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Introduction: Abnormal placental trophoblast function is the main cause of missed abortion (MA). Src kinase-associated phosphoprotein 2 (SKAP2) indirectly affects actin reunion, which is significantly associated with cell migration., Methods: Twenty women with MA and 20 healthy women who underwent voluntarily induced abortion were included in this study. Immunohistochemistry, qRT-PCR, and western blotting were used to determine SKAP2, WAVE2, and ARP2 expression in the villous tissues. We investigated the effects of SKAP2 and the W336K mutant (blocked SKAP2 Src homology 3 function) on growth and migration in HTR8/SVneo cells using the CCK8 assay, flow cytometry, and transwell assay. The effects of SKAP2 on the WAVE2-ARP2/3 signaling pathway in HTR8/SVneo cells were evaluated by western blotting and immunofluorescence., Results: Compared to the women in the voluntary abortion group, SKAP2 and WAVE2 expression levels were downregulated in the villous of patients with MA. In HTR8/SVneo cells, SKAP2 siRNA silencing regulated the growth and migration, while SKAP2 overexpression promoted growth and migration, and inhibited apoptosis. Additionally, SKAP2 regulated the expression of WAVE2 and ARP2, as well as the colocalization of actin with WAVE2. The SKAP2 W336K mutant could not alter WAVE2 and ARP2 expression, nor HTR8/SVneo cell growth and migration, with or without SKAP2 siRNA transfection., Discussion: SKAP2 could activate the WAVE2-ARP2/3 pathway resulting in an increase of growth and migration in trophoblasts. SKAP2 probably played an important role in MA by affecting the growth and migration of trophoblasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2022. Published by Elsevier Ltd.)

With few options available for the effective treatment of multidrug-resistant bacteria, photodynamic therapy (PDT) has emerged as a promising therapeutic strategy that does not promote the development of antibiotic resistance. Unfortunately, the beneficial bactericidal effect of PDT is oftentimes accompanied by the uncontrollable production of reactive oxygen species. To overcome this issue, a pore-forming toxin (PFT)-responsive biomimetic nanobubble is designed, which is constructed by co-encapsulating a perfluorocarbon nanoemulsion and a photosensitizer within the red blood cell membrane. It is shown that PFTs derived from three pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), group A Streptococcus (GAS), and Listeria monocytogenes (LM), can be effectively absorbed by the nanobubble. Upon toxin absorption, the formation of pores on the nanobubble surface allows the accelerated release of oxygen dissolved inside the nanoemulsion along with the photosensitizer, thus resulting in enhanced PDT and bactericidal efficacy. In three skin infection models, treatment with the nanobubbles results in significantly decreased lesion formation and reduced inflammation. In addition to oxygen, the platform can be used to deliver nitric oxide in a bacterial toxin-dependent manner. Overall, biomimetic nanobubbles may work as a broad gas delivery system that is capable of responding to a variety of PFT-based stimuli for precision PDT., (© 2022 Wiley-VCH GmbH.)

An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens., (© 2022 Wiley-VCH GmbH.)

Background: Spontaneous cervical internal carotid artery dissection (cICAD) is a common cause of stroke in young adults. Endovascular therapy is an indispensable treatment for cICAD in some cases, but it faces great challenges., Case Presentation: A bilateral spontaneous cICADs with hypoperfusion-related AIS after 72 h from the onset was presented herein. The patient responded well to primary Solitaire stent detachment at the critical flow-limiting site., Conclusions: Primary stent implantation at the critical flow-limiting site rather than covering the entire dissection may be a therapeutic option in spontaneous cICAD complicated with cerebral hypoperfusion. The Solitaire stent may be a good choice at the acute and subacute stages of cICAD., (© 2022. The Author(s).)

To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15-20 +6  weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer-lemeshow (H-L) test were used to investigate the predictive value of free β-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free β-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free β-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free β-hCG, followed by AFP-L2 + free β-hCG and AFP-L3 + free β-hCG, and finally AFP + free β-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free β-hCG is the best., (© 2022. The Author(s).)

