activity against various cancer cell lines by reactivating the P53‐dependent apoptotic processes and disrupting the mitochondrial membrane. In addition, this Sb‐rich POM was capable of suppressing the growth and metastasis of a breast cancer in vivo. This work demonstrates that Sb‐rich POMs are promising candidates for the development of new anticancer drugs.
A novel soluble and water‐stable giant Sb‐rich polyoxometalate (POM) has been developed, which shows the largest Sb−Ln−W cluster and has the greatest number of Sb centers in a cluster yet found in POM chemistry. Importantly, the Sb‐rich POM can exhibit broad‐spectrum antitumor and anti‐metastatic activities in vitro and in vivo without causing adverse effects, making it a promising candidate for a antitumor agent.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly malignant tumor worldwide. Hypoxia and related oxidative stress are heavily involved in the process of HCC ...development and its therapies. However, direct and accurate measurement of oxygen concentration and evaluation of hypoxic effects in HCC prove difficult. Moreover, the hypoxia-mediated mechanisms in HCC remain elusive. Here, we summarize recent major evidence of hypoxia in HCC lesions shown by measuring partial pressure of oxygen (pO
), the clinical importance of hypoxic markers in HCC, and recent advances in hypoxia-related mechanisms and therapies in HCC. For the mechanisms, we focus mainly on the roles of oxygen-sensing proteins (i.e., hypoxia-inducible factor and neuroglobin) and hypoxia-induced signaling proteins (e.g., matrix metalloproteinases, high mobility group box 1, Beclin 1, glucose metabolism enzymes, and vascular endothelial growth factor). With respect to therapies, we discuss mainly YQ23, sorafenib, 2-methoxyestradiol, and celastrol. This review focuses primarily on the results of clinical and animal studies.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor due to the lack of effective therapeutic drugs. Cancer therapy targeting programmed cell death protein 1 (PD-1) or programmed ...death ligand-1 (PD-L1) is of revolutionary. However, the role of intrinsic PD-L1, which determines immune-therapy outcomes, remains largely unclear. Here we demonstrated an oncogenic role of PD-L1 via binding and activating Ras in GBM cells. RNA-sequencing transcriptome data revealed that PD-L1 significantly altered gene expression enriched in cell growth/migration/invasion pathways in human GBM cells. PD-L1 overexpression and knockout or knockdown demonstrated that PD-L1 promoted GBM cell proliferation and migration in vitro and in vivo. Mechanistically, PD-L1 prominently activated epithelial mesenchymal transition (EMT) process in a MEK/Erk- but not PI3K/Akt-dependent manner. Further, we identified intracellular interactions of PD-L1 and H-Ras, which led to Ras/Erk/EMT activation. Finally, we demonstrated that PD-L1 overexpression promoted while knockdown abolished GBM development and invasion in orthotopic GBM models of rodents. Taken together, we found that intracellular PD-L1 confers GBM cell malignancy and aggressiveness via binding Ras and activating the downstream Erk-EMT signaling. Thus, these results shed important insights in improving efficacy of immune therapy for GBM as well as other malignant tumors.
•PD-L1 overexpression promoted while knockdown abolished orthotopic glioma growth.•PD-L1 promoted GBM migration in vivo and in vitro and facilitates epithelial mesenchymal transition.•This facilitation effect is dependent on MEK/Erk but not on PI3K/Akt signaling.•PD-L1 increases Ras activity by Ras binding to activate Ras/Erk/EMT axis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the hexaploid wheat genome, there are three Gα genes, three Gβ and twelve Gγ genes, but the function of Gβ in wheat has not been explored. In this study, we obtained the overexpression of
...Arabidopsis plants through inflorescence infection, and the overexpression of wheat lines was obtained by gene bombardment. The results showed that under drought and NaCl treatment, the survival rate of Arabidopsis seedlings' overexpression of
was higher than that of the wild type, while the survival rate of the related mutant
was lower than that of the wild type. The survival rate of wheat seedlings with
overexpression was higher than that of the control. In addition, under drought and salt stress, the levels of superoxide dismutase (SOD) and proline (Pro) in the wheat overexpression of
were higher than that of the control, and the concentration of malondialdehyde (MDA) was lower than that of the control. This indicates that
