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1.
Cell ; 185(10): 1777-1792.e21, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35512705

RESUMEN

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.


Asunto(s)
Organogénesis , Transcriptoma , Animales , ADN/genética , Embrión de Mamíferos , Femenino , Perfilación de la Expresión Génica/métodos , Mamíferos/genética , Ratones , Organogénesis/genética , Embarazo , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Transcriptoma/genética
2.
EMBO J ; 41(18): e110521, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35929182

RESUMEN

Viruses often usurp host machineries for their amplification, but it remains unclear if hosts may subvert virus proteins to regulate viral proliferation. Here, we show that the 17K protein, an important virulence factor conserved in barley yellow dwarf viruses (BYDVs) and related poleroviruses, is phosphorylated by host GRIK1-SnRK1 kinases, with the phosphorylated 17K (P17K) capable of enhancing the abundance of virus-derived small interfering RNAs (vsiRNAs) and thus antiviral RNAi. Furthermore, P17K interacts with barley small RNA-degrading nuclease 1 (HvSDN1) and impedes HvSDN1-catalyzed vsiRNA degradation. Additionally, P17K weakens the HvSDN1-HvAGO1 interaction, thus hindering HvSDN1 from accessing and degrading HvAGO1-carried vsiRNAs. Importantly, transgenic expression of 17K phosphomimetics (17K5D ), or genome editing of SDN1, generates stable resistance to BYDV through elevating vsiRNA abundance. These data validate a novel mechanism that enhances antiviral RNAi through host subversion of a viral virulence protein to inhibit SDN1-catalyzed vsiRNA degradation and suggest new ways for engineering BYDV-resistant crops.


Asunto(s)
Hordeum , Antivirales , Hordeum/genética , Hordeum/metabolismo , Enfermedades de las Plantas/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Viral/genética , Proteínas Virales/genética , Proteínas Virales/metabolismo , Virulencia
3.
Proc Natl Acad Sci U S A ; 120(30): e2301622120, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37459527

RESUMEN

Potassium vanadium fluorophosphate (KVPO4F) is regarded as a promising cathode candidate for potassium-ion batteries due to its high working voltage and satisfactory theoretical capacity. However, the usage of electrochemically inactive binders and redundant current collectors typically results in inferior electrochemical performance and low energy density, thus implying the important role of rational electrode structure design. Herein, we have reported a scalable and cost-effective synthesis of a cellulose-derived KVPO4F self-supporting electrode, which features a special surface hydroxyl chemistry, three-dimensional porous and conductive framework, as well as super flexible and stable architecture. The cellulose not only serves as a flexible substrate, a pore-forming agent, and a versatile binder for KVPO4F/conductive carbon but also enhances the K-ion migration ability. Benefiting from the special hydroxyl chemistry-induced storage mechanism and electrode structural stability, the flexible freestanding KVPO4F cathode exhibits high-rate performance (53.0% capacity retention with current densities increased 50-fold, from 0.2 C to 10 C) and impressive cycling stability (capacity retention up to 74.9% can be achieved over 1,000 cycles at a rate of 5 C). Such electrode design and surface engineering strategies, along with a deeper understanding of potassium storage mechanisms, provide invaluable guidance for better electrode design to boost the performance of potassium-ion energy storage systems.

4.
Chem Rev ; 123(18): 11047-11136, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37677071

RESUMEN

Advances in nanotechnology and nanomaterials have attracted considerable interest and play key roles in scientific innovations in diverse fields. In particular, increased attention has been focused on carbon-based nanomaterials exhibiting diverse extended structures and unique properties. Among these materials, zero-dimensional structures, including fullerenes, carbon nano-onions, carbon nanodiamonds, and carbon dots, possess excellent bioaffinities and superior fluorescence properties that make these structures suitable for application to environmental and biological sensing, imaging, and therapeutics. This review provides a systematic overview of the classification and structural properties, design principles and preparation methods, and optical properties and sensing applications of zero-dimensional carbon nanomaterials. Recent interesting breakthroughs in the sensitive and selective sensing and imaging of heavy metal pollutants, hazardous substances, and bioactive molecules as well as applications in information encryption, super-resolution and photoacoustic imaging, and phototherapy and nanomedicine delivery are the main focus of this review. Finally, future challenges and prospects of these materials are highlighted and envisaged. This review presents a comprehensive basis and directions for designing, developing, and applying fascinating fluorescent sensors fabricated based on zero-dimensional carbon nanomaterials for specific requirements in numerous research fields.

