Dissection of the long-range projections of specific neurons at the synaptic level in the whole mouse brain.

Through synaptic connections, long-range circuits transmit information among neurons and connect different brain regions to form functional motifs and execute specific functions. Tracing the synaptic distribution of specific neurons requires submicron-level resolution information. However, it is a great challenge to map the synaptic terminals completely because these fine structures span multiple regions, even in the whole brain. Here, we develop a pipeline including viral tracing, sample embedding, fluorescent micro-optical sectional tomography, and big data processing. We mapped the whole-brain distribution and architecture of long projections of the parvalbumin neurons in the basal forebrain at the synaptic level. These neurons send massive projections to multiple downstream regions with subregional preference. With three-dimensional reconstruction in the targeted areas, we found that synaptic degeneration was inconsistent with the accumulation of amyloid-ß plaques but was preferred in memory-related circuits, such as hippocampal formation and thalamus, but not in most hypothalamic nuclei in 8-month-old mice with five familial Alzheimer's disease mutations. Our pipeline provides a platform for generating a whole-brain atlas of cell-type-specific synaptic terminals in the physiological and pathological brain, which can provide an important resource for the study of the organizational logic of specific neural circuits and the circuitry changes in pathological conditions.

Nrf2 attenuates oxidative stress to mediate the protective effect of ciprofol against cerebral ischemia-reperfusion injury.

Neuroinflammation and oxidative stress damage are involved in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Ferroptosis emerged as a new player in the regulation of lipid peroxidation processes. This study aimed at exploring the potential involvement of ciprofol on ferroptosis-associated CIRI and subsequent neurological deficits in the mouse model of transient cerebral ischemia and reperfusion. Cerebral ischemia was built in male C57BL/6 J wild-type (WT) and Nrf2-knockout (Nrf2 KO) mice in the manner of middle cerebral artery occlusion (MCAO) followed by reperfusion. Ciprofol improved autonomic behavior, alleviated reactive oxygen species output and ferroptosis-induced neuronal death by nucleus transportation of NFE2 like BZIP transcription factor 2 (Nrf2) and the promotion of heme oxygenase 1 (Ho-1), solute carrier family 7 member 11 (SLC7A11/xCT), and glutathione peroxidase 4 (GPX4). Additionally, ciprofol improved neurological scores and reduced infarct volume, brain water content, and necrotic neurons. Cerebral blood flow in MCAO-treated mice was also improved. Furthermore, absence of Nrf2 abrogated the neuroprotective actions of ciprofol on antioxidant capacity and sensitized neurons to oxidative stress damage. In vitro, the primary-cultured cortical neurons from mice were pre-treated with oxygen-glucose deprivation/reperfusion (OGD/R), followed by ciprofol administration. Ciprofol effectively reversed OGD/R-induced ferroptosis and accelerated transcription of GPX4 and xCT. In conclusion, we investigated the ciprofol-induced inhibition effect of ferroptosis-sheltered neurons from lipid preoxidation in the pathogenesis of CIRI via Nrf2-xCT-GPX4 signaling pathway.

Acetamide- or Formamide-Assisted In Situ Approach to Carbon-Rich or Nitrogen-Deficient Graphitic Carbon Nitride for Notably Enhanced Visible-Light Photocatalytic Redox Performance.

Acetamide- or formamide-assisted in situ strategy is designed to synthesize carbon atom self-doped g-C3 N4 (AHCNx ) or nitrogen vacancy-modified g-C3 N4 (FHCNx ). Different from the direct copolymerization route that suffers from the problem of mismatched physical properties of acetamide (or formamide) with urea, the synthesis of AHCNx (or FHCNx ) starts from a crucial preorganization step of acetamide (or formamide) with urea via freeze drying-hydrothermal treatment so that the chemical structures as well as C-doping level in AHCNx and N-vacancy concentration in FHCNx can be precisely regulated. By using various structural characterization methods, well-defined AHCNx and FHCNx structures are proposed. At the optimal C-doping level in AHCNx or N-vacancy concentration in FHCNx , both AHCNx and FHCNx exhibit remarkably improved visible-light photocatalytic performance in oxidation of emerging organic pollutants (acetaminophen and methylparaben) and reduction of proton to H2 in comparison of unmodified g-C3 N4 . Combination of the experimental results with theoretical calculations, it is confirmed that AHCNx and FHCNx show different charge separation and transfer mechanisms, while the enhanced visible-light harvesting capacity and the localized charge distributions on HOMO and LUMO are responsible for this excellent photocatalytic redox performance of AHCNx and FHCNx .

Liposomes trigger bone marrow niche macrophage "foam" cell formation and affect hematopoiesis in mice.

Liposomes are the most widely used nanocarrier platform for the delivery of therapeutic and diagnostic agents, and a number of liposomes have been approved for use in clinical practice. After systemic administration, most liposomes are cleared by macrophages in the mononuclear phagocyte system, such as the liver and bone marrow (BM). However, the majority of studies have focused on investigating the therapeutic results of liposomal drugs, and too few studies have evaluated the potential side effects of empty nanocarriers on the functions of macrophages in the mononuclear phagocyte system. Here, we evaluate the potential effects of empty liposomes on the functions of BM niche macrophages. Following liposome administration, we observed lipid droplet (LD) accumulation in cultured primary macrophages and BM niche macrophages. We found that these LD-accumulating macrophages, similar to foam cells, exhibited increased expression of inflammatory cytokines, such as IL-1ß and IL-6. We further provided evidence that liposome deposition and degradation induced LD biogenesis on the endoplasmic reticulum membrane and subsequently disturbed endoplasmic reticulum homeostasis and activated the inositol-requiring transmembrane kinase/endoribonuclease 1α/NF-κB signaling pathway, which is responsible for the inflammatory activation of macrophages after liposome engulfment. Finally, we also showed the side effects of dysfunctional BM niche macrophages on hematopoiesis in mice, such as the promotion of myeloid-biased output and impairment of erythropoiesis. This study not only draws attention to the safety of liposomal drugs in clinical practice but also provides new directions for the design of lipid-based drug carriers in preclinical studies.

Quantum anomalous Hall effect in germanene by proximity coupling to a semiconducting ferromagnetic substrate NiI2.

Interfaces between materials are ubiquitous in materials science, especially in devices. As device dimensions continue to be reduced, understanding the physical characteristics that appear at interfaces is crucial to exploit them for applications, spintronics in this case. Here, based on first-principles calculations, we propose a general and tunable platform to realize an exotic quantum anomalous Hall effect (QAHE) with the germanene monolayer by proximity coupling to a semiconducting ferromagnetic NiI2 (Ge/NiI2). Through analysis of the Berry curvature and band structure with spin-orbit coupling, the QAHE phase with an integer Chern number (C = -1), which is induced by band inversion between Ge-p orbitals, can achieve complete spin polarization for low-dissipation electronic devices. Also, the proximity coupling between germanene and the NiI2 substrate makes the non-trivial bandgap reach up to 85 meV, and the Curie temperature of the Ge/NiI2 heterostructure (HTS) is enhanced to 238 K, which is much higher than that of pristine NiI2. An effective k·p model is proposed to clarify the quantum phenomena in the Ge/NiI2 HTS. These findings shed light on the possible role of magnetic proximity effects on condensed matter physics in germanene and open new perspectives for multifunctional spin quantum devices in spintronics.

Cell-type-specific and projection-specific brain-wide reconstruction of single neurons.

We developed a dual-adeno-associated-virus expression system that enables strong and sparse labeling of individual neurons with cell-type and projection specificity. We demonstrated its utility for whole-brain reconstruction of midbrain dopamine neurons and striatum-projecting cortical neurons. We further extended the labeling method for rapid reconstruction in cleared thick brain sections and simultaneous dual-color labeling. This labeling system may facilitate the process of generating mesoscale single-neuron projectomes of mammalian brains.

Generation of a whole-brain atlas for the cholinergic system and mesoscopic projectome analysis of basal forebrain cholinergic neurons.

The cholinergic system in the brain plays crucial roles in regulating sensory and motor functions as well as cognitive behaviors by modulating neuronal activity. Understanding the organization of the cholinergic system requires a complete map of cholinergic neurons and their axon arborizations throughout the entire brain at the level of single neurons. Here, we report a comprehensive whole-brain atlas of the cholinergic system originating from various cortical and subcortical regions of the mouse brain. Using genetically labeled cholinergic neurons together with whole-brain reconstruction of optical images at 2-µm resolution, we obtained quantification of the number and soma volume of cholinergic neurons in 22 brain areas. Furthermore, by reconstructing the complete axonal arbors of fluorescently labeled single neurons from a subregion of the basal forebrain at 1-µm resolution, we found that their projections to the forebrain and midbrain showed neuronal subgroups with distinct projection specificity and diverse arbor distribution within the same projection area. These results suggest the existence of distinct subtypes of cholinergic neurons that serve different regulatory functions in the brain and illustrate the usefulness of complete reconstruction of neuronal distribution and axon projections at the mesoscopic level.

Skeleton optimization of neuronal morphology based on three-dimensional shape restrictions.

BACKGROUND: Neurons are the basic structural unit of the brain, and their morphology is a key determinant of their classification. The morphology of a neuronal circuit is a fundamental component in neuron modeling. Recently, single-neuron morphologies of the whole brain have been used in many studies. The correctness and completeness of semimanually traced neuronal morphology are credible. However, there are some inaccuracies in semimanual tracing results. The distance between consecutive nodes marked by humans is very long, spanning multiple voxels. On the other hand, the nodes are marked around the centerline of the neuronal fiber, not on the centerline. Although these inaccuracies do not seriously affect the projection patterns that these studies focus on, they reduce the accuracy of the traced neuronal skeletons. These small inaccuracies will introduce deviations into subsequent studies that are based on neuronal morphology files. RESULTS: We propose a neuronal digital skeleton optimization method to evaluate and make fine adjustments to a digital skeleton after neuron tracing. Provided that the neuronal fiber shape is smooth and continuous, we describe its physical properties according to two shape restrictions. One restriction is designed based on the grayscale image, and the other is designed based on geometry. These two restrictions are designed to finely adjust the digital skeleton points to the neuronal fiber centerline. With this method, we design the three-dimensional shape restriction workflow of neuronal skeleton adjustment computation. The performance of the proposed method has been quantitatively evaluated using synthetic and real neuronal image data. The results show that our method can reduce the difference between the traced neuronal skeleton and the centerline of the neuronal fiber. Furthermore, morphology metrics such as the neuronal fiber length and radius become more precise. CONCLUSIONS: This method can improve the accuracy of a neuronal digital skeleton based on traced results. The greater the accuracy of the digital skeletons that are acquired, the more precise the neuronal morphologies that are analyzed will be.

Emergence of 2D high-temperature nodal-line half-metal in monolayer AgN.

Nodal-line half-metals (NLHMs) are highly desirable for future spintronic devices due to their exotic quantum properties. However, the experimental realization in spin-polarized materials is nontrivial to date. Herein we perform first-principles calculations to demonstrate a 2D honeycomb, AgN, as a promising candidate of NLHMs, which is thermodynamically and dynamically stable. Band structure analysis reveals that two concentric NLs coexist centered at a Γ point near EF, accompanied by the electron and hole pockets that touch each other linearly with single-spin components. Inclusion of SOC can enrich the electronic structures of AgN, sensitive to the protection of mirror reflection symmetry: the NLHM survives if the spin is perpendicular to the Mz mirror plane, while it tunes into Wyle nodal-points by rotating spins from the out-of-plane to the in-plane direction. The characteristics of HM and NL can be well maintained on semiconducting h-BN and is immune to mechanical strains. These tunable magnetic properties render 2D AgN suitable for exotic quantum transports in nodal fermions as well as related spintronic devices.

Correction: Prediction of topological property in TlPBr2 monolayer with appreciable Rashba effect.

Correction for 'Prediction of topological property in TlPBr2 monolayer with appreciable Rashba effect' by Min Yuan et al., Phys. Chem. Chem. Phys., 2018, 20, 4308-4316.

Prediction of topological property in TlPBr2 monolayer with appreciable Rashba effect.

A quantum spin Hall (QSH) insulator with high stability, large bulk band gap and tunable topological properties is crucial for both fundamental research and practical application due to the presence of dissipationless edge conducting channels. Recently, chemical functionalization has been proposed as an effective route to realize the QSH effect. Based on first-principles calculations, we predict that a two-dimensional TlP monolayer would convert into a topological insulator with the effect of bromination, accompanied by a large bulk band gap of 76.5 meV, which meets the requirement for room-temperature application. The topological nature is verified by the calculation of Z2 topological invariant and helical edge states. Meanwhile, an appreciable Rashba spin splitting of 77.2 meV can be observed. The bulk band gap can be effectively tuned with external strain and electric field, while the Rashba spin splitting shows a parabolic variation trend under an external electric field. We find that the topological property is available for the TlP film when the coverage rate is more than 0.75. BN and SiC are demonstrated as promising substrates to support the topological nature of TlPBr2 film. Our findings suggest that a TlPBr2 monolayer is an appropriate candidate for hosting the nontrivial topological state and controllable Rashba spin splitting, and shows great potential applications in spintronics.

