Peimenine unleashes therapeutic promise in urothelial bladder cancer: inhibition of proliferation, induction of cell death and modulation of key pathways.

Peimenine (PEI) is a steroid alkaloid substance isolated from Fritillaria thunbergii bulbs. It has various pharmacological activities, such as relief from coughs and asthma, expectorant properties, antibacterial effects, sedative qualities, and anti-inflammatory properties. Notably, PEI can effectively inhibit the proliferation and tumor formation of liver cancer and osteosarcoma cells by inducing autophagic cell death. However, the precise effect and mechanisms of PEI on urothelial bladder cancer (UBC) cells remain uncertain. Thus, this study aims to investigate the impact of PEI on UBC cells both in vivo and in vitro. The IC50 values of BIU-87 and EJ-1 cells after 48 h were 710.3 and 651.1 µg/mL, respectively. Additionally, PEI blocked the cell cycle in BIU-87 and EJ-1 cells during the G1 phase. Furthermore, it hindered the migration of BIU-87 and EJ-1 cells substantially. PEI significantly inhibited the tumor development of EJ-1 cells within the xenograft tumor model in vivo. Mechanically, PEI augmented the protein and mRNA expression of BIM, BAK1, and Cytochrome C (CYCS) in UBC cells. Taken together, PEI suppressed the proliferation of UBC cells both in vitro and in vivo by inducing cell death and cell cycle arrest, suggesting that PEI could be applied in the treatment of UBC.

Defect-Confinement Strategy for Constructing CuO Clusters on Carbon Nanotubes for Catalytic Oxidation of AsH3 at Room Temperature.

The efficient removal of the highly toxic arsine gas (AsH3) from industrial tail gases under mild conditions remains a formidable challenge. In this study, we utilized the confinement effect of defective carbon nanotubes to fabricate a CuO cluster catalyst (CuO/ACNT), which exhibited a capacity much higher than that of CuO supported on pristine multiwalled carbon nanotubes (MWCNT) (CuO/PCNT) for catalytically oxidizing AsH3 under ambient conditions. The experimental and theoretical results show that nitric acid steam treatment could induce MWCNT surface structural defects, which facilitated more stable anchoring of CuO and then improved the oxygen activation ability, therefore leading to excellent catalytic performance. Density functional theory (DFT) calculations revealed that the catalytic oxidation of AsH3 proceeded through stepwise dehydrogenation and subsequent recombination with oxygen to form As2O3 as the final product.

Medicarpin induces G1 arrest and mitochondria-mediated intrinsic apoptotic pathway in bladder cancer cells.

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study reve aled that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy.

Glabridin inhibits urothelial bladder carcinoma cell growth in vitro and in vivo by inducing cell apoptosis and cell cycle arrest.

Glabridin (GLA) has a variety of biological activities and therapeutic effects in cancers. Whereas the effect of GLA on urothelial bladder carcinoma (UBC) cells and its underlying mechanisms remain unknown. The study revealed the effect of GLA on UBC and the potential mechanism of inducing cell apoptosis in vivo and in vitro. After treated with different concentrations of GLA, the cell activity decreased in a time- and dose-dependent manner. The IC50 values of BIU-87 and EJ cells at 48 h were 6.02 µg/ml (18.6 µm) and 4.36 µg/ml (13.4 µm), respectively. Additionally, GLA-induced apoptosis and cycle arrest of BIU-87 and EJ cells in G2 phase. Furthermore, wound healing experiments showed that GLA significantly reduced the migration activities of BIU-87 and EJ cells. Mechanically, GLA obviously increased the expression of BIM, BAK1, and CYCS in both mRNA and protein levels, which led to the activation of the endogenous apoptotic pathway. Finally, GLA remarkably inhibited the growth of UBC tumors in vivo. In summary, GLA inhibited UBC cells growth in vitro and in vivo by inducing cell apoptosis and cell cycle arrest, highlighting that GLA could be utilized as a component to design a novel anti-UBC drug.

