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1.
Med Res Rev ; 44(2): 833-866, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38014919

RESUMEN

Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.


Asunto(s)
Lisina , Neoplasias , Humanos , Lisina/uso terapéutico , Histona Demetilasas/metabolismo , Histona Demetilasas/uso terapéutico , Inhibidores de la Monoaminooxidasa/uso terapéutico , Histonas , Neoplasias/tratamiento farmacológico , Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico
2.
Small ; 20(15): e2307473, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38009727

RESUMEN

With the advent of wireless technology, magnetic-carbon composites with strong electromagnetic wave (EMW) absorption capability in low-/middle-frequency range are highly desirable. However, it remains challenging for rational construction of such absorbers bearing multiple magnetic components that show uniform distribution and favorable magnetic loss. Herein, a facile metal-oxo cluster (MOC) precursor strategy is presented to produce high-efficiency magnetic carbon composites. Nanosized MOC Fe15 shelled with organic ligands is employed as a novel magnetic precursor, thus allowing in situ formation and uniform deposition of multicomponent magnetic Fe/Fe3O4@Fe3C and Fe/Fe3O4 nanoparticles on graphene oxides (GOs) and carbon nanotubes (CNTs), respectively. Owing to the good dispersity and efficient magnetic-dielectric synergy, quaternary Fe/Fe3O4@Fe3C-GO exhibits strong low-frequency absorption with RLmin of -53.5 dB at C-band and absorption bandwidth covering 3.44 GHz, while ultrahigh RLmin of -73.2 dB is achieved at X-band for ternary Fe/Fe3O4-CNT. The high performance for quaternary and ternary composites is further supported by the optimal specific EMW absorption performance (-15.7 dB mm-1 and -31.8 dB mm-1) and radar cross-section reduction (21.72 dB m2 and 34.37 dB m2). This work provides a new avenue for developing lightweight low-/middle-frequency EMW absorbers, and will inspire the investigation of more advanced EMW absorbers with multiple magnetic components and regulated microstructures.

3.
Small ; : e2404080, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38923218

RESUMEN

Functional fibers composed of textiles are considered a promising platform for constructing electronic skin (e-skin). However, developing robust electronic fibers with integrated multiple functions remains a formidable task especially when a complex service environment is concerned. In this work, a continuous and controllable strategy is demonstrated to prepare e-skin-oriented ceramic fibers via coaxial wet spinning followed by cold isostatic pressing. The resulting core-shell structured fiber with tightly compacted Al-doped ZnO nanoparticles in the core and highly ordered aramid nanofibers in the shell exhibit excellent tensile strength (316 MPa) with ultra-high elongation (33%). Benefiting from the susceptible contacts between conducting ceramic nanoparticles, the ceramic fiber shows both ultrahigh sensitivity (gauge factor = 2141) as a strain sensor and a broad working range up to 70 °C as a temperature sensor. Furthermore, the tunable core-shell structure of the fiber enables the optimization of impedance matching and attenuation of electromagnetic waves for the corresponding textile, resulting in a minimum reflection loss of -39.1 dB and an effective absorption bandwidth covering the whole X-band. Therefore, the versatile core-shell ceramic fiber-derived textile can serve as a stealth e-skin for monitoring the motion and temperature of robots under harsh conditions.

