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Low-temperature operation poses a significant challenge for current commercial rechargeable lithium-ion batteries (LIBs). Organic polymer electrode materials, exhibiting a nonintercalation redox mechanism, offer a viable solution to mitigate the decline in electrochemical performance at low temperatures in LIBs. Herein, a radical polymer P(DATPAPO-TPA) with a conjugated nitrogen-rich triphenylamine derivative as the backbone and high-density nitroxide pendants has been synthesized. Due to the large interstitial spaces between adjacent structural units and polymer chains, resulting from the significant torsion angle between the benzene rings in the P(DATPAPO-TPA) skeleton, ions could effectively transport. This structural feature demonstrated a notable discharge capacity of 143.3 mA h·g-1 and a high charge-discharge plateau at â¼3.75 V vs Li+/Li, outperforming most reported radical polymer cathode materials. In addition, its capacity retention could reach 83.1% after 2000 cycles at an ultrahigh current density of 50 C, showing excellent rate capability and promising cyclability. Also notable was P(DATPAPO-TPA)'s favorable low-temperature performance that maintains a high discharge capacity of 139.2 mA h·g-1 at 0 °C. The synthesized P(DATPAPO-TPA) is a tangible illustration of a viable design strategy for low-temperature electrode materials, thereby contributing to broadening applications for radical polymer electrode materials.
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AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.
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Zinc-ion batteries are promising candidates for large-scale energy storage. The side reactions of the hydrogen evolution reaction (HER) and zinc dendrite growth are major challenges for developing high-performance zinc-ion batteries. In this paper, a supramolecular gel electrolyte (BLO-ILZE) was self-assembled in an ionic liquid (EMIMBF4) with zinc tetrafluoroborate (Zn(BF4)2) on the separator in situ to obtain a gel electrolyte used in zinc-ion batteries. BLO-ILZE is demonstrated to significantly enhance conductivity over a broad temperature range between -70 and 100 °C. Interestingly, through testing and fitting, it is found that the supramolecular gel electrolyte satisfies the liquid state law over a wide temperature range, and even achieves high conductivity (2.12 mS cm-1) at -40 °C. It is equivalent to the conductivity of aqueous zinc-ion batteries (ZnSO4/H2O) at -10 °C, which is 2.33 mS cm-1. Moreover, the supramolecular gel electrolyte can effectively inhibit the HER, thus exhibiting a longer lifetime in Zn/Zn cells for 3470 h at 1 mA cm-2 compared to the aqueous zinc-ion batteries with the Zn(BF4)2 aqueous electrolyte (400 h at 1 mA cm-2). The assembled V2O5/BLO-ILZE/Zn full cells also showed cycling performance, with 5000 cycles at 0.5 mA g-1 at room temperature, a capacity of 98%, and a coulombic efficiency of about 100%.
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Pseudoexfoliation syndrome (PEX) is characterized by the deposition of fibrous pseudoexfoliation material (PEXM) in the eye, and secondary glaucoma associated with this syndrome has a faster and more severe clinical course. The incidence of PEX and pseudoexfoliative glaucoma (PEXG) exhibits ethnic clustering; however, few proteomic studies related to PEX and PEXG have been conducted in Asian populations. Therefore, we aimed to conduct proteomic analysis on the aqueous humor (AH) obtained from Uyghur patients with cataracts, those with PEX and cataracts, and those with PEXG and cataracts to better understand the molecular mechanisms of the disease and identify its potential biomarkers. To this end, AH was collected from patients with cataracts (n = 10, control group), PEX with cataracts (n = 10, PEX group), and PEXG with cataracts (n = 10, PEXG group) during phacoemulsification. Label-free quantitative proteomic techniques combined with bioinformatics were used to identify and analyze differentially expressed proteins (DEPs) in the AH of PEX and PEXG groups. Then, independent AH samples (n = 12, each group) were collected to validate DEPs by enzyme-linked immunosorbent assay (ELISA). The PEX group exhibited 25 DEPs, while the PEXG group showed 44 DEPs, both compared to the control group. Subsequently, we found three newly identified proteins in both PEX and PEXG groups, wherein FRAS1-related extracellular matrix protein 2 (FREM2) and osteoclast-associated receptor (OSCAR) exhibited downregulation, whereas coagulation Factor IX (F9) displayed upregulation. Bioinformatics analysis suggested that extracellular matrix interactions, abnormal blood-derived proteins, and lysosomes were mainly involved in the process of PEX and PEXG, and the PPI network further revealed F9 may serve as a potential biomarker for both PEX and PEXG. In conclusion, this study provides new information for understanding the proteomics of AH in PEX and PEXG.