KRS-Net: A Classification Approach Based on Deep Learning for Koi with High Similarity.

As the traditional manual classification method has some shortcomings, including high subjectivity, low efficiency, and high misclassification rate, we studied an approach for classifying koi varieties. The main contributions of this study are twofold: (1) a dataset was established for thirteen kinds of koi; (2) a classification problem with high similarity was designed for underwater animals, and a KRS-Net classification network was constructed based on deep learning, which could solve the problem of low accuracy for some varieties that are highly similar. The test experiment of KRS-Net was carried out on the established dataset, and the results were compared with those of five mainstream classification networks (AlexNet, VGG16, GoogLeNet, ResNet101, and DenseNet201). The experimental results showed that the classification test accuracy of KRS-Net reached 97.90% for koi, which is better than those of the comparison networks. The main advantages of the proposed approach include reduced number of parameters and improved accuracy. This study provides an effective approach for the intelligent classification of koi, and it has guiding significance for the classification of other organisms with high similarity among classes. The proposed approach can be applied to some other tasks, such as screening, breeding, and grade sorting.

Evaluation of salt tolerance in common vetch (Vicia sativa L.) germplasms and the physiological responses to salt stress.

Common vetch (Vicia sativa L.) is an important leguminous crop, providing humans with starch from seeds, feeding livestock with vegetative organs, or fertilizing soils by returning to field. It is aimed to evaluate salt tolerance in common vetch collections for breeding programs and to investigate the underlined physiological mechanisms. Relative germination rate and relative seedling growth showed great difference among common vetch collections in response to salt. A lower level of Na+ and higher levels of K+ and K+/Na+ ratio were maintained in both shoots and roots in salt-tolerant collections than in salt-sensitive ones under salt stress. Expression of the genes involved in transportation and redistribution of Na+ and K+ were cooperatively responsible for salt stress. Transcript levels of NHX7, HKT1, AKT2, and HAK17 in leaves and roots were induced after salt stress, with higher transcript levels in salt-tolerant collections compared with the sensitive ones. Proline and P5CS1 transcript levels were increased after salt stress, with higher levels in salt-tolerant collection compared with salt-sensitive ones. Both O2- and H2O2 were accumulated after salt stress, and lower levels were accumulated in salt-tolerant collection compared with salt-sensitive ones. Superoxide dismutase, catalase and ascorbate peroxidase activities were altered in response to salt and higher levels were maintained in salt-tolerant collections compared with salt-sensitive ones. It is suggested that salt tolerance in common vetch is associated with maintenance of K+ and Na+ homeostasis and the associated gene expression and promoted proline accumulation and antioxidant defense system.

Renal cancer associated with Xp11.2 translocation/TFE3 gene fusion: Clinicopathological analysis of 13 cases.

OBJECTIVE: To explore the clinicopathological characteristics, immunohistochemical phenotype, diagnosis and differential diagnosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion. METHODS: The clinical history, pathological morphology, immunohistochemical phenotype and related molecular test results of 13 cases of Xp11.2 translocation/TFE3 gene fusion-related renal cell carcinoma were retrospectively analyzed, and the relevant literature was reviewed. RESULTS: Of the 13 patients, 5 were males and 8 were females. The age of onset ranges from 8 to 73 years old, most of which were middle-aged and elderly patients. Among them, there were 3 cases of left kidney tumor and 10 cases of right kidney tumor. In the treatment method, 2 of the 13 patients underwent partial nephrectomy, and 11 underwent radical nephrectomy. Histopathological morphology showed papillary, nested, tubular and acinar structures. The cytoplasm was transparent or eosinophilic, and the interstitial fibrosis was accompanied by chronic inflammatory cell infiltration, hemosiderin deposition and foam cell aggregation. The immunohistochemical analysis of 13 patient specimens all expressed TFE3 antibody, and the expression intensity was strongly positive; gene FISH detection technology revealed the breakage and rearrangement of TFE3 gene in 12 assessable cases. One of thirteen patients had a metastasis at follow-up from 3 to 69 months. CONCLUSIONS: This type of kidney cancer was a rare subtype. Because of its complex and changeable shape, it has a high degree of overlap with other kidney cancer subtypes, and the missed diagnosis rate and misdiagnosis rate are extremely high. The diagnosis is mainly based on pathomorphology and immunohistochemistry, TFE3 positive expression and TFE3 gene destruction and rearrangement.

