Photo-thermal waxgels with fast wax layer regeneration ability for anti-icing.

Waxgels are known for their unique ability to generate sacrificial wax layers during anti-icing. To address the severe slow regrowth of the wax layer, here, carbon black is incorporated in the waxgel network to endow photothermal function. The rate of the regrowth of the wax layer is raised by >6 times under natural light conditions. Meanwhile, the photothermal waxgel showed improved anti-icing performances in terms of delayed ice formation and lower ice adhesion strength.

Characterization the prognosis role and effects of snoRNAs in melanoma patients.

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.

Comprehensive analysis of cuproptosis-related long non-coding RNAs in prognosis, immune microenvironment infiltration and chemotherapy response of hepatocellular carcinoma.

The objective of this study is to explore the relationship between cuproptosis-related long noncoding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). RNA-seq data, including lncRNAs and related clinical information of HCC patients, were downloaded from The Cancer Genome Atlas database. A signature composed 3 cuproptosis-related lncRNAs was constructed by LASSO analysis, and HCC patients were classified into high- and low-risk groups. Patients in the high-risk group had a poorer prognosis compared with the low-risk group. Univariate Cox and multivariate Cox regression analyses confirmed that the signature model was an independent risk factor compared to other clinical biomarkers. Furthermore, gene set enrichment analysis indicated that metabolism-related pathways were enriched in low-risk group, including drug metabolism, and fatty acid metabolism. Further research demonstrated that there were markedly differences in drug response between the high- and low-risk group. Immune related analysis showed that the most type of immune cells and immunological function in the high-risk group were different with the risk-group. Finally, TP53 mutation rate and the tumor mutational burden in the high-risk group were higher compared with the low-risk group. In conclusion, we constructed a prognostic signature based on the expression of cuproptosis-related lncRNAs to predict HCC patients' prognosis, drug response and immune microenvironment, and further research will be conducted to uncover the mechanisms.

The romantic history of signaling pathway discovery in cell death: an updated review.

Cell death is a fundamental physiological process in all living organisms. Processes such as embryonic development, organ formation, tissue growth, organismal immunity, and drug response are accompanied by cell death. In recent years with the development of electron microscopy as well as biological techniques, especially the discovery of novel death modes such as ferroptosis, cuprotosis, alkaliptosis, oxeiptosis, and disulfidptosis, researchers have been promoted to have a deeper understanding of cell death modes. In this systematic review, we examined the current understanding of modes of cell death, including the recently discovered novel death modes. Our analysis highlights the common and unique pathways of these death modes, as well as their impact on surrounding cells and the organism as a whole. Our aim was to provide a comprehensive overview of the current state of research on cell death, with a focus on identifying gaps in our knowledge and opportunities for future investigation. We also presented a new insight for macroscopic intracellular survival patterns, namely that intracellular molecular homeostasis is central to the balance of different cell death modes, and this viewpoint can be well justified by the signaling crosstalk of different death modes. These concepts can facilitate the future research about cell death in clinical diagnosis, drug development, and therapeutic modalities.

Benzylisoquinoline alkaloids inhibit lung fibroblast activation mainly via inhibiting TGF-ß1/Smads and ERK1/2 pathway proteins.

Backgrounds: Liensinine (Lien), Neferine (Nef), Isoliensinine (Iso) and Tetrandrine (Tet), benzylisoquinoline alkaloids (BIAs), have been shown inhibitory effects on pulmonary fibrosis (PF) through anti-inflammatory, anti-oxidative activities, inhibition of cytokines and NF-κB. Effects of other similar BIAs, Dauricine (Dau), Papaverine (Pap) and lotusine (Lot), on PF remain unclear. Here, we explored the effects of five bisbenzylisoquinoline (Lien, Nef, Iso, Tet and Dau) and two monobenzylisoquinoline (Pap, Lot) alkaloids on normal and PF fibroblasts. Methods: Primary normal and PF lung fibroblasts were cultured and treated with these alkaloids. Proliferation, activation, migration and apoptosis changes were detected by MTT, wound healing assay, flow cytometry. Protein level was analyzed by Western blot. Results: All BIAs inhibited proliferation of normal and PF lung fibroblasts induced by TGF-ß. α-SMA protein level in normal and PF lung fibroblasts decreased after Lien, Nef, Iso, Tet and Dau treatment. Pap and Lot had no influence on α-SMA expression. Dau showed the strongest inhibitory effects on proliferation and activation among alkaloids. The migration rates of normal and PF lung fibroblasts were inhibited by Lien, Nef, Iso, and Dau. Lien, Nef, Iso and Dau significantly promoted apoptosis, while Tet had no effect on apoptosis. Pap and Lot had no influence on activation, migration and apoptosis. Dau significantly inhibited Smad3/4 and p-ERK1/2 protein overexpression induced by TGF-ß1. Conclusions: Bisbenzylisoquinoline alkaloids had stronger effects on inhibiting lung fibroblasts than monobenzylisoquinoline alkaloids. Dau expressed the strongest inhibitory effects, which may be related to its inhibition of TGF-ß1/Smad3/4 and p-ERK1/2 pathway proteins.

