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Magnetic Resonance Imaging (MRI) is increasingly being used in treatment planning due to its superior soft tissue contrast, which is useful for tumor and soft tissue delineation compared to computed tomography (CT). However, MRI cannot directly provide mass density or relative stopping power (RSP) maps, which are required for calculating proton radiotherapy doses. Therefore, the integration of artificial intelligence (AI) into MRI-based treatment planning to estimate mass density and RSP directly from MRI has generated significant interest. A deep learning (DL) based framework was developed to establish a voxel-wise correlation between MR images and mass density as well as RSP. To facilitate the study, five tissue substitute phantoms were created, representing different tissues such as skin, muscle, adipose tissue, 45% hydroxyapatite (HA), and spongiosa bone. The composition of these phantoms was based on information from ICRP reports. Additionally, two animal tissue phantoms, simulating pig brain and liver, were prepared for DL training purposes. The phantom study involved the development of two DL models. The first model utilized clinical T1 and T2 MRI scans as input, while the second model incorporated zero echo time (ZTE) MRI scans. In the patient application study, two more DL models were trained: one using T1 and T2 MRI scans as input, and another model incorporating synthetic dual-energy computed tomography (sDECT) images to provide accurate bone tissue information. The DECT empirical model was used as a reference to evaluate the proposed models in both phantom and patient application studies. The DECT empirical model was selected as the reference for evaluating the proposed models in both phantom and patient application studies. In the phantom study, the DL model based on T1, and T2 MRI scans demonstrated higher accuracy in estimating mass density and RSP for skin, muscle, adipose tissue, brain, and liver. The mean absolute percentage errors (MAPE) were 0.42%, 0.14%, 0.19%, 0.78%, and 0.26% for mass density, and 0.30%, 0.11%, 0.16%, 0.61%, and 0.23% for RSP, respectively. The DL model incorporating ZTE MRI further improved the accuracy of mass density and RSP estimation for 45% HA and spongiosa bone, with MAPE values of 0.23% and 0.09% for mass density, and 0.19% and 0.07% for RSP, respectively. These results demonstrate the feasibility of using an MRI-only approach combined with DL methods for mass density and RSP estimation in proton therapy treatment planning. By employing this approach, it is possible to obtain the necessary information for proton radiotherapy directly from MRI scans, eliminating the need for additional imaging modalities.

To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS. [ABSTRACT FROM AUTHOR]

Abstract In order to analyze the influence of eccentric load on mechanical properties and damage process of concrete with initial damage, the eccentric load compression tests of concrete under different confining pressures were carried out with the help of PFC particle flow program. The results show that: the eccentric load does not change the relationship between peak stress, crack initiation stress and confining pressure of concrete under uniform load, but decrease the value of them. The peak stress increasing coefficient under uniform load is higher than that under eccentric load, and the peak stress increasing coefficient increases in a linear function with the confining pressure, and the increasing rate is approximately the same. Under uniaxial compression of eccentric load, a type I shear crack approximately parallel to the loading direction is formed, while under biaxial compression, a bending type shear crack with the lower tip of the initial crack as the inflection point is formed. The number of microcracks in concrete under uniform load and eccentric load can be divided into three stages: the calm period at the initial loading stage, the pre-peak expansion period from crack initiation point to peak point, and the rapid increase period after the peak.

Seeking better surface plasmon polariton (SPP) waveguides is of critical importance to construct the frequency-agile terahertz (THz) front-end circuits. We propose and investigate here a new class of semiconductor-based slot plasmonic waveguides for subwavelength THz transport. Optimizations of the key geometrical parameters demonstrate its better guiding properties for simultaneous realization of long propagation lengths (up to several millimeters) and ultra-tight mode confinement (~λ2/530) in the THz spectral range. The feasibility of the waveguide for compact THz components is also studied to lay the foundations for its practical implementations. Importantly, the waveguide is compatible with the current complementary metal-oxide-semiconductor (CMOS) fabrication technique. We believe the proposed waveguide configuration could offer a potential for developing a CMOS plasmonic platform and can be designed into various components for future integrated THz circuits (ITCs). [ABSTRACT FROM AUTHOR]

The ATP binding cassette (ABC) transporters superfamily is one of the largest classes of membrane proteins. The core of the ABC transporter protein is composed of transmembrane domains (TMDs) and nucleotide binding domains (NBD). Eukaryotes ABC transporters are classified into seven main families (ABCA to ABCG) based on sequence similarity and domain organizations. With different domain number and domain organizations, eukaryote ABC transporters show diverse structures: the single structure (NBD or TMD), the ABC2 structure (NBD-NBD), the half structure (TMD-NBD or NBD-TMD) and the full structure (TMD-NBD-TMD-NBD or NBD-TMD-NBD-TMD). However, studies on how various ABC transporter gene structures evolved is still absent. Therefore, in this study, we comprehensively investigated the structural evolution of eukaryotic ABC transporters. The seven eukaryote ABC transporter families (A to G) fell into three groups: A&G group, B,C&D group and E&F group. There were at least four times the number of NBD and TMD fusion events in the origin of the half structure transporter. Two fusion modes were found in the full and ABC2 structure origination. Based on these findings, we present a putative structural evolutionary path of eukaryote ABC transporters that will increase our understanding on their origin, divergence and function. [ABSTRACT FROM AUTHOR]

