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[Display omitted] • 2D In 2 O 3 is decorated on 2D BiOBr to form a Z-scheme heterojunction. • This work achieves improved internal electric field and charge separation. • The B 3 I 1 composite exhibits enhanced photocatalytic activity. • The mechanism of photocatalytic CO 2 reduction into CO is proposed. CO 2 photocatalytic reduction is an excellent strategy for promoting solar-to-chemical energy conversion and alleviating the severe environmental crisis. In this study, 2D indium oxide (IO) is decorated on 2D bismuth oxybromide (BOB) nanosheets to gain BOB/IO (B x I y) heterojunction. The optimal B 3 I 1 composite affords a CO production rate of 54.2 μmol⋅g−1, about 2.2 times and 11.3 times higher than those of the pristine BOB and IO, respectively. The introduction of IO significantly enhances the internal electric field (IEF), leading to accelerated charge transfer and prolonged lifetime of the photogenerated carriers. In the B x I y composite, the BOB and IO serve as the electron acceptor and donor, respectively, facilitating the reduction of CO 2 and oxidation of H 2 O. In-situ DRIFTs spectra are used to confirm the catalytic active sites and provide insights into the mechanism of CO 2 photoreduction. The results suggest *COOH and *CO 2 – species played a crucial role in the formation of CO. This work presents a valuable perspective on understanding the charge transfer route and developing highly efficient photocatalysts for CO 2 photoreduction. [ABSTRACT FROM AUTHOR]

By combining theoretical predictions and experiments, we reported a general strategy to engineer the electronic properties of iron-nitrogen-carbon (FeN 4 /C) catalysts via the incorporation of B atom for achieving improved catalytic activity in oxygen electrocatalysis. [Display omitted] Modulating the microenvironment of single-metal active sites holds excellent promises for developing highly efficiently oxygen electrocatalysts. Herein, by combining theoretical predictions and experiments, we reported a general strategy to engineer the electronic properties of iron-nitrogen-carbon (FeN 4 /C) catalysts via the incorporation of the boron (B) atom for achieving improved catalytic activity in oxygen electrocatalysis. Our theoretical results revealed that B modulation effectively tunes the d-band center of the iron (Fe) active site to optimize its adsorption strength with oxygenated species, greatly enhancing oxygen reduction reaction (ORR) and oxygen evolution reactions (OER) activity. Our experimental measurements then confirmed the above theoretical predictions: the as-synthesized B-doped FeN 4 /C (Fe-N 4 -B) material can perform as an eligible bifunctional catalyst for ORR and OER in alkaline media, and its catalytic activity even outperforms the commercial noble metal benchmarks. The present findings provide a promising strategy to further design the advanced catalysts for a wide range of electrochemical applications. [ABSTRACT FROM AUTHOR]

• In this work, we propose AntiMF, a deep learning model that utilizes multi-view mechanism based on different feature extraction models. • Comparative results show that our model has better performance than the state-of-the-art methods in the prediction of anticancer peptides. • By using an ensemble learning framework, AntiMF can capture the different dimensional information, which can make model representation more complete. In recent years, anticancer peptides have emerged as a new viable option in cancer therapy, with the ability to overcome the considerable side effects and poor outcomes of standard cancer therapies. Accurate anticancer peptide identification can facilitate its finding and speed up its application in treating cancer. However, many recent approaches are based on machine learning, which not only restricts the representation ability of the models but also requires a complex hand-crafted feature extraction process. Here, we propose AntiMF, a deep learning model that utilizes multi-view mechanism based on different feature extraction models. Comparative results show that our model has a better performance than the state-of-the-art methods in the prediction of anticancer peptides. By using an ensemble learning framework to extract representation, AntiMF can capture the different dimensional information, which can make model representation more complete. Moreover, we visualize what AntiMF learns on one of its ensemble models to intuitively show the effectivity of our model, indicating that AntiMF has the great potential ability to be an effective and useful model to identify anticancer peptides accurately. [ABSTRACT FROM AUTHOR]

The aim of the study was to explore different effects of exercise, metformin alone, or exercise combined with metformin on cardiovascular morphological and functional changes in early stage of type 2 diabetes mellitus. Eight-week-old diabetic db/db mice and BKS mice were recruited and exposed to three different treatments (exercise, metformin alone, or their combination) for 8 weeks. Metformin was administered intragastrically, and aerobic exercise was performed using treadmill with 7–12 m/min, 30–40 min/day, 5 days/week. In the combination group, aerobic exercise was carried out for 30 min after intragastric administration of metformin. The results showed that all three treatments improved cardiac fibrosis and aortic lipid deposition. Exercise intervention failed to alleviate myocardial hypertrophy, but it improved the declined heart rate and diastolic blood pressure in diabetic db/db mice. In contrast, metformin caused opposite effects in these mice. The combination of exercise and metformin had additive effects on glucose intolerance and insulin sensitivity rather than on the improvement of myocardial and aortic structure. In conclusion, metformin improved changes in the morphology and structure of the heart and aorta, while exercise alone or in combination with metformin demonstrated more advantages in cardiac functional reserve through the physiological hypertrophy of myocardium in diabetic db/db mice. • db/db mice show cardiovascular morphological and functional changes at 16 weeks old. • Only metformin works in alleviating myocardial hypertrophy. • Exercise might improve cardiac functional reserve through physiological hypertrophy. • Exercise plus metformin demonstrates no addictive effects on cardiovascular health. • All three treatments improve myocardial fibrosis and lipid accumulation of aorta. [ABSTRACT FROM AUTHOR]

[Display omitted] It is imperative to seek for novel materials with pronounced gas sensing performance towards triethylamine for the sake of human health. Herein, we successfully fabricate an outstanding triethylamine sensor based on CdS/ZnO composite with 0D/2D structure, which are prepared by in-situ growth of CdS quantum dots on ultra-thin ZnO nanosheets. The ratios between the two ingredients are adjusted and their effect is evaluated. The optimal sample exhibits the lowest operating temperature of 200 °C, the highest response value of ~20 and the fastest response time of 2 s. Besides, it also has the virtues of durable stability, excellent selectivity and superior anti-interference ability. The mechanism behind the aforementioned intriguing performance is investigated by X-ray photoelectron spectroscopy, Kelvin probe and density function theory (DFT) simulation. All the results verify that the enhanced gas sensing properties are derived from splendid 0D/2D structure, n - n heterojunction and large specific surface area. Additionally, this study opens an avenue for designing sensors with 0D/2D structure. [ABSTRACT FROM AUTHOR]

