A highly stretchable smart dressing for wound infection monitoring and treatment.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

Cu-Doped Spherical P2-Type Na0.7Fe0.23-xCuxMn0.77O2 Cathode for High-Performance Sodium-Ion Batteries.

Sodium-ion batteries (SIBs), owing to their abundant resources and cost-effectiveness, have garnered considerable interest in the realm of large-scale energy storage. The properties of cathode materials profoundly affect the cycle stability and specific capacity of batteries. Herein, a series of Cu-doped spherical P2-type Na0.7Fe0.23-xCuxMn0.77O2 (x = 0, 0.05, 0.09, and 0.14, x-NFCMO) was fabricated using a convenient hydrothermal method. The successful doping of Cu efficaciously mitigated the Jahn-Teller effect, augmented the electrical conductivity of the material, and diminished the resistance to charge transfer. The distinctive spherical structure remained stable and withstood considerable volumetric strain, thereby improving the cyclic stability of the material. The optimized 0.09-NFCMO cathode exhibited a high specific capacity of 168.6 mAh g-1 at 100 mA g-1, a superior rate capability (90.9 mAh g-1 at 2000 mA g-1), and a good cycling stability. This unique structure design and doping approach provides new insights into the design of advanced electrode materials for sodium-ion batteries.

Gelation and Plugging Performance of Low-Concentration Partially Hydrolyzed Polyacrylamide/Polyethyleneimine System at Moderate Temperature and in Fractured Low-Permeability Reservoir.

HPAM/PEI gel is a promising material for conformance control in hydrocarbon reservoirs. However, its use in low-permeability reservoirs is limited by the high polymer concentrations present. In this study, the gelation performance of an HPAM/PEI system with HPAM < 2.0 wt.% was systematically investigated. The gelation time for HPAM concentrations ranging from 0.4 to 2.0 wt.% varied from less than 1 h to 23 days, with the highest gel strength identified as grade H. The hydrodynamic radius manifested the primary effect of HPAM on the gelation performance. Branched PEI provided superior gelation performance over linear PEI, and the gelation performance was only affected when the molecular weight of the PEI varied significantly. The optimal number ratio of the PEI-provided imine groups and the HPAM-provided carboxylic acid functional groups was approximately 1.6:1~5:1. Regarding the reservoir conditions, the temperature had a crucial effect on the hydrodynamic radius of HPAM. Salts delayed the gelation process, and the order of ionic influence was Ca2+ > Na+ > K+. The pH controlled the crosslinking reaction, primarily due to the protonation degree of PEI and the hydrolysis degree of HPAM, and the most suitable pH was approximately 10.5. Plugging experiments based on a through-type fracture showed that multi-slug plugging could significantly improve the plugging performance of the system, being favorable for its application in fractured low-permeability reservoirs.

3D Bioprinting of Artificial Skin Substitute with Improved Mechanical Property and Regulated Cell Behavior through Integrating Patterned Nanofibrous Films.

Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many studies have presented improved effect of printing skin substitutes in wound healing, using hydrogel inks to fabricate 3D bioprinting architectures with complicated structures, mimicking mechanical properties, and appropriate cellular environments is still challenging. Inspired by collagen nanofibers withstanding stress and regulating cell behavior, a patterned nanofibrous film was introduced to the printed hydrogel scaffold to fabricate a composite artificial skin substitute (CASS). The artificial dermis was printed using gelatin-hyaluronan hybrid hydrogels containing human dermal fibroblasts with gradient porosity and integrated with patterned nanofibrous films simultaneously, while the artificial epidermis was formed by seeding human keratinocytes upon the dermis. The collagen-mimicking nanofibrous film effectively improved the tensile strength and fracture resistance of the CASS, making it sewable for firm implantation into skin defects. Meanwhile, the patterned nanofibrous film also provided the biological cues to guide cell behavior. Consequently, CASS could effectively accelerate the regeneration of large-area skin defects in mouse and pig models by promoting re-epithelialization and collagen deposition. This research developed an effective strategy to prepare composite bioprinting architectures for enhancing mechanical property and regulating cell behavior, and CASS could be a promising skin substitute for treating large-area skin defects.

Accurate Density Prediction of Sesquiterpenoid HEDFs and the Multiproperty Computing Server SesquiterPre.

