Effect of lignin on the structure-property behavior of metal-coordinated and chemically crosslinked ethylene-propylene-diene-monomer composites.

The efficient development and utilization of green biomass-based macromolecule engineering materials are essential for the sustainable development of human civilization. In this study, lignin-based ethylene-propylene-diene-monomer (EPDM) composites with excellent mechanical performance were fabricated using a simple method. The effects of water-insoluble enzymatically hydrolyzed lignin (EL) and alkali lignin (KL) on the mechanical performance of the composites were investigated separately. The results showed that the tensile strength of EPDM reinforced with KL and EL increased to 24.5 MPa and 22.1 MPa, respectively, surpassing that of the carbon black (CB)-reinforced EPDM. After 72 h of thermo-oxidative aging, the retention rates of the tensile strength and elongation at break in the lignin-reinforced EPDM were much better than those formed with pure CB, indicating that lignin significantly improved the thermo-oxidative aging resistance of the composites. In summary, the Zn2+ coordination bonds formed between the interface of EPDM and lignin in lignin/CB/EPDM ternary composites effectively improved the mechanical performance and aging resistance of the composites. This study has significant implications for enhancing the utilization of lignin and green functional polymer materials.

Hypoxia­regulated exosomal miR­185 inhibits esophageal squamous cell carcinoma progression and predicts prognosis.

Despite advances in treatment and diagnosis, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains poor. MicroRNAs (miRNAs/miRs) are associated with prognosis in esophageal cancer, indicating that they may help guide treatment decisions. The aim of the present study was to explore exosomal miR-185 as a candidate prognostic biomarker and therapeutic target in ESCC, to investigate its biological function and clinical significance, and to ascertain the applicability of circulating exosomal miR-185 for the development of targeted drugs for ESCC treatment. A GeneChip miRNA array was used to compare exosomal miRNA expression in ESCC cell lines under hypoxia with those under normoxia. Exosomal miR-185 expression was then confirmed by reverse transcription-quantitative PCR. Patient background and prognosis were compared between high and low miR-185 expression groups. Functional analyses were performed to evaluate the antitumor effects of miR-185 in ESCC cells. Global Gene Set Enrichment Analysis of The Cancer Genome Atlas data was also performed, and differentially expressed exosomal miRNAs under hypoxia were identified compared to those under normoxia. Hypoxia markedly decreased the expression of exosomal miR-185 in KYSE-960 and T.Tn cell culture media. Overexpression of miR-185 suppressed the migration, invasion and colony-forming abilities of ESCC lines, and also suppressed cell cycle progression and promoted apoptosis after cisplatin treatment. Notably, high miR-185 expression was associated with signaling pathways related to cell death, DNA damage and p53. Furthermore, circulating exosomal miR-185 levels were associated with cN and cStage, and could predict progression-free survival and disease-specific survival of patients with ESCC after initial treatment. In conclusion, miR-185 holds potential as a prognostic biomarker and therapeutic target in ESCC.

Core microbes identification and synthetic microbiota construction for the production of Xiaoqu light-aroma Baijiu.

Baijiu production has relied on natural inoculated Qu as a starter culture, causing the unstable microbiota of fermentation grains, which resulted in inconsistent product quality across batches. Therefore, revealing the core microbes and constructing a synthetic microbiota during the fermentation process was extremely important for stabilizing product quality. In this study, the succession of the microbial community was analyzed by high-throughput sequencing technology, and ten core microbes of Xiaoqu light-aroma Baijiu were obtained by mathematical statistics, including Acetobacter, Bacillus, Lactobacillus, Weissella, Pichia,Rhizopus, Wickerhamomyces, Issatchenkia, Saccharomyces, and Kazachstania. Model verification showed that the core microbiota significantly affected the composition of non-core microbiota (P < 0.01) and key flavor-producing enzymes (R > 0.8, P < 0.01), thus significantly affecting the flavor of base Baijiu. Simulated fermentation validated that the core microbiota can reproduce the fermentation process and quality of Xiaoqu light-aroma Baijiu. The succession of bacteria was mainly regulated by acidity and ethanol, while the fungi, especially non-Saccharomyces cerevisiae, were mainly regulated by the initial dominant bacteria (Acetobacter, Bacillus, and Weissella). This study will play an important role in the transformation of Xiaoqu light-aroma Baijiu fermentation from natural fermentation to controlled fermentation and the identification of core microbes in other fermented foods.

Ultrasound-Responsive Aligned Piezoelectric Nanofibers Derived Hydrogel Conduits for Peripheral Nerve Regeneration.

