Zwitterion-Modified MXene Quantum Dot as a Nanocarrier for Traditional Chinese Medicine Sanguinarine Delivery and Its Application for Photothermal-Chemotherapy Synergistic Antibacterial and Wound Healing.

The nanomaterialization of traditional Chinese medicine (TCM) has aroused widespread interest among researchers. Sanguinarine (SAN) is a kind of TCM with good antibacterial properties, which has important applications in anti-infection of wounds. Additionally, the combination of photothermal therapy and chemotherapy can overcome bacterial resistance, further improving bactericidal and wound healing efficiency. In this paper, we prepared an antibacterial agent by loading SAN on the zwitterion-modified MXene quantum dot nanocarrier (SAN@AHEP@Ta4C3), realizing pH/NIR controlled drug release and photothermal/chemotherapy synergistic antibacterial and wound healing. The particle size of SAN@AHEP@Ta4C3 is about 120 nm, and it has a good water solubility and stability. In addition, it also has excellent photothermal conversion performance (η = 39.2%), which can effectively convert light energy into heat energy under near-infrared (NIR) laser irradiation, further promoting drug release and achieving bactericidal effects by synergistic chemotherapy and photothermal therapy. The in vitro and in vivo experiments show that SAN@AHEP@Ta4C3 exhibits an excellent antibacterial effect against Staphylococcus aureus and Escherichia coli, and it can effectively promote the wound healing of mice. Moreover, the SAN@AHEP@Ta4C3 also has good biocompatibility and has no side effects on normal tissue and organs. This work introduces a multifunctional antibacterial agent based on TCM and hot-spot material MXene, which will have considerable application prospects in biomedical fields.

Nanomaterials and Nanotechnology in Agricultural Pesticide Delivery: A Review.

Pesticides play a crucial role in ensuring food production and food security. Conventional pesticide formulations can not meet the current needs of social and economic development, and they also can not meet the requirements of green agriculture. Therefore, there is an urgent need to develop efficient, stable, safe, and environmentally friendly pesticide formulations to gradually replace old formulations which have high pollution and low efficacy. The rise of nanotechnology provides new possibilities for innovation in pesticide formulations. Through reasonable design and construction of an environmentally friendly pesticide delivery system (PDS) based on multifunctional nanocarriers, the drawbacks of conventional pesticides can be effectively solved, realizing a water-based, nanosized, targeted, efficient, and safe pesticide system. In the past five years, researchers in chemistry, materials science, botany, entomology, plant protection, and other fields are paying close attention to the research of nanomaterials based PDSs and nanopesticide formulations and have made certain research achievements. These explorations provide useful references for promoting the innovation of nanopesticides and developing a new generation of green and environmentally friendly pesticide formulations. This Perspective summarizes the recent advances of nanomaterials in PDSs and nanopesticide innovation, aiming to provide useful guidance for carrier selection, surface engineering, controlled release conditions, and application in agriculture.

Graphene Oxide-Based Antifungal Pesticide Delivery System for Tobacco Fungal Disease (Tobacco Target Spot) Control.

In recent years, nanocarrier-based pesticide delivery systems have provided new possibilities for the efficient utilization of pesticides. In this research, we developed a hydroxypropyl-ß-cyclodextrin-modified graphene oxide (GO-HP-ß-CD) nanocarrier for pyraclostrobin (Pyr) delivery and studied its application for tobacco target spot disease control. GO-HP-ß-CD has excellent pesticide-loading performance for Pyr (adsorption capacity of 1562.5 mg/g) and good water dispersibility and stability. Besides, GO-HP-ß-CD shows pH-responsive release performance. In addition, GO-HP-ß-CD also has better leaf affinity than Pyr, and it can effectively adhere to the leaf surface after simulated washing. The results of antifungal experiments indicate that GO-HP-ß-CD-Pyr has a good preventive effect on tobacco target spot disease, and its EC50 value is 0.384 mg/L, which is lower than Pyr. Specifically, this nanopesticide formulation does not contain toxic organic solvent or additive, so it has good environmental friendliness. Therefore, we believe that the GO-HP-ß-CD-Pyr nanopesticide has brilliant potential in the prevention and control of tobacco diseases.

The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

MEF2D Functions as a Tumor Suppressor in Breast Cancer.

The myocyte enhancer factor 2 (MEF2) gene family play fundamental roles in the genetic programs that control cell differentiation, morphogenesis, proliferation, and survival in a wide range of cell types. More recently, these genes have also been implicated as drivers of carcinogenesis, by acting as oncogenes or tumor suppressors depending on the biological context. Nonetheless, the molecular programs they regulate and their roles in tumor development and progression remain incompletely understood. The present study evaluated whether the MEF2D transcription factor functions as a tumor suppressor in breast cancer. The knockout of the MEF2D gene in mouse mammary epithelial cells resulted in phenotypic changes characteristic of neoplastic transformation. These changes included enhanced cell proliferation, a loss of contact inhibition, and anchorage-independent growth in soft agar, as well as the capacity for tumor development in mice. Mechanistically, the knockout of MEF2D induced the epithelial-to-mesenchymal transition (EMT) and activated several oncogenic signaling pathways, including AKT, ERK, and Hippo-YAP. Correspondingly, a reduced expression of MEF2D was observed in human triple-negative breast cancer cell lines, and a low MEF2D expression in tissue samples was found to be correlated with a worse overall survival and relapse-free survival in breast cancer patients. MEF2D may, thus, be a putative tumor suppressor, acting through selective gene regulatory programs that have clinical and therapeutic significance.

Deep unsupervised adversarial domain adaptation for underwater source range estimation.

In this study, an underwater source range estimation method based on unsupervised domain adaptation (UDA) is proposed. In contrast to traditional deep-learning frameworks using real-world data, UDA does not require labeling of the measured data, making it more practical. First, a classifier based on a deep neural network is trained with labeled simulated data generated using acoustic propagation models and, then, the adaptive procedure is applied, wherein unlabeled measured data are employed to adjust an adaptation module using the adversarial learning algorithm. Adversarial learning is employed to alleviate the marginal distribution divergence, which reflects the difference between the measured and theoretically computed sound field, in the latent space. This divergence, caused by environmental parameter mismatch or other unknown corruption, can be detrimental to accurate source localization. After the completion of the adaptive procedure, the measured and simulated data are projected to the same space, eliminating distribution discrepancy, which is beneficial for source localization tasks. Experimental results show that range estimation based on UDA outperforms the match-field-processing method under four scenarios of few snapshots, few array elements, low signal-to-noise ratio, and environmental parameter mismatch, verifying the robustness of the method.

Comparative Proteomics Analysis of Exosomes Identifies Key Pathways and Protein Markers Related to Breast Cancer Metastasis.

Proteomics analysis of circulating exosomes derived from cancer cells represents a promising approach to the elucidation of cell-cell communication and the discovery of putative biomarker candidates for cancer diagnosis and treatment. Nonetheless, the proteome of exosomes derived from cell lines with different metastatic capabilities still warrants further investigation. Here, we present a comprehensive quantitative proteomics investigation of exosomes isolated from immortalized mammary epithelial cells and matched tumor lines with different metastatic potentials in an attempt to discover exosome markers specific to breast cancer (BC) metastasis. A total of 2135 unique proteins were quantified with a high confidence level from 20 isolated exosome samples, including 94 of the TOP 100 exosome markers archived by ExoCarta. Moreover, 348 altered proteins were observed, among which several metastasis-specific markers, including cathepsin W (CATW), magnesium transporter MRS2 (MRS2), syntenin-2 (SDCB2), reticulon-4 (RTN), and UV excision repair protein RAD23 homolog (RAD23B), were also identified. Notably, the abundance of these metastasis-specific markers corresponds well with the overall survival of BC patients in clinical settings. Together, these data provide a valuable dataset for BC exosome proteomics investigation and prominently facilitate the elucidation of the molecular mechanisms underlying primary tumor development and progression.

Cell-to-cell and type-to-type heterogeneity of signaling networks: insights from the crowd.

Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi-signaling networks across cells and cell types, with important implications to understand and treat diseases such as cancer. These technologies are, however, limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organized the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry dataset, covering 36 markers in over 4,000 conditions totaling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time-course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data.

Enhancing the potential of aged human articular chondrocytes for high-quality cartilage regeneration.

Autologous chondrocyte implantation (ACI) is a regenerative procedure used to treat focal articular cartilage defects in knee joints. However, age has been considered as a limiting factor and ACI is not recommended for patients older than 40-50 years of age. One reason for this may be due to the reduced capacity of aged chondrocytes in generating new cartilage. Currently, the underlying mechanism contributing to aging-associated functional decline in chondrocytes is not clear and no proven approach exists to reverse chondrocyte aging. Given that chondrocytes in healthy hyaline cartilage typically display a spherical shape, believed to be essential for chondrocyte phenotype stability, we hypothesize that maintaining aged chondrocytes in a suspension culture that forces the cells to adopt a round morphology may help to "rejuvenate" them to a younger state, thus, leading to enhanced cartilage regeneration. Chondrocytes isolated from aged donors displayed reduced proliferation potential and impaired capacity in generating hyaline cartilage, compared to cells isolated from young donors, indicated by increased hypertrophy and cellular senescence. To test our hypothesis, the "old" chondrocytes were seeded as a suspension onto an agarose-based substratum, where they maintained a round morphology. After the 3-day suspension culture, aged chondrocytes displayed enhanced replicative capacity, compared to those grown adherent to tissue culture plastic. Moreover, chondrocytes subjected to suspension culture formed new cartilage in vitro with higher quality and quantity, with enhanced cartilage matrix deposition, concomitant with lower levels of hypertrophy and cellular senescence markers. Mechanistic analysis suggested the involvement of the RhoA and ERK1/2 signaling pathways in the "rejuvenation" process. In summary, our study presents a robust and straightforward method to enhance the function of aged human chondrocytes, which can be conveniently used to generate a large number of high-quality chondrocytes for ACI application in the elderly.

Carboxymethyl Chitosan-Modified Graphene Oxide as a Multifunctional Vector for Deltamethrin Delivery and pH-Responsive Controlled Release, Enhanced Leaf Affinity, and Improved Mosquito-Killing Activity.

Traditional deltamethrin (DM) formulations (e.g., emulsifiable concentrates, wettable powders, etc.) have significant disadvantages of poor water dispersion stability, burst release, weak leaf affinity, short duration, poor efficacy, and high environmental toxicity. A nanomaterial-based pesticide delivery system (PDS) has provided effective strategies for green preparation and synergism of pesticide formulations. In this article, we developed carboxymethyl chitosan (CMCS)-modified graphene oxide (GO) as a vector for DM and constructed a pH-responsive PDS for Culex pipiens pallens control. GO-CMCS possesses excellent pesticide loading performance for DM (loading rate 87.76%). After being loading on GO-CMCS, the GO-CMCS-DM has a significantly improved dispersion stability in water. The GO-CMCS-DM exhibits pH-responsive controlled release performance, which can sustain the release of DM into the medium, maintaining an effective long-term concentration. Additionally, the leaf adhesion of GO-CMCS-DM is better than that for free DM, which can improve the pesticide utilization. Therefore, GO-CMCS-DM has a prolonged persistent period and sustained activity against Culex pipiens pallens. Considering the industrialization potential of GO, we believe that GO will play an important role in the pest control and antiepidemic fields.