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Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy.
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Biomarcadores Tumorais , Montagem e Desmontagem da Cromatina , Regulação Neoplásica da Expressão Gênica , Neoplasias , Humanos , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Prognóstico , Mutação , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Terapia de Alvo Molecular , Perfilação da Expressão GênicaRESUMO
Although enhanced performances of photovoltaic devices by embedding metal nanoparticals in charge transport layer, doping into active layer bulk, decorating the active layer surface, and inserting at the interface between semiconductor and the electrode were reported, the effect of incorporating metal NPs at the interface of single crystal semiconductor and perovskite is rarely tackled. Herein the effects of incorporating Ag nanoparticals (AgNPs) at p-Si/MAPbI3 perovskite interface on the photodiode performances were investigated. The results showed that compared with reference device (without AgNPs) the photoresponsivity of the device incorporating AgNPs is greatly improved with the exception for light with wavelengths fall in the spectral range where AgNPs have strong optical absorption. This effect is extremely significant for relatively shorter wavelengths in visible region, and a maximal improvement of around 10.6 times in photoresponsivity was achieved. The physical origin of the exception for spectral range that AgNPs have strong optical absorption is the cancelation of scatter resulted enhancement through AgNPs by band-to-band absorption resulted reduction of photocurrent, in which the generated electron has energy near the fermi level and the hole has large effective mass, which relax by nonradiative recombination, thus making not contribution to the photocurrent. More importantly, the AgNP decorated device showed much faster photo response speed than reference device, and a maximal improvement of around 7.9 times in rise and fall time was achieved. These findings provide a novel approach for high responsive and high speed detection for weak light.
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One-dimensional nanowire structures composed of perovskite are widely recognized for their exceptional optoelectronic performance and mechanical properties, making them a popular area of investigation in photodetection research. In this work, a perovskite nanowire/copper phthalocyanine heterojunction-based photodetector was fabricated, which exhibits high photoresponse in the visible-near-infrared region. The incorporation of a heterojunction significantly enhanced the photoelectric performance. Specifically, the photoresponsivity and external quantum efficiency of the nanowire-based device were elevated from 58.5 A W-1and 1.35 × 104% to 84.5 A W-1and 1.97 × 104% at 532 nm, respectively. The enhanced photoresponse of the heterojunction device can be attributed to the unique microstructure of nanowire arrays. The wrapping of the nanowires by copper phthalocyanine forms heterojunctions with a larger dissociation area, which facilitated exciton dissociation and enhanced device performance. This work provides a promising example for optimizing the performance of nanowire devices.
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Narrow-band photodetectors based on halide perovskite have recently attracted significant attention due to their exceptional narrow-band detection performance and tunable absorption peaks covering a wide optical range. In this work, we report mixed-halide CH3NH3PbClxBr3-xsingle crystal-based photodetectors have been fabricated, where the Cl/Br ratios were varied (3:0, 10:1, 5:1, 1:1, 1:7, 1:14 and 0:3). Vertical and parallel structures devices were fabricated which exhibited ultranarrow spectral responses under bottom illumination, with a full-width at half-maximum less than 16 nm. The observed performance can be ascribed to the unique carrier generation and extraction mechanisms within the single crystal under short and long wavelength of illumination. These findings offer valuable insights into the development of narrow-band photodetectors that do not necessitate the use of filters and hold tremendous potential for a diverse array of applications.
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Demethyleneberberine is an active component extracted from the Chinese herbal drug Cortex Phellodendri. It is also a metabolite of berberine in animals and humans. However, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine have not been reported. The present study aimed to investigate the pharmacokinetic parameters of demethyleneberberine by applying high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). After intragastric administration of demethyleneberberine in rats and mice, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine were comparatively studied for the first time. The plasma concentration of demethyleneberberine reached its peak within 5 min after intragastric administration in both rats and mice. Furthermore, its bioavailability was comparable, ranging from 4.47% to 5.94%, higher than that of berberine. The total excretion of demethyleneberberine in the urine, feces and bile was 7.28~9.77%. These findings provide valuable insights into the pharmacological and clinical research on demethyleneberberine.
