Identification of non-canonical antagonistic bacteria via interspecies contact-dependent killing.

BACKGROUND: Canonical biocontrol bacteria were considered to inhibit pathogenic bacteria mainly by secreting antibiotic metabolites or enzymes. Recent studies revealed that some biocontrol bacteria can inhibit pathogenic bacteria through contact-dependent killing (CDK) mediated by contact-dependent secretion systems. The CDK was independent of antibiotic metabolites and often ignored in normal biocontrol activity assay. RESULTS: In this study, we aimed to use a pathogen enrichment strategy to isolate non-canonical bacteria with CDK ability. Rhizosphere soil samples from Chinese cabbage showing soft rot symptom were collected and Pectobacterium carotovorum subsp. carotovorum (Pcc), the pathogen of cabbage soft rot, were added into these samples to enrich bacteria which attached on Pcc cells. By co-culture with Pcc, four bacteria strains (named as PcE1, PcE8, PcE12 and PcE13) showing antibacterial activity were isolated from Chinese cabbage rhizosphere. These four bacteria strains showed CDK abilities to different pathogenic bacteria of horticultural plants. Among them, PcE1 was identified as Chryseobacterium cucumeris. Genome sequencing showed that PcE1 genome encoded a type VI secretion system (T6SS) gene cluster. By heterologous expression, four predicted T6SS effectors of PcE1 showed antibacterial activity to Escherichia coli. CONCLUSION: Overall, this study isolated four bacteria strains with CDK activity to various horticultural plant pathogens, and revealed possible involvement of T6SS of Chryseobacterium cucumeris in antibacterial activity. These results provide valuable insight for potential application of CDK activity in biocontrol bacteria. © 2024 Society of Chemical Industry.

Improving Sensitivity and Reproducibility of Surface-Enhanced Raman Scattering Biochips Utilizing Magnetoplasmonic Nanoparticles and Statistical Methods.

Surface-enhanced Raman scattering (SERS) technology has been widely recognized for its remarkable sensitivity in biochip development. This study presents a novel sandwich immunoassay that synergizes SERS with magnetoplasmonic nanoparticles (MPNs) to improve sensitivity. By taking advantage of the unique magnetism of these nanoparticles, we further enhance the detection sensitivity of SERS biochips through the applied magnetic field. Despite the high sensitivity, practical applications of SERS biochips are often limited by the issues of stability and reproducibility. In this study, we introduced a straightforward statistical method known as "Gaussian binning", which involves initially binning the two-dimensional Raman mapping data and subsequently applying Gaussian fitting. This approach enables a more consistent and reliable interpretation of data by reducing the variability inherent in Raman signal measurements. Based on our method, the biochip, targeting for C-reactive protein (CRP), achieves an impressive detection limit of 5.96 fg/mL, and with the application of a 3700 G magnetic field, it further enhances the detection limit by 5.7 times, reaching 1.05 fg/mL. Furthermore, this highly sensitive and magnetically tunable SERS biochip is easily designed for versatile adaptability, enabling the detection of other proteins. We believe that this innovation holds promise in enhancing the clinical applicability of SERS biochips.

[Diurnal differences in acute gout attacks: A clinical study of male gout patients].

OBJECTIVE: To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment. METHODS: Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators. RESULTS: A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 ∶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks. CONCLUSION: No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.

Effects of bacteria on early-stage litter decomposition in Wudalianchi volcanic forest.

To understand the role of microorganisms in litter decomposition and nutrient cycling in volcanic forest ecosystem, we conducted in-situ litterbag decomposition experiment and used Illumina MiSeq high-throughput sequencing to analyze the response of bacterial community structure and diversity during the decomposition of litters from Larix gmelinii, Betula platyphylla and Populus davidiana, the dominant tree species in volcanic lava plateau of Wudalianchi. The results showed that mass remaining percentage of litters of three species after 18-month decomposition was 63.9%-68.1%. Litter of B. platyphylla decomposed the fastest, with significant difference in N, C:N, and N:P before and after decomposition. The richness of bacterial species and diversity index differed significantly among the three litters. Proteobacteria, Actinomycetes, and Bacteroidetes were the dominant bacterial groups at the phylum level, while Rhizobium, Sphingomonas, and Pseudomonas were the dominant groups at the genus level, with significant difference among the three litters. After 18 months, the dominant bacterial groups in litter tended to be consistent with those in volcanic lava platform soil. In the volcanic forest ecosystem, bacterial diversity and community structure were mainly affected by P, C:N, and N:P in the litter.

Depicting Defects in Metallic Glasses by Atomic Vibrational Entropy.

Due to the chaotic structure of amorphous materials, it is challenging to identify defects in metallic glasses. Here we tackle this problem from a thermodynamic point of view using atomic vibrational entropy, which represents the inhomogeneity of atomic contributions to vibrational modes. We find that the atomic vibrational entropy is correlated to the vibrational mean-square displacement and polyhedral volume of atoms, revealing the critical role of vibrational entropy in bridging dynamics, thermodynamics, and structure. On this method, the local vibrational entropy obtained by coarse-graining the atomic vibrational entropy in space can distinguish more effectively between liquid-like and solid-like atoms in metallic glasses and establish the correlation between the local vibrational entropy and the structure of metallic glasses, offering a route to predict the plastic events from local vibrational entropy. The local vibration entropy is a good indicator of thermally activated and stress-driven plastic events, and its predictive ability is better than that of the structural indicators.

Detecting the exponential relaxation spectrum in glasses by high-precision nanocalorimetry.

Nonexponential relaxations are universal characteristics for glassy materials. There is a well-known hypothesis that nonexponential relaxation peaks are composed of a series of exponential events, which have not been verified. In this Letter, we discover the exponential relaxation events during the recovery process using a high-precision nanocalorimetry, which are universal for metallic glasses and organic glasses. The relaxation peaks can be well fitted by the exponential Debye function with a single activation energy. The activation energy covers a broad range from α relaxation to ß relaxation and even the fast γ/ß' relaxation. We obtain the complete spectrum of the exponential relaxation peaks over a wide temperature range from 0.63Tg to 1.03Tg, which provides solid evidence that nonexponential relaxation peaks can be decomposed into exponential relaxation units. Furthermore, the contribution of different relaxation modes in the nonequilibrium enthalpy space is measured. These results open a door for developing the thermodynamics of nonequilibrium physics and for precisely modulating the properties of glasses by controlling the relaxation modes.

Comparison of demineralized bone matrix with different cycling crushing times in posterolateral fusion model of athymic rats.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.

Innovation network structure, government R&D investment and regional innovation efficiency: Evidence from China.

Based on the panel data of 30 provinces in China from 2011 to 2019, this paper uses a two-stage DEA model to measure regional innovation efficiency, then non-parametric test is used to examine the impact of innovation network structure and government R&D investment on regional innovation efficiency. The results show that, at the provincial level, innovation efficiency of regional R&D is not necessarily in direct proportion to the innovation efficiency in the commercialization stage. Commercialization efficiency is not necessarily high in provinces with high technical R&D efficiency. At the national level, the innovation efficiency gap between our country's R&D and commercialization stage is small, indicating that the development of the national innovation efficiency is more and more balanced. Innovation network structure can promote the R&D efficiency, but has no significant effect on the commercialization efficiency. Government R&D investment helps to improve the R&D efficiency, but it is not conducive to the improvement of commercialization efficiency. The interaction between innovation network structure and government R&D investment will have compound effects on regional innovation efficiency; the region with underdeveloped innovation network structure can increase the government R&D investment to make it have a higher level of R&D. This paper provides insights into how to improve innovation efficiency in different social networks and policy environments.

High-Conductivity Chalcogenide Glasses in Ag-Ga2Te3-SnTe Systems and Their Suitability as Thermoelectric Materials.

A novel high-conductivity Agx[(Ga2Te3)34(SnTe)66]100-x tellurium-based glassy system was fabricated via melt spinning with the glass formation area in the range of x = 0-15 mol %. A bulk Ag10[(Ga2Te3)34(SnTe)66]90 glass (A10) was obtained via spark plasma sintering at 450 K using a 5 min dwell time and 400 MPa pressure. The fabricated A10 glass exhibited higher room-temperature conductivity (σ300 K = 46 S m-1), larger glass transition temperature (Tg = 482 K), and ultralower thermal conductivity (∼0.19 W m-1 K-1) compared to those of previously reported Cu-Ge-Te, Cu-As-Te, Cu-Ge-As-Te, and Cu-As-Se-Te glassy systems with the approximate doping concentrations of 5-20%, demonstrating that this distinctive Ag-Ga2Te3-SnTe system is interesting materials for thermoelectric applications. The high-conductivity Ag-Ga2Te3-SnTe glassy system will extend investigations into similar glassy semiconductors and also can be used for preparing glass ceramics with potential applications in other fields.

Uncovering the bridging role of slow atoms in unusual caged dynamics and ß-relaxation of binary metallic glasses.

The origin of ß-relaxation in metallic glasses is still not fully understood, and the guidance of slow atoms for caged dynamics and ß-relaxation is rarely mentioned. Using molecular dynamics simulations, we reveal the bridging role of slow atoms on unusual caged dynamics and ß-relaxation. In the stage of unusual caged dynamics, slow atoms are bounded by neighboring atoms. It is difficult for the slow atoms to break the cage, producing more high-frequency vibration, which causes more atoms to jump out of the cage randomly in the next stage. Precisely, the movement of the slow atoms changes from individual atoms vibrating inside the cage and gradually breaking out of the cage into a string-like pattern. The string-like collective atomic jumps cause decay of the cages, inducing ß-relaxation. This situation generally exists in binary systems with the large atomic mass difference. This work offers valuable insights for understanding the role of slow atoms in unusual caged dynamics and ß-relaxation, complementing studies on the origin of ß-relaxation in metallic glasses and their glass-forming liquids.

Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study.

Objective: To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China. Methods: A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses. Results: The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001). Conclusion: Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.

Financial development, technological innovation and urban-rural income gap: Time series evidence from China.

The main purpose of the paper is to investigate the relationship between technological innovation and income inequality for China based on the financial Kuznets curve (FKC) hypothesis. The study uses time-series data from 1985 to 2019. We employ the Johansen cointegration, ARDL model and VECM Granger causality techniques to analyze the links between the variables. We also use the DOLS, FMOLS and CCR mechanisms to estimate the long-run parameters. The paper finds that the FKC is valid for China's economy in the long run. Technological innovation positively affects the urban-rural income gap, while there is an inverted-U shaped between financial development and the urban-rural income gap. The relationship between financial development and the urban-rural income gap is bi-directional causality. Technological innovation and the urban-rural income gap cause each other. Empirical results suggest a twofold policy meaning: i) to further the financial system and ii) to eliminate the adverse impacts of technological innovations on income distribution.

New Interpretation of Glass Formation in Isomeric Substances: Shifting from Melting-Point to Melting-Entropy.

Revealing the critical thermodynamic parameters determining the glass formation of substances is of great significance for understanding the glass transition and guiding the composition design of glass-forming materials. Nevertheless, the direct access to glass-forming ability (GFA) by thermodynamics for various substances remains to be substantiated. The strategy to seek the fundamental properties of glass formation is explored several decades ago, as pioneered by Angell, arguing that the GFA in isomeric xylenes depends on the low lattice energy manifested by the low melting point. Here, an in-depth study is advanced using two more isomeric systems. Surprisingly, the results do not constantly support the reported relationship between the melting point and glass formation among isomeric molecules. Instead, molecules with enhanced glass formability are featured by the properties of low melting entropy without exception. Comprehensive studies of isomeric molecules find that the low melting entropy is roughly accompanied by the low melting point, explaining the apparent link between melting point and glass formation. Progressively, the viscosity measurements of the isomers uncover a strong dependence of the melting viscosity on melting entropy. These results emphasize the significance of the melting entropy in governing the glass formability of substances.

Atomic Structural Origin of Fictive Temperature Revealed by AZnP3 O9 (A=K, Rb) Glasses.

The fictive temperature (Tf ) is widely applied to understand the relaxation thermodynamics of a glass; however, its atomic structural origin is still unclear. Here, we report two novel AZnP3 O9 glasses obtained by melting the composition identical single crystals. These glasses exhibit structural inheritance within 5 Šfrom the single crystal counterparts that is quantified by δ=nglass /ncry (0≤δ≤1, n is the number of pair correlation functions). Among the available glass-formers, glass KZnP3 O9 exhibits the highest structural inheritance (δ=1, nglass =8). More insightfully, a reverse correlation between δ and the relaxation thermodynamic parameters is observed in glass AZnP3 O9 , revealing for the first time the atomic structural origin of fictive temperature.

Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.

Poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA-deficient tumors. However, over 40% of BRCA-deficient patients fail to respond to PARPi. Here, we report that thioparib, a next-generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi-sensitive and -resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1-dependent DNA damage and replication stress, causing S-phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR-mediated DNA repair while increasing RAD51 foci formation. Notably, the on-target inhibition of PARP7 by thioparib-activated STING/TBK1-dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome-scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next-generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier-generation PARPi.

A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum.

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

Understanding the difference in the stretched structural relaxations probed by dielectric and enthalpic studies of glass forming substances.

We investigated the stretched dynamics of the structural relaxation in molecular glass formers by using dielectric and thermal (or enthalpic) relaxations. The dielectric stretching exponents ßdie are determined by the Havriliak-Negami function, while the enthalpic ßTNMH is quantified by using the Tool-Narayanaswamy-Moynihan-Hodge formalism. We found ßTNMH is anticorrelated with the degree of freedom, a molecule addressed by the concept of beads. Referring to the reported relation of ßdie to the dipole moment µ, we proposed a combined parameter of µ2*beads, which can rationalize the difference in stretching exponents obtained by dielectric and enthalpic relaxations. For the majority of glass-forming molecules, the difference is trivial, but for those molecules with both unusually high dipole moments and flexibility, a large difference is obvious. The interplay of the degree of freedom and dielectric dipole-dipole interaction in molecular dynamics is addressed.

Sensitivity enhancement of magneto-optical Faraday effect immunoassay method based on biofunctionalized γ-Fe2O3@Au core-shell magneto-plasmonic nanoparticles for the blood detection of Alzheimer's disease.

In this work, we conducted a proof-of-concept experiment based on biofunctionalized magneto-plasmonic nanoparticles (MPNs) and magneto-optical Faraday effect for in vitro Alzheimer's disease (AD) assay. The biofunctionalized γ-Fe2O3@Au MPNs of which the surfaces are modified with the antibody of Tau protein (anti-τ). As anti-τ reacts with Tau protein, biofunctionalized MPNs aggregate to form magnetic clusters which will hence induce the change of the reagent's Faraday rotation angle. The result showed that the γ-Fe2O3@Au core-shell MPNs can enhance the Faraday rotation with respect to the raw γ-Fe2O3 nanoparticles. Because of their magneto-optical enhancement effect, biofunctionalized γ-Fe2O3@Au MPNs effectively improve the detection sensitivity. The detection limit of Tau protein as low as 9 pg/mL (9 ppt) was achieved. Furthermore, the measurements of the clinical samples from AD patients agreed with the CDR evaluated by the neurologist. The results suggest that our method has the potential for disease assay applications.

Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.