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Background and Objectives: Dry fractionation, combining milling and air classification technology, offers an economical and sustainable pathway for the processing of value‐added protein ingredients from Australia's major pulse crops. Leveraging a wider range of pulses will help meet the growing demand for plant‐based protein ingredients. This study demonstrates the efficient processing of protein concentrates from Australian mungbean, which were characterized for key nutritional properties, phytochemical constituents, protein quality, and protein secondary structure. Findings: Milling and air classification of mungbean flour resulted in protein concentrates (fine fraction) with a protein content of 62.2 g/100 g (db), reflecting a two‐fold increase in protein content compared to the original flour (p <.05). Ash, fat, dietary fiber, and free phenolic and antioxidant compounds, also co‐concentrated with protein in the fine fraction (p <.05), imparting enhanced nutritional properties with the potential to deliver health benefits. The protein quality of dry fractionated mungbean protein concentrate was compared to a commercial source of mungbean protein isolate (88 g/100 g, [db]). Amino acid scores highlighted deficiencies in sulfur‐containing amino acids, methionine, and cysteine, as well as tryptophan and threonine. In vitro protein digestibility‐corrected amino acid scores for the mungbean protein concentrate and protein isolate were 63.7% and 59.5%, respectively. SDS‐PAGE protein profiles showed no major differences in protein composition, indicating that no specific types of proteins are lost during the dry fractionation process. Fourier transform infrared analysis of protein secondary structure showed that β‐sheets were the dominant structural component, with relative percentages of 36% and 49%, for the mungbean protein concentrate and isolate, respectively. Conclusions: There is significant potential for dry fractionation to deliver value‐added opportunities for Australian mungbean, through the production of protein concentrate ingredients with enhanced nutritional properties for use in new and existing foods. Significance and Novelty: Nutritional properties, protein quality, and protein secondary structure were compared for protein concentrates and protein isolates processed from Australian‐grown mungbean. Key findings from this study will inform pulse protein processors and pulse‐based food manufacturers. [ABSTRACT FROM AUTHOR]

This article discusses a study on double expressor lymphoma (DEL) subtypes and the therapeutic mechanism of epigenetic agents. The study identified three subtypes of DEL with unique characteristics and found that DEL had an inferior survival compared to double negative lymphoma (DNL). The subtypes of DEL were associated with different cell-of-origin and genetic classifications. The study also analyzed the effects of tucidinostat and doxorubicin treatment on different oncogenic transcriptional factors and signaling networks in these subtypes. The results showed distinct molecular heterogeneity and a complex tumor microenvironment in DEL, which contribute to resistance to standard treatment. However, tucidinostat plus doxorubicin demonstrated broad-spectrum sensitivity in vitro and in vivo. The study provides insights for optimizing current treatment paradigms in DEL. [Extracted from the article]

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non‐alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline‐deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl‐CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element‐binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid β‐oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH. [ABSTRACT FROM AUTHOR]

Chilli pepper is one of the most important and widely cultivated pepper types in China. It has high nutritional and economic value. Capsicum frutescens L. is one of the chilli pepper types in production. In October 2022, a new disease showing blight of the entire chilli pepper plant was observed in Nanchang City, Jiangxi Province. The fungal isolates consistently obtained from the diseased samples were identified as Diaporthe caryae C. M. Tian & Qin Yang based on morphological characteristics, pathogenicity test and phylogenetic analysis of four genes, including internal transcribed spacer region (rDNA‐ITS), translation elongation factor 1‐alpha gene (TEF1), beta‐tubulin gene (TUB2), and calmodulin (CAL). Although other Diaporthe species have been reported as pathogens of peppers previously, to our knowledge, this is the first report of D. caryae causing stem blight of pepper in the world. D. caryae was reported to be able to infect various fruit trees such as kiwifruit, peach, pear, and pecan, resulting in kiwifruit rot, peach constriction canker, pear shoot canker, and pecan dieback, respectively. The host range of D. caryae has expanded from fruit trees to vegetable crops. [ABSTRACT FROM AUTHOR]

CD47 overexpression is associated with tumor-associated macrophage infiltration and the progression of diffuse large B-cell lymphoma (DLBCL). High CD47 expression is linked to elevated serum lactic dehydrogenase levels and an increased proportion of non-germinal center B-cell subtype. Patients with high CD47 expression have lower progression-free survival and overall survival rates compared to those with low CD47 expression. CD47 is also involved in genetic mutations and dysregulated pathways in DLBCL, and it promotes the polarization of M2-polarized macrophages and an immunosuppressive microenvironment. CD47 expression can be evaluated using immunohistochemistry, and it serves as a potential immunotherapeutic target for DLBCL treatment. [Extracted from the article]

Lanthanide ions (Yb3+ or Er3+) alloying of CsPb(Cl1‐xBrx)3 quantum dots (QDs) to emit approaching 1000 nm show promise in near‐infrared light‐emitting diodes (NIR‐LEDs). High Yb3+ alloying ratio increases the electroluminance efficiency of emission at 990 nm and enables high external quantum efficiency (EQE) of NIR‐LEDs, however, the high alloying ratio also results in inferior material stability and PLQY drop because of Yb3+‐induced nanocrystal precipitation. This study finds that the heavy alloying of Yb3+ ions causes lattice distortion and coherent energy reduction of Yb3+: CsPb(Cl1‐xBrx)3 QDs, induced by two Yb3+ ions replacing three Pb2+, which leads to the collapse of the octahedral structure in ambient conditions. It posits that spontaneous monovalent ion (Na+) alloying can address the trade‐off between material stability and emission intensity. The Na+ occupies the vacancy of Pb2+ ions, relaxing the distortion in the lattice and improving the phase stability of octahedral structure, and this optimized structure in turn allows a higher Yb3+ alloying ratio. Stability measurements show that the Na+/Yb3+ co‐alloyed films show ten‐fold higher material stability and 2.0‐fold emission efficiency related to controls. It reports that as a result Na+/Yb3+ co‐alloyed NIR‐LEDs have an EQE of 6.4% at 990 nm, which is among the highest perovskite NIR‐LEDs beyond 950 nm. [ABSTRACT FROM AUTHOR]

