diffi culty in the generation of core-shell NPs with a lipid shell containing various amounts of water, which governs the rigidity of the NPs; larger amounts of interfacial water would result in more fl exible NPs. [13][14][15] Microfl uidic platforms can generate lipid-polymer hybrid NPs via rapid reaction and precise manipulation of fl uids inside microchannels; [16][17][18][19][20] however, the fabrication of hybrid NPs with varying water content has not been achieved by microfl uidics. Here, we develop a two-stage microfl uidic platform that can assemble core-shell poly(lactic-co -glycolic acid) (PLGA)-lipid NPs in a single-step. [ 16,21 ] Lipid-covered PLGA NPs or liposomes that have the same size and surface properties, but varying rigidity as a result of tuning the interfacial water layer, can be realized using the same microchip. It enables us to explore how the rigidity of NPs differentially regulates the cellular uptake and to elucidate the intrinsic mechanism. It also allows the treatment of various diseases through the use of specifi c particles.Particle rigidity is tuned by varying the amounts of interfacial water between the PLGA core and lipid shell of the hybrid NPs; this is achieved by altering the injection order of the PLGA and lipid-poly(ethylene glycol) (PEG) organic solutions in the microfl uidic chip. The microfl uidic device shown in Scheme 1 consists of two stages: 1) The fi rst stage comprises three inlets and a straight synthesis microchannel; 2) The second stage is composed of one centered inlet and a spiral mixing channel (see Supporting Information (SI), Figure S1 for more details). We synthesized particles of varying water content and rigidity using the same chip but different order of the introducing reagents. In mode 1, the fi rst stage is used for generating PLGA NPs through interfacial precipitation, while the second stage forms lipid-coated NPs as a result of hydrophobic attraction between the lipid tail and PLGA (P-L NPs; Scheme 1 A, Figure S2 (SI)). In mode 2, we change the injection order by introducing the lipid solution at the fi rst stage and the PLGA solution at the second stage. In this way, lipids form into a liposome in aqueous solution at the fi rst stage, followed by re-assembly onto the surface of PLGA NPs at the second stage through effective mixing (P-W-L NPs; Scheme 1 B, Figure S2 (SI)). The throughput of NPs by a single chip is 41 mL h −1 (≈8 mg h −1 for P-W-L NPs, and ≈6.5 mg h −1 for P-L NPs). For both mode 1 and mode 2, transmission electron microscopy (TEM) images ( Figure 1 A; Figure S2, SI) show complete lipid coverage on the surface of PLGA NPs. The different injection order of the solutions may result in the presence of interfacial water between the PLGA core and lipid shell of the P-W-L NPs (mode 2) but not in P-L NPs (mode 1), which is confi rmed by cryogenic TEM (cryo-TEM Figure 1 B; see also SI). For the P-L NPs, the lipid shell is tightly attached to the PLGA core, while for the P-W-L Even though much research has shown that nanoparticles (NPs) ca...

The mid-Pleistocene transition (MPT) is widely recognized as a shift in paleoclimatic periodicity from 41- to 100-kyr cycles, which largely reflects integrated changes in global ice volume, sea level, and ocean temperature from the marine realm. However, much less is known about monsoon-induced terrestrial vegetation change across the MPT. Here, on the basis of a 1.7-million-year δ13C record of loess carbonates from the Chinese Loess Plateau, we document a unique MPT reflecting terrestrial vegetation changes from a dominant 23-kyr periodicity before 1.2 Ma to combined 100, 41, and 23-kyr cycles after 0.7 Ma, very different from the conventional MPT characteristics. Model simulations further reveal that the MPT transition likely reflects decreased sensitivity of monsoonal hydroclimate to insolation forcing as the Northern Hemisphere became increasingly glaciated through the MPT. Our proxy-model comparison suggests varied responses of temperature and precipitation to astronomical forcing under different ice/CO2 boundary conditions, which greatly improves our understanding of monsoon variability and dynamics from the natural past to the anthropogenic future.

Mechanical exfoliation from bulk layered crystal is widely used for preparing two-dimensional (2D) layered materials, which involves not only out-of-plane interlayer cleavage but also in-plane fracture. Through a statistical analysis on the exfoliated 2D flakes, we reveal the in-plane cleavage behaviors of six representative layered materials, including graphene, h-BN, 2H phase MoS2, 1T phase PtS2, FePS3, and black phosphorus. In addition to the well-known interlayer cleavage, these 2D layered materials show a distinctive tendency to fracture along certain in-plane crystallography orientations. With theoretical modeling and analysis, these distinct in-plane cleavage behaviors can be understood as a result of the competition between the release of the elastic energy and the increase of the surface energy during the fracture process. More importantly, these in-plane cleavage behaviors provide a fast and noninvasive method using optical microscopy to identify the lattice direction of mechanical exfoliated 2D layered materials.

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This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h −1 , resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications.

Abstract. The global climate system has experienced a series of drastic changes during the Cenozoic. These include the climate transformation in Asia, from a zonal pattern to a monsoon-dominant pattern, the disappearance of subtropical aridity related to a planetary circulation system and the onset of inland deserts in central Asia. Despite of the major advances in the last two decades in characterizing and understanding these climate phenomena, disagreements persist relative to the timing, behaviors and underlying causes. This paper addresses these issues mainly based on two lines of evidence. Firstly, we newly collected the available Cenozoic geological indicators of environment in China to compile the paleoenvironmental maps of ten intervals with a more detailed examination within the Oligocene and Miocene. In confirming the earlier observation that a zonal climate pattern was transformed into a monsoonal one, the new maps within the Miocene indicate that this major change was achieved by the early Miocene, roughly consistent with the onset of loess deposition in China. Although a monsoon-like regime would have existed in the Eocene, it was restricted in the tropical-subtropical regions. The observed latitudinal oscillations of the climate zones during the Paleogene are likely attributable to the imbalanced evolution of polar ice-sheets between the two hemispheres. Secondly, we examine the relevant depositional and soil-forming processes of the Miocene loess-soil sequences to determine the circulation characteristics with special emphasis given to the early Miocene. Continuous eolian deposition in the middle reaches of the Yellow River since the early Miocene firmly indicates the formation of inland deserts, which has been constantly maintained in the past 22 Ma. Inter-section grain-size gradients indicate northerly dust-carrying winds and source location, as is regarded as the main criteria of the Asian winter monsoon system. Meanwhile, the well-developed Luvisols evidence the existence of circulations from the ocean, which brought moisture to northern China. These imply the coexistence of two kinds of circulations, one from the ocean as moisture carrier and another from the inland deserts as dust transporter. The accretionary properties of the early Miocene paleosols, resulted from interactive soil-forming and dust deposition processes, evidence two seasonally alternative circulations, i.e. a monsoonal climate regime. The much stronger development of the early Miocene soils compared to those in the Quaternary loess indicates significantly stronger summer monsoons. These lines of evidence indicate a joint change in circulations and inland aridity by the early Miocene, and suggest a dynamic linkage of them. Our recent numerical experiments reconfirm the potential roles of Tibetan uplift and Paratethys shrinkage in triggering this major climate reorganization, as revealed in peer studies, but yielded more details about their combined scenarios. These two factors would have coacted with the help of South China Sea spreading. Although the realistic effects of each factor remain to be further discriminated, probably through more paleoaltimetrical and tectonic approaches, the Miocene loess record provides a vital insight that tectonics had evolved to a threshold by the early Miocene to cause this major climate reorganization in Asia.

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