Direct Enantioselective α-C-H Conjugate Addition of Propargylamines to α,ß-Unsaturated Ketones via Carbonyl Catalysis.

Direct asymmetric α-C-H conjugate addition of propargylamines to α,ß-unsaturated ketones remains a great challenge due to the low α-amino C-H acidity of propargylamines and the nucleophilic interference of the NH2 group. Utilizing a new type of pyridoxals featuring a benzene-pyridine biaryl skeleton and a bulky amide side chain as carbonyl catalyst, we have accomplished direct asymmetric α-C-H conjugate addition of NH2-unprotected propargylamines to α,ß-unsaturated ketones. The adducts undergo subsequent in situ intramolecular cyclization, delivering a wide range of chiral polysubstituted 1-pyrrolines in high yields (up to 92%) with excellent diastereo- and enatioelectivities (up to >20:1 dr and 99% ee). This work has demonstrated a straightforward approach to access pharmaceutically important chiral 1-pyrrolines, and it has also provided an impressive instance of direct asymmetric functionalization of inert C-H bonds enabled by biomimetic organocatalysts.

Corynebacterium glutamicum cell factory design for the efficient production of cis, cis-muconic acid.

Cis, cis-muconic acid (MA) is widely used as a key starting material in the synthesis of diverse polymers. The growing demand in these industries has led to an increased need for MA. Here, we constructed recombinant Corynebacterium glutamicum by systems metabolic engineering, which exhibit high efficiency in the production of MA. Firstly, the three major degradation pathways were disrupted in the MA production process. Subsequently, metabolic optimization strategies were predicted by computational design and the shikimate pathway was reconstructed, significantly enhancing its metabolic flux. Finally, through optimization and integration of key genes involved in MA production, the recombinant strain produced 88.2 g/L of MA with the yield of 0.30 mol/mol glucose in the 5 L bioreactor. This titer represents the highest reported titer achieved using glucose as the carbon source in current studies, and the yield is the highest reported for MA production from glucose in Corynebacterium glutamicum. Furthermore, to enable the utilization of more cost-effective glucose derived from corn straw hydrolysate, we subjected the strain to adaptive laboratory evolution in corn straw hydrolysate. Ultimately, we successfully achieved MA production in a high solid loading of corn straw hydrolysate (with the glucose concentration of 83.56 g/L), resulting in a titer of 19.9 g/L for MA, which is 4.1 times higher than that of the original strain. Additionally, the glucose yield was improved to 0.33 mol/mol. These provide possibilities for a greener and more sustainable production of MA.

Magnetic-field-assisted optical fiber quantum temperature sensor with enhanced sensitivity.

In recent years, utilizing nitrogen-vacancy color centers in diamond for temperature sensing has drawn great attention. However, increasing the sensitivity has encountered challenges due to the intrinsic temperature-dependent energy level shift, i.e., temperature responsivity, being limited to -74 kHz/K. In this Letter, we take advantage of the magnetic field to regulate the energy level to enhance temperature sensitivity. The sensor is formed by adhering a micron-sized diamond on the end face of an optical fiber, and a small magnet is mounted at a certain distance with the diamond exploiting a cured polydimethylsiloxane block as the bridge. The temperature change leads to the variation of the distance between the diamond and the magnet, thus affecting the magnetic strength felt by the diamond. This finally contributes an additional temperature-induced energy level shift, giving rise to an enhanced sensitivity. Experimental results demonstrated the proposed scheme and achieved a 4.2-fold improvement in the temperature responsivity and a 2.1-fold enhancement in sensitivity. Moreover, the diamond and the fiber-optic integrated structure improve the portability of the sensor.

CCT2 prevented ß-catenin proteasomal degradation to sustain cancer stem cell traits and promote tumor progression in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is featured by rapid progression and dismal outcomes clinically. Chaperonin Containing TCP1 Subunit 2 (CCT2) was identified as a crucial regulator for tumor progression, however, its exact role in EOC remained largely unknown. METHODS: CCT2 expression and prognostic value in EOC samples were assessed according to TCGA dataset. Proliferation and mobility potentials were assessed by CCK8, colony-formation, wound healing, and Transwell assays. Cancer stem cell (CSC) traits were evaluated by RT-PCR, WB assays, sphere-forming assay and chemoresistance analysis. Bioinformatic analysis, co-IP assays and ubiquitin assays were performed to explore the mechanisms of CCT2 on EOC cells. RESULTS: CCT2 highly expressed in EOC tissues and predicted poor prognosis of EOC patients by TCGA analysis. Silencing CCT2 significantly restrained cell proliferation, migration, and invasion. Moreover, CCT2 could effectively trigger epithelial-mesenchymal transition to confer extensive invasion potentials to EOC cells, Importantly, CCT2 positively correlated with CSC markers in EOC, and CCT2 knockdown impaired CSC traits and sensitize EOC cells to conventional chemotherapy regimens. Contrarily, overexpressing CCT2 achieved opposite results. Mechanistically, CCT2 exerted its pro-oncogene function by triggering Wnt/ß-catenin signaling. Specifically, CCT2 could recruit HSP105-PP2A complex, a well-established dephosphorylation complex, to ß-catenin via direct physical interaction to prevent phosphorylation-induced proteasomal degradation of ß-catenin, resulting in intracellular accumulation of active ß-catenin and increased signaling activity. CONCLUSIONS: CCT2 was a novel promotor for EOC progression and a crucial sustainer for CSC traits mainly by preventing ß-catenin degradation. Targeting CCT2 may represent a promising therapeutic strategy for EOC.

FFAR4 activation inhibits lung adenocarcinoma via blocking respiratory chain complex assembly associated mitochondrial metabolism.

Despite notable advancements in the investigation and management of lung adenocarcinoma (LUAD), the mortality rate for individuals afflicted with LUAD remains elevated, and attaining an accurate prognosis is challenging. LUAD exhibits intricate genetic and environmental components, and it is plausible that free fatty acid receptors (FFARs) may bridge the genetic and dietary aspects. The objective of this study is to ascertain whether a correlation exists between FFAR4, which functions as the primary receptor for dietary fatty acids, and various characteristics of LUAD, while also delving into the potential underlying mechanism. The findings of this study indicate a decrease in FFAR4 expression in LUAD, with a positive correlation (P < 0.01) between FFAR4 levels and overall patient survival (OS). Receiver operating characteristic (ROC) curve analysis demonstrated a significant diagnostic value [area under the curve (AUC) of 0.933] associated with FFAR4 expression. Functional investigations revealed that the FFAR4-specific agonist (TUG891) effectively suppressed cell proliferation and induced cell cycle arrest. Furthermore, FFAR4 activation resulted in significant metabolic shifts, including a decrease in oxygen consumption rate (OCR) and an increase in extracellular acidification rate (ECAR) in A549 cells. In detail, the activation of FFAR4 has been observed to impact the assembly process of the mitochondrial respiratory chain complex and the malate-aspartate shuttle process, resulting in a decrease in the transition of NAD+ to NADH and the inhibition of LUAD. These discoveries reveal a previously unrecognized function of FFAR4 in the negative regulation of mitochondrial metabolism and the inhibition of LUAD, indicating its potential as a promising therapeutic target for the treatment and diagnosis of LUAD.

Characterization of airborne endotoxin in personal exposure to fine particulate matter (PM2.5) and bioreactivity for elderly residents in Hong Kong.

The heavy metals and bioreactivity properties of endotoxin in personal exposure to fine particulate matter (PM2.5) were characterized in the analysis. The average personal exposure concentrations to PM2.5 were ranged from 6.8 to 96.6 µg/m3. The mean personal PM2.5 concentrations in spring, summer, autumn, and winter were 32.1±15.8, 22.4±11.8, 35.3±11.9, and 50.2±19.9 µg/m3, respectively. There were 85 % of study targets exceeded the World Health Organization (WHO) PM2.5 threshold (24 hours). The mean endotoxin concentrations ranged from 1.086 ± 0.384-1.912 ± 0.419 EU/m3, with a geometric mean (GM) varied from 1.034 to 1.869. The concentration of iron (Fe) (0.008-1.16 µg/m3) was one of the most abundant transition metals in the samples that could affect endotoxin toxicity under Toll-Like Receptor 4 (TLR4) stimulation. In summer, the interleukin 6 (IL-6) levels showed statistically significant differences compared to other seasons. Spearman correlation analysis showed endotoxin concentrations were positively correlated with chromium (Cr) and nickel (Ni), implying possible roles as nutrients and further transport via adhering to the surface of fine inorganic particles. Mixed-effects model analysis demonstrated that Tumor necrosis factor-α (TNF-α) production was positively associated with endotoxin concentration and Cr as a combined exposure factor. The Cr contained the highest combined effect (0.205-0.262), suggesting that Cr can potentially exacerbate the effect of endotoxin on inflammation and oxidative stress. The findings will be useful for practical policies for mitigating air pollution to protect the public health of the citizens.

4-Octyl itaconate attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis.

Objectives: The aim of this study was to investigate the mechanism of itaconate's potential effect in diabetic kidney disease.Methods: Renal immune responsive gene 1 (IRG1) levels were measured in db/db mice and streptozotocin (STZ) + high-fat diet (HFD)-induced diabetic mice. Irg1 knockout mice were generated. db/db mice were treated with 4-octyl itaconate (4-OI, 50 mg/kg), a derivative of itaconate, for 4 weeks. Renal function and morphological changes were investigated. Ultrastructural alterations were determined by transmission electron microscopy.Results: Renal IRG1 levels were reduced in two diabetic models. STZ+HFD-treated Irg1 knockout mice exhibited aggravated renal tubular injury and worsened renal function. Treatment with 4-OI lowered urinary albumin-to-creatinine ratio and blood urea nitrogen levels, and restored renal histological changes in db/db mice. It improved mitochondrial damage, increased expressions of peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the renal cortex of db/db mice. These were confirmed in vitro; 4-OI improved high glucose-induced abnormal mitochondrial morphology and TFAM expression in HK-2 cells, effects that were inhibited by PGC-1α silencing. Moreover, 4-OI reduced the number of apoptotic cells in the renal cortex of db/db mice. Further study showed that 4-OI increased renal Nrf2 expression and decreased oxidative stress levels in db/db mice. In HK-2 cells, 4-OI decreased high glucose-induced mitochondrial ROS production, which was reversed by Nrf2 silencing. Nrf2 depletion also inhibited 4-OI-mediated regulation of PGC-1α, TFAM, and mitochondrial apoptotic protein expressions.Conclusions: 4-OI attenuates renal tubular injury in db/db mice by activating Nrf2 and promoting PGC-1α-mediated mitochondrial biogenesis.

High-sensitivity optical-fiber magnetic sensor based on diamond and magnetic flux concentrators.

Magnetic field detection exploiting nitrogen-vacancy (NV) centers in diamond has gained increasing attention and development in recent years. Combining diamond NV centers to optical fibers provides a way for achieving magnetic sensors with high integration and portability. Meanwhile, new methods or techniques are urgently desired to improve the detection sensitivity of such sensors. In this paper, we present an optical-fiber magnetic sensor based on the NV ensemble in diamond, and employ the well-designed magnetic flux concentrators to enhance the sensitivity up to 12 pT/Hz1/2, an outstanding level among the diamond-integrated optical-fiber magnetic sensors. The dependence of sensitivity on the key parameters including the size and gap width of the concentrators are investigated by simulations and experiments, based on which the predictions on the further enhancement of sensitivity to fT level are presented.

Co-Crystallization between Aliphatic Polyesters through Co-Inclusion Complexation with Small Molecule.

Crystalline/crystalline blends of polymer have shown advantages in the preparation of new polymeric materials. However, the regulation of co-crystallization in a blend is still full of challenges due to the preferential self-crystallization driven by thermodynamics. Here, an inclusion complex approach is proposed to facilitate the co-crystallization between crystalline polymers, because the crystallization process displays a prominent kinetics advantage when polymer chains are released from the inclusion complex. Poly(butylene succinate) (PBS), poly(butylene adipate) (PBA) and urea are chosen to form co-inclusion complexes, where PBS and PBA chains play as isolated guest molecules and urea molecules construct the host channel framework. The coalesced PBS/PBA blends are obtained by fast removing the urea framework and systematically investigated by differential scanning calorimetry, X-ray diffraction, proton nuclear magnetic resonance and Fourier transformation infrared spectrometry. It is demonstrated that PBA chains are co-crystallized into PBS extended-chain crystals in the coalesced blends, while such a phenomenon has not been detected in simply co-solution-blended samples. Though PBA chains could not be totally accommodated in the PBS extended-chain crystals, their co-crystallized content increases with the initial feeding ratio of PBA. Consequently, the melting point of the PBS extended-chain crystal gradually declines from 134.3 °C to 124.2 °C with an increasing PBA content. The PBA chains playing as defects mainly induce lattice expansion along the a-axis. In addition, when the co-crystals are soaked in tetrahydrofuran, some of the PBA chains are extracted out, leading to damage to the correlative PBS extended-chain crystals. This study shows that co-inclusion complexation with small molecules could be an effective way to promote co-crystallization behavior in polymer blends.

Transformation of CO2 with Glycerol to Glycerol Carbonate over ETS-10 Zeolite-Based Catalyst.

Catalytic conversion of CO2 with the surplus glycerol (GL) produced from biodiesel manufacturing has attracted much academic and industrial attention, which proves the urgent requirement for developing high-performance catalysts to afford significant environmental benefits. Herein, titanosilicate ETS-10 zeolite-based catalysts with active metal species introduced by impregnation were employed for coupling CO2 with GL to efficiently synthesize glycerol carbonate (GC). The catalytic GL conversion at 170 °C miraculously reached 35.0% and a 12.7% yield of GC was obtained on Co/ETS-10 with CH3CN as a dehydrating agent. For comparison, Zn/ETS- Cu/ETS-10, Ni/ETS-10, Zr/ETS-10, Ce/ETS-10, and Fe/ETS-10 were also prepared, which showed inferior coordination between GL conversion and GC selectivity. Comprehensive analysis revealed that the presence of moderate basic sites for CO2 adsorption-activation played a crucial role in regulating catalytic activity. Moreover, the appropriate interaction between cobalt species and ETS-10 zeolite was also of great significance for improving the glycerol activation capacity. A plausible mechanism was proposed for the synthesis of GC from GL and CO2 in the presence of CH3CN solvent over Co/ETS-10 catalyst. Moreover, the recyclability of Co/ETS-10 was also measured and it proved to be recycled at least eight times with less than 3% decline in GL conversion and GC yield after a simple regeneration process through calcination at 450 °C for 5 h in air.

Highly Recyclable and Tough Elastic Vitrimers from a Defined Polydimethylsiloxane Network.

Despite intensive research on sustainable elastomers, achieving elastic vitrimers with significantly improved mechanical properties and recyclability remains a scientific challenge. Herein, inspired by the classical elasticity theory, we present a design principle for ultra-tough and highly recyclable elastic vitrimers with a defined network constructed by chemically crosslinking the pre-synthesized disulfide-containing polydimethylsiloxane (PDMS) chains with tetra-arm polyethylene glycol (PEG). The defined network is achieved by the reduced dangling short chains and the relatively uniform molecular weight of network strands. Such elastic vitrimers with the defined network, i.e., PDMS-disulfide-D, exhibit significantly improved mechanical performance than random analogous, previously reported PDMS vitrimers, and even commercial silicone-based thermosets. Moreover, unlike the vitrimers with random network that show obvious loss in mechanical properties after recycling, those with the defined network enable excellent thermal recyclability. The PDMS-disulfide-D also deliver comparable electrochemical signals if utilized as substrates for electromyography sensors after the recycling. The multiple relaxation processes are revealed via a unique physical approach. Multiple techniques are also applied to unravel the microscopic mechanism of the excellent mechanical performance and recyclability of such defined network.

Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.

NIR-II Navigation with an EGFR-Targeted Probe Improves Imaging Resolution and Sensitivity of Detecting Micrometastases in Esophageal Squamous Cell Carcinoma Xenograft Models.

The survival rate of esophageal squamous carcinoma (ESCC) after surgical resection is estimated to be only 30.3% due to the difficulty in identifying microinfiltration and subtle metastases. In this study, we explored the value of near-infrared fluorescence in the second window (NIR-II) using an epidermal growth factor receptor (EGFR)-targeted probe (cetuximab-IR800) for the intraoperative navigation of ESCC in xenograft mouse models. Immunohistochemical results showed that EGFR was aberrantly expressed in 94.49% (120/127) of ESCC tissues and 90.63% (58/64) of metastatic lymph nodes. Western blot results demonstrated that EGFR protein was highly expressed in ESCC cell lines. Flow cytometry data revealed that cetuximab-IR800 showed a stronger binding specificity in EGFR-positive KYSE-30 cells than in A2780 control cells (P < 0.01). In vivo imaging data showed that the ratio of mean fluorescent intensity (MFI) and tumor to background (TBR) was significantly higher in KYSE-30 subcutaneous tumors with the infusion of cetuximab-IR800 than in those with the infusion of IgG1-IR800 (P < 0.05). Surgical navigation with NIR-II imaging showed that the TBR in orthotopic ESCC was significantly higher than that of NIR in the first window (NIR-I) (2.11 ± 0.46 vs 1.58 ± 0.31, P < 0.05), and NIR-II was more sensitive than NIR-I in detecting subcentimeter metastases (94.87% (37/39) vs 58.97% (23/39), P < 0.001). In conclusion, cetuximab-IR800 with high specificity for ESCC was first used in NIR-II surgical navigation. This probe showed better imaging resolution and higher sensitivity in detecting subtle metastases derived from an orthotopic ESCC model than NIR-I, which indicates that NIR-II has promise in guiding precise surgery for ESCC patients.

Protective Effects and Mechanisms of Melatonin on Stress Myocardial Injury in Rats.

ABSTRACT: Prolonged and intense stress can exceed the body's normal self-regulation and limited compensatory and repair capacity, resulting in pathological damage to the body. In this study, we established a rat stress myocardial injury (SMI) model to explore the protective effect of melatonin (MLT) on SMI and its possible mechanisms of action. Adult female Sprague Dawley (SD) rats were randomly divided into 5 groups: blank control group (NC), SMI group, MLT low-dose group, MLT medium-dose group, and MLT high-dose group, and 10 rats in each group were used to establish a SMI model by the water immersion restraint method. We observed the changes in body weight and tail vein glucose of each group. Serum levels of corticosterone (Cort), creatine kinase isoenzyme (CK-MB), and Troponin Ⅰ (Tn-Ⅰ) and activity of lactic acid dehydrogenase were measured by ELISA. Transcriptome sequencing was used to find differentially expressed genes in the control and model groups, and the results were verified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). HE staining was used to visualize the pathological changes in the heart tissue of each group, and Western blot was used to study the differences in protein expression in the cardiomyocytes of each group to further corroborate the results. The body weight growth rate of rats in the SMI group was significantly lower than that of the NC group ( P < 0.01), and the body weight growth rate of rats in the MLT high-dose group was significantly higher than that of the SMI group ( P < 0.05) with no significant difference compared with the NC group rats. The mean blood glucose of rats in the SMI group was significantly higher compared with the NC group ( P < 0.001), while the mean blood glucose of rats in the MLT administration groups was dose-dependently reduced compared with the SMI group. By RNA-seq and bioinformatics tools such as KEGG and Gene ontology, we found that the circadian clock-related genes Ciart , Arnt1 , Per1 , and Dbp were significantly downregulated in the SMI group during water immersion stress, and differentially expressed genes were enriched in the p38MAPK signaling pathway and p53 signaling pathway. Moreover, genes related to inflammation and apoptosis were differentially expressed. ELISA results showed that Cort, CK-MB, and Tn-Ⅰ levels were significantly higher in the SMI group compared with the NC group ( P < 0.01) and melatonin reduced the levels of Cort, CK-MB, and Tn-Ⅰ and decreased lactic acid dehydrogenase activity in rat serum. HE staining results showed that melatonin could attenuate stress-generated myocardial injury. Western blot showed that melatonin reduced the expression of p38MAPK, p53, Bax, and caspase-3 and increased the expression of Bcl-2 protein in rat heart. Melatonin can inhibit myocardial injury caused by water immersion, and its mechanism of action may be related to the regulation of the expression of circadian clock genes such as Ciart , Arnt1 , Per1 , and Dbp ; the inhibition of the expression of proapoptotic proteins such as p38MAPK, p53, Bax, and caspase-3; and the increase of the expression of Bcl-2 antiapoptotic protein.

A Monitoring Method Based on FDALM and Its Application in the Sintering Process of Ternary Cathode Material.

In industrial processes, the composition of raw material and the production environment are complex and changeable, which makes the production process have multiple steady states. In this situation, it is difficult for the traditional single-mode monitoring methods to accurately detect the process abnormalities. To this end, a multimode monitoring method based on the factor dynamic autoregressive hidden variable model (FDALM) for industrial processes is proposed in this paper. First, an improved affine propagation clustering algorithm to learn the model modal factors is adopted, and the FDALM is constructed by combining multiple high-order hidden state Markov chains through the factor modeling technology. Secondly, a fusion algorithm based on Bayesian filtering, smoothing, and expectation-maximization is adopted to identify model parameters. The Lagrange multiplier formula is additionally constructed to update the factor coefficients by using the factor constraints in the solving. Moreover, the online Bayesian inference is adopted to fuse the information of different factor modes and obtain the fault posterior probability, which can improve the overall monitoring effect of the model. Finally, the proposed method is applied in the sintering process of ternary cathode material. The results show that the fault detection rate and false alarm rate of this method are improved obviously compared with the traditional methods.

The impact of patient age and procedure type on postoperative opioid use following ambulatory pediatric urologic procedures.

PURPOSE: The aim of this study is to determine whether patient age and procedure type are associated with duration of opioid use in pediatric patients undergoing ambulatory urologic procedures. METHODS: We retrospectively reviewed pediatric patients who underwent outpatient urologic procedures from 2013 to 2017. At postoperative visits, parents reported the number of days their child took opioid pain medication. Factors associated with duration of opioid use were evaluated using negative binomial regression models. RESULTS: 805 patients were included: 320 infants (39.8%), 430 children (53.4%), and 55 adolescents (6.8%). Overall mean length of opioid use was 1.7 (± 2.6) days. On average, infants used opioids for the shortest duration: 1.5 (± 2.3) days, followed by children: 1.7 (± 2.5) days, and adolescents: 3.1 (± 4.6) days. In adjusted models, adolescents used opioids for 85.2% longer (95% CI 13.1-161.8%; p < 0.001) than children and infants used opioids for 19.4% shorter duration (95% CI 0.4-34.7%; p = 0.05) than children. Each 1-year increase in age was associated with 6.1% increased duration of opioid use (95% CI 3.9-8.5%; p < 0.0001). Patients who underwent circumcision, hypospadias repair, and penile reconstruction took opioids for 75.9% (95% CI 42.6-117.1%; p < 0.001), 144.2% (95% CI 76.4-238.0%; p < 0.001), and 126.7% (95% CI 48.8-245.3%; p < 0.001) longer respectively than patients who underwent inguinal procedures. CONCLUSIONS: Increasing age, circumcision, hypospadias repair, and penile reconstruction are associated with increased duration of opioid use.

A Novel Approach to Automated 3D Spalling Defects Inspection in Railway Tunnel Linings Using Laser Intensity and Depth Information.

The detection of concrete spalling is critical for tunnel inspectors to assess structural risks and guarantee the daily operation of the railway tunnel. However, traditional spalling detection methods mostly rely on visual inspection or camera images taken manually, which are inefficient and unreliable. In this study, an integrated approach based on laser intensity and depth features is proposed for the automated detection and quantification of concrete spalling. The Railway Tunnel Spalling Defects (RTSD) database, containing intensity images and depth images of the tunnel linings, is established via mobile laser scanning (MLS), and the Spalling Intensity Depurator Network (SIDNet) model is proposed for automatic extraction of the concrete spalling features. The proposed model is trained, validated and tested on the established RSTD dataset with impressive results. Comparison with several other spalling detection models shows that the proposed model performs better in terms of various indicators such as MPA (0.985) and MIoU (0.925). The extra depth information obtained from MLS allows for the accurate evaluation of the volume of detected spalling defects, which is beyond the reach of traditional methods. In addition, a triangulation mesh method is implemented to reconstruct the 3D tunnel lining model and visualize the 3D inspection results. As a result, a 3D inspection report can be outputted automatically containing quantified spalling defect information along with relevant spatial coordinates. The proposed approach has been conducted on several railway tunnels in Yunnan province, China and the experimental results have proved its validity and feasibility.

lncRNA SNHG11 promotes lung cancer cell proliferation and migration via activation of Wnt/ß-catenin signaling pathway.

Lung cancer ranks topmost among the most frequently diagnosed cancers. Despite increasing research, there are still unresolved mysteries in the molecular mechanism of lung cancer. Long noncoding RNA small nucleolar RNA host gene 11 (SNHG11) was found to be upregulated in lung cancer and facilitated lung cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition progression while suppressed cell apoptosis. Moreover, the high expression of SNHG11 was correlated with poor prognosis of lung cancer patients, TNM stage, and tumor size. Further assays demonstrated that SNHG11 functioned in lung cancer cells via Wnt/ß-catenin signaling pathway. Subsequently, Wnt/ß-catenin pathway was found to be activated through SNHG11/miR-4436a/CTNNB1 ceRNA axis. As inhibiting miR-4436 could only partly rescue the suppression of cell function induced by silencing SNHG11, it was suspected that ß-catenin might enter cell nucleus through other pathways. Mechanism investigation proved that SNHG11 would directly bind with ß-catenin to activate classic Wnt pathway. Subsequently, in vivo tumorigenesis was also demonstrated to be enhanced by SNHG11. Hence, SNHG11 was found to promote lung cancer progression by activating Wnt/ß-catenin pathway in two different patterns, implying that SNHG11 might contribute to lung cancer treatment by acting as a therapeutic target.

Towards Automated 3D Inspection of Water Leakages in Shield Tunnel Linings Using Mobile Laser Scanning Data.

On-site manual inspection of metro tunnel leakages has been faced with the problems of low efficiency and poor accuracy. An automated, high-precision, and robust water leakage inspection method is vital to improve the manual approach. Existing approaches cannot provide the leakage location due to the lack of spatial information. Therefore, an integrated deep learning method of water leakage inspection using tunnel lining point cloud data from mobile laser scanning is presented in this paper. It is composed of three parts as follows: (1) establishment of the water leakage dataset using the acquired point clouds of tunnel linings; (2) automated leakage detection via a mask-region-based convolutional neural network; and (3) visualization and quantitative evaluation of the water leakage in 3D space via a novel triangle mesh method. The testing result reveals that the proposed method achieves automated detection and evaluation of tunnel lining water leakages in 3D space, which provides the inspectors with an intuitive overall 3D view of the detected water leakages and the leakage information (area, location, lining segments, etc.).

Biodegradable Nanoagents with Short Biological Half-Life for SPECT/PAI/MRI Multimodality Imaging and PTT Therapy of Tumors.

Rapid clearance of nanoagents is a critical criterion for their clinical translation. Herein, it is reported that biodegradable and renal clearable nanoparticles are potentially useful for image-guided photothermal therapy of tumors. The multifunctional nanoparticles with excellent colloidal stability are synthesized through coordination reactions between Fe3+ ions and gallic acid (GA)/polyvinyl pyrrolidone (PVP) in aqueous solution. Detailed characterization reveals that the resulting Fe3+ /GA/PVP complex nanoparticles (FGPNs) integrate strong near-infrared absorption with paramagnetism well. As a result, the FGPNs present outstanding performance for photoacoustic imaging and magnetic resonance imaging of tumors, and outstanding photothermal ablation effect for tumor therapy owing to their high photothermal conversion efficiency. More importantly, the pharmacokinetic behaviors of the FGPNs determined through 125 I labeling suggest that the FGPNs are readily degraded in vivo showing a short biological half-life, and the decomposition products are excreted through either renal clearance pathway or bowel elimination pathway via stomach, which highlights the characteristics of the current multifunctional theranostic agent and their potential in clinical translation.