Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Irreversible repolarization of tumour-associated macrophages by low-Pi stress inhibits the progression of hepatocellular carcinoma.

Numerous studies have shown the positive correlation between high levels of Pi and tumour progression. A critical goal of macrophage-based cancer therapeutics is to reduce anti-inflammatory macrophages (M2) and increase proinflammatory antitumour macrophages (M1). This study aimed to investigate the relationship between macrophage polarization and low-Pi stress. First, the spatial populations of M2 and M1 macrophages in 22 HCC patient specimens were quantified and correlated with the local Pi concentration. The levels of M2 and M1 macrophage markers expressed in the peritumour area were higher than the intratumour levels, and the expression of M2 markers was positively correlated with Pi concentration. Next, monocytes differentiated from THP-1 cells were polarized against different Pi concentrations to investigate the activation or silencing of the expression of p65, IκB-α and STAT3 as well as their phosphorylation. Results showed that low-Pi stress irreversibly repolarizes tumour-associated macrophages (TAMs) towards the M1 phenotype by silencing stat6 and activating p65. Moreover, HepG-2 and SMCC-7721 cells were cultured in conditioned medium to investigate the innate anticancer immune effects on tumour progression. Both cancer cell lines showed reduced proliferation, migration and invasion, as epithelial-mesenchymal transition (EMT) was inactivated. In vivo therapeutic effect on the innate and adaptive immune processes was validated in a subcutaneous liver cancer model by the intratumoural injection of sevelamer. Tumour growth was significantly inhibited by the partial deprivation of intratumoural Pi as the tumour microenvironment under low-Pi stress is more immunostimulatory. The anticancer immune response, activated by low-Pi stress, suggests a new macrophage-based immunotherapeutic modality.

[Mechanism of gigantol in transmembrane transport in human lens epithelial cells].

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.

Depressing relaxation and conduction loss of polar polymer materials by inserting bulky charge traps for superior energy storage performance in high-pulse energy storage capacitor applications.

Polymer-based dielectrics are chiefly used in high-pulse energy storage capacitors for their high breakdown strength, prominent processability, and low cost. Nevertheless, state-of-the-art commercial polymer-based dielectrics such as biaxially oriented polypropylene (BOPP), cannot satisfy the high energy density requirement in many fields because of their low permittivity. Limited success has been achieved in developing polar polymeric dielectrics with high energy density because of the quickly increased energy loss from polarization relaxation and charge conduction under a high electric field and temperature. To achieve high energy density and low loss in polar polymer dielectrics simultaneously, electron-deficient vinyl quinoline (VQQ) units are pre-copolymerized with methyl methacrylate (MMA) followed by blending with a PMMA matrix. The bulky and electron-deficient VQQs have successfully depressed the relaxation of PMMA and significantly decreased charge conduction under an elevated electric field. As a result, a rather high energy discharging efficiency (over 90%) could be finely maintained up to 800 MV m-1, and an energy density of 16.1 J cm-3 could be obtained, which are much better than those of reported polymer dielectrics. The strong space charge trapping effect of the low content of VQQ is well addressed by thermally stimulated depolarization currents (TSDC) and density functional theory analysis (DFT) of increasing breakdown strength, energy density and discharging efficiency. This work offers a promising strategy for achieving high energy density and low loss in polar polymer dielectrics for their commercial application in energy storage capacitors.

Machine learning algorithms for integrating clinical features to predict intracranial hemorrhage in patients with acute leukemia.

BACKGROUND: Intracranial hemorrhage (ICH) in acute leukemia (AL) patients leads to high morbidity and mortality, treatment approaches for ICH are generally ineffective. Thus, early identification of which subjects are at high risk of ICH is of key importance. Currently, machine learning can achieve well predictive capability through constructing algorithms that simultaneously exploit the information coming from clinical features. METHODS: After rigid data preprocessing, 42 different clinical features from 948 AL patients were used to train different machine learning algorithms. We used the feature selection algorithms to select the top 10 features from 42 clinical features. To test the performance of the machine learning algorithms, we calculated area under the curve (AUC) values from receiver operating characteristic (ROC) curves along with 95% confidence intervals (CIs) by cross-validation. RESULTS: With the 42 features, RF exhibited the best predictive power. After feature selection, the top 10 features were international normalized ratio (INR), prothrombin time (PT), creatinine (Cr), indirect bilirubin (IBIL), albumin (ALB), monocyte (MONO), platelet (PLT), lactic dehydrogenase (LDH), fibrinogen (FIB) and prealbumin (PA). Among the top 10 features, INR, PT, Cr, IBIL and ALB had high predictive performance with an AUC higher than 0.8 respectively. CONCLUSIONS: The RF algorithm exhibited a higher cross-validated performance compared with the classical algorithms, and the selected important risk features should help in individualizing aggressive treatment in AL patients to prevent ICH. Efforts that will be made to test and optimize in independent samples will warrant the application of such algorithm and predictors in the future.

