Optimization of the synthesis of BET BD2 selective inhibitor XY153.

XY153 is a promising BET BD2 inhibitor with an IC50 value of 0.79 nM against BRD4 BD2. It shows 354-fold selectivity over BRD4-BD1 and 6-fold selectivity over other BET BD2 domains. However, the reported synthesis route of XY153 and its derivatives are extremely poor-yielding. After the synthesis of three key fragments, XY153 can only be obtained with a yield of 1.3 % in the original four-step reaction. In this study, we reported a three-step alternative route in the synthesis process of XY153. The reaction conditions for this route were thoroughly investigated and optimized, resulting in a significantly improved yield of 61.5 %. This efficient synthesis route establishes a robust chemical foundation for the rapid synthesis of XY153 derivatives as BET BD2 inhibitors in the near future.

Rational design, synthesis and biological evaluation of benzo[d]isoxazole derivatives as potent BET bivalent inhibitors for potential treatment of prostate cancer.

Multivalency is an attractive strategy for effective binding to target protein. Bromodomain and extra-terminal (BET) family features two tandem bromodomains (BD1, BD2), which are considered to be potential new targets for prostate cancer. Herein, we report the rational design, optimization, and evaluation of a class of novel BET bivalent inhibitors based on our monovalent BET inhibitor 7 (Y06037). The representative bivalent inhibitor 17b effectively inhibited the cell growth of LNCaP, exhibiting 32 folds more potency than monovalent inhibitor 7. Besides, 17b induced 95.1 % PSA regression in LNCaP cell at 2 µM. Docking study was further carried out to reveal the potential binding mode of 17b with two BET bromodomains. Our study demonstrates that 17b (Y13021) is a promising BET bivalent inhibitor for the treatment of prostate cancer.

High-Dimensional Bell Test without Detection Loophole.

Violation of Bell's inequalities shows strong conflict between quantum mechanics and local realism. Loophole-free Bell tests not only deepen understanding of quantum mechanics, but are also important foundations for device-independent (DI) tasks in quantum information. High-dimensional quantum systems offer a significant advantage over qubits for closing the detection loophole. In the symmetric scenario, a detection efficiency as low as 61.8% can be tolerated using four-dimensional states and a four-setting Bell inequality [Phys. Rev. Lett. 104, 060401 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.060401]. For the first time, we show that four-dimensional entangled photons violate a Bell inequality while closing the detection loophole in experiment. The detection efficiency of the four-dimensional entangled source is about 71.7%, and the fidelity of the state is 0.995±0.001. Combining the technique of multicore fibers, the realization of loophole-free high-dimensional Bell tests and high-dimensional quantum DI technologies are promising.

Entanglement Swapping and Quantum Correlations via Symmetric Joint Measurements.

We use hyperentanglement to experimentally realize deterministic entanglement swapping based on quantum elegant joint measurements. These are joint projections of two qubits onto highly symmetric, isoentangled bases. We report measurement fidelities no smaller than 97.4%. We showcase the applications of these measurements by using the entanglement swapping procedure to demonstrate quantum correlations in the form of proof-of-principle violations of both bilocal Bell inequalities and more stringent correlation criteria corresponding to full network nonlocality. Our results are a foray into entangled measurements and nonlocality beyond the paradigmatic Bell state measurement and they show the relevance of more general measurements in entanglement swapping scenarios.

Long-Distance Entanglement Purification for Quantum Communication.

High-quality long-distance entanglement is essential for both quantum communication and scalable quantum networks. Entanglement purification is to distill high-quality entanglement from low-quality entanglement in a noisy environment and it plays a key role in quantum repeaters. The previous significant entanglement purification experiments require two pairs of low-quality entangled states and were demonstrated in tabletop. Here we propose and report a high-efficiency and long-distance entanglement purification using only one pair of hyperentangled state. We also demonstrate its practical application in entanglement-based quantum key distribution (QKD). One pair of polarization spatial-mode hyperentanglement was distributed over 11 km multicore fiber (noisy channel). After purification, the fidelity of polarization entanglement arises from 0.771 to 0.887 and the effective key rate in entanglement-based QKD increases from 0 to 0.332. The values of Clauser-Horne-Shimony-Holt inequality of polarization entanglement arises from 1.829 to 2.128. Moreover, by using one pair of hyperentanglement and deterministic controlled-NOT gates, the total purification efficiency can be estimated as 6.6×10^{3} times than the experiment using two pairs of entangled states with spontaneous parametric down-conversion sources. Our results offer the potential to be implemented as part of a full quantum repeater and large-scale quantum network.

