Dendritic boron and nitrogen doped high-entropy alloy porous carbon fibers for high-efficiency hydrogen evolution reaction.

Among various electrocatalysts, high-entropy alloys (HEAs) have gained significant attention for their unique properties and excellent catalytic activity in the hydrogen evolution reaction (HER). However, the precise synthesis of HEA catalysts in small sizes remains challenging, which limits further improvement in their catalytic performance. In this study, boron- and nitrogen-doped HEA porous carbon nanofibers (HE-BN/PCNF) with an in situ-grown dendritic structure were successfully prepared, inspired by the germination and growth of tree branches. Furthermore, the dendritic fibers constrained the growth of HEA particles, leading to the synthesis of quantum dot-sized (1.67 nm) HEA particles, which also provide a pathway for designing HEA quantum dots in the future. This work provides design ideas and guiding suggestions for the preparation of borated HEA fibers with different elemental combinations and for the application of dendritic nanofibers in various fields.

Alternative splicing events and function in the tumor microenvironment: New opportunities and challenges.

Alternative splicing controls gene expression at the transcriptional level, producing structurally and functionally distinct protein heterodimers. Aberrant alternative splicing greatly affects cell development and plays an important role in the invasion and metastasis of many types of cancer. Recently, it has been shown that alternative splicing can alter the tumor microenvironment and regulate processes such as remodeling, immunity, and inflammation in the tumor microenvironment. However, there is no comprehensive literature review of the complex relationship between alternative splicing and the tumor microenvironment. Therefore, this review aims to collect all the latest data on this topic and provide a new perspective on the therapeutic and potential prognostic markers of cancer.

Over-expression of miR-3584-5p Represses Nav1.8 Channel Aggravating Neuropathic Pain caused by Chronic Constriction Injury.

Nav1.8, a tetrodotoxin-resistant voltage-gated sodium channels (VGSCs) subtype encoded by SCN10A, which plays an important role in the production and transmission of peripheral neuropathic pain signals. Studies have shown that VGSCs may be key targets of MicroRNAs (miRNAs) in the regulation of neuropathic pain. In our study, bioinformatics analysis showed that the targeting relationship between miR-3584-5p and Nav1.8 was the most closely. The purpose of this study was to investigate the roles of miR-3584-5p and Nav1.8 in neuropathic pain. The effects of miR-3584-5p on chronic constriction injury (CCI)-induced neuropathic pain in rats was investigated by intrathecal injection of miR-3584-5p agomir (an agonist, 20 µM, 15 µL) or antagomir (an antagonist, 20 µM, 15 µL). The results showed that over-expression of miR-3584-5p aggravated neuronal injury by hematoxylin-eosin (H&E) staining and mechanical/thermal hypersensitivity in CCI rats. MiR-3584-5p indirectly inhibited the expression of Nav1.8 by up-regulating the expression of key proteins in the ERK5/CREB signaling pathway, and also inhibited the current density of the Nav1.8 channel, changed its channel dynamics characteristic, thereby accelerating the transmission of pain signals, and further aggravating pain. Similarly, in PC12 and SH-SY5Y cell cultures, miR-3584-5p increased the level of reactive oxygen species (ROS) and inhibited mitochondrial membrane potential (Δψm) in the mitochondrial pathway, decreased the ratio of apoptosis-related factor Bcl-2/Bax, and thus promoted neuronal apoptosis. In brief, over-expression of miR-3584-5p aggravates neuropathic pain by directly inhibiting the current density of Nav1.8 channel and altering its channel dynamics, or indirectly inhibiting Nav1.8 expression through ERK5/CREB pathway, and promoting apoptosis through mitochondrial pathway.

EphA10 drives tumor progression and immune evasion by regulating the MAPK/ERK cascade in lung adenocarcinoma.

