Helicity and Polarization Gradient Optical Trapping in Evanescent Fields.

Optical traps using nonconservative forces instead of conservative intensity-gradient forces expand the trap parameter space. Existing traps with nonconservative helicity-dependent forces are limited to chiral particles and fields with helicity gradients. We relax these constraints by proposing helicity and polarization gradient optical trapping of achiral particles in evanescent fields. We further propose an optical switching system in which a microsphere is trapped and optically manipulated around a microfiber using polarization gradients. Our Letter deepens the understanding of light-matter interactions in polarization gradient fields and expands the range of compatible particles and stable trapping fields.

Polarization-Dependent Forces and Torques at Resonance in a Microfiber-Microcavity System.

Spin-orbit interactions in evanescent fields have recently attracted significant interest. In particular, the transfer of the Belinfante spin momentum perpendicular to the propagation direction generates polarization-dependent lateral forces on particles. However, it is still elusive as to how the polarization-dependent resonances of large particles synergize with the incident light's helicity and resultant lateral forces. Here, we investigate these polarization-dependent phenomena in a microfiber-microcavity system where whispering-gallery-mode resonances exist. This system allows for an intuitive understanding and unification of the polarization-dependent forces. Contrary to previous studies, the induced lateral forces at resonance are not proportional to the helicity of incident light. Instead, polarization-dependent coupling phases and resonance phases generate extra helicity contributions. We propose a generalized law for optical lateral forces and find the existence of optical lateral forces even when the helicity of incident light is zero. Our work provides new insights into these polarization-dependent phenomena and an opportunity to engineer polarization-controlled resonant optomechanical systems.

Resonators with tailored optical path by cascaded-mode conversions.

Optical resonators enable the generation, manipulation, and storage of electromagnetic waves. The physics underlying their operation is determined by the interference of electromagnetic waves, giving rise to the resonance spectrum. This mechanism causes the limitations and trade-offs of resonator design, such as the fixed relationship between free spectral range, modal linewidth, and the resonator's refractive index and size. Here, we introduce a new class of optical resonators, generating resonances by designing the optical path through transverse mode coupling in a cascaded process created by mode-converting mirrors. The generalized round-trip phase condition leads to resonator characteristics that are markedly different from Fabry-Perot resonators and can be tailored over a wide range. We confirm the existence of these modes experimentally in an integrated waveguide cavity with mode converters coupling transverse modes into one supermode. We also demonstrate a transverse mode-independent transmission and show that its engineered spectral properties agree with theoretical predictions.

Gene therapy using human FMRP isoforms driven by the human FMR1 promoter rescues fragile X syndrome mouse deficits.

Fragile X syndrome (FXS) is caused by the loss of the fragile X messenger ribonucleoprotein 1 (FMRP) encoded by the FMR1 gene. Gene therapy using adeno-associated virus (AAV) to restore FMRP expression is a promising therapeutic strategy. However, so far AAV gene therapy tests for FXS only utilized rodent FMRPs driven by promoters other than the human FMR1 promoter. Restoration of human FMRP in appropriate cell types and at physiological levels, preferably driven by the human FMR1 promoter, would be more suitable for its clinical use. Herein, we generated two human FMR1 promoter subdomains that effectively drive gene expression. When AAVs expressing two different human FMRP isoforms under the control of a human FMR1 promoter subdomain were administered into bilateral ventricles of neonatal Fmr1 -/y and wild-type (WT) mice, both human FMRP isoforms were expressed throughout the brain in a pattern reminiscent to that of mouse FMRP. Importantly, human FMRP expression attenuated social behavior deficits and stereotyped and repetitive behavior, and reversed dysmorphological dendritic spines in Fmr1 -/y mice, without affecting WT mouse behaviors. Our results demonstrate that human FMR1 promoter can effectively drive human FMRP expression in the brain to attenuate Fmr1 -/y mouse deficits, strengthening the notion of using AAV gene therapy for FXS treatment.

Microglial Tmem59 Deficiency Impairs Phagocytosis of Synapse and Leads to Autism-Like Behaviors in Mice.

