Prediction of Fuhrman grade of renal clear cell carcinoma by multimodal MRI radiomics: a retrospective study.

AIM: To explore the value of multimodal magnetic resonance imaging (MRI) radiomics combined with traditional radiologist-defined semantic characteristics and conventional (cMRI) and functional MRI (fMRI) texture features in predicting Fuhrman grade of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The data of 89 patients with histopathologically proven ccRCC (low-grade, 54; high-grade, 35) were collected. Texture features were extracted from cMRI (T1- and T2-weighted imaging) and fMRI (Dixon-MRI; blood-oxygen-level dependent [BOLD]-MRI; and susceptibility-weighted imaging [SWI]) images, and the traditional characteristics (TC) were evaluated. Logistic regression analysis was performed to develop models based on TC, cMRI, and fMRI texture features for grading. Receiver operating characteristic (ROC) curve analysis and leave-group-out cross-validation (LGOCV) were performed to test the reliability of combined models. RESULTS: Two T2-weighted imaging-based, two Dixon_W-based, one Dixon_F-based, one BOLD-based, and three SWI-based texture features, and three TC were extracted for feature selection. TC, cMRI, fMRI, cMRI+fMRI, cMRI+TC, fMRI+TC, and cMRI+fMRI+TC models were constructed. The AUC of the cMRI+fMRI+TC model for differentiating high- from low-grade ccRCC was 0.74, with 81.42% accuracy, 75.93% sensitivity, and 91.43% specificity. The fMRI+TC model exhibited a performance similar to that of the cMRI+fMRI+TC model (p>0.05). The areas under the curve (AUCs) of the fMRI+TC and cMRI+fMRI+TC models were significantly higher than those of the other five models (all p<0.05). For the cMRI+fMRI+TC model, the mean accuracy was 85.40% after 100 LGOCV for the test sets. CONCLUSION: Multimodal MRI radiomics combined with TC, cMRI, and fMRI texture features may be a reliable quantitative approach for differentiating high-grade ccRCC from low-grade ccRCC.

Neutral particles pushed or pulled by laser pulses: erratum.

We present an erratum to our Letter [Opt. Lett.41, 230 (2016)10.1364/OL.41.000230]. This erratum corrects three typing errors. The corrections have no influence on the results and conclusions of the original Letter.

Pregnancy outcome after in-vitro fertilization/intracytoplasmic sperm injection in women with congenital uterus didelphys.

OBJECTIVE: To investigate the pregnancy and obstetric outcomes of patients with congenital uterus didelphys who achieved clinical pregnancy after in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: This was a retrospective matched-cohort study of 83 infertile patients with uterus didelphys who underwent IVF/ICSI and achieved clinical pregnancy from January 2005 to December 2018 at our center. For each patient in the study group, three control patients with normal uterine morphology who underwent IVF/ICSI in 2018 were selected randomly. Patients in the two groups were matched for number of gestational sacs, maternal age, infertility type, cause of infertility, fertilization method, endometrial thickness 1 day before embryo transfer and number of embryos transferred. The classification of congenital uterine anomalies was based on the American Fertility Society system (1988). The pregnancy and obstetric outcomes of the didelphic and control groups were compared separately for singleton and twin pregnancies, and for all pregnancies combined. RESULTS: In singleton pregnancies, women with uterus didelphys had increased risk of preterm birth (odds ratio (OR), 4.68; rate difference (RD), 0.14; P < 0.001), Cesarean section (OR, 2.80; RD, 0.17; P = 0.016) and birth weight < 2500 g (OR, 4.06; RD, 0.10; P = 0.017) compared to women with normal uterine morphology. In twin pregnancies, the presence of uterus didelphys was associated with increased risk of preterm delivery (OR, 4.79; RD, 0.37; P = 0.006), perinatal mortality (OR, 3.16; RD, 0.19; P = 0.043) and birth weight < 2500 g (OR, 9.57; RD, 0.35; P = 0.001). CONCLUSIONS: The presence of uterus didelphys was associated with significantly increased risk of some adverse pregnancy outcomes compared to pregnancies with normal uterine morphology in women who underwent IVF/ICSI. A twin pregnancy in women with uterus didelphys was associated with worse perinatal outcome. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

High dose insulin promotes the proliferation of vascular smooth muscle cells via AP-1/SM-α pathway.

