Machine Learning for Single-Molecule Localization Microscopy: From Data Analysis to Quantification.

Single-molecule localization microscopy (SMLM) is a versatile tool for realizing nanoscale imaging with visible light and providing unprecedented opportunities to observe bioprocesses. The integration of machine learning with SMLM enhances data analysis by improving efficiency and accuracy. This tutorial aims to provide a comprehensive overview of the data analysis process and theoretical aspects of SMLM, while also highlighting the typical applications of machine learning in this field. By leveraging advanced analytical techniques, SMLM is becoming a powerful quantitative analysis tool for biological research.

Natural products fragment-based design and synthesis of a novel pentacyclic ring system as potential MAPK inhibitor.

The synthesis of compounds based on fragments derived from natural products (NPs) serves as a source of inspiration for the design of pseudo-natural products (PNPs), to identify bioactive molecules that exhibit similar characteristics to NPs. These novel molecular scaffolds exhibit previously unexplored biological activities as well. This study reports the development and synthesis of a novel pentacyclic ring system, the indole-pyrimidine-quinoline (IPQ) scaffold. The design of this scaffold was based on the structural characteristics of four natural products, namely tryptanthrin, luotonin A, rutaecarpine, and camptothecin. Several successive steps accomplished the effective synthesis of the IPQ scaffold. The constituent components of the pentacycle, containing the indole, quinazolinone, pyrimidone, and quinoline units, possess significant biological significance. Compound 1a demonstrated noteworthy anti-tumor activity efficacy against A549 cell lines among the tested compounds. The compound 1a was observed to elicit cell cycle arrest in both the G2/M and S phases, as well as trigger apoptosis in A549 cells. These effects were attributed to its ability to modulate the activation of mitochondrial-related mitogen-activated protein kinase (MAPK) signaling pathways.

Identification of Key lncRNAs Associated with Immune Infiltration and Prognosis in Gastric Cancer.

Long non-coding RNAs (lncRNAs), as promising novel biomarkers for cancer treatment and prognosis, can function as tumor suppressors and oncogenes in the occurrence and development of many types of cancer, including gastric cancer (GC). However, little is known about the complex regulatory system of lncRNAs in GC. In this study, we systematically analyzed lncRNA and miRNA transcriptomic profiles of GC based on bioinformatics methods and experimental validation. An lncRNA-miRNA interaction network related to GC was constructed, and the nine crucial lncRNAs were identified. These 9 lncRNAs were found to be associated with the prognosis of GC patients by Cox proportional hazards regression analysis. Among them, the expression of lncRNA SNHG14 can affect the survival of GC patients as a potential prognostic marker. Moreover, it was shown that SNHG14 was involved in immune-related pathways and significantly correlated with immune cell infiltration in GC. Meanwhile, we found that SNHG14 affected immune function in many cancers, such as breast cancer and esophageal carcinoma. Such information revealed that SNHG14 may serve as a potential target for cancer immunotherapy. As well, our study could provide practical and theoretical guiding significance for clinical application of non-coding RNAs.

Study on the simultaneous release of microfiber and indigo dye in denim fabric home washing.

In recent years, with the increasing global focus on environmental protection, the issue of microfiber release from denim during the washing process has gained attention. In this study, a programmable washing device simulating household drum washing was designed and developed, microfibers and indigo dyes released from denim washing were quantitatively detected, and we have also developed a novel method for estimating the release of microfibers during washing. The effects of washing time, washing temperature, and washing load on microfiber and indigo dye release from denim were explored. The results showed that the effect of washing load on microfiber and indigo dye release was greater than washing temperature and washing time. The research findings indicate that with an increase in washing time (35-95 min) and washing load (100-250 g), the shedding of microfibers and indigo dye significantly increases, reaching peak release levels of 343.6 µg/g fabric and 0.027 mg/L, respectively. However, there is a decreasing trend in the release of microfibers and indigo dye when the washing temperature exceeds 50 °C. Furthermore, our data suggests that an increase in washing load leads to a significant change in the number of microfibers (from 978 items/g fabric to 1997 items/g fabric) and their mass (from 156.87 µg/g fabric to 343.56 µg/g fabric). The influence of washing time, washing temperature, and washing load on microfiber length shows relatively small fluctuations within the range of 600-900 µm. This study provides new ideas and methods for estimating the release of microfiber and indigo dye in denim washing around the world.