Synaptic abnormality is an important pathologic feature of autism spectrum disorders (ASDs) and responsible for various behavioral defects in these neurodevelopmental disorders. Microglia are the major immune cells in the brain and also play an important role in synapse refinement. Although dysregulated synaptic pruning by microglia during the brain development has been associated with ASDs, the underlying mechanism has yet to be fully elucidated. Herein, we observed that expression of Transmembrane protein 59 (TMEM59), a protein recently shown to regulate microglial function, was decreased in autistic patients. Furthermore, we found that both male and female mice with either complete or microglia-specific loss of Tmem59 developed ASD-like behaviors. Microglial TMEM59-deficient mice also exhibited enhanced excitatory synaptic transmission, increased dendritic spine density, and elevated levels of excitatory synaptic proteins in synaptosomes. TMEM59-deficient microglia had impaired capacity for synapse engulfment both in vivo and in vitro. Moreover, we demonstrated that TMEM59 interacted with the C1q receptor CD93 and TMEM59 deficiency promoted CD93 protein degradation in microglia. Downregulation of CD93 in microglia also impaired synapse engulfment. These findings identify a crucial role of TMEM59 in modulating microglial function on synapse refinement during brain development and suggest that TMEM59 deficiency may contribute to ASDs through disrupting phagocytosis of excitatory synapse and thus distorting the excitatory-inhibitory (E/I) neuronal activity balance.SIGNIFICANCE STATEMENT Microglia play an important role in synapse refinement. Dysregulated synaptic pruning by microglia during brain development has been associated with autism spectrum disorders (ASDs). However, the underlying mechanism has yet to be fully elucidated. Herein, we observe that the expression of Transmembrane protein 59 (TMEM59), an autophagy-related protein, is decreased in autistic patients. Moreover, we find ASD-like behaviors in mice with complete loss and with microglia-specific loss of Tmem59 Mechanistic studies reveal that TMEM59 deficiency in microglia impairs their synapse engulfment ability likely through destabilizing the C1q receptor CD93, thereby leading to enhanced excitatory neurotransmission and increased dendritic spine density. Our findings demonstrate a crucial role of microglial TMEM59 in early neuronal development and provide new insight into the etiology of ASDs.

Liquid-Phase Exfoliation of Ta2NiS5 and Its Application in Near-Infrared Mode-Locked Fiber Lasers with Evanescent Field Interactions and Passively Q-Switched Bulk Laser.

We report on the application of a 1 µm solid-state passively Q-switched (PQS) laser and 1, 1.5 µm mode-locked (ML) fiber lasers based on ternary chalcogenide Ta2NiS5 saturable absorber (SA), which were successfully fabricated by liquid-phase exfoliation method (LPE). The nonlinear absorption of the Ta2NiS5-SA was characterized by 0.32 GW/cm2 and 0.25 GW/cm2 saturation intensities with 7.3% and 5.1% modulations depths at 1 µm and 1.5 µm, respectively. A PQS solid-state laser operating at 1.0 µm has been realized with the Ta2NiS5-SA. The maximum average output power, shortest pulse width, pulse energy, and pulse peak power from the PQS laser are 0.257 W, 180 ns, 1.265 µJ, and 7 W. Moreover, highly stable femtosecond laser centered at 1.5 µm, and picosecond centered at 1 µm, ML fiber lasers were obtained using the Ta2NiS5-SA. A 70 dB signal-to-noise ML laser with a pulse duration of 781 fs was observed in the telecommunication window, which is better than the duration of the previously reported lasers based on Ta2NiS5. The corresponding maximum single pulse energy and peak power are 0.977 nJ and 1251 W, respectively. The Ta2NiS5-SA fabricated by the LPE method was applied in near-infrared (NIR) ML fiber lasers (evanescent field interactions) and PQS bulk lasers. The results indicate that Ta2NiS5-SA prepared by the LPE method can be applied in a 1 µm bulk PQS laser and improved by the new combination mode (evanescent field interactions) for better output performance of the fiber laser.

Micro-scale opto-thermo-mechanical actuation in the dry adhesive regime.

Realizing optical manipulation of microscopic objects is crucial in the research fields of life science, condensed matter physics, and physical chemistry. In non-liquid environments, this task is commonly regarded as difficult due to strong adhesive surface force (~µN) attached to solid interfaces that makes tiny optical driven force (~pN) insignificant. Here, by recognizing the microscopic interaction mechanism between friction force-the parallel component of surface force on a contact surface-and thermoelastic waves induced by pulsed optical absorption, we establish a general principle enabling the actuation of micro-objects on dry frictional surfaces based on the opto-thermo-mechanical effects. Theoretically, we predict that nanosecond pulsed optical absorption with mW-scale peak power is sufficient to tame µN-scale friction force. Experimentally, we demonstrate the two-dimensional spiral motion of gold plates on micro-fibers driven by nanosecond laser pulses, and reveal the rules of motion control. Our results pave the way for the future development of micro-scale actuators in non-liquid environments.

