Priority Research Program Research Articles

Underwater acoustic metamaterial based on double Dirac cone characteristics in rectangular phononic crystals**Project supported by the National Natural Science Foundation of China (Grant Nos. 11602269, 11972034, and 11802213), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB22040301), and the Research Program of Beijing, China (Grant Nos. Z161100002616034 and Z171100000817010).

We theoretically construct a rectangular phononic crystal (PC) structure surrounded by water with C2v symmetry, and then place a steel rectangular scatterer at each quarter position inside each cell. The final complex crystal has two forms: the vertical type, in which the distance s between the center of the scatterer and its right-angle point is greater than 0.5a, and the transverse type, in which s is smaller than 0.5a (where a is the crystal constant in the x direction). Each rectangular scatterer has three variables: length L, width D, and rotation angle θ around its centroid. We find that, when L and D change and θ is kept at zero, there is always a linear quadruply degenerate state at the corner of the irreducible Brillouin zone. Then, we vary θ and find that the quadruply degenerate point splits into two doubly-degenerate states with odd and even parities. At the same time, the band structure reverses and undergoes a phase change from topologically non-trivial to topologically trivial. Then we construct an acoustic system consisting of a trivial and a non-trivial PC with equal numbers of layers, and calculate the projected band structure. A helical one-way transmission edge state is found in the frequency range of the body band gap. Then, we use the finite-element software Comsol to simulate the unidirectional transmission of this edge state and the backscattering suppression of right-angle, disorder, and cavity defects. This acoustic wave system with rectangular phononic crystal form broadens the scope of acoustic wave topology and provides a platform for easy acoustic operation.

Evaporation of saline colloidal droplet and deposition pattern**Project supported by the National Natural Science Foundation of China (Grant Nos. 11472275 and U1738118), the Chinese Academy of Sciences Key Technology Talent Program, and the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB22040301).

The dynamic process of the evaporation and the desiccation of sessile saline colloidal droplets, and their final deposition are investigated. During the evaporation, the movement of the colloidal particles shows a strong dependence on the salt concentration and the droplet shape. The final deposition pattern indicates a weakened coffee-ring effect in this mixed droplet system. The microscopic observation reveals that as evaporation proceeds, the particle motion trail is affected by the salt concentration of the droplet boundary. The Marangoni flow, which is induced by surface tension gradient originating from the local evaporative peripheral salt enrichment, suppresses the compensation flow towards the contact line of the droplet. The inhomogeneous density and concentration field induced by evaporation or crystallization can be the major reason for various micro-flows. At last stage, the distribution and crystallization of NaCl are affected by the colloidal particles during the drying of the residual liquid film.

Epitaxial growth and air-stability of monolayer Cu2Te**Project supported by the National Key Research & Development Program of China (Grant Nos. 2016YFA0202300 and 2018YF A0305800), the National Natural Science Foundation of China (Grant Nos. 61888102, 11604373, 61622116, and 51872284), the CAS Pioneer Hundred Talents Program, China, the Strategic Priority Research Program of Chinese Academy of Sciences (Grant Nos. XDB30000000 and XDB28000000),

A new two-dimensional atomic crystal, monolayer cuprous telluride (Cu2Te) has been fabricated on a graphene-SiC(0001) substrate by molecular beam epitaxy (MBE). The low-energy electron diffraction (LEED) characterization shows that the monolayer Cu2Te forms a superstructure with respect to the graphene substrate. The atomic structure of the monolayer Cu2Te is investigated through a combination of scanning tunneling microscopy (STM) experiments and density functional theory (DFT) calculations. The stoichiometry of the Cu2Te sample is verified by x-ray photoelectron spectroscopy (XPS) measurement. The angle-resolved photoemission spectroscopy (ARPES) data present the electronic band structure of the sample, which is in good agreement with the calculated results. Furthermore, air-exposure experiments reveal the chemical stability of the monolayer Cu2Te. The fabrication of this new 2D material with a particular structure may bring new physical properties for future applications.

