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1.
Neural Regen Res ; 18(1): 162-169, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799537

RESUMO

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique. Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury; as a result, in this study, we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration. First, in an in vitro biomimetic microenvironment, we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells. We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells. The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique. Compared with epithelium sutures and small gap sleeve bridging alone, the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

2.
Bioact Mater ; 19: 626-641, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35600968

RESUMO

Over 300 billion of cells die every day in the human body, producing a large number of endogenous apoptotic extracellular vesicles (apoEVs). Also, allogenic stem cell transplantation, a commonly used therapeutic approach in current clinical practice, generates exogenous apoEVs. It is well known that phagocytic cells engulf and digest apoEVs to maintain the body's homeostasis. In this study, we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles. Mechanistically, apoEVs activate the Wnt/ß-catenin pathway to facilitate their metabolism in a wave-like pattern. The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension, which is associated with the mechanical force-regulated expression of DKK1 in circulation. Furthermore, we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/ß-catenin pathway in skin and hair follicle mesenchymal stem cells. This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.

3.
Biotechnol Bioeng ; 119(3): 845-856, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34928500

RESUMO

Biocatalysis in high-concentration organic solvents (OSs) offers many advantages, but realizing this process remains a huge challenge. An R-selective ω-amine transaminase variant (AcATAM2 ) exhibited high activity toward 50 g/L pro-sitagliptin ketone 1-[1-piperidinyl]-4-[2,4,5-trifluorophenyl]-1,3-butanedione (PTfpB). However, AcATAM2 displayed unsatisfactory organic-cosolvent resistance against high-concentration dimethyl sulfoxide (DMSO), which is required to enhance the solubility of the hydrophobic substrate PTfpB. Located in the substrate-binding tunnel, enzyme gates are structural elements that undergo reversible conformational transitions, thus affecting the accessibility of the binding pocket to solvent molecules. Depending on the conformation of the enzyme gates, one can define an open or closed conformation on which the enzyme activity in OSs may depend. To enhance the DMSO resistance of AcATAM2 , we identified the beneficial residues at the "enzyme gate" region via computational analysis, alanine scanning, and site-saturation mutagenesis. Two beneficial variants, namely, AcATAM2 F56D and AcATAM2 F56V , not only displayed improved enzyme activity but also exhibited enhanced DMSO resistance (the half-life value increased from 25.71 to 42.49 h under 60% DMSO). Molecular dynamic simulations revealed that the increase in DMSO resistance was mainly caused by the decrease in the number of DMSO molecules in the substrate-binding pocket. Moreover, in the kilogram-scale experiment, the conversion of 80 g/L substrate was increased from 50% (AcATAM2 ) to 85% (M2F56D in 40% DMSO) with a high e.e. of >99% within 24 h.


Assuntos
Dimetil Sulfóxido , Simulação de Dinâmica Molecular , Biocatálise , Dimetil Sulfóxido/química , Solventes/química , Transaminases/genética
4.
Chem Sci ; 13(28): 8429-8435, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35919715

RESUMO

A novel classical kinetic resolution of 2-aryl-substituted or 2,3-disubstituted cyclobutanones of Baeyer-Villiger oxidation catalyzed by a Cu(ii)/SPDO complex is reported for the first time, producing normal lactones in excellent enantioselectivities (up to 96% ee) and regioselectivities (up to >20/1), along with unreacted ketones in excellent enantioselectivities (up to 99% ee). The current transformation features a wide substrate scope. Moreover, catalytic asymmetric total syntheses of natural eupomatilones 5 and 6 are achieved in nine steps from commercially available 3-methylcyclobutan-1-one.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121675, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35914355

RESUMO

The 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG) is the representative damaged nucleoside that may increase the risk of developing diseases. Accordingly, the selective detection of 8-oxoG in DNA with minimal disturbance to the native structure is important to have an in-depth understanding of the formation mechanism and becomes an attractive tool for genomic research. To identify the DNA adduct in real-time efficiently, a series of quasi-intrinsic optical probes are performed based on the natural adenine, which has preference to form a stable base pair with 8-oxoG in the syn conformation. The calculations revealed that the A-analogues in solution could bring red-shifted absorption spectra and bright photoluminescence arisen from the additional π-conjugation by means of fluorophore modification and the ring expansion. Especially, A1 possesses large Stokes shifts and the highest fluorescence intensity in emission, which is proposed as the biosensor to monitor the optical changes in the presence and absence of the considered 8-oxoG. It is found that the fluorescence is insensitive to base pairing with thymine, while the excited state intermolecular proton transfer (ESPT) induced efficient fluorescence quenching is observed upon pairing with the 8-oxoG. To evaluate the direct usefulness of the bright adenine analogues in biological environment, we further examined the influences of linking deoxyribose on the absorption and emission, which are consistent with the experimental data.

