Threatened by the energy crisis and environmental pollution, most countries in the world are vigorously developing new energy vehicles to promote low-carbon environmental protection and boost a green transportation system. Based on the intelligent manufacturing standard system, this study constructed a new energy vehicle intelligent manufacturing development-influencing factor model. Taking the intelligent manufacturing development ability as the dependent variable, taking external environment factors, commonalities among the new energy vehicle enterprises, and industry progress as independent variables, five hypotheses are proposed. This study used a structural equation model to test the hypotheses and reveal the mechanism of how factors influence the new energy vehicle intelligent manufacturing. The results show that external environment factors and industry progress directly and positively affect the development capability of intelligent manufacturing of new energy vehicles, while the commonalities among the NEV enterprises have an indirect effect through industry progress on intelligent manufacturing of new energy vehicles. Based on the analysis, this study puts forward some suggestions for better development of new energy vehicle intelligent manufacturing.

Exploring the underlying mechanisms of cancer development is useful for cancer treatment. In this paper, we analyzed the transcriptome profiles from the human normal pancreas, pancreatitis, pancreatic cancer and metastatic pancreatic cancer to study the intricate associations among pancreatic cancer progression. We clustered the transcriptome data, and analyzed the differential expressed genes. WGCNA was applied to construct co-expression networks and detect important modules. Importantly we selected the module in a different way. As the pancreatic disease deteriorates, the number of differentially expressed genes increases. The gene networks of T cells and interferon are upregulated in stages. In conclusion, the network-based study provides gradually activated gene networks in the disease progression of pancreatitis, pancreatic cancer, and metastatic pancreatic cancer. It may contribute to the rational design of anti-cancer drugs.

Konjac glucomannan (KGM) is a hypoglycemic polysaccharide with a wide range of molecular weights. But study on hypoglycemic effects of KGMs relate to molecular weight is limited. In this study, KGMs with high and medium molecular weights, and the degraded KGMs were analyzed with physicochemical properties, hypoglycemic effects and mechanisms. Results showed that as the molecular weight KGMs decreased, the viscosity decreased, molecular flexibility increased, while chemical groups, crystal structures and main chains showed little change. KGMs with medium molecular weights (KGM-M1, KGM-M2) showed better effects on increasing body weight, decreasing levels of fasting blood glucose, insulin resistance, total cholesterol and low density lipoprotein cholesterol, and enhancing integrity of pancreas and colon, than KGMs with high or low molecular weights (KGM-H, KGM-L) in type 2 diabetic rats. Mechanism analysis suggested that KGM-M1 and KGM-M2 had higher antioxidant and anti-inflammatory activities on elevating superoxide dismutase, decreasing malondialdehyde and tumor necrosis factor-α levels. Moreover, KGM-M1 and KGM-M2 increased gut microbiota diversity, Bacteroidetes/Firmicutes ratio and Muribaculaceae, decreased Romboutsia and Klebsiella, and improved 6 diabetic related metabolites. Combined, KGM-M1 and KGM-M2 showed higher hypoglycemic effects, due to regulatory activities of antioxidant, anti-inflammatory, intestinal microbiota, and relieved metabolic disorders.

Hemerocallis citrina Baroni (HC) is an edible plant in Asia, and it has been traditionally used for sleep-improvement. However, the bioactive components and mechanism of HC in sleep-improvement are still unclear. In this study, the sleep-improvement effect of HC hydroalcoholic extract was investigated based on a caffeine-induced insomnia model in Drosophila melanogaster (D. melanogaster), and the ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-ESI-Orbitrap-MS) and network pharmacology strategy were further combined to screen systematically the active constituents and mechanism of HC in sleep-improvement. The results suggested HC effectively regulated the number of nighttime activities and total sleep time of D. melanogaster in a dose-dependent manner and positively regulated the sleep bouts and sleep duration of D. melanogaster. The target screening suggested that quercetin, luteolin, kaempferol, caffeic acid, and nicotinic acid were the main bioactive components of HC in sleep-improvements. Moreover, the core targets (Akt1, Cat, Ple, and Sod) affected by HC were verified by the expression of the mRNA of D. melanogaster. In summary, this study showed that HC could effectively regulate the sleep of D. melanogaster and further clarifies the multi-component and multi-target features of HC in sleep-improvement, which provides a new insight for the research and utilization of HC.