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Humor Acuoso , Síndrome de Exfoliación , Proteínas del Ojo , Proteómica , Humanos , Síndrome de Exfoliación/metabolismo , Humor Acuoso/metabolismo , Proteómica/métodos , Masculino , Femenino , Anciano , Proteínas del Ojo/metabolismo , China/epidemiología , Glaucoma de Ángulo Abierto/metabolismo , Persona de Mediana Edad , Biomarcadores/metabolismo , Ensayo de Inmunoadsorción Enzimática , Catarata/metabolismo , Presión Intraocular/fisiologíaRESUMEN
Primary angle-closure glaucoma (PACG) is the leading cause of irreversible blindness in the world. Angle closure induced by pupil block and secondary iris synechia is the fundamental pathology of the PACG. The molecular mechanisms of angle closure have not yet been clearly illustrated. This study was designed to investigate the protein difference in the aqueous humour and explore new biomarker of the PACG. Aqueous humour (AH) was collected from patients with acute primary angle closure (APAC) and cataract (n = 10 in APAC group) and patients with cataract only (n = 10 in control group). Samples were pooled and measured using label-free proteome technology. Then, the differentially expressed proteins (DEPs) were verified by ELISA using independent AH samples (n = 20 each group). More than 400 proteins were revealed in both groups through proteomics. Comparing the two groups, there were 91DEPs. These proteins participate in biological activities such as inflammation, fibrosis, nerve growth and degeneration and metabolism. We found that the expression of transforming growth factor-ß2 and matrilin2 was downregulated in the APAC group. The two proteins are related to inflammation and extracellular matrix formation, which might be involved in angle closure. This study characterized DEPs in AH of the APAC and found a downregulated protein matrilin2.
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Humor Acuoso , Catarata , Humanos , Enfermedad Aguda , Humor Acuoso/metabolismo , Catarata/metabolismo , Ensayo de Inmunoadsorción Enzimática , Inflamación/metabolismo , Factor de Crecimiento Transformador beta2/metabolismo , Proteínas Matrilinas/metabolismoRESUMEN
Cardiac rehabilitation (CR) is a comprehensive and multidisciplinary secondary prevention care in coronary heart disease (CHD). There are barriers at the patient and health system levels that prevent CR from being utilized. Cardiac telerehabilitation led by nurses (Ne-CTR) can alleviate the obstacles to participation in CR. A patient perspective can improve CR access. This study was the first pre-program investigation to clarify the status of knowledge and participation in CTR. We sought to clarify the acceptability, the reasons for rejection, the desired form, components, and associated factors with the components needed for (Ne-CTR) in patients with CHD. The study aimed to help develop a protocol for Ne-CTR for Chinese patients with CHD. A cross-sectional study was conducted between 2020 and 2021. Hospitals in four provinces in China were included. The participants were 671 patients with CHD in hospitals located in three regions of China. A self-administered questionnaire collected information about demographics, knowledge, and participation in CTR, acceptability, preferred medium, and components of Ne-CTR. Student's t-test, analysis of variance, and multiple linear regression analyzed the factors associated with component needs. All the analyses were conducted using IBM SPSS version 25.0. Most participants (n = 434, 66.77%) had a poor understanding and participation in CTR. In addition, 65.38% (n = 439) of participants were willing to accept the Ne-CTR program, and 43.56% (n = 98) identified safety as reasons for not accepting such a program. In the group accepting Ne-CTR, 35% chose hospital-designed professional applications as a medium for Ne-CTR when offered. Education (4.44 ± 1.056) and drug information (4.44 ± 1.040) had the highest average need score. Education, monthly income, marital status, previous CTR participation, and health insurance were associated with the demand level scores of Ne-CTR. This study demonstrated high levels of need for Ne-CTR among patients with CHD and identified the desired medium, components, and associated factors of Ne-CTR. These findings provide reference information for the construction of a Ne-CTR program.