Proliferation of vascular smooth muscle cells (VSMCs) participates in multiple cardiovascular disorders, while the mechanism remains unclear. This study aims to investigate the effects of insulin on VSMC. Insulin was used to stimulate rat VSMCs, and the effects on cell cycle and proliferation were subsequently analyzed using flow cytometry. Furthermore, AP-1 and SM-α overexpression vectors were constructed and transfected into VSMCs. AP-1 and SM-α were inhibited by SR11302 and SM-α siRNA, respectively. The mRNA and protein expression levels were subsequently detected using the reversetranscription quantitative polymerase chain reaction and western blotting, respectively. AP-1 and SM-α gene promoter binding sites were determined using luciferase and chromatin immunoprecipitation assays. As a result, we found that high dose of insulin promoted proliferation of VSMCs and increased the percentage of cells in the S phase by downregulating AP-1. AP-1 was identified to bind to the SM-α gene promoter at locus 2-177 to upregulate SM-α gene expression. Inhibition of AP-1 led to the decrease of SM-α expression. Overexpression of SM-α directly suppressed proliferation of VSMCs, while knocking it down promoted the process. Therefore, this study revealed that insulin downregulated the expression of the SM-α gene by inhibiting AP-1, which in turn facilitated proliferation of VSMCs.

Expressions of SAA, CRP, and FERR in different severities of COVID-19.

OBJECTIVE: To explore the expression and significance of SAA, CRP and FERR in patients diagnosed with COVID-19. PATIENTS AND METHODS: A total of 225 patients diagnosed with COVID-19 who were admitted to the North Hospital of First Hospital in Changsha, China, from 9th February 2020 to 7th March 2020 were enrolled. Their general data, laboratory test results and levels of SAA, CRP and FERR were extracted from electronic medical records. RESULTS: Age was an important risk factor for the severity of COVID-19 in the patients. Compared with the non-severe group, the severe group showed statistical significance in the levels of total protein, albumin, ALT and AST in liver function, UA in renal function, myocardial enzyme CK-MB and LDH, and immunoglobulin IgG and IgM. The levels of SAA, CRP, and FERR were significantly increased in patients with severe COVID-19. ROC curve analysis results showed that the AUC, from small to large, was as follows: SAA+CRP+FERR, CRP + FERR, SAA + CRP, SAA + FERR, SAA, FERR, and CRP, which indicated the benefit of the combination of the three indicators. The sensitivity and specificity of the combined detection of the three indicators were higher than those of the detection of any single indicator or two combined indicators. A Spearman correlation analysis of the data showed that the initial CRP/SAA, SAA/FERR, and CRP/FERR were positively correlated. The continuous results of SAA, CRP and FERR throughout the study period showed that the values of the severe group on a given day were higher than those of the non-severe group; the values of the two groups peaked on the 5th or 7th day and then decreased, and the decreasing trend of the severe group was more evident. CONCLUSIONS: SAA, CRP and FERR are sensitive serological indicators used to evaluate the severity of COVID-19. The combined detection of serum SAA, FERR, and CRP, which are positively related to COVID-19 infection, offers guiding significance for the occurrence of COVID-19 infection and the severity of the disease. Such detection provides effective detection indicators for the progress and prognosis of COVID-19; these indicators will enable effective intervention measures to be implemented in time and the rates of severe illness and mortality to be reduced.

[Research progress in imaging characteristics of precancerous nodules in hepatocellular carcinoma cells].

Hepatocarcinogenesis is a multi-step process in which detection of precancerous lesions and advanced hepatocellular carcinoma in its progressive stage is crucially important for predicting tumor behavior, estimating the extent of lesions, implementing the optimal treatment strategy, and improving the survival of patients. The rapid development and wide application of liver imaging technology, especially the application of hepatocyte-specific gadoxetate disodium MRI contrast agent (Gd-EOB-DTPA MRI), not only provide information on vascular changes of liver nodules and hepatocyte function, but also has become a precise diagnostic method for differentiating cirrhotic regenerative nodule (RN), low-grade dysplastic nodule (LGDN), high-grade dysplastic nodule (HGDN), early hepatocellular carcinoma and HCC. Hence, the risk for malignant progression is stratified. This review summarizes the value of Gd-EOB-DTPA MRI for early HCC diagnosis and analyzes the key concepts in the multi-step process of HCC development as well as the imaging manifestations of precancerous lesions that may eventually be transformed into typical HCC.

[Risk analysis for hypervascular transformation of precancerous lesion of hepatocellular carcinoma].