6.
Bioorg Chem ; 128: 106065, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35930923

RESUMO

To further reveal the active ingredients of Danshen, we systematically studied its chemical components and obtained two new lithospermic acid derivatives (compounds 1 and 2) together with five known phenylpropionic acids (compounds 3-7) from the dried rhizomes of Salvia miltiorrhiza. The structures of the two new compounds were determined by multiple spectral analyses (UV, IR, HR-ESI-MS, NMR, and ECD). In addition, the absolute configurations were established by chiral analysis and calculated and experimental circular dichroism spectra. Biological research indicated that compound 1 could significantly inhibit the proliferation of isoproterenol (ISO)-treated cardiac fibroblasts (AC16 cells), and MMP9 was found to be the most likely target of compound 1. The protein expression and mRNA levels of MMP9 were increased in ISO-induced AC16 cells, which could be reversed by treatment with compound 1. Furthermore, this treatment could alleviate the migration and activation of ISO-induced cardiac fibroblasts.

7.
Immunity ; 55(8): 1448-1465.e6, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35931085

RESUMO

Brain macrophage populations include parenchymal microglia, border-associated macrophages, and recruited monocyte-derived cells; together, they control brain development and homeostasis but are also implicated in aging pathogenesis and neurodegeneration. The phenotypes, localization, and functions of each population in different contexts have yet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematically delineate brain macrophage populations. We show that the previously identified disease-associated microglia (DAM) population detected in murine Alzheimer's disease models actually comprises two ontogenetically and functionally distinct cell lineages: embryonically derived triggering receptor expressed on myeloid cells 2 (TREM2)-dependent DAM expressing a neuroprotective signature and monocyte-derived TREM2-expressing disease inflammatory macrophages (DIMs) accumulating in the brain during aging. These two distinct populations appear to also be conserved in the human brain. Herein, we generate an ontogeny-resolved model of brain myeloid cell heterogeneity in development, homeostasis, and disease and identify cellular targets for the treatment of neurodegeneration.


Assuntos
Doença de Alzheimer , Microglia , Envelhecimento , Doença de Alzheimer/genética , Animais , Encéfalo/patologia , Humanos , Macrófagos/patologia , Glicoproteínas de Membrana , Camundongos , Microglia/patologia , Receptores Imunológicos
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121630, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35944402

RESUMO

Laplacian Eigenmaps is a nonlinear dimensionality reduction algorithm based on graph theory. The algorithm adopted the Gaussian function to measure the affinity between a pair of points in the adjacency graph. However, the scaling parameter σ in the Gaussian function is a hyper-parameter tuned empirically. Once the value of σ is determined and fixed, the weight between two points depends wholly on the Euclidian distance between them, which is not suitable for multi-scale sample sets. To optimize the weight between two points in the adjacency graph and make the weight reflect the scale information of different sample sets, an adaptive LE improved algorithm is used in this paper. Considering the influence of adjacent sample points and multi-scale data, the Euclidean distance between the k-th nearest sample point to sample point xi is used as the local scaling parameter σi of xi, instead of using a single scaling parameter σ. The efficiency of the algorithm is testified by applying on two public near-infrared data sets. LE-SVR and ALE-SVR models are established after LE and ALE dimension reduction of SNV preprocessed data sets. Compared with the LE-SVR model, the R2 and RPD of the ALE-SVR model established on the two data sets are improved, while RMSE is decreased, indicating that the prediction effect and stability of the regression model are established by the ALE algorithm are better than that of the traditional LE algorithm. Experiments show that the ALE algorithm can achieve a better dimensionality reduction effect than the LE algorithm.

9.
Sci Adv ; 8(32): eabo0789, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35947662

RESUMO

Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys576, in a unique noncatalytic HUBL domain. By selectively modifying Cys576, EB allosterically inhibits USP7 to cause a ubiquitination-dependent degradation of Keap1. Keap1 function loss further results in an Nrf2-dependent transcription activation of anti-neuroinflammation genes in microglia. In vivo, pharmacological USP7 inhibition attenuates microglia activation and resultant neuron injury, thereby notably improving behavioral deficits in dementia and Parkinson's disease mouse models. Collectively, our findings provide an attractive future direction for neurodegenerative disease therapy by inhibiting microglia-mediated neuroinflammation by targeting USP7.