Of Mice and Children: Zika Virus Infection Leads to Variable Defects in Multiple Neurological Functions and Behaviors

Zika virus (ZIKV) has evolved into a global health threat because of its causal link to congenital Zika syndrome. Different case reports indicate that ZIKV infection of pregnant women may cause a spectrum of abnormalities in children. Here we evaluated a large cohort of children with perinatal exposure to ZIKV and identified a spectrum of neurodevelopmental abnormalities in the group. In addition, we show that infection of the mouse neonatal brain by a contemporary ZIKV strain instead of an Asian ancestral strain can cause microcephaly and various abnormal neurological functions. These include defects in social interaction and depression, impaired learning and memory, in addition to severe motor defects, which are present in adult mice as well as in our cohort of children. Importantly, although mouse brains infected later after birth do not have apparent abnormal brain structure, those mice still show significant impairments of visual cortical functions, circuit organization and experience-dependent plasticity. Thus, our study suggests that special attention should be paid to all children born to ZIKV infected mothers for screening of abnormal behaviors and sensory function during childhood. Funding Statement: This work was supported by the Strategic Priority Research Program and Innovation Program of the Chinese Academy of Sciences (No. XDB32020100, QYZDJ-SSW-SMC007), the National Natural Science Foundation of China (NSFC) (31730108, 31430037, U170220023, 81772176, 31670883, 91542201, 81590765, and 31500145), Beijing Municipal Science & Technology Commission (Z181100001518001), the Interdisciplinary Research Funds of Beijing Normal University, the CAMS Initiative Innovative Medicine (No. 2016-I2M-1-005), Major Project for Significant New Drugs Innovation and Development (2015ZX09102023), NIH R01 AI140718, AI069120, AI056154 and AI078389 502 grants, MOST (China, 2016YFD0500304). C.L. was supported by the PUMC Youth Fund (No. 3332016125). Declaration of Interests: The authors confirm that there are no known conflicts of interest associated with this publication. Ethics Approval Statement: The experimental procedures on mice were performed under biosafety level 2 (BSL-2) at Beijing Institute of Microbiology and Epidemiology with Institutional Biosafety Committee approval. The mouse care and experimentation were approved by the Animal Care and Use Committees of the Institutional Animal Care and Use Committee at Institute of Genetics and Developmental Biology (IGDB), Chinese Academy of Sciences, Beijing Institute of Microbiology and Epidemiology and the State Key Laboratory of Cognitive Neuroscience & Learning at Beijing Normal University. For the infant cohort, the study protocol was approved by the institutional review boards at Fundacao Oswaldo Cruz (Fiocruz) and the University of California, Los Angeles. All mothers provided written informed consent for themselves and for their children.

Observation of Simplest Water Chains on Surface Stabilized by a Hydroxyl Group at One End**Supported by the National Natural Science Foundation of China under Grant Nos 11774395 and 91753136, the Beijing Natural Science Foundation under Grant No 4181003, the Strategic Priority Research Program (B) of the Chinese Academy of Sciences under Grant Nos XDB30201000 and XDB28000000.

The key to fully understanding water-solid interfaces relies on the microscopic nature of hydrogen bond networks, including their atomic structures, interfacial interactions, and dynamic behaviors. Here, we report the observation of two types of simplest water chains on Au(111) surface which is expected unstable according to the rules of hydrogen network on noble metal surfaces. A common feature at the end of chain structures is revealed in high resolution scanning tunneling microscopy images. To explain the stability in observed hydrogen bond networks, we propose a structure model of the water chains terminated with a hydroxyl group. The model is consistent with detailed image analysis and molecular manipulation. The observation of simplest water chains suggests a new platform for exploring fundamental physics in hydrogen bond networks on surfaces.

The Unconventional Influence of a Nearby Molecule onto Transport of Single C60 Molecule Transistor**Supported by the National Key R&D Program of China (2016YFA0200800), the Strategic Priority Research Program of Chinese Academy of Sciences under Grant Nos XDB30000000 and XDB07030100, the Sinopec Innovation Scheme (A-381), and the Rise-Sinopec Fund (No 10010104-18-ZC0609-0003).

