Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China.

BACKGROUND: Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. METHODS: To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. RESULTS: We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2-4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. CONCLUSIONS: Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Synthesis and antitumor activity of dolutegravir derivatives bearing 1,2,3-triazole moieties.

Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization.

Insights into mechanism of peroxymonosufate activation by Mo single-atom catalysts: Singlet oxygen evolution and role of Mo-N coordination.

Recently, the Fenton-like reaction using peroxymonosulfate (PMS) has been acknowledged as a potential method for breaking down organic pollutants. In this study, we successfully synthesized a highly efficient and stable single atom molybdenum (Mo) catalyst dispersed on nitrogen-doped carbon (Mo-NC-0.1). This catalyst was then utilized for the first time to activate PMS and degrade bisphenol A (BPA). The Mo-NC-0.1/PMS system demonstrated the ability to completely degrade BPA within just 20 min. Scavenging tests and density functional theory (DFT) calculations have demonstrated that the primary reactive oxygen species was singlet oxygen (1O2) produced by Mo-N4 sites. The self-cycling of Mo facilitated PMS activation and the transition from a free radical activation pathway to a non-radical pathway mediated by 1O2. Simultaneously, the nearby pyridinic N served as adsorption sites to immobilize BPA and PMS molecules. The exceptionally high catalytic activity of Mo-NC-0.1 derived from its unique Mo-N coordination, which markedly reduced the distance for 1O2 to migrate to the BPA molecules. The Mo-NC-0.1/PMS system effectively reduced the acute toxicity of BPA and exhibited excellent cycling stability with minimal leaching. This study presented a new catalyst with high selectivity for 1O2 generation and provided valuable insights for the application of single atom catalysts in PMS-based AOPs.

Discovery of Dolutegravir Derivative against Liver Cancer via Inducing Autophagy and DNA Damage.

We introduced a terminal alkyne into the core structure of dolutegravir, resulting in the synthesis of 34 novel dolutegravir-1,2,3-triazole compounds through click chemistry. These compounds exhibited remarkable inhibitory activities against two hepatocellular carcinoma cell lines, Huh7 and HepG2. Notably, compounds 5e and 5p demonstrated exceptional efficacy, particularly against Huh7 cells, with IC50 values of 2.64 and 5.42 µM. Additionally, both compounds induced apoptosis in Huh7 cells, suppressed tumor cell clone formation, and elevated reactive oxygen species (ROS) levels, further promoting tumor cell apoptosis. Furthermore, compounds 5e and 5p activated the LC3 signaling pathway, inducing autophagy, and triggered the γ-H2AX signaling pathway, resulting in DNA damage in tumor cells. Compound 5e exhibited low toxicity, highlighting its potential as a promising anti-tumor drug.

[Air Microbial Contamination and Risk of Respiratory Exposure of Workers in Chicken Farms].

Animal farms are important sources of microbial contamination in the air environment. However, there are few reports on the time-regularity characteristics of airborne microbial contamination in farms. In the context of this situation, a study was conducted for more than 80 weeks using 16S rRNA gene amplicon sequencing to characterize the bacterial distribution and respiratory exposure in the farm air and fecal environment, respectively, taking a layer farm as an example. The results showed that 16S rRNA concentrations in air and manure samples ranged from 6.08×105-4.90×106 copies·m-3 and 4.27×108-1.15×1010 copies·g-1, respectively. The mean values of airborne bacterial concentrations were significantly higher in winter than in summer, whereas the biodiversity showed the opposite trend. The dominant bacterial phylum in both air and manure in the layer farm was Firmicutes. During the investigated time, the top three dominant genera in the air were relatively stable, in the order of Lactobacillus, Bacteroides, and Faecalibacterium, whereas the dominant genera in feces fluctuated with the increase in breeding time. The correlation between the community structure of bacteria and pathogenic bacteria in both air and manure was not significant, but the concentrations of both target microorganisms in different media were significantly correlated. The bioaerosolization index of bacteria in manure showed an increasing trend with increasing breeding time, whereas the opposite trend was observed for pathogenic bacteria. In this case, [Ruminococcus]_torques_group, Bacteroides, and Faecalibacterium were the top three pathogenic genera that were the most prone to aerosolization. There were seasonal differences in bacterial respiratory exposures of chicken farm workers, with mean intake values of 2.54×107 copies·d-1 and 2.87×105 copies·d-1 for bacteria and pathogenic bacteria, respectively. The results of this study will provide a scientific basis for systematically assessing the contamination characteristics and potential health risks of airborne microorganisms on farms and for developing corresponding industry standards for occupational exposure and prevention and control measures.

