Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Genome Res ; 33(7): 1124-1132, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37553263

RESUMO

Spatially resolved transcriptomics (SRT) technologies measure messenger RNA (mRNA) expression at thousands of locations in a tissue slice. However, nearly all SRT technologies measure expression in two-dimensional (2D) slices extracted from a 3D tissue, thus losing information that is shared across multiple slices from the same tissue. Integrating SRT data across multiple slices can help recover this information and improve downstream expression analyses, but multislice alignment and integration remains a challenging task. Existing methods for integrating SRT data either do not use spatial information or assume that the morphology of the tissue is largely preserved across slices, an assumption that is often violated because of biological or technical reasons. We introduce PASTE2, a method for partial alignment and 3D reconstruction of multislice SRT data sets, allowing only partial overlap between aligned slices and/or slice-specific cell types. PASTE2 formulates a novel partial fused Gromov-Wasserstein optimal transport problem, which we solve using a conditional gradient algorithm. PASTE2 includes a model selection procedure to estimate the fraction of overlap between slices, and optionally uses information from histological images that accompany some SRT experiments. We show on both simulated and real data that PASTE2 obtains more accurate alignments than existing methods. We further use PASTE2 to reconstruct a 3D map of gene expression in a Drosophila embryo from a 16 slice Stereo-seq data set. PASTE2 produces accurate alignments of multislice data sets from multiple SRT technologies, enabling detailed studies of spatial gene expression across a wide range of biological applications.


Assuntos
Algoritmos , Transcriptoma
2.
Genome Res ; 31(11): 2107-2119, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34426513

RESUMO

Coalescent methods are proven and powerful tools for population genetics, phylogenetics, epidemiology, and other fields. A promising avenue for the analysis of large genomic alignments, which are increasingly common, is coalescent hidden Markov model (coalHMM) methods, but these methods have lacked general usability and flexibility. We introduce a novel method for automatically learning a coalHMM and inferring the posterior distributions of evolutionary parameters using black-box variational inference, with the transition rates between local genealogies derived empirically by simulation. This derivation enables our method to work directly with three or four taxa and through a divide-and-conquer approach with more taxa. Using a simulated data set resembling a human-chimp-gorilla scenario, we show that our method has comparable or better accuracy to previous coalHMM methods. Both species divergence times and population sizes were accurately inferred. The method also infers local genealogies, and we report on their accuracy. Furthermore, we discuss a potential direction for scaling the method to larger data sets through a divide-and-conquer approach. This accuracy means our method is useful now, and by deriving transition rates by simulation, it is flexible enough to enable future implementations of various population models.


Assuntos
Genética Populacional , Modelos Genéticos , Animais , Simulação por Computador , Humanos , Densidade Demográfica , Recombinação Genética
3.
Angew Chem Int Ed Engl ; : e202411361, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39073279

RESUMO

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

4.
J Am Chem Soc ; 145(42): 23109-23120, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37820374

RESUMO

Coacervation has emerged as a prevalent mechanism to compartmentalize biomolecules in living cells. Synthetic coacervates help in understanding the assembly process and mimic the functions of biological coacervates as simplified artificial systems. Though the molecular mechanism and mesoscopic properties of coacervates formed from charged coacervates have been well investigated, the details of the assembly and stabilization of nonionic coacervates remain largely unknown. Here, we describe a library of coacervate-forming polyesteramides and show that the water-tertiary amide bridging hydrogen bonds and hydrophobic interactions stabilize these nonionic, single-component coacervates. Analogous to intracellular biological coacervates, these coacervates exhibit "liquid-like" features with low viscosity and low interfacial energy, and form coacervates with as few as five repeating units. By controlling the temperature and engineering the molar ratio between hydrophobic interaction sites and bridging hydrogen bonding sites, we demonstrate the tuneability of the viscosity and interfacial tension of polyesteramide-based coacervates. Taking advantage of the differences in the mesoscopic properties of these nonionic coacervates, we engineered multiphasic coacervates with core-shell architectures similar to those of intracellular biological coacervates, such as nucleoli and stress granule-p-body complexes. The multiphasic structures produced from these synthetic nonionic polyesteramide coacervates may serve as a valuable tool for investigating physicochemical principles deployed by living cells to spatiotemporally control cargo partitioning, biochemical reaction rates, and interorganellar signal transport.