Direction Matters: On Influence-Preserving Graph Summarization and Max-Cut Principle for Directed Graphs.

Summarizing large-scale directed graphs into small-scale representations is a useful but less-studied problem setting. Conventional clustering approaches, based on Min-Cut-style criteria, compress both the vertices and edges of the graph into the communities, which lead to a loss of directed edge information. On the other hand, compressing the vertices while preserving the directed-edge information provides a way to learn the small-scale representation of a directed graph. The reconstruction error, which measures the edge information preserved by the summarized graph, can be used to learn such representation. Compared to the original graphs, the summarized graphs are easier to analyze and are capable of extracting group-level features, useful for efficient interventions of population behavior. In this letter, we present a model, based on minimizing reconstruction error with nonnegative constraints, which relates to a Max-Cut criterion that simultaneously identifies the compressed nodes and the directed compressed relations between these nodes. A multiplicative update algorithm with column-wise normalization is proposed. We further provide theoretical results on the identifiability of the model and the convergence of the proposed algorithms. Experiments are conducted to demonstrate the accuracy and robustness of the proposed method.

Analysis of Behavior Trajectory Based on Deep Learning in Ammonia Environment for Fish.

Ammonia can be produced by the respiration and excretion of fish during the farming process, which can affect the life of fish. In this paper, to research the behavior of fish under different ammonia concentration and make the corresponding judgment and early warning for the abnormal behavior of fish, the different ammonia environments are simulated by adding the ammonium chloride into the water. Different from the existing methods of directly artificial observation or artificial marking, this paper proposed a recognition and analysis of behavior trajectory approach based on deep learning. Firstly, the three-dimensional spatial trajectories of fish are drawn by three-dimensional reconstruction. Then, the influence of different concentrations of ammonia on fish is analyzed according to the behavior trajectory of fish in different concentrations of ammonia. The results of comparative experiments show that the movement of fish and vitality decrease significantly, and the fish often stagnates in the water of containing ammonium chloride. The proposed approach can provide a new idea for the behavior analysis of animal.

Cinobufacini ameliorates experimental colitis via modulating the composition of gut microbiota.

BACKGROUND: Cinobufacini, the sterilized hot water extraction of dried toad skin, has been widely used in the treatment of inflammation and cancers. Recently we found cinobufacini could ameliorate dextran sulfate sodium (DSS)-induced colitis in mice, but the underlying mechanism was not fully understood. In current study, we explored the effect of cinobufacini on gut microbiota in DSS-induced acute colitic mouse model by pyrosequencing of colonic contents. METHODS: C57BL/6 mice were supplied with normal or 3.0% DSS containing drinking water. DSS-treat mice were gavaged daily either with vehicle (water) or cinobufacini (10.0 or 30.0 mg/kg) for 7 days. The composition of the gut microbiota was assessed by analyzing 16S rRNA gene sequences. RESULTS: Our data indicated that cinobufacini reversed DSS-induced gut dysbiosis and enhanced intestinal barrier integrity. Moreover, changing of some specific microbial groups such as Proteobacteria and Bacteroides was closely correlated with the re-establishment of intestinal equilibrium and the recovery of intestinal function. CONCLUSION: Cinobufacini prevents colitis in mice by modifying the composition and function of gut microbiota. The current study provides additional mechanistic insight in the therapeutic effect of cinobufacini treatment and may pave the way for clinical application of cinobufacini in colitis therapy.