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Berberina , Humanos , Ratos , Camundongos , Animais , Distribuição Tecidual , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodosRESUMO
With the continuous evolution of bacteria and the constant use of traditional antibiotics, the emergence of drug-resistant bacteria and super viruses has attracted worldwide attention. Antimicrobial therapy has become the most popular and important research field at present. Coordination Polymer (CP) and/or metal-organic framework (MOF) platforms have the advantages of a high biocompatibility, biodegradability, and non-toxicity, have a great antibacterial potential and have been widely used in antibacterial treatment. This paper reviewed the mechanism and antibacterial effect of three typical MOFs (pure Ag-MOFs, hybrid Ag-MOFs, and Ag-containing-polymer @MOFs) in silver-based coordination polymers. At the same time, the existing shortcomings and future views are briefly discussed. The study on the antibacterial efficacy and mechanism of Ag-MOFs can provide a better basis for its clinical application and, meanwhile, open up a novel strategy for the preparation of more advanced Ag-contained materials with antibacterial characteristics.
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Estruturas Metalorgânicas , Prata , Prata/farmacologia , Polímeros/farmacologia , Antibacterianos/farmacologia , Estruturas Metalorgânicas/farmacologiaRESUMO
Perception of road structures especially the traffic intersections by visual sensors is an essential task for automated driving. However, compared with intersection detection or visual place recognition, intersection re-identification (intersection re-ID) strongly affects driving behavior decisions with given routes, yet has long been neglected by researchers. This paper strives to explore intersection re-ID by a monocular camera sensor. We propose a Hybrid Double-Level re-identification approach which exploits two branches of Deep Convolutional Neural Network to accomplish multi-task including classification of intersection and its fine attributes, and global localization in topological maps. Furthermore, we propose a mixed loss training for the network to learn the similarity of two intersection images. As no public datasets are available for the intersection re-ID task, based on the work of RobotCar, we propose a new dataset with carefully-labeled intersection attributes, which is called "RobotCar Intersection" and covers more than 30,000 images of eight intersections in different seasons and day time. Additionally, we provide another dataset, called "Campus Intersection" consisting of panoramic images of eight intersections in a university campus to verify our updating strategy of topology map. Experimental results demonstrate that our proposed approach can achieve promising results in re-ID of both coarse road intersections and its global pose, and is well suited for updating and completion of topological maps.
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Partial least square (PLS) combining with Raman spectroscopy was applied to develop predictive models for plasma paclitaxel concentration detection. In this experiment, 312 samples were scanned by Raman spectroscopy. High performance liquid chromatography (HPLC) was applied to determine the paclitaxel concentration in 312 rat plasma samples. Monte Carlo partial least square (MCPLS) method was successfully performed to identify the outliers and the numbers of calibration set. Based on the values of degree of approach ( D a ), moving window partial least square (MWPLS) was used to choose the suitable preprocessing method, optimum wavelength variables and the number of latent variables. The correlation coefficients between reference values and predictive values in both calibration set ( R c2) and validation set ( R p2) of optimum PLS model were 0.933 1 and 0.926 4, respectively. Furthermore, an independent verification test was performed on the prediction model. The results showed that the correlation error of the 20 validation samples was 9.36%±2.03%, which confirmed the well predictive ability of established PLS quantitative analysis model.
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To develop an equation for the evaluation of renal function in rats using three dilutions of plasma samples and to validate this method by comparison with a reference method. The investigation was conducted in Sprague-Dawley (SD) rats after delivery of three doses of iohexol, with blood samples collected before and after dosage using a quantitative blood collection method. Plasma iohexol concentrations were detected by high performance liquid chromatography (HPLC). The extraction recovery of iohexol from plasma was >97.30% and the calibration curve was linear (r2 = 0.9997) over iohexol concentrations ranging from 10 to 1000 µg/mL. The method had an RE of <9.310 and intra- and inter-day RSD of <5.137% and <3.693%, respectively. The plasma clearance values obtained from the equation correlated closely (r = 0.763) with those obtained using the reference method. The relatively correlation in the results obtained using the method under investigation and the reference method indicate that this new equation can be used for preliminary assessment of renal function in rats.