Assuntos
Água , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Temperatura , Água/química
5.
Opt Lett ; 48(16): 4280-4283, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582012

RESUMO

We present a two-step diffraction method for an optical 360∘ cylindrical holographic display with a planar spatial light modulator (SLM) and a 45∘ conical mirror. The first step involves layered diffraction of the cylindrical object surface to obtain the complex amplitude distribution on the conical mirror, and the second step is the coordinate transformation, followed by plane-to-plane diffraction to finally obtain the hologram. Numerical simulations and optical experiments show that our proposed method offers improved accuracy in the propagation process compared with the previous method; furthermore, it enables better quality of reconstruction, particularly at large radius of object surface. We believe it is a solid step toward practicality for a cylindrical holographic display.

6.
Exp Physiol ; 108(11): 1409-1421, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37712355

RESUMO

The effect of different exercise intensities on the magnitude of post-exercise hypotension has not been rigorously clarified with respect to the metabolic thresholds that partition discrete exercise intensity domains (i.e., critical power and the gas exchange threshold (GET)). We hypothesized that the magnitude of post-exercise hypotension would be greater following isocaloric exercise performed above versus below critical power. Twelve non-hypertensive men completed a ramp incremental exercise test to determine maximal oxygen uptake and the GET, followed by five exhaustive constant load trials to determine critical power and W' (work available above critical power). Subsequently, criterion trials were performed at four discrete intensities matched for total work performed (i.e., isocaloric) to determine the impact of exercise intensity on post-exercise hypotension: 10% above critical power (10% > CP), 10% below critical power (10% < CP), 10% above GET (10% > GET) and 10% below GET (10% < GET). The post-exercise decrease (i.e., the minimum post-exercise values) in mean arterial (10% > CP: -12.7 ± 8.3 vs. 10% < CP: v3.5 ± 2.9 mmHg), diastolic (10% > CP: -9.6 ± 9.8 vs. 10% < CP: -1.4 ± 5.0 mmHg) and systolic (10% > CP: -23.8 ± 7.0 vs. 10% < CP: -9.9 ± 4.3 mmHg) blood pressures were greater following exercise performed 10% > CP compared to all other trials (all P < 0.01). No effects of exercise intensity on the magnitude of post-exercise hypotension were observed during exercise performed below critical power (all P > 0.05). Critical power represents a threshold above which the magnitude of post-exercise hypotension is greatly augmented. NEW FINDINGS: What is the central questions of this study? What is the influence of exercise intensity on the magnitude of post-exercise hypotension with respect to metabolic thresholds? What is the main finding and its importance? The magnitude of post-exercise hypotension is greatly increased following exercise performed above critical power. However, below critical power, there was no clear effect of exercise intensity on the magnitude of post-exercise hypotension.


Assuntos
Hipotensão Pós-Exercício , Masculino , Humanos , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Teste de Esforço/métodos
7.
BMC Cardiovasc Disord ; 21(1): 193, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879045

