Search

Traditional diagnostic strategies are unable to accurately discriminate between patients with poor and satisfied prognosis in colon cancer. Therefore, it is urgently recommended to identify new biomarkers in favor of better selection of patients at higher risk of recurrence or poor outcomes, with the aim of early intervention or avoiding overtreatment.The weighted gene correlation network analysis (WGCNA), together with the proportion of tumor infiltrating immune cells, were employed to screen the key module related to immune infiltration. Using these genes among the key module, a predictive signature was generated via LASSO and multi-Cox regression method. Moreover, a novel nomogram was further developed by combining important clinical parameters and the predictive signature.Genes among the green module, indicating the highest correlation with regulatory T cells (Tregs), were incorporated into the establishment of predictive model. Then, a Tregs-related risk signature (TRRS) consisting of four genes (NRG1, TEX11, OVOL3 and FCRL2) was established, which performed well in predicting the mortality risk of colon cancer in both internal and external validation groups (p=0.004 for TCGA training set, p=0.016 for TCGA testing set and p=0.03 for GSE39582 dataset). Combining TNM stage and age, we developed a nomogram for 1-, 3-, 5-year OS, presenting a more reliable predictive performance in survival based on the receiver operating characteristic (ROC) curves and calibration curves (3-year AUC: 0.83 and 0.74 in the TCGA and GEO database, respectively).We constructed a four-gene signature for predicting the prognosis of patients with colon cancer, and further developed the nomogram together with TNM stage and age to improve the predictive efficacy.

OBJECTIVE: To explore the mechanism of F.nucleatum-induced pyroptosis in macrophages and the regulatory role of inflammasomes. METHODS: Lactate dehydrogenase (LDH) cytotoxicity assay and Hoechst 33342/PI double fluorescence staining were used to analyze cytolysis in F.nucleatum-infected macrophage RAW264.7 cells.The expressions of pyroptosis-related proteins caspase-1, GSDMD and IL-1β were determined using Western blotting.Inflammasome activation in the cells was analyzed by detecting the mRNA expressions of NLRP3, NLRC4, AIM2, and NLRP1 with qRT-PCR.RNA interference technique was used to knock down the key molecules involved in pyroptosis regulation in the macrophages, and the pyroptosis and necrosis rates of the cells following F.nucleatum infection were examined. RESULTS: The results of LDH cytotoxicity assay and double-fluorescence staining showed that F.nucleatum infection caused swelling and lytic cell death in RAW264.7 cells.F.nucleatum infection resulted in the activation of caspase-1 and GSDMD and upregulated IL-1β expression in a multiplicity of infection (MOI)-and time-dependent manner (P < 0.05).qRT-PCR revealed significantly increased expression of NLRC4 mRNA in the macrophages after F.nucleatum infection (P < 0.05).NLRC4 silencing by siRNA strongly inhibited the activation of caspase-1/GSDMD pathway and reduced cell death (P < 0.05) and IL-1β expression in F.nucleatum-infected cells. CONCLUSION: NLRC4 inflammasome drives caspase-1/GSDMD-mediated pyroptosis and inflammatory signaling in F.nucleatum-infected macrophages, suggesting the potential of NLRC4 inflammasome as a therapeutic target for F.nucleatum infections.

ThePOGZgene has been found frequently mutated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability (ID). We have recently shown that POGZ maintains mouse embryonic stem cells (ESCs) as a chromatin regulator and a transcription factor. However, the exact mechanisms remain unclear. Here we show that POGZ plays important role in the maintenance of ESCs by silencing theDuxgene and certain endogenous retroviruses (ERVs). POGZ directly binds to theDuxgene and ERVs, and its depletion leads to up-regulation of 2C genes and the repetitive elements such as RLTR9E and IAP (the intracisternal A-type particles), resulting in transition to a 2C-like (2CLC) state and genome instability. POGZ regulates ESC heterochromatin state by association and recruiting TRIM28 and SETDB1, and its loss leads to increased H3K4me3 and H3K27ac, and decreased H3K9me3 at local chromatin. Activation of POGZ-bound ERVs is associated with up-regulation of nearby neural genes. Chimeric transcripts that are initiated within ERVs and spliced to genic exons are highly expressed inPogz−/−ESCs. Our findings establish that POGZ is required for the maintenance of ESCs by repressingDuxand silencing ERVs, which may provide important insights into the disease pathology caused by POGZ dysfunction.HighlightsPOGZ depletion leads to activation of 2C genesPOGZ depletion leads to deregulation of ERVsPOGZ directly binds and repressesDuxPOGZ associates with TRIM28/SETDB1 to maintain heterochromatin state to silence ERVsActivation of POGZ-bound ERVs is associated with up-regulation of nearby neural genes

OBJECTIVE: To compare a new thermosensitive recombinant human amelogenin (rhAm) carrier and traditional propylene glycol alginate (PGA) carrier for their characteristics, antibacterial activity, and biocompatibility with human periodontal membrane fibroblasts. METHODS: PGA-rhAm was prepared by mixing 3.3% PGA and rhAm, and CS-βGP-rhAm was prepared by mixing 2% chitosan (CS) with rhAm and then with 60% β-sodium glycerophosphate solution (βGP) as the crosslinking agent. The biophysical properties of the prepared carriers were characterized, and their antibacterial activity was assessed by observing Staphylococcus aureus growth. The biocompatibility of the carriers was evaluated in human periodontal membrane fibroblasts (hPDLFs) using CCK8 assay and scratch test, and mRNA and protein expressions of osteogenic genes of the cells incubated with the carriers were detected using RT-qPCR and Western blotting; osteogenic differentiation of the cells was detected using alkaline phosphatase staining. RESULTS: PGA-rhAm had a viscosity value of 3.262±0.055 Pa.s. CS-βGP-rhAm had a solidification capacity of 6 min at 37 ℃ with a pH value close to that of the oral cavity and a swelling rate of about 90%. CS-β GP-rhAm maintained sustained release of rhAm for over 2 weeks with a self-degradation time over 3 weeks. CS-βGPrhAm more effectively inhibited the growth of S. aureus than rhAm-loaded PGA. While PGA did not obviously affect the proliferation of hPDLFs, both CS-βGP and CS-βGP-rhAm significantly promoted the cell proliferation(P < 0.001). Scratch test showed that after rhAm loading, both CS-βGP and PGA promoted cell migration (P < 0.01). CS-βGP-rhAm significantly enhanced the mRNA expressions of RUNX2 and OCN mRNA level and the protein expressions of Ki67, RUNX2, collagen I, and β-catenin (P < 0.05); PGA-rhAm only enhanced RUNX2 (P < 0.05) and OCN (P < 0.01) mRNA expressions without significant effects on the protein expressions. Alkaline phosphatase staining results showed that CS-βGP, but not PGA, promoted osteogenic differentiation of hPDLFs. CONCLUSION: CS-βGP carrier is capable of sustained release of rhAm, inhibiting the growth of S. aureus, and improving the biological activity of hPDLFs without affecting the bioactivity of rhAm after drug loading.

Supersaturated solid–solutions in a W–Cr alloy system were fabricated by conventional milling and plasma milling. The different extension mechanisms of the solid solubility that were created by ball milling with and without discharge plasma were studied. The solid–solubility of Cr in W for the P-milling W–Cr alloy system was higher, which indicates that plasma milling promotes the formation of W(Cr) solid–solution more easily than conventional milling. According to Miedema’s model, in the W–Cr alloy system, the free-energy change to form a W(Cr) solid solution by plasma milling is reduced compared with conventional milling because of the heating effect of the discharge plasma. Therefore, a higher stored energy in the grain boundaries and dislocations of the W–Cr nanograins during plasma milling makes it easier to overcome the thermodynamic barrier in the formation of a solid–solution, when compared with conventional milling.