5.
Nano Lett ; 24(23): 6872-6880, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38683656

RESUMEN

The efficient cytosolic delivery of the CRISPR-Cas9 machinery remains a challenge for genome editing. Herein, we performed ligand screening and identified a guanidinobenzol-rich polymer to overcome the cascade delivery barriers of CRISPR-Cas9 ribonucleoproteins (RNPs) for genome editing. RNPs were stably loaded into the polymeric nanoparticles (PGBA NPs) by their inherent affinity. The polymer facilitated rapid endosomal escape of RNPs via a dynamic multiple-step cascade process. Importantly, the incorporation of fluorescence in the polymer helps to identify the correlation between cellular uptake and editing efficiency, increasing the efficiency up to 70% from the initial 30% for the enrichment of edited cells. The PGBA NPs efficiently deliver RNPs for in vivo gene editing via both local and systemic injections and dramatically reduce PCSK9 level. These results indicate that PGBA NPs enable the cascade delivery of RNPs for genome editing, showing great promise in broadening the therapeutic potential of the CRISPR-Cas9 technique.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Nanopartículas , Polímeros , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , Humanos , Polímeros/química , Nanopartículas/química , Animales , Ribonucleoproteínas/genética , Ribonucleoproteínas/química , Células HEK293 , Ratones , Guanidinas/química
6.
J Am Chem Soc ; 146(8): 5295-5304, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38363710

RESUMEN

Unveiling the mechanism behind chirality propagation and dissymmetry amplification at the molecular level is of significance for the development of chiral systems with comprehensively outstanding chiroptical performances. Herein, we have presented a straightforward Cu-mediated Ullmann homocoupling approach to synthesize perylene diimide-entwined double π-helical nanoribbons encompassing dimer, trimer, and tetramer while producing homochiral or heterochiral linking of chiral centers. A significant dissymmetry amplification was achieved, with absorption dissymmetry factors (|gabs|) increasing from 0.009 to 0.017 and further to 0.019, and luminescence dissymmetry factors (|glum|) rising from 0.007 to 0.013 and eventually to 0.015 for homochiral double π-helical oligomers. The disparity of magnetic transition dipole moment (m) densities in homochiral and heterochiral tetramers by time-dependent density functional theory calculations confirmed that homochiral oligomerization can maximize the total m, which is favorable for achieving ever-increasing g factors. Notably, these double π-helices exhibited exceptional photoluminescence quantum yields (ΦPL) ranging from 83 to 95%. The circularly polarized luminescence brightness (BCPL) eventually reached a remarkable 575 M-1 cm-1 for the homochiral tetramer, which is among the highest values reported for chiral small molecules. This kind of linearly extended double π-helices offers a platform for a comprehensive understanding of the mechanism behind chirality propagation and dissymmetry amplification.

7.
J Am Chem Soc ; 146(19): 13499-13508, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38696816

RESUMEN

Near-infrared (NIR) circularly polarized light absorbing or emitting holds great promise for highly sensitive and precise bioimaging, biosensing, and photodetectors. Aiming at designing NIR chiral molecular systems with amplified dissymmetry and robust chiroptical response, herein, we present a series of double π-helical dimers with longitudinally extended π-entwined substructures via Ullmann or Yamamoto homocoupling reactions. Circular dichroism (CD) spectra revealed an approximate linear bathochromic shift with the rising number of naphthalene subunits, indicating a red to NIR chiroptical response. Particularly, the terrylene diimide-entwined dimers exhibited the strongest CD intensities, with the maximal |Δε| reaching up to 393 M-1 cm-1 at 666 nm for th-TDI[2]; and a record-high chiroptical response (|ΔΔε|) between the neutral and dianionic species of 520 M-1 cm-1 at 833 nm for th-TDI[2]Cl was achieved upon further reduction to its dianionic state. Time-dependent density functional theory (TDDFT) calculations suggested that the pronounced intensification of the CD spectra originated from a simultaneous enhancement of both electric (µ) and magnetic (m) transition dipole moments, ultimately leading to an overall increase in the rotatory strength (R). Notably, the circularly polarized luminescence (CPL) brightness (BCPL) reached 77 M-1 cm-1 for th-TDI[2]Cl, among the highest values reported for NIR-CPL emitters. Furthermore, all chiral dianions exhibited excellent air stability under ambient conditions with half-life times of up to 10 days in N-methylpyrrolidone (NMP), which is significant for future biological applications and chiroptic switches.

