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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124949, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39153344

RESUMEN

A nonparametric point-by-point (NPP) method is presented for high-accuracy measurement of the time-dependent frequency (laser frequency) in tunable laser absorption spectroscopy, crucial for ensuring ultimate measurement accuracy. In wavelength modulation spectroscopy in particular, the parametric methods in current use for time-dependent frequency measurement are insufficiently accurate and are difficult to apply to complex modulation scenarios. Based on a multi-scale viewpoint, point-by-point measurement of the frequency is realized by linear superposition of the frequency information mapped from the interferometric signal on a unit scale and on a local scale. Validation experiments indicate that the measurement accuracy of the proposed NPP method is three times that of the existing parametric methods, while effectively immunizing against non-ideal tuning effects. Additionally, the NPP method is suitable for use with arbitrarily complex modulations such as square wave modulation, for which parametric methods are inapplicable.

2.
Biomaterials ; 312: 122743, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39111233

RESUMEN

Photodynamic therapy (PDT) is an appealing modality for cancer treatments. However, the limited tissue penetration depth of external-excitation light makes PDT impossible in treating deep-seated tumors. Meanwhile, tumor hypoxia and intracellular reductive microenvironment restrain the generation of reactive oxygen species (ROS). To overcome these limitations, a tumor-targeted self-illuminating supramolecular nanoparticle T-NPCe6-L-N is proposed by integrating photosensitizer Ce6 with luminol and nitric oxide (NO) for chemiluminescence resonance energy transfer (CRET)-activated PDT. The high H2O2 level in tumor can trigger chemiluminescence of luminol to realize CRET-activated PDT without exposure of external light. Meanwhile, the released NO significantly relieves tumor hypoxia via vascular normalization and reduces intracellular reductive GSH level, further enhancing ROS abundance. Importantly, due to the different ROS levels between cancer cells and normal cells, T-NPCe6-L-N can selectively trigger PDT in cancer cells while sparing normal cells, which ensured low side effect. The combination of CRET-based photosensitizer-activation and tumor microenvironment modulation overcomes the innate challenges of conventional PDT, demonstrating efficient inhibition of orthotopic and metastatic tumors on mice. It also provoked potent immunogenic cell death to ensure long-term suppression effects. The proof-of-concept research proved as a new strategy to solve the dilemma of PDT in treatment of deep-seated tumors.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Microambiente Tumoral , Fotoquimioterapia/métodos , Microambiente Tumoral/efectos de los fármacos , Animales , Nanopartículas/química , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Humanos , Ratones , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Transferencia de Energía , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Ratones Endogámicos BALB C , Luz , Ratones Desnudos , Óxido Nítrico/metabolismo
3.
Adv Sci (Weinh) ; : e2404608, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250325

RESUMEN

Post-translational modifications on the histone H3 tail regulate chromatin structure, impact epigenetics, and hence the gene expressions. Current chemical modulation tools, such as unnatural amino acid incorporation, protein splicing, and sortase-based editing, have allowed for the modification of histones with various PTMs in cellular contexts, but are not applicable for editing native chromatin. The use of small organic molecules to manipulate histone-modifying enzymes alters endogenous histone PTMs but lacks precise temporal and spatial control. To date, there has been no achievement in modulating histone methylation in living cells with spatiotemporal resolution. In this study, a new method is presented for temporally manipulating histone dimethylation H3K9me2 using a photo-responsive inhibitor that specifically targets the methyltransferase G9a on demand. The photo-caged molecule is stable under physiological conditions and cellular environments, but rapidly activated upon exposure to light, releasing the bioactive component that can immediately inhibit the catalytic ability of the G9a in vitro. Besides, this masked compound could also efficiently reactivate the inhibition of methyltransferase activity in living cells, subsequently suppress H3K9me2, a mark that regulates various chromatin functions. Therefore, the chemical system will be a valuable tool for manipulating the epigenome for therapeutic purposes and furthering the understanding of epigenetic mechanisms.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39250706