RESUMO

OBJECTIVES: Antegrade cerebral perfusion (ACP) under moderate hypothermic circulatory arrest is used during total aortic arch replacement surgery (TARS) in patients with acute type A aortic dissection, but it is associated with high mortality and morbidity. We hypothesized that combining ACP with retrograde inferior vena caval perfusion (RIVP) improves outcomes. METHODS: This pilot study was prospective, randomized, controlled and assessor-blinded. Patients scheduled for TARS were randomly treated with either ACP or RIVP + ACP. The primary outcome was a composite of mortality and major complications including paraplegia, postoperative renal failure, severe liver dysfunction, and gastrointestinal complications. Secondary outcomes included neurological complications, length of intubation and requirement of blood products. RESULTS: A total of 76 patients were recruited (n = 38 per group). Primary outcome occurred in 23 patients (61%) in the ACP group and 16 (42%) in the RIVP + ACP group (OR: 0.60, 95% CI: 0.21-1.62; p = 0.31). There was a lower incidence of transient neurological deficits in the RIVP + ACP group (26% vs. 58%, OR: 0.26; 95% CI: 0.10-0.67,p = 0.006;). The RIVP + ACP group underwent shorter intubation (25 vs 47 h, p = 0.022) and required fewer blood products (red cells, 3.8 units vs 6.5 units, p = 0.047; platelet: 2.0 units vs 2.0 units, p = 0.023) compared with the ACP group. CONCLUSIONS: RIVP + ACP may be associated with lower incidence of transient neurological deficits, shorter intubation and less blood transfusion requirement than ACP alone during TARS. Multi-center, randomized trials with larger samples are required to determine whether RIVP + ACP is associated with lower rates of mortality and major complications. TRIAL REGISTRATION: Pilot study of a RCT registered in clinicaltrials.gov (NCT03607786), Registered 30 July, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03607786 .


Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Perfusão , Veia Cava Inferior/fisiopatologia , Doença Aguda , Adulto , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Dissecção Aórtica/fisiopatologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/fisiopatologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Circulação Cerebrovascular , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão/efeitos adversos , Perfusão/mortalidade , Projetos Piloto , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Estudos Prospectivos , Fluxo Sanguíneo Regional , Fatores de Tempo , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem
8.
Bioinformatics ; 35(14): i370-i378, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31510688

RESUMO

MOTIVATION: Reticulate evolutionary histories, such as those arising in the presence of hybridization, are best modeled as phylogenetic networks. Recently developed methods allow for statistical inference of phylogenetic networks while also accounting for other processes, such as incomplete lineage sorting. However, these methods can only handle a small number of loci from a handful of genomes. RESULTS: In this article, we introduce a novel two-step method for scalable inference of phylogenetic networks from the sequence alignments of multiple, unlinked loci. The method infers networks on subproblems and then merges them into a network on the full set of taxa. To reduce the number of trinets to infer, we formulate a Hitting Set version of the problem of finding a small number of subsets, and implement a simple heuristic to solve it. We studied their performance, in terms of both running time and accuracy, on simulated as well as on biological datasets. The two-step method accurately infers phylogenetic networks at a scale that is infeasible with existing methods. The results are a significant and promising step towards accurate, large-scale phylogenetic network inference. AVAILABILITY AND IMPLEMENTATION: We implemented the algorithms in the publicly available software package PhyloNet (https://bioinfocs.rice.edu/PhyloNet). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Filogenia , Evolução Molecular , Genoma , Alinhamento de Sequência , Software
9.
Perfusion ; 35(7): 707-709, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32090681

RESUMO

Retrograde cerebral perfusion and retrograde inferior vena cava perfusion at a pressure of 25 mmHg can protect brain and visceral organs during hypothermic circulatory arrest. Total body retrograde perfusion has been proposed as an alternative during aortic arch surgery. We describe two patients who received total body retrograde perfusion during hemi-arch replacement. The procedure had to be terminated at 8 and 15 minutes due to severe fluid retention and decline in cerebral oxygen saturation. Delirium occurred in one patient after surgery. We concluded that total body retrograde perfusion may be associated with high risk of hypoperfusion and should not be recommended.