First report of Fusarium verticillioides causing blight on Ammopiptanthus mongolicus in China.

Ammopiptanthus mongolicus is the only evergreen broadleaf shrub and constructive species in the northwest desert of China (Hu et al. 2021). It also is listed as one of the national second-class endangered plants. Ammopiptanthus mongolicus has a good effect of water conservation, windbreak and sand fixation because its deep root system (Zhou et al. 2012; Dong et al. 2023). A large number of dead plants of Ammopiptanthus mongolicus were found in Etuoke county, Inner Mongolia Autonomous Region, China (40°4'28″-40°4'34″ N, 106°53'5″-106°53'31″ E). In September 2023, the investigation and research in the region found that the incidence of diseased plants in this field was about 30%, and for individual plant, the incidence of diseased branches was about 60%. The leaves of diseased branches initially became from green to yellow and then wilt and fall. Eventually the plant dies. (Figure 1). The miter cut of the root showed that the root steles of diseased plants had obvious black and brown color (Figure 2). For isolation, the 30 tissue blocks (10×10 mm) of from 10 symptomatic roots diseased were surface sterilized with 70% ethanol for 3 minutes and sodium hypochlorite (2.5% available chlorine) for 5 minutes, and rinsed three times with sterilized distilled water. Then, these tissue blocks were placed on potato dextrose agar (PDA) medium, and incubated from 3 to 5 days at 25°C. After 3 days on PDA, the surface of the colony was rough, the color were white-pink at the beginning, and deep purple pigment were produced in the later stage, making the colony bluish-purple to gray-purple, their undersides were bluish-purple. Mycelia were white. After 7 days on SNA, Microconidia were typical of the clavicular type, 8.5 ± 2.5 µm × 2.3 ± 0.2 µm(×400). Microconidia were usually very long conidial chains, sometimes the spore chain collapses and the conidia clump together to form an approximate pseudocephaly. The macroconidia were slender and long, slightly falcate or straight, 42.8 ± 3.4 µm × 3.8 ± 0.7 µm(×400) (Figure 4). Species identity was confirmed by sequencing the EF1-α gene (EF1 and EF2 primers)(O'Donnell et al. 1998), RPB1 (F5 and G2R primers)(O'Donnell et al. 2022) and RPB2 (5F2 and 11AR)(O'Donnell et al. 2022). The amplified sequences of a representative isolate (AmP10) have deposited in GenBank with accession number OR594338 (EF1-α), OR841329 (RPB1) and OR841331 (RPB2). Thee results of pairwise alignment in Fusarioid-ID datebase(Crous et al. 2021) showed that EF1-α sequence was 99.54% similarity and 89.96% overlap to the corresponding sequence KF499582 of ex-epitype CBS 218.76 of Fusarium verticillioides, Fusarium fujikuroi species complex (FFSC, previously GFSC) (Lecellier et al. 2014), RPB1 sequence was 100% similarity and 100% overlap to the corresponding sequence MW402638 of ex-epitype CBS 218.76 of Fusarium verticillioides, Fusarium fujikuroi species complex (FFSC, previously GFSC) (Yilmaz et al. 2021), RPB2 sequence was 99.94% similarity and 87.83% overlap to the corresponding sequence MW928835 of ex-epitype CBS 218.76 of Fusarium verticillioides, Fusarium fujikuroi species complex (FFSC, previously GFSC) (Crous et al. 2021). Moreover, the result of polyphasic identification in Fusarioid-ID datebase also showed EF1-α, RPB1 and RPB2 sequences were 100% similarity to the corresponding sequences of ex-epitype CBS 218.76 of Fusarium verticillioides, Fusarium fujikuroi species complex (FFSC, previously GFSC). To test the pathogenicity, the healthy green seedlings (64 days old) were planted into plastic pots containing sterilized soil in the greenhouse after the seeds of Ammopiptanthus mongolicus were surface sterilized with 70% ethanol for 3 minutes and 2.5% sodium hypochlorite for 3 minutes. The roots of 3 seedlings were inoculated with 1×106 /ml of the conidial suspension, and another 3 used as controls with inoculated sterile water. Then, all pots were placed in a greenhouse maintained at 18°C to 25°C. After incubation for 3-5 days, the typical symptoms similar to the symptoms in the field (Figure 5), brown root steles (Figure 6), developed on the plants inoculated with conidial suspension, whereas no symptoms were observed on the control plants. The same pathogen was consistently reisolated from the inoculated roots and confirmed as Fusarium verticillioides based on morphological and molecular analyses. To our knowledge, this is the first report of Fusarium verticillioides on Ammopiptanthus mongolicus in China. This study provides a basis for identifying pathogens causing blight on Ammopiptanthus mongolicus and managing the disease.

