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Persicae Semen is an edible Chinese herbal medicine that ameliorates myocardial ischemia. However, its pharmacodynamic properties and mechanisms of action remain unclear. This study aimed to investigate the ameliorative effect of Persicae Semen extract (PS) on acute myocardial ischemia (AMI) in rats and explore its mechanism of action. After the PS administration to rats, 12 compounds were identified in the plasma. PS can significantly improve cardiac function, regulate creatine kinase (CK), creatine kinase MB (CK-MB), cardiac troponin (cTn I), α-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels in the serum, and ameliorate the pathological injury of AMI in rats. Metabolomics and network pharmacology of components absorbed in to plasma showed that PS may regulate the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism, then ameliorate myocardial ischemic injury. This study found that PS significantly improved cardiac function in rats with AMI, through the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism.

Background Many studies have found an association between mood-disorder-related traits and endometriosis and adenomyosis. However, the cause–effect relationship remains unclear. Aims We conducted Mendelian randomisation analyses to evaluate any causal relationship between mood disorders and endometriosis as well as different sites of endometriosis. Method Summary-level statistics for mood-disorder-related traits and endometriosis (8288 cases, 68 969 controls) in European populations were derived from large-scale data-sets of genome-wide association studies. A two-sample Mendelian randomisation was performed using the inverse-variance weighted and weight median methods. Further sensitivity analyses, including heterogeneity, pleiotropy and leave-one-out analyses, were conducted to test the consistency of the results. Results Genetically determined mood swings (odds ratio = 2.557, 95% CI: 1.192–5.483, P = 0.016) and major depression (odds ratio = 1.233, 95% CI: 1.019–1.493, P = 0.031) were causally associated with an increased risk of endometriosis. Mood swings (odds ratio = 4.238, 95% CI: 1.194–15.048, P = 0.025) and major depression (odds ratio = 1.512, 95% CI: 1.052–2.173, P = 0.025) were also causally associated with the risk of adenomyosis. Sensitivity analyses confirmed the reliability of the results. Conclusions Our results suggest that mood-disorder-related traits increase the risk of endometriosis and adenomyosis. This study provides new insights into the potential pathogenesis of endometriosis and adenomyosis, and highlights the importance of preventing endometriosis and adenomyosis in patients with mood-disorder-related traits.

Microporous organic polymers (MOPs) are a new type of porous materials, which have advantages of synthetic diversity, chemical and physical stability, microporous size controllability, etc. MOPs indicate broad applications in various fields such as heterogeneous catalysis, gas adsorption, separation, and storage. In recent years, MOPs have attracted an enormous attention in greenhouse gas capture due to their great potential in physisorptive gas storage. Carbazole and its derivatives have been studied extensively as Metal-Organic Polyhedra (MOPs) building blocks due to their unique structural features and versatile functionalization possibilities. This paper systematically reviews the synthesis, characterization and application of carbazole-based polymers, and relationship of structures and properties of these polymers. The application of the polymers in carbon dioxide (CO2) capture field is analysed taking advantage of their adjustable microporous structure and electron rich properties. This review also provides novel insights regarding functional polymer materials that have high ability of greenhouse gas capture and absorbing selectivity will be obtained by reasonable molecular design and efficient synthesis.

Abstract To explore an appropriate time interval between oocyte retrieval and intracytoplasmic sperm injection (ICSI) for optimal embryological and clinical outcomes in ICSI cycles over 40 years of maternal age. A retrospective analysis of 1476 ICSI fresh cycles from women aged over 40 years, was performed at the Reproduction Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University, between December 2013 and August 2020. The fertilization rate and clinical pregnancy rate were the main outcomes. Multivariate linear regression and logistic regression analysis of factors showed that fertilization rate (P = 0.024) and clinical pregnancy rate (P = 0.011) were significantly associated with oocyte pick up (OPU)-ICSI interval. A longer OPU-ICSI interval (no more than 6 h) was associated with a higher fertilization rate but significantly decreased the clinical pregnancy rate when the OPU-ICSI interval was over 4 h (P

Abstract In this paper, we propose a scheme for autonomous exploration in unknown environments using a mobile robot. To reduce the storage consumption and speed up the search of frontiers, we propose a wave-features-based rapidly exploring random tree method, which can inhibit or promote the growth of sampling trees regionally. Then, we prune the frontiers with mean shift algorithm and use the pruned frontiers for decision-making. To avoid the repeated exploration, we develop a decision making method with consistency assessment, in which the status of the robot and frontiers are explicitly encoded and modeled as a fixed start open traveling salesman problem (FSOTSP). Furthermore, a re-decision mechanism is build to reduce the extra computing cost. Simulations and real-world experiments show the significant improvement of the proposed scheme.

Abstract Dual-atom catalysts, particularly those with heteronuclear active sites, have the potential to outperform the well-established single-atom catalysts for oxygen evolution reaction, but the underlying mechanistic understanding is still lacking. Herein, a large-scale density functional theory is employed to explore the feasibility of *O-*O coupling mechanism, which can circumvent the scaling relationship with improving the catalytic performance of N-doped graphene supported Fe-, Co-, Ni-, and Cu-containing heteronuclear dual-atom catalysts, namely, M’M@NC. Based on the constructed activity maps, a rationally designed descriptor can be obtained to predict homonuclear catalysts. Seven heteronuclear and four homonuclear dual-atom catalysts possess high activities that outperform the minimum theoretical overpotential. The chemical and structural origin in favor of *O-*O coupling mechanism thus leading to enhanced reaction activity have been revealed. This work not only provides additional insights into the fundamental understanding of reaction mechanisms, but also offers a guideline for the accelerated discovery of efficient catalysts.

