Pathway-selective optogenetics reveals the functional anatomy of top-down attentional modulation in the macaque visual cortex.

Spatial attention represents a powerful top-down influence on sensory responses in primate visual cortical areas. The frontal eye field (FEF) has emerged as a key candidate area for the source of this modulation. However, it is unclear whether the FEF exerts its effects via its direct axonal projections to visual areas or indirectly through other brain areas and whether the FEF affects both the enhancement of attended and the suppression of unattended sensory responses. We used pathway-selective optogenetics in rhesus macaques performing a spatial attention task to inhibit the direct input from the FEF to area MT, an area along the dorsal visual pathway specialized for the processing of visual motion information. Our results show that the optogenetic inhibition of the FEF input specifically reduces attentional modulation in MT by about a third without affecting the neurons' sensory response component. We find that the direct FEF-to-MT pathway contributes to both the enhanced processing of target stimuli and the suppression of distractors. The FEF, thus, selectively modulates firing rates in visual area MT, and it does so via its direct axonal projections.

Climate change determines the sign of productivity trends in US forests.

Forests are integral to the global land carbon sink, which has sequestered ~30% of anthropogenic carbon emissions over recent decades. The persistence of this sink depends on the balance of positive drivers that increase ecosystem carbon storage-e.g., CO2 fertilization-and negative drivers that decrease it-e.g., intensifying disturbances. The net response of forest productivity to these drivers is uncertain due to the challenge of separating their effects from background disturbance-regrowth dynamics. We fit non-linear models to US forest inventory data (113,806 plot remeasurements in non-plantation forests from ~1999 to 2020) to quantify productivity trends while accounting for stand age, tree mortality, and harvest. Productivity trends were generally positive in the eastern United States, where climate change has been mild, and negative in the western United States, where climate change has been more severe. Productivity declines in the western United States cannot be explained by increased mortality or harvest; these declines likely reflect adverse climate-change impacts on tree growth. In the eastern United States, where data were available to partition biomass change into age-dependent and age-independent components, forest maturation and increasing productivity (likely due, at least in part, to CO2 fertilization) contributed roughly equally to biomass carbon sinks. Thus, adverse effects of climate change appear to overwhelm any positive drivers in the water-limited forests of the western United States, whereas forest maturation and positive responses to age-independent drivers contribute to eastern US carbon sinks. The future land carbon balance of forests will likely depend on the geographic extent of drought and heat stress.

Generation of site-specifically labelled fluorescent human XPA to investigate DNA binding dynamics during nucleotide excision repair.

Nucleotide excision repair (NER) promotes genomic integrity by removing bulky DNA adducts introduced by external factors such as ultraviolet light. Defects in NER enzymes are associated with pathological conditions such as Xeroderma Pigmentosum, trichothiodystrophy, and Cockayne syndrome. A critical step in NER is the binding of the Xeroderma Pigmentosum group A protein (XPA) to the ss/ds DNA junction. To better capture the dynamics of XPA interactions with DNA during NER we have utilized the fluorescence enhancement through non-canonical amino acids (FEncAA) approach. 4-azido-L-phenylalanine (4AZP or pAzF) was incorporated at Arg-158 in human XPA and conjugated to Cy3 using strain-promoted azide-alkyne cycloaddition. The resulting fluorescent XPA protein (XPACy3) shows no loss in DNA binding activity and generates a robust change in fluorescence upon binding to DNA. Here we describe methods to generate XPACy3 and detail in vitro experimental conditions required to stably maintain the protein during biochemical and biophysical studies.

Effects of accelerated intermittent theta-burst stimulation in modulating brain of Alzheimer's disease.

Intermittent theta-burst stimulation (iTBS) is emerging as a noninvasive therapeutic strategy for Alzheimer's disease (AD). Recent advances highlighted a new accelerated iTBS (aiTBS) protocol, consisting of multiple sessions per day and higher overall pulse doses, in brain modulation. To examine the possibility of applying the aiTBS in treating AD patients, we enrolled 45 patients in AD at early clinical stages, and they were randomly assigned to either receive real or sham aiTBS. Neuropsychological scores were evaluated before and after treatment. Moreover, we detected cortical excitability and oscillatory activity changes in AD, by the single-pulse TMS in combination with EEG (TMS-EEG). Real stimulation showed markedly better performances in the group average of Auditory Verbal Learning Test scores compared to baseline. TMS-EEG revealed that aiTBS has reinforced this memory-related cortical mechanism by increasing cortical excitability and beta oscillatory activity underlying TMS target. We also found an enhancement of local natural frequency after aiTBS treatment. The novel findings implicated that high-dose aiTBS targeting left DLPFC is rapid-acting, safe, and tolerable in AD patients. Furthermore, TMS-related increase of specific neural oscillation elucidates the mechanisms of the AD cognitive impairment ameliorated by aiTBS.

