GXYLT2 accelerates cell growth and migration by regulating the Notch pathway in human cancer cells.

Glucoside xylosyltransferase2 (GXYLT2), a member of the human α-1,3-D-xylosyltransferases, functions to modify the first xylose to the O-Glucose residue on epidermal growth factor (EGF) repeats of Notch receptors. It is well-established that the Notch signaling pathway plays a critical role in proper development and homeostasis. However, the regulatory role of EGF xylosylation in Notch signaling and different cell activities in human cells remains unknown. In this study, we showed that knockdown of GXYLT2 suppressed human cell proliferation and induced G1/S phase cell cycle arrest. GXYLT2 downregulation also inhibited cell migration and invasion, whereas the overexpression of GXYLT2 had the opposite effects. Additionally, GXYLT2 activated Notch signaling and promoted the phosphorylation of MAPKs but not PI3K and Akt. Taken together, our findings indicated that GXYLT2 plays an important role in cell activities via regulation of the Notch signaling.

Physiological and proteomic responses of reactive oxygen species metabolism and antioxidant machinery in mulberry (Morus alba L.) seedling leaves to NaCl and NaHCO3 stress.

In this paper, the effects of 100 mM NaCl and NaHCO3 stress on reactive oxygen species (ROS) and physiological and proteomic aspects of ROS metabolism in mulberry seedling leaves were studied. The results showed that NaCl stress had little effect on photosynthesis and respiration of mulberry seedling leaves. Superoxide dismutase (SOD) activity and the expression of related proteins in leaves increased by varying degrees, and accumulation of superoxide anion (O2·-) not observed. Under NaHCO3 stress, photosynthesis and respiration were significantly inhibited, while the rate of O2·- production rate and H2O2 content increased. The activity of catalase (CAT) and the expression of CAT (W9RJ43) increased under NaCl stress. In response to NaHCO3 stress, the activity and expression of CAT were significantly decreased, but the ability of H2O2 scavenging of peroxidase (POD) was enhanced. The ascorbic acid-glutathione (AsA-GSH) cycle in mulberry seedling leaves was enhancement in both NaCl and NaHCO3 stress. The expression of 2-Cys peroxiredoxin BAS1 (2-Cys Prx BAS1), together with thioredoxin F (TrxF), thioredoxin O1 (TrxO1), thioredoxin-like protein CITRX (Trx CITRX), and thioredoxin-like protein CDSP32 (Trx CDSP32) were significantly increased under NaCl stress. Under NaHCO3 stress, the expression of the electron donor of ferredoxin-thioredoxin reductase (FTR), together with Trx-related proteins, such as thioredoxin M (TrxM), thioredoxin M4 (TrxM4), thioredoxin X (TrxX), TrxF, and Trx CSDP32 were significantly decreased, suggesting that the thioredoxin-peroxiredoxin (Trx-Prx) pathway's function of scavenging H2O2 of in mulberry seedling leaves was inhibited. Taken together, under NaCl stress, excessive production of O2·- mulberry seedlings leaves was inhibited, and H2O2 was effectively scavenged by CAT, AsA-GSH cycle and Trx-Prx pathway. Under NaHCO3 stress, despite the enhanced functions of POD and AsA-GSH cycle, the scavenging of O2·- by SOD was not effective, and that of H2O2 by CAT and Trx-Prx pathway were inhibited; and in turn, the oxidative damage to mulberry seedling leaves could not be reduced.

Toxic effects of heavy metals Pb and Cd on mulberry (Morus alba L.) seedling leaves: Photosynthetic function and reactive oxygen species (ROS) metabolism responses.

To explore the mechanism of how lead (Pb) and cadmium (Cd) stress affects photosynthesis of mulberry (Morus alba L.), we looked at the effects of different concentrations of Pb and Cd stress (at 100 and 200 µmol L-1), which are two heavy metal elements, on leaf chlorophyll (Chl), photosynthesis gas exchange, Chl fluorescence, and reactive oxygen species (ROS) metabolism in mulberry leaves. The results showed that higher concentrations of Pb and Cd reduced leaf Chl content, especially in Chl a where content was more sensitive than in Chl b. Under Pb and Cd stress, the photosynthetic carbon assimilation capacity of mulberry leaves was reduced, which was a consequence of combined limitations of stomatal and non-stomatal factors. The main non-stomatal factors were decreased photosystem II (PSII) and photosystem I (PSI) activity and carboxylation efficiency (CE). Damage to the donor side of the PSII reaction center was greater than the acceptor side. After being treated with 100 µmol L-1 of Pb and Cd, mulberry leaves continued to be able to dissipate excess excitation energy by starting non-photochemical quenching (NPQ), but when Pb and Cd concentrations were increased to 200 µmol L-1, the protection mechanism that depends on NPQ was impaired. Excessive excitation energy from chloroplasts promoted a great increase of ROS, such as superoxide anion (O2•-) and H2O2. Moreover, under high Pb and Cd stress, superoxide dismutase (SOD) and ascorbate peroxidase (APX) were also inhibited to some extent, and excessive ROS also resulted in a significantly higher degree of oxidative damage. Compared with Cd, the effect of Pb stress at the same concentration level displayed a significantly lower impact on Chl content, photosynthetic carbon assimilation, and stomatal conductance. Meanwhile, Pb stress mainly damaged activity of the oxygen-evolving complex (OEC) located on PSII donor side, but it reduced the electronic pressure on the PSII acceptor side and PSI. Furthermore, under Pb stress, the NPQ, SOD, and APX activity were all significantly higher than those under Cd stress. Thus under Pb stress, the degree of photoinhibition and oxidative damage of PSII and PSI in mulberry leaves were significantly lower than under Cd stress.

Chlorophyll synthesis and the photoprotective mechanism in leaves of mulberry (Morus alba L.) seedlings under NaCl and NaHCO3 stress revealed by TMT-based proteomics analyses.

Chlorophyll (Chl) and effective photoprotective mechanism are important prerequisites to ensure the photosynthetic function of plants under stress. In this study, the effects of 100 mmol L-1 NaCl and NaHCO3 stress on chlorophyll synthesis and photosynthetic function of mulberry seedlings were studied by physiological combined with proteomics technology. The results show that: NaCl stress had little effect on the expression of Chl synthesis related proteins, and there were no significant changes in Chl content and Chl a:b ratio. However, 13 of the 15 key proteins in the process of Chl synthesis were significantly decreased under NaHCO3 stress, and the contents of Chl a and Chl b were significantly decreased (especially Chl a). Although stomatal conductance (Gs) decreased significantly under NaCl stress, net photosynthetic rate (Pn), PSII maximum photochemical efficiency (Fv/Fm) and electron transfer rate (ETR) did not change significantly, but under NaHCO3 stress, not only Gs decreased significantly, PSII activity and photosynthetic carbon were the same. In the photoprotective mechanism under NaCl stress, NAD(P)H dehydrogenase (NDH)-dependent cyclic electron flow (CEF) enhanced, the expression of related proteins subunit, ndhH, ndhI, ndhK, and ndhM, the key enzyme of the xanthophyll cycle, violaxanthin de-epoxidase (VDE) were up-regulated, the ratio of (A + Z)/(V + A + Z) and non-photochemical quenching (NPQ) was increased. The expressions of proteins FTR and Fd-NiR were also significant up-regulated under NaCl stress, Fd-dependent ROS metabolism and nitrogen metabolism can effectively reduce the electronic pressure on Fd. Under NaHCO3 stress, the expressions of NDH-dependent CEF related proteins subunit (ndhH, ndhI, ndhK, ndhM and ndhN), VDE, ZE, FTR, Fd-NiR and Fd-GOGAT, were significant down-regulated, and ZE, CP26, ndhK, ndhM, Fd-NiR, Fd-GOGAT and FTR genes expression also significantly decreased, the photoprotective mechanism, like the xanthophyll cycle，CEF and Fd-dependent ROS metabolism and nitrogen metabolism might be damaged, resulting in the inhibition of PSII electron transfer and carbon assimilation in mulberry leaves under NaHCO3 stress.

Protein sequence information extraction and subcellular localization prediction with gapped k-Mer method.

BACKGROUND: Subcellular localization prediction of protein is an important component of bioinformatics, which has great importance for drug design and other applications. A multitude of computational tools for proteins subcellular location have been developed in the recent decades, however, existing methods differ in the protein sequence representation techniques and classification algorithms adopted. RESULTS: In this paper, we firstly introduce two kinds of protein sequences encoding schemes: dipeptide information with space and Gapped k-mer information. Then, the Gapped k-mer calculation method which is based on quad-tree is also introduced. CONCLUSIONS: >From the prediction results, this method not only reduces the dimension, but also improves the prediction precision of protein subcellular localization.

Photochemistry and proteomics of mulberry (Morus alba L.) seedlings under NaCl and NaHCO3 stress.

In order to explore the response and adaptation mechanisms of photosynthesis of the leaves of mulberry (Morus alba L.) seedlings to saline-alkali stress. Photosynthetic activity, and the response of related proteomics of M. alba seedling leaves under NaCl and NaHCO3 stress were studied by using chlorophyll fluorescence and gas exchange technique combined with TMT proteomics. The results showed that NaCl stress had no significant effect on photosystem II (PSII) activity in M. alba seedling leaves. In addition, the expressions of proteins of the PSII oxygen-evolving complex (OEE3-1 and PPD4) and the LHCII antenna (CP24 10A, CP26, and CP29) were increased, and the photosystem I (PSI) activity in the leaves of M. alba seedlings was increased, as well as expressions of proteins, such as PsaF, PsaG, PsaH, PsaL, PsaN, and Ycf4. Under NaHCO3 stress, the activity of PSII and PSI and the expression of their protein complexes and the electron transfer-related proteins significantly decreased. NaCl stress had little effect on RuBP regeneration during dark reaction in the leaves and the expressions of glucose synthesis related proteins and net photosynthetic rate (Pn) did not decrease significantly. The leaves could adapt to NaCl stress by reducing stomatal conductance (Gs) and increasing water use efficiency (WUE). Under NaHCO3 stress, the expression of dark reaction-related proteins was mostly down-regulated, while Gs was reduced, which indicated that non-stomatal factors can be responsible for inhibition of carbon assimilation.

Nop-7-associated 2 (NSA2) is required for ribosome biogenesis and protein synthesis.

Ribosome biogenesis is a fundamental cellular process and occurs mainly in the nucleolus in eukaryotes. The process is exceptionally complex and highly regulated by numerous ribosomal and non-ribosomal factors. A recent discovery strengthened the link between ribosome biogenesis and malignant transformation. Here, we determined that Nop-7-associated 2 (NSA2) is a nucleolar protein required for ribosome biogenesis. NSA2 knockdown reduced the rate of rRNA synthesis, diminishing the 60S ribosomal subunit. Moreover, we demonstrated that depletion of NSA2 suppressed protein synthesis. To investigate the signaling pathway affected by NSA2, NSA2 was depleted, which triggered the inactivation of the mTOR signaling pathway. Taken together, our findings reveal a novel function of NSA2 and provide insight into the regulation of ribosome biogenesis by NSA2.

Polydopamine-functionalized nanographene oxide: a versatile nanocarrier for chemotherapy and photothermal therapy.

For releasing both drug and heat to selected sites, a combination of chemotherapy and photothermal therapy in one system is a more effective way to destroy cancer cells than monotherapy. Graphene oxide (GO) with high drug-loading efficiency and near-infrared (NIR) absorbance has great potential in drug delivery and photothermal therapy, but it is difficult to load drugs with high solubility. Herein, we develop a versatile drug delivery nanoplatform based on GO for integrated chemotherapy and photothermal therapy by a facile method of simultaneous reduction and surface functionalization of GO with poly(dopamine) (PDA). Due to the excellent adhesion of PDA, both low and high solubility drugs can be encapsulated in the PDA-functionalized GO nanocomposite (rGO-PDA). The fabricated nanocomposite exhibits good biocompatibility, excellent photothermal performance, high drug loading capacity, an outstanding sustained release property, and efficient endocytosis. Moreover, NIR laser irradiation facilitates the release of loaded drugs from rGO-PDA. These features make the rGO-PDA nanocomposite achieve excellent in vivo synergistic antitumor therapeutic efficacy.

CMTM3 inhibits cell growth and migration and predicts favorable survival in oral squamous cell carcinoma.

Downregulation of CKLF-like MARVEL transmembrane domain-containing member 3 (CMTM3) has been reported in a number of human tumors. However, the role of CMTM3 in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we showed that the expression of CMTM3 was significantly reduced in OSCC cell lines and primary tumor specimens (P < 0.001). Methylation-specific PCR showed hypermethylation in CMTM3 promoter in a significant proportion of tumor tissues (61 %). The expression of CMTM3 was associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, and recurrence of OSCC patients (P < 0.05, n = 201). More importantly, CMTM3 expression was associated with the prognosis of OSCC patients (P < 0.001) and was an independent prognostic factor (hazard ratio = 0.593, 95 % confidence interval, 0.272-1.292; P = 0.039). Overexpression of CMTM3 inhibited the growth and migration of OSCC cells. In vivo experiments also showed that the growth of OSCC xenografts in nude mice was significantly inhibited by CMTM3 overexpression. These findings indicate that downregulation of CMTM3 due to promoter hypermethylation contributed to the proliferation and migration of OSCC cells and suggest that CMTM3 is an independent prognostic factor for the evaluation of the survival of OSCC patients.

CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma.

AtMYB72 aggravates photosynthetic inhibition and oxidative damage in Arabidopsis thaliana leaves caused by salt stress.

MYB transcription factor is one of the largest families in plants. There are more and more studies on plants responding to abiotic stress through MYB transcription factors, but the mechanism of some family members responding to salt stress is unclear. In this study, physiological and transcriptome techniques were used to analyze the effects of the R2R3-MYB transcription factor AtMYB72 on the growth and development, physiological function, and key gene response of Arabidopsis thaliana. Phenotypic observation showed that the damage of overexpression strain was more serious than that of Col-0 after salt treatment, while the mutant strain showed less salt injury symptoms. Under salt stress, the decrease of chlorophyll content, the degree of photoinhibition of photosystem II (PSII) and photosystem I (PSI) and the degree of oxidative damage of overexpressed lines were significantly higher than those of Col-0. Transcriptome data showed that the number of differentially expressed genes (DEGs) induced by salt stress in overexpressed lines was significantly higher than that in Col-0. GO enrichment analysis showed that the response of AtMYB72 to salt stress was mainly by affecting gene expression in cell wall ectoplast, photosystem I and photosystem II, and other biological processes related to photosynthesis. Compared with Col-0, the overexpression of AtMYB72 under salt stress further inhibited the synthesis of chlorophyll a (Chla) and down-regulated most of the genes related to photosynthesis, which made the photosynthetic system more sensitive to salt stress. AtMYB72 also caused the outbreak of reactive oxygen species and the accumulation of malondialdehyde under salt stress, which decreased the activity and gene expression of key enzymes in SOD, POD, and AsA-GSH cycle, thus destroying the ability of antioxidant system to maintain redox balance. AtMYB72 negatively regulates the accumulation of osmotic regulatory substances such as soluble sugar (SS) and soluble protein (SP) in A. thaliana leaves under salt stress, which enhances the sensitivity of Arabidopsis leaves to salt. To sum up, MYB72 negatively regulates the salt tolerance of A. thaliana by destroying the light energy capture, electron transport, and antioxidant capacity of Arabidopsis.

Zero-strain strategy incorporating TaC with Ta2O5 to enhance its rate capacity for long-term lithium storage.

Ta2O5 holds great potential for lithium storage due to its high theoretical capacity and long-life cycling. However, it still suffers from an unsatisfactory rate capability because of its low conductivity and significant volume expansion during the charging/discharging process. In this study, a zero-strain strategy was developed to composite Ta2O5 with zero-strain TaC as an anode for lithium-ion batteries (LIBs). The zero-strain TaC, featuring negligible lattice expansion, can alleviate the volume variation of Ta2O5 when cycling, thereby enhancing the rate capacity and long-term cycling stability of the whole electrode. Further, the formation of a heterostructure between Ta2O5 and TaC was confirmed, giving rise to an enhancement in the electrical conductivity and structural stability. As expected, this anode displayed a reversible specific capacity of 395.5 mA h g-1 at 0.5 A g-1 after 500 cycles. Even at an ultrahigh current density of 10 A g-1, the Ta2O5/TaC anode delivered a high capacity of 144 mA h g-1 and superior durability with a low-capacity decay rate of 0.08% per cycle after 1000 cycles. This zero-strain strategy provides a promising avenue for the rational design of anodes, sequentially contributing to the development of high-rate capacity and long cycling LIBs.

Effect of the axial load on the dynamic response of the wrapped CFRP reinforced concrete column under the asymmetrical lateral impact load.

