RESUMEN
Nano ferroelectrics holds the potential application promise in information storage, electro-mechanical transformation, and novel catalysts but encounters a huge challenge of size limitation and manufacture complexity on the creation of long-range ferroelectric ordering. Herein, as an incipient ferroelectric, nanosized SrTiO3 was indued with polarized ordering at room temperature from the nonpolar cubic structure, driven by the intrinsic three-dimensional (3D) tensile strain. The ferroelectric behavior can be confirmed by piezoelectric force microscopy and the ferroelectric TO1 soft mode was verified with the temperature stability to 500 K. Its structural origin comes from the off-center shift of Ti atom to oxygen octahedron and forms the ultrafine head-to-tail connected 90° nanodomains about 2 to 3 nm, resulting in an overall spontaneous polarization toward the short edges of nanoparticles. According to the density functional theory calculations and phase-field simulations, the 3D strain-related dipole displacement transformed from [001] to [111] and segmentation effect on the ferroelectric domain were further proved. The topological ferroelectric order induced by intrinsic 3D tensile strain shows a unique approach to get over the nanosized limitation in nanodevices and construct the strong strain-polarization coupling, paving the way for the design of high-performance and free-assembled ferroelectric devices.
RESUMEN
Fibers, originating from nature and mastered by human, have woven their way throughout the entire history of human civilization. Recent developments in semiconducting polymer materials have further endowed fibers and textiles with various electronic functions, which are attractive in applications such as information interfacing, personalized medicine, and clean energy. Owing to their ability to be easily integrated into daily life, soft fiber electronics based on semiconducting polymers have gained popularity recently for wearable and implantable applications. Herein, we present a review of the previous and current progress in semiconducting polymer-based fiber electronics, particularly focusing on smart-wearable and implantable areas. First, we provide a brief overview of semiconducting polymers from the viewpoint of materials based on the basic concepts and functionality requirements of different devices. Then we analyze the existing applications and associated devices such as information interfaces, healthcare and medicine, and energy conversion and storage. The working principle and performance of semiconducting polymer-based fiber devices are summarized. Furthermore, we focus on the fabrication techniques of fiber devices. Based on the continuous fabrication of one-dimensional fiber and yarn, we introduce two- and three-dimensional fabric fabricating methods. Finally, we review challenges and relevant perspectives and potential solutions to address the related problems.
RESUMEN
It is a challenge to efficiently integrate and present the tremendous amounts of single-cell data generated from multiple tissues of various species. Here, we create a new database named SPEED for single-cell pan-species atlas in the light of ecology and evolution for development and diseases (freely accessible at http://8.142.154.29 or http://speedatlas.net). SPEED is an online platform with 4 data modules, 7 function modules and 2 display modules. The 'Pan' module is applied for the interactive analysis of single cell sequencing datasets from 127 species, and the 'Evo', 'Devo', and 'Diz' modules provide comprehensive analysis of single-cell atlases on 18 evolution datasets, 28 development datasets, and 85 disease datasets. The 'C2C', 'G2G' and 'S2S' modules explore intercellular communications, genetic regulatory networks, and cross-species molecular evolution. The 'sSearch', 'sMarker', 'sUp', and 'sDown' modules allow users to retrieve specific data information, obtain common marker genes for cell types, freely upload, and download single-cell datasets, respectively. Two display modules ('HOME' and 'HELP') offer easier access to the SPEED database with informative statistics and detailed guidelines. All in all, SPEED is an integrated platform for single-cell RNA sequencing (scRNA-seq) and single-cell whole-genome sequencing (scWGS) datasets to assist the deep-mining and understanding of heterogeneity among cells, tissues, and species at multi-levels, angles, and orientations, as well as provide new insights into molecular mechanisms of biological development and pathogenesis.