Solar flare is one of the severest solar activities on the sun, and it has many important impacts on the near-earth space. It has been found that flight arrival delays will increase during solar flare. However, the detailed intrinsic mechanism of how solar flares influence the delays is still unknown. Based on 5-years huge amount of flight data, here we comprehensively analyze the flight departure delays during 57 solar flares. It is found that the averaged flight departure delay time during solar flares increased by 20.68% (7.67 min) compared to those during quiet periods. It is also shown that solar flare related flight delays reveal apparent time and latitude dependencies. Flight delays during dayside solar flares are more serious than those during nightside flares, and the longer (shorter) delays tend to occur in the lower (higher) latitude airport. Further analyses suggest that flight delay time and delay rate would be directly modulated by the solar intensity (soft X-ray flux) and the Solar Zenith Angle. For the first time, these results indicate that the communication interferences caused by solar flares will directly affect flight departure delay time and delay rate. This work also expands our conventional understandings to the impacts of solar flares on human society, and it could also provide us with brand new views to help prevent or cope with flight delays., submitted to APJL

Understanding the age distribution of groundwater can provide information on both the recharge history as well as the geochemical evolution of groundwater flow systems. Of the few candidates available that can be used to date old groundwater

We have studied the nuclear region of the previously detected dual AGN system in the galaxy pair IRAS 05589+2828 and 2MASX J06021107+2828382 through new optical spectroscopy observations, along with radio and X-ray archival data. Our multiwavelength data strongly suggest that the Sy1 \iras\, (z=0.0330$\pm$0.0002) conforms to a dual AGN system with the Sy2 \twomas\, (z=0.0334$\pm$0.0001) with a projected separation obtained from the radio data of 20.08\arcsec\, ($\sim$13.3\,kpc). Analysis of the optical spectra reveals a faint narrow extended emission from H$\alpha$ and [OIII] amidst the two AGN, supporting evidence for an ongoing merger. \iras\, is a double component narrow emission line AGN, with complex broad Balmer emission line profiles that clearly show a strong red-peaklet with a velocity shift of $\sim$3500\,km\,s$^{-1}$. The black hole mass estimates of \iras\, and \twomas\, are log\,M$\rm_{BH}$\,=\,8.59\,$\pm$\,0.14 (M$_\odot$) and log\,M$\rm_{BH}$\,=\,8.21$\pm$0.2 (M$_\odot$), respectively. In the X-ray bands, \iras\, is compatible with a Type 1 object, showing both spectral and flux variability. \chandra\, data of 2MASX\,J06021107+2828382 allowed us to measure a high hardness ratio in this source, providing evidence for a Type 2 AGN. The 22 GHz image obtained with the {\it Karl G. Jansky Very Large Array} has revealed that both AGN are compact radio objects with spectral indices -0.26$\pm$0.03 and -0.70$\pm$0.11, confirming for the first time its dual AGN nature in the radio bands., Comment: Accepted for publication in MNRAS. 20 pages, 15 figures

Enamel is the highly mineralized outer layer of teeth; the cells responsible for enamel formation are ameloblasts. Local hypoxia and hypoxia inducible factor (HIF) in embryonic tissues are important to promote normal organogenesis. However, hypoxic state in tooth germs and the roles of HIF in ameloblast differentiation have not been understood. The aim of this study is to clarify the role of HIF in ameloblast differentiation during tooth germ development. We found that tooth germs were under hypoxia and HIF-1α and HIF-2α were expressed in tooth germs in embryonic mice. Then, we used HIF inhibitors to evaluate the function of HIF during tooth germ development. The HIF-2α inhibitor significantly decreased the size of tooth germs in organ culture, while the HIF-1α inhibitor did not apparently affect the size of tooth germs. The HIF-2α inhibitor enhanced the expression of amelogenin, a marker of ameloblast differentiation, in the tooth germs in organ culture and rat dental epithelial SF2 cells. Moreover, we found that the HIF-2α inhibitor-stimulating amelogenin expression was regulated by hes-related family basic helix-loop-helix transcription factor with YRPW motif 2(Hey2) in SF2 cells. These findings suggest that the HIF-2α–Hey2 axis plays an important role in ameloblast differentiation during tooth germ development.

Schistosomiasis is a parasitic disease that seriously hinders socioeconomic developments and threatens public health security. To achieve the global elimination of schistosomiasis as a public health problem by 2030, WHO released the guideline on control and elimination of human schistosomiasis on February, 2022, with aims to provide evidence-based recommendations for schistosomiasis morbidity control, elimination of schistosomiasis as a public health problem, and ultimate interruption of schistosomiasis transmission in disease-endemic countries. Following concerted efforts for decades, great achievements have been obtained for schistosomiasis control in China where the disease was historically highly prevalent, and the country is moving towards schistosomiasis elimination. This article reviews the successful experiences from the national schistosmiasis control program in China, and summarizes their contributions to the formulation and implementation of the WHO guideline on control and elimination of human schistosomiasis. With the progress of the "Belt and Road" initiative, the world is looking forward to more China's solutions on schistosomiasis control.

On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.

The nucleus basalis of Meynert (NBM) is a key subcortical structure that is important in arousal, cognition, brain network modulation, and has been explored as a deep brain stimulation target. It has also been implicated in several disease states, including Alzheimer’s disease, Parkinson’s disease, and temporal lobe epilepsy (TLE). Given the small size of NBM and variability between patients, NBM is difficult to study; thus, accurate, patient-specific segmentation is needed. We investigated whether a deep learning network could produce accurate, patient-specific segmentations of NBM on commonly utilized 3T MRI. It is difficult to accurately segment NBM on 3T MRI, with 7T being preferred. Paired 3T and 7T MRI datasets of 21 healthy subjects were obtained, with 6 completely withheld for testing. NBM was expertly segmented on 7T MRI, providing accurate labels for the paired 3T MRI. An external dataset of 14 patients with TLE was used to test the model on brains with neurological disorders. A 3D-Unet convolutional neural network was constructed, and a 5-fold cross-validation was performed. The model was evaluated on healthy subjects using the held-out test dataset and the external dataset of TLE patients. The model demonstrated significantly improved dice coefficient over the standard probabilistic atlas for both healthy subjects (0.68MEAN±0.08SD vs. 0.47±0.06, p=0.0089, t-test) and TLE patients (0.63±0.08 vs. 0.38±0.19, p=0.0001). Additionally, the centroid distance was significantly decreased when using the model in patients with TLE (1.22±0.33mm, 3.25±2.57mm, p=0.0110). We developed the first model, to our knowledge, for automatic and accurate patient-specific segmentation of the NBM.

As-cast in-situ nanoparticle reinforced CuSn10Zn2Fe1.5Co0.5 (wt-%) alloy was selected as base metal (BM) and filler for welding. Butt joints were obtained by tungsten inert gas (TIG) welding. Micro...

The sliding belt assembly plays a key role in spin reduction to protect the electronic components and smoothly control the projectile posture. The complete guided projectile motion in the bore was reproduced by LS-DYNA software, where the gunpowder pressure was loaded on the projectile bottom. The dynamic parameters of the projectile obtained by simulation agree well with the test, including the axial velocity, acceleration and rotation speed. Great spin reduction occurs in the bore by the sliding belt assembly, which is indicated by the rotation speed and the motion of the sliding belt and projectile, respectively. From the interaction of the belt assembly at typical times, it is the escaping from the bases periodically of the belt ring so that greatly spin reduction of the projectile body is achieved.

Objective: The present study evaluated the effectiveness of a transdiagnostic group-based cognitive-behavioural therapy (CBT) programme for treating anxiety, comorbid depression, and functional imp...

Quorum sensing inhibitors (QSIs) can block the quorum sensing system and might be useful in therapy of drug-resistant bacterial infections. To explore the anti-quorum sensing actinomycetes from marine habitats, in this study, a marine actinobacterium exhibiting strong anti-quorum sensing activity was isolated from marine sediment and identified as Nocardiopsis dassonvillei JS106. Effects of different culture media on the bioactivity and metabolites production of JS106 were investigated by using single-factor and orthogonal experiments. The results showed that soybean meal and NaCl were two important factors in the culture medium, and could significantly affect both the bioactivity and metabolites production of JS106. By culturing in the optimized medium containing 10 g/L soluble starch, 10 g/L soybean meal, and 15 g/L NaCl at pH 6.5, both metabolites production and anti-quorum sensing activity of JS106 were significantly increased (302 and 241%, respectively) compared to the original condition. The culture liquid of JS106 also showed strong anti-biofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa with the inhibition rate of 77.94 and 50.56% at the concentration of 20 vol %, while it did not inhibit the growth of planktonic cells. Questiomycin A and a new compound 2-hydroxyacetate-3-hydroxyacetamido-phenoxazine (HHP) were isolated and identified from the cultures of JS106. The anti-quorum sensing activities (IC50) of questiomycin A and HHP against violacein production by Chromobacterium violaceum 12472 were 6.82 and 23.59 μg/mL, respectively. The strong anti-quorum sensing activity of N. dassonvillei JS106 indicated that this strain and its active phenoxazine metabolites could have good potential in anti-quorum sensing related applications.

Patient-submitted images can be helpful for medical decision-making when requested by dermatologists. However, unsolicited photographs may burden dermatologists and have variable clinical usefulness. In this survey study, we characterized dermatologists’ views on unsolicited patient photographs across various practice settings.

We report on a two-fold increase of the $^{39}Ar$ loading rate in an atom trap by enhancing the generation of metastable atoms in a discharge source. Additional atoms in the metastable $1s_5$ level (Paschen notation) are obtained via optically pumping both the $1s_4$ - $2p_6$ transition at 801 nm and the $1s_2$ - $2p_6$ transition at 923 nm. By solving the master equation for the corresponding six-level system, we identify these two transitions to be the most suitable ones and encounter a transfer process between $1s_2$ and $1s_4$ when pumping both transitions simultaneously. We calculate the previously unknown frequency shifts of the two transitions in $^{39}Ar$ and confirm the results with trap loading measurements. The demonstrated increase in the loading rate enables a corresponding decrease in the required sample size, uncertainty and measurement time for $^{39}Ar$ dating, a significant improvement for applications such as dating of ocean water and alpine ice cores., arXiv admin note: text overlap with arXiv:2005.11056

OBJECTIVE: To investigate the role of proline 4-hydroxylase Ⅱ (P4HA2) in the occurrence and progression of liver cancer. METHODS: GEPIA and Human Protein Atlas database were used to predict the expression of P4HA2 in hepatocellular carcinoma (HCC), and K-M plotter online database was used to analyze the relationship between P4HA2 expression and the prognosis of HCC. We also examined the expressions of P4HA2 in HCC cells and normal hepatocytes using qRT-PCR and Western blotting. With lentivirus-mediated RNA interference, P4HA2 expression was knocked down in hepatoma SNU-449 and Hep-3B cells, and the changes in cell proliferation, migration and invasion were assessed using cell counting kit-8 (CCK-8) assay, colony formation test, scratch test and Transwell assay. The changes in the expressions of epithelial-mesenchymal transition (EMT) and PI3K/Akt/mTOR signal pathway-related proteins were detected using Western blotting. RESULTS: Online database analysis showed that the expression of P4HA2 was significantly higher in HCC tissues than in normal liver tissues (P < 0.05). The expression levels of P4HA2 mRNA and protein were also significantly higher in HCC cell lines than in normal hepatocytes (P < 0.01). Lentivirus-mediated RNA interference of P4HA2 significantly lowered the expression levels of P4HA2 mRNA and protein in the hepatoma cells (P < 0.05) and caused obvious inhibition of cell proliferation, migration and invasion. P4HA2 knockdown significantly increased the expression of E-cadherin protein, lowered the expressions of N-cadherin and Snail, and obviously decreased the expressions of phosphorylated PI3K, AKT and mTOR (P < 0.05). CONCLUSION: P4HA2 enhances the proliferation, migration, invasion, and EMT of hepatoma cells by activating the PI3K/Akt/mTOR signaling pathway to promote the occurrence and progression of liver cancer.

The aim of the study was to explore the risk factors of ovarian hyperstimulation in patients undergoing long-acting gonadotropin-releasing hormone (GnRH) agonist protocol in follicular phase of ovulation induction therapy and to establish a predictive model.A total of 1289 patients who received Long-acting GnRH agonist protocol in follicular phase for ovulation induction in the Fujian Provincial Maternity and Child Health Hospital from July 1, 2018, to July 31, 2019, were selected. Among them, 33 patients developed moderate/severe ovarian hyperstimulation syndrome. The relevant indicators of the two groups were followed up for comparison, and Lasso regression was used to screen independent risk factors and construct a nomogram prediction model. A receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model.Univariate analysis suggested that the woman's age, basal antral follicle number (AFC), total gonadotropin (Gn) dose, Gn starting dose, basal estradiol (E2) level, basal anti-Müllerian hormone (AMH) value, number of follicles obtained, Gn start day E2, the difference in follicle-stimulating hormone (FSH) value and Gn starting day were statistically significant. Significant indicators of univariate analysis and clinical significance were included in the Lasso regression model, and AFC, woman's age, polycystic ovary syndrome, Gn starting dose and number of follicles obtained were finally screened as final predictors. The ROC curve indicated that the area under the curve (AUC) was 0.812.Ovarian hyperstimulation caused by long-acting GnRH agonist protocol in follicular phase for ovulation stimulation has a certain predictability. Paying attention to the patient's age, AFC, Gn starting dose, number of follicles obtained, and whether PCOS is evident may lead to early detection of ovarian hyperstimulation syndrome, which has clinical guiding significance.

OBJECTIVE: To assess the effect of early abdominal puncture drainage (APD) on autophagy and Nrf-2/HO-1 pathway in rats with severe acute pancreatitis (SAP) and explore the possibile mechanism. METHODS: Thirty-two male SD rats were randomly divided into sham-operated (SO) group, SAP group with retrograde injection of 4% sodium taurocholate, APD group with insertion of a drainage tube into the lower right abdomen after SAP induction, and APD + ZnPP group with intraperitoneal injection of 30 mg/kg ZnPP 12 h before APD modeling. Blood samples were collected from the rats 12 h after modeling for analysis of amylase and lipase levels and serum inflammatory factors. The pathological changes of the pancreatic tissue were observed with HE staining. Oxidative stress in the pancreatic tissue was detected with colorimetry, and sub-organelle structure and autophagy in pancreatic acinar cells were observed by transmission electron microscopy. The expressions of autophagy-related proteins and Nrf-2/HO-1 pathway were detected using RT-PCR and Western blotting. RESULTS: Compared with those in SAP group, the rats with APD treatment showed significantly alleviated pathologies in the pancreas, reduced serum levels of lipase, amylase and inflammatory factors, lowered levels of oxidative stress, and activated expressions of Nrf-2/HO-1 pathway in the pancreas. The ameliorating effect of ADP was significantly inhibited by ZnPP treatment before modeling. APD obviously reversed mitochondrial and endoplasmic reticulum damages and p62 accumulation induced by SAP. CONCLUSION: APD treatment can suppress oxidative stress and repair impaired autophagy in rats with SAP by activating the Nrf-2/HO-1 pathway, thereby reducing the severity of SAP.

An essential non-linear flow-energy converter based on fully-passive oscillating-foil is proposed to improve the adaptation under varied flow conditions. The converter consists of a C-shape foil elastically supported by two springs, an arm that transfers the plunging motion into swing motion and two dampers to absorb mechanical energy. For the purpose of improving performance within a broader range of exciting frequency under varied flow speeds the authors employ two essential non-linear springs in the converter. The adaptation and performance of an essential non-linear converter were assessed numerically. The effects of non-linear stiffness coefficients, varied damping factors, and speed ratios are investigated in detail. The results indicated that the effective range of speed ratio (range of synchronisation) is broadened from (0.4, 2.0) to (0.2, 4.0) with appropriately tuned non-linear stiffness, so the adaptation of the flow energy converter based on oscillating-foil is improved, rendering it more suitable for varied flow conditions and real applications. Besides, performance gains at the design point can be realised as compared with the linear converter. It is found that two fundamental mechanisms are advantageous to enhance the adaptation and performance of the converter: the increased effective stiffness with oscillating amplitude and the non-sinusoidal swing motion.

The magnetohydrodynamic (MHD) control has great potential in the applications of hypersonic vehicles. Typically, the MHD flowfield in these applications is low magnetic Reynolds (Rem ) compressible...

This study evaluated the bioequivalence of China-manufactured biosimilar, HLX02, to reference China (CN)- and European Union (EU)-sourced trastuzumab. This was a two-part Phase 1 study conducted in healthy Chinese males. Part 1 evaluated the safety of different doses of HLX02 (2, 4, 6 or 8 mg/kg; intravenous infusion over 90 min, n = 3 per group). Part 2, a randomized, double-blind study, investigated the pharmacokinetics (PK), safety and immunogenicity of study drugs (HLX02 [n = 37], CN-trastuzumab [n = 35] or EU-trastuzumab [n = 37] at the dose suggested by Part 1 results). The primary PK endpoint was the area under the serum concentration–time curve from time 0 to infinity (AUCinf). Equivalence was concluded if the 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) fell in the equivalence criteria of 0.80–1.25. In Part 1, all doses of HLX02 were well tolerated and 6 mg/kg was suggested for Part 2. The GLSMRs and 90% CIs for AUCinf were: 0.950 (0.891–1.013), 0.914 (0.858–0.973) and 0.962 (0.902–1.025) for HLX02 versus CN-trastuzumab, HLX02 versus EU-trastuzumab and CN-trastuzumab versus EU-trastuzumab, respectively. Secondary endpoints comparisons also fell in the equivalence criteria. Treatment-emergent adverse events were reported in 75.7, 86.5 and 70.3% of the subjects in HLX02, CN-trastuzumab, and EU-trastuzumab groups, respectively. No serious adverse events or deaths occurred. No treatment-related anti-drug antibodies were detected. This study demonstrated comparable safety profiles and PK bioequivalence among HLX02, CN-trastuzumab and EU-trastuzumab in healthy Chinese male subjects. ClinicalTrials.gov, NCT02581748, registered at October 19, 2015.

AIM To explore the activation of necroptosis triggered by Enterococcus faecalis in human osteoblastic MG63 cells and provide new insights into the pathogenesis of refractory apical periodontitis. METHODOLOGY The viability of MG63 cells exposed to live E. faecalis was investigated using the cell counting kit-8 assay. The relative expressions of specific markers for necroptosis, namely p-RIPK3 and p-MLKL, were determined by western blotting. Cells pretreated with necrosulfonamide and GSK'872, which are specific inhibitors for MLKL and RIPK3, respectively, were then subjected to lactate dehydrogenase (LDH) cytotoxicity assay, flow cytometry analysis and Hoechst 33342/PI double fluorescence staining. Lentiviral-delivered short hairpin RNA (shRNA) targeting MLKL was employed to further confirm the activation of necroptosis in MG63 cells infected with E. faecalis. Transmission electron microscopy was additionally used to observe the morphological characteristics. Statistical analysis was conducted using Student's t-tests or one-way ANOVA followed by the Student-Newman-Keuls test. RESULTS The infection with E. faecalis significantly inhibited the viability of MG63 cells in a multiplicity of infection- and infection time-dependent manners (P

In recent years, there has been an increase in the frequency of Cercospora beticola (Sacc.), the cause of Cercospora leaf spot (CLS) in sugarbeet (Beta vulgaris L.), isolates with demethylase inhib...

Model updating is a widely adopted method to minimize the error between test results from the real structure and outcomes from the finite element (FE) model for obtaining an accurate and reliable FE model of the target structure. However, uncertainties from the environment, excitation and measurement variability can reduce the accuracy of predictions of the updated FE model. The Bayesian model updating method using multiple Markov chains based on differential evolution adaptive metropolis (DREAM) algorithm is explored, which runs multiple chains simultaneously for a global exploration, and it automatically tunes the scale and orientation of the proposal distribution during the evolution of the posterior distribution. The performance of the proposed method is illustrated numerically with a beam model and a three-span rigid frame bridge. Results show that the DREAM algorithm is capable for updating the FE model in civil engineering. It extends the Bayesian model updating method to multiple Markov chains scenario, which provides higher accuracy than single chain algorithm such as the delayed rejection adaptive metropolis-hastings (DRAM) method. Moreover, results from both examples indicate that the proposed method is insensitive to values of initial parameters, which avoid errors resulting from inappropriate prior knowledge of parameters in the FE model updating.

Pulp and periapical diseases are common and frequently occurring diseases of which diagnosis and treatment must be dealt with by the dental clinicians. The diagnostic techniques of these diseases include evaluation of pulp vitality, measurement of pulp blood circulation and analysis and judgment of root canal anatomy. With the continuous emergence of digital and imaging technologies, the correct application of these technologies in clinic will help clinicians improve their abilities in diagnosis and treatment of related diseases. The present article summarizes and reviews the progress of assistant technology for diagnosing dental pulp and periapical diseases in recent years and puts forward some suggestions for its application.牙髓及根尖周疾病是口腔临床诊疗中的常见病和多发病，这类疾病的诊断技术涵盖了牙髓活力状态检测、牙髓血运状况测定以及根管解剖形态分析和判断。数字化技术和影像技术不断涌现并快速发展，将这些技术正确应用于牙体牙髓临床诊疗中，将有助于提高口腔临床医师对相关疾病的正确诊断率。本文就近年牙髓诊断辅助技术的进展作一总结、回顾，并提出应用建议。.

In drug resistant temporal lobe epilepsy, automated tools for seizure onset zone (SOZ) localization using brief interictal recordings would supplement presurgical evaluations and improve care. Thus, we sought to localize SOZs by training a multi-channel convolutional neural network on stereo-EEG (SEEG) cortico-cortical evoked potentials. We performed single pulse electrical stimulation with 10 drug resistant temporal lobe epilepsy patients implanted with SEEG. Using the 500,000 unique post-stimulation SEEG epochs, we trained a multi-channel one-dimensional convolutional neural network to determine whether an SOZ was stimulated. SOZs were classified with a mean leave-one-patient-out testing sensitivity of 78.1% and specificity of 74.6%. To achieve maximum accuracy, the model requires a 0-350 ms post stimulation time period. Post-hoc analysis revealed that the model accurately classified unilateral vs bilateral mesial temporal lobe seizure onset, and neocortical SOZs. This is the first demonstration, to our knowledge, that a deep learning framework can be used to accurately classify SOZs using cortico-cortical evoked potentials. Our findings suggest accurate classification of SOZs relies on a complex temporal evolution of evoked potentials within 350 ms of stimulation. Validation in a larger dataset could provide a practical clinical tool for the presurgical evaluation of drug resistant epilepsy.

Whether tumor mutational burden (TMB), which refers to the total number of somatic or acquired mutations per million bases in a particular region of the tumor genome, can serve as a predictive biomarker of immune checkpoint inhibitor (ICI) therapy for colon cancer remains unclear. Hereby, we retrospectively investigated the differentially expressed genes (DEGs) based on the level of TMB and tried to established a risk score model as a novel biomarker. The DNA mutation data were retrieved from the Masked Somatic Mutation in Genomic Data Commons data portal of the Cancer Genome Atlas, where the RNA sequencing data, clinical information, and survival outcomes of patients were downloaded. Patients with incomplete clinical information were excluded. The immune score and stromal score were calculated to investigate immune infiltration. The patients were grouped into TMB-high group and the TMB-low group based on the median value of TMB. An immune relevant gene set was obtained from the Immunology Database and Analysis Portal to identify immune-related DEGs. The Cox proportional hazard model and nomogram were applied to establish the risk model. In results: the TMB value was associated with age (p≤0.001), clinical stage (p≤0.001), N stage (p≤0.001), M stage (p=0.003), and immune score (p≤0.001). Twenty-nine immune-related DEGs were identified as enriched in immune response-related function or pathway and tumorigenesis signaling. Nine of 29 were determined to establish a riskScore model. The riskScore suggested a positive relationship with the TMB value (p=0.033), immune score (p≤0.001), and tumor immune dysfunction and exclusion (TIDE) (p=0.002) and presented an independent prognostic factor (p≤0.001, HR=1.04), which predicted the overall survival with good specificity. We concluded that the combination of TMB with transcriptome expression has a predictive and prognostic value for patients treated with ICIs.