Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.

DNAL7, a new allele of NAL11, has major pleiotropic effects on rice architecture.

MAIN CONCLUSION: dnal7, a novel allelic variant of the OsHSP40, affects rice plant architecture and grain yield by coordinating auxins, cytokinins, and gibberellic acids. Plant height and leaf morphology are the most important traits of the ideal plant architecture (IPA), and discovering related genes is critical for breeding high-yield rice. Here, a dwarf and narrow leaf 7 (dnal7) mutant was identified from a γ-ray treated mutant population, which exhibits pleiotropic effects, including dwarfing, narrow leaves, small seeds, and low grain yield per plant compared to the wild type (WT). Histological analysis showed that the number of veins and the distance between adjacent small veins (SVs) were significantly reduced compared to the WT, indicating that DNAL7 controls leaf size by regulating the formation of veins. Map-based cloning and transgenic complementation revealed that DNAL7 is allelic to NAL11, which encodes OsHSP40, and the deletion of 2 codons in dnal7 destroyed the His-Pro-Asp (HPD) motif of OsHSP40. In addition, expression of DNAL7 in both WT and dnal7 gradually increased with the increase of temperature in the range of 27-31 °C. Heat stress significantly affected the seedling height and leaf width of the dnal7 mutant. A comparative transcriptome analysis of WT and dnal7 revealed that DNAL7 influenced multiple metabolic pathways, including plant hormone signal transduction, carbon metabolism, and biosynthesis of amino acids. Furthermore, the contents of the cytokinins in leaf blades were much higher in dnal7 than in the WT, whereas the contents of auxins were lower in dnal7. The contents of bioactive gibberellic acids (GAs) including GA1, GA3, and GA4 in shoots were decreased in dnal7. Thus, DNAL7 regulates rice plant architecture by coordinating the balance of auxins, cytokinins, and GAs. These results indicate that OsHSP40 is a pleiotropic gene, which plays an important role in improving rice yield and plant architecture.

The supplementation of mannan oligosaccharide in diet promotes the skin wound healing of juvenile turbot, Scophthalmus maximus.

A 30-day feeding trial was conducted to investigate the effects of the supplementation of mannan oligosaccharide (MOS) in the diet on the skin wound healing process of juvenile turbot (Scophthalmus maximus). Two groups of diets were formulated, the control diet (CON) and the control diet supplemented with 0.16 % MOS (MOS), which were fed to the turbot separately. Each group had 3 replicates, with 20 fish per replicate. At the end of the feeding trial, all the fish were weighed and counted. Then four fish per tank were randomly selected for sampling, and the skin of the rest fish was wounded by a biopsy punch. The wounded fish continued to be fed as usual with the same diets respectively, and then sampled again at the 1, 3, and 7 day(s) post wounding (dpw). The results by image analysis showed that the wound closure rate of wounded fish was significantly improved by the supplementation of dietary MOS. As for the results of gene expression, dietary MOS promoted the expression of pro-inflammatory factors (il-1ß & tnf-α) and decreased the expression of anti-inflammatory factors (tgf-ß1 & il-10). It also enhanced the expression of genes related to re-epithelialization (mmp-9, fgf2, tgf-ß1, rock1), as well as new tissue formation and remodeling (fn1, lamb2, col1-α, vegf). Furthermore, dietary MOS promoted re-epithelialization, cell proliferation, collagen deposition, and angiogenesis according to the histomorphological observation. In addition, the supplementation of MOS modified the communities of skin microbiota, decreasing the abundance of Rolstonia, Pseudomonas, and Aeromonas, while increasing the abundance of Pseudoalteromonas luteoviolacea and Shewanella colwellianav. In conclusion, the supplementation of dietary MOS (0.16 %) can promote the re-epithelialization and the recruitment of inflammatory cells, stimulate ECM biosynthesis and angiogenesis, modify the communities of skin microbiota, and ultimately promote the skin wound healing process.

ICG-based laser treatments for ophthalmic diseases: Toward their safe and rapid strategy.