RESUMEN

Under purely inorganic conditions, a synthesis route was devised wherein elements were introduced stepwise via coprecipitation based on differences in compound solubility. This synthesis method can change the microscopic morphology of the material without relying on a templating agent, resulting in the formation of the multilayered lamellar Ce/Eu codoped zinc oxide solid solution (ZCEOSS) with a self-assembled nested imbrication structure. The study improves the critical matter of corrosion by focusing on the electron and energy transfer mechanisms. By introduction of the bandgap modulator cerium element and fluorescence enhancer europium element into the ZnO material, the anticorrosion material has been successfully endowed with both photocathodic protection and luminescent initiative/stress dual corrosion defense functions. Due to the energy level staircase protection mechanism synergistically generated by the 4f electron shell of rare-earth elements in concert with semiconductor zinc oxide, the energy band positions were modulated to progressively guide the direction of electron flow, thereby suppressing corrosion reactions. In particular, the ZCEOSS material synthesized by doping 1% cerium and 7% europium and adding rare-earth elements at pH 7 exhibited the best corrosion inhibition performance. After immersion in simulated seawater for 96 h, Tafel polarization test results showed that compared to epoxy resin and ZnO anticorrosion systems, the ZCEOSS anticorrosion system exhibited significantly improved corrosion inhibition efficiency with enhancements of 1028.3 and 402.9%, respectively. This study provides new insights into the development of highly efficient inorganic anticorrosion materials.

5.
J Mot Behav ; : 1-14, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250912

RESUMEN

This study examined whether target pursuit tracking by a performer-controlled computer cursor around a square diamond-shaped circuit, using isometric pinch grip force production, would show a significant difference in performance metrics dependent on the clockwise sense of the target movement along the trajectory path. The target template incorporated path segments requiring all four possible combinations of directional force modulation patterns (increasing and decreasing isometric pinch forces of the thumb and index finger). Overall, it was found that cursor positional accuracy was greater during counterclockwise pursuit, that steadiness was greater during clockwise pursuit, and that the cursor bearing angle with respect to target movement was biased toward cursor positioning being within the interior of the trajectory circuit regardless of clockwise sense.

6.
Phys Eng Sci Med ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39249664

RESUMEN

A novel phantom for measuring the 10% and 50% values of the modulation transfer function (MTF) for computed tomography scanners (CT) was investigated. The phantom was constructed by drilling rows of holes of different sizes and frequencies into a small block of polymethyl methacrylate (PMMA). The MTF at a given frequency was determined from the ratio of the range of Hounsfield units within the rows of holes at different frequencies, and the difference in Hounsfield units between air and PMMA. A MTF curve was plotted from measurements at different frequencies and the 10% and 50% MTF values were obtained from a cubic spline interpolation. The MTF results obtained with the drilled hole phantom method were compared to a conventional method - using a thin wire and Spice-CT ImageJ Plugin- and with identical acquisition and reconstruction parameters. The drilled hole phantom measured the 50% MTF with reasonable accuracy but underestimated the 10% MTF by 8.2% on average. MTF measurements were reproducible for repeated image acquisitions and with different users analysing the images, and the phantom was able to accurately measure the change in MTF when measured on images using different reconstruction kernels. The tool may find application as a cheap, easy to use method for routine QC testing of CT scanners.

7.
Environ Res ; 262(Pt 2): 119913, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39233030

RESUMEN

This study investigates the enhancement of ozone adsorption on diverse TiO2 crystal interfaces through an innovative electrochemical modulation approach. The research focuses on the effects of applied electric field strength and reaction sites on ozone interfacial adsorption energies for Ti/Anatase TiO2 (0 0 1) and Ti/Rutile TiO2 (1 1 0) interfaces. The findings reveal that positive electric fields significantly enhance ozone adsorption on both interfaces, with adsorption energies increasing by up to 18% for Ti/Anatase TiO2 (0 0 1) and 15% for Ti/Rutile TiO2 (1 1 0). Notably, double water molecule sites (≡(H2O)2) play a crucial role in this enhancement process. The study demonstrates that the applied electric field alters the charge distribution at the TiO2 catalytic interface, thereby increasing interfacial charge density and promoting charge migration to ozone. Furthermore, this process leads to enhanced overlap and hybridization between ≡(H2O)2 sites and the s and p orbitals of ozone molecules, resulting in the formation of chemical bonds with lower Fermi levels. These comprehensive results demonstrate the broad applicability of the electrochemical interfacial ozone adsorption enhancement method across different crystal types and surfaces. Consequently, this study provides essential data to support the advancement of greener and more energy-efficient heterogeneous catalytic ozonation processes, potentially contributing to significant improvements in ozone-based water treatment technologies.

