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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38701420

RESUMEN

The relationship between genotype and fitness is fundamental to evolution, but quantitatively mapping genotypes to fitness has remained challenging. We propose the Phenotypic-Embedding theorem (P-E theorem) that bridges genotype-phenotype through an encoder-decoder deep learning framework. Inspired by this, we proposed a more general first principle for correlating genotype-phenotype, and the P-E theorem provides a computable basis for the application of first principle. As an application example of the P-E theorem, we developed the Co-attention based Transformer model to bridge Genotype and Fitness model, a Transformer-based pre-train foundation model with downstream supervised fine-tuning that can accurately simulate the neutral evolution of viruses and predict immune escape mutations. Accordingly, following the calculation path of the P-E theorem, we accurately obtained the basic reproduction number (${R}_0$) of SARS-CoV-2 from first principles, quantitatively linked immune escape to viral fitness and plotted the genotype-fitness landscape. The theoretical system we established provides a general and interpretable method to construct genotype-phenotype landscapes, providing a new paradigm for studying theoretical and computational biology.


Asunto(s)
COVID-19 , Aprendizaje Profundo , Genotipo , Fenotipo , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Humanos , COVID-19/virología , COVID-19/genética , COVID-19/inmunología , Biología Computacional/métodos , Algoritmos , Aptitud Genética
2.
Nano Lett ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836517

RESUMEN

As a potential alternative to antibiotics, hyperbranched poly(ionic liquid)s (HPILs) have demonstrated significant potential in combating bacterial biofilms. However, their high cation density poses a high risk of toxicity, greatly limiting their in vivo applications. In this study, we constructed a biocompatible HPIL (HPIL-Glu) from a hyperbranched polyurea core with modified terminals featuring charge-convertible ionic liquids. These ionic liquid moieties consist of an ammonium-based cation and a gluconate (Glu) organic counter. HPIL-Glu could form a homogeneous nanoassembly in water and exhibited a pH-responsive charge conversion property. Under neutral conditions, Glu shielded the positively charged surface, minimizing the toxicity. In a mildly acidic environment, Glu protonation exposes cationic moieties to biofilm eradication. Comprehensive antimicrobial assessments demonstrate that HPIL-Glu effectively kills bacteria and promotes the healing of bacteria-infected chronic wounds. Furthermore, prolonged exposure to HPIL-Glu does not induce antimicrobial resistance.

3.
J Am Chem Soc ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981037

RESUMEN

Chiral acyclic α-tertiary amino ketones are widely present in various natural products and pharmaceuticals; however, the direct synthesis of this pharmacophore through a robust strategy still presents significant challenges. The emerging photocatalysis provides a powerful approach to construct chemical bonds that are difficult to form via a traditional two-electron pathway. Herein, we developed visible-light-induced chiral Lewis acid-catalyzed highly enantioselective acylation/alkylation of aldimines enabled by cooperative FLN (9-fluorenone) electron-shuttle catalysis via radical addition. An array of α-tertiary amino ketones, ß-amino alcohols, and chiral amines were achieved with high yields and good to excellent stereocontrol (87 examples, up to 84% yield, 96% ee). These products can be easily transformed into valuable and bioactive skeletons. Extensive control experiments, detailed mechanism studies, and density functional theory calculations elucidated the reaction process and highlighted the crucial role played by FLN.

4.
Biochem Cell Biol ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013204

RESUMEN

Atherosclerosis (AS) is an inflammatory arterial disorder that occurs due to the deposition of the excessive lipoprotein under the artery intima, mainly including low-density lipoprotein (LDL) and other apolipoprotein B-containing lipoproteins. G protein-coupled receptors (GPCRs) play a crucial role in transmitting signals in physiological and pathophysiological conditions. GPCRs recognize inflammatory mediators, thereby serving as important players during chronic inflammatory processes. It has been demonstrated that free fatty acids can function as ligands for various GPCRs, such as free fatty acid receptor (FFAR)1/GPR40, FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120, and the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). This review discusses GPR43 and its ligands in the pathogenesis of AS, especially focusing on its distinct role in regulating chronic vascular inflammation, inhibiting oxidative stress, ameliorating endothelial dysfunction and improving dyslipidemia. It is hoped that this review may provide guidance for further studies aimed at GPR43 as a promising target for drug development in the prevention and therapy of AS.

