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1.
Mater Horiz ; 11(18): 4519, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39206597

RESUMEN

Correction for 'High-performance one-dimensional halide perovskite crossbar memristors and synapses for neuromorphic computing' by Sujaya Kumar Vishwanath et al., Mater. Horiz., 2024, 11, 2643-2656, https://doi.org/10.1039/D3MH02055J.

2.
World J Clin Cases ; 12(21): 4717-4725, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39070850

RESUMEN

BACKGROUND: Abdominal aortitis can induce aneurysms, and tumor rupture can lead to organ ischemia or even sudden death. At present, there is a lack of extensive understanding and identification of key problems in the treatment of abdominal aortitis, which needs to be further analyzed using bibliometric analysis. AIM: To discuss the research hotspot and development trend of abdominal aortitis treatment. METHODS: We searched the English literature (published from January 1, 2000 to March 12, 2024) on the treatment of abdominal aortitis in the Web of Science database. Then, we identified and screened duplicate literature using CiteSpace 6.1R2 software. We conducted an analysis of the number of papers, a co-occurrence analysis of the authors and institutions, and co-occurrence and cluster analyses of the keywords. Then, we drew the author, institution, and keywords of the studies into graphs for visualization. Finally, we expounded on the author, institutional network interactions, and hot keywords of the studies on the treatment of abdominal aortitis. RESULTS: We included 210 English literature articles involving 190 authors; the author cooperation team was mainly represented by Caradu Caroline, Berard Xavier, Lu Guanyi, Harada Kenichi, and Sharma Ashish K. In the keyword analysis, high-frequency keywords include abdominal aortic aneurysm (38), abdominal aorta (24), Takayasu arteritis (22), etc. The three most central keywords were disease (0.69), classification (0.68), and abdominal aortic aneurysm (0.55). The first nine clusters of keywords are case report, abdominal aortic aneurysm, Takayasu arteritis, dyspnea hematuria, aortic elastic, IgG4-related disease, report, mid aortic dysplastic syndrome, and statin. In the keyword emergent analysis, 14 emergent words were obtained. Among them, seven keywords with strong abruptness were Takayasu arteritis, abdominal aortic aneurysm, disease, retroperitoneal fibrosis, expression, management, and large vessel vasculitis. In the past 3 years, the incidences of abdominal aortic aneurysm (intensity: 4.62) and inflammation (intensity: 1.99) were higher. CONCLUSION: The number of published papers is on the increase, but the cooperation among authors is scattered. The research focus is mainly on the pathogenesis and treatment of abdominal aortitis-related diseases.

3.
Adv Mater ; 36(36): e2406568, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032111

RESUMEN

The ability to perceive color by the retina can be attributed to both its trichromatic photoreceptors and the antagonistic neural wiring known as the opponent process. While neuromorphic sensors have been shown to demonstrate memory and adaptation capabilities, color perception is still challenging due to the intrinsic lack of spectral selectivity in narrow bandgap semiconductors. Furthermore, research on emulating neural wiring is severely lacking. The combination of halide perovskite materials with a tunable bandgap and a novel bipolar photodetector design emulates the efficiency of the retina in processing color information. The stimuli-responsive material is also responsible for maintaining partial color constancy-an adaptation feature. Leveraging the unique enhancement of color contrasts, an in-sensor data compression and edge detection can also be demonstrated. The color perception, chromatic adaptation, and color contrast enhancement make perovskite bipolar photodetectors a unique example where the sensor and neural wiring can be co-developed in conjunction.

4.
Mil Med Res ; 11(1): 33, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816888

RESUMEN

Orthopedic conditions have emerged as global health concerns, impacting approximately 1.7 billion individuals worldwide. However, the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders. The advent of single-cell RNA sequencing (scRNA-seq) technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity. Nevertheless, investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges. In this comprehensive review, we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines. By utilizing these methodologies, crucial insights into the developmental dynamics, maintenance of homeostasis, and pathological processes involved in spine, joint, bone, muscle, and tendon disorders have been uncovered. Specifically focusing on the joint diseases of degenerative disc disease, osteoarthritis, and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension. These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.


Asunto(s)
Análisis de Secuencia de ARN , Análisis de la Célula Individual , Humanos , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Enfermedades Óseas/terapia , Enfermedades Óseas/fisiopatología , Huesos , Biología Computacional/métodos
5.
Mater Horiz ; 11(11): 2643-2656, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38516931

RESUMEN

Despite impressive demonstrations of memristive behavior with halide perovskites, no clear pathway for material and device design exists for their applications in neuromorphic computing. Present approaches are limited to single element structures, fall behind in terms of switching reliability and scalability, and fail to map out the analog programming window of such devices. Here, we systematically design and evaluate robust pyridinium-templated one-dimensional halide perovskites as crossbar memristive materials for artificial neural networks. We compare two halide perovskite 1D inorganic lattices, namely (propyl)pyridinium and (benzyl)pyridinium lead iodide. The absence of conjugated, electron-rich substituents in PrPyr+ prevents edge-to-face type π-stacking, leading to enhanced electronic isolation of the 1D iodoplumbate chains in (PrPyr)[PbI3], and hence, superior resistive switching performance compared to (BnzPyr)[PbI3]. We report outstanding resistive switching behaviours in (PrPyr)[PbI3] on the largest flexible crossbar implementation (16 × 16) to date - on/off ratio (>105), long term retention (105 s) and high endurance (2000 cycles). Finally, we put forth a universal approach to comprehensively map the analog programming window of halide perovskite memristive devices - a critical prerequisite for weighted synaptic connections in artificial neural networks. This consequently facilitates the demonstration of accurate handwritten digit recognition from the MNIST database based on spike-timing-dependent plasticity of halide perovskite memristive synapses.

6.
Animals (Basel) ; 14(3)2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38338159

RESUMEN

The present study was undertaken to determine the effect of daily calcium chloride (CaCl2) supplementation from day of entry into the farrowing house until day of farrowing (6.4 ± 0.3 d) on stillbirth rates. Landrace × Large White sows (parities 4 to 6; n = 53) were offered 40 g/d CaCl2 (n = 28) or served as controls (n = 25). The morning before their estimated farrowing date, a blood sample was obtained from 25 sows for calcium measurement and a urine sample from 22 sows for pH measurement. The feeding of CaCl2 decreased urinary pH compared to the control group (p < 0.001), indicative of an induced metabolic acidosis, but there was no effect of feeding CaCl2 on serum calcium concentrations or the incidence of stillbirths. Nonetheless, regardless of treatment, sows with higher serum calcium concentrations (>2.5 vs. <2.5 mmol) or lower urine pH (<7.0 vs. >7.0) had fewer stillborn piglets (p < 0.001 for both). While showing that low serum calcium levels will increase stillbirth rates, our data indicate that the administration of 40 g/d CaCl2 for 6 d prior to farrowing was not sufficient to increase serum calcium or decrease stillbirth incidence.

7.
3D Print Med ; 10(1): 2, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38246981

RESUMEN

BACKGROUND: Surgical management for intracranial and extracranial communicating tumors is difficult due to the complex anatomical structures. Therefore, assisting methods are urgently needed. Accordingly, this study aimed to investigate the utility of a three-dimensional (3D)-printed model in the treatment of intracranial and extracranial communicating tumors as well as its applicability in surgical planning and resident education. METHODS: Individualized 3D-printed models were created for eight patients with intracranial and extracranial communicating tumors. Based on these 3D-printed models, a comprehensive surgical plan was made for each patient, after which the patients underwent surgery. The clinicopathological data of patients were collected and retrospectively analyzed to determine surgical outcomes. To examine the educational capability of the 3D-printed models, specialists and resident doctors were invited to review three of these cases and then rate the clinical utility of the models using a questionnaire. RESULTS: The 3D-printed models accurately replicated anatomical structures, including the tumor, surrounding structures, and the skull. Based on these models, customized surgical approaches, including the orbitozygomatic approach and transcervical approach, were designed for the patients. Although parameters such as operation time and blood loss varied among the patients, satisfactory surgical outcomes were achieved, with only one patient developing a postoperative complication. Regarding the educational applicability of the 3D-printed model, the mean agreement for all eight questionnaire items was above six (seven being complete agreement). Moreover, no significant difference was noted in the agreement scores between specialists and residents. CONCLUSION: The results revealed that 3D-printed models have good structural accuracy and are potentially beneficial in developing surgical approaches and educating residents. Further research is needed to test the true applicability of these models in the treatment of intracranial and extracranial communicating tumors.