8.
Gut Microbes ; 16(1): 2399360, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39287010

RESUMEN

The gut microbiome is a complex, unique entity implicated in the prevention, pathogenesis, and progression of common gastrointestinal diseases. While largely dominated by bacterial populations, advanced sequencing techniques have identified co-inhabiting fungal communities, collectively referred to as the mycobiome. Early studies identified that gut inflammation is associated with altered microbial composition, known as gut dysbiosis. Altered microbial profiles are implicated in various pathological diseases, such as inflammatory bowel disease (IBD), though their role as a cause or consequence of systemic inflammation remains the subject of ongoing research. Diet plays a crucial role in the prevention and management of various diseases and is considered to be an essential regulator of systemic inflammation. This review compiles current literature on the impact of dietary modulation on the mycobiome, showing that dietary changes can alter the fungal architecture of the gut. Further research is required to understand the impact of diet on gut fungi, including the metabolic pathways and enzymes involved in fungal fermentation. Additionally, investigating whether dietary modulation of the gut mycobiome could be utilized as a therapy in IBD is essential.


Asunto(s)
Dieta , Disbiosis , Hongos , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Micobioma , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/dietoterapia , Humanos , Hongos/clasificación , Hongos/genética , Hongos/aislamiento & purificación , Disbiosis/microbiología , Animales , Tracto Gastrointestinal/microbiología
9.
Somatosens Mot Res ; : 1-9, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269173

RESUMEN

INTRODUCTION: Conditioned pain modulation (CPM) allows to investigate endogenous pain modulation and its clinical outcomes. Although co-activation of emotions has been shown to affect CPM, the impact of 'threat,' which may accompany CPM stimulation itself, has been mostly neglected. A critical factor for the threat level of the conditioning stimulus (CS) may be its predictability. METHODS: 38 healthy participants (18 female) took part in a CPM study with pressure stimulation on the leg (blood-pressure cuff) serving as CS and heat stimulation on the forearm (contact thermode; CHEPS) serving as test stimulus (TS). While CS varied in intensity and -as operationalisation of threat- in temporary predictability, TS was kept constant. CPM effects were studied by EEG parameters (N2P2) and pain ratings. RESULTS: We found a significant CPM effect when considering N2P2, with low CS predictability augmenting CPM inhibition; in contrast, a surprisingly facilitatory CPM effect occurred in pain ratings (in the high CS predictability condition). The threat manipulation was only partially successful because CS intensity increased the threat ratings but not -as intended- CS predictability. Correlations between subjective and psychophysiological CPM responses were low. DISCUSSION: The differing CPM effects in subjective and psychophysiological responses, with both inhibitory and facilitatory effects, is puzzling but has already been observed earlier. The consideration of the CPM stimulation as major threat that is emotionally active is theoretically clearly justifiable but the operationalisation by means of different levels of CS predictability as in the present study might not have been ideal. Thus, further attempts of experimental verification are warranted.

10.
Biochem Pharmacol ; 229: 116521, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39251140

RESUMEN

Abscisic acid (ABA), a phytohormone traditionally recognized for its role in plant stress responses, has recently emerged as a significant player in mammalian defense mechanisms. Like plants, various mammalian cell types synthesize ABA in response to specific health challenges, although the precise pathways remain not fully elucidated. ABA is associated with the regulation of inflammation and insulin signaling, prompting extensive research into its potential as a therapeutic agent for various diseases. ABA exerts its effects through its receptors, particularly PPAR-γ and LANCL-2, which serve as signaling hubs regulating numerous pathways. Through these interactions, ABA profoundly impacts mammalian health, and new ABA targets continue to be identified. Numerous studies in animal models demonstrate ABA's benefit in managing conditions such as neurological and psychiatric disorders, cancer, and malaria infections, all of which involve significant inflammatory dysregulation. In this manuscript we review the studies covering ABA synthesis and release in cell cultures, the signaling pathways regulated by ABA, and how these impact health in preclinical models. Furthermore, we highlight recent research suggesting that measuring ABA levels in human body fluids could serve as a useful biomarker for pathological conditions, providing insights into disease progression and treatment efficacy. This comprehensive review outlines the current understanding of ABA in mammalian pathophysiology, identifying gaps in knowledge, particularly concerning ABA biosynthesis and metabolism in mammals. In addition, this study emphasizes the need for clinical trials to validate the effectiveness of ABA-based therapies and its reliability as a biomarker for various diseases.

11.
Cell Calcium ; 123: 102947, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39226841

RESUMEN

S100A1, a calcium-binding protein, plays a crucial role in regulating Ca2+ signaling pathways in skeletal and cardiac myocytes via interactions with the ryanodine receptor (RyR) to affect Ca2+ release and contractile performance. Biophysical studies strongly suggest that S100A1 interacts with RyRs but have been inconclusive about both the nature of this interaction and its competition with another important calcium-binding protein, calmodulin (CaM). Thus, high-resolution cryo-EM studies of RyRs in the presence of S100A1, with or without additional CaM, were needed. The elegant work by Weninger et al. demonstrates the interaction between S100A1 and RyR1 through various experiments and confirms that S100A1 activates RyR1 at sub-micromolar Ca2+ concentrations, increasing the open probability of RyR1 channels.


Asunto(s)
Canal Liberador de Calcio Receptor de Rianodina , Proteínas S100 , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Humanos , Animales , Proteínas S100/metabolismo , Proteínas S100/química , Calcio/metabolismo , Calmodulina/metabolismo
12.
Nano Lett ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235125

RESUMEN

To address food security challenges and climate change, the polyploid wild rice Oryza alta has been explored as a potential crop, although it suffers from seed shattering. We employed mesoporous silica nanoparticles (MSNs) to deliver small interfering RNAs (siRNAs) for targeted gene silencing. Foliar spraying of MSN-siRNA complexes effectively delivered siRNA, resulting in up to 70% gene silencing of the PDS gene and 75% silencing of the transgenic Ruby gene. Additionally, MSN-siRNAs were infiltrated into the panicles of O. alta to target four seed shattering major genes every other day for 2 weeks until heading outdoors. This method silenced all four shattering genes ranging from 10.7% to 49.4% and significantly reduced the formation of the abscission layer between rice grains and pedicels, which enhanced pedicel tensile strength. Our MSN-siRNA system provides a flexible, nonpermanent approach to modifying crop traits, offering a promising tool for sustainable agricultural practices.

13.
Int J Mol Sci ; 25(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39273327

RESUMEN

Periodontitis is a chronic inflammatory disease resulting from the dysbiosis of periodontal bacteria and the host's immune response, leading to tissue degradation and sustained inflammation. Traditional treatments, such as mechanical debridement and antimicrobial agents, often fail to fully eradicate pathogenic bacteria, especially in deep periodontal pockets. Consequently, the need for novel therapeutic approaches has increased the interest in bioactive natural extracts, such as that of Opuntia ficus-indica, known for its anti-inflammatory, antioxidant, and antimicrobial properties. This study investigates the encapsulation of Opuntia ficus-indica extract in OFI-loaded chitosan nanoparticles (OFI-NPs) via ionotropic gelation using a microfluidic system, allowing precise control over nanoparticle characteristics and enhancing protection against enzymatic degradation. To achieve localized and sustained release in periodontal pockets, a thermo-responsive hydrogel comprising hyaluronic acid and Pluronic F127 (OFI@tgels) was developed. The transition of OFI@tgels from a solution at low temperatures to a solid at body temperature enables prolonged drug release at inflammation sites. The in vitro application of the optimized formulation eradicated biofilms of S. mutans, P. aeruginosa (PAO1), and P. gingivalis over 36 h and disrupted extracellular polymeric substance formation. Additionally, OFI@tgel modulated immune responses by inhibiting M1 macrophage polarization and promoting a shift to the M2 phenotype. These findings suggest that OFI@tgel is a promising alternative treatment for periodontitis, effectively reducing biofilm formation and modulating the immune response.


