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It is still uncertain how the epidemic characteristics of COVID-19 in its early phase and subsequent waves contributed to the pre-delta epidemic size in the United States. We identified the early and subsequent characteristics of the COVID-19 epidemic and the correlation between these characteristics and the pre-delta epidemic size. Most (96.1% (49/51)) of the states entered a fast-growing phase before the accumulative number of cases reached (30). The days required for the number of confirmed cases to increase from 30 to 100 was 5.6 (5.1–6.1) days. As of 31 March 2021, all 51 states experienced at least 2 waves of COVID-19 outbreaks, 23.5% (12/51) experienced 3 waves, and 15.7% (8/51) experienced 4 waves, the epidemic size of COVID-19 was 19,275–3,669,048 cases across the states. The pre-delta epidemic size was significantly correlated with the duration from 30 to 100 cases (p = 0.003, r = −0.405), the growth rate of the fast-growing phase (p = 0.012, r = 0.351), and the peak cases in the subsequent waves (K1 (p < 0.001, r = 0.794), K2 (p < 0.001, r = 0.595), K3 (p < 0.001, r = 0.977), and K4 (p = 0.002, r = 0.905)). We observed that both early and subsequent epidemic characteristics contribute to the pre-delta epidemic size of COVID-19. This identification is important to the prediction of the emerging viral infectious diseases in the primary stage.

It is evident that, being a member of the organization, the team has to cue the influx of the green management concepts. This study focuses on the aspect of team management in green enterprises. Applying leadership theory to sample green enterprises, this paper proposes that political skills of team leadership have moderating effects on the relationship between team conflict (relationship conflict and task conflict) and performance at both the individual and team levels. Empirical data were collected from 85 dyads of leaders and team members in 36 green enterprises in China. It was found that the leaders’ political skills weakened the negative effects of relationship conflict on individual performance and team performance. Further, leaders’ political skills strengthened the positive effects of task conflict on individual and team performance. The results of this study deepen the cognition of two types of team conflict in theory and provide theoretical guidance for green enterprises in carrying out effective team conflict management and practical political skills training for leaders.

Biostimulants are gaining increasing interest because of their ability to provide a green and effective strategy towards sustainable crop production. Nonetheless, their mode of action remains often unknown. The object of this work was to unravel the mechanisms through which 4-Vita, a biostimulant plant extract, can mitigate drought stress in tomato. To this aim, tomato plants were treated with two foliar applications of 4-Vita and drought stress imposed to both treated and control plants. Phenomics investigations were coupled to mass spectrometric untargeted metabolomics, and raw data were elaborated by multivariate statistics and pathway analysis. The biostimulant elicited a broad reprogramming of the tomato’s secondary metabolism, including its phytohormones profile, corroborating an improved ability to cope with drought stress. A series of mechanisms could be identified in response to the biostimulant treatment under drought, pointing to the preservation of photosynthetic machinery functionality. The modulation of thylakoid membrane lipids, the increase in xanthins involved in ROS detoxification, and the modulation of chlorophylls synthesis could also be observed. Overall, a series of coordinated biochemical mechanisms were elicited by the biostimulant treatment, supporting the increased resilience to drought stress in tomato.

III–V group nanomaterials with a narrow bandgap have been demonstrated to be promising building blocks in future electronic and optoelectronic devices. Thus, revealing the underlying structural evolutions under various external stimuli is quite necessary. To present a clear view about the structure–property relationship of III–V nanowires (NWs), this review mainly focuses on key procedures involved in the synthesis, fabrication, and application of III–V materials-based devices. We summarized the influence of synthesis methods on the nanostructures (NWs, nanodots and nanosheets) and presented the role of catalyst/droplet on their synthesis process through in situ techniques. To provide valuable guidance for device design, we further summarize the influence of structural parameters (phase, defects and orientation) on their electrical, optical, mechanical and electromechanical properties. Moreover, the dissolution and contact formation processes under heat, electric field and ionic water environments are further demonstrated at the atomic level for the evaluation of structural stability of III–V NWs. Finally, the promising applications of III–V materials in the energy-storage field are introduced.

Drimia maritima (L.) Stearn (squill), belonging to the Asparagaceae family, is acknowledged as a medicinally valuable species from the Drimia genera. In this study, water, methanol, and ethyl acetate extracts of D. maritima aerial parts and bulbs were investigated for their polyphenols profile and evaluated for their antioxidant and enzyme inhibition properties. Phenolics were profiled through an untargeted metabolomics approach using an ultra-high pressure liquid chromatograph coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS). This analysis revealed an enrichment of low molecular weight phenolics and flavonoids in the aerial parts of D. maritima, while lignans mainly characterized bulb extracts. Antioxidant capacity was investigated by different assays, including phosphomolybdenum assays, radical scavenging (DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), as well as reducing ability (CUPRAC: cupric reducing antioxidant capacity; FRAP: ferric reducing antioxidant power), and metal chelating. In radical scavenging and reducing power assays, the water extract of aerial parts exhibited the strongest ability (DPPH: 36.99 mg trolox equivalent (TE)/g; ABTS: 85.96 mg TE/g; CUPRAC: 87.37 mg TE/g; FRAP: 55.43 mg TE/g). In general, the ethyl acetate extracts from aerial parts and bulbs provided the weakest antioxidant capacity. Concerning enzyme inhibitory activities, the water extracts of the bulb were poorly active, while the ethyl acetate extracts from both plant portions displayed the best α-amylase inhibitory abilities. The best acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) abilities were recorded by ethyl acetate extract of aerial parts (2.36 mg galantamine equivalent (GALAE)/g) and bulbs (5.10 mg GALAE/g), respectively. Overall, these results support the medicinal aptitude of D. maritima and its possible use as a natural source of antioxidants and enzyme inhibitors with functional potential.

The cylindroid describes the exact distribution of the ∞1 screw axes of the general two-system of screws. For the general three-system, this article introduces the surface on which lies the position vector endpoints of its ∞2 screw axes, and then develops the finite distribution zone in which they most densely distribute. In particular, this paper explores the inner structure of the zone by partitioning the general three-system into ∞1 two-subsystems, and then reveals the principle of constructing the distribution space of the general three-system by that of the general two-system in Euclidean three-space. In pursuit of a generalized decomposition method, we propose the varying-pitch ruled surface carrying the screws whose pitch value continuously varies according to any desired function rule, based on the pitch-hyperboloid carrying all the equal-pitch screws. This investigation provides some useful guides for the axode planning and then the motion planning of three degree-of-freedom parallel mechanisms.

