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An imbalance of energy intake and expenditure is commonly considered as the fundamental cause of obesity. However, individual variations in susceptibility to obesity do indeed exist in both humans and animals, even among those with the same living environments and dietary intakes. To further explore the potential influencing factors of these individual variations, male C57BL/6J mice were used for the development of obesity-prone and obesity-resistant mice models and were fed high-fat diets for 16 weeks. Compared to the obesity-prone mice, the obesity-resistant group showed a lower body weight, liver weight, adipose accumulation and pro-inflammatory cytokine levels. 16S rRNA sequencing, which was conducted for fecal microbiota analysis, found that the fecal microbiome's structural composition and biodiversity had changed in the two groups. The genera Allobaculumbiota, SMB53, Desulfovibrio and Clostridium increased in the obesity-prone mice, and the genera Streptococcus, Odoribacter and Leuconostoc were enriched in the obesity-resistant mice. Using widely targeted metabolomics analysis, 166 differential metabolites were found, especially those products involved in arachidonic acid (AA) metabolism, which were significantly reduced in the obesity-resistant mice. Moreover, KEGG pathway analysis exhibited that AA metabolism was the most enriched pathway. Significantly altered bacteria and obesity-related parameters, as well as AA metabolites, exhibited strong correlations. Overall, the phenotypes of the obesity-prone and obesity-resistant mice were linked to gut microbiota and AA metabolism, providing new insight for developing an in-depth understanding of the driving force of obesity resistance and a scientific reference for the targeted prevention and treatment of obesity. [ABSTRACT FROM AUTHOR]

More recently, short peptides in scorpion venom have received much attention because of their potential for drug discovery. Although various biological effects of these short peptides have been found, their studies have been hindered by the lack of structural information especially in modifications. In this study, small peptides from scorpion venom were investigated using high-performance liquid chromatography high-resolution mass spectrometry followed by de novo sequencing. A total of 156 sequences consisting of 2~12 amino acids were temporarily identified from Buthus martensii scorpion venom. The identified peptides exhibited various post-translational modifications including N-terminal and C-terminal modifications, in which the N-benzoyl modification was first found in scorpion venom. Moreover, a short peptide Bz-ARF-NH2 demonstrated both N-terminal and C-terminal modifications simultaneously, which is extremely rare in natural peptides. In conclusion, this study provides a comprehensive insight into the diversity, modifications, and potential bioactivities of short peptides in scorpion venom. [ABSTRACT FROM AUTHOR]

To make unmanned surface vehicles that are better applied to the field of environmental monitoring in inland rivers, reservoirs, or coasts, we propose a global path-planning algorithm based on the improved A-star algorithm. The path search is carried out using the raster method for environment modeling and the 8-neighborhood search method: a bidirectional search strategy and an evaluation function improvement method are used to reduce the total number of traversing nodes; the planned path is smoothed to remove the inflection points and solve the path folding problem. The simulation results reveal that the improved A-star algorithm is more efficient in path planning, with fewer inflection points and traversing nodes, and the smoothed paths are more to meet the actual navigation demands of unmanned surface vehicles than the conventional A-star algorithm. [ABSTRACT FROM AUTHOR]

In this study, a response surface methodology and an artificial neural network coupled with a genetic algorithm (RSM-ANN-GA) was used to predict and estimate the optimized ultrasonic-assisted extraction conditions of Poria cocos. The ingredient yield and antioxidant potential were determined with different independent variables of ethanol concentration (X1; 25–75%), extraction time (X2; 30–50 min), and extraction solution volume (mL) (X3; 20–60 mL). The optimal conditions were predicted by the RSM-ANN-GA model to be 55.53% ethanol concentration for 48.64 min in 60.00 mL solvent for four triterpenoid acids, and 40.49% ethanol concentration for 30.25 min in 20.00 mL solvent for antioxidant activity and total polysaccharide and phenolic contents. The evaluation of the two modeling strategies showed that RSM-ANN-GA provided better predictability and greater accuracy than the response surface methodology for ultrasonic-assisted extraction of P. cocos. These findings provided guidance on efficient extraction of P. cocos and a feasible analysis/modeling optimization process for the extraction of natural products. [ABSTRACT FROM AUTHOR]