Assuntos
Doenças Neurodegenerativas , Ubiquitina Tiolesterase , Animais , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Ubiquitina Tiolesterase/genética , Peptidase 7 Específica de Ubiquitina/metabolismo
10.
Biomed Environ Sci ; 35(7): 604-612, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35945175

RESUMO

Objective: This study aimed to analyze the temporal trends and characteristics associated with waist circumference (WC) among elderly Chinese people. Methods: We used data from 3,096 adults ≥ 65 years who participated in the China Health and Nutrition Survey (CHNS), an ongoing cohort study, between 1993 and 2015. We used longitudinal quantile regression models to explore the temporal trends and characteristics associated with WC. Results: WC increased gradually among the elderly Chinese population during the survey. The WC curves shifted to the right with wider distributions and lower peaks in men and women. All WC percentile curves shifted upward with similar growth rates in the 25th, 50th, and 75th percentiles. The WC means increased from 78 cm to 86 cm during the 22 years of our study. WC significantly increased with age and body mass index and decreased with physical activity (PA). These associations were stronger in the higher percentiles than in the lower percentiles. Conclusions: WC is rising among Chinese adults ≥ 65 years. Factors affecting WC in elderly people may have different effects on different percentiles of the WC distribution, and PA was the most important protective factor in the higher percentiles of the WC distribution. Thus, different interventional strategies are needed.


Assuntos
Circunferência da Cintura , Adulto , Idoso , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Inquéritos Nutricionais
11.
J Inflamm Res ; 15: 4395-4407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35945989

RESUMO

Objective: This study aimed to analyze biomarker changes in patients with TAK following treatment with glucocorticoids (GCs) and tofacitinib (TOF). Methods: Seventeen patients from a prospective TAK cohort treated with GCs and TOF and 12 healthy individuals were recruited. TAK associated cytokines, chemokines, growth factors, and MMPs were analyzed in these patients before and after GCs and TOF treatment, and healthy controls. Molecular signatures associated with clinical features were evaluated. Results: Patients' cytokines (PTX3, IL-6, IFN-γ), chemokines (IL-16, CCL22, CCL2), growth factors (VEGF), and MMP9 levels were significantly higher at baseline (all p < 0.05), while patients' FGF-2 levels were significantly lower (p = 0.02). After treatment, IL-10 was significantly increased at 6 months (p=0.007), and inflammatory cytokines such as PTX3, IL-6 demonstrated a downward trend. Patients without vascular occlusion had higher baseline CCL22 levels than patients with it (p = 0.05), which remained persistently higher after treatment. Radar plot analysis demonstrated that PTX3 was closely correlated with disease activity. In addition, patients without imaging improvement had relatively higher baseline levels of CCL22, FGF-2, and PDGF-AB (p = 0.056, p = 0.06 and p = 0.08 respectively) and lower baseline levels of TNFα, ESR, and CRP (p=0.04, p=0.056, p=0.07, respectively) compared with patients without it. Conclusion: GCs and TOF are effective in decreasing inflammatory molecules but have limited efficacy in regulating multiple other markers involved in TAK. PTX3 is a prominent marker for disease activity, and CCL22 may have a predictive value for vascular progression.

12.
Proc Natl Acad Sci U S A ; 119(32): e2202371119, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35917353

RESUMO

Epstein-Barr virus (EBV) infects more than 90% of the world's adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Animais , Anticorpos Neutralizantes , Células CHO , Comunicação Celular , Cricetinae , Microscopia Crioeletrônica , Herpesvirus Humano 4/fisiologia , Humanos , Fusão de Membrana , Camundongos , Proteínas do Envelope Viral/metabolismo
13.
BMC Cardiovasc Disord ; 22(1): 362, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941535