(F) Peripheral Treg cells of relapsed or refractory DLBCL patients with current HBV infection before or after lenalidomide plus R-ICE treatment. gl In conclusion, DLBCLs with current HBV infection may refer as a specific entity with aggressive disease course and resistance to immunochemotherapy. Dear Editor, Hepatitis B virus (HBV) is an oncogenic virus and a major risk factor for developing hepatocellular carcinoma.[1] Growing evidence also suggests that HBV infection is linked to an increased incidence of diffuse large B-cell lymphoma (DLBCL).[1] Among 1925 newly diagnosed DLBCL patients (Figure S1), we revealed that DLBCLs with current HBV infection (HBV-surface-antigen [HBsAg]+), instead of those with previous HBV infection (HBsAg- and antibodies against HBV-core-antigen+), correlated with high-risk clinical features (Table S1), as previously reported.[[2]] The prognostic impact of HBV infection in DLBCL remained controversial in the rituximab era,[[2]] largely due to the relatively small sample size of patients receiving rituximab-containing treatment. Besides, B-cell surface markers for B-cell development[5] were significantly higher in DLBCLs of current HBV infection than in non-HBV infection (Figure 1D). Here, among 1490 patients with R-CHOP treatment, we observed that the progression-free survival (PFS) and overall survival (OS) of DLBCLs with current HBV infection were significantly worse than those of non-HBV infection (Figure 1A,B). [Extracted from the article]

Background: Early and late recurrence of hepatocellular carcinoma (HCC) have different clinical outcomes, especially for those accompanied by microvascular invasion (MVI), but the definition of early recurrence remains controversial. Therefore, a reasonable identification of the early recurrence time for HCC is urgently needed. Methods: Resected recurrence patients were enrolled and divided into two cohorts, one for identification of the early recurrence time and another for verification of the accuracy of the point. Univariable and multivariable Cox regression analyses were adopted to identify the prognostic factors of recurrence HCC (rHCC) and Kaplan–Meier method was applied to analyze the overall survival (OS). The appropriate cutoff value was determined by the exhaustive method using different recurrence intervals from 1 to 24 months in turn. Results: In total, 292 resected rHCC patients were analyzed to calculate the early recurrence interval, and another 421 resected rHCC patients with MVI were enrolled to verify the efficacy of adjuvant transarterial chemoembolization (TACE) in this recurrence interval. MVI was identified as an independent risk factor by multivariable analysis. The OS of rHCC patients without MVI is better than that of patients with MVI when the recurrence time was within 13 months, while not beyond 13 months. The verification cohort demonstrated that adjuvant TACE provided longer survival for rHCC with MVI when the recurrence time was within 13 months, while not beyond 13 months. Conclusion: For HCC patients with MVI who underwent R0 resection, 13 months may be a reasonable early recurrence time point, and within this interval, postoperative adjuvant TACE may result in longer survival compared with surgery alone. [ABSTRACT FROM AUTHOR]

Perovskite solar cells (PSCs) have developed rapidly in recent years due to their excellent photoelectric properties. Among them, lead‐based perovskite photovoltaics have shown great potential for both outdoor and indoor applications, whose power conversion efficiency and stability are much higher than that of lead‐free PSCs. However, based on results of in vivo animal studies, Kyoto Encyclopedia of Genes and Genomes annotations and pathway analysis of microbiota and metabolites influenced by lead, it has been proved that lead exposure from PSCs probably causes systematic toxicity to human body. For the purpose of reducing lead leakage, some methods mainly based on polymer resin protective layers and self‐healing encapsulation have been introduced, which can increase lead capture rate up to 95% under harsh conditions. Eventually, the devices will still face damage and obsolescence, accompanied by lead leakage into the environment. Comprehensive recycling strategies are necessary to solve this problem from the root and also shorten the energy payback time for further transformation and upgrading of green energy. The vertical and in‐depth collaborative strategy for lead leakage prevention and comprehensive recycling would provide an environmentally‐friendly guarantee for the final large‐scale market of perovskite photovoltaics. [ABSTRACT FROM AUTHOR]

Based on the idea of local resonance, a class of hybrid acoustic metamaterials with interposed resonant strips is proposed in this article, and the bandgap characteristics and transmission properties are calculated by combining Bloch's theorem and lattice theory. The new structure is verified to have low‐frequency damping and noise reduction capability through the analysis of the stress cloud diagram at specific frequencies in the bandgap range. A comprehensive analysis of vibration modes, phase constant surfaces, group velocity, phase velocity, and wave propagation direction diagram is used to explore the wave propagation and bandgap opening mechanism, providing technical support and theoretical basis for subsequent bandgap optimization and structural improvement. The results show that this structure can open multiple bandgaps in the low‐frequency range below 500 Hz, and the stepped design of the single‐cell structure and the introduction of resonant strips provide a new design idea for low‐frequency vibration and noise reduction. [ABSTRACT FROM AUTHOR]

Herein, a novel star‐shaped hybrid acoustic metamaterial structure is proposed. Based on Bloch's theorem and the finite element method, the bandgap characteristics and the bandgap formation mechanism of different combinations of structures are first analyzed. Then, the propagation characteristics of elastic waves in Model C2 are studied with focus on equal frequency contours, phase velocity, and group velocity. And the attenuation of elastic waves in the finite size structure of Model C2 illustrates that the elastic waves are effectively suppressed in the bandgap frequency range, which further confirms the perfect correspondence between the bandgap and the vibration attenuation region. Finally, the influence of structural parameters on the bandgap is analyzed, as well as the change of the bandgap when the structure undergoes large deformation, which can realize the tunability and flexibility of the bandgap. This study provides important clues for the design of vibration isolators and metamaterials, and shows the good engineering application potential of the structure for vibration isolation. [ABSTRACT FROM AUTHOR]

