Aggregation Inducing Reversible Conformational Isomerization of Surface Staple in Au18SR14 Nanoclusters.

The conformation of molecules and materials is crucial in determining their properties and applications. Here, this work explores the reversible transformation between two distinct conformational isomers in metal nanoclusters. This work demonstrates the successful manipulation of a controllable and reversible isomerization of Au18SR14 within an aqueous solution through two distinct methods: ethanol addition and pH adjustment. The initial driver is the alteration of the solution environment, leading to the aggregation of Au18SR14 protected by ligands with smaller steric hindrance. At the atomic level, the folding mode of the unique Au4SR5 staple underpins the observed structural transformation. The reversal of staple conformation leads to color shifting between green and orange-red, and tailors a second emission peak at 725 nm originating from charge transfer from the thiolate to the Au9 core. This work not only deepens the understanding of the surface structure and dual-emission of metal nanoparticles, but also enhances the comprehension of their isomerization.

ISG15 targets glycosylated PD-L1 and promotes its degradation to enhance antitumor immune effects in lung adenocarcinoma.

BACKGROUND: Immunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation. Our published articles demonstrate that ISG15 inhibits lung adenocarcinoma progression. Whether ISG15 can enhance the efficacy of ICIs by modulating PD-L1 remains unknown. METHODS: The relationship between ISG15 and lymphocyte infiltration was identified by IHC. The effects of ISG15 on tumor cells and T lymphocytes were assessed using RT-qPCR and Western Blot and in vivo experiments. The underlying mechanism of PD-L1 post-translational modification by ISG15 was revealed by Western blot, RT-qPCR, flow cytometry, and Co-IP. Finally, we performed validation in C57 mice as well as in lung adenocarcinoma tissues. RESULTS: ISG15 promotes the infiltration of CD4+ T lymphocytes. In vivo and in vitro experiments demonstrated that ISG15 induces CD4+ T cell proliferation and invalidity and immune responses against tumors. Mechanistically, we demonstrated that the ubiquitination-like modifying effect of ISG15 on PD-L1 increased the modification of K48-linked ubiquitin chains thus increasing the degradation rate of glycosylated PD-L1 targeting proteasomal pathway. The expression of ISG15 and PD-L1 was negatively correlated in NSCLC tissues. In addition, reduced accumulation of PD-L1 by ISG15 in mice also increased splenic lymphocyte infiltration as well as promoted cytotoxic T cell infiltration in the tumor microenvironment, thereby enhancing anti-tumor immunity. CONCLUSIONS: The ubiquitination modification of PD-L1 by ISG15 increases K48-linked ubiquitin chain modification, thereby increasing the degradation rate of glycosylated PD-L1-targeted proteasome pathway. More importantly, ISG15 enhanced the sensitivity to immunosuppressive therapy. Our study shows that ISG15, as a post-translational modifier of PD-L1, reduces the stability of PD-L1 and may be a potential therapeutic target for cancer immunotherapy.

Borophene Concentric Superlattices via Self-Assembly of Twin Boundaries.

Due to its in-plane structural anisotropy and highly polymorphic nature, borophene has been shown to form a diverse set of linear superlattice structures that are not observed in other two-dimensional materials. Here, we show both theoretically and experimentally that concentric superlattice structures can also be realized in borophene via the energetically preferred self-assembly of coherent twin boundaries. Since borophene twin boundaries do not require the creation of additional lattice defects, they are exceptionally low in energy and thus easier to nucleate and even migrate than grain boundaries in other two-dimensional materials. Due to their high mobility, borophene twin boundaries naturally self-assemble to form novel phases consisting of periodic concentric loops of filled boron hexagons that are further preferred energetically by the rotational registry of borophene on the Ag(111) surface. Compared to defect-free borophene, concentric superlattice borophene phases are predicted to possess enhanced mechanical strength and localized electronic states. Overall, these results establish defect-mediated self-assembly as a pathway to unique borophene structures and properties.

A Large Family of Synthetic Two-Dimensional Metal Hydrides.

Synthetic two-dimensional (2D) materials without layered bulk allotropes are approaching a new frontier of materials flatland, one with properties richer than those of graphene-like materials. This is the case even as only a few chemical elements and blends have shown synthetic 2D forms. While hydrogen and metals are earth-abundant and form numerous compounds, rarely are 2D materials with only robust metal-hydrogen bonds. Here, a large new family of 2D materials is found from metal hydrides by high-throughput computational search augmented with first-principles calculations. There are 110 thermally and dynamically stable 2D materials that range from metallic materials to wide-gap semiconductors. A subgroup of these materials even varies from topological insulators to nodal-loop semimetals as well as from antiferromagnetic semiconductors to ferromagnetic half-metals. Unexpectedly, these monolayers resemble graphene in an ability to form weak interlayer interaction due to the variable multicenter bonding of hydrogen that eliminates the otherwise prevalent dangling bonds, rather than the covalent bonds between stacked layers as in previously reported synthetic 2D materials. This feature will favor potential experimental synthesis of these metal hydride monolayers.

Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis.

CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation ofCul4ain mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4bgerm cell-specific conditional knock-out (Cul4b(Vasa)),as well asCul4bglobal knock-out (Cul4b(Sox2)) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4bled to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore,Cul4b(Vasa)spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless,Cul4bglobal knock-out males lost their germ cells in an age-dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis.

Gold-Doping of Double-Crown Pd Nanoclusters.

Double-crown Ni, Pd, or Pt nanoclusters have attracted extensive interests due to their aesthetic structure and intriguing properties. However, their doping by other metals remains unknown until now. Herein, Pd4 (PET)8 and Pd5 (PET)10 (PET: SCH2 CH2 Ph) were successfully doped with gold and the doped nanoclusters were characterized by using multiple techniques such as mass spectrometry and X-ray crystallography. It is revealed that in the doping not one but two gold atoms replace one Pd with the other double-crown structure essentially unchanged, and the gold-doping results in the blue-shift of the maximum visible absorption, the increase of optical energy gap and the reduction of anti-aromaticity of monometal Pd nanoclusters. Importantly, it is found that Au4 Pd2 (PET)8 nanocluster bears chirality originating from not only the helixed Au4 Pd2 S8 framework, but also unanimous R or S configuration of sulfur atoms in the enantiomer. For the latter chirality origin, it was not previously reported or proposed. Au4 Pd2 (PET)8 reported here also represents the smallest chiral bimetal nanocluster so far to the best of our knowledge. This work advances one step toward both the tailoring of group 10 metal nanoclusters by doping and the understanding of chirality origin for metal nanoclusters.

CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis.

It is intuitively obvious that the ability of a cell to repair DNA damage is saturable, either by limitation of enzymatic activities, the time allotted to achieve their function, or both. However, very little is known regarding the mechanisms that establish such a threshold. Here we demonstrate that the CUL4A ubiquitin ligase restricts the cellular repair capacity by orchestrating the concerted actions of nucleotide excision repair (NER) and the DNA damage-responsive G1/S checkpoint through selective degradation of the DDB2 and XPC DNA damage sensors and the p21/CIP1/WAF1 checkpoint effector. We generated Cul4a conditional knockout mice and observed that skin-specific Cul4a ablation dramatically increased resistance to UV-induced skin carcinogenesis. Our findings reveal that wild-type cells do not operate at their full DNA repair potential, underscore the critical role of CUL4A in establishing the cellular DNA repair threshold, and highlight the potential augmentation of cellular repair proficiency by pharmacological CUL4A inhibition.

Self-homodyne free-space optical communication system based on orthogonally polarized binary phase shift keying.

A self-homodyne laser communication system based on orthogonally polarized binary phase shift keying is demonstrated. The working principles of this method and the structure of a transceiver are described using theoretical calculations. Moreover, the signal-to-noise ratio, sensitivity, and bit error rate are analyzed for the amplifier-noise-limited case. The reported experiment validates the feasibility of the proposed method and demonstrates its advantageous sensitivity as a self-homodyne communication system.

Adding two active silver atoms on Au25 nanoparticle.

Alloy nanoparticles with atomic monodispersity is of importance for some fundamental research (e.g., the investigation of active sites). However, the controlled preparation of alloy nanoparticles with atomic monodispersity has long been a major challenge. Herein, for the first time a unique method, antigalvanic reduction (AGR), is introduced to synthesize atomically monodisperse Au25Ag2(SC2H4Ph)18 in high yield (89%) within 2 min. Interestingly, the two silver atoms in Au25Ag2(SC2H4Ph)18 do not replace the gold atoms in the precursor particle Au25(SC2H4Ph)18 but collocate on Au25, which was supported by experimental and calculated results. Also, the two silver atoms are active to play roles in stabilizing the alloy nanoparticle, triggering the nanoparticle fluorescence and catalyzing the hydrolysis of 1,3-diphenylprop-2-ynyl acetate.

Mono-Mercury Doping of Au25 and the HOMO/LUMO Energies Evaluation Employing Differential Pulse Voltammetry.

Controlling the bimetal nanoparticle with atomic monodispersity is still challenging. Herein, a monodisperse bimetal nanoparticle is synthesized in 25% yield (on gold atom basis) by an unusual replacement method. The formula of the nanoparticle is determined to be Au24Hg1(PET)18 (PET: phenylethanethiolate) by high-resolution ESI-MS spectrometry in conjunction with multiple analyses including X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). X-ray single-crystal diffraction reveals that the structure of Au24Hg1(PET)18 remains the structural framework of Au25(PET)18 with one of the outer-shell gold atoms replaced by one Hg atom, which is further supported by theoretical calculations and experimental results as well. Importantly, differential pulse voltammetry (DPV) is first employed to estimate the highest occupied molecular orbit (HOMO) and the lowest unoccupied molecular orbit (LUMO) energies of Au24Hg1(PET)18 based on previous calculations.

Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediated degradation of HOXB4.

Direct transduction of the homeobox (HOX) protein HOXB4 promotes the proliferation of hematopoietic stem cells (HSCs) without induction of leukemogenesis, but requires frequent administration to overcome its short protein half-life (∼1 hour). We demonstrate here that HOXB4 protein levels are post-translationally regulated by the CUL4 ubiquitin ligase, and define the degradation signal sequence (degron) of HOXB4 required for CUL4-mediated destruction. Additional HOX paralogs share the conserved degron in the homeodomain and are also subject to CUL4-mediated degradation, indicating that CUL4 likely controls the stability of all HOX proteins. Moreover, we engineered a degradation-resistant HOXB4 that conferred a growth advantage over wild-type HOXB4 in myeloid progenitor cells. Direct transduction of recombinant degradation-resistant HOXB4 protein to human adult HSCs significantly enhanced their maintenance in a more primitive state both in vitro and in transplanted NOD/SCID/IL2R-γ(null) mice compared with transduction with wild-type HOXB4 protein. Our studies demonstrate the feasibility of engineering a stable HOXB4 variant to overcome a major technical hurdle in the ex vivo expansion of adult HSCs and early progenitors for human therapeutic use.

Novel optical scanning cryptography using Fresnel telescope imaging.

We propose a new method called modified optical scanning cryptography using Fresnel telescope imaging technique for encryption and decryption of remote objects. An image or object can be optically encrypted on the fly by Fresnel telescope scanning system together with an encryption key. For image decryption, the encrypted signals are received and processed with an optical coherent heterodyne detection system. The proposed method has strong performance through use of secure Fresnel telescope scanning with orthogonal polarized beams and efficient all-optical information processing. The validity of the proposed method is demonstrated by numerical simulations and experimental results.

Tilting double-prism scanner driven by cam-based mechanism.

A pair of orthogonal tilting prisms has been explored in our previous work to perform the orientation and position tracking function with tracking accuracy better than submicroradian order. Crucial to the function implementation, however, is the real-time nonlinear control of the tilting angles of double prisms for tracking a given target trajectory. In previous papers [Proc. SPIE5892, 1-5 (2005).PSISDG0277-786X; Appl. Opt.45, 8063 (2006).PSISDG0277-786X; Proc. SPIE6709, 41 (2007).PSISDG0277-786X; Appl. Opt.51, 356 (2011).10.1364/AO.51.000356APOPAI1559-128X; Appl. Opt.53, 3712 (2014).10.1364/AO.53.003712APOPAI1559-128X], a new driving method by a cam-based mechanism, which can transfer the control problem to the design of corresponding cam configuration, is investigated. The design process of a cam-based mechanism is explained from the mapping relation between the tilting angles of a prism and the configuration curve of a corresponding cam. Based on the designed cam-based mechanism, a tracking error less than 0.375% is depicted between the tracking trajectory and the original one. Moreover, the dynamic characteristic of the tracking mechanism is discussed in detail as well as the impacts of different tilting speeds on the tracking trajectory. The proposed tracking mechanism of a tilting double-prism scanner can create a new avenue for passively tracking a given target.

Inverse solutions for a Risley prism scanner with iterative refinement by a forward solution.

Risley prism scanners are increasingly used for laser beam steering due to their wide angular scanning range and high resolution. However, the inverse problem, which focuses on obtaining the required prisms' orientations for a given target position, has not been perfectly solved so far. The existing inverse solutions are not accurate or efficient enough for high-accuracy and real-time tracking. An iterative method that combines an approximate inverse solution with an iterative refinement by the forward solution is set forth in this paper. Two case studies indicate that the rotation motions of Risley prism pairs controlled by iterative solutions can slew the beam to create the desired tracking pattern quickly and accurately. Based on this method, a Risley prism scanner developed as a standard trajectory generator is implemented for the error measurement of a robotic manipulator in our experiments. The simulation and experimental results show that the inverse solution for one target point can be obtained within nine iterations for a prescribed tracking error threshold.

New coherent laser communication detection scheme based on channel-switching method.

