Cascading Failure in Cyber-Physical Systems: A Review on Failure Modeling and Vulnerability Analysis.

Cascading failures pose a significant security threat to networked systems, with recent global incidents underscoring their destructive potential. The security threat of cascading failures has always existed, but the evolution of cyber-physical systems (CPSs) has introduced novel dimensions to cascading failures, intensifying their threats owing to the intricate fusion of cyber and physical domains. Addressing these threats requires a nuanced understanding achieved through failure modeling and vulnerability analysis. By analyzing the historical failures in different CPSs, the cascading failure in CPSs is comprehensively defined as a complicated propagation process in coupled cyber and physical systems, initialized by natural accidents or human interference, which exhibits a progressive evolution within the networked structure and ultimately results in unexpected large-scale systemic failures. Subsequently, this study advances the development of instructions for modeling cascading failures and conducting vulnerability analyses within CPSs. The examination also delves into the core challenges inherent in these methodologies. Moreover, a comprehensive survey and classification of extant research methodologies and solutions are undertaken, accompanied by a concise evaluation of their advancements and limitations. To validate the performance of these methodologies, numerical experiments are conducted to ascertain their distinct features. In conclusion, this article advocates for future research initiatives, particularly emphasizing the exploration of uncertainty analysis, defense strategies, and verification platforms. By addressing these areas, the resilience of CPSs against cascading failures can be significantly enhanced.

Capturing acyl-enzyme intermediates with genetically encoded 2,3-diaminopropionic acid for hydrolase substrate identification.

Catalytic mechanism-based, light-activated traps have recently been developed to identify the substrates of cysteine or serine hydrolases. These traps are hydrolase mutants whose catalytic cysteine or serine are replaced with genetically encoded 2,3-diaminopropionic acid (DAP). DAP-containing hydrolases specifically capture the transient thioester- or ester-linked acyl-enzyme intermediates resulting from the first step of the proteolytic reaction as their stable amide analogs. The trapped substrate fragments allow the downstream identification of hydrolase substrates by mass spectrometry and immunoblotting. In this protocol, we provide a detailed step-by-step guide for substrate capture and identification of the peptidase domain of the large tegument protein deneddylase (UL36USP) from human herpesvirus 1, both in mammalian cell lysate and live mammalian cells. Four procedures are included: Procedure 1, DAP-mediated substrate trapping in mammalian cell lysate (~8 d); Procedure 2, DAP-mediated substrate trapping in adherent mammalian cells (~6 d); Procedure 3, DAP-mediated substrate trapping in suspension mammalian cells (~5 d); and Procedure 4, substrate identification and validation (~12-13 d). Basic skills to perform protein expression in bacteria or mammalian cells, affinity enrichment and proteomic analysis are required to implement the protocol. This protocol will be a practical guide for identifying substrates of serine or cysteine hydrolases either in a complex mixture, where genetic manipulation is challenging, or in live cells such as bacteria, yeasts and mammalian cells.

Design and deep learning of synthetic B-cell-specific promoters.

Synthetic biology and deep learning synergistically revolutionize our ability for decoding and recoding DNA regulatory grammar. The B-cell-specific transcriptional regulation is intricate, and unlock the potential of B-cell-specific promoters as synthetic elements is important for B-cell engineering. Here, we designed and pooled synthesized 23 640 B-cell-specific promoters that exhibit larger sequence space, B-cell-specific expression, and enable diverse transcriptional patterns in B-cells. By MPRA (Massively parallel reporter assays), we deciphered the sequence features that regulate promoter transcriptional, including motifs and motif syntax (their combination and distance). Finally, we built and trained a deep learning model capable of predicting the transcriptional strength of the immunoglobulin V gene promoter directly from sequence. Prediction of thousands of promoter variants identified in the global human population shows that polymorphisms in promoters influence the transcription of immunoglobulin V genes, which may contribute to individual differences in adaptive humoral immune responses. Our work helps to decipher the transcription mechanism in immunoglobulin genes and offers thousands of non-similar promoters for B-cell engineering.

A physicochemical double-cross-linked gelatin hydrogel with enhanced antibacterial and anti-inflammatory capabilities for improving wound healing.

BACKGROUND: Skin tissue is vital in protecting the body from injuries and bacterial infections. Wound infection caused by bacterial colonization is one of the main factors hindering wound healing. Wound infection caused by colonization of a large number of bacteria can cause the wound to enter a continuous stage of inflammation, which delays wound healing. Hydrogel wound dressing is composed of natural and synthetic polymers, which can absorb tissue fluid, improve the local microenvironment of wound, and promote wound healing. However, in the preparation process of hydrogel, the complex preparation process and poor biological efficacy limit the application of hydrogel wound dressing in complex wound environment. Therefore, it is particularly important to develop and prepare hydrogel dressings with simple technology, good physical properties and biological effects by using natural polymers. RESULTS: In this study, a gelatin-based (Tsg-THA&Fe) hydrogel was created by mixing trivalent iron (Fe3+) and 2,3,4-trihydroxybenzaldehyde (THA) to form a complex (THA&Fe), followed by a simple Schiff base reaction with tilapia skin gelatin (Tsg). The gel time and rheological properties of the hydrogels were adjusted by controlling the number of complexes. The dynamic cross-linking of the coordination bonds (o-phthalmictriol-Fe3+) and Schiff base bonds allows hydrogels to have good self-healing and injectable properties. In vitro experiments confirmed that the hydrogel had good biocompatibility and biodegradability as well as adhesion, hemostasis, and antibacterial properties. The feasibility of Tsg-THA&Fe hydrogel was studied by treating rat skin trauma model. The results showed that compared with Comfeel® Plus Transparent dressing, the Tsg-THA&Fe hydrogel could obvious reduce the number of microorganisms, prevent bacterial colonization, reduce inflammation and accelerate wound healing. Local distribution of the Tsg-THA&Fe hydrogel in the skin tissue did not cause organ toxicity. CONCLUSIONS: In summary, the preparation process of Tsg-THA&Fe hydrogel is simple, with excellent performance in physical properties and biological efficacy. It can effectively relieve inflammation and control the colonization of wound microbes, and can be used as a multi-functional dressing to improve wound healing.