Assuntos
Circulação Cerebrovascular/fisiologia , Hipotermia Induzida/efeitos adversos , Perfusão/métodos , Feminino , Humanos , Hipotermia Induzida/métodos , Masculino , Pessoa de Meia-Idade
10.
Bioorg Med Chem Lett ; 28(8): 1348-1351, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29534929

RESUMO

In the present work, we described the synthesis, antiviral profiles and metabolic stability in human plasma of compound 6, a potential carbonate prodrug of HIV-1 NNRTI drug candidate RDEA427. Compound 6 was found to inhibit the wild-type (WT) and K103N/Y181C double mutant HIV-1 strains at nano- and submicromolar concentrations, respectively. Moreover, it displayed potent HIV-1 reverse transcriptase inhibitory activity (IC50 = 0.264 µM). Further stability test in human plasma showed that 6 could release its active form RDEA427 in a linearly time-independent manner, possibly acting as a potential prodrug.


Assuntos
Fármacos Anti-HIV/farmacologia , Pró-Fármacos/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Alcinos , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/metabolismo , Benzoxazinas/farmacologia , Linhagem Celular Tumoral , Ciclopropanos , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Hidrólise , Mutação , Nevirapina/farmacologia , Nitrilas , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Piridazinas/farmacologia , Pirimidinas/síntese química , Pirimidinas/metabolismo , Pirróis/síntese química , Pirróis/metabolismo , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/metabolismo , Inibidores da Transcriptase Reversa/farmacologia
11.
Bioorg Med Chem ; 25(16): 4397-4406, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28659246

RESUMO

Crystallographic overlap studies and pharmacophoric analysis indicated that diarylpyrimidine (DAPY)-based HIV-1 NNRTIs showed a similar binding mode and pharmacophoric features as indolylarylsulfones (IASs), another class of potent NNRTIs. Thus, a novel series of DAPY-IAS hybrid derivatives were identified as newer NNRTIs using structure-based molecular hybridization. Some target compounds exhibited moderate activities against HIV-1 IIIB strain, among which the two most potent inhibitors possessed EC50 values of 1.48µM and 1.61µM, respectively. They were much potent than the reference drug ddI (EC50=76.0µM) and comparable to 3TC (EC50=2.54µM). Compound 7a also exhibited the favorable selectivity index (SI=80). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships, molecular modeling studies, and in silico calculation of physicochemical properties of these new inhibitors were also discussed.


Assuntos
Fármacos Anti-HIV/farmacologia , Descoberta de Drogas , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Linhagem Celular , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Transcriptase Reversa do HIV/metabolismo , Humanos , Indóis/química , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirimidinas/química , Pirimidinas/farmacologia , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade , Sulfonas/química , Sulfonas/farmacologia
12.
J Cosmet Dermatol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769823

RESUMO

OBJECTIVE: To investigate the effect of retaining the vessels around the orbicularis oculi muscle on reducing local swelling after blepharoplasty. METHODS: A total of 309 patients undergoing blepharoplasty (total incision) were observed and randomly assigned to three groups; (A) conventional operation; (B) preservation of deep vessels; (C) preservation of anterior vessels of orbicularis oculi muscle. The groups were compared based on intraoperative blood loss, operation time, swelling, satisfaction, and complications. RESULTS: Among the 309 patients, 39 were lost to follow-up. c Additionally, A had the shortest operation time, followed by C with slightly longer duration. On the 7th day, 15th day, and 1 month after surgery, both B and C demonstrated significantly lower levels of swelling compared to A. Moreover, patient satisfaction was higher in B and C than in A. CONCLUSION: Retaining either superficial or deep veins of the orbicularis oculi muscle can effectively reduce short-term postoperative swelling. However, when retaining the superficial central group of this muscle during surgery, it is crucial to strictly control the amount of surrounding tissue around vessels.