Background: A high mortality rate is associated with about 80% of all infections worldwide, mainly due to antimicrobial resistance. Various antimicrobial and cytotoxic activities have been proposed for Meliaceae species. This study aimed to evaluate the in vitro anti-virulence and cytotoxic effect of the leaf extracts of Aphanamixis polystachya, Toona ciliata and Melia azedarach against five MRSA strains and on three cancer cell lines, followed by biological correlation to their encompassed phytoconstituents. Material and Methods: We explored three plants of this family against a panel of Methicillin-resistant Staphylococcus aureus (MRSA) strains and several cancer cell lines to select the most promising candidates for further in vivo and preclinical studies. The phytochemical composition was evaluated by UHPLC–QTOF–MS untargeted profiling. Cell viability was assessed by SRB assay. Minimum Inhibitory Concentration was carried out by using the agar micro-dilution technique. Inhibition of biofilm formation and preformed biofilm disruption were assessed spectrophotomertically, according to the Sultan and Nabil method (2019). Results: A total of 279 compounds were putatively annotated to include different phytochemical classes, such as flavonoids (108), limonoids/terpenoids (59), phenolic acids (49) and lower-molecular-weight phenolics (39). A. polystachya extract showed the most potent cytotoxic activity against Huh-7, DU-145 and MCF-7 cell lines (IC50 = 3, 3.5 and 13.4 µg mL−1, respectively), followed by M. azedarach, with no effect recorded for T. ciliata extract. Furthermore, both A. polystachya and M. azedarach extracts showed promising anti-virulence and antimicrobial activities, with A. polystachya being particularly active against MRSA. These two latter extracts could inhibit and disrupt the biofilm, formed by MRSA, at sub-lethal concentrations. Interestingly, the extracts inhibited hemolysin-α enzyme, thus protecting rabbit RBCs from lysis. A. polystachya extract reduced the pigmentation and catalase enzyme activity of tested pigmented strains better than M. azedarach at both tested sub-MICs. Consequently, susceptibility of the extract-treated cells to oxidant killing by 200 mM H2O2 increased, leading to faster killing of the cells within 120 min as compared to the extract-non-treated cells, likely due to the lower antioxidant-scavenging activity of cells exhibiting less staphyloxanthin production. Conclusion: These findings suggested that both A. polystachya and M. azedarach natural extracts are rich in bioactive compounds, mainly limonoids, phenolics and oxygenated triterpenoids, which can combat MRSA biofilm infections and could be considered as promising sources of therapeutic cytotoxic, antibiofilm and anti-virulence agents.

The integration of photothermal therapy and chemotherapy has been recognized to be an efficient strategy through the instant thermally ablation and long-term chemical inhibition, thus achieving high therapeutical effect. In the present work, we designed and prepared Cu7S4@SiO2/DOX nanocomposites and used them as efficient nanoplatforms for synergistic photothermal-chemo therapy on melanoma tumors. The Cu7S4@SiO2/DOX was constructed by firstly synthesizing Cu7S4 nanocrystals, then in situ growing SiO2 shell on the surface of Cu7S4 nanocrystals, and finally loading DOX within SiO2 shell. The Cu7S4@SiO2/DOX was composed of Cu7S4 core as the photothermal transducer, SiO2 shell as DOX carrier and DOX as the model of anticancer drug. Once exposed to a 1064 nm laser, the Cu7S4@SiO2/DOX could simultaneous generate heat for photothermal therapy and accelerate the DOX release. When the Cu7S4@SiO2/DOX was injected into the center of tumor, the tumor exhibit rapid temperature elevation once exposed to the NIR laser and the tumor growth is significantly inhibited through the synergistic photothermal-chemo therapy, in comparison to the limited therapeutical effect of photothermal therapy or chemotherapy alone. Therefore, the Cu7S4@SiO2/DOX with photothermal-chemo function can be used as excellent nanoplatforms for treating solid tumor with high theoretical effect.

Uveal melanoma (UM) is the most common primary intraocular carcinoma in adults. Cinobufagin, secreted by the Asiatic toad Bufo gargarizans, is a traditional Chinese medicine, widely used in tumor treatment. Here, we explored the potential antitumor function of cinobufagin and investigated its biochemical mechanisms in UM cells. The antitumor potential of cinobufagin was determined via cell viability, cell cycle, and apoptosis assays. Colony formation assays confirmed that cinobufagin exerted potent antitumor activity in a dose-dependent manner. We found that cinobufagin could induce cell apoptosis and upregulate the expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), and cleaved caspase-9 in vivo and in vitro. In addition, after treatment with increased concentrations of cinobufagin, the intrinsic mitochondrial apoptosis pathway was also activated, which was demonstrated by increased cell apoptosis with increased expression of Bad and Bax, decreased expression of Bcl-2 and Bcl-xl, and reduced mitochondrial membrane potential (MMP) in OCM1 cells. Taken together, the results of this preclinical study suggest that cinobufagin can both inhibit cell survival and induce cell apoptosis in a dose-dependent manner in UM cells, which provides new insights into the biochemical mechanism of cinobufagin and its potential as a future chemotherapeutic agent for UM.

The functions of the class III PI3-kinase (PIK3C3) in gut homeostasis and innate immunity are poorly understood. Here the authors show that PIK3C3-deficient zebrafishes develop intestinal injury and inflammation due to mislocalization of cell junction proteins.

Although previous evidence has suggested that there is a genetic link between schizophrenia and creativity, the specific genetic variants that underlie the link are still largely unknown. To further explore the potential genetic link between schizophrenia and creativity, in a sample of 580 healthy Han Chinese subjects, this study aimed to (1) validate the role of Neuregulin 1 (NRG1) rs6994992 (one schizophrenia risk variant that has been previously linked to creativity in the European population) in the relationship between schizophrenia and creativity and (2) explore the associations between 10 other schizophrenia risk variants and creativity. For NRG1 rs6994992, the result validated its association with creativity measures. However, since NRG1 rs6994992 is not a schizophrenia risk variant in the Han Chinese population, the validated association suggested that ethnic difference may exist in the relationship between NRG1 rs6994992, schizophrenia and creativity. For other schizophrenia risk variants, the result only demonstrated a nominal association between ZNF536 rs2053079 and creativity measures which would not survive correction for multiple testing. No association between polygenic risk score for these 10 schizophrenia risk variants and creativity measures was observed. In conclusion, this study provides limited evidence for the associations between these schizophrenia risk variants and creativity in healthy Han Chinese subjects. Future studies are warranted to better understand the potential genetic link between schizophrenia and creativity.

Nitroreductases (NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T1-weighted magnetic resonance imaging (MRI) contrast agent Gd-DOTA-PNB (probe 1) has been designed and explored for the possible detection of NTR. Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections. KEY WORDS: Nitroreductase, MRI contrast agent, Smart imaging probes, Bacterial imaging, Bacterial infection

High-pressure solid-state metathesis (HPSSM) reaction is an effective route to novel metal nitrides. A recent advance in HPSSM reactions is presented for a number of examples, including 3d transition metal nitrides (ε-Fe3N, ε-Fe3−xCoxN, CrN, and Co4Nx), 4d transition metal nitrides (MoNx), and 5d transition metal nitrides (Re3N, WNx). Thermodynamic investigations based on density functional theory (DFT) calculations on several typical HPSSM reactions between metal oxides and boron nitride indicate that the pressure could reduce the reaction enthalpy ΔH. High-pressure confining environment thermodynamically favors an ion-exchange process between metal atom and boron atom, and successfully results in the formation of well-crystalized metal nitrides with potential applications.