4.
J Magn Reson Imaging ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996369

RESUMEN

BACKGROUND: Turbo spin-echo (TSE) diffusion-weighted imaging (DWI) sequences may reduce susceptibility artifacts and image distortion in sellar region, allowing better visualization of small pituitary lesions, and may be used to assist in the diagnosis of pituitary microadenomas. PURPOSE: To explore the application value of conventional MRI combined with DWI sequences in the diagnosis of microprolactinomas. STUDY TYPE: Prospective. POPULATION: Thirty-four patients in microprolactinomas with high signal on T2WI (HT2-PRL) group (34 females, 34 ± 7 years), 26 patients in microprolactinomas with equal or low signal on T2WI (ELT2-PRL) group (21 females, 34 ± 7 years), 35 patients with hyperprolactinemia (33 females, 32 ± 8 years), and 30 normal controls (25 females, 31 ± 7 years). FIELD STRENGTH/SEQUENCE: TSE sequence at 3 T. ASSESSMENT: Pituitary morphological parameters (such as length and volume), dynamic contrast-enhanced parameters (such as time to peak) and the apparent diffusion coefficients (ADCs) were measured in each group. STATISTICAL TESTS: ANOVA and Mann-Whitney U test were used to compare parameters among groups. Spearman's coefficient was used to evaluate the correlation between variables. ROC analysis was used to assess the performance of the parameters. A P-value <0.05 was considered statistically significant. RESULTS: The pituitary volume of patients in HT2-PRL, ELT2-PRL, and hyperprolactinemia group were 831.00 (747.60, 887.60), 923.63 ± 219.34, and 737.20 (606.40, 836.80) mm3. The pituitary maximum height in these three groups were 7.03 (6.43, 8.63), 8.03 ± 1.41, and 6.63 ± 1.28 mm, respectively. The lesion ADC value was significantly correlated with T2 relative signal intensity (the ratio of signal intensity of microprolactinoma or anterior pituitary to left temporal cortex) (r = 0.821). Compared with patients with hyperprolactinemia, the diagnostic efficacy of T2 relative signal intensity was higher in HT2-PRL group, with an AUC of 0.954, whereas the ADC value was the highest in ELT2-PRL group, with an AUC of 0.924. CONCLUSION: DWI sequences can be used to assist in the diagnosis of pituitary microadenomas. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

5.
Environ Toxicol ; 39(5): 2908-2926, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38299230

RESUMEN

BACKGROUND: Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD-related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction. METHOD: We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome-based CRC prognostic models. RESULT: Our integrated model successfully identified differentially expressed PCD-related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high-risk and low-risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis. CONCLUSION: The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC.


Asunto(s)
Apoptosis , Neoplasias Colorrectales , Humanos , Pronóstico , Aprendizaje Automático , Neoplasias Colorrectales/genética
6.
Water Sci Technol ; 89(12): 3208-3225, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39150421

RESUMEN

A carbon material Cu-corn straw-sludge biochar (Cu-CSBC) was prepared by hydrothermally modifying sewage sludge and corn stover. The composite coupled to ultrasound can effectively catalyze the activation of PS for organic pollutants degradation, and the removal rate of 20 mg/L TC reached 89.15% in 5 min in the presence of 0.5 g/L Cu-CSBC and 3 mM PS. The synergistic effect between the factors in the system, the reaction mechanism, and the efficient removal of TC in the aqueous environment were explored in a Cu-CSBC/US/PS system established for that purpose. Quenching experiments and electron paramagnetic resonance analysis both demonstrated the Cu-CSBC/US/PS system generated •OH, SO4-•, 1O2, and O2- •, which involved in the reaction. The Cu, carboxyl, and hydroxyl groups on the Cu-CSBC surface promoted the generation of radicals and non-radicals for the degradation process, which was dominated by both radical and non-radical pathways. The degradation pathway is proposed by measuring the intermediate products with LC-MS. Finally, the stability of the Cu-CSBC/US/PS system was tested under various reaction conditions. This study not only prepared a novel biochar composite material for the active degradation of organic pollutants by PS but also provided an effective method for the resource utilization of solid waste and sludge treatment.


Asunto(s)
Antibacterianos , Carbón Orgánico , Aguas del Alcantarillado , Contaminantes Químicos del Agua , Carbón Orgánico/química , Aguas del Alcantarillado/química , Antibacterianos/química , Contaminantes Químicos del Agua/química , Pirólisis , Biomasa , Sulfatos/química , Ondas Ultrasónicas , Eliminación de Residuos Líquidos/métodos
7.
Mod Rheumatol ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39119677

RESUMEN

OBJECTIVES: Baker's cyst (BC) is a complex complication of rheumatoid arthritis (RA), with a poor prognosis. This paper aimed to analyze the clinical features and risk factors for BC in patients with RA to assist clinicians in early warning and appropriate action. METHODS: The Clinical features of hospitalized RA patients with knee affected were analyzed retrospectively. The R software was used for the statistical analysis, while logistic regression analyses were used to determine independent risk factors. RESULTS: A total of 367 RA patients with knee affected were studied, and BC was diagnosis in 15.3% of them. The BC group exhibited a higher proportion of knee-only affected than the non-BC group (p < 0.05), while the attributes linked to disease activity exhibited no disparity. Logistic regression analyses selected two independent risk factors for BC: knee-only affected and anemia. 26.8% of patients with BC developed rupture, exhibiting a higher proportion of knee-only affected (p < 0.05), compared to those unruptured. CONCLUSIONS: The occurrence and rupture of BC in RA patients were significantly related to local inflammation, but not to systemic one. Incorporating local treatment may be a more advantageous option compared to solely relying on systemic therapy.