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Rehabilitación Cardiaca , Enfermedad Coronaria , Telerrehabilitación , Humanos , Estudios Transversales , Telerrehabilitación/métodos , Rol de la Enfermera , Enfermedad Coronaria/prevención & control , Enfermedad Coronaria/rehabilitación , Rehabilitación Cardiaca/métodosRESUMEN
BACKGROUND: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis. METHODS: We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin-eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, cytoskeleton, adhesion, reactive oxygen species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT-related markers, pERK1/2, pGSK3ß and ß-catenin. RESULTS: SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3ß and the expression of ß-catenin. CONCLUSION: SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3ß/ß-catenin pathways. Video Abstract SB431542 inhibits EMT in RPE cells under high glucose conditions.
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Neovascularización Coroidal , Enfermedades de la Retina , Humanos , beta Catenina , Glucógeno Sintasa Quinasa 3 beta , Especies Reactivas de Oxígeno , Homeostasis , Fibrosis , Glucosa/toxicidadRESUMEN
BACKGROUND: Genomic variants outside of the canonical splicing site (±2) may generate abnormal mRNA splicing, which are defined as non-canonical splicing variants (NCSVs). However, the clinical interpretation of NCSVs in neurodevelopmental disorders (NDDs) is largely unknown. METHODS: We investigated the contribution of NCSVs to NDDs from 345,787 de novo variants (DNVs) in 47,574 patients with NDDs. We performed functional enrichment and protein-protein interaction analysis to assess the association between genes carrying prioritised NCSVs and NDDs. Minigene was used to validate the impact of NCSVs on mRNA splicing. FINDINGS: We observed significantly more NCSVs (p = 0.02, odds ratio [OR] = 2.05) among patients with NDD than in controls. Both canonical splicing variants (CSVs) and NCSVs contributed to an equal proportion of patients with NDD (0.76% vs. 0.82%). The candidate genes carrying NCSVs were associated with glutamatergic synapse and chromatin remodelling. Minigene successfully validated 59 of 79 (74.68%) NCSVs that led to abnormal splicing in 40 candidate genes, and 9 of the genes (ARID1B, KAT6B, TCF4, SMARCA2, SHANK3, PDHA1, WDR45, SCN2A, SYNGAP1) harboured recurrent NCSVs with the same variant present in more than two unrelated patients with NDD. Moreover, 36 of 59 (61.02%) NCSVs are novel clinically relevant variants, including 34 unreported and 2 clinically conflicting interpretations or of uncertain significance NCSVs in the ClinVar database. INTERPRETATION: This study highlights the common pathology and clinical importance of NCSVs in unsolved patients with NDD. FUNDING: The present study was funded by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, the Hunan Youth Science and Technology Innovation Talent Project, the Provincial Natural Science Foundation of Hunan, The Scientific Research Program of FuRong laboratory, and the Natural Science Project of the University of Anhui Province.
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Trastornos del Neurodesarrollo , Adolescente , Humanos , Mutación , Trastornos del Neurodesarrollo/genética , Empalme del ARN/genética , Exones , ARN Mensajero , Histona Acetiltransferasas/genética , Proteínas Portadoras/genéticaRESUMEN
Recently, molybdenum disulfide (MoS2)/carbon has become a promising candidate for efficient microwave absorption. However, it is still challenging to simultaneously optimize the synergy of impedance matching and loss capability at the level of a thin absorber. Here, a new adjustment strategy is proposed by changing the concentration of precursor l-cysteine for MoS2/multi-walled carbon nanotubes (MWCNT) composites to unlock the basal plane of MoS2 and expand the interlayer spacing from 0.62 nm to 0.99 nm, leading to improved packing of MoS2 nanosheets and more active sites. Therefore, the tailored MoS2 nanosheets exhibit abundant sulfur-vacancies, lattice-oxygen, more metallic 1T-phase, and higher surface area. Such sulfur-vacancies and lattice-oxygen promote the electronic asymmetric distribution at the solid-air interface of MoS2 crystals and induce stronger microwave attenuation through interface/dipole polarization, which is further verified by first-principles calculations. In addition, the expansion of the interlayer spacing induces more MoS2 to deposit on the MWCNT surface and increases the roughness, improving the impedance matching and multiple scattering. Overall, the advantage of this adjustment method is that while optimizing impedance matching at the thin absorber level, composite still maintains a high attenuation capacity, which means enhancing the attenuation performance of MoS2 itself offsets the weakening of the composite's attenuation ability caused by the decrease in the relative content of MWCNT components. Most importantly, adjusting impedance matching and attenuation ability can be easily implemented by separate control of l-cysteine content. As a result, the MoS2/MWCNT composites achieve a minimum reflection loss value of -49.38 dB and an effective absorption bandwidth of 4.64 GHz at a thickness of only 1.7 mm. This work provides a new vision for the fabrication of thin MoS2-carbon absorbers.
