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Hepatocellular carcinoma (HCC) is the most common primary liver tumor and one of the leading causes of cancer-related death worldwide. Chemotherapeutic agents/regimens such as cisplatin (DDP) are frequently used for advanced HCC treatment. However, drug resistance remains a major hindrance and the underline mechanisms are not fully understood. In this study, we investigated the expression pattern and function of mitochondrial fission factor (Mff) in cisplatin-resistant HCC. We found that Mff is highly expressed in cisplatin-resistant HCC tissues and cell lines. Knockdown of Mff suppresses cell proliferation and promotes cell apoptosis of HCC/DDP cells. In addition, knockdown of Mff sensitizes Huh-7/DDP cells to cisplatin treatment, inhibits cell proliferation, migration and invasion, and enhances cell apoptosis. Confocal imaging showed that knockdown of Mff inhibits the mitochondrial fission and downregulates the expression of GTPase dynamin-related protein 1 (Drp1) in cisplatin-resistant Huh-7/DDP cells. Moreover, xenograft tumor model revealed that knockdown of Mff sensitizes Huh-7/DDP xenograft tumor to cisplatin treatment in vivo. In summary, our findings suggest that Mff regulates mitochondrial Drp1 expression and promotes cisplatin resistance in HCC, which provides a potential therapeutic target for the treatment of cisplatin-resistant HCC.

Click‐through rate (CTR) prediction is a pivotal challenge in recommendation systems. Existing models are prone to disturbances from noise and redundant features, hindering their ability to fully capture implicit and higher‐order feature interactions present in sparse feature data. Moreover, conventional dual‐tower models overlook the significance of layer‐level feature interactions. To address these limitations, this article introduces Gate‐enhanced Multi‐space Interactive Neural Networks (GMINN), a novel model for CTR prediction. GMINN adopts a dual‐tower architecture in which a multi‐space interaction layer is introduced after each layer in the dual‐tower deep neural network. This layer allocates features into multiple subspaces and employs matrix multiplication to establish layer‐level interactions between the dual towers. Simultaneously, a field‐aware gate mechanism is proposed to extract crucial latent information from the original features. Experimental validation on publicly available datasets, Criteo and Avazu, demonstrates the superiority of the proposed GMINN model. Comparative analyses against baseline models reveal that GMINN substantially improves up to 4.09% in AUC and a maximum reduction of 7.21% in Logloss. Additionally, ablation experiments provide further validation of the effectiveness of GMINN. [ABSTRACT FROM AUTHOR]

Protein degradation is a general process to maintain cell homeostasis. The intracellular protein quality control system mainly includes the ubiquitin‐proteasome system and the lysosome pathway. Inspired by the physiological process, strategies to degrade specific proteins have developed, which emerge as potent and effective tools in biological research and drug discovery. This review focuses on recent advances in targeted protein degradation techniques, summarizing the principles, advantages, and challenges. Moreover, the potential applications and future direction in biological science and clinics are also discussed. [ABSTRACT FROM AUTHOR]

Achieving smart circularly polarized luminescence (CPL) materials with large luminescence dissymmetry factor (glum) is in high demand for potential technological applications in the chiroptical fields. Herein, a series of chiral photonic crystals (CPCs) derived from cellulose nanocrystals (CNCs) and photosensitive inorganic polyoxometalates (POMs) through an evaporation‐induced self‐assembly strategy are reported. The photonic bandgaps (PBGs) of CPC films are well regulated by controlling the amount of doped POMs, yielding the tunable right‐handed CPL emission with tailored glum. By locating the maximum emission peak of POMs at the center of the PBG of CPC films, the composite shows remarkable CPL performance with a |glum| value up to 0.53. Furthermore, the CPL can be reversibly switched on/off through a fluorescence resonance energy transfer (FRET) process controlled by alternate UV irradiation reduction and air oxidation. The CPC films hold the great promise as next‐generation chiroptical memory devices. [ABSTRACT FROM AUTHOR]

Severe coloboma of ocular malignant neoplasms post‐resection poses a reconstructive challenge to surgeons. To compare the practicability, manipulability and outcomes of temporal (myocutaneous) flaps (TFs), forehead (supratrochlear artery/supraorbital artery) flaps (FFs) and buccal (facial artery) flaps (BFs) for periorbital defects reconstruction, a retrospective case series was conducted and evaluated between March 2014 and March 2021. Patient demographics and clinical parameters including age, gender, pathological diagnosis, operative methods, flap selection, operation time, aesthetic satisfaction and follow‐up period were collected. The differences in complications were compared and assessed of the three flaps, including flap survival, venous congestion and donor site healing. Totally, 68 patients who underwent periorbital reconstructive operations because of common ocular malignant tumours were reviewed in this study. As for aesthetic satisfaction, a score more than "moderately dissatisfied" was obtained in 21 patients with TFs (95.5%), and of which the scores in FFs group were 12 cases (60%) and 16 cases with BFs reconstruction (61.5%) (P <.05). Severe microvascular complications underwent re‐exploration operation occurred in one patient with FFs (1.5%) (P >.05). Notable flap necrosis was observed in two patients with BFs repair (2.9%) and in one case with FFs repair (1.5%), with no statistical difference between the three flap selections (P >.05). Moderate venous congestion occurred in one patient with TFs (1.5%), which was fully meliorated non‐surgically. The three familiar facial island flaps are considered as minor trauma and time‐saving process for reconstructing the extensive periorbital defects with comparable ranks of complications. [ABSTRACT FROM AUTHOR]

Sepsis is one of the most common causes of death, which is closely related to the uncontrolled systemic inflammation. Dysregulation of M1 macrophage polarization is the primary contributor to serious inflammation. In this study, it is revealed that the murine homologue of circRNA SCAR (steatohepatitis‐associated circRNA ATP5B regulator), denoted as circRNA mSCAR hereafter, decreases in the macrophages of septic mice, which correlates with the excessive M1 polarization. To restore circRNA mSCAR in mitochondria, exosomes encapsulated with circRNA mSCAR are further electroporated with poly‐D‐lysine‐graft‐triphenylphosphine (TPP‐PDL), and thus TPP‐PDL facilitates the bound circRNA delivered into mitochondria when the exosomes engulf by the recipient cells. In in vivo septic mouse model and in vitro cell model, it is shown that the exosome‐based mitochondria delivery system delivers circRNA mSCAR into mitochondria preferentially in the macrophages, favoring macrophage polarization toward M2 subtype. Accordingly, the systemic inflammation is attenuated by exosome‐based mitochondrial delivery of circRNA mSCAR, together with alleviated mortality. Collectively, the results uncover the critical role of circRNA mSCAR in sepsis, and provide a promising approach to attenuate sepsis via exosome‐based mitochondrial delivery of circRNA mSCAR. [ABSTRACT FROM AUTHOR]

This study introduced a novel method to reconstruct large areas of scarring caused by burns via combining autologous scar-related tissue with spit-thickness skin grafting (ASTCS). 25 patients underwent reconstruction after scar resection surgeries around the joints were analyzed between Jan 2012 and Jan 2018. Patient demographics and clinical parameters were collected, autologous scar-related tissue was modified to meshed structure, and the split-thickness skin was acquired from the scalp. The scar was resected and punched by a meshing machine with a thickness of 0.3–0.5 mm at a ratio of 1:1. The secondary wounds were covered by the epidermis from a donor site. The surgical areas were bandaged for 7–10 days before the first dressing change. 25 patients (mean [SD] age, 26.4 [18.8] years; 16 [64%] men) underwent wounds reconstructive operations due to scar resection were reviewed. Wound location of 9 (22%), 8 (19.5%), 9 (22%), 7 (17.1%) and 8 (19.5%) cases were reconstructed in axillary, hand and wrist, popliteal fossa, elbow and neck, respectively. 39 sites of transplanted tissues survived well, and 2 sites were cured after two weeks of dressing changes. Except the analysis of injury causes, nutritional status, wound area and hospital days, patients with scar deformities in joint areas achieved satisfactory function by assessing the Vancouver Burn Skin Score and the Barthel Index Scale Scores after 12-month follow-up. Combining autologous scar-related tissue with skin grafting provided a novel method for treating large areas of burn scars with better functional outcomes. [ABSTRACT FROM AUTHOR]

Chiral semiconductor nanostructures have received enormous attention due to their emerging circularly polarized luminescence (CPL) properties. However, compared with well‐studied photoluminescence (PL), the reported CPL is much weaker and more challenging to be modulated. Herein, we describe a new approach for acquiring the intense and tunable CPL from inorganic chiral photonic crystals (CPCs) doped with semiconductor quantum dots (QDs). Unprecedentedly, the sign, position and intensity of CPL peaks can be precisely controlled by manipulating either the photonic band gap of CPCs or luminescence wavelength of QDs and a giant absolute dissymmetry factor |glum| up to 0.25 is obtained. More importantly, the origin of the CPL modulation is clearly elucidated by both experiment and theory. This work lays the foundation for the construction of next‐generation high‐performance CPL‐based devices. [ABSTRACT FROM AUTHOR]

A PGP-1-specific one/two-photon fluorogenic probe (BH1), capable of high sensitivity, super selectivity, and visual imaging of endogenous PGP-1 activity from live mammalian cells and serum/skin tissues from patients by using one/two-photon fluorescence microscopy (O/TPFM). [ABSTRACT FROM AUTHOR]

MAO-A promotes the proliferation of human glioma cells. Herein, we report a series of MAO-A specific two-photon small molecular fluorescent probes (A1–5) based on an intramolecular charge transfer enhancing strategy. The activity of endogenous MAO-A can be selectively imaged using A3 as a representative probe in different biological samples including human glioma cells/tissues via two-photon fluorescence microscopy. The study provides new tools for the visual detection of glioma. [ABSTRACT FROM AUTHOR]

Therapeutically intervening the function of RNA in vivo remains a big challenge. We here developed an exosome-based strategy to deliver engineered RNA-binding protein for the purpose of recruiting specific RNA to the lysosomes for degradation. As a proof-of-principle study, RNA-binding protein HuR was fused to the C-terminus of Lamp2b, a membrane protein localized in both exosome and lysosome. The fusion protein was able to be incorporated into the exosomes. Moreover, exosomes engineered with Lamp2b-HuR successfully decreased the abundance of RNA targets possibly via lysosome-mediated degradation, especially when the exosomes were acidified. The system was specifically effective in macrophages, which are lysosome enriched and resistant to routine transfection mediated RNAi strategy. In the CCl4-induced liver injury mouse model, we found that delivery of acidified exosomes engineered with Lamp2b-HuR significantly reduced liver fibrosis, together with decreased miR-155 and other inflammatory genes. In summary, the established exosome-based RNA-binding protein delivery strategy, namely "exosome-mediated lysosomal clearance", takes the advantage of exosome in targeted delivery and holds great promise in regulating a set of genes in vivo. [ABSTRACT FROM AUTHOR]

Monoamine oxidases have two functionally distinct but structurally similar isoforms (MAO‐A and MAO‐B). The ability to differentiate them by using fluorescence detection/imaging technology is of significant biological relevance, but highly challenging with available chemical tools. Herein, we report the first MAO‐A‐specific two‐photon fluorogenic probe (F1), capable of selective imaging of endogenous MAO‐A enzymatic activities from a variety of biological samples, including MAO‐A‐expressing neuronal SY‐SY5Y cells, the brain of tumor‐bearing mice and human Glioma tissues by using two‐photon fluorescence microscopy (TPFM) with minimal cytotoxicity. [ABSTRACT FROM AUTHOR]

Sepsis is a complex inflammatory disorder in which high mortality is associated with an excessive inflammatory response. Inhibitor of growth 4 (ING4), which is a cofactor of histone acetyltransferase and histone deacetylase complexes, could negatively regulate this inflammation. However, the exact molecular signaling pathway regulated by ING4 remains uncertain. As a pivotal histone deacetylase, Sirtuin1 (SIRT1), which is widely accepted to be an anti‐inflammatory molecule, has not been found to be linked to ING4. This study investigated how ING4 is involved in the regulation of inflammation by constructing lipopolysaccharide (LPS)‐induced macrophage and mouse sepsis models. Our results revealed that ING4 expression decreased, whereas the levels of proinflammatory cytokines increased in LPS‐stimulated cultured primary macrophages and RAW 264.7 cells. ING4 transfection was confirmed to alleviate the LPS‐induced upregulation of proinflammatory cytokine expression both in vitro and in vivo. In addition, ING4‐overexpressing mice were hyposensitive to an LPS challenge and displayed reduced organ injury. Furthermore, immunoprecipitation indicated a direct interaction between ING4 and the SIRT1 protein. Moreover, ING4 could block nuclear factor‐kappa B (NF‐κB) P65 nuclear translocation and restrict P65 acetylation at lysine 310 induced by LPS treatment. These results are the first to clarify that the anti‐inflammatory role of ING4 is associated with SIRT1, through which ING4 inhibits NF‐κB signaling activation. Our studies provide a novel signaling axis involving ING4/SIRT1/NF‐κB in LPS‐induced sepsis. [ABSTRACT FROM AUTHOR]

The treatment of donor sites after split-thickness skin grafting (STSG) is a routine operation step, and complications at the donor site due to improper operation and care are unwelcome. This study evaluates whether the use of platelet-rich plasma (PRP) applied at the STSG area promotes wound healing and improves scar development. Clinical data of 30 patients who underwent STSG operations between January 2016 and January 2017 for various reasons were retrospectively analyzed. These 30 patients received two treatments and the data were summed up in two groups: the PRP group, which was the study group, included patients who received traditional petrolatum gauze dressing with PRP gel at the donor sites. The petrolatum gauze group, which was the control group, received only petrolatum gauze care without PRP gel. The time and frequency of dressing change were comparable between the two groups, and the mean wound healing times in the PRP group and petrolatum gauze group were 13.89 ± 4.65 and 17.73 ± 5.06 days, respectively, and the difference was statistically significant (p < 0.05). In addition, the total Vancouver scar scale (VSS) scores of the PRP group at 4, 12 and 52 weeks were 6.41 ± 0.77, 4.42 ± 0.43 and 2.41 ± 0.39, respectively, which were statistically significantly lower (p < 0.05) than those of the control group at 7.67 ± 0.64, 6.28 ± 0.62 and 4.29 ± 0.64, respectively. The use of PRP gel can promote wound healing, relieve scar development and alleviate pain at the donor site after STSG. [ABSTRACT FROM AUTHOR]

Although it is well known that the amazing iridescent colors of the cuticle of beetles reflect the intricate nanoscale organization of bio‐fibers, artificial inorganic materials with comparable optical responses have not yet been synthesized from abiotic nanoscale building blocks. Such materials could find broad applications, including in circular polarizers, to generate circularly polarized luminescence, or in lasers. Herein, we describe a general method for the fabrication of biomimetic chiral photonic crystals by Langmuir–Schaefer assembly of colloidal inorganic nanowires. We not only reproduced the intricate helical structure and circularly polarized color reflection observed in beetles, but also achieved the highest chiroptical activity with a dissymmetry factor of −1.6 ever reported for chiral inorganic nanostructures. More importantly, the programmable structural control based on the precise interlayer arrangement endows us with unprecedented freedom to manipulate the optical activity of as‐fabricated chiral photonic crystals. [ABSTRACT FROM AUTHOR]