Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)–Akt–mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N ...(GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K–Akt pathway and regulates the mTOR–ULK1 pathway in liver cancer cells.
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•Recent progresses made in the development of phthalocyanines for photodynamic therapy are outlined.•Representative water-soluble phthalocyanines are presented.•Main targeting ...strategies are discussed.•Future challenges are also presented.
Owing to their high extinction coefficients, long absorption wavelengths, and modification tunable photophysical and photochemical properties, phthalocyanines (Pcs) have been widely used as photosensitizers for photodynamic therapy (PDT). Advances made in the past five years on the development of Pcs as medicinal photosensitizers are reviewed and the main design considerations for medicinal applications of these substances are discussed.
Ferroelectricity and X‐ray detection property have been recently implemented for the first time in hybrid bromide double perovskites. It sheds a light on achieving photosensitive and ferroelectric ...multifunctional materials based on 2D lead‐free hybrid halide double perovskites. However, the low Tc, small Ps, and relatively low X‐ray sensitivity in the reported bromide double perovskites hinder practical applications. Herein, the authors demonstrate a novel 2D lead‐free iodide double perovskite (4,4‐difluoropiperidinium)4AgBiI8 (1) for high‐performance X‐ray sensitive ferroelectric devices. Centimeter‐sized single crystal of 1 is obtained and exhibits an excellent ferroelectricity including a high Tc up to 422 K and a large Ps of 10.5 μC cm−2. Moreover, due to a large X‐ray attenuation and efficient charge carrier mobility (μ)–charge carrier lifetime (τ) product, the crystal 1 also exhibits promising X‐ray response with a high sensitivity up to 188 μC·Gyair−1 cm−2 and a detection limit below 3.13 μGyair·s−1. Therefore, this finding is a step further toward practical applications of lead‐free halide perovskite in high‐performance photoelectronic devices. It will afford a promising platform for exploring novel photosensitive ferroelectric multifunctional materials based on lead‐free double perovskites.
Ferroelectricity and X‐ray detection are realized in lead‐free hybrid double perovskite (DFPIP)4AgBiI8. It achieves excellent ferroelectricity (Tc = 422 K, Ps = 10.5 µC cm−2) and superior sensitivity of 188 µC·Gyair−1 cm−2 as an X‐ray detector. This finding will stimulate extensive research interest in photosensitive molecular ferroelectrics based on lead‐free double perovskites.
To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID‐19). A retrospective cohort of ...COVID‐19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8‐14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5‐18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5‐27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19‐2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID‐19 patients.
Highlights
Corticosteroid treatment was associated with prolonged viral shedding in COVID‐19 patients
Grafting of C7 from the nonparalyzed to the paralyzed side in patients with arm paralysis resulted in greater improvements in power, spasticity, and function at 12 months than rehabilitation therapy ...alone, and functional connection to the ipsilateral cerebral hemisphere developed.
Objectives
The tyrosine kinase inhibitor (TKI)-sensitive mutations of the epidermal growth factor receptor (EGFR) gene is essential in the treatment of lung adenocarcinoma. To overcome the difficulty ...of EGFR gene test in situations where surgery and biopsy samples are too risky to obtain, we tried a noninvasive imaging method using radiomics features and random forest models.
Methods
Five hundred three lung adenocarcinoma patients who received surgery-based treatment were included in this study. The diagnosis and EGFR gene test were based on resections. TKI-sensitive mutations were found in 60.8% of the patients. CT scans before any invasive operation were gathered and analyzed to extract quantitative radiomics features and build random forest classifiers to identify EGFR mutants from wild types. Clinical features (sex and smoking history) were added to the image-based model. The model was trained on a set of 345 patients and validated on an independent test group (
n
= 158) using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.
Results
The performance of the random forest model with 94 radiomics features reached an AUC of 0.802. Its AUC was further improved to 0.828 by adding sex and smoking history. The sensitivity and specificity are 60.6% and 85.1% at the best diagnostic decision point.
Conclusion
Our results showed that radiomics could not only reflect the genetic differences among tumors but also have diagnostic value and the potential to be a diagnostic tool.
Key Points
•
Radiomics provides a potential noninvasive method for the prediction of EGFR mutation status.
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In situations where surgeries and biopsy are not available, CT image-based radiomics models could help to make treatment decisions.
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The accuracy, sensitivity, and specificity still need to be improved before the image-based EGFR identifier could be used in clinics.
