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Abstract Background Gallbladder cancer (GBC) is characterized by high mortality rate. Our study sought therapeutic candidates for GBC. Results Bioinformatics analysis identified significant upregulation of MST1R in GBC. In vitro experiments demonstrated that the MST1R inhibitor MGCD-265 effectively restrained GBC cell proliferation at lower concentrations. Additionally, it induced cycle arrest and apoptosis in GBC cells in a dose-dependent manner. Mouse models exhibited that MGCD-265 treatment significantly diminished the proliferative capacity of GBC-SD cells. Transcriptomics sequencing revealed significant transcriptome alterations, with 200 transcripts upregulated and 883 downregulated. KEGG and GO analyses highlighted enrichment in processes like cell adhesion and pathways such as protein digestion and absorption. Downstream genes analysis identified JMJD6 upregulation post-MGCD-265 treatment. In vivo experiments confirmed that combining MGCD-265 with the JMJD6 inhibitor SKLB325 enhanced the anticancer effect against GBC. Conclusion Overall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.

The land-based recirculating aquaculture system (RAS) has been widely applied to fish farming as a new eco-friendly culture model. This system consists of circular culture tanks on land integrated with water treatment and recycling systems. This study investigated the growth performance of juvenile gibel carp (Carassius gibelio) cultured at high stocking density (HSD, 0.3 kg/m3) and low stocking density (LSD, 0.15 kg/m3) conditions in RAS, and evaluated the comprehensive economic profit of RAS. The body weight, body length, weight gain rate, and condition factor of gibel carp in the LSD group were significantly higher than those in the HSD group (p < 0.05). The feed conversion ratio increased significantly in the HSD group (p < 0.05). A histological analysis revealed a significantly higher density of white muscle fibers in the LSD group (p < 0.05). Relative mRNA expression levels showed that ubiquitin–proteasome system (UPS)-related genes, ub, psma2, and mafbx, were significantly expressed in the HSD group, while the s6k1 expression was elevated in the LSD group (p < 0.05). The mRNA expression levels of keap1 and hsp70 in the dorsal muscle were significantly higher in the HSD group (p < 0.05). Throughout the rearing period, the water temperature remained consistent between the two density groups. The pH value gradually decreased and the dissolved oxygen levels in the HSD group were generally lower than in the LSD group. The nitrite nitrogen (NO2−-N) content was higher in the HSD group. Compared to the LSD group, the return on investment was significantly lower in the HSD group. In conclusion, the water quality and growth rates of juvenile gibel carp were better in the LSD group. An appropriate stocking density improved the growth performance and aquaculture economic efficiency.

In recent years, bacterial-based biocontrol agents (BCA) have become a new trend for the control of fungal diseases such as fusarium wilt that seriously threaten the yield and quality of cucumber, which are transmitted through infested soil and water. This study was set out with the aim of figuring the mechanism of the isolated rhizobacterial strain Paenibacillus polymyxa PJH16 in preventing Fusarium oxysporum f. sp. cucumerinum (Foc). Biocontrol and growth-promoting experiments revealed that bacterial strain causes effective inhibition of the fungal disease through a significant growth-promoting ability of plants, and had activities of β-1,3-glucanase, cellulase, amylase and protease. It could produce siderophore and indole-3-acetic acid, too. Using the high-throughput sequencing tool PacBio Sequel II system and the database annotation, the bacterial strain was identified as P. polymyxa PJH16 and contained genes encoding for presence of biofilm formation, antimicrobial peptides, siderophores and hydrolyases. From comparing data between the whole genome of P. polymyxa PJH16 with four closely related P. polymyxa strains, findings revealed markedly the subtle differences in their genome sequences and proposed new antifungal substances present in P. polymyxa PJH16. Therefore, P. polymyxa PJH16 could be utilized in bioengineering a microbial formulation for application as biocontrol agent and bio-stimulant, in the future.