We study the transport property of single C60 molecular transistors with special focus on the situation that other molecules are in vicinity. The devices are prepared using electromigration and thermal deposition techniques. Pure single C60 molecule transistors show typical coulomb blockade behavior at low temperature. When we increase the coverage of molecules slightly by extending the deposition time, the transport spectrum of devices displays a switching behavior in the general coulomb blockade pattern. We attribute this unconventional phenomenon to the influence from a nearby C60 molecule. By analyzing this transport behavior quantitatively based on the parallel-double-quantum-dot model, the interaction from the nearby molecule is proved to be of capacity and tunneling coupling. Thermal stimulation is also applied to the device to investigate the effect of local charging environment variation on intermolecular interaction.

Experimental Observations Indicating the Topological Nature of the Edge States on HfTe5**Supported by the Chinese Academy of Sciences, the National Natural Science Foundation of China under Grant No 11227903, the BM-STC under Grant No Z181100004218007, the National Basic Research Program of China under Grant Nos 2015CB921300 and 2015CB921304, National Key R&D Program of China under Grant No 2017YFA0302903, the Strategic

The topological edge states of two-dimensional topological insulators with large energy gaps furnish ideal conduction channels for dissipationless current transport. Transition metal tellurides XTe5 (X=Zr, Hf) are theoretically predicted to be large-gap two-dimensional topological insulators, and the experimental observations of their bulk insulating gap and in-gap edge states have been reported, but the topological nature of these edge states still remains to be further elucidated. Here, we report our low-temperature scanning tunneling microscopy/spectroscopy study on single crystals of HfTe5. We demonstrate a full energy gap of ∼80 meV near the Fermi level on the surface monolayer of HfTe5 and that such an insulating energy gap gets filled with finite energy states when measured at the monolayer step edges. Remarkably, such states are absent at the edges of a narrow monolayer strip of one-unit-cell in width but persist at both step edges of a unit-cell wide monolayer groove. These experimental observations strongly indicate that the edge states of HfTe5 monolayers are not trivially caused by translational symmetry breaking, instead they are topological in nature protected by the 2D nontrivial bulk properties.

Probing the minigap in topological insulator-based Josephson junctions under radio frequency irradiation**Project supported by the National Basic Research Program of China (Grant Nos. 2016YFA0300601, 2017YFA0304700, and 2015CB921402), the National Natural Science Foundation China (Grant Nos. 11527806, 91221203, 11174357, 91421303, and 11774405), and the Strategic Priority Research Program B of the Chinese Academy of Sciences (Grant Nos. XDB07010100 and XDB28000000), and

Recently, a contact-resistance-measurement method was developed to detect the minigap, hence the Andreev bound states (ABSs), in Josephson junctions constructed on the surface of three-dimensional topological insulators (3D TIs). In this work, we further generalize that method to the circumstance with radio frequency (rf) irradiation. We find that with the increase of the rf power, the measured minigap becomes broadened and extends to higher energies in a way similar to the rf power dependence of the outer border of the Shapiro step region. We show that the corresponding data of contact resistance under rf irradiation can be well interpreted by using the resistively shunted Josephson junction (RSJ) model and the Blonder–Tinkham–Klapwijk (BTK) theory. Our findings could be useful when using the contact-resistance-measurement method to study the Majorana-related physics in topological insulator-based Josephson junctions under rf irradiation.

Different behavior of upper critical field in Fe1−xSe single crystals**Project supported by the National Natural Science Foundation of China (Grant Nos. 11888101 and 11834016), the National Key Research and Development Program of China (Grant Nos. 2017YFA0303003 and 2016YFA0300300), and the Strategic Priority Research Program and Key Research Program of Frontier Sciences of the Chinese Academy of Sciences (Grant Nos. QYZDY-SSW-SLH001

The temperature dependences of upper critical field (Hc2) for a series of iron-deficient Fe1−xSe single crystals are obtained from the measurements of in-plane resistivity in magnetic fields up to 9 T and perpendicular to the ab plane. For the samples with lower superconducting transition temperature Tc (<7.2 K), the temperature dependence of Hc2 is appropriately described by an effective two-band model. For the samples with higher Tc (≳ 7.2 K), the temperature dependence can also be fitted by a single-band Werthamer–Helfand–Hohenberg formula, besides the two-band model. Such a Tc-dependent change in Hc2(T) behavior is discussed in connection with recent related experimental results, showing an inherent link between the changes of intrinsic superconducting and normal state properties in the FeSe system.