Direct enhancement of viral neutralising antibody potency by the complement system: a largely forgotten phenomenon.

Neutralisation assays are commonly used to assess vaccine-induced and naturally acquired immune responses; identify correlates of protection; and inform important decisions on the screening, development, and use of therapeutic antibodies. Neutralisation assays are useful tools that provide the gold standard for measuring the potency of neutralising antibodies, but they are not without limitations. Common methods such as the heat-inactivation of plasma samples prior to neutralisation assays, or the use of anticoagulants such as EDTA for blood collection, can inactivate the complement system. Even in non-heat-inactivated samples, the levels of complement activity can vary between samples. This can significantly impact the conclusions regarding neutralising antibody potency. Restoration of the complement system in these samples can be achieved using an exogenous source of plasma with preserved complement activity or with purified complement proteins. This can significantly enhance the neutralisation titres for some antibodies depending on characteristics such as antibody isotype and the epitope they bind, enable neutralisation with otherwise non-neutralising antibodies, and demonstrate a better relationship between in vitro and in vivo findings. In this review, we discuss the evidence for complement-mediated enhancement of antibody neutralisation against a range of viruses, explore the potential mechanisms which underpin this enhancement, highlight current gaps in the literature, and provide a brief summary of considerations for adopting this approach in future research applications.

Fibroblast growth factor receptor 1 inhibition suppresses pancreatic cancer chemoresistance and chemotherapy-driven aggressiveness.

AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often intrinsically-resistant to standard-of-care chemotherapies such as gemcitabine. Acquired gemcitabine resistance (GemR) can arise from treatment of initially-sensitive tumors, and chemotherapy can increase tumor aggressiveness. We investigated the molecular mechanisms of chemoresistance and chemotherapy-driven tumor aggressiveness, which are understood incompletely. METHODS: Differential proteomic analysis was employed to investigate chemotherapy-driven chemoresistance drivers and responses of PDAC cells and patient-derived tumor xenografts (PDX) having different chemosensitivities. We also investigated the prognostic value of FGFR1 expression in the efficacy of selective pan-FGFR inhibitor (FGFRi)-gemcitabine combinations. RESULTS: Quantitative proteomic analysis of a highly-GemR cell line revealed fibroblast growth factor receptor 1 (FGFR1) as the highest-expressed receptor tyrosine kinase. FGFR1 knockdown or FGFRi co-treatment enhanced gemcitabine efficacy and decreased GemR marker expression, implicating FGFR1 in augmentation of GemR. FGFRi treatment reduced PDX tumor progression and prolonged survival significantly, even in highly-resistant tumors in which neither single-agent showed efficacy. Gemcitabine exacerbated aggressiveness of highly-GemR tumors, based upon proliferation and metastatic markers. Combining FGFRi with gemcitabine or gemcitabine+nab-paclitaxel reversed tumor aggressiveness and progression, and prolonged survival significantly. In multiple PDAC PDXs, FGFR1 expression correlated with intrinsic tumor gemcitabine sensitivity. CONCLUSION: FGFR1 drives chemoresistance and tumor aggressiveness, which FGFRi can reverse.

Resonant Tunneling-Enhanced Photoresponsivity in a Twisted Graphene van der Waals Heterostructure.

Leveraging its ultrahigh carrier mobility, zero-bandgap linear dispersion, and extremely short response time, graphene exhibits remarkable potential in ultrafast broad-band photodetection. Nonetheless, the inherently low responsivity of graphene photodetectors, due to the low photogenerated carrier density, significantly impedes the development of practical devices. In this study, we present an improved photoresponse within a graphene-hexagonal boron nitride-graphene vertical tunnel junction device, where the crystallographic orientation of the two graphene electrodes is aligned. Through meticulous device structure design and the adjustment of bias and gate voltages, we observe a 2 orders of magnitude increase in tunneling photocurrent, which is attributed to the momentum-conserving resonant electron tunneling. The enhanced external photoresponsivity is evident across a wide temperature and spectral range and achieves 0.7 A/W for visible light excitation. This characteristic, coupled with the device's negative differential conductance, suggests a novel avenue for highly efficient photodetection and high-frequency, logic-based optoelectronics using van der Waals heterostructures.