CCAAT/enhancer-binding protein α (C/ebpα) is a transcription factor that plays important roles in the regulation of hepatogenesis, adipogenesis and hematopoiesis. Disruption of the C/EBPα gene in mice leads to disturbed liver architecture and neonatal death due to hypoglycemia. However, the precise stages of liver development affected by C/ebpα loss are poorly studied. Using the zebrafish embryo as a model organism, we show that inactivation of the cebpa gene by TALENs results in a small liver phenotype. Further studies reveal that C/ebpα is distinctively required for hepatic outgrowth but not for hepatoblast specification. Lack of C/ebpα leads to enhanced hepatic cell proliferation and subsequent increased cell apoptosis. Additional loss of p53 can largely rescue the hepatic defect in cebpa mutants, suggesting that C/ebpα plays a role in liver growth regulation via the p53 pathway. Thus, our findings for the first time demonstrate a stage-specific role for C/ebpα during liver organogenesis. [ABSTRACT FROM AUTHOR]

Cilia play important roles in sensing extracellular signals and directing fluid flow. Ciliary dysfunction is associated with a variety of diseases known as ciliopathies. Histone deacetylase 6 (HDAC6) has recently emerged as a major driver of ciliary disassembly, but little is known about the downstream players. Here we provide the first evidence that HDAC6-mediated deacetylation of α-tubulin and cortactin is critical for its induction of ciliary disassembly. HDAC6 is localized in the cytoplasm and enriched at the centrosome and basal body. Overexpression of HDAC6 decreases the levels of acetylated α-tubulin and cortactin without affecting the expression or localization of known ciliary regulators. We also find that overexpression of α-tubulin or cortactin or their acetylation-deficient mutants enhances the ability of HDAC6 to induce ciliary disassembly. In addition, acetylation-mimicking mutants of α-tubulin and cortactin counteract HDAC6-induced ciliary disassembly. Furthermore, HDAC6 stimulates actin polymerization, and inhibition of actin polymerization abolishes the activity of HDAC6 to trigger ciliary disassembly. These findings provide mechanistic insight into the ciliary role of HDAC6 and underscore the importance of reversible acetylation in regulating ciliary homeostasis. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that aquaporins (AQPs) may facilitate tumor development. The molecular pathways connecting the pathological functions of AQPs are unclear and need to be better defined. This study aimed to investigate whether AQP3, one of the AQPs expressed highly in breast cancer, had any clinical implication in estrogen-receptor (ER) positive breast cancer, and explore the regulatory mechanisms of AQP3 in estrogen-related breast cancer progression. Here we show that AQP3 is an important enforcer of migration and invasion in breast cancer. We, for the first time, reported that ER-positive breast cancer tissues obtained from premenopausal patients had higher AQP3 expression when compared to those obtained from postmenopausal patients. Estrogen directly upregulates AQP3 by activating ERE in the promoter of the AQP3 gene. The upregulation of AQP3 can influence the expression of molecules related to epithelial-mesenchymal transition and the reorganization of actin-cytoskeleton, resulting in enhancement of cell migration and invasion in ER-positive breast cancer cells. [ABSTRACT FROM AUTHOR]

Here we reported the phase formation of MxMg2Al4+xSi5−xO18:Eu2+ (M = K, Rb) solid solution phosphors, where M+ ions were introduced into the void channels of Mg2Al4Si5O18 via Al3+/Si4+ substitution to keep the charge balance. XRD results revealed that the as-prepared phosphors with different M+ contents were iso-structural with Mg2Al4Si5O18 phase. The combined analysis of the Rietveld refinement and high resolution transmission electron microscopy (HRTEM) results proved that M+ ions were surely introduced into the intrinsic channels in Mg2Al4Si5O18. The emission peaks of MxMg2Al4+xSi5−xO18:Eu2+ (M = K, Rb) phosphors with various x values performed a systematic red-shift tendency, which was ascribed to the elongation of [MgO6] octahedra. The temperature stable photoluminescence and internal quantum efficiency (QE) of MxMg2Al4+xSi5−xO18:Eu2+ (M = K, Rb) phosphors were enhanced owing to the filling of M+ in the void channels suggesting a new insight to design the solid solution phosphors with improved photoluminescence properties. [ABSTRACT FROM AUTHOR]