Objective: The aim of these studies was to ascertain if Camelina sativa oil is harmful in both the acute and subchronic states. Methods: Wistar rats of both sexes were used in an acute toxicity test, and the fatal dosage (LD50) of oral Camelina sativa oil was greater than 27.6 g/kg bw. Rats were gavaged with Camelina sativa oil at dosages of 0.00, 0.92, 1.84, and 3.68 g/kg bw per day for 90 days. In addition, satellite groups were established in the control and high-dose groups for a 28-day recovery period. The following factors were assessed: mortality, clinical anomalies, body weight, food intake, hematological, serum biochemistry, urine, gross necropsy, and histology. Results: There were no observable toxicity-related changes in any of the three dosage groups. There is no toxicological relevance to the change in the high-dose hematological indicator PLT at the conclusion of the recovery period because it was within the usual range for this strain in our laboratory. The test material did not result in any pathological alterations, according to a pathological examination. Conclusion: Since the results of the current study, the no-observed-adverse-effect-level (NOAEL) for Camelina sativa oil in rats has been determined to be greater than 3.68 g/kg bw.

This study sought to investigate whether Ganoderma lucidum polysaccharide (GLP) has a protective effect on lipopolysaccharide (LPS)-induced inflammatory injury to mammary epithelial HC-11 cells and to characterize the mechanism involved. Cell viability was assessed using the cell counting kit 8 (CCK-8) method, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β levels were measured by enzyme linked immunosorbent assay (ELISA), and IκBa, p65 NF-κB and STAT3 mRNA were determined using quantitative reverse transcription PCR (qRT-PCR), p65 and STAT3 protein expression were determined using Western blotting, respectively. GLP was shown to inhibit LPS-induced TNF-α, IL-6, and IL-1β production (P < 0.01 or P < 0.05), GLP was also shown to increase IκBα mRNA expression (P < 0.01), decrease p65 and STAT3 mRNA expression (P < 0.01 or P < 0.05), and decrease p-p65, p65, p-STAT3, and STAT3 protein expression in breast epithelial cells (P < 0.01 or P < 0.05). The findings suggest that GLP inhibits nuclear factor kappa-B (NF-κB) and signal transducers and activators of transcription (STAT) signaling by preventing IκBα degradation and p65 and STAT3 phosphorylation. This results in lower LPS-induced TNF-α, IL-6, and IL-1β production and prevents inflammatory cell injury.

In this study, a validated quality evaluation method with peony flower fingerprint chromatogram combined with simultaneous determination of sixteen bioactive constituents was established using UPLC-DAD-MS/MS. The results demonstrated that the method was stable, reliable, and accurate. The UPLC chemical fingerprints of 12 different varieties of peonies were established and comprehensively evaluated by similarity evaluation (SE), hierarchical cluster analysis (HCA), principal component analysis (PCA), and quantification analysis. The results of SE indicated that similar chemical components were present in these samples regardless of variety, but there were significant differences in the content of chemical components and material basis characteristics. The results of HCA and PCA showed that 12 varieties of samples were divided into two groups. Four flavonoids (11, 12, 13, and 16), five monoterpenes and their glycosides (3, 4, 6, 14, and 15), three tannins (7, 9, and 10), three phenolic acids (1, 2, and 5), and one aromatic acid (8) were identified from sixteen common peaks by standards and liquid chromatography–mass spectrometry (LC–MS). The simultaneous quantification of six types of components was conducted with the 12 samples, it was found that the sum contents of analytes varied obviously for peony flower samples from different varieties. The content of flavonoids, tannins, and monoterpenes (≥19.34 mg/g) was the highest, accounting for more than 78.45% of the total compounds. The results showed that the flavonoids, tannins, and monoterpenes were considered to be the key indexes in the classification and quality assessment of peony flower. The UPLC-DAD-MS/MS method coupled with multiple compounds determination and fingerprint analysis can be effectively applied as a feature distinguishing method to evaluate the compounds in peony flower raw material for product quality assurance in the food, pharmaceutical, and cosmetic industries. Moreover, this study provides ideas for future research and the improvement of products by these industries.