Controllable electronic and magnetic properties in a two-dimensional germanene heterostructure.

The control of spin without a magnetic field is one of the challenges in developing spintronic devices. Here, based on first-principles calculations, we predict a new kind of ferromagnetic half-metal (HM) with a Curie temperature of 244 K in a two-dimensional (2D) germanene van der Waals heterostructure (HTS). Its electronic band structures and magnetic properties can be tuned with respect to external strain and electric field. More interestingly, a transition from HM to bipolar-magnetic-semiconductor (BMS) to spin-gapless-semiconductor (SGS) in a HTS can be realized by adjusting the interlayer spacing. These findings provide a promising platform for 2D germanene materials, which hold great potential for application in nanoelectronic and spintronic devices.

Tunable electronic properties in the van der Waals heterostructure of germanene/germanane.

It is challenging to epitaxially grow germanene on conventional semiconductor substrates. Based on first-principles calculations, we investigate the structural and electronic properties of germanene/germanane heterostructures (HTSs). The results indicate that the Dirac cone with nearly linear band dispersion of germanene is maintained in the band gap of the substrate. Remarkably, the band gaps opened in these HTSs can be effectively modulated by the external electric field and strain, and they also feature very low effective masses and high carrier mobilities. These results provide a route to design high-performance FETs operating at room temperature in nanodevices.

An annotated street view image dataset for automated road damage detection.

Road damage is a great threat to the service life and safety of roads, and the early detection of pavement damage can facilitate maintenance and repair. Street view images serve as a new solution for the monitoring of pavement damage due to their wide coverage and regular updates. In this study, a road pavement damage dataset, the Street View Image Dataset for Automated Road Damage Detection (SVRDD), was developed using 8000 street view images acquired from Baidu Maps. Based on these images, over 20,000 damage instances were visually recognized and annotated. These instances were distributed in five administrative districts of Beijing City. Ten well-established object detection algorithms were trained and assessed using the SVRDD dataset. The results have demonstrated the performances of these algorithms in the detection of pavement damages. To the best of our knowledge, SVRDD is the first public dataset based on street view images for pavement damages detection. It can provide reliable data support for future development of deep learning algorithms based on street view images.

Analysis of the origin and invasion of prostate cancer from autopsy and radical prostatectomy specimens.

Background: Without a pseudocapsule, prostate cancer is invasive in volume growth and has some regularity in spatial distribution. Our study aims to explore the specific origin location, invasive characteristics, and morphology of prostate cancer. Methods: Ninety-eight clinical specimens with tumor volume equal to or less than one-third of the organ volume and 111 autopsy specimens were retrospectively analyzed. The origin location and invasion of prostate cancer in four horizontal quadrants and 11 vertical slides were demonstrated. In addition, the median maximum anteroposterior, left-right, horizontal, and vertical diameters of lesions were compared, and the spatial morphology of lesions was described. Results: There were 335 lesions in the autopsy and clinical specimens. There was no significant difference in the distribution of lesions confined to the horizontal quarter quadrant (P=0.064). The number of lesions with a single positive slide above the apex 0.5-1.4 cm was 75 (49.7%). No significant difference was found when compared with the maximum vertical and horizontal diameters (P=0.421). However, the maximum left-right and horizontal diameters were longer than the maximum anteroposterior diameter (P=0.046 and P<0.001). The number of lesions with a tumor area that decreased from the center to both sides was 85 (46.2%) and decreased from the center to one side was 81 (44.0%). Conclusions: Approximately 50% of the lesions originated from the apex above 0.5-1.4 cm. The invasive tendency of prostate cancer was consistent in the horizontal and vertical dimensions but less so in the anteroposterior direction. About ninety percent of lesions with tumor area decreased from the center to both sides or one side.

Uniaxial-Oriented Chiral Perovskite for Flexible Full-Stokes Polarimeter.