Objective: To investigate the risk factors for diagnosis of transformation of high-grade dysplastic nodules (HGDN) to hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease with gadoxetate disodium-enhanced magnetic resonance imaging (MRI). Methods: 2 037 cases that underwent gadoxetate disodium-enhanced magnetic resonance imaging from January 2012 to December 2014 were retrospectively analyzed. 51 cases of HGDN with a background of chronic liver disease were screened and followed-up for at least 2 times with gadoxetate disodium-enhanced MRI scans and contrast enhanced CT scans was performed within 1 month before and after the first MRI. The endpoint of study was transformation of HGDN to hypervascular hepatocellular carcinoma, with a deadline of April 2019. Transformation was divided into transformed (group A) and untransformed (group B) group according to the presence or absence of hypervascularization. Linear regression was used to analyze the possible risk factors for hypervascular transformation. Results: There were 36 nodules in group A and 79 nodules in group B, and hypervascular transformation rate was 31.3% (36/115). On univariate analysis, the length and diameter of nodule was > 10.2 mm (P = 0.034), with annual growth rate > 2% (P < 0.001), and lipid content (P = 0.007) was related to the occurrence of hypervascularity. On multivariate analysis, the annual growth rate of nodules was an independent risk factor for the occurrence of hypervascularity (P < 0.000 1). Conclusion: The annual growth rate of HGDN in patients with chronic liver disease diagnosed with gadoxetate disodium-enhanced MRI imaging can be used as a potential predictor of hypervascularization.

Molecular characterization of prophenoloxidase-1 (PPO1) and the inhibitory effect of kojic acid on phenoloxidase (PO) activity and on the development of Zeugodacus tau (Walker) (Diptera: Tephritidae).

Phenoloxidase (PO) plays a key role in melanin biosynthesis during insect development. Here, we isolated the 2310-bp full-length cDNA of PPO1 from Zeugodacus tau, a destructive horticultural pest. qRT-polymerase chain reaction showed that the ZtPPO1 transcripts were highly expressed during larval-prepupal transition and in the haemolymph. When the larvae were fed a 1.66% kojic acid (KA)-containing diet, the levels of the ZtPPO1 transcripts significantly increased by 2.79- and 3.39-fold in the whole larvae and cuticles, respectively, while the corresponding PO activity was significantly reduced; in addition, the larval and pupal durations were significantly prolonged; pupal weights were lowered; and abnormal phenotypes were observed. An in vitro inhibition experiment indicated that KA was an effective competitive inhibitor of PO in Z. tau. Additionally, the functional analysis showed that 20E could significantly up-regulate the expression of ZtPPO1, induce lower pupal weight, and advance pupation. Knockdown of the ZtPPO1 gene by RNAi significantly decreased mRNA levels after 24 h and led to low pupation rates and incomplete pupae with abnormal phenotypes during the larval-pupal interim period. These results proved that PO is important for the normal growth of Z. tau and that KA can disrupt the development of this pest insect.

Imaging findings of adrenal primitive neuroectodermal tumors: a series of seven cases.

OBJECTIVE: To explore the imaging features of adrenal primitive neuroectodermal tumors (PNETs). MATERIALS AND METHODS: This retrospective study included seven patients with surgically and pathologically confirmed adrenal PNETs. Among them, six underwent computed tomography (CT) scans, and one underwent magnetic resonance imaging. The imaging findings, including size, shape, margin, hemorrhage, calcification, cystic degeneration, regional lymph nodes involvement, tumor thrombus formation and enhancement pattern, were retrospectively analyzed. RESULTS: Among the seven adrenal PNET patients, six were male, and one was female. The median age was 26 years (range 2-56 years). The disease generally presented with either insidious symptoms (n = 4) or non-specific symptoms, including right flank pain (n = 1) and left upper abdominal discomfort (n = 2). On the pre-enhanced CT images, the tumor usually appeared as a well-defined, rounded or oval, heterogeneous mass without calcification. Certain tissue characteristics, such as cystic degeneration (n = 5), capsule (n = 4) and hemorrhage (n = 2), were observed. Regional lymph node involvement was observed in three cases, and renal vein thrombus was observed in one case. All cases showed mild heterogeneous enhancement of the tumor on the enhanced CT images. CONCLUSION: An adrenal PNET commonly presents as a relatively large, well-defined, heterogeneous mass with cystic degeneration, necrosis and a characteristic mild contrast-enhancement pattern on multiphase enhanced images. PNET should be considered when the diagnosis of common tumors is not favored by signs on images. CLINICAL TRIAL REGISTRATION STATEMENT: This study was approved by the medical ethics committee of Xiangya Hospital, Central South University. The approval number is 201512538.

Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma.

BACKGROUND: Allergic asthma is characterized by inflammation and airway remodelling. Airway remodelling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodelling. However, the role of calpain in airway smooth muscle remodelling remains unknown. OBJECTIVE: To investigate the role of calpain in asthmatic airway remodelling as well as the underlying mechanism. METHODS: The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analysed. RESULTS: Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodelling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein, which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis, and cell proliferation of ASMCs and attenuated airway smooth muscle remodelling in mouse asthma models. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signalling pathway, thereby regulating airway smooth muscle remodelling in asthma.

Osteoinduction of Calcium Phosphate Ceramics in Four Kinds of Animals for 1 Year: Dog, Rabbit, Rat, and Mouse.

INTRODUCTION: Bone grafts are in great demand. Synthetic materials have been extensively studied as substitutes for autografts. Calcium phosphate ceramics are promising synthetic bone replacement materials. Because they share chemical similarities with human bone mineral, they show excellent biocompatibility and osteoinductivity. OBJECTIVE: Calcium phosphate ceramics have been used to fill bone defects in preclinical study in a variety of animals. This study aimed to investigate the osteogenesis ability of calcium phosphate ceramics in 4 kinds of animals. METHODS: Φ3 × 5 mm hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) cylinders were implanted into the dorsal muscle of rats and mice, whereas Φ5 × 10 mm cylinders were implanted into the dorsal muscle of dogs and rabbits. One year after implantation, the ceramics were harvested to perform hematoxylin and eosin (HE) staining and Masson-trichrome staining. The new bone tissues were observed and the area percentage of new bone was compared in the 4 kinds of animals. RESULTS: A large number of new bone and bone marrow tissues were observed in dogs, rabbits, and mice, but not in rats; and the area percentage of new bone in mice was significantly higher than that in dogs and rabbits (P < .05). Calcium phosphate ceramics have good biocompability and biological safety, and the degree of ease of osteogenesis was as follows: mouse > dog > rabbit > rat. CONCLUSION: To achieve better effects for bone transplantation, mouse should be chosen as the preferred experimental model based on these advantages: economic, convenience, and osteogenesis ability.

CT findings of adrenal schwannoma.

AIM: To analyse the computed tomography (CT) imaging features of patients with adrenal schwannoma. MATERIALS AND METHODS: Eight cases of adrenal schwannoma confirmed by histopathology were included in this study. All eight patients had undergone multiphase CT examinations. The features of the adrenal schwannoma in the CT images were analysed retrospectively in detail, including size, shape, margin, radiodensity, calcification, and enhancement pattern. RESULTS: There were six male and two female patients, with a median age of 44.5 years (range, 25-52 years). Two patients complained of right flank pain, and two with left upper abdominal discomfort, while the remaining patients were diagnosed by routine ultrasound examinations. On unenhanced CT images, all cases of adrenal schwannoma were well circumscribed, rounded or oval, heterogeneous masses with cystic components, with two cases exhibiting calcification, and three cases with septa. On enhanced CT images, all cases displayed mild heterogeneous enhancement of the tumour during the arterial phase, and progressive enhancement during the portal venous phase and equilibrium phase. CONCLUSION: Adrenal schwannoma commonly presents as a well-defined unilateral mass with cystic degeneration, septa, and a characteristic progressive contrast-enhancement pattern on multiphase enhanced scans.

Neutral particles pushed or pulled by laser pulses.

Acceleration of neutral particles is of great importance in many areas, such as controlled chemical reactions, atomic nanofabrication, and atom optics. Recent experimental studies have shown that pulsed lasers can be used to push neutral Rydberg atoms forward [Nature 461, 1261 (2009)10.1038/nature08481; Nat. Photonics 6, 386 (2012)10.1038/nphoton.2012.87]. Our simulation shows that pulsed lasers can also be used to pull Rydberg atoms back toward a light source. In particular, we proposed a method of using two laser pulses on a neutral atom, then selective operations on the neutral atom (pushing or pulling) can be performed by adjusting the delay time between the two laser pulses.

Association of the genetic polymorphisms of NFKB1 with susceptibility to ovarian cancer.