Modeling and control of cable-driven continuum robot used for minimally invasive surgery.

Continuum robot has great advantages in minimally invasive surgery (MIS) due to the slenderness and dexterity. But the friction and backlash result in the low trajectory tracking accuracy. This paper aims to study the transmission process of the driving force and the error compensation method. The statics is performed considering the frictional transmission process, and the variation of friction force with driving force is revealed by the model. The hysteresis effect of the tip trajectory is revealed. Then the relationship between the load history and the robot shape is studied, next, the deflection of the robot subject to the different loading forces can be predicted. The correctness of the mechanical model is verified by numerical simulation and experiments. Furthermore, the control methods according to the cable length and the driving force are compared respectively, and a method of error compensation according to the cable length is worked out considering the mechanical model. The rationality of the compensation method is validated by experiment. The results show that the compensation method based on cable length greatly improves the control accuracy, and the maximum deviation is 1.08 mm. The established model and compensation method create conditions for clinical application of the proposed continuum robot.

Design and analysis of a continuum robot for transnasal skull base surgery.

BACKGROUND: The traditional surgical instruments for transnasal endoscopic skull base surgery have poor flexibility and continuum robot has attracted extensive attention for its high dexterity and safety. METHODS: A new type of micro continuum surgical robot is designed. On the basis of kinematic analysis, a superposition method is proposed to analyse the reachable configuration space of the system, and the workspace is analysed. The results obtained by superposition method can provide reference for the selection of joint parameters. At last, the static model of the system is established considering friction and coupling between two segments. RESULTS: The simulation results show that the workspace can meet the requirements of surgery. And the validity of the static model is verified by numerical simulation and experiment, which lays a foundation for the establishment of the driving force transmission system and precise control of the robot. CONCLUSIONS: The research results of this study contribute to the real-time control and movement of robot. The proposed continuum robot provides convenient conditions for the clinical application.

Deep Collocative Learning for Immunofixation Electrophoresis Image Analysis.

Immunofixation Electrophoresis (IFE) analysis is of great importance to the diagnosis of Multiple Myeloma, which is among the top-9 cancer killers in the United States, but has rarely been studied in the context of deep learning. Two possible reasons are: 1) the recognition of IFE patterns is dependent on the co-location of bands that forms a binary relation, different from the unary relation (visual features to label) that deep learning is good at modeling; 2) deep classification models may perform with high accuracy for IFE recognition but is not able to provide firm evidence (where the co-location patterns are) for its predictions, rendering difficulty for technicians to validate the results. We propose to address these issues with collocative learning, in which a collocative tensor has been constructed to transform the binary relations into unary relations that are compatible with conventional deep networks, and a location-label-free method that utilizes the Grad-CAM saliency map for evidence backtracking has been proposed for accurate localization. In addition, we have proposed Coached Attention Gates that can regulate the inference of the learning to be more consistent with human logic and thus support the evidence backtracking. The experimental results show that the proposed method has obtained a performance gain over its base model ResNet18 by 741.30% in IoU and also outperformed popular deep networks of DenseNet, CBAM, and Inception-v3.

Protective effect of syringic acid via restoring cells biomechanics and organelle structure in human lens epithelial cells.

We have previously reported that syringic acid (SA) extracted from D. aurantiacum var. denneanum (kerr) may be used to prevent diabetic cataract (DC). However, the underlying mechanisms through which SA prevents DC in human lens epithelial cells (HLECs) remained unclear. In the present study, we employed single-molecule optics technologies, including transmission electron microscopy (TEM), atomic force microscopy (AFM), laser scanning confocal microscopy (LSCM) and Raman spectroscopy, to monitor the effect of SA on HLECs biomechanics and organelle structure in real-time. TEM suggested that SA improved the ultrastructure of HLECs with regard to nuclear chromatin condensation and reducing mitochondrial swelling and degeneration, which may aid in the maintenance of HLECs integrity in the presence of glucose. AFM revealed a reduced surface roughness and stiffness following SA treatment, suggesting an improved viscoelasticity of HELCs. Raman spectrometry and LSCM further revealed that these changes were related to a modification of cell liquidity and cytoskeletal structure by SA. Taken together, these results provide insights into the effects of SA on the biomechanics of HLECs and further strengthen the evidence for its potential use as a novel therapeutic strategy for DC prevention.

Circular RNA circDNM3OS Functions as a miR-145-5p Sponge to Accelerate Cholangiocarcinoma Growth and Glutamine Metabolism by Upregulating MORC2.

BACKGROUND: Cholangiocarcinoma (CCA) is the second most common liver malignant tumor. CircRNA hsa_circ_0005230 (circDNM3OS) has been reported to exert an oncogenic role in CCA. However, the mechanisms related to circDNM3OS in CAA progression have not been fully elucidated. METHODS: The expression of circDNM3OS, microRNA (miR)-145-5p, and MORC2 (MORC Family CW-Type Zinc Finger 2) mRNA were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, colony formation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8), colony formation, transwell, wound-healing, and flow cytometry assays. The levels of glutamine, α-KG (α-ketoglutarate), and ATP (adenosine triphosphate) were detected using commercial kits. The relationship between circDNM3OS or MORC2 and miR-145-5p was verified by dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Protein level of MORC2 was measured by Western blotting. The role of circDNM3OS in CCA growth was verified by xenograft experiment. RESULTS: CircDNM3OS and MORC2 were upregulated while miR-145-5p was downregulated in CCA tissues and cells. Inhibition of circDNM3OS reduced xenograft tumor growth in vivo and constrained proliferation, colony formation, migration, invasion, induced apoptosis, and reduced glutamine metabolism of CCA cells in vitro. CircDNM3OS sponged miR-145-5p to elevate MORC2 expression. MiR-145-5p silencing overturned circDNM3OS knockdown-mediated influence on malignancy and glutamine metabolism of CCA cells. Also, MORC2 overexpression reversed the repressive impact of miR-145-5p mimic on malignancy and glutamine metabolism of CCA cells. CONCLUSION: CircDNM3OS facilitates CCA growth and glutamine metabolism by regulating the miR-145-5p/MORC2 pathway, offering a novel mechanism to understand the progression of CCA.

A Piezoelectric Tactile Sensor for Tissue Stiffness Detection with Arbitrary Contact Angle.

In this paper, a piezoelectric tactile sensor for detecting tissue stiffness in robot-assisted minimally invasive surgery (RMIS) is proposed. It can detect the stiffness not only when the probe is normal to the tissue surface, but also when there is a contact angle between the probe and normal direction. It solves the problem that existing sensors can only detect in the normal direction to ensure accuracy when the degree of freedom (DOF) of surgical instruments is limited. The proposed senor can distinguish samples with different stiffness and recognize lump from normal tissue effectively when the contact angle varies within [0°, 45°]. These are achieved by establishing a new detection model and sensor optimization. It deduces the influence of contact angle on stiffness detection by sensor parameters design and optimization. The detection performance of the sensor is confirmed by simulation and experiment. Five samples with different stiffness (including lump and normal samples with close stiffness) are used. Through blind recognition test in simulation, the recognition rate is 100% when the contact angle is randomly selected within 30°, 94.1% within 45°, which is 38.7% higher than the unoptimized sensor. Through blind classification test and automatic k-means clustering in experiment, the correct rate is 92% when the contact angle is randomly selected within 45°. We can get the proposed sensor can easily recognize samples with different stiffness with high accuracy which has broad application prospects in the medical field.

Development of a variable-stiffness and shape-detection manipulator based on low-melting-point-alloy for minimally invasive surgery.

