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1.
Nature ; 624(7991): 295-302, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38092907

RESUMO

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.


Assuntos
Eletrofisiologia , Polímeros , Água , Animais , alfa-Ciclodextrinas/química , Eletrodos , Eletrofisiologia/instrumentação , Eletrofisiologia/métodos , Eletrofisiologia/tendências , Coração , Músculos , Polietilenoglicóis/química , Polímeros/química , Seda/química , Aranhas , Água/química , Hidrogéis/química , Eletrônica/instrumentação , Eletrônica/métodos , Eletrônica/tendências
2.
Antimicrob Agents Chemother ; 67(1): e0135422, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36602346

RESUMO

The carbapenem-resistant Klebsiella pneumoniae (CRKP) strain GX34 was recovered from the respiratory tract of an elderly male with severe pneumonia, and only susceptible to amikacin, tigecycline, and colistin. Complete genome suggested that it belonged to K51-ST16 and harbored plasmid-encoded NDM-4 and OXA-181, located on IncFIB plasmid GX34p1_NDM-4 and ColKP3/IncX3 plasmid GX34p4_OXA-181, respectively. A series of transconjugants generated in the plasmid conjugation assays, including Escherichia coli J53-N1 (harboring a self-transmissible and blaNDM-1-producing plasmid Eco-N-1-p), J53-N2 (harboring a blaNDM-4-producing plasmid and a helper plasmid GX34p5), and J53-O (harboring a blaOXA-181-producing plasmid), could be stably inherited after 10 days of serial passage and no significant biological fitness costs were detected. Furthermore, we first reported the blaNDM-1 gene, derived from blaNDM-4 mutation (460C>A) under meropenem pressure, could be in vitro transferred into a self-conjugative, recombined plasmid Eco-N-1-p of J53-N1. Eco-N-1-p was mainly recombined by GX34p4_OXA-181 (40,449 bp, 75.16%) and GX34p1_NDM-4 (8,553 bp, 15.89%), in which IS26 and IS5-like probably played a major role. Eco-N-1-p could be transferred into the conjugation recipient K. pneumoniae KP54 and make the latter sacrifice fitness. The retention rates of blaNDM-1 remained high stability (>80% after 200 generations). The comparative genomic analysis of GX34 and those carrying blaNDM-4 or blaOXA-181 genes retrieved from the NCBI RefSeq database showed all blaNDM-4 (26/26, 100.00%) and blaOXA-181 (13/13, 100.00%) were surrounded by IS26. The immediate environment of blaNDM-4 and blaOXA-181 in GX34 and some retrieved strains shared identical features, hinting at their possible dissemination. Effective measures should be taken to monitor the spread of this clone.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Masculino , Idoso , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Elementos de DNA Transponíveis , Antibacterianos/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Escherichia coli/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/genética
3.
Antimicrob Agents Chemother ; 67(12): e0073523, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38014944

RESUMO

Cefiderocol is a siderophore cephalosporin that binds ferric iron and utilizes iron transporters to cross the cell membrane. Hypervirulent Klebsiella pneumoniae (hvKp) is known to produce more siderophores; in this case, the uptake of cefiderocol may be decreased. Therefore, the objective of this study was to evaluate the in vitro activity of cefiderocol against hvKp isolates. A total of 320 carbapenem-resistant K. pneumoniae (CRKp) isolates were collected in China between 2014 and 2022, including 171 carbapenem-resistant hvKp (CR-hvKp) and 149 carbapenem-resistant classical K. pneumoniae (CR-cKp). Quantitative detection of siderophores showed that the average siderophore production of CR-hvKp (234.6 mg/L) was significantly higher than that of CR-cKp (68.9 mg/L, P < 0.001). The overall cefiderocol resistance rate of CR-hvKp and CR-cKp was 5.8% (10/171) and 2.7% (4/149), respectively. The non-susceptible rates of both cefiderocol and siderophore production of CR-hvKp isolates were higher than those of CR-cKp in either NDM-1- or KPC-2-producing groups. The MIC90 and MIC50 for CR-hvKp and CR-cKp were 8 mg/L and 2 mg/L and 4 mg/L and 1 mg/L, respectively. The cumulative cefiderocol MIC distribution for CR-hvKp was significantly lower than that of CR-cKp isolates (P = 0.003). KL64 and KL47 consisted of 53.9% (83/154) and 75.7% (53/70) of the ST11 CR-hvKp and CR-cKp, respectively, and the former had significantly higher siderophore production. In summary, cefiderocol might be less effective against CR-hvKp compared with CR-cKp isolates, highlighting the need for caution regarding the prevalence of cefiderocol-resistant K. pneumoniae strains, particularly in CR-hvKp isolates.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Cefalosporinas/farmacologia , Cefiderocol , Sideróforos/metabolismo , Klebsiella pneumoniae , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Carbapenêmicos/farmacologia , Monobactamas , China , Ferro , Antibacterianos/farmacologia
4.
Small ; 19(21): e2208157, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36808873

