Proteomics and metabolomics analyses of urine for investigation of gallstone disease in a high-altitude area.

BACKGROUND: The incidence of gallstones is high in Qinghai Province. However, the molecular mechanisms underlying the development of gallstones remain unclear. METHODS: In this study, we collected urine samples from 30 patients with gallstones and 30 healthy controls. The urine samples were analysed using multi-omics platforms. Proteomics analysis was conducted using data-independent acquisition, whereas metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Among the patients with gallstones, we identified 49 down-regulated and 185 up-regulated differentially expressed proteins as well as 195 up-regulated and 189 down-regulated differentially expressed metabolites. Six pathways were significantly enriched: glycosaminoglycan degradation, arginine and proline metabolism, histidine metabolism, pantothenate and coenzyme A biosynthesis, drug metabolism-other enzymes, and the pentose phosphate pathway. Notably, 10 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers. CONCLUSION: The findings of our metabolomics and proteomics analyses provide new insights into novel biomarkers for patients with cholelithiasis in high-altitude areas.

Integration of bile proteomics and metabolomics analyses reveals novel insights into different types of gallstones in a high-altitude area.

BACKGROUND: To explore the pathogenesis of different subtypes of gallstones in high-altitude populations from a molecular perspective. METHODS: We collected bile samples from 20 cholesterol gallstone disease (CGD) patients and 20 pigment gallstone disease (PGD) patients. Proteomics analysis was performed by LC/MS DIA, while metabolomics analysis was performed by UPLC- Q-TOF/MS. RESULTS: We identified 154 up-regulated and 196 down-regulated differentially expressed proteins, which were significantly enriched in neurodegenerative diseases, energy metabolism, amino acid metabolism etc. In metabolomics analysis, 20 up-regulated and 63 down-regulated differentially expressed metabolites were identified, and they were significantly enriched in vitamin B6 metabolism. Three pathways of integrated proteomics and metabolomics were significantly enriched: porphyrin and chlorophyll metabolism, riboflavin metabolism and aminoacyl-tRNA biosynthesis. Remarkably, 7 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers. CONCLUSION: The findings of our metabolomics and proteomics analyses help to elucidate the underlying mechanisms of gallstone formation in high-altitude populations.

Accuracy of subtraction fractional flow reserve with computed tomography in identifying early revascularization in patients with coronary artery disease.

OBJECTIVES: The diagnostic performance of fractional flow reserve with computed tomography (FFR-CT) is affected by the presence of calcified plaque. Subtraction can remove the influence of calcification in coronary computed tomography angiography (CCTA) to increase confidence in the diagnosis of coronary artery stenosis. Our purpose is to investigate the accuracy of post-subtraction FFR-CT in predicting early revascularization. DESIGN: Based on CCTA data of 237 vessels from 79 patients with coronary artery disease, subtraction CCTA images were obtained at a local post-processing workstation, and the conventional and post-subtraction FFR-CT measurements and the difference in proximal and distal FFR-CT values of the narrowest segment of the vessel (ΔFFR-CT) were analyzed for their accuracy in predicting early coronary artery hemodynamic reconstruction. RESULTS: With FFR-CT ≤ 0.8 as the criterion, the accuracy of conventional and post-subtraction FFR-CT measurements in predicting early revascularization was 73.4% and 77.2% at the patient level, and 64.6% and 72.2% at the vessel level, respectively. The specificity of post-subtraction FFR-CT measurements was significantly higher than that of conventional FFR-CT at both the patient and vessel levels (P of 0.013 and 0.015, respectively). At the vessel level, the area under the curve of receiver operating characteristic was 0.712 and 0.797 for conventional and post-subtraction ΔFFR-CT, respectively, showing a difference (P = 0.047), with optimal cutoff values of 0.07 and 0.11, respectively. CONCLUSION: The post-subtraction FFR-CT measurements enhance the specificity in predicting early revascularization. The post-subtraction ΔFFR-CT value of the stenosis segment > 0.11 may be an important indicator for early revascularization.

Advances, Applications, and Emerging Opportunities in Electrostatic Hydrogels.

