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Breast cancer is the most common malignancy among women worldwide. Functional studies have demonstrated that miRNA dysregulation in many cases of cancer, in which miRNAs act as either oncogenes or tumor suppressor. Here we report that miR-345-3p is generally upregulated in breast cancer tissues and breast cancer cell lines. Overexpression and inhibition of miR-345-3p revealed its capacity in regulating proliferation and invasion of breast cancer cells. Further research identified protein phosphatase 2 catalytic subunit alpha (PPP2CA), a suppressor of AKT phosphorylation, as a candidate target of miR-345-3p. In vitro , miR-345-3p mimics promoted AKT phosphorylation by targeting its negative regulator, PPP2CA. Blocking miR-345-3p relieved its inhibition of PPP2CA, which attenuated PI3K-AKT signaling pathway. In vivo , inhibiting miR-345-3p by miR-345-3p-inhibition lentivirus suppressed tumor growth and invasiveness in mice. Together, the miR-345-3p/PPP2CA signaling axis exhibits tumor-promoting functions by regulating proliferation and invasion of breast cancer cells. These data provide a clue to novel therapeutic approaches for breast cancer. [ABSTRACT FROM AUTHOR]

Many intrusions with adakite-like affinities in collisional zones have obviously higher K2O contents and K2O/Na2O ratios compared with counterparts in subduction zones. A suite of Eocene post-collisional high-K2O adakite-like intrusions, mafic microgranular enclaves, and potassic–ultrapotassic lamprophyres in the Machangqing complex are associated with the Indian–Asian collision within the western Yangtze Craton, southeastern Tibet. The potassic–ultrapotassic lamprophyres, with a zircon U–Pb age of 34·1 ± 0·2 Ma, have high K2O and MgO contents, are enriched in light rare earth elements and large ion lithophile elements, and display high Rb/Sr, and low Ba/Rb and Nb/U ratios. They show enriched isotopic compositions [i.e. (87Sr/86Sr)i = 0·7070–0·7082, εNd(t) = −3·2 to −2·8], and zircon εHf(t) values (−1·6 to +2·6). Their parental magmas are inferred to have been derived from partial melting of an enriched lithospheric mantle, metasomatized by subduction-related fluids. The adakite-like intrusions, with zircon U–Pb ages of 35·4 ± 0·4 and 35·2 ± 0·3 Ma, are characterized by high SiO2 (68·8–71·1 wt%) and Al2O3 (14·0–15·3 wt%) contents, high Sr/Y (41–118) ratios, and low Y (5·3–14·7 ppm) contents. They show low contents of compatible elements (e.g. Ni = 9·5–36·2 ppm) and total REE, and lower Mg# values than the lamprophyres and mafic microgranular enclaves. The adakite-like intrusions have positive large ion lithophile element anomalies, especially potassium, negative high field strength element anomalies, negative εNd(t) (−5·5 to −3·3), and high (87Sr/86Sr)i (0·7064–0·7070) and zircon εHf(t) values (0·0 to +2·7), indicating that they were formed by partial melting of the juvenile lower crust. Mafic microgranular enclaves hosted in the adakite-like intrusions, with U–Pb ages similar to the lamprophyre of c. 34 Ma, exhibit disequilibrium textures, and some of them contain phlogopite. They exhibit potassic–ultrapotassic affinity, and relatively high compatible element contents. They are also characterized by enriched isotopic compositions with (87Sr/86Sr)i = 0·7063–0·7074, εNd(t) = −6·6 to −4·1, and variable zircon εHf(t) values (−0·6 to +3·2). Petrological and geochemical evidence suggests that the mafic microgranular enclaves were formed by magma mixing between potassic–ultrapotassic and pristine adakite-like melts. We propose a magma mixing model for the origin of the high-K2O adakite-like intrusions from the Machangqing complex. In this model, the formation of high-K2O adakite-like intrusions occurred in three stages: (1) partial melting of metasomatized lithospheric mantle generated potassic–ultrapotassic mafic melts; (2) underplating of these mafic melts beneath thickened juvenile lower crust resulted in partial melting of juvenile mafic lower crust and the generation of adakite-like melts; (3) magma mixing involved 80 % pristine adakite-like melts and 20 % potassic–ultrapotassic melts. This leads to the enrichment of K2O in these adakite-like intrusions, and magma differentiation further promotes K2O enrichment. These results are applicable to compositionally similar adakite-like rocks produced in other collisional zones, such as the Tibet, Sulu–Dabie and Zagros orogenic belts. From which we conclude that in continental collision zones, the post-collisional mantle-derived magmas characterized by potassic–ultrapotassic affinities are spatially associated with coeval collision-related adakite-like intrusions that originated from lower crustal melting. The emplacement of adakite-like and potassic–ultrapotassic rocks is controlled by the same fault systems, which increases the possibility of interaction between these two magma suites. [ABSTRACT FROM AUTHOR]

This study aimed to determine the mutational spectrum of familial Parkinson's disease and sporadic early-onset Parkinson's disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson's disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson's disease, 242 probands from families with autosomal-dominant Parkinson's disease, and 1242 sEOPD patients (age at onset ≤ 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson's disease-associated genes occurred more frequently in the autosomal-recessive Parkinson's disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson's disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/p.P144Qfs*2) were identified in our cohort. Furthermore, the age at onset of the 132 probands with genetic diagnoses (median, 31.5 years) was about 14.5 years earlier than that of patients without molecular diagnoses (i.e. non-carriers, median 46.0 years). Specifically, the age at onset of Parkinson's disease patients with pathogenic/likely pathogenic variants in ATP13A2, PLA2G6, PRKN, or PINK1 was significantly lower than that of non-carriers, while the age at onset of carriers with other gene pathogenic/likely pathogenic variants was similar to that of non-carriers. The clinical spectrum of Parkinson's disease-associated gene carriers in this mainland Chinese population was similar to that of other populations. We also detected 61 probands with GBA possibly pathogenic variants (3.64%) and 59 probands with GBA p.L444P (3.52%). These results shed insight into the genetic spectrum and clinical manifestations of Parkinson's disease in mainland China and expand the existing repertoire of pathogenic or likely pathogenic variants involved in known Parkinson's disease-associated genes. Our data highlight the importance of genetic testing in Parkinson's disease patients with age at onset < 40 years, especially in those from families with a recessive inheritance pattern, who may benefit from early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

This study is aimed to investigate the effects of ionising radiation (IR) on micronuclei (MN) formation and chromosome aberrations (CAs) in Chinese radiation workers. The study was conducted using peripheral blood lymphocytes from 1392 radiation workers from Public Hospitals of the city of Tangshan (the exposed group), and 143 healthy individuals as the control group. Fluorescence in situ hybridisation (FISH) was used to detect the unstable and stable nuclear CAs on metaphase. TheMN assay was performed using the cytochalasin B method for cytokinesis-block. The MN and CA frequencies were significantly higher in the exposed group than in healthy controls (both p < 0.001). Examination of the incidence rates of MN and CA showed an increasing trend among workers in some occupations compared with the others (all p < 0.05). There were also significant differences in MN and CA rates among workers with different exposure times (all p < 0.05). Stable CA rates demonstrated an increased trend among workers with different exposure times (all p < 0.05), while no significance of unstable CA rates was found among workers with different exposure times (all p < 0.05). Importantly, the frequencies of CA and MN increased among different cumulative radiation dose groups (all p < 0.05). Correlation analysis showed that the frequencies ofMN and CAwere positively associated with the cumulative radiation dose. Longterm exposure to IR may have harmful effects on the health of radiation workers. The data obtained here show an increased risk of genetic instability that correlated with occupation, exposure time and equivalent dose among Chinese radiation workers. [ABSTRACT FROM AUTHOR]