The presence of food contaminants can cause foodborne illnesses, posing a severe threat to human health. Therefore, a rapid, sensitive, and convenient method for monitoring food contaminants is eagerly needed. The complex matrix interferences of food samples and poor performance of existing sensing probes bring significant challenges to improving detection performances. Nanocomposites with multifunctional features provide a solution to these problems. The combination of the superior characteristics of magnetic nanoparticles (MNPs) and quantum dots (QDs) to fabricate magnetic fluorescent quantum dots (MNPs@QDs) nanocomposites are regarded as an ideal multifunctional probe for food contaminants analysis. The high-efficiency pretreatment and rapid fluorescence detection are concurrently integrated into one sensing platform using MNPs@QDs nanocomposites. In this review, the contemporary synthetic strategies to fabricate MNPs@QDs, including hetero-crystalline growth, template embedding, layer-by-layer assembly, microemulsion technique, and one-pot method, are described in detail, and their advantages and limitations are discussed. The recent advances of MNPs@QDs nanocomposites in detecting metal ions, foodborne pathogens, toxins, pesticides, antibiotics, and illegal additives are comprehensively introduced from the perspectives of modes and detection performances. The review ends with current challenges and opportunities in practical applications and prospects in food contaminants analysis, aiming to promote the enthusiasm for multifunctional sensing platform research. [ABSTRACT FROM AUTHOR]

Plants are the cradle of the traditional medicine system, assuaging human or animal diseases, and promoting health for thousands of years. However, many plant-derived medicines contain toxic alkaloids of varying degrees of toxicity that pose a direct or indirect threat to human and animal health through accidental ingestion, misuse of plant materials, or through the food chain. Thus, rapid, easy, and sensitive methods are needed to effectively screen these toxic alkaloids to guarantee the safety of plant-derived medicines. Antibodies, due to their inherent specificity and high affinity, have been used as a variety of analytical tools and techniques. This review describes the antigen synthesis and antibody preparation of the common toxic alkaloids in plant-derived medicines and discusses the advances of antibody-based immunoassays in the screening and detection of toxic alkaloids in plants or other related matrices. Finally, the limitations and prospects of immunoassays for toxic alkaloids are discussed. [ABSTRACT FROM AUTHOR]

The microstructure and texture of materials significantly influence the mechanical properties and fracture behavior; the effect of microstructure in different zones of friction stir-welded joints of 7A52 aluminum alloy on fracture behavior was investigated in this paper. The microstructural characteristics of sections of the welded joints were tested using the electron backscattered diffraction (EBSD) technique. The results indicate that the fracture is located at the advancing side of the thermomechanically affected zone (AS-TMAZ) and the stir zone (SZ) interface. The AS-TMAZ microstructure is vastly different from the microstructure and texture of other areas. The grain orientation is disordered, and the grain shape is seriously deformed under the action of stirring force. The grain size grows unevenly under the input of friction heat, resulting in a large amount of recrystallization, and there is a significant difference in the Taylor factor between adjacent grains and the AS-TMAZ–SZ interface. On the contrary, there are fine and uniform equiaxed grains in the nugget zone, the microstructure is uniform, and the Taylor factor is small at adjacent grains. Therefore, the uneven transition of microstructure and texture in the AS-TMAZ and the SZ provide conditions for crack initiation, which become the weak point of mechanical properties. [ABSTRACT FROM AUTHOR]

