Aqueous-Aqueous Triboelectric Nanogenerators Empowered Multifunctional Wound Healing System with Intensified Current Output for Accelerating Infected Wound Repair.

Triboelectric nanogenerators (TENGs) have emerged as promising devices for generating self-powered therapeutic electrical stimulation over multiple aspects of wound healing. However, the challenge of achieving full 100% contact in conventional TENGs presents a substantial hurdle in the quest for higher current output, which is crucial for further improving healing efficacy. Here, a novel multifunctional wound healing system is presented by integrating the aqueous-aqueous triboelectric nanogenerators (A-A TENGs) with a functionalized conductive hydrogel, aimed at advancing infected wound therapy. The A-A TENGs are founded on a principle of 100% contact interface and efficient post-contact separation of the immiscible interface within the aqueous two-phase system (ATPS), enhancing charge transfer and subsequently increasing current performance. Leveraging this intensified current output, this system demonstrates efficient therapeutic efficacies over infected wounds both in vitro and in vivo, including stimulating fibroblast migration and proliferation, boosting angiogenesis, enhancing collagen deposition, eradicating bacteria, and reducing inflammatory cells. Moreover, the conductive hydrogel ensures the uniformity and integrity of the electric field covering the wound site, and exhibits multiple synergistic therapeutic effects. With the capability to realize accelerated wound healing, the developed "A-A TENGs empowered multifunctional wound healing system" presenting an excellent prospect in clinical wound therapy.

Triboelectric Nanogenerators-Based Therapeutic Electrical Stimulation on Skin: from Fundamentals to Advanced Applications.

Discovery of the amazing and vital therapeutic roles of electrical stimulation (ES) on skin has sparked tremendous efforts to investigate ES suppliers. Among them, triboelectric nanogenerators (TENGs), as a self-sustainable bioelectronic system, can generate self-powered and biocompatible ES for achieving superior therapeutic effects on skin applications. Here, a brief review of the application of TENGs-based ES on skin is presented, with specific discussions of the fundamentals of TENGs-based ES and its feasibility to be applied for adjusting physiological and pathological processes of skin. Then, a comprehensive and in-depth depiction of emerging representative skin applications of TENGs-based ES is categorized and reviewed, with particular descriptions about its therapeutic effects on achieving antibacterial therapy, promoting wound healing, and facilitating transdermal drug delivery. Finally, the challenges and perspectives for further advancing TENGs-based ES toward a more powerful and versatile therapeutic strategy are discussed, particularly regarding opportunities in fundamental multidisciplinary research and biomedical applications.

NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in corticostriatal circuits.

BACKGROUND: Alcohol use disorders result from repeated binge and chronic alcohol consumption followed by negative effects, such as anxiety, upon cessation. This process is associated with the activation of NLRP3 inflammasome-mediated responses. However, whether and how inhibition of the NLRP3 inflammasome alters alcohol intake and anxiety behavior remains unclear. METHODS: A combination of drinking-in-the-dark and gavage was established in NLRP3-knockout and control mice. Behavior was assessed by open-field and elevated plus maze tests. Binge alcohol drinking was measured at 2 h and 4 h. A 2 h/4 h/24 h voluntary drinking was determined by a two-bottle choice paradigm. Western blotting and ELISA were applied to examine the levels of the NLRP3 inflammasome and- inflammatory factors, such as IL-1ß and TNF-α. Nissl staining was used to measure neuronal injury. The electrophysiological method was used to determine glutamatergic transmission in corticostriatal circuits. In vivo optogenetic LTP and LTD were applied to control the function of corticostriatal circuits on the behavior of mice. MCC950 was used to antagonize the NLRP3 inflammasome. RESULTS: The binge alcohol intake was decreased in NLRP3 KO mice compared to the control mice. During alcohol withdrawal, NLRP3 deficiency attenuated anxiety-like behavior and neuronal injury in the mPFC and striatum. Moreover, we discovered that glutamatergic transmission to striatal neurons was reduced in NLRP3 KO mice. Importantly, in vivo optogenetic induction of long-term potentiation (LTP) of corticostriatal circuits reversed the effects of NLRP3 deficiency on glutamatergic transmission and anxiety behavior. We also demonstrated that optogenetic induction of LTD decreased anxiety-like behavior and caused a reduction in glutamatergic transmission. Interestingly, NLRP3 deficiency or inhibition (MCC950 injection) attenuated the anxiety-like behavior, but it did not prevent DID + gavage paradigm-induced a persistent enhancement of drinking in a two-bottle choice at 2 and 4 days into withdrawal. CONCLUSION: Our results demonstrate that NLRP3 deficiency decreases binge alcohol intake and anxiety-like behavior through downregulation of glutamatergic transmission in corticostriatal circuits, which may provide an anti-inflammatory target for treating alcohol use disorders.

DaNet: dose-aware network embedded with dose-level estimation for low-dose CT imaging.

Many deep learning (DL)-based image restoration methods for low-dose CT (LDCT) problems directly employ the end-to-end networks on low-dose training data without considering dose differences. However, the radiation dose difference has a great impact on the ultimate results, and lower doses increase the difficulty of restoration. Moreover, there is increasing demand to design and estimate acceptable scanning doses for patients in clinical practice, necessitating dose-aware networks embedded with adaptive dose estimation. In this paper, we consider these dose differences of input LDCT images and propose an adaptive dose-aware network. First, considering a large dose distribution range for simulation convenience, we coarsely define five dose levels in advance as lowest, lower, mild, higher and highest radiation dose levels. Instead of directly building the end-to-end mapping function between LDCT images and high-dose CT counterparts, the dose level is primarily estimated in the first stage. In the second stage, the adaptively learned low-dose level is used to guide the image restoration process as the pattern of prior information through the channel feature transform. We conduct experiments on a simulated dataset based on original high dose parts of American Association of Physicists in Medicine challenge datasets from the Mayo Clinic. Ablation studies validate the effectiveness of the dose-level estimation, and the experimental results show that our method is superior to several other DL-based methods. Specifically, our method provides obviously better performance in terms of the peak signal-to-noise ratio and visual quality reflected in subjective scores. Due to the dual-stage process, our method may suffer limitations under more parameters and coarse dose-level definitions, and thus, further improvements in clinical practical applications with different CT equipment vendors are planned in future work.

The Anti-apoptotic Role of 3'-Untranslational Region in Response to Angiotensin II via Mcl1 Expression.

Myeloid cell leukemia 1 (Mcl1), an abundant protein in the myocardium, plays an essential role in fibrosis and anti-inflammation in cardiomyocytes to prevent heart failure. However, whether Mcl1 3'-untranslated regions (3'-UTR) has the cardio-protecting function remains unclear. Down-regulation of Mcl1 was observed in adult mice heart tissues after Angiotensin II (Ang II) treatment. Consistent with in vivo results, the reduction of Mcl1 expression was identified in Ang II-treated neonatal cardiomyocytes. Mechanistically, Mcl1 3'-UTR prevented Ang II-induced cardiac apoptosis via up-regulation of Mcl1 and an angiogenic factor with a G-patch domain and a forkhead-associated domain 1 (Aggf1), which plays cardiac-protective role. Our work broadens the scope of gene therapy targets and provides a new insight into gene therapy strategies involving mRNAs' 3'-UTRs application.