First report of Neocosmospora pisi causing blight on Ammopiptanthus mongolicus in China.

Ammopiptanthus mongolicus is the only evergreen broad-leaved shrub in the desert region of Northwest China, which is one of the dominant species in the desert vegetation of the region, playing an important role in maintaining the stability of the local desert ecosystem. A. mongolicus is also very hardy and drought resistant and can survive extreme temperatures (Liu et al. 2013; Yang et al. 2022). The large-scale death of A. mongolicus could cause desertification in the region. Two months after the discovery of Fusarium verticillioides causing blight on A. mongolicus in Etuoke county, Inner Mongolia Autonomous Region in September 2023 (Yang et al. 2024), a large number of A. mongolicus plants with symptoms of blights were found in Lingwu city, Ningxia Hui Autonomous Region, China (106.442368°E, 37.734026°N) in November 2023. The incidence of diseased plants in this field was about 30%. The field symptoms in Lingwu city were similar to those observed in Etuoke county. The diseased leaves initially turned yellow, then wilted and dehisced, eventually resulting in plant death (Figure 1). The roots of the diseased plants were cut diagonally and the central cylinder showed a brown color (Figure 2). In order to investigate whether the death of A. mongolicus was caused by the same pathogen as those identified previously, 30 roots were collected from 10 diseased plants. After rinsing and surface sterilization (70% ethanol for 3 min and 2.5% NaClO for 5 min, rinsed 3 times with sterile distilled water), diseased tissues (10×10 mm) were placed on potato dextrose agar (PDA) (3 pieces per plate) and incubated from 3 to 5 days at 25°C. The strain AmP5 was isolated and used for further study. After 3 days on PDA medium, fungal colonies were white to milky, the undersides of the cultures were yellowish to orange-brown (Figure 3). After 7 days on synthetic nutrient-poor agar (SNA), microconidia were ovoidal or with a rounded apex and truncate base, 10.5 ± 1.5 µm × 1.6 ± 0.2 µm (×400). The macroconidia were slightly curved or arcuate, 40.5 ± 3.5 µm × 5 ± 0.5 µm (×400) (Figure 4) (Sisic et al. 2018). The pathogen was confirmed to be Neocosmospora pisi by multigene phylogenetic analysis of TEF, RPB1 and RPB2 genes using primers EF1/EF2, F5/G2R and 5F2/11AR, respectively (O'Donnell et al. 2022). The sequences of PCR products were deposited in GenBank with accession numbers OR944631 (RPB1), OR988086 (TEF) and OR988087 (RPB2), respectively. The results of pairwise alignment in Fusarioid-ID database (Crous et al. 2021) showed 99.84% similarity and 83.96% overlap of the EF1-α sequence to the corresponding sequence LR583636 of ex-epitype CBS 123669 of Neocosmospora pisi (syn. Fusarium solani f. sp. pisi), 99.72% similarity and 85.66% overlap of the RPB1 sequence to the corresponding sequence MW834242 of ex-epitype CBS 123669 of N. pisi, and 99.47% similarity and 78.26% overlap of RPB2 sequence to the corresponding sequence LR583862 of ex-epitype CBS 123669 of N. pisi. Moreover, the result of polyphasic identification in the Fusarioid-ID database also showed EF1-a, RPB1, and RPB2 sequences had 99.15% similarity to the corresponding sequences of CBS 1233669. The pathogenicity of AmP5 was tested on potted 64 days old seedlings A. mongolicus plants. The roots of 3 seedlings were inoculated with conidial suspension (1×106 /ml), and another 3 used as controls were inoculated with sterile water, by gently peeling off the soil around the roots during inoculation, and pouring the conidial suspension around the roots (10 ml/seedling). All plants were placed in a growth chamber at 18-25℃ (10 h light; 14 h dark). After incubation for 3-5 days, the symptoms similar to those observed in the field (Figure 5), including brown rot of steles (Figure 6), developed on plants inoculated with conidial suspension, whereas no symptoms were observed on the control plants. The same pathogen was reisolated from inoculated roots and confirmed as N. pisi based on morphological and molecular analyses (TEF, RPB1 and RPB2). To our knowledge, this is the first report of blight on A. mongolicus caused by N. pisi in China. This study also indicates that blight on A. mongolicus can be caused by different fungal pathogens. Blight caused by different pathogens may have different in terms of control measures and pathogenic mechanisms, so the study of blight caused by different pathogens is of profound value.