This study investigated the impact of axial load on the dynamic response of reinforced concrete (RC) members to asymmetrical lateral impact loads. A series of asymmetrical-span impact tests were conducted on circular and square RC members with and without Carbon Fiber Reinforced Polymers (CFRP) while varying the axial compression ratios. The impact process was simulated using ABAQUS software, and the time history curves of deflection and impact were measured. The study found that specific impact loads caused bending and shearing failures. The axial compression ratio ranged from 0.05 to 0.13 when the impact curve reached its maximum deflection before the component's impact resistance decreased. Analysis of the impact point and inclined crack location revealed that axial load affects the maximum local concrete. The speed of inclined crack penetration and inclined cracks take longer to form, with weaker resistance to damage to local concrete when the axial compression ratio is between 0.05 and 0.13. When the axial compression ratio is greater than 0.13, inclined cracks form sooner with more brittle and severe damage to the impact point's concrete. The study also identified key parameters affecting the dynamic response of RC members, including impact height, CFRP layer thickness, axial force, and impact location. Thicker CFRP layers in RC can improve impact resistance, especially when the impact location is farther from the center. However, there is a limit to the impact of axial force on this resistance.

Cryptococcal meningitis in immunocompetent children.

To describe clinical characteristics, treatment and outcome of cryptococcal meningitis in immunocompetent children. Immunocompetent children with cryptococcal meningitis who attended Changzheng Hospital between 1998 and 2007 were retrospectively reviewed. During the 10 years reviewed, 11 children with cryptococcal meningitis were admitted to Changzheng hospital and identified as immunocompetent. The 11 children had a median age of 7.25 years. Headache (100%), fever (81.8%), nausea or vomiting (63.6%) and visual or hearing damage or loss (36.4%) were the most common symptoms before treatment. There is no evidence for other site infection of cryptococcus although all the cryptococcal antigen titre is high in blood. All the patients received amphotericin B or AmB liposome with 5-flucytosine for at least 6 weeks followed by fluconazole or itraconazole as consolidation treatment for at least 12 weeks. Nine patients were cured mycologically; however, sequela of visual damage was showed in one patient. Cryptococcal meningitis seems to be uncharacteristic of symptoms, and central nervous system may be the only common site for infection. Amphotericin B with 5-flucytosine should be the choice of induction treatment in this group of patients.

Cryptococcosis in China (1985-2010): review of cases from Chinese database.

BACKGROUND: Cryptococcosis is a potential fatal disease, especially in immunocompromised patients. In China, the profile of cryptococcosis is unclear. Therefore, we summarize the epidemiology and therapy of cryptococcosis in china. METHODS: All cases reports about cryptococcosis in China were collected from CBMdisk database (China Biology and Medicine data disc) with key words of cryptococcosis, or cryptococcal infection, or cryptococcus, and case. The features of the cryptococcosis were retrospectively analyzed. RESULTS: There were 1,032 reports about cryptococcosis, including 8,769 cases. Among them, there were 16% patient with AIDS/HIV, and 17% ones without underlying diseases. There were 2,371 cases of CNS infection. Among them of 2,068 cases, the treatment protocols and outcome were clearly described. The percentages of patients who received intrathecal treatment of amphotericin B(AmB), AmB + 5-FC(5-fluorocytosine), AmB + FCZ(fluconazole), and AmB + 5-FU + FCZ in each medication group were 10, 43, 53, and 33%, respectively. The mortalities were significantly lower in the AmB, Amb + 5-FC, AmB + FCZ intrathecal treatment groups compared with their non-intrathecal treatment controls (6% vs. 23%, 25% vs. 35%, 20% vs. 30%, respectively, P < 0.05), but not in the intrathecal AmB + 5-FU + FCZ group (35% vs. 26%, P > 0.05). CONCLUSION: The Chinese cryptococcosis had its own special clinical features, such as more patients without identifiable underlying diseases. Intrathecal injection of amphotericin B was effective treatment method for cryptococcal CNS infection in China.

Numerical study on existing RC circular section members under unequal impact collision.

Traffic accidents and derailed train-related incidents have occurred more often than ever in recent years, resulting in some economic damage and casualties. Reinforced concrete (RC) constructions often involve derailed train and vehicle accidents. Rarely are such side collisions studied in previous studies. To do this, high-fidelity simulation-based finite-element (FE) models are created in this paper to accurately simulate the collision of circular RC members with a derailed train. The reinforced concrete member structure is common in high-speed railway stations. The impact energy of the impact body is significant, causing structural member failure. It analyses the dynamic behavior of reinforced concrete members under unequal span impact loads. Numerical implementations of impact issues are discussed from the perspective of geometric, contact, and material properties. The reliability and precision of the ABAQUS code to solve impact issues are verified by comparing failure modes, impact, and deflection time history experimental outputs. By analysing the impact response characteristics, used the control variables to study the failure process and mode (including the characteristics of impact and reaction forces, deflection time history curve, impact force-deflection curve, and bearing reaction force-deflection curve). The reinforcement ratio, impact velocity, concrete strength, and slenderness ratio significantly affect shear crack pattern and development. Changes in impact velocity and slenderness ratio also affect member failure modes.

