Ciclopirox platinum(IV) conjugates suppress tumors by promoting mitophagy and provoking immune responses.

Mitophagy is an important target for antitumor drugs development. A series of ciclopirox (CPX) platinum(IV) hybrids targeting PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitophagy were designed and prepared as antitumor agents. The dual CPX platinum(IV) complex with cisplatin core was screened out as a candidate, which displayed promising antitumor activities both in vitro and in vivo. Mechanistically, it caused serious DNA damage in tumor cells. Then, remarkable mitochondrial damage was induced accompanied by the mitochondrial membrane depolarization and reactive oxygen species generation, which further promoted apoptosis through the Bcl-2/Bax/Caspase3 pathway. Furthermore, mitophagy was ignited via the PINK1/Parkin/P62/LC3 axis, and exhibited positive influence on promoting the apoptosis of tumor cells. The antitumor immunity was boosted by the block of immune check point programmed cell death ligand-1 (PD-L1), which further increased the density of T cells in tumors. Subsequently, the metastasis of tumor cells was inhibited by inhibiting angiogenesis in tumors.

2D/3D hierarchical porous structure of mNPC/SMOH@C to construct an electrochemical sensor for the simultaneous determination of p-acetylaminophenol and p-aminophenol.

BACKGROUND: As persistent organic pollutants (POPs), the accumulation of p-acetylaminophenol (PAT) and p-aminophenol (PAP) in water can seriously damage the health of plants and animals, ultimately leading to threats to human health and safety. Electrochemical sensors have the advantages of being fast, inexpensive, and accurate compared to the complex, expensive, and cumbersome conventional analytical methods. In this study, we designed and synthesized composites with two-dimensional/three-dimensional (2D/3D) porous structures to construct an efficient electrochemical platform for the simultaneous detection of PAT and PAP. RESULTS: In this work, a novel 3D foamy birnessite Na0.55Mn2O4·1.5H2O@C (SMOH@C) was synthesized, which was composited with 2D ordered mesoporous nanosheets (mNPC) to construct electrochemical sensors detecting PAT and PAP simultaneously. The prepared 2D/3D porous structure of mNPC/SMOH@C increased the exposure of active sites due to its large specific surface area. The introduction of a 3D carbon skeleton altered the charge transfer rate of SMOH@C, and the rich pore structure and oxygen-rich vacancies created favorable conditions for the diffusion and adsorption of PAP and PAT, which enabled the sensitive detection of PAT and PAP. The constructed mNPC/SMOH@C electrochemical sensor could simultaneously detect PAT (1 × 10-7 - 1 × 10-4 M) and PAP (5 × 10-8 - 1 × 10-4 M) with detection limits of 20.4 nM and 30.1 nM, respectively. The sensor has good repeatability (RSD <4 %) and reproducibility (RSD <4 %), and satisfactory recoveries (96.7-102.8 %) were obtained in the analysis of natural water samples. SIGNIFICANCE: In this paper, for the first time, we present the synthesis of 3D foam birnessite and its composite with mNPC for the electrochemical simultaneous detection of PAT and PAP. Our proposed strategy for fabricating 2D/3D porous composites lays the foundation for the design and synthesis of other porous materials. In addition, this study provides new ideas for developing efficient and practical electrochemical sensors for detecting pollutants in aquatic environments.

A hydroxychloroquine platinum(IV) conjugate displaying potent antimetastatic activities by suppressing autophagy to improve the tumor microenvironment.

Protective autophagy is a promising target for antitumor drug exploration. A hydroxychloroquine (HCQ) platinum(IV) complex with autophagy suppressing potency was developed, which displayed potent antitumor activities with a TGI rate of 44.2% against 4T1 tumors in vivo and exhibited a rather lower toxicity than cisplatin. Notably, it exhibited satisfactory antimetastatic activities toward lung pulmonary metastasis models with an inhibition rate of 49.6% and was obviously more potent than CDDP, which has an inhibition rate of 21.6%. Mechanism detection revealed that it caused serious DNA damage and upregulated the expression of γ-H2AX and p53. More importantly, the incorporation of an autophagy inhibitor HCQ endowed the platinum(IV) complex with potent autophagy impairing properties by perturbing the lysosomal function in tumor cells, which promoted apoptosis synergistically with DNA injury. Then, the impaired autophagy further led to the suppression of hypoxia and inflammation in the tumor microenvironment by downregulating ERK1/2, HIF-1α, iNOS, caspase1 and COX-2. Adaptive immune response was improved by inhibiting the immune checkpoint PD-L1 and further increasing CD4+ and CD8+ T cells in tumors. Then, tumor metastasis was effectively inhibited by restraining angiogenesis through inhibiting VEGFA, MMP-9, and CD34.

Electrochemical sensing platform using reduced graphene oxide and Sn MOF-derived hollow cubic composites for sensitive detection of catechol in environmental water samples.

Catechol, a polyphenolic molecule and significant organic chemical intermediate, is a highly dangerous environmental contaminant due to its unpredictable nature and potential harm to both humans and the environment. This study presents the development of Sn MOF@rGO-650, identified as a hollow cube by SEM and TEM, created by carbonizing rGO on the surface of Sn MOF after in situ encapsulation. The Sn MOF@rGO-650 modified glassy carbon electrode was successfully constructed for the electrochemical detection of catechol. Under optimal conditions, the sensor exhibited a detection limit of 33 nM, a linear range of 0.20 µM-28 µM, and good long-term stability and reproducibility. This work proves for the first time that Sn MOF@rGO-650 composites can effectively detect catechol in real environmental water samples, achieving recoveries between 95.7 % and 104.8 %, and is validated in UV spectroscopy, which highlights its potential for practical applications.

Facile synthesis of sulfur quantum dots with red light emission: Implications for electrochemiluminescence analysis application.

Sulfur quantum dots (SQDs) have been reported as a potential candidate due to their low toxicity and high luminescent performance. Here, SQDs with red light fluorescence (FL) emission were synthesized by a one-step hydrothermal method using Na2CO3 as an etching agent, using sublimed sulfur powder as a sulfur source, and using bovine serum albumin (BSA) as a stabilizer. The choice of etching agent (NaOH or Na2CO3) realized the tuning of SQDs' FL emission with blue and red light. The synthesized SQDs showed good FL stability and high FL efficiency, with a quantum yield of 1.03 % in an aqueous solution at 575 nm. In addition, stable and efficient electrochemiluminescence (ECL) emission was achieved by employing SQDs as ECL emitters with K2S2O8 as the co-reactant. The resorcinol (RS) can enhance the ECL intensity of the SQDs-K2S2O8 system, and the ECL intensity had a good linear relationship with the concentration of RS in a range from 2.5 nM to 25 nM with a detection limit of 0.61 nM. This work provides an emerging red-light luminescent SQDs, which would open up a way for the development of new types of luminophor in FL or ECL analysis. It also provides convenience for bio-labeling of live cells, in vivo imaging and provide new materials for photoelectric devices.

Canadine Platinum(IV) Complexes Targeting Epithelial-Mesenchymal Transition as Antiproliferative and Antimetastatic Agents.

Epithelial-mesenchymal transition (EMT) is a critical process for cancer progression, which is crucial in inhibiting the immunity in tumors and further boosting tumor metastasis. The suppression of EMT represents a promising strategy for inhibiting metastatic tumors. Herein, a series of new canadine platinum(IV) conjugates with potent antiproliferative and antimetastatic activities were developed, which activated by suppressing EMT and provoking immune response in tumors besides causing DNA injury. The complexes could covalently conjugate to DNA and induce mitochondria-mediated apoptosis via Bcl-2/Bax/caspase3 signaling. The EMT process was remarkably inhibited by suppressing the Wnt/ß-catenin pathway, reversing the inflammatory tumor microenvironment, and inhibiting the HIF-1α pathway, which further resulted in the inhibited angiogenesis in tumors. Moreover, the antitumor immunity was elevated by blocking immune checkpoints PD-L1 and CD47 accompanied by the improvement of CD3+ and CD8+ T lymphocytes and the macrophage polarization from M2- toward M1-type simultaneously in tumors.

METTL3-mediated N6-methyladenosine modification of STAT5A promotes gastric cancer progression by regulating KLF4.

N6-methyladenosine (m6A) is the predominant post-transcriptional RNA modification in eukaryotes and plays a pivotal regulatory role in various aspects of RNA fate determination, such as mRNA stability, alternative splicing, and translation. Dysregulation of the critical m6A methyltransferase METTL3 is implicated in tumorigenesis and development. Here, this work showed that METTL3 is upregulated in gastric cancer tissues and is associated with poor prognosis. METTL3 methylates the A2318 site within the coding sequence (CDS) region of STAT5A. IGF2BP2 recognizes and binds METTL3-mediated m6A modification of STAT5A through its GXXG motif in the KH3 and KH4 domains, leading to increased stability of STAT5A mRNA. In addition, both METTL3 and IGF2BP2 are positively correlated with STAT5A in human gastric cancer tissue samples. Helicobacter pylori infection increased the expression level of METTL3 in gastric cancer cells, thereby leading to the upregulation of STAT5A. Functional studies indicated that STAT5A overexpression markedly enhances the proliferation and migration of GC cells, whereas STAT5A knockdown has inhibitory effects. Further nude mouse experiments showed that STAT5A knockdown effectively inhibits the growth and metastasis of gastric cancer in vivo. Moreover, as a transcription factor, STAT5A represses KLF4 transcription by binding to its promoter region. The overexpression of KLF4 can counteract the oncogenic impact of STAT5A. Overall, this study highlights the crucial role of m6A in gastric cancer and provides potential therapeutic targets for gastric cancer.

An ultra-deep TSV technique enabled by the dual catalysis-based electroless plating of combined barrier and seed layers.

Silicon interposers embedded with ultra-deep through-silicon vias (TSVs) are in great demand for the heterogeneous integration and packaging of opto-electronic chiplets and microelectromechanical systems (MEMS) devices. Considering the cost-effective and reliable manufacturing of ultra-deep TSVs, the formation of continuous barrier and seed layers remains a crucial challenge to solve. Herein, we present a novel dual catalysis-based electroless plating (ELP) technique by tailoring polyimide (PI) liner surfaces to fabricate dense combined Ni barrier/seed layers in ultra-deep TSVs. In additional to the conventional acid catalysis procedure, a prior catalytic step in an alkaline environment is proposed to hydrolyze the PI surface into a polyamide acid (PAA) interfacial layer, resulting in additional catalysts and the formation of a dense Ni layer that can function as both a barrier layer and a seed layer, particularly at the bottom of the deep TSV. TSVs with depths larger than 500 µm and no voids are successfully fabricated in this study. The fabrication process involves low costs and temperatures. For a fabricated 530-µm-deep TSV with a diameter of 70 µm, the measured depletion capacitance and leakage current are approximately 1.3 pF and 1.7 pA at 20 V, respectively, indicating good electrical properties. The proposed fabrication strategy can provide a cost-effective and feasible solution to the challenge of manufacturing ultra-deep TSVs for modern 3D heterogeneous integration and packaging applications.

Small Feature-Size Transistors Based on Low-Dimensional Materials: From Structure Design to Nanofabrication Techniques.

For several decades after Moore's Law is proposed, there is a continuous effort to reduce the feature-size of transistors. However, as the size of transistors continues to decrease, numerous challenges and obstacles including severe short channel effects (SCEs) are emerging. Recently, low-dimensional materials have provided new opportunities for constructing small feature-size transistors due to their superior electrical properties compared to silicon. Here, state-of-the-art low-dimensional materials-based transistors with small feature-sizes are reviewed. Different from other works that mainly focus on material characteristics of a specific device structure, the discussed topics are utilizing device structure design including vertical structure and nano-gate structure, and nanofabrication techniques to achieve small feature-sizes of transistors. A comprehensive summary of these small feature-size transistors is presented by illustrating their operation mechanism, relevant fabrication processes, and corresponding performance parameters. Besides, the role of small feature-size transistors based on low-dimensional materials in further reducing the small footprint is also clarified and their cutting-edge applications are highlighted. Finally, a comparison and analysis between state-of-art transistors is made, as well as a glimpse into the future research trajectory of low dimensional materials-based small feature-size transistors is briefly outlined.

Mitral Geometry on the Mechanism of Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy.

OBJECTIVE: The mechanism of left ventricular outflow tract obstruction (LVOTO) is complex in hypertrophic cardiomyopathy (HCM). We aimed to evaluate the impact of mitral valve geometry on LVOTO by echocardiography. MATERIALS AND METHODS: The study population comprised 177 consecutive patients with HCM. Morphological findings of left ventricular hypertrophy and LVOTO-related abnormalities were assessed by comprehensive transthoracic echocardiography. Aortomitral angle, mitral leaflet length, and coaptation height were measured and analyzed at rest. Multivariable stepwise forward logistic regression analysis was performed to identify geometric predictors of LVOTO. RESULTS: One hundred thirty-seven patients had an LVOT gradient ≥30 mm Hg. Multivariable logistic regression showed that aortomitral angle (odds ratio [OR], 0.89; 95% CI, 0.83-0.95, P < .001), coaptation height (OR, 1.96; 95% CI, 1.41-2.72, P < .001), and accessory mitral valve chordae tendineae (OR, 13.1; 95% CI, 4.32-39.95; P < .001) were independently associated with LVOTO. Receiver operating characteristic analysis showed that the area under the curve of mitral coaptation height was higher (area under the curve = 0.815) than the other 2 indicators (P < .05). CONCLUSION: Mitral coaptation height, aortomitral angle, and accessory mitral valve chordae tendineae were important predictors of SAM and LVOTO in HCM independent of septal hypertrophy.

In-situ synthesized MgIn2S4/CdWO4 type-II heterojunction as a light-driven photoelectrochemical sensor for ultrasensitive detection of catechol in environmental water samples.

As an essential chemical intermediate, catechol (CC) residues may have adverse effects on human health. Herein, an effective and facile photoelectrochemical sensor platform based on MgIn2S4/CdWO4 composite is constructed for monitoring CC. MgIn2S4 increases light absorption range and activity, while CdWO4 enhances photoelectronic stability, and the type-II heterojunction formed can significantly enhance photocurrent response. Due to the autoxidation process, CC is converted into oligomeric products, which increase the spatial site resistance and attenuate the overall photocurrent response. It is worth noting that the cauliflower-like structure of MgIn2S4 can provide a large specific surface area, and the presence of Mg2+ promotes autoxidation, thus providing a suitable condition for detecting CC. Under optimal conditions, the MgIn2S4/CdWO4/GCE photoelectrochemical sensor has a prominent linear relationship in the range of CC concentration from 2 nM to 7 µM, with a limit of detection of 0.27 nM. With satisfactory selectivity, excellent stability, and remarkable reproducibility, this sensor provides a crucial reference value for effectively and rapidly detecting pollutants in environmental water samples.

Conductive MXene/Polymer Composites for Transparent Flexible Supercapacitors.

Transparent flexible energy storage devices are limited by the trade-off among flexibility, transparency, and charge storage capability of their electrode materials. Conductive polymers are intrinsically flexible, but limited by small capacitance. Pseudocapacitive MXene provides high capacitance, yet their opaque and brittle nature hinders their flexibility and transparency. Herein, the development of synergistically interacting conductive polymer Ti3C2Tx MXene/PEDOT:PSS composites is reported for transparent flexible all-solid-state supercapacitors, with an outstanding areal capacitance of 3.1 mF cm-2, a high optical transparency of 61.6%, and excellent flexibility and durability. The high capacitance and high transparency of the devices stem from the uniform and thorough blending of PEDOT:PSS and Ti3C2Tx, which is associated with the formation of O─H…O H-bonds in the composites. The conductive MXene/polymer composite electrodes demonstrate a rational means to achieve high-capacity, transparent and flexible supercapacitors in an easy and scalable manner.

Chinese text dual attention network for aspect-level sentiment classification.

English text has a clear and compact subject structure, which makes it easy to find dependency relationships between words. However, Chinese text often conveys information using situational settings, which results in loose sentence structures, and even most Chinese comments and experimental summary texts lack subjects. This makes it challenging to determine the dependency relationship between words in Chinese text, especially in aspect-level sentiment recognition. To solve this problem faced by Chinese text in the field of sentiment recognition, a Chinese text dual attention network for aspect-level sentiment recognition is proposed. First, Chinese syntactic dependency is proposed, and sentiment dictionary is introduced to quickly and accurately extract aspect-level sentiment words, opinion extraction and classification of sentimental trends in text. Additionally, in order to extract context-level features, the CNN-BILSTM model and position coding are also introduced. Finally, to better extract fine-grained aspect-level sentiment, a two-level attention mechanism is used. Compared with ten advanced baseline models, the model's capabilities are being further optimized for better performance, with Accuracy of 0.9180, 0.9080 and 0.8380 respectively. This method is being demonstrated by a vast array of experiments to achieve higher performance in aspect-level sentiment recognition in less time, and ablation experiments demonstrate the importance of each module of the model.

Boosting the Faraday Efficiency of Electrochemical Ammonia Synthesis via the Strain Effect Induced by Interfacial Hybrid Formation between BN and Carbon Nanotubes.

The electrochemical nitrogen reduction reaction (eNRR) is a highly promising alternative to the Haber-Bosch (H-B) process, but its commercial development is limited by the high bond energy of N2 molecules and the presence of the competitive hydrogen evolution reaction (HER). Here, a metal-free composite electrocatalyst of boron nitride (h-BNNs) and carbon nanotubes (CNTs) was explored through the interfacial hybridization of h-BNNs and CNTs, which showed a highly improved eNRR Faraday efficiency (FE) of 63.9% and an NH3 yield rate of 36.5 µg h-1 mgcat.-1 at -0.691 V (vs RHE). New chemical bonds of C-B and C-N were observed, indicating a strong interaction between CNTs and h-BNNs. According to the Raman spectra and the optimized model of h-BNNs/CNTs, an obvious strain effect between h-BNNs and CNTs was supposed to play a significant role in the highly improved FE, compared with the FE of h-BNNs alone (4.7%). Density functional theory (DFT) calculations further showed that h-BNNs/CNTs had lower energy barriers in eNRR, giving them higher N2 to NH3 selectivity, while h-BNNs have lower energy barriers in the HER. This work shows the important role of the strain effect in boosting the selectivity in the eNRR process.

Modern techniques in addressing facial acne scars: A thorough analysis.

BACKGROUND: Facial acne scars are a prevalent concern, leading to the development of various treatment modalities. OBJECTIVES: This review aims to explore the latest advancements in the treatment of facial acne scars, focusing on both surgical and non-surgical methods. METHODS: The non-surgical treatments reviewed include topical medications (such as retinoids and alpha hydroxy acids) and non-invasive procedures (like microdermabrasion and chemical peels). Surgical options discussed are punch excision, subcision, and fractional laser treatments. RESULTS: Combination therapy, integrating both surgical and non-surgical approaches, is frequently utilized to achieve optimal results in scar improvement. CONCLUSION: Recent advancements in the treatment of facial acne scars provide promising options for individuals seeking improvement. However, these treatments have associated risks and potential adverse effects, highlighting the importance of consulting a dermatologist before beginning any treatment regimen.

Multilayer Ti3C2-CNTs-Au Loaded with Cyclodextrin-MOF for Enhanced Selective Detection of Rutin.

In this work, multi-layer Ti3C2 - carbon nanotubes - gold nanoparticles (Ti3C2-CNTs-Au) and cyclodextrin metal-organic framework - carbon nanotubes (CD-MOF-CNTs) have been prepared by in situ growth method and used to construct the ultra-sensitive rutin electrochemical sensor for the first time. Among them, the large number of metal active sites of Ti3C2, the high electron transfer efficiency of CNTS, and the good catalytic properties of AuNPs significantly enhance the electrochemical properties of the composite carbon nanomaterials. Interestingly, CD-MOF has a unique host-guest recognition and a large number of cavities, molecular gaps, and surface reactive groups, which gives the composite outstanding accumulation properties and selectivity for rutin. Under the optimized conditions, the constructed novel sensor has satisfactory detection performance for rutin in the range of 2 × 10-9 to 8 × 10-7 M with a limit of detection of 6.5 × 10-10 M. In addition, the sensor exhibits amazing anti-interference performance against rutin in some flavonoid compounds and can be used to test natural plant samples (buckwheat, Cymbopogon distans, and flos sophorae immaturus). This work has promising applications in the field of environmental and food analysis, and exploring new directions for the application of Mxene-based composites.

Transformer guided self-adaptive network for multi-scale skin lesion image segmentation.

BACKGROUND: In recent years, skin lesion has become a major public health concern, and the diagnosis and management of skin lesions depend heavily on the correct segmentation of the lesions. Traditional convolutional neural networks (CNNs) have demonstrated promising results in skin lesion segmentation, but they are limited in their ability to capture distant connections and intricate features. In addition, current medical image segmentation algorithms rarely consider the distribution of different categories in different regions of the image and do not consider the spatial relationship between pixels. OBJECTIVES: This study proposes a self-adaptive position-aware skin lesion segmentation model SapFormer to capture global context and fine-grained detail, better capture spatial relationships, and adapt to different positional characteristics. The SapFormer is a multi-scale dynamic position-aware structure designed to provide a more flexible representation of the relationships between skin lesion characteristics and lesion distribution. Additionally, it increases skin lesion segmentation accuracy and decreases incorrect segmentation of non-lesion areas. INNOVATIONS: SapFormer designs multiple hybrid transformers for multi-scale feature encoding of skin images and multi-scale positional feature sensing of the encoded features using a transformer decoder to obtain fine-grained features of the lesion area and optimize the regional feature distribution. The self-adaptive feature framework, built upon the transformer decoder module, dynamically and automatically generates parameterizations with learnable properties at different positions. These parameterizations are derived from the multi-scale encoding characteristics of the input image. Simultaneously, this paper utilizes the cross-attention network to optimize the features of the current region according to the features of other regions, aiming to increase skin lesion segmentation accuracy. MAIN RESULTS: The ISIC-2016, ISIC-2017, and ISIC-2018 datasets for skin lesions are used as the basis for the experiment. On these datasets, the proposed model has accuracy values of 97.9 %, 94.3 %, and 95.7 %, respectively. The proposed model's IOU values are, in order, 93.2 %, 86.4 %, and 89.4 %. The proposed model's DSC values are 96.4 %, 92.6 %, and 94.3 %, respectively. All three metrics surpass the performance of the majority of state-of-the-art (SOTA) models. SapFormer's metrics on these datasets demonstrate that it can precisely segment skin lesions. Notably, our approach exhibits remarkable noise resistance in non-lesion areas, while simultaneously conducting finer-grained regional feature extraction on the skin lesion image. CONCLUSIONS: In conclusion, the integration of a transformer-guided position-aware network into semantic skin lesion segmentation results in a notable performance boost. The ability of our proposed network to capture spatial relationships and fine-grained details proves beneficial for effective skin lesion segmentation. By enhancing lesion localization, feature extraction, quantitative analysis, and classification accuracy, the proposed segmentation model improves the diagnostic efficiency of skin lesion analysis on dermoscopic images. It assists dermatologists in making more accurate and efficient diagnoses, ultimately leading to better patient care and outcomes. This research paves the way for advances in diagnosing and treating skin lesions, promoting better understanding and decision-making in the clinical setting.

Series of Desloratadine Platinum(IV) Hybrids Displaying Potent Antimetastatic Competence by Inhibiting Epithelial-Mesenchymal Transition and Arousing Immune Response.

Metastasis is the major obstacle to the survival of cancer patients. Herein, a series of new desloratadine platinum(IV) conjugates with promising antiproliferative and antimetastatic activities were developed and evaluated. The candidate complex caused significant DNA damage and stimulated mitochondrial apoptosis through the Bcl-2/Bax/caspase3 pathway. Then, it suppressed the epithelial-mesenchymal transition (EMT) process in tumors effectively through NMT-1/HPCAL1 and ß-catenin signaling. Subsequently, the angiogenesis was inhibited with the downregulation of key proteins HIF-1α, VEGFA, MMP-9, and CD34. Moreover, the antitumor immunity was effectively aroused by the synergism of EMT reversion and decrease of the histamine level; then, the macrophage polarization from M2- to M1-type and the increase of CD4+ and CD8+ T cells were triggered simultaneously in tumors.

Ubiquitin-specific Protease 35 Promotes Gastric Cancer Metastasis by Increasing the Stability of Snail1.

Deubiquitinase (DUB) dysregulation is closely associated with multiple diseases, including tumors. In this study, we used data from The Cancer Genome Atlas and Gene Expression Omnibus databases to analyze the expression of 51 ubiquitin-specific proteases (USPs) in gastric cancer (GC) tissues and adjacent non-neoplastic tissues. The Kaplan-Meier Plotter database was used to analyze the association of the differentially expressed USPs with the overall survival of patients with GC. The results showed that five USPs (USP5, USP10, USP13, USP21, and USP35) were highly expressed in GC tissues and were associated with poor prognosis in patients with GC. Because the epithelial-mesenchymal transition enables epithelial cells to acquire mesenchymal features and contributes to poor prognosis, we investigated whether these USPs had regulatory effects on the key epithelial-mesenchymal transition transcription factor Snail1. Our results showed that USP35 exhibited the most significant regulation on Snail1. Overexpression of USP35 increased and its knockdown decreased Snail1 protein levels. Mechanistically, USP35 interacted with Snail1 and removed its polyubiquitinated chain, thereby increasing its stability. Furthermore, USP35 promoted the invasion and migration of GC cells depending on its DUB activity. USP35 knockdown exhibited the opposite effect. Snail1 depletion partially abrogated the biological effects of USP35. Experiments using nude mouse tail vein injections indicated that wild-type USP35, but not the catalytically inactive USP35-C450A mutant, dramatically enhanced cell colonization and tumorigenesis in the lungs of mice. In addition, USP35 positively correlated with Snail1 expression in clinical GC tissues. Helicobacter pylori infection increased USP35 and Snail1 expression levels. Altogether, we found that USP35 can deubiquitinate Snail1 and increase its expression, thereby contributing to the malignant progression of GC. Therefore, USP35 may serve as a viable target for GC treatment.

Exogenous drug-induced mouse models of atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense pruritus. AD is harmful to both children and adults, but its pathogenic mechanism has yet to be fully elucidated. The development of mouse models for AD has greatly contributed to its study and treatment. Among these models, the exogenous drug-induced mouse model has shown promising results and significant advantages. Until now, a large amount of AD-related research has utilized exogenous drug-induced mouse models, leading to notable advancements in research. This indicates the crucial significance of applying such models in AD research. These models exhibit diverse characteristics and are highly complex. They involve the use of various strains of mice, diverse types of inducers, and different modeling effects. However, there is currently a lack of comprehensive comparative studies on exogenous drug-induced AD mouse models, which hinders researchers' ability to choose among these models. This paper provides a comprehensive review of the features and mechanisms associated with various exogenous drug-induced mouse models, including the important role of each cytokine in AD development. It aims to assist researchers in quickly understanding models and selecting the most suitable one for further investigation.