In this study, Ni-GQDs nanocomposite coatings were prepared by double-pulse electrodeposition under supercritical CO2 with graphene quantum dots (GQDs) as the second phase additive. The effects of supercritical CO2 conditions and reverse pulse current density on microstructure, crystal orientation, grain size, GQDs quality, mechanical properties, and corrosion resistance of Ni-GQDs nanocomposite coatings were investigated. The results show that when the reverse pulse current density is 0.8 A /dm2, the surface of Ni-GQDs-Ⅱ nanocomposite coating is compact and flat, GQDs is uniformly dispersed in the coating, and GQDs is closely bound to Ni grains. Compared with the coating prepared at normal temperature and pressure. The grain size of the Ni-GQDs-Ⅱ nanocomposite coating is 4.58 nm, and the grain size is reduced by 75.3 %. The quality of GQDs in the coating was improved. The coating hardness is 867.22 HV, which is significantly increased by 53.7 %. The roughness is 0.236 μm, which is significantly reduced by 37.2 %. The friction coefficient and volume wear were 0.262 and 3.395 × 107 μm3, respectively, which were significantly reduced by 27.4 % and 57.9 %. After electrochemical corrosion, the self-corrosion voltage of the coating was −139 mV, and the self-corrosion current density was 3.19 × 10−7 A/cm2. The self-corrosion voltage was significantly increased by 61.2 %, and the self-corrosion current density was significantly decreased by 71.2 %. The Rct value and Ndl value of the coating are 31594.53 Ω·cm2 and 0.862, respectively. Significantly increased by 226.2 % and 67.1 %, respectively. The coating has excellent mechanical properties and corrosion resistance.

The pharmacokinetics (PK) of Rhodiola crenulata in rats were studied, and pharmacokinetic–pharmacodynamic (PK-PD) correlation analysis was performed to elucidate their time–concentration–effect relationship. The myocardial ischemia model was made with pituitrin. Rats were divided into sham operation, sham operation administration, model, and model administration groups (SG, SDG, MG, and MDG, respectively; n = 6). Blood was collected from the fundus venous plexus at different time points after oral administration. The HPLC-QQQ-MS/MS method was established for the quantification of five components of Rhodiola crenulata. CK, HBDH, SOD, LDH, and AST at different time points were detected via an automatic biochemical analyzer. DAS software was used to analyze PK parameters and PK-PD correlation. The myocardial ischemia model was established successfully. There were significant differences in the PK parameters (AUC0–t, AUC0–∞, Cmax) in MDG when compared with SDG. Two PD indicators, CK and HBDH, conforming to the sigmoid-Emax model, had high correlation with the five components, which indicated a delay in the pharmacological effect relative to the drug concentration in plasma. The difference in the PK parameters between modeled and normal rats was studied, and the time–concentration–effect of composition and effect indicators were investigated. This study can provide reference for the rational clinical application of Rhodiola crenulata and for related studies of other anti-myocardial ischemia drugs.

Context Polygonum multiflorum Thunb. (Polygonaceae) (PM) can cause potential liver injury which is typical in traditional Chinese medicines (TCMs)-induced hepatotoxicity. The mechanism involved are unclear and there are no sensitive evaluation indicators.Objective To assess PM-induced liver injury, identify sensitive assessment indicators, and screen for new biomarkers using sphingolipidomics.Materials and methods Male Sprague–Dawley (SD) rats were randomly divided into four groups (control, model with low-, middle- and high-dose groups, n = 6 each). Rats in the three model groups were given different doses of PM (i.g., low/middle/high dose, 2.7/8.1/16.2 g/kg) for four months. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and liver were quantitatively analyzed. Fixed liver tissue sections were stained with haematoxylin and eosin and examined under a light microscope. The targeted sphingolipidomic analysis of plasma was performed using high-performance liquid chromatography tandem mass spectrometry.Results The maximal tolerable dose (MTD) of PM administered intragastrically to mice was 51 g/kg. Sphingolipid profiling of normal and PM-induced liver injury SD rats revealed three potential biomarkers: ceramide (Cer) (d18:1/24:1), dihydroceramide (d18:1/18:0)-1-phosphate (dhCer (d18:1/18:0)-1P) and Cer (d18:1/26:1), at 867.3–1349, 383.4–1527, and 540.5–658.7 ng/mL, respectively. A criterion for the ratio of Cer (d18:1/24:1) and Cer (d18:1/26:1) was suggested and verified, with a normal range of 1.343–2.368 (with 95% confidence interval) in plasma.Conclusions Three potential biomarkers and one criterion for potential liver injury caused by PM that may be more sensitive than ALT and AST were found.

Background and Aims: For non-obstructive azoospermia (NOA) patients, micro-TESE is considered to have higher sperm retrieval rate (SRR) than traditional surgery. However, various clinical parameters are not reliable predictors for the presence of focal spermatogenesis and SRR. This study summarized the characters of seminiferous tubules appearances and investigated their relationship with SRR. Method: This was a retrospective study. From September 2014 to April 2023, 638 NOA patients treated with micro-TESE were divided into six groups according to the seminiferous tubules appearances (Group-A: homogeneously thick, Group-B: homogeneously thin, Group-C: seminiferous tubules were severe thin and loss the tubal appearance, Group-D: the testicles were filled with hyperplastic Leydig cells, seminiferous tubules were severe thin and rare, Group-E, thick tubules mixed with thin tubules, Group-F, extensive testicular microlithiasis). Age, testicular volume, serum FSH, testosterone level, SRR and the heterogeneous seminiferous tubules presenting rate (HSTPR) were compared. Results: Sperms were successfully retrieved in 333 cases (SRR=52.2%). There were no statistical differences in age, testicular volume, FSH and testosterone level between the patients who succeeded and failed to obtain sperm (Table 1, all [Formula: see text]>0.05). The constituent ratio of etiology was different in the six groups (Table 2, [Formula: see text]

Development of methods for simultaneous single cell analysis of transcription and translation is still underway. Here, Hu et al. develop single-cell transcriptome and translatome dual-omics on human oocytes, which enables them to identify OOSP2 as an induction factor during human oocyte maturation.

Abstract Industrial piping structures often suffer from corrosion caused by biofouling or chemical etching, which can cause immediate structural failure. Polyurea coatings, which are fabricated for emergency leak sealing, are able to form high mechanical strength coating surfaces within seconds. After its further modification via Ce/La-doped TiO2, the polyurea coating will indicate an increment in mechanical strength, chemical durability, and reduction of microbial attachment. Due to the adsorption by the Ce/La-doped TiO2 and generation of reactive oxygen species (ROS), E. coli and Pseudomonas may lose their living conditions during the progress, and planktonic bacteria cells are prevented from enriching on the surface. The Ce/La‐dopants can also improve the original photocatalytic response of nano-TiO2 to UV light and environmental temperature. These Ce/La-doped TiO2 polyurea coatings illustrate an immediate application for emergency leak sealing purposes without any production interruption and it may prolong the time intervals for the maintenance service as well.

