AcrR1, a novel TetR/AcrR family repressor, mediates acid and antibiotic resistance and nisin biosynthesis in Lactococcus lactis F44.

Lactococcus lactis, widely used in the manufacture of dairy products, encounters various environmental stresses both in natural habitats and during industrial processes. It has evolved intricate machinery of stress sensing and defense to survive harsh stress conditions. Here, we identified a novel TetR/AcrR family transcription regulator, designated AcrR1, to be a repressor for acid and antibiotic tolerance that was derepressed in the presence of vancomycin or under acid stress. The survival rates of acrR1 deletion strain ΔAcrR1 under acid and vancomycin stresses were about 28.7-fold (pH 3.0, HCl), 8.57-fold (pH 4.0, lactic acid) and 2.73-fold (300 ng/mL vancomycin) greater than that of original strain F44. We also demonstrated that ΔAcrR1 was better able to maintain intracellular pH homeostasis and had a lower affinity to vancomycin. No evident effects of AcrR1 deletion on the growth and morphology of strain F44 were observed. Subsequently, we characterized that the transcription level of genes associated with amino acids biosynthesis, carbohydrate transport and metabolism, multidrug resistance, and DNA repair proteins significantly upregulated in ΔAcrR1 using transcriptome analysis and quantitative reverse transcription-PCR assays. Additionally, AcrR1 could repress the transcription of the nisin post-translational modification gene, nisC, leading to a 16.3% increase in nisin yield after AcrR1 deletion. Our results not only refined the knowledge of the regulatory mechanism of TetR/AcrR family regulator in L. lactis, but presented a potential strategy to enhance industrial production of nisin.

Strength Degradation of Foamed Lightweight Soil Due to Chemical Erosion and Wet-Dry Cycle and Its Empirical Model.

Foamed lightweight soils (FLS) have been extensively used as backfill material in the construction of transportation infrastructures. However, in the regions consisting of salt-rich soft soil, the earth structure made by FLS experiences both fluctuation of groundwater and chemical environment erosion, which would accelerate the deterioration of its long-term performance. This study conducted laboratory tests to explore the deterioration of FLS in strength after being eroded by sulfate attack and/or wet-dry cycling, where the influencing factors of FLS density, concentration of sulfate solution, and cation type (i.e., Na+ and Mg2+) were considered. An unconfined compressive test (UCT) was conducted, and the corrosion-resistant coefficient (CRC) was adopted to evaluate the erosion degree after the specimens experienced sulfate attack and/or dry-wet cycling for a certain period. The research results show that the erosion of the FLS specimen under the coupling effect of sulfate attack and dry-wet cycling was more remarkable than that only under chemical soaking, and Na2SO4 solution had a severe erosion effect as compared with MgSO4 solution when other conditions were kept constant. An empirical model is proposed based on the test results, and its reliability has been verified with other test results from the literature. The proposed model provides an alternative for engineers to estimate the strength deterioration of FLS on real structures in a preliminary design.

Expression signature, prognosis value and immune characteristics of cathepsin F in non-small cell lung cancer identified by bioinformatics assessment.

BACKGROUND: In recent years, immunotherapies and targeted therapies contribute to population-level improvement in NSCLC cancer-specific survival, however, the two novel therapeutic options have mainly benefit patients containing mutated driven genes. Thus, to explore other potential genes related with immunity or targeted therapies may provide novel options to improve survival of lung cancer patients without mutated driven genes. CTSF is unique in human cysteine proteinases. Presently, CTSF has been detected in several cell lines of lung cancer, but its role in progression and prognosis of lung cancer remains unclear. METHODS: CTSF expression and clinical datasets of lung cancer patients were obtained from GTEx, TIMER, CCLE, THPA, and TCGA, respectively. Association of CTSF expression with clinicopathological parameters and prognosis of lung cancer patients was analyzed using UALCAN and Kaplan-Meier Plotter, respectively. LinkedOmics were used to analyze correlation between CTSF and CTSF co-expressed genes. Protein-protein interaction and gene-gene interaction were analyzed using STRING and GeneMANIA, respectively. Association of CTSF with molecular markers of immune cells and immunomodulators was analyzed with Immunedeconv and TISIDB, respectively. RESULTS: CTSF expression was currently only available for patients with NSCLC. Compared to normal tissues, CTSF was downregulated in NSCLC samples and high expressed CTSF was correlated with favorable prognosis of NSCLC. Additionally, CTSF expression was correlated with that of immune cell molecular markers and immunomodulators both in LUAD and LUSC. Noticeably, high expression of CTSF-related CTLA-4 was found to be associated with better OS of LUAD patients. Increased expression of CTSF-related LAG-3 was related with poor prognosis of LUAD patients while there was no association between CTSF-related PD-1/PD-L1 and prognosis of LUAD patients. Moreover, increased expression of CTSF-related CD27 was related with poor prognosis of LUAD patients while favorable prognosis of LUSC patients. CONCLUSIONS: CTSF might play an anti-tumor effect via regulating immune response of NSCLC.

Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China.

BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively). CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.

Comparison of Different Protein Emulsifiers on Physicochemical Properties of ß-Carotene-Loaded Nanoemulsion: Effect on Formation, Stability, and In Vitro Digestion.

In this study, ß-carotene-loaded nanoemulsions are emulsified using four biomacromolecular proteins-peanut protein isolate (PPI), soy protein isolate (SPI), rice bran protein isolate (RBPI), and whey protein isolate (WPI)-in order to explore their emulsion stability and in vitro digestion characteristics. All four nanoemulsions attained high encapsulation levels (over 90%). During the three-stage in vitro digestion model (including oral, gastric, and small intestine digestion phases), the PPI-emulsified nanoemulsion showed the highest lipolysis rates (117.39%) and bioaccessibility (37.39%) among the four nanoemulsions. Moreover, the PPI-emulsified nanoemulsion (with the smallest droplet size) also demonstrated the highest stability during storage and centrifugation, while those for the RBPI-emulsified nanoemulsion (with the largest droplet size) were the lowest. In addition, all four nanoemulsions showed superior oxidation stability when compared with the blank control of corn oil. The oxidation rates of the PPI- and WPI-stabilized groups were slower than the other two groups.

Improvement of protein emulsion stability through glycosylated black bean protein covalent interaction with (-)-epigallocatechin-3-gallate.

This study investigated the effects of covalent conjugates combined by glycosylated black bean protein isolate (BBPI-G) and (-)-epigallocatechin-3-gallate (EGCG) on the emulsion stability. Fourier transform infrared (FTIR) spectroscopy showed that covalent binding of EGCG with BBPI-G made the protein molecule unfolded. Besides, the emulsifying properties of BBPI-G were increased after combined with EGCG. BBPI-G-EGCG emulsion had lower mean particle size and higher content of interfacial protein adsorption (AP), which resulted in thicker and more impact oil-water interface. Therefore, the stability of emulsions was significantly improved. Furthermore, the emulsions prepared by BBPI-G-EGCG compounds exhibited considerable stability in storage, oxidation, thermal treatments, freeze-thaw and freeze-dried powders resolubility. This study demonstrated that the covalent bond of glycosylated protein and polyphenols could advance the emulsifying performance of protein, and BBPI-G-EGCG covalent complex was an effective emulsifier for preparing high stability emulsions.

Comparison of protein hydrolysates against their native counterparts in terms of structural and antioxidant properties, and when used as emulsifiers for curcumin nanoemulsions.

This study investigated the stability and the in vitro digestion of curcumin nanoemulsions stabilized by three protein hydrolysates: peanut protein isolate (PPI), soybean protein isolate (SPI) and whey protein isolate (WPI). After enzymatic hydrolysis, the protein structure became more disordered, and increased antioxidant capacity was also observed for protein hydrolysates. The protein hydrolysates generated curcumin nanoemulsions with considerable stability over 28 days of storage. Moreover, protein hydrolysates more effectively improved the lipolysis rate and bioaccessibility of curcumin nanoemulsions than native proteins, and PPI hydrolysates exhibited the highest lipolysis rate (110.43%) and the highest bioaccessibility (53.24%). This study indicated that protein hydrolysates could be used as emulsifiers for preparing nanoemulsion delivery systems with high stability and bioaccessibility.

First measurements of the radiation dose on the lunar surface.

Human exploration of the Moon is associated with substantial risks to astronauts from space radiation. On the surface of the Moon, this consists of the chronic exposure to galactic cosmic rays and sporadic solar particle events. The interaction of this radiation field with the lunar soil leads to a third component that consists of neutral particles, i.e., neutrons and gamma radiation. The Lunar Lander Neutrons and Dosimetry experiment aboard China's Chang'E 4 lander has made the first ever measurements of the radiation exposure to both charged and neutral particles on the lunar surface. We measured an average total absorbed dose rate in silicon of 13.2 ± 1 µGy/hour and a neutral particle dose rate of 3.1 ± 0.5 µGy/hour.

A highly sensitive, selective ratiometric fluorescent probe for cobalt(II) and its applications for biological imaging.

Probe has been developed as the first ratiometric fluorescent cobalt probe with high sensitivity and selectivity based on internal charge transfer (ICT). Most importantly, the probe achieved the imaging and detection of cobalt in cells with ratiometric measurement.

Highly selective, naked-eye and fluorescent "off-on" probe for detection of histidine/histidine-rich proteins and its application in living cell imaging.

A highly selective colorimetric and fluorescence enhanced probe S1 (M2@Cu) for histidine and histidine-rich proteins has been developed. In neutral aqueous ethanol solution, probe S1 can selectively detect histidine out of twenty DNA encoded amino acids by showing a color change from brownish red to light green, and with a fluorescence enhancement up to 99-fold at 537 nm, simultaneously.

A highly selective space-folded photo-induced electron transfer fluorescent probe for carbonic anhydrase isozymes IX and its applications for biological imaging.

The first highly selective and sensitive fluorescent probe Z1 for detection of carbonic anhydrase IX (CA IX) over isoforms CA I and CA II was developed. As demonstrated, Z1 worked effectively in both enzymatic systems and living hypoxia cells.

Hybrid segmentation of mass in mammograms using template matching and dynamic programming.

RATIONALE AND OBJECTIVES: Accurate image segmentation for breast lesions is a critical step in computer-aided diagnosis systems. The objective of this study was to develop a robust method for the automatic segmentation of breast masses on mammograms to extract feasible features for computer-aided diagnosis systems. MATERIALS AND METHODS: The data set used in this study consisted of 483 regions of interest extracted from 328 patients. A hybrid method for segmenting breast masses was proposed on the basis of the template-matching and dynamic programming techniques. First, a template-matching technique was used to locate and obtain the rough region of masses. Then, on the basis of this rough region, a local cost function for dynamic programming was defined. Finally, the optimal contour was derived by applying dynamic programming as an optimization technique. The performance of this proposed segmentation method was evaluated using area-based and boundary distance-based similarity measures based on radiologists' manually marked annotations. A comparison with three different segmentation algorithms on the data set was provided. RESULTS: The mean overlap percentage for our proposed hybrid method was 0.727 ± 0.127, whereas those for Timp and Karssemeijer's dynamic programming method, Song et al's plane-fitting and dynamic programming method, and the normalized cut segmentation method were 0.657 ± 0.216, 0.636 ± 0.190, and 0.562 ± 0.199, respectively. All P values for the measure distribution of our proposed method and the other three algorithms were <.001. CONCLUSIONS: A hybrid method based on the template-matching and dynamic programming techniques was proposed to segment breast masses on mammograms. Evaluation results indicate that the proposed segmentation method can improve the accuracy of mass segmentation compared to three other algorithms. The proposed segmentation method shows better performance and has great potential in improving the accuracy of computer-aided diagnosis systems in interpreting mammograms.

A thioether-rich crown-based highly selective fluorescent sensor for Hg(2+) and Ag(+) in aqueous solution.

A new fluorescent sensor 1, based on the naphthalimide chromophore and thioether-rich crown receptor, exhibited dual signaling behaviors for Hg(2+) and Ag(+) in aqueous solution. Upon addition of Hg(2+), the fluorescence intensity enhanced in a linear fashion with a quantum yield increase of about 5-fold. Moreover, with the 1-Hg(2+) complex, Ag(+) was easily recognized by a marked fluorescence quenching. The living cells image experiments demonstrate the value of sensor 1 in fluorescent visualization of Hg(2+) ions in biological systems.

A highly sensitive and selective OFF-ON fluorescent sensor for cadmium in aqueous solution and living cell.

A highly selective and sensitive OFF-ON fluorescent sensor 1, employing the PET mechanism, was designed and synthesized. It could be used to detect Cd(2+) ion in aqueous solution and to image Cd(2+) ion in living cells. The fluorescence intensity significantly enhanced about 195-fold and the quantum yield increased almost 100-fold. Moreover the fluorescence intensity of 1 increased linearly with high sensitivity (0-1 microM) toward Cd(2+).

Multiple molecular logic functions and molecular calculations facilitated by surfactant's versatility.

Two isomeric compounds and , combining intramolecular charge transfer (ICT) and photoinduced electron transfer (PET) mechanisms together, were designed and used as logic gates with configurable multiple outputs; ten different logic functions (AND, NAND, OR, NOR, XNOR, INHIBIT, YES, NO, PASS 1 and PASS 0) were achieved by varying the inputs threshold or by altering the inputs; furthermore, half addition and half subtraction were performed within (or ); the concept demonstrated here may provide a strategy for constructing more integrated molecular level devices with multiple functions.

Molecular logic operations based on surfactant nanoaggregates.

Two molecular logic gates, FS1 and FS2, which display a UV and fluorescence behavior that is dependent on the pH value and the sodium dodecyl sulfate (SDS) surfactant concentration, are demonstrated based on the intramolecular charge-transfer mechanism. They are constructed according to the inorganic salts that induce transformation from premicelle to micelle. The absorption band of FS1 at 480 nm is significantly enhanced only when both SDS and Na(2)SO(4) are the input at high concentrations, in accordance with an AND logic gate. The OR logic function can be realized in a 3.5 mM SDS/FS2 aqueous solution with SDS and Na(2)SO(4) as inputs along with the emission intensity as output. Furthermore, half addition and half subtraction can be incorporated in FS1. This is facilitated by the surfactant, due to its versatility.