Electrochemical sensors based on molecularly imprinted polymers on Fe3O4/graphene modified by gold nanoparticles for highly selective and sensitive detection of trace ractopamine in water.

A novel molecular imprinting polymer (MIP)-based electrochemical senor, consisting of Fe3O4 nanobeads and gold nanoparticles on a reduced graphene oxide (RGO) substrate, was fabricated to detect ractopamine (RAC) in water using the reversible addition fragmentation chain transfer (RAFT) polymerization technique. The Au nanoparticles widely dispersed on RGO can significantly increase the response current for RAC detection in water, which is confirmed by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and theoretical calculations. By means of the differential pulse voltammetry technique, the as-prepared MIP-based electrode shows a dynamic linear range of 0.002 to 0.1 µM with a correlation coefficient of 0.992 and a remarkably low detection limit of 0.02 nM (S/N = 3). Additionally, the sensor exhibits high binding affinity and selectivity towards RAC with excellent reproducibility. Our study demonstrates the potential for the proposed electrochemical sensors in monitoring organic pollutants in water.

Conditional Mediation of Absorptive Capacity and Environment in International Entrepreneurial Orientation of Family Businesses.

This study analyzes the effect of conditional mediation of environment-absorptive capacity in international entrepreneurial orientation of family businesses. Results involve data from 218 Spanish family businesses, analyzed with SmartPLS 3.2.7 software. This paper presents a relevant contribution both to the academic field and the performance of family firms, helping to understand the process of transforming international entrepreneurial orientation into a better international performance through absorptive capacity while family businesses invest their efforts in aligning international entrepreneurial orientation and absorptive capacity with international results, bearing in mind the positive moderator effect of environment. The most relevant contribution of this work is to integrate in the same model the mediating effect of the absorption capacity and the moderating effect of the environment: the effect of the international entrepreneurial orientation on the international performance of family businesses improves with the mediation of the absorptive capacity (the variability of international performance goes from 32.5 to 40.6%) and the moderation of the environment (to variability of international performance goes from 40.6 to 45.3%).

Modification of chitosan/calcium alginate/Fe3O4 hydrogel microsphere for enhancement of Cu(II) adsorption.

Copper in drinking water causes a significant environmental problem. Composite material based on alginate hydrogel has been gaining attention in the field of Cu(II) adsorption. However, alginate-based hydrogel exhibits poor mechanical property and relative low adsorption capacity which limit their application. The present study is devoted to the modification of chitosan/calcium alginate/Fe3O4 (CAF) hydrogel microsphere by NaOH solution for enhancement of Cu(II) adsorption. Results reveal that modification of CAF via NaOH solution significantly improves the mechanical strength and Cu2+ adsorption capacity of pristine materials. FTIR and XRD analysis confirms that CAF and newly prepared materials (NACAF) are successfully prepared. SEM and EDX are employed to analyze the surface morphology and elemental composition, respectively, both before and after their loading with Cu2+. XPS study demonstrates adsorption mechanism is based on chelation and ion-exchange. Compressive stress-strain curves demonstrate NACAF has better mechanical performance than CAF. The adsorption kinetics of the two adsorbents follow a pseudo-second-order model. The equilibrium data were best described by Langmuir isotherm model, and the estimated maximum equilibrium sorption capacity, q m,is 261.31 mg/g for the NACAF, which is larger than that of CAF (145.39 mg/g). Hence, NACAF shows excellent mechanical strength and high sorption capacity for Cu2+. It has great potential for Cu(II) removal in aqueous solutions.

Preparation of a novel polyacrylic acid and chitosan interpenetrating network hydrogel for removal of U(vi) from aqueous solutions.