Nerve guidance conduits (NGCs) are considered as promising treatment strategy and frontier trend for peripheral nerve regeneration, while their therapeutic outcomes are limited by the lack of controllable drug delivery and available physicochemical cues. Herein, novel aligned piezoelectric nanofibers derived hydrogel NGCs with ultrasound (US)-triggered electrical stimulation (ES) and controllable drug release for repairing peripheral nerve injury are proposed. The inner layer of the NGCs is the barium titanate piezoelectric nanoparticles (BTNPs)-doped polyvinylidene fluoride-trifluoroethylene [BTNPs/P(VDF-TrFE)] electrospinning nanofibers with improved piezoelectricity and aligned orientation. The outer side of the NGCs is the thermoresponsive poly(N-isopropylacrylamide) hybrid hydrogel with bioactive drug encapsulation. Such NGCs can not only induce neuronal-oriented extension and promote neurite outgrowth with US-triggered wireless ES, but also realize the controllable nerve growth factor release with the hydrogel shrinkage under US-triggered heating. Thus, the NGC can positively accelerate the functional recovery and nerve axonal regeneration of rat models with long sciatic nerve defects. It is believed that the proposed US-responsive aligned piezoelectric nanofibers derived hydrogel NGCs will find important applications in clinic neural tissue engineering.

Aggregation-induced emission photosensitizer for antibacterial therapy of methicillin-resistant Staphylococcus aureus.

A cationic aggregation-induced emission photosensitizer (AIE-PS) MNNPyBB has been reported to have antibacterial effects against both Gram-positive and Gram-negative bacteria. The bacterial kill mechanism has been investigated and elucidated. In a methicillin-resistant Staphylococcus aureus subcutaneous infection model, wound closure has been achieved with normal re-epithelialization and preserved skin morphology.

Fortifying nematode resistance through susceptibility gene inactivation.

The predominant genetic defense mechanism against soybean cyst nematode (SCN) in 95% of the North America market is under threat by virulent SCN populations. Usovsky et al. identified GmSNAP02 as an SCN susceptibility gene through fine-mapping of unique bi-parental populations. Loss-of-function of GmSNAP02 confers enhanced resistance to more virulent SCN.

Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke.

Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment.

T6SS and T4SS redundantly secret effectors to govern the virulence and bacterial competition in Pectobacterium PccS1.

The previous studies revealed that the type VI secretion system (T6SS) has an essential role in bacterial competition and virulence in many gram-negative bacteria. However, the role of T6SS in virulence in Pectobacterium atrosepticum remains controversial. We examined a closely related strain, PccS1, and discovered that its T6SS comprises a single copy cluster of 17 core genes with a higher identity to homologs from P. atrosepticum. Through extensive phenotypic and functional analyses of over 220 derivatives of PccS1, we found that three of the five VgrGs could be classified into group I VgrGs. These VgrGs interacted with corresponding DUF4123 domain proteins, which were secreted outside of the membrane and were dependent on either T6SS or T4SS. This interaction directly governed virulence and competition. Meanwhile, supernatant proteomic analyses with stains defective in T6SS or/and T4SS confirm that effectors, such as FhaB, were secreted redundantly to control the virulence and suppress host callose-deposition in the course of infection. Notably, this redundant secretion mechanism between T6SS and T4SS is believed to be the first of its kind in bacteria.

Regulation of Root Exudation in Wheat Plants in Response to Alkali Stress.

Soil alkalization is an important environmental factor limiting crop production. Despite the importance of root secretion in the response of plants to alkali stress, the regulatory mechanism is unclear. In this study, we applied a widely targeted metabolomics approach using a local MS/MS data library constructed with authentic standards to identify and quantify root exudates of wheat under salt and alkali stresses. The regulatory mechanism of root secretion in alkali-stressed wheat plants was analyzed by determining transcriptional and metabolic responses. Our primary focus was alkali stress-induced secreted metabolites (AISMs) that showed a higher secretion rate in alkali-stressed plants than in control and salt-stressed plants. This secretion was mainly induced by high-pH stress. We discovered 55 AISMs containing -COOH groups, including 23 fatty acids, 4 amino acids, 1 amino acid derivative, 7 dipeptides, 5 organic acids, 9 phenolic acids, and 6 others. In the roots, we also discovered 29 metabolites with higher levels under alkali stress than under control and salt stress conditions, including 2 fatty acids, 3 amino acid derivatives, 1 dipeptide, 2 organic acids, and 11 phenolic acids. These alkali stress-induced accumulated carboxylic acids may support continuous root secretion during the response of wheat plants to alkali stress. In the roots, RNAseq analysis indicated that 5 6-phosphofructokinase (glycolysis rate-limiting enzyme) genes, 16 key fatty acid synthesis genes, and 122 phenolic acid synthesis genes have higher expression levels under alkali stress than under control and salt stress conditions. We propose that the secretion of multiple types of metabolites with a -COOH group is an important pH regulation strategy for alkali-stressed wheat plants. Enhanced glycolysis, fatty acid synthesis, and phenolic acid synthesis will provide more energy and substrates for root secretion during the response of wheat to alkali stress.