A critical review on bioremediation technologies of metal(loid) tailings: Practice and policy.

Globally, most high-grade ores have already been exploited. Contemporary mining tends to focus on the extraction of lower-grade ores thereby leaving large stored tailings open to the environment. As a result, current mines have emerged as hotspots for the migration of metal(loid)s and resistance genes, thereby potentially contributing to a looming public health crisis. Therefore, the management and remediation of tailings are the most challenging issues in environmental ecology. Bioremediation, a cost-effective solution for the treatment of multi-element mixed pollution (co-contamination), shows promise for the restoration of mine tailings. This review focuses on the bioremediation technologies developed to untangle the issues of non-ferrous metal mine tailings. These technologies address the environmental risks of multi-element exposure to the ecosystem and human health risks. It provides a review and comparison of current bioremediation technologies used to mineralize metal(loid)s. The role of plant-microorganisms and their mechanisms in the remediation of tailings are also discussed. The importance of "treating waste with wastes" is crucial for advancing bioremediation technologies. This approach underscores the potential for waste materials to contribute to environmental cleanup processes. The concept of a circular economy is pertinent in this context, emphasizing recycling and reuse. There's an immediate need for international collaboration. Collaboration is needed in policy-making, funding, and data accessibility. Sharing data is essential for the growth of bioremediation globally.

Bioindicator responses to extreme conditions: Insights into pH and bioavailable metals under acidic metal environments.

Acid mine drainage (AMD) caused environmental risks from heavy metal pollution, requiring treatment methods such as chemical precipitation and biological treatment. Monitoring and adapting treatment processes was crucial for success, but cost-effective pollution monitoring methods were lacking. Using bioindicators measured through 16S rRNA was a promising method to assess environmental pollution. This study evaluated the effects of AMD on ecological health using the ecological risk index (RI) and the Risk Assessment Code (RAC) indices. Additionally, we also examined how acidic metal stress affected the diversity of bacteria and fungi, as well as their networks. Bioindicators were identified using linear discriminant analysis effect size (LEfSe), Partial least squares regression (PLS-R), and Spearman analyses. The study found that Cd, Cu, Pb, and As pose potential ecological risks in that order. Fungal diversity decreased by 44.88% in AMD-affected areas, more than the 33.61% decrease in bacterial diversity. Microbial diversity was positively correlated with pH (r = 0.88, p = 0.04) and negatively correlated with bioavailable metal concentrations (r = -0.59, p = 0.05). Similarly, microbial diversity was negatively correlated with bioavailable metal concentrations (bio_Cu, bio_Pb, bio_Cd) (r = 0.79, p = 0.03). Acidiferrobacter and Thermoplasmataceae were prevalent in acidic metal environments, while Puia and Chitinophagaceae were identified as biomarker species in the control area (LDA>4). Acidiferrobacter and Thermoplasmataceae were found to be pH-tolerant bioindicators with high reliability (r = 1, P < 0.05, BW > 0.1) through PLS-R and Spearman analysis. Conversely, Puia and Chitinophagaceae were pH-sensitive bioindicators, while Teratosphaeriaceae was a potential bioindicator for Cu-Zn-Cd metal pollution. This study identified bioindicator species for acid and metal pollution in AMD habitats. This study outlined the focus of biological monitoring in AMD acidic stress environments, including extreme pH, heavy metal pollutants, and indicator species. It also provided essential information for heavy metal bioremediation, such as the role of omics and the effects of organic matter on metal bioavailability.