In this study, the impacts of high-temperature drying (80 °C) at varying moisture levels HT1 (30%) and HT2 (12%) on texture of dried noodles were investigated by considering the protein aggregation and pore distribution in both dried and cooked noodles. In comparison to medium-temperature drying (45 °C), an increase in protein aggregation was observed in dried noodles obtained under HT1. Additionally, HT1 conditions led to uneven gluten network and significant variations in pore size, which ultimately reduced the bending resistance of dried noodles from 9.45% to 31.82%. Upon cooking, the protein in noodles from HT1 underwent slight depolymerization, resulting in lower protein aggregation as compared to noodles from HT2, which negatively affected the edible quality of products from HT1. Our findings demonstrated that dried noodle qualities under HT2 increased up to 32.73% compared to medium-temperature drying and HT1, due to suitable protein aggregation and smaller pore distribution associated with HT2. Finally, the degree of protein aggregation in cooked noodles is a more accurate quality indicator than analyzing dried noodles. [Display omitted] • Noodles via high temperature drying under 12% moisture had better edible quality. • Excessive protein aggregation resulted into more large pores. • A uniform and dense gluten network structure corresponded to small and few pores. • Protein aggregation degree in cooked noodles was a more accurate quality indicator. • Smaller pores in dried noodles led to higher bending resistance and edible quality. [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies have found that dihydroartemisinin (DHA) has multiple functions such as anti-inflammatory, anti-tumor in addition to anti-malarial effects. Effect of DHA on monocrotaline-induced pulmonary hypertension in rats has been reported, while the specific mechanism is not known. Method A hypoxic model was established with human pulmonary arterial endothelial cells (HPAECs) to investigate the possible mechanism of DHA. Effects of DHA on proliferation of HPAECs were evaluated by CCK-8 and EdU assay. Effects of DHA on cell oxidative stress, cell migration, angiogenesis, cell cycle and autophagy, as well as the possible underlying mechanism were also detected by using the established normoxia/hypoxia cell models. Results DHA significantly inhibited hypoxia induced increase of HPAECs proliferation in a dose dependent manner, migratory ability and angiogenic ability. DHA also significantly reversed hypoxia induced oxidative stress as a reduction of ROS and NO, and an increase of SOD. Autophagosomes, LC3B protein and apoptotic proteins were significantly increased in DHA treated hypoxic HPAECs. Autophagy inhibitor 3-Methyladenine diminishes the anti-hypoxia effects of DHA on cell proliferation, migration, and autophagy and apoptosis protein expression in HPAECs. Conclusion DHA effectively inhibits hypoxia induced increase of cell proliferation, migration, and oxidative stress in HPAECs, and autophagy may be the underlying mechanism of DHA. Highlights • Dihydroartemisinin diminishes hypoxia increases proliferation and migration of HPAEC cells. • Hypoxia induced oxidative stress and autophagy in HPAEC cells can be inhibited by dihydroartemisinin. • Activation of autophagy pathway blunts the anti-hypoxic of dihydroartemisinin in HPAEC cells. [ABSTRACT FROM AUTHOR]

Abstract Hypoxia-induced pulmonary hypertension (HPH) is a progressive disease characterized by a sustained, elevated pulmonary arterial pressure and vascular remodeling. The latter pathogenesis mainly involves overproliferation of pulmonary artery smooth muscle cells (PASMCs). Fibroblast growth factor 21 (FGF21) has recently emerged as a novel regulator that prevents cardiac hypertrophic remodeling. However, its possible role in pulmonary remodeling remains unclear. The activation of peroxisome proliferator activated receptor γ (PPARγ) is reported to attenuate HPH by suppressing proliferative signals. Loss of PPARγ in the lung contributes to abnormal proliferation of PASMCs. FGF21 is a key regulator of PPARγ activity in adipocytes, but its role has not been elucidated in PASMCs. Therefore, we hypothesized that FGF21 may confer therapeutic effects in HPH by upregulating the expression of PPARγ. Sprague-Dawley rats were exposed to hypoxia and treated with FGF21 for 4 weeks. In parallel, hypoxic conditions and FGF21 were administered to rat PASMCs for 48 h. FGF21 attenuated the hypoxia-induced elevation in mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy (RVH), medial thickening and overproliferation of PASMCs. Furthermore, FGF21 abrogated the reductions in PPARγ expression and increases in TNF-α, IL-1 and IL-6 levels in PASMC culture media. Collectively, these results demonstrate that FGF21 could potentially attenuate the pathogenic derangements of HPH by targeting PPARγ and inflammatory cytokines. Highlights • FGF21 Attenuates Hypoxia-induced Pulmonary Hypertension as a Potential drug. • FGF21 may Inhibit Vascular Remodeling Through Suppressing PASMCs Proliferation. • FGF21 Upregulates PPARγ Expression and Inhibits Inflammatory Cytokines. [ABSTRACT FROM AUTHOR]

In this study, early indica rice and soluble soybean polysaccharide (SSPS) were used as materials. Single-screw and twin-screw extrusion processes were employed to investigate the impact of SSPS on the cooking and eating quality of rice noodles through chroma, textural properties, cooking quality, and sensory quality determinations. Then, the effect of SSPS on the quality of rice noodles was characterized through pasting properties, rheological properties, and X-ray diffraction (XRD) determinations based on the optimum addition of SPSS. The results demonstrated that the addition of SSPS improved the cooking and sensory quality of rice noodles at the optimum addition amount (3% SSPS). Compared with the single-screw extrusion, the rice noodles prepared by twin-screw extrusion had a more desired appearance, lower cooking loss (CL) rate (9.88%), and better taste. The results of pasting and rheological properties showed that the addition of SSPS reduced the pasting viscosity of rice flour by impeding the swelling and disintegration of starch granules. Additionally, XRD patterns indicated both the addition of SSPS and low moisture content inhibited the generation of the starch-ordered structure. Overall, the rice noodles of double-3% had the higher cooking and eating quality, L*, degree of intermolecular cross-linking, and intensity of V-type diffraction peak. • The optimal amount of SSPS added to rice flour was 3%. • Rice noodles with 3% SSPS has desirable cooking and eating quality. • The rice noodles of twin-screw extruder were better than the single-screw extruder. • SSPS and extrusion process can inhibit the generation of ordered structure of starch. [ABSTRACT FROM AUTHOR]

Torulaspora delbrueckii is a non- Saccharomyces cerevisiae that is widely used to improve the flavor of fruit wine. To investigate the effect of T. delbrueckii (Td) NCUF305.2 on the quality of navel orange wine (NOW), the physicochemical characteristics and volatile compounds of NOWs inoculated with different numbers of Td NCUF305.2 were evaluated. Results showed that the contents of ethanol and organic acids were increased by mixed fermentation. The esters contents in three mixed fermentation samples increased by 0.14–36.05% than those of pure fermentation with Sc NCUF309.2. The acetate esters contents in NOWs were significantly (p < 0.05) increased by mixed fermentation, especially in MF2 (mixed fermentation of Td NCUF305.2 and Sc NCUF309.2 at an inoculum ratio of 10:1) (8.76 mg/L). Moreover, the ethyl esters content in MF2 (1.15 mg/L) was also the highest among the mixed fermentation samples (0.69–1.15 mg/L). These compounds could give NOW strong fruity, flowery, and sweet scents. In addition, the contents of phenethyl alcohol, citronellol, and cis -carveol in MF2 were the highest. [Display omitted] • Navel orange wine made using T. delbrueckii with various inoculation numbers and S. cerevisiae. • The contents of ethanol and organic acids were increased by mixed fermentation. • Co-inoculation of Td NCUF305.2 + Sc NCUF309.2 (ratio = 10:1) increased important volatiles. [ABSTRACT FROM AUTHOR]

