Search

Background. Fuzheng Yiliu decoction (FZYLD) was a traditional prescription with an antitumor effect. We aimed to explore the antitumor effect of FZYLD and its active ingredient, quercetin, on prostate cancer (PCa). Methods. The effective components and potential targets of FZYLD were obtained from the TCMSP, Herb, and Batman databases. The relationship between the active compounds of FZYLD and PCa’s potential targets or pathways was analyzed by Cytoscape 3.8.0 software and the String database. The compound composition of FZYLD was detected by HPLC. The effects of quercetin, with the most effective active ingredient of FZYLD, on PC-3 cell growth, metastasis, and PI3K/AKT pathway were seen by CCK-8 Kit, transwell experiment, TUNEL assay, nude mouse tumorigenesis test, and Western blot analysis. Results. Through network pharmacological analysis, we screened 195 effective active components of FZYLD, covering 290 targets, of which 198 were related to PCa. Quercetin, luteolin, kaempferol, anhydroicaritin, and 7-O-methylismucronulatol were important active compounds. MAPK1, AKT1, MAPK3, STAT3, and Jun were common targets of PCa and FZYLD. Our in vivo and in vitro experimental results confirmed that quercetin inhibited PCa’s growth, cell migration, and the PI3K/AKT pathway and promoted cell apoptosis. Conclusions. As predicted by the network pharmacological strategy and verified by the basic experimental results, FZYLD might play an antitumor role through multiple components, targets, and pathways. These results provide a new basis for developing and applying FZYLD and its compound quercetin.

BackgroundWe previously found that occupational exposure to diesel engine exhaust (DEE) was associated with alterations to 19 biomarkers that potentially reflect the mechanisms of carcinogenesis. Whether DEE is associated with biological alterations at concentrations under existing or recommended occupational exposure limits (OELs) is unclear.MethodsIn a cross-sectional study of 54 factory workers exposed long-term to DEE and 55 unexposed controls, we reanalysed the 19 previously identified biomarkers. Multivariable linear regression was used to compare biomarker levels between DEE-exposed versus unexposed subjects and to assess elemental carbon (EC) exposure-response relationships, adjusted for age and smoking status. We analysed each biomarker at EC concentrations below the US Mine Safety and Health Administration (MSHA) OEL (3), below the European Union (EU) OEL (3) and below the American Conference of Governmental Industrial Hygienists (ACGIH) recommendation (3).ResultsBelow the MSHA OEL, 17 biomarkers were altered between DEE-exposed workers and unexposed controls. Below the EU OEL, DEE-exposed workers had elevated lymphocytes (p=9E-03, false discovery rate (FDR)=0.04), CD4+ count (p=0.02, FDR=0.05), CD8+ count (p=5E-03, FDR=0.03) and miR-92a-3p (p=0.02, FDR=0.05), and nasal turbinate gene expression (first principal component: p=1E-06, FDR=2E-05), as well as decreased C-reactive protein (p=0.02, FDR=0.05), macrophage inflammatory protein-1β (p=0.04, FDR=0.09), miR-423-3p (p=0.04, FDR=0.09) and miR-122-5p (p=2E-03, FDR=0.02). Even at EC concentrations under the ACGIH recommendation, we found some evidence of exposure-response relationships for miR-423-3p (ptrend=0.01, FDR=0.19) and gene expression (ptrend=0.02, FDR=0.19).ConclusionsDEE exposure under existing or recommended OELs may be associated with biomarkers reflective of cancer-related processes, including inflammatory/immune response.

Visual cryptography scheme is a method of encrypting secret image into n noiselike shares. The secret image can be reconstructed by stacking adequate shares. In the past two decades, many schemes have been proposed to realize the cheating prevention visual cryptography scheme (CPVCS). Significantly, Ren et al. [ 9 ] first introduced the idea of CPVCS with the help of Latin square. Inspired by their work, in this article, a new reliable scheme is proposed. More precisely, to facilitate the certification process, we embed meaningful characters into the randomly chosen authentication patterns in each divided blocks. Furthermore, we fix the security vulnerability in the stacked results of share S g and verification Ver g , where 1≤ g ≤ n . Since the improved scheme encrypts the secret image by utilizing random grids, the generated shares have no pixel expansion. Finally, theoretical analysis and experimental results are conducted to evaluate the efficiency and security of the proposed scheme.

