Prenatal, perinatal and parental risk factors for autism spectrum disorder in China: a case- control study.

BACKGROUND: Autism spectrum disorder (ASD) is heritable neurodevelopmental disorders (NDDs), but environmental risk factors have also been suggested to a play a role in its development. Prenatal, perinatal and parental factors have been associated with an increased risk of ASD in children. The aim of the present study was to explore the prenatal, perinatal, and parenting risk factors in children with autism spectrum disorder (ASD) from Beijing, China by comparing them with typically developing (TD) children. METHODS: A sample of 151 ASD children's parents who from rehabilitation institutions in Beijing were enrolled in this study, and an additional 151 children from kindergartens in Beijing were recruited as a control group (child age: mean = 4.4 years). TD children were matched according to age, sex and maternal education. We explored the maternal AQ (Autism Spectrum Quotient) scores (mean:19.40-19.71, no significant difference between two groups) to referring the genetic baseline. This study evaluated 17 factors with unadjusted and adjusted analyses. RESULTS: Birth asphyxia was associated with a more than a thirteen-fold higher risk of ASD (adjusted odds ratio (AOR) = 13.42). Breastfeeding difficulties were associated with a higher risk of ASD(AOR = 3.46). Parenting influenced the risk of ASD, with low responding (LR) and harsh or neglectful parenting associated with a higher risk of ASD in offspring (AOR = 2.37 for LR, AOR = 3.42 for harsh parenting and AOR = 3.01 for neglectful parenting). Maternal fever during pregnancy was associated with a higher risk of ASD in offspring (AOR = 3.81). CONCLUSIONS: Many factors were associated with ASD in offspring. Further assessment is needed to elucidate the role of modifiable environmental factors to inform prevention strategies.

Helicity-resolved Raman scattering of MoS2 bulk crystal.

Helicity-resolved Raman spectroscopy (HRRS) can effectively distinguish the Raman modes of two-dimensional (2D) layered materials by phonon symmetry. In this paper, we systematically investigated the phonon helicity selection of basal and edge planes of MoS2 bulk by HRRS. We find that the symmetry of the crystal structure changes the helicity selection of the E1g, E1 2g, and A1g modes in the edge plane. The theoretical calculation results confirm that the E1 2g and A1g modes of the basal plane exhibit a perfect helicity exchange, and the helicity selections of the E1 2g and A1g modes of the edge plane are eliminated or weakened. Our study provides references for phonon helicity selection of 2D layered materials represented by MoS2.

PCK1 activates oncogenic autophagy via down-regulation Serine phosphorylation of UBAP2L and antagonizes colorectal cancer growth.

Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme in gluconeogenesis. PCK1 is considered an anti-oncogene in several human cancers. In this study, we aimed to determine the functions of PCK1 in colorectal cancer (CRC). PCK1 expression in CRC tissues was tested by western blot and immunohistochemistry analyses and associations of PCK1 level with clinicopathological characteristics and disease survival evaluated. Further, we studied the effect of PCK1 on CRC cell proliferation and the underlying mechanisms. Our results show that PCK1 is expressed at significantly lower levels in CRC than in control tissues. High PCK1 expression was correlated with smaller tumor diameter and less bowel wall invasion (T stage). Overexpression and knockdown experiments demonstrated that PCK1 inhibits CRC cell growth both in vitro and in vivo. Mechanistically, PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454 and enhancing autophagy. Overall, our findings reveal a novel molecular mechanism involving PCK1 and autophagy, and highlight PCK1 as a promising candidate therapeutic target in CRC.

Electroreductive Hydroxymethylation of Imines with Ketones To Access ß-Amino Alcohols.

In this article, an electrochemical method for the direct synthesis of ß-amino alcohols from imines and ketones is described. Mechanistic studies, including a radical trapping experiment, electron paramagnetic resonance, cyclic voltammetry, and divided-cell electrolysis experiment, support the radical-involved reductive cross coupling of imines with ketones at the cathode. The use of abundant and easily prepared starting materials, high atom- and step-economy, and insensitivity to air and moisture make this synthetic strategy more efficient for the construction of various ß-amino alcohol derivatives.