In order to achieve the attenuation of low‐frequency sound, in this paper, a hybrid metamaterial structure with a complete band gap below 500 Hz is proposed, which is subjected to second‐order fractal, series fusion, and whether the structure is framed or not to form 8 different structures. Based on the finite element method and Bloch's theorem, the bandgap and transport properties of all model structures are evaluated, and the bandgap and propagation properties of metamaterial structures with different fractal levels are elucidated in terms of band structure and group velocity. In addition, the third‐order fractal structure and the dependence of the band gap on the material are also studied. The results show that the structure has a superior band gap width, and the complete band gap of its tandem fusion structure accounts for up to 45.502% in the range of 500 Hz, and the second‐order fractal has a complete band gap of 45.588% in the range of 1000 Hz. Compared with other structures, it can produce lower and better band gap. The research in this paper provides a new strategy for realizing acoustic metamaterial structures with low frequency band gaps. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major risk factor for cardiovascular diseases, which contributes to the worldwide mortality rate. Successful blood pressure control requires adherence to medications and lifestyle modifications. However, motivating patients with primary hypertension to change and sustain behaviors long‐term is challenging. A web‐based self‐care program centered on self‐efficacy theory could provide feedback for effective control of blood pressure. Purpose: To examine the effect of a web‐based self‐care program for patients with primary hypertension on cardiovascular risk‐factors (pulse pressure and lipids), self‐efficacy, and self‐care behaviors (medication adherence and lifestyle). Design A two‐armed randomized controlled trial with 3‐month and 6‐month follow‐ups. Setting and Participants: A total of 222 patients with primary hypertension were recruited between February 2017 and August 2018 at a cardiology clinic of a medical center in Taipei, Taiwan. Methods: Eligible patients were randomized by permuted block randomization into the intervention group (n = 111) and control group (n = 111). Patients in the intervention group received a 6‐month web‐based self‐care program, based on the theory of self‐efficacy, while patients in the control group received usual care. Baseline and outcome measures (3 and 6 months) included self‐efficacy, evaluated with the Chinese version of the 6‐item Self‐Efficacy for Managing Chronic Diseases (SEMC6), self‐care, using subscales of the Hypertension Self‐Care Activity Level Effects Scale (H‐SCALE) for lifestyle and medication adherence, and blood pressure and serum lipid data, collected through web‐based self‐reports and chart review. Generalized estimating equations evaluated the effects of the intervention. Findings At baseline, the control group had higher scores on the SEMC6, and lower cholesterol (HDL) compared with the intervention group (t = −2.70, p < 0.05; and t = 1.76, p < 0.05, respectively). Pulse pressure decreased significantly (β = −20.30, 95% CI −23.76, −16.83), and serum triglycerides and low‐density lipoprotein cholesterol levels were significantly lower compared with controls at 6 months (all p < 0.001). At 6 months, the intervention group had significantly higher mean scores for the SEMC6 compared with the control group (β = 21.84, 95% confidence interval [CI] 19.25, 24.42) and H‐SCALE subscale for medication adherence, diet, weight management, and physical activity compared with controls at 6 months (all, p < 0.001). Conclusions and clinical relevance: The greatest benefit of this program was allowing participants to immediately consult with the researchers about self‐care issues via the website. Lifestyles vary from person to person; therefore, the individuality of each participant was considered when providing feedback. We provided devising interventions for participants that would increase their confidence in self‐care for hypertension and ultimately achieve home blood pressure control. We encourage incorporating this program into standard clinical care for patients with hypertension. [ABSTRACT FROM AUTHOR]

Aim: Surgical treatment is the first‐line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A1 hepatocellular carcinoma (HCC), and postoperative monitoring improves long‐term survival. We aimed to establish a reasonable short‐interval follow‐up duration for patients with HCC. Methods: The cohort for this retrospective study included 1396 HCC patients with BCLC stage 0 or A1 disease who underwent curative resection from 2013 to 2016 at five centers in China. Hazard rates for recurrence were calculated using the hazard function. Results: The recurrence rates in patients with BCLC stage 0 and A1 HCC were 46.4% and 58.0%, respectively. The hazard curve for stage 0 patients was relatively flat, and the hazard rate was consistently low (peak hazard rate 0.0163). The hazard rate curve for recurrence was initially high (peak hazard rate 0.0441) in patients with BCLC stage A1 disease and showed a rapid decreasing trend within 1 year, followed by a slow decreasing trend, reaching a low level (<0.0163) at approximately 36 months. The time to low risk was 47, 41, and 51 months in patients with cirrhosis, hepatitis B virus (HBV) infection, and satellite lesions, respectively. Conclusions: A short‐interval follow‐up of 1 year is sufficient for HCC patients with BCLC stage 0 disease, whereas a short‐interval follow‐up time of 3 years should be considered for patients with stage A1 disease. The follow‐up period should be appropriately prolonged for patients with cirrhosis, HBV infection, and satellite lesions. [ABSTRACT FROM AUTHOR]

Aim: Transarterial chemoembolization (TACE) combined with a PD‐1 inhibitor and TACE combined with a PD‐1 inhibitor and lenvatinib have recently been reported as promising treatments to improve the prognosis of hepatocellular carcinoma (HCC) patients. This study aims to compare the efficacy of these two treatments. Methods: A retrospective study was conducted, and patients were recruited from two centers in China. Progression‐free survival (PFS) and overall survival (OS) were compared, and the objective response rate (ORR) and disease control rate (DCR) were evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Treatment‐related adverse events (AEs) were analyzed to assess safety. Results: The median follow‐up for the entire cohort was 11.4 months. Of the 103 patients included in this study, 56 received triple therapy, and 47 received doublet therapy. PFS was significantly higher in the triple therapy group than in the doublet therapy group (mPFS 22.5 vs. 14.0 months, P < 0.001). Similar results were obtained in terms of OS (P = 0.001). The ORR and DCR were also better in the triple therapy group (64.3% vs. 38.3%, P = 0.010; 85.7% vs. 57.4%, P = 0.002). The most common AEs in the triple therapy group were decreased albumin (55.3%), decreased platelet count (51.8%) and hypertension (44.6%). Conclusions: The combination of TACE with a PD‐1 inhibitor and lenvatinib in patients with BCLC stage B HCC might result in significantly improved clinical outcomes with a manageable safety profile compared with TACE with a PD‐1 inhibitor. [ABSTRACT FROM AUTHOR]

Evolutionarily conserved DDB1‐and CUL4‐associated factor 13 (DCAF13) is a recently discovered substrate receptor for the cullin RING‐finger ubiquitin ligase 4 (CRL4) E3 ubiquitin ligase that regulates cell cycle progression. DCAF13 is overexpressed in many cancers, although its role in breast cancer is currently elusive. In this study we demonstrate that DCAF13 is overexpressed in human breast cancer and that its overexpression closely correlates with poor prognosis, suggesting that DCAF13 may serve as a diagnostic marker and therapeutic target. We knocked down DCAF13 in breast cancer cell lines using CRISPR/Cas9 and found that DCAF13 deletion markedly reduced breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo. In addition, DCAF13 deletion promoted breast cancer cell apoptosis and senescence, and induced cell cycle arrest in the G1/S phase. Genome‐wide RNAseq analysis and western blotting revealed that loss of DCAF13 resulted in both mRNA and protein accumulation of p53 apoptosis effector related to PMP22 (PERP). Knockdown of PERP partially reversed the hampered cell proliferation induced by DCAF13 knockdown. Co‐immunoprecipitation assays revealed that DCAF13 and DNA damage‐binding protein 1 (DDB1) directly interact with PERP. Overexpression of DDB1 significantly increased PERP polyubiquitination, suggesting that CRL4DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation. In conclusion, DCAF13 and the downstream effector PERP occupy key roles in breast cancer proliferation and potentially serve as prognostics and therapeutic targets. [ABSTRACT FROM AUTHOR]