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Iohexol/farmacocinética , Testes de Função Renal , Rim/fisiologia , Modelos Biológicos , Animais , Biomarcadores/sangue , Calibragem , Cromatografia Líquida de Alta Pressão , Feminino , Iohexol/administração & dosagem , Testes de Função Renal/normas , Modelos Lineares , Masculino , Valor Preditivo dos Testes , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
To distinguish the randomness and chaos characteristics of physiological signals and to keep its performance independent of the signal length and parameters are the key judgement of performance of a complexity algorithm.We proposed an encoding Lempel-Ziv(LZ)complexity algorithm to try to explicitly discern between the randomness and chaos characteristics of signals.Our study also compared the effects of length of time series,the sensitivity to dynamical properties change of time series and quantifying the complexity between gauss noise and 1/f pink noise ELZ with those from classic LZ(CLZ),multi-state LZ(MLZ),sample entropy(SampEn)and permutation entropy(PE).The experimental results showed ELZ could not only distinguish the randomness and chaos characteristics of time series on all time length(i.e.100,500,5 000),but also reflected exactly that the complexity of gauss noise was lower than that of pink noise,and responded change of dynamic characteristics of time series in time.The congestive heart failure(CHF)RR Interval database and the normal sinus rhythm(NSR)RR Interval database created by Massachusetts Institute of Technology(MIT)and Boston Beth Israel Hospital(BIH)were used as real data in our study.The results revealed that the ELZ could show the complexity of congestive heart failure which was lower than that of normal sinus rhythm during all lengths of time series(P<0.01),and the ELZ algorithm had better generalization ability and was independent of length of time series.
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Algoritmos , Arritmias Cardíacas/diagnóstico , Insuficiência Cardíaca/diagnóstico , Análise de Sistemas , Entropia , Humanos , Processamento de Sinais Assistido por ComputadorRESUMO
This is a systemic review of plants used traditionally for neuroendocrinological diseases related to hypothalamus-pitutary-adrenal (HPA) and hypothalamus-pitutary-gland (HPG) axis. By searching from PubMed literature search system (1950-2013), Medline (1950-2013) and CNKI (China Journals of Full-text database; 1989-2013), 105 papers met the inclusion criteria were displayed in this review. 96 herbal drugs were classified into two parts which include hormones mainly related to HPA and HPG axis. The full scientific name of each herbal medicine, dose ranges and routes, models or diseases, affect on hormones and pertinent references are presented via synoptic tables. Herbal remedies that have demonstrable the activities of hormones have provided a potential to various diseases related to neunoendocrine and deserve increased attention in future studies. This review provides a basis for herbs use in neuroendocrinological diseases. The data collected here will benefit to further research associated to herbal medicines and hormones.
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Medicamentos de Ervas Chinesas/uso terapêutico , Doenças do Sistema Endócrino/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologiaRESUMO
The term "schizophrenia" can indeed carry stigmatizing connotations. Proposals to rename schizophrenia have emerged as a potential strategy to alleviate this stigma, but the impact of such a change is not yet fully understood. In several Asian countries that have adopted a new name for schizophrenia, there is evidence that renaming is associated with improved attitudes towards individuals with schizophrenia and an increased willingness to disclose diagnoses. However, the portrayal of schizophrenia in the media seems unaffected by these name changes. In other countries where "schizophrenia" is still the standard term, alternative names have been suggested, but research on their effectiveness in reducing stigma shows mixed results. Mental health professionals frequently support a name change, recognizing the term's negative implications. However, it is crucial to recognize that a mere semantic revision, devoid of substantial conceptual alterations, may only offer a temporary decrease in stigma. Thus, renaming schizophrenia, coupled with a re-conceptualization of the disorder, may be a constructive step toward reducing its stigmatization.