8.
Adv Mater ; 36(5): e2305857, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37640560

RESUMEN

Neuromorphic devices can help perform memory-heavy tasks more efficiently due to the co-localization of memory and computing. In biological systems, fast dynamics are necessary for rapid communication, while slow dynamics aid in the amplification of signals over noise and regulatory processes such as adaptation- such dual dynamics are key for neuromorphic control systems. Halide perovskites exhibit much more complex phenomena than conventional semiconductors due to their coupled ionic, electronic, and optical properties which result in modulatable drift, diffusion of ions, carriers, and radiative recombination dynamics. This is exploited to engineer a dual-emitter tandem device with the requisite dual slow-fast dynamics. Here, a perovskite-organic tandem light-emitting diode (LED) capable of modulating its emission spectrum and intensity owing to the ion-mediated recombination zone modulation between the green-emitting quasi-2D perovskite layer and the red-emitting organic layer is introduced. Frequency-dependent response and high dynamic range memory of emission intensity and spectra in a LED are demonstrated. Utilizing the emissive read-out, image contrast enhancement as a neuromorphic pre-processing step to improve pattern recognition capabilities is illustrated. As proof of concept using the device's slow-fast dynamics, an inhibition of the return mechanism is physically emulated.

9.
Biochimie ; 216: 181-193, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37748748

RESUMEN

Malassezia globosa is abundant and prevalent on sebaceous areas of the human skin. Genome annotation reveals that M. globosa possesses a repertoire of secreted hydrolytic enzymes relevant for lipid and protein metabolism. However, the functional significance of these enzymes is uncertain and presence of these genes in the genome does not always translate to expression at the cutaneous surface. In this study we utilized targeted RNA sequencing from samples isolated directly from the skin to quantify gene expression of M. globosa secreted proteases, lipases, phospholipases and sphingomyelinases. Our findings indicate that the expression of these enzymes is dynamically regulated by the environment in which the fungus resides, as different growth phases of the planktonic culture of M. globosa show distinct expression levels. Furthermore, we observed significant differences in the expression of these enzymes in culture compared to healthy sebaceous skin sites. By examining the in situ gene expression of M. globosa's secreted hydrolases, we identified a predicted aspartyl protease, MGL_3331, which is highly expressed on both healthy and disease-affected dermatological sites. However, molecular modeling and biochemical studies revealed that this protein has a non-canonical active site motif and lacks measurable proteolytic activity. This pseudoprotease MGL_3331 elicits a heightened IgE-reactivity in blood plasma isolated from patients with atopic dermatitis compared to healthy individuals and invokes a pro-inflammatory response in peripheral blood mononuclear cells. Overall, our study highlights the importance of studying fungal proteins expressed in physiologically relevant environments and underscores the notion that secreted inactive enzymes may have important functions in influencing host immunity.