Electrochemical Synthesis of ß-Iodoesters by 1,2-Iodoesterization of Unactivated Alkenes with Carboxylic Acids and Tetrabutylammonium Iodide.

We report a novel and highly selective electrochemical method for the synthesis of ß-iodoesters via difunctionalization of alkenes. The reaction is carried out in an undivided cell under constant current conditions without any additives, catalysts, oxidants, and sacrificial reagents. Inexpensive and readily available tetrabutylammonium iodide not only acts as an electrolyte but also serves as an iodine source. The reaction shows high selectivity and good functional group tolerance, providing products in yields of up to 98%. This method is applicable not only to the iodofunctionalization of alkenes but also to the chloro- and bromofunctionalization of alkenes. The successful modification of drugs and natural products demonstrates the potential utility of this approach.

Direct Hydroxylarylation of Benzylic Carbons (sp3/sp2/sp) via Radical-Radical Cross-Coupling Powered by Paired Electrolysis.

Diaryl alcohol moieties are widespread in pharmaceuticals. Existing methods for the synthesis of diaryl alcohols require the use of pre-functionalized benzylic alcohols, aromatic aldehydes, or ketones as starting materials. Herein, the first convergent paired electrochemical approach to the direct hydroxylarylation of unactivated benzylic carbons (sp3/sp2/sp) is proposed. This protocol features direct functionalization of unactivated benzylic C(sp3)-H bonds and benzylic sp2/sp-carbons, mild conditions (open air, room temperature), an environmentally friendly procedure (without any external catalyst/mediator/additive), and direct access to sterically hindered alcohols from inexpensive and readily available alkyl/alkenyl/alkynylbenzenes. Mechanistic studies, including divided-cell experiments, isotope labeling, radical trapping, electron paramagnetic resonance, reaction kinetics, and cyclic voltammetry, strongly support the proposed radical-radical cross-coupling between transient ketyl radicals and persistent radical anions. Gram-scale synthesis and diversification of drug derivatives have visualized the tremendous potential of this protocol for practical applications.

A/B-Site Management Strategy to Boost Electrocatalytic Overall Water Splitting on Perovskite Oxides in an Alkaline Medium.

In this paper, Pr0.7Sr0.3Co1-xRuxO3 perovskite oxides were synthesized by the sol-gel method as bifunctional catalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). The overpotentials of PSCR0.05 against HER and OER at 10 mA cm-2 were 319 and 321 mV in alkaline medium, respectively. The Tafel slopes of HER and OER were 87.32 and 118.1 mV/dec, respectively. PSCR0.05 showed the largest electrochemical active area, the smallest charge transfer resistance, and excellent long-term durability. Meanwhile, the PSCR0.05 electrocatalyst was applied for overall water splitting and its cell voltage was maintained at 1.77 V at 10 mA cm-2. The super-exchange interaction between adjacent RuO6-CoO6 octahedra in perovskite made of PSCR0.05 contains sufficient active sites (such as Co2+/Co3+, Ru3+/Ru4+, and O22-/O-). The increase of surface oxygen vacancy and active site is the main reason for the improvement of difunctional catalyst performance. In this work, the electrocatalytic performance of perovskite-type oxides was further optimized by the method of A- and B-site cationic doping regulation, which provides a new idea for perovskite-type bifunctional electrocatalysts.

Electrochemical C(sp2)-H/N-H "formal" cross-dehydrogenative coupling of olefins with benzotriazoles for synthesis of N-vinyl benzotriazoles.

The paper details an electrochemical method that couples olefins with benzotriazoles to form C(sp2)-N bonds, enabling the synthesis of N-vinyl benzotriazoles in moderate to good yields. nBu4NI functions as both an electrolyte and an iodine mediator, and the method does not require oxidants or metals. It is a highly atom-economical and clean reaction, with hydrogen as the sole byproduct.

Relationship of Microvascular Obstruction with Global and Regional Myocardial Function Determined by Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction.