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Tuning cell adhesion geometry can affect cytoskeleton organization and the distribution of cytoskeleton forces, which play critical roles in controlling cell functions. To elucidate the geometrical relationship with cytoskeleton force distribution, it is necessary to control cell morphology. In this study, a series of dextral vortex micropatterns were prepared to precisely control cell morphology for investigating the influence of the curvature degree of adhesion curves on intracellular force distribution and stem cell differentiation at a sub-cellular level. Peripherial actin filaments of micropatterned cells were assembled along the adhesion curves and showed different orientations, filament thicknesses and densities. Focal adhesion and cytoskeleton force distribution were dependent on the curvature degree. Intracellular force distribution was also regulated by adhesion curves. The cytoskeleton and force distribution affected the osteogenic differentiation of mesenchymal stem cells through a YAP/TAZ-mediated mechanotransduction process. Thus, regulation of cell adhesion curvature, especially at cytoskeletal filament level, is critical for cell function manipulation. STATEMENT OF SIGNIFICANCE: In this study, a series of dextral micro-vortexes were prepared and used for the culture of human mesenchymal stem cells (hMSCs) to precisely control adhesive curvatures (0°, 30°, 60°, and 90°). The single MSCs on the micropatterns had the same size and shape but showed distinct focal adhesion (FA) and cytoskeleton orientations. Cellular nanomechanics were observed to be correlated with the curvature degrees, subsequently influencing nuclear morphological features. As a consequence, the localization of the mechanotransduction sensor and activator-YAP/TAZ was affected, influencing osteogenic differentiation. The results revealed the pivotal role of adhesive curvatures in the manipulation of stem cell differentiation via the machanotransduction process, which has rarely been investigated.
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Diferenciação Celular , Adesões Focais , Mecanotransdução Celular , Células-Tronco Mesenquimais , Osteogênese , Adesões Focais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Mecanotransdução Celular/fisiologia , Humanos , Osteogênese/fisiologia , Actinas/metabolismo , Adesão Celular , Forma Celular , Proteínas de Sinalização YAPRESUMO
Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance in maintaining human health and improving the quality of life. It is increasingly challenging to address clinical needs with the present technologies for diagnosing and treating renal illness. Fortunately, metal-organic frameworks (MOFs) have shown great promise in the diagnosis and treatment of kidney diseases. This review summarizes the research progress of MOFs in the diagnosis and treatment of renal disease in recent years. Firstly, we introduce the basic structure and properties of MOFs. Secondly, we focus on the utilization of MOFs in the diagnosis and treatment of kidney diseases. In the diagnosis of kidney disease, MOFs are usually designed as biosensors to detect biomarkers related to kidney disease. In the treatment of kidney disease, MOFs can not only be used as an effective adsorbent for uremic toxins during hemodialysis but also as a precise treatment of intelligent drug delivery carriers. They can also be combined with nano-chelation technology to solve the problem of the imbalance of trace elements in kidney disease. Finally, we describe the current challenges and prospects of MOFs in the diagnosis and treatment of kidney diseases.
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We report a case of a 4-year-old boy with lysinuric protein intolerance in China. The patient presented with interstitial lung disease with obvious clubbing of the fingers and toes. During the course of diagnosis and treatment, we found he was averse to a high-protein diet, intolerant to activity, and had a history of diarrhea and fractures. Physical examination revealed hepatosplenomegaly and clubbing of the fingers and toes. Next-generation sequencing revealed compound heterozygous mutations (c.1387delG, c.958T > C) in SLC7A7, which was confirmed as a disease-causing gene for lysinuric protein intolerance. After a literature review, we found that c.958T > C had not been previously reported, and summarized the clinical and genetic characteristics of patients from different continents. His symptoms improved significantly after 3 months of being on a low-protein diet, supplementation with lysine, citrulline, carnitine, and trace elements, and oral corticosteroid treatment for 2 months. The patient is still under follow-up.
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L-Arabinose isomerase (L-AI) has been commonly used as an efficient biocatalyst to produce D-tagatose via the isomerization of D-galactose. However, it remains a significant challenge to efficiently synthesize D-tagatose using the native (wild type) L-AI at an industrial scale. Hence, it is extremely urgent to redesign L-AI to improve its catalytic efficiency towards D-galactose, and herein a structure-based molecular modification of Lactobacillus plantarum CY6 L-AI (LpAI) was performed. Among the engineered LpAI, both F118M and F279I mutants showed an increased D-galactose isomerization activity. Particularly, the specific activity of double mutant F118M/F279I towards D-galactose was increased by 210.1% compared to that of the wild type LpAI (WT). Besides the catalytic activity, the substrate preference of F118M/F279I was also largely changed from L-arabinose to D-galactose. In the enzymatic production of D-tagatose, the yield and conversion ratio of F118M/F279I were increased by 81.2% and 79.6%, respectively, compared to that of WT. Furthermore, the D-tagatose production of whole cells expressing F118M/F279I displayed about 2-fold higher than that of WT cell. These results revealed that the designed site-directed mutagenesis is useful for improving the catalytic efficiency of LpAI towards D-galactose.