8.
Small ; : e2310824, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38282374

RESUMEN

Structured passivation layers and hydrated Zn2+ solvation structure strongly influence Zn depositions on Zn electrodes and then the cycle life and electrochemical performance of aqueous zinc ion batteries. To achieve these, the electrolyte additive of sodium L-ascorbate (Ass) is introduced into aqueous zinc sulfate (ZnSO4 , ZS) electrolyte solutions. Combined experimental characterizations with theoretical calculations, the unique passivation layers with vertical arrayed micro-nano structure are clearly observed, as well as the hydrated Zn2+ solvation structure is changed by replacing two ligand water molecules with As- , thus regulating the wettability and interfacial electric field intensity of Zn surfaces, facilitating rapid ionic diffusions within electrolytes and electrodes together with the inhibited side reactions and uniform depositions of Zn2+ . When tested in Zn||Zn symmetric cell, the electrolyte containing Ass is extraordinarily stably operated for the long time ≈3700 h at both 1 mA cm-2 and 1 mAh cm-2 . In Zn||MnO2 full coin cells, the energy density can still maintain as high as ≈184 Wh kg-1 at the power density high up to 2 kW kg-1 , as well as the capacity retention can reach up to 80.5% even after 1000 cycles at 2 A g-1 , which are substantially superior to the control cells.

9.
Plant Biotechnol J ; 22(3): 572-586, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37855813

RESUMEN

Barley yellow dwarf viruses (BYDVs) cause widespread damage to global cereal crops. Here we report a novel strategy for elevating resistance to BYDV infection. The 17K protein, a potent virulence factor conserved in BYDVs, interacted with barley IMP-α1 and -α2 proteins that are nuclear transport receptors. Consistently, a nuclear localization signal was predicted in 17K, which was found essential for 17K to be transported into the nucleus and to interact with IMP-α1 and -α2. Reducing HvIMP-α1 and -α2 expression by gene silencing attenuated BYDV-elicited dwarfism, accompanied by a lowered nuclear accumulation of 17K. Among the eight common wheat CRISPR mutants with two to four TaIMP-α1 and -α2 genes mutated, the triple mutant α1aaBBDD /α2AAbbdd and the tetra-mutant α1aabbdd /α2AAbbDD displayed strong BYDV resistance without negative effects on plant growth under field conditions. The BYDV resistance exhibited by α1aaBBDD /α2AAbbdd and α1aabbdd /α2AAbbDD was correlated with decreased nuclear accumulation of 17K and lowered viral proliferation in infected plants. Our work uncovers the function of host IMP-α proteins in BYDV pathogenesis and generates the germplasm valuable for breeding BYDV-resistant wheat. Appropriate reduction of IMP-α gene expression may be broadly useful for enhancing antiviral resistance in agricultural crops and other economically important organisms.


Asunto(s)
Luteovirus , Triticum , Triticum/genética , alfa Carioferinas/genética , Resistencia a la Enfermedad/genética , Fitomejoramiento , Luteovirus/genética , Productos Agrícolas/genética , Expresión Génica , Enfermedades de las Plantas/genética
10.
Virol J ; 21(1): 72, 2024 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515187

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) infection is a public health problem that seriously threatens human health. This study aimed to investigate the clinical significance of glutathione peroxidase 4(GPX4) in the occurrence and development of chronic hepatitis B (CHB). METHODS: A total of 169 participants including 137 patients with CHB and 32 healthy controls (HCs) were recruited. We detected the expression of GPX4 and stimulator of interferon genes (STING) in peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (RT-qPCR). The methylation level of GPX4 gene promoter in PBMCs was detected by TaqMan probe-based quantitative methylation-specific PCR (MethyLight). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum levels of GPX4, IFN-ß, oxidative stress (OS) related molecules, and pro-inflammatory cytokines. RESULTS: The expression levels of GPX4 in PBMCs and serum of CHB patients were lower than those of HCs, but the methylation levels of GPX4 promoter were higher than those of HCs, especially in patients at the immune tolerance phase. STING mRNA expression levels in PBMCs and serum IFN-ß levels of patients at the immune activation phase and reactivation phase of CHB were higher than those at other clinical phases of CHB and HCs. GPX4 mRNA expression level and methylation level in PBMCs from patients with CHB had a certain correlation with STING and IFN-ß expression levels. In addition, the methylation level of the GPX4 promoter in PBMCs from patients with CHB was correlated with molecules associated with OS and inflammation. CONCLUSIONS: GPX4 may play an important role in the pathogenesis and immune tolerance of CHB, which may provide new ideas for the functional cure of CHB.