Abstract Zerumbone, the predominant sesquiterpenoid component of Zingiber zerumbet , exhibits diverse pharmacological properties. In this study, de novo production of zerumbone was achieved in a metabolically engineered yeast cell factory by introducing α-humulene synthase (ZSS1), α-humulene 8-hydroxylase (CYP71BA1) and zerumbone synthase variant (ZSD1S114A) from Z. zerumbet , together with AtCPR1 from Arabidopsis thaliana into the yeast strain. Multistep metabolic engineering strategies were applied, including the over-expression of the mevalonate (MVA) pathway rate-limiting enzymes tHMG1 and ERG20, regulation of ERG9 by an inducible promoter and competitive pathway deletion to redirect metabolic flux toward the desired product. In the engineered strain, α-humulene production increased by 18-fold, to 92 mg/L compared to that in the original strain. Five cytochrome P450 reductases (CPRs) from different sources were selected for CYP71BA1 adaptability tests, and AtCPR1 from A. thaliana was found to be the optimal, producing 113.16 μg/L of 8-hydroxy-α-humulene. Multicopy integration of CYP71BA1 , AtCPR1 , ZSS1 and ICE2 (type III membrane protein) genes resulting in strain LW14 increased the production of 8-hydroxy-α-humulene by 134-fold to 15.2 mg/L. Expressing ZSD1 S114A in the ura3 site of strain LW14 resulted in the production of 7 mg/L zerumbone. Multicopy integration of ZSD1 S114A increased the production of zerumbone to 20.6 mg/L. The high zerumbone-producing strain was used for batch and fed-batch fermentation in a 5-L bioreactor and zerumbone degradation by yeast was observed; the production of zerumbone finally reached 40 mg/L by fed-batch fermentation in a 5-L bioreactor. Highlights • Sesquiterpenoid zerumbone was de novo synthesized by engineered Saccharomyces cerevisiae for the first time. • CCytochrome P450 reductase（CPR）from Arabidopsis thaliana (AtCPR1) was found to adapt well with α-humulene hydroxylase. • TThe engineered strain LW16 could produce 1.3 g/L of α-humulene and 40 mg/L of zerumbone with fed-batch fermentation. [ABSTRACT FROM AUTHOR]

Abstract Chlorogenic acid (CGA) plays an important role in protecting plants against pathogens and promoting human health. Although CGA accumulates to high levels in potato tubers, the key enzyme p -coumaroyl quinate/shikimate 3′-hydroxylase (C3′H) for CGA biosynthesis has not been isolated and functionally characterized in potato. In this work, we cloned StC3′H from potato and showed that it catalyzed the formation of caffeoylshikimate and CGA (caffeoylquinate) from p -coumaroyl shikimate and p -coumaroyl quinate, respectively, but was inactive towards p -coumaric acid in in vitro enzyme assays. When the expression of StC3′H proteins was blocked through antisense (AS) inhibition under the control of a tuber-specific patatin promoter, moderate changes in tuber yield as well as phenolic metabolites in the core tuber tissue were observed for several AS lines. On the other hand, the AS and control potato lines exhibited similar responses to a bacterial pathogen Pectobacterium carotovorum. These results suggest that St C3′H is implicated in phenolic metabolism in potato. They also suggest that CGA accumulation in the core tissue of potato tubers is an intricately controlled process and that additional C3′H activity may also be involved in CGA biosynthesis in potato. Highlights • St C3′H catalyzed the formation of coumaroyl quinate and coumaroyl shikimate in vitro. • Antisense downregulation of St C3′H in potato tubers caused moderate increases in ferulic acid conjugates and chlorogenic acid. • A reduction in tuber yield was observed in antisense StC3′H lines, though their response to a bacterial pathogen was not significantly affected. [ABSTRACT FROM AUTHOR]

Sufu is a pleasant-tasting, traditional Chinese fermented soybean food that is rich in nutrients. The manufacture of sufu includes four steps: preparation of tofu, preparation of pehtze, salting of pehtze and ripening of salted pehtze in a dressing mixture. Based on electrophoresis and 1 H-NMR methods, the changes in protease and chemical compounds in the exterior and interior of sufu were investigated during fermentation. The results indicated that proteases with various molecular masses (162.6, 124.6, 104.3, 66.9, and 44.9 kDa) existed in both the exterior and interior of pehtze, salted pehtze, and ripened sufu, which proved that proteolytic reactions in the exterior and interior of sufu were occurring simultaneously. Furthermore, ethanol, ethylene glycol, glucose, isopropanol, and mannitol were the major carbonic compounds present in sufu, and amino acids were the predominant nitrogen compounds present in sufu. Correlation analysis revealed important links between protease activity and chemical compounds, e.g., succinate, histamine, and trimethylamine, were significantly positively correlated with protease activity in sufu. Through these results, the effect of protease on chemical compounds in sufu was identified, which can be useful for the improvement of enzymatically ripened sufu. [ABSTRACT FROM AUTHOR]

In this paper we investigate boundary blow-up solutions of the problem { − Δ p ( x ) u + f ( x , u ) = ± K ( x ) | ∇ u | m ( x ) in Ω , u ( x ) → + ∞ as d ( x , ∂ Ω ) → 0 , where Δ p ( x ) u = div ( | ∇ u | p ( x ) − 2 ∇ u ) is called the p ( x ) -Laplacian. Our results extend the previous work [25] of Y. Liang, Q.H. Zhang and C.S. Zhao from the radial case to the non-radial setting, and [46] due to Q.H. Zhang and D. Motreanu from the assumption that K ( x ) | ∇ u ( x ) | m ( x ) is a small perturbation, to the case in which ± K ( x ) | ∇ u | m ( x ) is a large perturbation. We provide an exact estimate of the pointwise different behavior of the solutions near the boundary in terms of d ( x , ∂ Ω ) and in terms of the growth of the exponents. Furthermore, the comparison principle is no longer applicable in our context, since f ( x , ⋅ ) is not assumed to be monotone in this paper. [ABSTRACT FROM AUTHOR]

Pattern texturing has been proved to effectively improve the water repellency on hydrophobic surfaces. To explore the effect of pattern profile on the dynamic wetting state, here, we conduct numerical study of a water droplet impinging on surfaces with a single trapezoid, rectangular, and V-shaped grooves, respectively. Simulations are performed using a volume-of-fluid method based interFoam solver shipped with OpenFOAM. We begin with a numerical validation by comparing with experiment. Subsequently, the wetting states of the droplet on these three substrates are examined, which demonstrate the capability of trapezoid topography to prevent being wetted. Theoretical model well explains that trapezoid structure can lead to a great increase in energy barrier brought by the penetration of liquid–air interface, which in turn improves its non-wetting ability even under impingement conditions. By masking the surface with mix-hydrophobicity, we also prove that wettability in grooves plays a significant role on the dynamic wetting state. A stable dry surface can be obtained by only masking the groove side-wall by superhydrophobic patterns. [ABSTRACT FROM AUTHOR]

Aquatic sediments are believed to be an important sink for carbon nanotubes (CNTs). With novel properties, CNTs can potentially disturb the fate and mobility of the co-existing contaminants in the sediments. Only toxic pollutants have been investigated previously, and to the best of our knowledge, no data has been published on how CNTs influence phosphorus (P) adsorption on aquatic sediments. In this study, multi-walled carbon nanotubes (MWCNTs) were selected as model CNTs. Experimental results indicated that compared to pseudo-first order and intraparticle diffusion models, the pseudo-second-order model is better for describing the adsorption kinetics of sediments and MWCNT-contaminated sediments. Adsorption isotherm studies suggested that the Langmuir model fits the isotherm data well. With the increase in the MWCNT-to-sediment ratio from 0.0% to 5.0%, the theoretical maximum monolayer adsorption capacity (Q max ) for P increased from 0.664 to 0.996 mg/g. However, the Langmuir isotherm coefficient (K L ) significantly decreased from 4.231 L/mg to 2.874 L/mg, indicating the decrease in the adsorption free energy of P adsorbed on the sediments after MWCNT contamination. It was suggested that P was released more easily to the overlying water after the re-suspension of sediments. Moreover, the adsorption of sediments and sediment-MWCNT mixture was endothermic and physical in nature. Results obtained herein suggested that the change in the specific surface area and zeta potential of sediments is related to MWCNT contamination, and the large adsorption capacity of MWCNTs is probably the main factor responsible for the variation in the adsorption of P on aquatic sediments. [ABSTRACT FROM AUTHOR]

The co-presence of perfluorooctane sulfonate (PFOS) and phosphate in wastewater of various industries has been detected. Removing PFOS and phosphate simultaneously before discharging sewage into natural water can decrease effectively the environmental risk caused by the combined pollution of PFOS and phosphate. In this study, laboratory batch experiments were conducted for investigating the co-adsorption of PFOS and phosphate on boehmite and the influences of temperature, phosphate initial concentration and pH on the co-adsorption. The adsorption thermodynamics and kinetics of PFOS and phosphate on boehmite were also investigated completely and systematically. The results showed that lower temperature favored the co-adsorptions of PFOS and phosphate. The adsorption of PFOS and phosphate on boehmite agreed well with the Langmuir isotherm and the adsorption parameters of thermodynamics are ΔH=−16.9 and −20.0 kJ mol −1 (PFOS and phosphate), ΔS=−5.69 and −7.63 J mol −1 K −1 (PFOS and phosphate) and ΔG <0 (PFOS and phosphate). It demonstrated that the co-adsorption of PFOS and phosphate on boehmite is a spontaneously exothermic process. Moreover, the co-adsorption process can be described well by a pseudo-second-order kinetic model. With increasing phosphate initial concentration, more phosphate could be adsorbed on boehmite, while the adsorption of PFOS decreased at phosphate initial concentration of less than 30 mg L −1 and increased at that of larger than 30 mg L −1 . In the co-adsorption process, the adsorption amount of PFOS decreased with pH increasing, but that of phosphate changed little. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the most malignant cancers, owing to extremely high aggressiveness and mortality. Yet, this condition currently incurs widely drug resistance and therapeutic deficiency. In this study, we proposed a novel functional metabolomics strategy as Spatial Temporal Operative Real Metabolomics (STORM) to identify the determinant functional metabolites in a dynamic and visualized pattern whose level changes are mechanistically associated with therapeutic efficiency of gemcitabine against PC. Integrating quantitative analysis and spatial-visualization characterization of functional metabolites in vivo, we identified that the AMP-cAMP axis was a novel therapeutic target of PC to intermediate therapeutic efficiency of gemcitabine. Gemcitabine could induce the dual accumulation of cyclic AMP (cAMP) and AMP in tumor tissues. Quantitative analysis of associated biosynthetic enzymes and genes revealed that two independent intracellular ATP derived biosynthetic pathways to promote the dual activation of AMP-cAMP axis in a lower-level energetic environment. Then, gemcitabine induced the dual accumulation of AMP and cAMP can separately activate signaling pathways of AMPK and PKA, leading to the inhibition of tumor growth by the upregulation of the downstream tumor suppressor GADD45A. Collectively, our new STORM strategy was the first time to identify novel target of PC from a metabolic perspective as the dual activation of AMP-cAMP axis induced by gemcitabine can efficiently suppress PC tumor growth. In addition, such discovery has the capability to lower drug resistance of gemcitabine by specifically interacting with novel target, contributing to the improvement of therapeutic efficiency. [Display omitted] [ABSTRACT FROM AUTHOR]

Traditional approaches for video classification treat the entire video clip as one data instance. They extract visual features from video frames which are then quantized (e.g., K-means) and pooled (e.g., average pooling) to produce a single feature vector. Such holistic representations of videos are further used as inputs of a classifier. Despite of efficiency, global and aggregate feature representation unavoidably brings in redundant and noisy information from background and unrelated video frames that sometimes overwhelms targeted visual patterns. Besides, temporal correlations between consecutive video frames are also ignored in both training and testing, which may be the key indicator of an action or event. To this end, we propose Weakly Supervised Sequence Modeling (WSSM), a novel framework that combines multiple-instance learning (MIL) and Conditional Random Field (CRF) model seamlessly. Our model takes each entire video as a bag and one video segment as an instance . In our framework, the salient local patterns for different video categories are explored by MIL, and intrinsic temporal dependencies between instances are explicitly exploited using the powerful chain CRF model. In the training stage, we design a novel conditional likelihood formulation which only requires annotation on videos. Such likelihood can be maximized using an alternating optimization method. The training algorithm is guaranteed to converge and is very efficient. In the testing stage, videos are classified by the learned CRF model. The proposed WSSM algorithm outperforms other MIL-based approaches in both accuracy and efficiency on synthetic data and realistic videos for gesture and action classification. [ABSTRACT FROM AUTHOR]

A novel pullulanase gene ( PbPulA ) from Paenibacillus barengoltzii was cloned. PbPulA has an open reading frame of 2028 bp encoding 675 amino acids. It was heterologously expressed in Escherichia coli as an intracellular soluble protein. The recombinant pullulanase (PbPulA) was purified to homogeneity with a molecular mass of about 75 kDa on SDS-PAGE. PbPulA was optimally active at pH 5.5 and 50 °C. It was stable within pH 5.5–10.5. The enzyme exhibited strict substrate specificity towards pullulan, but showed relatively low activity towards amylopectin and no activity towards other tested polysaccharides. The K m and V max values of the enzyme on pullulan were 2.94 mg/mL and 280.5 μmol/min/mg, respectively. The addition of PbPulA in gelatinized rice and maize starches significantly increased the resistant starch type 3 (RS3) yields. Final yields from rice and maize starches were 10.82 g/100 g and 11.41 g/100 g, respectively. These properties make PbPulA useful in starch industries. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is a common environmental pollutant. Mn exposure can lead to neurodegenerative diseases resembling Parkinson's disease, and has become a major public health concern. However, the mechanism of Mn-induced neurotoxicity in the brain is not clear. Fecal microbiome transplantation (FMT) may alleviate the neurotoxicity of Mn exposure by remodeling the gut microbiota. In this study, MnCl 2 (manganese chloride) was administered to mice as in drinking water (Mn: 200 mg/L), and fecal matter from donor mice was administered by oral gavage every other day to the recipient mice. The Mn exposure model (Mn group) and FMT model (Mn+FMT group) were established and analyzed 5 weeks post-exposure. The Wipi1 gene exhibited the most significant increase associated with Mn exposure and Mn+FMT treatment groups based on transcriptome analysis. Combined analysis of transcriptomics and proteomics demonstrated that the apelin signaling pathway is the main pathway affected by FMT during Mn exposure. Immunofluorescence and Western blot showed that the expression of key proteins (Beclin-1, LC-3B, and PINK1) associated with autophagy in the hippocampus was robustly activated in the Mn exposure group, but attenuation was observed in Mn+FMT mice, suggesting a critical role of autophagy in neurotoxicity induced by Mn exposure. Our research provides evidence for the neurotoxic effects of Mn exposure through autophagy activation and provides an underlying mechanism of FMT protection against Mn-induced neurotoxicity through regulation of the apelin signaling pathway. [Display omitted] • Wipi1 exhibited the most significant increase associated with Mn exposure. • Apelin signaling pathway is the main pathway affected by FMT during Mn exposure. • A critical role of autophagy in neurotoxicity induced by Mn exposure. • FMT protects against Mn-induced neurotoxicity by regulating apelin pathway. [ABSTRACT FROM AUTHOR]

ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER. [ABSTRACT FROM AUTHOR]

Highlights: [•] CNT supported rhodium catalysts with variable amounts of Mn promoter were synthesized and evaluated for CO hydrogenation. [•] The active phase of the promoter is identified by XANES and EELS as MnO. [•] The enhancement in the degree of metal–promoter interaction leads to an increase in the ethanol selectivity. [Copyright &y& Elsevier]

