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At present, China's economy keeps developing rapidly. It has begun to vigorously carry out the construction of ecological civilization. As a new format of forest and grass industry, it is necessary to develop forest-based health care. The author puts forward strategies for developing forest-based health care industry on the basis of combing the development process of it.

Mesoporous silica nanoparticles (MSNs) loaded with doxorubicin and then modified with hyaluronic acid (HA) and nanobody (DOX@MSNs-HA-11C12) is a pH- and redox-responsive drug delivery system, resulting in over 90% of LoVo cell apoptosis within 48 h.

Graph neural networks (GNNs) have many variants for graph representation learning. Several works introduce PageRank into GNNs to improve its neighborhood aggregation capabilities. However, these methods leverage the general PageRank to perform complex neighborhood aggregation to obtain the final feature representation, which leads to high computational cost and oversmoothing. In this paper, we propose simple hierarchical PageRank graph neural networks (SHP-GNNs), which first utilize the simple PageRank to aggregate different neighborhood ranges of each node, and then leverage a jumping architecture to combine these aggregated features to enable hierarchical structure-aware representation. In this case, first, the simple PageRank turns the neighborhood aggregation process to no-learning, thereby reducing the computational complexity of the model. Then, the jumping structure combines the aggregation features of each node's different hierarchy (neighborhood range) to learn more informative feature representation. Finally, the successful combination of the above methods alleviate the oversmoothing problem of deep GNNs. Our experimental evaluation demonstrates that SHP-GNNs achieve or match state-of-the-art results in node classification tasks, text classification tasks, and community prediction tasks. Moreover, since SHP-GNNs' neighborhood aggregation is a no-learning process, SHP-GNNs are successfully extended to node clustering tasks.

Drastic changes in network topology of Flying Ad Hoc Networks (FANETs) result in the instability of the single-hop delay and link status accordingly. Therefore, it is difficult to implement the congestion control with delay-sensitive traffic according to the instantaneous link status. To solve the above difficulty effectively, we formulate the delay-aware congestion control as a network utility maximization, which considers the link capacity and end-to-end delay as constraints. Next, we combine the Lagrange dual method and delay auxiliary variable to decouple the link capacity and delay threshold constraints, as well as to update single-hop delay bound with the delay-outage mode. Built on the methods above, a distributed optimization algorithm is proposed in this work by considering the estimated single-hop delay bound for each transmission, which only uses the local channel information to limit the end-to-end delay. Finally, we deduce the relationship between the primal and dual solutions to underpin the advantages of the proposed algorithm. Simulation results demonstrate that the proposed algorithm effectively can improve network performances in terms of packet time-out rate and network throughput.

Exploring new topological phases and phenomena has become a vital topic in condensed matter physics and materials sciences. Recent studies reveal that a braided colliding nodal pair can be stabilized in a multi-gap system with $$PT$$ P T or $${C}_{2z}T$$ C 2 z T symmetry. This exemplifies non-abelian topological charges beyond the scope of conventional single-gap abelian band topology. Here, we construct ideal acoustic metamaterials to realize non-abelian braiding with the fewest band nodes. By emulating the time with a sequence of acoustic samples, we experimentally observe an elegant but nontrivial nodal braiding process, including nodes creation, braiding, collision, and repulsion (i.e., impossible to annihilate), and measure the mirror eigenvalues to elucidate the braiding consequence. The latter, at the level of wavefunctions, is of prime importance since essentially braiding physics aims to entangle multi-band wavefunctions. Furthermore, we experimentally unveil the highly intricate correlation between the multi-gap edge responses and the bulk non-abelian charges. Our findings pave the way for developing non-abelian topological physics that is still in its infancy.

Topological features embedded in ancient braiding and knotting arts endow significant impacts on our daily life and even cutting-edge science. Recently, fast growing efforts are invested to the braiding topology of complex Bloch bands in non-Hermitian systems. This new classification of band topology goes far beyond those established in Hermitian counterparts. Here, we present the first acoustic realization of the topological non-Hermitian Bloch braids, based on a two-band model easily accessible for realizing any desired knot structure. The non-Hermitian bands are synthesized by a simple binary cavity-tube system, where the long-range, complex-valued, and momentum-resolved couplings are accomplished by a well-controlled unidirectional coupler. In addition to directly visualizing various two-band braiding patterns, we unambiguously observe the highly-elusive topological phase transitions between them. Not only do our results provide a direct demonstration for the non-Hermitian band topology, but also the experimental techniques open new avenues for designing unconventional acoustic metamaterials., Comment: Accepted by PRL