Objective To investigate the impact of microvascular obstruction (MVO) on the global and regional myocardial function by cardiac magnetic resonance feature-tracking (CMR-FT) in ST-segment-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1 - 7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study. Based on the presence or absence of MVO on late gadolinium enhancement images, patients were divided into groups with MVO and without MVO. The infarct zone, adjacent zone, and remote zone were determined based on a myocardial 16-segment model. The radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle (LV) and the infarct, adjacent, and remote zones were measured by CMR-FT from cine images and compared between patients with and without MVO using independent-samples t-test. Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients (mean age 56.66 ± 11.38 years) were enrolled. MVO was detected in 37.58% (59/157) of STEMI patients, and the mean size of MVO was 3.00 ±3.76 mL. Compared with patients without MVO (n =98 ), the MVO group had significantly reduced LV global RS (t= -4.30, P < 0.001), global CS (t= 4.99, P < 0.001), and global LS ( t= 3.51, P = 0.001). The RS and CS of the infarct zone in patients with MVO were significantly reduced (t= -3.38, P = 0.001; t= 2.64, P = 0.01; respectively) and the infarct size was significantly larger (t= 8.37, P < 0.001) than that of patients without MVO. The presence of LV MVO [OR= 4.10, 95%CI: 2.05 - 8.19, P<0.001) and its size [OR=1.38, 95%CI: 1.10-1.72, P=0.01], along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis, while only heart rate (OR=1.08, 95%CI: 1.03 - 1.13, P=0.001) and LV infarct size (OR=1.10, 95%CI: 1.03 - 1.16, P=0.003) were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO, and MVO deteriorates the global and regional LV myocardial function.

IL-6 promotes pluripotency of mouse embryonic stem cells and regulates cardiac differentiation in a development-dependent manner.

Interleukin 6 (IL-6), an important component of cardiac microenvironment, favors cardiac repair by improving cardiomyocyte regeneration in different models. This study aimed to investigate the effects of IL-6 on stemness maintenances and cardiac differentiation of mouse embryonic stem cells (mESCs). The mESCs were treated with IL-6 for two days, and then subjected to CCK-8 essay for proliferation analysis and quantitative real-time PCR (qPCR) to evaluate the mRNA expression of genes related to stemness and germinal layers differentiation. Phosphorylation levels of stem cell-related signal pathways were detected by Western blot. siRNA was used to interfere the function of STAT3 phosphorylation. Cardiac differentiation was investigated by the percentage of beating embryoid bodies (EBs) and qPCR analysis of cardiac progenitor markers and cardiac ion channels. IL-6 neutralization antibody was applied to block the endogenous IL-6 effects since the onset of cardiac differentiation (embryonic day of 0, EB0). The EBs were collected on EB7, EB10 and EB15 to investigate the cardiac differentiation by qPCR. On EB15, Western blot was applied to investigate the phosphorylation of several signaling pathways, and immunochemistry staining was adopted to trace the cardiomyocytes. IL-6 antibody was administered for two days (short term) on EB4, EB7, EB10 or EB15, and percentages of beating EBs at late developmental stage were recorded. The results showed that exogenous IL-6 promoted mESCs proliferation and favored maintenances of pluripotency, evidenced by up-regulated mRNA expression of oncogenes (c-fos, c-jun) and stemness markers (oct4, nanog), down-regulated mRNA expression of germ layer genes (branchyury, FLK-1, pecam, ncam, sox17), and increased phosphorylation of ERK1/2 and STAT3. siRNA targeting JAK/STAT3 partially attenuated the effects of IL-6 on cell proliferation and mRNA expression of c-fos and c-jun. During differentiation, long term IL-6 neutralization antibody application decreased the percentage of beating EBs, down-regulated mRNA expression of ISL1, GATA4, α-MHC, cTnT, kir2.1, cav1.2, and declined the fluorescence intensity of cardiac α actinin in EBs and single cell. Long term IL-6 antibody treatment decreased the phosphorylation of STAT3. In addition, short term (2 d) IL-6 antibody treatment starting from EB4 significantly reduced the percentage of beating EBs in late development stage, while short term IL-6 antibody treatment starting from EB10 significantly increased the percentage of beating EBs on EB16. These results suggest that exogenous IL-6 promotes mESCs proliferation and favors stemness maintenance. Endogenous IL-6 regulates mESC cardiac differentiation in a development-dependent manner. These findings provide important basis for the study of microenvironment on cell replacement therapy, as well as a new perspective for understanding the pathophysiology of heart diseases.

Roseicella aquatilis sp. nov., isolated from freshwater lake.

A novel Gram-stain-negative, non-motile, ellipsoidal-shaped, red-pigmented, facultatively aerobic strain designated NE82T was isolated from mud sample from Jiugongli Lake in Inner Mongolia Autonomous Region, China. Optimal growth occurred at 28-33 °C (range 15-42 °C) and pH 7.0-7.5 (range 5.5-8.5) with 0% (w/v) NaCl (range 0-1.0%). Cells of strain NE82T were 0.4-0.9 µm in diameter, catalase-positive and oxidase-negative. Q-10 was the sole respiratory quinone and the major cellular fatty acids (> 10%) in strain NE82T were summed feature 8 (C18:1 ω7c and C18:1 ω6c). The polar lipids of strain NE82T were phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, an unidentified aminophospholipid and four unidentified phospholipids. The G+C content of the genomic DNA was 72.0 mol%. Based on the 16S rRNA gene sequence, strain NE82T showed the highest similarity (97.2%) to Roseicella frigidaeris DB1506T within the family Acetobacteraceae, thus representing a novel species of the genus Roseicella, for which the name Roseicella aquatilis sp. nov. is proposed. The type strain is NE82T (= KCTC 62412T = MCCC 1H00292T).

Associations of Infarct Size and Regional Myocardial Function Examined by Cardiac Magnetic Resonance Feature Tracking Strain Analysis with the Infarct Location in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Objective To quantitatively evaluate the associations of infarct size, regional myocardial function examined by cardiac magnetic resonance feature tracking (CMR-FT) strain analysis with infarct location in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention.Methods Cardiac magnetic resonance images were retrospectively analyzed in 95 consecutive STEMI patients with successful reperfusion. The patients were divided into the anterior wall myocardial infarction (AWMI) and nonanterior wall myocardial infarction (NAWMI) groups. Infarct characteristics were assessed by late gadolinium enhancement. Global and regional strains and associated strain rates in the radial, circumferential and longitudinal directions were assessed by CMR-FT based on standard cine images. The associations of infarct size, regional myocardial function examined by CMR-FT strain analysis with infarct location in STEMI patients were evaluated by the Spearman or Pearsonmethod. Results There were 44 patients in the AWMI group and 51 in the NAWMI group. The extent of left ventricular enhanced mass was significantly larger in patients with AWMI compared with the NAWMI group (24.47±11.89, 21.06±12.08 %LV; t=3.928, P = 0.008). In infarct zone analysis, strains in the radial, circumferential and longitudinal directions were remarkably declined in the AWMI group compared with the NAWMI group (z=-20.873, -20.918, -10.357, all P < 0.001). The volume (end-systolic volume index), total enhanced mass and extent of enhanced mass of the left ventricular were correlated best with infarct zone strain in the AWMI group (all P < 0.001). Conclusion In STEMI patients treated by percutaneous coronary intervention, myocardial damage is more extensive and regional myocardial function in the infarct zone is lower in the AWMI group compared with the NAWMI group.

Full-color photon-counting single-pixel imaging.

We propose and experimentally demonstrate a high-efficiency single-pixel imaging (SPI) scheme by integrating time-correlated single-photon counting (TCSPC) with time-division multiplexing to acquire full-color images at an extremely low light level. This SPI scheme uses a digital micromirror device to modulate a sequence of laser pulses with preset delays to achieve three-color structured illumination, then employs a photomultiplier tube into the TCSPC module to achieve photon-counting detection. By exploiting the time-resolved capabilities of TCSPC, we demodulate the spectrum-image-encoded signals, and then reconstruct high-quality full-color images in a single round of measurement. Based on this scheme, strategies such as single-step measurement, high-speed projection, and undersampling can further improve imaging efficiency.