The effect of core segregation on the Cu and Zn isotope composition of the silicate Moon

Chinese Academy of Sciences (Strategic Priority Research Program (B) (Grant No. XDB18000000)); National Science Foundation of China (41325011, 41630206);

Nb-based Josephson parametric amplifier for superconducting qubit measurement**Project supported by the Science Funds from the Ministry of Science and Technology of China (Grant Nos. 2015CB921104 and 2016YFA0300601), the National Natural Science Foundation of China (Grant Nos. 11674380 and 11874063), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant Nos. XDB07010300 and XDB28000000), and the Key Research and

We report a fabrication process and characterization of the Josephson parametric amplifier (JPA) for the single-shot quantum state measurement of superconducting multiqubit system. The device is prepared using Nb film as its base layer, which is convenient in the sample patterning process like e-beam lithography and film etching. Our results show that the JPA has a bandwidth up to 600 MHz with gain above 15 dB and noise temperature approaching the quantum limit. The qubit state differentiation measurements demonstrate the signal-to-noise ratio around 3 and the readout fidelity above 97% and 91% for the ground and first-excited states, respectively.

1489 Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Growth of VK2 Vaginal Epithelial Cells through Micrornas In Vitro

Study Objective To investigate whether and how human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) could accelerate vaginal epithelium cell (VK2) growth. Design hucMSC and exosomes isolated from their conditioned medium were used to treat VK2. Setting Normal human fibroblasts (HFF-1) were used as negative control to hucMSC. Patients or Participants N/A Interventions VK2 cells were co-cultured with hucMSC whose paracrine effect on the viability, cell cycle and cell apoptosis of VK2 vaginal epithelial cells was further assessed by CCK-8 assay and flowcytometry. After identified by TEM-NTA-WB, hucMSC-Ex at different concentrations were used to treat VK2. High-throughput RNA sequencing was utilized to reveal the profile of microRNAs in hucMSC, HFF-1 and their exosomes. The functions of hucMSC-Ex specific microRNAs in VK2 were demonstrated by GeneOntology analysis and confirmed by phenotypic detection in microRNA mimics and inhibitors transfected VK2 and RNAi-hucMSC-Ex treated VK2 cells. Measurements and Main Results hucMSC stimulate VK2 growth through a paracrine route by promoting cell cycle and inhibiting apoptosis. Compared with control and low dose groups, hucMSC-Ex of high concentration (≥1000 ng/ml) significantly increased VK2’s growth after treatment in a dose-depended manner (P Conclusion Our findings indicate that hucMSC-Ex may play a significant role in accelerating VK2’s proliferation by promoting cell cycle and inhibiting apoptosis through exosomal microRNAs in vitro. This supports the potential use of hucMSC-Ex as a cell-free therapy of MRKHS after vaginoplasty. This study was supported by Chinese National Nature Sciences Foundation (grant number 91440107, 81471416 and 81771524) and Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19040102).

Full Conference Title: The 10th International Conference on Petroleum Geochemistry and Exploration in the Afro-Asian Region (AAAPG 2019)

Date of the Event: 10-12 May, 2019Location: Guangzhou, Guangdong, ChinaPrefaceThe 10th International Conference on Petroleum Geochemistry and Exploration in the Afro-Asian Region (AAAPG2019) is an international forum where the latest research and technological advances related to petroleum geochemistry in the Afro-Asian region are presented and exchanged. The objective of the AAAPG2019 is to promote international and interdisciplinary exchange of information, to foster co-operation among researchers in academia, research institutes and industry, and to stimulate growth and advances in the field of petroleum geochemistry across the Afro-Asian region.Scientific topics discussed in this conference include:• 1. Fossil fuel resources of Afro-Asian region & exploration priorities.• 2. Geochemistry of source rocks, petroleum accumulation and alteration.• 3. Oil and gas generation and migration.• 4. Biomarker and isotopic geochemistry.• 5. Novel geochemical technologies and basin modelling.• 6. Geochemistry and petro-physics of unconventional oil & gas.• 7. Environmental geochemistry and bio-geochemistry.• 8. International perspectives and alternative energy sources.The AAAPG2019 was held in Guangzhou, China, on May 10-12, 2019, 220 representatives from 18 countries and regions including India, Indonesia, Saudi Arabia, Nigeria, Sudan, the United States, the United Kingdom, Germany, Canada, Australia, Poland, and China participated in the meeting. A total of 141 abstracts were received, 74 abstracts were presented in oral and 41 abstracts were presented in poster.The papers included in this volume are expanded papers from parts of the abstracts presented in this conference. This volume was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA14010103), China national major S&T program (2017ZX05008-002-030).Guangzhou, China30 July, 2019Yunpeng Wang

