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Programmed autolytic bacteria, also termed controlled self-disruptive or self-destructive bacteria, are bacterial systems that express certain lytic genes and undergo cell lysis at a predetermined time point to release the intracellular contents or to commit suicide. Such systems have wide applications in high-throughput screening of protein libraries, synthesis and recovery of bio-products, population control of heterogeneous cultures or synthetic co-cultures, drug delivery, and food fermentation. Recently, great achievements have been reported regarding on-demand control of cell autolysis for different purposes, highlighting the potential of autolytic strains in biomanufacturing and biomedicine. In this review article, we first introduce the various applications of such bacteria, followed by a summarization of the approaches used in the establishment of autolytic bacterial systems, including cell autolysis mediated by cell wall hydrolases with or without facilitating proteins and by membrane-disturbing proteins. Next, we describe in detail the methodologies adopted to control and initiate cell lysis, including induction by chemical inducers, stimulation by physical signals, auto-induction by metabolic status or nutrient limitation, and constitutive expression of the lytic genes. This article is ended with discussions on the remaining problems and possible future directions. This review provides comprehensive information on autolytic bacteria and insightful guidance to the development of highly efficient, robust, and smart autolytic bacterial platforms.

The rapid preparation of safe and efficient wound dressings that meet the needs of the entire repair process remains a major challenge for effective therapeutic wound healing. Natural, sprayable Ion2+-COS/SA multifunctional dual-network gel films created by the in situ coordination of chitooligosaccharide (COS), metal ions and sodium alginate (SA) using casting and an in-situ spray method were synthesized. The gel films exhibited excellent physicochemical properties such as swelling, porosity and plasticity at a COS mass fraction of 3%. Furthermore, at this mass fraction, the addition of bimetallic ions led to the display of multifunctional properties, including significant antioxidant, antibacterial and cytocompatibility properties. In addition, experiments in a total skin defect model showed that this multifunctional gel film accelerates wound healing and promotes skin regeneration. These results suggest that the sprayable Ion2+-COS/SA multifunctional pro-healing gel film may be a promising candidate for the clinical treatment of allodermic wounds.

Peptide self-assembling materials have received significant attention from researchers in recent years, emerging as a popular field in biological, environmental, medical, and other new materials studies. In this study, we utilized controllable enzymatic hydrolysis technology (animal proteases) to obtain supramolecular peptide self-assembling materials (CAPs) from the Pacific oyster (Crassostrea gigas). We conducted physicochemical analyses to explore the pro-healing mechanisms of CAPs on skin wounds in both in vitro and in vivo experiments through a topical application. The results demonstrated that CAPs exhibit a pH-responsive behavior for self-assembly and consist of peptides ranging from 550 to 2300 Da in molecular weight, with peptide chain lengths of mainly 11–16 amino acids. In vitro experiments indicated that CAPs display a procoagulant effect, free radical scavenging activity, and promote the proliferation of HaCaTs (112.74% and 127.61%). Moreover, our in vivo experiments demonstrated that CAPs possess the ability to mitigate inflammation, boost fibroblast proliferation, and promote revascularization, which accelerates the epithelialization process. Consequently, a balanced collagen I/III ratio in the repaired tissue and the promotion of hair follicle regeneration were observed. With these remarkable findings, CAPs can be regarded as a natural and secure treatment option with high efficacy for skin wound healing. The potential of CAPs to be further developed for traceless skin wound healing is an exciting area for future research and development.