Searching for a distinguishable lost target in a bounded area automatically with unmanned aerial vehicle (UAV) is a fundamental problem in the theory of physical search. This paper studies the problem in detail, presents a new and more realistic Bayesian formula representing the problem by taking communication capability of UAVs into consideration, and focuses on the case of applying a team of multiple cooperative UAVs in the field for the search, where each UAV can autonomously search the area for the target using Bayesian filtering algorithm. The perturbation of the searching performance by the different prior belief probability distribution functions is investigated. Empirical evidence findings illustrate that our approach yields improved accuracy. [ABSTRACT FROM AUTHOR]

Ferroelectrics usually exhibit temperature‐triggered structural changes, which play crucial roles in controlling their physical properties. However, although light is very striking as a non‐contact, non‐destructive, and remotely controlled external stimuli, ferroelectric crystals with light‐triggered structural changes are very rare, which holds promise for optical control of ferroelectric properties. Here, an organic molecular ferroelectric, N‐salicylidene‐2,3,4,5,6‐pentafluoroaniline (SA‐PFA), which shows light‐triggered structural change of reversible photoisomerization between cis‐enol and trans‐keto configuration is reported. SA‐PFA presents clear ferroelectricity with the saturate polarization of 0.84 μC cm−2, larger than those of some typical organic ferroelectrics with thermodynamically structural changes. Benefit from the reversible photoisomerization, the dielectric real part of SA‐PFA can be reversibly switched by light. More strikingly, the photoisomerization enables SA‐PFA to show reversible optically induced ferroelectric polarization switching. Such intriguing behaviors make SPFA a potential candidate for application in next‐generation photo‐controlled ferroelectric devices. This work sheds light on further exploration of more excellent molecular ferroelectrics with light‐triggered structural changes for optical control of ferroelectric properties. [ABSTRACT FROM AUTHOR]

Diffuse large B‐cell lymphoma (DLBCL) is a genetically heterogeneous disease with complex tumor microenvironment (TME) alterations. However, immune cell signatures of TME and their prognostic value remain unclear in DLBCL. We aimed to identify high‐risk DLBCL with specific immune cell signatures in TME. Clinical and gene expression data of DLBCL patients were obtained from previously reported retrospective datasets in Gene Expression Omnibus (GSE108466 and GSE5378616) and a multi‐center prospective clinical trial NHL001 (NCT01852435). Patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (n = 159) from GSE10846 were referred as training cohort for CHOP regimen, while patients treated with rituximab‐CHOP (R‐CHOP) regimen (n = 192) from GSE10846 as training cohort for R‐CHOP regimen. Patients from NHL001 (n = 68) and GSE53786 (n = 57) were referred as validation cohorts for R‐CHOP regimen. CIBERSORT was applied to estimate the relative proportions of 22 subtype of immune cells. We established a prognostic model for model for R‐CHOP regimen included Age, performance status, lactate dehydrogenase, T cells follicular helper and macrophages M0, defining a low‐risk group with 2‐years OS of 92.9% and a high‐risk group with 2‐years OS of 52.5% (HR 6.57 [3.27–13.18], p < 0.0001). Immune cell signatures could be used as prognostic markers and provided further insights for individualized immunotherapeutic strategies in DLBCL. [ABSTRACT FROM AUTHOR]

Gene mutations were first screened in 180 patients with WGS/WES/targeted sequencing data, including 40 cases of EBER-positive DLBCL and 140 cases of EBER-negative DLBCL. As serum EBV DNA is mostly derived from tumor cells,6 our findings emphasized the advantage of serum EBV DNA as noninvasive biomarker for predicting tumor EBER status and prognostic factor of DLBCL. Epstein-Barr virus (EBV) is an important human oncogenic virus and closely related to the pathogenesis of diffuse large B-cell lymphoma.1 This is, to our knowledge, the first study to systematically evaluate the clinical impact of EBV infection on DLBCL, based on a prospective clinical trial (NHL-001, NCT01852435). [Extracted from the article]

Aim: Endometriosis is a common gynecological disorder characterized by chronic pelvic pain and infertility, which negatively affects women's health worldwide. AFAP1‐AS1 has been implicated in endometriosis lesions recently, but its mechanism of endometriosis progression remains unclear. Methods: Endometrial stromal cells (ESCs) were used to identify the role of AFAP1‐AS1 in endometriosis. The migratory capability was determined by transwell. Gene and protein expressions were identified by quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blotting. Cell viability and apoptosis were detected by MTT assays and flow cytometry, respectively. Luciferase report assays were used to identify the interaction of AFAP1‐AS1, miR‐424‐5p and signal transducer and activator of transcription 3 (STAT3). Results: AFAP1‐AS1 knockdown or miR‐424‐5p overexpression inhibited proliferation and migration, and promoted apoptosis in ESCs. In addition, knockdown of AFAP1‐AS1 repressed the expression of ki‐67 and Bcl‐2, and promoted the levels of cleaved caspase‐3 and Bax. Furthermore, knockdown of AFAP1‐AS1 inhibited the conversion of E‐cadherin to N‐cadherin and the expression of Snail. Moreover, AFAP1‐AS1 activated the STAT3/transforming growth factor‐β1 (TGF‐β1)/Smad2 axis via directly targeting miR‐424‐5p. The regulatory effect of AFAP1‐AS1 silencing in ESC migration, proliferation, and apoptosis was reversed by miR‐424‐5p inhibition or STAT3 overexpression. Conclusions: AFAP1‐AS1 silencing could inhibit cell proliferation and promote apoptosis by regulating STAT3/TGF‐β/Smad signaling pathway via targeting miR‐424‐5p in ESCs. AFAP1‐AS1 may be a potential therapeutic target of controlling the progression of endometriosis. [ABSTRACT FROM AUTHOR]