Polyelectrolyte complex (PEC) hydrogels, which self-assemble via complexation of oppositely charged block polymers, have recently risen to prominence owing to their unique characteristics such as hierarchical microstructure, tunable bulk properties, and the ability to precisely assimilate charged cargos (i.e., proteins and nucleic acids). Significant foundational research has delineated the structure-property relationship of PEC hydrogels for use in a wide range of applications. In this Perspective, we summarize key findings on the microstructure and bulk properties of PEC hydrogels and discuss how intrinsic and extrinsic factors can be tuned to create specifically tailored PEC hydrogels with desired properties. We highlight successful applications of PEC hydrogels while offering insight into strategies to overcome their shortcomings and elaborate on emerging opportunities in the field of electrostatic self-assemblies.

Factors associated with symptomatic intracranial haemorrhage after intravenous thrombolysis in severe white matter lesions: a retrospective analysis.

BACKGROUND AND PURPOSE: White matter lesions (WMLs) are thought to cause damage to the blood-brain barrier, thereby aggravating bleeding after intravenous thrombolysis. However, the risk factors for symptomatic cerebral haemorrhage after thrombolysis are still unclear. This study explored the risk factors for bleeding in patients with severe WMLs after intravenous thrombolysis to prevent bleeding as soon as possible. METHODS: A large single-centre observational study conducted a retrospective analysis of intravenous thrombolysis in patients with severe WMLs from January 2018 to March 2021. According to whether symptomatic cerebral haemorrhage occurred, the patients were divided into two groups, and then statistical analysis was performed. RESULTS: After a retrospective analysis of the data of nearly 1000 patients with intravenous thrombolysis and excluding invalid information, 146 patients were included, of which 23 (15.8%) patients had symptomatic cerebral haemorrhage. Univariate analysis showed that a history of hypertension (20% vs 4.9%, p=0.024), hyperlipidaemia (38.7% vs 9.6%, p<0.001), the National Institutes of Health Stroke Scale (NIHSS) score before thrombolysis (median 17 vs 6, p<0.001), low-density lipoprotein levels (median 2.98 vs 2.44, p=0.011), cholesterol levels (mean 4.74 vs 4.22, p=0.033), platelet count (median 161 vs 191, p=0.031), platelet distribution width (median 15.2 vs 12.1, p=0.001) and sodium ion levels (median 139.81 vs 138.67, p=0.043) were significantly associated with symptomatic cerebral haemorrhage. Further multivariate logistic regression analysis showed that hyperlipidaemia (OR=9.069; 95% CI 2.57 to 32.07; p=0.001) and the NIHSS score before thrombolysis (OR=1.33; 95% CI 1.16 to 1.52; p<0.001) were comprehensive risk factors for symptomatic cerebral haemorrhage. CONCLUSION: Hyperlipidaemia and the NIHSS score before thrombolysis are independent risk factors for bleeding after intravenous thrombolysis in patients with severe WMLs. Delaying the onset of white matter and preventing risk factors for bleeding will help improve the prognosis of cerebral infarction and reduce mortality. These risk factors need to be further evaluated in future studies.

Proteoglycans in the periodontium: A review with emphasis on specific distributions, functions, and potential applications.

Proteoglycans (PGs) are largely glycosylated proteins, consisting of a linkage sugar, core proteins, and glycosaminoglycans (GAGs). To date, more than 40 kinds of PGs have been identified, and they can be classified as intracellular, cell surface, pericellular, and extracellular PGs according to cellular locations. To illustrate, extracellular PGs are known for regulating the homeostasis of the extracellular matrix; cell-surface PGs play a role in mediating cell adhesion and binding various growth factors. In the field of periodontology, PGs are implicated in cellular proliferation, migration, adhesion, contractility, and anoikis, thereby exerting a profound influence on periodontal tissue development, wound repair, the immune response, biomechanics, and pathological process. Additionally, the expression patterns of some PGs are dynamic and cell-specific. Therefore, determining the roles and spatial-temporal expression patterns of PGs in the periodontium could shed light on treatments for wound healing, tissue regeneration, periodontitis, and gingival overgrowth. In this review, close attention is paid to the distributions, functions, and potential applications of periodontal PGs. Related genetically modified animal experiments and involved signal transduction cascades are summarized for improved understanding of periodontal PGs. To date, however, there is a large amount of speculation on this topic that requires rigorous experiments for validation.

High manganese exposure decreased the risk of high triglycerides in workers: a cross-sectional study.