Pathways for Entanglement-Based Quantum Communication in the Face of High Noise.

Entanglement-based quantum communication offers an increased level of security in practical secret shared key distribution. One of the fundamental principles enabling this security-the fact that interfering with one photon will destroy entanglement and thus be detectable-is also the greatest obstacle. Random encounters of traveling photons, losses, and technical imperfections make noise an inevitable part of any quantum communication scheme, severely limiting distance, key rate, and environmental conditions in which quantum key distribution can be employed. Using photons entangled in their spatial degree of freedom, we show that the increased noise resistance of high-dimensional entanglement can indeed be harnessed for practical key distribution schemes. We perform quantum key distribution in eight entangled paths at various levels of environmental noise and show key rates that, even after error correction and privacy amplification, still exceed 1 bit per photon pair and furthermore certify a secure key at noise levels that would prohibit comparable qubit based schemes from working.

Experimental High-Dimensional Quantum Teleportation.

Quantum teleportation provides a way to transmit unknown quantum states from one location to another. In the quantum world, multilevel systems which enable high-dimensional systems are more prevalent. Therefore, to completely rebuild the quantum states of a single particle remotely, one needs to teleport multilevel (high-dimensional) states. Here, we demonstrate the teleportation of high-dimensional states in a three-dimensional six-photon system. We exploit the spatial mode of a single photon as the high-dimensional system, use two auxiliary entangled photons to realize a deterministic three-dimensional Bell state measurement. The fidelity of teleportation process matrix is F=0.596±0.037. Through this process matrix, we can prove that our teleportation is both nonclassical and genuine three dimensional. Our work paves the way to rebuild complex quantum systems remotely and to construct complex quantum networks.

Research progress of the POP fugacity model: a bibliometrics-based analysis.

With the emergence of environmental issues regarding persistent organic pollutants (POPs), fugacity models have been widely used in the concentration prediction and exposure assessment of POPs. Based on 778 relevant research articles published between 1979 and 2020 in the Web of Science Core Collection (WOSCC), the current research progress of the fugacity model on predicting the fate and transportation of POPs in the environment was analyzed by CiteSpace software. The results showed that the research subject has low interdisciplinarity, mainly involving environmental science and environmental engineering. The USA was the most paper-published country, followed by Canada and China. The publications of the Chinese Academy of Sciences, Lancaster University, and Environment Canada were leading. Collaboration between institutions was inactive and low intensity. Keyword co-occurrence analysis showed that polychlorinated biphenyls, organochlorine pesticides, and polycyclic aromatic hydrocarbons were the most concerning compounds, while air, water, soil, and sediment were the most concerning environmental media. Through co-citation cluster analysis, in addition to the in-depth exploration of traditional POPs, research on emerging POPs such as cyclic volatile methyl siloxane and dechlorane plus were new research frontiers. The distribution and transfer of POPs in the soil-air environment have attracted the most attention, and the regional grid model based on fugacity has been gradually improved and developed. The co-citation high-burst detection showed that the research hotspots gradually shifted from pollutant persistence and long-range transport potential to pollutant distribution rules among the different environmental media and the long-distance transmission simulation.

Experimental one-step deterministic polarization entanglement purification.

Entanglement purification is to distill high-quality entangled states from low-quality entangled states. It is a key step in quantum repeaters, determines the efficiency and communication rates of quantum communication protocols, and is hence of central importance in long-distance communications and quantum networks. In this work, we report the first experimental demonstration of deterministic entanglement purification using polarization and spatial mode hyperentanglement. After purification, the fidelity of polarization entanglement arises from 0.268±0.002 to 0.989±0.001. Assisted with robust spatial mode entanglement, the total purification efficiency can be estimated as 109 times that of the entanglement purification protocols using two copies of entangled states when one uses the spontaneous parametric down-conversion sources. Our work may have the potential to be implemented as a part of full repeater protocols.

Validating the underlying assumption of quasi-induced exposure technique disaggregated by crash injury severity.