One challenge facing humans (and nonhuman animal) is that some options that appear attractive locally may not turn out best in the long run. To analyse this human learning problem, we explore human performance in a dynamic decision-making task that places local and global rewards in conflict. We found that experiences that included previous choices and rewards are not easily incorporated into people’s strategy to enhance their performance. Our results suggest that humans are easily driven by concerns about recent feedback, and that choice of a suboptimal behaviour option may be overcome by providing informative cues that indicate a clear immediate outcome for a better option.

Abstract Background MicroRNAs (miRNAs) have been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. miR-181a, -181b, -181c and -181d are miR-181 members of the family, which has been rarely studied, especially uveal melanoma. Methods The expression level of miR-181 family in human uveal melanoma cell lines was measured via real-time PCR (RT-PCR). The function of miR-181 on cell cycle was detected through Flow Cytometry assay. Microarray assay and Bioinformatics analysis were used to find the potential target of miR-181b, and dual-luciferase reporter assays further identified the target gene. Results MiR-181 family members were found to be highly homologous across different species and their upregulation significantly induces UM cell cycle progression. Of the family members, miR-181b was significantly overexpressed in UM tissues and most UM cells. Bioinformatics and dual luciferase reporter assay confirmed CTDSPL as a target of miR-181b. miR-181b over-expression inhibited CTDSPL expression, which in turn led to the phosphorylation of RB and an accumulation of the downstream cell cycle effector E2F1, promoting cell cycle progression in UM cells. Knockdown CTDSPL using siRNAs showing the same effect, including increase of E2F1 and the progression of cell cycle. Conclusions MiR-181 family members are key negative regulators of CTDSPL-mediated cell cycle progression. These results highlight that miR-181 family members, especially miR-181b, may be useful in the development of miRNA-based therapies and may serve as novel diagnostic and therapeutic candidate for UM.

Phenolic compounds constitute an important family of natural bioactive compounds responsible for the medicinal properties attributed to Bryophyllum plants (genus Kalanchoe, Crassulaceae), but their production by these medicinal plants has not been characterized to date. In this work, a combinatorial approach including plant tissue culture, untargeted metabolomics, and machine learning is proposed to unravel the critical factors behind the biosynthesis of phenolic compounds in these species. The untargeted metabolomics revealed 485 annotated compounds that were produced by three Bryophyllum species cultured in vitro in a genotype and organ-dependent manner. Neurofuzzy logic (NFL) predictive models assessed the significant influence of genotypes and organs and identified the key nutrients from culture media formulations involved in phenolic compound biosynthesis. Sulfate played a critical role in tyrosol and lignan biosynthesis, copper in phenolic acid biosynthesis, calcium in stilbene biosynthesis, and magnesium in flavanol biosynthesis. Flavonol and anthocyanin biosynthesis was not significantly affected by mineral components. As a result, a predictive biosynthetic model for all the Bryophyllum genotypes was proposed. The combination of untargeted metabolomics with machine learning provided a robust approach to achieve the phytochemical characterization of the previously unexplored species belonging to the Bryophyllum subgenus, facilitating their biotechnological exploitation as a promising source of bioactive compounds.

In the present study, a total of 12 extracts of Rhinanthus angustifolius subsp. grandiflorus, an understudied hemiparasitic species, were obtained using different extraction techniques, namely, homogenizer-assisted extraction (HAE), maceration (MAC), soxhlet (SOX), infusion, and solvents (ethyl acetate, methanol, ethanol, and water), and were evaluated for their in vitro antioxidant and enzyme-inhibiting properties. Additionally, untargeted profiling based on high-resolution mass spectrometry targeted different phytochemical classes, namely, polyphenols, terpenoids, and alkaloids. The highest total phenolic and flavonoid contents were detected using methanol as the extraction solvent. Multivariate statistics following the untargeted profiling revealed that the extraction solvent had a hierarchically higher impact than the extraction method when considering the recovery of bioactive compounds. The methanolic extracts displayed the highest radical-scavenging antioxidant capacity, as provided by CUPRAC and FRAP assays. On the other hand, the water extracts (MAC and HAE) and the infusion extract showed the highest activity as metal chelators (25.66–27.51 mg EDTAE/g). Similarly, the water extract obtained by HAE and the infusion extract revealed the highest phosphomolybdenum activity (3.92 ± 0.14 and 3.71 ± 0.01 mmol TE/g, respectively). The different extracts also exhibited different enzyme inhibition potentials. For instance, HAE and MAC ethanolic extracts inhibited only α-amylase (0.69 ± 0.01 and 0.70 ± 0.01 mmol ACAE/g), while all the other extracts showed a dual inhibition against both carbohydrate-hydrolyzing enzymes tested (i.e., α-amylase: 0.07–0.69 mmol ACAE/g; α-glucosidase: 0.03–1.30 mmol ACAE/g). Nevertheless, the other extracts inhibited acetyl-, butyryl-cholinesterases, or both; MAC–water extract displayed no inhibition against the enzymes. Additionally, all the studied extracts were found to inhibit tyrosinase, ranging from 10.62 to 52.80 mg KAE/g. In general, the water extracts showed weaker inhibition towards the enzymes than the other extracts. This study demonstrated that R. angustifolius is an excellent source of natural antioxidants and enzyme inhibitors that could be further investigated and exploited for pharmaceutical purposes.

Recent studies in the agronomic field indicate that the exogenous application of polyphenols can provide tolerance against various stresses in plants. However, the molecular processes underlying stress mitigation remain unclear, and little is known about the impact of exogenously applied phenolics, especially in combination with salinity. In this work, the impacts of exogenously applied chlorogenic acid (CA), hesperidin (HES), and their combination (HES + CA) have been investigated in lettuce (Lactuca sativa L.) through untargeted metabolomics to evaluate mitigation effects against salinity. Growth parameters, physiological measurements, leaf relative water content, and osmotic potential as well as gas exchange parameters were also measured. As expected, salinity produced a significant decline in the physiological and biochemical parameters of lettuce. However, the treatments with exogenous phenolics, particularly HES and HES + CA, allowed lettuce to cope with salt stress condition. Interestingly, the treatments triggered a broad metabolic reprogramming that involved secondary metabolism and small molecules such as electron carriers, enzyme cofactors, and vitamins. Under salinity conditions, CA and HES + CA distinctively elicited secondary metabolism, nitrogen-containing compounds, osmoprotectants, and polyamines.