13.
Front Neurol ; 15: 1357777, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737352

RESUMO

Background: Parkinson's disease (PD) is a common neurodegenerative disorder that affects motor and non-motor functions, significantly reducing patients' quality of life. No effective drug-based treatments are known to solve this problem. Non-drug therapies such as Yijinjing exercise have shown potential in improving cognitive and motor functions in PD patients. However, solid evidence must still be provided to support their clinical efficacy. This study aims to evaluate the clinical efficacy of Yijinjing exercise interventions in PD patients and explore the underlying mechanisms between the cognitive and motor functions in PD. Methods: This is a single-center randomized controlled trial in which 96 eligible PD patients will be randomly assigned to receive either Yijinjing exercise group or brisk walking group or control group in a ratio of 1:1:1. Interventions (Yijinjing exercise or brisk walking training, 40 min per session) will be provided in 3 sessions per week (Monday, Wednesday, Friday) for 12 weeks, with a total of 36 sessions. After the treatment, there will be a 1-month follow-up period. The primary outcomes will be measured using the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III). Secondary outcomes include balance function, executive function, walking function, sleep quality, and quality of life. Additionally, the prefrontal cerebral and sensorimotor cortex blood oxygen signal level will be collected to explore the underlying mechanisms. All outcomes will be assessed at baseline, at the end of 12 weeks of treatment and after an additional 1-month follow-up period. Discussion: The results of the study protocol will provide high-quality evidence for the potential of intervention measures based on the Yijinjing exercise to improve the cognitive and activity levels of Parkinson's disease patients. We envision the Yijinjing exercise as a non-pharmacological family activity that can provide a new and more effective method for the treatment of Parkinson's disease patients or those at risk. Clinical trial registration: This study was approved by the Ethics Committee of the Second Rehabilitation Hospital of Shanghai (2020-05-01). The trial has been registered in the China Clinical Trials Registry (ChiCTR2200055636).

14.
bioRxiv ; 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38496660

RESUMO

Spatially resolved transcriptomics (SRT) measures mRNA transcripts at thousands of locations within a tissue slice, revealing spatial variations in gene expression and distribution of cell types. In recent studies, SRT has been applied to tissue slices from multiple timepoints during the development of an organism. Alignment of this spatiotemporal transcriptomics data can provide insights into the gene expression programs governing the growth and differentiation of cells over space and time. We introduce DeST-OT (Developmental SpatioTemporal Optimal Transport), a method to align SRT slices from pairs of developmental timepoints using the framework of optimal transport (OT). DeST-OT uses semi-relaxed optimal transport to precisely model cellular growth, death, and differentiation processes that are not well-modeled by existing alignment methods. We demonstrate the advantage of DeST-OT on simulated slices. We further introduce two metrics to quantify the plausibility of a spatiotemporal alignment: a growth distortion metric which quantifies the discrepancy between the inferred and the true cell type growth rates, and a migration metric which quantifies the distance traveled between ancestor and descendant cells. DeST-OT outperforms existing methods on these metrics in the alignment of spatiotemporal transcriptomics data from the development of axolotl brain.

15.
Front Neurol ; 15: 1421772, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38938781

RESUMO

Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two most crucial factors influencing functional rehabilitation post peripheral nerve injury. Over time, traditional Chinese medicine (TCM) rehabilitation approaches such as acupuncture, Tuina, and microneedles serve as pivot means to activate the regeneration of injured nerve Schwann cells. By promoting axon regeneration, these approaches can accomplish nerve repair, reconstruction, and functional rehabilitation. Although TCM rehabilitation approaches have clinically demonstrated effectiveness in promoting the repair and regeneration of PNI, the related molecular mechanisms remain unclear. This significantly hampers the application and promotion of TCM rehabilitation in PNI recovery. Therefore, deeply delving into the cellular and molecular mechanisms of TCM rehabilitation technologies to foster nerve regeneration stands as the most pressing issue. On the other hand, in recent years, novel biomaterials represented by hydrogels, microfluidic platforms, and new chitosan scaffolds have showed their unique roles in treating various degrees of nerve injury. These methods exhibit immense potential in conducting high-throughput cell and organoid culture in vitro and synthesizing diverse tissue engineering scaffolds and drug carriers. We believe that the combination of TCM rehabilitation technology and novel biomaterials can more effectively address precise treatment issues such as identification of treatment target and dosage control. Therefore, this paper not only summarizes the molecular mechanisms of TCM rehabilitation technology and novel biomaterials in treating peripheral nerve injury individually, but also explores the research direction of precise treatment by integrating the two at both macro and micro levels. Such integration may facilitate the exploration of cellular and molecular mechanisms related to neurodegeneration and regeneration, providing a scientific and theoretical foundation for the precise functional rehabilitation of PNI in the future.