Full-Stokes polarization detection, with high integration and portability, offers an efficient path toward next-gen multi-information optoelectronic systems. Nevertheless, current techniques relying on optical filters create rigid and bulky configurations, limiting practicality. Here, a flexible, filter-less full-Stokes polarimeter featuring a uniaxial-oriented chiral perovskite film is first reported. It is found that, the strategic manipulation of the surfactant-mediated Marangoni effect during blade coating, is crucial for guiding an equilibrious mass transport to achieve oriented crystallization. Through this approach, the obtained uniaxial-oriented chiral perovskite films inherently possess anisotropy and chirality, and thereby with desired sensitivity to both linearly polarized light and circularly polarized light vectors. The uniaxial-oriented crystalline structure also improves photodetection, achieving a specific detectivity of 5.23 × 1013 Jones, surpassing non-oriented devices by 10×. The as-fabricated flexible polarimeters enable accurate capture of full-Stokes polarization without optical filters, exhibiting slight detection errors for the Stokes parameters: ΔS1 = 9.2%, ΔS2 = 8.6%, and ΔS3 = 6.5%, approaching the detection accuracy of optics-filter polarimeters. This proof of concept also demonstrates applications in matrix polarization imaging.

Coping with alpine habitats: genomic insights into the adaptation strategies of Triplostegia glandulifera (Caprifoliaceae).

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.

Targeted approaches to delineate neuronal morphology during early development.

Understanding the developmental changes that affect neurons is a key step in exploring the assembly and maturation of neural circuits in the brain. For decades, researchers have used a number of labeling techniques to visualize neuronal morphology at different stages of development. However, the efficiency and accuracy of neuronal labeling technologies are limited by the complexity and fragility of neonatal brains. In this review, we illustrate the various labeling techniques utilized for examining the neurogenesis and morphological changes occurring during the early stages of development. We compare the advantages and limitations of each technique from different aspects. Then, we highlight the gaps remaining in our understanding of the structure of neurons in the neonatal mouse brain.

SILENCING M 6 A READER YTHDC1 REDUCES INFLAMMATORY RESPONSE IN SEPSIS-INDUCED CARDIOMYOPATHY BY INHIBITING SERPINA3N EXPRESSION.

ABSTRACT: Sepsis-induced cardiomyopathy (SIC) is one of the most common complications of infection-induced sepsis. An imbalance in inflammatory mediators is the main factor leading to SIC . N 6 -methyladenosine (m 6 A) is closely related to the occurrence and development of sepsis. N 6 -methyladenosine reader YTH domain containing 1 (YTHDC1) is an m 6 A N 6 -methyladenosine recognition protein. However, the role of YTHDC1 in SIC remains unclear. Herein, we demonstrated that YTHDC1-shRNA inhibits inflammation, reduces inflammatory mediators, and improves cardiac function in a LPS-induced SIC mouse model. Based on the Gene Expression Omnibus database analysis, serine protease inhibitor A3N is a differential gene of SIC. Furthermore, RNA immunoprecipitation indicated that serine protease inhibitor A3N (SERPINA3N) mRNA can bind to YTHDC1, which regulates the expression of SERPINA3N. Serine protease inhibitor A3N-siRNA reduced LPS-induced inflammation of cardiac myocytes. In conclusion, the m 6 A reader YTHDC1 regulates SERPINA3N mRNA expression to mediate the levels of inflammation in SIC. Such findings add to the relationship between m 6 A reader YTHDC1 and SIC, providing a new research avenue for the therapeutic mechanism of SIC.

Two -dimensional semimetal AlSb monolayer with multiple nodal-loops and extraordinary transport properties under uniaxial strain.

Two-dimensional (2D) nodal-loop semimetal (NLSM) materials have attracted much attention for their high-speed and low-consumption transporting properties as well as their fantastic symmetry protection mechanisms. In this paper, using systematic first-principles calculations, we present an excellent NLSM candidate, a 2D AlSb monolayer, in which the conduction and valence bands cross with each other forming fascinating multiple nodal-loop (NL) states. The NLSM properties of the AlSb monolayer are protected by its glide mirror symmetry, which was confirmed using a symmetry-constrained six-band tight-binding model. The transport properties of the AlSb monolayer under in-plane uniaxial strains are also studied, based on a non-equilibrium Green's function method. It is found that both compressive and tensile strains from -10% to 10% improve the transporting properties of AlSb, and it is interesting to see that flexure configurations are energetically favored when compressive uniaxial strains are applied. Our studies not only provide a novel 2D NLSM candidate with a new symmetry protection mechanism, but also raise the novel possibility for the detection of out-of-plane flexure in 2D semimetal materials.