Artemisia annua L. (AA) has shown for many centuries important therapeutic virtues associated with the presence of artemisinin (ART). The aim of this study was to identify and quantify ART and other secondary metabolites in ethanolic extracts of AA and evaluate the biological activity in the presence of an inflammatory stimulus. In this work, after the extraction of the aerial parts of AA with different concentrations of ethanol, ART was quantified by HPLC and HPLC-MS. In addition, anthocyanins, flavanols, flavanones, flavonols, lignans, low-molecular-weight phenolics, phenolic acids, stilbenes, and terpenes were identified and semi-quantitatively determined by UHPLC-QTOF-MS untargeted metabolomics. Finally, the viability of human neuroblastoma cells (SH-SY5Y) was evaluated in the presence of the different ethanolic extracts and in the presence of lipopolysaccharide (LPS). The results show that ART is more concentrated in AA samples extracted with 90% ethanol. Regarding the other metabolites, only the anthocyanins are more concentrated in the samples extracted with 90% ethanol. Finally, ART and all AA samples showed a protective action towards the pro-inflammatory stimulus of LPS. In particular, the anti-inflammatory effect of the leaf extract of AA with 90% ethanol was also confirmed at the molecular level since a reduction in TNF-α mRNA gene expression was observed in SH-SY5Y treated with LPS.

The quest for sustainable strategies aimed at increasing the bioactive properties of plant-based foods has grown quickly. In this work, we investigated the impact of exogenously applied phenolics, i.e., chlorogenic acid (CGA), hesperidin (HES), and their combinations (HES + CGA), on Lactuca sativa L. grown under normal- and mild-salinity conditions. To this aim, the phenolic profile, antioxidant properties, and enzyme inhibitory activity were determined. The untargeted metabolomics profiling revealed that lettuce treated with CGA under non-stressed conditions exhibited the highest total phenolic content (35.98 mg Eq./g). Lettuce samples grown under salt stress showed lower phenolic contents, except for lettuce treated with HES or HES + CGA, when comparing the same treatment between the two conditions. Furthermore, the antioxidant capacity was investigated through DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,20-azinobis-(3-ethylbenzothiazoline-6-sulfonate)), and FRAP (ferric reducing antioxidant power) assays, coupled with metal-chelating activity and phosphomolybdenum capacity. An exciting increase in radical scavenging capacity was observed in lettuce treated with exogenous phenolics, in both stress and non-stress conditions. The inhibitory activity of the samples was evaluated against target health-related enzymes, namely cholinesterases (acetylcholinesterase; AChE; butyryl cholinesterase; BChE), tyrosinase, α-amylase, and α-glucosidase. Lettuce treated with HES + CGA under non-stress conditions exhibited the strongest inhibition against AChE and BChE, while the same treatment under salinity conditions resulted in the highest inhibition capacity against α-amylase. Additionally, CGA under non-stress conditions exhibited the best inhibitory effect against tyrosinase. All the functional traits investigated were significantly modulated by exogenous phenolics, salinity, and their combination. In more detail, flavonoids, lignans, and stilbenes were the most affected phenolics, whereas glycosidase enzymes and tyrosinase activity were the most affected among enzyme assays. In conclusion, the exogenous application of phenolics to lettuce represents an effective and green strategy to effectively modulate the phenolic profile, antioxidant activity, and enzyme inhibitory effects in lettuce, deserving future application to produce functional plant-based foods in a sustainable way.

Lupin seeds can represent a valuable source of phenolics and other antioxidant compounds. In this work, a comprehensive analysis of the phytochemical profile was performed on seeds from three Lupinus species, including one cultivar (Lupinus albus) and two wild accessions (Lupinus cossentinii and Lupinus luteus), collected from the northern region of Tunisia. Untargeted metabolomic profiling allowed to identify 249 compounds, with a great abundance of phenolics and alkaloids. In this regard, the species L. cossentinii showed the highest phenolic content, being 6.54 mg/g DW, followed by L. luteus (1.60 mg/g DW) and L. albus (1.14 mg/g DW). The in vitro antioxidant capacity measured by the ABTS assay on seed extracts ranged from 4.67 to 17.58 mg trolox equivalents (TE)/g, recording the highest values for L. albus and the lowest for L. luteus. The DPPH radical scavenging activity ranged from 0.39 to 3.50 mg TE/g. FRAP values varied between 4.11 and 5.75 mg TE/g. CUPRAC values for lupin seeds ranged from 7.20 to 8.95 mg TE/g, recording the highest for L. cossentinii. The results of phosphomolybdenum assay and metal chelation showed similarity between the three species of Lupinus. The acetylcholinesterase (AChE) inhibition activity was detected in each methanolic extract analyzed with similar results. Regarding the butyrylcholinesterase (BChE) enzyme, it was weakly inhibited by the Lupinus extracts; in particular, the highest activity values were recorded for L. albus (1.74 mg GALAE/g). Overall, our results showed that L. cossentinii was the most abundant source of polyphenols, consisting mainly in tyrosol equivalents (5.82 mg/g DW). Finally, significant correlations were outlined between the phenolic compounds and the in vitro biological activity measured, particularly when considering flavones, phenolic acids and lower-molecular-weight phenolics.

Cydonia oblonga Mill., normally known as the quince fruit, has been widely used in agro-food industries mainly to produce jams and jellies. However, other parts of the plants are still underutilized and not completely assessed for their nutraceutical profile. Therefore, in this work, the polyphenolic profile of C. oblonga was investigated using an untargeted metabolomics approach based on high-resolution mass spectrometry. Several compounds were identified in the different parts of the plants, including flavonoids (i.e., anthocyanins, flavones, flavan-3-ols, and flavonols), phenolic acids (both hydroxycinnamics and hydroxybenzoics), low-molecular-weight phenolics (tyrosol equivalents), lignans, and stilbenes. Overall, C. oblonga leaves showed the highest in vitro antioxidant potential, as revealed by 2,2-difenil-1-picrylhydrazyl (DPPH), 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) assays, being 189.5, 285.6, 158.9, and 348.8 mg Trolox Equivalent/g, respectively. The enzymes acetyl- and butyryl-cholinesterases were both inhibited by the different plant parts of C. oblonga, with stems showing the higher inhibitory potential. Interestingly, the fruit extracts were the only parts inhibiting the α-glucosidase, with a value of 1.36 mmol acarbose equivalents (ACAE)/g. On the other hand, strong tyrosinase inhibition was found for stems and leaves, being 72.11 and 68.32 mg Kojic acid Equivalent/g, respectively. Finally, a high number of significant (0.05 < p < 0.01) correlations were outlined between phenolics (mainly anthocyanins, flava-3-ols, and tyrosol equivalents) and the different biological assays. Taken together, our findings suggest a potential exploitation of C. oblonga leaves and stems for the food, pharmaceutical, and cosmetic industries.