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages.

Echinatin is an active ingredient in licorice, a traditional Chinese medicine used in the treatment of inflammatory disorders. However, the protective effect and underlying mechanism of echinatin against acute lung injury (ALI) is still unclear. Herein, we aimed to explore echinatin-mediated anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated ALI and its molecular mechanisms in macrophages. In vitro, echinatin markedly decreased the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated murine MH-S alveolar macrophages and RAW264.7 macrophages by suppressing inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression. Furthermore, echinatin reduced LPS-induced mRNA expression and release of interleukin-1ß (IL-1ß) and IL-6 in RAW264.7 cells. Western blotting and CETSA showed that echinatin repressed LPS-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways through targeting transforming growth factor-beta-activated kinase 1 (TAK1). Furthermore, echinatin directly interacted with Kelch-like ECH-associated protein 1 (Keap1) and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to enhance heme oxygenase-1 (HO-1) expression. In vivo, echinatin ameliorated LPS-induced lung inflammatory injury, and reduced production of IL-1ß and IL-6. These findings demonstrated that echinatin exerted anti-inflammatory effects in vitro and in vivo, via blocking the TAK1-MAPK/NF-κB pathway and activating the Keap1-Nrf2-HO-1 pathway.

Selective Oxidation of sp-Bonded Carbon in Graphdiyne/Carbon Nanotubes Heterostructures to Form Dominant Epoxy Groups for Two-Electron Oxygen Reduction.

Two-electron oxygen reduction reaction (2e- ORR) is of great significance to H2O2 production and reversible nonalkaline Zn-air batteries (ZABs). Multiple oxygen-containing sp2-bonded nanocarbons have been developed as electrocatalysts for 2e- ORR, but they still suffer from poor activity and stability due to the limited and mixed active sites at the edges as well as hydrophilic character. Herein, graphdiyne (GDY) with rich sp-C bonds is studied for enhanced 2e- ORR. First, computational studies show that GDY has a favorable formation energy for producing five-membered epoxy ring-dominated groups, which is selective toward the 2e- ORR pathway. Then based on the difference in chemical activity of sp-C bonds in GDY and sp2-C bonds in CNTs, we experimentally achieved conductive and hydrophobic carbon nanotubes (CNTs) covering O-modified GDY (CNTs/GDY-O) through a mild oxidation treatment combined with an in situ CNTs growth approach. Consequently, the CNTs/GDY-O exhibits an average Faraday efficiency of 91.8% toward H2O2 production and record stability over 330 h in neutral media. As a cathode electrocatalyst, it greatly extends the lifetime of 2e- nonalkaline ZABs at both room and subzero temperatures.

Isolation and Characterization of the Vascular Endothelial Growth Factor Receptor Targeting ScFv Antibody Fragments Derived from Phage Display Technology.

Angiogenesis, as a tumor hallmark, plays an important role in the growth and development of the tumor vasculature system. There is a huge amount of evidence suggesting that the vascular endothelial growth factor receptor (VEGFR-2)/VEGF-A axis is one of the main contributors to tumor angiogenesis and metastasis. Thus, inhibition of the VEGFR-2 signaling pathway by anti-VEGFR-2 mAb can retard tumor growth. In this study, we employ phage display technology and solution-phase biopanning (SPB) to isolate specific single-chain variable fragments (scFvs) against VEGFR-2 and report on the receptor binding characteristics of the candidate scFvs A semisynthetic phage antibody library to isolate anti-VEGFR-2 scFvs through an SPB performed with decreasing concentrations of the VEGFR-2-His tag and VEGFR-2-biotin. After successful expression and purification, the specificity of the selected scFv clones was further analyzed by enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunoblotting. The competition assay was undertaken to identify the VEGFR-2 receptor-blocking properties of the scFvs. Furthermore, the molecular binding characteristics of candidate scFvs were extensively studied by peptide-protein docking. Polyclonal ELISA analysis subsequent to four rounds of biopanning showed a significant enrichment of VEGFR-2-specific phage clones by increasing positive signals from the first round toward the fourth round of selection. The individual VEGFR-2-reactive scFv phage clones were identified by monoclonal phage ELISA. The sequence analysis and complementarity-determining region alignment identified the four unique anti-VEGFR-2-scFv clones. The soluble and purified scFvs displayed binding activity against soluble and cell-associated forms of VEGFR-2 protein in the ELISA and flow cytometry assays. Based on the inference from the molecular docking results, scFvs D3, E1, H1, and E9 recognized domains 2 and 3 on the VEGFR-2 protein and displayed competition with VEGF-A for binding to VEGFR-2. The competition assay confirmed that scFvs H1 and D3 can block the VEGFR-2/VEGF-A interaction. In conclusion, we identified novel VEGFR-2-blocking scFvs that perhaps exhibit the potential for angiogenesis inhibition in VEGFR-2-overexpressed tumor cells.

