Topology hierarchy of transition metal dichalcogenides built from quantum spin Hall layers

The evolution of the physical properties of two-dimensional material from monolayer limit to the bulk reveals unique consequences from dimension confinement and provides a distinct tuning knob for applications. Monolayer 1T'-phase transition metal dichalcogenides (1T'-TMDs) with ubiquitous quantum spin Hall (QSH) states are ideal two-dimensional building blocks of various three-dimensional topological phases. However, the stacking geometry was previously limited to the bulk 1T'-WTe2 type. Here, we introduce the novel 2M-TMDs consisting of translationally stacked 1T'-monolayers as promising material platforms with tunable inverted bandgaps and interlayer coupling. By performing advanced polarization-dependent angle-resolved photoemission spectroscopy as well as first-principles calculations on the electronic structure of 2M-TMDs, we revealed a topology hierarchy: 2M-WSe2, MoS2, and MoSe2 are weak topological insulators (WTIs), whereas 2M-WS2 is a strong topological insulator (STI). Further demonstration of topological phase transitions by tunning interlayer distance indicates that band inversion amplitude and interlayer coupling jointly determine different topological states in 2M-TMDs. We propose that 2M-TMDs are parent compounds of various exotic phases including topological superconductors and promise great application potentials in quantum electronics due to their flexibility in patterning with two-dimensional materials

The Role of SDF-1-CXCR4/CXCR7 Axis in the Therapeutic Effects of Hypoxia-Preconditioned Mesenchymal Stem Cells for Renal Ischemia/Reperfusion Injury

In vitro hypoxic preconditioning (HP) of mesenchymal stem cells (MSCs) could ameliorate their viability and tissue repair capabilities after transplantation into the injured tissue through yet undefined mechanisms. There is also experimental evidence that HP enhances the expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7, which are involved in migration and survival of MSCs in vitro, but little is known about their role in the in vivo therapeutic effectiveness of MSCs in renal ischemia/reperfusion (I/R) injury. Here, we evaluated the role of SDF-1-CXCR4/CXCR7 pathway in regulating chemotaxis, viability and paracrine actions of HP-MSCs in vitro and in vivo. Compared with normoxic preconditioning (NP), HP not only improved MSC chemotaxis and viability but also stimulated secretion of proangiogenic and mitogenic factors. Importantly, both CXCR4 and CXCR7 were required for the production of paracrine factors by HP-MSCs though the former was only responsible for chemotaxis while the latter was for viability. SDF-1α expression was upregulated in postischemic kidneys. After 24 h systemical administration following I/R, HP-MSCs but not NP-MSCs were selectively recruited to ischemic kidneys and this improved recruitment was abolished by neutralization of CXCR4, but not CXCR7. Furthermore, the increased recruitment of HP-MSCs was associated with enhanced functional recovery, accelerated mitogenic response, and reduced apoptotic cell death. In addition, neutralization of either CXCR4 or CXCR7 impaired the improved therapeutic potential of HP-MSCs. These results advance our knowledge about SDF-1-CXCR4/CXCR7 axis as an attractive target pathway for improving the beneficial effects of MSC-based therapies for renal I/R

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Altered Neural Processing of Reward and Punishment in Women With Methamphetamine Use Disorder

It has been suggested that the altered function of reward and punishment is an important vulnerability factor leading to the development of drug use disorders. Previous studies have identified evidence of neurophysiological dysfunction in the reward process of individuals with substance use disorders. To date, only a few event-related potential (ERP) studies have examined the neural basis of reward and punishment processing in women with methamphetamine (MA) use disorders. The current ERP research aims to investigate the neurophysiological mechanisms of reward and punishment in women with MA use disorder using a monetary incentive delay task. Nineteen women with MA use disorder (MA group) and 20 healthy controls (HC group) were recruited in this study. The behavioral data showed that the reaction time (RT) was faster and the response accuracy (ACC) was higher for the potential reward and punishment conditions compared to neutral conditions. During the monetary incentive anticipation stage, the Cue-P3, and stimulus-preceding negativity (SPN) were larger in the MA group than in the HC group. The SPN under the potential reward condition was larger than that under the neutral condition in the MA group but not in the HC group. During the monetary incentive consummation stage, the feedback-related negativity and feedback P3 (FB-P3) following positive feedback were significantly larger than negative feedback in the potential reward condition for the HC group, but not for the MA group. However, the FB-P3 following negative feedback was significantly larger than positive feedback in the potential punishment condition for the MA group, but not the HC group. The results suggest that women with MUD have stronger expectations of generic reward and stronger response of generic harm avoidance, which could be targeted in designing interventions for women with MA use disorder.</p

Characterization of the substrate scope of an alcohol dehydrogenase commonly used as methanol dehydrogenase