Asunto(s)
Hepatitis B Crónica , Humanos , Metilación de ADN , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Leucocitos Mononucleares/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , ARN Mensajero/genética
11.
Environ Sci Technol ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943037

RESUMEN

Although the impacts of exotic wetland plant invasions on native biodiversity, landscape features, and carbon-nitrogen cycles are well appreciated, biogeochemical consequences posed by ecological competition, such as the heterogeneity of dissolved organic matter (DOM) from plant detritus and its impact on the formation of reactive oxygen species, are poorly understood. Thus, this study delves into O2•- photogeneration potential of DOM derived from three different parts (stem, leaf, and panicle) of invasive Spartina alterniflora (SA) and native Phragmites australis (PA). It is found that DOM from the leaves of SA and the panicles of PA has a superior ability to produce O2•-. With more stable aromatic structures and a higher proportion of sulfur-containing organic compounds, SA-derived DOM generally yields more O2•- than that derived from PA. UVA exposure enhances the leaching of diverse DOM molecules from plant detritus. Based on the reported monitoring data and our findings, the invasion of SA is estimated to approximately double the concentration of O2•- in the surrounding water bodies. This study can help to predict the underlying biogeochemical impacts from the perspective of aquatic photochemistry in future scenarios of plant invasion, seawater intrusion, wetland degradation, and elevated solar UV radiation.

12.
Hepatol Res ; 54(4): 392-402, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37950561

RESUMEN

AIMS: Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin-3, a beta-galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin-3 levels in children with BA. METHODS: Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin-3 was measured using standard enzyme-linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing. RESULTS: Plasma Galectin-3 in late BA was significantly higher than in early BA (20.82 [12.45-30.46] vs. 11.30 [8.74-16.83] ng/mL, p = 0.0096). Galectin-3 levels correlated with markers of disease severity and interleukin-6. There were significantly more Galectin-3+ M2 macrophages in late BA in comparison to late other CLD (162 [157-233] vs. 49 [33-59] cells/mm2, p = 0.03). The number of Galectin-3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation. CONCLUSIONS: Plasma Galectin-3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin-3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin-3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA.

13.
Nature ; 555(7696): 363-366, 2018 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-29513654

RESUMEN

Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.


Asunto(s)
Agricultura/métodos , Conservación de los Recursos Naturales , Productos Agrícolas/crecimiento & desarrollo , Eficiencia Organizacional , Agricultores , China , Técnicas de Apoyo para la Decisión , Grano Comestible/crecimiento & desarrollo , Política Ambiental , Fertilizantes/estadística & datos numéricos , Abastecimiento de Alimentos/métodos , Efecto Invernadero , Nitrógeno/metabolismo , Oryza/crecimiento & desarrollo , Triticum/crecimiento & desarrollo , Zea mays/crecimiento & desarrollo
14.
J Med Genet ; 60(7): 655-661, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36446583

RESUMEN

BACKGROUND: Diagnosis of a genetic disease and determination of the causative molecular lesion rely on the availability of the disease-associated pedigrees. Microphthalmia is a congenital eye defect due to an insufficiently developed visual system; its prevalence is 1-3 in 10 000 live births. OBJECTIVE: We analysed a pedigree exhibiting autosomal dominant inheritance of microphthalmia to determine the genetic lesion; used AlphaFold2 to predict the changes in the protein's 3-Dimensional structure; and compared wild-type and variant proteins in cultured cells or Drosophila model was used to explore the cellular or developmental function of the encoded product. RESULTS: We identified a novel missense variation, F52L, in MAB21L1 that is absent in population databases and present exclusively in the individuals diagnosed with microphthalmia in this pedigree. Common structural changes were predicted for the disease-associated variants clustered at amino acids 49-52, and these variant products were also predominantly trapped in the cytoplasm of cultured human lens epithelia. To recapitulate its dominant effect in development, we expressed the Drosophila homologue corresponding to MAB21L1F52L and caused malformation of sensory organs. CONCLUSION: Mutations at the residues 49-52 of MAB21L1 compromise eye development. We recommend including MAB21L1 in the genetic testing panel for congenital eye disorders.


