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1.
EMBO J ; 43(8): 1499-1518, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38528181

RESUMEN

The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.


Asunto(s)
Cadenas Ligeras de Miosina , Salmonella enterica , Cadenas Ligeras de Miosina/genética , Cadenas Ligeras de Miosina/metabolismo , Actinas/metabolismo , Células Epiteliales/metabolismo , Macrófagos/metabolismo
2.
Hepatology ; 78(2): 468-485, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35815363

RESUMEN

BACKGROUND AND AIMS: Natural killer (NK) cells are key players in tumor immunosurveillance, and metabolic adaptation manipulates their fate and functional state. The nicotinamide adenine dinucleotide (NAD + ) has emerged as a vital factor to link cellular metabolism and signaling transduction. Here, we identified NAD + metabolism as a central hub to determine the homeostasis and function of NK cells. APPROACH AND RESULTS: NAD + level was elevated in activated NK cells. NAD + supplementation not only enhanced cytokine production and cytotoxicity but also improved the proliferation and viability of NK cells. Intriguingly, the salvage pathway was involved in maintaining NAD + homeostasis in activated NK cells. Genetic ablation or pharmacological blockade of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD + salvage pathway, markedly destroyed the viability and function of NK cells. Mechanistically, NAD + salvage dictated the mitochondrial homeostasis and oxidative phosphorylation activity to support the optimal function of NK cells. However, in human HCC tissues, NAMPT expression and NAD + level were significantly down-regulated in tumor-infiltrating NK cells, which negatively correlated with patient survival. And lactate accumulation in the tumor microenvironment was at least partially responsible for the transcriptional repression of NAMPT in NK cells. Further, deficiency of Nampt in NK cells accelerated the growth of HCC and melanoma. Supplementation of the NAD + precursor nicotinamide mononucleotide (NMN) significantly improved NK antitumor response in both mouse and human cell-derived xenografts. CONCLUSIONS: These findings reveal NAD + salvage as an essential factor for NK-cell homeostasis and function, suggesting a potential strategy for invigorating NK cell-based immunotherapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Ratones , Animales , NAD/metabolismo , Mononucleótido de Nicotinamida/metabolismo , Citocinas/metabolismo , Células Asesinas Naturales/metabolismo , Microambiente Tumoral
3.
Biomacromolecules ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38820501

RESUMEN

The development of a natural, additive-free, absorbable sponge with procoagulant activity for noncompressible hemostasis remains a challenging task. In this study, we extracted high molecular weight keratin (HK) from human hair and transformed it into a hemostatic sponge with a well-interconnected pore structure using a foaming technique, freeze-drying, and oxidation cross-linking. By controlling the cross-linking degree, the resulting sponge demonstrated excellent liquid absorption ability, shape recovery characteristics, and robust mechanical properties. The HK10 sponge exhibited rapid liquid absorption, expanding up to 600% within 5 s. Moreover, the HK sponge showed superior platelet activation and blood cell adhesion capabilities. In SD rat liver defect models, the sponges demonstrated excellent hemostatic performance by sealing the wound and expediting coagulation, reducing the hemostatic time from 825 to 297 s. Furthermore, HK sponges have excellent biosafety, positioning them as a promising absorbable sponge with the potential for the treatment of noncompressible hemostasis.

4.
Br J Clin Pharmacol ; 90(2): 452-462, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37749762

RESUMEN

AIMS: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. METHODS: Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. RESULTS: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. CONCLUSIONS: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Adulto , Humanos , Teicoplanina/uso terapéutico , Antibacterianos , Estudios Retrospectivos , Monitoreo de Drogas , Albúmina Sérica , Infecciones Estafilocócicas/tratamiento farmacológico
5.
J Wound Care ; 33(1): 22-27, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38197281