The eye is a very important organ, and keratitis, corneal neovascularization, floaters, age-related macular degeneration, and other vision problems have seriously affected people's quality of life. Among the ophthalmic treatments, laser photocoagulations have been proposed and have shown therapeutic effects in clinical settings. However, corneal thinning and bleeding lesions induced by laser damage have led to limit its applications. To treat the issues of traditional hyperthermia treatments, photosensitizers [e.g., indocyanine green (ICG)] have been investigated to increase the therapeutic effects of corneal neovascularization and choroidal neovascularization. In the recent study, with the help of ICG, laser-induced nanobubble was proposed to treat vitreous opacities. The developed strategies could enlarge the effect of laser irradiation and reduce the side effects, so as to expand the scope of laser treatments in clinical ophthalmic diseases.

Fishmeal Protein Replacement by Defatted and Full-Fat Black Soldier Fly Larvae Meal in Juvenile Turbot Diet: Effects on the Growth Performance and Intestinal Microbiota.

A 12-week feeding trial was conducted to investigate the effect of the same fishmeal protein level replaced by black soldier fly larvae (Hermetia illucens) meal (BSFL) with different lipid contents on the growth performance and intestinal health of juvenile turbot (Scophthalmus maximus L.) (initial body weight 12.64 g). Three isonitrogenous and isolipidic diets were formulated: fish meal-based diet (FM), diets DF and FF, in which 14% fish meal protein of the FM diet was replaced by defatted and full-fat BSFL, respectively. There were no significant differences in growth performance, intestinal morphology, and mucosal barrier function between the DF and the FM group. However, diet FF markedly reduced the growth performance, intestinal perimeter ratio, and the gene expression of anti-inflammatory cytokine TGF-ß (P < 0.05). Compared to group FF, the communities of intestinal microbiota in group DF were more similar to group FM. Moreover, diet DF decreased the abundance of some potential pathogenic bacteria and enriched the potential probiotics, such as Bacillus. Diet FF obviously altered the composition of intestinal microbiota and increased the abundance of some potential pathogenic bacteria. These results suggested that the application of defatted BSFL showed more positive effects on fish growth and intestinal health than the full-fat BSFL, and the intestinal microbiota was closely involved in these effects.

Steering Nonlinear Twisted Valley Photons of Monolayer WS2 by Vector Beams.

Monolayer transition metal dichalcogenides have intrinsic spin-valley degrees of freedom, drawing broad interests due to their potential applications in information storage and processing. Here, we demonstrate the possibility of using cylindrical vector pumped beams, which are nonseparable in their polarization and spatial modes, to manipulate nonlinear valley-locked twisted-vortex emissions in monolayer tungsten disulfide (WS2). The second-harmonic (SH) photons from K and K' valleys are encoded with opposite optical vortices, thus allowing the SH beams to emerge as cylindrical vector beams with doubled topological orders compared to the fundamental beams. The conically refracted pumped beams allow us to generate the first-order SH cylindrical vector and full Poincaré beams via tuning the valley-locked emitted light field profiles. With fanshaped WS2 films breaking the axial symmetry of SH beams, the SH valley photons are routed to opposite directions. Our results pave the way to develop atomically thin nonlinear photonic devices and valleytronic nanodevices.

Self-powered and high-performance all-fiber integrated photodetector based on graphene/palladium diselenide heterostructures.

An all-fiber integrated photodetector is proposed and demonstrated by assembling a graphene/palladium diselenide (PdSe2) Van der Waals heterostructure onto the endface of a standard optical fiber. A gold film is covered on the heterostructure working as an electrode and a mirror, which reflects back the unabsorbed residual light for further reusage. Owing to the low bandgap of PdSe2, the all-fiber photodetector shows a broadband photoresponse from 650 to 1550 nm with a high photoresponsivity of 6.68×104 AW-1, enabling a low light detection of 42.5 pW. And the fastest temporal response is about 660 µs. Taking advantage of heterostructures, the photodetector can work in self-powered mode with the on/off ratio about 82. These findings provide new strategies for integrating two-dimensional materials into optical fibers to realize integrated all-fiber devices with multi-function applications.

Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity.