Epidemiology of tuberculosis among children in Beijing, China, 2012-2021.

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.

CRISPR/CasΦ2-mediated gene editing in wheat and rye.

The compact CRISPR/CasΦ2 system provides a complementary genome engineering tool for efficient gene editing including cytosine and adenosine base editing in wheat and rye with high specificity, efficient use of the protospacer-adjacent motif TTN, and an alternative base-editing window.

Interfacial oxygen atom modification of a PdSn alloy to boost oxygen reduction in zinc-air batteries.

Modifying the surface of a catalyst with heteroatoms can regulate the interfacial atomic valence state and adjust the charge distribution, which is promising for obtaining desirable platinum carbon catalyst (Pt/C)-matched oxygen reduction reaction (ORR) catalytic performance. Here, we developed an efficient method to access O-rich crystalline interfacial-exposed palladium-tin alloy (111) crystal surfaces [Pd3Sn (111)] for highly efficient ORR via direct reduction of Pd/Sn metal salt species that are well dispersed in a nitrogen, phosphorus-doped carbonaceous (NPC) substrate. In addition to the other materials, preembedded Pd/Sn metal salt species in NPC control the release of metal sources upon reduction in the liquid phase, resulting in the grafting of an as-prepared PdSn alloy with many merits, such as efficient electron conduction, short-range crystallinity and increased crystal interface exposure. The presence of a considerable quantity of oxygen atoms at the interface of small-sized PdSn alloys on NPC substrates has been methodically verified by powder X-ray diffraction, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy characterizations. The PdSn-O sample exhibited excellent ORR activity, achieving an onset potential of âˆ¼0.99 V and a half-wave potential of âˆ¼0.88 V at 1600 rpm in O2-saturated 1.0 M KOH. Density functional theory simulations of pure Pd, Pd-O, the PdSn alloy and PdSn-O suggest that interfacial oxygen atom modification is responsible for the significantly improved ORR activity. The assembled zinc-air battery provides a high specific power of 218.9 mW cm-2 and a specific capacity of 810.6 mAh gZn-1. Our approach has the potential to stimulate the preparation of O-rich crystalline interfacial-exposed alloy compounds for other energy conversion applications.

Diagnostic value of tNGS vs Xpert MTB/RIF in childhood TB.

Objectives: To evaluate the diagnostic value of targeted next generation sequencing (tNGS) in childhood tuberculosis (TB) and compare the accuracy with Xpert MTB/RIF method. Methods: Children aged ≤18 years with symptoms suggestive of TB during July 2021 to December 2022 at Beijing Children's Hospital were included, and the performances of tNGS and Xpert were evaluated. Results: A total of 103 children with suspected TB were recruited, including 72 discharge diagnosis of TB and 31 non-TB cases. The mean age was 7.37 ± 4.77 years, and 62.1 % were male. The most common type of specimens was gastric aspirate (GA) (59, 57.3 %). Among all the 72 TB patients, tNGS showed higher sensitivity than Xpert, but the difference was not significant (34.7 %, 25/72 vs 20.8 %, 15/72; P = 0.063). The specificities of tNGS and Xpert were 87.1 % (27/31) and 96.8 % (30/31), respectively (P = 0.162). Among different types of specimen, the highest sensitivity of tNGS on sputum and pus was observed (80.0 %, 4/5), followed by pleural effusion (50.0 %, 2/4). One rifampin resistance and one protionamide resistance were detected in bacteriologically confirmed TB by tNGS. Conclusion: tNGS had a higher sensitivity but lower specificity compared to Xpert in diagnosis of children TB. tNGS yielded higher sensitivity than Xpert on gastric aspirate and sputum and pus.

Interferon-gamma release assay for screening of tuberculosis infection in children.

BACKGROUND: Interferon-gamma release assay (IGRA) is the main tool for the diagnosis of latent tuberculosis (TB) infection (LTBI). However, the indeterminate results were more frequent in children, and the underlying reasons were largely speculative. We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) with X.DOT-TB (XDOT) for diagnosing LTBI, and to identify the risk factors associated with indeterminate results in children. METHODS: A retrospective study for children<18 years old, at risk for LTBI or progression to TB disease, received either QFT-GIT or X.DOT-TB tests was performed at Beijing Children's Hospital from August 2019 to August 2022. RESULTS: A total of 33,662 children were recruited, including 15,129 (44.9%) tested with X.DOT-TB and 18,533 (55.1%) with QFT-GIT. Proportion of positive and indeterminate results in children with respiratory disease was significantly higher than did that with other diseases, respectively (P < 0.001). The indeterminate rate of X.DOT-TB and QFT-GIT results decreased with increasing age (P < 0.001). Proportion of QFT-GIT indeterminate results was higher than that of X.DOT-TB across age groups. Male, age and disease classification all presented a statistically significant association with indeterminate IGRA results. CONCLUSIONS: The positive rates of X.DOT-TB and QFT-GIT in children were 3.1% and 1.8%, respectively. The X.DOT-TB assay performed better than QFT-GIT in children, and male, age and underlying diseases were associated with an increased risk of indeterminate IGRA results.