RESUMEN

Patients with diabetes who undergo a kidney transplant are at a great risk of undergoing amputations, usually associated with severe infection and necrosis. The treatment of severe diabetic foot necrosis is challenging in clinic, and the function of the limb is often hugely compromised. A 74-year-old male who had been diagnosed with severe post-renal transplant diabetic foot necrosis refused the option of below-knee amputation from previous surgeons, and requested to keep his left foot. The patient was treated with integrated traditional Chinese medicine (TCM) and Western medicine, with positive results. TCM therapeutic principles included 'clearing heat, removing toxicity, regulating Qi, resolving dampness, activating stagnant blood and nourishing yin as well as tonifying Qi and blood'. Treatment with Western medicine included wound debridement, internal fixation or joint fusion, and use of insulin, antibiotics and vasodilators. The patient was treated with a staged and diverse approach (i.e., a combination of TCM and Western medicine, surgical management and education for diabetic foot care), which ultimately helped the patient achieve limb salvage and regain normal function. A combination therapy of Western medicine and TCM may be a promising approach to heal diabetic foot ulcers.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Anciano , Humanos , Masculino , Terapia Combinada , Pie Diabético/cirugía , Pie , Resultado del Tratamiento , Medicina Tradicional China
6.
Drug Dev Res ; 85(1): e22131, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37943623

RESUMEN

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Proproteína Convertasa 9 , Humanos , Proproteína Convertasa 9/metabolismo , LDL-Colesterol/metabolismo , Subtilisinas , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico
7.
Plant Foods Hum Nutr ; 79(1): 48-58, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37962805

RESUMEN

Angiotensin I-converting enzyme (ACE)-inhibiting peptides were isolated from walnut protein isolate (WPI) using ultrasound-assisted extraction. This study aimed to assess the impact of ultrasonic pretreatment on the physicochemical properties of WPI. The optimal extraction conditions for WPI were determined as a 15-min ultrasonic treatment at 400 W. Subsequently, the hydrolysate exhibiting the highest in vitro ACE-inhibiting activity underwent further processing and separation steps, including ultrafiltration, ion exchange chromatography, liquid chromatography-tandem mass spectrometry, ADMET screening, and molecular docking. As a result of this comprehensive process, two previously unidentified ACE-inhibiting peptides, namely Tyr-Ile-Gln (YIQ) and Ile-Tyr-Gln (IYQ), were identified. In addition, a novel peptide, Ile-Lys-Gln (IKQ), was synthesized, demonstrating superior ACE-inhibiting activity and temperature stability. In silico analysis estimated an in vivo utilization rate of 21.7% for IKQ. These peptides were observed to inhibit ACE through an anti-competitive mechanism, with molecular docking simulations suggesting an interaction mechanism involving hydrogen bonding. Notably, both IYQ and IKQ peptides exhibited no discernible toxicity to HUVECs cells and promoted nitric oxide (NO) generation. These findings underscore the potential of ultrasonicated WPI in the separation of ACE-inhibiting peptides and their utility in the development of novel ACE inhibitors for functional food applications.


Asunto(s)
Juglans , Juglans/química , Juglans/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Hidrolisados de Proteína/química
8.
Angew Chem Int Ed Engl ; : e202408653, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819994

RESUMEN

Multi-excitonic emitting materials in luminescent metal halides are emerging candidates for anti-counterfeiting and information encryption applications. Herein, ATPP2SnCl6 (ATPP = acetonyltriphenylphosphonium) phase was designed and synthesized by rationally choosing emissive organic reagent of ATPPCl and non-toxic stable metal ions of Sn4+, and Sb3+ was further doped into ATPP2SnCl6 to tune the photoluminescence with external self-trapped excitons emission. The derived non-toxic ATPP2SnCl6 shows multi-excitonic luminescent centers verified by optical study and differential charge-density from density functional theory calculations. Incorporation of Sb3+ dopants and the increasing concentrations induce the efficient energy transfer therein, thus enhancing photoluminescence quantum yield from 5.1% to 73.8%. The multi-excitonic emission inspires the creation of information encryption and decryption by leveraging the photoluminescence from ATPPCl to ATPP2SnCl6 host and ATPP2SnCl6:Sb3+. This study facilitates the anti-counterfeiting application by employing solution-processable luminescent metal halides materials with excitation-dependent PL properties.