8.
Inorg Chem ; 62(19): 7376-7384, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37134020

RESUMEN

Copper-based halides have been found to be a new family of lead-free materials with high stability and superior optoelectrical properties. In this work, we report the photoluminescence of the known (C8H14N2)CuBr3 and the discovery of three new compounds, (C8H14N2)CuCl3, (C8H14N2)CuCl3·H2O, and (C8H14N2)CuI3, which all exhibit efficient light emissions. All these compounds have monoclinic structures with the same space group (P21/c) and zero-dimensional (0D) structures, which can be viewed as the assembly of promising aromatic molecules and different copper halide tetrahedrons. Upon the irradiation of deep ultraviolet light, (C8H14N2)CuCl3, (C8H14N2)CuBr3,, and (C8H14N2)CuI3 show green emission peaking at ∼520 nm with a photoluminescent quantum yield (PLQY) of 3.38, 35.19, and 17.81%, while (C8H14N2)CuCl3·H2O displays yellow emission centered at ∼532 nm with a PLQY of 2.88%. A white light-emitting diode (WLED) was successfully fabricated by employing (C8H14N2)CuBr3 as a green emitter, demonstrating the potential of copper halides for applications in the green lighting field.

9.
Angew Chem Int Ed Engl ; 62(39): e202308344, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37485998

RESUMEN

The atom-cluster interaction has recently been exploited as an effective way to increase the performance of metal-nitrogen-carbon catalysts for oxygen reduction reaction (ORR). However, the rational design of such catalysts and understanding their structure-property correlations remain a great challenge. Herein, we demonstrate that the introduction of adjacent metal (M)-N4 single atoms (SAs) could significantly improve the ORR performance of a well-screened Fe atomic cluster (AC) catalyst by combining density functional theory (DFT) calculations and experimental analysis. The DFT studies suggest that the Cu-N4 SAs act as a modulator to assist the O2 adsorption and cleavage of O-O bond on the Fe AC active center, as well as optimize the release of OH* intermediates to accelerate the whole ORR kinetic. The depositing of Fe AC with Cu-N4 SAs on nitrogen doped mesoporous carbon nanosheet are then constructed through a universal interfacial monomicelles assembly strategy. Consistent with theoretical predictions, the resultant catalyst exhibits an outstanding ORR performance with a half-wave potential of 0.92 eV in alkali and 0.80 eV in acid, as well as a high power density of 214.8 mW cm-2 in zinc air battery. This work provides a novel strategy for precisely tuning the atomically dispersed poly-metallic centers for electrocatalysis.

10.
Lab Invest ; 102(4): 341-351, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34775493

RESUMEN

This study aimed to investigate the effects of renal denervation (RDN) on diabetic cardiomyopathy (DCM) and explore the related mechanisms. Male Sprague-Dawley rats were fed high-fat chow and injected with low-dose streptozotocin to establish a DCM model. Six rats served as controls. The surviving rats were divided into three groups: control group, DCM group and DCM + RDN group. RDN surgery was performed in the fifth week. At the end of the experiment, all rats were subjected to 18F-FDG PET/CT and metabolic cage studies. Cardiac function and structure were evaluated by echocardiography and histology. Myocardial substrate metabolism and mitochondrial function were assessed by multiple methods. In the 13th week, the DCM rats exhibited cardiac hypertrophy and interstitial fibrosis accompanied by diastolic dysfunction. RDN ameliorated DCM-induced cardiac dysfunction (E/A ratio: RDN 1.07 ± 0.18 vs. DCM 0.93 ± 0.12, P < 0.05; E/E' ratio: RDN 10.74 ± 2.48 vs. DCM 13.25 ± 1.99, P < 0.05) and pathological remodeling (collagen volume fraction: RDN 5.05 ± 2.05% vs. DCM 10.62 ± 2.68%, P < 0.05). Abnormal myocardial metabolism in DCM rats was characterized by suppressed glucose metabolism and elevated lipid metabolism. RDN increased myocardial glucose uptake and oxidation while reducing the absorption and utilization of fatty acids. Meanwhile, DCM decreased mitochondrial ATP content, depolarized the membrane potential and inhibited the activity of respiratory chain complexes, but RDN attenuated this mitochondrial damage (ATP: RDN 30.98 ± 7.33 µmol/gprot vs. DCM 22.89 ± 5.90 µmol/gprot, P < 0.05; complexes I, III and IV activity: RDN vs. DCM, P < 0.05). Furthermore, both SGLT2 inhibitor and the combination treatment produced similar effects as RDN alone. Thus, RDN prevented DCM-induced cardiac dysfunction and pathological remodeling, which is related to the improvement of metabolic disorders and mitochondrial dysfunction.