Abstract: This paper is concerned with the local well-posedness and the precise blow-up scenario for a periodic 2-component -Hunter–Saxton system in Besov spaces. Moreover, we state a new global existence result to the system. Our obtained results for the system improve considerably earlier results. [Copyright &y& Elsevier]

Abstract: Trefoil factor family 2 (TFF2) participates in mucus stabilization and repair, apoptosis, and inflammatory responses. Previously published reports have indicated that several growth factors and basal transcription factors are associated with the expression of TFF2. However, the detailed mechanisms that regulate TFF2 expression are not fully understood. The present study was designed to assess the essential role of the transcription factor SP3 with respect to TFF2 expression. We first demonstrated that there was a negative correlation between the expression levels of SP3 and TFF2. Thus, in the examined cells, the overexpression of SP3 decreased the expression level of TFF2, whereas the inhibition of SP3 increased the expression level of TFF2. Moreover, we discovered two GC boxes in the TFF2 promoter and confirmed the specific binding of SP3 to this promoter. On the whole, this study indicated that Sp3 was a major regulator of TFF2 expression. This knowledge should contribute to our understanding of the role that is played by SP3 in the regulation of TFF2 expression. [Copyright &y& Elsevier]

Abstract: The present work is mainly concerned with blow-up phenomena and global existence for a modified two-component Camassa–Holm equation. Firstly, a new blow-up criterion and the precise blow-up rate are presented. Then, a new global existence result for strong solutions to the equation is given. [Copyright &y& Elsevier]

Abstract: β-glucan is an immuno-stimulating agent that has been used to treat cancer and infectious disease for many years with varying and unpredictable efficacy. Recent studies have unraveled the action mode of yeast-derived β-glucan in combination with anti-tumor monoclonal antibodies (mAbs) in cancer therapy. It has demonstrated that particulate or large molecular weight soluble β-glucans are ingested and processed by macrophages. These macrophages secrete the active moiety that primes neutrophil complement receptor 3 (CR3) to kill iC3b-opsonized tumor cells. In vitro and in vivo data demonstrate that successful combination therapy requires complement activation and deposition on tumors and CR3 expression on granulocytes. Pre-clinical animal studies have demonstrated the efficacy of combined β-glucan with anti-tumor mAb therapy in terms of tumor regression and long-term survival. Clinical trials are underway using anti-epidermal growth factor receptor mAb (cetuximab) in combination with β-glucan for metastatic colorectal cancer. This review provides a brief overview of this combination therapy in cancer and describes in detail the β-glucan composition and structure, mechanism of action, and preclinical studies in human carcinoma xenograft models. It is proposed that the addition of β-glucan will further improve the therapeutic efficacy of anti-tumor mAbs in cancer patients. [Copyright &y& Elsevier]

Insulin, as a growth factor, can increase the risk of certain types of cancer. The present study showed that insulin promoted the proliferation of hepatocellular carcinoma cells in vitro and in vivo through pyruvate kinase M2 (PKM2), which is a rate-limiting enzyme in the process of glycolysis. Moreover, the expression of PKM2 was up-regulated by insulin at the posttranslational level in a nuclear orphan receptor TR3-dependent manner. In addition, insulin could enhance the interaction between PKM2 and TR3 and protect PKM2 from degradation. Our results identified a specific mechanism of insulin affecting cancer metabolism and thus promoting cancer progression, and they contribute to a better understanding of the observation that insulin is linked to an increased cancer risk under hyperinsulinemic conditions. • Insulin induced PKM2 expression. • Insulin enhanced the interaction between PKM2 with TR3 and protected PKM2 from degradation. • Insulin promoted the proliferation of hepatoma cells in vitro and vivo in a PKM2-dependant manner. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality rates. It has been shown that pirfenidone (PFD) and nintedanib (Ofev) can slow down the decline in lung function of IPF patients, but their efficacy remains suboptimal. Some studies have suggested that the combination of PFD and Ofev may yield promising results. However, there is a lack of research on the combined application of these two medications in the treatment of IPF. A mouse model of bleomycin-induced (BLM) pulmonary fibrosis was established to investigate the impact of combination therapy on pulmonary fibrosis of mice. The findings demonstrated a significant reduction in lung tissue damage in mice treated with the combination therapy. Subsequent transcriptome analysis identified the differential gene secreted phosphoprotein 1 (SPP1), which was found to be associated with macrophages and fibroblasts based on multiple immunofluorescence staining results. Analysis of a phosphorylated protein microarray indicated that SPP1 plays a regulatory role in macrophages and fibroblasts via the AKT pathway. Consequently, the regulation of macrophages and fibroblasts in pulmonary fibrosis by the combination of PFD and Ofev is mediated by SPP1 through the AKT pathway, potentially offering a novel therapeutic option for IPF patients. Further investigation into the targeting of SPP1 for the treatment of pulmonary fibrosis is warranted. • Combination of pirfenidone and nintedanib improves the antifibrotic efficacy in vivo. • Transcriptome sequencing screened significantly differentially expressed gene SPP1. • Multiple immunofluorescence reveals that SPP1 relates to macrophages and fibroblasts. • Phosphorylated protein microarrays indicates that SPP1 mainly regulates AKT pathway. • Pirfenidone and Nintedanib exert additive antifibrotic effects by SPP1-AKT pathway. [ABSTRACT FROM AUTHOR]

Multi-layered carbon accommodation of MnO 2 enhanced ion intercalating and electron transferring, which rendered the resulting batteries ultra-stable cycling. [Display omitted] • Multi-layered carbon accommodation of MnO 2 enhanced ion intercalating and electron transferring. • Spray-coating preparation without any binder agent and conductive carbon black rendered the resulting batteries ultra-stable cycling. • Large-scale and easy preparation prompted the practical application of the aqueous zinc ion batteries for stationary storage at low cost. Large-scale durable aqueous zinc ion batteries for stationary storage are realized by spray-coating conductive PEDOT(Poly(3,4-ethylenedioxythiophene)) wrapping MnO 2 /carbon microspheres hybrid cathode in this work. The porous carbon microspheres with multiple layers deriving from sucrose provide suitable accommodation for MnO 2 active materials, exposing more redox active sites and enhancing the contact surface between electrolyte and active materials. As a result, MnO 2 /microspheres are adhered to the current collector by a conductive PEDOT coating without any binder. The ternary design retards the structural degradation during cycling and shortens the electron and ion transport path, rendering the full batteries high capacity and long cycle stability. The resulting batteries perform the capacity of 277, 227, 110, 85 and 50 mAh/g at 0.2, 0.5, 1, 2 and 5 A/g, respectively. After 3000 cycles the initial capacity retains 86%, and 80% after 5000 cycles. GITT indicates PEDOT wrapping MnO 2 /microspheres cathode enables better ion intercalating kinetics than conventional MnO 2. The work could represent a novel and significant step forward in the studies on the large-scale application of zinc ion batteries. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the most aggressive malignancies with high mortality due to a complex and latent pathogenesis leading to the severe lack of early diagnosis methods. To improve clinical diagnosis and enhance therapeutic outcome, we employed the newly developed precision-targeted metabolomics method to identify and validate metabolite biomarkers from the plasma samples of patients with pancreatic cancer that can sensitively and efficiently diagnose the onsite progression of the disease. Many differential metabolites have the capacity to markedly distinguish patients with pancreatic cancer (n = 60) from healthy controls (n = 60). To further enhance the specificity and selectivity of metabolite biomarkers, a dozen tumor tissues from PC patients and paired normal tissues were used to clinically validate the biomarker performance. We eventually verified five new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid), which can be used to readily diagnose pancreatic cancer in a clinical setting. Excitingly, we proposed a panel biomarker by integrating these five individual metabolites into one pattern, demonstrating much higher accuracy and specificity to precisely diagnose pancreatic cancer than conventional biomarkers (CA125, CA19-9, CA242 and CEA); moreover, this plasma panel biomarker used for PC diagnosis is also quite convenient to implement in clinical practice. Using the same metabolomics method, we characterized succinic acid and gluconic acid as having a great capability to monitor the progression and metastasis of pancreatic cancer at different stages. Taken together, this metabolomics method was used to identify and validate metabolite biomarkers that can precisely and sensitively diagnose the onsite progression and metastasis of pancreatic cancer in a clinical setting. Furthermore, such effort should leave clinicians with the correct time frame to facilitate early and efficient therapeutic interventions, which could largely improve the five-year survival rate of PC patients by significantly lowering clinical mortality. [ABSTRACT FROM AUTHOR]

