Scanning Electrochemical Probe Lithography for Ultra-Precision Machining of Micro-Optical Elements with Freeform Curved Surface.

Two challenges should be overcome for the ultra-precision machining of micro-optical element with freeform curved surface: one is the intricate geometry, the other is the hard-to-machining optical materials due to their hardness, brittleness or flexibility. Here scanning electrochemical probe lithography (SECPL) is developed, not only to meet the machining need of intricate geometry by 3D direct writing, but also to overcome the above mentioned mechanical properties by an electrochemical material removal mode. Through the electrochemical probe a localized anodic voltage is applied to drive the localized corrosion of GaAs. The material removal rate is obtained as a function of applied voltage, motion rate, scan segment, etc. Based on the material removal function, an arbitrary geometry can be converted to a spatially distributed voltage. Thus, a series of micro-optical element are fabricated with a machining accuracy in the scale of 100 s of nanometers. Notably, the spiral phase plate shows an excellent performance to transfer parallel light to vortex beam. SECPL demonstrates its excellent controllability and accuracy for the ultra-precision machining of micro-optical devices with freeform curved surface, providing an alternative chemical approach besides the physical and mechanical techniques.

Seasonal variations of organophosphate esters (OPEs) in atmospheric deposition, and their contribution to soil loading.

Organophosphate esters (OPEs) are ubiquitous in surface soil, and atmospheric deposition is considered to be the major pollution source. However, the research on the environmental transport behaviors of OPEs between atmospheric deposition and soil is very limited. In this study, we investigated the contamination levels and seasonal variations of OPEs in atmospheric deposition samples (n = 33) collected from an area of South China every month between February 2021 and January 2022, and evaluated the contribution of OPEs in atmospheric deposition to soil. The concentrations of ∑21target-OPEs ranged from 3670 to 18,600 ng/g dry weight (dw), with a mean of 8200 ng/g dw (median: 7600 ng/g dw). ∑21target-OPEs concentrations in all atmospheric deposition samples exhibited significant seasonal differences (p < 0.05) with higher concentrations observed in winter and lower concentrations in summer. Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was the most dominant target OPE in atmospheric deposition (4870 ng/g dw), and its seasonal variation trend was consistent with ∑21OPEs (p < 0.05). Simultaneously, in order to further explore the effect of atmospheric deposition on the levels of OPEs in soil of the study region, input fluxes and accumulation increments were estimated. Ten OPEs (including seven target OPEs and three suspect OPEs) exhibited high input flux means and accumulation increments, indicating that these compounds are prone to accumulate in soil via atmospheric deposition. It is noteworthy that the non-target phosphonate analyte bis(2,4-di-tert-butylphenyl) dibutyl ethane-1,2-diylbis(phosphonate) (BDTBPDEDBP) was detected at highest median concentration (8960 ng/g dw) in atmospheric deposition. Correspondingly, the average input flux and accumulation increment of BDTBPDEDBP were higher than those of all target and suspect OPEs. Collectively, this study quantifies the environmental transport behavior of OPEs between atmospheric deposition and soil, and provides new evidences for the fact that atmospheric deposition is the important pollution source of OPEs in soil.

All-in-One Electrokinetic Strategy Coupled with a Miniaturized Chip for SERS Detection of Multipesticides.

Complexed and tiresome pretreatment processes have significantly impeded in-field analysis of environmental specimens. Herein, an all-in-one sample separation and enrichment strategy based on a compact charge-selective capture/nanoconfined enrichment (CSC/NCE) device is exploited for marker-free surface-enhanced Raman spectroscopy (SERS) detection of charged pesticides in matrix specimens. This tactic incorporating in situ separations, seizing, and nanoconfined enhancement can greatly elevate the effectiveness of sample pretreatment. Importantly, CSC/NCE with excellent adsorption performances and excellent plasmonic features facilitates concentration and signal amplification of electrically charged pesticides. With the introduction of an electric field on this integrated CSC/NCE, the matrix effect in samples could be significantly eradicated, and a distinct SERS response is witnessed for targeted analytes. Accurate quantification of multipesticides is achieved by synergizing the CSC/NCE chip and chemometrics, and the contents found by the CSC/NCE-based sensing strategy agree with those obtained from chromatography assays with relative deviations lower than 10%. The facile and versatile all-in-one tactic infused in a compact chip exhibits enormous potential for field-test application in chemical measurement and food safety.