Plasmonic Diamond Membranes for Ultrafast Silicon Vacancy Emission.

Silicon vacancy centers (SiVs) in diamond have emerged as a promising platform for quantum sciences due to their excellent photostability, minimal spectral diffusion, and substantial zero-phonon line emission. However, enhancing their slow nanosecond excited-state lifetime by coupling to optical cavities remains an outstanding challenge, as current demonstrations are limited to ∼10-fold. Here, we couple negatively charged SiVs to sub-diffraction-limited plasmonic cavities and achieve an instrument-limited ≤8 ps lifetime, corresponding to a 135-fold spontaneous emission rate enhancement and a 19-fold photoluminescence enhancement. Nanoparticles are printed on ultrathin diamond membranes on gold films which create arrays of plasmonic nanogap cavities with ultrasmall volumes. SiVs implanted at 5 and 10 nm depths are examined to elucidate surface effects on their lifetime and brightness. The interplay between cavity, implantation depth, and ultrathin diamond membranes provides insights into generating ultrafast, bright SiV emission for next-generation diamond devices.

Brownian Motion Governs the Plasmonic Enhancement of Colloidal Upconverting Nanoparticles.

Upconverting nanoparticles are essential in modern photonics due to their ability to convert infrared light to visible light. Despite their significance, they exhibit limited brightness, a key drawback that can be addressed by combining them with plasmonic nanoparticles. Plasmon-enhanced upconversion has been widely demonstrated in dry environments, where upconverting nanoparticles are immobilized, but constitutes a challenge in liquid media where Brownian motion competes against immobilization. This study employs optical tweezers for the three-dimensional manipulation of an individual upconverting nanoparticle, enabling the exploration of plasmon-enhanced upconversion luminescence in water. Contrary to expectation, experiments reveal a long-range (micrometer scale) and moderate (20%) enhancement in upconversion luminescence due to the plasmonic resonances of gold nanostructures. Comparison between experiments and numerical simulations evidences the key role of Brownian motion. It is demonstrated how the three-dimensional Brownian fluctuations of the upconverting nanoparticle lead to an "average effect" that explains the magnitude and spatial extension of luminescence enhancement.

Fluorescence Enhancement in Topologically Optimized Gallium Phosphide All-Dielectric Nanoantennas.

Nanoantennas capable of large fluorescence enhancement with minimal absorption are crucial for future optical technologies from single-photon sources to biosensing. Efficient dielectric nanoantennas have been designed, however, evaluating their performance at the individual emitter level is challenging due to the complexity of combining high-resolution nanofabrication, spectroscopy and nanoscale positioning of the emitter. Here, we study the fluorescence enhancement in infinity-shaped gallium phosphide (GaP) nanoantennas based on a topologically optimized design. Using fluorescence correlation spectroscopy (FCS), we probe the nanoantennas enhancement factor and observe an average of 63-fold fluorescence brightness enhancement with a maximum of 93-fold for dye molecules in nanogaps between 20 and 50 nm. The experimentally determined fluorescence enhancement of the nanoantennas is confirmed by numerical simulations of the local density of optical states (LDOS). Furthermore, we show that beyond design optimization of dielectric nanoantennas, increased performances can be achieved via tailoring of nanoantenna fabrication.

DNA Framework-Programmed Nanoscale Enzyme Assemblies.

Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined enzyme activity in vitro remains unexplored, primarily owing to limitations in precisely controlling the spatial topological configuration. Herein, we introduce a nanoscale 3D enzyme assembly using a tetrahedral DNA framework (TDF), enabling the replication of spatial topological configuration and maintenance of an identical edge-to-edge distance akin to natural enzymes. Our results demonstrate that 3D nanoscale enzyme assemblies in both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) and three-enzyme systems (amylglucosidase (AGO)/GOx/HRP) lead to enhanced cascade catalytic activity compared to the low-dimensional structure, resulting in ∼5.9- and ∼7.7-fold enhancements over homogeneous diffusional mixtures of free enzymes, respectively. Furthermore, we demonstrate the enzyme assemblies for the detection of the metabolism biomarkers creatinine and creatine, achieving a low limit of detection, high sensitivity, and broad detection range.