A mathematical model is developed to describe the photochemical processes in two-photon nanolithography, including two-step absorption leading to initiation and self-deactivation of the photoinitiator by laser irradiance, polymer chain propagation, termination, inhibition, and inhibitor and photoinitiator diffusion. This model is solved numerically to obtain the concentrations of the reaction species as a function of time and space as a laser beam is scanned through a volume of photoresist, from which a voxel size or linewidth is determined. The most impactful process parameters are determined by fitting the model to experimentally measured linewidths for a range of laser powers and scanning speeds, while also obtaining effective nonlinearities that are similar to previously measured values. The effects and sensitivities of the different process parameters are examined. It is shown that the photopolymerization process is dominated by diffusion of photoinitiators and oxygen inhibitors, and that self-deactivation can lead to higher effective nonlinearities in two-photon nanolithography.

Objectives: This study was designed to explore the relationship between Helicobacter pylori (Hp) infection and reflux laryngopharyngitis (RLP) and to evaluate the outcome of anti-Hp therapy in improving RLP symptoms., Methods: A total of 410 patients with RLP were enrolled and tested for Hp infection. The association of Hp infection with reflux symptom index (RSI) and reflux finding score (RFS) was determined. Hp-positive patients received either a proton pump inhibitor (PPI) omeprazole alone (control group) or a combination regimen (experimental group) consisting of omeprazole, mosapride citrate, amoxicillin, and clarithromycin. Therapeutic outcomes were compared 4 weeks later., Results: Of the 410 participants, 290 were Hp-positive and 120 Hp-negative. Both RSI and RFS were significantly higher in Hp-positive patients than in Hp-negative patients. Hp infection status was positively correlated with RSI ( P < 0.05) and RFS ( P < 0.05). The overall response rate was higher in the experimental group than in the control group. Both the groups had a significant reduction in RSI and RFS after therapy, with a greater improvement in the experimental group ( P < 0.05)., Conclusion: Our findings establish a link between Hp infection and RLP. Anti-Hp therapy improves RSI and RFS in RLP patients. Therefore, Hp eradication drugs may be added to the PPI-based regimen in the treatment of RLP., Competing Interests: The authors declare that there are no conflicts of interest related to this study., (Copyright © 2022 Huili Shen et al.)

The correlation of maternal serum alpha-fetoprotein (AFP) variants (AFP-L2, AFP-L3), free beta-human chorionic gonadotropin (free β-hCG), and open neural tube defects (ONTDs) during the second trimester, and the screening efficiency of different risk models remain indistinct. We conducted a retrospective case-control study, and studied 57 pregnant women with ONTD fetuses and 569 pregnant women with normal fetuses. The receiver operating characteristic curve method indicated the best cutoff value and area under the curve (AUC). The predictive value of ONTD risk models by free β-hCG, AFP, AFP-L2, and AFP-L3 was investigated via integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Compared to the control group, AFP, AFP-L2, and AFP-L3 levels were significantly higher, while free β-hCG level was significantly lower in the study group. The triple-index model of free β-hCG + AFP-L2 + AFP-L3 and the dual-index model of AFP-L2 + AFP-L3 showed the best predictive values, respectively (AUC = 0.905; AUC = 0.885). The order of the single-index model AUCs was AFP-L3 > AFP-L2 > AFP > free β-hCG. The negative predictive value, false positive rate, and negative likelihood ratio of AFP-L2, AFP-L3 alone, or combined with free β- hCG were better than those of AFP alone; however, the positive likelihood ratio was the opposite. The replacement of AFP by AFP-L2 or AFP-L3 combined with free β-hCG increased the IDI and NRI for predicting ONTD. The top five DCAs were AFP-L2 + free β-hCG, free β-hCG, AFP-L3, AFP + free β-hCG, and AFP. Indicators of maternal serum free β-hCG, AFP-L2, and AFP-L3 in the second trimester exhibited high sensitivity and specificity screening for ONTD fetuses. Risk models constructed using AFP-L2 + AFP-L3 and AFP-L2 + AFP-L3 + free β-hCG demonstrated better screening efficiency.