A new coherent laser communication detection scheme based on the channel-switching method is proposed. The detection front end of this scheme comprises a 90° optical hybrid and two balanced photodetectors which outputs the in-phase (I) channel and quadrature-phase (Q) channel signal current, respectively. With this method, the ultrahigh speed analog/digital transform of the signal of the I or Q channel is not required. The phase error between the signal and local lasers is obtained by simple analog circuit. Using the phase error signal, the signals of the I/Q channel are switched alternately. The principle of this detection scheme is presented. Moreover, the comparison of the sensitivity of this scheme with that of homodyne detection with an optical phase-locked loop is discussed. An experimental setup was constructed to verify the proposed detection scheme. The offline processing procedure and results are presented. This scheme could be realized through simple structure and has potential applications in cost-effective high-speed laser communication.

Lensless optical image processing based on two-dimensional Fresnel diffraction for synthetic-aperture imaging ladar.

A principle scheme of a lensless optical processor for synthetic-aperture imaging ladar (SAIL) is proposed. The collected data from SAIL is initially digitally added with a quadratic phase in the range direction. These data are then uploaded on a liquid crystal spatial light modulator to modulate the incident light. The target image is obtained through two-dimensional (2D) free-space Fresnel diffraction. The imaging process is mathematically analyzed using a 2D data-collection equation of strip-mode side-looking SAIL. The design equation, imaging resolutions, and target-image compression ratios are presented. Based on this principle scheme, we construct an experimental optical SAIL processor and present the imaging result of data obtained from one SAIL demonstrator. The optical processor is found to exhibit the flexible property of digital processing, as well as the fast processing capability of optical means, because this optical processor is a lensless system.

Dynamic characteristics analysis of a large-aperture rotating prism with adjustable radial support.

Support elements as key components in performing the opto-mechanical function have been an important topic for optical system development. Focusing on a rotation prism with a large aperture and asymmetric loading, a radial multi-segment support is developed to solve the dynamic mounting issue. In order to explore the actual surface deformations over the full rotation, a novel dynamic analysis method to extract the transient load spectrum is established to access the surface deformations, including dynamic load extraction to connect varying loads with corresponding rotation positions, typical position analysis to obtain maximum deformation values, and vibration analysis. The results show that a maximum peak-to-valley value on the plane side reaches 103.16 nm when the prism rotates to 159.84°, and that of the wedge side is 74.38 nm when the prism rotates to 213.84°, both of which are less than λ/4 (λ=632.8 nm). However, when excited by the external loads with response frequency, the surface deformations become more serious. Because the dynamic characteristics obtained can reflect the actual usage situation, the proposed method is preferable for system development.

Inverse solutions for tilting orthogonal double prisms.

An analytical reverse solution and actual examples are given to show how to direct a laser beam from a pair of orthogonal prisms to given targets in free space. Considering the influences of double-prism structural parameters, a lookup table method to seek the numerical reverse solution of each prism's tilting angle is also proposed for steering the double-prism orientation to track a target position located in the near field. Some case studies, as well as a specified elliptical target trajectory scanned by the cam-based driving double prisms, exhibit the significant application values of the theoretical derivation. The analytic reverse and numerical solutions can be generalized to investigate the synthesis of scanning patterns and the controlling strategy of double-prism tilting motion, the potentials of which can be explored to perform the orientation and position tracking functions in applications of precision engineering fields.

Optical image processing for synthetic-aperture imaging ladar based on two-dimensional Fourier transform.

A two-dimensional (2D) Fourier transform algorithm for the image reconstruction of synthetic-aperture imaging ladar (SAIL) collected data is suggested. This algorithm consists of quadratic phase compensation in azimuth direction and 2D fast Fourier transform. Based on this algorithm and the parallel 2D Fourier transform capability of spherical lens, an optical principle scheme that processes the SAIL data is proposed. The basic principle, design equations, and necessary analysis are presented. To verify this principle scheme, an experimental optical SAIL processor setup is constructed. The imaging results of SAIL data obtained by our SAIL demonstrator are presented. The optical processor is compact, lightweight, and consumes low power. This optical processor can also provide inherent parallel and speed-of-light computing capability, and thus has potential applications in on-board and satellite-borne SAIL systems.

Performance analysis of pupil-matching optical differential receivers in space-to-ground laser communication.

In the paper, the principle and structure of a pupil-matching optical differential receiver consisting of double 4f confocal lens groups is introduced to overcome atmosphere turbulences in space-to-ground laser communication. Using the scalar diffraction theory, a systematic analysis of 4f lens groups is formulated mathematically. Based on Seidel aberration, lens aberrations produced by the inherent unideal lens and mutual alignment errors of double 4f lens groups primarily caused by relative axial displacement of the foci and vertical position change of the optical axes are studied mathematically and detailed. Under the effects of varying aberrations on the double 4f lens groups, we evaluate the performance of this receiving system by the model of power penalty for a given 10(-9) bit error ratio. Simulated results of the relationship between power penalty and the different root-mean-square errors are concluded in order to put forward the requirement of machining precision of individual components. That will be helpful in optimizing the design of these groups in the optical receiver.