ObjectivesWe investigated the protective effect of Rehmannia glutinosa oligosaccharides (RGO) on lipopolysaccharide (LPS)-induced intestinal inflammation and barrier injury among mice.MethodsRGO is prepared from fresh rehmannia glutinosa by water extraction, active carbon decolorization, ion exchange resin impurity removal, macroporous adsorption resin purification, and decompression drying. LPS could establish the model for intestinal inflammation and barrier injury in mice. Three different doses of RGO were administered for three consecutive weeks. Then the weight, feces, and health status of the mice were recorded. After sacrificing the mice, their colon length and immune organ index were determined. The morphological changes of the ileum and colon were observed using Hematoxylin-eosin (H&E) staining, followed by measuring the villus length and recess depth. RT-qPCR was utilized to detect the relative mRNA expression of intestinal zonula occludens-1 (ZO-1) and occludin. The expression of inflammatory factors and oxidation markers within ileum and colon tissues and the digestive enzyme activities in the ileum contents were detected using ELISA. The content of short-chain fatty acids (SCFAs) in the colon was determined with GC. The gut microbial composition and diversity changes were determined with 16S-rRNA high-throughput sequencing. The association between intestinal microorganisms and SCFAs, occludins, digestive enzymes, inflammatory factor contents, and antioxidant indexes was also analyzed.ResultsRGO significantly increased the weight, pancreatic index, thymus index, and colon length of mice compared with the model group. Moreover, it also improved the intestinal tissue structure and increased the expression of intestinal barrier-related junction proteins ZO-1 and Occludin. The contents of IL-6, IL-17, IL-1β, and TNF-α in the intestinal tissues of mice were significantly reduced. Additionally, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were elevated. In contrast, the malondialdehyde (MDA) content decreased. Trypsin and pancreatic lipase activities in the ileum enhanced, and the SCFA contents such as acetic acid, propionic acid, and butyric acid in the colon increased. The study on intestinal flora revealed that RGO could enhance the abundance of intestinal flora and improve the flora structure. After RGO intervention, the relative abundance of Firmicutes, Lactobacillus, and Akkermania bacteria in the intestinal tract of mice increased compared with the model group, while that of Actinomycetes decreased. The intestinal microbiota structure changed to the case, with probiotics playing a dominant role. The correlation analysis indicated that Lactobacillus and Ackermann bacteria in the intestinal tract of mice were positively associated with SCFAs, Occludin, ZO-1, pancreatic amylase, SOD, and CAT activities. Moreover, they were negatively correlated with inflammatory factors IL-6, IL-17, IL-1β, and TNF-α.ConclusionsRGO can decrease LPS-induced intestinal inflammation and intestinal barrier injury in mice and protect their intestinal function. RGO can ameliorate intestinal inflammation and maintain the intestinal barrier by regulating intestinal flora.

Ammonia-oxidizing archaea (AOA) and bacteria (AOB) play an important role in nitrification, which is essential in the global nitrogen cycle. However, their dynamics and the underlying community processes in agricultural ecosystems under disturbance remain largely unknown. In this study we examined the spatiotemporal dynamics of AOA and AOB communities and analyzed their community processes in the sediment of aquaculture ponds across three different areas in China. We found some significant temporal changes in AOA and AOB community diversity and abundances, but no temporal changes in community composition, despite the significant variations in sediment properties between different sampling times. Nevertheless, significant differences were found for AOA and AOB communities between different areas. Distinct area-specific taxa were detected, and they were found to be important in determining the response of AOA and AOB communities to environmental factors. In addition, geographic distance was found to be significantly correlated with AOA and AOB community composition, which demonstrates that dispersal limitation could significantly contribute to the variations in AOA and AOB communities, and stochastic processes were found to be important in structuring AOA/AOB communities in aquaculture ponds. Taken together, our study indicates that the dynamics of AOA and AOB are based on their community characteristics in aquaculture pond sediment. Our results, for the first time, provide evidence for the dynamics of AOA and AOB communities being driven by stochastic factors in a disturbed environment, and might also be of use in the management of the aquaculture environment.

Objective To evaluate the risk of major infections and the relationship between major infections and mortality in patients with newly diagnosed SLE.Methods A newly diagnosed (10, peripheral lymphocyte count 104 µmol/L was established to identify patients at low risk (3%–5%) or high risk (37%–39%) of major infections within the first 4 months.Conclusions Newly onset active SLE is susceptible to major infections, which is probably due to underlying profound immune disturbance. Identifying high-risk patients using an appropriate prediction tool might lead to better tailored management and better outcome.

Microcystin-LR (MC-LR) is widely distributed in the natural environment and causes hepatotoxicity. However, whether MC-LR promotes liver tumor progression remains controversial. krasV12 transgenic zebrafish were used as an inducible liver tumor model to evaluate the potential tumor-promoting effect of MC-LR. First, krasV12 transgenic larvae were exposed to 0, 0.1 and 1 mg/L MC-LR with 20 mg/L doxycycline (Dox) for 4 d. The gray values and histopathological examinations of the liver demonstrated that MC-LR aggravated liver tumor progression, which could be inhibited by the Protein arginine methyltransferase 5 (Prmt5) inhibitor compound 5 (CMP5). Second, 1-month-old juvenile transgenic zebrafish were exposed to 0, 20 mg/L Dox, 1 μg/L MC-LR, and 20 mg/L Dox with 0.1 or 1 μg/L MC-LR for 15 d to determine whether the exposure to environmental concentrations of MC-LR promoted hepatocellular carcinoma (HCC) progression. We found that environmental concentrations of MC-LR increased the hepatosomatic index (HSI) and gray value (intensity/area) and promoted HCC progression. The results indicate that environmental concentrations of MC-LR have the potential to promote liver tumor progression. Taken together, the present study demonstrates that MC-LR can promote tumor in krasV12 transgenic zebrafish and that the upregulation of prmt5 expression might contribute to MC-LR-mediated promotion of liver tumorigenesis.

Ammonia-oxidizing bacteria (AOB) and archaea (AOA) play important roles in nitrogen removal in aquaculture ponds, but their distribution and the environmental factors that drive their distribution are largely unknown. In this study, we collected surface sediment samples from Ctenopharyngodon idellus ponds in three different areas in China that practice aquaculture. The community structure of AOB and AOA and physicochemical characteristics in the ponds were investigated. The results showed that AOA were more abundant than AOB in all sampling ponds except one, but sediment AOB and AOA numbers varied greatly between ponds. Correlation analyses indicated a significant correlation between the abundance of AOB and arylsulfatase, as well as the abundance of AOA and total nitrogen (TN) and arylsulfatase. In addition, AOB/AOA ratio was found to be significantly correlated with the microbial biomass carbon. AOB were grouped into seven clusters affiliated to Nitrosospira and Nitrosomonas, and AOA were grouped into six clusters affiliated to Nitrososphaera, Nitrososphaera sister group, and Nitrosopumilus. AOB/AOA diversity in the surface sediments of aquaculture ponds varied according to the levels of total organic carbon (TOC), and AOB and AOA diversity was significantly correlated with arylsulfatase and β-glucosidase, respectively. The compositions of the AOB communities were also found to be significantly influenced by sediment eutrophic status (TOC and TN levels), and pH. In addition, concentrations of acid phosphatase and arylsulfatase in surface sediments were significantly correlated with the prominent bacterial amoA genotypes, and concentrations of TOC and urease were found to be significantly correlated with the prominent archaeal amoA genotype compositions. Taken together, our results indicated that AOB and AOA communities in the surface sediments of Ctenopharyngodon idellus aquaculture ponds are regulated by organic matter and its availability to the microorganisms.

Abstract Background Suture knotting is the basis of surgical skills. In the process of surgical skills learning, the surrounding environment, especially the light, will affect the efficiency of learning. This study investigated the effect of optical environment on the learning of stitching and knotting skills. Methods A total of 44 medical students were randomly divided into four groups and participated in the study of suture knotting in four different optical environments. During the process, we assess objective pressure level by testing salivary amylase activity Likert scale and objective structured clinical examination (OSCE) was used to estimate the subjective psychological state and overall skill mastery in surgical suturing respectively. Results Under high illumination conditions (700 lx), the salivary amylase activity of the high color temperature group (6000 K) was significantly higher than that of the low color temperature group (4000 K) (p

Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen “green” natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Abstract Objective Promoting angiogenesis is crucial for tissue repair. Adipose-derived mesenchymal stem cells (ADSCs) are endowed with the ability of paracrine secretion of various angiogenic cytokines and the differentiation potential into endothelium-like cells to directly participate in angiogenesis. ADSCs are key seed cells for promoting angiogenesis in regenerative medicine and tissue engineering. This study aimed to explore the role and mechanism of C9orf106 (LINC02913) in the angiogenesis of ADSCs. Methods The microarray dataset GSE12884 was analyzed to identify the differentially expressed lncRNAs in ADSCs under normoxia and hypoxia. The expression of the key genes was detected using qRT-PCR, western blot assay (western blot), and immunofluorescence (IF) staining. The adipogenic ability and tube formation ability of ADSCs was detected using oil red O staining and tube formation assay, respectively. The regulatory relationship between hypoxia-inducible factor-1alpha (HIF1A) and LINC02913 was verified using chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay. A skin wound healing nude mice model was established. Hematoxylin and eosin (H&E) staining was applied to detect pathological skin damage. Immunohistochemistry (IHC) staining was used to determine the level of CD31 in skin tissues. Results LINC02913 expression was decreased in ADSCs under hypoxia; LINC02913 overexpression inhibited the proliferation, adipogenic ability, endothelial differentiation ability, and tube formation ability of ADSCs. ChIP assay and dual-luciferase reporter gene assay results showed that HIF1A could directly bind to the LINC02913 promoter region to inhibit its transcription. Through RNAact prediction and analysis of the correlation with LINC02913 expression, it was found that IGF1R may directly interact with LINCO02913. The HIF1A/LINC02913/IGF1R axis could activate the PI3K/AKT pathway to promote the biological function of ADSCs. Hypoxia-ADSCs significantly promoted vascularization in the wounded skin. The regulatory effect of LINC02913/IGF1R axis on hypoxia-ADSCs treated skin wound healing were verified. Conclusion The HIF1A/LINC02913/IGF1R axis promoted the proliferation, adipogenic ability, and tube formation ability of ADSCs under hypoxia via activating the PI3K/AKT pathway.

Energy storage efficiency (η) and large recoverable energy density (Wre) are necessary for antiferroelectric materials in order to develop antiferroelectric-based dielectric capacitors with exceptional energy storage capacity. In the present paper, the effect of doping La3+ on the energy storage capacity of Pb1−xLax(Hf0.45Sn0.55)0.995O3 antiferroelectric ceramics was studied. Adjusting the content of La and changing the phase structure of PLHS from antiferroelectric to relaxor ferroelectric gradually, which narrowed its hysteresis loop, yielded a high energy storage efficiency of 81.9% and the maximum breakdown field strength of 200 kV/cm when x = 2 mol%. In addition, the recoverable energy density and energy storage efficiency both showed excellent temperature stability and frequency stability in the temperature range of 10–110 °C and the frequency range of 10–100 Hz, suggesting that Pb0.98La0.02(Hf0.45Sn0.55)0.995O3 are favorable materials candidates for the preparation of pulsed-power capacitors that can be used in a wide range of conditions.

ObjectiveHormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor