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Understanding global communications among cells requires accurate representation of cell-cell signaling links and effective systems-level analyses of those links. We construct a database of interactions among ligands, receptors and their cofactors that accurately represent known heteromeric molecular complexes. We then develop CellChat, a tool that is able to quantitatively infer and analyze intercellular communication networks from single-cell RNA-sequencing (scRNA-seq) data. CellChat predicts major signaling inputs and outputs for cells and how those cells and signals coordinate for functions using network analysis and pattern recognition approaches. Through manifold learning and quantitative contrasts, CellChat classifies signaling pathways and delineates conserved and context-specific pathways across different datasets. Applying CellChat to mouse and human skin datasets shows its ability to extract complex signaling patterns. Our versatile and easy-to-use toolkit CellChat and a web-based Explorer ( http://www.cellchat.org/ ) will help discover novel intercellular communications and build cell-cell communication atlases in diverse tissues. Single-cell methods record molecule expressions of cells in a given tissue, but understanding interactions between cells remains challenging. Here the authors show by applying systems biology and machine learning approaches that they can infer and analyze cell-cell communication networks in an easily interpretable way.

Theranostics, an integrated therapeutic and diagnostic system, can simultaneously monitor the real-time response of therapy. Different imaging modalities can combine with a variety of therapeutic moieties in theranostic nanoagents. In this study, a multi-functionalized, integrated theranostic nanoagent based on folate-conjugated reducible polyethylenimine passivated carbon dots (fc-rPEI-Cdots) is developed and characterized. These nanoagents emit visible blue photoluminescence under 360 nm excitation and can encapsulate multiple siRNAs (EGFR and cyclin B1) followed by releasing them in intracellular reductive environment. In vitro cell culture study demonstrates that fc-rPEI-Cdots is a highly biocompatible material and a good siRNA gene delivery carrier for targeted lung cancer treatment. Moreover, fc-rPEI-Cdots/pooled siRNAs can be selectively accumulated in lung cancer cells through receptor mediated endocytosis, resulting in better gene silencing and anti-cancer effect. Combining bioimaging of carbon dots, stimulus responsive property, gene silencing strategy and active targeting motif, this multi-functionalized, integrated theranostic nanoagent may provide a useful tool and platform to benefit clinicians adjusting therapeutic strategy and administered drug dosage in real time response by monitoring the effect and tracking the development of carcinomatous tissues in diagnostic and therapeutic aspects.

As a prominent approach to treat intervertebral disc (IVD) degeneration, disc transplantation still falls short to fully reconstruct and restore the function of native IVD. Here, we introduce an IVD scaffold consists of a cellulose‐alginate double network hydrogel‐based annulus fibrosus (AF) and a cellulose hydrogel‐based nucleus pulposus (NP). This scaffold mimics native IVD structure and controls the delivery of Growth Differentiation Factor‐5 (GDF‐5), which induces differentiation of endogenous mesenchymal stem cells (MSCs). In addition, this IVD scaffold has modifications on MSC homing peptide and RGD peptide which facilitate the recruitment of MSCs to injured area and enhances their cell adhesion property. The benefits of this double network hydrogel are high compressibility, shape memory effect, and mechanical strength comparable to native IVD. In vivo animal study demonstrates successful reconstruction of injured IVD including both AF and NP. These findings suggest that this double network hydrogel can serve as a promising approach to IVD regeneration with other potential biomedical applications.

High-resolution ultrasound is preferred as the first-line imaging modality for evaluation of superficial soft tissues, such as the facial muscles. In contrast to magnetic resonance imaging and computed tomography, which require specifically designated planes (axial, coronal and sagittal) for imaging, the ultrasound transducer can be navigated based on the alignment of facial muscles. Botulinum toxin injections are widely used in facial cosmetic procedures in recent times. Ultrasonography is recognized as a useful tool for pre-procedure localization of target muscles. In this pictorial review, we discuss the detailed sonoanatomy of facial muscles and their clinical relevance, particularly with regard to botulinum toxin injections. Furthermore, we have summarized the findings of clinical studies that report ultrasonographic imaging of facial muscles.

Adipocyte-macrophage crosstalk plays a critical role to regulate adipose tissue microenvironment and cause chronic inflammation in the pathogenesis of obesity. Interleukin-29 (IL-29), a member of type 3 interferon family, plays a role in host defenses against microbes, however, little is known about its role in metabolic disorders. We explored the function of IL-29 in the pathogenesis of obesity-induced inflammation and insulin resistance. We found that serum IL-29 level was significantly higher in obese patients. IL-29 upregulated IL-1β, IL-8, and monocyte chemoattractant protein-1 (MCP-1) expression and decreased glucose uptake and insulin sensitivity in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes through reducing glucose transporter 4 (GLUT4) and AKT signals. In addition, IL-29 promoted monocyte/macrophage migration. Inhibition of IL-29 could reduce inflammatory cytokine production in macrophage-adipocyte coculture system, which mimic an obese microenvironment. In vivo, IL-29 reduced insulin sensitivity and increased the number of peritoneal macrophages in high-fat diet (HFD)-induced obese mice. IL-29 increased M1/M2 macrophage ratio and enhanced MCP-1 expression in adipose tissues of HFD mice. Therefore, we have identified a critical role of IL-29 in obesity-induced inflammation and insulin resistance, and we conclude that IL-29 may be a novel candidate target for treating obesity and insulin resistance in patients with metabolic disorders.SummaryIL-29 was expressed in adipose tissue macrophages (ATM) and adipocytes in obese patients. IL-29 promoted adipose tissue inflammation, macrophage chemotaxis, and systemic insulin resistance in vitro and in vivo. These findings suggest that IL-29 secretion by adipocytes that promote ATMs retention in visceral white adipose tissue (WAT) and foster the chronic inflammation that leads to metabolic disorder.