Asunto(s)
Quitosano , Hidrogeles , Nanopartículas , Opuntia , Periodontitis , Extractos Vegetales , Quitosano/química , Opuntia/química , Nanopartículas/química , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Periodontitis/terapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hidrogeles/química , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Streptococcus mutans/efectos de los fármacos , Humanos , Biopelículas/efectos de los fármacos , Porphyromonas gingivalis/efectos de los fármacos , Liberación de Fármacos , Portadores de Fármacos/química , Poloxámero/química , Pseudomonas aeruginosa/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química
14.
IEEE Trans Power Electron ; 39(3): 3289-3299, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39281019

RESUMEN

Multilevel converters have enabled various applications that are not possible with conventional two-level converters. Many of these applications, however, need a high output bandwidth, often approaching the switching rate limit of the transistors, with high quality, e.g., to actively stabilize and dampen a DC grid or specifically excite certain molecules or neural circuits in medical applications. A high bandwidth approaching the switching rate challenges existing modulation methods: carrier-based switching modulation is fine at low frequencies but experiences interaction between the carrier and the signal at the upper end of the spectrum; fundamental-frequency switching, such as nearest-level modulation (NLM), perform well at high frequencies but cause intolerable distortion for low frequency contents. We propose a hybrid modulation concept that can combine any methods from these two classes. It passes the error of a fundamental frequency method through a filtered switching modulator to combine the high output quality of the latter with the high bandwidth of the former. We optimize the filter to avoid under-modulation of the signal with the carrier of the modulator and to achieve the minimum overall distortion throughout a wide output bandwidth. We demonstrate the performance experimentally with a cascaded-bridge converter and compare it with the best prior arts. This technique ensures a usable output bandwidth up to 100% of the switching rate and maintains a total distortion level below 3%.

15.
Stem Cell Res Ther ; 15(1): 308, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285485

RESUMEN

BACKGROUND: Articular cartilage degeneration can result from injury, age, or arthritis, causing significant joint pain and disability without surgical intervention. Currently, the only FDA cell-based therapy for articular cartilage injury is Autologous Chondrocyte Implantation (ACI); however, this procedure is costly, time-intensive, and requires multiple treatments. Mesenchymal stromal cells (MSCs) are an attractive alternative autologous therapy due to their availability and ability to robustly differentiate into chondrocytes for transplantation with good safety profiles. However, treatment outcomes are variable due to donor-to-donor variability as well as intrapopulation heterogeneity and unstandardized MSC manufacturing protocols. Process improvements that reduce cell heterogeneity while increasing donor cell numbers with improved chondrogenic potential during expansion culture are needed to realize the full potential of MSC therapy. METHODS: In this study, we investigated the potential of MSC metabolic modulation during expansion to enhance their chondrogenic commitment by varying the nutrient composition, including glucose, pyruvate, glutamine, and ascorbic acid in culture media. We tested the effect of metabolic modulation in short-term (one passage) and long-term (up to seven passages). We measured metabolic state, cell size, population doubling time, and senescence and employed novel tools including micro-magnetic resonance relaxometry (µMRR) relaxation time (T2) to characterize the effects of AA on improved MSC expansion and chondrogenic potential. RESULTS: Our data show that the addition of 1 mM L-ascorbic acid-2-phosphate (AA) to cultures for one passage during MSC expansion prior to initiation of differentiation improves chondrogenic differentiation. We further demonstrate that AA treatment reduced the proportion of senescent cells and cell heterogeneity also allowing for long-term expansion that led to a > 300-fold increase in yield of MSCs with enhanced chondrogenic potential compared to untreated cells. AA-treated MSCs with improved chondrogenic potential showed a robust shift in metabolic profile to OXPHOS and higher µMRR T2 values, identifying critical quality attributes that could be implemented in MSC manufacturing for articular cartilage repair. CONCLUSIONS: Our results suggest an improved MSC manufacturing process that can enhance chondrogenic potential by targeting MSC metabolism and integrating process analytic tools during expansion.


Asunto(s)
Cartílago Articular , Condrocitos , Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Cartílago Articular/metabolismo , Humanos , Condrocitos/metabolismo , Condrocitos/citología , Condrogénesis/efectos de los fármacos , Diferenciación Celular , Células Cultivadas , Proliferación Celular , Trasplante de Células Madre Mesenquimatosas/métodos , Animales
16.
Adv Mater ; : e2406939, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291877

RESUMEN

Dual-band electrochromic materials have attracted significant attention due to their ability to independently control sunlight and solar heat. However, these materials generally exhibit notable limitations, and the mechanisms for their dual-band independent regulation remain poorly understood. Here, the visible-NIR-independent regulation capabilities of hexagonal WO3 (h-WO3) are introduced for the first time. A structure-activity relationship that perfectly links the microscopic ion insertion sequence and cavity characteristics to the macroscopic dual-band electrochromic properties is established. The progressive ion intercalation process and the distinctive optical activity of the cavities are keys for enabling h-WO3 to independently modulate "bright," "cool," and "dark" modes. Notably, h-WO3 demonstrates superior dual-band electrochromic performance with a broadband full shielding effect from 550 to 2000 nm, achieving the widest full shielding band in dual-band electrochromic studies. Additionally, h-WO3 shows a high discharge capacity of 270.9 mAh m- 2 at 0.25 A m- 2, and requires only 49.1 and 209.7 mAh m- 2 to complete a full round-trip switch between "bright-cool" and "bright-dark" modes, respectively. The constructed device offers a dynamic temperature control range of up to 10.5 °C and supports a maximum voltage of 2.86 V, underscoring its considerable potential for practical applications and energy efficiency.

17.
J Bacteriol ; : e0014224, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292012

RESUMEN

The increase in antibiotic resistance in bacteria has prompted the efforts in developing new alternative strategies for pathogenic bacteria. We explored the feasibility of targeting Vibrio cholerae by neutralizing bacterial cellular processes rather than outright killing the pathogen. We investigated the efficacy of delivering engineered regulatory small RNAs (sRNAs) to modulate gene expression through DNA conjugation. As a proof of concept, we engineered several sRNAs targeting the type VI secretion system (T6SS), several of which were able to successfully knockdown the T6SS activity at different degrees. Using the same strategy, we modulated exopolysaccharide production and motility. Lastly, we delivered an sRNA targeting T6SS into V. cholerae via conjugation and observed a rapid knockdown of the T6SS activity. Coupling conjugation with engineered sRNAs represents a novel way of modulating gene expression in V. cholerae opening the door for the development of novel prophylactic and therapeutic applications. IMPORTANCE: Given the prevalence of antibiotic resistance, there is an increasing need to develop alternative approaches to managing pathogenic bacteria. In this work, we explore the feasibility of modulating the expression of various cellular systems in Vibrio cholerae using engineered regulatory sRNAs delivered into cells via DNA conjugation. These sRNAs are based on regulatory sRNAs found in V. cholerae and exploit its native regulatory machinery. By delivering these sRNAs conjugatively along with a real-time marker for DNA transfer, we found that complete knockdown of a targeted cellular system could be achieved within one cell division cycle after sRNA gene delivery. These results indicate that conjugative delivery of engineered regulatory sRNAs is a rapid and robust way of precisely targeting V. cholerae.