5.
Small ; : e2403947, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38948958

RESUMEN

Converting hierarchical biomass structure into cutting-edge architecture of electrocatalysts can effectively relieve the extreme dependency of nonrenewable fossil-fuel-resources typically suffering from low cost-effectiveness, scarce supplies, and adverse environmental impacts. A cost-effective cobalt-coordinated nanocellulose (CNF) strategy is reported for realizing a high-performance 2e-ORR electrocatalysts through molecular engineering of hybrid ZIFs-CNF architecture. By a coordination and pyrolysis process, it generates substantial oxygen-capturing active sites within the typically oxygen-insulating cellulose, promoting O2 mass and electron transfer efficiency along the nanostructured Co3O4 anchored with CNF-based biochar. The Co-CNF electrocatalyst exhibits an exceptional H2O2 electrosynthesis efficiency of ≈510.58 mg L-1 cm-2 h-1 with an exceptional superiority over the existing biochar-, or fossil-fuel-derived electrocatalysts. The combination of the electrocatalysts with stainless steel mesh serving as a dual cathode can strongly decompose regular organic pollutants (up to 99.43% removal efficiency by 30 min), showing to be a desirable approach for clean environmental remediation with sustainability, ecological safety, and high-performance.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(7): 797-802, 2024 Jul 10.
Artículo en Zh | MEDLINE | ID: mdl-38946360

RESUMEN

OBJECTIVE: To assess the efficiency of modified enrichment method for cell-free fetal DNA (cffDNA) through purified superparamagnetic beads during non-invasive prenatal testing (NIPT). METHODS: A total of 26 252 pregnant women undergoing NIPT at the Maternal and Child Health Care Hospital of Haidian District from December 2017 to September 2022 were recruited and randomly assigned into the conventional group (n = 10 573) and the modified enrichment group (n = 15 679), who were then subjected to the screening and enrichment of the cffDNA using a conventional and a modified technique, respectively. High-risk pregnant women detected by NIPT were subjected to invasive prenatal diagnosis. All women were followed up for their pregnancy outcomes, and the detection efficacy of the two methods was compared in terms of fragment size, concentration of cffDNA, duplicate detection rate, and indices of clinical laboratory tests. RESULTS: The fragment size of the main peak of the cell-free DNA library of the modified enrichment group was significantly lower than that of the conventional group [267 (264, 269) bp vs. 294 (292, 296) bp, P < 0.01], while the concentration of cffDNA was significantly higher [21.86% (17.61%, 26.36%) vs. 9.08% (6.87%, 11.87%), P < 0.01]. In addition, the duplicate detection rate (0.740% vs. 2.02%, X2 = 83.90, P < 0.01) and detection failure rate (0.006% vs. 0.057%, P < 0.05) in the modified enrichment group were significantly lower than those of the conventional group. The combined positive predictive value (PPV) in both high-risk (64.3% vs. 76.1%) and low-risk (35.3% vs. 45.5%) pregnant women from the modified enrichment group was slightly lower than those from the conventional group, though no significant difference was detected. There was one false negative case for trisomy 21 among the high-risk pregnant women from the conventional group, and no false negative case was found in the modified enrichment group. CONCLUSION: The modified technique to screen and enrich the cffDNA has significantly enhanced the relative concentration of cffDNA and reduced the failure and duplication detection rate of NIPT, which has significantly reduced the incidence of false negative cases due to the low concentration of cffDNA, and greatly increased the overall detection efficacy of NIPT.


Asunto(s)
Ácidos Nucleicos Libres de Células , Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Ácidos Nucleicos Libres de Células/aislamiento & purificación , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Adulto , Pruebas Prenatales no Invasivas/métodos , Diagnóstico Prenatal/métodos , Feto
7.
Angew Chem Int Ed Engl ; 63(8): e202317942, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38179820