Asunto(s)
Alérgenos , Malassezia , Humanos , Alérgenos/metabolismo , Malassezia/genética , Malassezia/metabolismo , Leucocitos Mononucleares/metabolismo , Piel/metabolismo , Lipasa/metabolismo
10.
Cell Death Dis ; 14(11): 759, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993428

RESUMEN

Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous in tumor microenvironment (TME). Cross-talk between cancer cells and CAFs results in cancer progression. Here, we demonstrated that a distinct cancer-associated fibroblasts subset with podoplanin (PDPN) positive expression (PDPN+ CAFs) was correlated with poor survival in oral squamous cell carcinoma (OSCC). PDPN+ CAFs promoted the progression of OSCC by transferring exosomal lncRNA FTX to OSCC cells. Mechanically, FTX bound to flap endonuclease-1 (FEN1), forming an RNA‒protein complex. FTX enhanced promoter demethylation of FEN1 by recruiting ten-eleven translocation-2 (TET2). In addition, FTX/FEN1 axis promoted OSCC cells motility by inhibiting ferroptosis. In xenograft experiments, RSL-3, a ferroptosis-inducing agent, suppressed the tumorigenesis potential of FEN1-overexpressed OSCC cells. Furthermore, Acyl-CoA synthetase long-chain family member 4 (ACSL4) was confirmed to participate in the motility promotion induced by FEN1 overexpression. FEN1 could bind to promoter region of ACSL4 and then inhibit ferroptosis in OSCC cells. Our study reveals that PDPN+ CAFs promote the invasiveness of OSCC cells by inhibiting ferroptosis through FTX/FEN1/ACSL4 signaling cascade. PDPN+ CAFs may serve as a novel potential therapeutic target for OSCC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Carcinoma de Células Escamosas , Ferroptosis , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , ARN Largo no Codificante , Humanos , Carcinoma de Células Escamosas/patología , Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de la Boca/patología , Ferroptosis/genética , Fibroblastos/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Microambiente Tumoral , Glicoproteínas de Membrana/metabolismo
11.
Molecules ; 28(13)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37446928

RESUMEN

Formononetin (FNT) is a plant-derived isoflavone natural product with anti-inflammatory, antioxidant, and anti-allergic properties. We showed previously that FNT inhibits immunoglobulin E (IgE)-dependent mast cell (MC) activation, but the effect of FNT on IgE-independent MC activation is yet unknown. Our aim was to investigate the effects and possible mechanisms of action of FNT on IgE-independent MC activation and pseudoallergic inflammation. We studied the effects of FNT on MC degranulation in vitro with a cell culture model using compound C48/80 to stimulate either mouse bone marrow-derived mast cells (BMMCs) or RBL-2H3 cells. We subsequently measured ß-hexosaminase and histamine release, the expression of inflammatory factors, cell morphological changes, and changes in NF-κB signaling. We also studied the effects of FNT in several in vivo murine models of allergic reaction: C48/80-mediated passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), and 2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). The results showed that FNT inhibited IgE-independent degranulation of MCs, evaluated by a decrease in the release of ß-hexosaminase and histamine and a decreased expression of inflammatory factors. Additionally, FNT reduced cytomorphological elongation and F-actin reorganization and attenuated NF-κB p65 phosphorylation and NF-κB-dependent promoter activity. Moreover, the administration of FNT alleviated pseudoallergic responses in vivo in mouse models of C48/80-stimulated PCA and ASA, and DNCB-induced AD. In conclusion, we suggest that FNT may be a novel anti-allergic drug with great potential to alleviate pseudoallergic responses via the inhibition of IgE-independent MC degranulation and NF-κB signaling.


Asunto(s)
Anafilaxia , Antialérgicos , Isoflavonas , Ratones , Animales , Mastocitos , p-Metoxi-N-metilfenetilamina/farmacología , FN-kappa B/metabolismo , Degranulación de la Célula , Dinitroclorobenceno/metabolismo , Anafilaxia/tratamiento farmacológico , Isoflavonas/metabolismo , Inmunoglobulina E/metabolismo , Antialérgicos/uso terapéutico
12.
Bioengineering (Basel) ; 10(5)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37237590

