Systematic Chemical Analysis of Crude Glycan Isolates from the Seven-Herb Decoction Quanzhenyiqitang with Anti-COPD Activity.

The classical Chinese Medicine prescription, Quanzhenyiqitang (QZYQT), containing seven tonic herbs (Shudi, Dangshen, Maidong, Baizhu, Niuxi, Fuzi, and Wuweizi) is clinically used to treat chronic obstructive pulmonary disease (COPD). Although there are studies on the pharmacological effects of QZYQT, little attention has been paid to its active carbohydrate ingredients. We performed a systematic chemical analysis of the crude glycan isolates from the seven-herb decoction (GI-QZYQT) after confirming its anti-COPD activity. GI-QZYQT could enhance lung function, reduce lung damage, and alleviate inflammatory response in mice with COPD. Moreover, two monosaccharides (fructose and glucose) and six oligosaccharides (sucrose, melibiose, 1-kestose, raffinose, mannotriose, and stachyose), accounting for 40.23 % of GI-QZYQT, were discovered using hydrophilic interaction liquid chromatography-evaporative light-scattering detection. Inulin-type fructan with an average molecular weight of 2112 Da was identified using high-performance gel-permeation chromatography in combination with monosaccharide mapping analysis, accounting for 20.10 % of GI-QZYQT in mass. The comparison study showed that the identified monosaccharides, oligosaccharides, and the inulin-type fructan of GI-QZYQT were mainly derived from herbs of Shudi, Dangshen, Maidong, Baizhu, and Niuxi. These findings provide crucial information on the chemical composition of GI-QZYQT, which is vital for the in-depth understanding of its bioactivity, mechanism, and product development.

Metal-semiconductor-metal solar-blind ultraviolet photodetector based on Al0.55Ga0.45N/Al0.4Ga0.6N/Al0.65Ga0.35N heterostructures.

We have designed a metal-semiconductor-metal (MSM) solar-blind ultraviolet (UV) photodetector (PD) by utilizing Al0.55Ga0.45N/Al0.4Ga0.6N/Al0.65Ga0.35N heterostructures. The interdigital Ni/Au metal stack is deposited on the Al0.55Ga0.45N layer to form Schottky contacts. The AlGaN hetero-epilayers with varying Al content contribute to the formation of a two-dimensional electron gas (2DEG) conduction channel and the enhancement of the built-in electric field in the Al0.4Ga0.6N absorption layer. This strong electric field facilitates the efficient separation of photogenerated electron-hole pairs. Consequently, the fabricated PD exhibits an ultra-low dark current of 1.6 × 10-11 A and a broad spectral response ranging from 220 to 280 nm, with a peak responsivity of 14.08 A/W at -20 V. Besides, the PD demonstrates an ultrahigh detectivity of 2.28 × 1013 Jones at -5 V. Furthermore, to investigate the underlying physical mechanism of the designed solar-blind UV PD, we have conducted comprehensive two-dimensional device simulations.

Persistence and potential risks of tetracyclines and their transformation products in two typical different animal manure composting treatments.

Abundant residues of tetracyclines in animal manures and manure-derived organic fertilizers can pose a substantial risk to environments. However, our knowledge on the residual levels and potential risk of tetracyclines and their transformation products (TPs) in manure and manure-derived organic fertilizers produced by different composting treatments is still limited. Herein, the occurrence and distribution of four veterinary tetracyclines (tetracycline, oxytetracycline, chlortetracycline, and doxycycline) and ten of their TPs were investigated in paired samples of fresh manure and manure-derived organic fertilizers. Tetracyclines and TPs were frequently detected in manure and manure-derived organic fertilizer samples in ranging from 130 to 118,137 µg·kg-1 and 54.6 to 104,891 µg·kg-1, respectively. Notably, the TPs concentrations of tetracycline and chlortetracycline were comparable to those of the parent compounds, with 4-epimers being always dominant and retained antibacterial potency. Based on paired-sampling strategy, the removal efficiency of tetracyclines and TPs in thermophilic composting was higher than that in manure storage. Toxicological data in the soil environment and the data derived from equilibrium partitioning method, indicated that tetracyclines and some TPs like 4-epitetracycline, 4-epichlortetracycline and isochlortetracycline could pose median to high ecological risk to terrestrial organisms. Total concentrations of TPs in manure-derived organic fertilizers were significantly correlated with the absolute abundance of tet(X) family genes, which provide evidence to evaluate the effects of TPs on the levels of antibiotic resistance in the environment. Among them, the 4-epitetracycline could pose ecological risk and retain antibacterial potency. Our findings emphasize the importance of monitoring and controlling the prevalence of tetracyclines and their TPs in livestock-related environments.

Uncovering the diverse hosts of tigecycline resistance gene tet(X4) in anaerobic digestion systems treating swine manure by epicPCR.

The tet(X4) gene is a clinically important tigecycline resistance gene and has shown high persistence in livestock-related environments. However, the bacterial hosts of tet(X4) remain unknown due to the lack of appropriate approaches. Herein, a culture-independent and high-throughput epicPCR (emulsion, paired isolation, and concatenation polymerase chain reaction) method was developed, optimized, and demonstrated for the identification of bacterial hosts carrying tet(X4) from environmental samples. Considering the high sequence similarity between tet(X4) and other tet(X)-variant genes, specific primers and amplification conditions were screened and optimized to identify tet(X4) accurately and link tet(X4) with the 16S rRNA gene, which were further validated using artificially constructed bacterial communities. The epicPCR targeting tet(X4) was applied for the identification of bacterial hosts carrying this resistance gene in anaerobic digestion systems treating swine manure. A total of 19 genera were identified as tet(X4) hosts, which were distributed in the phyla Proteobacteria, Bacteroidota, Firmicutes, and Caldatribacteriota. Sixteen genera and two phyla that were identified have not been previously reported as tet(X4) bacterial hosts. The results indicated that a far more diverse range of bacteria was involved in harboring tet(X4) than previously realized. Compared with the tet(X4) hosts determined by correlation-based network analysis and metagenomic binning, epicPCR revealed a high diversity of tet(X4) hosts even at the phylum level. The epicPCR method developed in this study could be effectively employed to reveal the presence of tet(X4) bacterial hosts from a holistic viewpoint.

Schisandrin A regulates the Nrf2 signaling pathway and inhibits NLRP3 inflammasome activation to interfere with pyroptosis in a mouse model of COPD.

Chronic obstructive pulmonary disease (COPD) is a serious chronic lung disease. Schisandrin A (SchA) is one of the most important active ingredients in Schisandra chinensis and has been used to treat various lung diseases in several countries. Here, we studied the pharmacological effect of SchA on airway inflammation induced by cigarette smoke (CS) and explored the therapeutic mechanism of SchA in COPD model mice. Our results showed that SchA treatment significantly improved the lung function of CS-induced COPD model mice and reduced the recruitment of leukocytes and hypersecretion of interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF). H&E staining showed that SchA treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. In addition, we found that SchA treatment can stimulate the expression of heme oxygenase-1 (HO-1) through the nuclear factor-erythroid 2-related factor (Nrf2) pathway, significantly reduce oxidative stress, increase catalase (CAT) and superoxide dismutase (SOD) levels, and suppress the level of malondialdehyde (MDA) in COPD model mice. Moreover, SchA treatment suppressed the generation of the NLRP3/ASC/Caspase1 inflammasome complex to inhibit the inflammatory response caused by IL-1ß and IL-18 and pyroptosis caused by GSDMD. In conclusion, our study shows that SchA treatment can inhibit the production of ROS and the activation of the NLRP3 inflammasome by upregulating Nrf-2, thereby producing anti-inflammatory effects and reducing lung injury in COPD model mice. More importantly, SchA exhibited similar anti-inflammatory effects to dexamethasone in COPD model mice, and we did not observe substantial side effects of SchA treatment. The high safety of SchA makes it a potential candidate drug for the treatment of COPD.

Occurrence and transfer characteristics of blaCTX-M genes among Escherichia coli in anaerobic digestion systems treating swine waste.

Livestock waste is a known reservoir of Escherichia coli (E. coli) carrying clinically important CTX-M-type extended-spectrum ß-lactamase genes (blaCTX-M), however, the occurrence and transfer characteristics of blaCTX-M genes during anaerobic digestion (AD) remain unclear. Herein, four full-scale and two parallel lab-scale AD systems treating swine waste under ambient and mesophilic conditions were investigated by both molecular- and culture-based methods to reveal the occurrence and transfer behaviors of blaCTX-M genes during AD. Real-time TaqMan polymerase chain reaction revealed 1.3 × 104-6.8 × 105 and 3.0 × 104-7.0 × 105 copies/mL of blaCTX-M groups 1 and 9 in all feeding substrates. While AD reduced the absolute abundance of groups 1 and 9 by 0.63-2.24 and 0.08-1.30 log (P < 0.05), 5.0 × 102-4.1 × 103 and 1.1 × 104-3.5 × 104 copies/mL of groups 1 and 9 remained in the anaerobic effluent, respectively. In total, 141 blaCTX-M-carrying E. coli isolates resistant to cefotaxime were obtained from the AD reactors. Whole-genome sequencing showed that blaCTX-M-65 mainly carried by E. coli ST155 was the most frequently detected group 9 subtype in the feeding substrate; whereas blaCTX-M-14 associated with the dominant clones E. coli ST6802 and ST155 became the major subtype in AD effluent. Furthermore, blaCTX-M-14 was flanked by ΔIS26 upstream and ΔIS903B downstream. The ΔIS26-blaCTX-M-14-ΔIS903B element was mainly located on the IncHI2 plasmid in E. coli ST48 and ST6802 and also the IncFIB plasmid in ST155 in anaerobic effluent. Conjugation assays showed that the plasmids harboring blaCTX-M-14 could be successfully transferred at a frequency of 10-3-10-2 cells per recipient cell. This study revealed that blaCTX-M genes remained in both the full-scale and lab-scale AD effluents of swine waste. Thus, additional efforts should be implemented to block the discharge and spread of antibiotic resistance genes to the environment.

Mobile tigecycline resistance gene tet(X4) persists with different animal manure composting treatments and fertilizer receiving soils.

The emergence of plasmid-mediated tigecycline-resistant genes [tet(X3)to tet(X6)] in animals and humans has raised serious concerns over their possible cross-environmental dissemination. However, behavior of these emerging mobile tet(X)-variant genes in manure treatment processes, particularly for different composting treatments, has not yet been studied. Here, we explored the environmental behavior of mobile tet(X)-variant genes in two typical manure composting treatments and amended soils based on a large-scale molecular investigation across eight provinces in China. Results showed that tet(X4) was the predominant mobile tet(X)-variant gene in fresh manure, natural and thermophilic composting products with both the highest detection frequency (82.5% ± 14.7%), and absolute abundance of tet(X4)[4.26 ± 0.09) × 1010] copies/g dry weight, followed by tet(X3), tet(X6), and tet(X5). The occurrence of all mobile tet(X)-variant genes, particularly tet(X4), in receiving soil following composting fertilizer application indicated their transmission from manure to soil. Paired-sampling strategy revealed no significant reduction in mobile tet(X)-variant genes by natural composting, while thermophilic composting exhibited clear efficacy in removing tet(X)-variant genes. After thermophilic composting, tet(X4) exhibited the lowest reduction (94.1%) compared with other mobile tet(X)-variant genes (96.9%-99.9%), which may be attributable to its significant correlation with ISCR2 (P < 0.05) facilitating its transfer to various hosts including persisted thermotolerant bacteria. Thus, tet(X4) showed better persistence in livestock-related environments. Collectively, this study highlights the importance of controlling the environmental dissemination of clinically relevant mobile tet(X)-variant genes by establishing a sound process and operational strategy.

Taurine suppresses ROS-dependent autophagy via activating Akt/mTOR signaling pathway in calcium oxalate crystals-induced renal tubular epithelial cell injury.

Oxidative stress and autophagy are the key promoters of calcium oxalate (CaOx) nephrolithiasis. Taurine is an antioxidant that plays a protective role in the pathogenesis of kidney disease. Previous studies found that taurine suppressed cellular oxidative stress, and inhibited autophagy activation. However, the effect of taurine on CaOx kidney stone formation remains unknown. In the present work, we explored the regulatory effects of taurine on CaOx crystals-induced HK-2 cell injury. Results showed that pretreatment with taurine significantly enhanced the viability of HK-2 cells and ameliorated kidney tissue injury induced by CaOx crystals. Taurine also markedly reduced the levels of inflammatory cytokines, apoptosis, and CaOx crystals deposition. Furthermore, we observed that taurine supplementation alleviated CaOx crystals-induced autophagy. Mechanism studies showed that taurine reduced oxidative stress via increasing SOD activity, reducing MDA concentration, alleviating mitochondrial oxidative injury, and decreasing the production of intracellular ROS. Taurine treatment also effectively activated Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cells both in vitro and in vivo. In summary, the current study shows that taurine inhibits ROS-dependent autophagy via activating Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cell and kidney injury, suggesting that taurine may serve as an effective therapeutic agent for the treatment of CaOx nephrolithiasis.