Background and aims: MACHs are present in common everyday products and are defined as endocrine disrupting chemicals (EDCs) that can negatively impact human health by interfering with the endocrine system. There is a lack of human studies on the association between MACHs and the microbiota in the female reproductive tract. In this study, we recruited a prospective randomized controlled cohort to investigate potential correlations between MACHs exposure and the vaginal microbiota, as well as their potential impacts on embryo implantation. Methods: This study recruited a randomized controlled cohort prospectively to investigate the correlation between MACHs exposure and the vaginal microbiota, as well as their potential impact on embryo implantation. The types and concentrations of MACHs exposure were detected using LC-MS, while the vaginal microbiota was characterized by metagenomics. Results: The findings reveal that exposure to MEHP, Methyl N-methylanthranilate, and Benzene was associated with a disruption of the microbial community structure in the recurrent implantation failure (RIF). The RIF group exhibited an instable vaginal microbial community structure, with reduced abundance of Lactobacillus spp. and increased abundance of potentially pathogenic bacteria, such as Streptococcus anginosus, Peptoniphilus asaccharolyticus. The atypical composition of the vaginal microbiota was associated with unfavorable pregnancy outcomes. Impairment of sphingolipid metabolism was a crucial factor for abnormal microbiota to trigger unfavorable pregnancy outcomes. Furthermore, exposure to Methyl N-methylanthranilate and MEHP was associated with reduced abundance of Lactobacillus spp. (including L.crispatus and L.jensenii) and reduction of the protective barrier function of the reproductive tract. Conclusions: Multiple MACHs, such as Benzene, Methyl N-methylanthranilate, and MEHP, were associated with changes in the RIF group’s vaginal microbiota. MACHs exposure might cause embryo implantation failure by affecting the vaginal microbial composition.

A graphene quantum dots (GQDs)-reinforced nickel-based composite coating was electrodeposited on the surface of a copper plate with a supercritical carbon dioxide fluid (SC-CO2)-assisted DC power supply. The effect of the current density on surface morphology, microstructure, average grain size, hardness, and corrosion resistance of the resulting coatings was investigated in detail. It was found that the GQDs composite coating showed a more compact surface, a smaller grain size, higher microhardness, and stronger corrosion resistance than the pure Ni coating produced in SC-CO2 and a texture coefficient indicative of a (111) preferred orientation. When the current density was 8 A/dm2, the surface morphology of the GQDs composite coating showed a high density, and the grain size was about 23 nm. In addition, the micro-hardness and corrosion resistance of the GQDs composite coating was greatly improved compared with those of the pure nickel coating; at the same time, its wear rate, friction coefficient, and self-corrosion current density were decreased by 73.2%, 17.5%, and 9.2%, respectively.

Objective: To explore the possible mechanisms of cholestasis induced by Polygoni Multiflori Radix (PM).Methods: Low and high doses of water extract of PM were given to mice by gavage for 8 weeks. The serum biochemical indexes of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT) alkaline phosphatase (ALP) and so on were detected in the second, fourth, sixth, and eighth weeks after administration. At the end of the eighth week of administration, the bile acid metabolic profiles of liver and bile were screened by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS). Liver pathological changes were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA transcription of the target genes and Western blotting (WB) was used to the detect target protein expression.Results: Biochemical tests results showed the values of ALP and GGT were two and three times greater than the normal values respectively, and the value of R was less than 2. Histopathology also showed that PM caused lymphocyte infiltration, a small amount of hepatocyte necrosis and nuclear fragmentation in mouse liver. The proliferation of bile duct epithelial cells was observed in the high group. These results indicated that PM may lead to cholestatic liver injury. HPLC-QQQ-MS/MS analysis with the multivariate statistical analysis revealed significant alterations of individual bile acids in liver and gallbladder as compared to those of the control group. RT-qPCR showed that the transcription of Fxr, Shp, Bsep, Bacs, Mdr2, and Ugt1a1 were downregulated and that of Cyp7a1, Mrp3, and Cyp3a11 was significantly upregulated in the treatment group. WB demonstrated that PM also markedly downregulated the protein expression of FXR, BSEP, and MDR2, and upregulated CYP7A1.Conclusion: PM inhibited the expression of FXR, which reduced the expression of MDR2 and BSEP, leading to the obstruction of bile acids outflow, and increased the expression of CYP7A1, resulting in an increase of intrahepatic bile acid synthesis, which can lead to cholestasis.

Serum thymidine kinase 1 protein (STK1p) concentration has been used successfully as a reliable proliferating serum biomarker in early tumour discovery and clinical settings. It is detected by an enhanced chemiluminescence (ECL) dot blot assay with the biotin-streptavidin (BSA) platform (a gold standard) based on chicken anti-human thymidine kinase 1 IgY polyclonal antibody (hTK1-IgY-pAb). However, ECL dot blotting is a semiautomatic method that has been limited to large-scale applications due to the differences among batches of antibodies from individual hens, and the skill level of operation technicians sometimes results in unstable STK1p values. Therefore, a highly stable recombinant chicken full-length IgY monoclonal antibody in combination with a fully automated sandwich biotin-streptavidin (sandwich-BSA) platform was developed. Hens were immunized with 31-peptide, a key sequence of human TK1 (hTK1), before constructing an immune phage display scFv library. Finally, a recombinant full-length IgY monoclonal antibody (hTK1-IgY-rmAb#5) with high-affinity binding with human recombinant TK1 (rhTK1) (3.95×10−10 mol/L), high sensitivity with hTK1 calibrators (slope of linear curve: 89.98), and high specificity with low/elevated STK1p (r≈0.92-0.963) was identified. hTK1-IgY-rmAb#5 showed a specific immune response with thymidine kinase 1 (TK1) in TK1-positive/negative cell lysates by Western blotting and immunohistochemistry (IHC) in normal and cancer tissues. In particular, the detection of TK1 serum samples from health centres showed a high coincidence rate (r=0.988,n=90) between hTK1-IgY-rmAb#5 and hTK1-IgY-pAb and between the semiautomatic ECL dot blot BSA platform and the novel automatic chemiluminescence sandwich-BSA platform (r=0.857,n=292). hTK1-IgY-rmAb#5 is stable and highly sensitive for detecting the lowest STK1p value at 0.01 pmol/L (pM). The accuracy is high (SD