Metabolic Dysfunction-associated Fatty Liver Disease is Associated with Greater Impairment of Lung Function than Nonalcoholic Fatty Liver Disease.

Background and Aims: We compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD. Methods: In this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of anthropometric parameters, biochemical variables, liver ultrasonography, and spirometry. The severity of liver disease was assessed by the fibrosis (FIB)-4 score. Results: The prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alcohol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was diminished by 0.507 (95% CI: -0.840, -0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: -0.739, -0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women. Conclusions: MAFLD was significantly associated with a greater impairment of lung function parameters than NAFLD.

Hemodynamics model of fluid-solid interaction in internal carotid artery aneurysms.

The objective of this study is to present a relatively simple method to reconstruct cerebral aneurysms as 3D numerical grids. The method accurately duplicates the geometry to provide computer simulations of the blood flow. Initial images were obtained by using CT angiography and 3D digital subtraction angiography in DICOM format. The image was processed by using MIMICS software, and the 3D fluid model (blood flow) and 3D solid model (wall) were generated. The subsequent output was exported to the ANSYS workbench software to generate the volumetric mesh for further hemodynamic study. The fluid model was defined and simulated in CFX software while the solid model was calculated in ANSYS software. The force data calculated firstly in the CFX software were transferred to the ANSYS software, and after receiving the force data, total mesh displacement data were calculated in the ANSYS software. Then, the mesh displacement data were transferred back to the CFX software. The data exchange was processed in workbench software. The results of simulation could be visualized in CFX-post. Two examples of grid reconstruction and blood flow simulation for patients with internal carotid artery aneurysms were presented. The wall shear stress, wall total pressure, and von Mises stress could be visualized. This method seems to be relatively simple and suitable for direct use by neurosurgeons or neuroradiologists, and maybe a practical tool for planning treatment and follow-up of patients after neurosurgical or endovascular interventions with 3D angiography.

Emerging role of RNA interference in immune cells engineering and its therapeutic synergism in immunotherapy.

RNAi effectors (e.g. siRNA, shRNA and miRNA) can trigger the silencing of specific genes causing alteration of genomic functions becoming a new therapeutic area for the treatment of infectious diseases, neurodegenerative disorders and cancer. In cancer treatment, RNAi effectors showed potential immunomodulatory actions by down-regulating immuno-suppressive proteins, such as PD-1 and CTLA-4, which restrict immune cell function and present challenges in cancer immunotherapy. Therefore, compared with extracellular targeting by antibodies, RNAi-mediated cell-intrinsic disruption of inhibitory pathways in immune cells could promote an increased anti-tumour immune response. Along with non-viral vectors, DNA-based RNAi strategies might be a more promising method for immunomodulation to silence multiple inhibitory pathways in T cells than immune checkpoint blockade antibodies. Thus, in this review, we discuss diverse RNAi implementation strategies, with recent viral and non-viral mediated RNAi synergism to immunotherapy that augments the anti-tumour immunity. Finally, we provide the current progress of RNAi in clinical pipeline.

Is One Ear Good Enough? Unilateral Hearing Loss and Preschoolers' Comprehension of the English Plural.

Purpose The plural is one of the first grammatical morphemes acquired by English-speaking children with normal hearing (NH). Yet, those with hearing loss show delays in both plural comprehension and production. However, little is known about the effects of unilateral hearing loss (UHL) on children's acquisition of the plural, where children's ability to perceive fricatives (e.g., the /s/ in cats ) can be compromised. This study therefore tested whether children with UHL were able to identify the grammatical number of newly heard words, both singular and plural. Method Eleven 3- to 5-year-olds with UHL participated in a novel word two-alternative forced choice task presented on an iPad. Their results were compared to those of 129 NH 3- to 5-year-olds. During the task, children had to choose whether an auditorily presented novel word was singular (e.g., tep, koss) or plural (e.g., teps, kosses) by touching the appropriate novel picture. Results Like their NH peers, children with UHL demonstrated comprehension of novel singulars. However, they were significantly less accurate at identifying novel plurals, with performance at chance. However, there were signs that their ability to identify novel plurals may improve with age. Conclusion While comparable to their NH peers at identifying novel singulars, these results suggest that young children with UHL do not yet have a robust representation of plural morphology, particularly on words they have not encountered before.