Signal recognition particle RNA is critical for genetic competence and virulence of Streptococcus pneumoniae.

Streptococcus pneumoniae (pneumococcus) causes a wide range of important human infectious diseases, including pneumonia, pneumonia-derived sepsis, otitis media, and meningitis. Pneumococcus produces numerous secreted proteins that are critical for normal physiology and pathogenesis. The membrane targeting and translocation of these secreted proteins are partly mediated by the signal recognition particle (SRP) complex, which consists of 4.5S small cytoplasmic RNA (ScRNA), and the Ffh, and FtsY proteins. Here, we report that pneumococcal ∆scRNA, ∆ffh, and ∆ftsY mutants were significantly impaired in competence induction, competence pili production, exogenous DNA uptake, and genetic transformation. Also, the ∆scRNA mutant was significantly attenuated in the mouse models of bacteremia and pneumonia. Interestingly, unlike the ∆scRNA, both ∆ffh and ∆ftsY mutants had growth defects on Todd-Hewitt Agar, which were alleviated by the provision of free amino acids or serum. Differences in nutritional requirements between ∆ffh and ∆ftsY vs ∆scRNA suggest that Ffh and FtsY may be partially functional in the absence of ScRNA. Finally, the insertase YidC2, which could functionally rescue some SRP mutations in other streptococcal species, was not essential for pneumococcal genetic transformation. Collectively, these results indicate that ScRNA is crucial for the successful development of genetic competence and virulence in pneumococcus. IMPORTANCE: Streptococcus pneumoniae (pneumococcus) causes multiple important infectious diseases in humans. The signal recognition particle (SRP) complex, which comprised 4.5S small cytoplasmic RNA (ScRNA), and the Ffh and FtsY proteins, mediates membrane targeting and translocation of secreted proteins in all organisms. However, the role of SRP and ScRNA has not been characterized during the induction of the competence system for genetic transformation and virulence in pneumococcus. By using a combination of genetic, biochemical, proteomic, and imaging approaches, we demonstrated that the SRP complex plays a significant role in membrane targeting of competence system-regulated effectors important for genetic transformation, virulence during bacteremia and pneumonia infections, and nutritional acquisition.

Fusion of laser-induced breakdown spectroscopy technology and deep learning: a new method to identify malignant and benign lung tumors with high accuracy.

Precisely distinguishing between malignant and benign lung tumors is pivotal for suggesting therapeutic strategies and enhancing prognosis, yet this differentiation remains a daunting task. The growth rates, metastatic potentials, and prognoses of benign and malignant tumors differ significantly. Developing specialized treatment protocols tailored to various tumor types is essential for enhancing patient survival outcomes. Employing laser-induced breakdown spectroscopy (LIBS) in conjunction with a deep learning methodology, we attained a high-precision differential diagnosis of malignant and benign lung tumors. First, LIBS spectra of malignant tumors, benign tumors, and normal tissues were collected. The spectra were preprocessed and Z score normalized. Then, the intensities of the Mg II 279.6, Mg I 285.2, Ca II 393.4, Cu II 518.3, and Na I 589.6 nm lines were analyzed in the spectra of the three tissues. The analytical results show that the elemental lines have different contents in the three tissues and can be used as a basis for distinguishing between the three tissues. Finally, the RF-1D ResNet model was constructed by combining the feature importance assessment method of random forest (RF) and one-dimensional residual network (1D ResNet). The classification accuracy, precision, sensitivity, and specificity of the RF-1D ResNet model were 91.1%, 91.6%, 91.3%, and 91.3%, respectively. And the model demonstrates superior performance with an area under the curve (AUC) value of 0.99. The above results show that combining LIBS with deep learning is an effective way to diagnose malignant and benign tumors.

Designing cyclic competence-stimulating peptide (CSP) analogs with pan-group quorum-sensing inhibition activity in Streptococcus pneumoniae.

Streptococcus pneumoniae is an opportunistic human pathogen that utilizes the competence regulon, a quorum-sensing circuitry, to acquire antibiotic resistance genes and initiate its attack on the human host. Interception of the competence regulon can therefore be utilized to study S. pneumoniae cell-cell communication and behavioral changes, as well as attenuate S. pneumoniae infectivity. Herein we report the design and synthesis of cyclic dominant negative competence-stimulating peptide (dnCSP) analogs capable of intercepting the competence regulon in both S. pneumoniae specificity groups with activities at the low nanomolar range. Structural analysis of lead analogs provided important insights as to the molecular mechanism that drives CSP receptor binding and revealed that the pan-group cyclic CSPs exhibit a chimeric hydrophobic patch conformation that resembles the hydrophobic patches required for both ComD1 and ComD2 binding. Moreover, the lead cyclic dnCSP, CSP1-E1A-cyc(Dap6E10), was found to possess superior pharmacological properties, including improved resistance to enzymatic degradation, while remaining nontoxic. Lastly, CSP1-E1A-cyc(Dap6E10) was capable of attenuating mouse mortality during acute pneumonia caused by both group 1 and group 2 S. pneumoniae strains. This cyclic pan-group dnCSP is therefore a promising drug lead scaffold against S. pneumoniae infections that could be administered individually or utilized in combination therapy to augment the effects of current antimicrobial agents.

Simultaneous co-Photocatalytic CO2 Reduction and Ethanol Oxidation towards Synergistic Acetaldehyde Synthesis.

Photocatalytic conversion of CO2 is of great interest but it often suffers sluggish oxidation half reaction and undesired by-products. Here, we report for the first the simultaneous co-photocatalytic CO2 reduction and ethanol oxidation towards one identical value-added CH3 CHO product on a rubidium and potassium co-modified carbon nitride (CN-KRb). The CN-KRb offers a record photocatalytic activity of 1212.3 µmol h-1 g-1 with a high selectivity of 93.3 % for CH3 CHO production, outperforming all the state-of-art CO2 photocatalysts. It is disclosed that the introduced Rb boosts the *OHCCHO fromation and facilitates the CH3 CHO desorption, while K promotes ethanol adsorption and activation. Moreover, the H+ stemming from ethanol oxidation is confirmed to participate in the CO2 reduction process, endowing near ideal overall atomic economy. This work provides a new strategy for effective use of the photoexcited electron and hole for high selective and sustainable conversion of CO2 paired with oxidation reaction into identical product.

Streptococcus pneumoniae Elaborates Persistent and Prolonged Competent State during Pneumonia-Derived Sepsis.

The competence regulon of pneumococcus regulates both genetic transformation and virulence. However, competence induction during host infection has not been examined. By using the serotype 2 strain D39, we transcriptionally fused the firefly luciferase (luc) to competence-specific genes and spatiotemporally monitored the competence development in a mouse model of pneumonia-derived sepsis. In contrast to the universally reported short transient burst of competent state in vitro, the naturally developed competent state was prolonged and persistent during pneumonia-derived sepsis. The competent state began at approximately 20 h postinfection (hpi) and facilitated systemic invasion and sepsis development and progressed in different manners. In some mice, acute pneumonia quickly led to sepsis and death, accompanied by increasing intensity of the competence signal. In the remaining mice, pneumonia lasted longer, with the competence signal decreasing at first but increasing as the infection became septic. The concentration of pneumococcal inoculum (1 × 106 to 1 × 108 CFU/mouse) and postinfection lung bacterial burden did not appreciably impact the kinetics of competence induction. Exogenously provided competence stimulating peptide 1 (CSP1) failed to modulate the onset kinetics of competence development in vivo The competence shutoff regulator DprA was highly expressed during pneumonia-derived sepsis but failed to turn off the competent state in mice. Competent D39 bacteria propagated the competence signal through cell-to-cell contact rather than the classically described quorum-sensing mechanism. Finally, clinical pneumococcal strains of different serotypes were also able to develop natural competence during pneumonia-derived sepsis.

FOXA2 depletion leads to mucus hypersecretion in canine airways with respiratory diseases.

Because of exposure to environmental pollutants, infectious agents, and genetic predisposition, companion animals develop respiratory illnesses similar to those in humans. Older dogs of smaller breeds develop canine infectious respiratory disease, chronic bronchitis, and chronic obstructive pulmonary disease, with chronic lung infection, airway goblet cell hyperplasia and metaplasia, and mucus hypersecretion. Excessive mucus clogs airways, reduces gas exchanges, disables the mucociliary clearance, and reduces drug penetration. The Forkhead box protein A2 (FOXA2) is a key transcriptional regulator that maintains airway mucus homeostasis. Prior studies have shown that FOXA2 expression is frequently depleted in diseased human airways. Unfortunately, FOXA2 depletion has not been examined in dogs. Our current study indicated that both single bacterial infection by Pseudomonas aeruginosa and Bordetella bronchiseptica and polymicrobial infection by viral/bacterial pathogens depleted FOXA2 in canine airways, resulting in goblet cell hyperplasia and metaplasia and excessive mucus production. Furthermore, P. aeruginosa virulence factor pyocyanin activated the antagonistic STAT6 and epidermal growth factor receptor signalling pathways to inhibit FOXA2. Unravelling the mechanism of FOXA2 inactivation will hasten the development of non-antibiotic therapeutics to improve mucociliary clearance of pathogens in canine airway.

A comparative study on phenazone degradation by sulfate radicals based processes.

In this paper, a comparative study on removal of the emerging pollutant phenazone (PNZ) by two treatment processes UVA/Fe(II)/persulfate (PS) and UVA/Fe(II)/peroxymonosulfate (PMS) was conducted. The two processes showed high efficiency in PNZ degradation, followed by a reasonable mineralization. The treatment system with PMS was found to be more efficient for PNZ degradation than that with PS due to the larger amounts of radicals generated. While the treatment process UVA/Fe(II)/PS showed higher ΔTOC/ΔSMX (TOC removal per unit of PNZ decay) than UVA/Fe(II)/PMS process. The sulfate and hydroxyl radicals played dominant roles in PNZ degradation in the UVA/Fe(II)/PS and UVA/Fe(II)/PMS process, respectively. Six and seven intermediates during PNZ degradation by UVA/Fe(II)/PS and UVA/Fe(II)/PMS process were detected, respectively. Among the detected intermediates, six of them are found for the first time. It takes shorter time for toxicity elimination by UVA/Fe(II)/PS process than UVA/Fe(II)/PMS, possibly due to the lower Kow values of hydroxylated products. The results demonstrate that UVA/Fe(II)/PMS process is more efficient in PNZ degradation, while UVA/Fe(II)/PS is more efficient in detoxification of PNZ. The two sulfate radicals based processes have good potentials in degradation, mineralization and detoxification of the emerging contaminants such as PNZ.

DprA-Dependent Exit from the Competent State Regulates Multifaceted Streptococcus pneumoniae Virulence.

Streptococcus pneumoniae (pneumococcus) causes multiple infectious diseases. The pneumococcal competence system facilitates genetic transformation, spreads antibiotic resistance, and contributes to virulence. DNA-processing protein A (DprA) regulates the exit of pneumococcus from the competent state. Previously, we have shown that DprA is important in both bacteremia and pneumonia infections. Here, we examined the mechanisms of virulence attenuation in a ΔdprA mutant. Compared to the parental wild-type D39, the ΔdprA mutant enters the competent state when exposed to lower concentrations of the competence-stimulating peptide CSP1. The ΔdprA mutant overexpresses ComM, which delays cell separation after division. Additionally, the ΔdprA mutant overexpresses allolytic factors LytA, CbpD, and CibAB and is more susceptible to detergent-triggered lysis. Disabling of the competent-state-specific induction of ComM and allolytic factors compensated for the virulence loss in the ΔdprA mutant, suggesting that overexpression of these factors contributes to virulence attenuation. Finally, the ΔdprA mutant fails to downregulate the expression of multiple competence-regulated genes, leading to the excessive energy consumption. Collectively, these results indicate that an inability to properly exit the competent state disrupts multiple cellular processes that cause virulence attenuation in the ΔdprA mutant.

Development of a Dominant Negative Competence-Stimulating Peptide (dnCSP) that Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute Pneumonia.

Streptococcus pneumoniae (pneumococcus) is a prevalent human pathogen responsible for a variety of diseases, including pneumonia, bacteremia, sepsis, meningitis and otitis media, with a death toll of >22 000 a year in the United States alone. Pneumococcus uses the competence regulon and its associated signaling peptide, the competence stimulating peptide (CSP), to initiate its attack on the host and establish an infection. In this work, we set out to: 1) develop a pan-group quorum sensing inhibitor that could effectively interact with both the pneumococcus ComD1 and ComD2 receptors; and 2) evaluate the utility of dominant-negative CSPs (dnCSPs) in attenuating pneumococcus infectivity. Our results highlight the potential of inhibiting the competence regulon as a therapeutic approach to combat pneumococcus infections.

Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes virulence determinants that are dependent or independent of competence induction.

The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 'late' competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes.

Disentangling competence for genetic transformation and virulence in Streptococcus pneumoniae.

Horizontal gene transfer mediated by the competence regulon is a major driver of genome plasticity in Streptococcus pneumoniae. When pneumococcal cells enter the competent state, about 6% of the genes in the genome are up-regulated. Among these, some genes are essential for genetic transformation while others are dispensable for the process. Exhaustive deletion analyses show that some up-regulated genes dispensable for genetic transformation contribute to pneumococcal-mediated pneumonia and bacteremia infections. Interestingly, virulence functions of such genes are either dependent or independent of the competent state. Among the competent-state-dependent genes are those mediating allolysis, a process where small fraction of non-competent cells within the pneumococcal population are lysed by their competent counterparts, releasing DNA presumably for transformation. Inadvertently, the pore-forming toxin pneumolysin is also released during allolysis, contributing to virulence. In this review, we discuss recent advances in our understanding of pneumococcal virulence processes mediated by the competence regulon. We proposed that coupling of competence induction and bacterial fitness drives the natural selection to favor an intact competence regulon, which in turn, provides the long-term benefits of genetic plasticity.

Decision-level data fusion based on laser-induced breakdown and Raman spectroscopy: A study of bimodal spectroscopy for diagnosis of lung cancer at different stages.

Lung cancer staging is crucial for personalized treatment and improved prognosis. We propose a novel bimodal diagnostic approach that integrates LIBS and Raman technologies into a single platform, enabling comprehensive tissue elemental and molecular analysis. This strategy identifies critical staging elements and molecular marker signatures of lung tumors. LIBS detects concentration patterns of elemental lines including Mg (I), Mg (II), Ca (I), Ca (II), Fe (I), and Cu (II). Concurrently, Raman spectroscopy identifies changes in molecular content, such as phenylalanine (1033 cm-1), tyrosine (1174 cm-1), tryptophan (1207 cm-1), amide III (1267 cm-1), and proteins (1126 cm-1 and 1447 cm-1), among others. The bimodal information is fused using a decision-level Bayesian fusion model, significantly enhancing the performance of the convolutional neural network architecture in classification algorithms, with an accuracy of 99.17 %, sensitivity of 99.17 %, and specificity of 99.88 %. This study provides a powerful new tool for the accurate staging and diagnosis of lung tumors.

Investigating the mechanistic impact of pork soft tissue preparation techniques on the classification precision of laser-induced breakdown spectroscopy.

The investigation of the mechanism underlying the impact of biological soft tissue sample preparation methods on laser-induced breakdown spectroscopy (LIBS) signals can enhance the stability of LIBS signals. Our study focused on four specific preparation methods applied to pork samples: rapid freezing, fresh slicing, drying, and pressing. The influence of various preparation techniques on the signal-to-noise ratio and fluctuation of Ca, Na, Mg, and CN bands within the sample spectra was assessed. The signal-to-noise ratios for samples that were dried and pressed notably improved. And the pressing method effectively mitigated the uneven distribution of pork tissue components, displaying superior spectral line stability. To explain this phenomenon, we used the Saha-Boltzmann diagram to estimate the plasma temperature. Remarkably, there was a significant reduction in plasma temperature fluctuations across four pressed samples, with a standard deviation of 108.53. Furthermore, we undertook a classification analysis employing support vector machine models to corroborate the generalization efficacy of the sample preparation technique. Dried and pressed samples demonstrated notably higher classification accuracy, precision, and recall (all >93%) compared to frozen and fresh samples, where these metrics remained below 86%. The performance of the SVM model was ultimately evaluated using Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC). The AUC for the frozen, fresh, dried, and pressed samples was 0.854, 0.907, 0.989, and 0.996, respectively. The findings revealed that the pressing method exhibited superior performance, followed by drying, fresh slicing, and freezing, in descending order of effectiveness.

Research on a new multiple-screening method for laser-induced plasma spectroscopy utilizing Lorentz.

In the field of Laser Induced Breakdown Spectroscopy (LIBS) research, the screening and extraction of complex spectra play a crucial role in enhancing the accuracy of quantitative analysis. This paper introduces a novel approach for multiple screenings of LIBS spectra using Lorentz Screening and Sensitivity and Volatility Analysis. Initially, Create symmetrical sampling standards for Lorentz fitting. Then the Lorentz fitting is used to uniformly screen the collected spectral information on both sides in order to eliminate adjacent interference peaks. Subsequently, Sensitivity and Volatility Analysis is employed to further remove overlapping peaks and select spectra with low volatility and high sensitivity. Sensitivity and Volatility Analysis is a spectral discrimination method proposed on the premise of intensity's correlation with concentration. It utilizes a Z-score method that incorporates both deviation and standard deviation for effective analysis. Furthermore, it meticulously selects spectral lines with minimal interference and volatility, thereby augmenting the precision of quantitative analysis. The quantitative accuracy (R2) for Chromium (Cr) and Nickel (Ni) elements can reach 0.9919 and 0.9768, respectively. Their average errors can be reduced to 0.0566 % and 0.1024 %. The study demonstrates that Lorentz Screening and Sensitivity and Volatility Analysis can select high-quality characteristic spectral lines to improve the performance of the model.

Time-resolved RNA-seq analysis to unravel the in vivo competence induction by Streptococcus pneumoniae during pneumonia-derived sepsis.

Competence development in Streptococcus pneumoniae (pneumococcus) is tightly intertwined with virulence. In addition to genes encoding genetic transformation machinery, the competence regulon also regulates the expression of allolytic factors, bacteriocins, and cytotoxins. Pneumococcal competence system has been extensively interrogated in vitro where the short transient competent state upregulates the expression of three distinct phases of "early," "late," and "delayed" genes. Recently, we have demonstrated that the pneumococcal competent state develops naturally in mouse models of pneumonia-derived sepsis. To unravel the underlying adaptive mechanisms driving the development of the competent state, we conducted a time-resolved transcriptomic analysis guided by the spatiotemporal live in vivo imaging system of competence induction during pneumonia-derived sepsis. Mouse lungs infected by the serotype 2 strain D39 expressing a competent state-specific reporter gene (D39-ssbB-luc) were subjected to RNA sequencing guided by monitoring the competence development at 0, 12, 24, and, at the moribund state, >40 hours post-infection (hpi). Transcriptomic analysis revealed that the competence-specific gene expression patterns in vivo were distinct from those under in vitro conditions. There was significant upregulation of early, late, and some delayed phase competence-specific genes as early as 12 hpi, suggesting that the pneumococcal competence regulon is important for adaptation to the lung environment. Additionally, members of the histidine triad (pht) gene family were sharply upregulated at 12 hpi followed by a steep decline throughout the rest of the infection cycle, suggesting that Pht proteins participate in the early adaptation to the lung environment. Further analysis revealed that Pht proteins execute a metal ion-dependent regulatory role in competence induction.IMPORTANCEThe induction of pneumococcal competence for genetic transformation has been extensively studied in vitro but poorly understood during lung infection. We utilized a combination of live imaging and RNA sequencing to monitor the development of a competent state during acute pneumonia. Upregulation of competence-specific genes was observed as early as 12 hour post-infection, suggesting that the pneumococcal competence regulon plays an important role in adapting pneumococcus to the stressful lung environment. Among others, we report novel finding that the pneumococcal histidine triad (pht) family of genes participates in the adaptation to the lung environment and regulates pneumococcal competence induction.

A study of the spectral signal effect of self-holes in metal additive manufacturing components using laser-induced breakdown spectroscopy (LIBS).

Understanding the detection mechanism of hole defects in metal additive manufacturing (AM) components is of great significance for the detection of metal AM component defects using laser-induced breakdown spectroscopy (LIBS). In this work, the mapping relationship between the hole defects of metal AM components and the LIBS spectral signal was studied using the controlled variable method. The effect of hole defects mostly showed a suppression effect and peaked at a hole depth of 1.0 mm when the LIBS system was at its optimal excitation parameter. To explore the possible reasons behind the inhibitory effect of self-holes, the variation law of the plasma temperature with and without hole defects was further investigated. Our results showed that the plasma temperature change curve was similar to the spectral line intensity change trend. Finally, the linear relationship between the focal length effect and the hole effect, and the relationship between the constraint effect and the hole effect were studied. The minimum fitting R2 between the constraint effect and the hole effect was 0.979. We believed that the inhibition of the hole effect was mainly caused by the absorption and loss of energy in the plasma during the process of plasma radiation and shock wave reflection from the hole wall. By studying the detection mechanism of hole defects in metal additive manufacturing components excited by LIBS and finding the effective characteristics of hole defects in metal AM components, it is helpful to achieve higher precision and higher sensitivity defect detection.

catena-Poly[[[triaqua-europium(III)]-µ-(1H-benzimidazole-5,6-dicarboxyl-ato-κO:O)-µ-(1H,3H-benzimidazol-3-ium-5,6-dicarboxyl-ato-κO:O,O)] dihydrate].

In the title one-dimensional coordination polymer, {[Eu(C(9)H(4)N(2)O(4))(C(9)H(5)N(2)O(4))(H(2)O)(3)]·2H(2)O}(n), one of the 1H-benzimidazole-5,6-dicarboxyl-ate (Hbdc) ligands is protonated at the imidazole group (H(2)bdc). The Eu(III) ion is eight-coordinated by two O atoms from two Hbdc ligands, three O atoms from two H(2)bdc ligands and three water mol-ecules, showing a distorted square-anti-prismatic geometry. The Eu(III) ions are bridged by the carboxyl-ate groups of the Hbdc and H(2)bdc ligands, forming a chain along [110], with an Eu⋯Eu separation of 5.4594 (3) Å. These chains are further connected by inter-molecular O-H⋯O, N-H⋯O and N-H⋯N hydrogen bonds, as well as π-π inter-actions between the imidazole and benzene rings [centroid-centroid distances = 3.558 (3), 3.906 (2), 3.397 (3), 3.796 (2) and 3.898 (2) Å], into a three-dimensional supra-molecular network.

A one-dimensional triaqua-europium(III)-1H,3H-benzimidazol-3-ium-5,6-dicarboxyl-ate-sulfate polymeric structure.

In the title coordination polymer, catena-poly[[[triaqua-europium(III)]-bis-(µ-1H,3H-benzimidazol-3-ium-5,6-dicarb-oxyl-ato-κ(3)O(5),O(5'):O(6))-[triaqua-europium(III)]-di-µ-sulfato-κ(3)O:O,O';κ(3)O,O':O'] hexahydrate], [Eu(2)(C(9)H(5)N(2)O(4))(2)(SO(4))(2)(H(2)O)(6)]·6H(2)O}(n), the 1H,3H-benzimidazol-3-ium-5,6-dicarb-oxy-l-ate ligand is protonated at the imidazole group (H(2)bdc). The Eu(III) ion is coordinated by nine O atoms from two H(2)bdc ligands, two sulfate anions and three water mol-ecules, displaying a bicapped trigonal prismatic geometry. The carboxyl-ate groups of the H(2)bdc ligands and the sulfate anions link the Eu(III) ions, forming a chain along [010]. These chains are further connected by N-H⋯O and O-H⋯O hydrogen bonds and π-π inter-actions between the imidazole and benzene rings [centroid-centroid distances = 3.997 (4), 3.829 (4) and 3.573 (4) Å] into a three-dimensional supra-molecular network.

A Review of Processes for Removing Antibiotics from Breeding Wastewater.

Antibiotic pollution has become an increasingly serious issue due to the extensive application of antibiotics, their resistance to removal, and the harmful effects on aquatic environments and humans. Breeding wastewater is one of the most important sources of antibiotics in the aquatic environment because of the undeveloped treatment systems in breeding farms. It is imperative to establish an effective antibiotic removal process for breeding wastewater. This paper reviews the treatment methods used to remove antibiotics from breeding wastewater. The mechanisms and removal efficiency of constructed wetlands, biological treatments, advanced oxidation processes (AOPs), membrane technology, and combined treatments are explained in detail, and the advantages and disadvantages of the various treatment methods are compared and analyzed. Constructed wetlands have high removal rates for sulfonamide (SM), tetracycline (TC), and quinolone (QN). The antibiotic removal efficiency of biological treatment methods is affected by various processes and environmental factors, whereas AOPs and combined treatment methods have better antibiotic removal effects. Although it has broad application prospects, the application of membrane technology for the treatment of antibiotics in breeding wastewater needs further research.

Random Peptide Mixtures as Safe and Effective Antimicrobials against Pseudomonas aeruginosa and MRSA in Mouse Models of Bacteremia and Pneumonia.

Antibiotic resistance is a daunting challenge in modern medicine, and novel approaches that minimize the emergence of resistant pathogens are desperately needed. Antimicrobial peptides are newer therapeutics that attempt to do this; however, they fall short because of low to moderate antimicrobial activity, low protease stability, susceptibility to resistance development, and high cost of production. The recently developed random peptide mixtures (RPMs) are promising alternatives. RPMs are synthesized by incorporating a defined proportion of two amino acids at each coupling step rather than just one, making them highly variable but still defined in their overall composition, chain length, and stereochemistry. Because RPMs have extreme diversity, it is unlikely that bacteria would be capable of rapidly evolving resistance. However, their efficacy against pathogens in animal models of human infectious diseases remained uncharacterized. Here, we demonstrated that RPMs have strong safety and pharmacokinetic profiles. RPMs rapidly killed both Pseudomonas aeruginosa and Staphylococcus aureus efficiently and disrupted preformed biofilms by both pathogens. Importantly, RPMs were efficacious against both pathogens in mouse models of bacteremia and acute pneumonia. Our results demonstrate that RPMs are potent broad-spectrum therapeutics against antibiotic-resistant pathogens.