There is an increasingly popularity for the continuum robot in minimally invasive surgery(MIS), because of the compliance and dexterity. In the first place, a variable stiffness manipulator can resolve the two contradictions of the demands for predominant flexibility and strong payload capacity. In the second place, to control the continuum robot more precisely and avoid the collision between robot and human body, real-time tracking of the shape of the continuum robot is of great significance. A new type of flexible manipulator with variable stiffness is proposed which can track the bending shape timely. The low-melting-point-alloy (LMPA) is used to realize the variable stiffness and shape detection for the flexible manipulator. The concept design for a single module is put forward. Then the stiffness control method and finite element simulation, the method of shape detection are presented. Moreover, the presented method of shape detection is evaluated by experiments.

Palpation-Based Multi-Tumor Detection Method Considering Moving Distance for Robot-assisted Minimally Invasive Surgery.

A novel palpation-based tumor detection method for robot-assisted minimally invasive surgery (RMIS) is proposed in this paper. A tactile stiffness sensor based on piezoelectric vibration is designed to detect tissue stiffness just by gentle contacting, without the risk of injuring the organ. A novel multi-tumor detection method is proposed to solve the problem that existing tumor detection methods can only detect a single tumor. In addition, the moving distance of the sensor during palpation is introduced into the sampling strategy function as a new factor, so that the total moving distance of sensor can be considered and optimized during the tumor palpation process. Simulation studies are carried out to compare the new method with existing methods in tumor detection. It shows that the proposed method can identify and locate multiple tumors successfully with the highest performance (F1 score > 0.99), and the total moving distance during palpation is reduced by 43% without any compromise in the detection accuracy.

Identification of key miRNAs in the progression of hepatocellular carcinoma using an integrated bioinformatics approach.

BACKGROUD: It has been shown that aberrant expression of microRNAs (miRNAs) and transcriptional factors (TFs) is tightly associated with the development of HCC. Therefore, in order to further understand the pathogenesis of HCC, it is necessary to systematically study the relationship between the expression of miRNAs, TF and genes. In this study, we aim to identify the potential transcriptomic markers of HCC through analyzing common microarray datasets, and further establish the differential co-expression network of miRNAs-TF-mRNA to screen for key miRNAs as candidate diagnostic markers for HCC. METHOD: We first downloaded the mRNA and miRNA expression profiles of liver cancer from the GEO database. After pretreatment, we used a linear model to screen for differentially expressed genes (DEGs) and miRNAs. Further, we used weighed gene co-expression network analysis (WGCNA) to construct the differential gene co-expression network for these DEGs. Next, we identified mRNA modules significantly related to tumorigenesis in this network, and evaluated the relationship between mRNAs and TFs by TFBtools. Finally, the key miRNA was screened out in the mRNA-TF-miRNA ternary network constructed based on the target TF of differentially expressed miRNAs, and was further verified with external data set. RESULTS: A total of 465 DEGs and 215 differentially expressed miRNAs were identified through differential genes expression analysis, and WGCNA was used to establish a co-expression network of DEGs. One module that closely related to tumorigenesis was obtained, including 33 genes. Next, a ternary network was constructed by selecting 256 pairs of mRNA-TF pairs and 100 pairs of miRNA-TF pairs. Network mining revealed that there were significant interactions between 18 mRNAs and 25 miRNAs. Finally, we used another independent data set to verify that miRNA hsa-mir-106b and hsa-mir-195 are good classifiers of HCC and might play key roles in the progression of HCC. CONCLUSION: Our data indicated that two miRNAs-hsa-mir-106b and hsa-mir-195-are identified as good classifiers of HCC.

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-ß signaling pathway.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated with high morbidity and ranks sixth among malignancies worldwide. Increasing evidence suggests that microRNAs (miRNAs or miRs) play a critical role in regulating cancer stem cells (CSCs), which drive the proliferation and spread of OSCC. Therefore, based on the alteration of aberrantly expressed miR-495 and homeobox C6 (HOXC6) by Gene Expression Omnibus (GEO) analysis, we subsequently explore the potential effect of miR-495 on the progression of CSCs in OSCC. METHODS: After the isolation of CSCs from the clinical tissue samples of OSCC patients, the expression of miR-495 and HOXC6 was determined, followed by the validation of the relationship between miR-495 and HOXC6. Subsequently, gain- and loss-function approach was performed to detect the role of miR-495 and HOXC6 in cell proliferation, migration, invasion, cell cycle entry, apoptosis, and epithelial-mesenchymal transition (EMT) of CSCs in OSCC, as well as the tumor growth in vivo. RESULTS: HOXC6 was highly expressed while miR-495 was poorly expressed in OSCC. HOXC6 was verified to be a target gene of miR-495, and miR-495 could inhibit the activation of the TGF-ß signaling pathway. CSCs with miR-495 overexpression or HOXC6 silencing exhibited reversed EMT process; reduced abilities of proliferation, migration, and invasion; and promoted cell apoptosis in vitro. Moreover, inhibited tumor growth was observed in vivo after injection with miR-495 agomir or sh-HOXC6. In contrast, the downregulation of miR-495 showed an induced role in the progression of OSCC. CONCLUSION: These findings suggest that miR-495 may suppress HOXC6 to inhibit EMT, proliferation, migration, and invasion while promoting apoptosis of CSCs in OSCC by inhibiting the TGF-ß signaling pathway.