9.
Angew Chem Int Ed Engl ; 63(18): e202401716, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38372050

RESUMEN

High-capacity Ni-rich layered oxides are promising cathode materials for fabrication of lithium-ion batteries (LIBs) with high energy density. However, thermal runaway of LIBs with these cathodes leads to great safety concerns. In this study, single crystalline LiNi0.9Co0.05Mn0.05O2 (NCM-SC) has been prepared and a flexible optical fiber was buried inside the pouch-type LIBs with NCM-SC cathode to in situ study its real-time temperature evolution during charge/discharge process. NCM-SC exhibits an enhanced Li+ ions transportation efficiency and electrode reaction kinetics, which can effectively reduce the generation of polarization heat and mitigate the internal temperature rise of the pouch-type battery. Meanwhile, solid-electrolyte interface (SEI) film decomposition and gas accumulation are effectively alleviated, due to the enhanced thermal stability of SEI film formed on NCM-SC. Moreover, the single crystal architecture can effectively retard layered to spinal and rock-salt phase transition, mitigate the crack formation and structural collapse. Consequently, NCM-SC exhibits an excellent electrochemical performance and enhanced thermal stability.

10.
J Proteome Res ; 22(10): 3332-3347, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37616386

RESUMEN

Brown adipose tissue (BAT) thermogenesis confers beneficial effects on metabolic diseases such as obesity and type-2 diabetes. Nevertheless, the mechanism and lipid driving the process that evokes this response have not been investigated yet. Here, a multiomics approach of integrative transcriptomics and lipidomics is used to explore the mechanism of regulating thermogenesis in BAT and providing promising lipid biomarkers and biomarker genes for thermogenic activators as antiobesity drugs. Lipidomics analysis demonstrated that a high abundance of glycerophospholipids and sphingolipids was more significant in BAT than in WAT. Enrichment analysis of upregulated DEGs between WAT and BAT screened suggested that the differences were mainly involved in lipid metabolism. Besides, ß3-adrenergic agonist stimulation reduced the levels of TAG and DAG and increased the content of PC, PE, CL, and LPC and expression of genes involved in thermogenesis, fatty acid elongation, and glycerophospholipid metabolism in BAT. In this study, based on interpreting the inherent characterization of BAT as thermogenic tissue through comparison with WAT as fat storage tissue, adrenergic stimulation-induced BAT thermogenesis further identified specific lipid biomarkers (7 TAG species, 10 PC species, 1 LPC species, and 1 CL species) and Elovl3 and Crat gene biomarkers, which may provide targets for combating obesity by boosting BAT thermogenesis.

11.
Immunology ; 168(1): 49-62, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35908188

RESUMEN

Obesity is generally associated with low-grade inflammation. Adipose tissue macrophages (ATMs) orchestrate metabolic inflammation. The classical (M1-like) or alternative (M2-like) activation of ATMs is functionally coupled with the metabolic status of fat tissues. It has been found that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) inhibits inflammation by regulating macrophages. However, the exact role of Tim-4 in macrophage polarization and obesity remains unknown. Here, we identified Tim-4 as a critical switch governing macrophage M1/M2 polarization and energy homeostasis. Tim-4 deletion led to spontaneous obesity in elder mice and promoted obesity severity of db/db mice. Obesity microenvironment enhanced the expression of Tim-4 in white adipose tissue and ATMs. In vitro, we detected an increase in M1-like cells and decrease in M2-like cells in both peritoneal macrophages and bone marrow-derived macrophages from Tim-4 knockout mice. Mechanistically, we demonstrated that Tim-4 promoted M2-like macrophages polarization via suppressing nuclear factor kappa B (NF-κB) signaling pathway. In addition, we found that Tim-4 promoted TLR4 internalization, which might contribute to regulation of NF-κB signaling. Collectively, these results indicated that Tim-4 maintained adipose tissue homeostasis by regulating macrophage polarization via NF-κB pathway, which would provide a new target for obesity intervention.


