Reconstruction of engineered yeast factory for high yield production of ginsenosides Rg3 and Rd.

Panax notoginseng is one of the most valuable traditional Chinese herbs. The main active ingredients, dammarane-type ginsenosides, show multiple pharmacological activities. Recently, the key UDP-dependent glycosyltransferases (UGTs) involved in the biosynthesis of common ginsenosides have been widely studied. However, only a few UGTs that catalyze ginsenoside formation have been reported. This study further investigated the new catalytic function of 10 characterized UGTs from the public database. PnUGT31(PnUGT94B2) and PnUGT53 (PnUGT71B8)exhibited promiscuous sugar-donor specificity of UDP-glucose and UDP-xylose, which could catalyze the glycosylation of C20-OH sites and elongation of the sugar chain at the C3 and/or C20 sites. We further analyzed the expression patterns in P. notoginseng and predicted the catalytic mechanisms of PnUGT31 and PnUGT53 using molecular docking simulations. Moreover, different gene modules were built to increase the yield of ginsenosides in engineered yeast. The metabolic flow of the proginsenediol (PPD) synthetic pathway was enhanced by LPPDS gene modules based on the engineered strain. The resulting yeast was constructed to produce 1.72 g/L PPD in a shaking flask, but cell growth was significantly inhibited. EGH and LKG gene modules were constructed to achieve high-level production of dammarane-type ginsenosides. The production of G-Rg3 controlled by LKG modules increased 3.84 times (254.07 mg/ L), whereas the G-Rd titer reached 56.68 mg/L after 96 h in shaking flask culture under the control of all modules, both of which yielded the highest values for known microbes.

Height-Switching Dynamics of Mixed Polymer Brushes with Polymers of Different Stiffnesses.

Mixed brushes consisting of flexible and semiflexible polymers of the same chain length exhibit a height-switching phenomenon because of rigidity-dependent critical adsorption [Yang et al. Macromolecules 2020, 53, 7369]. Semiflexible polymers stand higher at weak surface attraction (high temperature), but they close to the attractive surface at strong attraction (low temperature). In this work, the height-switching dynamics of the mixed polymer brushes is studied by Metropolis Monte Carlo simulation. The height-switching time is calculated by a sudden change in the surface attraction. Two surface attraction change modes, i.e., the weak-to-strong mode where the attraction is changed from weak to strong and the strong-to-weak mode where it is changed from strong to weak, are investigated. Simulation results show that the height-switching time is related to the grafting density, the polymer stiffness, and surface attraction change mode. We find that the height-switching time is significantly decreased for the strong-to-weak mode. And our results also show that the height switching in the mixed polymer brushes is reversible.

Langevin dynamics simulation on optimal conditions for large and stable loops of adsorbed homopolymers on substrates.

Adsorption of polymer chains on a solid surface is a universal interfacial behavior. Loops in the adsorbed chains are considered to exert a significant effect on the overall properties of a substrate-supported polymer film via entanglement with non-adsorbed chains in the film. In this work, the size and stability of loops formed by adsorbed homopolymer chains on an attractive substrate were studied by Langevin dynamics simulations. The size of loops decreases while the stability increases with increasing attraction strength of the substrate. In contrast, with an increase in the polymer concentration, the size of loops increases but the stability decreases. However, both the size and stability of loops increase with increasing chain length. Simulation results show that the optimal conditions for forming large and stable loops are long homopolymer chains, substrates with moderate attraction strength, and moderate polymer concentration.

PanaxGDB: A Comprehensive Platform for Panax.