Nuclear factor-κB (NF-κB), a transcription factor that is activated by various stimuli, is associated with the pathogenesis of several cancers. One functional polymorphism, -94 insertion/deletion ATTG (rs28362491), in the human NFKB1 gene (one member of the NF-κB gene family) is associated with increased risk of various cancers. However, only one study has reported that rs28362491 is significantly associated with ovarian cancer. The aim of this study was to analyze the association between single nucleotide polymorphisms (SNPs) and haplotypes in the NFKB1 gene and the risk of ovarian cancer in a Chinese population. We examined the potential association between ovarian cancer and 15 SNPs (rs28362491, rs3774932, rs1598856, rs230531, rs230530, rs230528, rs230521, rs230498, rs230539, rs1005819, rs3774956, rs4648055, rs4648068, rs3774964, rs3774968) of the NFKB1 gene using the MassARRAY system. Participants included 411 patients with ovarian cancer and 438 healthy controls. The results showed that the allelic or genotypic frequencies of three polymorphisms, including rs28362491 (promoter region), rs230521 (intron 4), and rs4648068 (intron 12), in the patients with ovarian cancer, were significantly different from those in the healthy controls. Strong linkage disequilibrium was observed in four blocks (D' > 0.9). Significantly more A-C (block 2: rs230528-rs230521) haplotypes (P = 0.0003 after Bonferroni's corrections) and G-A-A (block 4: rs4648068-rs3774964-rs3774968) haplotypes (P = 0.021) were found in the patients with ovarian cancer. These findings point to a role of the NFKB1 polymorphism in patients with ovarian cancer among a Chinese Han population, and may be informative for future genetic or biological studies on ovarian cancer.

Drastic Pressure Effect on the Extremely Large Magnetoresistance in WTe2: Quantum Oscillation Study.

The quantum oscillations of the magnetoresistance under ambient and high pressure have been studied for WTe2 single crystals, in which extremely large magnetoresistance was discovered recently. By analyzing the Shubnikov-de Haas oscillations, four Fermi surfaces are identified, and two of them are found to persist to high pressure. The sizes of these two pockets are comparable, but show increasing difference with pressure. At 0.3 K and in 14.5 T, the magnetoresistance decreases drastically from 1.25×10(5)% under ambient pressure to 7.47×10(3)% under 23.6 kbar, which is likely caused by the relative change of Fermi surfaces. These results support the scenario that the perfect balance between the electron and hole populations is the origin of the extremely large magnetoresistance in WTe2.

Two-dimensional Fermi surfaces in Kondo insulator SmB6.

In the Kondo insulator samarium hexaboride (SmB6), strong correlation and band hybridization lead to an insulating gap and a diverging resistance at low temperature. The resistance divergence ends at about 3 kelvin, a behavior that may arise from surface conductance. We used torque magnetometry to resolve the Fermi surface topology in this material. The observed oscillation patterns reveal two Fermi surfaces on the (100) surface plane and one Fermi surface on the (101) surface plane. The measured Fermi surface cross sections scale as the inverse cosine function of the magnetic field tilt angles, which demonstrates the two-dimensional nature of the conducting electronic states of SmB6.

Luminescence properties of different Eu sites in LiMgPO4:Eu(2+), Eu(3+).

The effect of temperature on the luminescence properties of LiMgPO4 doped with Eu(3+) and Eu(2+) are presented. Depending on the excitation wavelength, luminescence spectra consist of two distinct broad emission bands peaking at 380 nm and 490 nm related to 4f(6)5d(1) â†’ 4f(7) ((8)S7/2) luminescence of Eu(2+) and to europium-trapped exciton, respectively, and/or several sharp lines between the 580 nm and 710 nm region, ascribed to the (5)D0 â†’ (7)FJ (J = 0, 1, 2, 3 and 4) transitions in Eu(3+). To explain all the features of the Eu(2+) and Eu(3+) luminescence we discussed the existence of two different Eu sites substituting for Li(+), with short and long distance compensation. The evident effect of increasing the intensity of the Eu(2+) luminescence with increasing temperature was observed. It was considered that the charge compensation mechanism for Eu(3+) and Li(+) as well as Eu(2+) replacing Li(+) in the LiMgPO4 is a long distance compensation that allows for the existence of some of the europium ions either as Eu(3+) at low temperature or as Eu(2+) at high temperature. We concluded that Eu(2+) in the Li(+) site with long distance compensation yields only 4f(6)5d(1) â†’ 4f(7) luminescence, whereas Eu(2+) in the Li(+) site with short distance compensation yields 4f(6)5d(1) â†’ 4f(7) luminescence and europium-trapped exciton emission.

Capacitive deionization of seawater effected by nano Ag and Ag@C on graphene.

Drinking water shortage has become worse in recent decades. A new capacitive deionization (CDI) method for increasing water supplies through the effective desalination of seawater has been developed. Silver as nano Ag and Ag@C which was prepared by carbonization of the Ag(+)-ß-cyclodextrin complex at 573 K for 30 min can add the antimicrobial function into the CDI process. The Ag@C and Ag nanoparticles dispersed on reduced graphene oxide (Ag@C/rGO and nano Ag/rGO) were used as the CDI electrodes. The nano Ag/rGO and Ag@C/rGO electrodes can reduce the charging resistant, and enhance the electrosorption capability. Better CDI efficiencies with the nano Ag/rGO and Ag@C/rGO electrodes can therefore be obtained. When reversed the voltage, the electrodes can be recovered up to 90% within 5 min. This work presents the feasibility for the nano Ag and Ag@C on rGO electrodes applied in CDI process to produce drinking water from seawater or saline water.

Loss of TAK1 increases cell traction force in a ROS-dependent manner to drive epithelial-mesenchymal transition of cancer cells.

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFß-SMAD signaling pathway as an inductor of EMT in many tumor types is well recognized. However, the role of non-canonical TGFß-TAK1 signaling in EMT remains unclear. Herein, we show that TAK1 deficiency drives metastatic skin squamous cell carcinoma earlier into EMT that is conditional on the elevated cellular ROS level. The expression of TAK1 is consistently reduced in invasive squamous cell carcinoma biopsies. Tumors derived from TAK1-deficient cells also exhibited pronounced invasive morphology. TAK1-deficient cancer cells adopt a more mesenchymal morphology characterized by higher number of focal adhesions, increase surface expression of integrin α5ß1 and active Rac1. Notably, these mutant cells exert an increased cell traction force, an early cellular response during TGFß1-induced EMT. The mRNA level of ZEB1 and SNAIL, transcription factors associated with mesenchymal phenotype is also upregulated in TAK1-deficient cancer cells compared with control cancer cells. We further show that TAK1 modulates Rac1 and RhoA GTPases activities via a redox-dependent downregulation of RhoA by Rac1, which involves the oxidative modification of low-molecular weight protein tyrosine phosphatase. Importantly, the treatment of TAK1-deficient cancer cells with Y27632, a selective inhibitor of Rho-associated protein kinase and antioxidant N-acetylcysteine augment and hinders EMT, respectively. Our findings suggest that a dysregulated balance in the activation of TGFß-TAK1 and TGFß-SMAD pathways is pivotal for TGFß1-induced EMT. Thus, TAK1 deficiency in metastatic cancer cells increases integrin:Rac-induced ROS, which negatively regulated Rho by LMW-PTP to accelerate EMT.

Traditional Chinese medicine and related active compounds: a review of their role on hepatitis B virus infection.

Since the significant public health hazard of Hepatitis B virus (HBV) infection and obvious drug resistance and dose-dependent side effects for common antiviral agents (e.g., interferon α, lamivudine, and adefovir), continuous development of agents to treat HBV infection is urgently needed. Traditional Chinese medicine (TCM) is an established segment of the health care system in China. Currently, it is widely used for chronic hepatitis B (CHB) in China and many parts of the world. Over a long period of time in clinical practice and in basic research progress, the effectiveness and beneficial contribution of TCM on CHB have been gradually known and confirmed. Based upon our review of related papers and because of our prior knowledge and experience, we have selected some Chinese medicines, including Chinese herbal formulas (e.g., Xiao-Chai-Hu-Tang, Xiao-Yao-San, and Long-Dan-Xie-Gan-Tang), single herbs (e.g., Phyllanthus niruri, Radix astragali, Polygonum cuspidatum, Rheum palmatum, and Salvia miltiorrhiza) and related active compounds (e.g., wogonin, artesunate, saikosaponin, astragaloside IV, and chrysophanol 8-O-beta-Dglucoside) and Chinese medicine preparations (e.g., silymarin, silibinin, kushenin, and cinobufacini), which seem effective and worthy of additional and indepth study in treating CHB, and we have given them a brief review. We conclude that these Chinese herbal medicines exhibit significant anti-HBV activities with improved liver function, and enhanced HBeAg and HBsAg sero-conversion rates as well as HBV DNA clearance rates in HepG2 2.2.15 cells, DHBV models, or patients with CHB. We hope this review will contribute to an understanding of TCM and related active compounds as an effective treatment for CHB and provide useful information for the development of more effective antiviral drugs.