Although aberrant microRNA (miRNA) expression has frequently been observed in inflammatory bowel disease (IBD), its biological functions and targets remain largely unknown. Present study found that miR-19b was significantly downregulated in active Crohn's disease (CD). Using bioinformatics analysis, suppressor of cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive immunity that controls several immuno-inflammatory diseases, was predicted to be a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3 protein levels, but not mRNA, was identified in active-CD intestinal tissue samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29 cells, it was experimentally validated that miR-19b is a direct regulator of SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly recognizes the 3'-untranslated region (3'-UTR) of SOCS3. Furthermore, overexpression of miR-19b decreased SOCS3 expression, leading to increased production of macrophage-inflammatory protein-3α (MIP-3α) in Caco2 cells. In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3α. Finally, intracolonically delivered miR-19b decreased the severity of colitis induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our findings suggest that miR-19b suppresses the inflammatory response by inhibiting SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and thereby prevents the pathogenesis of CD. [ABSTRACT FROM AUTHOR]

The small ubiquitin-related modifier (SUMO) participates in various cellular processes, including maintenance of genome integrity, nuclear transport, transcription and signal transduction. However, the biological function of sumoylation in hematopoiesis has not been fully explored. We show here that definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO-deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent. Critically, a SUMO-C/ebpα fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in part through restored runx1 expression. While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis. [ABSTRACT FROM AUTHOR]

Following the first human infection with the influenza A (H10N8) virus in Nanchang, China in December 2013, we identified two additional patients on January 19 and February 9, 2014. The epidemiologic, clinical, and virological data from the patients and the environmental specimen collected from 23 local live poultry markets (LPMs) were analyzed. The three H10N8 cases had a history of poultry exposure and presented with high fever (>38°C), rapidly progressive pneumonia and lymphopenia. Substantial high levels of cytokines and chemokines were observed. The sequences from an isolate (A/Environment/Jiangxi/03489/2013 [H10N8]) in an epidemiologically linked LPM showed highly identity with human H10N8 virus, evidencing LPM as the source of human infection. The HA and NA of human and environmental H10N8 isolates showed high identity (99.1-99.9%) while six genotypes with internal genes derived from H9N2, H7N3 and H7N9 subtype viruses were detected in environmental H10N8 isolates. The genotype of the virus causing human infection, Jiangxi/346, possessed a whole internal gene set of the A/Environment/Jiangxi/10618/2014(H9N2)-like virus. Thus, our findings support the notion that LPMs can act as both a gene pool for the generation of novel reassortants and a source for human infection, and intensive surveillance and management should therefore be conducted. [ABSTRACT FROM AUTHOR]

Anxiety is a frequent and serious complication of children and adolescents receiving dialysis. Low serum vitamin D levels have been associated with anxiety in non-pediatric patients. This study sought to examine the possible association between serum vitamin D levels and the presence of anxiety in children and adolescents with dialysis in China. A total of 156 pediatric patients who were on hemodialysis or peritoneal dialysis and 100 healthy controls were included in the current study. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by using a competitive protein-binding assay. Anxiety was assessed by using the Chinese version of the Screen for Child Anxiety Related Emotional Disorders (SCARED, = 25 as cutoff). Among 156 patients, 110 had a current anxiety (70.5%) and 46 did not (29.5%). Serum levels of 25(OH)D were significantly lower in patients with anxiety than in normal controls (19.4 ± 10.3 vs. 38.6 ± 15.5 ng/ml, P < 0.001). Serum 25(OH)D levels (≤15.0 ng/ml) were independently associated with the existent of anxiety in children and adolescents receiving dialysis (OR 4.650, 95% CI 1.663-13.001, P = 0.003). Our research demonstrates that low serum levels of vitamin D are independently associated with anxiety among children and adolescents on dialysis, which needs to be confirmed in future experimental and clinical studies.

Gene expression is negatively regulated by microRNAs (miRNAs), which commonly act as tumor oncogenes or suppressors. Previous results were inconsistent concerning the relationship between polymorphisms in miRNAs and risk of urological neoplasms. Here, we conducted a comprehensive literature research on diverse databases aiming at enrolling all eligible studies up to August 31, 2016. A total of 13 publications comprising 29 case-control studies were enrolled for three polymorphisms in three miRNAs. Overall analyses suggested significant associations between miR-146a rs2910164 polymorphism and urological neoplasms risk in allelic, homozygote and recessive models. In the stratified analysis by ethnicity, we uncovered a significant association between rs2910164 polymorphism and risk of urological neoplasms in Asian populations in allelic, homozygote and recessive models. Highlighted, when stratified analysis was conducted by cancer type, rs2910164 polymorphism was also significantly associated with an increased risk of bladder cancer in allelic, homozygote and recessive models. Although for rs11614913 and rs3746444 polymorphisms, overall analyses suggested negative results, for rs11614913 polymorphism, when subgroup analysis was conducted by cancer type, a significantly decreased risk of renal cell cancer was identified in recessive model. In brief, current work indicated that miR-146a rs2910164 polymorphism is a risk factor for urological neoplasms, particularly for bladder cancer.

