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Cisplatin-based chemotherapy is the current standard care for lung cancer patients; however, drug resistance frequently develops during treatment, thereby limiting therapeutic efficacy.The molecular mechanisms underlying cisplatin resistance remain elusive. In this study, we conducted an analysis of microarray data from the Gene Expression Omnibus (GEO) database under the accession numbers GSE21656, which encompassed expression profiling of cisplatin-resistant H460 (DDP-H460)and the parental cells (H460). Subsequently, we calculated the differentially expressed genes (DEGs) between DDP-H460 and H460. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs demonstrated significant impact on the Rap1, PI3K/AKT and MAPK signaling pathways. Moreover, protein and protein interaction (PPI) network analysis identified PRKCA, DET1, and UBE2N as hub genes that potentially contribute predominantly to cisplatin resistance. Ultimately, PRKCA was selected for validation due to its significant prognostic effect, which predicts unfavorable overall survival and disease-free survival in patients with lung cancer. Network analysis conducted on The Cancer Genome Atlas (TCGA) database revealed a strong gene-level correlation between PRKCA and TP53, CDKN2A, BYR2, TTN, KRAS, and PIK3CA; whereas at the protein level, it exhibited a high correlation with EGFR, Lck, Bcl2, and Syk. The in vitro experiments revealed that PRKCA was upregulated in the cisplatin-resistant A549 cells (DDP-A549), while knockdown of PRKCA increased DDP-A549 apoptosis upon cisplatin treatment. Moreover, we observed that PRKCA knockdown attenuated DDP-A549 proliferation, migration and invasion ability. Western blot analysis demonstrated that PRKCA knockdown downregulated phosphorylation of PI3K expression while upregulated the genes involved in ferroptosis signaling. In summary, our results elucidate the role of PRKCA in acquiring resistance to cisplatin and underscore its potential as a therapeutic target for cisplatin-resistant lung cancer.

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

Being overweight is a risk for various chronic diseases. Alginate, a soluble dietary fiber extracted from seaweed, has been linked to weight loss with unclear mechanisms. We conducted a double-blind, randomized trial in overweight or normal-weight adults to explore alginate’s weight loss effect and mechanism. Normal-weight or overweight participants were randomized to receive either alginate (15 g/day) or maltodextrin (13.8 g/day) for 14 weeks. Compared to maltodextrin (−0.91 kg; 95% CI, −1.91 to 0.10), alginate helped overweight subjects lose weight (−2.67 kg; 95% CI, −3.89 to −1.46) (P = 0.0017) after 14 weeks. In overweight subjects, alginate increased fecal-conjugated bile acids (taurocholate acid and taurochenodeoxycholic acid) and reduced bile acid-related bacteria (Bacteroides, Oscillibacter and Eubacterium). Our results indicate that alginate decreases weight and increases bile acid excretion in overweight subjects, related to gut microbiota alterations and inhibited intestinal bile acid absorption.

The process of recognizing the same vehicle in different scenes is called vehicle re-identification. However, due to the different locations of the surveillance cameras, there may be obstacles in the captured vehicle pictures and multiple viewpoints may make the same vehicle look different. In order to effectively reduce the interference of obstacle occlusion, multiple viewpoints, and other factors on vehicle re-identification, in this paper, we propose a multi-fine-grained feature extraction network. While retaining the global information of vehicles, we extract the finegrained features of vehicles precisely by segmenting the vehicle feature map. In addition, we introduce a new evaluation metric mean Inverse Negative Penalty (mINP) to evaluate the vehicle re-identification model more comprehensively. Our method achieves superior accuracy over the state-of-the-art methods on the challenging vehicle datasets: VeRi-776, VehicleID, and VRIC.

There may be close links among yeast protein (Saccharomyces cerevisiae) supplementation, gut microbiota and skeletal muscle aging. In present study, nineteen-month-old mice received yeast protein (1.0 g/kg/d) for three months by gavage. Histological and ultrasonographical improvements in muscle as well as an increase in myofiber size were observed after yeast protein supplementation. Moreover, yeast protein activated Akt/mTOR/4E-BP1 pathway and regulated myogenic regulatory factors (Myog, Myf4, Myf5, and Myod1) to promote muscle protein synthesis and muscle regeneration and differentiation. Meanwhile, alpha and beta diversities as well as the ratio of Firmicutes and Bacteroidetes were elevated after yeast protein supplementation. Changes in the abundance of gut microbiota after yeast protein supplementation were significantly correlated with glycan biosynthesis and metabolism, amino acid metabolism and lipid metabolism, closely involved in the process of muscle aging. Hence, yeast protein supplementation could contribute to ameliorating muscle aging, which may be associated with gut microbiota.

In China, Hongyang Kiwifruit (Actinidia chinesis) is considered to be economically valuable because of its appealing red flesh, unique flavor and beneficial metabolites. A continuous 3-year field experiment was conducted in a private orchard in Dujiangyan, Sichuan Province, China, to determine the effect of different NPK ratios and organic fertilizer application on growth and yield. Approximately 162 vines were selected in a completely random design with nine fertilization treatments (PK; NK; NP; NPK; 2NPK; N2PK; NP2K; NPK + OM (organic matter)). Data on leaf number, leaf area, stem diameter, photosynthetic parameters, leaf N, P and K, chlorophyll content, yield and fruit quality were collected from individual kiwi vines for each treatment during the years 2011–2013. The application of inorganic fertilizer significantly increased fruit yield, leaf number, and leaf area and stem diameter increment as well as leaf photosynthetic rates and the concentrations of N, P and K in the leaves. However, the fruit yields were reduced in the unbalanced fertilizer treatments, NP, NK, and PK and in excess nutrient treatments, 2NPK, N2PK, NP2K, in contrast to the optimum NPK treatment. This was due to lower leaf photosynthetic rates and fewer photo-assimilates being available to the fruit. Moreover, the addition of organic fertilizer along with inorganic fertilizer (optimum NPK) did not increase plant growth, photosynthetic rates or fruit yields compared with only NPK fertilizer application, but significantly enhanced the fruit quality as a result of improving fruit chemical composition, such as soluble solids and reduced sugar.

Introduction: The objective is to investigate the influence of ghrelin administration on both the insulin secretion and the expression of ATP-sensitive K(+) channels in islet., Methods: Ghrelin and [D-Lys] growth hormone releasing peptide-6 were administered via intraperitoneal injection in Wistar rats at the doses 10 and 10 μmol/kg/d for 2 weeks, respectively. Then glucose tolerance tests were performed and plasma insulin concentrations were measured. Islets were isolated for insulin release experiments. Single β cells were isolated for electrophysiological experiments. Determination of the Kir6.2 and SUR1 mRNA and protein expression levels in islets was performed by polymerase chain reaction and western blotting., Results: Intraperitoneal administration of exogenous ghrelin significantly (P < 0.05) increased blood glucose concentrations, attenuated insulin responses during glucose tolerance tests, reduced insulin release from the isolated islets induced by 11.1 and 16.7 mmol/L glucose, hyperpolarized the resting membrane potential and increased the Kir6.2 mRNA and protein expression levels. In contrast, counteraction of ghrelin by intraperitoneal injection of [D-Lys(3)] growth hormone releasing peptide-6 significantly (P < 0.05) attenuated the aforementioned changes. SUR1 expression levels were not altered in this study., Conclusions: Ghrelin via pancreatic growth hormone secretagogue receptor up-regulates the Kir6.2 expression in islet by hyperpolarizing the resting membrane potential which results in the inhibition of insulin release.