Asunto(s)
Bases de Datos Factuales , Análisis de la Célula Individual , Humanos , Animales , Evolución Biológica , Plantas/genética , EcologíaRESUMEN
BACKGROUND: In epigenetic modification, histone modification and DNA methylation coordinate the regulation of spermatogonium. Not only can methylcytosine dioxygenase 1 (TET1) function as a DNA demethylase, converting 5-methylcytosine to 5-hydroxymethylcytosine, it can also form complexes with other proteins to regulate gene expression. H3K27me3, one of the common histone modifications, is involved in the regulation of stem cell maintenance and tumorigenesis by inhibiting gene transcription. METHODS: we examined JMJD3 at both mRNA and protein levels and performed Chip-seq sequencing of H3K27me3 in TET1 overexpressing cells to search for target genes and signaling pathways of its action. RESULTS: This study has found that JMJD3 plays a leading role in spermatogonia self-renewal and proliferation: at one extreme, the expression of the self-renewal gene GFRA1 and the proliferation-promoting gene PCNA was upregulated following the overexpression of JMJD3 in spermatogonia; at the other end of the spectrum, the expression of differentiation-promoting gene DAZL was down-regulated. Furthermore, the fact that TET1 and JMJD3 can form a protein complex to interact with H3K27me3 has also been fully proven. Then, through analyzing the sequencing results of CHIP-Seq, we found that TET1 targeted Pramel3 when it interacted with H3K27me3. Besides, TET1 overexpression not only reduced H3K27me3 deposition at Pramel3, but promoted its transcriptional activation as well, and the up-regulation of Pramel3 expression was verified in JMJD3-overexpressing spermatogonia. CONCLUSION: In summary, our study identified a novel link between TET1 and H3K27me3 and established a Tet1-JMJD3-H3K27me3-Pramel3 axis to regulate spermatogonia self-renewal and proliferation. Judging from the evidence offered above, we can safely conclude that this study provides new ideas for further research regarding the mechanism of spermatogenesis and spermatogenesis disorders on an apparent spectrum.
Asunto(s)
Histonas , Espermatogonias , Masculino , Humanos , Histonas/metabolismo , Espermatogonias/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo , Diferenciación Celular/genética , Proliferación CelularRESUMEN
Monosubstituted tetrazines are important bioorthogonal reactive tools due to their rapid ligation with trans-cyclooctene. However, their application is limited by the reactivity-stability paradox in biological environments. In this study, we demonstrated that steric effects are crucial in resolving this paradox through theoretical methods and developed a simple synthetic route to validate our computational findings, leading to the discovery of 1,3-azole-4-yl and 1,2-azole-3-yl monosubstituted tetrazines as superior bioorthogonal tools. These new tetrazines surpass previous tetrazines in terms of high reactivities and elevated stabilities. The most stable tetrazine exhibits a reasonable stability (71% remaining after 24 h incubation in cell culture medium) and an exceptionally high reactivity (k2 > 104 M-1 s-1 toward trans-cyclooctene). Due to its good stability in biological systems, a noncanonical amino acid containing such a tetrazine side chain was genetically encoded into proteins site-specifically via an expanded genetic code. The encoded protein can be efficiently labeled using cyclopropane-fused trans-cyclooctene dyes in living mammalian cells with an ultrafast reaction rate exceeding 107 M-1 s-1, making it one of the fastest protein labeling reactions reported to date. Additionally, we showed its superiority through in vivo reactions in living mice, achieving an efficient local anchoring of proteins. These tetrazines are expected to be optimal bioorthogonal reactive tools within living systems.
RESUMEN
A comprehensive understanding of carrier transport in photoisomeric molecular junctions is crucial for the rational design and delicate fabrication of single-molecule functional devices. It has been widely recognized that the conductance of azobenzene (a class of photoisomeric molecules) based molecular junctions is mainly determined by photoinduced conformational changes. In this study, it is demonstrated that the most probable conductance of amine-anchored azobenzene-based molecular junctions increases continuously upon UV irradiation. In contrast, the conductance of pyridyl-anchored molecular junctions with an identical azobenzene core exhibits a contrasting trend, highlighting the pivotal role that anchoring groups play, potentially overriding (even reversing) the effects of photoinduced conformational changes. It is further demonstrated that the molecule with cis-conformation cannot be fully mechanically stretched into the trans-conformation, clarifying that it is a great challenge to realize a reversible molecular switch by purely mechanical operation. Additionally, it is revealed that the coupling strength of pyridyl-anchored molecules is dramatically weakened when the UV irradiation time is prolonged, whereas it is not observed for amine-anchored molecules. The mechanisms for these observations are elucidated with the assistance of density functional theory calculations and UV-Vis spectra combined with flicker noise measurements which confirm the photoinduced conformational changes, providing insight into understanding the charge transport in photoisomeric molecular junctions and offering a routine for logical designing synchro opto-mechanical molecular switches.
RESUMEN
As an important component of highly heterogeneous exosomes, exosomal microRNAs (miRNAs) have great potential as noninvasive biomarkers for cancer diagnosis. Therefore, a sensitive and simple sensor is the key for its clinical application. Herein, we designed an exponential amplification reaction (EXPAR) to induce the reactivation of the CRISPR-associated protein 9/small guide RNA (Cas9/sgRNA) complex, thus achieving sensitive and visual exosomal miRNAs-21 (miR-21) fluorescence sensing. In this design, we inactivated the sgRNA by hybridizing sgRNA and blocker DNA. Then, we used a trigger DNA to hybridize with miR-21 and produced a lot of activated DNA by EXPAR. Those activated DNA further hybridized with blocker DNA and released the free sgRNA to form the activated Cas9/sgRNA complex. Based on the quick cleavage of activated Cas9/sgRNA complex, the reporter DNA labeled by SYBR Green I was released from the surface of the magnetic nanoparticles (MNPs) into the supernatant, and thus was used to sensitively quantify the miRNAs concentration with a limit of detection of 3 × 103 particles/mL. In addition, this fluorescence sensor has also been successfully employed to distinguish healthy people and cancer patients by naked-eye observation of the fluorescence, thus demonstrating its great potential for accurate and point-of-care cancer diagnosis.
Asunto(s)
MicroARNs , Neoplasias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Sistemas CRISPR-Cas/genética , ARN Guía de Sistemas CRISPR-Cas , ADN/genética , Neoplasias/diagnóstico , Neoplasias/genéticaRESUMEN
Phosphorus is regarded as a promising material for high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity, appropriate lithiation potential, and low lithium-ion diffusion barrier. Phosphorus/carbon composites (PC) are engineered to serve as high-capacity high-rate anodes; the interaction between phosphorus and carbon, long-term capacity retention, and safety problems are important issues that must be well addressed simultaneously. Herein, an in situ polymerization approach to fabricate a poly-melamine-hybridized (pMA) phosphorus/carbon composite (pMA-PC) is employed. The pMA hybridization enhances the density and electrical conductivity of the PC, improves the structural integrity, and facilitates stable electron transfer within the pMA-PC composite. Moreover, the pMA-PC composite exhibits efficient adsorption of lithium polysulfides, enabling stable transport of Li+ ions. Therefore, the pMA-PC anode demonstrates a high specific charging capacity of 1,381 mAh g-1 at 10 A g-1, and a great capacity retention of 86.7% at 1 A g-1 over 500 cycles. The synergistic effect of phosphorus and nitrogen further confers excellent flame retardant properties to the pMA-PC anode, including self-extinguishing in 2.5 s, and a much lower combustion temperature than PC. The enhanced capacity and safety performance of pMA-PC show potential in future high-capacity and high-rate LIBs.
RESUMEN
DNA degradation has been a thorny problem in forensic science. Shortening the amplicon length of the genetic markers improves the analysis of degraded DNA effectively. Microhaplotype (MH) has been proposed as a potential genetic marker that can be used for degraded DNA analysis. In the present study, a 146-plex MH-next-generation sequencing (NGS) system with an average Ae of 6.876 was constructed. Unlike other MH studies, a single-primer extension (SPE)-based NGS library preparation method was used to improve the detection of MH markers for degraded DNA. SPE employs a locus-specific and universal primer to amplify target fragments, reducing the necessity for complete fragment sequences. SPE might effectively mitigate the impact of degradation on amplification. However, SPE produces amplicons of varying lengths, posing challenges in allele calling for SPE-NGS data. To address this issue, this study proposed a flexible allele-calling strategy to improve amplicon detection. In addition, this study evaluated the forensic efficacy of the system using 12 low-template samples (from 1 ng to 7.8 pg), 10 mock-degraded DNA with various degrees of degradation, and 8 forensic casework samples. When the template is as low as 7.8 pg, our system can accurately detect at least 37 loci and achieves a random match probability (RMP) of 10-30 using the complete allele-calling strategy. Eighty-two loci can be detected, and RMP can reach 10-54 using a flexible allele-calling strategy. After 150 min of 98°C treatment, 36 loci can still be detected, and an RMP of 10-5 can be obtained using the flexible allele-calling strategy. Furthermore, the number of single nucleotide polymorphism detected at different DNA amounts and degradation levels suggests that the SPE method combined with a flexible allele-calling strategy is effective.
RESUMEN
It has been theoretically predicted that perturbation of the Berry curvature by electromagnetic fields gives rise to intrinsic nonlinear anomalous Hall effects that are independent of scattering. Two types of nonlinear anomalous Hall effects are expected. The electric nonlinear Hall effect has recently begun to receive attention, while very few studies are concerned with the magneto-nonlinear Hall effect. Here, we combine experiment and first-principles calculations to show that the kagome ferromagnet Fe_{3}Sn_{2} displays such a magneto-nonlinear Hall effect. By systematic field angular and temperature-dependent transport measurements, we unambiguously identify a large anomalous Hall current that is linear in both applied in-plane electric and magnetic fields, utilizing a unique in-plane configuration. We clarify its dominant orbital origin and connect it to the magneto-nonlinear Hall effect. The effect is governed by the intrinsic quantum geometric properties of Bloch electrons. Our results demonstrate the significance of the quantum geometry of electron wave functions from the orbital degree of freedom and open up a new direction in Hall transport effects.
RESUMEN
BACKGROUND: The Glasgow Prognostic Score (GPS) has proven to be a good biomarker for lung cancer prognosis. However, its usefulness in lung cancer patients receiving checkpoint inhibitor immunotherapy remains controversial. Therefore, we performed a meta-analysis to explore the prognostic value of the GPS in non-small cell lung cancer patients receiving immunotherapy. METHODS: PubMed, Web of Science, Scopus, and Embase were systematically searched for relevant studies up to May 31, 2023, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were merged to investigate the prognostic value of the GPS for overall survival (OS) and progression-free survival (PFS). RESULTS: Seven studies comprising 833 patients were included in the primary analysis, and the pooled results indicated that a higher baseline GPS was associated with poorer OS and PFS in non-small cell lung cancer patients treated with immune checkpoint inhibitors (ICIs) (OS: HR = 1.95, 95% CI: 1.47-2.58, p < 0.01; PFS: HR = 1.63, 95% CI: 1.26-2.11, p < 0.01). These findings were robust after subgroup and sensitivity analyses. CONCLUSIONS: The GPS can serve as a biomarker in non-small cell lung cancer patients receiving immunotherapy with significant prognostic value; however, these findings require more prospective evidence for validation.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inmunoterapia/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Pronóstico , Estudios ProspectivosRESUMEN
Developmental arsenic exposure has been associated with cognitive deficits in epidemiological studies, but the underlying mechanisms remain poorly understood. Here, we establish a mouse model of developmental arsenic exposure exhibiting deficits of recognition and spatial memory in the offspring. These deficits are associated with genome-wide DNA hypomethylation and abnormal expression of cognition-related genes in the hippocampus. Arsenic atoms directly bind to the cysteine-rich ADD domain of DNA methyltransferase 3A (DNMT3A), triggering ubiquitin- and proteasome-mediated degradation of DNMT3A in different cellular contexts. DNMT3A degradation leads to genome-wide DNA hypomethylation in mouse embryonic fibroblasts but not in non-embryonic cell lines. Treatment with metformin, a first-line antidiabetic agent reported to increase DNA methylation, ameliorates the behavioral deficits and normalizes the aberrant expression of cognition-related genes and DNA methylation in the hippocampus of arsenic-exposed offspring. Our study establishes a DNA hypomethylation effect of developmental arsenic exposure and proposes a potential treatment against cognitive deficits in the offspring of pregnant women in arsenic-contaminated areas.
Asunto(s)
Arsénico , Metilación de ADN , ADN Metiltransferasa 3A , Animales , Arsénico/toxicidad , Cognición , Femenino , Fibroblastos/metabolismo , Humanos , Ratones , EmbarazoRESUMEN
OBJECTIVES: Anti-HER2 targeted therapy significantly reduces risk of relapse in HER2 + breast cancer. New measures are needed for a precise risk stratification to guide (de-)escalation of anti-HER2 strategy. METHODS: A total of 726 HER2 + cases who received no/single/dual anti-HER2 targeted therapies were split into three respective cohorts. A deep learning model (DeepTEPP) based on preoperative breast magnetic resonance (MR) was developed. Patients were scored and categorized into low-, moderate-, and high-risk groups. Recurrence-free survival (RFS) was compared in patients with different risk groups according to the anti-HER2 treatment they received, to validate the value of DeepTEPP in predicting treatment efficacy and guiding anti-HER2 strategy. RESULTS: DeepTEPP was capable of risk stratification and guiding anti-HER2 treatment strategy: DeepTEPP-Low patients (60.5%) did not derive significant RFS benefit from trastuzumab (p = 0.144), proposing an anti-HER2 de-escalation. DeepTEPP-Moderate patients (19.8%) significantly benefited from trastuzumab (p = 0.048), but did not obtain additional improvements from pertuzumab (p = 0.125). DeepTEPP-High patients (19.7%) significantly benefited from dual HER2 blockade (p = 0.045), suggesting an anti-HER2 escalation. CONCLUSIONS: DeepTEPP represents a pioneering MR-based deep learning model that enables the non-invasive prediction of adjuvant anti-HER2 effectiveness, thereby providing valuable guidance for anti-HER2 (de-)escalation strategies. DeepTEPP provides an important reference for choosing the appropriate individualized treatment in HER2 + breast cancer patients, warranting prospective validation. CLINICAL RELEVANCE STATEMENT: We built an MR-based deep learning model DeepTEPP, which enables the non-invasive prediction of adjuvant anti-HER2 effectiveness, thus guiding anti-HER2 (de-)escalation strategies in early HER2-positive breast cancer patients. KEY POINTS: ⢠DeepTEPP is able to predict anti-HER2 effectiveness and to guide treatment (de-)escalation. ⢠DeepTEPP demonstrated an impressive prognostic efficacy for recurrence-free survival and overall survival. ⢠To our knowledge, this is one of the very few, also the largest study to test the efficacy of a deep learning model extracted from breast MR images on HER2-positive breast cancer survival and anti-HER2 therapy effectiveness prediction.
Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Imagen por Resonancia Magnética , Receptor ErbB-2 , Trastuzumab , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Trastuzumab/uso terapéutico , Adulto , Anciano , Resultado del Tratamiento , Medición de Riesgo , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Estudios Retrospectivos , Radiómica , Anticuerpos Monoclonales HumanizadosRESUMEN
Exosomes are bilayer lipid bodies and contain a variety of bioactive molecules such as proteins, lipids, and nucleic acids, and so forth. Exosomes derived from solid tumors may play critical roles in tumor development and immune evasion. However, the underlying effects of tumor-derived exosomes on immune function in modulating intercellular crosstalk within the bone marrow niche during acute myeloid leukemia (AML) development and immune evasion remain largely elusive. In this study, we aimed to explore the role of AML-exos in AML immune evasion. First, we isolated tumor-derived exosomes from AML cells (AML-exos) and revealed the presence of programmed cell death ligand-1 (PD-L1) protein in AML-exos. Next, we demonstrated that AML-exos can directly suppress the activation of natural killer (NK) cells and inhibit the cytotoxicity of NK cells, probably through activating the programmed cell death-1 (PD-1)/PD-L1 pathway. Furthermore, the inhibitory effect of AML-exos on NK cells could be alleviated by either PD-L1 inhibitor or antagonist. In summary, we demonstrated that AML-exos possess a PD-L1-dependent tumor-promoting effect which may contribute to immune tolerance in antitumor therapy, but blocking the PD-1/PD-L1 pathway may alleviate the tumor immunosuppression induced by AML-exos. Our findings in this study may offer a new immunotherapy strategy to cure AML.
RESUMEN
Designing friction materials with high electron storage capacity, high work function, low cost, and high stability is an important method to improve the output performance of a triboelectric nanogenerator (TENG). Here, we report two kinds of friction materials based on Keggin-type polyoxometalates (POMs)-modified graphite carbon nitride (g-C3N4), namely, g-C3N4@PMo12 and g-C3N4@PW12, and form TENG with commercial indium tin oxide/poly(ethylene terephthalate) (ITO/PET) electrodes. The performance test shows that the g-C3N4@PMo12 TENG device exhibits a high output voltage of about 78 V, a current of about 657 nA, and a transfer charge of about 15 nC, which is more than 3 times higher than that of unmodified TENG. This performance improvement is attributed to the fact that POM loaded on the surface of g-C3N4 can be used as a shallow electron trap to increase the electron storage capacity through electron interaction and to increase the charge density on the surface of the material by increasing the work function of the composite. This work not only broadens the choices of TENG friction materials but also offers a practical means of enhancing TENG's output performance.
RESUMEN
BACKGROUND: The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined. METHODSâANDâRESULTS: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). CONCLUSIONS: Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.
Asunto(s)
Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/cirugía , Circulación Coronaria , Vasos Coronarios/fisiopatología , Infarto del Miocardio/fisiopatología , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
Chemotherapy-induced diarrhea causes dehydration, debilitation, infection, and even death, but there are currently no Food and Drug Administration (FDA)-approved drugs for treatment of chemotherapy-induced diarrhea. It is generally believed that the timely regulation of intestinal stem cell (ISC) fate may provide a meaningful solution for intestinal injuries. However, the lineage plasticity of ISCs during and after chemotherapy remains poorly understood. Here, we demonstrated that palbociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, regulated the fate of active or quiescent ISCs, provided multilineage protection from the toxicity of several different chemotherapeutics, and accelerated gastrointestinal epithelium recovery. Consistent with in vivo results, we determined that palbociclib enhanced intestinal organoid and ex vivo tissue survival after chemotherapy. Lineage tracing studies have shown that palbociclib protects active ISCs marked by Lgr5 and Olfm4 during chemotherapy and unexpectedly activates quiescent ISCs marked by Bmi1 to immediately participate in crypt regeneration after chemotherapy. Furthermore, palbociclib does not decrease the efficacy of cytotoxic chemotherapy in tumor grafts. The experimental evidence suggests that the combination of CDK4/6 inhibitors with chemotherapy could reduce damage to the gastrointestinal epithelium in patients. © 2023 The Pathological Society of Great Britain and Ireland.
Asunto(s)
Antineoplásicos , Diarrea , Humanos , Diarrea/patología , Diferenciación Celular , Células Madre/patología , Reino Unido , Mucosa Intestinal/patología , Quinasa 4 Dependiente de la CiclinaRESUMEN
BACKGROUND: Proteasome inhibition is a promising strategy for cancer therapy. Bortezomib, which primarily targets the chymotrypsin-like activity of PSMB5, has demonstrated efficacy in various tumors. However, there is variable sensitivity to bortezomib, which could be attributed, in part, to variations in the expression of proteasome subunits. METHODS AND RESULTS: In this study, we investigated whether miR-383 affects the expression of proteasome subunits in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between the cytotoxicity of bortezomib and the expression level of the proteasome 20S core particle subunit ß5 (PSMB5). Intriguingly, we identified PSMB5 as a direct target of miR-383. Increased expression of miR-383 resulted in decreased PSMB5 expression and increased sensitivity to bortezomib in OS cells. CONCLUSIONS: In summary, our findings present the initial comprehensive analysis of the function of miR-383 in OS. The outcomes indicate that miR-383 may augment the anticancer effect of bortezomib through PSMB5 repression, offering a novel therapeutic approach in OS and a fresh pathway for proteasome regulation.
Asunto(s)
Neoplasias Óseas , MicroARNs , Osteosarcoma , Humanos , Bortezomib/farmacología , Complejo de la Endopetidasa Proteasomal/genética , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , MicroARNs/genéticaRESUMEN
Dynamic infrared radiation regulation has been widely explored for smart windows because of its vital importance for comfortable and energy-efficient buildings. However, it remains a great challenge to synchronously achieve high visible transmittance and pronounced infrared tunability. Here, we propose a dynamic infrared tunable metamaterial composed of indium tin oxide (ITO) gratings, an air insulator, and an ITO reflector. The ITO grating-based infrared radiation regulator exhibits a high emissivity tunability of 0.73 at 8-13 µm while maintaining a high visible transmittance of 0.65 and 0.72 before and after actuation, respectively. By adjusting the geometric parameters, the tunable bandwidth can be further extended to 3-30 µm and the ultra-broadband tunability reaches 0.62. The excellent infrared tunable performance arises from the insulator thickness-dependent effect of Fabry-Pérot and propagating surface plasmon resonance coupling and decoupling, which lead to perfect and low absorption, respectively. This work provides potential for the advancement of smart window technology and makes a significant contribution to sustainable buildings.
RESUMEN
The two-dimensional (2D) MA2Z4 family has received extensive attention in manipulating its electronic structure and achieving intriguing physical properties. However, engineering the electronic properties remains a challenge. Herein, based on first-principles calculations, we systematically investigate the effect of biaxial strains on the electronic structure of 2D Rashba MoSiGeN4 (MSGN), and further explore how the interlayer interactions affect the Rashba spin splitting (RSS) in such strained layered MSGN systems. After applying biaxial strains, the band gap decreases monotonically with increasing tensile strains but increases when the compressive strains are applied. An indirect-direct-indirect band gap transition is induced by applying a moderate compressive strain (<5%) in the MSGN systems. Due to the symmetry breaking and moderate spin-orbit coupling (SOC), the monolayer MSGN possesses an isolated RSS near the Fermi level, which could be effectively regulated to the Lifshitz-type spin splitting (LSS) by biaxial strain. For instance, the LSS â RSS â LSS transformation of the Fermi surface is presented in the monolayer and a more complex and changeable LSS â RSS â LSS â RSS evolution is observed in bilayer and trilayer MSGN systems as the biaxial strain varies from -8% to 12%, which actually depends on the appearance, variation, and vanish of the Mexican hat band in the absence of SOC under different strains. The contribution of the Mo-dz2 orbital hybridized with the N-pz orbital in the highest valence band plays a dominant role in band evolution under biaxial strains, where the RSS â LSS evolution corresponds to the decreased Mo-dz2 orbital contribution. Our study highlights the biaxial strain controllable RSS, in particular the introduction and even the evolution of LSS near the Fermi surface, which makes the strained MSGN systems promising candidates for future applications in spintronic devices.