Abstract There is a strong rationale to therapeutically target the PI3K/Akt/mTOR and MAPK/ERK pathways in cervical carcinoma since they are highly deregulated in this disease. Previous study by our group have demonstrated that Zeylenone (Zey) exhibited strong suppressive activity on PI3K/AKT/mTOR and MAPK/ERK signaling, providing a foundation to investigate its antitumor activity in cervical carcinoma. Herein, the present study aimed to investigate suppressive effect of Zey on HeLa and CaSki cells, and further explore the underlying mechanisms. Cells were treated with Zey for indicated time, followed by measuring its effects on cell viability, colony formation, cell cycle, cell apoptosis, and signal pathways. In vivo antitumor activity of Zey was then assessed with nude xenografts. We found that Zey substantially suppressed cell proliferation, induced cell cycle arrest, and increased cell apoptosis, accompanied by increased production of ROS, decreased mitochondrial membrane potential, activated caspase apoptotic cascade, and attenuated PI3K/Akt/mTOR and MAPK/ERK pathways. Additionally, in vivo experiments showed that Zey exerted good antitumor efficacy against HeLa bearing mice models via decreasing levels of p-PI3K and p-ERK. Collectively, these data clearly demonstrated the antitumor activity of Zey in cervical carcinoma cells, which is most likely via the regulation of PI3K/Akt/mTOR and MAPK/ERK pathways.

The objective of this study is to propose a new operation method based on the universal grey number to overcome the shortcomings of typical interval operation in solving system fault trees. First, the failure probability ranges of the bottom events are described according to the conversion rules between the interval number and universal grey number. A more accurate system reliability calculation is then obtained based on the logical relationship between the AND gates and OR gates of a fault tree and universal grey number arithmetic. Then, considering an aircraft landing gear retraction system as an example, the failure probability range of the top event is obtained through universal grey operation. Next, the reliability of the aircraft landing gear retraction system is evaluated despite insufficient statistical information describing failures. The example demonstrates that the proposed method provides many advantages in resolving the system reliability problem despite poor information, yielding benefits for the function of the interval operation, and overcoming the drawback of solution interval enlargement under different orders of interval operation.

Aims: The purpose of this study was to assess the relationship between genetic variants and steroid-induced osteonecrosis of the femoral head (SONFH) in steroid use populations.Methods: We searched the public databases up to April 15, 2018. This study analyzed only the single-nucleotide polymorphisms (SNPs) that have appeared in more than three studies and assessed the level of evidence by classifying the outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Results: The ABCB1 rs1045642 C>T mutation had a protective effect against SONFH in the allelic model (I2 = 50.2%; OR: 0.74; 95% CI: 0.55–1.00; p = 0.046). The rs2032582 mutation in the ABCB1 gene showed no relationship to SONFH (allelic model: I2 = 63.4%; OR: 0.85; 95% CI: 0.58–1.23; p = 0.382). In ApoB rs693, four models showed that mutations can increase SONFH risk, but the allelic model did not. The ApoB rs1042031 mutation increased SONFH risk in the dominant model (I2 = 50.3%; OR: 2.90; 95% CI: 1.49–5.66; p = 0.002).Conclusion: An allelic model of ABCB1 rs1045642 showed that mutations have a protective effect against SONFH at a very low level of evidence. The mutations in ApoB rs693 and rs1042031 increase the SONFH risk with moderate levels of evidence.

Gynostemma pentaphyllum (var. Ginpent) (GP) is a variety of Cucurbit with anti-inflammatory and antioxidant effects in patients. In this manuscript, the main components present in the dry extract of GP have been identified using Ultra High Performance Liquid Chromatography quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). In addition, the anti-inflammatory action of GP was evaluated in animal models with acute peripheral inflammation and motor alteration induced by lipopolysaccharide. The results showed that GP dry extract is rich in secondary metabolites with potential antioxidant and anti-inflammatory properties. We found that the treatment with GP induced a recovery of motor function measured with the rotarod test and pole test, and a reduction in inflammatory cytokines such as interleukin-1β and interleukin-6 measured with the ELISA test. The data collected in this study on the effects of GP in in vivo models may help integrate the therapeutic strategies of inflammatory-based disorders.

Mineral elements are essential for plant growth and development and strongly affect crop yield and quality. To cope with an everchanging environment, plants have developed specific responses to combined nutrient variations. In this work, we investigated the effects of multifactorial treatments with three macrocations (K, Ca, and Mg) on lettuce (Lactuca sativa L.) varieties that strongly diverge in leaf pigmentation (full red or green). Specifically, we monitored main leaf parameters and metabolomics profiles of hydroponically grown plants fed with isosmotic nutrient solutions that have different proportions of macroelements. The result revealed a high biochemical plasticity of lettuce, significantly affected by the genotype, the nutrient solution, and their interaction. Our work also provided evidence and insights into the different intraspecific responses to multifactorial variation of macrocations, with two varieties having distinct strategies to metabolically respond to nutrient variation. Overall, plant adaptive mechanisms increased the phytochemical diversity between the varieties both among and within the main classes of plant secondary metabolites. Finally, our work also implies that the interaction of a pre-existing phytochemical diversity with the management of multiple mineral elements can offer added health-related benefits to the edible product specific to the variety.

During the past few decades, colorectal cancer (CRC) incidence and mortality have significantly increased, and CRC has become the leading cause of cancer-related death worldwide. Thus, exploring novel effective therapies for CRC is imperative. In this study, we investigated the effect of oncolytic adenovirus CD55-Smad4 on CRC cell growth. Cell viability assay, animal experiments, flow cytometric analysis, cell migration, and invasion assays, and Western blotting were used to detect the proliferation, apoptosis, migration, and invasion of CRC cells. The oncolytic adenovirus CD55-Smad4 was successfully constructed and effectively suppressed CRC cell proliferation in vivo and in vitro. Notably, CD55-Smad4 activated the caspase signaling pathway, inducing the apoptosis of CRC cells. Additionally, the generated oncolytic adenovirus significantly suppressed migration and invasion of CRC cells by overexpressing Smad4 and inhibiting Wnt/β-catenin/epithelial-mesenchymal transition (EMT) signaling pathway. Moreover, CRC cells treated with CD55-Smad4 formed less and smaller spheroid colonies in serum-free culture than cells in control groups, suggesting that CD55-Smad4 suppressed the stemness of CRC cells by inhibiting the Wnt/β-catenin pathway. Together, the results of this study provide valuable information for the development of a novel strategy for cancer-targeting gene-virotherapy and provide a deeper understanding of the critical significance of Smad4 in gene therapy of CRC.