Insight into the microbial community of denitrification process using different solid carbon sources: Not only bacteria.

There is a lack of understanding about the bacterial, fungal and archaeal communities' composition of solid-phase denitrification (SPD) systems. We investigated four SPD systems with different carbon sources by analyzing microbial gene sequences based on operational taxonomic unit (OTU) and amplicon sequence variant (ASV). The results showed that the corncob-polyvinyl alcohol sodium alginate-polycaprolactone (CPSP, 0.86±0.04 mg NO3--N/(g·day)) and corncob (0.85±0.06 mg NO3--N/(g·day)) had better denitrification efficiency than polycaprolactone (PCL, 0.29±0.11 mg NO3--N/(g·day)) and polyvinyl alcohol-sodium alginate (PVA-SA, 0.24±0.07 mg NO3--N/(g·day)). The bacterial, fungal and archaeal microbial composition was significantly different among carbon source types such as Proteobacteria in PCL (OTU: 83.72%, ASV: 82.49%) and Rozellomycota in PVA-SA (OTU: 71.99%, ASV: 81.30%). ASV methods can read more microbial units than that of OTU and exhibit higher alpha diversity and classify some species that had not been identified by OTU such as Nanoarchaeota phylum, unclassified_ f_ Xanthobacteraceae genus, etc., indicating ASV may be more conducive to understand SPD microbial communities. The co-occurring network showed some correlation between the bacteria fungi and archaea species, indicating different species may collaborate in SPD systems. Similar KEGG function prediction results were obtained in two bioinformatic methods generally and some fungi and archaea functions should not be ignored in SPD systems. These results may be beneficial for understanding microbial communities in SPD systems.

Mitochondria-mediated self-cycling nanoreactor enabling uninterrupted oxidative damage for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), which employs intracellular H2O2 to produce toxic hydroxyl radicals to kill cancer cells, has received great attention due to its specificity to tumors. However, the relatively insufficient endogenous H2O2 and the short-lifetime and limited diffusion distance of •OH compromise the therapeutic efficacy of CDT. Mitochondria, which play crucial roles in oncogenesis, are highly vulnerable to elevated oxidative stress. Herein, we constructed a mitochondria-mediated self-cycling system to achieve high dose of •OH production through continuous H2O2 supply. Cinnamaldehyde (CA), which can elevate H2O2 level in the mitochondria, was loaded in Cu(II)-containing metal organic framework (MOF), termed as HKUST-1. After actively targeting mitochondria, the intrinsic H2O2 in mitochondria of cancer cells could induce degradation of MOF, releasing the initial free CA. The released CA further triggered the upregulation of endogenous H2O2, resulting in the subsequent adequate release of CA and the final burst growth of H2O2. The cycle process greatly promoted the Fenton-like reaction between Cu2+ and H2O2 and induced long-term high oxidative stress, achieving enhanced chemodynamic therapy. In a word, we put forward an efficient strategy for enhanced chemodynamic therapy.

Long-term, observational, real-world study of dupilumab for the treatment of moderate-to-severe atopic dermatitis: a 52-week single-center retrospective analysis in China.