Neutron Powder Diffraction Study on the Non-Superconducting Phases of ThFeAsN1−xOx (x = 0.15, 0.6) Iron Pnictide**Supported by the Strategic Priority Research Program of Chinese Academy of Sciences under Grant Nos XDB07020300 and XDB25000000, the National Key Research and Development Program of China under Grant Nos 2017YFA0303103, 2017YFA0302903 and 2016YFA0300502, the National Natural Science Foundation of China under Grant Nos 11374011,

We use neutron powder diffraction to study the non-superconducting phases of ThFeAsN1−xOx with x = 0.15, 0.6. In our previous results of the superconducting phase ThFeAsN with Tc = 30 K, no magnetic transition is observed by cooling down to 6 K, and possible oxygen occupancy at the nitrogen site is shown in the refinement [Europhys. Lett. 117 (2017) 57005]. Here in the oxygen doped system ThFeAsN1−xOx, two superconducting regions (0 ⩽ x ⩽ 0.1 and 0.25 ⩽ x ⩽ 0.55) are identified by transport experiments [J. Phys.: Condens. Matter 30 (2018) 255602]. However, within the resolution of our neutron powder diffraction experiment, neither the intermediate doping x = 0.15 nor the heavily overdoped compound x = 0.6 shows any magnetic order from 300 K to 4 K. Therefore, while it shares the common phenomenon of two superconducting domes as most 1111-type iron-based superconductors, the magnetically ordered parent compound may not exist in this nitride family.

Superconductivity of the FeSe/SrTiO3 Interface in View of BCS–BEC Crossover**Supported by the National Key R&D Program of China under Grant Nos 2017YFA0303600, 2016YFA0300600 and 2016YFA0202300, the National Natural Science Foundation of China under Grant No 11634016, the Strategic Priority Research Program (B) of Chinese Academy of Sciences under Grant No XDB07030100, the Research Program of Beijing Academy of Quantum Information

In paired Fermi systems, strong many-body effects exhibit in the crossover regime between the Bardeen–Cooper–Schrieffer (BCS) and the Bose–Einstein condensation (BEC) limits. The concept of the BCS–BEC crossover, which is studied intensively in the research field of cold atoms, has been extended to condensed matters. Here by analyzing the typical superconductors within the BCS–BEC phase diagram, we find that FeSe-based superconductors are prone to shift their positions in the BCS–BEC crossover regime by charge doping or substrate substitution, since their Fermi energies and the superconducting gap sizes are comparable. Especially at the interface of single-layer FeSe on SrTiO3 substrate, the superconductivity is relocated closer to the crossover unitary than other doped FeSe-based materials, indicating that the pairing interaction is effectively modulated. We further show that hole-doping can drive the interfacial system into the phase with possible pre-paired electrons, demonstrating its flexible tunability within the BCS–BEC crossover regime.

Dramatic Spectral Broadening of Ultrafast Laser Pulses in Molecular Nitrogen Ions**Supported by the National Key Research and Development Program of China under Grant No 2018YFB0504400, the National Natural Science Foundation of China under Grant Nos 11822410, 11734009 and 61575211, the Strategic Priority Research Program of the Chinese Academy of Sciences under Grant No XDB16030300, the Key Research Program of Frontier

We investigate nonlinear interaction of nitrogen molecules with a two-color laser field composed by an intense 800 nm laser pulse and a weak 400 nm laser pulse. It is demonstrated that the spectrum of 400 nm pulses is dramatically broadened when the two beams temporally overlap. In comparison, the spectral broadening in argon is less pronounced, although argon atoms and nitrogen molecules have comparable ionization potentials. We reveal that the dramatic spectral broadening originates from the greatly enhanced nonlinear optical effects in the near-resonant condition of interaction between the 400 nm pulses and the nitrogen molecular ions.