Asunto(s)
Anomalías del Ojo , Microftalmía , Humanos , Microftalmía/genética , Aminoácidos/genética , Pruebas Genéticas , Anomalías del Ojo/genética , Mutación , Linaje , Proteínas de Homeodominio/genética
15.
BMC Surg ; 24(1): 103, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600472

RESUMEN

BACKGROUND: There is no effective consensus on the choice of internal fixation method for the Masquelet technique in the treatment of large segmental bone defects of the distal tibia. Thus, the study aimed to investigate the outcomes of the Masquelet technique combined with double plate fixation in the treatment of large segmental bone defects. METHODS: This was a retrospective study involving 21 patients with large segmental bone defects of the distal tibia who were treated between June 2017 and June 2020. The length of bone defect ranged from 6.0 cm to 11 cm (mean, 8.19 cm). In the first stage of treatment, following complete debridement, a cement spacer was placed to induce membrane formation. In the second stage, double plate fixation and autologous cancellous bone grafting were employed for bone reconstruction. Each patient's full weight-bearing time, bone healing time, and Iowa ankle score were recorded, and the occurrence of any complications was noted. RESULTS: All patients were followed up for 16 to 26 months (mean, 19.48 months). The group mean full weight-bearing time and bone healing time after bone grafting were 2.41 (± 0.37) months and 6.29 (± 0.66) months, respectively. During the treatment, one patient had a wound infection on the medial side of the leg, so the medial plate was removed. The wound completely healed after debridement without any recurrence. After extraction of iliac bone for grafting, one patient had a severe iliac bone defect, which was managed by filling the gap with a cement spacer. Most patients reported mild pain in the left bone extraction area after surgery. The postoperative Iowa ankle score range was 84-94 (P < 0.05). In this cohort, 15 cases were rated as "excellent", and 6 cases as "good" on the Iowa ankle scoring system. CONCLUSION: The Masquelet technique combined with double plate fixation is a safe and effective method for the treatment of large segmental bone defects of the distal tibia.


Asunto(s)
Procedimientos de Cirugía Plástica , Fracturas de la Tibia , Humanos , Tibia/cirugía , Estudios Retrospectivos , Extremidad Inferior/cirugía , Fijación Interna de Fracturas , Trasplante Óseo/métodos , Resultado del Tratamiento , Fracturas de la Tibia/cirugía
16.
Sensors (Basel) ; 24(10)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38793842

RESUMEN

Hyperspectral images (HSIs) contain subtle spectral details and rich spatial contextures of land cover that benefit from developments in spectral imaging and space technology. The classification of HSIs, which aims to allocate an optimal label for each pixel, has broad prospects in the field of remote sensing. However, due to the redundancy between bands and complex spatial structures, the effectiveness of the shallow spectral-spatial features extracted by traditional machine-learning-based methods tends to be unsatisfying. Over recent decades, various methods based on deep learning in the field of computer vision have been proposed to allow for the discrimination of spectral-spatial representations for classification. In this article, the crucial factors to discriminate spectral-spatial features are systematically summarized from the perspectives of feature extraction and feature optimization. For feature extraction, techniques to ensure the discrimination of spectral features, spatial features, and spectral-spatial features are illustrated based on the characteristics of hyperspectral data and the architecture of models. For feature optimization, techniques to adjust the feature distances between classes in the classification space are introduced in detail. Finally, the characteristics and limitations of these techniques and future challenges in facilitating the discrimination of features for HSI classification are also discussed further.

17.
Nano Lett ; 23(22): 10350-10359, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37930173

RESUMEN

Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy by inducing the immunogenic death (ICD) of cancer cells and activating the stimulator of the interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tumor tissue and in situ generate •OH for the ICD effect. Moreover, Mn2+ activated the STING and synergistically induced the secretion of type I interferon and inflammatory cytokines for specific T cell responses. Meanwhile, MONPs relieved the immunosuppression of TME through decreasing Tregs and polarizing M2 macrophages to the M1 type to unleash a cascade adaptive immune response. In combination with the anti-PD-1 antibody, MONPs showed superior efficacy in inhibiting tumor growth and preventing lung metastasis. Our study demonstrates the feasibility of functional nanoparticles to amplify STING innate stimulation, showing a prominent strategy for cancer immunotherapy.


