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Fu Ping : a novel
\"Nainai has lived in Shanghai for many years, and the time has come to find a wife for her adopted grandson. But when the bride she has chosen arrives from the countryside, it soon becomes clear that the orphaned girl has ideas of her own. Her name is Fu Ping, and the more she explores the residential lanes and courtyards behind Shanghai's busy shopping streets, the less she wants to return to the country as a dutiful wife. As Fu Ping wavers over her future, she learns the city through the stories of the nannies, handymen, and garbage collectors whose labor is bringing life and bustle back to postwar Shanghai. Fu Ping is a keenly observed portrait of the lives of lower-class women in Shanghai in the early years of the People's Republic of China. Wang Anyi, one of contemporary China's most acclaimed authors, explores the daily lives of migrants from rural areas and other people on the margins of urban life. In shifting perspectives rich in detail and psychological insight, she sketches their aspirations, their fears, and the subtle ties that bind them together. In Howard Goldblatt's masterful translation, Fu Ping reveals Wang Anyi's precise renderings of history, class, and the human heart\"-- Provided by publisher.
Book
A general method to synthesize and sinter bulk ceramics in seconds
Ceramics are an important class of materials with widespread applications because of their high thermal, mechanical, and chemical stability. Computational predictions based on first principles methods can be a valuable tool in accelerating materials discovery to develop improved ceramics. It is essential to experimentally confirm the material properties of such predictions. However, materials screening rates are limited by the long processing times and the poor compositional control from volatile element loss in conventional ceramic sintering techniques. To overcome these limitations, we developed an ultrafast high-temperature sintering (UHS) process for the fabrication of ceramic materials by radiative heating under an inert atmosphere. We provide several examples of the UHS process to demonstrate its potential utility and applications, including advancements in solid-state electrolytes, multicomponent structures, and high-throughput materials screening.
Journal Article
High electronic conductivity as the origin of lithium dendrite formation within solid electrolytes
Solid electrolytes (SEs) are widely considered as an ‘enabler’ of lithium anodes for high-energy batteries. However, recent reports demonstrate that the Li dendrite formation in Li
7
La
3
Zr
2
O
12
(LLZO) and Li
2
S–P
2
S
5
is actually much easier than that in liquid electrolytes of lithium batteries, by mechanisms that remain elusive. Here we illustrate the origin of the dendrite formation by monitoring the dynamic evolution of Li concentration profiles in three popular but representative SEs (LiPON, LLZO and amorphous Li
3
PS
4
) during lithium plating using time-resolved operando neutron depth profiling. Although no apparent changes in the lithium concentration in LiPON can be observed, we visualize the direct deposition of Li inside the bulk LLZO and Li
3
PS
4
. Our findings suggest the high electronic conductivity of LLZO and Li
3
PS
4
is mostly responsible for dendrite formation in these SEs. Lowering the electronic conductivity, rather than further increasing the ionic conductivity of SEs, is therefore critical for the success of all-solid-state Li batteries.
Despite its importance in lithium batteries, the mechanism of Li dendrite growth is not well understood. Here the authors study three representative solid electrolytes with neutron depth profiling and identify high electronic conductivity as the root cause for the dendrite issue.
Journal Article
Negating interfacial impedance in garnet-based solid-state Li metal batteries
Garnet-type solid-state electrolytes have attracted extensive attention due to their high ionic conductivity, approaching 1 mS cm
−1
, excellent environmental stability, and wide electrochemical stability window, from lithium metal to ∼6 V. However, to date, there has been little success in the development of high-performance solid-state batteries using these exceptional materials, the major challenge being the high solid–solid interfacial impedance between the garnet electrolyte and electrode materials. In this work, we effectively address the large interfacial impedance between a lithium metal anode and the garnet electrolyte using ultrathin aluminium oxide (Al
2
O
3
) by atomic layer deposition. Li
7
La
2.75
Ca
0.25
Zr
1.75
Nb
0.25
O
12
(LLCZN) is the garnet composition of choice in this work due to its reduced sintering temperature and increased lithium ion conductivity. A significant decrease of interfacial impedance, from 1,710 Ω cm
2
to 1 Ω cm
2
, was observed at room temperature, effectively negating the lithium metal/garnet interfacial impedance. Experimental and computational results reveal that the oxide coating enables wetting of metallic lithium in contact with the garnet electrolyte surface and the lithiated-alumina interface allows effective lithium ion transport between the lithium metal anode and garnet electrolyte. We also demonstrate a working cell with a lithium metal anode, garnet electrolyte and a high-voltage cathode by applying the newly developed interface chemistry.
Garnet-type electrolytes are attractive for lithium metal batteries due to their high ionic conductivity. A strategy to decrease interfacial impedance between a lithium metal anode and garnet electrolyte is found promising for all-solid-state batteries.
Journal Article
Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis
Most
BRCA1
-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis.
In vitro
studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of
BRCA1
mutation carriers. Furthermore, R-loops are enriched at the 5′ end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of
Cobra1
, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in
Brca1
-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to
BRCA1
-associated R-loop accumulation and breast cancer development.
The vast majority of BRCA1-driven breast cancers derive from luminal progenitor cells but the mechanisms of this lineage specificity are unclear. Here the authors show that dangerous accumulation of DNA-RNA hybrid structures due to RNA polymerase II pausing, occurs specifically in luminal epithelial cells.
Journal Article
Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation, and Functional Outcomes After Chronic Denervation Injury
This study investigates the efficacy of systemic growth hormone (GH) therapy in ameliorating the deleterious effects of chronic denervation (CD) injury on nerve regeneration and resulting motor function. Using a forelimb CD model, 4 groups of Lewis rats were examined (n = 8 per group):
Group-1 (negative control)
8 weeks of median nerve CD followed by ulnar-to-median nerve transfer;
Group-2 (experimental)
8 weeks of median nerve CD followed by ulnar-to-median nerve transfer and highly purified lyophilized pituitary porcine GH treatment (0.6 mg/day);
Group-3 (positive control)
immediate ulnar-to-median nerve transfer without CD;
Group-4 (baseline)
naïve controls. All animals underwent weekly grip strength testing and were sacrificed 14 weeks following nerve transfer for histomorphometric analysis of median nerve regeneration, flexor digitorum superficialis atrophy, and neuromuscular junction reinnervation. In comparison to untreated controls, GH-treated animals demonstrated enhanced median nerve regeneration as measured by axon density (p < 0.005), axon diameter (p < 0.0001), and myelin thickness (p < 0.0001); improved muscle re-innervation (27.9% vs 38.0% NMJs re-innervated; p < 0.02); reduced muscle atrophy (1146 ± 93.19 µm
2
vs 865.2 ± 48.33 µm
2
; p < 0.02); and greater recovery of motor function (grip strength: p < 0.001). These findings support the hypothesis that GH-therapy enhances axonal regeneration and maintains chronically-denervated muscle to thereby promote motor re-innervation and functional recovery.
Journal Article
Controlled Heat Stress Promotes Myofibrillogenesis during Myogenesis
Hyperthermia therapy has recently emerged as a clinical modality used to finely tune heat stress inside the human body for various biomedical applications. Nevertheless, little is known regarding the optimal timing or temperature of heat stress that is needed to achieve favorable results following hyperthermia therapy for muscle regeneration purposes. The regeneration of skeletal muscle after injury is a highly complex and coordinated process that involves a multitude of cellular mechanisms. The main objective of this study was to characterize the effects of hyperthermal therapy on the overall behavior of myoblasts during myogenic differentiation. Various cellular processes, including myogenesis, myofibrillogenesis, hypertrophy/atrophy, and mitochondrial biogenesis, were studied using systematic cellular, morphological, and pathway-focused high-throughput gene expression profiling analyses. We found that C2C12 myoblasts exhibited distinctive time and temperature-dependence in biosynthesis and regulatory events during myogenic differentiation. Specifically, we for the first time observed that moderate hyperthermia at 39°C favored the growth of sarcomere in myofibrils at the late stage of myogenesis, showing universal up-regulation of characteristic myofibril proteins. Characteristic myofibrillogenesis genes, including heavy polypeptide 1 myosin, heavy polypeptide 2 myosin, alpha 1 actin, nebulin and titin, were all significantly upregulated (p<0.01) after C2C12 cells differentiated at 39°C over 5 days compared with the control cells cultured at 37°C. Furthermore, moderate hyperthermia enhanced myogenic differentiation, with nucleus densities per myotube showing 2.2-fold, 1.9-fold and 1.6-fold increases when C2C12 cells underwent myogenic differentiation at 39°C over 24 hours, 48 hours and 72 hours, respectively, as compared to the myotubes that were not exposed to heat stress. Yet, atrophy genes were sensitive even to moderate hyperthermia, indicating that strictly controlled heat stress is required to minimize the development of atrophy in myotubes. In addition, mitochondrial biogenesis was enhanced following thermal induction of myoblasts, suggesting a subsequent shift toward anabolic demand requirements for energy production. This study offers a new perspective to understand and utilize the time and temperature-sensitive effects of hyperthermal therapy on muscle regeneration.
Journal Article
Amorphous cellulose thin films
Amorphous cellulose thin films with thicknesses of 8–100 nm and sub-nanometer roughness have been fabricated by spin-casting from molecular solutions of cellulose in mixtures of ionic liquids and organic solvents. Combining X-ray, optical and scanning probe measurements, cellulose films have been found to be fully amorphous, and their mass densities are comparable to that of the bulk amorphous cellulose. Full amorphization of cellulose films is achieved through sequential removal of solvents, successive diffusion of ionic liquid molecules out of cellulose films, and simultaneous formation of hydrogen bonding among cellulose chains.Graphic abstract
Journal Article
Enhanced efficacy of chemically modified curcumin in experimental periodontitis: systemic implications
Dental microbial biofilm initiates gingival inflammation, and its suppression is the current dominant strategy for treating periodontitis. However, the host response to the biofilm is largely responsible for the connective tissue breakdown including alveolar bone loss, which is mediated by proinflammatory cytokines and matrix metalloproteinases (MMPs).
The current study compared the efficacy of a novel host-modulation compound, a chemically modified curcumin (CMC 2.24), to that of its parent compound (natural curcumin), in both lipopolysaccharide (LPS) (a bacterial endotoxin)-induced cell culture and in vivo models of periodontitis.
In cell culture, both CMC 2.24 and curcumin appeared similarly effective in suppressing LPS-induced cytokine (IL-1β and TNF-α) secretion by mononuclear inflammatory cells; however, CMC 2.24 significantly reduced MMP-9 secretion by 78% (
<0.05) whereas curcumin was ineffective. In vivo, CMC 2.24 administration was more effective than curcumin in suppressing (a) IL-1β in gingival tissue and (b) MMP-9 in both gingiva and plasma, the latter indicating a reduced severity of systemic inflammation. The difference in primary clinical outcome between the two treatments was that CMC 2.24 reduced the pathologically excessive alveolar bone loss, assessed morphometrically at multiple sites, by 80%-90% (
<0.01), whereas curcumin, surprisingly, either increased (
<0.05) or had no effect on alveolar bone loss at these sites.
These data, plus that from previous studies, support the therapeutic potential of CMC 2.24 in the management of inflammatory periodontal disease and its ability to reduce the risk of associated systemic diseases. The current study also indicates that the MMP-9 inhibitor efficacy is associated with the ability of CMC 2.24 (but not curcumin) to inhibit alveolar bone loss in this rat model of periodontitis.
Journal Article