Plasmon reflection reveals local electronic properties of natural graphene wrinkles**Project supported by the National Key Research and Development Program of China (Grant No. 2016YFA0203500), the National Natural Science Foundation of China (Grant No. 11874407), and Strategic Priority Research Program of Chinese Academy of Sciences (Grant No. XDB 30000000).

We systematically studied surface plasmons reflection by graphene wrinkles with different heights on SiC substrate. Combined with numerical simulation, we found that the geometry corrugation of a few nanometer height wrinkle alone does not causes a reflection of graphene plasmons. Instead, the separated wrinkle from substrate exhibits a nonlinear spatial Fermi energy distribution along the wrinkle, which acts as a heterojunction. Therefor a higher graphene wrinkle induces a stronger damped region when propagating graphene surface plasmons encounter the wrinkle and get reflected.

Phase I Study of Apatinib in Combination with Gefitinib As First-Line Treatment in Patients with EGFR-Mutant Advanced Non-Squamous Non-Small Cell Lung Cancer

Background: Dual blockade of the EGFR and VEGFR pathways in EGFR-mutant NSCLC have shown enhanced anti-tumor efficacy versus a (v)EGFR inhibitor alone. This phase I study evaluated the safety, pharmacokinetic (PK) profile and antitumor activity of apatinib, an orally effective VEGFR-2 tyrosine kinase inhibitor (TKI), plus gefitinib as a first-line treatment for EGFR-mutant advanced NSCLC. Methods: Advanced non-squamous NSCLC patients with the EGFR 19 deletion or the 21 L858R mutation who met this study's eligibility criteria were included. There were two cohorts. Cohort A: apatinib 500mg + gefitinib 250mg. Cohort B: apatinib 250mg + gefitinib 250mg. The primary endpoint was safety profile. Other endpoints included PK analysis, objective response rate (ORR) and progression free survival (PFS). Exploratory analysis was conducted using next generation sequencing of plasma circulating-tumor DNA with samples collected at baseline, best of response and after progression disease. Findings: Between July 2016 and April 2017, 13 patients with NSCLC were enrolled in this study. Six patients were enrolled in Cohort A and seven in Cohort B. Most adverse events (AEs) were grade 1-2 and the treatment-related AEs (TRAEs) were similar in both cohorts: rash (100% v 71.4%), diarrhea (66.7% v 71.4%), hypertension (66.7% v 71.4%), proteinuria (66.7% v 42.9%), and hand-foot skin reaction (33.3% v 28.6%). The area under the plasma concentration-time curve (AUC) for the steady state of apatinib was 2864.73 ± 2605.54 ng/ml*h in Cohort A and 2445.09 ± 1550.89 ng/ml*h Cohort B. Median follow-up was 29.7 months. The ORR was 80.0% and the median PFS was 19.2 months in Cohort and it 83.3% and 13.4 months in Cohort B. Patients without a concomitant mutation at baseline had a longer PFS compared with those with a detected concomitant mutation (20.99 months v 13.21 months, P=0.0624). The EGFR-T790M mutation remained the dominant resistance mechanism. Interpretation: Apatinib (500mg) plus gefitinib (250mg) had a tolerable safety profile and promising antitumor activity for EGFR-mutant NSCLC patients in the first-line setting. Phase III trials of apatinib (500mg) plus gefitinib (250mg) are warranted. Funding: This work was supported by National Key R&D Program of China (Grant number: 2016YFC0905500, 2016YFC0905503), The Science and Technology Planning Project of Guangdong Province of China (Grant number: 2017B020227001)，Natural Science Foundation of Guangdong Province of China (Grant number: 2018A0303130243) and The 5010 Clinical Research Foundation of Sun Yat-sen University (Grant number: 2016001). Li Zhang has received research support from the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA12020101 to J.D.). Yan Huang has received research support from Science and Technology Program of Guangzhou (201704020072). Yunpeng Yang was supported by Outstanding Young Talents Program of Sun Yat-sen University Cancer Center (16zxyc03) and Central Basic Scientific Research Fund for Colleges-Young Teacher Training Program of Sun Yat-sen University (17ykpy85). Declaration of Interest: All authors declare no competing interests. Ethical Approval: This trial has been approved by the institutional review boards (ID: 2016-FXY-023) and the independent ethics committees of Sun Yat-sen University Cancer Center (Ethic approval ID: 5010-2016-03). And other participating centers have also obtained the approval from their institutional review boards/independent ethics committees before enrollment. All patients will be required to sign the informed consent form before enrollment.

Loss of Scribble confers cisplatin resistance during NSCLC chemotherapy via Nox2/ROS and Nrf2/PD-L1 signaling.

BackgroundCisplatin resistance remains a major clinical obstacle to the successful treatment of non-small cell lung cancer (NSCLC). Scribble contributes to ROS-induced inflammation and cisplatin-elevated toxic reactive oxygen species (ROS) promotes cell death. However, it is unknown whether and how Scribble is involved in the cisplatin-related cell death and the underlying mechanism of Scribble in response to chemotherapies and in the process of oxidative stress in NSCLC.MethodsWe used two independent cohorts of NSCLC samples derived from patients treated with platinum-containing chemotherapy and xenograft modeling in vivo. We analyzed the correlation between Scribble and Nox2 or Nrf2/PD-L1 both in vivo and in vitro, and explored the role of Scribble in cisplatin-induced ROS and apoptosis.FindingsClinical analysis revealed that Scribble expression positively correlated with clinical outcomes and chemotherapeutic sensitivity in NSCLC patients. Scribble protected Nox2 protein from proteasomal degradation. Scribble knockdown induced cisplatin resistance by blocking Nox2/ROS and apoptosis in LRR domain-dependent manner. In addition, low levels of Scribble correlated with high levels of PD-L1 via activation of Nrf2 transcription in vivo and in vitro.InterpretationsOur study revealed that polarity protein Scribble increased cisplatin-induced ROS generation and is beneficial to chemotherapeutic outcomes in NSCLC. Although Scribble deficiency tends to lead to cisplatin resistance by Nox2/ROS and Nrf2/PD-L1, it is still possible that Scribble deficiency-induced PD-L1 may yield benefits in immunotherapy.FundNational Key R&D Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, National Natural Science Foundation of China, China Postdoctoral Science Foundation.

Ultrasmall Sn Nanodots Dispersed in Cross-Linked N-Doped Carbon Cages for High-Performance Lithium Storage

Sn based materials are the promising anodes in Li-ion batteries for the advantages of high theoretical capacity (994 mAh g-1 for LIBs), high conductivity and low cost. However, the drastic volume change during charging and discharging process results in poor cycling stability. Dispersing nano-sized Sn particles in carbon matrix is an effective way to mitigate the volume change, but the thick carbon matrix may retard ion diffusion. Consider this, we designed nano-Sn/N-doped carbon microcages composites (Sn/NMCs) with Sn nanodots uniformly dispersed inside the N-doped carbon microcages through a simple spray drying process, followed by thermal treatment. The interconnected N-doped carbon skeleton enhances the electronic conductivity, meanwhile the internal channels supply fast paths for Li+ transmission. Taking the advantages of ultrasmall Sn and soft carbon matrix, the Sn/NMCs exhibit excellent electrochemical performance as Li-ion battery anode. It delivers an initial charging capacity of 780 mAh g-1 at 200 mA g-1, and maintains 472 mAh g-1 after 500 cycle.; 323 mAh g-1 is still maintained even at a high current density of 10 A g-1. Moreover, this Sn/NMCs is accessible to scale up and the modification strategy can be extended to other electrode materials. Figure 1 TEM image of Sn/NMCs and the schematic diagram of Li+ and electron transportation processes in Sn/NMCs Acknowledgments This work is supported by the National Natural Science Foundation of China (Grant No. 51371186), the “Strategic Priority Research Program” of the Chinese Project Academy of Science (Grant No.XDA09010201), Ningbo 3315 International Team of Advanced Energy Storage Materials, Zhejiang Province Key Science and Technology Innovation Team (2013TD16). Figure 1