RESUMO

Anti-dehydration hydrogels have attracted considerable attention due to their promising applications in stretchable sensors, flexible electronics, and soft robots. However, anti-dehydration hydrogels prepared by conventional strategies inevitably depend on additional chemicals or suffer from cumbersome preparation processes. Here, inspired by the succulent Fenestraria aurantiaca a one-step wetting-enabled three-dimensional interfacial polymerization (WET-DIP) strategy for constructing organogel-sealed anti-dehydration hydrogels is developed. By virtue of the preferential wetting on the hydrophobic-oleophilic substrate surfaces, the organogel precursor solution can spread on the three-dimensional (3D) surface and encapsulate the hydrogel precursor solution, forming anti-dehydration hydrogel with 3D shape after in situ interfacial polymerization. The WET-DIP strategy is simple and ingenious, and accessible to discretionary 3D-shaped anti-dehydration hydrogels with a controllable thickness of the organogel outer layer. Strain sensors based on this anti-dehydration hydrogel also exhibit long-term stability in signal monitoring. This WET-DIP strategy shows great potentialities for constructing hydrogel-based devices with long-term stability.

5.
Nat Mater ; 21(12): 1357-1365, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36357689

RESUMO

The hygroscopic deformation of pine cones, featured by opening and closing their scales depending on the environmental humidity, is a well-known stimuli-responsive model system for artificial actuators. However, it has not been noted that the deformation of pine cones is an ultra-slow process. Here, we reveal that vascular bundles with unique parallelly arranged spring/square microtubular heterostructures dominate the hygroscopic movement, characterized as ultra-slow motion with the outer sclereids. The spring microtubes give a much larger hygroscopic deformation than that of the square microtubes along the longitudinal axis direction, which bends the vascular bundles and consequently drives the scales to move. The outer sclereids with good water retention enable the vascular-bundle-triggered deformation to proceed ultra-slowly. Drawing inspiration, we developed soft actuators enabling controllable yet unperceivable motion. The motion velocity is almost two orders of magnitude lower than that of the same-class actuators reported, which made the as-developed soft actuators applicable in camouflage and reconnaissance.


Assuntos
Movimento , Cone de Plantas , Molhabilidade , Modelos Biológicos
6.
Thromb J ; 21(1): 37, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37016388

RESUMO

BACKGROUND: Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs. METHODS: This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death. RESULTS: After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P<0.001], thrombosis [OR 0.535 (95% CI, 0.316-0.908), P=0.020] and the composite endpoint [ OR 0.835 (95% CI, 0.710-0.982), P=0.029]. In the RFA PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. In the no RFA PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 ( 95% CI, 0.535-0.811), P<0.001]. CONCLUSION: Among patients with NVAF treated with DOACs, RFA was a negative correlate of major bleeding, thrombosis, and composite endpoints but was not associated with total bleeding or all-cause mortality.