The development of an efficient and convenient material to improve skin tissue regeneration is a major challenge in healthcare. Inspired by the theory of moist wound healing, portable chitooligosaccharide (COS)/sodium alginate (SA) dual-net gel films containing multiple metal ions were prepared by a casting and in-situ spray method, which can be used to significantly promote wound healing without the use of therapeutic drugs. A variety of divalent cations was introduced in this experiment to improve the advantages of each metal ion by forming metal ion chelates with COS. Moreover, the physicochemical properties and antioxidant properties of nIon2+-COS/SA gel films were systematically characterized and evaluated by in vitro experiments. The gel films showed good antibacterial activity against Gram-negative and Gram-positive bacteria. In addition, the gel films showed good cytocompatibility in cellular experiments, and the gel films with Zn2+ and Sr2+ addition significantly accelerated wound healing in whole skin defect model experiments. Therefore, this nIon2+-COS/SA gel film is an ideal candidate material for wound dressing.

Developing convenient, efficient, and natural wound dressings remain the foremost strategy for treating skin wounds. Thus, we innovatively combined the semi-dissolved acidified sol-gel conversion method with the internal gelation method to fabricate SA (sodium alginate)/CS (chitosan)/Zn2+ physically cross-linked double network hydrogel and named it SA/CS/Zn2+ PDH. The characterization results demonstrated that increased Zn2+ content led to hydrogels with improved physical and chemical properties, such as rheology, water retention, and swelling capacity. Moreover, the hydrogels exhibited favorable antibacterial properties and biocompatibility. Notably, the establishment of an in vitro pro-healing wound model further confirmed that the hydrogel had a superior ability to repair wounds and promote skin regeneration. In future, as a natural biomaterial with antimicrobial properties, it has the potential to promote wound healing.

Snow drifts and accumulates under wind actions, leading to a complex distribution of snow around and on the surface of structures with openings, which in turn has a detrimental influence on the structures. There is no relevant code provision for this situation. Therefore, a wind tunnel study was carried out to experimentally investigate how opening size and vertical location (for cubes with single openings) and how the relative positions of different openings (for cubes with multiple openings) influenced the wind-induced snowdrifts around and on the surface of cubes with openings. A roughness coefficient was introduced to characterize the snow around cubes. It was found that snow accumulation at the side of the cube produced a greater uneven snow load. The number and vertical location of openings were the main factors influencing the roughness of the snow. The snow depth coefficient ( C s ) around and on the surface of a cube is approximately negatively correlated with opening size and approximately positively correlated with opening vertical location. The simultaneous existence of openings on the windward, side and top faces of a cube adversely affected the safety of the surroundings of the cube. The variation pattern of fractal characteristic of particles, D , was similar to that of C s when the snow was fully eroded at the windward corner of the cube. These findings will help improve the accuracy of snow distribution pattern prediction and enhance the safety and rationality of the structural design of buildings.

Depletion of mitochondrial copper, which shifts metabolism from respiration to glycolysis and reduces energy production, is known to be effective against cancer types that depend on oxidative phosphorylation. However, existing copper chelators are too toxic or ineffective for cancer treatment. Here we develop a safe, mitochondria-targeted, copper-depleting nanoparticle (CDN) and test it against triple-negative breast cancer (TNBC). We show that CDNs decrease oxygen consumption and oxidative phosphorylation, cause a metabolic switch to glycolysis and reduce ATP production in TNBC cells. This energy deficiency, together with compromised mitochondrial membrane potential and elevated oxidative stress, results in apoptosis. CDNs should be less toxic than existing copper chelators because they favorably deprive copper in the mitochondria in cancer cells instead of systemic depletion. Indeed, we demonstrate low toxicity of CDNs in healthy mice. In three mouse models of TNBC, CDN administration inhibits tumor growth and substantially improves survival. The efficacy and safety of CDNs suggest the potential clinical relevance of this approach. Triple-negative breast cancer is inhibited by depleting mitochondrial copper in mice.