For dupilumab, real-world long-term follow-up data remain scarce, and studies on optimized treatment modes as well as drug survival rate and its predictors are lacking. To explore the effectiveness of different treatment modes of dupilumab and to understand the drug survival rates of dupilumab in China and its predictive factors. This retrospective study included patients with moderate-to-severe AD who received dupilumab treatment. Their clinical data were collected and analyzed. Compared with baseline, the SCORing Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), numerical rating scale (NRS), and Atopic Dermatitis Control Tool (ADCT) scores significantly decreased at 12, 24, and 52 weeks (p < 0.0001), and the continuous medication group had more significant improvements in SCORAD, EASI, NRS, and ADCT scores at 52 weeks than the noncontinuous medication group (p < 0.05). The 6-month and 1-year drug survival rates of dupilumab were 59.7% and 51.9%, respectively. The most common reason for treatment discontinuation was the satisfactory control of AD. Patients with adult-onset AD (adjusted odds ratio [OR]: 0.15, 95% confidence interval [CI]: 0.03-0.73) , not complicated by other systemic diseases (adjusted OR: 0.17, 95% CI: 0.04-0.84) and eosinophilia at baseline (adjusted OR: 3.71, 95% CI: 1.12-12.26) had a higher probability of drug discontinuation. In real-world practice in China, dupilumab has exhibited good long-term effectiveness and safety for the treatment of moderate-to-severe AD, and continuous administration can benefit patients in the long term.

Cisplatin-activated and hemoglobin-mediated injectable hydrogel system for antitumor chemodynamic and chemotherapy.

Low specificity and hypoxia-induced drug resistance are significant challenges in traditional cancer treatment. To enhance the anticancer efficacy, an injectable hydrogel system is developed through the formation of dynamic covalent bonds in hyaluronic acid, allowing for localized controlled release of drugs. This system also utilizes double-stranded DNA sequences for the intercalation delivery of the chemotherapeutic drug, enabling a multifaceted approach to therapy. Cisplatin not only serves as a chemotherapy drug but also acts as a catalyst for chemodynamic therapy (CDT) to initiate CDT cascades by creating hydrogen peroxide for the Fenton reaction. Hemoglobin, enclosed in PLGA nanoparticles, provides ferrous ions that react with hydrogen peroxide in an acidic environment, yielding hydroxyl radicals that induce cancer cell death. Additionally, oxygen released from hemoglobin mitigates hypoxia-induced chemoresistance, bolstering overall anticancer efficacy. Results demonstrate the shear-thinning properties and injectability of the hydrogel. Cisplatin elevates intracellular hydrogen peroxide levels in tumor cells, while hemoglobin efficiently releases ferrous ions and generates reactive oxygen species (ROS) in the presence of hydrogen peroxide. In in vitro and in vivo study, the combinational use of chemo- and chemodynamic therapies achieves a synergistic anticancer effect on combating glioblastoma. In summary, our CDT-based hydrogel, activated by endogenous cues and mediated by chemo drugs, spontaneously produces ROS and ameliorates the adverse tumor microenvironment with rational and selective antitumor strategies.

A comprehensive meta-analysis on the association of SGLT2is and GLP-1RAs with vascular diseases, digestive diseases and fractures.

AIM: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are two new classes of antidiabetic agents. We aimed to evaluate the association between these two drug classes and risk of various vascular diseases, digestive diseases and fractures. METHODS: Large randomized trials of SGLT2is and GLP-1RAs were included. Outcomes of interest were the various serious adverse events related to vascular diseases, digestive diseases and fractures. We performed meta-analyses using synthesize risk ratio (RR) and 95% confidence interval (CI) as effect size. RESULTS: We included 27 large trials. SGLT2is had significant association with less hypertension (RR 0.70, 95% CI 0.54-0.91), hypertensive crisis (RR 0.63, 95% CI 0.47-0.84), varicose vein (RR 0.34, 95% CI 0.13-0.92), and vomiting (RR 0.55, 95% CI 0.31-0.97); but more spinal compression fracture (RR 1.73, 95% CI 1.02-2.92) and tibia fracture. GLP-1RAs had significant association with more deep vein thrombosis (RR 1.92, 95% CI 1.23-3.00), pancreatitis (RR 1.54, 95% CI 1.07-2.22), and cholecystitis acute (RR 1.51, 95% CI 1.08-2.09); but less rib fracture (RR 0.59, 95% CI 0.35-0.97). Sensitivity analyses suggested that our findings were robust. CONCLUSIONS: SGLT2is may have protective effects against specific vascular and digestive diseases, whereas they may increase the incidence of site-specific fractures (e.g., spinal compression fracture). GLP-1RAs may have protective effects against site-specific fractures (i.e., rib fracture), whereas they may increase the incidence of specific vascular and digestive diseases. These findings may help to make a choice between SGLT2is and GLP-1RAs in clinical practice.

Pharmaceutical treatment status of patients with COPD in the community based on medical Internet of Things: a real-world study.

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.

Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation.

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.