Clinical value of Vitamin-D combined with budesonide/formoterol and theophylline sodium glycinate sustained-release tablets in the treatment of chronic obstructive pulmonary disease patients.

Objective: To explore the clinical value of Vitamin-D combined with budesonide/formoterol (BF) and theophylline sodium glycinate (TSG) sustained-release tablets in the treatment of patients with chronic obstructive pulmonary disease (COPD). Methods: Medical records of 114 patients with CODP, treated in Wenzhou Geriatric Hospital from October 2020 to February 2023, were retrospectively analyzed. Of them, 59 received treatment with Vitamin-D combined with BF and TSG sustained-release tablets (Group-A), and 55 patients received treatment with BF combined with TSG sustained-release tablets (Group-B). Lung function indicators, blood gas status, inflammatory factors, fractional exhaled nitric oxide (FeNO), and 25-hydroxyvitamin D [25(OH)D] levels before and after the treatment in both groups were collected. Results: After the treatment, lung function indicators, blood gas status, inflammatory factors, FeNO, and 25 (OH) D levels in both groups were significantly improved compared to pretreatment levels, and were significantly better in the Group-A compared to Group-B (P<0.05). Conclusions: The combination of Vitamin-D, BF, and TSG sustained-release tablets can effectively regulate the blood gas status of patients with COPD, improve lung function, regulate FeNO and 25 (OH) D, and effectively downregulate the levels of inflammatory factors, thus reducing the degree of inflammatory response.

Characteristics of resistome and bacterial community structure in constructed wetland during dormant period: A fullscale study from Annan wetland.

As a green technology, constructed wetlands (CWs) can provide a low-cost solution for wastewater treatment. Either as a standalone treatment or integrated with conventional treatment, nutrients, antibiotic resistant bacteria (ARB)/antibiotic resistance genes (ARGs) can be removed by CW efficiently. While, few studies have focused on characteristics of resistome and bacterial community (BC) structure in CW during dormant period. Therefore, in this study, Annan CW (a full-scale hybrid CW) was selected to characterize resistome and BC during dormant period. The profiles of bacteria / ARGs were monitored in combination of shotgun sequencing and metagenomic assembly analysis. And multidrug ARGs are the most abundant in Annan CW, and surface flow wetland had the relatively high ARG diversity and abundance compared with subsurface flow wetland and the front pond. The most dominant phylum in CW is Proteobacteria, while the other dominant phylum in three parts have different order. COD, TP, TN, ARGs, and mobile genetic genes (MGEs) were removed by subsurface flow CW with better performance, but virulent factors (VFs) were removed by surface flow CW with better performance. Based on the spatiotemporal distribution of ARGs, the internal mechanism of ARGs dynamic variation was explored by the redundancy analysis (RDA) and variation partitioning analysis (VPA). BCs, MGEs and environmental factors (EFs) were responsible for 45.6 %, 28.3 % and 15.4 % of the ARGs variations. Among these factors, BCs and MGEs were the major co-drivers impacting the ARG profile, and EFs indirectly influence the ARG profile. This study illustrates the specific functions of ARG risk elimination in different CW components, promotes a better understanding of the efficiency of CWs for the reduction of ARG and ARB, contributing to improve the removal performance of constructed wetlands. And provide management advice to further optimize the operation of CWs during dormant period.

Jointly considering multi-medium and full-cycle to better reveal distribution and removal of antibiotic resistance genes in long-term constructed wetland.

Constructed wetlands (CWs) have been proven to effectively remove antibiotic resistance genes (ARGs) at different experimental scales; however, there is still a lack of researches on the removal and monitoring of ARGs during the actual operation of full-scale CWs. To fill this gap, this study selected the Annan constructed wetland in Beijing as a case study and utilized quantitative sequencing, metagenomic analysis, and other technical methods to determine characteristics of ARGs in CWs during different operating periods. Furthermore, we analysed the overall removal characteristics of ARGs in the CW during different operating periods and differences of ARG distribution in three media. The dominant ARGs in the CW were quinolone, ß-lactam and tetracycline, with subtypes of tufA and fusA. ARG distributions are significantly influenced by anthropic activities and seasonal changes. Three periods of the CW had good removal effects on special ARGs, but there were differences in the removal characteristics of different types and subtypes of ARGs. The CW had removal effects on four types of ARGs (such as multidrugs), 16 types of fusidic acid, and nine types of ARGs (such as bleomycin) during the dormancy, start-up, and operation periods, respectively. Among ARG subtypes, the CW had removal effects on 37, 53, and 51 subtypes during the dormancy, start-up, and operation periods, respectively. The subtypes that were removed mainly included those containing tetracycline, efflux pump, and ß-lactam, mcr-1, and mcr-5 (colistin ARGs). For individual parts of CWs, the removal effects on the total abundance of ARGs were as follows: forebay > surface flow wetland > subsurface flow wetland. These findings provide insights for optimizing the purification efficiency of CWs for ARGs.

Response of microbial community to different media in start-up period of Annan constructed wetland in Beijing of China.

Microbial community, as the decomposers of constructed wetland (CW), plays crucial role in biodegradation and biotransformation of pollutants, nutrient cycling and the maintenance of ecosystem balance. In this study, 9 water samples, 6 sediment samples, and 8 plant samples were collected in Annan CW, which has the functions of water treatment and wetland culture park. The characteristics of microbial community structure in different media were illustrated by using of high-throughput sequencing-based metagenomics approach and statistical analysis. Meanwhile, this study identified and classified human pathogens in CW to avoid potential risks to human health. The results showed that dominant bacteria phyla in CW include Proteobacteria, Bacteroides, Actinobacteria, Firmicutes and Verrucomicrobia. The distribution of microorganisms in three media is different, but not significant. And the pH and DO profoundly affected microbe abundance, followed by water temperature. The microbial diversity in sediments is the highest, which is similar with the detection of human pathogens in sediments. Moreover, compared with Calamus, Lythrum salicaria and Reed, Scirpus tabernaemontani has fewer pathogenic microorganisms. The distribution of microorganisms in the CW is complex, and a variety of human pathogens are detected, which is more prone to create potential risks to human health and should receive additional attention.

A facile alternative strategy of upcycling mixed plastic waste into vitrimers.

Chemical depolymerization has been identified as a promising approach towards recycling of plastic waste. However, complete depolymerization may be energy intensive with complications in purification. In this work, we have demonstrated upcycling of mixed plastic waste comprising a mixture of polyester, polyamide, and polyurethane through a reprocessable vitrimer of the depolymerized oligomers. Using poly(ethylene terephthalate) (PET) as a model polymer, we first demonstrated partial controlled depolymerization, using glycerol as a cleaving agent, to obtain branched PET oligomers. Recovered PET (RPET) oligomer was then used as a feedstock to produce a crosslinked yet reprocessable vitrimer (vRPET) despite having a wide molecular weight distribution using a solventless melt processing approach. Crosslinking and dynamic interactions were observed through rheology and dynamic mechanical analysis (DMA). Tensile mechanical studies showed no noticeable decrease in mechanical strength over multiple repeated melt processing cycles. Consequently, we have clearly demonstrated the applicability of the above method to upcycle mixed plastic wastes into vitrimers and reprocessable composites. This work also afforded insights into a potentially viable alternative route for utilization of depolymerized plastic/mixed plastic waste into crosslinked vitrimer resins manifesting excellent mechanical strength, while remaining reprocessable/ recyclable for cyclical lifetime use.

Synthesis of dideoxymycobactin antigens presented by CD1a reveals T cell fine specificity for natural lipopeptide structures.

Mycobacterium tuberculosis survival in cells requires mycobactin siderophores. Recently, the search for lipid antigens presented by the CD1a antigen-presenting protein led to the discovery of a mycobactin-like compound, dideoxymycobactin (DDM). Here we synthesize DDMs using solution phase and solid phase peptide synthesis chemistry. Comparison of synthetic standards to natural mycobacterial mycobactins by nuclear magnetic resonance and mass spectrometry allowed identification of an unexpected alpha-methyl serine unit in natural DDM. This finding further distinguishes these pre-siderophores as foreign compounds distinct from conventional peptides, and we provide evidence that this chemical variation influences the T cell response. One synthetic DDM recapitulated natural structures and potently stimulated T cells, making it suitable for patient studies of CD1a in infectious disease. DDM analogs differing in the stereochemistry of their butyrate or oxazoline moieties were not recognized by human T cells. Therefore, we conclude that T cells show precise specificity for both arms of the peptide, which are predicted to lie at the CD1a-T cell receptor interface.

Ablation Behavior of a Carbon Fabric Reinforced Phenolic Composite Modified by Surface-Decorated ZrB2/SiC.

Carbon fabric reinforced phenolic composites were widely used as TPSs (thermal protection system) material in the aerospace industry. However, their limited oxidative ablation resistance restricted their further utility in more serious service conditions. In this study, the surface-decorated ZrB2/SiC and its modified carbon fabric reinforced phenolic composites have been successfully prepared. The self-modification mechanism of the surface-decorated ZrB2/SiC particles were characterized. The mechanical performance and ablation behavior of the composites were investigated. Results showed that the ZrB2/SiC particles possessed a good surface-decorated effect, which achieved good compatibility with the phenolic resin. The mechanical performance of the modified phenolic composite was effectively improved. The anti-oxidative ablation performance of the composite was improved. The mass ablation rate of the surface-decorated ZrB2-SiC-modified carbon fabric reinforced phenolic composites was 25% lower than that of the unmodified composites. The formed ZrO2 ceramic layer attached to the surface of the residual chars prevented the heat energy and oxygen from the inner material. Meanwhile, the volatilization of SiO2 and B2O3 effectively increased the heat dissipation. All these results confirmed that the ZrB2-SiC particles can effectively improve the ablation resistance of the composite, which provided a basis for the application of the composites to more serious service environments.

Utilization of microbial iron assimilation processes for the development of new antibiotics and inspiration for the design of new anticancer agents.

Pathogenic microbes rapidly develop resistance to antibiotics. To keep ahead in the "microbial war", extensive interdisciplinary research is needed. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (ie., beta-lactamase) and even induction of efflux mechanisms. A combination of chemical syntheses, microbiological and biochemical studies demonstrate that the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron-chelating compounds called siderophores. Our studies, and those of others, demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics) and induction of iron limitation/starvation (Development of new agents to block iron assimilation). Recent extensions of the use of siderophores for the development of novel potent and selective anticancer agents are also described.

[Study on structure and spectra of 1,4-bis[(p-methoxyphenoxy) carbonyl]].

Theoretical studies on 1,4-bis [(p-methoxyphenoxy) carbonyl] and ramification were carried out using the density functional theory at B3LYP/6-31+G* level to obtain optimized equilibrium structure, vibrational spectra and electronic spectra. The calculation results indicate that the carbon and oxygen (in the ester group) come into being different large pi bonds with the benzene circles because of place blocking and conjugate effect. On this basis, the first excited state electronic transition energy was calculated by time-dependent density function theory. The calculated results show that the largest absorption spectra of the title compounds were obtained from the pi --> pi* electron transition from the highest occupied molecular orbital to the lowest unoccupied molecular orbital. And lambda(max) was obtained in 370-384 nm, belonging to the UV absorption area. The computed results show that the lateral substitutent of 1,4-bis [(p-methoxyphenoxy) carbonyl] has little effects on molecular structure. Because of place blocking, the dihedral angle between benzene (1) and benzene (2) augments 3 degrees-4 degrees. The introduction of the lateral substitutents has effects on vibrational spectra. The results showed that with the introduction of hydroxy the difference between E(HOMO) and E(LUMO) of the compound becomes small. While lambda(max) becomes large. Meanwhile, the difference between E(HOMO) and E(LUMO) reduces by 0.120 9 eV with the introduction of fluorin. This causes the biggest absorption wavelength to red shift 14 nm.

Molecular mechanism of lipopeptide presentation by CD1a.

CD1a is expressed on Langerhans cells (LCs) and dendritic cells (DCs), where it mediates T cell recognition of glycolipid and lipopeptide antigens that contain either one or two alkyl chains. We demonstrate here that CD1a-restricted T cells can discriminate the peptide component of didehydroxymycobactin lipopeptides. Structure analysis of CD1a cocrystallized with a synthetic mycobactin lipopeptide at 2.8 A resolution further reveals that the single alkyl chain is inserted deep within the A' pocket of the groove, whereas its two peptidic branches protrude along the F' pocket to the outer, alpha-helical surface of CD1a for recognition by the TCR. Remarkably, the cyclized lysine branch of the peptide moiety lies in the shallow F' pocket in a conformation that closely mimics that of the alkyl chain in the CD1a-sulfatide structure. Thus, this structural study illustrates how a single chain lipid can be presented by CD1 and that the peptide moiety of the lipopeptide is recognized by the TCR.

Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR.

We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC(50)=45 nM) and cellular activity (IC(50)=0.4 microM).

Design and synthesis of statine-containing BACE inhibitors.

Utilizing structure-based techniques and solid-phase synthesis, statine-based tetrapeptide BACE inhibitors were designed and synthesized using a heptapeptide BACE transition-state mimetic, 1, as the starting point. Structure-activity relationship studies at the P(3), P(2), and P(2)' positions as well as the N-terminal capping group on scaffold 5 led to the discovery of potent inhibitors 27, 32, and 34 (IC(50) <100 nM). In addition, computational analysis and the X-ray structure of BACE-inhibitor 38 are discussed.

Biochemical and kinetic characterization of BACE1: investigation into the putative species-specificity for beta- and beta'-cleavage sites by human and murine BACE1.

Beta-amyloid peptides (Abeta) are produced by a sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. The lack of Abeta production in beta-APP cleaving enzyme (BACE1)(-/-) mice suggests that BACE1 is the principal beta-secretase in mammalian neurons. Transfection of human APP and BACE1 into neurons derived from wild-type and BACE1(-/-) mice supports cleavage of APP at the canonical beta-secretase site. However, these studies also revealed an alternative BACE1 cleavage site in APP, designated as beta', resulting in Abeta peptides starting at Glu11. The apparent inability of human BACE1 to make this beta'-cleavage in murine APP, and vice versa, led to the hypothesis that this alternative cleavage was species-specific. In contrast, the results from human BACE1 transgenic mice demonstrated that the human BACE1 is able to cleave the endogenous murine APP at the beta'-cleavage site. To address this discrepancy, we designed fluorescent resonance energy transfer peptide substrates containing the beta- and beta'-cleavage sites within human and murine APP to compare: (i) the enzymatic efficiency; (ii) binding kinetics of a BACE1 active site inhibitor LY2039911; and (iii) the pharmacological profiles for human and murine recombinant BACE1. Both BACE1 orthologs were able to cleave APP at the beta- and beta'-sites, although with different efficiencies. Moreover, the inhibitory potency of LY2039911 toward recombinant human and native BACE1 from mouse or guinea pig was indistinguishable. In summary, we have demonstrated, for the first time, that recombinant BACE1 can recognize and cleave APP peptide substrates at the postulated beta'-cleavage site. It does not appear to be a significant species specificity to this cleavage.