Distinct behavior of electronic structure under uniaxial strain in BaFe_(2)As_(2)

We report a study of the electronic structure of BaFe_(2)As_(2) under uniaxial strains using angle-resolved photoemission spectroscopy and transport measurements. Two electron bands at the MY point, with an energy splitting of 50 meV in the strain-free sample, shift downward and merge into each other under a large uniaxial strain, while three hole bands at theГ point shift downward together. However, we also observed an enhancement of the resistance anisotropy under uniaxial strains by electrical transport measurements, implying that the applied strains strengthen the electronic nematic order in BaFe_(2)As_(2). These observations suggest that the splitting of these two electron bands at the MY point is not caused by the nematic order in BaFe_(2)As_(2).

From Claringbullite to a New Spin Liquid Candidate Cu_3Zn(OH)_6FCl

The search for quantum spin liquid(QSL) materials has attracted significant attention in the field of condensed matter physics in recent years, however so far only a handful of them are considered as candidates hosting QSL ground state. Owning to their geometrically frustrated structures, Kagome materials are ideal systems to realize QSL. We synthesize the kagome structured material claringbullite(Cu_4(OH)_6FCl) and then replace inter-layer Cu with Zn to form Cu_3Zn(OH)_6FCl. Comprehensive measurements reveal that doping Zn^(2+) ions transforms magnetically ordered Cu_4(OH)_6FCl into a non-magnetic QSL candidate Cu_3Zn(OH)_6FCl. Therefore,the successful syntheses of Cu_4(OH)_6FCl and Cu_3Zn(OH)_6FCl provide not only a new platform for the study of QSL but also a novel pathway of investigating the transition between QSL and magnetically ordered systems.

A Secure Three-Factor Authenticated Key Agreement Scheme for Multi-Server Environment

Multi-server authenticated key agreement schemes have attracted great attention to both academia and industry in recent years.However,traditional authenticated key agreement schemes in the single-server environment are not suitable for the multi-server environment because the user has to register on each server when he/she wishes to log in various servers for different service.Moreover,it is unreasonable to consider all servers are trusted since the server in a multi-server environment may be a semi-trusted party.In order to overcome these difficulties,we designed a secure three-factor multi-server authenticated key agreement protocol based on elliptic curve cryptography,which needs the user to register only once at the registration center in order to access all semi-trusted servers.The proposed scheme can not only against various known attacks but also provides high computational efficiency.Besides,we have proved our scheme fulfills mutual authentication by using the authentication test method.

Common (π,π) Band Folding and Surface Reconstruction in Fe As-Based Superconductors

High resolution angle-resolved photoemission spectroscopy(ARPES)measurements are carried out on CaKFe_4 As_4,KCa_2 Fe_4 As_4 F_2 and(Ba_(0.6)K_(0.4))Fe_2 As_2 superconductors.Clear evidence of band folding between the Brillouin zone center and corners with a(π,π)wave vector has been found from the measured Fermi surface and band structures in all the three kinds of superconductors.A dominant √2×√2 surface reconstruction is observed on the cleaved surface of CaKFe_4As_4 by scanning tunneling microscopy(STM)measurements.We propose that the commonly observed √2×√2 reconstruction in the FeAs-based superconductors provides a general scenario to understand the origin of the(π,π)band folding.Our observations provide new insights in understanding the electronic structure and superconductivity mechanism in iron-based superconductors.

Excess-iron driven spin glass phase in Fe_(1+y)Te_(1-x)S_(ex)

The iron-chalcogenide superconductor FeTe_(1-x)Se_(x) displays a variety of exotic features distinct from iron pnictides.Although much effort has been devoted to understanding the interplay between magnetism and superconductivity near x=0.5,the existence of a spin glass phase with short-range magnetic order in the doping range(x~0.1-0.3)has rarely been studied.Here,we use DC/AC magnetization and(quasi)elastic neutron scattering to confirm the spin-glass nature of the short-range magnetic order in a Fe_(1.07)Te_(0.8)Se_(0.2) sample.The AC-frequency dependent spin-freezing temperature T_(f) generates a frequency sensitivityΔT_(f)(ω)/[T_(f)(ω)Δlog_(10)ω]≈0.028 and the description of the critical slowing down withτ=τ0(T_(f)/T_(SG-1))^(-zv) gives T_(SG)≈22 K and zv≈10,comparable to that of a classical spin-glass system.We have also extended the frequency-dependent T_(f) to the smaller time scale using energy-resolution-dependent neutron diffraction measurements,in which the T_(N) of the short-range magnetic order increases systematically with increasing energy resolution.By removing the excess iron through annealing in oxygen,the spin-freezing behavior disappears,and bulk superconductivity is realized.Thus,the excess Fe is the driving force for the formation of the spin-glass phase detrimental to bulk superconductivity.

Observation of a Ubiquitous(π,π)-Type Nematic Superconducting Order in the Whole Superconducting Dome of Ultra-Thin BaFe_(2-x)Ni_(x)As_(2) Single Crystals

In iron-based superconductors,the(0,π) or(π,0) nematicity,which describes an electronic anisotropy with a fourfold symmetry breaking,is well established and believed to be important for understanding the superconducting mechanism.However,how exactly such a nematic order observed in the normal state can be related to the superconducting pairing is still elusive.Here,by performing angular-dependent in-plane magnetoresistivity using ultra-thin flakes in the steep superconducting transition region,we unveil a nematic superconducting order along the(π,π) direction in electron-doped BaFe_(2-x)Ni_(x)As_(2) from under-doped to heavily overdoped regimes with x=0.065- 0.18.It shows superconducting gap maxima along the(π,π) direction rotated by 45° from the nematicity along(0, π) or(π,0) direction observed in the normal state.A similar(π,π)-type nematicity is also observed in the under-doped and optimally doped hole-type Ba1-yKyFe2 As_(2),with y=0.2-0.5.These results suggest that the(π,π) nematic superconducting order is a universal feature that needs to be taken into account in the superconducting pairing mechanism in iron-based superconductors.

Ultrafast optical spectroscopy evidence of pseudogap and electronphonon coupling in an iron-based superconductor KCa_(2)Fe_(4)As_(4)F_(2)

We use ultrafast optical spectroscopy to study the nonequilibrium quasiparticle relaxation dynamics of the iron-based superconductor KCa_(2)Fe_(4)A_(s4)F_(2)with T_(c)= 33.5 K. Our results reveal a possible pseudogap(△_(PG)=(2.4 ± 0.1) me V) below T*≈ 50 K but prior to the opening of a superconducting gap(△SC(0) ≈(4.3 ± 0.1) me V). Measurements under high pump fluence reveal two distinct, coherent phonon oscillations with 1.95 and 5.51 THz frequencies, respectively. The high-frequency A1 g(2) mode corresponds to the c-axis polarized vibrations of Fe As planes with a nominal electron-phonon coupling constant λA1 g(2)= 0.194 ± 0.02.Our findings suggest that the pseudogap is likely a precursor of superconductivity, and the electron-phonon coupling may play an essential role in the superconducting pairing in KCa_(2)Fe_(4)A_(s4)F_(2).

Design, synthesis, molecular modeling, and biological evaluation of acrylamide derivatives as potent inhibitors of human dihydroorotate dehydrogenase for the treatment of rheumatoid arthritis

Human dihydroorotate dehydrogenase(DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis(RA), psoriasis and multiple sclerosis(MS). Herein, a series of acrylamide-based novel DHODH inhibitors as potential RA treatment agents were designed and synthesized. 2-Acrylamidobenzoic acid analog 11 was identified as the lead compound for structureeactivity relationship(SAR) studies. The replacement of the phenyl group with naphthyl moieties improved inhibitory activity significantly to double-digit nanomolar range.Further structure optimization revealed that an acrylamide with small hydrophobic groups(Me, Cl or Br)at the 2-position was preferred. Moreover, adding a fluoro atom at the 5-position of the benzoic acid enhanced the potency. The optimization efforts led to potent compounds 42 and 53-55 with IC50 values of 41, 44, 32, and 42 nmol/L, respectively. The most potent compound 54 also displayed favorable pharmacokinetic(PK) profiles and encouraging in vivo anti-arthritic effects in a dose-dependent manner.

Evidence for charge and spin density waves in single crystals of La_(3)Ni_(2)O_(7) and La_(3)Ni_(2)O_(6)

Charge and spin orders are intimately related to superconductivity in copper oxide superconductors.Elucidation of the competing orders in various nickel oxide compounds is crucial,given the fact that superconductivity has been discovered in Nd_(0.8)Sr_(0.2)NiO_(2)films.Herein,we report structural,electronic transport,magnetic,and thermodynamic characterizations of single crystals of La_(3)Ni_(2)O_(7)and La_(3)Ni_(2)O_(6).La_(3)Ni_(2)O_(7)is metallic with mixed Ni^(2+)and Ni^(3+)valent states.Resistivity measurements yield two transition-like kinks at~110 and 153 K.The kink at 153 K is further revealed from magnetization and specific heat measurements,indicative of the formation of charge and spin density waves.La_(3)Ni_(2)O_(6)single crystals obtained from the topochemical reduction of La_(3)Ni_(2)O_(7)are insulating and show an anomaly at~176 K on magnetic susceptibility.The transition-like behaviors of La_(3)Ni_(2)O_(7)and La_(3)Ni_(2)O_(6)are analogous to those observed in La_(4)Ni_(3)O_(10) and La_(4)Ni_(3)O_(8),suggesting that charge and spin density waves are a common feature in the ternary La-Ni-O system with mixed-valent states of nickel.

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

Neuropsychiatric disorders are multifactorial disorders with diverse aetiological factors.Identifying treatment targets is challenging because the diseases are resulting from heterogeneous biological,genetic,and environmental factors.Nevertheless,the increasing understanding of G protein-coupled receptor(GPCR)opens a new possibility in drug discovery.Harnessing our knowledge of molecular mechanisms and structural information of GPCRs will be advantageous for developing effective drugs.This review provides an overview of the role of GPCRs in various neurodegenerative and psychiatric diseases.Besides,we highlight the emerging opportunities of novel GPCR targets and address recent progress in GPCR drug development.

Exploration on learning molecular docking with deep learning models

Background:Molecular docking-based virtual screening(VS)aims to choose ligands with potential pharmacological activities from millions or even billions of molecules.This process could significantly cut down the number of compounds that need to be experimentally tested.However,during the docking calculation,many molecules have low affinity for a particular protein target,which waste a lot of computational resources.Methods:We implemented a fast and practical molecular screening approach called DL-DockVS(deep learning dock virtual screening)by using deep learning models(regression and classification models)to learn the outcomes of pipelined docking programs step-by-step.Results:In this study,we showed that this approach could successfully weed out compounds with poor docking scores while keeping compounds with potentially high docking scores against 10 DUD-E protein targets.A self-built dataset of about 1.9 million molecules was used to further verify DL-DockVS,yielding good results in terms of recall rate,active compounds enrichment factor and runtime speed.Conclusions:We comprehensively evaluate the practicality and effectiveness of DL-DockVS against 10 protein targets.Due to the improvements of runtime and maintained success rate,it would be a useful and promising approach to screen ultra-large compound libraries in the age of big data.It is also very convenient for researchers to make a well-trained model of one specific target for predicting other chemical libraries and high docking-score molecules without docking computation again.

Superconducting state in Ba_((1-x)) Sr_(x)Ni_(2)As_(2) near the quantum critical point

In the phase diagram of the nickel-based superconductor Ba_(1-x)Sr_(x)Ni_(2)As_(2),T_(C) has been found to be enhanced sixfold near the quantum critical point(QCP) x=0.71 compared with the parent compound.However,the mechanism is still under debate.Here,we report a detailed investigation of the superconducting properties near the QCP(x≈0.7) by utilizing scanning tunneling microscopy and spectroscopy.The temperature-dependent superconducting gap and magnetic vortex state were obtained and analyzed in the framework of the Bardeen-Cooper-Schrieffer model.The ideal isotropic s-wave superconducting gap excludes the long-speculated nematic fluctuations while preferring strong electron-phonon coupling as the mechanism for T_(C) enhancement near the QCP.The lower than expected gap ratio of Δ/(k_(B) T_(C)) is rooted in the fact that Ba_(1-x)Sr_(x)Ni_(2)As_(2) falls into the dirty limit with a serious pair breaking effect similar to the parent compound.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,we identified two potent inhibitors of human DHODH,S312 and S416,with favorable drug-likeness and pharmacokinetic profiles,which all showed broad-spectrum antiviral effects against various RNA viruses,including influenza A virus,Zika virus,Ebola virus,and particularly against SARS-CoV-2.Notably,S416 is reported to be the most potent inhibitor so far with an EC5o of 17 nmol/L and an SI value of 10,505.88 in infec-ted cells.Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells.This work demonstrates that both S312/S416 and old drugs(Leflunomide/Teriflunomide)with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide,no matter such viruses are mutated or not.

Design and Synthesis of a Series of Novel Macrocycle Janus Kinase 2 Inhibitors

Summary of main observation and conclusion Macrocycle has attracted the attention of many researchers in the field of medicinal chemistry due to its unique advantages and good prospects,but the difficulties in drug design and synthesis of macrocycle limit its applications.In this study,a series of macrocyclic derivatives designed from anaplastic lymphoma kinase(ALK)inhibitor lorlatinib were synthesized as Janus kinase 2(JAK2)selective inhibitors.Among them,17f had the best inhibitory activity(IC50=0.177μmol·L^-1)and selectivity for JAK2 over JAK1 and JAK3,which indicated that design of the macrocyclic derivatives might be a feasible strategy for the discovery of novel selective JAK2 inhihitors.

Superconductivity and spin fluctuations

在常规超导体，库柏对被声子调停，它是在声子和电子的电荷性质之间的关联仅仅被需要的一个过程。然而，超导性能也从基本刺激的另外的类型被导出。旋转变化可以证明是能调停的最有希望的候选人如此的异乎寻常的超导性。在一些象 cuprates，基于 Fe 的超导体和重费米子的超导体那样的重要系统，尽管仍然有许多争论，旋转变化在他们的超导性的机制起一个关键作用。在这份报纸，我们将在在旋转变化和超导性之间的关联上给简短评论。

Anisotropic magnetoelastic response in the magnetic Weyl semimetal Co_(3)Sn_(2)S_(2)

Co_(3)Sn_(2)S_(2) is a recently identified magnetic Weyl semimetal in Shandite compounds. Upon cooling, Co_(3)Sn_(2)S_(2) undergoes a ferromagnetic transition with c-axis polarized moments(0.3 μ_(B)/Co) around T_(C)= 175 K, followed by another magnetic anomaly around T_(A)≈ 140 K. A large intrinsic anomalous Hall effect is observed in the magnetic state below TC with a maximum of anomalous Hall angle near T_(A). Here, we report an elastic neutron scattering on the crystalline lattice of Co_(3)Sn_(2)S_(2) in a magnetic field up to 10 T. A strongly anisotropic magnetoelastic response is observed, while only a slight enhancement of the Bragg peaks is observed when B//c. The in-plane magnetic field(B//ab) dramatically suppresses the Bragg peak intensity probably by tilting the moments and lattice toward the external field direction. The in-plane magnetoelastic response commences from T_(C), and as it is further strengthened below T_(A), it becomes nonmonotonic against the field between T_(A) and T_(C) because of the competition from another in-plane magnetic order. These results suggest that a magnetic field can be employed to tune the Co_(3)Sn_(2)S_(2) lattice and its related topological states.

Design, Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4(DPP-4)is a clinically validated target for the treatment of type 2 diabetes mellitus(T2DM).To discover novel and potent DPP-4 inhibitors,three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine.Among the designed compounds,41d-1 was the most po tent one with an IC_(50) value of 16.00 nM.

Discovery of a natural fluorescent probe targeting the Plasmodium falciparum cysteine protease falcipain-2

The Plasmodium falciparum cysteine protease falcipain-2(FP-2) is an attractive antimalarial target. Here, we discovered that the natural compound NP1024 is a nonpeptidic inhibitor of FP-2 with an IC50 value of 0.44 μmol L–1. The most exciting finding is that both in vitro and in vivo, NP1024 directly targets FP-2 in malaria parasite-infected erythrocytes as a natural fluorescent probe, thereby paving the way for an integration of malaria diagnosis and treatment.

Spin excitations and spin wave gap in the ferromagnetic Weyl semimetal Co3Sn2S2

We report a comprehensive neutron scattering study on the spin excitations in the magnetic Weyl semimetal Co3Sn2S2 with a quasi-two-dimensional structure.Both in-plane and out-of-plane dispersions of the spin waves were revealed in the ferromagnetic state.Similarly,dispersive but damped spin excitations were found in the paramagnetic state.The effective exchange interactions were estimated using a semi-classical Heisenberg model to consistently reproduce the experimental TCand spin stiffness.However,a full spin wave gap below Eg=2.3 meV was observed at T=4 K.This value was considerably larger than the estimated magnetic anisotropy energy(~0.6 meV),and its temperature dependence indicated a significant contribution from the Weyl fermions.These results suggest that Co3Sn2S2 is a three-dimensional correlated system with a large spin stiffness,and the low-energy spin dynamics can interplay with the topological electron states.

Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Figure 1.Discovery of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and S416.The detailed descriptions of the discovery workflow are in Method.Binding analysis of S312(B)and S416(C).Thermodynamic analysis of the binding of S312 and S416 to DHODH was carried out at 25 C on a MicroCal iTC200 instrument.Kinetic analysis of the binding of S312 and S416 to DHODH was performed with a Biacore T200 instrument.