This study aimed to explore the phenolic compounds (PCs) present in three Chinese olive (Canarium album L.) cultivars and the contribution of these PCs to the anti-inflammatory activities of the cultivars.

Penicillium italicum is the principal pathogen causing blue mold of citrus. Searching for novel antifungal agents is an important aspect of the post-harvest citrus industry because of the lack of higher effective and low toxic antifungal agents. Herein, the effects of 2-methoxy-1,4-naphthoquinone (MNQ) on P. italicum and its mechanism were carried out by a series of methods. MNQ had a significant anti-P. italicum effect with an MIC value of 5.0 µg/mL. The label-free protein profiling under different MNQ conditions identified a total of 3037 proteins in the control group and the treatment group. Among them, there were 129 differentially expressed proteins (DEPs, up-regulated > 2.0-fold or down-regulated < 0.5-fold, p < 0.05), 19 up-regulated proteins, 26 down-regulated proteins, and 67 proteins that were specific for the treatment group and another 17 proteins that were specific for the control group. Of these, 83 proteins were sub-categorized into 23 hierarchically-structured GO classifications. Most of the identified DEPs were involved in molecular function (47%), meanwhile 27% DEPs were involved in the cellular component and 26% DEPs were involved in the biological process. Twenty-eight proteins identified for differential metabolic pathways by KEGG were sub-categorized into 60 classifications. Functional characterization by GO and KEGG enrichment results suggests that the DEPs are mainly related to energy generation (mitochondrial carrier protein, glycoside hydrolase, acyl-CoA dehydrogenase, and ribulose-phosphate 3-epimerase), NADPH supply (enolase, pyruvate carboxylase), oxidative stress (catalase, glutathione synthetase), and pentose phosphate pathway (ribulose-phosphate 3-epimerase and xylulose 5-phosphate). Three of the down-regulated proteins selected randomly the nitro-reductase family protein, mono-oxygenase, and cytochrome P450 were verified using parallel reaction monitoring. These findings illustrated that MNQ may inhibit P. italicum by disrupting the metabolic processes, especially in energy metabolism and stimulus response that are both critical for the growth of the fungus. In conclusion, based on the molecular mechanisms, MNQ can be developed as a potential anti-fungi agent against P. italicum.

Persistent HPV16 infection is the leading risk factor for developing cervical cancer. Anti-L1 antibodies against HPV16 produced in HPV16 infections play diverse roles in the clearance of virus infection and prevention of persistence. It has been implicated that the cervicovaginal squamous epithelial cells actually express TRIM21 and that some HPV16 particles could escape leaky endosomal compartment into the cytosol and that Fc receptor TRIM21 directly neutralize infection by targeting antibody-opsonized viruses for proteasomal degradation. We explored whether anti-L1 antibody opsonized HPV16 pseudovirus (PsV) entered into the cytosol could be neutralized by TRIM21-mediated activation of a proteasomal pathway to reduce the chance of persistent HPV16 infection.

Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen-glucose deprivation (OGD).

The function of Hemerocallis citrina Baroni (daylily) on promoting lactation is reported in several ancient Chinese medicine books. However, nowadays, there is no conclusive data to support this statement. In this study, we investigated the effect of Hemerocallis citrina Baroni extract (HCE) on lactation insufficiency in chronic unpredictable mild stress (CUMS) dams and further explored the mechanism and functional components through network pharmacology. The results showed that HCE could increase the offspring's weight, serum prolactin (PRL), and oxytocin (OT) level of CUMS dams. Network pharmacology analysis revealed that the facilitation of HCE on lactation is the result of the comprehensive action of 62 components on 209 targets and 260 pathways, among this network, quercetin, kaempferol, thymidine, etc., were the vital material basis, signal transducer and activator of transcription 3 (STAT3), mitogen activity protein kinase 1 (MAPK1), tumor protein P53 (TP53), etc., were the core targets, and the prolactin signaling pathway was the core pathway. In addition, verification test results showed that HCE regulated the abnormal expression of the prolactin signaling pathway, including STAT3, cyclin D1 (CCND1), MAPK1, MAPK8, nuclear factor NF-kappa-B p105 subunit (NFKB1), and tyrosine-protein kinase (JAK2). In conclusion, HCE exhibited a facilitation of lactation insufficiency, in which quercetin, kaempferol, thymidine, etc., were the most important material basis. The mechanism of this promotional effect is mediated by the prolactin signaling pathway in mammary gland.