RESUMEN

CO2 electroreduction (CO2 R) operating in acidic media circumvents the problems of carbonate formation and CO2 crossover in neutral/alkaline electrolyzers. Alkali cations have been universally recognized as indispensable components for acidic CO2 R, while they cause the inevitable issue of salt precipitation. It is therefore desirable to realize alkali-cation-free CO2 R in pure acid. However, without alkali cations, stabilizing *CO2 intermediates by catalyst itself at the acidic interface poses as a challenge. Herein, we first demonstrate that a carbon nanotube-supported molecularly dispersed cobalt phthalocyanine (CoPc@CNT) catalyst provides the Co single-atom active site with energetically localized d states to strengthen the adsorbate-surface interactions, which stabilizes *CO2 intermediates at the acidic interface (pH=1). As a result, we realize CO2 conversion to CO in pure acid with a faradaic efficiency of 60 % at pH=2 in flow cell. Furthermore, CO2 is successfully converted in cation exchanged membrane-based electrode assembly with a faradaic efficiency of 73 %. For CoPc@CNT, acidic conditions also promote the intrinsic activity of CO2 R compared to alkaline conditions, since the potential-limiting step, *CO2 to *COOH, is pH-dependent. This work provides a new understanding for the stabilization of reaction intermediates and facilitates the designs of catalysts and devices for acidic CO2 R.

8.
Small ; 19(23): e2301146, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36879476

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused COVID-19 pandemic has rapidly escalated into the largest global health emergency, which pushes to develop detection kits for the detection of COVID-19 with high sensitivity, specificity, and fast analysis. Here, aptamer-functionalized MXene nanosheet is demonstrated as a novel bionanosensor that detects COVID-19. Upon binding to the spike receptor binding domain of SARS-CoV-2, the aptamer probe is released from MXene surface restoring the quenched fluorescence. The performances of the fluorosensor are evaluated using antigen protein, cultured virus, and swab specimens from COVID-19 patients. It is evidenced that this sensor can detect SARS-CoV-2 spike protein at final concentration of 38.9 fg mL-1 and SARS-CoV-2 pseudovirus (limit of detection: 7.2 copies) within 30 min. Its application for clinical samples analysis is also demonstrated successfully. This work offers an effective sensing platform for sensitive and rapid detection of COVID-19 with high specificity.


Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Pandemias , Oligonucleótidos
9.
Langmuir ; 39(18): 6399-6405, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37105949

RESUMEN

Ex-service SF6 adsorbents in SF6 gas-insulated electric equipment contain many toxic substances. Inside, HF and H2S are two typical toxic gases. Based on the first principle, the interaction process between HF/H2S and α-Al2O3 (0001) surfaces was calculated using the density functional theory (DFT). The results showed that the adsorption of HF on α-Al2O3 (0001) is stronger than that of H2S. Under the five adsorption sites, the adsorption effect of HF-H and HF-F was similar. At O-2 site, the adsorption energy of H2S-H adsorption configuration is significantly higher than that of the other four sites. The density of states (DOS) indicated that new peaks appeared after adsorption. The DOS and partial density of states (PDOS) indicated that the adsorption of HF and H2S occurs via chemical adsorption. The DOS and PDOS shifted to the right when the S atom was approaching, proving that the system shifts to instability. Compared with the energy gap of α-Al2O3 (0001), HF and H2S adsorption systems decreased significantly. The energy gap of the HF adsorption system was 1.173 eV larger than that of the H2S system and the geometry was relatively stable, which is consistent with the DOS and PDOS adsorption calculation results. Thus, the adsorption of HF and H2S on α-Al2O3 (0001) surfaces was clearly different. The findings of this study may provide theoretical guidance for the adsorption of other gases or developing a new adsorbent.

10.
J Periodontal Res ; 58(4): 841-851, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37243354

RESUMEN

BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial inflammatory disease that leads to the destruction of supporting structures of the teeth. DNA damage-inducible transcript 3 (DDIT3) plays crucial roles in cell survival and differentiation. DDIT3 regulates bone mass and osteoclastogenesis in femur. However, the role of DDIT3 in periodontitis has not been elucidated. This research aimed to explore the role and mechanisms of DDIT3 in periodontitis. METHODS: DDIT3 gene knockout (KO) mice were generated using a CRISPR/Cas9 system. Experimental periodontitis models were established to explore the role of DDIT3 in periodontitis. The expression of DDIT3 in periodontal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The alveolar bone phenotypes were observed by micro-CT and stereomicroscopy. The inflammation levels and osteoclast activity were examined by histological staining, immunostaining, and qRT-PCR. Bone marrow-derived macrophages (BMMs) were isolated to confirm the effects of DDIT3 on osteoclast formation and function in vitro. RESULTS: The increased expression of DDIT3 in murine inflamed periodontal tissues was detected. DDIT3 knockout aggravated alveolar bone loss and enhanced expression levels of inflammatory cytokines in murine periodontitis models. Increased osteoclast formation and higher expression levels of osteoclast-specific markers were observed in the inflamed periodontal tissues of KO mice. In vitro, DDIT3 deficiency promoted the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts and the bone resorption activity of mature osteoclasts. CONCLUSIONS: Our results demonstrate that DDIT3 deletion aggravated alveolar bone loss in experimental periodontitis through enhanced inflammatory reactions and osteoclastogenesis. The anti-inflammation and the inhibition of bone loss by DDIT3 in murine periodontitis provides a potential novel therapeutic strategy for periodontitis.


Asunto(s)
Pérdida de Hueso Alveolar , Resorción Ósea , Periodontitis , Animales , Ratones , Pérdida de Hueso Alveolar/patología , Daño del ADN , Inflamación/patología , Osteoclastos/metabolismo , Periodontitis/tratamiento farmacológico , Ligando RANK/metabolismo
11.
Exp Cell Res ; 417(1): 113191, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35513074

RESUMEN

Diabetic cataract (DC) is a common complication of diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a crucial event in the development of DC. Murine double minute 2 (MDM2) is an E3 ubiquitin ligase that promotes EMT by regulating diverse targets. However, little is known about how MDM2 is involved in the pathogenesis of DC. We found the mRNA and protein levels of MDM2 were up-regulated in the lens of DC patients and rats. Thus, high glucose (HG)-induced human lens epithelial cells (HLECs) were constructed for further investigation. The results showed that the level of MDM2 was increased in HG-cultured HLECs, and the MDM2 knockdown alleviated HG-induced abnormal migration, EMT, and oxidative stress damage. Moreover, co-immunoprecipitation and ubiquitination assays demonstrated that MDM2 down-regulated LKB1 expression by ubiquitination degradation. LKB1 was found to be lower expressed in human and rat DC lenses, and HG-stimulated HLECs. Also, LKB1 overexpression mitigated HG-induced dysfunction of HLECs. Finally, our data showed that the changes related to EMT and oxidative stress induced by MDM2 knockdown were restored by down-regulation of LKB1. Together, MDM2 may involve in the pathogenesis of DC through down-regulating LKB1. MDM2 might be an effective therapeutical target of DC.


Asunto(s)
Catarata , Diabetes Mellitus , Cristalino , Animales , Catarata/genética , Catarata/patología , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/genética , Humanos , Cristalino/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Ratas , Ubiquitinación
12.
World J Surg Oncol ; 21(1): 285, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37697366

RESUMEN

BACKGROUND: To compare the surgical effects of lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) for pheochromocytoma of different sizes. METHODS: Data on patients with pheochromocytoma from 2014 to 2023 were collected from our hospital. According to different surgical approaches and tumor size, all patients were divided into four groups: tumor size < 6 cm for LTA and PRA and tumor size ≥ 6 cm for LTA and PRA. We compared these two surgical methods for pheochromocytoma of different sizes. RESULTS: A total of 118 patients with pheochromocytoma underwent successful laparoscopic surgery, including PRA group (n = 80) and LTA group (n = 38). In tumor size < 6 cm, the outcomes were no significant difference in LTA and PRA. In tumor size ≥ 6 cm, there was a significant difference in operation time (214.7 ± 18.9 vs. 154.3 ± 8.2, P = 0.007) and intraoperative blood loss (616.4 ± 181.3 vs. 201.4 ± 45.8, P = 0.037) between LTA and PRA. CONCLUSION: LTA and PRA were performed safely with similar operative outcomes in patients with pheochromocytoma size < 6 cm. While both LTA and PRA were executed with a commendable safety profile and comparable operative results in patients afflicted by pheochromocytomas < 6 cm, the PRA technique distinctly showcased advantages when addressing large-scale pheochromocytomas (≥ 6 cm). Notably, this manifested in reduced operative time, diminished intraoperative blood loss, decreased hospitalization expenses, and a paucity of procedural complications.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Humanos , Feocromocitoma/cirugía , Pérdida de Sangre Quirúrgica , Estudios Retrospectivos , Neoplasias de las Glándulas Suprarrenales/cirugía , Hospitalización
13.
Phytother Res ; 37(10): 4722-4739, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37443453

RESUMEN

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.


Asunto(s)
Neoplasias Ováricas , Trombospondina 1 , Animales , Ratones , Humanos , Femenino , Carcinoma Epitelial de Ovario , Trabectedina/uso terapéutico , Trombospondina 1/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Células Endoteliales/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Línea Celular Tumoral , Proliferación Celular/genética
14.
Sensors (Basel) ; 23(19)2023 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-37837132

RESUMEN

The impedance change in an induction coil surrounding a metal tube adapter is investigated using the truncated region eigenfunction expansion (TREE) method. The conventional TREE method is inapplicable to this problem as a consequence of the numerical overflow of the eigenfunctions of the air-metal multi-subdomain regions. The difficulty is surmounted by a normalization procedure for the numerical eigenfunctions obtained from the 1D finite element method (FEM). An efficient algorithm is devised by the Clenshaw-Curtis quadrature rule for integrals involving the numerical eigenfunctions. The numerical results of the TREE and FEM simulation coincide very well in all cases, and the efficiency of the proposed method is also confirmed.

15.
Angew Chem Int Ed Engl ; 62(32): e202306146, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37302984

RESUMEN

The α-methylene-γ-butyrolactone motif is a widely encountered unit in many natural products and pharmaceutical compounds. Herein, a practical and efficient synthesis of α-methylene-γ-butyrolactones from readily available allylic boronates and benzaldehyde derivatives was developed with chiral N,N'-dioxide/AlIII complex as the catalyst. The key success of this transformation was the kinetic resolution of allylboration intermediate via asymmetric lactonization. This protocol enabled to assemble all of four stereoisomers from the same set of starting materials upon variable lactonization. Taking advantage of the current method as the key step, catalytic asymmetric total synthesis of eupomatilones 2, 5, and 6 was accomplished. Control experiments were carried out to probe into the tandem reaction as well as the origin of stereoselectivities.

16.
Immunology ; 165(1): 88-98, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34435359

RESUMEN

B-cell development undergoes a series of steps from the bone marrow to the secondary lymphoid organs. A defect in B-cell development can lead to immunodeficiency or malignant disorders, such as leukaemia or lymphoma. Long non-coding RNAs have been reported to act as important regulators of many pathological processes. However, very little is known regarding the role of lncRNAs during B-cell development and the regulation of their expression. In this study, we explored the expression and role of lncRNA Gme00492 in B-cell development. We observed that lnc00492 was highly expressed in B-cell development and primarily expressed in the nucleus. Lnc00492-deficient mice had fewer marginal zone B cells in the spleen, likely due to a developmental block. Importantly, lnc00492 interacts with CTBP1 and targets it for ubiquitination and degradation during B-cell development, whereas the transcriptional corepressor factor CTBP1 plays a critical role in Notch2 signalling. Thus, we identified a novel regulatory axis between lnc00492 and CTBP1 in B cells, suggesting that lnc00492 is essential for marginal zone B-cell development.


Asunto(s)
Linfocitos B/citología , Linfocitos B/metabolismo , Diferenciación Celular/genética , Linfopoyesis/genética , ARN Largo no Codificante/genética , Oxidorreductasas de Alcohol/metabolismo , Animales , Linfocitos B/inmunología , Biomarcadores , Médula Ósea/inmunología , Médula Ósea/metabolismo , Médula Ósea/patología , Diferenciación Celular/inmunología , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Inmunofenotipificación , Ratones , Ratones Noqueados , Modelos Biológicos , Unión Proteica , Receptor Notch2/metabolismo , Transducción de Señal , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , Ubiquitinación
17.
Small ; 18(20): e2200993, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35451111

RESUMEN

Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV. The nano-adjuvant displays a deep tumor penetration capacity via loosening the dense extracellular matrix of tumors. Upon NIR-II light irradiation, the nano-adjuvant significantly inhibits the tumor growth, induces a cascade of immune responses, generates an obvious adaptive immunity against the re-challenged cancers, boosts the abscopal effect, and completely inhibits the pulmonary metastases. The study highlights an advanced nano-adjuvant formulation featuring deep tumor penetration for NIR-II-triggered ISTV.