RESUMO

BACKGROUND: Systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio), a new marker of inflammation, is associated with adverse cardiovascular events, but its relationship with coronary slow flow phenomenon (CSFP) is unclear. Therefore, we aimed to investigate the relationship between SII and CSFP. METHODS: We enrolled consecutive patients who presented with chest pain, with normal/near-normal coronary angiography findings (n = 89 as CSFP group; n = 167 as control group). The baseline characteristics, laboratory parameters and angiographic characteristics of the two groups were compared. RESULTS: SII levels were significantly higher in the CSFP group than in the control group (409.7 ± 17.7 vs. 396.7 ± 12.7, p < 0.001). A significant positive correlation between SII and the mean thrombolysis in myocardial infarction frame count (mTFC) was found (r = 0.624, p < 0.001). SII increased with the number of coronary arteries involved in CSFP. In multivariate logistic regression analysis, SII/10 was an independent predictor of CSFP (odds ratio: 1.739, p < 0.001). In addition, the SII level > 404.29 was a predictor of CSFP with 67.4% sensitivity and 71.9% specificity. CONCLUSIONS: SII can predict the occurrence of CSFP.


Assuntos
Infarto do Miocárdio , Fenômeno de não Refluxo , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Humanos , Inflamação/diagnóstico , Fenômeno de não Refluxo/diagnóstico por imagem
14.
World J Clin Cases ; 10(18): 5934-5945, 2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35949837

RESUMO

The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) proteins constitute the innate adaptive immune system in several bacteria and archaea. This immune system helps them in resisting the invasion of phages and foreign DNA by providing sequence-specific acquired immunity. Owing to the numerous advantages such as ease of use, low cost, high efficiency, good accuracy, and a diverse range of applications, the CRISPR-Cas system has become the most widely used genome editing technology. Hence, the advent of the CRISPR/Cas technology highlights a tremendous potential in clinical diagnosis and could become a powerful asset for modern medicine. This study reviews the recently reported application platforms for screening, diagnosis, and treatment of different diseases based on CRISPR/Cas systems. The limitations, current challenges, and future prospectus are summarized; this article would be a valuable reference for future genome-editing practices.

15.
World J Clin Cases ; 10(18): 6211-6217, 2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35949851

RESUMO

BACKGROUND: Craniopharyngioma is a benign tumor that usually develops in children; however, it is located in the center and close to sensitive structures, such as the pituitary gland and hypothalamus. As the hypothalamus plays a crucial role in the homeostasis of anterior pituitary hormone synthesis, damage to the hypothalamus leads to multiple pituitary hormone deficiencies and non-alcoholic fatty liver disease, including hepatopulmonary syndrome (HPS). HPS has limited treatment and poor prognosis. CASE SUMMARY: A girl aged 13 years and 6 mo underwent surgery for craniopharyngioma 6 years prior. Right craniotomy was performed with total resection via the corpus callosum approach, and the tumor at the base was approximately 3.5 cm × 3.5 cm × 4.0 cm. At 1 year postoperatively, she exhibited abdominal distension and weakness, and the laboratory tests revealed fatty liver disease. Thereafter, she had not visited the outpatient clinic for 2 years. Two years ago, she developed decreased activity endurance, severe cyanosis, chest tightness, wheezing, and intermittent and recurrent low fever after mild physical labor. Hepatobiliary ultrasonography, liver biopsy, and contrast echocardiography of the right heart showed cirrhosis and multiple pituitary hormone deficiencies, indicating HPS. After 1 year of treatment with recombinant human growth hormone, the liver function and oxygenation improved; she did not undergo liver transplantation. CONCLUSION: Craniopharyngioma surgery can easily cause hypopituitarism, which can lead to nonalcoholic steatohepatitis and HPS in children. Early growth hormone therapy is important to improve the prognosis of these diseases.

16.
Int Immunopharmacol ; 111: 109118, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963156

RESUMO

Fyn, a non-receptor tyrosine kinase, plays an important role in microglial-mediated neuroinflammation and may serve as a candidate therapeutic target for neuropsychiatric diseases. In this study, we discovered that chrysin, a natural flavonoid compound, suppressed the activation of Fyn kinase and further alleviated neuroinflammation-induced neuron damage and behavior deficits. Functionally, chrysin improved lipopolysaccharide (LPS)-induced memory impairment and depressive behaviors in mice, it also protected against LPS-induced neuronal degeneration and loss and synaptic defects in mice. Our study demonstrated that chrysin inhibited the activation of microglia and reduced the expression of NLRP3 and IL-1ß. Furthermore, our data indicated that chrysin blocked phosphorylation of Fyn and activation of NF-κB. Transfection with siRNA-Fyn validated that knockdown of Fyn partly abolished the inhibitory effect of chrysin on the expression of the NLRP3 inflammasome and NF-κB activation. Taken together, our findings revealed that chrysin alleviated LPS-induced neuron damage and behavioral deficits by inhibiting the expression of the NLRP3 inflammasome and NF-κB pathway, which might be mediated by inhibition of Fyn.