IntroductionAn approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed. Material and methodsThe novel N-IgY-pAb and its intranasal spray response against the wild type (“‘WH-Human 1”) SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray.ResultsSeventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475 ), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305) four are in the C1/2-terminal (561PFQQFGRDIADTTDA575,571DTTDAVRDPQTLEIL585,581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675 ), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835) one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (614HHANEYRLYLDAYNM642, ORF10-3 (21MNSRNYIAQVDVVNFNLT38, ORF7a-1(1MKIILFLALITLATC15) and ORF7a-12 (1116TLCFTLKRKTE121).Discussion and conclusionWe concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and “cocktails” of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.

Abstract Background In-vitro-grow (IVG) of preantral follicles is essential for female fertility preservation, while practical approach for improvement is far from being explored. Studies have indicated that neurotrophin-4 (NT-4) is preferentially expressed in human preantral follicles and may be crucial to preantral follicle growth. Methods We observed the location and expression of Tropomyosin-related kinase B (TRKB) in human and mouse ovaries with immunofluorescence and Western blot, and the relation between oocyte maturation and NT-4 level in follicular fluid (FF). Mice model was applied to investigate the effect of NT-4 on preantral follicle IVG. Single-cell RNA sequencing of oocyte combined with cell-specific network analysis was conducted to uncover the underlying mechanism of effect. Results We reported the dynamic location of TRKB in human and mouse ovaries, and a positive relationship between human oocyte maturation and NT-4 level in FF. Improving effect of NT-4 was observed on mice preantral follicle IVG, including follicle development and oocyte maturation. Transcriptome analysis showed that the reparative effect of NT-4 on oocyte maturation might be mediated by regulation of PI3K-Akt signaling and subsequent organization of F-actin. Suppression of advanced stimulated complement system in granulosa cells might contribute to the improvement. Cell-specific network analysis revealed NT-4 may recover the inflammation damage induced by abnormal lipid metabolism in IVG. Conclusions Our data suggest that NT-4 is involved in ovarian physiology and may improve the efficiency of preantral follicle IVG for fertility preservation.

Early discover of risk progression of invisible carcinomas is important for a prerequisite successful treatment. Here, we investigated whether concentration of human thymidine kinase 1 (HTK1) discover invisible malignant human tumours. The HTK1 concentration of tumour cellular based on HTK1 IgY-polyclonal-antibody (HTK1-IgY-pAb) was determined by using a novel automatic chemiluminescence analyser with sandwich biotin-streptavidin (SBSA) platform. Minimum number of cells able to be detected by this technology used cells with low and high concentration of HTK1. The limit visibility by tumour imaging is approximately 1 mm in diameter, corresponding to approximately 109 cells with a cell diameter of 1 µm. Based on a HTK1 standard curve and a molecular weight of HTK1 of 96 kD, the HTK1protein (HTK1p) concentration per cell was calculated to be 0.021 pg. Assuming 200 pg in total protein/cell, approximately 50 × 106 growing malignant cells in the body were calculated to releases HTK1 into 5-liter blood. A HTK1 values of 3.914, 0.435 and 0.009 pmol/L corresponds to 10 × 105, 2 × 105 and 1 × 105 growing malignant cells, respectively. The lowest detectable sensitivity of HTK1 is 0.009 pmol/L in 1 × 105 growing malignant cells and 0.01 pmol/L in blood serum, detectable in health screening. Comparing the novel automatic chemiluminescence analyser with the original ECL dot-blot assay using serum HTK1p (health screening, n = 265) showed high correlation (r = 0.8743, P

An electronic nose (e‐nose) mimics the mammalian olfactory system in identifying odors and expands human olfaction boundaries by tracing toxins and explosives. However, existing feature‐based odor recognition algorithms rely on domain‐specific expertise, which may limit the performance due to information loss during the feature extraction process. Inspired by human olfaction, a smart electronic nose enabled by an all‐feature olfactory algorithm (AFOA) is proposed, whereby all features in a gas sensing cycle of semiconductor gas sensors, including the response, equilibrium, and recovery processes are utilized. Specifically, our method combines 1D convolutional and recurrent neural networks with channel and temporal attention modules to fully utilize complementary global and dynamic information. It is further demonstrated that a novel data augmentation method can transform the raw data into a suitable representation for feature extraction. Results show that the e‐nose simply comprising of six semiconductor gas sensors achieves superior performances to state‐of‐the‐art methods on the Chinese liquor data. Ablation studies reveal the contribution of each sensor in odor recognition. Therefore, a deep‐learning‐enabled codesign of sensor arrays and recognition algorithms can reduce the heavy demand for a huge amount of highly specialized gas sensors and provide interpretable insights into odor recognition dynamics in an iterative way.

Objective: To investigate whether the cumulative clinical pregnancy rates (CCPR) and cumulative live birth rates (CLBR) increase as the oocyte retrieval cycle increases in women with poor ovarian response. Design: Retrospective cohort study. Setting: Not applicable. Patient(s): Women diagnosed of poor ovarian response (POR) according to the Bologna criteria and who completed in vitro fertilization or intracytoplasmic sperm injection cycles between January 2014 and December 2018. Intervention(s): Not applicable. Main Outcome Measure(s): The conservative and optimistic estimations of CCPR and CLBR. Result(s): The conservative and optimistic estimates of CCPR peaked at the 6th complete cycle, reaching 36.44% and 71.61%, respectively. However, the conservative and optimistic estimates of CLBR peaked at the 4th complete cycle, reaching 20.22% and 38.31%, respectively. The live birth rate per complete cycle of mild stimulation protocol was comparable to other protocols after adjusting for the confounding factors. For patients ≤35 years, the live birth rate per complete cycle of progestin-primed ovarian stimulation (adjusted odds ratio = 0.51, 95% confidence interval: 0.30–0.87) and gonadotropin-releasing hormone antagonist protocol (adjusted odds ratio=0.45, 95% confidence interval: 0.24–0.81) were significantly lower than that of the mild stimulation. Conclusion(s): It is not advisable to initiate more than four complete cycles for POR patients since CLBR do not increase after that. For POR patients ≤35 years, the live birth rate per complete cycle increased in women with mild stimulation protocol.