Purpose: Secondary prevention of coronary artery disease, self‐management behavior, and blood pressure control are important to cardiovascular event prevention and promotion of quality of life (QOL), but they are underutilized. The purpose of this study was to investigate the effects of a self‐efficacy theory–based health information technology intervention implemented through blood control and patient self‐management. Design: A clinical randomized waitlist‐controlled trial. Methods: The study was conducted at a medical center in Taipei, Taiwan. A total of 60 subjects were randomly assigned to either the immediate intervention (experimental) group or the waitlist control group. The primary endpoint was systolic blood pressure at 3 months; secondary end points included self‐management behavior and QOL. Treatment for the immediate intervention group lasted 3 months, while the waitlist control group received routine care for the first 3 months, at which point they crossed over to the intervention arm and received the same intervention as the experimental group for another 3 months. Both groups were evaluated by questionnaires and physiological measurements at both 3 and 6 months postadmission. The results were analyzed using generalized estimating equations. Results: Systolic blood pressure significantly improved for the intervention group participants at 3 months, when there was also significant improvement in self‐management behavior and QOL. There was no significant or appreciable effect of time spent in the waitlist condition, with treatments in the two conditions being similarly effective. Conclusion: The use of a theory‐based health information technology treatment compared with usual care resulted in a significant improvement in systolic blood pressure, self‐management behavior, and QOL in patients with coronary artery disease. Clinical Relevance: This treatment would be a useful strategy for clinical care of cardiovascular disease patients, improving their disease self‐management. It also may help guide further digital health care strategies during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) have been emerged as prognostic biomarkers in diffuse large B‐cell lymphoma (DLBCL). To understand the potential underlying mechanisms and translate these findings into clinical prediction on lymphoma progression, large patient cohorts should be evaluated. Here, using miRNA PCR array, we analyzed the miRNA expression profiles in serum samples of 20 DLBCL patients at diagnosis, remission and relapse. Four candidate miRNA were identified and subsequently evaluated for their ability to predict relapse and survival. A prognostic model based on four circulating miRNA (miR21, miR130b, miR155 and miR28) was established and tested in a training cohort of 279 patients and in a validation cohort of 225 patients (NCT01852435). The prognostic value of the 4‐circulating miRNA model was assessed by univariate and multivariate analyses. The novel 4‐circulating miRNA prognostic model significantly predicted clinical outcome of DLBCL, independent of International Prognostic Index in the training cohort [hazard ratio (HR) = 2.83, 95% CI 2.14–3.51, P < 0.001] and in the validation cohort (HR = 2.71, 95% CI 1.91–3.50, P < 0.001). Moreover, DNA‐ and RNA‐sequencing was performed on tumor samples to detect genetic mutations and signaling pathway dysregulation. DNA‐sequencing data showed no significant difference of tumor mutation burden between the low‐risk and the high‐risk groups of the 4‐circulating miRNA model. RNA‐sequencing revealed a correlation between the 4‐circulating miRNA model and aberrant Ras protein signaling transduction. The impact of the miRNA signature on oncogenic signaling and tumor microenvironment was analyzed in vitro and in vivo. In B‐lymphoma cells, modulation of the miRNA regulated IGF1 and JUN expression, thereby altering MDSC and Th17 cells. In DLBCL patients, the high‐risk group presented Ras signaling activation, increased MDSC and Th17 cells, and immunosuppressive status compared with the low‐risk group. In conclusion, the easy‐to‐use 4‐circulating miRNA prognostic model effectively predicted relapse and survival in DLBCL. Moreover, the tumor microenvironment contributes to the role of the 4‐circulating miRNA model in DLBCL progression. [ABSTRACT FROM AUTHOR]

The cellular and molecular mechanisms underlying leptin‐mediated brain protection against cerebral ischemia were investigated at the blood–brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 μg/kg, intracisternally) could block the I/R‐increased BBB permeability, activation of matrix metallopeptidase 9 (MMP‐9) and brain infiltration of blood–borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO‐1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin‐inhibited brain infiltration of neutrophils. Leptin‐mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose–oxygen–serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R‐increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO‐1 and VE‐Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood‐borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B‐cell lymphoma (DLBCL) is an aggressive subtype of lymphoma, and multiple extranodal involvement (ENI) indicates adverse clinical outcomes. The aim of this study was to investigate the influence of oncogenic mutations and tumor microenvironment alterations on ENI in DLBCL. Methods: The clinical features of 1960 patients with newly diagnosed DLBCL were analyzed, and DNA and RNA sequencing was performed on 670 and 349 patients, respectively. Oncogenic mutations and tumor microenvironment alterations were compared according to ENI and evaluated in zebrafish patient‐derived tumor xenograft models. Results: Multiple ENI was significantly associated with poor performance status, advanced stage, elevated serum lactate dehydrogenase, low response rate, and inferior prognosis. Lymphoma invasion of the bones, spleen, bone marrow, liver, and central nervous system were independent unfavorable prognostic factors. MYD88 was frequently mutated in patients with multiple ENI, co‐occurred with mutations in CD79B, PIM1, TBL1XR1, BTG1, MPEG1, and PRDM1, and correlated with invasion of the bones, kidney/adrenal glands, breasts, testes, skin, and uterus/ovaries. For tumor microenvironment alterations, patients with multiple ENI showed higher regulatory T‐cell (Treg)‐recruiting activity, but lower extracellular matrix‐encoding gene expression, than those without ENI and with single ENI. Elevated Treg‐recruiting activity was related to mutations in B2M, SGK1, FOXO1, HIST1H1E, and ARID1A, and correlated with invasion of the bone marrow and thyroid. Additionally, mutations in MYD88, PIM1, TBL1XR1, SGK1, FOXO1, HIST1H1E, and ARID1A were associated with decreased major histocompatibility complex class I expression. Zebrafish models further revealed relationships between MYD88 mutations and invasion of the kidneys and gonads, as well as B2M mutations and invasion of the bone marrow. Increased CXCR4 expression is linked to bone marrow invasion in an organotropic way. Conclusions: Our findings thus contribute to an improved understanding of the biological behavior of multiple ENI and provide a clinical rationale for targeting ENI in DLBCL. [ABSTRACT FROM AUTHOR]

Contrast‐enhanced ultrasonography provides a more functional diagnostic image than conventional ultrasonography. This prospective exploratory study compared the novel contrast agent, Visphere™, with commercial contrast agents in five healthy Beagle dogs. Visphere™ has the smallest diameter and highest concentration compared with Sonazoid® and SonoVue®. Each dog received an intravenous injection of Visphere™, Sonazoid®, or SonoVue®. Images were recorded for 300, 600, and 60 s in the heart, liver, and left kidney, respectively. The mean pixel values of the regions of interest for each organ were expressed as time intensity curves (TIC). The agents all improved the visualization of left ventricular endocardial border delineation in the heart, and had similar TICs and clinical useful durations. In contrast, Visphere™ expressed the highest mean pixel value in the liver parenchyma at an early observation time and maintained the intensity until 600 s, like Sonazoid®. The renal evaluation results indicated there were no statistically significant differences in time‐to‐peak for the renal cortex or medulla among the agents. Compared with the other two agents, SonoVue® had the lowest peak enhancement for the renal cortex and medulla. No dogs had any adverse reactions during or after the study. All three agents provided adequate results for left ventricular endocardial border delineation, and Visphere™ may have the same potential as Sonazoid® to detect and characterize hepatic lesions. Visphere™ and Sonazoid® may offer better visualization quality to evaluate renal function. In conclusion, the novel contrast agent, Visphere™, is comparable with commercial agents and could be applied in different major organs in dogs. [ABSTRACT FROM AUTHOR]

Lymphangiography can be useful for preoperative planning in chylothorax. Conventional ultrasound‐guided intranodal injection can be difficult in some cases and is dependent upon operator skill. Alternative methods have been proposed to simplify the procedure, but their feasibility has not been sufficiently evaluated in clinical cases. The primary purpose of this multicenter, retrospective, descriptive study was to assess the feasibility and describe the clinical findings of CT lymphangiography by intrametatarsal pad injection in dogs with naturally occurring chylothorax. Twenty dogs were analyzed, and enhancement of thoracic ducts (TDs) was successful in 18 (90%) dogs within 5‐14 min after initiating the injection, while successful enhancement of the lymphatic vessels cranial to the popliteal lymph nodes was seen in all dogs within 5 min after injection. The dose with good success to achieve TD enhancement was 1 mL/kg (concentration 350 mg I/kg). Only two dogs had mild discomfort after recovery from general anesthesia. Computed tomography lymphangiography by intrametatarsal pad injection is a feasible, easy, and safe procedure, which could provide adequate TD and cisterna chyli enhancement, identify TD number and cisterna chyli location and structure, and contribute to surgical planning. [ABSTRACT FROM AUTHOR]

Tree peony (Paeonia Sect. Moutan) is a famous ornamental plant, with huge historical, cultural, and economic significance worldwide. In this study, we reported the ~13.79 Gb draft genome of a wide‐grown Paeonia suffruticosa cultivar "Luo shen xiao chun," representing the largest sequenced genome in dicots to date. Phylogenetic analyses based on genome sequences demonstrated that P. suffruticosa was placed as sister to Vitales, and they together formed a clade that was sister to Rosids, weakly supporting a relationship of ((Saxifragales and Vitales) and Rosids). The identification and expression analysis of MADS‐box genes based on the genome assembly and de novo transcriptome assembly of P. suffruticosa revealed that the function of C class genes was restricted in flower development, which might be responsible for the stamen petalody in tree peony cultivars. Overall, the first sequenced genome in the family Paeoniaceae provides an important resource for the origin, domestication, and evolutionary study as well as cultivar breeding in tree peony. [ABSTRACT FROM AUTHOR]

Objective: To compare the psychiatric service utilization between patients who only received long‐acting injectable antipsychotics (LAIAs) and those who only received oral antipsychotics (OAPs) in the maintenance treatment of chronic schizophrenia. Methods: We constructed a cohort of chronic schizophrenia patients who underwent maintenance treatment from the Taiwan National Health Insurance Research Database in 2011 and followed these patients for 12 months. We included patients who had been diagnosed with schizophrenia for at least 3 years, were not hospitalized in 2011, and had received 1 year of maintenance treatment. Inverse probability of treatment weighting logistic, linear, and negative binomial regression models were used to estimate associated psychiatric services utilization and adjust for covariate imbalances between the LAIAs and OAPs groups. Results: Among 40,194 patients, 948 (2.36%) received only LAIAs and 39,246 (97.64%) received only OAPs. Compared with those who received only OAPs, the sole LAIAs users were associated with a lower percentage of psychiatric hospitalization (8.4% and 5.8%, respectively; odds ratio: 0.63, p <.01), shorter lengths of hospitalization days (82.8 and 65.9, respectively; coefficient [b]: −16.87, p =.03), and fewer emergency room visits (2.3 and 1.8, respectively; b: −0.24, p <.01) per patient. Conclusions: Chronic schizophrenia patients who received only LAIs had a lower risk of disease relapse and a reduction in psychiatric service utilization than those receiving only OAPs. [ABSTRACT FROM AUTHOR]

Several previous studies have emphasized the importance of situating students in authentic learning or problem‐solving contexts to enhance their learning performances. However, some challenges of situated learning have been stated, such as the lack of effective learning support or concrete objective design to improve students' learning engagement, problem‐solving competences and their active thinking. In this study, a mobile technology‐supported experiential learning system was developed to improve students' problem‐solving competences as well as their learning performances, attitudes and collective efficacy. Moreover, an experiment was conducted on an environmental science course in an elementary school to compare the effects of this method with those of the conventional situated mobile learning approach on students' learning effectiveness. The experimental results display that the implemented approach can significantly enhance students' learning achievements, environmental attitudes and collective efficacy; furthermore, the students who learned with the implemented approach showed higher problem‐solving competence than those who learned with the conventional situated mobile learning approach, implying a noticeable reference for conducting experiential learning activities in environmental science education. Furthermore, the promotion of students' active thinking in the mobile technology‐supported experiential learning is discussed. Practitioner NotesWhat is already known about this topic The importance of situating students in authentic learning or problem‐solving contexts to enhance their learning performances has been emphasized.Some challenges of situated learning have been stated, such as the lack of effective learning support or concrete objective design to improve students' learning engagement, problem‐solving competences and active thinking.Properly integrating technology into instruction is most effective in an authentic learning context.What this paper adds A mobile technology‐supported experiential learning system was designed to conduct an authentic learning activity.The proposed approach can significantly enhance students' learning achievements, environmental attitudes and collective efficacy.The students who learned with the proposed approach showed higher problem‐solving competence than those who learned with the conventional situated mobile learning approach.The promotion of students' active thinking while learning with the mobile technology‐supported experiential learning system is discussed.Implications for practice and/or policy The mobile technology‐supported experiential learning system is beneficial to students in an authentic learning environment as it triggers their active thinking.Such an approach can be designed with authentic learning activities in other courses by replacing the authentic objects and learning materials.It would be interesting to probe students' social interactions and learning patterns in an experiential collective learning activity. [ABSTRACT FROM AUTHOR]

Background and Aim: Portal vein tumor thrombus (PVTT) predicts a poor prognosis in hepatocellular carcinoma (HCC) patients. Platelets (PLTs) play an important role in HCC progression and metastasis. However, the relationship between PLTs and PVTT remains unclear. This study aimed to evaluate the value of PLT counts in the prognosis of HCC patients with PVTT after hepatectomy. Methods: From January 2002 to December 2012, 694 HCC patients with PVTT after hepatectomy were evaluated. The patients were divided into the thrombocytopenia group (PLT < 100 × 109/L), the normal group, and the thrombocytosis group (PLT > 300 × 109/L) based on the preoperative PLT level. A propensity score matching (PSM) analysis was used. Results: Before the PSM, PVTT patients with thrombocytopenia exhibited longer recurrence‐free survival (RFS) and overall survival (OS) compared with those with normal PLT counts (both P < 0.001) or thrombocytosis (P = 0.008 and P = 0.046). For the thrombocytopenia group and the normal group, the 1‐, 2‐, and 3‐year RFS values were 30.0%, 17.6%, and 15.7% and were 10.8%, 6.6%, and 5.8% (P < 0.001), respectively; the 1‐, 2‐, and 3‐year OS values were 61.9%, 37.9%, and 31.2% and were 38.3%, 23.3%, and 16.0% (P < 0.001), respectively. After the PSM, the median survival time was 16.6 versus 8.6 months (P < 0.002) in the two groups. A subgroup analysis revealed that thrombocytopenia is associated with improved OS in those with type I PVTT (P = 0.021) or type II PVTT (P = 0.029). Conclusion: According to the PSM, preoperative thrombocytopenia predicts an increased RFS and OS in HCC patients with PVTT after hepatectomy. [ABSTRACT FROM AUTHOR]

We previously found that circulating β2‐glycoprotein I inhibits human endothelial cell migration, proliferation, and angiogenesis by diverse mechanisms. In the present study, we investigated the antitumor activities of β2‐glycoprotein I using structure‐function analysis and mapped the critical region within the β2‐glycoprotein I peptide sequence that mediates anticancer effects. We constructed recombinant cDNA and purified different β2‐glycoprotein I polypeptide domains using a baculovirus expression system. We found that purified β2‐glycoprotein I, as well as recombinant β2‐glycoprotein I full‐length (D12345), polypeptide domains I‐IV (D1234), and polypeptide domain I (D1) significantly inhibited melanoma cell migration, proliferation and invasion. Western blot analyses were used to determine the dysregulated expression of proteins essential for intracellular signaling pathways in B16‐F10 treated with β2‐glycoprotein I and variant recombinant polypeptides. Using a melanoma mouse model, we found that D1 polypeptide showed stronger potency in suppressing tumor growth. Structural analysis showed that fragments A and B within domain I would be the critical regions responsible for antitumor activity. Annexin A2 was identified as the counterpart molecule for β2‐glycoprotein I by immunofluorescence and coimmunoprecipitation assays. Interaction between specific amino acids of β2‐glycoprotein I D1 and annexin A2 was later evaluated by the molecular docking approach. Moreover, five amino acid residues were selected from fragments A and B for functional evaluation using site‐directed mutagenesis, and P11A, M42A, and I55P mutations were shown to disrupt the anti‐melanoma cell migration ability of β2‐glycoprotein I. This is the first study to show the therapeutic potential of β2‐glycoprotein I D1 in the treatment of melanoma progression. [ABSTRACT FROM AUTHOR]

BACKGROUND Astragalus membranaceus is a traditional Chinese medicine that has a long history of medical applications. It is of interest to investigate the functional components of A. membranaceus waste with regard to its development and utilization and increasing resource utilization. RESULTS: The protein AMWP was isolated from the A. membranaceus waste. This protein was further purified by DEAE‐cellulose‐52 chromatography and Sephadex G‐200 size‐exclusion chromatography to obtain three fractions, named AMWPDG2, AMWPDG4 and AMWPDG6. Then, their immunomodulatory activities were evaluated by using cell model experiments. The results indicated that the protein fractions could significantly increase the proliferation of splenic lymphocytes, peritoneal macrophages and bone‐marrow‐derived cells (BMDCs). AMWPDG2 showed the highest immunocompetence. AMWPDG2, AMWPDG4 and AMWPDG6 not only significantly improved the phagocytosis and immunomodulatory factors (interleukin (IL)‐6, tumor necrosis factor‐α, nitric oxide, hydrogen peroxide) secretion of peritoneal macrophages, but also promoted the expression of inflammatory cytokines (IL‐6, IL‐12 p40, IL‐1β, IL‐1α) and chemokines (CXCL1, CCL3) in BMDCs. CONCLUSION: Taken together, these results indicated that three protein fractions from the A. membranaceus waste might be a potential natural immunomodulator. Moreover, it also provided the theoretical basis for further researching the mechanism of AMWPDG2, AMWPDG4 and AMWPDG6 on improving the immune response. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Aim: Because of the rarity of hepatic vein tumor thrombus (HVTT) in patients with hepatocellular carcinoma (HCC), little is known about HVTT. Thus, the survival benefit of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) for HCC patients with HVTT or inferior vena cava tumor thrombus (IVCTT) remains controversial. We aimed to explore the survival benefits of LR versus TACE for the treatment of these patients. Methods: From 2012 to 2016, a total of 276 patients with HVTT or IVCTT who underwent liver resection or TACE were enrolled in this study. Patients in the LR group were matched at a 1:1 ratio with patients treated with TACE as an initial treatment (TACE group). Clinical characteristics, overall survival, and disease‐free survival were analyzed. Results: The median survival time in the LR group was 4.7 months longer than that in the TACE group before PSM (19.4 vs. 14.7 months, P = 0.006) and 6.9 months longer than that in the TACE group after PSM (20.9 vs. 14.0 months, P = 0.019). The median disease‐free survival time in the LR group was 3.2 months longer than that in the TACE group before PSM (12.3 vs. 9.1 months, P = 0.038) and 5.8 months longer than that in the TACE group after PSM (13.0 vs. 7.2 months, P = 0.011). Conclusion: Liver resection provides a good prognosis for HCC patients with HVTT or IVCTT compared with patients undergoing TACE, and coexistence with portal vein tumor thrombus is the most important factor related to survival. [ABSTRACT FROM AUTHOR]

Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity. Twelve 3‐week‐old male C57BL/6J mice were divided into two groups, receiving deionized drinking water (control group) or 50 mg/L of sodium arsenite (via drinking water) for 24 weeks. Learning and memory abilities were tested by Morris water maze (MWM) test. Pathological and morphological changes of hippocampus and cerebellum were captured via transmission electron microscopy (TEM). Metabolic alterations were analyzed by gas chromatography‐mass spectrometry (GC‐MS). MWM test confirmed impairments of learning and memory abilities of mice after chronic As exposure. Metabolomics identifications indicated that tyrosine increased and aspartic acid (Asp) decreased simultaneously in both hippocampus and cerebellum. Intermediates (succinic acid) and indirect involved components of tricarboxylic acid cycle (proline, cysteine, and alanine) were found declined in cerebellum, indicating disordered energy metabolism. Our findings suggest that these metabolite alterations are related to As‐induced disorders of amino acids and energy metabolism, which might therefore, play an important part in mechanisms of As neurotoxicity. [ABSTRACT FROM AUTHOR]

Mitomycin C (MC) is a well‐known DNA alkylating agent. MC analog, 10‐decarbamoyl mitomycin C (DMC), unlike MC, has stronger effects on cancer with p53 mutation. We previously demonstrated that MC/DMC could activate p21WAF1/CIP1 in MCF‐7 (p53‐proficient) and K562 (p53‐deficient) cells in a p53‐independent mode. This study aimed to elucidate the upstream signaling pathway of p21WAF1/CIP1 activation triggered by MC/DMC. Besides p53, Akt plays an important role on deactivating p21WAF1/CIP1. The results showed that MC/DMC inhibited Akt in MCF‐7 cells, but not in K562 cells. By knocking down p53, the Akt inhibition in MCF‐7 cells was alleviated. This implied that the deactivated Akt caused by MC/DMC was p53‐dependent. With Akt activator (SC79), p21WAF1/CIP1 activation triggered by MC/DMC in MCF‐7 cells was not reduced. This indicated that Akt inhibition triggered by MC/DMC was not associated with MC/DMC‐induced p21WAF1/CIP1 activation. Label‐free quantitative proteomic profiling analysis revealed that DMC has a stronger effect on down‐regulating the PI3K/Akt signaling pathway in MCF‐7 cells as compared to MC. No significant effect of MC/DMC on PI3K/Akt in K562 cells was observed. In summary, MC/DMC regulate Akt activation in a p53‐dependent manner. This Akt deactivation is not associated with p21WAF1/CIP1 activation in response to MC/DMC. Deactivation of AKT was observed in MCF‐7 cells treated with mitomycin C (MC) and its analog 10‐decarbamoyl mitomycin C (DMC) in a p53‐dependent manner. However, deactivation of Akt did not associate with p21 activation in response to MC and DMC in MCF‐7 cells. Proteomic profiling analysis showed that DMC has a stronger effect on down‐regulation of Akt protein expression in MCF‐7 cells as compared to MC, while there is no effect of MC/DMC on Akt signaling pathway in K562 cells. [ABSTRACT FROM AUTHOR]

Abstract: Mitomycin C (MC), an antitumor drug, and decarbamoylmitomycin C (DMC), a derivative of MC, alkylate DNA and form deoxyguanosine monoadducts and interstrand crosslinks (ICLs). Interestingly, in mammalian culture cells, MC forms primarily deoxyguanosine adducts with a 1“‐R stereochemistry at the guanine–mitosene bond (1”‐α) whereas DMC forms mainly adducts with a 1“‐S stereochemistry (1”‐β). The molecular basis for the stereochemical configuration exhibited by DMC has been investigated using biomimetic synthesis. Here, we present the results of our studies on the monoalkylation of DNA by DMC. We show that the formation of 1“‐β‐deoxyguanosine adducts requires bifunctional reductive activation of DMC, and that monofunctional activation only produces 1”‐α‐adducts. The stereochemistry of the deoxyguanosine adducts formed is also dependent on the regioselectivity of DNA alkylation and on the overall DNA CG content. Additionally, we found that temperature plays a determinant role in the regioselectivity of duplex DNA alkylation by mitomycins: At 0 °C, both deoxyadenosine (dA) and deoxyguanosine (dG) alkylation occur whereas at 37 °C, mitomycins alkylate dG preferentially. The new reaction protocols developed in our laboratory to investigate DMC‐DNA alkylation raise the possibility that oligonucleotides containing DMC 1“‐β‐deoxyguanosine adducts at a specific site may be synthesized by a biomimetic approach. [ABSTRACT FROM AUTHOR]

Background: The coexistence of hepatic iron and fat is common in patients with hyperferritinemia, which plays an interactive and aggressive role in the progression of diseases (fibrosis, cirrhosis, and hepatocellular carcinomas).Purpose: To evaluate a modified high-speed T2 -corrected multi-echo, single voxel spectroscopy sequence (HISTOV) for liver iron concentration (LIC) quantification in patients with hyperferritinemia, with simultaneous fat fraction (FF) estimation.Study Type: Retrospective cohort study.Population: Thirty-eight patients with hyperferritinemia were enrolled.Field Strength/sequence: HISTOV, a fat-saturated multi-echo gradient echo (GRE) sequence, and a spin echo sequence (FerriScan) were performed at 1.5T.Assessment: R2 of the water signal and FF were calculated with HISTOV, and R2* values were derived from the GRE sequence, with R2 and LIC from FerriScan serving as the references.Statistical Tests: Linear regression, correlation analyses, receiver operating characteristic analyses, and Bland-Altman analyses were conducted.Results: Abnormal hepatic iron load was detected in 32/38 patients, of whom 10/32 had coexisting steatosis. Strong correlation was found between R2* and FerriScan-LIC (R2 = 0.861), and between HISTOV-R2_ water and FerriScan-R2 (R2  = 0.889). Furthermore, HISTOV-R2_ water was not correlated with HISTOV-FF. The area under the curve (AUC) for HISTOV-R2_ water was 0.974, 0.971, and 1, corresponding to clinical FerriScan-LIC thresholds of 1.8, 3.2, and 7.0 mg/g dw, respectively. No significant difference in the AUC was found between HISTOV-R2_ water and R2* at any of the LIC thresholds, with P-values of 0.42, 0.37, and 1, respectively. HISTOV-LIC showed excellent agreement with FerriScan-LIC, with a mean bias of 0.00 ± 1.18 mg/g dw, whereas the mean bias between GRE-LIC and FerriScan-LIC was 0.53 ± 1.49 mg/g dw.Data Conclusion: HISTOV is useful for the quantification and grading of liver iron overload in patients with hyperferritinemia, particularly in cases with coexisting steatosis. HISTOV-LIC showed no systematic bias compared with FerriScan-LIC, making it a promising alternative for iron quantification.Level Of Evidence: 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018. [ABSTRACT FROM AUTHOR]

Abstract: Adipocyte fatty acid‐binding protein (FABP4) is abundant in macrophage and adipocyte. It is known to be involved in lipid metabolism. The role of FABP4 has been reported in various cancers, such as non‐small cell lung cancer, breast cancer, ovarian cancer, and prostatic cancer. However, its role remains unclear in hepatocellular carcinoma (HCC). In our study, we investigated the expression of FABP4 at both mRNA and protein levels, and by examining 175 cases of patients with cancer of the liver tissue microarray, the significance between the expression of FABP4 and clinical characteristics had been discussed. We found that FABP4 was lowly expressed in HCC tissues compared to the corresponding tissue adjacent, and the expression of FABP4 was significantly associated with the tumor size, PVTT, recurrence‐free survival and overall survival. Moreover, multivariate Cox regression analysis indicated that the expression of FABP4, Alb, AFP, HBsAg, and PVTT were independent risk factors for overall survival, and the expression of FABP4, AFP, GGT, tumor size, and encapsulation were independent risk factors for HCC recurrence. In addition, we revealed that FABP4 suppressed HCC cell proliferation and invasion in vitro. Moreover, overexpression of FABP4 led to inhibit tumor growth and decreased tumor volume in vivo. These phenotypes were associated with altered expression of Snail and p‐STAT3. Our studies thus suggest that FABP4 could be a potential target for HCC chemotherapy. [ABSTRACT FROM AUTHOR]