Organic Synaptic Transistors with Environmentally Friendly Core/Shell Quantum Dots for Wavelength-Selective Memory and Neuromorphic Functions.

Organic transistors based on organic semiconductors together with quantum dots (QDs) are attracting more and more interest because both materials have excellent optoelectronic properties and solution processability. Electronics based on nontoxic QDs are highly desired considering the potential health risks but are limited by elevated surface defects, inadequate stability, and diminished luminescent efficiency. Herein, organic synaptic transistors based on environmentally friendly ZnSe/ZnS core/shell QDs with passivating surface defects are developed, exhibiting optically programmable and electrically erasable characteristics. The synaptic transistors feature linear multibit storage capability and wavelength-selective memory function with a retention time above 6000 s. Various neuromorphic applications, including memory enhancement, optical communication, and memory consolidation behaviors, are simulated. Utilizing an established neuromorphic model, accuracies of 92% and 91% are achieved in pattern recognition and complicated electrocardiogram signal processing, respectively. This research highlights the potential of environmentally friendly QDs in neuromorphic applications and health monitoring.

Giant Photoluminescence Enhancement of Monolayer WSe2 Using a Plasmonic Nanocavity with On-Demand Resonance.

Monolayer transition metal dichalcogenides (TMDs) are considered promising building blocks for next-generation photonic and optoelectronic devices, owing to their fascinating optical properties. However, their inherent weak light absorption and low quantum yield severely hinder their practical applications. Here, we report up to 18000-fold photoluminescence (PL) enhancement in a monolayer WSe2-coupled plasmonic nanocavity. A spectroscopy-assisted nanomanipulation technique enables the assembly of a nanocavity with customizable resonances to simultaneously enhance the excitation and emission processes. In particular, precise control over the magnetic cavity mode facilitates spectral and spatial overlap with the exciton, resulting in plasmon-exciton intermediate coupling that approaches the maximum emission rate in the hybrid system. Meanwhile, the cavity mode exhibits high radiation directivity, which overwhelmingly directs surface-normal PL emission and leads to a 17-fold increase in the collection efficiency. Our approach opens up a new avenue to enhance the PL intensity of monolayer TMDs, facilitating their implementation in highly efficient optoelectronic devices.

Large-Area Near-Infrared Emission Enhancement on Single Upconversion Nanoparticles by Metal Nanohole Array.

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

A Gold Needle Tip Array Ultrafast Electron Source with High Beam Quality.

Electron sources are crucial elements in diverse applications such as electron microscopes, synchrotrons, and free-electron lasers. Nanometer-sharp needle tips are electron emitters with the highest beam quality, yet for a single needle the current is limited. Combining the emission of multiple needles promises large current yields while preserving the individual emitters' favorable properties. We present an ultrafast electron source consisting of a lithographically fabricated array of sharp gold tips illuminated with 25 fs laser pulses. The source provides up to 2000 electrons per pulse for moderate laser peak intensities of 1011 W/cm2 and a narrow energy width of 0.5 ± 0.05 eV at low current. The electron beam has a well-behaved Gaussian profile and is highly collimated, yielding a small normalized emittance on the order of nm·rad. These properties are well suited for applications requiring both high current and spatial resolution, such as free-electron light sources and chip-based particle accelerators.

Enhanced Circular Dichroism for Achiral Sensing Based on a DNA-Origami-Empowered Anapole Metasurface.

Circular dichroism (CD) spectroscopy has been extensively utilized for detecting and distinguishing the chirality of diverse substances and structures. However, CD spectroscopy is inherently weak and conventionally associated with chiral sensing, thus constraining its range of applications. Here, we report a DNA-origami-empowered metasurface sensing platform through the collaborative effect of metasurfaces and DNA origami, enabling achiral/slightly chiral sensing with high sensitivity via the enhanced ΔCD. An anapole metasurface, boasting over 60 times the average optical chirality enhancement, was elaborately designed to synergize with reconfigurable DNA origami. We experimentally demonstrated the detection of achiral/slightly chiral DNA linker strands via the enhanced ΔCD of the proposed platform, whose sensitivity was a 10-fold enhancement compared with the platform without metasurfaces. Our work presents a high-sensitivity platform for achiral/slightly chiral sensing through chiral spectroscopy, expanding the capabilities of chiral spectroscopy and inspiring the integration of multifunctional artificial nanostructures across diverse domains.