A clean and simple method has been developed for preparation of interpenetrating polymer networks using polyacrylic acid (PAA) and chitosan (CS) for extraction of uranium from polluted water. The peak of Fourier transform infrared spectroscopy (FTIR) occurred at 928 cm-1 indicating combination of uranium and PAA/CS. The energy dispersive X-ray (EDX) and the scanning electron microscope (SEM) studies illustrated the formation of a crosslinking structure and excellent binding ability of uranium on PAA/CS. The maximum adsorption capacity was 289.6 mg g-1 calculated using the equation of the Langmuir model. The adsorption capacity reached a plateau at pH 4 and the sorption process fits the pseudo-second-order model well. The PAA/CS composite has stability of reuse, with the adsorbent capacity decreasing slowly with increasing usage frequency. The experimental results confirm that the PAA/CS hydrogel could be a novel alternative for highly efficient removal of uranium from wastewater.

Discovery of 3-n-butyl-2,3-dihydro-1H-isoindol-1-one as a potential anti-ischemic stroke agent.

To develop novel anti-ischemic stroke agents with better therapeutic efficacy and bioavailability, we designed and synthesized a series of 3-alkyl-2,3-dihydro-1H-isoindol-1-ones compounds (3a-i) derivatives, one of which (3d) exhibited the strongest inhibitory activity for the adenosine diphosphate-induced and arachidonic acid-induced platelet aggregation. This activity is superior to that of 3-n-butylphthalide and comparable with aspirin and edaravone. Meanwhile, 3d not only exhibited a potent activity in scavenging free radicals and improving the survival of HT22 cells against the reactive oxygen species-mediated cytotoxicity in vitro but also significantly attenuated the ischemia/reperfusion-induced oxidative stress in ischemic rat brains. Results from transient middle cerebral artery occlusion and permanent middle cerebral artery occlusion model, indicated that 3d could significantly reduce infarct size, improve neurobehavioral deficits, and prominently decrease attenuation of cerebral damage. Most importantly, 3d possessed a very high absolute bioavailability and was rapidly distributed in brain tissue to keep high plasma drug concentration for the treatment of ischemic strokes. In conclusion, our findings suggest that 3-alkyl-2,3-dihydro-1H-isoindol-1-ones, a novel series of compounds, might be candidate drugs for the treatment of acute ischemic strokes, and 3d may be a promising therapeutic agent for the primary and secondary prevention of ischemic stroke.

Association between Tp-e/QT ratio and prognosis in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

BACKGROUND: Both the Tpeak-Tend interval (Tp-e) and the Tp-e/QT ratio have been linked to increased risk for arrhythmia. Patient Tp-e/QT ratios were investigated prior to primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). HYPOTHESIS: Tp-e/QT ratio maybe associated with the prognosis in patients with ST-segment elevation. METHODS: A total of 338 patients (N = 338) with STEMI treated by pPCI were included. The Tp-e and Tp-e/QT ratio were determined using electrocardiograms in the subjects exhibiting ST-segment elevation. RESULTS: The Tp-e/QT ratio was correlated with both short- and long-term outcomes. Analysis of the receiver operating characteristic curve demonstrated that the optimal cutoff value for outcome prediction was a Tp-e/QT ratio of 0.29. Of the 388 patients enrolled, 115 (34.0%) exhibited a Tp-e/QT ratio ≥ 0.29. Patients with a Tp-e/QT ratio ≥ 0.29 showed elevated rates of both in-hospital death (21.9% vs 2.3%; P < 0.001) and main adverse cardiac events (MACE) (48.1% vs 15.3%; P < 0.005). After discharge, Tp-e/QT ratios ≥ 0.29 remained an independent predictor of all-cause death (35.5% vs 5.2%, P < 0.001) and cardiac death (32.3% vs 2.6%, P < 0.001). CONCLUSIONS: The Tp-e/QT ratio may serve as a prognostic predictor of adverse outcomes after successful pPCI treatment in STEMI patients.