Efficient ultraviolet blocking film on the lignin-rich lignocellulosic nanofibril from bamboo.

The ultraviolet (UV) blocking performance of current bio-based devices is always limited by delignification and exploited chemical treatment. Lignocellulosic nanofibril (LCNF) is a promising green alternative that could efficiently impede UV radiation. Herein, we proposed a robust LCNF film that achieved 99.8 ± 0.19 % UVB blocking, 96.1 ± 0.23 % UVA blocking, and was highly transparent without complex chemical modification. Compared to conventional lignin composites, this LCNF method involves 29.5 ± 2.31 % lignin content directly extracted from bamboo as a broad-spectrum sun blocker. This bamboo-based LCNF film revealed an excellent tensile strength of 94.9 ± 3.6 MPa and outstanding stability, adapting to the natural environment's variability. The residual hemicellulose could also embed the link between lignin and cellulose, confirming high lignin content in the network. The connection between lignin and hemicelluloses in the cellulose network was explored and described for the fibrillation of lignocellulosic nanofibrils. This research highlights the promising development of LCNFs for UV protection and bio-based solar absorption materials.

Muscle-inspired anisotropic carboxymethyl cellulose-based double-network conductive hydrogels for flexible strain sensors.

Conductive hydrogels are considered one of the most promising materials for preparing flexible sensors due to their flexible and extensible properties. However, conventional hydrogels' weak mechanical and isotropic properties are greatly limited in practical applications. Here, the internal structure of the hydrogel was regulated by pre-stretching synergistic ion crosslinking to construct a carboxymethyl cellulose-based double network-oriented hydrogel similar to muscle. The introduction of pre-stretching increased the tensile strength of the double-network hydrogel from 1.45 MPa to 4.32 MPa, and its light transmittance increased from 67.3 % to 84.5 %. In addition, the hydrogel's thermal stability and electrical conductivity were improved to a certain extent. Its good mechanical properties and conductive properties can be converted into stable electrical signal output during deformation. The carboxymethyl cellulose-based double network oriented hydrogels were further assembled as flexible substrates into flexible sensor devices. The hydrogel sensors can monitor simple joint movements as well as complex spatial movements, which makes them have potential application value in the research field of intelligent response electronic devices such as flexible wearables, intelligent strain sensing, and soft robots.

Discovery of Pyrimidinediamine Derivatives as Potent Methuosis Inducers for the Treatment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a leading malignancy among women that currently lack effective targeted therapeutic agents, and the limitations of treatment have prompted the emergence of new strategies. Methuosis is a novel vacuole-presenting cell death modality that promotes tumor cell death. Hence, a series of pyrimidinediamine derivatives were designed and synthesized through evaluation of their abilities that inhibit proliferation as well as induce methuosis against TNBC cells. Among them, JH530 showed excellent anti-proliferative activities and vacuolization capacity in TNBC. The mechanism research indicated that JH530 caused cell death through inducing methuosis of cancer cells. Furthermore, JH530 inhibited tumor growth remarkably in the HCC1806 xenograft model without an apparent decrease in body weight. Overall, JH530 is a methuosis inducer that displayed remarkable suppression of TNBC growth in vitro and in vivo, which provides a basis for the future progress of more small molecules for TNBC treatment.

A novel methuosis inducer DZ-514 possesses antitumor activity via activation of ROS-MKK4-p38 axis in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most malignant tumors with poor prognosis. Methuosis is a new type of nonapoptotic cell death characterized by the accumulation of cytoplasmic vacuoles. In this study, we synthesized and screened a series of N-phenyl-4-pyrimidinediamine derivatives in TNBC cells, finding that DZ-514 was the best compound with high toxicity independent of the inhibition of BCL6. DZ-514 decreased cell viability, inhibited cell cycle progression, and induced caspase-independent cell death in TNBC cells. Interestingly, DZ-514 induced cytoplasm vacuolation, which could be blocked by Baf A1, the V-ATPase inhibitor. Furthermore, we found that DZ-514-induced vacuoles were derived from macropinosomes rather than autophagosomes. Most importantly, methuosis induced by DZ-514 was partially mediated by activating the ROS-MKK4-p38 axis. Finally, we demonstrated that DZ-514 significantly inhibited tumor growth in an HCC1806 xenograft mouse model. These findings revealed that the novel methuosis inducer DZ-514 could be developed for TNBC treatment.

RNF126-Mediated MRE11 Ubiquitination Activates the DNA Damage Response and Confers Resistance of Triple-Negative Breast Cancer to Radiotherapy.

Triple-negative breast cancer (TNBC) has higher molecular heterogeneity and metastatic potential and the poorest prognosis. Because of limited therapeutics against TNBC, irradiation (IR) therapy is still a common treatment option for patients with lymph nodes or brain metastasis. Thus, it is urgent to develop strategies to enhance the sensitivity of TNBC tumors to low-dose IR. Here, the authors report that E3 ubiquitin ligase Ring finger protein 126 (RNF126) is important for IR-induced ATR-CHK1 pathway activation to enhance DNA damage repair (DDR). Mechanistically, RNF126 physically associates with the MRE11-RAD50-NBS1 (MRN) complex and ubiquitinates MRE11 at K339 and K480 to increase its DNA exonuclease activity, subsequent RPA binding, and ATR phosphorylation, promoting sustained DDR in a homologous recombination repair-prone manner. Accordingly, depletion of RNF126 leads to increased genomic instability and radiation sensitivity in both TNBC cells and mice. Furthermore, it is found that RNF126 expression is induced by IR activating the HER2-AKT-NF-κB pathway and targeting RNF126 expression with dihydroartemisinin significantly improves the sensitivity of TNBC tumors in the brain to IR treatment in vivo. Together, these results reveal that RNF126-mediated MRE11 ubiquitination is a critical regulator of the DDR, which provides a promising target for improving the sensitivity of TNBC to radiotherapy.

Lupeol Alleviates Myocardial Ischemia-Reperfusion Injury in Rats by Regulating NF-[Formula: see text]B and Nrf2 Pathways.

Cardiovascular disease is a global health problem. Previous studies revealed that it involves acute myocardial infarction and ischemia-reperfusion (I/R) injury. The mechanism of myocardial I/R injury is complex. But recognizing its mechanisms will bring important clinical significance. Lupeol is widely found in Chinese medicinal herbs and has been shown to have a variety of bio-activities. However, the pharmacological action of lupeol in the progress of myocardial ischemia-reperfusion injury (MIRI) is unclear. This study used a rat myocardial I/R model and the morphological changes in myocardium were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of IL-10, IL-1[Formula: see text], TNF-[Formula: see text], and IL-6 were assessed by quantitative real-time PCR (qRT-PCR) and ELISA. The expression levels of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) level and inflammatory cytokines were quantified using ELISA. The cellular apoptotic rate was determined by TUNEL staining. The findings showed that lupeol significantly decreased myocardial infarction after I/R and ameliorated I/R-induced myocardial inflammation, apoptosis, and oxidative stress. Furthermore, our results suggested that lupeol protected against MIRI-induced myocardial infarction through modulation of NF-[Formula: see text]B and Nrf2 signaling pathways. In summary, this study first clarified the cardioprotective effects of lupeol against I/R-induced myocardial infarction in rats, which could be due to its anti-oxidant, anti-inflammatory, and anti-apoptotic activities. Our study also highlighted a mechanism of NF-[Formula: see text]B and Nrf2 signaling, through which lupeol could be a promising agent in protecting against I/R-induced myocardial infarction.

Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) accounts for approximately 15% of all breast cancer cases, and patients with BLBC have a low survival rate. Our previous study demonstrated that the KLF5 transcription factor promotes BLBC cell proliferation and tumor growth. In this study, we demonstrated that the histone deacetylase inhibitors (HDACi), suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA), increased KLF5 acetylation at lysine 369 (K369), downregulated KLF5 protein expression levels, and decreased cell viability in BLBC cell lines. HDACi target KLF5 for proteasomal degradation by promoting KLF5 protein ubiquitination. K369 acetylation of KLF5 decreases the binding between KLF5 and its deubiquitinase, BAP1. These findings revealed a novel mechanism by which HDACi suppress BLBC, and a novel crosstalk between KLF5 protein acetylation and ubiquitination.

Preparation of PVA-CS/SA-Ca2+ Hydrogel with Core-Shell Structure.

Hydrogels are highly hydrophilic polymers that have been used in a wide range of applications. In this study, we prepared PVA-CS/SA-Ca2+ core-shell hydrogels with bilayer space by cross-linking PVA and CS to form a core structure and chelating SA and Ca2+ to form a shell structure to achieve multiple substance loading and multifunctional expression. The morphology and structure of core-shell hydrogels were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The factors affecting the swelling properties of the hydrogel were studied. The results show that the PVA-CS/SA-Ca2+ hydrogel has obvious core and shell structures. The SA concentration and SA/Ca2+ cross-linking time show a positive correlation with the thickness of the shell structure; the PVA/CS mass ratio affects the structural characteristics of the core structure; and a higher CS content indicates the more obvious three-dimensional network structure of the hydrogel. The optimal experimental conditions for the swelling degree of the core-shell hydrogel were an SA concentration of 5%; an SA/Ca2+ cross-linking time of 90 min; a PVA/CS mass ratio of 1:0.7; and a maximum swelling degree of 50 g/g.

The variation of grain size distribution in rock granular material in seepage process considering the mechanical-hydrological-chemical coupling effect: an experimental research.

As a common solid waste in geotechnical engineering, rock granular material should be properly treated and recycled. Rock granular material often coexists with water when it is used as the filling material in geotechnical engineering. Water flowing in rock granular materials is a complex progress with the mechanical-hydrological-chemical (MHC) coupling effect, i.e. the water scours in the gaps and spaces in the rock granular material structure, produces chemical reactions with rock grains, rock grains squeeze each other under the water pressure and compression leading to re-breakage and producing secondary rock grains, and the fine rock grains are migrated with water and rushed out. In this process, rock grain size distribution (GSD) changes, it affects the physical and mechanical characteristics of the rock granular materials, and even influences the seepage stability of the rock granular materials. To study the variation of GSD in the rock granular material considering the MHC coupling effect after the seepage process, seepage experiments of rock grain samples are carried out and analysed in this paper. The result is expected to have a positive impact on further studies of the properties of the rock granular material.

Myricetin inhibits Kv1.5 channels in HEK293 cells.

Myricetin (Myr) is a flavonoid that exerts anti-arrhythmic effects. However, its potential effects on ion channels have remained elusive. The aim of the present study was to investigate the effects of Myr on Kv1.5 channels in HEK293 cells. The current of Kv1.5 channels (Ikur) in HEK293 cells was recorded using the whole-cell patch-clamp technique and the expression of the Kv1.5 protein was measured using western blot analysis 24 h after treatment with Myr. The results showed that 5 µM Myr significantly reduced Ikur from 215.04 ± 40.59 to 77.72 ± 17.94 pA/pF (P<0.05; n=5). Myr increased the current suppression from 0 to 0.31 ± 0.12 and 0.55 ± 0.11 over 5 or 20 min, respectively. In addition, Ikur decreased from 376.23 ± 1.30 to 270.19 ± 4.28 pA/pF when the frequency was increased from 0.5 to 4 Hz in HEK293 cells treated with 10 µM Myr for 5 min. Furthermore, Myr reduced hKv1.5 protein expression in a dose-dependent manner. These results demonstrated that Myr inhibited Ikur and the expression of hKv1.5 in HEK293 cells in a dose-, time- and frequency-dependent manner. These observations partly explained the mechanisms by which Myr exerts anti-arrhythmic effect.