Senegalia macrostachya (Reichenb. ex DC.) Kyal. & Boatwr seed (SMS) is a wild legume used as food and medicine in many African countries. In the current study, a novel polysaccharide (SMSP2) was extracted from SMS using hot water and purified with DEAE-52 cellulose. Its structure was characterized, and the immunomodulatory activity and possible molecular mechanism in murine macrophage RAW264.7 were explored. The results revealed that SMSP2 was a uronic acid-rich polysaccharide (51.6%, w/w) with a molecular weight of 52.07 kDa. The neutral sugars were mainly arabinose, xylose, mannose, and galactose at a molar ratio of 1.00 : 0.84 : 0.90 : 0.07. Interestingly, SMSP2 treatment markedly promoted macrophage proliferation and phagocytosis and induced the expression of inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10. SMSP2-induced macrophage stimulation occurs through the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, macrophage surface complement receptor 3 (CR3) might play an important role in SMSP2-induced macrophage activation. This study revealed that SMSP2 is a potent immunomodulator, which could be used as a functional food and a pharmaceutical adjuvant in treating immune-compromising diseases.

BACKGROUND We aimed to insure the accuracy and reproducibility of alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (free ß-hCG), and unconjugated estriol (uE3) concentrations for the screening for trisomy 21 (T21) and neural tube defects (NTD) in the second trimester. We conducted an external quality assessment of 6 laboratories, using maternal serum specimens. MATERIAL AND METHODS Serum specimens collected from 87 women of singleton pregnancies (4 with T21, 5 with NTD, and 78 with normal fetuses) were divided into 6 equivalent-volume fractions and transported to 6 laboratories (A, B, C, D, E, and F). All laboratories used the time-resolved fluorescence analyzer and supporting reagents to measure concentrations of AFP, free ß-hCG, and uE3. The screening efficacies of T21 and NTD were compared with the certified or accredited status of the participants' quality systems. RESULTS Concentrations of AFP measured by laboratory F were low compared with those determined by the other 5 laboratories, and the differences were significant (P<0.01). There was no statistically significant difference in the free ß-hCG and uE3 concentrations measured by the 6 laboratories (P>0.05). The correlation coefficients for the 3 multiples of the median values were all >0.900. The McNemar paired chi-squared test showed the differences in the positivity and detection rates were not statistically significant (P=1.000). CONCLUSIONS AFP, free ß-hCG, and uE3 values measured by the other 5 laboratories were comparable with those of laboratory A, with good linear correlation. When used in the maternal prenatal screening of T21 and NTD, the test results met the clinical requirements.

Background: The expression of Coiled-Coil Domain Containing 134(CCDC134) is up-regulated in different pan-cancer species. However, its prognostic value and correlation with immune infiltration in breast cancer are unclear. Therefore, we evaluated the prognostic role of CCDC134 in breast cancer and its correlation with immune invasion., Methods: We downloaded the transcription profile of CCDC134 between breast cancer and normal tissues from the Cancer Genome Atlas (TCGA). CCDC134 protein expression was assessed by the Clinical Proteomic Cancer Analysis Consortium (CPTAC) and the Human Protein Atlas. Gene set enrichment analysis (GSEA) was also used for pathway analysis. Receiver operating characteristic (ROC) curve was used to differentiate breast cancer from adjacent normal tissues. Kaplan-Meier method was used to evaluate the effect of CCDC134 on survival rate. The protein-protein interaction (PPI) network is built from STRING. Function expansion analysis is performed using the ClusterProfiler package. Through tumor Immune Estimation Resource (TIMER) and tumor Immune System Interaction database (TISIDB) to determine the relationship between CCDC134 expression level and immune infiltration. CTD database is used to predict drugs that inhibit CCDC134 and PubChem database is used to determine the molecular structure of identified drugs., Results: The expression of CCDC134 in breast cancer tissues was significantly higher than that of CCDC134 mRNA expression in adjacent normal tissues. ROC curve analysis showed that the AUC value of CCDC134 was 0.663. Kaplan-meier survival analysis showed that patients with high CCDC134 had a lower prognosis (57.27 months vs 36.96 months, P = 2.0E-6). Correlation analysis showed that CCDC134 mRNA expression was associated with tumor purity immune invasion. In addition, CTD database analysis identified abrine, Benzo ( A) Pyrene, bisphenol A, Soman, Sunitinib, Tetrachloroethylene, Valproic Acid as seven targeted therapy drugs that may be effective treatments for seven targeted therapeutics. It may be an effective treatment for inhibiting CCDC134., Conclusion: In breast cancer, upregulated CCDC134 is significantly associated with lower survival and immune infiltrates invasion. Our study suggests that CCDC134 can serve as a biomarker of poor prognosis and a potential immunotherapy target in breast cancer. Seven drugs with significant potential to inhibit CCDC134 were identified., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Yang, Chen, Li, Huang, Chen, Liu, Wang and Yu.)