Effects of soil metal(loid)s pollution on microbial activities and environmental risks in an abandoned chemical smelting site.

Abandoned chemical smelting sites containing toxic substances can seriously threaten and pose a risk to the surrounding ecological environment. Soil samples were collected from different depths (0 to 13 m) and analyzed for metal(loid)s content and fractionation, as well as microbial activities. The potential ecological risk indices for the different soil depths (ordered from high to low) were: 1 m (D-1) > surface (S-0) > 5 m (D-5) > 13 m (D-13) > 9 m (D-9), ranging between 1840.65-13,089.62, and representing extremely high environmental risks, of which Cd (and probably not arsenic) contributed to the highest environmental risk. A modified combined pollution risk index (MCR) combining total content and mobile proportion of metal(loid)s, and relative toxicities, was used to evaluate the degree of contamination and potential environmental risks. For the near-surface samples (S-0 and D-1 layers), the MCR considered that As, Cd, Pb, Sb, and Zn achieved high and alarming degrees of contamination, whereas Fe, Mn, and Ti were negligible or low to moderate pollution degrees. Combined microcalorimetry and enzymatic activity measurements of contaminated soil samples were used to assess the microbial metabolic activity characteristics. Correlation analysis elucidated the relationship between metal(loid)s exchangeable fraction or content and microbial activity characteristics (p < 0.05). The microbial metabolic activity in the D-1 layer was low presumably due to heavy metal stress. Enzyme activity indicators and microcalorimetric growth rate (k) measurements were considered sensitive indicators to reflect the soil microbial activities in abandoned chemical smelting sites.

High expression of SDC1 in stromal cells is associated with good prognosis in colorectal cancer.

We have previously reported that patients with high Syndecan 1 (SDC1) expression in colorectal cancer (CRC) cells have a favorable prognosis, and we also found that stromal cells showed upregulation of SDC1, but the clinical significance is unclear. The expression of SDC1 in the stroma cells was assessed by immunohistochemistry using a tissue microarray comprising representative cores from 513 CRC patients. The correlation between the expression of SDC1 in the stroma cells and the clinicopathological features of patients was analyzed. The data showed that the expression of SDC1 in the stroma cells was correlated with the degree of differentiation ( P = 0.012) and tumor location (up or down) ( P = 0.005). Also, CRCs patients with high expression of SDC1 in the stromal cells have a good prognosis ( P = 0.0369). Accumulating evidence indicates that SDC1, whether in tumor cells or stromal cells, plays a tumor-suppressor role in CRCs.

Autonomous ratcheting by stochastic resetting.

We propose a generalization of the stochastic resetting mechanism for a Brownian particle diffusing in a one-dimensional periodic potential: randomly in time, the particle gets reset at the bottom of the potential well it was in. Numerical simulations show that in mirror asymmetric potentials, stochastic resetting rectifies the particle's dynamics, with a maximum drift speed for an optimal average resetting time. Accordingly, an unbiased Brownian tracer diffusing on an asymmetric substrate can rectify its motion by adopting an adaptive stop-and-go strategy. Our proposed ratchet mechanism can model the directed autonomous motion of molecular motors and micro-organisms.

Performance and mechanisms for Cd(II) and As(III) simultaneous adsorption by goethite-loaded montmorillonite in aqueous solution and soil.

A series of goethite-modified montmorillonite (GMt) materials was synthesized for the amelioration of cationic cadmium (Cd) and anionic arsenic (As) complex contaminants in soil and water bodies. The results showed that goethite (Gt) was successfully loaded onto the surface of montmorillonite (Mt), which possessed more functional groups (such as Fe-O, and Fe-OH) and a larger specific surface area. GMt-0.5 (Mt loaded with Gt at a ratio of 0.5:1) showed the highest adsorption capacity for Cd(II) and As(III) with the maximum of 50.61 mg/g and 57.58 mg/g, respectively. The removal rate of Cd(II) was highly pH dependent, while the removal rate of As(III) showed little dependence on pH. The goethite on montmorillonite might contribute to the formation of surface complexes with As(III) and oxidation of As(III) to As(V). In the binary system, both, synergistic and competitive adsorption existed simultaneously. Importantly, in the binary system, the removal of As(III) was more favorable because of the electrostatic interaction, formation of a ternary complex, and co-precipitation. In addition, the amendment of GMt-0.5 significantly reduced the availability of Cd and As in the soil. This study suggests that GMt-0.5 is a promising candidate for the simultaneous immobilization of metal (loid)s in both, aqueous solution and mine soil.

Potential Environmental Contaminants: Exploring Hydrolyzed Dyes in Household Washing Sources and Electrochemical Degradation.

Reactive dyes are often released into the environment during the washing process due to their susceptibility to hydrolysis. The hydrolysis experiment of a pure reactive dye, red 195 (RR 195), and the washing experiment of RR 195-colored fabrics (CFSCs) were carried out successively to explore the sources of hydrolyzed dyes in the washing microenvironment. Reversed-phase high-performance liquid chromatography (RP-HPLC) was used for the analysis of hydrolysis intermediates and final products of reactive red 195. The experimental results indicated that the structure of the dye washing shed is consistent with the final hydrolysate of reactive red 195, which is the main colored contaminant in washing wastewater. To eliminate the hydrolyzed dyes from the source, an electrochemical degradation device was designed. The degradation parameters, including voltage, electrolyte concentration, and dye shedding concentration are discussed in the electrochemical degradation experiment. The electrochemical degradation device was also successfully implemented and verified in a home washing machine.

[Chemical constituents of Helleborus thibetanus].

The chemical constituents of Helleborus thibetanus were isolated and purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and semi-preparative RP-HPLC, and the structures of all compounds were identified by modern spectrographic technology(MS, NMR). The MTT method was used to measure the cytotoxicity of compounds 1-8. Twelve compounds were isolated from the roots and rhizomes of H. thibetanus and were identified as(25R)-22ß,25-expoxy-26-[(O-ß-D-glucopyranosyl)oxy]-1ß,3ß-dihydroxyfurosta-5-en(1), ß-sitosterol myristate(2), ß-sitosterol lactate(3), ß-sitosterol 3-O-ß-D-glucopyrannoside(4), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(5), 1,3,5-trimethoxybenzene(6), 7,8-dimethylbenzo pteridine-2,4(1H,3H)-dione(7), 1H-indole-3-carboxylic acid(8), p-hydroxy cinnamic acid(9), lauric acid(10), n-butyl α-L-arabinofuranoside(11) and methyl-α-D-fructofuranoside(12), respectively. Among them, compound 1 is a new compound and named thibetanoside L; compounds 2, 5-8, 11 are first isolated from the family Ranunculaceae; compound 12 is isolated from the genus Helleborus for the first time. The results of MTT assay showed that the IC_(50) values of compounds 1-8 against HepG2 and HCT116 cells were greater than 100 µmol·L~(-1).

Study on the interaction mechanism between luteoloside and xanthine oxidase by multi-spectroscopic and molecular docking methods.

Gout is an inflammatory joint disease caused by urate crystal deposition, which is associated with hyperuricemia. Gout will take place when the uric acid accumulates. Xanthine oxidase (XO) is a crucial enzyme in the formation of uric acid. Inhibiting XO is one of the means to ameliorate gout. Luteoloside is a kind of natural flavonoid, which has an excellent prospect for relieving gout. But there are few reports on the interaction mechanism between luteoloside and XO currently. In this study, the interaction mechanism between luteoloside and XO was explored using spectroscopy and molecular docking. The fluorescence spectroscopy results indicated that luteoloside could make the intrinsic fluorescence of XO quenched, and the binding constant between luteoloside and XO was (1.85 ± 0.22) × 103 L mol-1 at 298 K. The synchronous fluorescence spectroscopy results showed that the absorption peaks of Tyr and Trp shifted blue, and the hydrophobicity of the microenvironment increased. Moreover, CD spectra showed that α-helix of XO decreased, ß-sheet and ß-turn increased after adding luteoloside. The results of molecular docking analysis showed that XO could combine with luteoloside through hydrogen bonds and hydrophobic force. The results indicated that luteoloside could remarkably interact with XO. Insights into the interaction mechanism provide a necessary basis for the search for low-toxic natural products as targets of XO. HIGHLIGHTS: Luteoloside and xanthine oxidase was a strong binding mode and had only one binding site. Luteoloside could cause α-helix reduced, ß-sheet and ß-turn increased, and change the secondary structure of XO. The binding between luteoloside and xanthine oxidase was a spontaneous process. The main binding force was hydrophobic force between luteoloside and xanthine oxidase.

Binding mechanism of lipase with Lentinus edodes mycelia polysaccharide by multi-spectroscopic methods.

It is an effective strategy to avoid obesity by inhibiting the activity of lipase. In this study, the binding mechanism of lipase and Lentinus edodes mycelia polysaccharide (LMP) were explored with multi-spectral methods, for example, three-dimensional (3D) fluorescence, Fourier-transformed infrared (FT-IR), and Raman spectra. At 290 K, the binding constant was 2.44 × 105 L/mol, there was only one binding site between LMP and lipase. Static quenching was the quenching mechanism. The major forces were hydrogen bonding and van der Waals force. The binding of LMP to lipase impacted the microenvironment around tyrosine and tryptophan residues. The polarity around these residues was decreased and hydrophobicity was enhanced. This study not only revealed the binding mechanism of LMP on lipase but also provided scientific evidence for expanding the application of LMP in functional food industries.

Artificial Selection Drives SNPs of Olfactory Receptor Genes into Different Working Traits in Labrador Retrievers.

Labs as guide dogs or sniffer dogs in usage have been introduced into China for more than 20 years. These two types of working dogs own blunt or acute olfactory senses, which have been obtained by artificial selection in relatively closed populations. In order to attain stable olfactory attributes and meet use-oriented demands, Chinese breeders keep doing the same artificial selection. Though olfactory behavior is canine genetic behavior, genotypes of OR genes formed by breeding schemes are largely unknown. Here, we characterized 26 SNPs, 2 deletions, and 2 insertions of 7 OR genes between sniffer dogs and guide dogs in order to find out the candidate alleles associated with working specific traits. The results showed that there were candidate functional SNP alleles in one locus that had statistically severely significant differences between the two subpopulations. Furthermore, the levels of polymorphism were not high in all loci and linkage disequilibrium only happened within one OR gene. Hardy-Weinberg equilibrium (HWE) tests showed that there was a higher ratio not in HWE and lower FST within the two working dog populations. We conclude that artificial selection in working capacities has acted on SNP alleles of OR genes in a dog breed and driven the evolution in compliance with people's intentions though the changes are limited in decades of strategic breeding.

A multicenter, randomized, open, controlled trial to evaluate the efficacy of Honglilai Vaginal Cream and Premarin Vaginal Cream for Genitourinary Syndrome of Menopause in different subgroups of Chinese postmenopausal women.