With undetermined etiology and limited treatment option, idiopathic pulmonary fibrosis (IPF) an age related disease is extremely lethal. Persistent injury of epithelial cells, abnormal activation of fibroblasts/myofibroblasts, and superabundant deposition of extracellular matrix protein pathologically characterize IPF. Redox imbalance is reported to play a vital role in both IPF development and senescence. This study aim to investigate whether and how Liproxstatin-1 (Lip-1), a strong lipid autoxidation inhibitor, regulates bleomycin (BLM) induced pulmonary fibrosis both in vivo and in vitro. It's demonstrated that Lip-1 exerted a potent anti-fibrotic function in BLM-induced mice pulmonary fibrosis via alleviating inflammatory, reshaping redox equilibrium, and ameliorating collagen deposition. Lip-1 reduced the level of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA), promoted the expression of glutathione (GSH), catalase (CAT), and total superoxide dismutase (T-SOD) after BLM treatment. Moreover, in vitro experiments verified that Lip-1 protected A549 cells from BLM-induced injury and fibrosis. Lip-1 seemed to attenuate BLM-induced fibrosis by targeting ROS/p53/α-SMA signaling both in vivo and in vitro. In summary, this study demonstrates that Lip-1 administration performs a protective role in against pulmonary fibrosis and lights up the potential of Lip-1 treatment for patient with IPF in future. • IPF is a terminal disease with undetermined etiology and limited treatment option. • Redox imbalance plays a vital role in the development of IPF. • Liproxstatin-1 is a potent lipid autoxidation inhibitor. • Liproxstatin-1 alleviates pulmonary fibrosis by reshaping redox equilibrium and suppressing ROS/p53/α-SMA pathway. [ABSTRACT FROM AUTHOR]

Optimal selections of innate behaviors that enable animals to adapt to particular conditions, whether environmental or internal, remain poorly understood. We report that mice under acute (8 h) sleep deprivation had an enhanced innate escape response and upregulation of c-fos expression in multiple brain areas that regulate wakefulness. By comparison, adrenalectomized mice under the same sleep deprivation condition displayed an even more exaggerated escape response and these wake-regulating brain areas were even more active. This suggests that acute sleep deprivation enhances innate escape response, possibly by altering wake state without causing significant anxiety. We also report that the hypothalamic–pituitary–adrenal axis feedback under sleep deprivation prevents an exaggerated escape response by modulating wake-regulating brain areas. Taken together, our findings suggest that animals prioritize escape response over sleep, as the need of both behaviors simultaneously increase. We also provide an insight into the neural mechanisms underlying the interaction between sleep and innate escape response. • Sleep deprivation enhances the looming-induced escape response. • Negative feedback in the HPA axis prevents exaggerated escape response. • The brain areas involved in wakefulness regulation are under the control of the HPA axis in response to sleep deprivation [ABSTRACT FROM AUTHOR]

This article has been retracted at the request of the authors and/or the Editor-in-Chief. Reason: The main theorem of the paper, Theorem 4.1, contains serious technical mistakes which cannot be fixed. At the request of the authors and with the concurrence of the editors, this article has been retracted. [ABSTRACT FROM AUTHOR]

• The VLE data of the R1234ze(E) + R245fa system were measured at T=(293.15 ∼ 323.15)K. • Experimental data were correlated with the PR - vdWs and PR - HV - NRTL models. • The results of the prediction by two models were compared. A static analytical device was used in this investigation to collect the vapor pressures of R245fa and R1234ze(E), as well as the vapor liquid equilibrium (VLE) data of their combination, when the temperature was altered from T = 293.15 K to T = 323.15 K. According to the existing literature, no informative data about this combination exists in this temperature range. We also present the uncertainty of the acquired temperature, pressure, and molar fraction of the experimental equipment for the scientific accuracy of the data. The phase equilibrium values were regressed by two models (Peng-Robinson EoS + van der Waals rule model and the Peng-Robinson EoS + Huron-Vidal rule with non-random two liquid activity coefficient model), respectively, to compare their correlation results, which shows that the performances of both models are satisfactory, with the second model being more appropriate because the deviation of pressure correlation is smaller. Zeotropic behaviors have been found during the temperature range. [ABSTRACT FROM AUTHOR]

Dithiolopyrrolone group antibiotics characterized by an electronically unique dithiolopyrrolone heterobicyclic core are known for their antibacterial, antifungal, insecticidal and antitumor activities. Recently the biosynthetic gene clusters for two dithiolopyrrolone compounds, holomycin and thiomarinol, have been identified respectively in different bacterial species. Here, we report a novel dithiolopyrrolone biosynthetic gene cluster ( aut ) isolated from Streptomyces thioluteus DSM 40027 which produces two pyrrothine derivatives, aureothricin and thiolutin. By comparison with other characterized dithiolopyrrolone clusters, eight genes in the aut cluster were verified to be responsible for the assembly of dithiolopyrrolone core. The aut cluster was further confirmed by heterologous expression and in-frame gene deletion experiments. Intriguingly, we found that the heterogenetic thioesterase HlmK derived from the holomycin ( hlm ) gene cluster in Streptomyces clavuligerus significantly improved heterologous biosynthesis of dithiolopyrrolones in Streptomyces albus through coexpression with the aut cluster. In the previous studies, HlmK was considered invalid because it has a Ser to Gly point mutation within the canonical Ser-His-Asp catalytic triad of thioesterases. However, gene inactivation and complementation experiments in our study unequivocally demonstrated that HlmK is an active distinctive type II thioesterase that plays a beneficial role in dithiolopyrrolone biosynthesis. [ABSTRACT FROM AUTHOR]

MiR-217 is a well-known tumor suppressor, and its down-regulation has been shown in a wide range of solid and leukaemic cancers. However, the biological role of miR-217 in psoriasis pathogenesis, especially in keratinocyte hyperproliferation and differentiation, is not clearly understood. In this study, we found the expression of miR-217 was markedly down-regulated in psoriasis keratinocytes of psoriatic patients. In addition, overexpression of miR-217 inhibited the proliferation and promoted the differentiation of primary human keratinocytes. On the contrary, inhibition of endogenous miR-217 increased cell proliferation and delayed differentiation. Furthermore, Grainyhead-like 2 (GRHL2) was identified as a direct target of miR-217 by luciferase reporter assay. The expression of miR-217 and GRHL2 was inversely correlated in both transfected keratinocytes and in psoriasis lesional skin. Moreover, knocking down GRHL2 expression by siRNA enhanced keratinocyte differentiation. Taken together, our results demonstrate a role for miR-217 in the regulation of keratinocyte differentiation, partially through the regulation of GRHL2. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study provided a robust phylogenetic framework of Polygonatum , based on whole-plastome data. • Polygonatum originated in the HHM region during the early Miocene (c. 20.10 Ma), as well as began to radiate and disperse to other regions since the mid-Miocene. • Decreasing dysploidy accompanied by karyotype change and polyploidization in Polygonatum appears to be associated with its diversification and colonization. Clarifying the process of formation of diversity hotspots and the biogeographic connection between regions is critical in understanding the impact of environmental changes on organismal evolution. Polygonatum (Asparagaceae) is distributed across the Northern Hemisphere. It displays an uneven distribution, with more than 50% of its species occurring in the Himalaya-Hengduan Mountains (HHM). Here, we generated a time-calibrated phylogeny of Polygonatum , based on whole-plastome data, to reconstruct the genus' biogeographical history and morphological/chromosomal evolution. Our phylogenetic analyses strongly support the monophyly of Polygonatum and its division into three sections (i.e., Verticillata , Sibirica , and Polygonatum). Polygonatum originated from the HHM region during the early-Miocene (c. 20.10 Ma), and began to radiate since the mid-Miocene, driven by the uplift of the Qinghai–Tibet Plateau (QTP), increasingly colder/arid climates following the mid-Miocene Climatic Optimum (MMCO), and intensification of the East Asian winter monsoon. Dispersal from the HHM region to other regions was facilitated by the intensification of East Asian summer monsoon in response to global climatic warming during the MMCO. Decreasing dysploidy accompanied by karyotype change and polyploidization in Polygonatum appears to be associated with its diversification and colonization of new ecological niches. Our results highlight the importance of regional tectonic activities and past climatic changes from the Neogene onwards to the spatial–temporal diversification and distribution patterns of plant lineages with a wide distribution in the Northern Hemisphere. They also contribute to the knowledge of the uneven species richness between East Asia and other regions. [ABSTRACT FROM AUTHOR]

• The VLE data of the R290 + R1216 system were measured at T = (283.15 ∼ 313.15)K. • Experimental data were correlated with the PR-vdWs and PR-HV-NRTL models. • The results of the prediction by two models were compared. Based on the study of the mixture containing 1,1,2,3,3,3-hexafluoro-1-propene (R1216) and propane (R290) by a set of static-analytical type experimental apparatus, this paper presents a series of vapour-liquid equilibrium data at the temperature from 283.15 K to 313.15 K. It is the first time to report the VLE data at a temperature below 313.15 K. Moreover, the uncertainties of pressure, temperature, and mole fraction in this experiment were determinate. The PR equation of state (EoS) combined with the following two models respectively, the van der Waals (vdWs) mixing rule and the Huron-Vidal (HV) mixing rule relating to the non-random two-liquid (NRTL) activity coefficient model were used to correlate the experimental VLE data of the binary system. Two models all presented an extremely content correlation of the experimental data for the R290 + R1216 mixtures, and the second model is more suitable as the pressure's maximum average relative and absolute deviation are 0.003 and 0.0026, respectively, and the maximum average absolute deviation of the vapor phase mole fraction AAD(y) is 0.0045. Near azeotropic phenomenon occurred within the temperature range of the experiment when the proportion of R290 is about 0.6 to 0.7. [ABSTRACT FROM AUTHOR]

Abstract: The hydrogenation of acrolein was studied on a series of silica-supported silver catalysts with various particle sizes (1–9nm). Particle sizes were determined by EXAFS and confirmed by TEM as well. The selectivity to allyl alcohol (as opposed to propanal) and turnover frequency increased with increasing particle size. The results are somewhat unusual in that the most active catalyst is also the most selective. Increasing the total pressure from 1 to 5atm was also found to increase the selectivity and decrease the activation energy. The results suggest that the orientation of acrolein on flat surfaces with high coverage is desirable for high selectivity and high activity. However, the selectivity to allyl alcohol decreases with increasing conversion due to the isomerization of allyl alcohol to propanal. [Copyright &y& Elsevier]

The high activity of T7 RNA polymerase has made the T7 RNA polymerase-based expression system very powerful for high-level expression of recombinant protein. However, the overactivity of T7 RNA polymerase would also bring about negative effects on plasmid stability and protein production, especially when expressing a toxic protein. If the latter role is dominant, it is necessary to adopt some measures to attenuate the activity or the amount of T7 RNA polymerase in the cells. Apart from the stringent regulation by inserting some genes reducing the amount or the activity of T7 RNA polymerase into plasmids, optimizing the culture conditions would be another way. In this work, we have studied the effects of various culture conditions on the plasmid stability and the target protein yield including selective pressure, culture temperature, toxicity of the target protein and the catabolite repression caused by glucose. The results have indicated that adding antibiotic after induction has little effect in increasing plasmid stability, but inducing expression at low temperature and adding glucose to the medium improved the plasmid stability and the protein yield to a large extent. [Copyright &y& Elsevier]

One of the hirudin variants HV3 was efficiently expressed in Escherichia coli using the l-asparaginase II signal sequence and the product was secreted into the culture medium. For the secretory manufacture of HV3, the l-asparaginase II signal sequence containing a single NheI restriction site at its 3′ end was designed using the degenerate codons and PCR-amplified from E. coli chromosomal DNA. The synthetic HV3 coding sequence was fused to the signal sequence in-frame by its 5′ NheI restriction site. The above signal-HV3 fusion gene was inserted into an expression vector pTA, which was derived from pkk223-3 such that its expression was under the control of the tac promotor. The resulting HV3 secretion expression vector pTASH thus constructed was introduced into an E. coli host cell AS1.357 with high l-asparaginase II producing level. After inducing with IPTG, the expression product was efficiently secreted into the culture medium and shake-flask culturing gave a yield of approximately 5×105 ATU/L (∼60 mg/L). The secreted HV3 was easily purified from culture supernatant using ultrafiltration, ion-exchange column chromatography, and FPLC reverse-phase chromatography. The purified rHV3 from the culture supernatant had the expected N-terminal amino sequence and strong antithrombin activity, suggesting that the signal sequence was completely removed and the product was processed accurately during the secretion process. [Copyright &y& Elsevier]

• Inflammatory cytokines are closely related to inflammatory arthritis. • M-CSF, TRAIL, and β- NGF may be a factor related to the etiology of AS. • IL-10, IL-12p70, IL-13, and VEGF were positively linked to the risk of PsA. • IL-1rα exhibited a positive association with the risk of RA-POS. Previous studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). We conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. The results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016–1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (β-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81–0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696–0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057–1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049–1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024–1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05–1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044–1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. This study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis. [ABSTRACT FROM AUTHOR]

The organic matter in sediments can mineralize over time, which impacts the morphology of the heavy metals therein, which in turn affects the assessment of the risks posed by heavy metals. We used the sediments of Bohai Bay as the study object and analyzed the effects of different organic carbon mineralization levels on the concentrations of heavy metals (Cr, Pb, Cu, Zn, and Cd) using water extraction and potassium permanganate oxidation. The mean concentrations of Cd, Pb, Cu, and Zn in Bohai Bay were within the limits recommended by the World Health Organization. The proportions of the active and inert organic carbon fractions were 61.72% and 32.94%, respectively. Organic carbon mineralization most strongly impacted Cd and Pb levels, with releases accounting for 47.92% and 25.75%, respectively, of the oxidizable fractions. The release of all heavy metals, except for Cr, increased with increases in organic carbon mineralization, and heavy metals were released at a maximum rate of 12.94% when the organic carbon was highly mineralized, whereas Cr was released at a maximum of 0.023% during the first stage of organic carbon mineralization. In terms of spatial distribution, the concentration of mineralizable organic carbon in the sediments of the estuaries was substantially higher than that in other marine areas. Estuary sediments were more easily affected by organic carbon mineralization; therefore, the heavy metals in the oxidizable fraction of the estuarine region were more easily transformed into unstable heavy metal forms, posing high risk levels. Therefore, this study highlights the effects of organic carbon mineralization on heavy metal morphology and stability, when evaluating the ecological risk of heavy metals in marine sediments. [Display omitted] • The proportions of the active and inert organic carbon fractions were 61.72% and 32.94%, respectively. • The mineralization of organic carbon exerts the most significant effects on Cd and Pb. • The release of Cd, Pb, Zn, and Cu increased with increases in organic carbon mineralization. • The heavy metals in the oxidizable fraction of the estuarine region are more easily affected. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are unstable metabolites produced during cellular respiration that can cause extensive damage to the body. Here we report a unique structural metalloprotein called RSAP p for the first time, which exhibits robust ROS-scavenging activity, high thermostability, and stress resistance. RSAP p is a previously uncharacterized DUF2935 (domain of unknown function, accession number: cl12705) family protein from Paenibacillus , containing a highly conserved four-helix bundle with binding sites for variable-valence metal ions (Mn2+/Fe2+/Zn2+). Enzymatic characterization results indicated that RSAP p displays the functionality of three different antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). In particular, RSAP p exhibits a significant SOD-like activity that is remarkably effective in eliminating superoxide radicals (up to k cat / K M = 2.27 × 1011 mol−1 s−1), and maintains the catalytical active in a wide range of temperatures (25–100 °C) and pH (pH 2.0–9.0), as well as resistant to high temperature, alkali and acidic pH, and 55 different concentrations of detergent agents, chemical solvents, and inhibitors. These properties make RSAP p an attractive candidate for various industrial applications, including cosmetics, food, and pharmaceuticals. [Display omitted] • A novel ROS-scavenging metalloprotein (RSAP) from Paenibacillus was identified. • Its highly conserved 4-helix region endows a compact, stable and scalable structure. • RSAP can mimic catalytic activity of superoxide dismutase, catalase and peroxidase. • RSAP significantly tolerates high-temperature, extreme pH, and chemical agents. • Unique RSAP holds great expansibility and potential for industrial applications. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) has been broadly used for the personalized treatment of many diseases in China for thousands of years. In the past century, TCM was also introduced to other Asian countries and even the Western world. Increasing evidence has shown that TCM has the capacity to treat numerous complex diseases in the clinic, such as cardiovascular diseases (CVDs), infectious diseases, metabolic diseases, and neurodegenerative diseases. However, the earlier lack of analytical strategies to annotate the chemical complexity has severely impeded the modern study and translational application of TCM. This critical review aims to explore and exploit applications of systems biology–driven omics methods in TCM against a diversity of diseases, toward the specific use of TCM to treat patients with different diseases. Such effort shall enhance the applicability of systems biology–driven omics strategies in deciphering the mechanisms by which TCM treats different diseases and may lead to the discovery of new therapeutic directions. In addition, we proposed the possible strategies to innovate the applicable pattern of omics technologies in TCM niches, such as precision-modification metabolomics and chinmedomics methods, allowing to unveil the complexity of TCM, which must enable TCM to serve better for the population-health. Taken together, this review eventually shall highlight the core value of omics technologies in innovating TCM to combat the diseases in a new horizon. [ABSTRACT FROM AUTHOR]

Cow mastitis, caused by Streptococcus infection of the mammary glands, is a common clinical disease that can lead to decreased milk quality and threaten animal welfare and performance. Esculetin (ESC) is a coumarin with anti-inflammatory and anti-asthmatic effects. However, whether ESC has therapeutic effects on mastitis remains unexplored. This study was conducted to investigate the protective effect of ESC against murine mastitis caused by Streptococcus isolated from bovine mammary glands and elucidate the underlying mechanisms. Streptococcus uberis was used to construct a mouse model of mastitis. The results showed that the mice exhibited edema and thickening of the acinar wall with inflammatory infiltration after S. uberis treatment. Intraperitoneal injection of ESC significantly reduced inflammatory cell infiltration, restored normal physiological function, and inhibited the production of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analysis revealed that ESC reduced P38 phosphorylation, further inhibited the influence of mammary Streptococcus on cytoplasmic translocation of nuclear factor-κB (P65), and inhibited the transcriptional activation of P65, thus inhibiting the generation of inflammatory cells. Collectively, ESC may inhibit mitogen-activated protein kinase and nuclear factor-κB, thereby highlighting its potential for the treatment and prevention of mastitis. • Mastitis can lead to decreased milk quality, threatening animal welfare and performance, and affecting human health. • A mouse model of mastitis was constructed using Streptococcus mammary of bovine origin. • The natural herb esculetin protects against mastitis in mice caused by streptococcus isolated from bovine mammary glands. [ABSTRACT FROM AUTHOR]

Abstract Protein kinase RNA-like Endoplasmic Reticulum Kinase (PERK) is an endoplasmic reticulum stress sensor that possesses pro-survival capability and contributes to cell homeostasis and survival. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) has been recognized as a stem cell marker in intestinal epithelial cells. To determine whether PERK modulates the proliferation of intestinal stem cells, we investigated the effects of PERK knock-down on intestinal Lgr5-positive stem cells in mice. Lgr5-EGFP knock-in mice were fed with lentivirus-PERK shRNA twice a day for three days. Isolated intestinal Lgr5-positive stem cells were treated with lentivirus-PERK shRNA. The number of Lgr5-positive cells, the proliferation and apoptotic indices, several biomarkers for proliferation and differentiation, and Akt expression in intestinal stem cells were detected in vivo, in vitro and in two intestinal epithelial injury models caused by radiotherapy and sepsis. PERK knock-down could significantly diminish the number and proliferation of Lgr5-positive cells, induce the low expression of several proliferation markers and the high expression of several differentiation markers in Lgr5-positive cells, enhance the apoptotic Lgr5-positive cells, and reduce the Akt expression in intestinal Lgr5-positive stem cells. Similar results were observed in radiotherapy- and sepsis-induced intestinal injuries. Moreover, PERK inhibition markedly decreased the survival of mice in response to radiation and sepsis. These results suggest a critical role for PERK in the proliferation and survival of intestinal stem cells in mice. [ABSTRACT FROM AUTHOR]

Human spermatozoa cryopreservation is an important means of assisted reproductive technology and male fertility preservation. Although this technique is particularly useful, sperm cryopreservation significantly reduces the quality of spermatozoa after freezing and thawing. The objective of the study is to examine the efficacy of mitochondria-targeted antioxidant MitoTEMPO in improving sperm quality during semen cryopreservation processes. Semen samples were collected and cryopreserved in extenders containing different concentrations (0.0, 0.5, 5, 50, and 500 μM) of MitoTEMPO. Sperm motility, viability, membrane integrity, mitochondrial membrane potential and antioxidant activities were measured and analyzed. The results showed that the addition of MitoTEMPO (5–50 μM) significantly improved post-thaw sperm motility, viability, membrane integrity and mitochondrial membrane potential (P < .05). Meanwhile, antioxidant enzymes activities were enhanced and MDA content were decreased in the group supplemented with MitoTEMPO. In conclusion, mitochondria-targeted antioxidant MitoTEMPO improves the post-thaw sperm quality and antioxidant enzymes profile. [ABSTRACT FROM AUTHOR]