Most early Bluetooth-based exposure notification apps use three binary classifications to recommend quarantine following SARS-CoV-2 exposure: a window of infectiousness in the transmitter, ≥15 minutes duration, and Bluetooth attenuation below a threshold. However, Bluetooth attenuation is not a reliable measure of distance, and infection risk is not a binary function of distance, nor duration, nor timing. We model uncertainty in the shape and orientation of an exhaled virus-containing plume and in inhalation parameters, and measure uncertainty in distance as a function of Bluetooth attenuation. We calculate expected dose by combining this with estimated infectiousness based on timing relative to symptom onset. We calibrate an exponential dose-response curve based on infection probabilities of household contacts. The probability of current or future infectiousness, conditioned on how long postexposure an exposed individual has been symptom-free, decreases during quarantine, with shape determined by incubation periods, proportion of asymptomatic cases, and asymptomatic shedding durations. It can be adjusted for negative test results using Bayes' theorem. We capture a 10-fold range of risk using six infectiousness values, 11-fold range using three Bluetooth attenuation bins, ∼sixfold range from exposure duration given the 30 minute duration cap imposed by the Google/Apple v1.1, and ∼11-fold between the beginning and end of 14 day quarantine. Public health authorities can either set a threshold on initial infection risk to determine 14-day quarantine onset, or on the conditional probability of current and future infectiousness conditions to determine both quarantine and duration., (© 2021 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Serum N-glycan patterns from 50 Crohn's disease (CD) patients and 50 healthy controls were acquired using a carbon matrix, from which eight N-glycans with significant difference were screened out to reveal remarkale performance for CD diagnosis. This research is expected to help future glycan-based disease detection not limited to CD.

Many lectins have been reported to have antitumor activities; identifying the glycan ligands in tumor cells of lectins is crucial for lectin clinical application. An edible mushroom galectin, Agrocybe aegerita lectin (AAL/AAGL), that has a high antitumor activity has been reported. In this paper, based on the glycan array data, it is showed that the Thomsen-Friedenreich antigen (TF antigen)-related O -glycans were found to be highly correlated with the antitumor activity of AAL/AAGL. Further glycosyltransferase quantification suggested that the ratio between GAL3ST2 and ST3GAL1 (GAL3ST2/ST3GAL1), which determined the 3'-sulfo-TF expression level, was highly correlated with the antitumor activity of AAL/AAGL. Overexpressing the enzyme of GAL3ST2 in HL60 and HeLa cell lines could increase the growth inhibition ratio of AAL/AAGL from 22.7 to 43.9% and 27.8 to 39.1%, respectively. However, ST3GAL1 in Jurkat cells could decrease the growth inhibition ratio from 44.7 to 35.6%. All the data suggested that the 3'-sulfo-TF antigen is one of the main glycan ligands that AAL/AAGL recognizes in tumor cells. AAL/AAGL may potentially serve as a reagent for cancer diagnosis and a targeted therapy for the 3'-sulfo-TF antigen., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Objective: The aim of this study is to develop a rapid and sensitive UPLC-MS/MS approach to determine the sophoridine (SOP) level in rat plasma and the pharmacokinetics of the substance., Significance: Sophoridine is used as an anti-inflammatory, anti-virus, anti-microbial, and anti-tumor alkaloid. It is essential to explore specific detection methods for the quantitative analysis of SOP in the blood circulation., Methods: The rat plasma samples were prepared by one-step protein precipitation with acetonitrile. Subsequently, the samples were separated by chromatography using a UPLC BEH C18 reversed-phase with an initial mobile phase of methanol and 0.1% formic acid aqueous solution. The gradient elution was performed at a fixed flow rate of 0.4 mL/min, and multiple reaction monitoring (MRM) mode with an electrospray positive ionization source was employed to detect the transitions of m/z 249.1 → 84.2 for SOP and m/z 264.3 → 69.8 for dendrobine (IS). The entire process required 3.5 min for each sample., Results: A linear correlation was established over the range of 2-2000 ng/mL ( r 2 ≥0.9954) for SOP in rat plasma with a lower limit of quantification (LLOQ) at 2 ng/mL. The range of accuracy was tested between 94.90% and 100.80%, and the relative standard deviations (RSDs) toward both intra- and inter-day precision were <10%. Thus, this method was successfully applied to a pharmacokinetic study, and the subsequent results demonstrated a low absolute bioavailability of 2.32%., Conclusion: The present study established a reliable method that quantified the SOP concentration in rat plasma after administering a dose of 2 mg/kg intravenously or 20 mg/kg orally.