Inspired by the newly emergent valleytronics, great interest has been attracted to the topological valley transport in classical metacrystals. The presence of nontrivial domain-wall states is interpreted with a concept of valley Chern number, which is well defined only in the limit of small bandgap. Here, we propose a new visual angle to track the intricate valley topology in classical systems. Benefiting from the controllability of our acoustic metacrystals, we construct Weyl points in synthetic three-dimensional momentum space through introducing an extra structural parameter (rotation angle here). As such, the two-dimensional valley-projected band topology can be tracked with the strictly quantized topological charge in three-dimensional Weyl crystal, which features open surface arcs connecting the synthetic Weyl points and gapless chiral surface states along specific Weyl paths. All theoretical predictions are conclusively identified by our acoustic experiments. Our findings may promote the development of topological valley physics, which is less well-defined yet under hot debate in multiple physical disciplines., Comment: Phys.Rev.Lett. Accepted

Nanobodies show a great potential in biomedical and biotechnology applications. Bacterial expression is the most widely used expression system for nanobody production. However, the yield of nanobodies is relatively low compared to that of eukaryotic systems. In this study, the repetitive amino acid sequence motifs (GAGAGS) found in silk fibroin protein (SFP) were developed as a novel fusion tag (SF-tag) to enhance the expression of nanobodies in Escherichia coli. SF-tags of 1 to 5 hexapeptide units were fused to the C-terminus of 4G8, a nanobody against human epididymis protein 4 (HE4). The protein yield of 4G8 variants was increased by the extension of hexapeptide units and achieved a 2.5 ~ 7.1-fold increase compared with that of untagged 4G8 (protein yield of 4G8-5C = 0.307 mg/g vs that of untagged 4G8 = 0.043 mg/g). Moreover, the fusion of SF-tags not only had no significant effect on the affinity of 4G8, but also showed a slight increase in the thermal stability of SF-tag-fused 4G8 variants. The fusion of SF-tags increased the transcription of 4G8 by 2.3 ~ 7.0-fold, indicating SF-tags enhanced the protein expression at the transcriptional level. To verify the applicability of the SF-tags for other nanobody expression, we further investigated the protein expression of two other anti-HE4 nanobodies 1G8 and 3A3 upon fusion with the SF-tags. Results indicated that the SF-tags enhanced the protein expression up to 5.2-fold and 5.7-fold for 1G8 and 3A3, respectively. For the first time, this study reported a novel and versatile fusion tag system based on the SFP for improving nanobody expression in Escherichia coli, which may enhance its potential for wider applications.Key points• A silk fibroin protein-based fusion tag (SF-tag) was developed to enhance the expression of nanobodies in Escherichia coli.• The SF-tag enhanced the nanobody expression at the transcriptional level.• The fusion of SF-tag had no significant effect on the affinity of nanobodies and could slightly increase the thermal stability of nanobodies.

In urban roads, the safety service of vehicular ad hoc networks is particularly important because of the frequent traffic accidents. In order to minimise redundancy and delay of network and ensure the high reception rate of vehicles in the target area when spreading the emergency message. In this study, the authors propose a reliable broadcast mechanism based on the layout information of the road. Different from existing mechanisms, in the straight, the proposed mechanism regards effective communication distance based on prediction rather than fix distance as one of the parameters of waiting time calculation. Considering the obstacles such as buildings around the intersection in the actual urban scenario, the vehicle in the intersection area (IA) of the target area will have an additional broadcast, if there are no vehicles in the IA, the vehicle in the pre-selected area for intersections (IPA) has chance to broadcast when it enters IA, which avoids the failure of emergency message transmission in some direction because of the obstacles around the intersection and ensures the coverage and reliability of emergency message. The simulation results verify that the novel scheme has better performance than the compared schemes in terms of reliability and delay.