Inhibiting NLRP3 inflammasome activation is a prospective therapeutic strategy for uncontrolled inflammatory diseases. It is the first time that dronedarone, a multiply ion channel blocker, was identified as a NLRP3-inflammasome inhibitor with an IC50 value of 6.84 µM against IL-1ß release. A series of novel 5-amide benzofuran derivatives were designed and synthesized as NLRP3-inflammasome inhibitors. Compound 8c showed slightly increased activity (IC50 = 3.85 µM) against IL-1ß release. Notably, treatment with 8c could significantly inhibit NLRP3-mediated IL-1ß release and ameliorate peritoneal inflammation in a mouse model of sepsis. Collectively, 8c is a promising lead compound for further chemical development as a NLRP3 inhibitor with anti-inflammation effects.

Photonic spin Hall effect in twisted bilayer graphene.

Here, we investigate the photonic spin Hall effect in twisted bilayer graphene. The optical conductivities for several rotation angles of twisted bilayer graphene are calculated by first principles, based on which a theoretical framework is established to describe the light-matter interaction. To enhance the photonic spin Hall effect, twisted bilayer graphene is placed on a BK7 glass substrate and a Gaussian beam is launched near the Brewster angle. The spin splitting as well as Goos-Hänchen shifts are investigated, which are associated, respectively, with the imaginary and real parts of the surface conductivities of the twisted bilayer graphene. These findings provide a deeper understanding of the photonic spin Hall effect in two-dimensional materials and have potential application in characterizing bilayer graphene.

Black phosphorus terahertz sensing based on photonic spin Hall effect.

A novel terahertz (THz) sensing scheme is proposed based on the photonic spin Hall effect (PSHE). By illumining a paraxial Gaussian THz beam onto a black phosphorus (BP)-based Tamm structure, the reflected beam will undergo in-plane spin splitting, i.e., the centroids of two opposite spin components separate spatially. Due to Tamm plasmon resonance, one of the spin components is very sensitive to the refractive index changes of the analyte layer sandwiched by monolayer BP and distributed Bragg reflector. The sensitivity of the spin-dependent shift can be up to 2804 mm/RIU with a refractive index resolution of ∼10-8 RIU. The sensitivity and dynamic sensing region can be flexibly tuned by the BP rotation angle, thickness of analyte layer, or operation frequency. Therefore, the proposed PSHE-based THz sensing provides a new avenue for the development of high-performance THz sensors; thus, we may find applications in chemical sensing and biosensing.

Exploiting black phosphorus based-Tamm plasmons in the terahertz region.

Polarization-sensitive Tamm plasmons are investigated in a multi-layer photonic configuration where a monolayer black phosphorus (BP) is coated on a Bragg mirror separated by a dielectric. Owing to the in-plane anisotropy of BP, the Tamm plasmon can be excited selectively by tuning the BP carrier density. Cross-polarization conversion occurs when the armchair direction of BP makes an angle with the incident plan, i.e., ϕ≠0 or 90°. The BP-based Tamm device can be used as an intensity modulator with a modulation depth up to ∼100% and an insertion loss smaller than -0.55 dB. By analyzing the polarization evolution carefully, a multichannel polarization division multiplexing scheme is proposed and discussed. These findings open a new avenue for exploiting versatile tunable THz devices based on the monolayer of BP.

Tunable asymmetric spin splitting by black phosphorus sandwiched epsilon-near-zero-metamaterial in the terahertz region.

In-plane photonic spin splitting effect is investigated in tunneling terahertz waves through an epsilon-near-zero metamaterial sandwiched between monolayer black phosphorus (BP). The strong in-plane anisotropy of BP layers will induce in-plane asymmetric spin splitting. The asymmetric spin splitting can be flexibly tuned by the angles between the incident plane and the armchair crystalline directions of the top and bottom BP layers, i.e., ϕ1 and ϕ2. Based on this, an angle-resolved barcode-encryption scheme is discussed. For the special case of ϕ1 = ϕ2 = 0 or 90°, the transmitted beam undergoes Goos-Hänchen shift, which varies with the carrier density of BP. We believe these findings can facilitate the development of novel optoelectronic devices in the Terahertz region.

Redox proteomic identification of carbonylated proteins in autism plasma: insight into oxidative stress and its related biomarkers in autism.

