Elevated Fibrinogen-to-Albumin Ratio Correlates with Incident Stroke in Cerebral Small Vessel Disease.

Purpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients. Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients. Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0-53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043-1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063-1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06-1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05-1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age. Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.

Antitumor Therapy through Photothermal Performance Synergized with Catalytic Activity Based on the Boron Cluster Supramolecular Frameworks.

Chemodynamic therapy (CDT) has received widespread attention as a tumor optical treatment strategy in the field of malignant tumor therapy. Nonmetallic multifunctional nanomaterials as CDT agents, due to their low toxicity, long-lasting effects, and safety characteristics, have promising applications in the integrated diagnosis and treatment of cancer. Here, we modified the supramolecular framework of boron clusters, coupled with a variety of dyes to develop a series of metal-free agent compounds, and demonstrated that these nonmetallic compounds have excellent CDT activities through experiments. Subsequently, the best performing Methylene Blue/[closo-B12H12]2- (MB@B12H12) was used as an example. Through theoretical calculations, electron paramagnetic resonance spectroscopy, and 808 nm light irradiation, we confirmed that MB@B12H12 exhibited photothermal performance and CDT activity further. More importantly, we applied MB@B12H12 to melanoma cells and subcutaneous tumor, demonstrating its effective suppression of melanoma growth in vitro and in vivo through the synergistic effects of photothermal performance and CDT activity. This study emphasizes the generalizability of the coupling of dyes to [closo-B12H12]2- with important clinical translational potential for CDT reagents. Among them, MB@B12H12 may have a brighter future, paving the way for the rapid development of metal-free CDT reagents.

Synthesis of iron-boride/carbon-nitride composites and their applications in chemodynamic therapy.

Chemodynamic therapy (CDT) is an emerging treatment strategy that inhibits tumor growth by catalyzing the generation of reactive oxygen species (ROS), such as hydroxyl radicals (•OH), using specific nanomaterials. Herein, we have developed a new class of iron-based nanomaterials, i.e., iron-based borides (FeB), using the superchaotropic effect of a boron cluster (closo-[B12H12]2-) and organic ligands, followed by high-temperature calcination. Experimental data and theoretical calculations revealed that FeB nanoparticles exhibit a Fenton-like effect, efficiently decomposing hydrogen peroxide into •OH and thus increasing the concentration of ROS. FeB nanomaterials demonstrate excellent catalytic performance, efficiently generate ROS, and exert significant antitumor effects in cell experiments and animal models. Therefore, FeB nanomaterials have considerable potential for application in tumor treatment and offer new insights for the development of novel and efficient cancer therapy strategies.

Genomic and Transcriptomic Insights into the Evolution and Divergence of MIKC-Type MADS-Box Genes in Carica papaya.

MIKC-type MADS-box genes, also known as type II genes, play a crucial role in regulating the formation of floral organs and reproductive development in plants. However, the genome-wide identification and characterization of type II genes as well as a transcriptomic survey of their potential roles in Carica papaya remain unresolved. Here, we identified and characterized 24 type II genes in the C. papaya genome, and investigated their evolutional scenario and potential roles with a widespread expression profile. The type II genes were divided into thirteen subclades, and gene loss events likely occurred in papaya, as evidenced by the contracted member size of most subclades. Gene duplication mainly contributed to MIKC-type gene formation in papaya, and the duplicated gene pairs displayed prevalent expression divergence, implying the evolutionary significance of gene duplication in shaping the diversity of type II genes in papaya. A large-scale transcriptome analysis of 152 samples indicated that different subclasses of these genes showed distinct expression patterns in various tissues, biotic stress response, and abiotic stress response, reflecting their divergent functions. The hub-network of male and female flowers and qRT-PCR suggested that TT16-3 and AGL8 participated in male flower development and seed germination. Overall, this study provides valuable insights into the evolution and functions of MIKC-type genes in C. papaya.

Performance and mechanism of ammonia production by electrocatalytic nitrate reduction based on dodecahydro-closo-dodecaborate hybrid.

Ammonia is an essential food and fertilizer component and is a fundamental raw material for industry and agriculture. In contrast, nitrate is the main pollutant that causes eutrophication in water. Electrocatalysis is a clean and efficient method for simultaneous nitrate removal and ammonia production. However, because ammonia production from the electrocatalytic nitrate reduction reaction (NO3RR) is a complex eight-electron process with slow kinetics, designing the cathode catalyst is critical for improving the ammonia yield. In this study, boron (B) doped metal oxides (TiZn2O4@B-x) obtained by coupling dodecahydro-closo-dodecaborate anions ([closo-B12H12]2-) and ZnTi-layered double hydroxides (ZnTi-LDH) after calcination was used as the cathode for the NO3RR. Specifically, TiZn2O4@B-700 exhibited excellent ammonia yield (21809.24 µg h-1 mgcat-1) and Faraday efficiency (FE) of (93.15%) at -1.8 V versus saturated calomel electrode (SCE). Furthermore, TiZn2O4@B-700 exhibited superior cycling stability and resistance to ionic interference. Moreover, density functional theory (DFT) calculations indicated that incorporating B increased the electron transfer rate and reduced the free energy required for the rate-limiting step of ammonia production via the NO3RR, thereby increasing the ammonia yield. This study provides a new concept for designing catalysts for green ammonia synthesis.

Evanescent Wave Optical-Fiber Aptasensor for Rapid Detection of Zearalenone in Corn with Unprecedented Sensitivity.

Zearalenone (ZEN) is a common mycotoxin pollutant found in agricultural products. Aptamers are attractive recognition biomolecules for the development of mycotoxin biosensors. Even though numerous aptasensors have been reported for the detection of ZEN in recent years, many of them suffer from problems including low sensitivity, low specificity, tedious experimental steps, high-cost, and difficulty of automation. We report here the first evanescent wave optical-fiber aptasensor for the detection of ZEN with unprecedented sensitivity, high specificity, low cost, and easy of automation. In our aptasensor, a 40-nt ZEN-specific aptamer (8Z31) is covalently immobilized on the fiber. The 17-nt fluorophore Cy5.5-labeled complementary DNA strand and ZEN competitively bind with the aptamer immobilized on the fiber, enabling the signal-off fluorescent detection of ZEN. The coating of Tween 80 enhanced both the sensitivity and the reproducibility of the aptasensor. The sensor was able to detect ZEN spiked-in the corn flour extract with a semilog linear detection range of 10 pM-10 nM and a limit of detection (LOD, S/N = 3) of 18.4 ± 4.0 pM (equivalent to 29.3 ± 6.4 ng/kg). The LOD is more than 1000-fold lower than the maximum ZEN residue limits set by China (60 µg/kg) and EU (20 µg/kg). The sensor also has extremely high specificity and showed negligible cross-reactivity to other common mycotoxins. In addition, the sensor was able to be regenerated for 28 times, further decreasing its cost. Our sensor holds great potential for practical applications according to its multiple compelling features.

Biological role of Actinobacillus pleuropneumoniae type IV pilus proteins encoded by the apf and pil operons.

Actinobacillus pleuropneumoniae is a species of Gram-negative bacteria that colonizes the respiratory tract, causing porcine pleuropneumoniae. Given the high agricultural impact of this disease, a detailed understanding of the pathogenesis of A. pleuropneumoniae is crucial. Previous work found that only the apfABCD (apf) operon encodes type IV pili (Tfp), which promotes bacterial adherence to host cells, in A. pleuropneumoniae. However, the detailed biogenesis and function of Tfp in A. pleuropneumoniae remained unclear. Here, we found that the apfABCD and pilMNOPQ (pil) gene clusters are operons, and the products of each gene within the apf and pil loci are required for Tfp biogenesis and function. Sequencing analysis revealed that the apf and pil operons are highly conserved among different serotypes of A. pleuropneumoniae. Our data demonstrate that the transcription of the pil operon was greatly upregulated upon bacterial contact with host cells. Mutants with single deletions of each gene in the pil and apf operons had defective adherence when they were in contact with host cells and, additionally, these mutants were also deficient in biofilm formation in vitro. In conclusion, these results indicate that the products of each gene within the apf and pil operons are necessary for the normal biogenesis and function of Tfp in A. pleuropneumoniae.

The CpxA/CpxR Two-Component System Affects Biofilm Formation and Virulence in Actinobacillus pleuropneumoniae.

Gram-negative bacteria have evolved numerous two-component systems (TCSs) to cope with external environmental changes. The CpxA/CpxR TCS consisting of the kinase CpxA and the regulator CpxR, is known to be involved in the biofilm formation and virulence of Escherichia coli. However, the role of CpxA/CpxR remained unclear in Actinobacillus pleuropneumoniae, a bacterial pathogen that can cause porcine contagious pleuropneumonia (PCP). In this report, we show that CpxA/CpxR contributes to the biofilm formation ability of A. pleuropneumoniae. Furthermore, we demonstrate that CpxA/CpxR plays an important role in the expression of several biofilm-related genes in A. pleuropneumoniae, such as rpoE and pgaC. Furthermore, The results of electrophoretic mobility shift assays (EMSAs) and DNase I footprinting analysis demonstrate that CpxR-P can regulate the expression of the pgaABCD operon through rpoE. In an experimental infection of mice, the animals infected with a cpxA/cpxR mutant exhibited delayed mortality and lower bacterial loads in the lung than those infected with the wildtype bacteria. In conclusion, these results indicate that the CpxA/CpxR TCS plays a contributing role in the biofilm formation and virulence of A. pleuropneumoniae.

A signal-accumulating DNAzyme-crosslinked hydrogel for colorimetric sensing of hydrogen peroxide.

A signal-accumulating DNAzyme-crosslinked hydrogel was designed and prepared for colorimetric sensing of hydrogen peroxide. In this hydrogel-based sensing system, sensing signal molecules were effectively accumulated inside the gel and the concentrated DNAzyme inside the gel remarkably increased the catalytic activity, resulting in a rapid and highly sensitive detection of hydrogen peroxide.

A dual functional peptide carrying in vitro selected catalytic and binding activities.

When minimal functional sequences are used, it is possible to integrate multiple functions on a single peptide chain, like a "single stroke drawing". Here a dual functional peptide was designed by combining in vitro selected catalytic and binding activities. For catalytic activity, we performed in vitro selection for a peptide aptamer binding to hemin by using ribosome display and isolated a peptide that had peroxidase activity in the presence of hemin. By combining the selected catalytic peptide with a peptide antigen, which can be recognized by an antibody, an enzyme-antibody conjugate-like peptide was obtained. This study demonstrates a successful strategy to create dual functionalized peptide chains for use in immunoassays.