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Evidence on the link of long-term exposure to ozone (O3) with childhood asthma, rhinitis, conjunctivitis and eczema is inconclusive. We did a population-based cross-sectional survey, including 177,888 children from 173 primary and middle schools in 14 Chinese cities. A satellite-based spatiotemporal model was employed to assess four-year average O3 exposure at both residential and school locations. Information on asthma, allergic rhinitis, eczema and conjunctivitis was collected by a standard questionnaire developed by the American Thoracic Society. We used generalized non-linear and linear mixed models to test the associations. We observed linear exposure-response associations between O3 and all outcomes. The odds ratios of doctor-diagnosed asthma, rhinitis, eczema, and conjunctivitis associated with per interquartile increment in home-school O3 concentration were 1.31 (95 % confidence interval [CI]: 1.28, 1.34), 1.25 (95 %CI: 1.23, 1.28), 1.19 (95 %CI: 1.16, 1.21), and 1.28 (95 %CI: 1.21, 1.34), respectively. Similar associations were observed for asthma-related outcomes including current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough. Moreover, stronger associations were observed among children who were aged > 12 years, physically inactive, and exposed to higher temperature. In conclusion, long-term O3 exposure was associated with higher risks of asthma, allergic rhinitis, conjunctivitis and eczema in children.
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BACKGROUND: Pulmonary abscesses resulting from epididymitis caused by extended spectrum ß-lactamase-producing hypervirulent Klebsiella pneumoniae (ESBL-hvKp) in a nondiabetic patient are extremely uncommon. The infection caused by this disseminated drug-resistant bacteria, which is generally considered an intractable case, poses a potential challenge in clinical practice. CASE PRESENTATION: In this case report, we present the clinical course of a 71-year-old male patient with epididymitis, who subsequently developed cough and dyspnea following anti-infection treatment. Imaging examinations revealed severe pneumonia and pulmonary abscess. The infection of ESBL-hvKp in the epididymis led to bacteremia and subsequent lung lesions. Due to poor response to anti-infection therapy, the patient required an extended duration of anti-infection treatment and ultimately chosed to discontinue treatment. CONCLUSIONS: Acute epididymitis caused by ESBL-hvKP infection can result in the spread of the infection through the bloodstream, leading to severe pneumonia and lung abscess. Given the critical condition of the patient, even with active anti-infection treatment, there is a risk of treatment failure or potentially fatal outcomes.
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Epididimitis , Infecciones por Klebsiella , Klebsiella pneumoniae , Absceso Pulmonar , beta-Lactamasas , Humanos , Masculino , Klebsiella pneumoniae/patogenicidad , Anciano , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , beta-Lactamasas/metabolismo , Epididimitis/microbiología , Epididimitis/tratamiento farmacológico , Absceso Pulmonar/microbiología , Absceso Pulmonar/tratamiento farmacológico , Antibacterianos/uso terapéuticoRESUMEN
Background: Pulmonary stenosis (PS) is one rare congenital heart disease (CHD) featuring obstruction of right ventricular outflow tract. Critical pulmonary stenosis (CPS) is neonatal PS having cyanosis and evidence of patent ductus arteriosus (PDA) dependency. There is limited data on the clinical outcomes of CPS with different modes of transportation. This study aimed to investigate clinical features and outcomes of CPS through the intrauterine transport (IT) and postnatal transport (PT). Methods: Single-center retrospective research was performed. Neonates with CPS were grouped into the IT group and PT group. Clinical characteristics and outcomes of the neonates were compared between the two groups. Results: Totally 110 neonates with PS were included in this study, 77 with CPS and 33 with non-CPS. In the infants with CPS, there were 53 and 24 in the IT and PT group respectively. Echocardiography showed that transvalvular pulmonary gradient (TVG) stayed lower in the IT group than that in the PT group {77.0 [interquartile range (IQR), 60.5-91.5] vs. 92.0 (IQR, 73.3-125.0) mmHg, P=0.006}. Levels of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I also remained lower in the IT group than those in the PT group [2,256 (IQR, 1,054-4,527) vs. 3,708 (IQR, 2,138-6,789) pg/mL, P=0.02; 0.020 (IQR, 0.011-0.034) vs. 0.042 (IQR, 0.027-0.072) ng/mL, P<0.001, respectively]. All infants with CPS received percutaneous balloon pulmonary valvuloplasty (PBPV) therapy in neonatal period and were discharged from the hospital. Length of hospital stay remained shorter in the IT group than that in the PT group [13.0 (IQR, 11.0-15.0) vs. 15.5 (IQR, 10.8-22.8) days, P=0.03]. Conclusions: IT and early management after birth could effectively reduce the severity of CPS before PBPV treatment and shorten the length of hospital stay among neonates suffering from CPS.
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A 3 × 3 coupler multiphase demodulation scheme is proposed to eliminate the impact of working point drifting and the laser relative intensity noise (RIN) on a 3 × 3 coupler interferometric system. An ellipse-fitting algorithm (EFA) is applied to fit the two interference signals of the 3 × 3 coupler in order, then the ATAN algorithm is applied to obtain three noise-containing signals with specific trigonometric relationships. By averaging the three signals, the demodulated phase noise induced from RIN can be effectively eliminated. The experimental results show that compared with the asymmetric demodulation scheme without intensity noise control, the noise floor of the proposed scheme decreases from 4.5 to 1â µrad/âHz at 1â kHz and 2.7 to 0.8â µrad/âHz at 3â kHz. At high frequencies, the average noise floor level is reduced from 10 to 0.9â µrad/âHz, a reduction of about 21â dB. Furthermore, the variation range of the average noise floor is reduced from 5.4 to 0.17â µrad /âHz within 100â s.
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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.
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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.
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Resinas Acrílicas , Glucanos , Hidrogeles , Nanocompuestos , Nanocompuestos/química , Hidrogeles/química , Glucanos/química , Resinas Acrílicas/química , Elasticidad , Materiales Biocompatibles/química , Fuerza CompresivaRESUMEN
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.
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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.
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Resinas de Intercambio Aniónico , Carbón Orgánico , Contaminantes Químicos del Agua , beta-Ciclodextrinas , Adsorción , beta-Ciclodextrinas/química , Resinas de Intercambio Aniónico/química , Contaminantes Químicos del Agua/química , Carbón Orgánico/química , Fluorocarburos/química , Purificación del Agua/métodos , Polímeros/químicaRESUMEN
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 (DPPHâ¢) 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.
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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.
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Fibrosis Pulmonar Idiopática , Macrófagos Alveolares , Monocitos , Humanos , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/genética , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patología , Monocitos/metabolismo , Masculino , Perfilación de la Expresión Génica , Femenino , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Persona de Mediana Edad , Fenotipo , Pulmón/patología , Pulmón/metabolismo , Regulación de la Expresión GénicaRESUMEN
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.
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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.
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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.
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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.
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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.
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Folículo Piloso , Células Madre Mesenquimatosas , Ratones Desnudos , Envejecimiento de la Piel , Rayos Ultravioleta , Animales , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Humanos , Ratones , Folículo Piloso/efectos de la radiación , Fibroblastos/efectos de la radiación , Vesículas Extracelulares/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Trasplante de Células Madre Mesenquimatosas/métodos , Células Cultivadas , Piel/efectos de la radiación , Piel/patologíaRESUMEN
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.
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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.
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Acinetobacter baumannii , Tetraciclinas , Tipificación de Secuencias Multilocus , Antibacterianos/farmacología , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carbapenémicos/farmacología , ARN sin Sentido , China/epidemiología , Pruebas de Sensibilidad MicrobianaRESUMEN
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.
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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.