Asunto(s)
Diabetes Mellitus , Cardiomiopatías Diabéticas , Transportador 2 de Sodio-Glucosa/metabolismo , Adenosina Trifosfato , Animales , Desnervación/métodos , Riñón , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Ratas , Ratas Sprague-Dawley
11.
Clin Exp Hypertens ; 44(2): 175-180, 2022 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-34821188

RESUMEN

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease.Bone morphogenetic proteins (BMPs) and their receptors were required for PAH-induced right ventricular hypertrophy. Emerging data suggest that restoration of BMP type II receptor (BMPR2) signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. BMPR2 mutations have been identified in >70% of familial and roughly 15% of sporadic PAH cases. Wingless (Wnt) are a family of secreted glycoproteins with varying expression patterns and a range of functions, Wnt signaling pathway is divided into canonical signaling pathway and non-canonical signaling pathway. A recent study reports that interaction between BMP and Wnt closely associated with lung development, those cascade coordination regulation stem cell fate which determine lung branching morphogenes. The promoting effect of BMPR2 on proliferation, survival, and motility of endothelial cells was through recruiting Wnts signaling pathway, the interaction between BMP and Wnt closely associated with lung development.Therefore, in this review, we outline the latest advances of BMP and Wnt signaling pathway in the pathogenesis of PAH and disease progression.


Asunto(s)
Proteínas Morfogenéticas Óseas , Hipertensión Arterial Pulmonar , Vía de Señalización Wnt , Proteínas Morfogenéticas Óseas/genética , Células Endoteliales , Humanos , Hipertensión Arterial Pulmonar/genética , Arteria Pulmonar
12.
Nano Lett ; 21(1): 700-708, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33301324

RESUMEN

The greatest challenge for lithium-sulfur (Li-S) batteries application is the development of cathode hosts to address the low conductivity, huge volume change, and shuttling effect of sulfur or lithium polysulfides (LiPs). Herein, we demonstrate a composite host to circumvent these problems by confining sub-nanometric manganous oxide clusters (MOCs) in nitrogen doped mesoporous carbon nanosheets. The atomic structure of MOCs is well-characterized and optimized via the extended X-ray absorption fine structure analysis and density functional theory (DFT) calculations. Benefiting from the unique design, the assembled Li-S battery displays remarkable electrochemical performances including a high reversible capacity (990 mAh g-1 after 100 cycles at 0.2 A g-1) and a superior cycle life (60% retention over 250 cycles at 2 A g-1). Both the experimental results and DFT calculations demonstrate that the well-dispersed MOCs could significantly promote the chemisorption of LiPs, thus greatly improving the capacity and rate performance.

13.
Yi Chuan ; 44(11): 1063-1071, 2022 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-36384998

RESUMEN

Glycogen storage disease type V is an autosomal recessive genetic disorder caused by muscle glycogen phosphorylase (PYGM) deficiency, which is characterized by exercise intolerance, second wind phenomena and high level of serum creatine kinase. In this study, we reported a Chinese young man with glycogen storage disease type V, with lower extremity weakness after exercise, increased creatine kinase, and slight fat infiltration in the posterior group of thigh muscle by magnetic resonance imaging (MRI). The proband had complex heterozygous PYGM disease-causing mutations, including c.308T>C (p.L103P) variant transmitted from the mother and c.260_261delCT (p.S87Ffs*23) from the father, of which the former was a novel PYGM mutation. This study enriched the PYGM pathogenic gene mutation spectrum, contributed to improve clinicians' understanding of glycogen storage disease type V and provided a reference for further genetic study of the disease.