Up-regulated microRNA-33b inhibits epithelial-mesenchymal transition in gallbladder cancer through down-regulating CROCC.

Gallbladder cancer (GBC) is a relatively rare but fatal gastrointestinal tumor. The microRNA-33b (miR-33b), a member of miR-33 family, is reported to function as a tumor suppressor in various cancers. Notably, miR-33 was predicted to target CROCC based on microarray-based analysis. Hereby, we aimed to characterize the effect of miR-33b on epithelial-mesenchymal transition (EMT) in GBC and the potential mechanism involved with the regulation of CROCC. In GBC cell lines, miR-33b expressed at low levels, and CROCC expressed at high levels, with enhanced EMT process. To further examine the specific mechanism of miR-33b and CROCC in GBC, the GBC cells were treated with the miR-33b mimic/inhibitor or siRNA-CROCC to assess the expression alteration of EMT-related genes and cell proliferation, migration, and invasion. MiR-33b was verified to target and down-regulate the expression of CROCC. The miR-33b up-regulation or CROCC silencing was observed to increase the level of E-cadherin but decrease the levels of N-cadherin and Vimentin, corresponding to impeded cell proliferation, migration, invasion, EMT, and tumor growth. The findings suggest that miR-33b up-regulation hinders GBC development through down-regulating CROCC, which was achieved by inhibition of EMT. The present study may provide an insight on a novel target for GBC treatment.

miR­21 inhibitor facilitates the anticancer activity of doxorubicin loaded nanometer in melanoma.

MicroRNA­21 (miR­21) is a potential therapeutic target for melanoma. Whether miR­21 inhibitor affects the anti­cancer activity of doxorubicin assisted by c(RGDyK)­modified liposome (DLN) in melanoma and the underlying mechanisms are largely unknown. In this study, in vitro and animal models were used to explore the effect of DLN combined with miR­21 inhibitor on melanoma cells. The data demonstrated that treatment with 5 µl DLN (final concentration of doxorubicin 5 mg/ml) for 72 h effectively inhibited melanoma cell growth (~75% inhibition). The experiments were then divided into five groups: Control group, vector group, DLN group, miR­21 inhibitor group and miR­21 inhibitor + DLN group. Compared with the control group, DLN (5 µl) or miR­21 inhibitor significantly reduced migration and invasion of melanoma cells, promoted apoptosis and arrested cells at the G1 phase. Notably, the combined application of DLN with miR­21 inhibitor further promoted the anti­cancer effects (reducing migration and invasion of melanoma cells, promoting apoptosis and arresting cells at G1 phase) compared with individual application of DLN or miR­21 inhibitor. Mechanically, DLN did not function by reducing miR­21 expression, whereas DLN and miR­21 inhibitor downregulated B­cell lymphoma-2 (BCL­2) expression, and facilitated BCL­2­associated X protein (Bax) and P53 expression in melanoma cells. DLN and miR­21 inhibitor together displayed stronger effects on Bcl­2, Bax and P53 expression that each alone. In vivo data further demonstrated that DLN inhibited tumor growth further than a similar dose of doxorubicin only. Furthermore, miR­21 inhibitor and DLN exerted the optimal anti­cancer effect compared with single application of DLN or miR­21 inhibitor. Together, the findings demonstrated miR­21 inhibitor facilitated the anti­cancer activity of DLN in melanoma, and the mechanisms involved Bcl­2, Bax and P53 expression.

MicroRNA-1305 Inhibits the Stemness of LCSCs and Tumorigenesis by Repressing the UBE2T-Dependent Akt-Signaling Pathway.