AIM: In a randomized, multicenter, open, controlled trial, we compared the effects of Honglilai Vaginal Cream and Premarin Vaginal Cream in different age subgroups and menopausal year subgroups (trial registration numbers: 02003L00493). METHODS: Postmenopausal women with Genitourinary Syndrome of Menopause (GSM) were divided into Honglilai group (n = 319) and Premarin group (n = 116), while subgroups were divided according to their different characteristics of age and menopausal years. Honglilai Vaginal Cream (0.625 mg/g) or Premarin Vaginal Cream (0.625 mg/g) once daily for 3 weeks. RESULTS: In the subgroup of participates >60 years, there were no significant differences of Vaginal Cell Maturation Index (VMI) between the two groups after treatment (p = .171). In the subgroup of 50-59 years, the VMI of Honglilai group was significantly lower than Premarin group (Honglilai group: 74.37 ± 22.76; Premarin group: 80.06 ± 16.15; p = .02). There were no significant differences of Vaginal symptom scores between Honglilai group and Premarin group in every sub-group (p > .05). CONCLUSIONS: Honglilai Vaginal Cream had comparable efficacy with Premarin Vaginal Cream in Chinese women older than 60 years.

Investigating the molecular mechanisms of glyoxal-induced cytotoxicity in human embryonic kidney cells: Insights from network toxicology and cell biology experiments.

Glyoxal, a reactive carbonyl species, can be generated both endogenously (glucose metabolism) and exogenously (cigarette smoke and food system). Increasing evidence demonstrates that glyoxal exacerbates the development and progression of diabetic nephropathy, but the underlying mechanisms of glyoxal toxicity to human embryonic kidney (HEK293) cells remain unclear. In this work, the molecular mechanisms of glyoxal-induced cytotoxicity in HEK293 cells were explored with network toxicology and cell biology experiments. Network toxicology results showed that oxidative stress and advanced glycation end products (AGEs)/RAGE signaling pathways played a crucial role in glyoxal toxicity. Next, further validation was performed at the cellular level. Glyoxal activated the AGEs-RAGE signaling pathway, caused the increase of cellular ROS, and activated the p38MAPK and JNK signaling pathways, causing cellular oxidative stress. Furthermore, glyoxal caused the activation of the NF-κB signaling pathway and increased the expression of TGF-ß1, indicating that glyoxal caused cellular inflammation. Moreover, glyoxal caused cellular DNA damage accompanied by the activation of DNA damage response pathways. Finally, the mitochondrial apoptosis pathway was activated. The results that obtained in cell biology were consistent with network toxicology, which corroborated each other and together indicated that glyoxal induced HEK293 cells damage via the process of oxidative stress, the AGEs-RAGE pathway, and their associated signaling pathways. This study provides the experimental basis for the cytotoxicity of glyoxal on HEK293 cells.

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis.

Acrolein is a ubiquitous environmental pollutant that produced by the incomplete combustion of cigarette smoke, forest fires, petroleum fuels, plastic materials, and cooking fumes. Inhalation is a common form of people exposure to acrolein, increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells. However, the molecular mechanism of the cytotoxicity of acrolein exposure on vascular endothelial cells remains unclear. This work focused on the toxicity of acrolein on human umbilical vein endothelial cells (HUVECs). The molecular mechanism was studied based on oxidative stress, DNA damage response (DDR), and mitochondrial apoptosis pathways. After HUVECs were treated with 12.5, 25, and 50 µM acrolein for 24 h, cell viability, cell colony formation, mitochondrial membrane potential, and adenosine triphosphate content significantly reduced, and acrolein increased intracellular reactive oxygen species, apoptosis rate, and 8-hydroxy-2 deoxyguanosine (8-OHdG) level. Furthermore, p38MAPK and c-Jun N-terminal kinase signaling pathways were activated in response to oxidative stress. Moreover, acrolein induced G0/G1phase arrest, promoted the expression of γ-H2AX, activated the DDR signaling pathway (Ataxia-Telangiectasia-Mutated [ATM] and Rad-3-related/Chk1 and ATM/Chk2), and triggered the consequent cell cycle checkpoints. Finally, the protein expression of Bax/Bcl-2 and cleaved Caspase-3 was up-regulated, suggesting apoptosis was induced by triggering the mitochondrial apoptosis pathway. All these results indicated that acrolein induced HUVECs cytotoxicity by regulating oxidative stress, DNA damage, and apoptosis. This study provides a novel perspective on the mechanism of acrolein-induced cardiovascular toxicity, it will be helpful for the prevention of acrolein-induced cardiovascular disease.