Due to the dynamically changing topology of Internet of Vehicles (IoV), it is a challenging issue to achieve efficient data dissemination in IoV. This paper considers strongly connected IoV with a number of heterogenous vehicular nodes to disseminate information and studies distributed replication-based data dissemination algorithms to improve the performance of data dissemination. Accordingly, two data replication algorithms, a deterministic algorithm and a distributed randomised algorithm, are proposed. In the proposed algorithms, the number of message copies spread in the network is limited and the network will be balanced after a series of average operations among the nodes. The number of communication stages needed for network balance shows the complexity of network convergence as well as network convergence speed. It is proved that the network can achieve a balanced status after a finite number of communication stages. Meanwhile, the upper and lower bounds of the time complexity are derived when the distributed randomised algorithm is applied. Detailed mathematical results show that the network can be balanced quickly in complete graph; thus highly efficient data dissemination can be guaranteed in dense IoV. Simulation results present that the proposed randomised algorithm outperforms the present schemes in terms of transmissions and dissemination delay.

Symmetry plays a critical role in classifying phases of matter. This is exemplified by how crystalline symmetries enrich the topological classification of materials and enable unconventional phenomena in topologically nontrivial ones. After an extensive study over the past decade, the list of topological crystalline insulators and semimetals seems to be exhaustive and concluded. However, in the presence of gauge symmetry, common but not limited to artificial crystals, the algebraic structure of crystalline symmetries needs to be projectively represented, giving rise to unprecedented topological physics. Here we demonstrate this novel idea by exploiting a projective translation symmetry and constructing a variety of Möbius-twisted topological phases. Experimentally, we realize two Möbius insulators in acoustic crystals for the first time: a two-dimensional one of first-order band topology and a three-dimensional one of higher-order band topology. We observe unambiguously the peculiar Möbius edge and hinge states via real-space visualization of their localiztions, momentum-space spectroscopy of their 4π periodicity, and phase-space winding of their projective translation eigenvalues. Not only does our work open a new avenue for artificial systems under the interplay between gauge and crystalline symmetries, but it also initializes a new framework for topological physics from projective symmetry.

Cloud storage provides elastic storage services for enterprises and individuals remotely. However, security problems such as data integrity are becoming a major obstacle. Recently, blockchain-based verification approaches have been extensively studied to get rid of a centralized third-party auditor. Most of these schemes suffer from poor scalability and low search efficiency and even fail to support data dynamic update operations on blockchain, which limits their large-scale and practical applications. In this work, we propose a blockchain-based dynamic data integrity verification scheme for cloud storage with T-Merkle hash tree. A decentralized scheme is proposed to eliminate the restrictions of previous centralized schemes. The data tags are generated by the technique of ZSS short signature and stored on blockchain. An improved verification method is designed to check the integrity of cloud data by transferring computation from a verifier to cloud server and blockchain. Furthermore, a storage structure called T-Merkle hash tree which is built based on T-tree and Merkle hash tree is designed to improve storage utilization of blockchain and support binary search on chain. Moreover, we achieve efficient and secure dynamic update operations on blockchain by an append-only manner. Besides, we extend our scheme to support batch verification to handle massive tasks simultaneously; thus, the efficiency is improved and communication cost is reduced. Finally, we implemented a prototype system based on Hyperledger Fabric to validate our scheme. Security analysis and performance studies show that the proposed scheme is secure and efficient.

Recently, injectable hydrogels have shown great potential in cell therapy and drug delivery. They can easily fill in any irregular-shaped defects and remain in desired positions after implantation using minimally invasive strategies. Here, we developed hydrogels prepared from tilapia skin collagen and chitosan (HCC). The residual mass rate of HCC was affected by the pH at the time of preparation, which was 29.1 % at pH 7 in 36 h. By comparison, the residual mass ratios of HCC at pH values of 6 and 5 were only approximately 8.4 % and 0, respectively. In addition, the stability of HCC was also affected by the concentration of these two components. HCC10 catalyzed by 10 mg mL−1 tilapia skin collagen and 10 mg mL−1 chitosan was more stable than HCC5 catalyzed by 5 mg mL−1 tilapia skin collagen and 10 mg mL−1 chitosan; therefore, we studied that ability of HCC10 to deliver two model nanobodies: 2D5 and KPU. As the concentration of nanobodies increased, the cumulative release rate of 2D5 decreased, and the release rate of KPU increased. Meanwhile, the cumulative release rate of 2D5 was the highest (68.3 %) at pH 5.5, followed by pH 6.8 (56.4 %) and 7.4 (28.4 %). However, the cumulative release rates of KPU were similar at pH 5.5 (45.1 %), 6.8 (46.5 %), and 7.4 (44.9 %). HCC is biodegradable, and can facilitate the release nanobodies; thus, HCC could be developed into an intelligent responsive tumor treatment matrix for use in cancer therapy.

