Biological effect abundance analysis of hemolytic pathogens based on engineered biomimetic sensor.

Conventional pathogen detection strategies based on the molecular structure or chemical characteristics of biomarkers can only provide the "physical abundance" of microorganisms, but cannot reflect the "biological effect abundance" in the true sense. To address this issue, we report an erythrocyte membrane-encapsulated biomimetic sensor cascaded with CRISPR-Cas12a (EMSCC). Taking hemolytic pathogens as the target model, we first constructed an erythrocyte membrane-encapsulated biomimetic sensor (EMS). Only hemolytic pathogens with biological effects can disrupt the erythrocyte membrane (EM), resulting in signal generation. Then the signal was amplified by cascading CRISPR-Cas12a, and more than 6.67 × 104-fold improvement in detection sensitivity compared to traditional erythrocyte hemolysis assay was achieved. Notably, compared with polymerase chain reaction (PCR) or enzyme linked immunosorbent assay (ELISA)-based quantification methods, EMSCC can sensitively respond to the pathogenicity change of pathogens. For the detection of simulated clinical samples based on EMSCC, we obtained an accuracy of 95% in 40 samples, demonstrating its potential clinical value.

Lantern-shaped flexible RNA origami for Smad4 mRNA delivery and growth suppression of colorectal cancer.

mRNA delivery has shown high application value in the treatment of various diseases, but its effective delivery is still a major challenge at present. Herein, we propose a lantern-shaped flexible RNA origami for mRNA delivery. The origami is composed of a target mRNA scaffold and only two customized RGD-modified circular RNA staples, which can compress the mRNA into nanoscale and facilitate its endocytosis by cells. In parallel, the flexible structure of the lantern-shaped origami allows large regions of the mRNA to be exposed and translated, exhibiting a good balance between endocytosis and translation efficiency. The application of lantern-shaped flexible RNA origami in the context of the tumor suppressor gene, Smad4 in colorectal cancer models demonstrates promising potential for accurate manipulation of protein levels in in vitro and in vivo settings. This flexible origami strategy provides a competitive delivery method for mRNA-based therapies.

Surveillance of the Antimicrobial Susceptibility and Molecular Characteristics of Neisseria gonorrhoeae Isolates Collected in Changsha, China from 2016 to 2021.

Antibiotic treatment is critical for individuals infected with gonorrhea and preventing disease transmission. This study aimed to analyze the antimicrobial susceptibility and molecular epidemiological characteristics of Neisseria gonorrhoeae isolates in Changsha, China. A total of 271 N.gonorrhoeae isolates collected from the clinical laboratories of two hospitals between 2016 and 2021 were analyzed for antimicrobial susceptibility using the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was conducted for genotyping, and phylogenetic analysis was performed using the porB and tbpB sequences. The results showed that antimicrobial resistance against ciprofloxacin, tetracycline, and penicillin was high, and these drugs are no longer recommended for the treatment of gonorrhea. All isolates were susceptible to spectinomycin. However, in 2016-2021, a total of 15 (5.5%) ceftriaxone (CRO)-resistant strains and 31 (11.4%) isolates with decreased susceptibility to CRO were found, and the resistance rate to azithromycin had reached 7.1% in 2016-2017. Epidemiologically, the mosaic penA allele was identified in all CRO-resistant isolates. Based on NG-MAST, ST5061 was the most prevalent ST. Phylogenetic analysis suggested that the resistant isolates did not cluster independently. Despite focus on the local situation, this study raises the need for better gonorrhea medication and highlights that CRO may not be adequate as first-line treatment for gonorrhea in Changsha.

Surface environment complication makes Ag29 nanoclusters more robust and leads to their unique packing in the supracrystal lattice.

Silver nanoclusters have received unprecedented attention in cluster science owing to their promising functionalities and intriguing physical/chemical properties. However, essential instability significantly impedes their extensive applications. We herein propose a strategy termed "surface environment complication" to endow Ag29 nanoclusters with high robustness. The Ag29(S-Adm)18(PPh3)4 nanocluster with monodentate PPh3 ligands was extremely unstable and uncrystallizable. By substituting PPh3 with bidentate PPh2py with dual coordination sites (i.e., P and N), the Ag29 cluster framework was twisted because of the generation of N-Ag interactions, and three NO3 ligands were further anchored onto the nanocluster surface, yielding a new Ag29(S-Adm)15(NO3)3(PPh2py)4 nanocluster with high stability. The metal-control or ligand-control effects on stabilizing the Ag29 nanocluster were further evaluated. Besides, Ag29(S-Adm)15(NO3)3(PPh2py)4 followed a unique packing mode in the supracrystal lattice with several intercluster channels, which has yet been observed in other M29 cluster crystals. Overall, this work presents a new approach (i.e., surface environment complication) for tailoring the surface environment and improving the stability of metal nanoclusters.

Influence of Serum Albumin on HbA1c and HbA1c-Defined Glycemic Status: A Retrospective Study.

Background: Glycated hemoglobin (HbA1c) is commonly used in the diagnosis and evaluation of glycemic control in diabetes, and it may be influenced by several non-glycemic and glycemic factors, including albumin. This retrospective study investigated the influence of albumin on HbA1c and HbA1c-defined glycemic status. Methods: The demographic, hematological, and biochemical data were collected for 11,922 patients undergoing routine physical examination. Univariate and multivariate linear regression analyses, stratified analyses and interaction analyses, and multiple logistic regression were conducted to identify the association between albumin and HbA1c in people with different glycemic status. Results: HbA1c levels were inversely associated with serum albumin level (P < 0.0001) in all participants. Risk factors leading to the association included age > 45 years, high fasting plasma glucose (≥7.0 mmol/L), and anemia. The negative association between HbA1c and albumin was curved (P < 0.0001) and had a threshold effect in the HbA1c-defined diabetic population; the association was significantly stronger when the albumin level fell below 41.4 g/L (ß: -0.31, 95% CI: -0.45 to -0.17, P < 0.0001). A 2 g/L increase in albumin reduced the odds of HbA1c-defined dysglycemia, diabetes, and poor glycemia control by 12% to 36%, after adjustment for all possible confounders. Conclusions: HbA1c was inversely associated with albumin level in all participants, and the association was significantly stronger in people with diabetes (defined by HbA1c criteria). For diabetic patients with lower albumin level, there was an increased risk of an erroneous HbA1c-based identification and management of glycemic status.

Emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains harbouring a novel mosaic penA gene in China.

OBJECTIVES: The continuous emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains threatens the effectiveness of current treatment regimens for gonorrhoea. The objective of the present study was to characterize three ceftriaxone-resistant N. gonorrhoeae strains with a novel mosaic penA allele isolated in China. METHODS: Three ceftriaxone-resistant Neisseria gonorrhoeae strains (GC150, GC161 and GC208) isolated in 2017 were characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST), MLST and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR). Recombination analyses were performed using the SimPlot software. RESULTS: Three strains had the same antibiotic resistance profiles, with resistance to ceftriaxone (MIC 0.5 mg/L), ciprofloxacin (MIC 8.0 mg/L), penicillin (MIC 2.0 mg/L) and tetracycline (MIC 2.0-8.0 mg/L). STs were assigned as MLST7360, NG-MAST14292 and NG-STAR1611/NG-STAR1612. The penA gene of these three strains differed from previous ceftriaxone-resistant gonococcal strains and harboured a novel mosaic allele (penA-121.001). Like N. gonorrhoeae FC428, a widely disseminated ceftriaxone-resistant strain that was initially described in Japan in 2015, all strains also possessed substitutions A311V and T483S in PBP2, which are associated with resistance to ceftriaxone. Potential recombination events were detected in penA between N. gonorrhoeae strain FC428 and commensal Neisseria species. Our results provide further evidence that the commensal Neisseria species (Neisseria cinerea and Neisseria perflava) can serve as a reservoir of ceftriaxone resistance-mediating penA sequences in clinical gonococcal strains. CONCLUSIONS: The emergence of such strains may be the result of the interspecies recombination of penA genes between N. gonorrhoeae strain FC428 and commensal Neisseria species.

Polymorphism of Au11(PR3)7Cl3 clusters: understanding C-H⋯π interaction and C-H⋯Cl-C van der Waals interaction on cluster assembly by surface modification.

The C-H⋯π interaction and the C-H⋯Cl-C van der Waals interaction play a crucial role in the crystallization of nanoclusters. In this paper, we present an example of a crystal system transformation of Au11(PR3)7Cl3 from monoclinic (M) to trigonal (T) by surface modification. Atomically-resolved gold nanoclusters containing tris(4-chlorophenyl)phosphine and chloride ligands were synthesized and determined to be Au11(p-ClPPh3)7Cl3 (p-ClPPh3 = tris(4-chlorophenyl)phosphine) by X-ray crystallography. Crystal data demonstrated that the C-H⋯Cl-C interaction is dominant in a trigonal crystal system of Au11(p-ClPPh3)7Cl3 with a R3̄ space group. However, the C-H⋯π interaction is the major driving force to form a monoclinic crystal system of Au11(PPh3)7Cl3 (PPh3 = triphenylphosphine) with a P2(1)/n space group. Moreover, UV-vis absorption spectra and X-ray photoelectron spectra reveal that the electronic structure of the Au11(p-ClPPh3)7Cl3 nanocluster is greatly influenced by p-ClPPh3. This work provides critical implications for the crystallization of metal nanoclusters, as well as a better understanding of the non-covalent interaction on the nanocluster assembly and the crystal engineering by surface modification.

Identification of multidrug-resistant Neisseria gonorrhoeae isolates with combined resistance to both ceftriaxone and azithromycin, China, 2017-2018.

The growing multidrug-resistant Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. During 2017-2018, we identified a rare multidrug-resistant (ceftriaxone and azithromycin) strain (GC250) and four strains (GC185, GC195, GC196 and GC249) with both resistance to ceftriaxone and decreased susceptibility to azithromycin. All strains belonged to NG-STAR ST1143, including the mosaic penA-60.001, which is closely related to ceftriaxone resistance. The characterization of antimicrobial resistance (AMR) determinants and phylogenetic analysis showed these five strains were closely related to internationally spreading ceftriaxone-resistant N. gonorrhoeae FC428, but with higher azithromycin MIC. Findings here demonstrated that this clone not only initiated clonal expansion in China, but acquired azithromycin resistance.

Rational construction of a library of M29 nanoclusters from monometallic to tetrametallic.

Exploring intermetallic synergy has allowed a series of alloy nanoparticles with prominent chemical-physical properties to be produced. However, precise alloying based on a maintained template has long been a challenging pursuit, and little has been achieved for manipulation at the atomic level. Here, a nanosystem based on M29(S-Adm)18(PPh3)4 (where S-Adm is the adamantane mercaptan and M is Ag/Cu/Au/Pt/Pd) has been established, which leads to the atomically precise operation on each site in this M29 template. Specifically, a library of 21 species of nanoclusters ranging from monometallic to tetrametallic constitutions has been successfully prepared step by step with in situ synthesis, target metal-exchange, and forced metal-exchange methods. More importantly, owing to the monodispersity of each nanocluster in this M29 library, the synergetic effects on the optical properties and stability have been mapped out. This nanocluster methodology not only provides fundamental principles to produce alloy nanoclusters with multimetallic compositions and monodispersed dopants but also provides an intriguing nanomodel that enables us to grasp the intermetallic synergy at the atomic level.

Metal synergistic effect on cluster optical properties: based on Ag25 series nanoclusters.

Due to their high biological stability and strong fluorescence, thiolated metal nanoclusters have shown great potential as a new generation of bio-nano-materials. However, the ambiguous mechanism of fluorescence impedes the design and synthesis of highly fluorescent nanoclusters. In this work, Ag25 nanocluster and its dopants were chosen as a model to study the effect of metal synergy on the optical properties. Significantly, when the valence electrons shrank to the center of the metal kernel, an enhanced fluorescence was observed, and vice versa. This finding will hopefully make a significant contribution to the property regulations of the metal nanoclusters and stimulate more excellent applications of the luminescent nanoclusters.

Total structural determination of [Au1Ag24(Dppm)3(SR)17]2+ comprising an open icosahedral Au1Ag12 core with six free valence electrons.

Herein, we report the first silver-rich nanocluster containing an open icosahedral Au1Ag12 core. This nanocluster is determined to be [Au1Ag24(Dppm)3(SR)17]2+ (where Dppm is short for bis-(diphenylphosphino)methane and SR is short for cyclohexyl mercaptan) by single-crystal X-ray diffraction and electrospray ionization mass spectrometry (ESI-MS). The Au1Ag24 consists of an open icosahedral Au1Ag12, which contains six free valence electrons surrounded by a big ring motif Ag12(Dppm)3(SR)15 and two SR groups. Density Functional Theory (DFT) provided insight into the relationship between the structure and its performance.