Asunto(s)
Glucógeno Fosforilasa de Forma Muscular , Enfermedad del Almacenamiento de Glucógeno Tipo V , Humanos , Masculino , Creatina Quinasa/genética , Pruebas Genéticas , Glucógeno Fosforilasa de Forma Muscular/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Mutación
14.
Small ; 17(9): e1904022, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-31643131

RESUMEN

Mesoporous materials have drawn more and more attention in the field of biosensors due to their high surface areas, large pore volumes, tunable pore sizes, as well as abundant frameworks. In this review, the progress on mesoporous materials-based biosensors from enzymatic to nonenzymatic are highlighted. First, recent advances on the application of mesoporous materials as supports to stabilize enzymes in enzymatic biosensing technology are summarized. Special emphasis is placed on the effect of pore size, pore structure, and surface functional groups of the support on the immobilization efficiency of enzymes and the biosensing performance. Then, the development of a nonenzymatic strategy that uses the intrinsic property of mesoporous materials (carbon, silica, metals, and composites) to mimic the behavior of enzymes for electrochemical sensing of some biomolecules is discussed. Finally, the challenges and perspective on the future development of biosensors based on mesoporous materials are proposed.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Metales , Dióxido de Silicio
15.
BMC Infect Dis ; 21(1): 481, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-34039295

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated. METHODS: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified. RESULTS: The overall HCFR in China was estimated to be 4.6% (95% CI 4.5-4.8%, P < 0.001). It increased with age and was higher in males than females. Although the highest HCFR observed was in male patients ≥70 years old, the relative risks for death outcome by sex varied across age groups, and the greatest HCFR risk ratio for males vs. females was shown in the age group of 50-60 years, higher than age groups of 60-70 and ≥ 70 years. Differential age/sex HCFR patterns across geographical regions were found: the age effect on HCFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher HCFR was associated with older age (both P < 0.001), and male sex (both P < 0.001). Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher HCFR. CONCLUSIONS: This up-to-date and comprehensive picture of COVID-19 HCFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.


Asunto(s)
COVID-19/epidemiología , COVID-19/mortalidad , Mortalidad Hospitalaria , Hospitalización , SARS-CoV-2 , Adulto , Factores de Edad , Anciano , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , Tiempo de Tratamiento
16.
Appl Microbiol Biotechnol ; 105(10): 3873-3882, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33907890

RESUMEN

Saccharomyces cerevisiae is a widely used microorganism and a greatly popular cell factory for the production of various chemicals. In order to improve the yield of target chemicals, it is often necessary to increase the copy numbers of key genes or engineer the related metabolic pathways, which traditionally required time-consuming repetitive rounds of gene editing. With the development of gene-editing technologies such as meganucleases, TALENs, and the CRISPR/Cas system, multiplex genome editing has entered a period of rapid development to speed up cell factory optimization. Multi-copy insertion and removing bottlenecks in biosynthetic pathways can be achieved through gene integration and knockout, for which multiplexing can be accomplished by targeting repetitive sequences and multiple sites, respectively. Importantly, the development of the CRISPR/Cas system has greatly increased the speed and efficiency of multiplex editing. In this review, the various multiplex genome editing technologies in S. cerevisiae were summarized, and the principles, advantages, and the disadvantages were analyzed and discussed. Finally, the practical applications and future prospects of multiplex genome editing were discussed. KEY POINTS: • The development of multiplex genome editing in S. cerevisiae was summarized. • The pros and cons of various multiplex genome editing technologies are discussed. • Further prospects on the improvement of multiplex genome editing are proposed.


Asunto(s)
Edición Génica , Saccharomyces cerevisiae , Sistemas CRISPR-Cas , Saccharomyces cerevisiae/genética
17.
Yi Chuan ; 43(6): 531-544, 2021 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-34284986

RESUMEN

Rare diseases refer to diseases with low incidence. Currently, there are over 8000 rare diseases in the world. Effective prevention and treatment of rare diseases is an important part of 'healthy China'. In this paper, status and drug development of rare diseases were reported. These results indicate that research on rare diseases is growing rapidly driven by technology and policy. The hotspots include the identification of gene mutations, the development of therapies, and the key points of technology include the development of drugs for rare diseases, the development of viral vectors for gene therapy, and the diagnosis and management system for rare diseases. In terms of drug development, 880 drugs have been launched by December 28, 2020, and a large number of drugs are in the pre-clinical stage. Generally, a new technology or drug is applicable to various diseases. In the future, with policy support and the development of emerging technologies such as gene editing, more and more rare diseases will be diagnosed and intervened early, even be cured, and the quality of life of patients is expected to be improved.


