Multiomic analysis of monocyte-derived alveolar macrophages in idiopathic pulmonary fibrosis.

BACKGROUND: Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq analysis has proven valuable in the transcriptome profiling of Mo_AMs, the integration analysis of multi-omics may provide additional dimensions of understanding of these cellular populations. METHODS: We performed multi-omics analysis on 116 scRNAseq, 119 bulkseq and five scATACseq lung tissue samples from IPF. We built a large-scale IPF scRNAseq atlas and conducted the Monocle 2/3 as well as the Cellchat to explore the developmental path and intercellular communication on Mo_AMs. We also reported the difference in metabolisms, tissue repair and phagocytosis between Mo_AMs and tissue-resident alveolar macrophages (TRMs). To determine whether Mo_AMs affected pulmonary function, we projected clinical phenotypes (FVC%pred) from the bulkseq dataset onto the scRNAseq atlas. Finally, we used scATATCseq to uncover the upstream regulatory mechanisms and determine key drivers in Mo_AMs. RESULTS: We identified three Mo_AMs clusters and the trajectory analysis further validated the origin of these clusters. Moreover, via the Cellchat analysis, the CXCL12/CXCR4 axis was found to be involved in the molecular basis of reciprocal interactions between Mo_AMs and fibroblasts through the activation of the ERK pathway in Mo_AMs. SPP1_RecMacs (RecMacs, recruited macrophages) were higher in the low-FVC group than in the high-FVC group. Specifically, compared with TRMs, the functions of lipid and energetic metabolism as well as tissue repair were higher in Mo_AMs than TRMs. But, TRMs may have higher level of phagocytosis than TRMs. SPIB (PU.1), JUNB, JUND, BACH2, FOSL2, and SMARCC1 showed stronger association with open chromatin of Mo_AMs than TRMs. Significant upregulated expression and deep chromatin accessibility of APOE were observed in both SPP1_RecMacs and TRMs. CONCLUSION: Through trajectory analysis, it was confirmed that SPP1_RecMacs derived from Monocytes. Besides, Mo_AMs may influence FVC% pred and aggravate pulmonary fibrosis through the communication with fibroblasts. Furthermore, distinctive transcriptional regulators between Mo_AMs and TRMs implied that they may depend on different upstream regulatory mechanisms. Overall, this work provides a global overview of how Mo_AMs govern IPF and also helps determine better approaches and intervention therapies.

Encapsulation and Evolution of Polyynes Inside Single-Walled Carbon Nanotubes.

Polyyne is an sp-hybridized linear carbon chain (LCC) with alternating single and triple carbon-carbon bonds. Polyyne is very reactive; thus, its structure can be easily damaged through a cross-linking reaction between the molecules. The longer the polyyne is, the more unstable it becomes. Therefore, it is difficult to directly synthesize long polyynes in a solvent. The encapsulation of polyynes inside carbon nanotubes not only stabilizes the molecules to avoid cross-linking reactions, but also allows a restriction reaction to occur solely at the ends of the polyynes, resulting in long LCCs. Here, by controlling the diameter of single-walled carbon nanotubes (SWCNTs), polyynes were filled with high yield below room temperature. Subsequent annealing of the filled samples promoted the reaction between the polyynes, leading to the formation of long LCCs. More importantly, single chiral (6,5) SWCNTs with high purity were used for the successful encapsulation of polyynes for the first time, and LCCs were synthesized by coalescing the polyynes in the (6,5) SWCNTs. This method holds promise for further exploration of the synthesis of property-tailored LCCs through encapsulation inside different chiral SWCNTs.

A short linear glucan nanocomposite hydrogel formed by in situ self-assembly with highly elastic, fatigue-resistant and self-recovery.

Polyacrylamide (PAM) hydrogels are widely used in wide-ranging applications in biology, medicine, pharmaceuticals and environmental sectors. However, achieving the requisite mechanical properties, fatigue resistance, self-recovery, biocompatibility, and biodegradability remains a challenge. Herein, we present a facile method to construct a nanocomposite hydrogel by integrating short linear glucan (SLG), obtained by debranching waxy corn starch, into a PAM network through self-assembly. The resulting composite hydrogel with 10 % SLG content exhibited satisfactory stretchability (withstanding over 1200 % strain), along with maximum compressive and shear strengths of about 490 kPa and 39 kPa at 90 % deformation, respectively. The hydrogel demonstrated remarkable resilience and could endure repeated compression and stretching. Notably, the nanocomposite hydrogel with 10 % SLG content exhibited full stress recovery at 90 % compression deformation after 20 s, without requiring specific environmental conditions, achieving an energy dissipation recovery rate of 98 %. Meanwhile, these hydrogels exhibited strong adhesion to various soft and hard substrates, including skin, glasses and metals. Furthermore, they maintain solid integrity at both 37 °C and 50 °C after swelling equilibrium, unlike traditional PAM hydrogels, which exhibited softening under similar conditions. We hope that this PAM-SLG hydrogel will open up new avenues for the development of multifunctional electronic devices, offering enhanced performance and versatility.

Systemic lidocaine versus erector spinae plane block for improving quality of recovery after laparoscopic cholecystectomy: A randomized controlled trial.

STUDY OBJECTIVE: To compare intravenous lidocaine, ultrasound-guided erector spinae plane block (ESPB), and placebo on the quality of recovery and analgesia after laparoscopic cholecystectomy. DESIGN: A prospective, triple-arm, double-blind, randomized, placebo-controlled non-inferiority trial. SETTING: A single tertiary academic medical center. PATIENTS: 126 adults aged 18-65 years undergoing elective laparoscopic cholecystectomy. INTERVENTIONS: Patients were randomly allocated to one of three groups: intravenous lidocaine infusion (1.5 mg/kg bolus followed by 2 mg/kg/h) plus bilateral ESPB with saline (25 mL per side); bilateral ESPB with 0.25% ropivacaine (25 ml per side) plus placebo infusion; or bilateral ESPB with saline (25 ml per side) plus placebo infusion. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. The non-inferiority of lidocaine versus ESPB was assessed with a margin of -6 points and 97.5% confidence interval (CI). Secondary outcomes included 24-h area under the curve (AUC) for pain scores, morphine consumption, and adverse events. MAIN RESULTS: 124 patients completed the study. Median (IQR) 24-h QoR-15 scores were 123 (117-127) for lidocaine, 124 (119-126) for ESPB, and 112 (108-117) for placebo. Lidocaine was non-inferior to ESPB (median difference  -1, 97.5% CI: -4 to ∞). Both lidocaine (median difference 9, 95% CI: 6-12, P < 0.001) and ESPB (median difference 10, 95% CI: 7-13, P < 0.001) were superior to placebo. AUC for pain scores and morphine use were lower with lidocaine and ESPB versus placebo (P < 0.001 for all), with no significant differences between lidocaine and ESPB. One ESPB patient reported a transient metallic taste; no other block-related complications occurred. CONCLUSIONS: For patients undergoing laparoscopic cholecystectomy, intravenous lidocaine provides a non-inferior quality of recovery compared to ESPB without requiring specialized regional anesthesia procedures. Lidocaine may offer a practical and accessible alternative within multimodal analgesia pathways.

Perfluoroalkyl acid adsorption by styrenic ß-cyclodextrin polymers, anion-exchange resins, and activated carbon is inhibited by matrix constituents in different ways.