Tensile property of coarse grain heat affected zone(CGHAZ)is one of the important mechanical property of DP780 cold-rolled dual phase steel, and factors influencing tensile property of CGHAZ include peak temperature, heating rate and cooling rate. Based on response surface method (RSM), two response surfaces models were established. By using Design-Expert software, three factors were combined in pairs. Analysis of variance (ANOVA) was performed on the response surface models. The results showed that tensile property of DP780 was influenced by peak temperature most, then cooling rate, and heating rate made the least influence.

Vehicular Ad Hoc Networks (VANETs) provide safety management and entertainment services in smart city scenarios. However, due to the highly time-varying network topology caused by vehicles’ movement and non-line-of-sight (NLOS) areas in complex urban environment, the connection time between vehicles might be very short, leading to limited transmission capacity between vehicles. As a result, large file transmission such as online video sharing might be unavailable. To alleviate this issue, we study high-integrity based file transmission using pure vehicle-to-vehicle (V2V) communication at urban intersections. First, we develop the analytical models to evaluate file transmission at intersections, including vehicle mobility model, connection time prediction model, and V2V communication model. Then, we derive the relationship between transmission capacity and vehicles’ mobility. Based upon this analysis, we propose a cooperative file transmission strategy for the transmitting vehicle, which helps transmit the target file to the receiving vehicle. The proposed strategy includes three phases: transmission capacity evaluation, cluster establishment, and cooperative file transmission. By taking advantage of the cluster characteristics, the strategy can achieve file transmission with high integrity. Through extensive simulations, we demonstrate the accuracy of the proposed system model which matches our analysis well, and show the effectiveness of the proposed strategy by comparing with other file transmission strategies in aspects of transmission success rate and data transmission volume.

Innate lymphoid cells (ILCs) are generated early during ontogeny and persist predominantly as tissue-resident cells. Here, we examined how ILCs are maintained and renewed within tissues. We generated a single cell atlas of lung ILC2s and found that Il18r1+ ILCs comprise circulating and tissue-resident ILC progenitors (ILCP) and effector-cells with heterogeneous expression of the transcription factors Tcf7 and Zbtb16, and CD103. Our analyses revealed a continuous differentiation trajectory from Il18r1+ ST2- ILCPs to Il18r- ST2+ ILC2s, which was experimentally validated. Upon helminth infection, recruited and BM-derived cells generated the entire spectrum of ILC2s in parabiotic and shield chimeric mice, consistent with their potential role in the renewal of tissue ILC2s. Our findings identify local ILCPs and reveal ILCP in situ differentiation and tissue adaptation as a mechanism of ILC maintenance and phenotypic diversification. Local niches, rather than progenitor origin, or the developmental window during ontogeny, may dominantly imprint ILC phenotypes in adult tissues.

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer-enriched miRNA is required for prostate tumorigenesis. We identify miR-205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR-205 is not required for normal prostate development and homeostasis, genetic deletion of miR-205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR-205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR-205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR-205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR-205 in the progression of Pten null-induced prostate cancer.

Recently, intense efforts have been devoted to realizing classical analogues of various topological phases of matter. In this Letter, we explore the intriguing Weyl physics by a simple one-dimensional sonic crystal, in which two extra structural parameters are combined to construct a synthetic three-dimensional space. Based on our underwater ultrasonic experiments, we have not only observed the synthetic Weyl points directly, but also probed the novel reflection phase singularity that connects inherently with the topological robustness of Weyl points. As a smoking gun evidence of the topological states of matter, the presence of nontrivial interface modes has been demonstrated further. All experimental data agree well with our full-wave simulations. As the first realization of topological acoustics in synthetic space, our study exhibits great potential of probing high-dimensional topological phenomena by such easily-fabricated and -detected low-dimension acoustic systems., Comment: Accepted by PRL

Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4+ T cells but was important for limiting the activation of CD8+ T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of Treg cells separable from signaling via the T cell antigen receptor.