Accurate and rapid evaluation of density is crucial for evaluating the packing and combustion characteristics of high-energy-density fuels (HEDFs). This parameter is pivotal in the selection of high-performance HEDFs. Our study leveraged a polycyclic compound density data set and quantum chemical (QC) descriptors to establish a correlation with the target properties using the XGBoost algorithm. We utilized a recursive feature elimination method to simplify the model and developed a concise and interpretable density prediction model incorporating only six QC descriptors. The model demonstrated robust performance, achieving coefficients of determination (R 2) of 0.967 and 0.971 for internal and external test sets, respectively, and root-mean-square errors (RMSE) of 0.031 and 0.027 g/cm3, respectively. Compared to the other two mainstream methods, the marginal discrepancy between the predicted and actual molecular densities underscores the model's superior predictive ability and more usefulness for energy density calculation. Furthermore, we developed a web server (SesquiterPre, https://sespre.cmdrg.com/#/) that can simultaneously calculate the density, enthalpy of combustion, and energy density of sesquiterpenoid HEDFs, which greatly facilitates the use of researchers and is of great significance for accelerating the design and screening of novel sesquiterpenoid HEDFs.

Radiotherapy and immunology.

The majority of cancer patients receive radiotherapy during the course of treatment, delivered with curative intent for local tumor control or as part of a multimodality regimen aimed at eliminating distant metastasis. A major focus of research has been DNA damage; however, in the past two decades, emphasis has shifted to the important role the immune system plays in radiotherapy-induced anti-tumor effects. Radiotherapy reprograms the tumor microenvironment, triggering DNA and RNA sensing cascades that activate innate immunity and ultimately enhance adaptive immunity. In opposition, radiotherapy also induces suppression of anti-tumor immunity, including recruitment of regulatory T cells, myeloid-derived suppressor cells, and suppressive macrophages. The balance of pro- and anti-tumor immunity is regulated in part by radiotherapy-induced chemokines and cytokines. Microbiota can also influence radiotherapy outcomes and is under clinical investigation. Blockade of the PD-1/PD-L1 axis and CTLA-4 has been extensively investigated in combination with radiotherapy; we include a review of clinical trials involving inhibition of these immune checkpoints and radiotherapy.

Targeting the dendritic cell-secreted immunoregulatory cytokine CCL22 alleviates radioresistance.

PURPOSE: Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that dendritic cells (cDC) maintain Treg we sought to identify and target cDC signaling to block Treg infiltration after radiation. EXPERIMENTAL DESIGN: Transcriptomics and high dimensional flow cytometry revealed changes in murine tumor cDC that not only mediate Treg infiltration after RT, but associate with worse survival in human cancer datasets. Antibodies perturbing a cDC-CCL22-Treg axis were tested in syngeneic murine tumors. A prototype interferon-anti-epidermal growth factor receptor fusion protein (αEGFR-IFNα) was examined to block Treg infiltration and promote a CD8+ T cell response after RT. RESULTS: Radiation expands a population of mature cDC1 enriched in immunoregulatory markers that mediates Treg infiltration via the Treg-recruiting chemokine CCL22. Blocking CCL22 or Treg depletion both enhanced RT efficacy. αEGFR-IFNα blocked cDC1 CCL22 production while simultaneously inducing an antitumor CD8+ T cell response to enhance RT efficacy in multiple EGFR-expressing murine tumor models, including following systemic administration. CONCLUSIONS: We identify a previously unappreciated cDC mechanism mediating Treg tumor infiltration after RT. Our findings suggest blocking the cDC1-CCL22-Treg axis augments RT efficacy. αEGFR-IFNα added to RT provided robust antitumor responses better than systemic free interferon administration, and may overcome clinical limitations to interferon therapy. Our findings highlight the complex behavior of cDC after RT and provide novel therapeutic strategies for overcoming RT-driven immunosuppression to improve RT efficacy.

Synchronous supraclavicular vascularized lymph node transfer and liposuction for gynecological cancer-related lower extremity lymphedema: a clinical comparative analysis of three different procedures.

OBJECTIVE: Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, supraclavicular vascularized lymph node transfer (SC-VLNT) is a favored approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction. METHODS: A cohort of 35 patients with GC-LEL was examined, comprising 13 patients who underwent single lymph nodes flap with a skin paddle (SLNF+P), 12 who received single lymph nodes flap without a skin paddle (SLNF), and 10 who accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and postoperative variables. RESULTS: The median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patients noted subjective improvements in Lymphedema Quality of Life scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage Ⅱ). The median follow-up time was 16 months (range, 12-36 months), with no reported severe postoperative complications. CONCLUSIONS: For advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization.