Asunto(s)
Oro , Neoplasias , Línea Celular Tumoral , Humanos , Rayos Infrarrojos , Neoplasias/terapia , Fototerapia , Vacunación
18.
Bioconjug Chem ; 33(7): 1319-1327, 2022 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-35729781

RESUMEN

The nontraditional intrinsic fluorescence (NTIF) of polymers containing heteroatoms has gained considerable attention due to its promising applications in label-free bioimaging. Aliphatic hyperbranched polyureas (aBPUs), which have recently shown great promise in the field of nanomedicine, bear controllable urea groups distributed on the branch points and thus are potential candidate luminogens. However, their NTIF properties and how their structures influence the NTIF properties have not been illustrated yet. Here, we addressed these issues by synthesizing a series of aBPUs with different degrees of branching (DBs) or different modifications. aBPUs exhibited an obvious NTIF phenomenon and with the increase of DBs, the NTIF enhanced as well. Chemical modifications either at the branching ends or in the interior of aBPUs could affect the NTIF performances, which were highly dependent on the types of modification. Disruption of the intra-/intermolecular hydrogen-bonding interactions decreased the NTIF. In addition, poly(ethylene glycol) (PEG)-modified aBPUs could self-assemble into nanospheres, and the formation of nanoassembly led to 89% enhancement on NTIF compared with the homogeneous solution of aBPUs-PEG in dimethylformamide (DMF). Finally, aBPUs-PEG nanoassembly demonstrated a capability in realizing label-free material imaging in vitro. These results shed light on the rational design of the polymer structures to achieve desired fluorescence with unconventional luminophores.


Asunto(s)
Polietilenglicoles , Polímeros , Fluorescencia , Nanomedicina/métodos , Polietilenglicoles/química , Polímeros/química
19.
Phys Rev Lett ; 129(19): 197201, 2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36399728

RESUMEN

Developing a microscopic understanding of spin decoherence is essential to advancing quantum technologies. Electron spin decoherence due to atomic vibrations (phonons) plays a special role as it sets an intrinsic limit to the performance of spin-based quantum devices. Two main sources of phonon-induced spin decoherence-the Elliott-Yafet and Dyakonov-Perel mechanisms-have distinct physical origins and theoretical treatments. Here, we show calculations that unify their modeling and enable accurate predictions of spin relaxation and precession in semiconductors. We compute the phonon-dressed vertex of the spin-spin correlation function with a treatment analogous to the calculation of the anomalous electron magnetic moment in QED. We find that the vertex correction provides a giant renormalization of the electron spin dynamics in solids, greater by many orders of magnitude than the corresponding correction from photons in vacuum. Our Letter demonstrates a general approach for quantitative analysis of spin decoherence in materials, advancing the quest for spin-based quantum technologies.

20.
Phys Chem Chem Phys ; 24(4): 2527-2533, 2022 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-35023523

RESUMEN

Terahertz functional devices have been instrumental in the development of terahertz technology. Moreover, the advent of metamaterials has greatly contributed to the advancement of terahertz devices. However, most of today's metamaterials in the terahertz band exhibit poor performance and are mono-functional. This greatly limits the scalability and application potential of the devices. To achieve diversification and tunability of device functionality, we propose a combination of metamaterial structures and vanadium dioxide film. A metamaterial absorber based on the thermotropic phase change material VO2 has been designed. Flexible switching of absorption performance (complete reflection and ultra-broadband perfect absorption) can be achieved through temperature adjustment. Moreover, the perfectly absorbed bandwidth is a staggering 3.3 THz. The thermal tuning of spectral absorbance has a maximal range of 0.01 to 0.999. The shift in absorption properties is explained by the phase change process of vanadium oxide (MIT). The electric field intensity on the absorber surface at different temperatures was monitored and analysed as a way to correlate the VO2 film phase transition process. The impedance matching theory is applied to explain the high level of absorption generated by the absorber. Finally, the effects of the structural parameters on the performance of the absorber are analysed. This work will have many applications in the terahertz field and offers a wide range of ideas for the design of terahertz-enabled devices.

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