Hundred-Fold Enhancement in the Anomalous Hall Effect Induced by Hydrogenation.

The anomalous Hall effect (AHE) is one of the most fascinating transport properties in condensed matter physics. However, the AHE magnitude, which mainly depends on net spin polarization and band topology, is generally small in oxides and thus limits potential applications. Here, we demonstrate a giant enhancement of AHE in a LaCoO3-induced 5d itinerant ferromagnet SrIrO3 by hydrogenation. The anomalous Hall resistivity and anomalous Hall angle, which are two of the most critical parameters in AHE-based devices, are found to increase to 62.2 µΩ·cm and 3%, respectively, showing an unprecedentedly large enhancement ratio of ∼10000%. Theoretical analysis suggests the key roles of Berry curvature in enhancing AHE. Furthermore, the hydrogenation concomitantly induces the significant elevation of Curie temperature from 75 to 160 K and 40-fold reinforcement of coercivity. Such giant regulation and very large AHE magnitude observed in SrIrO3 could pave the path for 5d oxide devices.

Probing Temperature-Induced Plasmonic Nonlinearity: Unveiling Opto-Thermal Effects on Light Absorption and Near-Field Enhancement.

Precise measurement and control of local heating in plasmonic nanostructures are vital for diverse nanophotonic devices. Despite significant efforts, challenges in understanding temperature-induced plasmonic nonlinearity persist, particularly in light absorption and near-field enhancement due to the absence of suitable measurement techniques. This study presents an approach allowing simultaneous measurements of light absorption and near-field enhancement through angle-resolved near-field scanning optical microscopy with iterative opto-thermal analysis. We revealed gold thin films exhibit sublinear nonlinearity in near-field enhancement due to nonlinear opto-thermal effects, while light absorption shows both sublinear and superlinear behaviors at varying thicknesses. These observations align with predictions from a simple harmonic oscillation model, in which changes in damping parameters affect light absorption and field enhancement differently. The sensitivity of our method was experimentally examined by measuring the opto-thermal responses of three-dimensional nanostructure arrays. Our findings have direct implications for advancing plasmonic applications, including photocatalysis, photovoltaics, photothermal effects, and surface-enhanced Raman spectroscopy.

Harmonic Generation up to Fifth Order from Al/Au/CuS Nanoparticle Films.

Dual heterostructures integrating noble-metal and copper chalcogenide nanoparticles have attracted a great deal of attention in nonlinear optics, because coupling of their localized surface plasmon resonances (LSPRs) substantially enhances light-matter interactions through local-field effects. Previously, enhanced cascaded third-harmonic generation was demonstrated in Au/CuS heterostructures mediated by harmonically coupled surface plasmon resonances. This suggests a promising approach for extending nonlinear enhancement to higher harmonics by adding an additional nanoparticulate material with higher-frequency harmonic resonances to the hybrid films. Here we report the first observation of enhanced cascaded fourth- and fifth-harmonic generation in Al/Au/CuS driven by coupled LSPRs at the fundamental (1050 nm), second harmonic (525 nm), and third harmonic (350 nm) of the pump frequency. An analytical model based on incoherent dipole-dipole interactions among plasmonic nanoparticles accounts for the observed enhancements. The results suggest a novel design for efficiently generating higher harmonics in resonant plasmonic structures by means of multiple sum-frequency cascades.

Photothermal Enhancement of Prussian Blue Cathodes for Li-Ion Batteries.

Photoenhanced batteries, where light improves the electrochemical performance of batteries, have gained much interest. Recent reports suggest that light-to-heat conversion can also play an important role. In this work, we study Prussian blue analogues (PBAs), which are known to have a high photothermal heating efficiency and can be used as cathodes for Li-ion batteries. PBAs were synthesized directly on a carbon collector electrode and tested under different thermally controlled conditions to show the effect of photothermal heating on battery performance. Our PBA electrodes reach temperatures that are 14% higher than reference electrodes using a blue LED, and a capacity enhancement of 38% was achieved at a current density of 1600 mA g-1. Additionally, these batteries show excellent cycling stability with a capacity retention of 96.6% in dark conditions and 94.8% in light over 100 cycles. Overall, this work shows new insights into the effects leading to improved battery performance in photobatteries.