Increasing evidence indicates that pyroptosis, a new type of programmed cell death, may participate in random flap necrosis and play an important role. ROS-induced lysosome malfunction is an important inducement of pyroptosis. Transcription factor E3 (TFE3) exerts a decisive effect in oxidative metabolism and lysosomal homeostasis. We explored the effect of pyroptosis in random flap necrosis and discussed the effect of TFE3 in modulating pyroptosis. Histological analysis via hematoxylin-eosin staining, immunohistochemistry, general evaluation of flaps, evaluation of tissue edema, and laser Doppler blood flow were employed to determine the survival of the skin flaps. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were used to calculate the expressions of pyroptosis, oxidative stress, lysosome function, and the AMPK-MCOLN1 signaling pathway. In cell experiments, HUVEC cells were utilized to ensure the relationship between TFE3, reactive oxygen species (ROS)-induced lysosome malfunction and cell pyroptosis. Our results indicate that pyroptosis exists in the random skin flap model and oxygen and glucose deprivation/reperfusion cell model. In addition, NLRP3-mediated pyroptosis leads to necrosis of the flaps. Moreover, we also found that ischemic flaps can augment the accumulation of ROS, thereby inducing lysosomal malfunction and finally initiating pyroptosis. Meanwhile, we observed that TFE3 levels are interrelated with ROS levels, and overexpression and low expression of TFE3 levels can, respectively, inhibit and promote ROS-induced lysosomal dysfunction and pyroptosis during in vivo and in vitro experiments. In conclusion, we found the activation of TFE3 in random flaps is partially regulated by the AMPK-MCOLN1 signal pathway. Taken together, TFE3 is a key regulator of ROS-induced pyroptosis in random skin flaps, and TFE3 may be a promising therapeutic target for improving random flap survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Lou, Yu, Chen, Chen, Chen, Wu, Ding, Xu, Jiang, Xu, Zhu, Gao and Zhou.)

Background: This study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free β-subunit of human chorionic gonadotropin (free β-hCG) in the second trimester could be used to predict hypertensive disorders of pregnancy (HDP)., Materials and Methods: In this retrospective case-control study, the data of gravidas patients who delivered at hospital were divided into the following groups: control (n = 136), gestational hypertension (GH, n = 126), preeclampsia (PE, n = 53), and severe preeclampsia (SPE, n = 41). Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of maternal serum DD, AFP, and free β-hCG levels for HDP., Results: DD levels of the GH, PE, and SPE groups were significantly higher than that of the control group (P < 0.001). The order of effectiveness for models predicting HDP was as follows: DD + AFP + free β-hCG > DD > DD + AFP > DD + free β-hCG > AFP + free β-hCG > AFP > free β-hCG. For predicting different types of HDP, DD alone had the best diagnostic value for SPE, followed by PE and GH. DD alone had a sensitivity of 100% with a 0% false negative rate and had the highest positive likelihood ratio (+ LR) for SPE. DD alone in combination with AFP alone, free β-hCG alone and AFP + free β-hCG could reduce false positive rate and improve + LR., Conclusion: DD is possible the best individual predictive marker for predicting HDP. Levels of DD alone in the second trimester were positively correlated with the progression of elevated blood pressure in the third trimester, demonstrating the predicting the occurrence of HDP. The risk calculation model constructed with DD + free β-hCG + AFP had the greatest diagnostic value for SPE.

The thermodynamic stability and mechanical properties of titanium carbonitrides TiC x N 1- x (0 ⩽ x ⩽ 1) are investigated by a combination of the universal cluster expansion method and the first-principles calculations. By considering the ordering of the N/C distributions on the anion sublattice sites of TiC x N 1- x , a binary diagram of the heat of formation is constructed, and seven kinds of ground-state structures are predicted in the whole range of 0 ⩽ x ⩽ 1. These predicted ground-state TiC x N 1- x structures are further proved to be dynamically and mechanically stable by examining their phonon dispersion spectra and elastic constants. Further studies indicate that the mechanical and thermodynamic properties of the ternary TiC x N 1- x structures are generally better than those of the binary TiC or TiN, while the differences within the ternary systems are insignificant. The possible origin of the enhancement of the mechanical and thermodynamic properties of the predicted ground-state TiC x N 1- x are discussed together with the electronic structures., (© 2021 IOP Publishing Ltd.)

Background: The present study aimed to develop and validate a rapid, selective, and reproducible ultra-performance liquid chromatography-tandem mass spectrometry separation method for the simultaneous determination of the levels of parecoxib and its main metabolite valdecoxib in rat plasma. Moreover, this method was applied to investigate the pharmacokinetics of parecoxib and valdecoxib in rats., Methods: Following the addition of celecoxib as an internal standard, one-step protein precipitation by acetonitrile was used for sample preparation. The effective chromatographic separation was carried out using an ACQUITY UPLC®BEH C18 reversed phase column (2.1 mm × 50 mm, 1.7 μm particle size) with acetonitrile and water (containing 0.1% formic acid) as the mobile phase. The procedure was performed in less than 3 min with a gradient elution pumped at a flow rate of 0.4 ml/min. The electrospray ionization source was applied and operated in the positive ion mode and multiple reaction monitoring mode was used for quantification using the following: target fragment ions: m/z 371 → 234 for parecoxib, m/z 315 → 132 for valdecoxib and m/z 382 → 362 for celecoxib., Results: The method validation demonstrated optimal linearity over the range of 50-10,000 ng/ml (r 2  ≥ 0.9996) and 2.5-500 ng/ml (r 2  ≥ 0.9991) for parecoxib and valdecoxib in rat plasma, respectively., Conclusions: The present study demonstrated a simple, sensitive and applicable method for the quantification of parecoxib and its main pharmacologically active metabolite valdecoxib following sublingual vein administration of 5 mg/kg parecoxib in rats.