Recognition of transformed cells by the immune system can sometimes generate a rate-limiting “equilibrium phase,” wherein tumor outgrowth is prevented without complete neoplasm elimination. Targeting premalignancies during this immune-controlled bottleneck is a promising strategy for rational cancer prevention. Thus far, immune equilibrium has been difficult to model in a traceable way and most immunoediting systems have been limited to mesenchymal tumor types. Here, we introduce a mouse model for fluorescent tracing of somatic, epithelial transformation. We demonstrate that transplantation can be used to prevent a confounding, artificial tolerance that affects autochthonous, inducible models. Using this system, we observe the expected dichotomy of outcomes: immune-deficient contexts permit rapid tumorigenesis, while initiated clones in immunocompetent mice undergo elimination or equilibrium. Strikingly, the equilibrium phase correlates with localization within hair follicles, which have been previously characterized as relatively immune-privileged sites. Given this, we posit that valleys in the immune surveillance landscape of a normal tissue can provide a cell-extrinsic alternative to the canonical, cell-intrinsic adaptations believed to establish the equilibrium phase. Our model is a prototype for tracing immunoediting in vivo and could serve as a novel screening platform for therapies targeted against immune-controlled premalignancies.

Summary How embryonic progenitors coordinate cell fate specification and establish transcriptional and signaling competence is a fundamental question in developmental biology. Here, we show that transcription factor ΔNp63 profoundly changes the transcriptome and remodels thousands of open chromatin regions of Krt8+ progenitors during epidermal fate specification. ATAC-seq and single-cell RNA-seq reveal that ΔNp63-dependent programs govern epidermal lineage formation, and ΔNp63-independent programs, mediated by AP2 and AP1 transcription factors, promote epidermal differentiation and epithelial-to-mesenchymal transition. ΔNp63 promotes Wnt signaling by directly upregulating Wnt ligands, Frizzled receptors, and transcription factors. Deletion of β-catenin in Krt8+ progenitors delays their maturation into Krt5+ progenitors. The lack of epidermal Wnt production in the absence of ΔNp63 also incapacitates Wnt activation in the underlying dermal cells. These findings reveal the remarkable changes of the transcriptome, open chromatin, and signaling pathways at the onset of skin development and uncover the molecular cascade for epidermal lineage formation.

Fan et al. have identified a population of recirculating Treg cells with greater suppressive ability and a unique tissue distribution. Using single-cell RNA-seq, they place these Treg cells at the apex of the Treg developmental trajectory and show that similar cells may exist in humans., Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs and nonlymphoid tissues. While unique subsets of Treg cells have been described in some nonlymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. Furthermore, it is possible that Treg cells from similar tissue types share largely similar properties. We have identified a short-lived effector Treg cell subset that expresses the α2 integrin, CD49b, and exhibits a unique tissue distribution, being abundant in peripheral blood, vasculature, skin, and skin-draining lymph nodes, but uncommon in the intestines and in viscera-draining lymph nodes. CD49b+ Treg cells, which display superior functionality revealed by in vitro and in vivo assays, appear to develop after multiple rounds of cell division and TCR-dependent activation. Accordingly, single-cell RNA-seq analysis placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues.

Significance Wavefront shaping with spatial light modulators has recently motivated many studies in the field of light manipulation in diffusive media. Here, we extend this concept to acoustic waves by designing and building a binary phase-modulating spatial sound modulator (SSM). The SSM is an acoustic metasurface consisting of unit cells with two states, switchable through programmed electronics. We demonstrate in audible frequencies, and in a reverberating environment, the capability of controlling and reshaping any complex sound field. Our work will not only open avenues to study wave propagation in complex and chaotic media but also inspire applications in acoustic engineering., A reverberating environment is a common complex medium for airborne sound, with familiar examples such as music halls and lecture theaters. The complexity of reverberating sound fields has hindered their meaningful control. Here, by combining acoustic metasurface and adaptive wavefield shaping, we demonstrate the versatile control of reverberating sound fields in a room. This is achieved through the design and the realization of a binary phase-modulating spatial sound modulator that is based on an actively reconfigurable acoustic metasurface. We demonstrate useful functionalities including the creation of quiet zones and hotspots in a typical reverberating environment.

Natural killer (NK) cells are innate lymphocytes that display features of adaptive immunity during viral infection. Biallelic mutations in IRF8 have been reported to cause familial NK cell deficiency and susceptibility to severe viral infection in humans; however, the precise role of this transcription factor in regulating NK cell function remains unknown. Here, we show that cell-intrinsic IRF8 was required for NK cell-mediated protection against mouse cytomegalovirus infection. During virus exposure, NK cells upregulated IRF8 through interleukin-12 (IL-12) signaling and the transcription factor STAT4, which promoted epigenetic remodeling of the Irf8 locus. Moreover, IRF8 facilitated the proliferative burst of virus-specific NK cells by promoting expression of cell cycle genes, and directly controlling Zbtb32, a master regulator of virus-driven NK cell proliferation. These findings identify the function and cell type-specific regulation of IRF8 in NK cell-mediated antiviral immunity, and provide a mechanistic understanding of virus susceptibility in patients with IRF8 mutations.