Hydroxycamptothecin (SN38) is a natural plant extract isolated from Camptotheca acuminate. It has a broad spectrum of anticancer activity through inhibition of DNA topoisomerase I, which could affect DNA synthesis and lead to DNA damage. Thus, the action of SN38 against cancers could inevitably affect endogenous levels of ribonucleotide (RNs) and deoxyribonucleotide (dRNs) that play critical roles in many biological processes, especially in DNA synthesis and repair. However, the exact impact of SN38 on RNs and dRNs is yet to be fully elucidated. In this study, we evaluated the anticancer effect and associated mechanism of SN38 in human colorectal carcinoma HCT 116 cells. As a result, SN38 could decrease the cell viability and induce DNA damage in a concentration-dependent manner. Furthermore, cell cycle arrest and intracellular nucleotide metabolism were perturbed due to DNA damage response, of which ATP, UTP, dATP, and TTP may be the critical metabolites during the whole process. Combined with the expression of deoxyribonucleoside triphosphates synthesis enzymes, our results demonstrated that the alteration and imbalance of deoxyribonucleoside triphosphates caused by SN38 was mainly due to the de novo nucleotide synthesis at 24 h, and subsequently the salvage pathways at 48 h. The unique features of SN38 suggested that it might be recommended as an effective supplementary drug with an anticancer effect. [ABSTRACT FROM AUTHOR]

Interferon (IFN) helps cells fight viral infections by further inducing the expression of many downstream IFN-stimulated genes (ISGs). Human interferon-inducible transmembrane proteins (IFITM) are one of these ISGs. The antiviral function of human IFITM1, IFITM2, and IFITM3 are well known. In this study, we report that IFITM can significantly inhibit EMCV infectivity in HEK293 cells. Overexpression of IFITM proteins could promote IFN-β production. Meanwhile, IFITMs facilitated type I IFN signaling pathway adaptor MDA5 expression. We detected the binding of IFITM2 to MDA5 in a co-immunoprecipitation assay. It was also found that the ability of IFITM2 to activate IFN-β was significantly inhibited after interfering with MDA5 expression, suggesting that MDA5 may play an important role in the activation of the IFN-β signaling pathway by IFITM2. Moreover, the N-terminal domain plays an active role in the antiviral activity and the activation of IFN-β by IFITM2. These findings suggest that IFITM2 plays a vital role in antiviral signaling transduction. In addition, a positive feed-forward loop between IFITM2 and type I IFN establishes a key role for IFITM2 in enforcing innate immune responses. [ABSTRACT FROM AUTHOR]

In this paper, the supercavitation of the parallel and tandem projectiles moving underwater with high-speed under the condition with/without lateral flows is numerically simulated by the volume of fraction (VOF) model. The motion of the projectiles was handled by the overlapping grid and six degrees of freedom (DOF) techniques. The supercavitation evolution and the hydrodynamic characteristics of the projectiles were analyzed for the parallel and tandem projectiles under different conditions. The results show that the cavity shape is symmetrical under the condition without lateral flows, but is no longer symmetrical under the conditions with lateral flows. The asymmetry of the cavity contour increases with the velocity of the lateral flow. For the parallel projectiles, the change trends of the axial velocity of projectile 1 and projectile 2 are nearly the same. The offset velocity of projectile 1 and projectile 2 increases with the increase in the velocity of the lateral flow. The deflection angle of projectile 1 decreases with the increase in the lateral flow velocity but that of projectile 2 increases with the increase in the lateral flow velocity. At t = 3.0 ms, the deflection angle of projectile 2 is up to 20° under the condition of the lateral flow velocity of 11.25%, while the deflection angle of projectile 1 and 2 under other conditions is in the range of 5°. For the tandem projectiles, the axial velocity of projectile 1 gradually decreases. The change trend of the axial velocity of projectile 2 at first is the same as that of projectile 1, and then the change is dependent on the velocity of the lateral flow. Under the condition of the lateral flow velocity with 11.25%Vp, projectile 2 cannot enter the cavity of the front projectile. The change trend of the axial velocity of projectile 2 is similar as but somewhat slower than that of projectile 1. For the parallel projectiles, the ballistic stability of the projectile on the oncoming side is better than that of the projectile on the backflow side. Whether parallel or tandem projectiles, the ballistic stability of projectile 2 becomes worse with the increase in the lateral flow velocity. [ABSTRACT FROM AUTHOR]

It has been reported that the giant triton snail (Charonia tritonis) inserts its large proboscis and then injects venom or acid saliva from its salivary gland into its prey, the crown-of-thorns starfish Acanthaster planci (COTS), paralyzing it. A full-length cDNA sequence of the C. tritonis Ct-kunitzin gene was obtained by RACE PCR based on a transcriptomic database constructed by our laboratory (data not published), which contains an open reading frame (ORF) sequence with a length of 384 bp including a 1–32aa Kunitz domain. The Ct-kunitzin peptide was synthesized by solid-phase polypeptide methods according to its conserved amino acid sequence, with a molecular weight of 3746.0 as well as two disulfide bonds. Renatured Ct-kunitzin was injected into mice ventricles to evaluate its potential function. Compared with the normal control group (physiological saline), the spontaneous locomotor activity of the Ct-kunitzin group decreased significantly. There was a significant effect on Ct-kunitzin on mice grip strength in the grip strength test. In addition, Ct-kunitzin exhibited remarkable biological activity in suppressing pain in the pain thresholds test. There were no significant differences between the Ct-kunitzin group and the normal control group in terms of various hematological indexes and histopathological observations. When tested in COTS, the most significant histological change was the destruction, disorganization, and significant reduction in the amount of COTS tube feet tissues. Altogether, the potential paralyzing effect on mice suggests that Ct-kunitzin is a possible agent for novel drug development. [ABSTRACT FROM AUTHOR]

Plastid-encoded RNA polymerase (PEP)-dependent transcription is an essential process for chloroplast development and plant growth. It is a complex event that is regulated by numerous nuclear-encoded proteins. In order to elucidate the complex regulation mechanism of PEP activity, identification and characterization of PEP activity regulation factors are needed. Here, we characterize Plastid Deficient 1 (PD1) as a novel regulator for PEP-dependent gene expression and chloroplast development in Arabidopsis. The PD1 gene encodes a protein that is conserved in photoautotrophic organisms. The Arabidopsis pd1 mutant showed albino and seedling-lethal phenotypes. The plastid development in the pd1 mutant was arrested. The PD1 protein localized in the chloroplasts, and it colocalized with nucleoid protein TRXz. RT-quantitative real-time PCR, northern blot, and run-on analyses indicated that the PEP-dependent transcription in the pd1 mutant was dramatically impaired, whereas the nuclear-encoded RNA polymerase-dependent transcription was up-regulated. The yeast two-hybrid assays and coimmunoprecipitation experiments showed that the PD1 protein interacts with PEP core subunit β (PEP-β), which has been verified to be essential for chloroplast development. The immunoblot analysis indicated that the accumulation of PEP-β was barely detected in the pd1 mutant, whereas the accumulation of the other essential components of the PEP complex, such as core subunits α and β′, were not affected in the pd1 mutant. These observations suggested that the PD1 protein is essential for the accumulation of PEP-β and chloroplast development in Arabidopsis, potentially by direct interaction with PEP-β. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is the third leading cause for cancer related death, in which metastasis exerts a pivotal role. Therefore, we aim to find out the possible mechanism underlying CRC metastasis. We found that the level of miR-125b was elevated in normal, primary CRC, and distant metastasis tissues stepwise, and high level miR-125b was positively correlated with lymph node metastasis and tumor differentiation. In vitro and in vivo assays showed miR-125b significantly promoted CRC migration and invasion. To elucidate the potential mechanism, cystic fibrosis transmembrane conductance regulator (CFTR) and cingulin (CGN) were defined as two target genes of miR-125b. On the one hand, miR-125b promoted epithelial-mesenchymal transition (EMT) and the production and secretion of urokinase plasminogen activator (uPA) by inhibiting CFTR; on the other hand, miR-125b activated Ras Homolog Family Member A (RhoA)/Rho Kinase (ROCK) signaling by repressing CGN. Therefore, we provided a potential biomarker for CRC prevention and treatment in the future. Metastasis contributes to the poor prognosis of colorectal cancer, the causative factor of which is not fully understood. Previously, we found that miR-125b (Accession number: MIMAT0000423) contributed to cetuximab resistance in colorectal cancer (CRC). In this study, we identified a novel mechanism by which miR-125b enhances metastasis by targeting cystic fibrosis transmembrane conductance regulator (CFTR) and the tight junction-associated adaptor cingulin (CGN) in CRC. We found that miR-125b expression was upregulated in primary CRC tumors and metastatic sites compared with adjacent normal tissues. Overexpression of miR-125b in CRC cells enhanced migration capacity, while knockdown of miR-125b decreased migration and invasion. RNA-sequencing (RNA-seq) and dual-luciferase reporter assays identified CFTR and CGN as the target genes of miR-125b, and the inhibitory impact of CFTR and CGN on metastasis was further verified both in vitro and in vivo. Moreover, we found that miR-125b facilitated the epithelial-mesenchymal transition (EMT) process and the expression and secretion of urokinase plasminogen activator (uPA) by targeting CFTR and enhanced the Ras Homolog Family Member A (RhoA)/Rho Kinase (ROCK) pathway activity by targeting CGN. Together, these findings suggest miR-125b as a key functional molecule in CRC and a promising biomarker for the diagnosis and treatment of CRC. [ABSTRACT FROM AUTHOR]

Micro-molecular drugs have special advantages to cope with challenging diseases, however their structure, physical and chemical properties, stability, and pharmacodynamics have more requirements for the way they are delivered into the body. Carrier-based drug delivery systems can circumvent many limited factors of drug delivery and increase their bioavailability. In this context, stable drug nanocarriers of alkaline amino acids (arginine, Arg) modified conjugated linoleic acid-carboxymethyl chitosan (CLA-CMCS) conjugate were developed, which could generate supramolecular micelles to effectively encapsulate the tyrosinase inhibitor phenylethyl resorcinol (PR). The resulting CCA-NPs were spherical nanoparticles with a mean size around 175 nm. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cellular uptake investigation demonstrated that the CCA-NPs were non-cytotoxic and had excellent cell transport ability. In addition, these CCA-NPs were able to effectively deliver PR and inhibited melanin formation to reduce pigmentation by enhancing cellular uptake. In conclusion, our research indicated that nanocarriers based on self-assembly amphiphilic polymers constituted a promising and effective drug delivery system in hyperpigmentation targeting. [ABSTRACT FROM AUTHOR]

Small heat shock proteins (sHsps) function mainly as molecular chaperones that play vital roles in response to diverse stresses, especially high temperature. However, little is known about the molecular characteristics and evolutionary history of the sHsp family in Salix suchowensis, an important bioenergy woody plant. In this study, 35 non-redundant sHsp genes were identified in S. suchowensis, and they were divided into four subfamilies (C, CP, PX, and MT) based on their phylogenetic relationships and predicted subcellular localization. Though the gene structure and conserved motif were relatively conserved, the sequences of the Hsp20 domain were diversified. Eight paralogous pairs were identified in the Ssu-sHsp family, in which five pairs were generated by tandem duplication events. Ka/Ks analysis indicated that Ssu-sHsps had undergone purifying selection. The expression profiles analysis showed Ssu-Hsps tissue-specific expression patterns, and they were induced by at least one abiotic stress. The expression correlation between two paralogous pairs (Ssu-sHsp22.2-CV/23.0-CV and 23.8-MT/25.6-MT) were less than 0.6, indicating that they were divergent during the evolution. Various cis-acting elements related to stress responses, hormone or development, were detected in the promoter of Ssu-sHsps. Furthermore, the co-expression network revealed the potential mechanism of Ssu-sHsps under stress tolerance and development. These results provide a foundation for further functional research on the Ssu-sHsp gene family in S. suchowensis. [ABSTRACT FROM AUTHOR]