Anti-adhesion therapies interfere with the bacterial adhesion to the host and thus avoid direct disruption of bacterial cycles for killing, which may alleviate resistance development. Herein, an anti-adhesion nanomedicine platform is made by wrapping synthetic polymeric cores with bacterial outer membranes. The resulting bacterium-mimicking nanoparticles (denoted "OM-NPs") compete with source bacteria for binding to the host. The "top-down" fabrication of OM-NPs avoids the identification of the adhesins and bypasses the design of agonists targeting these adhesins. In this study, OM-NPs are made with the membrane of Helicobacter pylori and shown to bind with gastric epithelial cells (AGS cells). Treatment of AGS cells with OM-NPs reduces H. pylori adhesion and such anti-adhesion efficacy is dependent on OM-NP concentration and its dosing sequence., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Combining siRNA and other chemotherapeutic agents into one nanocarrier can overcome the multidrug resistance (MDR) phenomenon by synergistically MDR relative genes silencing and elevated chemotherapeutic activity. Most of these systems are typically fabricated through complicated procedures, which involves materials preparation, drug loading and modifications. Herein, the purpose of this study is to develop a new and fast co-delivery system of siRNA and doxorubicin for potentially synergistic cancer treatment. Methods: The co-delivery system is constructed conveniently by a stable complex consisting of doxorubicin bound to siRNA via intercalation firstly, followed by interacting with (3-Aminopropyl)triethoxysilane (APTES) electrostatically and Tetraethyl orthosilicate (TEOS) co-condensed, and the characterizations of the resultant nanocarrier are also investigated. Furthermore, this study evaluates the synergistic anti-cancer efficacy in MCF-7/MDR cells after treatment of siRNA and doxorubicin 'two in one' nanocarriers. Results: We establish a new and fast method to craft a co-delivery system of siRNA and doxorubicin with controllable and nearly uniform size, and the entire fabrication process only costs in about 10 minutes. The resultant co-delivery system presents high loading capacities of siRNA and doxorubicin, and the encapsulated doxorubicin plays a pH-responsive control release. Further, biological functionality tests of the synthesized co-delivery nanocarriers show high inhibition of P-gp protein encoded by MDR-1 gene in MCF-7/MDR cells (a variant of human breast cancer cell line with drug resistance) after transfection of these nanocarriers carrying MDR-1 siRNA and doxorubicin simultaneously, which sensitize the MCF-7/MDR cells to doxorubicin, overall leading to improved cell suppression. Conclusion: Collectively, this co-delivery system not only serves as potent therapeutics for synergistic cancer therapy, it also may facilitate the bench-to-bedside translation of combinatorial delivery system as a robust drug nanocarrier by allowing for fabricating a simply and fast nanocarrier for co-delivery of siRNA and doxorubicin with predictable high production rate., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: To evaluate a classification model of contrast-enhanced ultrasound (CEUS) and examine the characteristics of patients with false-negative diagnosis., Patients and Methods: A retrospective secondary analysis of a multicenter trial of CEUS for breast cancer diagnosis (from August 2015 to April 2017) was undertaken. Patients (n=1,023) with Breast Imaging Reporting and Data System 4-5 lesions on B-mode ultrasound underwent CEUS. Pathological diagnoses were available from surgical or biopsy specimens for correlation. Lesion maximum diameter (LMD), distance to the papilla (DtP), distance from the superficial edge of the lesion to the skin (DtS), distance from the deep edge of the lesion to the pectoralis muscle (DtPM), and body mass index (BMI) were evaluated., Results: Median age and BMI were 48.0 and 41.2 years and 23.2 and 22.4 kg/m 2 for patients with malignant and benign lesions, respectively. Overall sensitivity, specificity, and accuracy of CEUS for malignancy were 89.4%, 65.3%, and 75.8%, respectively. The patients with true-positive and false-negative diagnosis (ie, with malignant lesion) were older than those with false-positive and true-negative diagnosis (ie, with benign lesion). Patients with true-positive and false-positive diagnoses had higher BMI than patients with true-negative and false-negative diagnoses ( P =0.004). Patients with true-positive and false-negative diagnoses had larger LMD and DtP, as well as smaller DtS and DtPM., Conclusion: Older age, higher BMI, larger LMD and DtP, and smaller DtS and DtPM were associated with malignant lesions on CEUS. Patients with these characteristics should undergo further imaging., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

HMGB1 (High mobility group box 1) expressions in adenocarcinoma (AC) and squamous cell/adenosquamous (SC/ASC) carcinoma of gallbladder, as well as its prognostic significance, have not yet been evaluated. We investigated HMGB1 expression in 80 cases of AC gallbladder cancer and 52 cases of SC/ASC gallbladder cancer. Survival information was concomitantly collected. The association of HMGB1 expression with clinicopathological characteristics and the possible prognostic role of HMGB1 for two aforementioned subtypes of gallbladder cancers were also analyzed. siRNA technique was utilized to explore the role of HMGB1 in proliferation and invasion of gallbladder cancer cells in vitro. HMGB1 overexpression is present in AC and SC/ASC gallbladder cancers. HMGB1 expression significantly associates with growth and metastasis of AC and SC/ASC gallbladder cancers. In vitro cell experiments based on siRNA demonstrated that HMGB1 downregulation inhibits proliferation and invasion of gallbladder cancer cells. Kaplan-Meier analysis revealed that HMGB1 expression is negatively associated with overall survival time of patients with AC or SC/ASC gallbladder cancer. Cox multivariate analysis confirmed that HMGB1 is an independent risk factor for survival of patients with AC or SC/ASC gallbladder cancer. HMGB1 overexpression closely correlates with progression and poor prognosis of AC and SC/ASC gallbladder cancers.

Objective: To explore the diagnostic value of ultrasonography for Kimura's disease (KD)., Methods: Retrospectively analyzed the results of two dimension and color Doppler of 21 Kimura's disease carried by 19 patients who were resected and confirmed by pathologhy., Results: Twenty-one KD cases were detected by the ultrasound while none of them was diagnosed by ultrasonography. 21 cases were showed in the lymph nodes (42.9%, 9/21), parotid gland (4.8%, 1/21) and soft tissues (52.4%, 11/21). The masses both in the lymph and in the parotid gland marked hypoechogenicity and round or like-round. Cases in the soft tissues marked hypoechogencity or hyperechogenicity. Color Doppler flow pattern II to III were showed in 19 cases (90.5%, 19/21)., Conclusion: Ultrasonography enables a confident preoperative diagnosis of Kimura's disease.

Therapeutic antiangiogenesis strategies have demonstrated significant antitumor efficacy in ovarian cancer. Recently, RNA interference (RNAi) has come to be regarded as a promising technology for treatment of disease, especially cancer. In this study, vascular endothelial growth factor (VEGF)-small interfering RNA (siRNA) was encapsulated into a magnetic mesoporous silica nanoparticle (M-MSN)-based, polyethylenimine (PEI)-capped, polyethylene glycol (PEG)-grafted, fusogenic peptide (KALA)-functionalized siRNA delivery system, termed M-MSN&#95;VEGF siRNA@PEI-PEG-KALA, which showed significant effectiveness with regard to VEGF gene silencing in vitro and in vivo. The prepared siRNA delivery system readily exhibited cellular internalization and ease of endosomal escape, resulting in excellent RNAi efficacy without associated cytotoxicity in SKOV3 cells. In in vivo experiments, notable retardation of tumor growth was observed in orthotopic ovarian tumor-bearing mice, which was attributed to significant inhibition of angiogenesis by systemic administration of this nanocarrier. No obvious toxic drug responses were detected in major organs. Further, the magnetic core of M-MSN&#95;VEGF siRNA@PEI-PEG-KALA proved capable of probing the site and size of the ovarian cancer in mice on magnetic resonance imaging. Collectively, the results demonstrate that an M-MSN-based delivery system has potential to serve as a carrier of siRNA therapeutics in ovarian cancer.

Lung cancer has been the leading type of cancers with regard to mortality and mobility. New versions of RNAi-based therapy are greatly required to tackle the challenges of lung cancer. In this study, we developed a novel siRNA delivery vector based on our magnetic mesoporous silica nanoparticles (M-MSNs) platform. This nanocarrier was constructed by loading siRNAs into the mesopores of M-MSNs, followed by polyethylenimine (PEI) capping, PEGylation and fusogenic peptide KALA modification. The resultant delivery system exhibited prolonged half-life in bloodstream, enhanced cell membrane translocation and endosomal escapablity, and favorable tissue biocompatibility and biosafety. Systemic application of vascular endothelial growth factor (VEGF) siRNA via this nanocarrier resulted in remarkable tumor suppression, both in subdermal and orthotopic lung cancer models, while tumor metastasis was also significantly reduced, overall leading to improved survival. In addition, the magnetic core of the particles and the functionalized fluorescence markers conveniently enabled in vivo imaging of target tissues. Taken together, this M-MSNs-based siRNA delivery vehicle has shown very favorable applicability for cancer therapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Chick embryo egg hydrolysates (CEEH) were obtained by enzymatic hydrolysis of chick embryo egg in vitro-simulated gastrointestinal digestion. The antioxidant activities of CEEH were investigated by employing three in vitro assays, including the 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate)/1,1-diphenyl-2-picrylhydrazyl (ABTS/DPPH)/hydroxyl radical-scavenging assays. The radical-scavenging effect of CEEH (1.0 mg/mL) was in a dose-dependent manner, with the highest trolox equivalent antioxidant capacity for ABTS, DPPH, and that of hydroxyl radicals found to be 569, 2097, and 259.6 μmol/L, respectively; whereas the trolox equivalent antioxidant capacity of unhatched egg for ABTS, DPPH, and that of hydroxyl radicals were found to be 199, 993, and 226.5 μmol/L, respectively. CEEH showed stronger scavenging activity than the hydrolysates of unhatched egg against free radicals such as ABTS, DPPH, and hydroxyl radicals. The antioxidant amino acid analysis indicated that the 14-day CEEH possess more antioxidant amino acids than that of the unhatched egg. In addition, essential amino acids analysis showed that the 14-day CEEH have the highest nutritional value. Combined with the results of the amino acid profiles, CEEH were believed to have higher nutritive value in addition to antioxidant activities than the unhatched egg.