Objective: To evaluate the diagnostic efficiency of spent blastocyst culture medium (BCM) in noninvasive preimplantation genetic testing (niPGT) by comparing the karyotype concordance with corresponding inner cell mass (ICM) among initial trophectoderm (TE) biopsy, TE re-biopsy, and BCM sampling. Design: Re-analysis aneuploid/mosaic blastocysts donated for research by couples. Setting: Institutional in vitro fertilization center. Patient(s): A total of 12 couples donated their blastocysts, which had previously been diagnosed as aneuploid or mosaic by initial TE-biopsy preimplantation genetic testing for aneuploidy (PGT-A) for research. Intervention(s): A total of 26 frozen−thawed blastocysts were re-analyzed by TE re-biopsy, ICM biopsy, and the collection of spent BCM. Main Outcome Measure(s): Karyotype concordance rates. Result(s): For 23 embryos diagnosed as aneuploid by initial TE biopsy, 78.3% of initial TE samples, 87.0% of TE re-biopsies samples, and 78.3% of BCM samples were concordant with corresponding ICM samples, and for three mosaic embryos, the concordance rates with ICM of these three groups were 0%, 100%, and 100%, respectively. With the corresponding ICM result as the true result, sensitivity of both niPGT-A and initial TE were 100%; however, the false-positive rate (FPR) of initial TE was higher than that of niPGT-A (100% vs. 0). Conclusion(s): niPGT-A using BCM had diagnostic efficiency similar to that of TE-biopsy PGT-A. In the case of mosaic embryos, niPGT-A using BCM may be more reliable for predicting karyotypes of ICM than initial TE biopsy.

Context α-Hederin, a potent bioactive compound of Pulsatilla chinensis (Bunge) Regel (Ranunculaceae), has many pharmacological uses, but its effect on cancer cell metabolism is still unclear. Objective To elucidate the role of α-hederin in the glucose metabolism of lung cancer cells. Materials and methods Cell Counting Kit 8 and colony formation assays were employed to assess the antiproliferative effects of α-hederin. Glucose uptake, ATP generation, and lactate production were measured. Glycolysis-related proteins were detected using western blotting, and a sirtuin 6 (SIRT6) inhibitor was used to verify A549 cell proliferation. Sixty male BALB/c nude mice were divided into normal control, 5-FU (25 mg/kg), and α-hederin (5 and 10 mg/kg) groups to assess the antitumor effect for 32 days. Glycolysis-related protein expression was evaluated using immunohistochemical analysis. Results α-Hederin inhibited A549 (IC50 = 13.75 μM), NCI-H460 (IC50 = 17.57 μM), and NCI-H292 (IC50 = 18.04 μM) proliferation; inhibited glucose uptake and ATP generation; and reduced lactate production. Furthermore, α-hederin (10 and 15 μM) markedly inhibited hexokinase 2, glucose transporter 1, pyruvate kinase M2, lactate dehydrogenase A, monocarboxylate transporter, c-Myc, hypoxia-inducible factor-1α, and activated SIRT6 protein expression. Using a SIRT6 inhibitor, we demonstrated that α-hederin inhibits glycolysis by activating SIRT6. A tumour xenograft mouse model of lung cancer confirmed that α-hederin (5 and 10 mg/kg) inhibits lung cancer growth by inhibiting glycolysis in vivo. Discussion and conclusions α-Hederin inhibits A549 cell growth by inhibiting SIRT6-dependent glycolysis. α-Hederin might serve as a potential agent to suppress cancer.

Context Erzhi pills are a classic Chinese medicine prescription, but their effects on Alzheimer’s disease (AD) are not clear. Objective The protective effects of Erzhi pills in AD rats and their potential mechanisms were investigated. Materials and methods An AD rat model was established by ovariectomy combined with d-galactose and Aβ1-40 injection. Rats were randomly divided into five groups: sham-operated, model, oestradiol valerate (0.80 mg/kg), Erzhi pills high-dose (1.50 g/kg), and Erzhi pills low-dose (0.75 g/kg). Learning and memory abilities were evaluated with the Morris water maze test, oestrogen levels with an ELISA kit, and hippocampal neuron morphology and Nissl bodies in the cytoplasm with H&E and Nissl staining. The expression of ERβ, Aβ1–40, and p-tau404 was determined by immunohistochemistry. Nano LC-LTQ-Orbitrap Proteomics determined potential targets and related signalling pathways. Western blotting was used to detect the expression of the related proteins. Results Erzhi pills (1.5, 0.75 g/kg) markedly reduced escape latencies on the MWM, increased numbers of platform crossings, numbers of neurons, Nissl bodies, oestrogen levels (100.18, 43.04 pg/mL), and ERβ-positive cells (57.42, 39.83); Aβ1–40 (18.85, 36.83)- and p-tau404 (14.42, 29.71)-positive cells were significantly decreased. Proteomics identified more than 100 differentially expressed proteins involved in 48 signalling pathways, five of which are involved in the PI3K/Akt signalling pathway. Western blotting showed decreased expression of GSK3β and Bad, while Akt, PI3K, 14-3-3, Bcl-xl, and Bcl-2 were upregulated. Discussion and conclusion Erzhi pills may serve as a potential agent for AD therapeutics by improving learning and memory.

Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially attributed to their undefined developmental origins. The lateral mesoderm is also a developmental source of MSCs that constitute appendicular skeletal elements in the developing vertebrate embryo. However, it is difficult to isolate homogeneous lateral mesoderm (LM)-derived MSCs from bone tissues or bone marrow due to the lack of understanding of their characteristics. Herein, we successfully established an efficient differentiation protocol for the derivation of MSCs with a LM origin from human pluripotent stem cells (hPSCs) under specific conditions. LM-MSCs resembled bone marrow-derived MSCs (BMSCs) with regard to cell surface markers, global gene profiles, and immunoregulatory activity and showed a homeodomain transcription factor (HOX) gene expression pattern typical of skeletal MSCs in long bones. Moreover, we demonstrated that LM-MSCs had an increased osteogenic/chondrogenic differentiation capacity and hematopoietic support potential compared to BMSCs. These homogeneous LM-MSCs may serve as a powerful tool for elucidating their precise role in bone formation and hematopoiesis and could be a potentially ideal cell source for therapeutic applications.

Objective: To investigate cumulative live birth rate (cLBR) per oocyte retrieval in infertile patients aged 40 years and over undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycles and to identify the possible predictors. Methods: A total of 1,613 patients at a university hospital in China from January 2013 to May 2017 were enrolled in this retrospective study. All data for fresh and subsequent frozen-thawed cycles were analyzed. Multivariate logistic regression analysis with stepwise selection of possible predictors for cLBR was performed, and Loess curve was constructed to determine the association between cLBR and the number of oocytes retrieved. Results: cLBR significantly increased with the number of oocytes retrieved and reached up to 75% when > 20 oocytes were retrieved ( P < 0.001). Variables of antral follicle count (AFC) and the number of oocytes retrieved were selected using multiple logistic regression analysis with stepwise selection to predict the significance of cLBR. cLBR demonstrated an obvious upward trend as the number of oocytes retrieval increased in the Loess curve. Conclusions: For patients aged 40 years and over, AFC and the number of oocytes retrieved were two key predictors for cLBR and maximization of ovarian reserve exploitation was pivotal to increase the chance of live birth.

Extracellular vesicles (EVs) have been identified as cell-cell communication agents, and EVs derived from mesenchymal stem cells (MSCs) exhibit therapeutic effects similar to those of the cells of origin. Precipitation methods have been used extensively for EV harvests, such as UC- (ultracentrifugation-) or PEG- (polyethylene glycol-) based methods, and the difference in EVs derived from MSCs by UC and PEG is not fully understood. We harvested EVs from amniotic fluid MSCs (AF-MSCs) by UC- or PEG-based precipitation methods and conducted a comparison study of those EVs derived by the two methods: output, RNA, and protein expression of EVs and EV biological reaction in a THP-1-cell model of LPS induction, which was considered an infection model. There was no difference in morphology, size, or specific marker-positive ratio of PEG-EVs and UC-EVs, but PEG obtained more EV particles, protein, and RNA than the UC method. In our THP-1 model of LPS induction, MSC-EVs did not lead to a change in protein expression but inhibited the LPS-induced increase in cytokine secretion. UC-EVs were more effective for TNF-α inhibition, and PEG-EVs were more effective for IL10 inhibition. Thus, our findings provide evidence that PEG-based precipitation is a more efficient mesenchymal stem cell-extracellular vesicle-derived method than UC.

ObjectiveTo investigate the Interaction between chronic endometritis (CE) caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure (RIF).MethodTranscriptome sequencing analysis of the endometrial of 112 patients was preform by using High-Throughput Sequencing. The endometrial microbiota of 43 patients was analyzed by using 16s rRNA sequencing technology.ResultIn host endometrium, CD4 T cell and macrophage exhibited significant differences abundance between CE and non-CE patients. The enrichment analysis indicated differentially expressed genes mainly enriched in immune-related functional terms. Phyllobacterium and Sphingomonas were significantly high infiltration in CE patients, and active in pathways related to carbohydrate metabolism and/or fat metabolism. The increased synthesis of lipopolysaccharide, an important immunomodulator, was the result of microbial disorders in the endometrium.ConclusionThe composition of endometrial microorganisms in CE and non-CE patients were significantly different. Phyllobacterium and Sphingomonas mainly regulated immune cells by interfering with the process of carbohydrate metabolism and/or fat metabolism in the endometrium. CE endometrial microorganisms might regulate Th17 response and the ratio of Th1 to Th17 through lipopolysaccharide (LPS).

Polygonum multiflorum Thunb. (PMT), a commonly used Chinese herbal medicine for treating diseases such as poisoning and white hair, has attracted constant attention due to the frequent occurrence of liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential hepatotoxic mechanisms are still unclear. In order to clarify the HEMs of PMT and further explore the potential mechanisms of hepatotoxicity, firstly, the chemical constituents in PMT extract were globally characterized, and the fingerprints of PMT extracts were established along with the detection of their hepatotoxicity in vivo. Then, the correlations between hepatotoxic features and component contents were modeled by chemometrics to screen HEMs of PMT, which were then further evaluated. Finally, the hepatotoxic mechanisms of PMT were investigated using liver metabolomics and molecular docking. The results show that the chemical combination of 2,3,5,4-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) and emodin-8-O-glucoside (EG) was discovered as the HEMs of PMT through pre-screening and verifying process. Liver metabolomics revealed that PMT caused liver injury by interfering with purine metabolism, which might be related to mitochondrial function disorder and oxidative injury via the up-regulations of xanthosine and xanthine, and the down-regulation of 5′ nucleotidase (NT5E) and adenylate kinase 2 (AK2). This study not only found that the HEMs of PMT were TSG and EG, but also clarified that PMT might affect purine metabolism to induce liver injury, which contributed to our understanding of the underlying mechanisms of PMT hepatotoxicity.

Polygonum multiflorum (PM) has been used as a tonic and anti-aging remedy for centuries in Asian countries. However, its application in the clinic has been hindered by its potential to cause liver injury and the lack of investigations into this mechanism. Here, we established a strategy using a network pharmacological technique combined with integrated pharmacokinetics to provide an applicable approach for addressing this issue. A fast and sensitive HPLC-QQQ-MS method was developed for the simultaneous quantification of five effective compounds (trans-2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside, emodin-8-O-β-d-glucoside, physcion-8-O-β-d-glucoside, aloe-emodin and emodin). The method was fully validated in terms of specificity, linearity, accuracy, precision, extraction recovery, matrix effects, and stability. The lower limits of quantification were 0.125–0.500 ng/mL. This well-validated method was successfully applied to an integrated pharmacokinetic study of PM extract in rats. The network pharmacological technique was used to evaluate the potential liver injury due to the five absorbed components. Through pathway enrichment analysis, it was found that potential liver injury is primarily associated with PI3K-Akt, MAPK, Rap1, and Ras signaling pathways. In brief, the combined strategy might be valuable in revealing the mechanism of potential liver injury due to PM.

Objective: In this study, we mainly explored two questions: Which microorganisms were functionally active in the endometrium of patients with endometrial cancer (EC)? What kind of response did the human host respond to functionally active microorganisms?Methods: Nine endometrial cancer patients and eight normal subjects were included in this study. HMP Unified Metabolic Analysis Network 3 (HUMAnN3) was used to obtain functional information of microorganisms. In addition, metaCyc-based GSEA functional enrichment analysis was used to obtain information on the metabolic pathways of the human host. At the same time, the O2PLS model and Spearman correlation analysis were used to analyze the microorganisms–host interaction.Results: With the novel metatranscriptome analysis pipeline, we described the composition of more than 5,000 functionally active microorganisms and analyzed the difference in microorganisms between the EC and the normal group. Our research found that these microorganisms were involved in part of the metabolic process of endometrial cancer, such as 6-sulfo-sialyl Lewis x epitope, N-acetyl-beta-glucosaminyl. In addition, the host–microbiota crosstalk of EC endometrium also included many biological processes, mainly functions related to tumor migration and the Apelin signaling pathway.Conclusion: The functionally active microorganisms in the EC endometrium played an essential role in the occurrence and migration of tumors. This meant that functionally active microorganisms could not be ignored in the treatment of endometrial cancer. This study helped to better understand the possible role of endometrial functional, active microorganisms in the occurrence and development of EC in patients with endometrial cancer and provided new information for new attempts to treat EC.

BackgroundRecurrent implantation failure (RIF) is an obstacle in the process of assisted reproductive technology (ART). At present, there is limited research on its pathogenesis, diagnosis, and treatment methods.Methods and ResultsIn this study, a series of analytical tools were used to analyze differences in miRNAs, mRNAs, and lncRNAs in the endometrium of patients in a RIF group and a control group. Then the competing endogenous RNA (ceRNA) network was built to describe the relationship between gene regulation in the endometrium of the RIF group. Based on the results of the logistic regression of co-expression miRNAs between serum and endometrial samples, we built a predictive model based on circulating miRNAs.ConclusionThe stability and non-invasiveness of the circular miRNA prediction model provided a new method for diagnosis in RIF patients.

Abstract Background Hepatitis C virus (HCV) is a leading cause of chronic liver disease. As yet there is no approved vaccine protects against contracting hepatitis C. HCV seriously affects many people’s health in the world. Methods In this article, an epidemiological model is proposed and discussed to understand the transmission and prevalence of hepatitis C in mainland China. This research concentrates on hepatitis C data from Chinese Center for Disease Control and Prevention (China’s CDC). The optimal parameters of the model are obtained by calculating the minimum chi-square value. Sensitivity analyses of the basic reproduction number and the endemic equilibrium are conducted to evaluate the effectiveness of control measures. Results Vertical infection is not the most important factor that causes hepatitis C epidemic, but contact transmission is. The proportion of acute patients who are transformed into chronic patients is about 82.62%. The possibility of the hospitalized patients who are restored to health is about 76.24%. There are about 92.32% of acute infected are not treated. The reproduction number of hepatitis C in mainland China is estimated as approximately 1.6592. Conclusion We find that small changes of transmission infection rate of acutely infected population, transmission infection rate of exposed population, transition rate for the acutely infected, and rate of progression to acute stage from the exposed can achieve the purpose of controlling HCV through sensitivity analysis. Finally, based on the results of sensitivity analysis, we find out several preventions and control strategies to control the Hepatitis C.

Context: Eucommia ulmoides Oliver (Eucommiaceae) has various medicinal properties. Our previous studies revealed that Eucommia ulmoides has a protective effect on hyperuricaemia. Objective: This study investigates the effect of Eucommia ulmoides cortex ethanol extract (EU) on hyperuricaemia and explores the underlying mechanism in Kunming mice and Sprague–Dawley rats. Material and methods: Sixty mice and sixty rats were divided into normal control, hyperuricaemia, allopurinol (10 mg/kg) and three EU groups. The EU groups received intragastric EU at 80, 160, 320 mg/kg in mice and 100, 200, 400 mg/kg in rats for 7 days. Serum uric acid (SUA) was measured using a kit. mRNA and proteins were quantified by RT-qPCR and immunohistochemical assays (IHC), respectively. Results: The Maximal Tolerable Dose (MTD) of EU administered intragastrically was 18 g/kg in mice. The intermediate (160 mg/kg) and high (320 mg/kg) EU treatment significantly reduced (p

Abstract Background Epidemiological studies have suggested that noise exposure may increase the risk of type 2 diabetes mellitus (T2DM), and experimental studies have demonstrated that noise exposure can induce insulin resistance in rodents. The aim of the present study was to explore noise-induced processes underlying impaired insulin sensitivity in mice. Methods Male ICR mice were randomly divided into four groups: a control group without noise exposure and three noise groups exposed to white noise at a 95-dB sound pressure level for 4 h/day for 1, 10, or 20 days (N1D, N10D, and N20D, respectively). Systemic insulin sensitivity was evaluated at 1 day, 1 week, and 1 month post-noise exposure (1DPN, 1WPN, and 1MPN) via insulin tolerance tests (ITTs). Several insulin-related processes, including the phosphorylation of Akt, IRS1, and JNK in the animals’ skeletal muscles, were examined using standard immunoblots. Biomarkers of inflammation (circulating levels of TNF-α and IL-6) and oxidative stress (SOD and CAT activities and MDA levels in skeletal muscles) were measured via chemical analyses. Results The data obtained in this study showed the following: (1) The impairment of systemic insulin sensitivity was transient in the N1D group but prolonged in the N10D and N20D groups. (2) Noise exposure led to enhanced JNK phosphorylation and IRS1 serine phosphorylation as well as reduced Akt phosphorylation in skeletal muscles in response to exogenous insulin stimulation. (3) Plasma levels of TNF-α and IL-6, CAT activity, and MDA concentrations in skeletal muscles were elevated after 20 days of noise exposure. Conclusions Impaired insulin sensitivity in noise-exposed mice might be mediated by an enhancement of the JNK/IRS1 pathway. Inflammation and oxidative stress might contribute to insulin resistance after chronic noise exposure.