18.
Artículo en Inglés | MEDLINE | ID: mdl-39287656

RESUMEN

PURPOSE: The aim of this study was to develop a methodology, based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls). The "Modulation Transfer Function through-object" (MTF through-object) based on vergence object displacement was calculated for different pupil sizes and pseudophakic eyes. Tilt and decentration were also analysed in a realistic cornea eye model. METHODS: For comparison between the different IOLs, an optical quality criterion based on a minimum value the MTF through-object and the recognition of simulated vision optotypes was introduced. Five IOLs were used in this study: Tecnis Eyhance, Mini Well, Tecnis Symfony, Tecnis Synergy and RayOne EMV. RESULTS: The technique was validated with previous methodologies. A general narrowing of the through-object MTF curve compared to the through-focus MTF curve was shown, resulting in greater distances between near and intermediate points and less depth of field around the far peak. The comparison between the IOLs showed that variations in corneal aberrations, pupil size and decentration caused relevant changes in IOL performance. A decrease of the SA produced a hypermetropic shift of the far focus between + 0.3 D and + 0.4 D. Most of IOLs worsen the optical quality as pupil size increased, even the MTF through-object shape changed. Decentration was an important factor in IOL implantation, causing a significant change in MTF through-object shape in most of IOLs. CONCLUSIONS: This study highlights the need to evaluate pre-operative patients for corneal aberrations and pupillary size to have the best optical success after cataract surgery in multifocal or extended depth of focus IOLs. KEY MESSAGES: What is known MTF(Modulation Transfer Function) through-focus curves (calculated in image space by moving the detector plane) can be obtained from optical bench assembly or from commercial devices. Recently, some studies proposed to characterize the lens surface design based on the profilometric measurements What is new A novel methodology based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls) was shown. The "Modulation Transfer Function through-object" based on vergence object displacement was introduced in order to analyse five premium IOLs. MTF through-object curve is more appropriate for studying clinical behaviour, as it provides further near and intermediate points distances and lower depth of focus around far peak compare to MTF through-focus curves. The optical behaviour of the five IOLs can vary considerably depending on the eye model and pupil size. The effect of tilt and decentration on the MTF through-object the IOLs was analysed.

19.
J Athl Train ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288152

RESUMEN

CONTEXT: Patellofemoral pain (PFP) has poor long-term recovery outcomes. Central sensitization describes central nervous system changes altering pain modulation, which can complicate recovery (poorer prognosis, worse function). Signs of central sensitization include amplified pain facilitation, pain hypersensitivity, and impaired pain inhibition, which can be measured with temporal summation of pain (TSP), pressure pain thresholds (PPTs) and conditioned pain modulation (CPM), respectively. Sex differences exist for these test responses, but female-only PFP investigations of sensitization are uncommon. Understanding pain modulation in females with PFP could improve treatment protocols. OBJECTIVE: To determine whether females with PFP exhibit signs of central sensitization (greater TSP, lower PPTs, reduced CPM) compared to pain-free females. DESIGN: Cross-sectional Setting: Laboratory Patients or Other Participants: Thirty-three females [(20 PFP, 13 pain-free); Age: PFP 29.2 ± 7 years, pain-free 28 ± 7 years; Height: PFP 166.7 ± 5.9cm, pain-free 166 ± 9.5cm, Mass: PFP 66.7 ± 9.6kg, pain-free 69.3 ± 7.5kg). MAIN OUTCOME MEASURES: TSP was assessed with ten punctate stimuli applied to the knee and calculated by the difference in pain intensity between beginning and end responses. PPTs were tested at four sites [3 for local hypersensitivity (knee), 1 for widespread hypersensitivity (hand)]. CPM was conducted by comparing PPTs during two conditions (baseline, ice immersion). CPM response was defined as the percent difference between conditions. Between-group differences in TSP response were analyzed with a Welch's test. Separate Welch's tests analyzed group comparisons of PPTs and CPM responses at four sites. RESULTS: Females with PFP exhibited greater TSP response (P=0.019) and lower CPM response at patella center (P=0.010) and hand sites (P=0.007) than pain-free females. PPT group differences were not observed at any site (P>0.0125). CONCLUSIONS: Females with PFP modulate pain differently than pain-free females. Clinicians should recognize signs of central sensitization and their potential impact on treatment options.

20.
Nano Lett ; 24(37): 11358-11366, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39225503

RESUMEN

The elimination of Co from Ni-rich layered cathodes is critical to reduce the production cost and increase the energy density for sustainable development. Herein, a delicate strategy of crystal-facet modulation is designed and explored, which is achieved by simultaneous Al/W-doping into the precursors, while the surface role of the crystal-facet is intensively revealed. Unlike traditional studies on crystal structure growth along a certain direction, this work modulates the crystal-facet at the nanoscale based on the effect of W-doping dynamic migration with surface energy, successfully constructing the core-shell (003)/(104) facet surface. Compared to the (003) plane, the induced (104) facet at the surface can provide more space for Li+-activity, enabling lower interfacial polarization and higher Li+-transport rate. Additionally, bulk Al-doping is beneficial for enhancing the Li+-diffusion from the exterior surface to the interior lattice. With improved interfacial stability and restrained surface erosion, the product exhibits superior capacity retention and boosted rate performance under the elevated temperature.

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