Fractures are key geological features in hot dry rock structures and fulfill a decisive role in determining productivity and reservoir stability. Adopting the Xudong fault zone in the Songliao Basin as the research object, a multifracture heat extraction model was constructed using COMSOL software to systematically analyze productivity and various field under different numbers and locations of horizontal and vertical fractures. Moreover, the influences of vertical fracture connectivity and the characteristics of seepage and heat transfer between the upper and lower rock layers on the temperature field were evaluated. The findings are as follows: (1) The production flow obtained with nine horizontal fractures is 2.25 to 2.28 times that obtained with four horizontal fractures. Increasing the number of horizontal fractures also increases the production temperature and heat extraction efficiency at the early stages of heat extraction but reduces productivity at the later stages and adversely affects reservoir stability. After 30 years of heat extraction, the production temperature, average subsidence, maximum subsidence, and average in situ stress obtained with nine horizontal fractures are 79.38% and 1.87, 1.61, and 1.45 times, respectively, those obtained with four horizontal fractures. (2) The influence of the number of vertical fractures on the geothermal reservoir characteristics is similar to but slightly smaller than that of horizontal fractures. However, the influences of vertical fractures on the production flow at the early stages and the maximum reservoir temperature at the later stages are opposite to those of horizontal fractures. When vertical fractures are located close to the injection well, productivity is low at the early stages but high at the later stages. The maximum subsidence, average in situ stress, and maximum in situ stress slightly increase, whereas the average subsidence decreases. (3) After 30 years of heat extraction, the average reservoir temperature is highest when seepage and heat transfer between the upper and lower rock layers occur and when vertical fractures do not penetrate the reservoir. When these conditions are reversed, the average temperature is lowest, with the former approximately 0.42°C higher than the latter. The findings of this study provide a reference for the construction of reservoir fracture systems.

Glioma is the most common type of primary malignant tumor in the central nervous system with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is a novel and distinct type of programmed cell death, playing a regulatory role in the progression of tumors. However, the role of ferroptosis or ferroptosis-related genes (FRGs) in glioma progression has not been extensively studied. In our study, a novel ferroptosis-related prognostic model, including 7 genes, was established, in which patients classified into the high-risk group had more immuno-suppressive status and worse prognosis. Among these 7 genes, we screened solute carrier family 1 member 5 (SLC1A5), an FRG, as a possible new target for glioma treatment. Our results showed that the expression of SLC1A5 was significantly upregulated in glioblastoma tissues compared with the low-grade gliomas. In addition, SLC1A5 knockdown could significantly inhibit glioma cell proliferation and invasion, and reduce the sensitivity of ferroptosis via the GPX4-dependent pathway. Furthermore, SLC1A5 was found to be related to immune response and SLC1A5 knockdown decreased the infiltration and M2 polarization of tumor-associated macrophages. Pharmacological inhibition of SLC1A5 by V9302 was confirmed to promote the efficacy of anti-PD-1 therapy. Overall, we developed a novel prognostic model for glioma based on the seven-FRGs signature, which could apply to glioma prognostic and immune status prediction. Besides, SLC1A5 in the model could regulate the proliferation, invasion, ferroptosis and immune state in glioma, and be applied as a prognostic biomarker and potential therapeutic target for glioma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. However, the immune tolerance limits the effect of chemotherapeutic drugs. Therefore, the mechanism of cisplatin in promoting PD-L1 expression by YAP1 was investigated in the present study, and we found that cisplatin increased the expression level of YAP1 in the mouse liver with H22 cells. Meanwhile, cisplatin improved the expression level of PD-L1, IL-1β and CCL2 in the tumor microenvironment. Further, cisplatin also enhanced the expression level of YAP1 in shYAP1 HepG2215 cells. The expression of PD-L1 was decreased by Verteporfin, YAP1 inhibitor, during the treatment of DEN/TCPOBOP-induced liver cancer in C57BL/6 mice. These results suggested that cisplatin could deteriorate the immunosuppressive microenvironment through increasing PD-L1, CCL2, IL-1β by upregulated YAP1 expression. Therefore, the study suggested that YAP1 blockade destroyed the immunosuppressive microenvironment of cancer to improve the effect of chemotherapy in HCC.