Backgrounds Lung adenocarcinoma is the most frequent histological type among patients with lung cancer. Ephrin receptor A10 (EphA10), a member of the receptor tyrosine kinase family, has been reported to participate in tumor progression, but its role in lung adenocarcinoma (LUAD) remains unknown. Methods Immunohistochemistry staining and real-time PCR were employed to determine the expression of EphA10 in clinical LUAD samples. EphA10 silencing or overexpression in LUAD cells was achieved by transduction of lentivirus. The effects of EphA10 on LUAD cells were evaluated by CCK-8, EdU staining, flow cytometry, Transwell, and Western blot. The in vivo tumor growth was assessed in the xenograft mice model. Results EphA10 was overexpressed in LUAD tissues. Higher EphA10 expression was observed in the tissues at the advanced tumor stage and was positively correlated with the EGFR. Mechanistically, silencing of EphA10 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition of LUAD cells. Additionally, EphA10 knockdown significantly reduced the PD-L1 expression in LUAD cells and enhanced NK cell-mediated anti-tumor effects. Furthermore, EphA10 activated the MAPK/ERK pathway, and U0126, an inhibitor of MEK, markedly reversed the promoting impacts of EphA10 overexpression on LUAD cells. Consistently, results from subcutaneous tumor xenografts in nude mice confirmed that EphA10 knockdown significantly inhibited tumor growth in vivo. Conclusions This work demonstrates that EphA10 drives tumor progression and immune evasion by regulating the MAPK/ERK cascade in LUAD, implying that EphA10 has the potential to be a therapeutic target in treating LUAD.

Endogenous thrombopoietin promotes non-small-cell lung carcinoma cell proliferation and migration by regulating EGFR signalling.

Thrombopoietin (TPO) is a haematopoietic cytokine mainly produced by the liver and kidneys, which stimulates the production and maturation of megakaryocytes. In the past decade, numerous studies have investigated the effects of TPO outside the haematopoietic system; however, the role of TPO in the progression of solid cancer, particularly lung cancer, has not been well studied. Exogenous TPO does not affect non-small-cell lung cancer (NSCLC) cells as these cells show no or extremely low TPO receptor expression; therefore, in this study, we focused on endogenous TPO produced by NSCLC cells. Immunohistochemical analysis of 150 paired NSCLC and adjacent normal tissues indicated that TPO was highly expressed in NSCLC tissues and correlated with clinicopathological parameters including differentiation, P-TNM stage, lymph node metastasis and tumour size. Suppressing endogenous TPO by small interfering RNA inhibited the proliferation and migration of NSCLC cells. Moreover, TPO interacted with the EGFR protein and delayed ligand-induced EGFR degradation, thus enhancing EGFR signalling. Notably, overexpressing TPO in EGF-stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC.

The lncRNA RHPN1-AS1 downregulation promotes gefitinib resistance by targeting miR-299-3p/TNFSF12 pathway in NSCLC.

Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has exhibited notable clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of gefitinib resistance. The present study aimed to investigate the effects of the long non-coding RNA, RHPN1-AS1 on gefitinib resistance in NSCLC and explore the underlying mechanisms. In this study, RHPN1-AS1 was observed to be downregulated in gefitinib resistant patients and NSCLC cell lines. Besides, decreased expression of RHPN1-AS1 was found to be associated with poor prognosis of NSCLC patients. RHPN1-AS1 knockdown conferred gefitinib resistance to gefitinib sensitive NSCLC cells, whereas the overexpression of RHPN1-AS1 sensitized gefitinib resistant NSCLC cells to gefitinib treatment. Mechanistically, RHPN1-AS1 was found to positively regulate the expression of TNFSF12 by directly interacting with miR-299-3p. Collectively, RHPN1-AS1 modulates gefitinib resistance through miR-299-3p/TNFSF12 pathway in NSCLC. Our findings indicate that RHPN1-AS1 may serve as not only a prognostic biomarker for gefitinib resistance but also as a promising therapeutic biomarker and target for the treatment of NSCLC patients.

[High mobility group box 1 contributes to the endoplasmic reticulum stress of liver in rats with trauma].

OBJECTIVE: To investigate the role of high mobility group box 1 (HMGB1) in hepatic endoplasmic reticulum stress (ERS) in rats with trauma. METHODS: Sixty SPF Sprague-Dawley (SD) rats were randomly divided into groups (n = 6). The rat model of liver injury following traumatic stress was established by continuous compressing the bilateral hind-limbs of rats for 3 hours and then intermittent compressing and decompressing for 30 minutes respectively three times with standard weight of 15 kg. The experiment 1 was divided into two groups: control group and 6, 18, 30 hours after crush. The experiment 2 was divided into control group, crush model group (18 hours after crush), HMGB1 inhibitor sodium butyrate (SB) or ethyl pyruvate (EP) groups, and SB or EP treatment groups (500 mg/kg SB solution or 40 mg/kg EP solution was injected intraperitoneally after 3 hours crush). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were measured with automatic biochemistry analyzer. Histopathological severity of liver injury was assessed by hematoxylin and eosin (HE) staining. The expressions of HMGB1 and ERS-related proteins were detected with Western Blot. The expression and translocation of HMGB1 in liver tissue were evaluated by immuno-histochemical technique. RESULTS: (1) Compared with the control group, the pathological changes of liver injury, the levels of AST and ALT in serum and protein expression of HMGB1 as well as ERS-related proteins such as glucose regulated protein 78 (GRP78), caspase-12, and inositol-requiring enzyme 1α (IRE1α) in liver tissue were significantly increased after traumatic stress, and reached the peak at 18 hours. The expression of C/EBP-homologous protein (CHOP) was increased in a time-dependent manner and peaked at 30 hours after crush. Immunohistochemistry showed that HMGB1 expression increased at 6 hours after crush, some HMGB1 shifted from nucleus to cytoplasm, and the expression was more obvious at 18 hours. (2) Compared with crush model group, the expressions of HMGB1 and ERS-related proteins were significantly decreased following the administration of HMGB1 inhibitors SB or EP (HMGB1/ß-actin: 0.703±0.213, 0.512±0.075 vs. 1.041±0.186; GRP78/ß-actin: 0.614±0.052, 0.450±0.115 vs. 0.847±0.120; caspase-12/ß-actin: 0.636±0.066, 0.812±0.142 vs. 1.086±0.130; CHOP/ß-actin: 0.314±0.046, 0.621±0.123 vs. 0.996±0.764; IRE1α/ß-actin: 0.473±0.033, 0.519±0.094 vs. 0.742±0.054, all P < 0.05), the levels of serum AST and ALT were significantly decreased [AST (U/L): 1 030.50±427.73, 1 414.50±347.86 vs. 2 122.20±322.76; ALT (U/L): 285.75±11.30, 368.50±80.58 vs. 473.80±33.54, all P < 0.01], the degree of acute liver injury was reduced. Only SB or EP could not affect the parameters mentioned above. CONCLUSIONS: HMGB1-ERS pathway was involved in mediating traumatic stress-induced acute liver injury in rats.

Experimental investigation into the oxidation reactivity and nanostructure of particulate matter from diesel engine fuelled with diesel/polyoxymethylene dimethyl ethers blends.

This paper focuses on oxidation reactivity and nanostructural characteristics of particulate matter (PM) emitted from diesel engine fuelled with different volume proportions of diesel/polyoxymethylene dimethyl ethers (PODEn) blends (P0, P10 and P20). PM was collected using a metal filter from the exhaust manifold. The collected PM samples were characterized using thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The TGA results indicated that the PM produced by P20 had the highest moisture and volatility contents and the fastest oxidation rate of solid carbon followed by P10 and P0 derived PM. SEM analysis showed that PM generated from P20 was looser with a lower mean value than PM emitted from P10 and P0. Quantitative analysis of high-resolution TEM images presented that fringe length was reduced along with increased separation distance and tortuosity with an increase in PODEn concentration. These trends improved the oxidation reactivity. According to Raman spectroscopy data, the intensity, full width at half-maximum and intensity ratio of the bands also changed demonstrating that PM nanostructure disorder was correlated with a faster oxidation rate. The results show the use of PODEn affects the oxidation reactivity and nanostructure of PM that is easier to oxidize.