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Dimension and solvent molecules affect the performance of energetic metal-organic frameworks (EMOFs). High-dimensional EMOFs are usually characterized by high stability and low sensitivity due to their complex network structure. However, solvent molecules affect the detonation performance of EMOFs, and these molecules may be removed at low temperatures, resulting in structural collapse and affecting the stability of EMOFs. In this work, zero-dimensional (0D) Co(AFTO)2·(H2O)2 (EMOF 1) and Ni(AFTO)2·(H2O)2 (EMOF 2) with coordinated water molecules and [Co(AFTO)2]n·EtOH (EMOF 3) and [Ni(AFTO)2]n (EMOF 4) (AFTO = 5-(4-amino-furazan-3-yl)-1-hydroxytetrazole) with high-dimensional structure were synthesized using hydrothermal and self-assembly methods in ethanol, respectively. Structural and performance tests show that EMOF 3 and 4 exhibit remarkable thermal stability and low mechanical sensitivity. This method is a simple, effective, and green technique for synthesizing high-dimensional EMOFs with high stability through self-assembly in ethanol solution. In addition, EMOF 3 and 4 can be used as primary green laser explosives.
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Microwave-induced thermoacoustic (TA) imaging (MTAI) combines pulsed microwave excitation and ultrasound detection to provide high contrast and spatial resolution images through dielectric contrast, which holds great promise for clinical applications. However, artifacts caused by microwave dielectric effect will seriously affect the accuracy of MTAI images that will hinder the clinical translation of MTAI. In this work, we propose a deep learning-based method fully dense generative adversarial network (FD-GAN) for removing artifacts caused by microwave dielectric effect in MTAI. FD-GAN adds the fully dense block to the generative adversarial network (GAN) based on the mutual confrontation between generator and discriminator, which enables it to learn both local and global features related to the removal of artifacts and generate high-quality images. The practical feasibility was tested in simulated, experimental data. The results demonstrate that FD-GAN can effectively remove the artifacts caused by the microwave dielectric effect, and shows superiority in denoising, background suppression, and improvement of image distortion. Our approach is expected to significantly improve the accuracy and quality of MTAI images, thereby enhancing the diagnostic accuracy of this innovative imaging technique.
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Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non-small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction.
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Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/metabolismo , Microfluídica/métodos , Análise de Célula Única/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/sangue , Fenótipo , Linhagem Celular Tumoral , Imunoterapia/métodos , Perfilação da Expressão Gênica/métodos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Técnicas Analíticas Microfluídicas/métodos , Técnicas Analíticas Microfluídicas/instrumentaçãoRESUMO
Although mechanochemistry is increasingly becoming an alternative to traditional chemical synthesis, highly efficient continuous mechanochemical synthesis techniques are still rare. In this work, a novel spiral gas-solid two-phase flow (S-GSF) synthesis technique for the mechanochemical synthesis of salophen complexes has been reported, which is an approach for continuous synthesis based solely on airflow impacting the reaction. The synthesis of salophen-Br-Cu was used as a model reaction to optimize the reaction conditions, and three other salophen complexes, namely, salophen-Br-Co, salophen-Br-Ni, and salophen-Br-Zn were synthesized on this basis. The structure and thermal stability of the obtained products were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, UV-vis spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, and differential thermal analysis (DTA). The results showed that these complexes can be obtained continuously at a rate close to 4 g min-1, and the corresponding space-time yield is close to 1.2 × 105 kg m-3 day-1. In addition, DTA was used to analyze the catalytic performance of the complex for ammonium perchlorate (AP). The results showed that compared to the conditions for pure AP, salophen-Br-Co and salophen-Br-Cu could significantly reduce the high-temperature decomposition of AP pyrolysis to 77.0 and 102.1 °C, respectively. According to the method of Kissinger calculations, the Ea of AP decomposition decreased from 217.3 kJ mol-1 to 131.0 and 118.5 kJ mol-1, respectively. The TG data at different heating rates were analyzed using two isoconversion methods, i.e. Flynne-Walle-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS). The activation energies of AP, AP + 10 wt% salophen-Br-Co, and AP + 10 wt% salophen-Br-Cu were calculated. When the conversion degree (α) is between 0.1 and 0.9, the Ea values obtained from the two isoconversion methods are similar and exhibit certain matching. These two isoconversion methods also confirm Kissinger's calculations.
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Optical endoscopy, as one of the common clinical diagnostic modalities, provides irreplaceable advantages in the diagnosis and treatment of internal organs. However, the approach is limited to the characterization of superficial tissues due to the strong optical scattering properties of tissue. In this work, a microwave-induced thermoacoustic (TA) endoscope (MTAE) was developed and evaluated. The MTAE system integrated a homemade monopole sleeve antenna (diameter = 7 mm) for providing homogenized pulsed microwave irradiation to induce a TA signal in the colorectal cavity and a side-viewing focus ultrasonic transducer (diameter = 3 mm) for detecting the TA signal in the ultrasonic spectrum to construct the image. Our MTAE, system combined microwave excitation and acoustic detection; produced images with dielectric contrast and high spatial resolution at several centimeters deep in soft tissues, overcome the current limitations of the imaging depth of optical endoscopy and mechanical wave-based imaging contrast of ultrasound endoscopy, and had the ability to extract complete features for deep location tumors that could be infiltrating and invading adjacent structures. The practical feasibility of the MTAE system was evaluated i n vivo with rabbits having colorectal tumors. The results demonstrated that colorectal tumor progression could be visualized from the changes in electromagnetic parameters of the tissue via MTAE, showing its potential clinical application.
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Neoplasias Colorretais , Micro-Ondas , Animais , Coelhos , Diagnóstico por Imagem , Ultrassonografia , Neoplasias Colorretais/diagnóstico por imagem , Endoscopia , AcústicaRESUMO
The breeding of crops with improved nitrogen use efficiency (NUE) is crucial for sustainable agriculture, but the involvement of epigenetic modifications remains unexplored. Here, we analyze the chromatin landscapes of two wheat cultivars (KN9204 and J411) that differ in NUE under varied nitrogen conditions. The expression of nitrogen metabolism genes is closely linked to variation in histone modification instead of differences in DNA sequence. Epigenetic modifications exhibit clear cultivar-specificity, which likely contributes to distinct agronomic traits. Additionally, low nitrogen (LN) induces H3K27ac and H3K27me3 to significantly enhance root growth in KN9204, while remarkably inducing NRT2 in J411. Evidence from histone deacetylase inhibitor treatment and transgenic plants with loss function of H3K27me3 methyltransferase shows that changes in epigenetic modifications could alter the strategy preference for root development or nitrogen uptake in response to LN. Here, we show the importance of epigenetic regulation in mediating cultivar-specific adaptation to LN in wheat.
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Nitrogênio , Triticum , Triticum/metabolismo , Nitrogênio/metabolismo , Epigênese Genética , Histonas/genética , Histonas/metabolismo , Melhoramento VegetalRESUMO
Precise quantification of low-dose ionizing radiation is of great significance in protecting people from damage caused by clinical radiotherapy or environmental radiation. Traditional techniques for detecting radiation, however, remain extreme challenges to achieve high sensitivity and speed in quantifying radiation dosage. In this work, we report a Cas13a-Microdroplet platform that enables sensitive detection of ultra-low doses of radiation (0.5 Gy vs. 1 Gy traditional) within 1 h. The micro-platform adopts an ideal, specific radiation-sensitive marker, m6A on NCOA4 gene (NCOA4-m6A) that was first reported in our recent work. Microfluidics of the platform generate uniform microdroplets that encapsulate a CRISPR/Cas13a detection system and NCOA4-m6A target from the whole RNA extraction, achieving 10-fold enhancement in sensitivity and significantly reduced limit of detection (LOD). Systematic mouse models and clinical patient samples demonstrated its superior sensitivity and LOD (0.5 Gy) than traditional qPCR, which show wide potentials in radiation tracking and damage protection.
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Técnicas Biossensoriais , Animais , Camundongos , Humanos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Modelos Animais de Doenças , Limite de Detecção , Doses de Radiação , Fatores de Transcrição , Coativadores de Receptor NuclearRESUMO
To minimize and control the transmission of infectious diseases, a sensitive, accurate, rapid, and robust assay strategy for application on-site screening is critical. Here, we report single-molecule RNA capture-assisted digital RT-LAMP (SCADL) for point-of-care testing of infectious diseases. Target RNA was captured and enriched by specific capture probes and oligonucleotide probes conjugated to magnetic beads, replacing laborious RNA extraction. Droplet generation, amplification, and the recording of results are all integrated on a microfluidic chip. In assaying commercial standard samples, quantitative results precisely corresponded to the actual concentration of samples. This method provides a limit of detection of 10 copies mL-1 for the N gene within 1 h, greatly reducing the need for skilled personnel and precision instruments. The ultrasensitivity, specificity, portability, rapidity and user-friendliness make SCADL a competitive candidate for the on-site screening of infectious diseases.
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As a member of Xenes family, germanene has excellent nonlinear saturable absorption characteristics. In this work, we prepared germanene nanosheets by liquid phase exfoliation and measured their saturation intensity as 0.6 GW/cm2 with a modulation depth of 8%. Then, conventional solitons with a pulse width of 946 fs and high-energy noise-like pulses with a pulse width of 784 fs were obtained by using germanene nanosheet as a saturable absorber for a mode-locked Erbium-doped fiber laser. The characteristics of the two types of pulses were investigated experimentally. The results reveal that germanene has great potential for modulation devices in ultrafast lasers and can be used as a material for creation of excellent nonlinear optical devices to explore richer applications in ultrafast photonics.
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ETHNOPHARMACOLOGICAL RELEVANCE: Naru-3 is a prescribed formulation based on the theory of Mongolian medicine for the treatment of rheumatoid arthritis (RA). Naru-3 consists of three medicinal agents: Aconitum kusnezoffii Reichb (caowu), Terminalia chebula Retz (hezi), and Piper longum L (biba). These medicinal agents are widely distributed in the Mongolian area of China and have been used to treat rheumatism for centuries. BACKGROUND: Mongolian medicine Naru-3 is commonly prescribed to treat RA, but its mechanism of action is unknown. METHODS: A rat collagen-induced arthritis (CIA) model was established to investigate the mechanism of Naru-3. Rats were treated with Naru-3, Etanercept (ETN), and sodium carboxymethylcellulose (CMC) for four weeks. After treatment was terminated, paw thickness, ankle diameter, and arthritis index (AI) were scored. Synovial hyperplasia was evaluated using hematoxylin and eosin (H&E) staining and two-dimensional ultrasonography. Synovitis and neovascularization were assayed using power Doppler imaging (PDI) and contrast-enhanced ultrasonography (CEUS). Levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1, and CD31 in the serum or synovium were detected using ELISA and immunohistochemistry analyses. RESULTS: Naru-3 and ETN alleviated the symptoms of CIA as evidenced by diminished paw thickness, ankle diameter, and AI scores. Mechanistically, Naru-3 inhibited synovial hyperplasia, synovitis, and neovascularization by diminishing systemic and local inflammation, as indicated by the relative expression of CD31, VEGF and IL-1 in the serumor synovium. After four weeks of treatment, no significant neovascularization was observed in the Naru-3 group, but neovascularization and synovitis occurred in the ETN group, as demonstrated by H&E staining, PDI, and CEUS examination. CONCLUSION: Naru-3 inhibited inflammation, synovial hyperplasia, and neovascularization and alleviates RA in our CIA rat model. No symptom recurrence was observed four weeks after drug treatment.
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Artrite Experimental , Artrite Reumatoide , Sinovite , Ratos , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Hiperplasia/patologia , Membrana Sinovial/metabolismo , Inflamação/patologia , Artrite Reumatoide/patologia , Sinovite/metabolismo , Sinovite/patologia , Neovascularização Patológica/tratamento farmacológicoRESUMO
Variants in myosin-binding protein C3 (MYBPC3) gene are a main cause of hypertrophic cardiomyopathy (HCM), accounting for 30% to 40% of the total number of HCM mutations. Gene editing represents a potential permanent cure for HCM. The aim of this study was to investigate whether genome editing of MYBPC3 using the CRISPR/Cas9 system in vivo could rescue the phenotype of rats with HCM. We generated a rat model of HCM ("1098hom") that carried an Mybpc3 premature termination codon mutation (p.W1098x) discovered in a human HCM pedigree. On postnatal day 3, the CRISPR/Cas9 system was introduced into rat pups by a single dose of AAV9 particles to correct the variant using homology-directed repair (HDR). Analysis was performed 6 months after AAV9 injection. The 1098hom rats didn't express MYBPC3 protein and developed an HCM phenotype with increased ventricular wall thickness and diminished cardiac function. Importantly, CRISPR HDR genome editing corrected 3.56% of total mutations, restored MYBPC3 protein expression by 2.12%, and normalized the HCM phenotype of 1098hom rats. Our work demonstrates that the HDR strategy is a promising approach for treating HCM associated with MYBPC3 mutation, and that CRISPR technology has great potential for treating hereditary heart diseases.
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Cardiomiopatia Hipertrófica , Proteínas de Transporte , Humanos , Animais , Ratos , Proteínas de Transporte/genética , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/terapia , Mutação , Fenótipo , LinhagemRESUMO
Attention should be paid to the sulfate reduction behavior in a pressure-bearing leachate saturated zone. In this study, within the relative pressure range of 0-0.6 MPa, the ambient temperature with the highest sulfate reduction rate of 50°C was selected to explore the difference in sulfate reduction behavior in a pressure-bearing leachate saturated zone. The results showed that the sulfate reduction rate might further increase with an increase in pressure; however, owing to the effect of pressure increase, the generated hydrogen sulfide (H2S) could not be released on time, thereby decreasing its highest concentration by approximately 85%, and the duration extended to about two times that of the atmospheric pressure. Microbial community structure and functional gene abundance analyses showed that the community distribution of sulfate-reducing bacteria was significantly affected by pressure conditions, and there was a negative correlation between disulfide reductase B (dsrB) gene abundance and H2S release rate. Other sulfate reduction processes that do not require disulfide reductase A (dsrA) and dsrB genes may be the key pathways affecting the sulfate reduction rate in the pressure-bearing leachate saturated zone. This study improves the understanding of sulfate reduction in landfills as well as provides a theoretical basis for the operation and management of landfills.
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Pressão Atmosférica , Dissulfetos , Fenômenos Químicos , Fenômenos Físicos , SulfatosRESUMO
Two new three-dimensional (3D) energetic metal-organic frameworks (EMOFs), namely, [Cu(OBTT)(NC2H8)2]n (1) and [Cd3(OBTT)2(H2O)2]n·4H2O (2), where H3OBTT = 4,5-bis(1-hydroxytetrazol-5-yl)-1,2,3-triazole, were prepared, and their structures were characterized by single-crystal X-ray diffraction analysis, which revealed that the EMOFs feature a rigid 3D framework architecture. The possibility of these two EMOFs as potential catalysts for the thermal decomposition of ammonium perchlorate (AP) was investigated. The results show that they have significant catalytic activity, up to reducing the peak temperature of AP decomposition from 704.0 to 613.6 K and contracting the decomposition temperature range from 451 to 320 K, which is almost one-third less than the decomposition temperature range of pure AP. The Kissinger and Ozawa-Doyle methods were used to calculate the kinetic parameters of the thermal decomposition of pure and mixed AP samples. The experimental results suggest that compound 1 has potential applications in the field of explosives and propellants. All properties suggest that compound 1 can be used as a potential catalyst.
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Cryptorchidism is a common congenital malformation in pediatric urology. Although there have been many studies on the etiology of the disease, it has not been fully clarified, and while its diagnostic and treatment models have gradually approached standardization and systematization, some controversies regarding treatment remain. Additionally, although ultrasound is a non-invasive examination without ionizing radiation, its role in the evaluation of cryptorchidism remains controversial. The main basis for treating cryptorchidism is orchidopexy, and the main view on treatment age is that treatment should be performed between 6 and 12 months after birth, but no more than 18 months after birth. The view on hormone therapy is still controversial because most scholars believe that early surgery is the key to treatment. There are many surgical treatment methods for cryptorchidism, including traditional open surgery and laparoscopic surgery, which provide satisfactory results. In conclusion, the treatment of undescended testis (UDT) had been largely standardized, apart from the treatment of high intra-abdominal testis (IAT), which remains a matter of debate.
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The protein encoded by CD3D is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. Previous studies have shown that CD3D is associated with prognosis and treatment response in breast, colorectal, and liver cancer. However, the expression and clinical significance of CD3D in gastric cancer are not clear. In this study, we collected 488 gastric cancer tissues and 430 paired adjacent tissues to perform tissue microarrays (TMAs). Then, immunohistochemical staining of CD3D, CD3, CD4, CD8 and PD-L1 was conducted to investigate the expression of CD3D in gastric cancer and the correlation between the expression of CD3D and tumor infiltrating lymphocytes (TILs) and PD-L1. The results showed that CD3D was highly expressed in gastric cancer tissues compared with paracancerous tissues (P<0.000). Univariate and multivariate analyses showed that CD3D was an independent good prognostic factor for gastric cancer (P=0.004, HR=0.677, 95%CI: 0.510-0.898 for univariate analyses; P=0.046, HR=0.687, 95%CI: 0.474-0.994 for multivariate analyses). In addition, CD3D was negatively correlated with the tumor location, Borrmann type and distant metastasis (P=0.012 for tumor location; P=0.007 for Borrmann type; P=0.027 for distant metastasis). In addition, the expression of CD3D was highly positively correlated with the expression of CD3, CD4, CD8, and PD-L1, and the combination of CD3D with CD3, CD4, CD8 and PD-L1 predicted the best prognosis (P=0.043). In summary, CD3D may play an important regulatory role in the tumor immune microenvironment of gastric cancer and may serve as a potential indicator of prognosis and immunotherapy response.
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Most studies on the interaction between coagulation and NOM (natural organic matter) currently focus on pollutant removal and coagulant species distribution, while studies on floc aging are lacking. Investigation onto the effects of floc aging could guide further processes that utilize flocs, such as densadeg sludge recirculation, floc predeposition for ultrafiltration, sludge condensation, and other traditional sludge reflux processes. In this study, flocs generated by Al13 and AlCl3 in microparticle- and nanoparticle-containing water were investigated, and the effect of floc aging on NOM was quantified based on several organic matter characterization techniques. Flocs absorb and release organics during aging. The flocs generated from micro-SiO2 have a significant absorbing effect for LWM-N (low-molecular-weight neutral substances) and protein-like substances, while the absorption of NOM by flocs generated from nano-SiO2 is insignificant. HS (humic substances) with high aromaticity are released during floc aging. From the molecular perspective, the molecules released during floc aging are those with higher double bond equivalents and higher aromaticity, while the absorbed molecules are those with lower double bond equivalents and lower aromaticity. 2D-COS (two-dimensional correlation spectroscopy) demonstrated that the flocs generated by Al13 and AlCl3 had the same organic release patterns but different intensities, while the flocs generated in the micro-SiO2 and nano-SiO2 systems had different organics release patterns. Abundant aluminum hydrolysates with low polymerization and amorphous Al(OH)3 would be produced from AlCl3 during the coagulation process and then undergo hydroxylbridging reaction and crystallization during floc aging, thus releasing more HS with high aromaticity into the supernatant; in comparison, prehydrolyzed Al13 produces a more stable floc and releases less HS during aging. The flocs produced by nano-SiO2 and Al-based coagulants release higher aromaticity HS into the water than those produced by micro-SiO2, which may be related to the formation of more highly polymerized degree hydrolysates and nanocrystalline Al(OH)3 in the nano-SiO2 system. The flocs generated in water with micro-SiO2 may contain a large amount of Al-OH and have a loose structure, thus further absorbing NOM, such as protein-like substances and LWM-N. In contrast, the flocs generated from nano-SiO2 possess abundant adsorbed water and a denser structure; thus, organic matter cannot be absorbed stably.
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Purificação da Água , Floculação , Tamanho da Partícula , Esgotos , Dióxido de Silício , Água , Purificação da Água/métodosRESUMO
This article reports a highly integrated watch for noninvasive continual blood glucose monitoring. The watch employs a Nafion-coated flexible electrochemical sensor patch fixed on the watchband to obtain interstitial fluid (ISF) transdermally at the wrist. This reverse iontophoresis-based extraction method eliminates the pain and inconvenience that traditional fingerstick blood tests pose in diabetic patients' lives, making continual blood glucose monitoring practical and easy. All electronic modules, including a rechargeable power source and other modules for signal processing and wireless transmission, are integrated onto a watch face-sized printed circuit board (PCB), enabling comfortable wearing of this continual glucose monitor. Real-time blood glucose levels are displayed on the LED screen of the watch and can also be checked with the smartphone user interface. With 23 volunteers, the watch demonstrated 84.34% clinical accuracy in the Clarke error grid analysis (zones A + B). In the near future, commercial products could be developed based on this lab-made prototype to provide the public with noninvasive continual glucose monitoring.
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Rationale: Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic disease characterized by liver steatosis. Excessive reactive oxygen species (ROS) originating from dysfunctional mitochondria is the major pathophysiological contributor in the development of NAFLD and is thought to be a promising therapeutic target. A few reports demonstrate the antioxidative treatments for NAFLD. Methods: Male C57 mice were fed on a normal chow diet (ND) or high-fat diet (HFD) for 8 weeks. PBS or N-acetyl cysteine (NAC) was gavaged to mice. LO2 human liver cell line treated with palmitic acid (PA) was applied as a cellular model. Western blot, immunofluorescence, biochemistry assay, and pathological staining were used to investigate the mechanism of suppressing lipid accumulation of NAC. Results: NAC treatment was able to prevent HFD-induced NAFLD, as evidenced by less hepatic triglyceride accumulation and lipid droplet formation compared with that of mice in the HFD group. NAC could preserve mitochondrial function by inhibiting excessive mitophagy and promoting mitochondria biogenesis to prevent ROS production. NAC also activated Sirt1 and preserved its protein level and subsequently promoted mitochondria biogenesis via deacetylating PGC1a. Conclusion: We demonstrated that NAC may be an effective drug to treat NAFLD, which was related to its antioxidative and mitochondrial protective effect.