Asunto(s)
Neoplasias Pulmonares , Nanopartículas , Neoplasias , Humanos , Manganeso/uso terapéutico , Inmunoterapia , Nanopartículas/uso terapéutico , Microambiente Tumoral , Peróxidos , Zinc , Neoplasias/tratamiento farmacológico
18.
Angew Chem Int Ed Engl ; 63(19): e202319997, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38499464

RESUMEN

High ambipolar mobility emissive conjugated polymers (HAME-CPs) are perfect candidates for organic optoelectronic devices, such as polymer light emitting transistors. However, due to intrinsic trade-off relationship between high ambipolar mobility and strong solid-state luminescence, the development of HAME-CPs suffers from high structural and synthetic complexity. Herein, a universal design principle and simple synthetic approach for HAME-CPs are developed. A series of simple non-fused polymers composed of charge transfer units, π bridges and emissive units are synthesized via a two-step microwave assisted C-H arylation and direct arylation polymerization protocol with high total yields up to 61 %. The synthetic protocol is verified valid among 7 monomers and 8 polymers. Most importantly, all 8 conjugated polymers have strong solid-state emission with high photoluminescence quantum yields up to 24 %. Furthermore, 4 polymers exhibit high ambipolar field effect mobility up to 10-2 cm2 V-1 s-1, and can be used in multifunctional optoelectronic devices. This work opens a new avenue for developing HAME-CPs by efficient synthesis and rational design.

19.
Angew Chem Int Ed Engl ; 63(22): e202402255, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38551062

RESUMEN

With the prosperity of the development of carbon nanorings, certain topologically or functionally unique units-embedded carbon nanorings have sprung up in the past decade. Herein, we report the facile and efficient synthesis of three cyclooctatetraene-embedded carbon nanorings (COTCNRs) that contain three (COTCNR1 and COTCNR2) and four (COTCNR3) COT units in a one-pot Yamamoto coupling. These nanorings feature hoop-shaped segments of Gyroid (G-), Diamond (D-), and Primitive (P-) type carbon schwarzites. The conformations of the trimeric nanorings COTCNR1 and COTCNR2 are shape-persistent, whereas the tetrameric COTCNR3 possesses a flexible carbon skeleton which undergoes conformational changes upon forming host-guest complexes with fullerenes (C60 and C70), whose co-crystals may potentially serve as fullerene-based semiconducting supramolecular wires with electrical conductivities on the order of 10-7 S cm-1 (for C60⊂COTCNR3) and 10-8 S cm-1 (for C70⊂COTCNR3) under ambient conditions. This research not only describes highly efficient one-step syntheses of three cyclooctatetraene-embedded carbon nanorings which feature hoop-shaped segments of distinctive topological carbon schwarzites, but also demonstrates the potential application in electronics of the one-dimensional fullerene arrays secured by COTCNR3.

20.
Hum Mol Genet ; 30(17): 1569-1578, 2021 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-33864361

RESUMEN

CLP1, TSEN complex, and VCP are evolutionarily conserved proteins whose mutations are associated with neurodegenerative diseases. In this study, we have found that they are also involved in germline differentiation. To optimize both quantity and quality in gametes production, germ cells expand themselves through limited mitotic cycles prior to meiosis. Stemming from our previous findings on the correlation between mRNA 3'-processing and meiosis entry, here we identify that the RNA kinase Cbc, the Drosophila member of the highly conserved CLP1 family, is a component of the program regulating the transition from mitosis to meiosis. Using genetic manipulations in Drosophila testis, we demonstrate that nuclear Cbc is required to promote meiosis entry. Combining biochemical and genetic methods, we reveal that Cbc physically and/or genetically intersects with Tsen54 and TER94 (VCP ortholog) in this process. The C-terminal half of Tsen54 is both necessary and sufficient for its binding with Cbc. Further, we illustrate the functional conservation between Cbc and mammalian CLP1 in the assays of subcellular localization and Drosophila fertility. As CLP1, TSEN complex, and VCP have also been identified in neurodegenerations of animal models, a mechanism involving these factors seems to be shared in gametogenesis and neurogenesis.


Asunto(s)
Meiosis/genética , Proteínas Nucleares/metabolismo , Fosfotransferasas/metabolismo , Espermatogénesis/genética , Factores de Transcripción/metabolismo , Animales , Animales Modificados Genéticamente , Diferenciación Celular/genética , Drosophila melanogaster/metabolismo , Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/genética , Células Germinativas/metabolismo , Masculino , Meiosis/fisiología , Mutación , ARN/genética , Espermatogénesis/fisiología , Testículo/embriología , Testículo/metabolismo
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