16.
bioRxiv ; 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36711750

RESUMO

Spatially resolved transcriptomics (SRT) technologies measure mRNA expression at thousands of locations in a tissue slice. However, nearly all SRT technologies measure expression in two dimensional slices extracted from a three-dimensional tissue, thus losing information that is shared across multiple slices from the same tissue. Integrating SRT data across multiple slices can help recover this information and improve downstream expression analyses, but multi-slice alignment and integration remains a challenging task. Existing methods for integrating SRT data either do not use spatial information or assume that the morphology of the tissue is largely preserved across slices, an assumption that is often violated due to biological or technical reasons. We introduce PASTE2, a method for partial alignment and 3D reconstruction of multi-slice SRT datasets, allowing only partial overlap between aligned slices and/or slice-specific cell types. PASTE2 formulates a novel partial Fused Gromov-Wasserstein Optimal Transport problem, which we solve using a conditional gradient algorithm. PASTE2 includes a model selection procedure to estimate the fraction of overlap between slices, and optionally uses information from histological images that accompany some SRT experiments. We show on both simulated and real data that PASTE2 obtains more accurate alignments than existing methods. We further use PASTE2 to reconstruct a 3D map of gene expression in a Drosophila embryo from a 16 slice Stereo-seq dataset. PASTE2 produces accurate alignments of multi-slice datasets from multiple SRT technologies, enabling detailed studies of spatial gene expression across a wide range of biological applications. Code availability: Software is available at https://github.com/raphael-group/paste2.

17.
Front Cardiovasc Med ; 10: 1109401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063959

RESUMO

One treatment for acute type A aortic dissection is to replace the ascending aorta and aortic arch with a graft during circulatory arrest of the lower body, but this is associated with high mortality and morbidity. Maintaining the balance between oxygen supply and demand during circulatory arrest is the key to reducing morbidity and is the primary challenge during body perfusion. The aim of this review is to summarize current knowledge of body perfusion techniques and to predict future development of this field. We present three perfusion techniques based on deep hypothermic circulatory arrest (DHCA): DHCA alone, DHCA with selective cerebral perfusion, and DHCA with total body perfusion. DHCA was first developed to provide a clear surgical field, but it may contribute to stroke in 4%-15% of patients. Antegrade or retrograde cerebral perfusion can provide blood flow for the brain during circulatory arrest, and it is associated with much lower stroke incidence of 3%-9%. Antegrade cerebral perfusion may be better than retrograde perfusion during longer arrest. In theory, blood flow can be provided to all vital organs through total body perfusion, which can be implemented via either arterial or venous systems, or by combining retrograde inferior vena caval perfusion with antegrade cerebral perfusion. However, whether total body perfusion is better than other techniques require further investigation in large, multicenter studies. Current techniques for perfusion during circulatory arrest remain imperfect, and a technique that effectively perfuses the upper and lower body effectively during circulatory arrest is missing. Total body perfusion should be systematically compared against selective cerebral perfusion for improving outcomes after circulatory arrest.