Asunto(s)
Tejido Adiposo , Macrófagos , Proteínas de la Membrana , Animales , Ratones , Homeostasis , Inmunoglobulinas/metabolismo , Inflamación/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/metabolismo , Obesidad/metabolismo , Linfocitos T/metabolismo , Transducción de Señal
12.
Curr Issues Mol Biol ; 46(1): 153-170, 2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38248314

RESUMEN

Adaptation to thermal conditions in tidal mudflats always involves tolerating frequent fluctuations and often extreme environmental temperatures. Regulation of gene expression plays a fundamental role in the evolution of these thermal adaptations. To identify the key gene regulatory networks associated with the thermal adaptation, we investigated the capability of cold tolerance, as well as the transcriptomic changes under cold stress in two mudflat inhabitants (Odontamblyopus lacepedii and O. rebecca) with contrasting latitude affinity. Our results revealed a remarkable divergent capacity of cold tolerance (CTmin: 0.61 °C vs. 9.57 °C) between the two gobies. Analysis of transcriptomic changes under cold stress unveiled 193 differentially expressed genes exhibiting similar expression profiles across all tissues and species, including several classic metabolic and circadian rhythm molecules such as ACOD and CIART that may represent the core cold response machinery in eel gobies. Meanwhile, some genes show a unique expression spectrum in the more cold-tolerant O. lacepedii suggesting their roles in the enhanced cold tolerance and hence the extreme thermal adaptations. In addition, a weighted gene co-expression network analysis (WGCNA) revealed a subset of metabolic hub genes including MYH11 and LIPT2 showing distinct down-regulation in O. lacepedii when exposed to cold stress which highlights the role of reduced energy consumption in the enhanced cold tolerance of eel gobies. These findings not only provide new insights into how mudflat teleosts could cope with cold stress and their potential evolutionary strategies for adapting to their thermal environment, but also have important implications for sound management and conservation of their fishery resources in a scenario of global climate warming in the marine realm.

13.
Anal Chem ; 95(2): 1618-1626, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36541937

RESUMEN

CRISPR/Cas12a shows excellent potential in disease diagnostics. However, insensitive signal conversion strategies hindered its application in detecting protein biomarkers. Here, we report a metal-organic framework (MOF)-based DNA bio-barcode integrated with the CRISPR/Cas12a system for ultrasensitive detection of protein biomarkers. In this work, zirconium-based MOF nanoparticles were comodified with antibodies and bio-barcode phosphorylated DNA as an efficient signal converter, which not only recognized the protein biomarker to form the sandwich complex but also released the bio-barcode DNA activators after MOF dissociation to activate the trans-cleavage activity of Cas12a. Due to the obvious advantages, including numerous loaded oligonucleotides, a convenient release process, and the nontoxic release reagent, this MOF-DNA bio-barcode strategy could amplify the CRISPR/Cas12a system to achieve simple and highly sensitive detection of tumor protein biomarkers with detection limits of 0.03 pg/mL (PSA) and 0.1 pg/mL (CEA), respectively. Furthermore, this platform could detect PSA directly in clinical serum samples, offering a powerful tool for early disease diagnosis.


Asunto(s)
Técnicas Biosensibles , Estructuras Metalorgánicas , Sistemas CRISPR-Cas/genética , Biomarcadores de Tumor/genética , ADN , Anticuerpos
14.
Ann Neurol ; 91(5): 716-729, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35178738

RESUMEN

OBJECTIVE: The objective of this study is to develop a novel method for monitoring the integrity of motor neurons in vivo by quantifying net retrograde axonal transport. METHODS: The method uses single photon emission computed tomography to quantify retrograde transport to spinal cord of tetanus toxin fragment C (125 I-TTC) following intramuscular injection. We characterized the transport profiles in 3 transgenic mouse models carrying amyotrophic lateral sclerosis (ALS)-associated genes, aging mice, and SOD1G93A transgenic mice following CRISPR/Cas9 gene editing. Lastly, we studied the effect of prior immunization of tetanus toxoid on the transport profile of TTC. RESULTS: This technique defines a quantitative profile of net retrograde axonal transport of TTC in living mice. The profile is distinctly abnormal in transgenic SOD1G93A mice as young as 65 days (presymptomatic) and worsens with disease progression. Moreover, this method detects a distinct therapeutic benefit of gene editing in transgenic SOD1G93A mice well before other clinical parameters (eg, grip strength) show improvement. Symptomatic transgenic PFN1C71G/C71G ALS mice display gross reductions in net retrograde axonal transport, which is also disturbed in asymptomatic mice harboring a human C9ORF72 transgene with an expanded GGGGCC repeat motif. In wild-type mice, net retrograde axonal transport declines with aging. Lastly, prior immunization with tetanus toxoid does not preclude use of this assay. INTERPRETATION: This assay of net retrograde axonal transport has broad potential clinical applications and should be particularly valuable as a physiological biomarker that permits early detection of benefit from potential therapies for motor neuron diseases. ANN NEUROL 2022;91:716-729.