Establishment of a Necroptosis-Related Prognostic Signature to Reveal Immune Infiltration and Predict Drug Sensitivity in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a common type of primary liver cancer and has a poor prognosis. In recent times, necroptosis has been reported to be involved in the progression of multiple cancers. However, the role of necroptosis in HCC prognosis remains elusive. Methods: The RNA-seq data and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Differentially expressed genes (DEGs) and prognosis-related genes were explored, and the nonnegative matrix factorization (NMF) clustering algorithm was applied to divide HCC patients into different subtypes. Based on the prognosis-related DEGs, univariate Cox and LASSO Cox regression analyses were used to construct a necroptosis-related prognostic model. The relationship between the prognostic model and immune cell infiltration, tumor mutational burden (TMB), and drug response were explored. Results: In this study, 13 prognosis-related DEGs were confirmed from 18 DEGs and 24 prognostic-related genes. Based on the prognosis-related DEGs, patients in the TCGA cohort were clustered into three subtypes by the NMF algorithm, and patients in C3 had better survival. A necroptosis-related prognostic model was established according to LASSO analysis, and HCC patients in TCGA and ICGC were divided into high- and low-risk groups. Kaplan-Meier (K-M) survival analysis revealed that patients in the high-risk group had a shorter survival time compared to those in the low-risk group. Using univariate and multivariate Cox analyses, the prognostic model was identified as an independent prognostic factor and had better survival predictive ability in HCC patients compared with other clinical biomarkers. Furthermore, the results revealed that the high-risk patients had higher stromal, immune, and ESTIMATE scores; higher TP53 mutation rate; higher TMB; and lower tumor purities compared to those in the low-risk group. In addition, there were significant differences in predicting the drug response between the high- and low-risk groups. The protein and mRNA levels of these prognostic genes were upregulated in HCC tissues compared to normal liver tissues. Conclusion: We established a necroptosis-related prognostic signature that may provide guidance for individualized drug therapy in HCC patients; however, further experimentation is needed to validate our results.

PDE4D binds and interacts with YAP to cooperatively promote HCC progression.

The role of cAMP in the development of hepatocellular carcinoma (HCC) is controversial and the biological function of cAMP-hydrolysing enzyme phosphodiesterase 4D (PDE4D) in HCC remains unclear. In this study, we observed markedly higher PDE4D expression in HCC patients with poor survival. PDE4D bound to yes-associated protein (YAP), and PDE4D expression positively correlated with YAP expression in HCC. Overexpression of PDE4D increased YAP dephosphorylation and activity and promoted HCC cell growth in vitro and in vivo, which was attenuated by the YAP inhibitor verteporfin. In contrast, silencing PDE4D reduced YAP expression and HCC cell growth. Notably, forced expression of YAP promoted PDE4D and YAP target gene expression and cell growth, which were abrogated by the PDE4D inhibitor roflumilast. Mechanistically, silencing of YAP caused PDE4D downregulation and HCC cell apoptosis via extracellular signal-regulated kinase (ERK) activation. Roflumilast activated cAMP-PKA signaling and induced cAMP-PKA-dependent YAP phosphorylation at serine 127, resulting in YAP degradation and suppression of HCC growth, which were reversed by the PKA inhibitor PKI. Additionally, transfection of the YAP-S127A mutant reversed roflumilast-mediated suppression of YAP and cell growth. Taken together, our findings indicate that PDE4D binds to and interacts with YAP to promote HCC progression. Targeting the PDE4D-YAP interaction with roflumilast may be an effective strategy for HCC treatment.

Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice.

Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and γδT cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, γδT and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.

Role of canonical transient receptor potential channel-3 in acetylcholine-induced mouse airway smooth muscle cell proliferation.