A new approach to monitoring typical organophosphorus compounds (OPs) in environmental media: From database building to suspect screening.

Organophosphorus compounds (OPs) are widely used as flame retardants (FRs) and plasticizers, yet strategies for comprehensively screening of suspect OPs in environmental samples are still lacking. In this work, a neoteric, robust, and general suspect screening technique was developed to identify novel chemical exposures by use of ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). We firstly established a suspect chemical database which had 7,922 OPs with 4,686 molecular formulas, and then conducted suspect screening in n = 50 indoor dust samples, n = 76 sediment samples, and n = 111 water samples. By use of scoring criteria such as retention time prediction models, we successfully confirmed five compounds by comparison with their authentic standards, and prioritized three OPs candidates including a nitrogen/fluorine-containing compound, that is dimethyl {1H-indol-3-yl[3-(trifluoromethyl)anilino]methyl} phosphonate (DMITFMAMP). Given that the biodegradation half-life values in water (t1/2,w) of DMITFMAMP calculated by EPI Suite is 180 d, it is considered to be potentially persistent. This strategy shows promising potential in environmental pollution assessment, and can be expected to be widely used in future research.

Surface-Enhanced Raman Scattering Imaging Assisted by Machine Learning Analysis: Unveiling Pesticide Molecule Permeation in Crop Tissues.

Surface-enhanced Raman scattering (SERS) imaging technology faces significant technical bottlenecks in ensuring balanced spatial resolution, preventing image bias induced by substrate heterogeneity, accurate quantitative analysis, and substrate preparation that enhances Raman signal strength on a global scale. To systematically solve these problems, artificial intelligence techniques are applied to analyze the signals of pesticides based on 3D and dynamic SERS imaging. Utilizing perovskite/silver nanoparticles composites (CaTiO3/Ag@BONPs) as enhanced substrates, enabling it not only to cleanse pesticide residues from the surface to pulp of fruits and vegetables, but also to investigate the penetration dynamics of an array of pesticides (chlorpyrifos, thiabendazole, thiram, and acetamiprid). The findings challenge existing paradigms, unveiling a previously unnoticed weakening process during pesticide invasion and revealing the surprising permeability of non-systemic pesticides. Of particular note is easy to overlook that the combined application of pesticides can inadvertently intensify their invasive capacity due to pesticide interactions. The innovative study delves into the realm of pesticide penetration, propelling a paradigm shift in the understanding of food safety. Meanwhile, this strategy provides strong support for the cutting-edge application of SERS imaging technology and also brings valuable reference and enlightenment for researchers in related fields.

Human amniotic epithelial stem cell-derived dopaminergic neuron-like cells ameliorate motor dysfunction in a rat model of Parkinson's disease.

AIMS: Parkinson's disease (PD) remains a substantial clinical challenge due to the progressive loss of midbrain dopaminergic (DA) neurons in nigrostriatal pathway. In this study, human amniotic epithelial stem cells (hAESCs)-derived dopaminergic neuron-like cells (hAESCs-DNLCs) were generated, with the aim of providing new therapeutic approach to PD. MATERIALS AND METHODS: hAESCs, which were isolated from discarded placentas, were induced to differentiate into hAESCs-DNLCs by following a "two stages" induction protocol. The differentiation efficiency was assessed by quantitative real-time PCR (qRT-PCR), immunocytochemistry (ICC), and ELISA. Immunogenicity, cell viability and tumorigenicity of hAESCs-DNLC were analyzed before in vivo experiments. Subsequently, hAESCs-DNLCs were transplanted into PD rats, behavioral tests were monitored after graft, and the regeneration of DA neurons was detected by immunohistochemistry (IHC). Furthermore, to trace hAESCs-DNLCs in vivo, cells were pre-labeled with PKH67 green fluorescence. KEY FINDINGS: hAESCs were positive for pluripotent markers and highly expressed neural stem cells (NSCs) markers. Based on this, we established an induction method reliably generates hAESCs-DNLCs, which was evidenced by epithelium-to-neuron morphological changes, elevated expressions of neuronal and DA neuronal markers, and increased secretion of dopamine. Moreover, hAESCs-DNLCs maintained high cell viability, no tumorigenicity and low immunogenicity, suggesting hAESCs-DNLCs an attractive implant for PD therapy. Transplantation of hAESCs-DNLCs into PD rats significantly ameliorated motor disorders, as well as enhanced the reinnervation of TH+ DA neurons in nigrostriatal pathway. SIGNIFICANCE: Our study has demonstrated evident therapeutic effects of hAESCs-DNLCs, and provides a safe and promising solution for PD.

Dissection of the spatial dynamics of biosynthesis, transport, and turnover of major amino acids in tea plants (Camellia sinensis).

High levels of free amino acids (AAs) in tea leaves are crucial for tea flavor and health function; however, the dynamic AA biosynthesis, transport, and turnover in tea plants remain elusive. Here we dissected whole tea plants for these dynamics by assessing AA profiles and transcriptomes of metabolic pathway genes in tea roots, stems, and leaves and revealing their distinctive features with regard to AA synthesis, transport, and degradation/recycling. Nitrogen assimilation dominated in the roots wherein glutamine (Gln), theanine, and arginine (Arg) were actively synthesized. Arg was transported into trunk roots and stems, together with Glu, Gln, and theanine as the major AAs in the xylem sap for long-distance root-to-leaf transport. Transcriptome analysis revealed that genes involved in Arg synthesis were highly expressed in roots, but those for Arg transport and degradation were highly expressed in stems and young leaves, respectively. CsGSIa transcripts were found in root meristem cells, root, stem and leaf vascular tissues, and leaf mesophyll where it appeared to participate in AA synthesis, transport, and recycling. Overexpression of CsGSIa in tea transgenic hairy roots and knockdown of CsGSIa in transgenic hairy roots and tea leaves produced higher and lower Gln and theanine than wild-type roots and leaves, respectively. This study provides comprehensive and new insights into AA metabolism and transport in the whole tea plant.

"Age" of tea: The impact of long-term storage on the aroma of Tuo tea and age prediction.

This study investigates the dynamic changes in the aroma profile of Tuo tea during long-term storage, a process not well understood yet critical to the formation of aged tea's unique characteristics. Aroma profiling of Tuo tea samples stored for 2 to 25 years was conducted using sensory evaluation and the HS-SPME/GC × GC-QTOFMS technique, revealing a progressive transition from fresh, fruity, and floral scents to more stale, woody, and herbal notes. Among 275 identified volatiles, 55 were correlated with storage duration (|r| > 0.8, p < 0.05), and 49 differential compounds (VIP > 1, FC > 1.2, FC < 0.833, p < 0.05) were identified across three storage stages (2-4, 5-10, and 13-25 years). Furthermore, theaspirane, eucalyptol, o-xylene, and 1-ethylidene-1H-indene were selected as potential markers of Tuo tea aging, incorporating the implementation of a Random Forest (RF) model. Additionally, our model exhibited high accuracy in predicting the age of Tuo tea within a prediction error range of -2.51 to 2.84 years. This research contributes to a comprehensive understanding of the impact of storage time on tea aroma and aids in the precise identification of tea age.

Macrophage scavenger receptor-A1 promotes skeletal muscle regeneration after hindlimb ischemia.

Macrophages mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia. Thus, it's necessary to exploit macrophages based therapeutic targets for ischemic disease. Here, we found mRNA level of SR-A1 was elevated in patients with critical limb ischemia by analysis of gene expression omnibus (GEO) database. Then we investigated the role and the underlined mechanisms of macrophage SR-A1 in a mouse HLI model. Compared with the SR-A1 fl/fl mice, the Lyz Cre/+/SR-A1 flox/flox (SR-A1 ΔMΦ) mice showed significantly lower laser doppler blood flow in the ischemic limb at day 7 after HLI. Consistently, histological analysis exhibited that ischemic limb of SR-A1 ΔMΦ mice displayed more sever and sustained necrotic morphology, inflammation and fibrosis, decreased vessel density and regeneration rate, compared with which of control SR-A1 fl/fl mice. Furthermore, restoration of wild-type myeloid cells to SR-A1 knock-out mice effectively relieved the doppler perfusion in the ischemic limb and restrained skeletal muscle damage 7 days post HLI. In line with in vivo findings, when co-cultivating macrophages with the mouse myoblast line C2C12, SR-A1 -/- bone marrow macrophage significantly inhibited myoblast differentiation in vitro. Mechanically, SR-A1 enhanced skeletal muscle regeneration response to HLI by inhibiting the oncostatin M (OSM) production via suppressed NF-κB signaling activation. These results indicates that SR-A1 is a promising candidate molecule to improve tissue repair and regeneration in peripheral ischemic arterial disease.

Effects of isolated scenting on the taste quality of broken green tea based on metabolomics.

Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate analysis were used to characterize the nonvolatile compounds of broken green tea and explore the effect of isolated scenting on metabolic profile and taste quality of broken green tea in this research. A total of 236 nonvolatile compounds were identified and 13 compounds were believed to be the key characteristic taste compounds of scented broken green tea. Meanwhile, the optimal isolated scenting time of broken green tea was determined to be 10 h based on the sensory evaluation and PLS results. The contents and types of flavonoids, organic acids and catechins lead to the difference of taste quality at different scenting times. Overall, these findings provided a theoretical basis for scenting to improve the taste of broken green tea, and provide a new idea for improving the taste of broken green tea.

Unmasking Bacterial Identities: Exploiting Silver Nanoparticle 'Masks' for Enhanced Raman Scattering in the Rapid Discrimination of Diverse Bacterial Species and Antibiotic-Resistant Strains.

Unraveling bacterial identity through Raman scattering techniques has been persistently challenging due to homogeneously amplified Raman signals across a wide variety of bacterial molecules, predominantly protein- or nucleic acid-mediated. In this study, we present an approach involving the use of silver nanoparticles to completely and uniformly "mask" adsorption on the surface of bacterial molecules through sodium borohydride and sodium chloride. This approach enables the acquisition of enhanced surface-enhanced Raman scattering (SERS) signals from all components on the bacterial surface, facilitating rapid, specific, and label-free bacterial identification. For the first time, we have characterized the identity of a bacterium, including its DNA, metabolites, and cell walls, enabling the accurate differentiation of various bacterial strains, even within the same species. In addition, we embarked on an exploration of the origin and variability patterns of the main characteristic peaks of Gram-positive and Gram-negative bacteria. Significantly, the SERS peak ratio was found to determine the inflection point of accelerated bacterial death upon treatment with antimicrobials. We further applied this platform to identify 15 unique clinical antibiotic-resistant bacterial strains, including five Escherichia coli strains in human urine, a first for Raman technology. This work has profound implications for prompt and accurate identification of bacteria, particularly antibiotic-resistant strains, thereby significantly enhancing clinical diagnostics and antimicrobial treatment strategies.

Varying ratios of M/G in alginate to modulate macrophages polarization and its application for wound healing in diabetic.

Alginate (SA) comprises repeating unis of ß-1, 4 linked ß-D-mannuronic acid (M) and α-L-guloronic acid (G) in varying proportions. The M/G ratio greatly impacts its anti-inflammatory properties in tissue healing wound, as less knowledge reported. This study examined the performances of both SA and SA hydrogel crosslinked with copper ions (SA-Cu) with different M/G ratios are studied. SA with higher M/G ratios stimulated macrophage migration and shifted from M0 to the pro-inflammatory Ml phenotype, while lower M/G ratios shifted from M1 to the pro-repair M2 phenotype. Furthermore, SA-Cu hydrogels with lower M/G ratios exhibited enhanced cross-linking degree, mechanical and rheological properties, as well Cu releasing rate. The reason may be attributed to a relative easy binding between Cu ions and G unit among Cu ions, M unit and G unit. In vitro cell evaluation showed that SA-Cu hydrogel with M/G ratio of 1:1 activated M2 macrophages and up-regulated anti-inflammatory cytokines expression more effectively than those of SA-Cu ratios (2:1) and (1:2). In vivo, SA-Cu hydrogel with M/G ratio of 1:1 expedited diabetic wound healing, accelerating infiltration and phenotype shift of M2 macrophages, and enhancing anti-inflammatory factors, epithelialization and collagen deposition in healing phases. This research highlights the significant role of M/G ratios in SA materials in influencing macrophage behavior and inflammatory responses, which would benefit its application field.

Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation.

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the "gut microbiota-barrier-liver axis" are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman's correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.

The Protective Effects of L-Theanine against Epigallocatechin Gallate-Induced Acute Liver Injury in Mice.

Epigallocatechin-3-gallate (EGCG) is a main bioactive constituent in green tea. Being a redox-active polyphenol, high-dose EGCG exhibits pro-oxidative activity and could cause liver injury. L-theanine is a unique non-protein amino acid in green tea and could provide liver-protective effects. The purpose of this study was to investigate the hepatoprotective effects of L-theanine on EGCG-induced liver injury and the underlying mechanisms. A total of 300 mg/kg L-theanine was administrated to ICR mice for 7 days. Then, the acute liver injury model was established through intragastric administration of 1000 mg/kg EGCG. Pretreatment with L-theanine significantly alleviated the oxidative stress and inflammatory response caused by high-dose EGCG through modulation of Nrf2 signaling and glutathione homeostasis. Furthermore, metabolomic results revealed that L-theanine protects mice from EGCG-induced liver injury mainly through the regulation of amino acid metabolism, especially tryptophan metabolism. These findings could provide valuable insights into the potential therapeutic applications of L-theanine and highlight the importance of the interactions between dietary components.

Characterization of key odorants in 'Baimaocha' black teas from different regions.

'Baimmaocha' is a distinctive resource for production of high-quality black tea, and its processed black tea has unique aroma characteristics. 190 volatile compounds were identified by comprehensive two-dimensional gas chromatography-olfactometry-quadrupole-time-of-flight mass spectrometry(GC × GC-O-Q-TOMS), and among them 23 compounds were recognized as key odorants contributing to forming different aroma characteristics in 'Baimaocha' black teas of Rucheng, Renhua, and Lingyun (RCBT, RHBT, LYBT). The odor activity value coupled with GC-O showed that methyl salicylate (RCBT), geraniol (RHBT), trans-ß-ionone and benzeneacetaldehyde (LYBT) might be the most definitive aroma compounds identified from their respective regions. Furthermore, PLS analysis revealed three odorants as significant contributors to floral characteristic, four odorants related to fruity attribute, four odorants linked to fresh attribute, and three odorants associated with roasted attribute. These results provide novel insights into sensory evaluation and chemical substances of 'Baimaocha' black tea and provide a theoretical basis for controlling and enhancement tea aroma quality.

Targeting TYK2 alleviates Rab27A-induced malignant progression of non-small cell lung cancer via disrupting IFNα-TYK2-STAT-HSPA5 axis.

Rab27A is a small GTPase-mediating exosome secretion, which participates in tumorigenesis of multiple cancer types. Understanding the biological role of Rab27A in non-small cell lung cancer (NSCLC) is of great importance for oncological research and clinical treatment. In this study, we investigate the function and internal mechanism of Rab27A in NSCLC. Results show that Rab27A is overexpressed in NSCLC, and regulates the tumor proliferation, migration, invasion, and cell motility in vitro and in vivo, and is negatively regulated by miR-124. Further research reveals that upregulated Rab27A can induce the production of IFNα in the medium by mediating exosome secretion. Then IFNα activates TYK2/STAT/HSPA5 signaling to promote NSCLC cell proliferation and metastasis. This process can be suppressed by TYK2 inhibitor Cerdulatinib. These results suggest that Rab27A is involved in the pathogenesis of NSCLC by regulating exosome secretion and downstream signaling, and inhibitors targeting this axis may become a promising strategy in future clinical practice.