Profiling of Sexually Dimorphic Genes in Neural Cells to Identify Eif2s3y, Whose Overexpression Causes Autism-Like Behaviors in Male Mice.

Many neurological disorders exhibit sex differences and sex-specific therapeutic responses. Unfortunately, significant amounts of studies investigating molecular and cellular mechanisms underlying these neurological disorders use primary cell cultures with undetermined sexes; and this may be a source for contradictory results among different studies and impair the validity of study conclusion. Herein, we comprehensively compared sexual dimorphism of gene expression in primary neurons, astrocytes, and microglia derived from neonatal mouse brains. We found that overall sexually dimorphic gene numbers were relatively low in these primary cells, with microglia possessing the most (264 genes), neurons possessing the medium (69 genes), and astrocytes possessing the least (30 genes). KEGG analysis indicated that sexually dimorphic genes in these three cell types were strongly enriched for the immune system and immune-related diseases. Furthermore, we identified that sexually dimorphic genes shared by these primary cells dominantly located on the Y chromosome, including Ddx3y, Eif2s3y, Kdm5d, and Uty. Finally, we demonstrated that overexpression of Eif2s3y increased synaptic transmission specifically in male neurons and caused autism-like behaviors specifically in male mice. Together, our results demonstrate that the sex of primary cells should be considered when these cells are used for studying the molecular mechanism underlying neurological disorders with sex-biased susceptibility, especially those related to immune dysfunction. Moreover, our findings indicate that dysregulation of sexually dimorphic genes on the Y chromosome may also result in autism and possibly other neurological disorders, providing new insights into the genetic driver of sex differences in neurological disorders.

Plasmon-driven nanowire actuators for on-chip manipulation.

Chemically synthesized metal nanowires are promising building blocks for next-generation photonic integrated circuits, but technological implementation in monolithic integration will be severely hampered by the lack of controllable and precise manipulation approaches, due to the strong adhesion of nanowires to substrates in non-liquid environments. Here, we demonstrate this obstacle can be removed by our proposed earthworm-like peristaltic crawling motion mechanism, based on the synergistic expansion, friction, and contraction in plasmon-driven metal nanowires in non-liquid environments. The evanescently excited surface plasmon greatly enhances the heating effect in metal nanowires, thereby generating surface acoustic waves to drive the nanowires crawling along silica microfibres. Advantages include sub-nanometer positioning accuracy, low actuation power, and self-parallel parking. We further demonstrate on-chip manipulations including transporting, positioning, orientation, and sorting, with on-situ operation, high selectivity, and great versatility. Our work paves the way to realize full co-integration of various functionalized photonic components on single chips.

Solvent-Free Nanofabrication Based on Ice-Assisted Electron-Beam Lithography.

Advances in electron-beam lithography (EBL) have fostered the prominent development of functional micro/nanodevices. Nonetheless, traditional EBL is predominantly applicable to large-area planar substrates and often suffers from chemical contamination and complex processes for handling resists. This paper reports a streamlined and ecofriendly approach to implement e-beam patterning on arbitrary shaped substrates, exemplified by solvent-free nanofabrication on optical fibers. The procedure starts with the vapor deposition of water ice as an electron resist and ends in the sublimation of the ice followed by a "blow-off" process. Without damage and contamination from chemical solvents, delicate nanostructures and quasi-3D structures are easily created. A refractive index sensor is further demonstrated by decorating plasmonic nanodisk arrays on the end face of a single-mode fiber. Our study provides a fresh perspective in EBL-based processing, and more exciting research exceeding the limits of traditional approaches is expected.

Remote structuring of near-field landscapes.

The electromagnetic near field enables subwavelength applications such as near-field microscopy and nanoparticle manipulation. Present methods to structure the near field rely on optical antenna theory, involving nanostructures that locally convert propagating waves into confined near-field patterns. We developed a theory of remote rather than local near-field shaping, based on cascaded mode conversion and interference of counterpropagating guided waves with different propagation constants. We demonstrate how to structure at will the longitudinal and transverse variation of the near field, allowing for distributions beyond the conventional monotonic decay of the evanescent field. We provide an experimental realization that confirms our theory. Our method applies to fields with arbitrary polarization states and mode profiles, providing a path toward three-dimensional control of the near field.

Atomic switches of metallic point contacts by plasmonic heating.

Electronic switches with nanoscale dimensions satisfy an urgent demand for further device miniaturization. A recent heavily investigated approach for nanoswitches is the use of molecular junctions that employ photochromic molecules that toggle between two distinct isoforms. In contrast to the reports on this approach, we demonstrate that the conductance switch behavior can be realized with only a bare metallic contact without any molecules under light illumination. We demonstrate that the conductance of bare metallic quantum contacts can be reversibly switched over eight orders of magnitude, which substantially exceeds the performance of molecular switches. After the switch process, the gap size between two electrodes can be precisely adjusted with subangstrom accuracy by controlling the light intensity or polarization. Supported by simulations, we reveal a more general and straightforward mechanism for nanoswitching behavior, i.e., atomic switches can be realized by the expansion of nanoelectrodes due to plasmonic heating.

Nanoscale Lamb wave-driven motors in nonliquid environments.

Achieving light-driven motions in nonliquid environments presents formidable challenges, because microsized objects experience strong dry adhesion and intend to be stuck to contact surfaces with great tenacity. Here, in air and vacuum, we show rotary locomotion of a micrometer-sized metal plate with ~30 nm thickness, revolving around a microfiber. This motor is powered by pulsed light guided into the fiber as a coordinated consequence of an optically excited Lamb wave on the plate and favorable configuration of plate-fiber geometry. The motor, actuated by designed light pulses, crawls stepwise with subnanometer locomotion resolution. Furthermore, we can control the rotation velocity and step resolution by varying the repetition rate and pulse power, respectively. A light-actuated micromirror scanning with 0.001° resolution is then demonstrated on the basis of this motor. It offers unprecedented application potential for integrated micro-opto-electromechanical systems, outer-space all-optical precision mechanics and controls, and laser scanning for miniature lidar systems.

Fabrication of controllably variable sub-100 nm gaps in silver nanowires by photothermal-induced stress.

A technique to fabricate nanogaps with controllably variable gap width in silver (Ag) nanowires (NWs) by photothermal-induced stress utilizing a focused continuous-wave laser (532 nm) is presented. For the case of an Ag NW on gold thin film, a gap width starting from ∼20 nm is achieved with a critical minimum power (CMP) of about 160 mW, whereas in the case of an Ag NW placed on top of a zinc oxide NW, the attained gap width is as small as a few nm (<10 nm) with a CMP of only ∼100 mW. In both cases, the CMP is much lower as compared to the required CMP (∼280 mW) for an Ag NW placed on a bare silica substrate. The photothermal-induced stress combined with Rayleigh instability, melting, and sublimation of Ag aids in breaking the Ag NW. In particular, the former one plays a key role in attaining an extremely narrow gap. This technique to fabricate sub-100 nm nanogaps in metal NWs can be extensively implemented in fabrication and maintenance of nanomechanical, nanoplasmonic, and nanoelectronic devices.

Light-Induced Pulling and Pushing by the Synergic Effect of Optical Force and Photophoretic Force.

Optical force, coming from momentum exchange during light-matter interactions, has been widely utilized to manipulate microscopic objects, though mostly in vacuum or in liquids. By contrast, due to the light-induced thermal effect, photophoretic force provides an alternative and effective way to transport light-absorbing particles in ambient gases. However, in most cases these forces work independently. Here, by employing the synergy of optical force and photophoretic force, we propose and experimentally demonstrate a configuration which can drive a micron-size metallic plate moving back and forth on a tapered fiber with supercontinuum light in ambient air. Optical pulling and oscillation of the metallic plate are experimentally realized. The results might open exhilarating possibilities in applications of optical driving and energy conversion.

Mitochondrial dysfunction in human TDP-43 transfected NSC34 cell lines and the protective effect of dimethoxy curcumin.

TAR-DNA-binding protein of 43kDa (TDP-43) was recently found to be one of the major disease proteins in the pathological inclusions of amyotrophic lateral sclerosis (ALS). The effect of TDP-43 on mitochondrial function remains poorly understood. Here, we show that human TDP-43 caused mitochondrial morphologic abnormality, decrease of mitochondrial complex I activity and mitochondrial transmembrane potential, and increased expression of mitochondrial uncoupling protein 2 (UCP2) in human TDP-43 stably transfected NSC-34 cells by using flow cytometric analysis, spectrophotometric assays, electron microscopy and Western blotting. We also show that dimethoxy curcumin (DMC) could ameliorate mitochondrial dysfunction in mutated TDP-43 stably transfected cell lines. DMC could be potentially useful for neurodegenerative diseases linked with mutated TDP-43.