Particle-size stratification of airborne antibiotic resistant genes, mobile genetic elements, and bacterial pathogens within layer and broiler farms in Beijing, China.

The particle-size distribution of antimicrobial resistant (AMR) elements is crucial in evaluating their environmental behavior and health risks, and exposure to the fecal microbiome via particle mass (PM) is an important route of transmission of AMR from livestock to humans. However, few studies have explored the association between air and fecal AMR in farm environments from the perspective of particle-size stratification. We collected feces and PMs of different sizes from layer and broiler farms, quantified antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and human pathogenic bacteria (HPB) using Droplet digital PCR (ddPCR), and analyzed the bacterial communities based on 16S rRNA sequencing. The particle-size distributions of 16S rRNA and AMR elements were similar and generally increased with larger particle sizes in chicken farms. In broiler farms, we observed a bimodal distribution with two peaks at 5.8-9.0 µm and 3.3-4.7 µm. The dominant airborne bacterial phyla were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. The dominant phyla in the feces were the same as those in the air, but the order of relative abundance varied. The particle-size distributions of specific bacterial genera differed between the animal-farm types. Overall, the degree of association between feces and different particulates increased with increasing particle size. The microbial communities in the coarse particles were similar to those in fecal samples. Escherichia coli, Staphylococcus spp., Campylobacter spp., and sul 2 (sulfonamide ARGs) tended to attach to small particles. We highlight the particle size-specific relationship between fecal and air microbes involving ARGs, MGEs, and HPB and provide valuable information for comprehensively assessing the transmission of fecal microorganisms through the airpath and its environmental and occupational health risks.

Synthesis and biological evaluation of novel 1,2,3-triazole hybrids of cabotegravir: identification of potent antitumor activity against lung cancer.

In pursuit of discovering novel anticancer agents, we designed and synthesized a series of novel 1,2,3-triazole hybrids based on cabotegravir analogues. These compounds were subjected to initial biological evaluations to assess their anticancer activities against non-small-cell lung cancer (NSCLC). Our findings indicated that some of these compounds exhibited promising antitumor abilities against H460 cells, while demonstrated less efficacy against H1299 cells. Notably, compound 5i emerged as the most potent, displaying an IC50 value of 6.06 µM. Furthermore, our investigations into cell apoptosis and reactive oxygen species (ROS) production revealed that compound 5i significantly induced apoptosis and triggered ROS generation. Additionally, Western blot analysis revealed the pronounced elevation of LC3 expression in H460 cells and γ-H2AX expression in H1299 cells subsequent to treatment with compound 5i. These molecular responses potentially contribute to the observed cell death phenomenon. These findings highlight the potential of compound 5i as a promising candidate for further development as an anticancer agent especially lung cancer.

Design, synthesis and antitumour activity evaluation of novel dolutegravir derivatives.

Based on the modification of the structure of dolutegravir, we introduced 1,2,3-triazole moieties with different substituted groups and obtained a lot of novel dolutegravir derivatives. The activity of A549 cells treated with the derivatives was examined, and most compounds showed good inhibitory effects. Among them, compounds 4b and 4g were the most effective, and inhibited the growth of A549 cells with IC50 values of 8.72 ± 0.11 µM and 12.97 ± 0.32 µM, respectively. In addition, compound 4g induced apoptosis and clonal suppression in A549 tumor cells. Compound 4g also activated the LC3 signaling pathway to induce autophagy in tumor cells, and activated the γ-H2AX signaling pathway to induce DNA damage in tumor cells.

Identification of two Bacillus thuringiensis Cry3Aa toxin-binding aminopeptidase N from Rhynchophorus ferrugineus (Coleoptera: Curculionidae).