Circular RNA Expression of Peripheral Blood Mononuclear Cells Associated with Risk of Acute Exacerbation in Smoking Chronic Obstructive Pulmonary Disease.

Purpose: Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening. Patients and Methods: We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The T-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators. Results: Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P<0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P<0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P<0.0001) as well as the year after (r=0.72, P<0.0001). AUC: 0.79, 95% CI: 0.1210-0.3209, P<0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: -0.1972--0.0739 (P <0.0001). Conclusion: This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.

Prediction model and assessment of malnutrition in patients with stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) combined with malnutrition results in decreased exercise capacity and a worse quality of life. We aimed to develop an observational case-control study to explore the effective and convenient method to identify potential individuals is lacking. This study included data from 251 patients with COPD and 85 participants in the control group. Parameters and body composition were compared between groups, and among patients with varied severity. The LASSO approach was employed to select the features for fitting a logistic model to predict the risk of malnutrition in patients with stable COPD. Patients with COPD exhibited significantly lower 6-min walk distance (6MWD), handgrip strength, fat-free mass index (FFMI), skeletal muscle mass (SMM) and protein. The significant predictors identified following LASSO selection included 6MWD, waist-to-hip ratio (WHR), GOLD grades, the COPD Assessment Test (CAT) score, and the prevalence of acute exacerbations. The risk score model yielded good accuracy (C-index, 0.866 [95% CI 0.824-0.909]) and calibration (Brier score = 0.150). After internal validation, the adjusted C-index and Brier score were 0.849, and 0.165, respectively. This model may provide primary physicians with a simple scoring system to identify malnourished patients with COPD and develop appropriate rehabilitation interventions.

The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study.

BACKGROUND: The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. RESULTS: COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis-COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. CONCLUSION: COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD.

Demethylzeylasteral (T-96) Alleviates Allergic Asthma via Inhibiting MAPK/ERK and NF-κB Pathway.

INTRODUCTION: Demethylzeylasteral (T-96), a new extract of Tripterygium wilfordii Hook F, exerted immunomodulatory properties in autoimmune diseases, but its effect on airway inflammatory diseases remains unclear. Our study aims to explore the protective effect and underlying mechanism of T-96 in allergic asthma. METHODS: The OVA-induced asthmatic mice were administered by gavage with T-96 (0.1 mg/10 g, 0.3 mg/10 g, or 0.6 mg/10 g) 1 h before each challenge. The airway hyperresponsiveness was assessed, pathological changes were evaluated by HE and PAS staining, and expressions of Th2 cytokines were determined by PCR and ELISA. The activation of MAPK/ERK and NF-κB pathway was assessed by western blot. RESULTS: T-96 significantly relieved airway hyperresponsiveness in asthmatic mice, evidenced by reduced airway resistance (Raw) and increased lung compliance dynamic compliance (Cdyn). Also, enhanced inflammatory infiltration and mucus hypersecretion were ameliorated in lungs of asthmatic mice following increasing doses of T-96 treatment, accompanied by decreased eosinophils in bronchoalveolar lavage fluid (BALF), IgE and OVA-specific IgE levels in serum, and downregulated IL-5 and IL-13 expressions in BALF and lung tissues as well. Notably, phosphorylation levels of p38 MAPK, ERK, and p65 NF-κB were obviously increased in asthmatic mice compared with the control group, which were then abrogated upon T-96 treatment. CONCLUSION: This study first revealed that T-96 alleviated allergic airway inflammation and airway hyperresponsiveness via inhibiting MAPK/ERK and NF-κB pathway. Thus, T-96 could potentially act as a new anti-inflammatory agent in allergic asthma.