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In addition, this article briefly reviews the recent five-year progress of NIR-II AIE luminophores in tumor imaging and phototherapy applications. The research status is also summarized and prospected, with the hope of contributing to further research.Immunotherapy maintains the cancer-immunity cycle via re-activating the immune system, so as to achieve the purpose of anti-tumor. However, the response rate of current tumor immunotherapy strategies is still low. Even the most reported immune checkpoint block (ICB), the objective response rate (ORR) is only about 10-30%. Here, aiming at obtaining a higher response rate, we designed a cascade amplification nanocomposite consisting of the immune adjuvant polyinosinicpolycytidylic acid [Poly (IC)] and aggregation-induced emission luminogen (AIEgen)-modified modular peptide (named PMRA). The PMRA includes DPPA-1 peptide (P), an immune checkpoint inhibitor; PLGLAG peptide (M), a matrix metalloproteinase 2 (MMP-2) responsive sequence to promote the release of DPPA-1; RRRRRRRR peptide (R), for loading the Poly (IC); PyTPA (A), a photosensitizer with AIE property. In cancer-immunity cycle, photodynamic therapy (PDT) mediated by PyTPA promotes the release of tumor-associated antigens (TAAs), and primes T lymphocytes. The cytokines coming from the stimulation of PDT and Poly (IC) promote the activation of T lymphocytes. The high level of chemokines in tumor microenvironment promotes immune cells migration and infiltration in tumor with the assistance of PDT. Finally, through ICB with DPPA-1 peptide, T lymphocytes enhance the recognition of tumor cells and killing tumor cells. Immunogenic cell death induces the release of more TAAs, which will enter the next cycle and complete the full-loop again. Taking advantages of whole cancer-immunity cycle, the cascade amplification nanocomposite achieved almost 100% ORR in vivo. This concept of whole cancer-immunity cycle enhanced immunotherapy provides a novel perspective for tumor treatment.Electrical stimulation can facilitate wound healing with high efficiency and limited side effects. However, current electrical stimulation devices have poor conformability with wounds due to their bulky nature and the rigidity of electrodes utilized. Here, a flexible electrical patch (ePatch) made with conductive hydrogel as electrodes to improve wound management was reported. The conductive hydrogel was synthesized using silver nanowire (AgNW) and methacrylated alginate (MAA), with the former chosen as the electrode material considering its antibacterial properties, and the latter used due to its clinical suitability in wound healing. The composition of the hydrogel was optimized to enable printing on medical-grade patches for personalized wound treatment. The ePatch was shown to promote re-epithelization, enhance angiogenesis, mediate immune response, and prevent infection development in the wound microenvironment. In vitro studies indicated an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to electrical stimulation. An in vivo study in the Sprague-Dawley rat model revealed a rapid wound closure within 7 days compared to 20 days of usual healing process in rodents.In recent years, cancer metabolism has attracted attention as a therapeutic target, and glutamine metabolism is considered one of the most important metabolic processes in cancer. Solute carrier family 1 member 5 (SLC1A5) is a sodium channel that functions as a glutamine transporter. In various cancer types, SLC1A5 gene expression is enhanced, and cancer cell growth is suppressed by inhibition of SLC1A5. However, the involvement of SLC1A5 in clear cell renal cell carcinoma (ccRCC) is unclear. Therefore, in this study, we evaluated the clinical importance of SLC1A5 in ccRCC using The Cancer Genome Atlas database. Our findings confirmed that SLC1A5 was a prognosis factor for poor survival in ccRCC. Furthermore, loss-of-function assays using small interfering RNAs or an SLC1A5 inhibitor (V9302) in human ccRCC cell lines (A498 and Caki1) showed that inhibition of SLC1A5 significantly suppressed tumor growth, invasion, and migration. Additionally, inhibition of SLC1A5 by V9302 in vivo significantly suppressed tumor growth, and the antitumor effects of SLC1A5 inhibition were related to cellular senescence. Our findings may improve our understanding of ccRCC and the development of new treatment strategies for ccRCC.Sustained inflammatory responses delay wound repair in diabetic skin. The stimulator of interferon genes (STING) plays a vital role in the innate immune responses. However, its function in diabetic skin wound repair, and the underlying mechanism remains unclear. Here, we reported that STING activation is a pathogenic marker that correlates with delayed wound repair in diabetic skin. Firstly, we found that STING expression is enhanced in the epidermis of STZ induced diabetes mouse model and db/db mouse model. Consistently, we also found that STING expression was upregulated in keratinocytes with the high-glucose (HG) treatment. Moreover, silencing of STING accelerated wound healing in vitro. In vivo, inhibition of STING by c176 inhibited inflammatory response in the epidermis and accelerated wound healing in diabetic skin. In addition, we found that autophagy dysfunction is correlated with the expression of STING in epidermis of diabetic mice. Induction of autophagy by rapamycin significantly reduced STING expression in keratinocytes. Collectively, these results indicated that defects of autophagy might lead to the activation of STING and finally delay the diabetic wound healing.It is well known that the initiation of the reflex arcs of the vertebrate vestibular system occurs in the receptors of the labyrinthine organs which transmit the sensory signals via the ribbon synapses to the vestibular nerve afferents (an interneuron). In invertebrate species, and in particular, the statocyst of pulmonate mollusks, it is thought that the receptors send their axons out of the statocyst in the vestibular connective and establish the first synapse onto cerebral ganglia neurons, thereby bypassing the interneuron in the reflex arc. Morphological and electrophysiological techniques were used in this study to identify the first synapse in the vestibular arc of the mollusk Helix is actually within the vestibular connective on its way from the statocyst to cerebral ganglia. Mepazine concentration Cerebral interneurons were found that sent their neurites to the vestibular nerve, and thus have the potential to respond to the statocyst output or send efferent input to the statocyst.BARD1 is a tumor suppressor that is necessary for the functioning and stability of BRCA1, with which it forms a heterodimer and participates in the repair of DNA double-strand breaks. The cellular level of BARD1 and its interaction with BRCA1 are crucial for BRCA1/BARD1 function in homologous recombination and tumor suppression. However, the regulatory mechanism underpinning the stability of BARD1 is largely unclear. In this study, we identified DCAF8L2, a DDB1-Cullin associated factor (DCAF) associated with CRL4 E3 ligase, as a negative regulator of BARD1. Mechanistically, DCAF8L2 interacts with and targets BARD1 for ubiquitination and degradation. In addition, the interaction of DCAF8L2 with BARD1 through the RING domain could compete with the dimerization of BRCA1 and BARD1, leading to increased cellular uncoupling of BARD1 and BRCA1, subjecting the latter to degradation. The overexpression of DCAF8L2 compromises the homologous recombination process and confers cells with increased sensitivity to DNA damage. Furthermore, DCAF8L2 was aberrantly expressed in breast cancer cell lines. Our findings suggest that DCAF8L2 may play an oncogenic role in the pathogenesis of breast cancer, possibly by negative regulation of BARD1.Material recovery facilities (MFRs) play an important role in today's waste management systems to maximize recycling efficiency for several waste materials. These facilities face multiple challenges, often due to a poor understanding of the mechanisms occurring within the sorting equipment. Improving modeling techniques of these unit operations appear to be a promising opportunity to mitigates these challenges. Mechanical sorting efficiency of municipal solid waste is often predicted from simple transfer coefficients, which are obtained for a specific set of operating conditions of the sorting equipment and sorting sequence configuration. When these transfer coefficients are used in situations that are different to those in which they were obtained, poor predictions can be expected. To overcome these limitations, a new predictive tool, based on the integration of mechanistic models and transfer coefficients, is presented. Mechanistic models are developed only for the most influential unit operations in a MRF, in order to predict their sorting efficiency based on the physical phenomena occurring. Integration of these models with the use of transfer coefficients for the other unit operations allows the entire predictive tool to remain as simple as possible while providing high prediction accuracy and flexibility. The use of the tool is validated with a real case study of a material recovery facility. Results indicate a good prediction of the mass flows of the facility. Moreover, a new modeling technique is proposed for the representation of a ballistic separator based on the shape factor of the waste items.This paper analyses the role of selected institutional factors on the costs of waste management in the Czech Republic, a country with extreme territorial fragmentation. The analysis is based on two original datasets from 2,065 municipalities. A model is constructed which determines the relevance of selected factors with respect to the unit cost of waste management service and also highlights the differences between 2014 and 2019. The results are, largely extent, similar to the findings of existing international research related to this topic, but with some specificities. Our data show a significant effect of contracting out on cost reduction and a statistically insignificant effect of public mode of production on unit costs. They also suggest that intermunicipal cooperation has a cost-reducing effect, but public-private partnerships, increased market concentration and the provision by multinationals have a cost-increasing effect. The impact of economies of scale on cost reduction is somehow visible but cannot be confirmed, especially for larger scale territories. The data also suggest a possible beginning of a process of remunicipalisation, but the time series is insufficient to demonstrate this trend.
Accumulative evidences have shown that dysregulation of biological pathways contributed to the initiation and progression of malignant tumours. Several methods for pathway activity measurement have been proposed, but they are restricted to making comparisons between groups or sensitive to experimental batch effects.
We introduced a novel method for individualized pathway activity measurement (IPAM) that is based on the ranking of gene expression levels in individual sample. Taking advantage of IPAM, we calculated the pathway activity of 318 pathways from KEGG database in the 10528 tumour/normal samples of 33 cancer types from TCGA to identify characteristic dysregulated pathways among different cancer types.
IPAM precisely quantified the level of activity of each pathway in pan-cancer analysis and exhibited better performance in cancer classification and prognosis prediction over five widely used tools. The average ROC-AUC of cancer diagnostic model using tumour-educated platelets (TEPs) reached 92.84%, suggesting the potential of our algorithm in early diagnosis of cancer.