Due to the high mobility of vehicles, the frequent path failures caused by dynamic network topology, and a variety of obstructions, efficient data dissemination with delay constraint in vehicular ad hoc networks (VANETs) is a challenging issue. To address these problems, a novel mobile relaying technique by employing unmanned aerial vehicles (UAVs) is considered to facilitate data dissemination in vehicular environments where the communication infrastructures are not available or the network connectivity is poor. This paper studies and formulates the throughput maximization problem in UAV-assisted VANETs, which aims to achieve high throughput while guarantee the delay constraint of data flows to the vehicles in the area. To maximize the network throughput, the maximization problem tries to find an optimal delivery strategy for data dissemination by optimizing the transmission rate. To solve the problem, the knapsack problem can be reduced to the maximization problem, which is proved NP-hard. A polynomial time approximation scheme is proposed to achieve an approximate solution. Detailed theoretical analysis including time complexity and approximation ratio of the proposed algorithm is presented. Simulation results demonstrate the effectiveness of the proposed algorithm.

Reflection and refraction occur at interface between two different media. These two fundamental phenomena form the basis of fabricating various wave components. Specifically, refraction, dubbed positive refraction nowadays, appears in the opposite side of the interface normal with respect to the incidence. Negative refraction, emerging in the same side by contrast, has been observed in artificial materials1-5 following a prediction by Veslago6, which has stimulated many fascinating applications such as super-resolution imaging7. Here we report the first discovery of negative refraction of the topological surface arc states of Weyl crystals, realized for airborne sound in a novel woodpile phononic crystal. The interfaces are one-dimensional edges that separate different crystal facets. By tailoring the surface terminations of such a Weyl phononic crystal, open equifrequency contours of surface acoustic waves can be delicately designed to produce the negative refraction, to contrast the positive counterpart realized in the same sample. Strikingly different from the conventional interfacial phenomena, the unwanted reflection can be made forbidden by exploiting the open nature of the surface equifrequency contours, which is a topologically protected surface hallmark of Weyl crystals8-12., Comment: An updated version has been published in Nature

Valley pseudospin, labeling quantum states of energy extrema in momentum space, is attracting tremendous attention1-13 because of its potential in constructing new carrier of information. Compared with the non-topological bulk valley transport realized soon after predictions1-5, the topological valley transport in domain walls6-13 is extremely challenging owing to the inter-valley scattering inevitably induced by atomic scale imperfectness, until the recent electronic signature observed in bilayer graphene12,13. Here we report the first experimental observation of topological valley transport of sound in sonic crystals. The macroscopic nature of sonic crystals permits the flexible and accurate design of domain walls. In addition to a direct visualization of the valley-selective edge modes through spatial scanning of sound field, reflection immunity is observed in sharply curved interfaces. The topologically protected interface transport of sound, strikingly different from that in traditional sound waveguides14,15, may serve as the basis of designing devices with unconventional functions.

Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. We found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of Treg cells. A boost in Treg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.

Skin stem cells (SCs) are specified and rapidly expanded to fuel body growth during early development. However, the molecular mechanisms that govern the amplification of skin SCs remain unclear. Here we report an essential role for miR-205, one of the most highly expressed microRNAs in skin SCs, in promoting neonatal expansion of these cells. Unlike most mammalian miRNAs, genetic deletion of miR-205 causes neonatal lethality with severely compromised epidermal and hair follicle growth. In the miR-205 knockout skin SCs, phospho-Akt is significantly downregulated, and the SCs prematurely exit the cell cycle. In the hair follicle, this accelerates the transition of the neonatal SCs towards quiescence. We identify multiple miR-205-targeted negative regulators of PI(3)K signalling that mediate the repression of phospho-Akt and restrict the proliferation of SCs. Our findings reveal an essential role for miR-205 in maintaining the expansion of skin SCs by antagonizing negative regulators of PI(3)K signalling.