Objective: To analyze spontaneous abortion rate and its associated risk factors in patients with polycystic ovary syndrome (PCOS) after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Methods: This was a retrospective cohort study on 2,231 PCOS patients undergoing IVF/ICSI treatment. For comparison, we enrolled another 2,231 patients with tubular factors in control group. Spontaneous abortion rate and chromosomal abnormality rate were compared between the two groups. Furthermore, clinical data were compared between the patients with spontaneous abortion and those with ongoing pregnancy using univariate and multivariate analysis for risk factors of spontaneous abortion in PCOS patients. Results: Patients in the PCOS group had significantly higher spontaneous abortion rate (24.15%) than that in the control group (12.75%, P < 0.001). Chromosomal abnormality rate was significantly lower in the PCOS group (36.05%, 31/86) than in the control group (55.56%, 50/90, P = 0.009). In the PCOS group, patients with spontaneous abortion had significantly elder age, higher body mass index (BMI), and homeostasis model assessment for insulin resistance (HOMA-IR) than those with ongoing pregnancy. The logistic regression analysis confirmed that the age, BMI, and HOMA-IR were the risk factors of spontaneous abortion in the PCOS patients. There were no significant differences between groups in the type of cycles, the quality of embryos transferred, the number of embryos transferred, fasting blood glucose, fasting insulin, and so on. Conclusions: Compared with non-PCOS patients, PCOS patients had higher spontaneous abortion rate, but the chromosomal abnormality was not a major factor for the high spontaneous abortion rate in the PCOS patients. Age, BMI, and HOMA-IR were risk factors for spontaneous abortion after IVF/ICSI-ET in PCOS patients.

Background: Mumps, an infectious viral disease, classically manifested by inflammation of salivary glands and is best known as a common childhood viral disease with no specific treatment. Although it can be protected by vaccine, there are more than 100,000 reported mumps cases according to the Chinese Center for Disease Control and Prevention. However, the factors and mechanisms behind the persistence and prevalence of mumps have not been well understood. Methods: A mumps model with seasonal fluctuation is formulated and investigated. We evaluate the basic reproduction number â0 and analyze the dynamical behavior of the model. We also use the model to simulate the monthly data of mumps cases and carry out some sensitivity analysis of â0 in terms of various model parameters. Results: It is shown that there exists only disease-free solution which is globally asymptotically stable if â0Â Â 1. â0 is a threshold parameter, and its magnitude determines the extinction or persistence of the disease. Conclusion: Our analysis shows that vaccination rate and invalid vaccination rate play important roles in the spread of mumps. Hence, Our study suggests to increase the vaccine coverage and make two doses of MMR (Measles, mumps and rubella vaccine) vaccine freely available in China. Keywords: Mumps, Basic reproduction number, Periodic solution, Vaccination

The aim of this retrospective analysis is to explore whether growth hormone (GH) pretreatment is beneficial for patients with poor ovarian reserve undertaking in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Poor ovarian reserve patients with anti-Mullerian hormone (AMH)

A simple design of an ultrabroadband and high-efficiency reflective linear polarization convertor is presented in the optical frequency region. This ultrabroadband convertor is formed from the planar anisotropic metasurface using a meander wire structure. The numerical simulation demonstrates that the polarization conversion ratio over 90% is achieved from 181 to 506 THz, which is equivalent to 94.6% relative bandwidth fory -polarized incident lights under normal incidence. Further simulation results show that the high polarization conversion efficiency can be sustained well when the incident angle increases to 45° for both transverse electric (TE) and transverse magnetic (TM) modes. By taking advantage of surface current distribution, the physical mechanisms are elucidated in detail. The further theoretical calculation results based on the interference theory are good agreement with the simualtion. Our design provides a unique approach in realizing the polarization manipulation with high performances in the optical frequency region.

Epidemiological studies have revealed that noise exposure was associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the exact nature of that association remains to be elucidated. The present study is designed to examine the effects of chronic noise exposure on the development of T2DM in combination with a high-fat-diet (HFD) in mice. Here we show that chronic noise exposure at 85 dB SPL (4 h /day, below the safety limit for occupational noise exposure) exaggerated multiple metabolic abnormalities induced by HFD in C57BL/6J male mice, including worsened glucose intolerance, insulin resistance, fasting hyperglycemia and dyslipidemia. Furthermore, noise exposure exhibited a paradoxical impact on fat accumulation and circulating levels of free fatty acid, indicating a potential stimulating effect of noise on lipolysis. These results provide first in vivo supporting evidence for the causative role of noise exposure in diabetogenesis and pinpoint a noise-associated increase in blood free fatty acid levels as a possible mediator accelerating the effect of noise on the development of insulin resistance and T2DM.

AbstractScaffolds featuring spatiotemporal control of drug release is highly desirable for bone tissue regeneration. The objective of this study was to construct a scaffold with gradient porosity and drug distribution and evaluate the effect of scaffold structure on drug release kinetics and cell bioactivity. Nano-hydroxyapatite/collagen/phosphatidylserine scaffolds embedded with steroidal saponin loaded collagen microparticles were prepared using a porogen leaching protocol. Morphological characterization showed that the scaffolds consisted of dense layer and loose layer, and pores were interconnective. The microparticles were entrapped at the center of the scaffolds follow a gradient distribution. Release kinetics correlated with the structure. The loose layer showed greater drug release amount as compared to the dense layer. Such differences in release kinetics have distinct effects on cell bioactivity. Cell proliferated much more in loose layer than that in the dense layer. Such spatial and temporal control over drug deposition and delivery within the scaffolds could provide opportunities for tissue regeneration associated with optimum drug doses at wound site, and lessen undesirable drug release and side-effects at uninjured site.

Contemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC) require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available.Recent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (