East Asian winter monsoon intensification over the Northwest Pacific Ocean driven by late Miocene atmospheric CO2 decline.

East Asian winter monsoon (EAWM) activity has had profound effects on environmental change throughout East Asia and the western Pacific. Much attention has been paid to Quaternary EAWM evolution, while long-term EAWM fluctuation characteristics and drivers remain unclear, particularly during the late Miocene when marked global climate and Asian paleogeographic changes occurred. To clarify understanding of late Miocene EAWM evolution, we developed a high-precision 9-million-year-long stacked EAWM record from Northwest Pacific Ocean abyssal sediments based on environmental magnetism, sedimentology, and geochemistry, which reveals a strengthened late Miocene EAWM. Our paleoclimate simulations also indicate that atmospheric CO2 decline played a vital role in this EAWM intensification over the Northwest Pacific Ocean compared to other factors, including central Asian orogenic belt and northeastern Tibetan Plateau uplift and Antarctic ice-sheet expansion. Our results expand understanding of EAWM evolution from inland areas to the open ocean and indicate the importance of atmospheric CO2 fluctuations on past EAWM variability over large spatial scales.

Intraplate thrust orogeny of the Altai Mountains revealed by deep seismic reflection.

The Altai orogen is a typical intracontinental orogen in Central Asia that experienced far-field deformation associated with Indian-Eurasian plate convergence. This region is characterized by uplift comparable to that of the Tianshan Mountains but has a distinct strain rate. Half of the Indo-Asia strain is accommodated by the Tianshan Mountains, whereas the Altai Mountains accommodates only 10%. To elucidate how the Altai Mountains produced such a large amount of uplift with only one-fifth of the strain rate of the Tianshan Mountains, we constructed a detailed crustal image of the Altai Mountains based on a new 166.8-km deep seismic reflection profile. The prestack migration images reveal an antiform within the Erqis crust, an âˆ¼10 km Moho offset between the Altai arc and the East Junggar area, and a major south-dipping (30° dip) thrust in the lower crust beneath the Altai Mountains, which is connected to the Moho offset. The south-dipping thrust not only records the southward subduction of the Ob-Zaisan Ocean in the Paleozoic but also controlled the Altai deformation pattern in the Cenozoic with the Erqis antiform. The Erqis antiform prevented the extension of deformation to the Junggar crust. The south-dipping thrust in the lower crust of the Altai area caused extrusion of the lower crust, generating uplift at the surface, thickening of the crust, and steep (∼10 km) Moho deepening in the Altai Mountains. This process significantly widened the deformation zone of the Altai Mountains. These findings provide a new geodynamic model for describing how inherited crustal structure controls intraplate deformation without strong horizontal stress.

Preoperative prediction of sonic hedgehog and group 4 molecular subtypes of pediatric medulloblastoma based on radiomics of multiparametric MRI combined with clinical parameters.

Purpose: To construct a machine learning model based on radiomics of multiparametric magnetic resonance imaging (MRI) combined with clinical parameters for predicting Sonic Hedgehog (SHH) and Group 4 (G4) molecular subtypes of pediatric medulloblastoma (MB). Methods: The preoperative MRI images and clinical data of 95 patients with MB were retrospectively analyzed, including 47 cases of SHH subtype and 48 cases of G4 subtype. Radiomic features were extracted from T1-weighted imaging (T1), contrast-enhanced T1 weighted imaging (T1c), T2-weighted imaging (T2), T2 fluid-attenuated inversion recovery imaging (T2FLAIR), and apparent diffusion coefficient (ADC) maps, using variance thresholding, SelectKBest, and Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms. The optimal features were filtered using LASSO regression, and a logistic regression (LR) algorithm was used to build a machine learning model. The receiver operator characteristic (ROC) curve was plotted to evaluate the prediction accuracy, and verified by its calibration, decision and nomogram. The Delong test was used to compare the differences between different models. Results: A total of 17 optimal features, with non-redundancy and high correlation, were selected from 7,045 radiomics features, and used to build an LR model. The model showed a classification accuracy with an under the curve (AUC) of 0.960 (95% CI: 0.871-1.000) in the training cohort and 0.751 (95% CI: 0.587-0.915) in the testing cohort, respectively. The location of the tumor, pathological type, and hydrocephalus status of the two subtypes of patients differed significantly (p < 0.05). When combining radiomics features and clinical parameters to construct the combined prediction model, the AUC improved to 0.965 (95% CI: 0.898-1.000) in the training cohort and 0.849 (95% CI: 0.695-1.000) in the testing cohort, respectively. There was a significant difference in the prediction accuracy, as measured by AUC, between the testing cohorts of the two prediction models, which was confirmed by Delong's test (p = 0.0144). Decision curves and nomogram further validate that the combined model can achieve net benefits in clinical work. Conclusion: The combined prediction model, constructed based on radiomics of multiparametric MRI and clinical parameters can potentially provide a non-invasive clinical approach to predict SHH and G4 molecular subtypes of MB preoperatively.

Voluminous continental growth of the Altaids and its control on metallogeny.

The Altaids is generally considered to be the largest Phanerozoic accretionary orogen on Earth, but it is unclear whether it was associated with extensive continental crustal growth and whether there is a link between the crustal growth and ore mineralization. This paper reviews whole-rock Nd and zircon Hf isotope data for felsic-intermediate-mafic igneous rocks in the Altaids and presents Nd + Hf isotopic contour maps for this region. The maps highlight the 3D lithospheric compositional architecture of the Altaids and make it possible to quantitatively evaluate the crustal growth and its relationship with ore deposits. The Altaids hosts ∼4 107 350 km2 and ∼184 830 750 km3 (assuming a crustal thickness of 40-50 km) juvenile crust (ϵ Nd(t) > 0), accounting for 58% by isotope-mapped area (∼7 010 375 km2) of almost all outcrops of the Altaids (∼8 745 000 km2) and formed during 1000-150 Ma (mainly 600-150 Ma). The juvenile crustal, slightly juvenile-reworked crustal and slightly reworked crustal provinces controlled the Cu-Au, the Pb-Zn-Ag and the Li-Be, Nb-Ta and W-Sn ore deposits. According to the crustal architecture and background of deep compositions, we propose that the ore deposits can be grouped into three types: juvenile crust-related, mixed-source (or slightly juvenile crust)-related and reworked crust-related. This highlights the close relationship between accretion, continental growth and mineralization, and will facilitate exploration for specific ore-deposit types in the Altaids.

A new biologic paleoaltimetry indicating Late Miocene rapid uplift of northern Tibet Plateau.

The uplift of the Tibet Plateau (TP) during the Miocene is crucial to understanding the evolution of Asian monsoon regimes and alpine biodiversity. However, the northern Tibet Plateau (NTP) remains poorly investigated. We use pollen records of montane conifers (Tsuga, Podocarpus, Abies, and Picea) as a new paleoaltimetry to construct two parallel midrange paleoelevation sequences in the NTP at 1332 ± 189 m and 433 ± 189 m, respectively, during the Middle Miocene [~15 million years ago (Ma)]. Both midranges increased rapidly to 3685 ± 87 m in the Late Miocene (~11 Ma) in the east, and to 3589 ± 62 m at ~7 Ma in the west. Our estimated rises in the east and west parts of the NTP during 15 to 7 Ma, together with data from other TP regions, indicate that during the Late Miocene the entire plateau may have reached a high elevation close to that of today, with consequent impacts on atmospheric precipitation and alpine biodiversity.

The value of cardiac magnetic resonance imaging in endocardial fibroelastosis.

Introduction: Endocardial fibroelastosis (EFE), an uncommon congenital heart disorder often occurring in infants, has a poor prognosis. It is of great significance to perform early diagnosis and accurately analyze cardiac function to enable further clinical treatment and prognosis decisions. This study aimed to explore the findings of cardiac magnetic resonance (CMR) in patients with EFE, including morphological changes and cardiac function analyses. Additionally, we compared the difference in the evaluation of the cardiac function between CMR and echocardiography (Echo). Methods: Eleven patients with EFE (nine females and two males, aged between 0.3 and 1.9 years), treated in our hospital, were analyzed retrospectively. Left ventricular posterior wall thickness (LVPW), anterior wall thickness (LVAW), fractional shortening (FS), ejection fraction (EF), end-systolic diameter (ESD), end-diastolic diameter (EDD), end-systolic volume (ESV), and end-diastolic volume (EDV) were assessed using both Echo and CMR. The Original Ross classification and the New York Heart Association functional classification were used to grade the patients' cardiac function. The correlations between clinical cardiac function classification and MRI- and Echo-derived imaging data were determined. Results: All patients showed a thickened endocardium and left ventricle globular dilatation on CMR. We observed significant systolic dysfunction and whole or segmental abnormal ventricular movement. Compared with those measured by Echo, the EF, FS, and EDV values were significantly lower when measured using CMR. Compared with Echo measurements, the ESV, ESD, LVAW, and LVPW values were significantly higher when measured using CMR. CMR-measured EF and FS correlated better with the clinical cardiac functional score than those derived from Echo (EF, r = 0.646 > 0.224; FS, r = 0.627 > 0.245, respectively). Conclusion: In patients with EFE, the characteristic morphological changes of the heart could be displayed accurately using CMR. The parameters measured by CMR were more accurate than those of Echo and correlated well with clinical cardiac function scores, mainly because it does not make invalid geometrical assumptions.

Late Miocene Tarim desert wetting linked with eccentricity minimum and East Asian monsoon weakening.

Periodic wetting is an inherent feature of many monsoon marginal region deserts. Previous studies consistently demonstrate desert wetting during times of Earth's high orbital eccentricity and strong summer monsoon. Here we report the first evidence demonstrating desert wetting during Earth's low orbital eccentricity from the late Miocene strata of the northwestern Tarim Basin of northern China, which is commonly thought to be beyond the range of Asian monsoon precipitation. Using mechanisms for modern Tarim wetting as analogs, we propose that East Asian summer monsoon weakening enhanced westward moisture transport and caused opposite desert wetting pattern to that observed in monsoon marginal region deserts. This inference is supported by our model simulations. This result has far-reaching implications for understanding environmental variations in non-monsoonal deserts in the next few thousands of years under high atmospheric CO2 content and low eccentricity.

Intracontinental deformation of the Tianshan Orogen in response to India-Asia collision.

How the continental lithosphere deforms far away from plate boundaries has been long debated. The Tianshan is a type-example of ongoing lithospheric deformation in an intracontinental setting. It formed during the Paleozoic accretion of the Altaids and was rejuvenated in the Cenozoic, which might be a far-field response to the India-Asia collision. Here we present seismic images of the lithosphere across the central Tianshan, which were constructed from receiver functions and Rayleigh wave dispersions along a N-S-trending linear seismic array. We observe an extensively deformed lithosphere in the Tianshan with inherited, structurally controlled brittle deformation in the shallow crust and plastic deformation near the Moho. We find that earlier multiple accretionary structures were preserved in the crust, which was deformed by pure-shear shortening in the south and thick-skinned tectonics in the north but was limitedly underthrusted by surrounding blocks. A balanced cross-section of Moho discontinuities supports the concept that intracontinental deformation in the Tianshan intensified synchronously with the direct contact between the underthrusting Indian slab and the Tarim Craton in the Late Miocene (~10 Ma). These findings provide a robust and unified seismic model for the Tianshan Orogen, and confirm that effective delivery of the India-Asia collision stress induced the rejuvenation of this intracontinental orogen.

Rollback, scissor-like closure of the Mongol-Okhotsk Ocean and formation of an orocline: magmatic migration based on a large archive of age data.

Tracing the closure of oceans with irregular margins and the formation of an orocline are crucial for understanding plate reconstruction and continental assembly. The eastern Central Asian Orogenic Belt, where the Mongol-Okhotsk orocline is situated, is one of the world's largest magmatic provinces. Using a large data set of U-Pb zircon ages, we updated the timing of many published igneous rocks, which allowed us to recognize tightly 'folded' linear Carboniferous-Jurassic magmatic belts that wrap around the Mongol-Okhotsk suture and their migrations both sutureward and suture-parallel. The new successive magmatic belts reveal a rollback, scissor-like (or zipper-like) closure of the Mongol-Okhotsk Ocean that was fundamentally controlled by coeval subduction rollback and rotation of the Siberian and Mongolian-Erguna blocks. This study also demonstrates the complex mechanisms and processes of the closure of an ocean with irregular margins and the formation of a consequent orocline.

Eccentricity forcing of East Asian monsoonal systems over the past 3 million years.

The East Asian summer monsoon and the precipitation it brings are relevant for millions of people. Because of the monsoon's importance, there has been a substantial amount of work attempting to describe the driving mechanisms behind its past variability. However, discrepancies exist, with speleothem-based East Asian monsoon reconstructions differing from those based on loess records from the Chinese Loess Plateau during the late Quaternary. The periodicity of wet and dry phases experienced by desert areas that lie on the periphery of the East Asian monsoon's influence offer another independent view of monsoonal variability. Here, we provide environmental records based on magnetic parameters for the last 3 million years from the Tengger Desert, China, one such marginal arid region. Our results reveal wet-dry cycles at a dominant frequency of 405 kiloyears, with drier intervals corresponding to eccentricity minima. These findings are consistent with previous reconstructions of East Asian summer and North African summer monsoon precipitation variability. Our records emphasize the dominant role of eccentricity in forcing East Asian monsoonal precipitation as well as monsoonal-derived environmental fluctuations experienced in peripheral desert areas. These results challenge the traditional view that high-latitude ice sheets are the primary driver of East Asian monsoon precipitation during the Quaternary based on Chinese loess records.

Liposomes modified with double-branched biotin: A novel and effective way to promote breast cancer targeting.

Although active targeting liposomes with cancer-specific ligands can bind and internalize into cancer cells, only a few high-efficiency liposomes have been developed so far because traditional single branched ligand modified liposomes generally failed to deliver adequate therapeutic payload. In this paper, we broke the traditional design concept and synthesized the double branched biotin modified cholesterol (Bio2-Chol) for the first time. On this basis, different biotin density modified liposomes ((Bio-Chol)Lip, (Bio-Chol)2Lip and (Bio2-Chol)Lip) were successfully prepared and used as active targeting drug delivery systems for the treatment of breast cancer. The in vitro and in vivo breast cancer-targeting ability of these liposomes were systemically studied using paclitaxel (PTX) as the model drug. And the uptake mechanism of (Bio2-Chol)Lip was investigated. The results showed that (Bio2-Chol)Lip had the best breast cancer-targeting ability compared with naked paclitaxel, unmodified Lip, (Bio-Chol)Lip and (Bio-Chol)2Lip. In particular, the relative uptake efficiency (RE) and concentration efficiency (CE) of (Bio2-Chol)Lip were respectively enhanced by 5.61- and 5.06-fold compared to that of naked paclitaxel. Both distribution data and pharmacokinetic parameters suggested that the double branched biotin modified liposome ((Bio2-Chol)Lip) is a very promising drug delivery carrier for breast cancer.

Liposomes actively recognizing the glucose transporter GLUT1 and integrin αv ß3 for dual-targeting of glioma.

The treatment of glioma is a great challenge because of the existence of the blood-brain barrier (BBB). In order to develop an efficient glioma-targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs and target glioma, a novel glioma-targeted glucose-RGD (Glu-RGD) derivative was designed and synthesized as ligand for preparing liposomes to effectively deliver paclitaxel (PTX) to cross the BBB and target glioma. The liposomes were prepared and characterized for particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis, and cell cytotoxicity. Also, the Glu-RGD modified liposomes showed superior targeting ability in in vitro and in vivo evaluation as compared to naked PTX, non-coated, singly modified liposomes and liposomes co-modified by physical blending. The relative uptake efficiency and concentration efficiency were enhanced by 4.41- and 4.72-fold compared to that of naked PTX, respectively. What is more, the Glu-RGD modified liposomes also displayed the maximum accumulation of DiD-loaded liposomes at tumor sites compared to the other groups in in vivo imaging. All the results in vitro and in vivo suggested that Glu-RGD-Lip would be a potential delivery system for PTX to treat integrin αv ß3 -overexpressing tumor-bearing mice.

Ascorbic acid-modified brain-specific liposomes drug delivery system with "lock-in" function.

In this study, a novel brain targeting ascorbic acid (AA) derivative with "lock-in" function was designed and synthesized as a liposome ligand to prepare novel liposomes to achieve the effective delivery of drug formulations to brain via glucose transporter 1 (GLUT1) and the Na+-dependent vitamin C transporter (SVCT2). The liposome was prepared and characterized in terms of the particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cell cytotoxicity. The preliminary evaluation in vivo demonstrated that the AA-thiamine disulfide system (TDS)-coated liposome had an improved targeting ability and significantly increased the brain concentration of docetaxel (DTX) as compared to the naked docetaxel, the non-coated and the AA-coated liposomes. The relative uptake efficiency and concentration efficiency were enhanced by 3.24- and 5.62-fold compared to that of the naked docetaxel, respectively. Both distribution data and pharmacokinetic parameters suggested that the ascorbic acid thiamine disulfide delivery system was a promising carrier to enhance central nervous system (CNS) drug's delivery ability into brain.

Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation.

The treatment of glioma has become a great challenge because of the existence of brain barrier (BB). In order to develop an efficient brain targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs, a novel brain-targeted glucose-vitamin C (Glu-Vc) derivative was designed and synthesized as liposome ligand for preparing liposome to effectively deliver paclitaxel (PTX). The liposome was prepared and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cytotoxicity were also characterized. What's more, the cellular uptake of CFPE-labeled Glu-Vc-Lip on GLUT1- and SVCT2-overexpressed C6 cells was 4.79-, 1.95-, 4.00- and 1.53-fold higher than that of Lip, Glu-Lip, Vc-Lip and Glu + Vc-Lip. Also, the Glu-Vc modified liposomes showed superior targeting ability in vivo evaluation compared with naked paclitaxel, non-coated, singly-modified and co-modified by physical blending liposomes. The relative uptake efficiency was enhanced by 7.53 fold to that of naked paclitaxel, while the concentration efficiency was up to 7.89 times. What's more, the Glu-Vc modified liposomes also displayed the maximum accumulation of DiD-loaded liposomes at tumor sites with the strongest fluorescence in the brain in vivo imaging. Our results suggest that chemical modification of liposomes with warheads of glucose and vitamin C represents a promising and efficient strategy for the development of brain-specific liposomes drug delivery system by utilizing the endogenous transportation mechanism of the warheads.

Design, synthesis, and neuroprotective effects of dual-brain targeting naproxen prodrug.

A new dual-targeting naproxen prodrug conjugated with glucose and ascorbic acid for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver naproxen to the brain. Naproxen could be released from the prepared prodrugs when incubated with various buffers, mouse plasma, and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vivo over naproxen. Our results suggest that chemical modification of therapeutics with warheads of glucose and ascorbic acid represents a promising and efficient strategy for the development of brain targeting prodrugs by utilizing the endogenous transportation mechanism of the warheads.

Linking magmatism with collision in an accretionary orogen.

A compilation of U-Pb age, geochemical and isotopic data for granitoid plutons in the southern Central Asian Orogenic Belt (CAOB), enables evaluation of the interaction between magmatism and orogenesis in the context of Paleo-Asian oceanic closure and continental amalgamation. These constraints, in conjunction with other geological evidence, indicate that following consumption of the ocean, collision-related calc-alkaline granitoid and mafic magmatism occurred from 255 ± 2 Ma to 251 ± 2 Ma along the Solonker-Xar Moron suture zone. The linear or belt distribution of end-Permian magmatism is interpreted to have taken place in a setting of final orogenic contraction and weak crustal thickening, probably as a result of slab break-off. Crustal anatexis slightly post-dated the early phase of collision, producing adakite-like granitoids with some S-type granites during the Early-Middle Triassic (ca. 251-245 Ma). Between 235 and 220 Ma, the local tectonic regime switched from compression to extension, most likely caused by regional lithospheric extension and orogenic collapse. Collision-related magmatism from the southern CAOB is thus a prime example of the minor, yet tell-tale linking of magmatism with orogenic contraction and collision in an archipelago-type accretionary orogen.

Paleoproterozoic high-pressure metamorphism in the northern North China Craton and implications for the Nuna supercontinent.

The connection between the North China Craton (NCC) and contiguous cratons is important for the configuration of the Nuna supercontinent. Here we document a new Paleoproterozoic high-pressure (HP) complex dominated by garnet websterite on the northern margin of the NCC. The peak metamorphism of the garnet websterite was after ∼1.90 Ga when it was subducted to eclogite facies at ∼2.4 GPa, then exhumed back to granulite facies at ∼0.9 GPa before ∼1.82 Ga. The rock associations with their structural relationships and geochemical affinities are comparable to those of supra-subduction zone ophiolites, and supported by subduction-related signatures of gabbros and basalts. We propose that a ∼1.90 Ga oceanic fragment was subducted and exhumed into an accretionary complex along the northern margin of the NCC. Presence of the coeval Sharyzhalgai complex with comparable HP garnet websterites in the southern Siberian active margin favours juxtaposition against the NCC in the Paleoproterozoic.

Petrology, geochemistry and geodynamics of basic granulite from the Altay area, North Xinjiang, China.

The basic granulite of the Altay orogenic belt occurs as tectonic lens in the Devonian medium- to lower-grade metamorphic beds through fault contact. The Altay granulite (AG) is an amphibole plagioclase two-pyroxene granulite and is mainly composed of two pyroxenes, plagioclase, amphibole and biotite. Its melano-minerals are rich in Mg/(Mg+Fe2+), and its amphibole and biotite are rich in TiO2. The AG is rich in Mg/(Mg+Fe2+), Al2O3 and depletion of U, Th and Rb contents. The AG has moderate SigmaREE and LREE-enriched with weak positive Eu anomaly. The AG shows island-arc pattern with negative Nb, P and Ti anomalies, reflecting that formation of the AG may be associated with subduction. Geochemical and mineral composition data reflect that the protolith of the AG is calc-alkaline basalt and formed by granulite facies metamorphism having peak P-T conditions of 750 degrees C-780 degrees C and 0.6-0.7 Gpa. The AG formation underwent two stages was suggested. In the early stage of oceanic crustal subduction, calc-alkaline basalt with island-arc environment underwent granulite facies metamorphism to form the AG in deep crust, and in the late stage, the AG was thrust into the upper crust.