AIMS: Canonical transient receptor potential channel-3 (TRPC3)-encoded Ca2+-permeable nonselective cation channel (NSCC) has been proven to be an important native constitutively active channel in airway smooth muscle cell (ASMC), which plays significant roles in physiological and pathological conditions by controlling Ca2+ homeostasis in ASMC. Acetylcholine (ACh) is generally accepted as a contractile parasympathetic neurotransmitter in the airway. Recently studies have revealed the pathological role of ACh in airway remodeling, however, the mechanisms remain unclear. Here, we investigated the role of TRPC3 in ACh-induced ASMC proliferation. MATERIALS AND METHODS: Primary mouse ASMCs were cultured with or without ACh treatment, then cell viability, TRPC3 expression, NSCC currents and [Ca2+]i changes were examined by MTT assay, cell counting, Western blotting, standard whole-cell patch clamp recording and calcium imaging, respectively. Small interfering RNA (siRNA) technology was used to confirm the contribution of TRPC3 to ACh-induced ASMC proliferation. KEY FINDINGS: TRPC3 blocker Gd3+, antibody or siRNA largely inhibited ACh-induced up-regulation of TRPC3 protein, enhancement of NSCC currents, resting [Ca2+]i and KCl-induced changes in [Ca2+]i, eventually inhibiting ACh-induced ASMC proliferation. SIGNIFICANCE: Our data suggested ACh could induce ASMC proliferation, and TRPC3 may be involved in ACh-induced ASMC proliferation that occurs with airway remodeling.

TRPC3-mediated Ca(2+) entry contributes to mouse airway smooth muscle cell proliferation induced by lipopolysaccharide.

Airway remodeling is a histopathological hallmark of chronic respiratory diseases that includes airway smooth muscle cell (ASMC) proliferation. Canonical transient receptor potential channel-3 (TRPC3)-encoded nonselective cation channels (NSCCs) are important native constitutively active channels that play significant roles in physiological and pathological conditions in ASMCs. Lipopolysaccharides (LPSs), known as lipoglycans and endotoxin, have been proven to be inducers of airway remodeling, though the mechanisms remain unclear. We hypothesized that TRPC3 is important in LPS-induced airway remodeling by regulating ASMC proliferation. To test this hypothesis, mouse ASMCs were cultured with or without LPS for 48h. Cell viability, TRPC3 protein expression, NSCC currents and changes in intracellular calcium concentration ([Ca(2+)]i) were then analyzed using an MTT assay, western blotting, whole-cell patch clamp and calcium imaging, respectively. The results showed that LPS treatment significantly induced ASMC proliferation, up-regulation of TRPC3 protein expression and enhancement of NSCC currents, resting [Ca(2+)]i and ACh-elicited changes in [Ca(2+)]i. TRPC3 blocker Gd(3+), TRPC3 blocking antibody or TRPC3 gene silencing by siRNA significantly inhibited LPS-induced up-regulation of TRPC3 protein, enhancement of NSCC currents, resting [Ca(2+)]i and ACh-elicited changes in [Ca(2+)]i, eventually inhibiting LPS-induced ASMCproliferation. These results demonstrated that TRPC3-mediated Ca(2+) entry contributed to LPS-induced ASMC proliferation and identified TRPC3 as a possible key target in airway remodeling intervention.

[Value of 16-slice spiral CT in the diagnosis of tumor-like bronchial tuberculosis].

OBJECTIVE: To evaluate the value of 16-slice multi-detector CT (MDCT) in the diagnosis of tumor-like bronchial tuberculosis. METHODS: Twenty-five patients with tumor-like bronchial tuberculosis underwent 16-slice CT scanning and the CT data were analyzed. RESULTS: Tumor-like bronchial tuberculosis were classified into 4 types according to the imaging features, namely intra-lumen nodule, intra-lumen mass, compression from outside of the bronchial lumens, and lung hilum mass. Tumor-like bronchial tuberculosis was featured by irregular bronchial wall thickening which led to decreased internal diameter of the bronchi with the external diameter remaining unchanged, ring-shaped enhancement, and absence of clear boundaries between the lesion and normal bronchi. CONCLUSION: 16-slice MDCT can be advantageous in displaying tumor-like bronchial tuberculosis, and axial scan with 16-slice spiral CT combined with image reconstruction allows detection of the lesions inside the trachea and bronchus.