Asunto(s)
Calidad de Vida , Enfermedades Raras , China , Edición Génica , Terapia Genética , Humanos , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Enfermedades Raras/terapia
18.
Yi Chuan ; 43(11): 1011-1022, 2021 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-34815205

RESUMEN

Familial hypercholesterolemia (FH) is an autosomal inherited disease characterized by a significant increase in low density lipoprotein cholesterol (LDL-C), tendon xanthoma and premature coronary artery disease (PCAD). In this paper, we analyze the current research status of FH, summarize the reported mutation gene loci in Chinese FH patients and treatment for them, and elaborate the current status of patents and drug researches. The results show that scientific outcomes of FH are increasing with a good developmental trend and the most popular topics of FH study are pathogenesis, treatment of FH, and research on juvenile FH patients. In terms of patents, large pharmaceutical companies, such as Regeneron Pharmaceuticals Inc, AstraZeneca Plc, Merck & Co Inc, are actively engaged in FH detection, diagnosis and treatment. In addition, 12 drugs have been launched in the United States, Japan, Europe and other countries or regions, bringing hope to FH patients.


Asunto(s)
Enfermedad de la Arteria Coronaria , Hiperlipoproteinemia Tipo II , LDL-Colesterol/genética , Europa (Continente) , Humanos , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/genética , Mutación , Estados Unidos
19.
Rare Metals ; 40(8): 2017-2025, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33679100

RESUMEN

Owing to their high performance and earth abundance, copper sulfides (Cu2-x S) have attracted wide attention as a promising medium-temperature thermoelectric material. Nanostructure and grain-boundary engineering are explored to tune the electrical transport and phonon scattering of Cu2-x S based on the liquid-like copper ion. Here multiscale architecture-engineered Cu2-x S are fabricated by a room-temperature wet chemical synthesis combining mechanical mixing and spark plasma sintering. The observed electrical conductivity in the multiscale architecture-engineered Cu2-x S is four times as much as that of the Cu2-x S sample at 800 K, which is attributed to the potential energy filtering effect at the new grain boundaries. Moreover, the multiscale architecture in the sintered Cu2-x S increases phonon scattering and results in a reduced lattice thermal conductivity of 0.2 W·m-1·K-1 and figure of merit (zT) of 1.0 at 800 K. Such a zT value is one of the record values in copper sulfide produced by chemical synthesis. These results suggest that the introduction of nanostructure and formation of new interface are effective strategies for the enhancement of thermoelectric material properties. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12598-020-01698-6) contains supplementary material, which is available to authorized users.

20.
Angew Chem Int Ed Engl ; 60(20): 11487-11493, 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33683786

RESUMEN

Electrochemical carbon dioxide (CO2 ) reduction reaction (CO2 RR) is an attractive approach to deal with the emission of CO2 and to produce valuable fuels and chemicals in a carbon-neutral way. Many efforts have been devoted to boost the activity and selectivity of high-value multicarbon products (C2+ ) on Cu-based electrocatalysts. However, Cu-based CO2 RR electrocatalysts suffer from poor catalytic stability mainly due to the structural degradation and loss of active species under CO2 RR condition. To date, most reported Cu-based electrocatalysts present stabilities over dozens of hours, which limits the advance of Cu-based electrocatalysts for CO2 RR. Herein, a porous chlorine-doped Cu electrocatalyst exhibits high C2+ Faradaic efficiency (FE) of 53.8 % at -1.00 V versus reversible hydrogen electrode (VRHE ). Importantly, the catalyst exhibited an outstanding catalytic stability in long-term electrocatalysis over 240 h. Experimental results show that the chlorine-induced stable cationic Cu0 /Cu+ species and the well-preserved structure with abundant active sites are critical to the high FE of C2+ in the long-term run of electrochemical CO2 reduction.

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