Rhynchophorus ferrugineus is a quarantine pest that mainly damages plants in tropical regions, which are essential economic resources. Cry3Aa has been used to control coleopteran pests and is known to be toxic to R. ferrugineus. The binding of the Cry toxin to specific receptors on the target insect plays a crucial role in the toxicological mechanism of Cry toxins. However, in the case of R. ferrugineus, the nature and identity of the receptor proteins involved remain unknown. In the present study, pull-down assays and mass spectrometry were used to identify two proteins of aminopeptidase N proteins (RfAPN2a and RfAPN2b) in the larval midguts of R. ferrugineus. Cry3Aa was able to bind to RfAPN2a (Kd = 108.5 nM) and RfAPN2b (Kd = 68.2 nM), as well as midgut brush border membrane vesicles (Kd = 482.5 nM). In silico analysis of both RfAPN proteins included the signal peptide and anchored sites for glycosyl phosphatidyl inositol. In addition, RfAPN2a and RfAPN2b were expressed in the human embryonic kidney 293T cell line, and cytotoxicity assays showed that the transgenic cells were not susceptible to activated Cry3Aa. Our results show that RfAPN2a and RfAPN2b are Cry3Aa-binding proteins involved in the Cry3Aa toxicity of R. ferrugineus. This study deepens our understanding of the action mechanism of Cry3Aa in R. ferrugineus larvae.

Performance of two interferon-gamma release assays for tuberculosis infection screening in Kawasaki children before immunosuppressive therapy.

Objective: We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) and X.DOT-TB for screening latent tuberculosis infection (LTBI) in kawasaki patients, and to identify the risk factors associated with indeterminate IGRA results. Methods: We conducted a retrospective study on children with KD, who were screened for mycobacterium tuberculosis (Mtb) infection by either ELISA-based QFT-GIT or ELISPOT-based X.DOT-TB tests, admitted in Department of Cardiology, Beijing Children's Hospital from July 2019 to April 2022. Results: A total of 1327 cases were included. Among them, 932 cases were tested by QFT-GIT and 395 cases by X.DOT-TB. The positive rate of children was 0.1% and 0.2%, and the indeterminate rate was 68.2% and 6.1% for QFT-GIT and X.DOT-TB, respectively. Patients with hypoproteinemia had a higher risk of indeterminate X.DOT-TB result. Female, critical ill, shock or hypoproteinemia presented statistically significant associations with an increased risk of indeterminate QFT-GIT result. High-dose of IVIG inhibited the release of IFN-γ by more than 90%, which might account for the high indeterminate incidence. Conclusion: It is recommended to perform X.DOT-TB rather than QFT-GIT to screen LTBI in patients with high level of the mitogen that can inhibit IFN-γ release. For KD children with positive IGRA results, it has a higher risk of activation TB infection when treated with immunosuppressive therapy in the future. Children with KD aged <5 years old had higher frequency of indeterminate IGRA results.

Aerosolization behavior of antimicrobial resistance in animal farms: a field study from feces to fine particulate matter.

Antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in animal feces can be released into the atmosphere via aerosolization, posing a high health risk to farm workers. So far, little attention has been paid to the characterization of the aerosolization process. In this study, fecal and fine particulate matter (PM2.5) samples were collected from 20 animal farms involving swine, cattle, layers, and broilers, and the ARGs, ARB, and human pathogenic bacteria (HPB) were loaded in these two media. The results showed that approximately 70% of ARGs, 60% of ARBs, and 43% of HPBs were found to be preferential aerosolization. The bioaerosolization index (BI) of target 30 ARGs varied from 0.04 to 460.07, and the highest value was detected from tetW. The highest BI values of erythromycin- and tetracycline-resistant bacteria were for Kocuria (13119) and Staphylococcus (24746), respectively, and the distribution of BI in the two types of dominant ARB was similar. Regarding the bioaerosolization behavior of HPB, Clostridium saccharolyticum WM1 was the most easily aerosolized pathogen in swine and broiler farms, and Brucella abortus strain CNM 20040339 had the highest value in cattle and layer farms. Notably, the highest BI values for ARGs, ARB, and HPB were universally detected on chicken farms. Most ARGs, ARB, and HPB positively correlated with animal age, stocking density, and breeding area. Temperature and relative humidity have significant effects on the aerosolization behavior of targets, and the effects of these two parameters on the same target are usually opposite. The results of this study provide a basis for a better understanding of the contribution of animal feces to airborne ARGs and HPBs in farms, as well as for controlling the transport of the fecal microbiome to the environment through the aerosolization pathway.

Awareness of intratumoral bacteria and their potential application in cancer treatment.

Hitherto, the recognition of the microbiota role in tumorigenesis and clinical studies mostly focused on the intestinal flora. In contrast to the gut microbiome, microorganisms resident in tumor tissue are in close contact with cancer cells and therefore have the potential to have similar or even different functional patterns to the gut flora. Some investigations have shown intratumoral bacteria, which might come from commensal microbiota in mucosal areas including the gastrointestinal tract and oral cavity, or from nearby normal tissues. The existence, origin, and interactions of intratumoral bacteria with the tumor microenvironment all contribute to intratumoral microorganism heterogeneity. Intratumoral bacteria have a significant role in tumor formation. They can contribute to cancer at the genetic level by secreting poisons that directly damage DNA and also intimately related to immune system response at the systemic level. Intratumoral bacteria have an impact on chemotherapy and immunotherapy in cancer. Importantly, various properties of bacteria such as targeting and ease of modification make them powerful candidates for precision therapy, and combining microbial therapies with other therapies is expected to improve the effectiveness of cancer treatment. In this review, we mainly described the heterogeneity and potential sources of intratumoral bacteria, overviewed the important mechanisms by which they were involved in tumor progression, and summarized their potential value in oncology therapy. At last, we highlight the problems of research in this field, and look forward to a new wave of studies using the various applications of intratumoral microorganisms in cancer therapy.

Morphologies and composition changes in nonculprit subclinical atherosclerosis in diabetic versus nondiabetic patients with acute coronary syndrome who underwent long-term statin therapy.

Although patients are undergoing similar lipid-lowering therapy (LLT) with statins, the outcomes of coronary plaque in diabetic mellitus (DM) and non-DM patients are different. Clinical data of 239 patients in this observational study with acute coronary syndrome was from our previous randomized trial were analyzed at 3 years, and 114 of them underwent OCT detection at baseline and the 1-year follow-up were re-anlayzed by a novel artificial intelligence imaging software for nonculprit subclinical atherosclerosis (nCSA). Normalized total atheroma volume changes (ΔTAVn) of nCSA were the primary endpoint. Plaque progression (PP) was defined as any increase in ΔTAVn. DM patients showed more PP in nCSA (ΔTAVn; 7.41 (- 2.82, 11.85) mm3 vs. - 1.12 (- 10.67, 9.15) mm3, p = 0.009) with similar reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 1-year. The main reason is that the lipid component in nCSA increases in DM patients and non-significantly decreases in non-DM patients, which leads to a significantly higher lipid TAVn (24.26 (15.05, 40.12) mm3 vs. 16.03 (6.98, 26.54) mm3, p = 0.004) in the DM group than in the non-DM group at the 1-year follow-up. DM was an independent predictor of PP in multivariate logistic regression analysis (OR = 2.731, 95% CI 1.160-6.428, p = 0.021). Major adverse cardiac events (MACEs) related to nCSA at 3 years were higher in the DM group than in the non-DM group (9.5% vs. 1.7%, p = 0.027). Despite a comparable reduction in LDL-C levels after LLT, more PP with an increase in the lipid component of nCSA and a higher incidence of MACEs at the 3-year follow-up was observed in DM patients.Trial registration: ClinicalTrials.gov. identifier: NCT02140801.

Hierarchical porous tri-metallic NiCoFe-Se/CFP derived from Ni-Co-Fe Prussian blue analogues as efficient electrocatalyst for oxygen evolution reaction.

The progress of inexpensive, high-efficiency, and steady oxygen evolution reaction (OER) electrocatalysts is of great importance to promoting water splitting for green hydrogen production. Herein, tri-metallic NiCoFe selenide catalyst backed up by carbon fiber paper (CFP) was synthesized by a facile selenization of NiCoFe Prussian blue analogues (PBAs) for OER in alkaline solutions. The NiCoFe-Se/CFP inherited the porous nanostructure of the metal-organic frameworks (MOFs) precursors prepared by rapid cyclic voltammetry electrodeposition. Benefiting from the 3D hierarchical porous structure, optimized electronic structure of NiCoFe selenides and high conductivity, the synthesized electrocatalyst exhibits outstanding catalytic activity to the corresponding mono-metallic or bi-metallic selenides. Specifically, the NiCoFe-Se/CFP electrode demands an overpotential of 221 mV to attain the 10 mA cm-2 current density in 1.0 M KOH solution and a low Tafel slope of 38.6 mV dec-1. The prepared catalyst also displays good stability and durability. These findings prove a feasible strategy to further improve the catalytic activities of non-precious metal based OER electrocatalysts by the cooperation of structure design and chemical component modification.