Mutations in the TNF family of proteins have been associated with inherited forms of immune deficiency. Using an array-based sequencing assay, we identified an autosomal-dominant deficiency in TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) in a kindred with recurrent infection and impaired antibody responses to protein and polysaccharide vaccines. This mutation occurs in the sixth exon of TWEAK and results in the amino acid substitution R145C within the conserved TNF-homology domain of the full-length protein. TWEAK mutant protein formed high molecular weight aggregates under nonreducing conditions, suggesting an increased propensity for intermolecular interactions. As a result, mutant TWEAK associated with B-cell–activating factor (BAFF) protein and down-regulated the BAFF-mediated activation of the noncanonical NF-κB pathway through inhibition of p100 processing to p52, resulting in inhibition of BAFF-dependent B-cell survival and proliferation. As BAFF mediates T-cell–independent isotype switching and B-cell survival, our data implicate TWEAK as a disease-susceptibility gene for a humoral immunodeficiency.

International audience; Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-γ was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response~to dysregulated local proinflammatory cytokine production.

Small immune complexes cause type III hypersensitivity reactions that frequently result in tissue injury. The responsible mechanisms, however, remain unclear and differ depending on target organs. Here, we identify a kidney-specific anatomical and functional unit, formed by resident macrophages and peritubular capillary endothelial cells, which monitors the transport of proteins and particles ranging from 20 to 700 kDa or 10 to 200 nm into the kidney interstitium. Kidney-resident macrophages detect and scavenge circulating immune complexes “pumped” into the interstitium via trans-endothelial transport and trigger a FcγRIV-dependent inflammatory response and the recruitment of monocytes and neutrophils. In addition, FcγRIV and TLR pathways synergistically “super-activate” kidney macrophages when immune complexes contain a nucleic acid. These data identify a physiological function of tissue-resident kidney macrophages and a basic mechanism by which they initiate the inflammatory response to small immune complexes in the kidney.

Photomorphogenesis is controlled by multiple signaling pathways, including the light and brassinosteroid (BR) pathways. BR signaling activates the BZR1 transcription factor, which is required for suppressing photomorphogenesis in the dark. We identified a suppressor of the BR hypersensitive mutant bzr1-1D and named it bzr1-1D suppressor1-Dominant (bzs1-D). The bzs1-D mutation was caused by overexpression of a B-box zinc finger protein BZS1, which is transcriptionally repressed by BZR1. Overexpression of BZS1 causes de-etiolation in the dark, short hypocotyls in the light, reduced sensitivity to BR treatment, and repression of many BR-activated genes. Knockdown of BZS1 by co-suppression partly suppressed the short hypocotyl phenotypes of BR-deficient or insensitive mutants. These results support that BZS1 is a negative regulator of BR response. BZS1 overexpressors are hypersensitive to different wavelengths of light and loss of function of BZS1 reduces plant sensitivity to light and partly suppresses the constitutive photomorphogenesis 1 (cop1) mutant in the dark, suggesting a positive role in light response. BZS1 protein accumulates at an increased level after light treatment of dark-grown BZS1-OX plants and in the cop1 mutants, and BZS1 interacts with COP1 in vitro, suggesting that light regulates BZS1 through COP1-mediated ubiquitination and proteasomal degradation. These results demonstrate that BZS1 mediates the crosstalk between BR and light pathways.

In skeletal muscle and many other cell types, mitochondria exist as an elaborate and dynamic network in which "individual" mitochondria exist only transiently even under nonstimulated conditions. The balance of continuous mitochondrial fission and fusion defines the morphology of the mitochondrial reticulum. Environmental stimuli, such as oxidative stress, can influence fusion and fission rates, resulting in a transformation of the network's connectivity. Using confocal laser scanning microscopy of C(2)C(12) mouse myocytes, we show that acute exposure to the reactive oxygen species (ROS) hydrogen peroxide (H(2)O(2)) induces a slow fragmentation of the mitochondrial reticulum that is reversible over 24h. Although H(2)O(2) decomposes rapidly in culture medium, the full extent of fragmentation occurs 5-6h posttreatment, suggesting that H(2)O(2) affects mitochondrial morphology by modulating cellular physiology. Supraphysiological (>1 mM) concentrations of H(2)O(2) are cytotoxic, but lower concentrations (250 μM) sufficient to induce transient fragmentation do not lower cell viability. H(2)O(2)-induced mitochondrial fragmentation is preceded by decreases in inner mitochondrial membrane potential and maximal respiratory rate, suggesting a possible mechanism. Because H(2)O(2) is produced in contracting muscle, our results raise the possibility that ROS generation may contribute to exercise-induced changes in mitochondrial morphology in vivo.