Asunto(s)
Esclerosis Amiotrófica Lateral , Transporte Axonal , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/genética , Animales , Transporte Axonal/genética , Biomarcadores , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Transgénicos , Profilinas , Médula Espinal/diagnóstico por imagen , Médula Espinal/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Toxoide Tetánico
15.
Altern Ther Health Med ; 29(8): 172-177, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37535926

RESUMEN

Objective: To investigate the response of (BM-MSCs) to the Ruan Jian Qing Mai formula (RJQM) in the treatment of atherosclerotic occlusion (ASO), and consequently promoting the development of collateral circulation and angiogenesis. Method: 35 male rats were randomly assigned to 6 experimental groups and A control group. 0.9% NaCl solution and 2.7, 5.4, 10.8, 16.2, 21.6, and 27 g × kg-1 × d-1 of RJQM formula were gavaged to the experimental groups twice a day for 8 days. After the last administration, medicated serum was prepared from the blood collected from the abdominal aorta. The human BM-MSCs were divided into an experimental group and a control group. A blank group of cells was added with a complete medium without rat serum; an experimental group of cells was added with the prepared drug-containing serum. Under hypoxic conditions, the drug-containing serum was used to treat BM-MSCs and/or endothelial cells of human umbilical vein (HUVECs). A Cell counting kit (CCK8) was used to detect cell proliferation. Western blot (WB) and quantitative real-time PCR (qPCR) were used to identify related genes expression. Results: The results of this study showed that the purity of the BM-MSCs was >95%. The drug-containing serum significantly rise in CCND1 expression (encoding cyclin D1) and MYC, especially when the concentration of medicated serum was 10.8 g × kg-1 × d-1. Treatment of either BM-MSCs or HUVECs alone or both with medicated serum aids in the spread of mesenchymal stem cells from the bone marrow to HUVECs. qPCR results showed that the mRNA expression of CCL2, CCL3, CCL25, IL8, IGF1, and PDGFB increased dramatically after treatment with medicated serum. The expression of the corresponding receptors for these up-regulated chemokines was detected in BM-MSCs, and it was found that CXCR1, CXCR4, CXCR7, and PDGFRB were up-regulated. Conclusion: This study provides a preliminary understanding of the mechanism of RJQM in the treatment of ASO.


Asunto(s)
Células Endoteliales , Células Madre Mesenquimatosas , Humanos , Masculino , Ratas , Animales , Médula Ósea , Proliferación Celular , Transducción de Señal , Células Madre Mesenquimatosas/metabolismo
16.
Sensors (Basel) ; 23(10)2023 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-37430635

RESUMEN

For maritime broadband communications, atmospheric ducts can enable beyond line-of-sight communications or cause severe interference. Due to the strong spatial-temporal variability of atmospheric conditions in near-shore areas, atmospheric ducts have inherent spatial heterogeneity and suddenness. This paper aims to evaluate the effect of horizontally inhomogeneous ducts on maritime radio propagation through theoretical analysis and measurement validation. To make better use of meteorological reanalysis data, we design a range-dependent atmospheric duct model. Then, a sliced parabolic equation algorithm is proposed to improve the prediction accuracy of path loss. We derive the corresponding numerical solution and analyze the feasibility of the proposed algorithm under the range-dependent duct conditions. A 3.5 GHz long-distance radio propagation measurement is utilized to verify the algorithm. The spatial distribution characteristics of atmospheric ducts in the measurements are analyzed. Based on actual duct conditions, the simulation results are consistent with the measured path loss. The proposed algorithm outperforms the existing method during the multiple duct periods. We further investigate the influence of different duct horizontal characteristics on the received signal strength.