Purpose:Mistletoe extract (ME) is widely used for patients with cancer to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration.Materials and Methods:This phase I trial of intravenous mistletoe (Helixor M) aimed to determine the recommended phase II dosing and to evaluate safety. Patients with solid tumor progressing on at least one line of chemotherapy received escalating doses of Helixor M three times a week. Assessments were also made of tumor marker kinetics and QoL.Results:Twenty-one patients were recruited. The median follow-up duration was 15.3 weeks. The MTD was 600 mg. Treatment-related adverse events (AE) occurred in 13 patients (61.9%), with the most common being fatigue (28.6%), nausea (9.5%), and chills (9.5%). Grade 3+ treatment-related AEs were noted in 3 patients (14.8%). Stable disease was observed in 5 patients who had one to six prior therapies. Reductions in baseline target lesions were observed in 3 patients who had two to six prior therapies. Objective responses were not observed. The disease control rate (percentage of complete/partial response and stable disease) was 23.8%. The median stable disease was 15 weeks. Serum cancer antigen-125 or carcinoembryonic antigen showed a slower rate of increase at higher dose levels. The median QoL by Functional Assessment of Cancer Therapy-General increased from 79.7 at week 1 to 93 at week 4.Conclusions:Intravenous mistletoe demonstrated manageable toxicities with disease control and improved QoL in a heavily pretreated solid tumor population. Future phase II trials are warranted.Significance:Although ME is widely used for cancers, its efficacy and safety are uncertain. This first phase I trial of intravenous mistletoe (Helixor M) aimed to determine phase II dosing and to evaluate safety. We recruited 21 patients with relapsed/refractory metastatic solid tumor. Intravenous mistletoe (600 mg, 3/week) demonstrated manageable toxicities (fatigue, nausea, and chills) with disease control and improved QoL. Future research can examine ME's effect on survival and chemotherapy tolerability.

Background In recent years, genome editing technology represented by clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 （CRISPR/Cas9） has been developed and applied in transgenic research and development, and transgenic products have been developed for a variety of applications. Gene editing products, unlike traditional genetically modified crops, which are generally obtained by target gene deletion, insertion, base mutation, etc., may not differ significantly at the gene level from conventional crops, which increases the complexity of testing. Objective We established a specific and sensitive CRISPR/Cas12a-mediated gene editing system to detect target fragments in a variety of transgenic rice lines and commercial rice-based processing products. Methods In this study, the CRISPR/Cas12a visible detection system was optimized for the visualization of nucleic acid detection in gene-edited rice. The fluorescence signals were detected by both gel electrophoresis and fluorescence-based methods. Results The detection limit of the CRISPR/Cas12a detection system established in this study was more precise, especially for low-concentration samples. In addition to achieving single-base detection in gene-edited rice, we showed that different base mutations in the target sequence have different detection efficiencies by sitewise variant compact analysis. The CRISPR/Cas12a system was verified via a common transgenic rice strain and commercial rice sources. The results proved that the detection method could not only be tested in samples with multiple mutation types but could also effectively detect target fragments in commercial rice products. Conclusion We have developed a set of efficient detection methods with CRISPR/Cas12a for gene-edited rice detection to provide a new technical basis for rapid field detection of gene-edited rice. Highlights The CRISPR/Cas12a-mediated visual detection method used to detect gene-edited rice was evaluated for its specificity, sensitivity, and robustness.

High salinity, an adverse environmental factor affecting about 20% of irrigated arable land worldwide, inhibits plant growth and development by causing oxidative stress, damaging cellular components, and disturbing global metabolism. However, whether and how reactive oxygen species disturb the metabolism of salt-stressed plants remain elusive. Here, we report that salt-induced hydrogen peroxide (H2O2) inhibits the activity of plastid triose phosphate isomerase (pdTPI) to promote methylglyoxal (MG) accumulation and stimulates the sulfenylation of pdTPI at cysteine 74. We also show that MG is a key factor limiting the plant growth, as a decrease in MG levels completely rescued the stunted growth and repressed salt stress tolerance of the pdtpi mutant. Furthermore, targeting CATALASE 2 into chloroplasts to prevent salt-induced overaccumulation of H2O2 conferred salt stress tolerance, revealing a role for chloroplastic H2O2 in salt-caused plant damage. In addition, we demonstrate that the H2O2-mediated accumulation of MG in turn induces H2O2 production, thus forming a regulatory loop that further inhibits the pdTPI activity in salt-stressed plants. Our findings, therefore, illustrate how salt stress induces MG production to inhibit the plant growth.

Glucagon-secreting pancreatic α-cells play pivotal roles in the development of diabetes. Glucagon promotes insulin secretion from β-cells. However, the long-term effect of glucagon on the function and phenotype of β-cells had remained elusive. In this study, we found long-term intervention of glucagon or glucagon intervention with the presence of palmitic acid downregulated the β-cell specific markers, and inhibited insulin secretion in cultured β-cells. These results suggested that glucagon induced β-cell dedifferentiation under pathological conditions. Glucagon blockage by a glucagon receptor (GCGR) monoclonal antibody (mAb) attenuated glucagon-induced β-cell dedifferentiation. In primary islets, GCGR mAb treatment upregulated β-cell specific markers and increased insulin content, suggesting that blockage of endogenous glucagon inhibited β-cell dedifferentiation. To investigate the possible mechanism, we found glucagon decreased FoxO1 expression. FoxO1 inhibitor mimicked the effect of glucagon, while FoxO1 overexpression reversed the glucagon-induced β-cell dedifferentiation. In db/db mice and β-cell lineage-tracing diabetic mice, GCGR mAb lowered glucose level, upregulated plasma insulin level, increased β-cell area and inhibited β-cell dedifferentiation. In the aged β-cell specific FoxO1 knockout mice (with the blood glucose level elevated as a diabetic model), the glucose-lowering effect of GCGR mAb was attenuated, and the plasma insulin level, β-cell area and β-cell dedifferentiation was not affected by GCGR mAb. Our results proved that glucagon induced β-cell dedifferentiation under pathological conditions, and the effect was partially mediated by FoxO1. Our study reveals a novel crosstalk between α- and β-cells, and is helpful to understand the pathophysiology of diabetes and discover new targets for the diabetes treatment.

Surface acoustic wave (SAW) technology has been extensively used in communications and sensing applications. This review summarizes the recent advancement of micro- and nanostructured sensing materials in enhancing the gas sensing performance of SAW devices.

In this study, we propose a cross-domain multi-objective speech assessment model called MOSA-Net, which can estimate multiple speech assessment metrics simultaneously. Experimental results show that MOSA-Net can improve the linear correlation coefficient (LCC) by 0.026 (0.990 vs 0.964 in seen noise environments) and 0.012 (0.969 vs 0.957 in unseen noise environments) in PESQ prediction, compared to Quality-Net, an existing single-task model for PESQ prediction, and improve LCC by 0.021 (0.985 vs 0.964 in seen noise environments) and 0.047 (0.836 vs 0.789 in unseen noise environments) in STOI prediction, compared to STOI-Net (based on CRNN), an existing single-task model for STOI prediction. Moreover, MOSA-Net, originally trained to assess objective scores, can be used as a pre-trained model to be effectively adapted to an assessment model for predicting subjective quality and intelligibility scores with a limited amount of training data. Experimental results show that MOSA-Net can improve LCC by 0.018 (0.805 vs 0.787) in MOS prediction, compared to MOS-SSL, a strong single-task model for MOS prediction. In light of the confirmed prediction capability, we further adopt the latent representations of MOSA-Net to guide the speech enhancement (SE) process and derive a quality-intelligibility (QI)-aware SE (QIA-SE) approach accordingly. Experimental results show that QIA-SE provides superior enhancement performance compared with the baseline SE system in terms of objective evaluation metrics and qualitative evaluation test. For example, QIA-SE can improve PESQ by 0.301 (2.953 vs 2.652 in seen noise environments) and 0.18 (2.658 vs 2.478 in unseen noise environments) over a CNN-based baseline SE model.

Organic–inorganic halide perovskites (OIHPs) are very eye-catching due to their chemical tunability and rich physical properties such as ferroelectricity, magnetism, photovoltaic properties and photoluminescence.

A new ferroelastic organic salt nicotinic acid bromide (N–Br) with high Tc, reversible ferroelastic transition and white light was obtained by halogen substitution.

We report two dual-step reversible dielectric switching materials with photoluminescence properties.

Purpose This study aimed to assess the diagnostic performance of [18F]FAPI-42 PET/CT and compare it with that of 2-[18F]FDG PET/CT in patients with differentiated thyroid cancer (DTC) with biochemical elevations in Tg or anti-Tg antibodies. Methods A total of 42 patients with DTC with biochemical elevations in Tg or anti-Tg antibodies underwent [18F]FAPI-42 PET/CT as part of this study; of which, 11 additionally underwent 2-[18F]FDG PET/CT within 7 days. Images were semi-quantitatively and visually interpreted, and the quantity, location, and uptake values of lesions were noted. The diagnostic capacity of [18F]FAPI-42 PET/CT and biomarkers affecting the uptake of [18F]FAPI-42 were evaluated. In addition, the diagnostic performance and uptake of [18F]FAPI-42 and 2-[18F]FDG were compared, and the correlation between lesion diameter and quantitative parameters was investigated. Results A total of 161 lesions were detected in 27 (64%) patients on [18F]FAPI-42 PET/CT. FAPI-positive local recurrence showed the highest uptake intensity, followed by lymphatic, other site-associated (bone and pleura), and pulmonary lesions (mean SUVmax, 4.7 versus 3.7 versus 3.0 versus 2.2, respectively; P < 0.0001). The levels of TSH, Tg, and Tg-Ab did not affect the uptake value of lesions (median SUVmax: 2.4 versus 3.2, P = 0.56; 2.9 versus 2.4, P = 0.0935; 2.8 versus 2.6, P = 0.0525, respectively). A total of 90 positive lesions were detected in 7 patients using both modalities. All positive lesions showed statistically higher uptake of 2-[18F]FDG than that of [18F]FAPI-42 (SUVmax, 2.6 versus 2.1; P = 0.026). However, the SUVmax of [18F]FAPI-42 was higher than that of 2-[18F]FDG in local recurrences and lymphatic lesions (SUVmax, 4.2 versus 2.9 and 3.9 versus 3.4, respectively; P > 0.05). Conclusion [18F]FAPI-42 can be used for detecting lesions and reflecting FAP expression during local recurrence and metastasis in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies. The diagnostic performance of [18F]FAPI-42 PET/CT is comparable with that of 2-[18F]FDG PET/CT in such patients.