BACKGROUND: Autism is a severe childhood neurological disorder with poorly understood etiology and pathology. Currently, there is no authentic laboratory test to confirm the diagnosis of autism. Oxidative damage may play a central role in the pathogenesis of autism. Present study is an effort to search for possible biomarkers of autism and further clarify the molecular changes associated with oxidative stress that occurs in the plasma of autistic children. METHODS: We performed redox proteomics analysis to compare carbonylated proteins in the plasma of autistic subjects and healthy controls. Immunoprecipitation and Western blot analysis were used to validate carbonylated proteins identified by the redox proteomics. RESULTS: Protein carbonylation levels in two proteins, complement component C8 alpha chain and Ig kappa chain C were found to be significantly increased in autistic patients compared with controls. These two proteins were successfully validated via immunoprecipitation and Western blot analysis. CONCLUSIONS: The results further highlight the role of oxidative stress in the pathogenesis of autism and provide some information for the diagnosis and/or monitoring of autism.

Biomimetic nanocomplex based corneal neovascularization theranostics.

Corneal neovascularization (CNV) is a major cause of blindness worldwide. However, the recent drug treatment is limited by repeated administration and low drug bioavailability. In this work, SU6668 (an inhibitor of receptor tyrosine kinases) and indocyanine green (ICG) are loaded onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and then coated with anti-VEGFR2 single chain antibody (AbVr2 scFv) genetically engineered cell membrane vesicles. The nanomedicine is delivered via eye drops, and the hyperthermia induced by laser irradiation could block the blood vessels. Meanwhile, the photothermal effect can also cause the degradation of nanomaterials and release chemotherapeutic drugs in the blocked area, thereby continuously inhibit the neovascularization. Furthermore, SU6668 could inhibit the expression of heat shock protein 70 (HSP70), promoting the cell death induced by photothermal effect. In conclusion, the combination of photothermal and chemotherapy drugs provides a novel, effective and safe approach for the treatment of CNV.

Revolutionizing eye care: the game-changing applications of nano-antioxidants in ophthalmology.

Since the theory of free radical-induced aging was proposed in 1956, it has been constantly proven that reactive oxygen species (ROS) produced by oxidative stress play a vital role in the occurrence and progression of eye diseases. However, the inherent limitations of traditional drug therapy hindered the development of ophthalmic disease treatment. In recent years, great achievements have been made in the research of nanomedicine, which promotes the rapid development of safe theranostics in ophthalmology. In this review, we focus on the applications of antioxidant nanomedicine in the treatment of ophthalmology. The eye diseases were mainly classified into two categories: ocular surface diseases and posterior eye diseases. In each part, we first introduced the pathology of specific diseases about oxidative stress, and then presented the representative application examples of nano-antioxidants in eye disease therapy. Meanwhile, the nanocarriers that were used, the mechanism of function, and the therapeutic effect were also presented. Finally, we summarized the latest research progress and limitations of antioxidant nanomedicine for eye disease treatment and put forward the prospects of future development.

A Synergistic Therapy With Antioxidant and Anti-VEGF: Toward its Safe and Effective Elimination for Corneal Neovascularization.

Corneal neovascularization (CNV) is one of the leading causes of blindness in the world. In clinical practice; however, it remains a challenge to achieve a noninvasive and safe treatment. Herein, a biocompatible shell with excellent antioxidant and antivascularity is prepared by co-assembly of epigallocatechin gallate/gallic acid and Cu (II). After loading glucose oxidase (GOx) inside, the shell is modified with dimeric DPA-Zn for codelivering vascular endothelial growth factor (VEGF) small interfering RNA (VEGF-siRNA). Meanwhile, the Arg-Gly-Asp peptide (RGD) peptide-engineered cell membranes coating improves angiogenesis-targeting and is biocompatible for the multifunctional nanomedicine (CEGs/RGD). After eye drops administration, CEGs/RGD targets enrichment in neovascularization and CEGs NPs enter cells. Then, the inner GOx consumes glucose with a decrease in local pH, which in turn leads to the release of EGCE and VEGF-siRNA. As a result, the nanomedicines significantly reduce angiogenesis and inhibit CNV formation through synergistic effect of antioxidant and antivascular via down-regulation of cluster of differentiation 31 and VEGF. The nanomedicine represents a safe and efficient CNV treatment through the combined effect of antioxidant/gene, which provides important theoretical and clinical significance.