BACKGROUND: Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear. METHODS: This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m3. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m3. Mn-TWA levels and dyslipidaemia were assessed. RESULTS: After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p <  0.01). The results of males and females were consistent (OR = 0.53; 95% CI: 0.34, 0.81; p <  0.01) and (OR = 0.47; 95% CI: 0.24, 0.94; p <  0.01), respectively. By performing interactions analyses of workers overall, we observed no significant interactions among confounders. Mn-TWA levels and pack-years on high TG risk (relative excess risk for the interactions (RERI = 2.29, 95% CI: - 2.07, 6.66), (RERI) = 2.98, 95% CI: - 2.30, 8.26). Similarly, smoking status, drinking status, high-fat diet frequency, and Waist-to-Hip Ratio (WHR) showed non-significant interactions with Mn-TWA levels on high TG risk. CONCLUSIONS: This research indicates that high Mn exposure was negatively related to high TG risk in workers.

Occupational exposure to manganese and risk of creatine kinase and creatine kinase-MB elevation among ferromanganese refinery workers.

BACKGROUND: Elevated exposure to manganese (Mn) could induce cardiovascular dysfunction. However, limited research is available on the effects of occupational Mn exposure on myocardial enzymes. We aimed to evaluate the relationships between Mn exposure and myocardial enzyme elevation among Mn-exposed workers. METHODS: Data were from a follow-up investigation of a Mn-exposed workers healthy cohort in 2017. A total of 744 workers were divided into low-exposure and high-exposure groups according to Mn time-weighted average (Mn-TWA) of less than or equal to 0.15 mg/m3 or greater than 0.15 mg/m3 , respectively. Serum levels of myocardial enzymes, including creatine kinase (CK) and creatine kinase-MB (CK-MB), lactic dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate transaminase, were assessed, as well as airborne Mn exposure levels. RESULTS: After adjustment for sex, body mass index, seniority, education, current smoking status, current drinking status, and hypertension, Mn-TWA levels were positively associated with the risk of CK elevation (odds ratio [OR] = 1.47 (95% confidence interval [CI]: 1.18-1.83) per interquartile range [IQR] increase), and risk of CK-MB elevation [OR = 1.57 (95% CI: 1.03-2.38) per IQR increase]. In a stratified analysis, Mn-TWA levels were positively correlated with CK elevation in workers of seniority greater than 19 years, male workers, current smokers, and drinkers. CONCLUSION: Our results suggest that occupational exposure to Mn is associated with increased risk of CK and CK-MB elevation. The potential mechanisms of the associations between airborne exposure to Mn and increased risk of these myocardial enzyme elevations warrant further investigation.

Establishment and evaluation of chronic obstructive pulmonary disease model by chronic exposure to motor vehicle exhaust combined with lipopolysaccharide instillation.

NEW FINDINGS: What is the central question of this study? In this study, by using motor vehicle exhaust (MVE) exposure with or without lipopolysaccharide (LPS) instillation, we established, evaluated and compared MVE, LPS and MVE+LPS treatment-induced chronic obstructive pulmonary disease (COPD) models in mice. What is the main finding and its importance? Our study demonstrated that the combination of chronic exposure to MVE with early LPS instillation can establish a mouse model with some features of COPD, which will allow researchers to investigate the underlying molecular mechanisms linking air pollution and COPD pathogenesis. ABSTRACT: Although it is well established that motor vehicle exhaust (MVE) has a close association with the occurrence and exacerbation of chronic obstructive pulmonary disease (COPD), very little is known about the combined effects of MVE and intermittent or chronic subclinical inflammation on COPD pathogenesis. Therefore, given the crucial role of inflammation in the development of COPD, we wanted to establish an animal model of COPD using both MVE exposure and airway inflammation, which could mimic the clinical pathological changes observed in COPD patients and greatly benefit the study of the molecular mechanisms of COPD. In the present study, we report that mice undergoing chronic exposure to MVE and intratracheal instillation of lipopolysaccharide (LPS) successfully established COPD, as characterized by persistent air flow limitation, airway inflammation, inflammatory cytokine production, emphysema and small airway remodelling. Moreover, the mice showed significant changes in ventricular and vascular pathology, including an increase in right ventricular pressure, right ventricular hypertrophy and remodelling of pulmonary arterial walls. We have thus established a new mouse COPD model by combining chronic MVE exposure with early intratracheal instillation of LPS, which will allow us to study the relationship between air pollution and the development of COPD and to investigate the underlying molecular mechanisms.

Follow-up of the manganese-exposed workers healthy cohort (MEWHC) and biobank management from 2011 to 2017 in China.

BACKGROUND: Long-term excess exposure to environmental manganese (Mn) can lead to multi-system damage, especially in occupational populations. Therefore, we established a manganese-exposed workers healthy cohort (MEWHC), focusing on the systemic health effects related to Mn exposure. Here, we aimed to describe the follow-up activity for the MEWHC study and establish a standardized biological sample bank for the scientific management of high-quality biospecimens and the attached data from 2011 to 2017. METHODS: Baseline examinations for onsite workers were conducted, and the biobank for the MEWHC was first established in 2011; follow-up examinations occurred four times between July 2012 and November 2017. All questionnaires, clinical data and biological samples were routinely collected during each follow-up activity. Additional workers were recruited in 2016, which further enriched the resources of the biobank. RESULTS: A total of 2359 onsite workers and 612 retired workers at a ferromanganese refinery were enrolled in the prospective cohort, and their biological samples were obtained in the preliminary baseline survey and the follow-up investigation, including 2971 blood and urine samples from the cohort. In addition, 1524 hair samples, 1404 nail (toe and finger nails) and 1226 fecal samples were also collected. All specimens were preserved in the biobank, and the data were scientifically managed using a computer system. CONCLUSIONS: The MEWHC study in China provides an effective way to obtain biological samples such as plasma, DNA, hair and urine for storage in a biobank for further study. The standardized management of various samples is crucial for accessing high-quality biospecimens.

Study Design and Interim Outcomes of Guangzhou Institute of Respiratory Disease COPD Biobank.

BACKGROUND: GIRD COPD Biobank is a multicenter observational study blood-based database with local characteristics, in order to investigate the causes, risk factors, pathogenesis, prevalence patterns and trends of COPD and promote new pathogenic insights in China. METHODS: We enrolled 855 clinically COPD patients and 660 controls with normal lung function. Extensive data collection has been undertaken with questionnaires, clinical measurements, and collection and storage of blood specimens, following Standard Operating Procedures (SOP). All surveys had similar quality controls, supervisions, and training of the investigator team. RESULTS: Since September 2010, a total of 1515 subjects (1116 [73.7%] males; 855 [56.4%] diagnosed with COPD) were enrolled. Analyses of the design and interim results of the GIRD COPD Biobank Study identified patients with COPD were older, lower educational level, a longer history of pack-year smoking, less in kitchen fan usage, X-ray exposure, and history of disease (P < 0.01 for all); Most of the COPD subjects belonged to moderately severe or worse, stratified according to Global Lung Function Initiative (GLI); COPD patients had relatively more co-morbidities than controls; Environmental hazard exposures might be the main contributors to the reported respiratory symptoms; Cold air, haze, and influenza acted the top three factors to induce respiratory symptoms in both COPD cases and controls. CONCLUSION: The GIRD COPD Biobank Study has the potential to provide substantial novel insights into the genetics, biomarkers, environmental and lifestyle aspects of COPD. It is expected to provide new insights for pathogenesis and the long-term progression of COPD.

Bone morphogenetic protein 4 inhibits liposaccharide-induced inflammation in the airway.

Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-ß superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-α. BMP4 mutant (BMP4(+/-) ) mice presented with more severe lung inflammation in response to LPS or Pseudomonas aeruginosa, and lower bacterial load compared with that in BMP4(+/+) mice. Knockdown of BMP4 by siRNA increased LPS and TNF-α-induced IL-8 expression in 16HBE human airway epithelial cells and in primary human bronchial epithelial cells. Similarly, peritoneal macrophages from BMP4(+/-) mice produced greater levels of TNF-α and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4(+/+) mice. Administration of exogenous BMP4 attenuated the upregulation of TNF-α, IL-8, or KC induced by LPS and/or TNF-α in airway epithelial cells, and peritoneal macrophages. Finally, partial deficiency of BMP4 in BMP4(+/-) mice protected the animals from restrictive lung function reduction upon chronic LPS exposure. These results indicate that BMP4 plays an important anti-inflammatory role, controlling the strength and facilitating the resolution of acute lung inflammation; yet, BMP4 also contributes to lung function impairment during chronic lung inflammation.

[Nose-only cigarette smoke exposure plus airway lipopolysaccharide inhalation induced chronic obstructive pulmonary disease and associated pulmonary hypertension in mice].

OBJECTIVE: To establish a mouse model of chronic obstructive pulmonary disease (COPD) and associated pulmonary hypertension (COPD-PH) induced by nose-only cigarette smoking exposure plus airway lipopolysaccharide (LPS) inhalation. METHODS: There were 24 male C57B6 mice divided into a control group and a model group at random. The model group was given LPS by intranasal inhalation on day 1 and day 14 and exposed to the cigarette smoke in a nose-only exposure system, while the control group was given physiological saline and exposed to normal air. The model establishment was evaluated according the following parameters: the lung function and the right heart pressure, the total and differential cell numbers in bronchial alveolar lavage fluid (BALF), and the pathological changes of lung tissues. RESULTS: The functional residual capacity data of the model group and the control group were (0.402 ± 0.057) and (0.243 ± 0.064) ml respectively (P<0.05). The inspiratory resistance data of the model group and the control group were (1.056 ± 0.121) and (0.789 ± 0.063) cmH(2)O · ml(-1) · s(-1) (1 cmH(2)O=0.098 kPa) respectively (P<0.05). The static lung compliance data of the model group and the control group were (0.084 ± 0 .007) and (0.056 ± 0.004) cmH(2)O/ml respectively (P<0.05). The right ventricular mean pressure of the model group and the control group were (11.3 ± 1.3) and (7.9 ± 1.1) mmHg (1 mmHg=0.133 kPa) respectively (P<0.05), while the right ventricular hypertrophy index of the model group and the control group were (0.267 ± 0.019) and (0.195 ± 0.023) respectively (P<0.05). Moreover, the histological staining showed that goblet cell hyperplasia, lung inflammation and thickening of smooth muscle layers of bronchial and pulmonary small vessels occurred in the model group, which indicated ongoing airway and blood vessel remodeling. CONCLUSIONS: A COPD-PH mouse model was established by nose-only cigarette smoking exposure plus airway LPS inhalation in a short period of time, and this method was more similar to the smoking behavior of human.

T2 Relaxation Time in Extraocular Muscles of Patients with Mild Thyroid- Associated Ophthalmopathy: Comparing T2 Mapping With and Without Fat Suppression Using Different Measurement Methods.

OBJECTIVE: This study aimed to compare the parametric value of T2 with and without fat suppression (FS) on T2 mapping for the evaluation of extraocular muscles (EOMs) in mild thyroid-associated ophthalmopathy (TAO). METHODS: We prospectively recruited 44 consecutive patients with mild TAO seen between May 2020 and October 2022 and 26 healthy controls with no history of eye- or thyroid-related or other autoimmune diseases. Patients with mild TAO were subdivided into active and inactive groups based on their clinical activity scores. The T2 of each EOM was measured over a large and small area of interest on T2-mapping images with and without FS. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of T2 for detecting TAO activity. RESULTS: The T2 was significantly and heterogeneously higher in the active group than in the inactive and control groups (P < 0.05). FS-T2-mapping images had better signal display within and at the edges of the EOMs than those without FS. It was possible to observe high-signal aggregation visible in the periphery of some EOMs, and the central part showed relatively low signals. The maximum T2 measured in small or large areas with and without FS had good diagnostic efficacy for TAO activity, with that of no-FS being better (the area under the ROC curve of the maximum T2 measured in a small area and a large area without FS was 1.0 and 1.0 and P values of < 0.001 and < 0.001, respectively). CONCLUSION: Maximal T2 with or without FS can facilitate the early clinical detection of mild TAO activity. The maximum T2 in a small area can facilitate active staging of patients with mild TAO.

A Propolis-Derived Small Molecule Tectochrysin Ameliorates Type 2 Diabetes in Mice by Activating Insulin Receptor ß.

SCOPE: Propolis has been found to decrease glucose levels and increase insulin sensitivity in type 2 diabetes. However, the active ingredient responsible for these effects and its regulating mechanism are not fully understood. METHODS AND RESULTS: To address this, molecular docking screening is used to screen the effective hypoglycemic ingredient in propolis and found that tectochrysin (TEC) has a high affinity to the insulin receptor (IR), highlighting its potential for glycemic control. In vivo tests show that TEC decreases glucose levels and enhances insulin sensitivity in db/db mice. By hyperinsulinemic euglycemic clamp test, this study further finds that TEC promotes glucose uptake in adipose tissue and skeletal muscle, as well as inhibits hepatic gluconeogenesis. Moreover, it finds that TEC promotes glucose uptake and adipocytes differentiation in 3T3-L1 cells like insulin, suggesting that TEC exerts an insulin mimetic effect. Mechanistically, pharmacology inhibition of IRß abolishes the effects of TEC on glucose uptake and the phosphorylation of IR. The study further demonstrates that TEC binds to and activates IRß by targeting its E1077 and M1079. CONCLUSION: Therefore, this study sheds light on the mechanism underlying propolis' potential for ameliorating type 2 diabetes, offering a natural food-derived compound as a promising therapeutic option.

Emulsion template fabricated gelatin-based scaffold functionalized by dialdehyde starch complex with antibacterial antioxidant properties for accelerated wound healing.

Gelatin and starch are considered as promising sustainable materials for their abundant production and good biodegradability. Efforts have been made to explore their medical application. Herein, scaffolds based on gelatin and starch with a preferred microstructure and antibacterial antioxidant property were fabricated by the emulsion template method. The dialdehyde starch was firstly combined with silver nanoparticles and curcumin to carry out the efficient hybrid antibacterial agent. Then, the gelatin microsphere of appropriate size was prepared by emulsification and gathered by the above agent to obtain gelatin-based scaffolds. The prepared scaffolds showed porous microstructures with high porosity of over 74 % and the preferred pore sizes of ∼65 µm, which is conducive to skin regeneration. Moreover, the scaffolds possessed a good swelling ability of over 640 %, good degradability of over 18 days, excellent blood compatibility, and cell compatibility. The promising antibacterial and antioxidant properties came from the hybrid antibacterial agent were affirmed. As expected, the gelatin-based scaffolds fabricated by the emulsion template method with a preferred microstructure can facilitate more adhered fibroblasts. In summary, gelatin-based scaffolds functionalized by starch-based complex expanded the application of abundant sustainable materials in the biomedical field, especially as antibacterial antioxidant wound dressings.

Block Polyelectrolyte Additives That Modulate the Viscoelasticity and Enhance the Printability of Gelatin Inks at Physiological Temperatures.

We demonstrate the utility of block polyelectrolyte (bPE) additives to enhance viscosity and resolve challenges with the three-dimensional (3D) printability of extrusion-based biopolymer inks. The addition of oppositely charged bPEs to solutions of photocurable gelatin methacryloyl (GelMA) results in complexation-driven self-assembly of the bPEs, leading to GelMA/bPE inks that are printable at physiological temperatures, representing stark improvements over GelMA inks that suffer from low viscosity at 37 °C, leading to low printability and poor structural stability. The hierarchical microstructure of the self-assemblies (either jammed micelles or 3D networks) formed by the oppositely charged bPEs, confirmed by small-angle X-ray scattering, is attributed to the enhancements in the shear strength and printability of the GelMA/bPE inks. Varying bPE concentration in the inks is shown to enable tunability of the rheological properties to meet the criteria of pre- and postextrusion flow characteristics for 3D printing, including prominent yielding behavior, strong shear thinning, and rapid recovery upon flow cessation. Moreover, the bPE self-assemblies also contribute to the robustness of the photo-cross-linked hydrogels; photo-cross-linked GelMA/bPE hydrogels are shown to exhibit higher shear strength than photo-cross-linked GelMA hydrogels. Last, the assessment of the printability of GelMA/bPE inks indicates excellent printing performance, including minimal swelling postextrusion, satisfactory retention of the filament shape upon deposition, and satisfactory shape fidelity of the various printed constructs. We envision this study to serve as a practical guide for the printing of bespoke extrusion inks where bPEs are used as scaffolds and viscosity enhancers that can be emulated in a range of photocurable precursors.

Dissolving Hyaluronic Acid-Based Microneedles to Transdermally Deliver Eugenol Combined with Photothermal Therapy for Acne Vulgaris Treatment.

A microneedle transdermal drug delivery system simultaneously avoids systemic toxicity of oral administration and low efficiency of traditional transdermal administration, which is of great significance for acne vulgaris therapy. Herein, eugenol-loaded hyaluronic acid-based dissolving microneedles (E@P-EO-HA MNs) with antibacterial and anti-inflammatory activities are developed for acne vulgaris therapy via eugenol transdermal delivery integrated with photothermal therapy. E@P-EO-HA MNs are pyramid-shaped with a sharp tip and a hollow cavity structure, which possess sufficient mechanical strength to penetrate the stratum corneum of the skin and achieve transdermal delivery, in addition to excellent in vivo biocompatibility. Significantly, E@P-EO-HA MNs show effective photothermal therapy to destroy sebaceous glands and achieve antibacterial activity against deep-seated Propionibacterium acnes (P. acnes) under near-infrared-light irradiation. Moreover, cavity-loaded eugenol is released from rapidly dissolved microneedle bodies to play a sustained antibacterial and anti-inflammatory therapy on the P. acnes infectious wound. E@P-EO-HA MNs based on a synergistic therapeutic strategy combining photothermal therapy and eugenol transdermal administration can significantly alleviate inflammatory response and ultimately facilitate the repair of acne vulgaris. Overall, E@P-EO-HA MNs are expected to be clinically applied as a functional minimally invasive transdermal delivery strategy for superficial skin diseases therapy in skin tissue engineering.

Integrated approach of network pharmacology, molecular docking, and clinical observations in evaluating the efficacy and safety of Bufei Huoxue capsules for pulmonary hypertension associated with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a persistent and progressive disorder characterized by airway or alveolar abnormalities, commonly leading to pulmonary hypertension (PH). This clinical observational study investigates the therapeutic mechanisms of Bufei Huoxue capsules (BHC) in treating PH in patients with COPD-linked PH (COPD-PH) using network pharmacology and molecular docking methods, and assesses the therapeutic efficacy and safety of BHCs. The active compounds and their target proteins in BHCs were sourced from the Traditional Chinese Medicine Systems Pharmacology database, with additional target proteins derived from the GeneCards and OMIM databases. An active network was constructed using Cytoscape 3.7.1, and interaction networks were established. Intersecting targets underwent Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Metascape database. Network pharmacology and molecular docking studies demonstrated favorable binding affinities of BHC active ingredients, such as quercetin, bavachalcone, and isobavachin, for key targets including PTGS1, ESR1, and PTGS2. Gene Ontology enrichment analysis highlighted the involvement of these targets in processes such as the positive regulation of locomotion, the transmembrane receptor protein tyrosine kinase signaling pathway, and peptidyl-tyrosine phosphorylation. KEGG pathway analysis indicated their roles in pathways related to cancer, AGE-RAGE signaling in diabetic complications, and prostate cancer. BHCs exhibit therapeutic effects on COPD-PH through multi-component, multi-target, and multi-pathway interactions. This clinical observational study confirms the efficacy and safety of BHCs in improving cardiac and pulmonary functions, enhancing exercise tolerance, and elevating the quality of life in patients with COPD-PH.

Pulmonary fibrosis in primary Sjögren syndrome: computed tomography, clinical features, and associated clinical factors.

INTRODUCTION: Interstitial lung disease (ILD) is common in patients with primary Sjögren syndrome (pSS). Pulmonary fibrosis significantly reduces the patient's quality of life. Therefore, better understanding of the characteristics of patients with pulmonary fibrosis is necessary. OBJECTIVES: The aim of the study was to evaluate the computed tomography (CT) and clinical features of pSS­related ILD and to explore the factors associated with fibrotic ILD in patients with pSS. PATIENTS AND METHODS: In total, 151 patients with pSS­related ILD were retrospectively studied for their demographic and clinical characteristics. The patients were categorized into the nonfibrosing ILD and fibrosing ILD groups based on their CT findings. The clinicl, laboratory, and CT findings from both groups were compared to determine the influencing factors associated with the condition. RESULTS: The nonfibrosing ILD and fibrosing ILD groups comprised 103 and 48 patients, respectively. As compared with the nonfibrosing ILD group, the fibrosing ILD group had a shorter disease duration, higher frequency of dry cough and shortness of breath, more patients with ground­glass opacity, mediastinal lymph node disease, and pleural lesions on chest CT, and lower frequency of dry mouth and eyes. Dry cough and shortness of breath were independent predictors of pulmonary fibrosis in the patients with pSS (P = 0.01 and P = 0.02, respectively). CONCLUSIONS: The presence of dry cough and shortness of breath in the patients with pSS may indicate concomitant pulmonary fibrosis. High­resolution chest CT can be used for better insights on the occurrence and severity of pulmonary fibrosis in these patients.