18.
Am J Respir Cell Mol Biol ; 47(5): 597-603, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22721831

RESUMO

Acute lung injury (ALI) induced by systemic inflammatory response syndrome (SIRS) is characterized by deterioration in pulmonary function and leukocyte-associated lung inflammation. Actin fragment (F-actin) reorganization is required for leukocyte activation, adhesion, and transcription of inflammatory factors. We tested the hypothesis that F-actin plays a central role in SIRS-induced ALI. ALI was produced in a rat model with extracorporeal circulation. Cytochalasin B (CB) pretreatment to block F-actin reorganization improved oxygenation and reduced BAL inflammatory factors and pulmonary neutrophil sequestration, but did not reduce the adhesive molecules of blood leukocytes. We challenged blood neutrophils with TNF-α in vitro to explore the underlying mechanisms. Upon activation, neutrophils became polarized and formed a protrusive leading edge, with an aggregation of CD11b molecules. This effect could be blocked by CB, leading to reduced neutrophil adhesion. In addition, after LPS challenge, we observed F-actin reorganization and the up-regulation of inflammatory factors in pulmonary monocytes, which could also be blocked by CB pretreatment. F-actin reorganization initiates lung inflammation via increased blood neutrophil adhesion and migration, and by the production of inflammatory factors by pulmonary monocytes. Thus, blocking F-actin reorganization may potentially prevent and treat SIRS-induced ALI.


Assuntos
Citoesqueleto de Actina/metabolismo , Pneumonia/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Actinas/antagonistas & inibidores , Actinas/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Animais , Líquido da Lavagem Broncoalveolar , Antígeno CD11b/metabolismo , Adesão Celular , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Citocalasina B/farmacologia , Citocalasina B/uso terapêutico , Citocinas/metabolismo , Células Endoteliais/patologia , Células Endoteliais/fisiologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Infiltração de Neutrófilos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Pneumonia/etiologia , Pneumonia/imunologia , Pneumonia/prevenção & controle , Transporte Proteico , Ratos , Ratos Sprague-Dawley , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Fator de Necrose Tumoral alfa/fisiologia
19.
Open Life Sci ; 17(1): 1064-1074, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36133426

RESUMO

Mitogen-activated protein kinase (MAPK) cascades are conserved and universal signal transduction modules that play important roles in regulating stress responses in plants. Although MAP3K, MP2K, and MPK family in tea plant (Camellia sinensis) have been investigated, little is known about MPK family genes responding to various abiotic stresses in tea plant. In this study, we performed a comprehensive genome-wide analysis of the tea plant MAPKs (CsMPKs) family gene based on the genomic data of tea plants by bioinformatics-based methods. Here, 21 putative CsMPK genes were identified in the tea plant and divided into 4 subfamilies according to the homologous to Arabidopsis and their phylogenetic relationships. The gene structure and conserved motifs of these CsMPKs in the same group showed high similarity, suggesting that they were highly conserved and might have a similar function. The expression profiles of the CsMPK genes were further investigated by quantitative real-time reverse transcription PCR, indicating that many CsMPK genes were involved in response to cold, drought, heat, or heat combined with drought treatment, suggesting their potential roles in abiotic stress responses in tea plant. These results would provide valuable information for further exploring the functional characterization of CsMPK genes in tea plants.

20.
Front Chem ; 10: 988051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051622

RESUMO

Arthritis is a group of highly prevalent joint disorders, and osteoarthritis (OA) and rheumatoid arthritis are the two most common types. The high prevalence of arthritis causes severe burdens on individuals, society and the economy. Currently, the primary treatment of arthritis is to relieve symptoms, but the development of arthritis cannot be effectively prevented. Studies have revealed that the disrupted balance of enzymes determines the pathological changes in arthritis. In particular, the increased levels of matrix metalloproteinases and the decreased expression of endogenous antioxidant enzymes promote the progression of arthritis. New therapeutic strategies have been developed based on the expression characteristics of these enzymes. Biomaterials have been designed that are responsive when the destructive enzymes MMPs are increased or have the activities of the antioxidant enzymes that play a protective role in arthritis. Here, we summarize recent studies on biomaterials associated with MMPs and antioxidant enzymes involved in the pathological process of arthritis. These enzyme-related biomaterials have been shown to be beneficial for arthritis treatment, but there are still some problems that need to be solved to improve efficacy, especially penetrating the deeper layer of articular cartilage and targeting osteoclasts in subchondral bone. In conclusion, enzyme-related nano-therapy is challenging and promising for arthritis treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA