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BackgroundIt is currently unknown if disease severity modifies response to therapy in pulmonary arterial hypertension (PAH). We aimed to explore if disease severity, as defined by established risk-prediction algorithms modified response to therapy in randomized clinical trials in PAH.MethodsWe performed a meta-analysis using individual participant data from 18 randomized clinical trials of therapy for PAH submitted to the United States Food and Drug Administration to determine if predicted risk of one-year mortality at randomization modified the treatment effect on three outcomes: change in six-minute walk distance (6MWD), clinical worsening at 12 weeks, and time-to-clinical worsening.ResultsOf 6561 patients with a baseline U.S. Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL 2.0) score, we found that individuals with higher baseline risk had higher probabilities of clinical worsening but no difference in change in 6MWD. We detected a significant interaction of REVEAL 2.0 risk and treatment assignment on change in 6MWD. For every three-point increase in REVEAL 2.0 score, there was a 12.49 meter (95%CI 5.86–19.12, p=0.001) greater treatment effect in change in 6MWD. We did not detect a significant risk by treatment interaction on clinical worsening with most of the risk prediction algorithms.ConclusionsWe found that predicted risk of one-year mortality in PAH modified treatment effect as measured by 6MWD, but not clinical worsening. Our findings highlight the importance of identifying sources of treatment heterogeneity by predicted risk to tailor studies to patients most likely to have the greatest treatment response.

To probe the coupling effect of the electron and Li ion conductivities in Ni-rich layered materials (LiNi0.8Co0.15Al0.05O2, NCA), lithium lanthanum titanate (LLTO) nanofiber and carbon-coated LLTO fiber (LLTO@C) materials were introduced to polyvinylidene difluoride in a cathode. The enhancement of the conductivity was indicated by the suppressed impedance and polarization. At 1 and 5 C, the cathodes with coupling conductive paths had a more stable cycling performance. The coupling mechanism was analyzed based on the chemical state and structure evolution of NCA after cycling for 200 cycles at 5 C. In the pristine cathode, the propagation of lattice damaged regions, which consist of high-density edge-dislocation walls, destroyed the bulk integrity of NCA. In addition, the formation of a rock-salt phase on the surface of NCA caused a capacity loss. In contrast, in the LLTO@C modified cathode, although the formation of dislocation-driven atomic lattice broken regions and cation mixing occurred, they were limited to a scale of several atoms, which retarded the generation of the rock-salt phase and resulted in a pre-eminent capacity retention. Only NiO phase “pitting” occurred. A mechanism based on the synergistic transport of Li ions and electrons was proposed.

A coupled level set and volume–of–fraction method is applied to investigate hollow oil droplet impacts on heated walls. Results show that given the increase in impact velocity, three evolutionary processes of spreading, transition, and central jet occur after the hollow oil droplet impact on a heated wall. The variation in the spreading length of hollow oil droplets is similar in different evolutionary processes, but the variation in the center height of hollow oil droplets is relatively different. The wall heat flux and the position of the maximum heat flux increase with impact velocity. In addition, the wall temperature influences the flow and heat transfer characteristics of the hollow oil droplet impingement. Considering the viscosity–temperature characteristics of the lubricating oil, the spreading length of the hollow oil droplet increases with the wall temperature, but the central height of the hollow oil droplet is unaffected by the wall surface temperature. The wall heat flux and the position of the maximum heat flux also increase with the impact velocity. Pressure and velocity distribution indicate that the bubble rupture at the central jet originates from the combined effect of inertial force and surface tension. The results of this study provide a basis for an improved understanding of the flow and heat transfer characteristics of hollow oil droplet impact on a heated wall and serve as a theoretical reference for investigating the effect of bubbles on oil–gas lubrication processes.

The pre-processing of samples is important factors that affect the results of the RNA-sequencing (RNA-seq) data. However, the effects of frozen sections storage conditions on the integrity of RNA and sequencing results haven’t been reported. The study of frozen section protection schemes can provide reliable experimental results for single-cell and spatial transcriptome sequencing. In this study, RNA was isolated to be studied for RNA from brain section at different temperatures (RT: room temperature, −20 °C) and storage time (0 h, 2 h, 4 h, 8 h, 12 h, 16 h, 24 h, 7day, 3week, 6month). The stability of reference genes was validated using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that the storage at room temperature significantly affected RNA integrity number (RIN), and the RIN value was lower with the prolongation of storage, while the storage at −20 °C exerted less effect on the RIN value. Cresyl violet staining for brain tissue sections had little effect on RNA integrity. 1925, 899 and 3390 differential expression genes (DEGs) were screened at 2 h, 4 h and 8 h at room temperature, respectively. A total of 892, 478 and 619 genes were shown to be differentially expressed at −20 °C for 7d, 3w and 6 m, respectively. Among them, the expression of glycoprotein m6a (Gpm6a), calmodulin 1 (Calm1), calmodulin 1 (Calm2), thymosin, beta 4, X chromosome (Tmsb4x), ribosomal protein S21 (Rps21) and so on were correlated with RNA quality. According to the expression stability of 4 reference genes (Actb: beta-actin; Gapdh: glyceraldehyde-3-phosphate dehydrogenase; 18S: 18S ribosomal; Hprt1: hypoxanthine phosphoribosyltransferase 1), 18S is the most stable reference gene in the brain. In conclusion, the storage temperature and time of frozen sections have significant effects on RNA integrity and sequencing results. But there are still some genes that are stable and not affected by worsening of overall RNA integrity ie the decrease of RIN value. In addition, 1% cresyl violet staining can protect RNA.