Bone marrow mesenchymal stem cell (BMSC) transplantation is effective for repairing spinal cord injuries (SCIs); however, there are limitations of clinical BMSC applications. Previously, we reported that dermal papilla cells (DPCs) secrete brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor more actively than BMSCs. To analyze the therapeutic function of DPCs in SCI, primary DPCs and BMSCs were cultured from the same green fluorescence protein-transgenic rat. The cells were suspended in rat-tail collagen I and transplanted separately into completely transected spinal cord lesion sites. Grafted-cell survival was examined with a small animal in vivo imaging detection system, and lesion sites were examined histochemically. In vivo imaging revealed enhanced lesion filling and survival with DPC grafts compared with BMSC grafts on days 14 and 21 post-transplantation. Hematoxylin and eosin staining demonstrated that lesion area sizes in the two groups were not markedly different. In the DPC transplant group, more axons formed within the lesion sites. CD31-positive vessel-like structures were more abundant in lesion sites near the grafted cells in the DPC group. The results of the present study suggest that DPCs may be a valuable alternative source of stem cells for autologous cell therapy for the treatment of SCI.

Metastasis is the primary contributor to colorectal cancer mortality. High-intensity focused ultrasound (HIFU) is an emerging technology for tumor therapy that exerts its effects through tumor ablation, mechanical disruption, and enhancement of immune responses. However, it remains unclear whether HIFU can influence tumor metastasis. Here, we examined the effect of HIFU on tumor metastasis of colorectal cancer cells and the underlying mechanisms. HIFU was observed to inhibit migration of HCT-116 cells in vitro and suppress lung metastasis in a mouse model of colon cancer. In addition, HIFU up-regulated microRNA (miR) -124 expression, which inhibited the activation of signal transducer and activator of transcription 3 (STAT3) and inhibited migration of HCT-116 cells. Treatment with an inhibitor of miR-124 reversed the effect of HIFU on cell migration. In conclusion, our results suggest that HIFU exerts anti-metastatic effects in colon cancer, and this effect is possibly mediated via up-regulation of miR-124 and subsequent miR-124-mediated STAT3 suppression.

Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

Chang-wei-qing (CWQ) is a Chinese herbal recipe with clinical efficacy. However, the molecular mechanism underlying its recognized therapeutic benefits against colorectal cancer is still elusive.

The inadequacy of available detection methods and a naturally aggressive progression have made colon cancer the third most common type of cancer, accounting for ~10% of all cancer cases. The heterogeneity and genomic instability of colon cancer tumors make current treatments unsatisfactory. This study evaluated a novel nanoscale delivery platform comprising phosphonated calixarenes (P4C6) co-loaded with paclitaxel (PTX) and carboplatin (CPT). The nanoparticles showed average hydrodynamic sizes of 84 ± 8 nm for empty P4C6 nanoparticle and 119 ± 13 nm for PTX-CPT-P4C6. The corresponding zeta potentials were -40.8 ± 8.8 and -35.4 ± 4.2 mV. The optimal CPT:PTX ratio was 5.22:1, and PTX-CPT-P4C6 with this ratio was more cytotoxic against HT-29 cells than against Caco-2 cells (IC50, 0.4 ± 0.02 vs. 2.1 ± 0.3 μM), and it induced higher apoptosis in HT-29 cells (56.6 ± 4.5 vs. 44.9 ± 3.44%). PTX-CPT-P4C6 inhibited the invasion and migration of HT-29 cells more strongly than the free drugs. It also inhibited the growth of HT-29 tumors in mice to the greatest extent of all formulations, with negligible side effects. This research demonstrates the potential of P4C6 to deliver two chemotherapeutic agents to colon cancer tumors to provide synergistic efficacy than single drug administration.