17.
Nano Lett ; 22(23): 9714-9722, 2022 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-36412588

RESUMEN

CRISPR/Cas12a has shown great potential in molecular diagnostics, but its application in sensing of microRNAs (miRNAs) was limited by sensitivity and complexity. Here, we have sensitively and conveniently detected microRNAs by reasonably integrating metal-organic frameworks (MOFs) based biobarcodes with CRISPR/Cas12a assay (designated as MBCA). In this work, DNA-functionalized Zr-MOFs were designed as the converter to convert and amplify each miRNA target into activators that can initiate the trans-cleavage activity of CRISPR/Cas12a to further amplify the signal. Such integration provides a universal strategy for sensitive detection of miRNAs. By tuning the complementary sequences modified on nanoprobes, this assay achieves subattomolar sensitivity for different miRNAs and was selective to single-based mismatches. With the proposed method, the expression of miR-21 in different cancer cells can be assessed, and breast cancer patients and healthy individuals can be differentiated by analyzing the target miRNAs extracted from serum samples, holding great potential in clinical diagnosis.


Asunto(s)
Técnicas Biosensibles , Neoplasias de la Mama , Estructuras Metalorgánicas , MicroARNs , Humanos , Femenino , MicroARNs/genética , Sistemas CRISPR-Cas/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Diferenciación Celular
18.
Drug Dev Res ; 84(2): 326-336, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36567647

RESUMEN

Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Administración del Tratamiento Farmacológico , Farmacéuticos , Quimioterapia Combinada , Antibacterianos/farmacología , Resultado del Tratamiento
19.
Int J Mol Sci ; 24(16)2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37629073

RESUMEN

Amblyopinae is one of the lineage of bony fish that preserves amphibious traits living in tidal mudflat habitats. In contrast to other active amphibious fish, Amblyopinae species adopt a seemly more passive lifestyle by living in deep burrows of mudflat to circumvent the typical negative effects associated with terrestriality. However, little is known about the genetic origin of these mudflat deep-burrowing adaptations in Amblyopinae. Here we sequenced the first genome of Amblyopinae species, Taenioides sp., to elucidate their mudflat deep-burrowing adaptations. Our results revealed an assembled genome size of 774.06 Mb with 23 pseudochromosomes anchored, which predicted 22,399 protein-coding genes. Phylogenetic analyses indicated that Taenioides sp. diverged from the active amphibious fish of mudskipper approximately 28.3 Ma ago. In addition, 185 and 977 putative gene families were identified to be under expansion, contraction and 172 genes were undergone positive selection in Taenioides sp., respectively. Enrichment categories of top candidate genes under significant expansion and selection were mainly associated with hematopoiesis or angiogenesis, DNA repairs and the immune response, possibly suggesting their involvement in the adaptation to the hypoxia and diverse pathogens typically observed in mudflat burrowing environments. Some carbohydrate/lipid metabolism, and insulin signaling genes were also remarkably alterated, illustrating physiological remolding associated with nutrient-limited subterranean environments. Interestingly, several genes related to visual perception (e.g., crystallins) have undergone apparent gene losses, pointing to their role in the small vestigial eyes development in Taenioides sp. Our work provide valuable resources for understanding the molecular mechanisms underlying mudflat deep-burrowing adaptations in Amblyopinae, as well as in other tidal burrowing teleosts.


Asunto(s)
Aclimatación , Perciformes , Animales , Filogenia , Mapeo Cromosómico , Secuencia de Bases , Anguilas
20.
Ergonomics ; : 1-13, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37824713

RESUMEN

This study identified the key factors of spousal support that influence the outcomes and willingness of female knowledge workers to work from home (WFH). A questionnaire of 59 items was developed, covering basic personal information, spousal support, work perception, work-life balance, and willingness to WFH: 139 valid responses from female participants were collected and analysed. Exploratory factor analysis revealed six distinct factors of spousal support. Regression analysis found that personal-related emotional support, personal-related instrumental support, work-related emotional support, and work-related instrumental support demonstrated positive correlations with work perception and work-life balance, while family-related instrumental support positively correlated with work-life balance. Personal-related emotional support and personal-related instrumental support positively correlated with the willingness to WFH. Notably, personal-related emotional support exhibited the strongest correlation coefficients for willingness and outcomes. The findings could provide information on how a husband could improve his wife's well-being when WFH.Practitioner summary: A survey was conducted among female knowledge workers to examine the influence of different factors of spousal support on the outcomes and willingness of WFH. The results shed light on how husbands can improve their wives' well-being during WFH, offering practical guidance for supporting spouses in this context.

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