8.
Opt Express ; 30(11): 19855-19870, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36221751

RESUMO

We propose a novel single-plane phase retrieval method to realize high-quality sample reconstruction for lensfree on-chip microscopy. In our method, complex wavefield reconstruction is modeled as a quadratic minimization problem, where total variation and joint denoising regularization are designed to keep a balance of artifact removal and resolution enhancement. In experiment, we built a 3D-printed field-portable platform to validate the imaging performance of our method, where resolution chart, dynamic target, transparent cell, polystyrene beads, and stained tissue sections are employed for the imaging test. Compared to state-of-the-art methods, our method eliminates image degradation and obtains a higher imaging resolution. Different from multi-wavelength or multi-height phase retrieval methods, our method only utilizes a single-frame intensity data record to accomplish high-fidelity reconstruction of different samples, which contributes a simple, robust, and data-efficient solution to design a resource-limited lensfree on-chip microscope. We believe that it will become a useful tool for telemedicine and point-of-care application.


Assuntos
Microscopia , Poliestirenos , Microscopia/métodos
9.
BMC Cancer ; 22(1): 691, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739510

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is a third most common tumor of the urinary system. Nowadays, Immunotherapy is a hot topic in the treatment of solid tumors, especially for those tumors with pre-activated immune state. METHODS: In this study, we downloaded genomic and clinical data of RCC samples from The Cancer Genome Atlas (TCGA) database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. Then we established a prognostic risk model consisting of the genes most related to prognosis from four signatures to value prognosis of the RCC samples via Kaplan-Meier (KM) survival analysis. An independent data from International Cancer Genome Consortium (ICGC) database were used to test the predictive stability of the model. Furthermore, we performed landscape analysis to assess the difference of gene mutant in the RCC samples from TCGA. Finally, we explored the correlation between the selected genes and the level of tumor immune infiltration via Tumor Immune Estimation Resource (TIMER) platform. RESULTS: We used four genetic signatures to construct prognostic risk models respectively and found that each of the models could divide the RCC samples into high- and low-risk groups with significantly different prognosis, especially in advanced RCC. A comprehensive prognostic risk model was constructed by 8 candidate genes from four signatures (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) dividing the advanced RCC samples from TCGA database into high-risk and low-risk groups with a significant difference in cancer-specific survival (CSS). The stability of the model was verified by independent data from ICGC database. And the classification efficiency of the model was stable for the samples from different subgroups. Landscape analysis showed that mutation ratios of some genes were different between two risk groups. In addition, the expression levels of the selected genes were significantly correlated with the infiltration degree of immune cells in the advanced RCC. CONCLUSIONS: Sum up, eight immune-related genes were screened in our study to construct prognostic risk model with great predictive value for the prognosis of advanced RCC, and the genes were associated with infiltrating immune cells in tumors which have potential to conduct personalized treatment for advanced RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Prognóstico , Fatores de Risco
10.
BMC Cardiovasc Disord ; 22(1): 335, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902799

RESUMO

BACKGROUND: Intermediate-risk acute pulmonary embolism (APE) patients are usually defined as hemodynamically stable, comprehending a great therapeutic dilemma. Although anticoagulation therapy is sufficient for most intermediate-risk APE patients, some patients can deteriorate and eventually require a systemic fibrinolytic agent or thrombectomy. Hence, this study aimed to evaluate the predictive value of differences in clinical data for the short-term prognosis of intermediate-risk APE patients. METHODS: A retrospective cohort of 74 intermediate-risk APE patients confirmed by computed tomography pulmonary angiography was analyzed in the present study. Adverse clinical event outcomes included PE-related in-hospital deaths, critical systolic blood pressure consistently under 90 mmHg, refractory to volume loading and vasopressor infusion requirements, mechanical ventilation, and cardiopulmonary resuscitation. The APE patients were stratified into two groups: adverse outcome (n = 25) and control (n = 49) groups. Then, the clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were used to explore the predictive value of white blood cell (WBC) counts and the right to left ventricular short-axis (RV/LV) ratio. Model calibration was assessed using the Hosmer-Lemeshow goodness-of-fit statistic. RESULTS: The brain natriuretic peptide, WBC count, and the RV/LV ratio were higher in patients with adverse outcomes compared to controls. The APE patients with adverse outcomes presented significantly higher rates of syncope, Negative T waves (NTW) in V1-V3, intermediate-high risk, thrombolytic therapy, and low arterial oxygen saturation (SaO2) compared to controls. In the multivariate logistic regression analysis, the SaO2 < 90%, [odds ratio (OR) 5.343, 95% confidence interval (CI) 1.241-23.008; p = 0.024], RV/LV ratio (OR 7.429, 95% CI 1.145-48.209; p = 0.036), Syncope (OR 12.309, 95% CI 1.702-89.032; p = 0.013), NTW in V1-V3 (OR 5.617, 95% CI 1.228-25.683; p = 0.026), and WBC count (OR 1.212, 95% CI 1.035-1.419; p = 0.017) were independent predictors of in-hospital adverse outcomes among APE patients. The ROC curve analysis indicated that the RV/LV ratio can be used to predict adverse outcomes (AUC = 0.748, p < 0.01) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.070). Moreover, an RV/LV ratio > 1.165 was predictive of adverse outcomes with sensitivity and specificity of 88.00 and 59.20%, respectively. The WBC counts were also able to predict adverse outcomes (AUC = 0.752, p < 0.01) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.251). A WBC count > 9.05 was predictive of adverse outcomes with sensitivity and specificity of 68.00 and 73.50%, respectively. CONCLUSION: Overall, a SaO2 < 90%, RV/LV ratio, Syncope, NTW in V1-V3, and WBC counts could independently predict adverse outcomes in hospitalized intermediate-risk APE patients.


Assuntos
Embolia Pulmonar , Disfunção Ventricular Direita , Doença Aguda , Arritmias Cardíacas , Humanos , Valor Preditivo dos Testes , Prognóstico , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Estudos Retrospectivos , Síncope
11.
Neurochem Res ; 46(3): 675-685, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33471295

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder disease, disturbing people's normal life. Syringin was mentioned to antagonize Amyloid-ß (Aß)-induced neurotoxicity. However, the action mechanism is still not fully elucidated. This study aimed to explore a molecular mechanism of syringin in defending Aß-induced neurotoxicity. SK-N-SH and SK-N-BE cells were treated with amyloid ß-protein fragment 25-35 (Aß25-35) to induce cell neurotoxicity. The injury effects were distinguished by assessing cell viability and cell apoptosis using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of Cleaved-caspase3 (Cleaved-casp3), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and BH3 interacting domain death agonist (BID) at the protein level was determined by western blot. The expression of miR-124-3p and BID was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-124-3p and BID was predicted by the online database starBase and confirmed by dual-luciferase reporter assay plus RNA pull-down assay. Aß25-35 treatment inhibited cell viability and induced cell apoptosis, while the addition of syringin recovered cell viability and suppressed cell apoptosis. MiR-124-3p was significantly downregulated in Aß25-35-treated SK-N-SH and SK-N-BE cells, and BID was upregulated. Nevertheless, the addition of syringin reversed their expression. BID was a target of miR-124-3p, and its downregulation partly prevented Aß25-35-induced injuries. Syringin protected against Aß25-35-induced neurotoxicity by enhancing miR-124-3p expression and weakening BID expression, and syringin strengthened the expression of miR-124-3p to diminish BID level. Syringin ameliorated Aß25-35-induced neurotoxicity in SK-N-SH and SK-N-BE cells by regulating miR-124-3p/BID pathway, which could be a novel theoretical basis for syringin to treat AD.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Glucosídeos/farmacologia , MicroRNAs/metabolismo , Fragmentos de Peptídeos/toxicidade , Fenilpropionatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Humanos , Regulação para Cima
12.
Clin Transplant ; 35(11): e14469, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34448256

RESUMO

Kidney transplantation is the best therapy for end-stage renal disease. Demand for kidney transplantation rises year-on-year, and the gap between kidney supply and demand remains large. To meet this clinical need, a gradual expansion in the supply of donors is required. However, clinics lack appropriate tools capable of quickly and accurately predicting post-transplant renal allograft function, and thus assess donor-kidney quality before transplantation. Mitochondrial DNA (mtDNA) is a key component of damage-associated molecular patterns (DAMPs) and plays an important part in ischemia-reperfusion injury (IRI), accelerating the progression of IRI by inducing inflammation and type I interferon responses. mtDNA is known to be closely involved in delayed graft function (DGF) and acute kidney injury (AKI) after transplantation. Thus, mtDNA is a potential biomarker able to predict post-transplant renal allograft function. This review summarizes mtDNA biology, the role mtDNA plays in renal transplantation, outlines advances in detecting mtDNA, and details mtDNA's able to predict post-transplant renal allograft function. We aim to elucidate the potential value of mtDNA as a biomarker in the prediction of IRI, and eventually provide help for predicting donor-kidney quality.


Assuntos
Transplante de Rim , Traumatismo por Reperfusão , Biomarcadores , DNA Mitocondrial/genética , Função Retardada do Enxerto , Humanos , Rim , Doadores de Tecidos
13.
Ann Noninvasive Electrocardiol ; 26(6): e12836, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33629476

RESUMO

A 23-year-old woman with palpitations for 9 years was referred for catheter ablation. ECG showed an irregular narrow complex tachycardia with alternating and gradually changing QRS morphologies after alternating and changing RR intervals, with a clear pattern of 2 alternating QRS complexes. An electrophysiology study was performed and confirmed that the mechanism of tachycardia was an automatic left-side His-Purkinje system (HPS) ventricular tachycardia. The gradually changing type-2 QRS complexes was the conduction delayed in the left anterior fascicle due to the short RR interval or the short left-side HH interval. Nine months after the index electrophysiology study, the patient encounter a progressive of heart failure with increased heart rate to 130-150 bpm during rest. Radiofrequency ablation was performed at the upper-septum for eliminating the tachycardia and resulted in complete atrioventricular block. A permanent pacemaker with left bundle branch pacing was implanted. Twelve months after the ablation, the enlarged heart shrink to normal with normal left ventricular ejection fraction. In conclusion, careful interpretation of the ECG can identify the sinus P waves followed by irregular narrow complexes, thus avoiding misdiagnosis and unnecessary treatment. Unifocal HPS tachycardia could present with alternating and gradually changing narrow QRS complexes tachycardia and lead to tachycardia cardiomyopathy. Electrophysiology study and catheter ablation were useful for the diagnosis and treatment of HPS tachycardia but with high risk of atrioventricular block. However, successfully elimination the tachycardia would resolve and reverse the enlarged heart and deteriorative heart function.


Assuntos
Ablação por Cateter , Insuficiência Cardíaca , Taquicardia Ventricular , Adulto , Bloqueio de Ramo/cirurgia , Eletrocardiografia , Feminino , Humanos , Volume Sistólico , Taquicardia Ventricular/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Função Ventricular Esquerda , Adulto Jovem
14.
Nucleic Acids Res ; 47(D1): D1110-D1117, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30380087

RESUMO

Recently, the pharmaceutical industry has heavily emphasized phenotypic drug discovery (PDD), which relies primarily on knowledge about phenotype changes associated with diseases. Traditional Chinese medicine (TCM) provides a massive amount of information on natural products and the clinical symptoms they are used to treat, which are the observable disease phenotypes that are crucial for clinical diagnosis and treatment. Curating knowledge of TCM symptoms and their relationships to herbs and diseases will provide both candidate leads and screening directions for evidence-based PDD programs. Therefore, we present SymMap, an integrative database of traditional Chinese medicine enhanced by symptom mapping. We manually curated 1717 TCM symptoms and related them to 499 herbs and 961 symptoms used in modern medicine based on a committee of 17 leading experts practicing TCM. Next, we collected 5235 diseases associated with these symptoms, 19 595 herbal constituents (ingredients) and 4302 target genes, and built a large heterogeneous network containing all of these components. Thus, SymMap integrates TCM with modern medicine in common aspects at both the phenotypic and molecular levels. Furthermore, we inferred all pairwise relationships among SymMap components using statistical tests to give pharmaceutical scientists the ability to rank and filter promising results to guide drug discovery. The SymMap database can be accessed at http://www.symmap.org/ and https://www.bioinfo.org/symmap.


Assuntos
Biologia Computacional/métodos , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Terapia de Alvo Molecular/métodos , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Medicina Tradicional Chinesa/estatística & dados numéricos , Fitoterapia/métodos
15.
Proc Natl Acad Sci U S A ; 115(40): 10046-10051, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30224464

RESUMO

Bird feathers have aroused tremendous attention for their superdurability against tears during long flights through wind and even bushes. Although feathers may inevitably be unzipped, the separated feather vanes can be repaired easily by bill stroking. However, the mechanism underlying bird feathers' superdurability against tears remains unclear. Here, we reveal that the superdurability of bird feathers arises from their repairable cascaded slide-lock system, which is composed of hooklets, a slide rail, and spines at the end of the slide rail as terminating structures. Microscopy with a micronano manipulating system and 3D X-ray microscopy provided high-level visibility into the 3D fine structures and the entire unzipping process of feathers. The hooklets can slide along the slide rail reversibly when suffering external forces, and the sliding hooklet can be locked by the spine at the ends of barbules when larger pulling forces are applied and even slide farther away due to the unzipping of the interlocking structure with large deformation of the barbules. The elongation before separation of adjacent barbs can reach up to 270%, and the separation force can be maintained above 80% of the initial value even after 1,000 cycles of separating and repairing. These results prove that the cascaded slide-lock system ensures the superdurability of bird feathers against tears.


Assuntos
Aves/anatomia & histologia , Plumas/ultraestrutura , Animais
16.
Pharmacol Res ; 156: 104797, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32278044

RESUMO

Chronic pain is highly prevalent and poorly controlled, of which the accurate underlying mechanisms need be further elucidated. Herbal drugs have been widely used for controlling various pain disorders. The systematic integration of pain herbal data resources might be promising to help investigate the molecular mechanisms of pain phenotypes. Here, we integrated large-scale bibliographic literatures and well-established data sources to obtain high-quality pain relevant herbal data (i.e. 426 pain related herbs with their targets). We used machine learning method to identify three distinct herb categories with their specific indications of symptoms, targets and enriched pathways, which were characterized by the efficacy of treatment to the chronic cough related neuropathic pain, the reproduction and autoimmune related pain, and the cancer pain, respectively. We further detected the novel pathophysiological mechanisms of the pain subtypes by network medicine approach to evaluate the interactions between herb targets and the pain disease modules. This work increased the understanding of the underlying molecular mechanisms of pain subtypes that herbal drugs are participating and with the ultimate aim of developing novel personalized drugs for pain disorders.


Assuntos
Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Aprendizado de Máquina , Limiar da Dor/efeitos dos fármacos , Preparações de Plantas/uso terapêutico , Biologia de Sistemas , Integração de Sistemas , Analgésicos/química , Analgésicos/classificação , Animais , Dor Crônica/metabolismo , Dor Crônica/fisiopatologia , Bases de Dados Factuais , Humanos , Estrutura Molecular , Terapia de Alvo Molecular , Farmacopeias como Assunto , Preparações de Plantas/química , Preparações de Plantas/classificação , Mapas de Interação de Proteínas , Transdução de Sinais , Relação Estrutura-Atividade
17.
BMC Cardiovasc Disord ; 20(1): 85, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066388

RESUMO

BACKGROUND: Coronary microembolization (CME) has a poor prognosis, with ventricular arrhythmia being the most serious consequence. Understanding the underlying mechanisms could improve its management. We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on connexin-43 (Cx43) expression and ventricular arrhythmia susceptibility after CME. METHODS: Forty male rabbits were randomized into four groups (n = 10 each): Sham, CME, G-CSF, and AG490 (a JAK2 selective inhibitor). Rabbits in the CME, G-CSF, and AG490 groups underwent left anterior descending (LAD) artery catheterization and CME. Animals in the G-CSF and AG490 groups received intraperitoneal injection of G-CSF and G-CSF + AG490, respectively. The ventricular structure was assessed by echocardiography. Ventricular electrical properties were analyzed using cardiac electrophysiology. The myocardial interstitial collagen content and morphologic characteristics were evaluated using Masson and hematoxylin-eosin staining, respectively. RESULTS: Western blot and immunohistochemistry were employed to analyze the expressions of Cx43, G-CSF receptor (G-CSFR), JAK2, and STAT3. The ventricular effective refractory period (VERP), VERP dispersion, and inducibility and lethality of ventricular tachycardia/fibrillation were lower in the G-CSF than in the CME group (P < 0.01), indicating less severe myocardial damage and arrhythmias. The G-CSF group showed higher phosphorylated-Cx43 expression (P < 0.01 vs. CME). Those G-CSF-induced changes were reversed by A490, indicating the involvement of JAK2. G-CSFR, phosphorylated-JAK2, and phosphorylated-STAT3 protein levels were higher in the G-CSF group than in the AG490 (P < 0.01) and Sham (P < 0.05) groups. CONCLUSION: G-CSF might attenuate myocardial remodeling via JAK2-STAT3 signaling and thereby reduce ventricular arrhythmia susceptibility after CME.


Assuntos
Arritmias Cardíacas/prevenção & controle , Doença da Artéria Coronariana/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Janus Quinase 2/metabolismo , Infarto do Miocárdio/prevenção & controle , Miocárdio/enzimologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/enzimologia , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Conexina 43/metabolismo , Doença da Artéria Coronariana/enzimologia , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Modelos Animais de Doenças , Fibrose , Masculino , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Fosforilação , Coelhos , Receptores de Fator Estimulador de Colônias de Granulócitos/metabolismo , Período Refratário Eletrofisiológico/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
18.
Angew Chem Int Ed Engl ; 59(49): 21840-21856, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32091148

RESUMO

Interfacial polymerization, where a chemical reaction is confined at the liquid-liquid or liquid-air interface, exhibits a strong advantage for the controllable fabrication of films, capsules, and fibers for use as separation membranes and electrode materials. Recent developments in technology and polymer chemistry have brought new vigor to interfacial polymerization. Here, we consider the history of interfacial polymerization in terms of the polymerization types: interfacial polycondensation, interfacial polyaddition, interfacial oxidative polymerization, interfacial polycoordination, interfacial supramolecular polymerization, and some others. The accordingly emerging functional materials are highlighted, as well as the challenges and opportunities brought by new technologies for interfacial polymerization. Interfacial polymerization will no doubt keep on developing and producing a series of fascinating functional materials.

19.
Small ; 15(15): e1900030, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30740887

RESUMO

Self-organization is a fundamental and indispensable process in a living system. To understand cell behavior in vivo such as tumorigenesis, 3D cellular aggregates, instead of 2D cellular sheets, have been employed as a vivid in vitro model for self-organization. However, most focus on the macroscale wetting and fusion of cellular aggregates. In this study, it is reported that self-organization of cells from simple to complex aggregates can be induced by multiscale topography through confined templates at the macroscale and cell interactions at the nanoscale. On the one hand, macroscale templates are beneficial for the organization of individual cells into simple and complex cellular aggregates with various shapes. On the other hand, the realization of these macro-organizations also depends on cell interactions at the nanoscale, as demonstrated by the intimate contact between nanoscale pseudopodia stretched by adjacent frontier cells, much like holding hands and by the variation in the intermolecular interactions based on E-cadherin. Therefore, these findings may be very meaningful for clarifying the organizational mechanism of tumor development, tissue engineering and regenerative medicine.


Assuntos
Células/metabolismo , Agregação Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células/efeitos dos fármacos , Humanos , Hidrogéis/farmacologia , Microscopia de Fluorescência
20.
Opt Express ; 27(24): 35216-35229, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31878694

RESUMO

In lensfree on-chip microscopy, the iterative phase retrieval with defocused images easily enables a high-resolution and whole field reconstruction. However, on the reconstruction of the dense sample, conventional methods suffer from the stagnation problem and noise affection under two intensity measurements, which gives rise to a remarkable loss of the image contrast and resolution. Here we propose a novel dual-plane phase retrieval algorithm to perform a stable and versatile lensless reconstruction. A weighted feedback constraint was utilized to speed up the convergence. Then, a gradient descent minimization based on total variation metric was proposed to suppress the noise affection. With these two object constraints, a smoothed but resolution-preserving result can be achieved. Numerical simulations of Gaussian and Poisson noise were given to prove the noise-robustness of our method. The experiments of USAF resolution target, H&E stained pathological slide, and label-free microglia cell demonstrated the superior performance of our approach compared to other state-of-the-art methods.

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