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Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.
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Matrix stiffness has been disclosed as an essential regulator of cell fate. However, it is barely studied how the matrix stiffness affects stem cell functions when cell morphology changes. Thus, in this study, the effect of hydrogel stiffness on adipogenic differentiation of human bone-marrow-derived mesenchymal stem cells (hMSCs) with controlled morphology was investigated. Micropatterns of different size and elongation were prepared by a photolithographical micropatterning technique. The hMSCs were cultured on the micropatterns and showed a different spreading area and elongation following the geometry of the underlying micropatterns. The cells with controlled morphology were embedded in agarose hydrogels of different stiffnesses. The cells showed a different level of adipogenic differentiation that was dependent on both hydrogel stiffness and cell morphology. Adipogenic differentiation became strong when the cell spreading area decreased and hydrogel stiffness increased. Adipogenic differentiation did not change with cell elongation. Therefore, cell spreading area and hydrogel stiffness could synergistically affect adipogenic differentiation of hMSCs, while cell elongation did not affect adipogenic differentiation. A change of cell morphology and hydrogel stiffness was accompanied by actin filament alignment that was strongly related to adipogenic differentiation. The results indicated that cell morphology could affect cellular sensitivity to hydrogel stiffness. The results will provide useful information for the elucidation of the interaction of stem cells and their microenvironmental biomechanical cues.
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Hidrogéis , Células-Tronco Mesenquimais , Humanos , Hidrogéis/farmacologia , Diferenciação Celular , Células Cultivadas , Proliferação de CélulasRESUMO
Cancer is one of the greatest challenges in medical science today as it poses a serious threat to human life. In view of this, myriad of therapeutic strategies are being developed for the treatment of cancer. Despite the use of various therapeutic approaches, they are still insufficient for the treatment of cancer. The rapid advancement of nanotechnology currently offers exciting possibilities for the creation of novel cancer therapy approaches. Metal organic frameworks (MOFs) are emerging multifunctional nanomaterials that find prospective applications in the biomedical field owing to their porosity, large specific surface area, and diversified structures. Amongst varied categories of MOFs, Hf(IV)-based MOFs that have been developed since 2012 and currently have been finding new applications and hence this class of MOFs are gaining immense attention amongst the material and biomaterial chemists. Most importantly, Hf(IV)-MOFs comprising high Z-Hf metal content may be capable of offering new therapeutic options for cancer therapy, nonlinear optics, as fluorescent sensors, and photoresponsive devices. In this review, the progress in Hf(IV)-based MOFs for the treatment of cancer using radiotherapy, chemotherapy, immunotherapy, phototherapeutic techniques, or a combination of two or more of these techniques have been explored. This review also provides insight regarding the current limitations and future prospects of Hf(IV)-MOFs for cancer therapy.
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Estruturas Metalorgânicas , Nanoestruturas , Neoplasias , Humanos , Estruturas Metalorgânicas/uso terapêutico , Imunoterapia , Materiais Biocompatíveis , Corantes , Neoplasias/tratamento farmacológicoRESUMO
The mechanical properties of an extracellular microenvironment can affect cell functions. The effects of elasticity and viscoelasticity on cell functions have been extensively studied with hydrogels of tunable mechanical properties. However, investigation of the viscosity effect on cell functions is still very limited and it can be tricky to explore how viscosity affects cells in three-dimensional (3D) culture due to the lack of appropriate tools. In this study, agarose hydrogel containers were prepared and used to encapsulate viscous media for 3D cell culture to investigate the viscosity effect on the functions of bovine articular chondrocytes (BACs). Polyethylene glycol of different molecular weights was used to adjust culture medium viscosity in a large range (72.8-679.2 mPa s). The viscosity affected gene expression and secretion of cartilagenious matrices, while it did not affect BAC proliferation. The BACs cultured in the lower viscosity medium (72.8 mPa s) showed a higher level of cartilaginous gene expression and matrix secretion.