RESUMEN

Unbiased metagenomic sequencing is conceptually well-suited for first-line diagnosis as all known and unknown infectious entities can be detected, but costs, turnaround time and human background reads in complex biofluids, such as plasma, hinder widespread deployment. Separate preparations of DNA and RNA also increases costs. In this study, we developed a rapid unbiased metagenomics next-generation sequencing (mNGS) workflow with a human background depletion method (HostEL) and a combined DNA/RNA library preparation kit (AmpRE) to address this issue. We enriched and detected bacterial and fungal standards spiked in plasma at physiological levels with low-depth sequencing (<1 million reads) for analytical validation. Clinical validation also showed 93% of plasma samples agreed with the clinical diagnostic test results when the diagnostic qPCR had a Ct < 33. The effect of different sequencing times was evaluated with the 19 h iSeq 100 paired end run, a more clinically palatable simulated iSeq 100 truncated run and the rapid 7 h MiniSeq platform. Our results demonstrate the ability to detect both DNA and RNA pathogens with low-depth sequencing and that iSeq 100 and MiniSeq platforms are compatible with unbiased low-depth metagenomics identification with the HostEL and AmpRE workflow.

13.
Mil Med Res ; 10(1): 16, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36978167

RESUMEN

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.


Asunto(s)
Materiales Biocompatibles , Materiales Biomiméticos , Humanos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Materiales Biocompatibles/química , Ingeniería de Tejidos , Medicina Regenerativa , Biomimética , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/uso terapéutico , Materiales Biomiméticos/química
14.
Huan Jing Ke Xue ; 44(1): 219-230, 2023 Jan 08.
Artículo en Chino | MEDLINE | ID: mdl-36635810

RESUMEN

Lake Luoma is an important storage lake for the Eastern route of the South-to-North Water Diversion Project (NSBD), which has many functions including flood control and irrigation, drinking water supply, and ecological maintenance. In order to understand the succession patterns and driving factors of water quality in Lake Luoma, we used monthly monitoring data from 2009 to 2020 in combination with historical data from 1996 to 2008. The long-term succession patterns, seasonal dynamics, and spatial patterns of total nitrogen (TN), total phosphorus (TP), permanganate index, and ammonia nitrogen (NH+4-N) were examined, and the influence of meteorological and hydrological factors on water quality was explored through correlation analyses and generalized additive models. The results showed that it remained in the status of grade Ⅳ-inferior Ⅴ over the past 25 years. The concentration of TN, which was the main pollutant, changed significantly (1.06-3.49 mg·L-1), experiencing three stages of gradual decline (1996-2002), significant interannual fluctuation (2002-2015), and significant increase (2015-2020). Permanganate index decreased significantly (2.97-6.38 mg·L-1), whereas TP and NH+4-N concentration fluctuated slightly, ranging from 0.024-0.076 mg·L-1 and 0.11-0.69 mg·L-1, respectively. The concentration of TN and TP increased abnormally in the summer of 2017-2020, reaching 3.30 mg·L-1 and 0.14 mg·L-1 in August, respectively, which was approximately 1.5 and 2.4 times the annual average. In terms of seasonal dynamics, the seasonal variation in water quality between summer/autumn and winter/spring reversed after 2015, with water quality in summer/autumn being worse than that in winter and spring, indicating the exacerbation of eutrophication. The water quality in the southern area was obviously better than that in the northern area. The input of pollutants from the Yihe River and Middle Canal increased with water quantity since 2015, which drove the water quality deterioration through nutrients. Our results suggested that the water quality of Lake Luoma should be improved by strengthening exogenous pollution reduction, endogenous control, polder dismantling, and ecological restoration.


Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Calidad del Agua , Lagos , Monitoreo del Ambiente/métodos , Inundaciones , Fósforo/análisis , Nitrógeno/análisis , Eutrofización , Contaminantes Químicos del Agua/análisis , Contaminantes Ambientales/análisis , China
15.
Angiology ; 74(6): 509-518, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36366730