MicroRNAs (miRNAs) are involved in the maintenance of the cancer stem cell (CSC) phenotype by binding to genes and proteins that modulate cell proliferation and/or cell apoptosis. In our study, we aimed to investigate the role of miR-1305 in the proliferation and self-renewal of liver CSCs (LCSCs) via the ubiquitin-conjugating enzyme E2T (UBE2T)-mediated Akt-signaling pathway. Differentially expressed genes in human hepatocellular carcinoma (HCC) were obtained by in silico analysis. The relationship between miR-1305 and UBE2T was verified by dual luciferase reporter gene assay. qRT-PCR and western blot analysis were performed to determine the expression of UBE2T, the Akt-signaling pathway, and stemness-related factors in LCSCs. In addition, miR-1305 disrupted the activation of the Akt-signaling pathway by targeting UBE2T, and, ultimately, it repressed the sphere formation, colony formation, and proliferation, as well as tumorigenicity of LCSCs. In summary, miR-1305 targeted UBE2T to inhibit the Akt-signaling pathway, thereby suppressing the self-renewal and tumorigenicity of LCSCs. Those findings may provide an enhanced understanding of miR-1305 as a therapeutic target to limit the progression of LCSCs.

A systematic in silico prediction of gibberellic acid stimulated GASA family members: A novel small peptide contributes to floral architecture and transcriptomic changes induced by external stimuli in rice.

The GASA (GA-stimulated Arabidopsis) gene family is highly specific to plants, signifying a crucial role in plant growth and development. Herein, we retrieved 119 GASA genes in 10 different plant species in two major lineages (monocots and eudicots). Further, in the phylogenetic tree we classified these genes into four well-conserved subgroups. All the proteins contain a conserved GASA domain with similar characteristics and a highly specific 12-cysteine residue of the C-terminus position. According to the global microarray data and qRT-PCR based analysis, the OsGASA gene family was dominantly expressed in the seedling and transition phase of floral stages. Despite this, OsGASA genes profoundly contribute to rice grain size and length, whereas the highest abundance of transcript level was noticed in stage-2 (Inf 6, 3.0-cm-long spikelet) and stage-3 (Inf 7, 5.0-cm-long spikelet) under GA treatment during panicle formation. Additionally, the maximum expression level of these genes was recorded in response to GA and ABA in young seedlings. Further, in response to abiotic stresses, OsGASA1/8/10 was up- regulated by salt, OsGASA2/5/7 by drought, OsGASA3/6 by cold, and OsGASA4/9 by heat stress. With the exception of OsGASA4, the higher transcription levels of all the other GASA genes were induced by Cd and Cr metal stresses (8-10 fold changes) at various time points. Finally, the GO ontology analysis of GASAs revealed the biological involvement in the GA-mediated signaling pathway and abiotic stresses. Prominently, most of these proteins are localized in cellular components such as the cell wall and extracellular region, where the molecular functions such as ATP binding and protein binding were observed. These results imply that GASAs are significantly involved in rice panicle developmental stages, responses to external stimuli, and hormones.

c[RGDyk]-coated liposomes loaded with adriamycin and miR-21 mimics inhibit the growth of hepatoma cell line SMCC-7721 via up-regulating Bax and p53.

BACKGROUND: This study was conducted to investigate the effects of c[RGDyk]-coated liposomes loaded with Adriamycin (nanodrug) and miR-21 mimics on hepatoma cell line SMCC-7721. METHODS: SMCC-7721 cells were divided into five groups: control (receiving no treatment), nanodrug, miR-21 mimics + nanodrug and miR-21 mimics and empty vector. The concentration and duration of treatments were determined using the MTT assay. Cell apoptosis was detected using flow cytometer. The expression of Bax, Bcl-2 and p53 was measured using qPCR and Western blot analysis. RESULTS: MTT showed that the nanodrug inhibited cell proliferation. Nanodrug and miR-21 led to cell arrest at S phase and apoptosis. qPCR showed that cells treated with nanodrug and miR-21 increased the expression of Bax and p53. Western blot analysis indicated that Bcl-2 expression was significantly reduced. CONCLUSIONS: Our work demonstrates that nanodrug and miR-21 have inhibitory effect on SMCC-7721 cells via up-regulating Bax and p53.