An increasing number of cancer patients die of cardiovascular diseases. The cardiotoxicity of chemotherapy is particularly important in triple-negative breast cancer (TNBC) with limited therapeutic options. Cardiac autophagy is an important mechanism of cardiotoxicity. This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC, screen the susceptible population, and determine the relationship between cardiotoxicity and autophagy-related polymorphisms.

Despite intensive research, ovarian cancer has the highest mortality rates among gynecological malignancies, partly because of its rapid acquisition of chemoresistance to platinum therapy. Hence, strategies are needed to effectively treat carboplatin-resistant ovarian cancer. In this study, we designed and prepared hyaluronic acid-decorated metal-organic frameworks for the targeted delivery of GSK-J1, a JMJD3 demethylase inhibitor (HA@MOF@GSK-J1) for the synergistic treatment of carboplatin-resistant ovarian cancer. HA@MOF@GSK-J1 showed outstanding effectiveness in the inhibition of ovarian cancer in vitro. Furthermore, HA@MOF@GSK-J1 demonstrated higher induction of apoptosis, reduced cell motility, and diminished cell spheroids by attenuating HER2 activity through the effectual activation of H3K27 methylation in its promoter area. Finally, our in vivo results confirmed that HA@MOF@GSK-J1 had better treatment efficacy for carboplatin-resistant ovarian tumor xenografts. Our results highlight the potential of HA@MOF@GSK-J1 as an effective strategy to improve the treatment of carboplatin-resistant ovarian cancer.

Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC).

This research aims to assess the anti-hyperlipidemia effects of alliin in vivo and its potential mechanisms through transcriptomics and metabolomics analysis. A hyperlipidemia mode was established in C57BL/6 mice fed a high-fat diet, and the related physiological parameters of the animals were recorded. Serum TC and MDA in livers significantly decreased by 12.34% and 29.59%, respectively, and SOD and CAT in livers significantly increased by 40.64% and 39.05%, respectively, after high doses of alliin interventions. In total, 148 significantly different genes, particularly Cel, Sqle, Myc, and Ugt1a2, were revealed for their potential roles in HFD-induced alliin, mainly through steroid biosynthesis, triglyceride metabolism, drug metabolism-cytochrome P450, and the PI3K-Akt signaling pathway, according to transcriptomics analysis. Metabolomics results revealed 18 significantly different metabolites between the alliin group and HFD group, which were classified as carboxylic acids, such as N-undecanoylglycine, adipic acid, D-pantothenic acid, cyprodenate, and pivagabine. We found pantothenic acid played a vital role and was effective through pantothenic acid and CoA biosynthesis metabolism. The "steroid biosynthesis pathway" was identified as the most significant metabolic pathway by integrated transcriptomics and metabolomics analysis. This work offered a theoretical framework for the mechanism of alliin lipid lowering in the future. The development and utilization of alliin will be a viable strategy to improve the health status of people with hyperlipidemia, suggesting prospective market opportunities.

Metabolites play critical roles in regulating nutritional qualities of plants, thereby influencing their consumption and human health. However, the genetic basis underlying the metabolite-based nutrient quality and domestication of root and tuber crops remain largely unknown.

Aquaporins (AQPs) function to selectively control the flow of water and other small molecules through biological membranes, playing crucial roles in various biological processes. However, little information is available on the AQP gene family in bananas. In this study, we identified 47 banana AQP genes based on the banana genome sequence. Evolutionary analysis of AQPs from banana, Arabidopsis, poplar, and rice indicated that banana AQPs (MaAQPs) were clustered into four subfamilies. Conserved motif analysis showed that all banana AQPs contained the typical AQP-like or major intrinsic protein (MIP) domain. Gene structure analysis suggested the majority of MaAQPs had two to four introns with a highly specific number and length for each subfamily. Expression analysis of MaAQP genes during fruit development and postharvest ripening showed that some MaAQP genes exhibited high expression levels during these stages, indicating the involvement of MaAQP genes in banana fruit development and ripening. Additionally, some MaAQP genes showed strong induction after stress treatment and therefore, may represent potential candidates for improving banana resistance to abiotic stress. Taken together, this study identified some excellent tissue-specific, fruit development- and ripening-dependent, and abiotic stress-responsive candidate MaAQP genes, which could lay a solid foundation for genetic improvement of banana cultivars.