Traditional Chinese medicine (TCM) follows the principle of formulae, in which the pharmacological activity of a single herb can be enhanced or potentiated by addition of other herbs. Nevertheless, the involved synergy mechanisms in formulae remain unknown. Here, a systems-based method is proposed and applied to three representative Chinese medicines in compound saffron formula (CSF): two animal spices (Moschus, Beaver Castoreum), and one herb Crocus sativus which exert synergistic effects for cardiovascular diseases (CVDs). From the formula, 42 ingredients and 66 corresponding targets are acquired based on the ADME evaluation and target fishing model. The network relationships between the compounds and targets are assembled with CVDs pathways to elucidate the synergistic therapeutic effects between the spices and the herbs. The results show that different compounds of the three medicines show similar curative activity in CVDs. Additionally, the active compounds from them shared CVDs-relevant targets (multiple compounds-one target), or functional diversity targets but with clinical relevance (multiple compounds-multiple targets-one disease). Moreover, the targets of them are largely enriched in the same CVDs pathways (multiple targets-one pathway). These results elucidate why animal spices and herbs can have pharmacologically synergistic effects on CVDs, which provides a new way for drug discovery.

Ethanol-induced hepatic lipophagy plays an important cytoprotective role against liver injury, but its mechanism is not fully determined. In the present study, ethanol-induced lipophagy was studied in an immortalized mouse hepatocyte line, AML12. We found that ethanol treatment elevated lipid content in these cells, which could be regulated by autophagy. To determine the potential mechanism, we investigated the role of a key adaptor molecule SQSTM1/p62. SQSTM1 can bind to LC3 on autophagosomes and ubiquitinated molecules on cargos, thus facilitating the autophagic engulfment of the cargo. We found that both LC3 and SQSTM1 could colocalize with lipid droplets (LDs) following ethanol treatment. Colocalization of LC3 with LDs was significantly inhibited by SQSTM1 knockdown, which also reduced ethanol-induced lipid elevation. In addition, increased ubiquitin signals were found to colocalize with SQSTM1 on LDs in response to ethanol. Moreover, the SQSTM1 signal was colocalized with that of perilipin1, a major protein on LDs. Finally, perilipin1 knockdown significantly altered ethanol-induced lipophagy. Taken together, these data support a model in which autophagosomes were directed to the LDs via SQSTM1, which bound to ubiquitinated proteins, possibly including perilipin 1, on LDs. This study provides a potential mechanistic explanation to how ethanol induces lipophagy in hepatocytes.

Mesoderm induction early response 1, family member 3 (MIER3) has recently been identified as a potential cancer susceptibility gene. However, the expression pattern and the role of MIER3 in the progression of colorectal cancer (CRC) have not yet been well characterized. Here, we reported that MIER3 was significantly reduced in human primary colorectal cancer and was associated with CRC metastasis and poor prognosis. Moreover, the up-regulation of MIER3 expression significantly inhibited CRC cell proliferation, migration and invasion in vitro and repressed tumor growth and metastasis in vivo. In contrast, down-regulation of MIER3 could promote the aggressive behaviors of CRC cells. Furthermore, our study showed that MIER3 inhibited cell proliferation and invasion partially via reduction of Sp1 and subsequent suppression of epithelial-mesenchymal transition (EMT). In conclusion, our data suggested that MIER3 plays a potential tumor suppressor role in CRC progression and may be a potentially valuable clinical prognostic marker of this disease.

Cartilage injury induced by acute excessive contact stress is common and mostly affects young adult. Although early detection of cartilage injury may prevent serious and lifelong arthritic complications, early detection and treatment is not possible due to the lack of a reliable detection method. Since chondrocyte injury and subsequent cell death are the early signs of cartilage injury, it is likely that cartilage cell apoptosis can be used to predict the extent of injury. To test this hypothesis, a near infrared probe was fabricated to have high affinity to apoptotic cells. In vitro tests show that this apoptosis probe has low toxicity, high specificity, and high affinity to apoptotic cells. In addition, there is a positive relationship between apoptotic cell numbers and fluorescence intensities. Using a mouse xiphoid injury model, we found significant accumulation of the apoptosis probes at the injured xiphoid cartilage site. There was also a positive correlation between probe accumulation and the number of apoptotic chondrocytes within the injured xiphoid cartilage, which was confirmed by TUNEL assay. The results support that the apoptosis probes may serve as a powerful tool to monitor the extent of mechanical force-induced cartilage injury in vivo.