Many alcohol dehydrogenases (ADHs) catalyze oxidation of a broad scope of alcohols. When an NAD-dependent ADH oxidizes methanol, albeit at a poor rate, it may be treated as methanol dehydrogenase (MDH). One ADH from Geobacillus stearothermophilus DSM 2334 (GsADH) has been widely used as MDH, but its actual substrate scope remains less characterized. Here we purified recombinant GsADH from Escherichia coli and determined its crystal structure. We collected kinetics data of this enzyme towards a number of short chain alcohols, and found that isopropanol is by far the most favorable substrate. Moreover, molecular docking analysis suggested that substrate preference is mainly attributed to the conformer energy of the protein-substrate complex. Our data clarified the substrate scope of GsADH and provided structural insights, which may facilitate more efficient cofactor regeneration and rational metabolic engineering

Structural Insights into Phosphite Dehydrogenase Variants Favoring a Non-natural Redox Cofactor

Implementation of a non-natural cofactor alternative to the ubiquitous redox cofactor nicotinamide adenosine dinucleotide (NAD) is of great scientific and biotechnological interest. Several redox enzymes have been engineered to favor nicotinamide cytosine dinucleotide (NCD), a smaller-sized NAD analogue. However, molecular interactions involving NAD analogues remain elusive, preventing us from devising more enzymes to accept those analogues. Here we took a semirational approach to evolve phosphite dehydrogenase (Pdh) and identified variants with substantially improved NCD preference. These mutants are valuable components for regeneration of reduced NCD by using phosphite as the electron donor. We then collected X-ray crystal structures of three Pdh variants and their NCD-complexes to delineate molecular basis for NCD binding. It was found that the incorporation of amino acid residues with large side chains enclosing the NAD-binding pocket led to compacted environment favoring NCD over NAD, and additional interactions between NCD and these side chains. These results guided successful engineering of more Pdh mutants with good NCD preference. As many redox enzymes share key structural features, our strategy may be readily adopted to devise NCD-favoring enzymes. We expected that, in the near future, more synthetic systems linked to non-natural cofactors will be created as alternative tools for widespread applications to address challenging problems by chemical and synthetic biologists

Effects of HP on the expression of SDF-1α, CXCR4, CXCR7 in MSCs.

<p>(A) Semiquantitative RT-PCR was used for the analysis of SDF-1α, CXCR4 and CXCR7 mRNA levels in MSCs. GAPDH was used as a control. Lane 1 indicates bone marrow mononuclear cells (BMMCs); lanes 2 to 4, MSC cultures at passage 1 to 3; and lane 5, MSCs at passage 3 and exposed to hypoxia (3% O₂) for 24 h. (B) Western blot analysis was performed to detect CXCR4, CXCR7 and SDF-1α protein expression. β-actin was used as a control. Lanes 1 indicates BMMCs; lanes 2 to 5, MSC cultures at passage 1 to 4; and lane 6, MSCs at the third passage to hypoxia for 24 h. (C) FCM was used to detect extracellular expression of CXCR4 or CXCR7 in MSCs exposed to the indicated periods of hypoxia. *<i>P</i><0.05, vs 0 h. (D) ELISA analysis was performed to determine production of SDF-1α from MSCs exposed to the indicated periods of hypoxia. *<i>P</i><0.05, vs 0 h.</p

The effects of SDF-1-CXCR4/CXCR7 pathway on the therapeutic efficacy of HP-MSCs for treatment of I/R-AKI.

<p>(A and B) BUN (A) and Scr (B) levels as measured in I/R-AKI mice received HP-MSCs, NP-MSCs or vehicle (DMEM). *<i>P</i><0.05 vs DMEM; ^†<i>P</i><0.05 vs NP-MSCs. (C) The histological score of kidney (HSK) in I/R-AKI mice received HP-MSCs, NP-MSCs or vehicle, respectively, was calculated. *<i>P</i><0.05 vs DMEM; ^†<0.05 vs NP-MSCs. (D and E) HP-MSC-treated mice showed a significantly earlier rise in proliferating cells (D), and simultaneous reduction of number of apoptotic cells compared with NP-MSC-treated mice (E). *<i>P</i><0.05 vs DMEM; ^†<i>P</i><0.05 vs NP-MSCs; ^‡<i>P</i><0.05 vs pre-transplantation. (F through J) BUN levels (F), Scr levels (G), HSK (H), renal PCNA expression (I), and renal TUNEL-apoptosis (J) were evaluated in mice treated with HP-MSCs+IgG2B-isotype control antibody, HP-MSCs+anti-CXCR4 antibody, HP-MSCs+IgG-isotype control antibody, and HP-MSCs+anti-CXCR7 antibody, respectively. *<i>P</i><0.05, vs the respective isotype-matched control antibodies.</p