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Monocyte activation plays an important role in diabetic complications such as diabetic retinopathy (DR). However, the regulation of monocyte activation in diabetes remains elusive. Fenofibrate, an agonist of peroxisome proliferator-activated receptor-α (PPARα), has shown robust therapeutic effects on DR in patients with type 2 diabetes. Here we found that PPARα levels were significantly downregulated in monocytes from patients with diabetes and animal models, correlating with monocyte activation. Fenofibrate attenuated monocyte activation in diabetes, while PPARα knockout alone induced monocyte activation. Furthermore, monocyte-specific PPARα overexpression ameliorated, while monocyte-specific PPARα knockout aggravated monocyte activation in diabetes. PPARα knockout impaired mitochondrial function while also increasing glycolysis in monocytes. PPARα knockout increased cytosolic mitochondrial DNA release and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in monocytes under diabetic conditions. STING knockout or STING inhibitor attenuated monocyte activation induced by diabetes or by PPARα knockout. These observations suggest that PPARα negatively regulates monocyte activation through metabolic reprogramming and interaction with the cGAS-STING pathway.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Fenofibrato , Animales , PPAR alfa/genética , PPAR alfa/metabolismo , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Monocitos/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Retinopatía Diabética/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismoRESUMEN
Background: Common polygenic risk and de novo variants (DNVs) capture a small proportion of autism spectrum disorder (ASD) liability, and ASD phenotypic heterogeneity remains difficult to explain. Integrating multiple genetic factors contribute to clarifying the risk and clinical presentation of ASD. Methods: In our study, we investigated the individual and combined effects of polygenic risk, damaging DNVs (including those in ASD risk genes), and sex among 2,591 ASD simplex families in the Simons Simplex Collection. We also explored the interactions among these factors, along with the broad autism phenotypes of ASD probands and their unaffected siblings. Finally, we combined the effects of polygenic risk, damaging DNVs in ASD risk genes, and sex to explain the total liability of ASD phenotypic spectrum. Results: Our findings revealed that both polygenic risk and damaging DNVs contribute to an increased risk for ASD, with females exhibiting higher genetic burdens than males. ASD probands that carry damaging DNVs in ASD risk genes showed reduced polygenic risk. The effects of polygenic risk and damaging DNVs on autism broad phenotypes were inconsistent; probands with higher polygenic risk exhibited improvement in some behaviors, such as adaptive/cognitive behaviors, while those with damaging DNVs exhibited more severe phenotypes. Siblings with higher polygenic risk and damaging DNVs tended to have higher scores on broader autism phenotypes. Females exhibited more severe cognitive and behavioral problems compared to males among both ASD probands and siblings. The combination of polygenic risk, damaging DNVs in ASD risk genes, and sex explained 1-4% of the total liability of adaptive/cognitive behavior measurements. Conclusion: Our study revealed that the risk for ASD and the autism broad phenotypes likely arises from a combination of common polygenic risk, damaging DNVs (including those in ASD risk genes), and sex.
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Purpose: We sought to evaluate the efficacy and safety of plasmin injection in the capsular bag during the cataract operation for the prevention of posterior capsule opacification. Methods: Thirty-seven anterior capsular flaps taken from phacoemulsification surgery were immersed in either 1 µg/mL plasmin (plasmin group, n = 27) or phosphate-buffered saline (control group, n = 10) for 2 minutes and photographed after fixation and nuclear staining to compare the numbers of residual lens epithelial cells. In the animal experiments, the plasmin solution was injected into the capsular bag and remained for 5 minutes during hydrodissection or after lens extraction. The degree of posterior capsular opacity of the rabbits at 2 months were photographed by slit lamp biomicroscopy. In HLE-B3 cell culture, the cell detachment rate, proliferation, and apoptosis after the plasmin digestion were analyzed. Results: The residual lens epithelial cell numbers on the capsule after plasmin treatment were 168 ± 190.7/mm2 in the 1 µg/mL plasmin group, which was significantly lower than that of the control (1012 ± 798.8/mm2; P < 0.0001). In a rabbit model, the treatment of plasmin resulted in a significantly clearer posterior capsule compared with that of the control group at 2 months postoperatively. Conclusions: This study suggested that plasmin injection can induce effective lens epithelial cell detachment, which could be a promising adjunctive treatment to further improve the success rate in posterior capsule opacification prevention. Translational Relevance: Plasmin injection for lens epithelial cell detachment could significantly decrease the number of residual lens epithelial cells. This approach could be a promising treatment incorporating the current treatment approach to further improve the success rate in posterior capsule opacification prevention.
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Opacificación Capsular , Cápsula del Cristalino , Facoemulsificación , Animales , Conejos , Opacificación Capsular/prevención & control , Fibrinolisina/farmacología , Células Epiteliales , Facoemulsificación/métodosRESUMEN
Mitochondria are important places for the oxidative phosphorylation of glucose and the maintenance of cell oxidation and antioxidant stability. However, mitochondrial dysfunction causes cell dysfunction. Meanwhile, retinal vascular endothelial cell dysfunction may cause vascular inflammation, hemorrhage, angiogenesis, and other manifestations. Our previous studies have shown that Bone morphogenetic protein 4 (BMP4) is an important target for the treatment of retinal neovascularization, but the mechanism remains unclear. Therefore, our study aims to observe the effects of BMP4 on vascular endothelial cells and hopes to provide a new target for diabetic retinopathy. 4-Hydroxynonenal (4HNE), a kind of lipid peroxide, was used to induce the oxidative stress model. Human retinal microvascular endothelial cells (HRMECs) were randomly divided into control, 4HNE, negative control, and siBMP4 groups. Si-BMP4 significantly reduced leukocyte adhesion and 4HNE-induced high ROS level and restored the mitochondrial membrane potential and OCR. This indicates that BMP4 plays an important role in inducing leukocyte adhesion, oxidative stress, and mitochondrial dysfunction. The relationship between BMP4 and retinal vascular endothelial cell dysfunction is preliminarily confirmed by this study. Mitochondrial dysfunction and oxidative stress may be involved in BMP4-mediated retinal vascular endothelial cell dysfunction.
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Flexible polymer dielectrics for capacitive energy storage that can function well at elevated temperatures are increasingly in demand for continuously advancing and miniaturizing electrical devices. However, traditional high-resistance polymer dielectrics composed of aromatic backbones have a compromised band gap (Eg) and hence suffer from low breakdown strength and a huge loss at high temperatures. Here, based on the density functional theory (DFT) calculations, rigid and non-coplanar alicyclic segments are introduced into the polyimide backbone to overcome the incompatibility of a high glass transition temperature (Tg) and large Eg. Thanks to the large optical Eg (â¼4.6 eV) and high Tg (â¼277 °C), the all-alicyclic polyimide at 200 °C delivers a maximum discharge energy density (Ue) of 5.01 J cm-3 with a charge-discharge efficiency (η) of 78.1% at 600 MV m-1, and a record Ue of 2.55 J cm-3 at η = 90%, which is 10-fold larger than that of the state-of-art commercial polyetherimides (PEIs). In addition, compared with aromatic polyimides, the all-alicyclic polyimide possesses a better self-clearing characteristic due to a smaller ratio of carbon to hydrogen and oxygen, which facilitates its long-term reliability in practical applications.