Perfluoroalkyl acids (PFAAs) are ubiquitous environmental contaminants of global concern, and adsorption processes are the most widely used technologies to remove PFAAs from water. However, there remains little data on the ways that specific water matrix constituents inhibit the adsorption of PFAAs on different adsorbents. In this study, we evaluated the adsorption of 13 PFAAs on two styrene-functionalized ß-cyclodextrin (StyDex) polymers, an activated carbon (AC), and an anion-exchange resin (AER) in the absence and presence of specific water matrix constituents (16 unique water matrices) in batch experiments. All four adsorbents exhibited some extent of adsorption inhibition in the presence of inorganic ions and/or humic acid (HA) added as a surrogate for natural organic matter. Two PFAAs (C5-C6 perfluorocarboxylic acids (PFCAs)) were found to exhibit relatively weak adsorption and five PFAAs (C6-C8 perfluorosulfonic acids (PFSAs) and C9-C10 PFCAs) were found to exhibit relatively strong adsorption on all four adsorbents across all matrices. Adsorption inhibition was the greatest in the presence of Ca2+ (direct site competition) and HA (direct site competition and pore blockage) for AC, NO3- (direct site competition) and Ca2+ (chemical complexation) for the AER, and SO42- (compression of the double layer) for the StyDex polymers. The pattern of adsorption inhibition of both StyDex polymers were similar to each other but different from AC and AER, which demonstrates the distinctive PFAA adsorption mechanism on StyDex polymers. The unique performance of each type of adsorbent confirms unique adsorption mechanisms that result in unique patterns of adsorption inhibition in the presence of matrix constituents. These insights could be used to develop models to predict the performance of these adsorbents in real water matrices and afford rational selection of adsorbents based on water chemistry for specific applications.

Evaluation of the clinical performance of multiple serum sIgE detection systems based on component-resolved diagnosis.

BACKGROUND: Serum allergen-specific IgE (sIgE) detection is an important tool in the diagnosis of allergic diseases. However, the absence of international standards for sIgE detection systems raises questions about the comparability of different systems. OBJECTIVE: This study aims to evaluate three common allergen sIgE detection systems, with a primary focus on detecting dust mite allergens. METHODS: We recruited 85 children with rhinitis and 15 healthy control children. The subjects underwent testing with three different sIgE detection systems, including magnetic particle flow fluorescence, magnetic particle chemiluminescence, and protein chip, to detect sIgE levels to HDM extracts. In addition, skin prick testing (SPT) was conducted, and protein chip technology was performed to measure sIgE levels to component proteins. RESULTS: Our findings reveal strong consistency between SPT and the three in vitro detection systems, with consistency exceeding 71.76% for dust mite allergens. Moreover, there was excellent consistency and RAST class consistency among the three in vitro detection systems, with scores exceeding 94.12% and 89.00%, respectively. And for the 13 additional allergens crude extracts sIgE simultaneously detected by systems 1 and 2, the results showed that the consistency of both systems was above 87.00%, and the RAST class consistency was above 82.00%. CONCLUSION: The three serum sIgE detection systems exhibited an approximate 80% concordance rate with SPT in identifying dust mite allergens. Furthermore, these systems demonstrated excellent consistency and RAST class consistency among themselves. These findings suggest that the three assays introduced in this study are interchangeable in allergen diagnosis.

Design and Characterization of a Novel Core-Shell Nano Delivery System Based on Zein and Carboxymethylated Short-Chain Amylose for Encapsulation of Curcumin.

Curcumin is a naturally occurring hydrophobic polyphenolic compound with a rapid metabolism, poor absorption, and low stability, which severely limits its bioavailability. Here, we employed a starch-protein-based nanoparticle approach to improve the curcumin bioavailability. This study focused on synthesizing nanoparticles with a zein "core" and a carboxymethylated short-chain amylose (CSA) "shell" through anti-solvent precipitation for delivering curcumin. The zein@CSA core-shell nanoparticles were extensively characterized for physicochemical properties, structural integrity, ionic stability, in vitro digestibility, and antioxidant activity. Fourier-transform infrared (FTIR) spectroscopy indicates nanoparticle formation through hydrogen-bonding, hydrophobic, and electrostatic interactions between zein and CSA. Zein@CSA core-shell nanoparticles exhibited enhanced stability in NaCl solution. At a zein-to-CSA ratio of 1:1.25, only 15.7% curcumin was released after 90 min of gastric digestion, and 66% was released in the intestine after 240 min, demonstrating a notable sustained release effect. Furthermore, these nanoparticles increased the scavenging capacity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH•) free radical compared to those composed solely of zein and were essentially nontoxic to Caco-2 cells. This research offers valuable insights into curcumin encapsulation and delivery using zein@CSA core-shell nanoparticles.

Structural Features of Styrene-Functionalized Cyclodextrin Polymers That Promote the Adsorption of Perfluoroalkyl Acids in Water.

Cross-linked ß-cyclodextrin (ß-CD) polymers are promising adsorbents for the removal of per- and polyfluoroalkyl substances (PFAS) from contaminated water sources, including contaminated groundwater, drinking water, and wastewater. We previously reported porous, styrene-functionalized ß-cyclodextrin (StyDex) polymers derived from radical polymerization with vinyl comonomers. Because of the versatility of these polymerizations, StyDex polymer compositions are tunable, which facilitates efforts to establish structure-adsorption relationships and to discover improved materials. Here, we evaluate the material properties and PFAS adsorption of 20 StyDex derivatives with varied comonomer structure and loading, regiochemistry of styrene placement on the CD monomer, and CD size. A StyDex polymer containing N,N'-dimethylbutyl ammonium ions exhibited the most effective PFAS adsorption in batch experiments. Furthermore, a StyDex polymer containing ß-CD exhibited size-selective host-guest interactions with perfluoroalkyl acids (PFAAs) and neutral contaminants in aqueous electrolyte when compared to similar polymers containing either α-CD or γ-CD. Polymers based on ß-CD monomers with an average of seven styrene groups randomly positioned over the 21 available hydroxyl groups performed similarly to those based on a ß-CD monomer functionalized regiospecifically at each of the seven 6' positions. The former ß-CD monomer is prepared in a single step from unmodified ß-CD, so the ability to use it without compromising performance demonstrates promise for developing economically competitive adsorbents. These results offered important insights into structure-adsorption properties of StyDex polymers and will inform the design of improved StyDex formulations.

The Construction of Sodium Alginate/Carboxymethyl Chitosan Microcapsules as the Physical Barrier to Reduce Corn Starch Digestion.

To enhance the resistant starch (RS) content of corn starch, in this work, carboxymethyl chitosan/corn starch/sodium alginate microcapsules (CMCS/CS/SA) with varying concentrations of SA in a citric acid (CA) solution were designed. As the SA concentration increased from 0.5% to 2%, the swelling of the CMCS/CS/SA microcapsule decreased from 15.28 ± 0.21 g/g to 3.76 ± 0.66 g/g at 95 °C. Comparatively, the onset, peak, and conclusion temperatures (To, Tp, and Tc) of CMCS/CS/SA microcapsules were higher than those of unencapsulated CS, indicating that the dense network structure of microcapsules reduced the contact area between starch granules and water, thereby improving thermal stability. With increasing SA concentration, the intact and dense network of CMCS/CS/SA microcapsules remained less damaged after 120 min of digestion, suggesting that the microcapsules with a high SA concentration provided better protection to starch, thereby reducing amylase digestibility. Moreover, as the SA concentration increased from 0.5% to 2%, the RS content of the microcapsules during in vitro digestion rose from 42.37 ± 0.07% to 57.65 ± 0.45%, attributed to the blocking effect of the microcapsule shell on amylase activity. This study offers innovative insights and strategies to develop functional starch with glycemic control properties, holding significant scientific and practical value in preventing diseases associated with abnormal glucose metabolism.

The role and mechanism of engineered nanovesicles derived from hair follicle mesenchymal stem cells in the treatment of UVB-induced skin photoaging.

BACKGROUND: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are effective in the treatment of skin photoaging; however, their low yield and functional decline with passage progression limit their clinical application. Cell-derived nanovesicles (CNVs) are potential alternatives that can address the limitations of EVs derived from MSCs and are conducive to clinical transformations. Hair follicle mesenchymal stem cells (HFMSCs), a type of MSCs, have demonstrated the function of repairing skin tissues; nevertheless, the efficacy of CNVs from HFMSCs (HFMSC-CNVs) in the treatment of skin photoaging remains unclear. Therefore, ultraviolet radiation B (UVB)-induced photoaging nude mice and human dermal fibroblasts (HDFs) were used as experimental models to investigate the therapeutic effects of HFMSC-CNVs in photoaging models. METHODS: HFMSC-CNVs were successfully prepared using the mechanical extrusion method. UVB-induced nude mice and HDFs were used as experimental models of photoaging. Multiple approaches, including hematoxylin-eosin and Masson staining, immunohistochemistry, immunofluorescence, detection of reactive oxygen species (ROS), flow cytometry, western blotting, and other experimental methods, were combined to investigate the possible effects and mechanisms of HFMSC-CNVs in the treatment of skin photoaging. RESULTS: In the nude mouse model of skin photoaging, treatment with HFMSC-CNVs reduced UVB-induced skin wrinkles (p < 0.05) and subcutaneous capillary dilation, alleviated epidermis thickening (p < 0.001), and dermal thinning (p < 0.001). Furthermore, HFMSC-CNVs upregulated proliferating cell nuclear antigen (PCNA) expression (p < 0.05) and decreased the levels of ROS, ß-galactosidase (ß-Gal), and CD86 (p < 0.01). In vitro experiments, treatment with HFMSC-CNVs enhanced the cellular activity of UVB-exposed HDFs (p < 0.05), and reduced ROS levels and the percentage of senescent cells (p < 0.001), and alleviated cell cycle arrest (p < 0.001). HFMSC-CNVs upregulated the expression of Collagen I (Col I), SMAD2/3, transforming growth factor beta (TGF-ß), catalase (CAT), glutathione peroxidase-1 (GPX-1), and superoxide dismutase-1 (SOD-1) (p < 0.05) and downregulated the expression of cycle suppressor protein (p53), cell cycle suppressor protein (p21), and matrix metalloproteinase 3 (MMP3) (p < 0.05). CONCLUSION: Conclusively, the anti-photoaging properties of HFMSC-CNVs were confirmed both in vivo and in vitro. HFMSC-CNVs exert anti-photoaging effects by alleviating cell cycle arrest, decreasing cellular senescence and macrophage infiltration, promoting cell proliferation and extracellular matrix (ECM) production, and reducing oxidative stress by increasing the activity of antioxidant enzymes.

Antibacterial Activity and Mechanism of Candesartan Cilexetil against Enterococcus faecalis.

Enterococcus faecalis infections pose a significant clinical challenge due to their multidrug resistance and propensity for biofilm formation. Exploring alternative treatment options, such as repurposing existing drugs, is crucial in addressing this issue. This study investigates the antibacterial activity of candesartan cilexetil against E. faecalis and elucidates its mechanism of action. Candesartan cilexetil exhibited notable antibacterial activity against both E. faecalis and Enterococcus faecium, with minimum inhibitory concentration (MIC) of ≤25 µM. Time-kill curves demonstrated concentration-dependent bactericidal effects. Candesartan cilexetil could significantly inhibited biofilm formation at the concentration of 1/4× MIC and induced alterations in biofilm structure. Permeability assays revealed compromised bacterial membranes, accompanied by the dissipation of membrane potential in E. faecalis cells after treatment with candesartan cilexetil. Checkerboard analysis showed that bacterial membrane phospholipids phosphatidylglycerol and cardiolipin could neutralize the antibacterial activity of candesartan cilexetil in a dose-dependent manner. Biolayer interferometry (BLI) assay indicated specific interactions between candesartan cilexetil and phosphatidylglycerol or cardiolipin. This study demonstrates the promising antibacterial and antibiofilm activities of candesartan cilexetil against multidrug-resistant E. faecalis. The mechanism of action involves disruption of bacterial membranes, possibly by interacting with membrane phospholipids. These findings underscore the potential utility of candesartan cilexetil as an effective therapeutic agent for combating E. faecalis infections, offering a valuable strategy in the battle against antibiotic-resistant pathogens.

Efficient and Stable Proton Exchange Membrane Water Electrolysis Enabled by Stress Optimization.

Proton exchange membrane water electrolysis (PEMWE) is a promising solution for the conversion and storage of fluctuating renewable energy sources. Although tremendously efficient materials have been developed, commercial PEMWE products still cannot fulfill industrial demands regarding efficiency and stability. In this work, we demonstrate that the stress distribution, a purely mechanical parameter in electrolyzer assembly, plays a critical role in overall efficiency and stability. The conventional cell structure, which usually adopts a serpentine flow channel (S-FC) to deliver and distribute reactants and products, resulted in highly uneven stress distribution. Consequently, the anode catalyst layer (ACL) under the high stress region was severely deformed, whereas the low stress region was not as active due to poor electrical contact. To address these issues, we proposed a Ti mesh flow channel (TM-FC) with gradient pores to reduce the stress inhomogeneity. Consequently, the ACL with TM-FC exhibited 27 mV lower voltage initially and an 8-fold reduction in voltage degradation rate compared to that with S-FC at 2.0 A/cm2. Additionally, the applicability of the TM-FC was demonstrated in cross-scale electrolyzers up to 100 kW, showing a voltage increase of only 20 mV (accounting for less than 2% of overall voltage) after three orders of magnitude scaleup.

Targeted drug delivery of engineered mesenchymal stem/stromal-cell-derived exosomes in cardiovascular disease: recent trends and future perspectives.

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

The Changing and Predicted Trends in Chronic Obstructive Pulmonary Disease Burden in China, the United States, and India from 1990 to 2030.

Background: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade. Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes. Results: From 1990 to 2019, China's age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India's rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China's age-standardized incidence rate is projected to rise. Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.

AMXT-1501 targets membrane phospholipids against Gram-positive and -negative multidrug-resistant bacteria.

The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)50/MIC90 values for AMXT-1501 in the range of 3.13-12.5 µM (2.24-8.93 µg /mL), including for methicillin-resistant Staphylococcus aureus (MRSA), CR Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. AMXT-1501 was more effective against MRSA and CR E. coli than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of S. aureus and Enterococcus faecalis. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.

Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways.

BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.

Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study.

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.

A nature-inspired multifunctional adhesive for cartilage tissue-biomaterial integration.

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.

Biomechanical evaluation on a new type of vertebral titanium porous mini-plate and mechanical comparison between cervical open-door laminoplasty and laminectomy: a finite element analysis.

Objective: Compare the spine's stability after laminectomy (LN) and laminoplasty (LP) for two posterior surgeries. Simultaneously, design a new vertebral titanium porous mini plate (TPMP) to achieve firm fixation of the open-door vertebral LP fully. The objective is to enhance the fixation stability, effectively prevent the possibility of "re-closure," and may facilitate bone healing. Methods: TPMP was designed by incorporating a fusion body and porous structures, and a three-dimensional finite element cervical model of C2-T1 was constructed and validated. Load LN and LP finite element models, respectively, and analyze and simulate the detailed processes of the two surgeries. It was simultaneously implanting the TPMP into LP to evaluate its biomechanical properties. Results: We find that the range of motion (ROM) of C4-C5 after LN surgery was greater than that of LP implanted with different plates alone. Furthermore, flexion-extension, lateral bending, and axial rotation reflect this change. More noteworthy is that LN has a much larger ROM on C2-C3 in axial rotation. The ROM of LP implanted with two different plates is similar. There is almost no difference in facet joint stress in lateral bending. The facet joint stress of LN is smaller on C2-C3 and C4-C5, and larger more prominent on C5-C6 in the flexion-extension. Regarding intervertebral disc pressure (IDP), there is little difference between different surgeries except for the LN on C2-C3 in axial rotation. The plate displacement specificity does not significantly differ from LP with vertebral titanium mini-plate (TMP) and LP with TPMP after surgery. The stress of LP with TPMP is larger in C4-C5, C5-C6. Moreover, LP with TMP shows greater stress in the C3-C4 during flexion-extension and lateral bending. Conclusion: LP may have better postoperative stability when posterior approach surgery is used to treat CSM; at the same time, the new type of vertebral titanium mini-plate can achieve almost the same effect as the traditional titanium mini-plate after surgery for LP. In addition, it has specific potential due to the porous structure promoting bone fusion.