Identification of a multidrug resistance genomic island harboring a nonfunctional optrA gene in Campylobacter coli of chicken origin.

Campylobacter spp., such as Campylobacter jejuni and Campylobacter coli, are important zoonotic Gram-negative pathogens that cause acute intestinal diseases in humans. In this study, a retrospective analysis was conducted on previously collected Campylobacter isolates from antimicrobial resistance surveillance. A total of 29 optrA-positive C. coli strains were identified and subjected to second-generation sequencing. Multilocus sequence typing and single nucleotide polymorphism analyses demonstrated that the 29 optrA-positive isolates were genetically homogeneous. Notably, among the 29 isolated strains, the ΔoptrA variants exhibit a nonsense mutation at position 979 where the base C is substituted by T, leading to the formation of a premature termination codon. The alignment of sequences and genetic environmental characteristics suggested that ΔoptrA located on a chromosomally carried multidrug-resistant genomic island. There are other resistant genes on the multidrug resistance genomic island, such as aph(2'')-If, aph(3')-III, aadE, tet(O), tet(L), cat, erm(A), optrA and blaOXA-61. As a result, the 29 ΔoptrA-positive strains displayed susceptibility to both florfenicol and linezolid. The ΔoptrA gene is linked to the erm(A) gene, resulting in the formation of translocatable unit (TU) that are encompassed by two copies of IS1216 mobile elements. Multiple occurrences of similar TUs have been documented in numerous C. coli and provided evidence for the significance of TUs in facilitating the transfer of drug resistance genes in C. coli.

QuanDB: a quantum chemical property database towards enhancing 3D molecular representation learning.

Previous studies have shown that the three-dimensional (3D) geometric and electronic structure of molecules play a crucial role in determining their key properties and intermolecular interactions. Therefore, it is necessary to establish a quantum chemical (QC) property database containing the most stable 3D geometric conformations and electronic structures of molecules. In this study, a high-quality QC property database, called QuanDB, was developed, which included structurally diverse molecular entities and featured a user-friendly interface. Currently, QuanDB contains 154,610 compounds sourced from public databases and scientific literature, with 10,125 scaffolds. The elemental composition comprises nine elements: H, C, O, N, P, S, F, Cl, and Br. For each molecule, QuanDB provides 53 global and 5 local QC properties and the most stable 3D conformation. These properties are divided into three categories: geometric structure, electronic structure, and thermodynamics. Geometric structure optimization and single point energy calculation at the theoretical level of B3LYP-D3(BJ)/6-311G(d)/SMD/water and B3LYP-D3(BJ)/def2-TZVP/SMD/water, respectively, were applied to ensure highly accurate calculations of QC properties, with the computational cost exceeding 107 core-hours. QuanDB provides high-value geometric and electronic structure information for use in molecular representation models, which are critical for machine-learning-based molecular design, thereby contributing to a comprehensive description of the chemical compound space. As a new high-quality dataset for QC properties, QuanDB is expected to become a benchmark tool for the training and optimization of machine learning models, thus further advancing the development of novel drugs and materials. QuanDB is freely available, without registration, at https://quandb.cmdrg.com/ .

Versatile chondroitin sulfate-based nanoplatform for chemo-photodynamic therapy against triple-negative breast cancer.

Versatile nanoplatform equipped with chemo-photodynamic therapeutic attributes play an important role in improving the effectiveness of tumor treatments. Herein, we developed multifunctional nanoparticles based on chondroitin sulfate A (CSA) for the targeted delivery of chlorin e6 (Ce6) and doxorubicin (DOX), in a combined chemo-photodynamic therapy against triple-negative breast cancer. CSA was chosen for its hydrophilic properties and its affinity to CD44 receptor-overexpressed tumor cells. The CSA-ss-Ce6 (CSSC) conjugate was synthesized utilizing a disulfide linker. Subsequently, DOX-loaded CSSC (CSSC-D) nanoparticles were fabricated, showcasing a nearly spherical shape with an average particle size of 267 nm. In the CSSC-D nanoparticles, the chemically attached Ce6 constituted 1.53 %, while the physically encapsulated DOX accounted for 8.11 %. Both CSSC-D and CSSC nanoparticles demonstrated a reduction-sensitive release of DOX or Ce6 in vitro. Under near-infrared (NIR) laser irradiation, CSSC-D showed the enhanced generation of reactive oxygen species (ROS), improving cytotoxic effects against triple-negative breast cancer 4T1 and MDA-MB-231 cells. Remarkably, the CSSC-D with NIR exhibited the most potent tumor growth inhibition in comparison to other groups in the 4T1-bearing Balb/c mice model. Overall, this CSSC-D nanoplatform shows significant promise as a powerful tool for a synergetic approach in chemo-photodynamic therapy in triple-negative breast cancer.

Polymorphisms of IFN signaling genes and FOXP4 influence the severity of COVID-19.

BACKGROUND: The clinical manifestations of COVID-19 range from asymptomatic, mild to moderate, severe, and critical disease. Host genetic variants were recognized to affect the disease severity. However, the genetic landscape differs among various populations. Therefore, we explored the variants associated with COVID-19 severity in the Guangdong population. METHODS: A total of 314 subjects were selected, of which the severe and critical COVID-19 patients were defined as "cases", and the mild and moderate patients were defined as "control". Twenty-two variants in interferon-related genes and FOXP4 were genotyped using the MassARRAY technology platform. RESULTS: IFN signaling gene MX1 rs17000900 CA + AA genotype was correlated with a reduced risk of severe COVID-19 in males (P = 0.001, OR = 0.050, 95%CI = 0.008-0.316). The AT haplotype comprised of MX1 rs17000900 and rs2071430 was more likely to protect against COVID-19 severity (P = 6.3E-03). FOXP4 rs1886814 CC genotype (P = 0.001, OR = 3.747, 95%CI = 1.746-8.043) and rs2894439 GA + AA genotype (P = 0.001, OR = 5.703, 95% CI = 2.045-15.903) were correlated with increased risk of severe COVID-19. Haplotype CA comprised of rs1886814 and rs2894439 was found to be correlated with adverse outcomes (P = 7.0E-04). FOXP4 rs1886814 CC (P = 0.0004) and rs2894439 GA + AA carriers had higher neutralizing antibody titers (P = 0.0018). The CA + AA genotype of MX1 rs17000900 tended to be correlated with lower neutralizing antibody titers than CC genotype (P = 0.0663), but the difference was not statistically significant. CONCLUSION: Our study found a possible association between MX1 and FOXP4 polymorphisms and the severity of COVID-19. Distinguishing high-risk patients who develop severe COVID-19 will provide clues for early intervention and individual treatment strategies.

Pathological Characteristics and Classification of Unstable Coronary Atherosclerotic Plaques.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.

Radiotherapy Enhances Metastasis Through Immune Suppression by Inducing PD-L1 and MDSC in Distal Sites.

PURPOSE: Radiotherapy (RT) is a widely employed anticancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. The purpose of this study is to investigate immune suppressive factors of radiotherapy. EXPERIMENTAL DESIGN: We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated. RESULTS: Through analysis of PD-L1 expression and myeloid-derived suppressor cells (MDSC) frequencies using patient peripheral blood mononuclear cells and murine two-tumor and metastasis models, we report that local irradiation can induce a systemic increase in MDSC, as well as PD-L1 expression on dendritic cells and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, nonirradiated tissue. In a mouse model using two distinct tumors, we found that PD-L1 induction by ionizing radiation was dependent on elevated chemokine CXCL10 signaling. Inhibiting PD-L1 or MDSC can potentially abrogate RT-induced metastasis and improve clinical outcomes for patients receiving RT. CONCLUSIONS: Blockade of PD-L1/CXCL10 axis or MDSC infiltration during irradiation can enhance abscopal tumor control and reduce metastasis.

The TET-Sall4-BMP regulatory axis controls craniofacial cartilage development.

Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.

Development of a screening system of gene sets for estimating the time of early skeletal muscle injury based on second-generation sequencing technology.

The present study is aimed to address the challenge of wound age estimation in forensic science by identifying reliable genetic markers using low-cost and high-precision second-generation sequencing technology. A total of 54 Sprague-Dawley rats were randomly assigned to a control group or injury groups, with injury groups being further divided into time points (4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, and 32 h after injury, n = 6) to establish rat skeletal muscle contusion models. Gene expression data were obtained using second-generation sequencing technology, and differential gene expression analysis, weighted gene co-expression network analysis (WGCNA) and time-dependent expression trend analysis were performed. A total of six sets of biomarkers were obtained: differentially expressed genes at adjacent time points (127 genes), co-expressed genes most associated with wound age (213 genes), hub genes exhibiting time-dependent expression (264 genes), and sets of transcription factors (TF) corresponding to the above sets of genes (74, 87, and 99 genes, respectively). Then, random forest (RF), support vector machine (SVM) and multilayer perceptron (MLP), were constructed for wound age estimation from the above gene sets. The results estimated by transcription factors were all superior to the corresponding hub genes, with the transcription factor group of WGCNA performed the best, with average accuracy rates of 96% for three models' internal testing, and 91.7% for the highest external validation. This study demonstrates the advantages of the indicator screening system based on second-generation sequencing technology and transcription factor level for wound age estimation.

Garcinone C attenuates RANKL-induced osteoclast differentiation and oxidative stress by activating Nrf2/HO-1 and inhibiting the NF-kB signaling pathway.

Osteoporosis is the result of osteoclast formation exceeding osteoblast production, and current osteoporosis treatments targeting excessive osteoclast bone resorption have serious adverse effects. There is a need to fully understand the mechanisms of osteoclast-mediated bone resorption, identify new drug targets, and find better drugs to treat osteoporosis. Gar C (Gar C) is a major naturally occurring phytochemical isolated from mangosteen, and is a derivative of the naturally occurring phenolic antioxidant lutein. We used an OP mouse model established by ovariectomy (OVX). We found that treatment with Gar C significantly increased bone mineral density and significantly decreased the expression of TRAP, NFATC1 and CTSK relative to untreated OP mice. We found that Garcinone C could disrupt osteoclast activation and resorption functions by inhibiting RANKL-induced osteoclast differentiation as well as inhibiting the formation of multinucleated osteoclasts. Immunoblotting showed that Gar C downregulated the expression of osteoclast-related proteins. In addition, Gar C significantly inhibited RANKL-induced ROS production and affected NF-κB activity by inhibiting phosphorylation Formylation of P65 and phosphorylation and degradation of ikba. These data suggest that Gar C significantly reduced OVX-induced osteoporosis by inhibiting osteoclastogenesis and oxidative stress in bone tissue. Mechanistically, this effect was associated with inhibition of the ROS-mediated NF-κB pathway.

A high-grade breast mucoepidermoid carcinoma without MAML2 rearrangement: A case report and literature review.

INTRODUCTION: Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare primary breast tumor. Between 1979 and June 2022, only 50 cases were reported. The pathological morphology and biological behavior of breast MEC remain poorly understood. PATIENT CONCERNS: A 47-year-old female was presented with a 10-day-old left breast mass detected by physical examination. DIAGNOSES: Ultrasonography could not distinguish whether the breast tumor was benign or malignant. After a biopsy of a breast tumor excision specimen, combined with immunohistochemical results, the patient was diagnosed with high-grade mucoepidermoid breast carcinoma. INTERVENTIONS: The patient underwent a modified radical mastectomy for her left breast. OUTCOMES: The patient was still free from local recurrence or metastases at 1-year follow-up. CONCLUSION: A high-grade MEC case without MAML2 rearrangement shows good recovery without complications. The diagnosis was confirmed by histomorphology and immunohistochemical markers. It is sometimes necessary to distinguish it from adenosquamous, adenoid cystic, or mucinous carcinoma. The primary treatment is surgical resection, and the prognosis is closely related to the pathological grade.

Harnessing Catalytic RNA Circuits for Construction of Artificial Signaling Pathways in Mammalian Cells.

Engineering of genetic networks with artificial signaling pathways (ASPs) can reprogram cellular responses and phenotypes under different circumstances for a variety of diagnostic and therapeutic purposes. However, construction of ASPs between originally independent endogenous genes in mammalian cells is highly challenging. Here we report an amplifiable RNA circuit that can theoretically build regulatory connections between any endogenous genes in mammalian cells. We harness the system of catalytic hairpin assembly with combination of controllable CRISPR-Cas9 function to transduce the signals from distinct messenger RNA expression of trigger genes into manipulation of target genes. Through introduction of these RNA-based genetic circuits, mammalian cells are endowed with autonomous capabilities to sense the changes of RNA expression either induced by ligand stimuli or from various cell types and control the cellular responses and fates via apoptosis-related ASPs. Our design provides a generalized platform for construction of ASPs inside the genetic networks of mammalian cells based on differentiated RNA expression.