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Purpose: Using previously approved medications for new indications can expedite the lengthy and expensive drug development process. We describe a bioinformatics pipeline that integrates genomics and proteomics platforms to identify already-approved drugs that might be useful to treat diabetic retinopathy (DR). Methods: Proteomics analysis of vitreous humor samples from 12 patients undergoing pars plana vitrectomy for DR and a whole genome dataset (UKBiobank TOPMed-imputed) from 1330 individuals with DR and 395,155 controls were analyzed independently to identify biological pathways associated with DR. Common biological pathways shared between both datasets were further analyzed (STRING and REACTOME analyses) to identify target proteins for probable drug modulation. Curated target proteins were subsequently analyzed by the BindingDB database to identify chemical compounds they interact with. Identified chemical compounds were further curated through the Expasy SwissSimilarity database for already-approved drugs that interact with target proteins. Results: The pathways in each dataset (proteomics and genomics) converged in the upregulation of a previously unknown pathway involved in DR (RUNX2 signaling; constituents MMP-13 and LGALS3), with an emphasis on its role in angiogenesis and blood-retina barrier. Bioinformatics analysis identified U.S. Food and Drug Administration (FDA)-approved medications (raltitrexed, pemetrexed, glyburide, probenecid, clindamycin hydrochloride, and ticagrelor) that, in theory, may modulate this pathway. Conclusions: The bioinformatics pipeline described here identifies FDA-approved drugs that can be used for new alternative indications. These theoretical candidate drugs should be validated with experimental studies. Translational Relevance: Our study suggests possible drugs for DR treatment based on an integrated proteomics and genomics pipeline. This approach can potentially expedite the drug discovery process by identifying already-approved drugs that might be used for new indications.
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Diabetes Mellitus , Retinopatía Diabética , Estados Unidos , Humanos , Proteómica , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/genética , GenómicaRESUMEN
The dissemination of bioaerosols in the westerly wind from the Asian continent to the northwestern Pacific constantly links the land and marine ecosystems. Several observation campaigns targeting bioaerosols were conducted in the coastal city Qingdao of China (QD), at a coast site of Kumamoto in southwestern Japan (KM), and in the northwestern Pacific (NP) between 2014 and 2016. We compared the concentration of bioaerosols in the range of 1.1-7.0 µm obtained in those campaigns to investigate their variation in the westerly wind. The substantial influence of westerlies on bioaerosol concentration was confirmed in the three areas. In the case of non-dust air, the arrival of the continental air led to a 29 % decrease of bioaerosols at KM while a 57 % increase at NP, indicating that the concentration in non-dust air was lower than the local level in the island air while higher than that in the remote marine air. In case of dust occurrence, bioaerosols in the air decreased with the distance from the Asian continent at KM and NP consecutively, and the arrival of the air caused a 2-fold increase at KM and a 1.7-fold increase at NP. The relative concentration increase rate of bioaerosols (IRRC), defined as the ratio of the increment of bioaerosols caused by long-distance transported air to the local level in each area, decreased rapidly after the air left the continent in the dust cases, which is similar to the decrease of the dry deposition flux of dust reported in the literature. This result indicates that the reduction of bioaerosols in the dusty air was likely dominated by the removal of bioaerosols attached to dust particles.
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Contaminantes Atmosféricos , Humanos , Aerosoles/análisis , Microbiología del Aire , Contaminantes Atmosféricos/análisis , Polvo/análisis , Ecosistema , Monitoreo del Ambiente , VientoRESUMEN
BACKGROUND: Lacrimal adenoid cystic carcinoma (LACC) is the most common orbital malignant epithelial neoplasm. LACC with high-grade transformation (LACC-HGT) has higher rates of recurrence, metastasis, and mortality than LACC without HGT. This study investigated the effects of microRNA-29a-3p (miR-29a-3p) in the pathogenesis of LACC-HGT. METHODS: An Agilent human miRNA microarray was used to screen the differentially expressed miRNAs (DEMs) in LACC and LACC-HGT tumor tissues. Then, the primary cells obtained in previous studies were used to determine the effect of miR-29a-3p. RESULTS: The expression of miR-29a-3p was abnormally lower in LACC-HGT than in LACC. miR-29a-3p can specifically target the 3' UTR of Quaking mRNA and down-regulate Quaking expression, thereby inhibiting the proliferation, migration, and epithelial-mesenchymal transition of LACC cells. CONCLUSIONS: This study illustrated that miR-29a-3p functions as a tumor suppressor by down-regulating the expression of Quaking to inhibit the tumorigenesis of LACC cells. This study may also reveal the pathogenesis of HGT in LACC cells and provide a reference for LACC-HGT targeted diagnosis.