To enhance the adsorption performance of 2D graphene-like materials Ti3C2Tx (T = OH, O, F) on methylene blue (MB) and realize its reuse, sodium alginate (SA) was used to immobilize Ti3C2Tx to form ...Ti3C2Tx/SA beads. The beads were fabricated with Ti3C2Tx powder and SA by ionic crosslinking. Based on the SEM, FTIR and XRD analysis, Ti3C2Tx was bound to SA tightly, which avoided the loss of adsorbent and improved the adsorption effect. The adsorption characteristics of MB were investigated at different material ratios, temperature, pH and initial concentration. The results indicated that Ti3C2Tx/SA-30% was chosen as the appropriate mass ratio, the maximum adsorption capacity of which was 92.17 mg/g at pH 7 and 298 K. The MB adsorption efficiency was maintained 81.36% after three cycles. The adsorption process was conformed to pseudo-second-order kinetics, and fitted well with Langmuir isotherm model. Thermodynamic analysis suggested that the process of MB adsorbed on Ti3C2Tx/SA beads was endothermic and spontaneous. The results showed that Ti3C2Tx/SA beads had potential application in pollutants removal for efficient adsorption and superior reusability.
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•Ti3C2TX was synthesized with a milder, low-toxicity etchant (NH4HF2).•Ti3C2TX/SA beads is an effective and environmental-friendly adsorbent.•Ti3C2TX/SA beads can be easily separated, showing superior reusability.•MB adsorption onto Ti3C2TX/SA follows Langmuir isotherm and pseudo-second order.
Purpose:
The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury.
Methods:
The C57BL/6 J mice in 2 experiments were assigned into control ...group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors.
Results:
Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1β and increased IL-10 level.
Conclusions:
CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.
Aim
Genome‐wide association studies (GWAS) have identified multiple susceptibility loci associated with insulin resistance (IR)‐relevant phenotypes. However, the genes responsible for these ...associations remain largely unknown. We aim to identify susceptibility genes for IR‐relevant phenotypes via a transcriptome‐wide association study.
Materials and Methods
We conducted a large‐scale multi‐tissue transcriptome‐wide association study for IR (Insulin Sensitivity Index, homeostasis model assessment‐IR, fasting insulin) and lipid‐relevant traits (high‐density lipoprotein cholesterol, triglycerides, low‐density lipoprotein cholesterol and total cholesterol) using the largest GWAS summary statistics and precomputed gene expression weights of 49 human tissues. Conditional and joint analyses were implemented to identify significantly independent genes. Furthermore, we estimated the causal effects of independent genes by Mendelian randomization causal inference analysis.
Results
We identified 1190 susceptibility genes causally associated with IR‐relevant phenotypes, including 58 genes that were not implicated in the original GWAS. Among them, 11 genes were further supported in differential expression analyses or a gene knockout mice database, such as KRIT1 showed both significantly differential expression and IR‐related phenotypic effects in knockout mice. Meanwhile, seven proteins encoded by susceptibility genes were targeted by clinically approved drugs, and three of these genes (H6PD, CACNB2 and DRD2) have been served as drug targets for IR‐related diseases/traits. Moreover, drug repurposing analysis identified four compounds with profiles opposing the expression of genes associated with IR risk.
Conclusions
Our study provided new insights into IR aetiology and avenues for therapeutic development.
Invasive species pose increasing threats to global biodiversity and ecosystems. While previous studies have characterized successful invaders based on ecological traits, characteristics related to ...evolutionary processes have rarely been investigated. Here we compared gene flow and local adaptation using demographic analyses and outlier tests in two co‐occurring moth pests across their common native range of China, one of which (the peach fruit moth, Carposina sasakii) has maintained its native distribution, while the other (the oriental fruit moth, Grapholita molesta) has expanded its range globally during the past century. We found that both species showed a pattern of genetic differentiation and an evolutionary history consistent with a common southwestern origin and northward expansion in their native range. However, for the noninvasive species, genetic differentiation was closely aligned with the environment, and there was a relatively low level of gene flow, whereas in the invasive species, genetic differentiation was associated with geography. Genome scans indicated stronger patterns of climate‐associated loci in the noninvasive species. While strong local adaptation and reduced gene flow across its native range may have decreased the invasiveness of C. sasakii, this requires further validation with additional comparisons of invasive and noninvasive species across their native range.
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