Microporous annealed particle (MAP) scaffolds are flowable, in situ crosslinked, microporous scaffolds composed of microgel building blocks and were previously shown to accelerate wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow MAP degradation by switching the chirality of the crosslinking peptides from l - to d -amino acids. Unexpectedly, despite showing the predicted slower enzymatic degradation in vitro, d -peptide crosslinked MAP hydrogel ( d -MAP) hastened material degradation in vivo and imparted significant tissue regeneration to healed cutaneous wounds, including increased tensile strength and hair neogenesis. MAP scaffolds recruit IL-33 type 2 myeloid cells, which is amplified in the presence of d -peptides. Remarkably, d -MAP elicited significant antigen-specific immunity against the d -chiral peptides, and an intact adaptive immune system was required for the hydrogel-induced skin regeneration. These findings demonstrate that the generation of an adaptive immune response from a biomaterial is sufficient to induce cutaneous regenerative healing despite faster scaffold degradation. Microporous annealed-particle degradable scaffolds have been developed and shown to induce type 2 innate and adaptive immune response that facilitated skin wound healing.

Prior investigations have been primarily conducted in a laboratory to examine the effects of the smartphone use on the neck and head positions, whether these results are applicable to actual conditions is still unknown. This field survey thus analyzed the neck flexion (NF), head flexion (HF), gaze angle (GA), and viewing distance (VD) of smartphone users in public areas in Taipei, Taiwan. Six hundred smartphone users (300 men and 300 women) were photographed sagittally in standing, supported sitting, or unsupported sitting postures while using a smartphone. Results showed that women had significantly less NF and HF and shorter VDs than male users. Regardless of gender, higher NF was observed for standing than for sitting. Women had similar NF and HF while sitting supported and unsupported, but both were significantly lower than those while standing. By contrast, male users had higher NF and HF during unsupported sitting than during supported sitting. The NF (45°–50°) was much greater than the recommended maximum safe NF of 15°. Women may be at higher risk of visual strain because of shorter VD.

The facial and submental regions are supplied by complicated neurovascular networks; therefore, facial aesthetic injections may be associated with serious adverse events such as skin necrosis and blindness. Pre-injection localization of neurovascular structures using high-resolution ultrasound can theoretically prevent unexpected complications. Therefore, a systematic protocol that focuses on these facial neurovascular structures is warranted. In this pictorial essay, we discuss the sonoanatomy of facial and submental neurovascular structures and its relevance to aesthetic injections. Moreover, we have highlighted the mechanisms underlying potential neurovascular injuries during aesthetic injections.

Background Total hip arthroplasty (THA) is the treatment of choice for posttraumatic arthritis with failed internal fixation for hip fractures. However, the postoperative prognosis is not clear. Questions/purposes The primary aim of the study is to report the postoperative outcome, prognosis, and complication rates of total hip arthroplasty in posttraumatic hip arthritis after failed internal fixation of fractures around the hip. The secondary aim of the study is to report results among different fracture types around the hip. Patients and methods We enrolled salvage THA patients after failed internal fixation of fractures around the hip and matched control patients undergoing primary THA for hip osteoarthritis. Subgroup analysis was performed to compare the postoperative outcomes, prognosis, and complication rates of salvage THA in posttraumatic hip arthritis after failed internal fixation of different fracture types around the hip. Results A total of 315 THAs (105 salvage THAs and 210 primary THAs) were analyzed. Patients with salvage THA had a longer operative time, lower postoperative hemoglobin (Hb) level, more Hb drop (2.2 ± 1.4 vs. 1.7 ± 1.2 gm/dl, p  = 0.002), and delayed ambulation. The salvage THA group also had a higher dislocation rate within 2 months after salvage THA (9.5% vs. 1.9%, p  = 0.002), reoperation rate (10.5% vs. 3.8%, p  = 0.019, including debridement, open and closed reduction under sedation, revision surgery, surgical fixation for periprosthetic fractures), and revision rate (5.7% vs. 0.5%, p  = 0.003) than patients undergoing primary THA. Patients who had failed fixation for acetabular fractures were younger and tended to recover well. Patients with previous intertrochanteric fracture had the longest operative time, more hip pain (83.8%, p  = 0.022) and more complications. Conclusion Salvage THA in posttraumatic hip arthritis after failed internal fixation required a longer operative time and led to more blood loss and postoperative complications. The dislocation, reoperation, and revision rates after salvage THA were higher than those after primary THA. Patients with salvage THA after failed internal fixation for intertrochanteric fractures were the most susceptible to more complications compared to those with femoral neck fracture or acetabular fracture. Level of Evidence level III

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration 1 . Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi 2 , 3 , we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue 4 , we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders. Senescent melanocytes of skin nevi drive hyperactivation of hair growth through the signalling factor SPP1.