could improve the drought resistance and salt tolerance of Arabidopsis and wheat by scavenging active oxygen. Overall, this work provides a theoretical basis for wheat G-protein β-subunits in a further study, and new genetic resources for the cultivation of drought-tolerant and salt-tolerant wheat varieties.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
At present, phenolic acid derivatives and triazole derivatives have a good antifungal effect, which has attracted widespread attention. A series of novel phenolic acid triazole derivatives were ...synthesized, and their structures were characterized by IR, MS, NMR, and X-ray crystal diffraction. Compound methyl 4-(2-bromoethoxy)benzoate, methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate, 4-(2-(1H-1,2,4-triazol-1-yl)ethoxy)benzoic acid and 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)-3-methoxybenzoic acid crystallize in the monoclinic system with space group P21/n, the monoclinic system with space group P21, the monoclinic system with space group P21 and the orthorhombic system with space group Pca21, respectively. At a concentration of 100 μg/mL and 200 μg/mL, the antifungal activity against seven plant pathogen fungi was determined. Compound methyl 4-(2-bromoethoxy)benzoate has the best inhibitory effect on Rhizoctonia solani AG1, and the inhibitory rate reached 88.6% at 200 μg/mL. The inhibitory rates of compound methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate against Fusarium moniliforme and Sphaeropsis sapinea at a concentration of 200 μg/mL were 76.1% and 75.4%, respectively, which were better than that of carbendazim.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Two isostructural Co(Cd)-antimony-oxo tartrate cluster-based compounds with a one-dimensional (1-D) belt-like structure, namely H
9.2
Co(H
2
O)
6
{
M
0.5
(H
2
O)
3.5
{
M
′(H
2
O)
4
Sb
V
O
6
Co
4.2
(H
...2
O)
5
Sb
III
6
(μ
3
-O)
2
(tta)
6
}}
2
·
n
H
2
O (
M
= Co,
M
′ = Co,
n
= 9 (
1
);
M
= Cd
0.39
/Co
0.61
,
M
′ = Cd
0.24
/Co
0.76
,
n
= 7 (
2
); H
4
tta = tartaric acid), have been synthesized by solvothermal methods. It is noteworthy that the relatively rare mixed-valence Sb(
iii
,
v
) exists in the structures. The anionic clusters in both compounds appear to be in a sandwich configuration; the top and bottom layers are based on {Sb
3
(μ
3
-O)(tta)
3
} brackets, and the intermediate layer is occupied by {Sb
V
O
6
Co
4.2
(H
2
O)
5
}. The title compounds have been characterized by single-crystal X-ray diffraction, powder X-ray diffraction, elemental analyses, thermogravimetric analyses, and UV-Vis spectroscopy. We chose compound
2
as a representative to test its proton conductivity, and the results show that the conductivity can reach 1.42 × 10
−3
S cm
−1
at 85 °C under 98% relative humidity.
Isostructural mixed-valence compounds H
9.2
Co(H
2
O)
6
{
M
0.5
(H
2
O)
3.5
{
M
'(H
2
O)
4
Sb
V
O
6
Co
4.2
(H
2
O)
5
Sb
III
6
(μ
3
-O)
2
(tta)
6
}}
2
·
n
H
2
O (
M
= Co,
M
' = Co,
n
= 9 (
1
);
M
= Cd
0.39
/Co
0.61
,
M
' = Cd
0.24
/Co
0.76
,
n
= 7 (
2
)) were synthesized. The proton conductivity of
2
is 1.42 × 10
−3
S·cm
−1
at 85 °C and 98% RH.
Aim： To investigate the effects of piperlongumine （PL）, an anticancer alkaloid from long pepper plants, on the primary myeloid leukemia cells from patients and the mechanisms of action. Methods： ...Human BM samples were obtained from 9 patients with acute or chronic myeloid leukemias and 2 patients with myelodysplastic syndrome （MDS）. Bone marrow mononuclear cells （BMMNCs） were isolated and cultured. Cell viability was determined using MTT assay, and apoptosis was examined with PI staining or flow cytometry. ROS levels in the cells were determined using DCFH-DA staining and flow cytometry. Expression of apoptotic and autophagic signaling proteins was analyzed using Western blotting. Results： PL inhibited the viability of BMMNCs from the patients with myeloid leukemias （with IC50 less than 20 μmol/L）, but not that of BMMNCs from a patient with MDS. Furthermore, PL （10 and 20 μmol/L） induced apoptosis of BMMNCs from the patients with myeloid leukemias in a dose-dependent manner. PL markedly increased ROS levels in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the antioxidant N-acetyl-L-cysteine abolished PL-induced ROS accumulation and effectively reduced PL-induced cytotoxicity. Moreover, PL markedly increased the expression of the apoptotic proteins （Bax, Bci-2, and caspase-3） and autophagic proteins （Beclin-1 and LC3B）, and phosphorylation of p38 and JNK in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the specific p38 inhibitor SB203580 or the specific JNK inhibitor SP600125 partially reversed PL-induced ROS production, apoptotic/autophagic signaling activation and cytotoxicity. Conclusion： Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways.
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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
The assembly of heterometallic cluster substituted polyoxometalates (POMs) remains a great challenge for inorganic synthetic chemistry up to now. Herein, a series of 5p–4f heterometallic cluster ...substituted POMs were successfully isolated by a facile one-step hydrothermal reaction method, namely H17(H2en)3SbIII 9SbVLn3O14(H2O)3(SbW9O33)3(PW9O34)·28H2O(1-Ln, Ln = Ce, Sm, Eu, Gd, Tb, Dy) (en = ethylenediamine). Interestingly, by replacing en with imidazole, another series of 5p–4f heterometallic cluster substituted POMs H13(HIm)4K2Na4(H2O)9SbIII 9SbVLn3O14(H2O)3(SbW9O33)3(PW9O34)·26H2O (2-Ln, Ln = Sm, Eu, Gd, Tb, Dy, Im = imidazole) were obtained. Structural analyses indicate that both 1-Ln and 2-Ln are made up of an unprecedented 5p–4f heterometallic {Sb10Ln3O14(H2O)3} cluster stabilized simultaneously by mixed trilacunary heteropolyanions including {A-α-PW9O34} and {B-α-SbW9O33}. Impedance measurements indicate that both compounds exhibit different proton conduction properties, and the conductivity of 2 can reach up to 1.64 × 10–2 S cm–1 at 85 °C under 98% relative humidity. Moreover, the fluorescence emission behaviors of both compounds have been studied.
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IJS, KILJ, NUK, PNG, UL, UM
The hominin record from southern Asia for the early Late Pleistocene epoch is scarce. Well-dated and well-preserved fossils older than ∼45,000 years that can be unequivocally attributed to Homo ...sapiens are lacking. Here we present evidence from the newly excavated Fuyan Cave in Daoxian (southern China). This site has provided 47 human teeth dated to more than 80,000 years old, and with an inferred maximum age of 120,000 years. The morphological and metric assessment of this sample supports its unequivocal assignment to H. sapiens. The Daoxian sample is more derived than any other anatomically modern humans, resembling middle-to-late Late Pleistocene specimens and even contemporary humans. Our study shows that fully modern morphologies were present in southern China 30,000-70,000 years earlier than in the Levant and Europe. Our data fill a chronological and geographical gap that is relevant for understanding when H. sapiens first appeared in southern Asia. The Daoxian teeth also support the hypothesis that during the same period, southern China was inhabited by more derived populations than central and northern China. This evidence is important for the study of dispersal routes of modern humans. Finally, our results are relevant to exploring the reasons for the relatively late entry of H. sapiens into Europe. Some studies have investigated how the competition with H. sapiens may have caused Neanderthals' extinction (see ref. 8 and references therein). Notably, although fully modern humans were already present in southern China at least as early as ∼80,000 years ago, there is no evidence that they entered Europe before ∼45,000 years ago. This could indicate that H. neanderthalensis was indeed an additional ecological barrier for modern humans, who could only enter Europe when the demise of Neanderthals had already started.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The peptidase M24 (Metallopeptidase 24, M24) superfamily is essential for plant growth, stress response, and pathogen defense. At present, there are few systematic reports on the identification and ...classification of members of the peptidase M24 proteins superfamily in wheat. In this work, we identified 53 putative candidate TaM24 genes. According to the protein sequences characteristics, these members can be roughly divided into three subfamilies: I, II, III. Most TaM24 genes are complex with multiple exons, and the motifs are relatively conserved in each sub-group. Through chromosome mapping analysis, we found that the 53 genes were unevenly distributed on 19 wheat chromosomes (except 3A and 3D), of which 68% were in triads. Analysis of gene duplication events showed that 62% of TaM24 genes in wheat came from fragment duplication events, and there were no tandem duplication events to amplify genes. Analysis of the promoter sequences of TaM24 genes revealed that cis-acting elements were rich in response elements to drought, osmotic stress, ABA, and MeJA. We also studied the expression of TaM24 in wheat tissues at developmental stages and abiotic stress. Then we selected TaM24-9 as the target for further analysis. The results showed that TaM24-9 genes strengthened the drought and salt tolerance of plants. Overall, our analysis showed that members of the peptidase M24 genes may participate in the abiotic stress response and provided potential gene resources for improving wheat resistance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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