Nonlinear geometric phase coded ferroelectric nematic fluids for nonlinear soft-matter photonics.

Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.

Application of Self-Assembly Nanoparticles Based on DVDMS for Fenton-Like Ion Delivery and Enhanced Sonodynamic Therapy.

Upon harnessing low-intensity ultrasound to activate sonosensitizers, sonodynamic therapy (SDT) induces cancer cell death through the reactive oxygen species (ROS) mediated pathway. Compared with photodynamic therapy (PDT), SDT possesses numerous advantages, including deeper tissue penetration, higher accuracy, fewer side effects, and better patient compliance. Sinoporphyrin sodium (DVDMS), a sonosensitizer approved by the FDA, has drawn abundant attention in clinical research, but there are some deficiencies. In order to further improve the efficiency of DVDMS, many studies have applied self-assembly nanotechnology to modify it. Furthermore, the combined applications of SDT/chemodynamic therapy (CDT) have become a research hotspot in tumor therapy. Therefore, we explored the self-assembly of nanoparticles based on DVDMS and copper to combine SDT and CDT. A cost-effective sonosensitizer was synthesized by dropping CuCl2 into the DVDMS solution with the assistance of PVP. The results revealed that the nanostructures could exert excellent treatment effects on tumor therapy and perform well for PET imaging, indicating the potential for cancer theranostics. In vitro and in vivo experiments showed that the nanoparticles have outstanding biocompatibility, higher ROS production efficiency, and antitumor efficacy. We believe this design can represent a simple approach to combining SDT and CDT with potential applications in clinical treatment and PET imaging.

Self-assembled liquid crystal architectures for soft matter photonics.

Self-assembled architectures of soft matter have fascinated scientists for centuries due to their unique physical properties originated from controllable orientational and/or positional orders, and diverse optic and photonic applications. If one could know how to design, fabricate, and manipulate these optical microstructures in soft matter systems, such as liquid crystals (LCs), that would open new opportunities in both scientific research and practical applications, such as the interaction between light and soft matter, the intrinsic assembly of the topological patterns, and the multidimensional control of the light (polarization, phase, spatial distribution, propagation direction). Here, we summarize recent progresses in self-assembled optical architectures in typical thermotropic LCs and bio-based lyotropic LCs. After briefly introducing the basic definitions and properties of the materials, we present the manipulation schemes of various LC microstructures, especially the topological and topographic configurations. This work further illustrates external-stimuli-enabled dynamic controllability of self-assembled optical structures of these soft materials, and demonstrates several emerging applications. Lastly, we discuss the challenges and opportunities of these materials towards soft matter photonics, and envision future perspectives in this field.

Binocular Encoding in the Damselfly Pre-motor Target Tracking System.

Akin to all damselflies, Calopteryx (family Calopterygidae), commonly known as jewel wings or demoiselles, possess dichoptic (separated) eyes with overlapping visual fields of view. In contrast, many dragonfly species possess holoptic (dorsally fused) eyes with limited binocular overlap. We have here compared the neuronal correlates of target tracking between damselfly and dragonfly sister lineages and linked these changes in visual overlap to pre-motor neural adaptations. Although dragonflies attack prey dorsally, we show that demoiselles attack prey frontally. We identify demoiselle target-selective descending neurons (TSDNs) with matching frontal visual receptive fields, anatomically and functionally homologous to the dorsally positioned dragonfly TSDNs. By manipulating visual input using eyepatches and prisms, we show that moving target information at the pre-motor level depends on binocular summation in demoiselles. Consequently, demoiselles encode directional information in a binocularly fused frame of reference such that information of a target moving toward the midline in the left eye is fused with information of the target moving away from the midline in the right eye. This contrasts with dragonfly TSDNs, where receptive fields possess a sharp midline boundary, confining responses to a single visual hemifield in a sagittal frame of reference (i.e., relative to the midline). Our results indicate that, although TSDNs are conserved across Odonata, their neural inputs, and thus the upstream organization of the target tracking system, differ significantly and match divergence in eye design and predatory strategies. VIDEO ABSTRACT.