17.
Front Neurol ; 13: 931437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959401

RESUMO

Background: Ischemic stroke (IS) is a complex neurological disease affected by genetics and environment. Matrix metalloproteinase-2 (MMP2) is involved in extracellular matrix (ECM) degradation, inflammation and angiogenesis to regulate the development and recovery of IS. Purposes: The aim of this study was to explore the association of rs1053605, rs243849 and rs14070 in MMP2 with the risk of IS in Chinese Shaanxi population. Methods: In this study, 677 IS patients and 681 normal controls were recruited. Rs1053605, rs243849 and rs14070 in MMP2 were genotyped. Logistic regression analysis was applied to evaluate the association of rs1053605, rs243849 and rs14070 in MMP2 with IS susceptibility and the association of environmental factors with MMP2 genetic susceptibility to IS. Results: The results of the overall analysis demonstrated that rs14070 in MMP2 significantly reduced the risk of IS in Chinese Shaanxi population (OR = 0.767, 95% CI = 0.619-0.952, P = 0.016). Subgroup analysis illustrated that rs243849 in MMP2 evidently increased the risk of IS among drinkers, while rs14070 in MMP2 apparently reduced IS susceptibility among females, participants with aged >55, smokers and drinkers. Conclusions: Collectively, rs243849 and rs14070 in MMP2 were significantly associated with the risk of IS in Chinese Shaanxi population, and the effect of MMP2 to IS may be associated with its genetic susceptibility.

18.
Small ; : e2202109, 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35957527

RESUMO

The design and synthesis of advanced semiconductors is crucial for the full utilization of solar energy. Herein, colloidal selective-epitaxial hybrid of tripartite semiconducting sulfides CuInS2 Cd(In)SMoS2 heteronanostructures (HNs) via lateral- and vertical-epitaxial growths, followed by cation exchange reactions, are reported. The lateral-epitaxial CuInS2 and Cd(In)S enable effective visible to near-infrared (NIR) solar spectrum absorption, and the vertical-epitaxial ultrathin MoS2 offer sufficient edge sulfur sites for the hydrogen evolution reaction (HER). Furthermore, the integrated structures exhibit unique epitaxial-staggered type II band alignments for continuous charge separation. They achieve the H2 evolution rate up to 8 mmol h-1 g-1 , which is ≈35 times higher than bare CdS and show no deactivation after long-term cycling, representing one of the most efficient and robust noble-metal-free photocatalysts. This design principle and transformation protocol open a new way for creating all-in-one multifunctional catalysts in a predictable manner.

19.
Nanoscale ; 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35959864

RESUMO

The infinite availability of solar energy grants the potential of fulfilling the energy demands and environmental sustainability requirements with more feasible and reliant renewable energy forms through photocatalysis. In the past decade, the intensive plasmonic effect, suitable work function, superior electrical conductivity and physiochemical properties have made Ag-based photocatalysts attractive components for emerging applications. The local surface plasmon resonance effect (LSPR) provides extra hot-carriers to participate in the photocatalytic process, and Schottky/Ohmic contacts would facilitate charge transfer. Here, recent studies focused on Ag-based photocatalysts for emerging applications are reviewed. Notably, the mechanisms of LSPR, the Schottky barrier and ohmic contacts are introduced together with urgent issues in CO2 reduction, antibacterial application, H2 generation, and environmental hazard removal. Additionally, some perspectives and directions on more comprehensive designs on material system, band alignment and functionalization are given to further the exploration in this research area.

20.
Blood Cancer Discov ; 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35960210

RESUMO

Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacological profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models. Integration with genomic data uncovered new gene-drug associations, suggesting actionable therapeutic vulnerabilities. Transcriptome profiling further identified gene expression signatures associated with on- and off-target drug responses. We also demonstrated the feasibility of drug screening-guided treatment for children with high-risk AML, with two evaluable cases achieving remission. Collectively, this study offers a high-dimensional gene-drug-clinical dataset that could be leveraged to research the unique biology of pediatric AML, and sets the stage for realizing functional precision medicine for clinical management of the disease.

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