INTRODUCTION: Quasi-induced exposure (QIE) technique has been popularly applied in the field of traffic safety research for decades. One of the basic assumptions of QIE theory is that the not-at-fault driving parties (D2s) involved in the crashes are the random selection of overall driving population at the event of crash occurrence. Very few literatures, however, can be identified to validate the assumption for crashes with specific injury severities that may not be satisfied in reality. METHOD: The study aims to check the validity of the assumption categorized by crash injury severity with the use of Michigan crash data. Latent class analysis is employed to generate several latent classes for the crashes with specific injury outcomes. Chi-square test is adopted to identify the significance of the similarity of D2 distributions among the latent classes. RESULTS: The results indicate that: (a) for fatal crashes the statistical tests do not identify the significant discrepancies for D2 distributions of driver gender, age, and vehicle type between latent classes; (b) for injury crashes, both D2 driver gender and age have the similar distributions between/among various classes, while the D2 vehicle types show the inconsistent distributions; and (c) with respect to property damage only crashes, the distributions of three vehicle-driver characteristics are significantly different among the latent classes. It implies that the underlying assumption may not entirely hold true for all the injury severities and driver-vehicle characteristics. Practical Applications: The findings pinpoint the applicability of the QIE technique under specific scenarios and highlight the importance of validating the underlying assumption of QIE prior to its application.

Selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells.

Membrane proteins on the cell surface perform a myriad of biological functions; however, ligand discovery for membrane proteins is highly challenging, because a natural cellular environment is often necessary to maintain protein structure and function. DNA-encoded chemical libraries (DELs) have emerged as a powerful technology for ligand discovery, but they are mainly limited to purified proteins. Here we report a method that can specifically label membrane proteins with a DNA tag, and thereby enable target-specific DEL selections against endogenous membrane proteins on live cells without overexpression or any other genetic manipulation. We demonstrate the generality and performance of this method by screening a 30.42-million-compound DEL against the folate receptor, carbonic anhydrase 12 and the epidermal growth factor receptor on live cells, and identify and validate a series of novel ligands for these targets. Given the high therapeutic significance of membrane proteins and their intractability to traditional high-throughput screening approaches, this method has the potential to facilitate membrane-protein-based drug discovery by harnessing the power of DEL.

Effect of Zhuang Jing Decoction on Learning and Memory Ability in Aging Rats.

With the average life span of humans on the rise, aging in the world has drawn considerable attentions. The monoamine neurotransmitters and neurotrophic factors in brain areas are involved in learning and memory processes and are an essential part of normal synaptic neurotransmission and plasticity. In the present study, the effect of Zhuang Jing Decoction (ZJD) on the learning and memory ability in aging rats was examined in vivo using Morris water maze. Furthermore, the levels of monoamine neurotransmitters and neurotrophic factors in brain were detected by high-performance liquid chromatography with a fluorescence detector and enzyme-linked immunosorbent assay, respectively. These data showed that oral administration with ZJD at the dose of 30 g·kg(-1) exerted an improved effect on learning and memory ability in aging rats. The results revealed that ZJD could effectively adjust the monoamine neurotransmitters and neurotrophic factors, restore the balance of the level of monoamine neurotransmitters and neurotrophic factors in brain, and finally attenuate the degeneration of learning and memory ability. These findings suggested that ZJD might be a potential agent as cognitive-enhancing drug in improving learning and memory ability. It may exert through regulating the levels of monoamine neurotransmitters and neurotrophic factors in brain, which demonstrated that ZJD had certain antiaging effects.

[Study on display of acupuncture meridian based on electric signal transfer characteristics].

OBJECTIVE: To analyze the real-time effects of electroacupuncture (EA) stimulation by means of multiport network theory and measurement of the electric signals transfer coefficient, so as to explore a way for determining the running course of acupuncture meridian and for characterizing its physiological activities in the living body. METHODS: The body was modeled as a complex inhomogeneous 3-dimensions multi-port network, and the meridians were assumed to be "the most smoothly channels for signal transmission". Experiments were performed in 12 beheaded toads whose forelimbs and hindlimbs were divided into proportional coordinates. A concentric electrode with a conical tip was inserted into the toad leg for electrical stimulation of the local muscle, and another electrode alike was inserted into different spots of the limbs to detect the spreading signals in a 3-dimensional scanning mode. Following detecting the response electric voltage values of various spots and calculating their transfer coefficients, the spots which acquired a maximum signal value were considered to be the "acupoints". The imaginary connective lines passing the "acupoints" were regarded as the running courses of acupuncture meridians. RESULTS: A total of twelve 3-dimensional curves were detected based on the connected lines of electric signal transfer function extremum spots 2 mm beneath the skin of the ipsilateral fore- and hind-limbs of 12 spinal toads. CONCLUSION: The present study initially validates the feasibility of electric signal transfer coefficient measurement for displaying the running course of acupuncture meridian in the toad fore- and hindlimbs.

XRCC7 rs#7003908 Polymorphism and Helicobacter pylori Infection-Related Gastric Antrum Adenocarcinoma.

The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03-8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89-22.77) for XRCC7-TG and 38.49 (22.82-64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (ORinteraction = 1.49). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA.

[Study on signal transmission characteristics of meridian based on electrical network theory and experiments].

Study on features of acupoints with resistance test in the past half century is reviewed in this article. Mechanism and technology of the method are introduced as well as its shortcomings. The determination method of signal transmission along meridians with the combination of electrical network theories and practice is advanced. And the result of a series experiments on one meridian at the superficial part of the body are given as well. Thus, it is concluded that the signals of the point-in/point-out and the signals along a non-meridian path with the same distance are significantly different, which gives a verification of the feasibility of the method by using electrical network theories to set out characteristics of signal transmission along meridians dynamically.

Correlation of vertebral body deformity and adjacent disc degeneration in patients with old thoracolumbar compression fractures / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the correlation between vertebral body deformity and degeneration of the adjacent intervertebral discs in patients with old thoracolumbar compression fractures.</p><p><b>METHODS</b>Seventy-one patients who had been conservatively treated after single segment thoracolumbar compression fractures between April, 2011 and May, 2014 were enrolled in this study. Both radiographic and magnetic resonance (MR) images of the thoracolumbar segment were obtained. The involved vertebral body deformity was rated on radiography according to the Genant criterion, and the degeneration of the adjacent cephalic and caudal discs was assessed on MR images using the Oner and Pfirrmann classification schemes, respectively. The relationship between vertebral body deformity and adjacent disc changes was assessed using correlation analysis, and the changes in the adjacent cranial and caudal discs was compared.</p><p><b>RESULTS</b>The Genant classification of the involved vertebral bodies was moderately correlated with Oner morphological scores (r=0.48, P<0.01), but not with the Pfirrmann signal scores of the adjacent cephalic discs or with the Genant or Pfirrmann scores of the adjacent caudal discs (P>0.05). The Oner classification of the adjacent cephalic discs was higher than that of the adjacent caudal discs (P<0.01), but their Pfirrmann classification did not differ significantly.</p><p><b>CONCLUSION</b>The deformity of vertebral body affects the adjacent cephalic discs proportionally but not the adjacent caudal discs.</p>

MR imaging of acute thigh muscle strains in male football athletes / 实用放射学杂志

Objective To investigate MR findings of acute thigh muscle strains in male football athletes.Methods Twenty five thighs of 21 football athletes with acute muscle strains were analyzed retrospectively.All subjects were examined with MR unit.The anatomical location,size,severity,signal features of the acute strained muscles were analyzed by two experienced radiologists based on MR images.Results There were 32 muscles involved totally,including 1 9 hamstring muscles,5 adductor muscles,7 quadriceps femoris,and 1 sartorius muscle.18 muscles were MR grade 1 injuries,14 of grade 2,and these was no grade 3 injuries.Conclusion Thigh muscle injury of football athletes most frequently involved the hamstring muscle,and MR is an effective tool for detecting acute muscle strains of the thigh.

Correlation of Lumbar Bone Marrow Fat Content with Age, Gender, Body Mass Index and Waist Circumference / 中国医学影像学杂志

PurposeTo investigate the physical characteristics of the lumbar bone marrow fat content by analyzing the correlation of the lumbar bone marrow fat content with age, gender, body mass index (BMI) and waist circumference. It may be helpful to deepen the understanding the occurrence regularity of osteoporosis. Materials and Methods A total of 144 subjects were recruited including both healthy volunteers and the patients with chronic low back pain. The height, weight and waist circumference were measured, and the body mass index was calculated. All the subjects took spectroscopy sequence at the third lumber vertebra with single-voxel point resolved spectroscopy (PRESS) method. Lipid (1.3 ppm) to water (4.67 ppm) ratio (LWR) and lipid fractions (FF%) were measured. LWR and FF% of L3 were compared among the patients with different gender, age, BMI and waist circumference. The correlation of LWR and FF% of L3 and age were analyzed.Results The LWR and FF% of L3 showed no signiifcant difference between the male and female (t=-0.267 and-0.993,P>0.05). There was statistical difference of LWR and FF% among the different age groups (F=3.723 and 5.478,P70 year-old group (P70 year-old group (P0.05). Age was positive correlated with FF% of L3 (r=0.321,P<0.05).Conclusion The lumbar bone marrow fat content is correlated with age, but is not correlated with gender, BMI and waist circumference.