We have investigated a suite of Miocene high-Mg diorite porphyries from Qulong in southern Tibet, the largest porphyry Cu-Mo deposit in China. Laser ablation inductively coupled plasma mass spectrometry zircon U-Pb dating shows that the high-Mg diorite porphyry was emplaced at 15·7 ± 0·2 Ma, which is slightly younger than the Qulong adakite-like Rongmucuola pluton (c. 19·5-16·4 Ma). The Qulong high-Mg diorites have phenocrysts showing disequilibrium textures and include high-Mg# clinopyroxene (0·91-0·97). These porphyry rocks exhibit both ultrapotassic and adakite-like features, and are characterized by high contents of MgO (4·2-5·1 wt %), K2O (3·2-3·6 wt %), and compatible trace elements (e.g. Ni: 115-142 ppm; Cr: 214-291 ppm), as well as by high Sr/Y and La/Yb ratios. The rocks have highly radiogenic isotopic compositions with (87Sr/86Sr)i = 0·707004-0·707198, εNd(t) = -5·1 to -5·5, 207Pb/204Pb = 15·697-15·704, and 208Pb/204Pb = 39·082-39·116, as well as variable zircon εHf values of -3·0 to +5·9. Petrographic, elemental, and isotopic evidence suggests that the Qulong high-Mg diorites were formed by mixing between ultrapotassic and adakite-like melts, derived from metasomatized Tibetan lithospheric mantle and juvenile lower crust, respectively. In contrast, the Qulong pre-ore Rongmucuola pluton is characterized by high SiO2 (66·3-68·9 wt %) and Al2O3 (16·4-17·0 wt %) contents, high Sr/Y ratios (121-151), low compatible element contents (e.g. Ni = 16·0-17·4 ppm; Cr = 14·5-20·2 ppm), low Mg# values (0·44-0·52), positive large-ion lithophile element (LILE) anomalies, marked negative high field strength element (HFSE) anomalies, positive εNd(t) values (+0·4 to +2·5), and low (87Sr/86Sr)i values (0·704847-0·705237). These features indicate that the Rongmucuola pluton was formed by partial melting of subduction-modified juvenile lower crust within the garnet stability field. The newly identified Qulong high-Mg diorite allows us to propose a mixing model for the origin of the Gangdese high-K, adakite-like rocks. In this model, the formation of these rocks occurred in two stages: (1) partial melting of highly metasomatized lithospheric mantle that generated ultrapotassic mafic melts; (2) underplating of such melts beneath thickened juvenile lower crust, which resulted in melting of the lower crust and the generation of adakite-like magmas. Mixing of the adakite-like melt with ultrapotassic magmas elevated the K2O, MgO, and other LILE (e.g. Rb and Ba) contents of the adakite-like melt. Exogenous water necessary for formation of the Gangdese porphyry Cu systems was mainly added during mixing of ultrapotassic magma with adakite-like melt at lower- and/or upper-crustal depths, reflecting the large decrease in the H2O solubility of the ultrapotassic mafic melt upon ascent and decompression. Upper-crustal fractionation of the Rongmucuola magma could also possibly increase the water content of mineralization-related, adakite-like porphyry intrusions at Qulong. Fluid exsolution from the ultrapotassic magma is likely to have been a key process in the generation of the Gangdese porphyry Cu deposits, as well as other porphyry Cu deposits in the Tibetan collisional orogens. [ABSTRACT FROM AUTHOR]

Coeval potassic adakite-like and shoshonitic felsic intrusions in the western Yunnan province of SW China are spatially and temporally associated with Eocene–Oligocene shoshonitic mafic volcanic rocks. The shoshonitic syenite and quartz monzonite intrusions are characterized by high K2O contents (4·9–6·8 wt %) and K2O/Na2O ratios (1·1–1·7), high Y (1·7–34·8 ppm) and Yb (1·50–3·16 ppm) contents, nearly flat heavy rare earth element (HREE) patterns and moderate Eu anomalies (Eu/Eu* = 0·65–0·78). The potassic adakite-like granite and quartz monzonite intrusions are characterized by enrichment in light rare earth elements (LREE), depletion in HREE and fractionated HREE patterns, high Sr (328–1423 ppm), Sr/Y (38–243) and La/Yb (23–62), and low Y and Yb contents. The shoshonitic syenite and quartz monzonites have the same Sr–Nd–Pb isotope compositions as the shoshonitic mafic volcanic rocks. They define linear trends on Harker diagrams, and have similar REE and trace element patterns to the shoshonitic mafic volcanic rocks. These observations suggest that the shoshonitic syenite and quartz monzonite magmas were differentiated from parental shoshonitic mafic melts by fractional crystallization of olivine, clinopyroxene and feldspar. The parent magmas originated from a metasomatized lithospheric mantle source. The shoshonitic syenite and quartz monzonites have higher magmatic zircon δ18O values (6·26–7·05‰) than the mantle, which suggests some 18O enrichment during earlier subduction-related metasomatism of their lithospheric mantle source. The potassic adakite-like granites have Sr–Nd–Pb isotopic compositions that overlap those of lower-crustal amphibolites. They have low Mg#, MgO, Ni and Cr contents, abundant inherited zircons, high zircon &varepsilon;Hf (0–5·5) and mantle-like δ18O (4·78–6·25‰) values. These granites were plausibly derived by partial melting of a thickened, potassic, mafic, lower crust with minor input from an older igneous felsic component. The potassic adakite-like quartz monzonites contain abundant mafic microgranular enclaves, and have transitional major and trace element characteristics between the adakite-like granite and the shoshonitic mafic magma. The quartz monzonites generally have higher Mg#, MgO, Ni and Cr contents than the lower crust-derived adakite-like rocks. They have no inherited zircons and have uniform zircon &varepsilon;Hf and δ18O values. It is suggested that they were derived by variable degrees of mixing between lower-crustal melts and shoshonitic mafic magmas. The coeval shoshonitic and potassic adakite-like rocks appear to be associated with thinning of overthickened lithospheric mantle along the trans-lithospheric Jinsha suture following the collision between India and Asia. This lithospheric thinning could have resulted in the upwelling of the asthenosphere beneath western Yunnan, which induced partial melting of the residual metasomatized lithospheric mantle as well as the thickened lower crust in the Eocene. [ABSTRACT FROM AUTHOR]