The surface wettability of thermo-responsive random poly (ethylene glycol methyl ether methacrylate-co-triethylene glycol methyl ether methacrylate), abbreviated as P(MEOMA-co-MEO3MA), was investigated in thin film. UV-Vis spectroscopy shows that the LCST of P(MEOMA-co-MEO3MA) with molar ratios of 0:20, 6:14 and 9:11 were 43°C, 32 oC and 25 oC, respectively. LCST shifts towards lower temperature when molar ratio of MEOMA increases. ATR-FTIR indicates that P(MEOMA-co-MEO3MA) thin film experienced a collapse when the temperature passes its LCST. The contact angle of the paraffin oil on the film decreases 15o when the temperature is above its LCST, which confirms the surface wettability can be controlled. Atomic force microscopy shows the surface of the swollen thin film becomes rougher when above it LCST.

RNA degradation can significantly affect the results of gene expression profiling, with subsequent analysis failing to faithfully represent the initial gene expression level. It is urgent to have an artificial intelligence approach to better utilize the limited data to obtain meaningful and reliable analysis results in the case of data with missing destination time. In this study, we propose a method based on signal decomposition technique and deep learning, named Multi-LSTM. It is divided into two main modules, one decomposes the collected gene expression sequences by empirical mode decomposition (EMD) algorithm to obtain a series of subsequences with different frequencies to improve data stability and reduce modeling complexity. The other is based on long short-term memory (LSTM) as the core predictor, aiming to deeply explore the temporal nonlinear relationships embedded in the subsequences. Finally, the prediction results of subsequences are reconstructed to obtain the final prediction results of time-series transcriptomic gene expression. The results show that EMD can efficiently reduce the nonlinearity of the original sequences, which provides a reliable theoretical support to reduce the complexity and improve the robustness of LSTM models. Overall, the decomposition-combination prediction framework can effectively predict gene expression levels at unknown time points.

Increasing the rotating speed of the axial piston pump is effective in improving the power-to-weight ratio. However, the cylinder block tilts severely at high speed, which causes significant leakage. In this paper, a dynamic model of the rotating assembly in a high-speed axial piston pump is established to investigate the tilt behavior of the cylinder block when fully considering the relevant factors within the whole rotating assembly, such as the tilt moments due to the inertia of piston-slipper assemblies and the periodic pressure in piston chambers, the elastic deformation of the shaft, and the nonlinear bearing characteristics of the oil film. Furthermore, the cylinder block tilt behavior is measured to validate the established dynamic model. The theoretical and experimental results show that the tilt angle of the cylinder block increases with the increasing rotating speed. And at high rotating speed, the cylinder block tilts much more severely under low outlet pressure. Finally, the bearing capacities of the oil film and the spline coupling are analyzed to find out the dominant factors affecting the tilt behavior of the cylinder block.

To explore the genetic basis for a fetus with structural brain abnormalities.The karyotypes of the fetus and its parents were analyzed by conventional G-banding. Chromosome microarray analysis (CMA) was carried out to detect chromosomal microdeletion and microduplication.No kartotypic abnormality was detected in the fetus and its parents. CMA has identified a 194 kb microduplication at Xq25 in the fetus, which encompassed exons 4-35 of the STAG2 gene and was derived from its mother.The Xq25 duplication encompassing part of the STAG2 gene probably underlay the brain malformation in the fetus.

The incidence of prostate cancer (PCa) is on the rise in China. The risk level of patients with PCa is associated with disease-free survival rate at 10 years after radical prostatectomy. Predicting prognosis in advance according to the degree of risk can provide a reference for patients, especially treatment options and postoperative adjuvant treatment measures for high-risk/extremely high-risk patients.To explore the predictive value of the prognostic nutritional index (PNI) for biological recurrence in Chinese patients with high/extremely high-risk PCa after radical prostatectomy.The biochemical test results and clinical data of 193 patients who underwent radical prostatectomy for the first time from January 2015 to December 2020 were retrospectively collected. The PNI value of peripheral blood within 1 wk before surgery was calculated, and during the follow-up period, prostate-specific antigen ≥ 0.2 ng/mL was considered to have biological recurrence. The receiver operating characteristic (ROC) curve was used to calculate the optimal critical value and area under the curve (AUC) of the patients. According to the critical value, the progression-free survival of the high PNI group and low PNI group was compared. The independent influencing factors of the patients' prognosis were obtained by the Cox proportional hazards regression model.The non-biological recurrence rates at 1, 3, and 5 years were 92.02%, 84.05%, and 74.85%, respectively. The optimal critical value for PNI to predict biological recurrence was 46.23, and the AUC was 0.789 (95% confidence interval: 0.651-0.860;The PNI has predictive value for the prognosis of patients with high/extremely high-risk PCa, and is an independent prognostic factor. Patients with low PNI value have a shorter time of non-biological recurrence after prostatectomy. It is expected that the combined prediction of other clinicopathological data will further improve the accuracy and guide postoperative adjuvant therapy to improve the quality of prognosis.

The excess pore water pressure (EPWP) generated under the combined vertical and horizontal earthquake excitations is generally greater than that under the unidirectional excitation, which may further affect the dynamic response of soil-pile-superstructure-quay wall (SPSQ) system. This study conducted a coupled effective-stress analysis for the response of SPSQ system to liquefaction-induced lateral displacement under horizontal and vertical earthquake excitations. To accurately describe the lateral displacement behind the quay wall, the liquefaction behavior of soils was described by a modified generalized plasticity model with parameters properly determined from laboratory tests. The numerical model of the SPSQ system was validated against the previously reported centrifuge model tests. The results show that the earthquake excitation with abundant low-frequency component causes greater residual lateral displacements of footing (ux,RF) and quay wall (ux,RQ ) than that with abundant high-frequency component. The ux,RF and ux,RQ tend to increase as the peak vertical acceleration increases for both vertical and inclined piles. Increasing the fixity of the quay wall significantly reduces the influence of vertical ground motion on the ux,RF and ux,RQ. The polarity reversal of the vertical ground motion also has a significant effect on the ux,RF and ux,RQ and should be considered in the analyses. In addition, the lateral displacement of liquefied ground causes an amount of rotation of the cap of the inclined pile, probably leading to the potential shear failure at the head of piles.

The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic chromophores are water-insoluble, and therefore, the derivatization and modification of these chromophores are difficult. Herein, we demonstrated a simple platform for the fabrication of organic nanoemitters by loading ten different organic dyes (molar masses of 479.1-1081.7 g/mol) into water-soluble polymer nanosponges composed of poly(styrene-alt-maleic acid) (PSMA). This nanolization strategy enables the incorporation of small commercial dyes (3.7–50% loading) and newly synthesized large photosensitive molecules (> 85% loading) into PSMA NPs and prevents the spontaneous aggregation of these hydrophobic chromophores in aqueous solutions. These low-cytotoxicity organic nanoparticles exhibited tunable red to near-infrared fluorescence emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-photosensitive molecules were fabricated, and photodynamic therapy with these dye-loaded PSMA NPs for the photolysis of cancer cells was achieved when coupled with 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.

Effective adjuvants that enhance immune responses have great potential for vaccine development and disease prevention. A major challenge is the effective delivery of vaccine component to specific c...

Parabolic equation models discretized with the finite difference method have been extensively studied for a long time. However, several explicit and implicit schemes exist in the literature. The advantage in explicit schemes is its simplicity, while its disadvantage is conditional stability. On the other hand, implicit schemes are unconditionally stable but require special treatment for a fast and accurate solution such as the Crank-Nicolson (CN) method. This method becomes computationally intensive for problems with dense meshes. The resulting matrix from the CN in two and three-dimensional cases requires high computational resources. This paper applies hierarchical interpolative factorization (HIF) to reduce the computational cost of the CN method. Numerical experiments are conducted to validate the proposed HIF acceleration.

Research on hash-based cross-modal retrieval has been a hotspot in the field of content-based multimedia retrieval research. Most deep cross-modal hashing methods only consider inter-modal loss that can remain local information of training data, and ignore the loss within data samples of the same modality that can remain the global information of dataset. In addition, they also ignore the factor that different scales of single modal data contain different semantic information, which affects the representation of data features. In this paper, we propose a semantics-preserving hashing method based on multi-scale fusion. More concretely, a multi-scale fusion pooling model is proposed for both image feature training network and text feature training network. Therefore, we can extract the multi-scale features of image dataset and solve the sparsity problem of text BOW vectors. When constructing the loss function, we consider intra-modal loss while considering inter-modal loss. Therefore, the output hash code retains both global and local underlying semantic correlation when image and text feature training network are trained. Experiment results on NUS-WIDE and MIRFlickr-25 K prove that against other existing methods, our algorithm improves cross-modal retrieval accuracy.

N6-methyladenosine (m6A), a methylation in the N6 position of adenosine especially in the mRNA, exerts diverse physiological and pathological functions. However, the precise role of m6A methylation in hypoxic preconditioning (HPC) is still unknown. Here, we observed that HPC treatment protected H9c2 cells against H2O2-induced injury, upregulated the m6A level in the total RNA and the expression of methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14), and long noncoding RNA (lncRNA) H19. Either knockdown of METTL3 or METTL14 notably reversed the HPC-induced enhancement of cell viability, anti-apoptosis ability, and H19 expression. Methylated RNA immunoprecipitation (IP) indicated that knockdown of METTL3 or METTL14 decreased m6A level in the lncRNA H19. Gain-of-function assay demonstrated that H19 overexpression could partially rescue the decreased protection mediated by METTL3 or METTL14 knockdown in HPC-treated H9c2 cells. RNA binding protein immunoprecipitation (RIP) assay showed that METTL3 and METTL14 could directly bind with H19. Our study identified a novel pattern of posttranscriptional regulation in HPC treatment. Since METTL3, METTL14, and lncRNA H19 were involved in HPC protection, they could be considered as potential biomarkers and therapeutic targets in HPC-derived cardiac rehabilitation and therapeutic approaches.

Rationale: Obesity is associated with an increased risk of pulmonary hypertension (PH); however, regional adipose tissue deposition is heterogeneous with distinct cardiovascular phenotypes. Objectives: To determine the association of body mass index (BMI) and thoracic visceral and subcutaneous adipose tissue areas (VAT and SAT, respectively) with PH in patients with advanced lung disease referred for lung transplantation. Methods: We studied patients undergoing evaluation for lung transplantation at three centers from the Lung Transplant Body Composition Study. PH was defined as mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥3 Wood units. VAT and SAT were measured on chest computed tomography and normalized to height squared. Results: One hundred thirty-seven (34%) of 399 patients included in our study had PH. Doubling of thoracic VAT was associated with significantly lower pulmonary vascular resistance (β, −0.24; 95% confidence interval [95% CI], −0.46 to −0.02; P = 0.04), higher pulmonary arterial wedge pressure (β, 0.79; 95% CI, 0.32 to 1.26; P = 0.001), and decreased risk of PH (relative risk, 0.86; 95% CI, 0.74 to 0.99; P = 0.04) after multivariate adjustment. Vaspin levels were higher in patients without PH (median, 101.8 vs. 92.0 pg/ml; P