RESUMEN

Patients undergoing transcatheter aortic valve implantation (TAVI) commonly have co-morbidities requiring anticoagulation. However, the optimal post-procedural anticoagulation regimen is not well-established. This meta-analysis investigates safety and efficacy outcomes of direct oral anticoagulants (DOACs) and Vitamin K Antagonist (VKA), with or without concomitant antiplatelet therapy. We searched EMBASE and MEDLINE for appropriate studies. Subgroup analyses were performed for anticoagulant monotherapy and combined therapy with antiplatelet agents. Eleven studies (6359 patients) were included. Overall, there were no differences between DOACs and VKA for all-cause mortality (Odds Ratio [OR]: .69; Credible Interval [CrI]: .40-1.06), cardiovascular-related mortality (OR: .76; Crl: .13-3.47), bleeding (OR: .95; CrI: .75-1.17), stroke (OR: 1.04; CrI: .65-1.63), myocardial infarction (OR: 1.51; CrI: .55-3.84), and valve thrombosis (OR: .29; CrI: .01-3.54). For DOACs vs VKA monotherapy subgroup, there were no differences in outcomes. For the combined therapy subgroup, there was decreased odds of all-cause mortality in the DOACs group compared with the VKA group (OR: .13; CrI: .02-.65), but no differences for bleeding and stroke. DOACs and VKA have similar safety and efficacy profiles for post-TAVI patients with anticoagulation indication. However, if concomitant antiplatelet therapy is required, DOACs were more favorable than VKA for all-cause mortality.


Asunto(s)
Accidente Cerebrovascular , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Teorema de Bayes , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Fibrinolíticos , Accidente Cerebrovascular/tratamiento farmacológico , Vitamina K , Administración Oral
16.
Proc Natl Acad Sci U S A ; 119(49): e2212533119, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36442106

RESUMEN

Malassezia form the dominant eukaryotic microbial community on the human skin. The Malassezia genus possesses a repertoire of secretory hydrolytic enzymes involved in protein and lipid metabolism which alter the external cutaneous environment. The exact role of most Malassezia secreted enzymes, including those in interaction with the epithelial surface, is not well characterized. In this study, we compared the expression level of secreted proteases, lipases, phospholipases, and sphingomyelinases of Malassezia globosa in healthy subjects and seborrheic dermatitis or atopic dermatitis patients. We observed upregulated gene expression of the previously characterized secretory aspartyl protease MGSAP1 in both diseased groups, in lesional and non-lesional skin sites, as compared to healthy subjects. To explore the functional roles of MGSAP1 in skin disease, we generated a knockout mutant of the homologous protease MFSAP1 in the genetically tractable Malassezia furfur. We observed the loss of MFSAP1 resulted in dramatic changes in the cell adhesion and dispersal in both culture and a human 3D reconstituted epidermis model. In a murine model of Malassezia colonization, we further demonstrated Mfsap1 contributes to inflammation as observed by reduced edema and inflammatory cell infiltration with the knockout mutant versus wildtype. Taken together, we show that this dominant secretory Malassezia aspartyl protease has an important role in enabling a planktonic cellular state that can potentially aid in colonization and additionally as a virulence factor in barrier-compromised skin, further highlighting the importance of considering the contextual relevance when evaluating the functions of secreted microbial enzymes.


Asunto(s)
Proteasas de Ácido Aspártico , Dermatitis Atópica , Malassezia , Humanos , Animales , Ratones , Péptido Hidrolasas/genética , Malassezia/genética , Inflamación , Ácido Aspártico Endopeptidasas
17.
JID Innov ; 2(4): 100130, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35860448

RESUMEN

Atopic dermatitis (AD) is a skin inflammatory disease in which the opportunistic pathogen Staphylococcus aureus is prevalent and abundant. S. aureus harbors several secreted virulence factors that have well-studied functions in infection models, but it is unclear whether these extracellular microbial factors are relevant in the context of AD. To address this question, we designed a culture-independent method to detect and quantify S. aureus virulence factors expressed at the skin sites. We utilized RNase-H‒dependent multiplex PCR for preamplification of reverse-transcribed RNA extracted from tape strips of patients with AD sampled at skin sites with differing severity and assessed the expression of a panel of S. aureus virulence factors using qPCR. We observed an increase in viable S. aureus abundance on sites with increased severity of disease, and many virulence factors were expressed at the AD skin sites. Surprisingly, we did not observe any significant upregulation of the virulence factors at the lesional sites compared with those at the nonlesional control. Overall, we utilized a robust assay to directly detect and quantify viable S. aureus and its associated virulence factors at the site of AD skin lesions. This method can be extended to study the expression of skin microbial genes at the sites of various dermatological conditions.

18.
ACS Nano ; 16(2): 2942-2952, 2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35040632

RESUMEN

Extending halide perovskites' optoelectronic properties to stimuli-responsive chromism enables switchable optoelectronics, information display, and smart window applications. Here, we demonstrate a band gap tunability (chromism) via crystal structure transformation from three-dimensional FAPbBr3 to a ⟨110⟩ oriented FAn+2PbnBr3n+2 structure using a mono-halide/cation composition (FA/Pb) tuning. Furthermore, we illustrate reversible photochromism in halide perovskite by modulating the intermediate n phase in the FAn+2PbnBr3n+2 structure, enabling greater control of the optical band gap and luminescence of a ⟨110⟩ oriented mono-halide/cation perovskite. Proton transfer reaction-mass spectroscopy carried out to precisely quantify the decomposition product reveals that the organic solvent in the film is a key contributor to the structural transformation and, therefore, the chromism in the ⟨110⟩ structure. These intermediate n phases (2 ≤ n ≤ ∞) stabilize in metastable states in the FAn+2PbnBr3n+2 system, which is accessible via strain or optical or thermal input. The structure reversibility in the ⟨110⟩ perovskite allowed us to demonstrate a class of photochromic sensors capable of self-adaptation to lighting.

19.
Infect Immun ; 90(1): e0039721, 2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34606369

RESUMEN

The human skin is our outermost layer and serves as a protective barrier against external insults. Advances in next-generation sequencing have enabled the discoveries of a rich and diverse community of microbes-bacteria, fungi, and viruses that are residents of this surface. The genomes of these microbes also revealed the presence of many secretory enzymes. In particular, proteases which are hydrolytic enzymes capable of protein cleavage and degradation are of special interest in the skin environment, which is enriched in proteins and lipids. In this minireview, we will focus on the roles of these skin-relevant microbial secreted proteases, in terms of both their widely studied roles as pathogenic agents in tissue invasion and host immune inactivation and their recently discovered roles in intermicrobial interactions and modulation of virulence factors. From these studies, it has become apparent that while microbial proteases are capable of a wide range of functions, their expression is tightly regulated and highly responsive to the environments the microbes are in. With the introduction of new biochemical and bioinformatics tools to study protease functions, it will be important to understand the roles played by skin microbial secretory proteases in cutaneous health, especially the less studied commensal microbes with an emphasis on contextual relevance.


Asunto(s)
Endopeptidasas , Interacciones Microbiota-Huesped , Microbiota , Piel/microbiología , Factores de Virulencia , Bacterias/enzimología , Biomarcadores , Susceptibilidad a Enfermedades , Hongos/enzimología , Interacciones Huésped-Patógeno , Humanos
20.
Nat Commun ; 12(1): 3681, 2021 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-34140514

RESUMEN

Physical Unclonable Functions (PUFs) address the inherent limitations of conventional hardware security solutions in edge-computing devices. Despite impressive demonstrations with silicon circuits and crossbars of oxide memristors, realizing efficient roots of trust for resource-constrained hardware remains a significant challenge. Hybrid organic electronic materials with a rich reservoir of exotic switching physics offer an attractive, inexpensive alternative to design efficient cryptographic hardware, but have not been investigated till date. Here, we report a breakthrough security primitive exploiting the switching physics of one dimensional halide perovskite memristors as excellent sources of entropy for secure key generation and device authentication. Measurements of a prototypical 1 kb propyl pyridinium lead iodide (PrPyr[PbI3]) weak memristor PUF with a differential write-back strategy reveals near ideal uniformity, uniqueness and reliability without additional area and power overheads. Cycle-to-cycle write variability enables reconfigurability, while in-memory computing empowers a strong recurrent PUF construction to thwart machine learning attacks.

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