The rostromedial tegmental nucleus is essential for non-rapid eye movement sleep.

The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

A review on extracorporeal membrane oxygenation and kidney injury.

Extracorporeal membrane oxygenation (ECMO) is inevitable external life support in case of cardiac and respiratory failure since the 1970s. Acute kidney injury (AKI) and the requirement of renal replacement therapy (RRT) is a potential risk among these patients. This review aims to give an overview of the risk of AKI, RRT, and associated mortality among the patients who received ECMO for any of its indications. PubMed database was searched to find the relevant literature and the reference list of included studies was also searched for additional studies. The incidence of AKI ranged from 30% to 78% and RRT from 47% to 60% in ECMO patients. The pathophysiology of AKI in ECMO is multifactorial, and includes ischaemia, RBCs breakdown, comorbidity, conversion of zymogen form of pro-inflammatory mediators, structural alteration of the kidney, coadministration of nephrotoxic drugs, coagulation abnormality, and oxidative stress. ECMO was associated with the higher incidence of renal abnormalities, AKI, requirement of RRT, and associated mortality. Patients who underwent RRT had improved renal function and reduced overall mortality compared to the non-RRT group among the ECMO patients. Currently, there is no consensus evidence to support the superior use of the inline hemofilter system over continuous renal replacement therapy among patients who had AKI during ECMO.

Cardiac fibroblast paracrine factors modulate mouse embryonic stem cells.

The study aims to investigate the effects of cardiac fibroblast (CF) paracrine factors on murine embryonic stem cells (ESCs). Conditioned mediums from either neonatal cardiac fibroblasts (ConM-NCF) or adult cardiac fibroblasts (ConM-ACF) were diluted by 1:50 and 1:5, respectively, to investigate whether these conditioned mediums impact murine ESCs distinctly with RT-real time PCR techniques, cell proliferation essay, ELISA and by counting percentage of beating embryoid bodies (EBs) during ESCs differentiation. The data showed that the paracrine ability of CFs changed dramatically during development, in which interleukin 6 (IL6) increased with maturation. ConM-NCF 1:50 and ConM-NCF 1:5 had opposite effects on the pluripotent markers, although they both reduced mouse ESC proliferation. ConM-ACF 1:50 promoted ESCs pluripotent markers and proliferation, while ConM-ACF 1:5 exerted negative effects. All CF-derived conditioned mediums inhibited cardiac differentiation, but with distinguishable features: ConM-NCF 1:50 slightly decreased the early cardiac differentiation without altering the maturation tendency or cardiac specific markers in EBs at differentiation of day 17; ConM-ACF 1:50 had more significant inhibitory effects on early cardiac differentiation than ConM-NCF 1:50 and impeded cardiac maturation with upregulation of cardiac specific markers. In addition, IL6 neutralization antibody attenuated positive effect of ConM-ACF 1:50 on ESCs proliferation, but had no effects on ConM-NCF 1:50. Long-term IL6 neutralization reduced the percentage of beating EBs at early developmental stage, but did not alter the late cardiac differentiation. Taken together, both the quality and quantity of factors and cytokines secreted by CFs are critical for the ESC fate. IL6 could be a favorable cytokine for ESC pluripotency and the early cardiac differentiation.

[Effects of Regulating Smad7 Gene on Epithelial-Mesenchymal Transition in Keloid Keratinocyte].

OBJECTIVE: The effect of Smad7 on epithelial-Mesenchymal Transition (EMT) of keloid keratinocytes was studied. METHODS: Culture formed keloid cutin cells (KK) and normal skin cutin cell (NK cells), built the Smad7 too slow virus slow virus vector and Smad7 interference expression vector, screening the best expression and interfering with the slow virus infection NK and KK cells respectively, and contrast carrier puro screening stable expression cell lines, stem cells can be divided into 8 groups: NK-Control (normal training of NK cells); NK-NC (NK cells screened against lentivirus); NK-shSmad7 (NK cells that interfere with lentivirus screening); NK-mSmad7 (NK cells screened for overexpression of lentivirus); KK-control (normal cultured KK cells); KK-NC (KK cells screened against lentivirus); KK-shSmad7 (KK cells that interfere with lentivirus screening); KK-mSmad7 (KK cells screened for overexpression of lentivirus). Cell proliferation was observed by the CCK-8 method, cell apoptosis was detected by flow cytometry, cell migration ability was detected by Transwell chamber, and expression of key proteins (N-cadherin and Occludin) in epithelium-interstitial transform was detected by Western blot. RESULTS: The Smad7 interfering lentivirus vector and Smad7 overexpressing lentivirus vector were successfully constructed. Interference with Smad7 can promote NK cell and KK cell proliferation and migration, and inhibit KK cell apoptosis, but it has no significant effect on NK cell apoptosis ( P>0.05). Overexpression of Smad7 inhibited the proliferation and migration of NK cells and KK cells, and promoted their apoptosis. After interfering with lentivirus infection, NK cells and KK cells showed decreased expression of Occludin protein compared with NC group ( P<0.01), increased N-cadherin protein expression in KK cells ( P<0.01), but there was no significant change in N-cadherin protein expression in NK cells ( P>0.05); After lentivirus overexpression, NK and KK cells showed increased expression of Occludin protein ( P<0.05), the expression of N-cadherin protein in NK cells decreased ( P<0.05), but there was no significant change in N-cadherin protein expression in KK cells ( P>0.05). CONCLUSION: The regulation of Smad7 gene can affect the EMT in normal skin keratinocytes and keloid keratinocytes, and further regulate the ability of cell proliferation, migration and apoptosis. The effect of Smad7 gene regulation on EMT in keloid keratinocytes was greater than that on normal skin keratinocytes.

[Inhibition of Copper Transporter-1 by Ammonium Tetrathiocarbolybdate in the Treatment of Pancreatic Cancer].

OBJECTIVE: To examine copper transporter 1 (CTR1) expression in pancreatic carcinoma cells, orthotopic xenograft pancreatic tumor model and clinical samples, and verify the effect of copper chelating agent ammonium tetrathiomolybdate (TM) regulate the expression of CTR1 in pancreatic carcinoma cells and the inhibition of pancreatic carcinoma. METHODS: The expressions of copper transporter CTR1 and antioxidant protein 1 (ATOX1) in 22 clinical pancreatic ductal carcinoma and paracancer tissues 0.5-1 cm away from the tumor were measured by immunohistochemistry (IHC). PANC-1 cells were used to construct 5 orthotopic xenograft pancreatic tumor of nude mice models. Pancreatic cancer tissues and corresponding normal pancreatic tissues were collected, and the expressions of CTR1 and ATOX1 were detected by IHC and compared with clinical tissues. The proliferation of pancreatic carcinoma cells PANC-1 treated with 10, 30, 50, 100 µmol/L TM for 24 h, 48 h, 72 h was measured by CCK8 assay. The migration abilities of PANC-1 cells treated with 50 µmol/L TM for 24 h, 48 h were detected by scratch test. The expressions of CTR1, vascular endothelial growth factor (VEGF) and CyclinD1 proteins in PANC-1 cells treated with 10, 30, 50, 100 µmol/L TM for 48 h were measured by Western blot. Then the subcutaneous tumor-bearing model of nude mice were established with PANC-1 cells, and the growth of tumor was observed after oral administration of 0.3 mg/d and 1.0 mg/d of TM, respectively. RESULTS: The immunohistochemical results indicated that 19 of the 22 clinical pancreatic ductal cancer tissues of carcinoma patients had high expression of CTR1, and the same high expression of CTR1 was found in the orthotopic transplanted tumor tissues of PANC-1 nude mice. The proliferation inhibition of PANC-1 cells increased with the concentration of TM increased and the treatment time prolonged. The expressions of intracellular CTR1, VEGF and CyclinD1 all decreased with the concentration of TM increased. The cell migration ability decreased after the PANC-1 cells treated with TM. The tumor growth of PANC-1 tumor-bearing nude mice was inhibited after different doses of TM were delivered. The reduction in tumor volume and weight was more pronounced in the high-dose TM group (P<0.05). CONCLUSION: The expression of CTR1 is abnormally elevated in pancreatic carcinoma, and treatment with copper chelating agent for this target may help to inhibit pancreatic carcinoma.

[Mechanism of "herb soaking with exact amount of water" during moistening process of ginseng based on needle pressure sensor].

In this study, the texture analyzer acupuncture pressure sensor was used to objectively characterize the "herb soaking with exact amount of water" for moistening process of ginseng. The single factor rotation experiment was used to investigate the effects of puncture speed, puncture depth and puncture site on puncture force and work. According to ginseng processing method in Chinese Pharmacopoeia, ginseng medicinal materials with diameters of about 1 cm and 2 cm were selected, and puncture experiments were carried out at the set measurement time to determine the hardness, work and water absorption of the ginseng moistening process. The endpoint threshold for the ginseng softening process was determined and verified. To reflect the actual internal conditions of the ginseng softening process, the puncture depth was preferably 70%, and the puncture speed was 30 mm·min~(-1). In the ginseng moistening process, the softening hardness and the puncture work were in accordance with the first-order kinetic equation y=a×exp(-k×x). The 0 h initial hardness a of 1 cm and 2 cm ginseng herbs were 289.8 N and 1 227 N, and the rate constants K were 0.149 4 N·h~(-1) and 0.100 7 N·h~(-1), respectively. After the ginseng was completely softened, the force required for puncture was 10 N, which can be used as the standard for "drug penetration". At this time, the water absorption rate of ginseng was 70%-100%. The softening time of ginseng with a diameter of 1 cm was about 20-22 h, and the softening time of ginseng with a diameter of 2 cm was about 40-46 h. A needle-type pressure sensor was used to accurately determine the end point of the softening process of ginseng and reduce the loss of active ingredients. The study results provide reference for the softening process kinetics and the process intelligent monitoring of other dried roots and rhizomes.

[Discovery of cytochrome P450 enzymes-inhibiting components in traditional Chinese medicine].

With the widespread use of traditional Chinese medicine(TCM) and the integration of TCM and western medicine, drug-drug interaction(DDI) is considered as a major cause of therapeutic failures and side effects. Cytochrome P450 enzymes(CYPs) are responsible for large number of drug metabolism. CYP3 A4 and CYP2 D6, two important CYP isoforms, are responsible for about 80% drug metabolism of CYPs super family. The inhibition of CYPs is likely to be the most common factor leading to adverse DDI. Therefore, it is of great significance to predict potential CYP3 A4 and CYP2 D6 inhibitors to prevent the DDI. A fast and low-cost me-thod for calculating and predicting CYP inhibiting components was established in this paper, namely support vector machine(SVM) and molecular docking technology which are used to predict and screen drugs. Firstly, 12 qualitative models of two targets were established by using SVM, and the optimal model was selected to predict the compounds in traditional Chinese medicine database(TCMD). Then, molecular docking technology was used to establish docking model. By analyzing the key amino acids involved in drug-target interactions and combining with SVM model, potential inhibitors of CYP3 A4 and CYP2 D6 were found. From the computational results, astin D and epiberberine exhibited inhibition effect on CYP3 A4 and CYP2 D6, respectively. Astin D was only found in astins family from Aster tataricus, while epiberberine was considered to be the active constituent of Coptidis Rhizoma. Therefore, for the risk of DDI, extra attention should be paid to the source of these potential inhibitors, Asteris Radix et Rhizoma and Coptidis Rhizoma. This computational method provides technical support for discovering potential natural inhibitors of CYPs from Chinese herbs by using SVM and molecular docking model, and it is also helpful to recognize the CYPs-mediated DDI existing in TCM, providing research ideas for further pharmacovigilance of integrated therapy.