To investigate age-related changes on passive muscle stiffness in healthy individuals and measure the shear modulus in different age groups. Shear wave elastography (SWE) movies of gastrocnemius medialis (GM) were collected during passive stretching induced by ankle rotation from plantarflexion (PF) to dorsiflexion (DF). A series of SWE images at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, 0°, DF 10°, DF 20°, and DF 30° were collected and shear moduli measured accordingly for analyses. Eighty-six healthy volunteers (27 children, 31 middle-aged adults, and 28 older people) were recruited. No significant difference was observed in the shear modulus between the three groups at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, and 0° (p > 0.05). The difference in the shear modulus among the three groups became significant as DF increased. At ankle angles of DF 10°, DF 20°, and DF 30°, the shear modulus was the greatest in the older group, followed by the middle-aged group and then the children group (p = 0.007, 0.000, and 0.000, respectively). Passive muscle stiffness increases with age, and the difference between age groups was pronounced only after reaching a certain degree of stretching. • The influence of age on passive muscle stiffness becomes pronounced only after reaching a certain degree of stretching. • Age should be considered when evaluating passive muscle stiffness in muscular disorders.

Background Large cohort studies provide conflicting evidence regarding the prognostic value of early repolarization pattern (ERP) in the general population, complicated by the complex or heterogeneous definitions of ERP applied in different studies. Hypothesis We hypothesized that ERP was associated with increased cardiovascular risk with the definition of ERP recommended by the expert consensus statements. Methods A total of 13673 middle-aged subjects from the prospective, population-based Atherosclerosis Risk in Communities (ARIC) study were included in this analysis. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. ERP was defined as ST-segment elevation ≥0.1mV at the end of the QRS or J wave on the QRS downstroke in two or more contiguous leads. Results Compared with those without ERP, subjects with ERP had a significantly increased risk of developing sudden cardiac death (SCD) (HR, 1.48; 95% CI, 1.08-2.04) and death from coronary heart disease (CHD) (HR, 1.45; 95% CI, 1.10-1.92) after a median follow-up of 20.1 years. ERP was significantly predictive of SCD in females, whites, younger people, and subjects with relatively low cardiovascular risk. ERP with ST-segment elevation appeared to indicate poor cardiovascular outcomes. ERP was associated with an absolute risk increase of 93.3 additional SCDs per 100 000 person-years. Conclusions Our findings suggest that ERP was an independent predictor of SCD and CHD death in the middle-aged biracial population.

Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cells. However, elevated antioxidant defense systems in cancer cells result in resistance to the therapy involving ROS. Here we describe a highly effective phototherapy through regulation of redox homeostasis with a biocompatible and versatile nanotherapeutic to inhibit tumor growth and metastasis. We systematically explore and exploit methylene blue adsorbed polydopamine nanoparticles as a targeted and precise nanocarrier, oxidative stress amplifier, photodynamic/photothermal agent, and multimodal probe for fluorescence, photothermal and photoacoustic imaging to enhance anti-tumor efficacy. Remarkably, following the glutathione-stimulated photosensitizer release to generate exogenous ROS, polydopamine eliminates the endogenous ROS scavenging system through depleting the primary antioxidant, thus amplifying the phototherapy and effectively suppressing tumor growth in vitro and in vivo. Furthermore, this approach enables a robust inhibition against breast cancer metastasis, as oxidative stress is a vital impediment to distant metastasis in tumor cells. Innovative, safe and effective nanotherapeutics via regulation of redox balance may provide a clinically relevant approach for cancer treatment., Amplified oxidative stress achieved by modulating redox homeostasis with PDA–MB for highly effective synergistic phototherapy to inhibit primary tumors and metastases.

Glucose fluctuations may contribute to large conductance calcium activated potassium (BK) channel dysfunction. However, the underlying mechanisms remain elusive. The aim of this study was to investigate the molecular mechanisms involved in BK channel dysfunction as a result of glucose fluctuations. A rat diabetic model was established through the injection of streptozotocin. Glucose fluctuations in diabetic rats were induced via consumption and starvation. Rat coronary arteries were isolated and coronary vascular tensions were measured after three weeks. Rat coronary artery smooth muscle cells were isolated and whole-cell BK channel currents were recorded using a patch clamp technique. Human coronary artery smooth muscle cells in vitro were used to explore the underlying mechanisms. After incubation with iberiotoxin (IBTX), the Δ tensions (% Max) of rat coronary arteries in the controlled diabetes mellitus (C-DM), the uncontrolled DM (U-DM) and the DM with glucose fluctuation (GF-DM) groups were found to be 84.46 ± 5.75, 61.89 ± 10.20 and 14.77 ± 5.90, respectively (P .05), while the current densities of the BK channels in the three groups were 43.09 ± 4.35 pA/pF, 34.23 ± 6.07 pA/pF and 17.87 ± 4.33 pA/pF, respectively (P .05). The Δ tensions (% Max) of rat coronary arteries after applying IBTX in the GF-DM rats injected with 0.9% sodium chloride (NaCl) (GF-DM + NaCl) and the GF-DM rats injected with N-acetyl-L-cysteine (NAC) (GF-DM + NAC) groups were found to be 8.86 ± 1.09 and 48.90 ± 10.85, respectively (P .05). Excessive oxidative stress and the activation of protein kinase C (PKC) α and nuclear factor (NF)-κB induced by glucose fluctuations promoted the decrease of BK-β1 expression, while the inhibition of reactive oxygen species (ROS), PKCα, NF-κB and muscle ring finger protein 1 (MuRF1) reversed this effect. Glucose fluctuations aggravate BK channel dysfunction via the ROS overproduction and the PKCα/NF-κB/MuRF1 signaling pathway.

Background Pathology education provides information on pathology and guides students to become pathologists. Recently, the Ministry of Education of the People’s Republic of China required the establishment of the system of ‘High-quality Online and Offline Courses’, which indicates that online courses will play an important role in higher education. Furthermore, the number of pathologists currently cannot satisfy clinical needs. To solve this health issue and implement the policy from the Ministry of Education, it is necessary to improve the current state of pathology education. First, we need to know students’ opinions of the current courses and their professional choices. Methods Online questionnaires covering the quality of traditional courses, attitudes towards online courses, and suggestions for optimizing courses were designed and applied. Whether students want to become pathologists and the underlying reasons for this interest are also included in this survey. Participants are medical students from certain colleges in Nanjing. The collected data were assessed by statistical analyses, and p-values less than 0.05 were considered significant. Results Of the 342 valid responses, 60.94% of undergraduate students showed their interest in pathology courses, and among them, 48.72% expressed that they may become pathologists. However, the corresponding percentage is only 29.59% in the group without interest. To optimize curricula, the top two suggestions are introducing more clinical cases (undergraduate students, 64.45%; graduate students, 79.09%) and making the classes lively and interesting (undergraduate students, 59.77%; graduate students, 62.79%). Approximately 80.00% of students consider online courses to be good supplementary materials to traditional courses, and approximately half prefer an online-offline mixed learning model. Salary, interest, and employment status are the main factors influencing students’ professional choices. Conclusions Students are generally satisfied with traditional pathology courses, and online courses are good supplementary materials in their opinions. It has been suggested that clinical cases be introduced in classes. It is more likely that students who have an interest in pathology will become pathologists. The data from this survey also show that the main causes of the shortage of pathologists are a lack of engaging work and an unsatisfactory salary.

Objective: To compare the efficacy and mechanism of zoledronic acid and Tc-MDP in the treatment of osteoporosis. Methods: From July 2011 to November 2015, 232 patients with primary osteoporosis were selected and treated in The First Affiliated Hospital of Hainan Medical College were selected and were divided into the 116 patients in the Tc-MDP group and 116 patients in the zoledronic acid group accorded to the treatment ways. The zoledronic acid group were given zoledronic acid treatment, 1 time in one year. The Tc-MDP group were given Tc-MDP treatment, and the treatment were treated for 10 days for 1 course, 1 course for 3 months, and a total of 3 years of treatment were observed. The prognosis and the changes of bone mineral density and hematological parameters were recorded. Results: The total effective rates of the zoledronic acid group and Tc-MDP group were 99.1% and 90.0%, respectively, and the zoledronic acid group were significantly higher than the Tc-MDP group (P0.05), and the erythroeyte sedimentation rate (ESR) levels were lower than before treatment (P

A skeletonization scheme is proposed to accelerate the evaluation of scattering/radiation fields. The proposed scheme performs well for targets with multiscale feature as well as scenarios where multiple excitations are involved. Numerical experiments on targets with complex configurations are conducted to show the performance of the proposed method.

Tumor targeting of drug to specific site via use of folate is one the choicest method for enhancing specificity of Cisplatin. Chitosan was conjugated with folate via amino acylation method and Folate-chitosan-Cisplatin-nanoparticles (FA-CS-Cis-NP's) were prepared using ionotropic gelation method. Thus prepared nanoparticles were evaluated for various parameters such as particles size, % encapsulation efficiency, % drug release, cytotoxic assay, cellular uptake. The average particle size of nanoparticles was found to be 265 nm with encapsulation efficiency of 89.43%. The cumulative release of drug from dosage form was found to be 82.31% for 240 min. The higher level of intra-cellular accumulation of Cisplatin was found to be in case of FA-CS-Cis-NP's than conventional drug delivery when cultured with folate. The results indicate that targeting of FA-CSCis-NP's is possible with folate targeting and are proved as potential folate receptor positive tumor cell targeting drug delivery system.

Stratigraphic uncertainty widely exists in geotechnical structures. An efficient generalized coupled Markov chain (GCMC) model was proposed to simulate the stratigraphic uncertainty in the past. This model, however, cannot be directly applied to geotechnical problems because of the difficulty in directly estimating the horizontal transition probability matrices (HTPMs) of the GCMC from boreholes with large hole-to-hole distance. This paper, therefore, aims at addressing the above problem by using a maximum likelihood estimation (MLE) method and utilizing the MLE modified GCMC model to characterize stratigraphic uncertainty. In the framework of the GCMC, the validity of the proposed method is verified, and information entropy method is adopted to quantify the stratigraphic uncertainty. As an illustration, the proposed model is applied to a construction site in Hong Kong to characterize the stratigraphic uncertainty. A systematic comparison of coupled Markov chain (CMC) and GCMC model for stratigraphic uncertainty simulation was conducted. The influences of borehole layout scheme on transition probability matrices (TPMs) estimation and stratigraphic uncertainty simulation are explored. Results showed that the result of stratigraphic uncertainty simulation of the GCMC model is more reasonable than that of the CMC model. The borehole layout scheme is very important for estimating TPMs and significantly influences the stratigraphic uncertainty simulation. The information entropy map has the potential to become a useful guideline for the design of the borehole layout scheme in geotechnical engineering practice.

EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.

The discovery of cell-free DNA (cfDNA) in maternal plasma has opened up new promises for the development of non-invasive prenatal testing (NIPT). Application of cfDNA in NIPT of fetus diseases and abnormalities is restricted by the low amount of fetal DNA molecules in maternal plasma. Fetus-derived cfDNA in maternal plasma are shorter than maternal DNA, thus leveraging the maternal and fetus-derived cfDNA molecules size difference has become a novel and more accurate method for NIPT. However, multiple biological properties such as size distribution of plasma DNA, proportion of fetal-derived DNA and methylation levels in maternal plasma across different gestational ages still remain largely unknown. Further insights into the size distribution and fragmentation pattern of circulating plasma cfDNA will shed light on the origin and fragmentation mechanisms of cfDNA during physiological and pathological processes in prenatal diseases and enhance our ability to take the advantage of plasma cfDNA as a molecular diagnostic tool. In the review, we start by summarizing the research techniques for the determination of the fragmentation profiles of cfDNA in maternal plasma. We then summarize the main progress and findings in size profiles of maternal plasma cfDNA and cffDNA. Finally, we discuss the potential diagnostic applications of plasma cfDNA size profiling.

Polycystic ovarian syndrome (PCOS) is considered to be one of the most prevalent endocrine disorders affecting women of reproductive age. CiRS-126, an innovative circular microRNA, has previously been proven to be a promising miR-21 sponge. However, a proper understanding of the impact of ciRS-126 on PCOS is needed. Circular RNA (CiRS) profiles were initially evaluated in ovarian cortex samples obtained from 18 women with PCOS as well from 9 women without PCOS. Insulin-induced ovarian granulosa cells isolated from mice were utilized for the functional study. CiRS microarray analysis and quantitative real-time PCR indicated that ciRs-126 expression was downregulated while miR-21 expression was upregulated in PCOS samples and insulin-induced granulosa cells as compared with non-PCOS samples and non-insulin-induced granulosa cells. Furthermore, ectopic overexpression of ciRS-126 was associated with a reduction in proliferation and increased apoptosis in insulin-treated granulosa cells. Meanwhile, bioinformatic prediction and the results of the dual-luciferase reporter assay indicated the presence of consecutive binding in the ciRS-126-miR-21-programmed cell death protein 4 (PDCD4) axis. Moreover, overexpression of miR-21 blocked ciRS-126 repression of proliferation and triggered the death of insulin-induced granulosa cells. Excessive PDCD4 expression counteracted the influence of miR-21 on cell death and proliferation. The data indicated that PDCD4 played a regulatory role in ROS generation, which is reportedly involved in apoptosis. Therefore, ciRS-126 reduction in PCOS granulosa cells targeted the miR-21-PDCD4 axis to reduce proliferation and promote apoptosis. CiRS-126 shows potential as a promising predictor of clinical outcome as well as a therapeutic target in PCOS.

Objective To assess the value of chromosome microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with cerebellar vermis defects (CVD). Methods From 2013 to 2019, we performed CMA on 43 fetuses with CVD, who were divided into cerebellar vermis hypoplasia (CVH) group and Dandy-Walker malformation (DWM) group according to morphological subtypes. Subsequently, WES was performed on 19 fetuses with normal CMA results to identify diagnostic genetic variants (DGVs). Results Chromosome aneuploidies and clinically significant copy number variants were identified in 23.3% (10/43) of fetuses, and a significantly higher positive rate was found in fetuses with multiple compared with isolated malformations (36% vs 5.6%, P = .028). STAG2 genes related to Xq25 duplication syndrome was possibly a novel candidate gene for CVD. WES detected eight DGVs in seven genes among the 19 fetuses tested. Autosomal recessive ciliopathies (4/8) caused by TMEM231, CSPP1, and CEP290 mutations, were the most frequent monogenetic diseases, followed by Opitz GBBB syndrome (2/8) caused by MID1 and SPECC1L variants. Conclusion The combined use of CMA and WES has the potential to provide genetic diagnoses in 42% (18/43) of fetal CVD. WES should be offered when CMA results are normal.

Purpose: The aim of this study is to evaluate the impact of the utility of maternal cell-free DNA (cfDNA) on the number of chorionic villus sampling (CVS) at a mainland Chinese maternal hospital.Methods: This was a retrospective cohort study conducted in consecutive singleton pregnancies that underwent CVS between the 11th and 14th gestational weeks at a Chinese maternal hospital during a nine-year period. The indications, complications and prenatal diagnosis results were evaluated.Results: This study consisted of 5108 CVS procedures, including 2000 performed for fetal karyotyping, and 3108 performed for fetal single-gene genotyping. During the period with the introduction of cfDNA, the proportion of the number of CVS procedures for the indication of positive serum screening declined significantly, and abnormal ultrasound was the main indication for CVS performed for fetal karyotyping. Thalassemia was always the main indication for CVS, accounting for 50.5% of all CVS cases.Conclusions: cfDNA has changed the spectrum of CVS indications. CVS is now the invasive procedure performed for patients with a fetus having a very high risk of fetal genetic defects, including fetuses having major abnormal ultrasound or having a risk of single-gene disorder inherited from their parents.

In this paper, a 0.6 V subthsheshold CMOS voltage reference (CVR) achieving wide temperature range and high power supply ripple rejection (PSRR) is presented. The proposed CVR structure can compensate the high temperature leakage and current mirror induced mismatches so as to increase the operating temperature range. The generated reference voltage of the proposed CVR circuit is the threshold voltage difference of two NMOS transistors, leading to relatively small variations. Moreover, the enhanced current source helps achieve high PSRR. The proposed CVR circuit is implemented in a standard 0.18-μm CMOS technology. Measurement results show that, with one single trimming, a mean output of 344 mV with standard deviation of only 2.89 mV and average TC of 44.6 ppm/°C over a wide temperature range from −40 °C to 125 °C is achieved. The measured PSRR is −68 dB, −52 dB and −52 dB at 10 Hz, 100 kHz and 10 MHz, respectively. The measured line sensitivity (LS) is 0.06%/V with a power supply from 0.6 V to 2 V while consuming 19.8 nW at 0.6 V supply. The active area is 0.019 mm2.

This study investigated the correlation of four single nucleotide polymorphisms (SNPs) in Apolipoprotein M (ApoM) with the risk of type 2 diabetes mellitus (T2DM) and effects of the interactions of this gene and obesity. The effects of SNP and obesity interaction on T2DM was examined by generalized multifactor dimensionality reduction (GMDR) combined with the logistic regression model. T2DM patient-control haplotype was analyzed in silico using the haplotype analysis algorithm SHEsis. The rs805296-C allele or 724-del allele indicted high risk of T2DM. The incidence of T2DM in individuals with rs805296-C allele polymorphism (TC + CC) was higher than those without (TT), adjusted OR (95%CI) = 1.29 (1.10–1.66) (p p Psign]=0.0107). The T2DM risk in obese individuals having TC or CC genotype was higher than non-obese individuals with TT genotype (OR = 2.38, 95% CI = 1.58–3.53). Haplotype analysis suggests that rs805297-C and rs9404941-C alleles haplotype indicate high risk of T2DM, OR (95%CI) = 1.62 (1.29–2.16), p

Background Anastomosis is one of the important factors affecting anastomotic complications after esophagectomy, and multiple reports have compared anastomotic complications among various techniques. However, there is insufficient evidence in the literature to definitively recommend one anastomotic technique over another. Method We retrospectively evaluated 34 consecutive patients who underwent an improved totally mechanical side-to-side: posterior-to-posterior linear stapled (TM-STS) technique for minimally invasive Ivor Lewis esophagogastric anastomosis, performed by a single surgeon between February 2015 to November 2017. The operative techniques and short-term outcomes are analyzed in this study. Results There were no conversions to an open approach and a complete resection was achieved in all patients undergoing this improved procedure. During the first half of the series, the median operation time was 355 minutes, ranging from 257 to 480 minutes. Over the second half of this series, the median operation time was reduced to 256 minutes. There were no mortalities or serious postoperative complications. Only one patient (2.9%) had an anastomotic leak, which resolved without intervention. Another patient (2.9%) experienced transient, delayed conduit emptying which upper gastrointestinal radiography determined was due to a mechanical obstruction caused by an abnormally long gastric tube in the chest cavity. Conclusions The results of our study suggest that this improved TM-STS technique is safe and effective for minimally invasive Ivor Lewis esophagectomy, and can be considered as one of the alternative procedure for patients with lower esophageal as well as Siewert types I/II gastroesophageal junction carcinoma.

OBJECTIVE The aim of this study is to explore the utility of rapid medical trio exome sequencing (ES) for prenatal diagnosis using the skeletal dysplasia as an exemplar. METHOD Pregnant women who were referred for genetic testing because of ultrasound detection of fetal abnormalities suggestive of a skeletal dysplasia were identified prospectively. Fetal samples (amniocytes or cord blood), along with parental blood, were send for rapid copy number variations testing and medical trio ES in parallel. RESULTS Definitive molecular diagnosis was made in 24/27 (88.9%) cases. Chromosomal abnormality (partial trisomy 18) was detected in one case. Sequencing results had explained the prenatal phenotype enabling definitive diagnoses to be made in 23 cases. There were 16 de novo dominant pathogenic variants, four dominant pathogenic variants inherited maternally or paternally, two recessive conditions with pathogenic variants inherited from unaffected parents, and one X-linked condition. The turnaround time from receipt of samples in the laboratory to reporting sequencing results was within 2 weeks. CONCLUSION Medical trio ES can yield very timely and high diagnostic rates in fetuses presenting with suspected skeletal dysplasia. These definite diagnoses aided parental counseling and decision making in most of cases.

A high-temperature sealing adhesive was prepared using kyanite, andalusite, and magnesia fully stabilized zirconia (Mg-FSZ) as raw materials and nanozirconia (ZrO2) sol as binder. The adhesive is chemically near-neutral and suitable for bonding acid, neutral, or alkaline materials at 1560 °C. The mineral composition, volume expansion, and air permeability of multiple thermal cycles were analyzed. Results showed that the volume expansion caused by the mullitization of kyanite and andalusite can compensate for the sintering shrinkage high temperature. MgO could gradually desolvatize from the Mg-FSZ particles and react with SiO2 and Al2O3 to produce a stable forsterite and magnesium aluminate spinel. Hence, Mg-FSZ became unstable, and cubic ZrO2 transformed into monoclinic ZrO2 when cooled, leading to a volume expansion of the adhesive, which ensured the sealing effect. A larger critical particle size of Mg-FSZ can provide the adhesive with a more persistent volume expansion during thermal cycles due to the more durable desolvatization of MgO. The nanoZrO2 sol binder can improve the sintering of the adhesive and bonding of the joint, resulting in a low gas permeability.

Photodynamic therapy (PDT) has extraordinary promise for the treatment of many cancers. However, its clinical progress is impaired by the intrinsic hypoxic tumor microenvironment that limits PDT efficacy and the safety concern associated with biological specificity of photosensitizers or vehicles. Now it is demonstrated that rationally designed DNA nanosponges can load and delivery photosensitizer effectively, target tumor precisely, and relieve hypoxia-associated resistance remarkably to enhance the efficacy of PDT. Specifically, the approach exhibits a facile assembly process, provides programmable and versatile nanocarriers, and enables robust in vitro and in vivo anti-cancer efficacy with excellent biosafety. These findings represent a practical and safe approach by designer DNA nanoassemblies to combat cancer effectively and suggest a powerful strategy for broad biomedical application of PDT.

The pluripotent mouse embryonal carcinoma cell line P19 is widely used as a model for research on all-trans-retinoid acid (RA)-induced neuronal differentiation; however, the signaling pathways involved in this process remain unclear. This study aimed to reveal the molecular mechanism underlying the RA-induced neuronal differentiation of P19 cells. Real-time quantitative polymerase chain reaction and Western blot analysis were used to determine the expression of neuronal-specific markers, whereas flow cytometry was used to analyze cell cycle and cell apoptosis. The expression profiles of messenger RNAs (mRNAs) in RA-induced neuronal differentiation of P19 cells were analyzed using high-throughput sequencing, and the functions of differentially expressed mRNAs (DEMs) were determined by bioinformatics analysis. RA induced an increase in both class III β-tubulin (TUBB3) and neurofilament medium (NEFM) mRNA expression, indicating that RA successfully induces neuronal differentiation of P19 cells. Cell apoptosis was not affected; however, cell proliferation decreased. We found 4117 DEMs, which were enriched in the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, Wnt signaling pathway, and cell cycle. Particularly, a few DEMs could be identified in the PI3K/Akt signaling pathway networks, such as PI3K, Akt, glycogen synthase kinase-3β (GSK3β), cyclin-dependent kinase 4 (CDK4), P21, and Bax. RA significantly increased the protein expression of PI3K, Akt, phosphorylated Akt, GSK3β, phosphorylated GSK3β, CDK4, and P21, but it reduced Bax protein expression. The Akt inhibitor affected the increase of TUBB3 and NEFM mRNA expression in RA-induced P19 cells. The molecular mechanism underlying the RA-induced neuronal differentiation of P19 cells is potentially involved in the PI3K/Akt/GSK3β signaling pathway. The decreased cell proliferation ability of neuronally differentiated P19 cells could be associated with the expression of cell cycle proteins.

A message passing interface (MPI) parallel scheme on distributed memory platforms is developed for the low-rank decomposition to accommodate the memory requirement during angular sweeping of a rough surface in terms of tapered wave incidence. Numerical examples, including that conducted on a $160\times 160$ square wavelength rough surface, are carried out to demonstrate the performance of the proposed MPI angular sweeping with respect to accuracy, efficiency, scalability, and the peak memory requirement.

Despite significant advances in parallel single-cell RNA sequencing revealing astonishing cellular heterogeneity in many tissue types, the spatial information in the tissue context remains missing. Spatial transcriptome sequencing technology is designed to distinguish the gene expression of individual cells in their original location. The technology is important for the identification of tissue function, tracking developmental processes, and pathological and molecular detection. Encoding the position information is the key to spatial transcriptomics because different methods have different encoding efficiencies and application scenarios. In this review, we focus on the latest technologies of single-cell spatial transcriptomics, including technologies based on microwell plates, barcoded bead arrays, microdissection, in situ hybridization, and barcode in situ targeting, as well as mixed separation-based technologies. Moreover, we compare these encoding methods for use as a reference when choosing the appropriate technology.

To present the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS)/PAFAH1B1-related lissencephaly to further determine fetal phenotypes of this syndrome.This was a retrospective study of ten pregnancies with fetal MDS/PAFAH1B1-related lissencephaly identified by chromosomal microarray (CMA)/exome sequencing (ES). Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, CMA or ES results and pregnancy outcomes.Two cases were diagnosed in the first trimester because of an increased nuchal translucency. The remaining eight cases were identified at late gestation, including four in the second trimester because of fetal cardiac anomalies or ventriculomegaly, and four in the third trimester because of ventriculomegaly. CMA revealed 17p13.3 deletions in nine cases, and ES detected a de novo PAFAH1B1 missense mutation in one case.The prenatal presentation of MDS/PAFAH1B1-related lissencephaly depended on the gestational age when the diagnosis was made. Mild ventriculomegaly was the most common prenatal sonographic sign identified in cases of MDS/PAFAH1B1-related lissencephaly. It is important that fetal MRI and invasive testing with CMA should be considered in fetuses with apparently 'isolated' mild ventriculomegaly.

The discharging of ammonium from industrial, domestic, and livestock sewage has caused eutrophication of the water environment. The objectives of this study are to synthesize magnetic zeolite (M-Zeo) by an eco-friendly, economical, and easy procedure and to investigate its suitability as an adsorbent to remove ammonium from an aqueous solution. Based on characterization from XRD, BET, and SEM-EDS, Fe3O4 was proved to successfully load on natural zeolite. The effect of pH, temperatures, reacting times, initial ammonium concentrations, and regeneration cycles on ammonium adsorption was examined by batch experiments. The ammonium adsorption process can be best described by the Freundlich isotherm and the maximum adsorptive capacity of 172.41 mg/g was obtained. Kinetic analysis demonstrated that the pseudo-second-order kinetic model gave the best description on the adsorption. The value of pH is a key factor and the maximum adsorption capacity was obtained at pH 8. By using a rapid sodium chloride regeneration method, the regeneration ratio was up to 97.03% after five regeneration cycles, suggesting that M-Zeo can be recycled and magnetically recovered. Thus, the economic-efficient, great ammonium affinity, and excellent regeneration characteristics of M-Zeo had an extensively promising utilization on ammonium treatment from liquid.