The study of the relationship between cultivated plants and environmental factors can provide information ranging from a deeper understanding of the plant biological system to the development of more effective management strategies for improving yield, quality, and sustainability of the produce. In this article, we present a comprehensive metabolomics dataset of two phytochemically divergent lettuce (Lactuca sativa L.) butterhead varieties under different growing conditions. Plants were cultivated in hydroponics in a growth chamber with ambient control. The pre-harvest factors that were independently investigated were light intensity (two levels), the ionic strength of the nutrient solutions (three levels), and the molar ratio of three macroelements (K, Mg, and Ca) in the nutrient solution (three levels). We used an untargeted, mass-spectrometry-based approach to characterize the metabolomics profiles of leaves harvested 19 days after transplant. The data revealed the ample impact on both primary and secondary metabolism and its range of variation. Moreover, our dataset is useful for uncovering the complex effects of the genotype, the environmental factor(s), and their interaction, which may deserve further investigation.

To fully understand potential changes in hydrological regime over the Lhasa River Basin (LRB) and the upstream of Niyang River Basin (UNRB) in Tibetan Plateau under global warming, the VIC-glacier model was employed to analyze the responses of rainfall runoff and melt water to recent climate change, and we also quantify their roles in controlling the trend of river streamflow during 1963–2012. The hydrological model was calibrated using the observed streamflow, glacier mass balance, and MODIS snow cover. The simulations indicate that there is a significant increasing trend in glacier runoff for both basins during 1963–2012, especially in the period of 2000s when it exhibits a large increment up to about 45% relative to baseline period. Rainfall runoff suggests a rising tendency whereas snowmelt runoff displays a general decreasing tendency. For both basins, increasing rainfall runoff was identified as the dominant driver for the upward trend in total runoff during 1963–2012. The role of glacier runoff in controlling the trend of total runoff is also obvious, especially in the more glaciated UNRB where increased glacier runoff accounts for up to 41% of the tendency in river discharge. Snowmelt runoff plays a minor role in affecting the trend of total runoff.

Sub-optimal growing conditions have a major effect on plants; therefore, large efforts are devoted to maximizing the availability of agricultural inputs to crops. To increase the sustainable use of non-renewable inputs, attention is currently given to the study of plants under non-optimal conditions. In this work, we investigated the impact of sub-optimal macrocations availability and light intensity in two lettuce varieties that differ for the accumulation of secondary metabolites (i.e., ‘Red Salanova’ and ‘Green Salanova’). Photosynthesis-related measurements and untargeted metabolomics were used to identify responses and pathways involved in stress resilience. The pigmented (‘Red’) and the non-pigmented (‘Green Salanova’) lettuce exhibited distinctive responses to sub-optimal conditions. The cultivar specific metabolomic signatures comprised a broad modulation of metabolism, including secondary metabolites, phytohormones, and membrane lipids signaling cascade. Several stress-related metabolites were altered by either treatment, including polyamines (and other nitrogen-containing compounds), phenylpropanoids, and lipids. The metabolomics and physiological response to macrocations availability and light intensity also implies that the effects of low-input sustainable farming systems should be evaluated considering a range of cultivar-specific positive and disadvantageous metabolic effects in addition to yield and other socio-economic parameters.

Accidental failures of rotating machinery components such as rolling bearings may trigger the sudden breakdown of the whole manufacturing system, thus, fault diagnosis is vital in industry to avoid these massive economical costs and casualties. Since convolutional neural networks (CNN) are poor in extracting reliable features from original signal data, the time-frequency analysis method is usually called for to transform 1D signal into a 2D time-frequency coefficient matrix in which richer information could be exposed more easily. However, realistic fault diagnosis applications face a dilemma in that signal time-frequency analysis and fault classification cannot be implemented together, which means manual signal conversion work is also needed, which reduces the integrity and robustness of the fault diagnosis method. In this paper, a novel network named WPT-CNN is proposed for end-to-end intelligent fault diagnosis of rolling bearings. WPT-CNN creatively uses the standard deep neural network structure to realize the wavelet packet transform (WPT) time-frequency analysis function, which seamlessly integrates fault diagnosis domain knowledge into deep learning algorithms. The overall network architecture can be trained with gradient descent backpropagation algorithms, indicating that the time-frequency analysis module of WPT-CNN is also able to learn the dataset characteristics, adaptively representing signal information in the most suitable way. Two experimental rolling bearing fault datasets were used to validate the proposed method. Testing results showed that WPT-CNN obtained the testing accuracies of 99.73% and 99.89%, respectively, in two datasets, which exhibited a better and more reliable diagnosis performance than any other existing deep learning and machine learning methods.

Considering that functional components of plant foods are mainly secondary-metabolism products, we investigated the shaping of health-promoting compounds in hydroponically grown butterhead lettuce (Lactuca sativa L. var. capitata) as a function of the strength of the nutrient solution utilized. To this aim, untargeted metabolomics profiling, in vitro antioxidant capacity (total phenolics, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays), and the inhibition of selected enzyme activities were investigated in two butterhead lettuce cultivars with different pigmentation, i.e., green and red Salanova. Full-strength nutrition, together with half- and quarter-strength solutions of macronutrients, was tested. Our results indicate that by reducing the nutrients strength, we could elicit a distinctive shaping of the phenolic profile of lettuce. It is noteworthy that only specific classes of phenolics (namely, lignans and phenolic acids, followed by flavones and anthocyanins) were modulated by the induction of nutritional eustress (fold-change values in the range between −5 and +11). This indicates that specific responses, rather than a generalized induction of phenolic compounds, could be observed. Nonetheless, a genotype-dependent response could be observed, with the red cultivar being much more responsive to nutritional deprivation than the green Salanova lettuce. Indeed, analysis of variance (ANOVA) confirmed a genotype x nutrition interaction in red Salanova (p < 0.001). As a consequence of the changes in phenolic composition, also the antioxidant capacity (p < 0.001) and amylase inhibition (p < 0.001) properties were affected by the growing conditions. However, the effect on cholinesterase and tyrosinase inhibition was poorly affected by the nutritional strength. Provided that yields are not compromised, the application of a controlled nutritional eustress in hydroponically cultivated lettuce may represent a valuable strategy to produce food with tailored functional features in a sustainable manner.

With the application of finite element method on structure design and engineering analysis more and more widely, this paper presents a response surface model hybrid artificial bee colony method to optimize the thermal boundary conditions in finite element thermal analysis of a machine tool spindle to improve its finite element simulation precision. Initially, the thermal experiment and finite element thermal analysis of the machine tool spindle with initials that were calculated by empirical formulas were conducted, respectively. Additionally, focusing on thermal boundary conditions, a response surface model is designed to establish the explicit expression between thermal boundary conditions and the simulation errors; then, an artificial bee colony algorithm is used to solve the mixed-variable optimization problems of a response surface model. Finally, the optimized thermal boundary conditions are brought into the finite element method of a machine tool system, and the simulation accuracy has been greatly improved .

The CoCrFeNiVx (x = 0, 0.25, 0.5, 0.7, 0.8, 0.9, and 1.0) high-entropy alloys (HEAs) were fabricated by the copper mold casting process. The microstructure, phase constitution, and mechanical properties were investigated by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy analyses and compressive testing. It revealed that, when x ≤ 0.25, the alloys solidified into a single fcc phase. When 0.5 ≤ x ≤ 0.8, the alloys solidified into a dendritic structure of the fcc phase with the formation of the σ phase in the interdendrite region. Interestingly, when x exceeded 0.9, the alloys presented a typical core-shell equiaxed grain morphology. The core region consisting of a mixture of fcc + σ phases was surrounded by the shell of the single σ phase and the interdendrite region solidified into the single fcc phase. The dual-phase “eutectiod” structure in the core region of the equiaxed grain might be formed from the decomposition of the unidentified metastable phase. As the V fraction increased, the compressive yield strength of the CoCrFeNiVx alloys gradually increased from 164 MPa (x = 0) to 458 MPa (x = 0.8), and then sharply increased to 722 MPa (x = 0.9) and 1493 MPa (x = 1.0).

Centriolar satellites are non-membrane cytoplasmic granules that deliver proteins to centrosome during centrosome biogenesis and ciliogenesis. Centriolar satellites are highly dynamic during cell cycle or ciliogenesis and how they are regulated remains largely unknown. We report here that sorting nexin 17 (SNX17) regulates the homeostasis of a subset of centriolar satellite proteins including PCM1, CEP131, and OFD1 during serum-starvation-induced ciliogenesis. Mechanistically, SNX17 recruits the deubiquitinating enzyme USP9X to antagonize the mindbomb 1 (MIB1)-induced ubiquitination and degradation of PCM1. SNX17 deficiency leads to enhanced degradation of USP9X as well as PCM1 and disrupts ciliogenesis upon serum starvation. On the other hand, SNX17 is dispensable for the homeostasis of PCM1 and USP9X in serum-containing media. These findings reveal a SNX17/USP9X mediated pathway essential for the homeostasis of centriolar satellites under serum starvation, and provide insight into the mechanism of USP9X in ciliogenesis, which may lead to a better understating of USP9X-deficiency-related human diseases such as X-linked mental retardation and neurodegenerative diseases.

Objective This study aimed to investigate the damage pattern of the stress transfer path (STP) for the Japanese Investigation Committee (JIC) classification of pre-collapse osteonecrosis of the femoral head. We aimed to provide a specific biomechanical basis for treatment decisions of each subtype. Methods Five computational models were used in the experiment. Different necrotic classifications were simulated based on the JIC classification system. Damage patterns of the STP were used for qualitative assessment and average stresses were used for quantitative analysis. Results The STP of type A showed a strong similarity to the healthy level, which was consistent with the bone density distribution in X-rays and previous simulations results. The damaged area of principal stress of type B was approximately 25% of the healthy level. The STPs of types C1 and C2 were broken and the damaged areas of principal stress were more than 50% of the healthy level. The efficiency of stress transfer was reduced. Conclusions These results indicate that the damage patterns and stress transfer efficiency of the femoral head are associated with necrotic classifications.

Fibromyalgia (FM) and obesity are closely related. However, little is known about how obesity contributes to FM. Importantly, adequate evidence has shown that tumor necrosis factor alpha (TNF-α) plays a critical role in obesity. Thus, we hypothesized that obesity-induced TNF-α release may potentiate FM-associated pain. To test this hypothesis, we investigated the role of TNF-α in the development of FM-like pain in a mouse model of acid saline injection-induced FM. Consistent with previous reports, we showed that repeated acid saline injections induced bilateral mechanical hyperalgesia, and this effect lasted for at least 4 days after acid saline injections. This phenomenon was associated with increased levels of TNF-α in plasma, muscles, and spinal cord. Furthermore, we found that 24 weeks of high fat diet treatment significantly potentiated acid saline-induced bilateral mechanical hyperalgesia. High fat diet-treated mice exhibited robustly increased levels of TNF-α in plasma, muscles, and spinal cord after acid saline injections compared with low fat diet-treated mice. Additionally, using immunofluorescence staining, we found that the number of TNF-α positive cells in dorsal root ganglion (DRG) was increased after acid saline injections, and high fat diet treatment further sensitized this increase. Finally, we reported that acid saline-induced FM-like pain behaviors were abolished in TNFRp55-/- mice, confirming the critical role of TNF-α in the development of FM-like pain. Taken together, our results suggested that high fat diet treatment may sensitize acid saline-induced FM-like pain via increasing TNF-α levels in plasma, muscles, and DRG.

Red mud, a Fe-rich waste generated from the aluminum industry, was recovered as an adsorbent for wastewater treatment. The separation process of red mud from water after adsorption, including centrifugation and filtration, was complicated. This study demonstrated an alternative option to recycle red mud for preparing magnetic adsorbent via a facile hydrothermal route using ascorbic acid as reductant. Red mud is weakly magnetized and consists of andradite, muscovite, hematite, and cancrinite. After hydrothermal treatment, andradite in red mud was reductively dissolved by ascorbic acid, and transformed into magnetite and morimotoite. With increasing hydrothermal temperature, the dissolution of andradite accelerated, and the crystallite size of magnetite increased. When the hydrothermal temperature reached 200 °C, the prepared adsorbent P-200 showed a desirable saturation magnetization of 4.1 Am2/kg, and could be easily magnetically separated from water after adsorption. The maximum adsorption capacity of P-200 for Zn2+ was 89.6 mg/g, which is eight-fold higher than that of the raw red mud. The adsorption of Zn2+ by P-200 fitted the Langmuir model, where cation exchange was the main adsorption mechanism. The average distribution coefficient of Zn2+ at low ppm level was 16.81 L/g for P-200, higher than those of the red mud (0.3 L/g) and the prepared P-120 (1.48 L/g) and P-270 (5.48 L/g), demonstrating that P-200 had the best adsorption capacity for Zn2+ and can be served as a practical adsorbent for real-world applications. To our knowledge, this is the first study to report the conversion of red mud into a magnetic adsorbent under mild conditions.

A series of novel self-cleaning hybrid photocatalytic ultrafiltration (UF) membranes were fabricated to separate polyacrylamide, which is widely used as a commercial flocculant. To maximize the self-cleaning and anti-fouling properties of hybrid membranes, high surface area TiO2 nanotubes (TNTs) with excellent photocatalytic activity were homogeneously introduced into a poly(aryl ether sulfone) matrix by chemical bonds. The chemical structure, micromorphology, hydrophilicity, separation efficiency, fouling behavior, and self-cleaning property of the prepared hybrid membranes were well characterized and evaluated. For the optimal sample, the flux recovery ratio increased from ~40% to ~80% after simulated sunlight irradiation for 20 min, which was attributable to the homogeneous dispersion and efficient photocatalytic degradation ability of TNTs. Furthermore, the intelligent fabrication strategy enhanced the anti-aging ability of the hybrid membranes via the use of a fluorine-containing poly matrix. This work provided new insight into the fabrication of high-performance self-cleaning inorganic/organic hybrid membranes.

When reclaimed water was recharged into groundwater containing a low content of ferrous iron, Fe-rich particles were generated and started to transport into the porous medium. X-ray powder diffraction and Mössbauer spectroscopy analysis showed that the generated Fe-rich particles were in a poorly crystallized ferrihydrite phase. After the formation of ferrihydrite particles, the mass loss of contaminants was calculated, which was 88.2% for Al, 93.3% for Zn, and 41.6% for chemical oxygen demand (COD). Protein-like compounds were predominant in the removed COD. Bovine serum albumin (BSA) was used as a model to investigate the effect of proteins on the transport of ferrihydrite particles in porous medium. Results showed that the attachment efficiency of ferrihydrite particles on the porous medium decreased from 100% to 75% with the increase of BSA concentration from 10 mg/L to 100 mg/L. BSA was attached to the surface of ferrihydrite particles via electrostatic adsorption. Thus, the zeta potential of ferrihydrite particles changed from positive to negative, and the particles became less aggregated, thereby enhancing particle mobility. This observation provided evidence that protein residues in reclaimed water enhance the transport of Fe-rich particles in saturated porous medium.

Glycoside Hydrolase 3 (GH3) is a phytohormone-responsive family of proteins found in many plant species. These proteins contribute to the biological activity of indolacetic acid (IAA), jasmonic acid (JA), and salicylic acid (SA). They also affect plant growth and developmental processes as well as some types of stress. In this study, GH3 genes were identified in 48 plant species, including algae, mosses, ferns, gymnosperms, and angiosperms. No GH3 representative protein was found in algae, but we identified 4 genes in mosses, 19 in ferns, 7 in gymnosperms, and several in angiosperms. The results showed that GH3 proteins are mainly present in seed plants. Phylogenetic analysis of all GH3 proteins showed three separate clades. Group I was related to JA adenylation, group II was related to IAA adenylation, and group III was separated from group II, but its function was not clear. The structure of the GH3 proteins indicated highly conserved sequences in the plant kingdom. The analysis of JA adenylation in relation to gene expression of GH3 in potato (Solanum tuberosum) showed that StGH3.12 greatly responded to methyl jasmonate (MeJA) treatment. The expression levels of StGH3.1, StGH3.11, and StGH3.12 were higher in the potato flowers, and StGH3.11 expression was also higher in the stolon. Our research revealed the evolution of the GH3 family, which is useful for studying the precise function of GH3 proteins related to JA adenylation in S. tuberosum when the plants are developing and under biotic stress.

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to encapsulate ranibizumab in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs) for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy.

Increasing evidence suggests that aberrant long non-coding RNAs (lncRNAs) are significantly correlated with the pathogenesis, development and metastasis of cancers. RHPN1 antisense RNA 1 (RHPN1-AS1) is a 2030-bp transcript originating from human chromosome 8q24. However, the role of RHPN1-AS1 in uveal melanoma (UM) remains to be clarified. In this study, we aimed to elucidate the molecular function of RHPN1-AS1 in UM. The RNA levels of RHPN1-AS1 in UM cell lines were examined using the quantitative real-time polymerase chain reaction (qRT-PCR). Short interfering RNAs (siRNAs) were designed to quench RHPN1-AS1 expression, and UM cells stably expressing short hairpin (sh) RHPN1-AS1 were established. Next, the cell proliferation and migration abilities were determined using a colony formation assay and a transwell migration/invasion assay. A tumor xenograft model in nude mice was established to confirm the function of RHPN1-AS1 in vivo. RHPN1-AS1 was significantly upregulated in a number of UM cell lines compared with the normal human retinal pigment epithelium (RPE) cell line. RHPN1-AS1 knockdown significantly inhibited UM cell proliferation and migration in vitro and in vivo. Our data suggest that RHPN1-AS1 could be an oncoRNA in UM, which may serve as a candidate prognostic biomarker and target for new therapies in malignant UM.

Background: Sorting nexins are a large family of proteins that are associated with various components of the endosome system and they play many roles in processes such as endocytosis, intracellular protein trafficking and cell signaling. The subcellular distribution patterns of many of them remain controversial and their in vivo functions have not been characterized yet. Results: We investigated the subcellular distribution and function of SNX16 in this study. SNX16 is detected on Rab5-positive endosomes localized adjacent to focal adhesions at cell cortex. Inhibition of SNX23, polymerization of microtubule filaments as well as the PI3-kinase all disrupt the cell cortex distribution of SNX16. Ectopic expression of SNX16 reduces the migration and the tumor formation activity of MCF-7 cells. Conclusion: Our results indicate that, in addition to the PI3P, there is a SNX23- and microtubule-dependent cargo transport pathway required for the proper subcellular distribution of SNX16. SNX16 plays a negative regulatory role during cell migration and tumorigenesis.

The flow transport of a 420 × 320 × 90 mm beam blank continuous casting mold that used open-stream pouring combined with submerged refractory funnels was studied. By considering the dynamic similarity, geometric similarity, and air entrapment quantity similarity, a full-size water model was established. Meanwhile, the 3D mathematical models that included three phases were applied. Through the combination of the water model and the mathematical model, the distribution and morphology of the phases in the mold were investigated. The results indicate that bubbles existed in the molten steel due to entrapment and the flow pattern was different from that of the full protection-poured mold. Furthermore, the effects of funnel immersion depth and funnel diameter on the bubbles’ impact depth, funnel’s inside wall shear stress, and overall area of the air/steel interface were discussed. The results provide useful information for the industrial continuous casting process.

Notch signaling pathway plays an important role in tumorigenesis by maintaining the activity of self-renewal of cancer stem cells, and therefore, it is hypothesized that interference of Notch signaling may inhibit tumor formation and progression. H101 is a recombinant oncolytic adenovirus that is cytolytic in cells lacking intact p53, but it is unable to eradicate caner stem cells. In this study, we tested a new strategy of tumor gene therapy by combining a Notch1-siRNA with H101 oncolytic adenovirus. In HeLa-S3 tumor cells, the combined therapy blocked the Notch pathway and induced apoptosis in tumors that are p53-inactive. In nude mice bearing xenograft tumors derived from HeLa-S3 cells, the combination of H101/Notch1-siRNA therapies inhibited tumor growth. Moreover, Notch1-siRNA increased Hexon gene expression at both the transcriptional and the translational levels, and promoted H101 replication in tumors, thereby enhancing the oncolytic activity of H101. These data demonstrate the feasibility to combine H101 p53-targted oncolysis and anti-Notch siRNA activities as a novel anti-cancer therapy.