The genus Panax is a valuable natural medicinal source used worldwide that contains high levels of triterpenoid saponins with extensive pharmacological activities. In past decades, molecular biotechnology and breeding techniques have been respectively used to generate omics data and information on cultivars primarily from Panax ginseng (ginseng), Panax quinquefolium (American ginseng), and Panax notoginseng (Sanqi) to biosynthesize valuable saponins, improve product quality, and conduct cost-controlled cultivation. Although much data have been produced, there are concerns that redundant data might be generated and that relatively scattered data might be overlooked. Therefore, many scientists desire a reliable, comprehensive omics database of the Panax genus that could save time and promote integrated analysis. Therefore, to provide all-inclusive, reliable, and valuable information on the Panax genus, PanaxGDB, an open comprehensive database that integrates data on omics and information on varieties, was established. The database contains information on nearly 600 compounds from 12 Panax species, draft genomic sequences with annotations and gene expression levels, single nucleotide polymorphisms, genome-wide association analysis based on agronomic traits, globally collected germplasm information, summaries, omics data of the Panax genus, and online versatile analytic tools. The Panax genus database will be updated when new data are released to continue serving as a central portal to boost research on the biology and functions of Panax. PanaxGDB is available at: http://panaxGDB.ynau.edu.cn.

Terahertz magneto-optical response of bismuth-gadolinium-substituted rare-earth garnet film.

We report the magneto-optical Faraday response of bismuth-gadolinium-substituted rare-earth iron garnet at terahertz frequencies ranging from 100 GHz to 1.2 THz. The maximum transmittance of ±45° component is about 60% near the frequency point of 0.63 THz. When the external magnetic field change from -100 mT to +100 mT, the Faraday rotation angle is between -6° and +7.5°. The overall change of ellipticity is relatively small. The maximum value of the Verdet constant is about 260 °/mm/T at 0.1 THz and then gradually decreases to 80 °/mm/T at 1.2 THz. Within the considered frequency range, the thick film exhibits magnetically tunable, non-reciprocal characters and a strong magneto-optical effect within a small external magnetic field at room temperature, which will be widely used for the terahertz isolators, circulators, nonreciprocal phase shifters, and magneto-optical modulators.

Inhibition of TNFAIP1 ameliorates the oxidative stress and inflammatory injury in myocardial ischemia/reperfusion injury through modulation of Akt/GSK-3ß/Nrf2 pathway.

Tumor necrosis factor α-induced protein 1 (TNFAIP1) has been documented as a vital regulator of apoptosis and oxidative stress under various pathological conditions. However, whether TNFAIP1 plays a role in myocardial ischemia/reperfusion (I/R) injury has not been well investigated. This work aimed to evaluate the possible role of TNFAIP1 in mediating myocardial I/R injury. Firstly, we demonstrated that TNFAIP1 expression was dramatically increased in rat cardiomyocytes following hypoxia/reoxygenation (H/R) in vitro, and in rat myocardial tissues following I/R treatment in vivo. Silencing of TNFAIP1 alleviated H/R-induced apoptosis, oxidative stress and inflammatory response in rat cardiomyocytes in vitro. Moreover, knockdown of TNFAIP1 ameliorated I/R-induced myocardial injury, infarction size, cardiac apoptosis, oxidative stress and inflammatory response in vivo. Further investigation elucidated that knockdown of TNFAIP1 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3ß (GSK-3ß) pathway in vitro and in vivo. Inhibition of Akt markedly abrogated TNFAIP1-knockdown-mediated Nrf2 activation in cardiomyocytes following H/R injury. In addition, suppression of Nrf2 significantly diminished TNFAIP1-knockdown-induced cardioprotective effects in H/R-exposed cardiomyocytes. In summary, this work elucidates that inhibition of TNFAIP1 ameliorates myocardial I/R injury by potentiating Nrf2 signaling via the modulation of the Akt/GSK-3ß pathway. Our study highlights a vital role of the TNFAIP1/Akt/GSK-3ß/Nrf2 pathway in mediating myocardial I/R injury and suggests TNFAIP1 as an attractive target for treatment of this disease.

Simulation study on the critical adsorption and diffusion of polymer chains on heterogeneous surfaces with random adsorption sites.

The critical adsorption and diffusion of a linear polymer chain on a heterogeneous surface with randomly distributed adsorption sites are studied using dynamic Monte Carlo simulations. Results show that the critical fraction of the adsorption sites at which critical adsorption takes place decreases exponentially with the increasing polymer-surface attraction strength and, at the same time, decreases with the increasing intra-polymer attraction strength. For adsorbed polymers with large intra-polymer attraction strength, we also find an adsorption-induced structural transition from a three-dimensional compact globule to a two-dimensional compacted pancake with an increasing fraction of adsorption sites. Anomalous sub-diffusion is observed for the adsorbed polymer diffusion on heterogeneous surfaces, in contrast to the normal diffusion on a homogeneous surface. The polymer on heterogeneous surfaces shows larger fluctuation in the total surface attraction energy and a longer waiting time.

Terahertz magneto-optical effect of wafer-scale La: yttrium iron garnet single-crystal film with low loss and high permittivity.

The wafer-scale La:YIG single crystal thick films were fabricated on a three-inch gadolinium gallium garnet (GGG) substrate by liquid phase epitaxy method. The terahertz (THz) optical and magneto-optical properties of La:YIG film were demonstrated by THz time domain spectroscopy (THz-TDS). The results show that a high refractive index of approximately 4.09 and a low absorption coefficient of 10-50 cm-1 from 0.1 to 1.6 THz for this La:YIG film. Moreover, the THz Faraday rotation effect of La:YIG film was measured by the orthogonal polarization detection method in THz-TDS system, which can be actively manipulated by a weak longitudinal magnetic field of up to 0.155 T. With 5 samples stacked together, the Faraday rotation angle varies linearly from -15° to 15°, and the Verdet constant of La:YIG is about 100 °/mm/T within the saturation magnetization. This magneto-optical single crystal thick film with large area shows low loss, high permittivity and strong magneto-optical effect in the THz regime, which will be widely used in magneto-optical polarization conversion, nonreciprocal phase shifter and isolator for THz waves.

Proximity-Induced Magnetic Order in a Transferred Topological Insulator Thin Film on a Magnetic Insulator.

Breaking the time reversal symmetry (TRS) in a topological insulator (TI) by introducing a magnetic order gives rise to exotic quantum phenomena. One of the promising routes to inducing a magnetic order in a TI is utilizing magnetic proximity effect between a TI and a strong magnetic insulator (MI). In this article, we demonstrate a TI/MI heterostructure prepared through transferring a molecular beam epitaxy (MBE)-grown Bi2Se3 film onto a yttrium iron garnet (YIG) substrate via wet transfer. The transferred Bi2Se3 exhibits excellent quality over a large scale. Moreover, through wet transfer we are able to engineer the interface and perform a comparative study to probe the proximity coupling between Bi2Se3 and YIG under different interface conditions. A detailed investigation of both the anomalous Hall effect and quantum corrections to the conductivity in magnetotransport measurements reveals an induced magnetic order as well as TRS breaking in the transferred Bi2Se3 film on YIG. In contrast, a thin layer of AlO x at the interface obstructs the proximity coupling and preserves the TRS, indicating the critical role of the interface in mediating magnetic proximity effect.

Dynamics of adsorbed polymers on attractive homogeneous surfaces.

Dynamic behaviors of polymer chains adsorbed on an attractive, homogeneous surface are studied by using dynamic Monte Carlo simulations. The translational diffusion coefficient Dxy parallel to the surface decreases as the intra-polymer attraction strength EPP or the polymer-surface attraction strength EPS increases. The rotational relaxation time τR increases with EPS, but the dependence of τR on EPP is dependent on the adsorption state of the polymer. We find that τR decreases with increasing EPP for a partially adsorbed polymer but it increases with EPP for a fully adsorbed polymer. Scaling relations Dxy ~ N-α and τR ~ Nß are found for long polymers. The scaling exponent α is independent of EPS for long polymers but increases with EPP from α = 1.06 at EPP = 0. While ß ≈ 2.7 is also roughly independent of EPS for the adsorbed polymer at EPP = 0, but ß increases with EPS at EPP > 0. Moreover, we find that ß always decreases with increasing EPP. Our results reveal different effects of the attractive surface on the diffusion and rotation of adsorbed polymers.

TACE Combined with Implantation of Irradiation Stent Versus TACE Combine with Bare Stent for HCC Complicated by IVCTT.

PURPOSE: This study was designed to evaluate the safety and efficacy of transarterial chemoembolization (TACE) combined with intra-IVC implantation of an irradiation stent for the treatment of hepatocellular carcinoma (HCC) complicated by inferior vena cava tumor thrombosis (IVCTT). METHODS: Sixty-one consecutive patients with HCC complicated by IVCTT treated by TACE combined with IVC stenting were retrospectively analysed. IVC stenting was performed using a stent loaded with (125)I seeds strands (the irradiation stent) in 33 patients (Group A) and 28 patients with a bare stent (Group B). Propensity score matching eliminated the baseline differences. Overall survival, oedema related to IVC obstruction remission rate and procedure-related adverse events were compared between the two groups. RESULTS: The adverse effect rate was similar for both Group A and Group B patients, and complications were adequately handled by medical treatment. TACE combined with implantation of an irradiation stent showed a significant median survival benefit over TACE combined with a bare stent, with a median survival time of 203.0 ± 28.135 days versus 93.0 ± 24.341 days (p = 0.006). The propensity score-matched (24 pairs) cohort analyses (200 ± 31.231 days vs. 66 ± 23.270 days, p = 0.019). The oedema remission rate was 97.0 % in group A patients and 96.4 % in group B, respectively. TACE-irradiation stent and object tumor response were the independent prognostic factors of favorable survival. CONCLUSIONS: TACE combined with irradiation stent implantation is a safe and effective treatment modality for patients with HCC complicated by IVCTT and may extend their survival time.

Promoter methylation and expression of SOCS-1 affect clinical outcome and epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Abnormal DNA methylation can cause gene silencing in colorectal cancer (CRC) patients. A gene that is suspected to have a crucial role in various types of cancers is the suppressor of cytokine signaling 1 (SOCS-1). Thus, this study will analyze the ramifications of SOCS-1 promoter methylation in CRC patients. This study will also test the therapeutic effects of hypomethylation as a possible CRC therapy. METHODS: First, 97CRC patients' tumor and adjacent normal tissues were collected. Next, the methylation status of the SOCS-1 promoter region was assessed by methylation-specific polymerase chain reaction (MS-PCR); SOCS-1 protein and mRNA expression were also measured. A 48-month median follow-up period was used for the survival analysis of research participants. Lastly, to analyze the changes in cell invasion and migration in conjunction with protein and mRNA expression, the demethylating agent 5-azacytidine was applied in vitro to human CRC cells. RESULTS: The results showed increased SOCS-1 hypermethylation in CRC samples compared to controls. Methylated SOCS-1 was associated with significant suppression of SOCS-1 expression in tumors. Additionally, SOCS-1 hypermethylation was significantly correlated with lymph node metastasis and TNM stage. The study also found a poor overall survival rate to be significantly correlated with reduced expression of SOCS-1. After 5-azacytidine treatment, reduced in vitro DNA methylation and increased SOCS-1 expression were observed, and decreased cell migration and epithelial-mesenchymal transition biomarker expression alteration were further confirmed. CONCLUSIONS: In colorectal cancer tissues, the rate of methylation in the SOCS-1 promoter region is high. Through promoter hypermethylation, the SOCS-1 gene was severely down-regulated in the CRC tissue samples, thereby revealing a plausible therapeutic target for CRC therapy.

Effects of silencing the ATP-binding cassette protein E1 gene by electroporation on the proliferation and migration of EC109 human esophageal cancer cells.

In the present study, the gene expression of ATP-binding cassette protein E1 (ABCE1) in the EC109 human esophageal cancer cell line was silenced using electroporation to examine the effect if the ABCE1 gene on the growth migration and cell cycle of cancer cells. The small interference (si)RNA sequence of ABCE1 was designed and synthesized to transfect the EC109 cells by electroporation. The mRNA and protein expression levels of ABCE1 were then detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The analysis of the cell cycle and apoptosis was performed using flow cytometry. The effect of silencing the ABCE1 gene on the proliferation, migration and invasive ability of the EC109 human esophageal cancer cells were assessed using a Cell counting kit-8 (CCK-8) and with proliferation, wound-healing and cell invasion assays. The mRNA and protein expression levels of ABCE1 were significantly lower in the experimental group compared with the control group (P<0.05). The apoptotic rate of the experimental group was markedly higher than the control group and blank group (P<0.01). The CCK-8 proliferation assay revealed that, compared with the control and blank groups, the proliferation of the EC109 cells in the experimental group was significantly inhibited (P<0.05). The wound healing assay revealed that the migration capacity of the cells in the experimental group was significantly decreased (P<0.05). The Transwell chamber assay demonstrated that the invasive ability of the EC109 cells in the experimental group was significantly decreased (P<0.01). These results revealed that ABCE1 is closely associated with cell proliferation, invasion and migration in esophageal cancer and silencing the ABCE1 gene by electroporation can significantly reduce the proliferation, invasion and migration capacity of EC109 cells in vitro.

Graphene based all-optical spatial terahertz modulator.

We demonstrate an all-optical terahertz modulator based on single-layer graphene on germanium (GOG), which can be driven by a 1.55 µm CW laser with a low-level photodoping power. Both the static and dynamic THz transmission modulation experiments were carried out. A spectrally wide-band modulation of the THz transmission is obtained in a frequency range from 0.25 to 1 THz, and a modulation depth of 94% can be achieved if proper pump power is applied. The modulation speed of the modulator was measured to be ~ 200 KHz using a 340 GHz carrier. A theoretical model is proposed for the modulator and the calculation results indicate that the enhanced THz modulation is mainly due to the third order nonlinear effect in the optical conductivity of the graphene monolayer.

High-speed and broadband terahertz wave modulators based on large-area graphene field-effect transistors.

We present a broadband terahertz wave modulator with improved modulation depth and switch speed by cautiously selecting the gate dielectric materials in a large-area graphene-based field-effect transistor (GFET). An ultrathin Al2O3 film (∼60 nm) is deposited by an atomic-layer-deposition technique as a high-k gate dielectric layer, which reduces the Coulomb impurity scattering and cavity effect, and thus greatly improves the modulation performance. Our modulator has achieved a modulation depth of 22% and modulation speed of 170 kHz in a frequency range from 0.4 to 1.5 THz, which is a large improvement in comparison to its predecessor of SiO2-based GFET.

Dynamics of a polymer adsorbed to an attractive homogeneous flat surface.

The adsorption of a bond fluctuation self-avoiding walk polymer on an attractive homogeneous flat surface at temperature below the critical adsorption point is studied using dynamic Monte Carlo simulation. Results show that the apparent size Rg,xy(2) of the polymer parallel to the surface increases exponentially with time during the adsorption process. The relaxation time for Rg,xy(2) reaching its asymptotic value σeq decreases with the increase in the polymer-surface attraction strength Eps, whereas σeq increases with Eps, indicating that the polymer is adsorbed faster and becomes more extended at stronger adsorption. The polymer's asphericity Axy parallel to the surface is sensitive to intra-polymer interaction and its behavior is different from that of Rg,xy(2). Simulation results also show that the two-dimensional behaviors of Rg,xy(2) and Axy are different from that of the three-dimensional conformational size Rg(2) and asphericity A during the adsorption process. During the adsorption, the surface contacted monomer number M increases with time, but Rg(2) and A show novel behavior as they first increase with M at small M, then decrease with M at moderate M and finally increase with M again at large M. Whereas Rg,xy(2) and Axy first decrease with M and then increase with M during the adsorption.

Study on the polymer diffusion in a media with periodically distributed nano-sized fillers.

The effect of nano-sized fillers on the equilibrium and dynamical properties of a linear polymer is studied by using off-lattice Monte Carlo simulation. Fillers are arranged periodically in the system with period d and Lennard-Jones interaction between polymer and fillers is considered. Results show that the statistical dimension and dynamical diffusion of the polymer are dependent on the polymer-filler interaction strength ɛ(pf) and the relative size between R(G0) and d, here R(G0) is the radius of gyration of polymer in dilute solution. Normal diffusion of polymer is always observed in the regime 2R(G0) > d. And the diffusion coefficient D is scaled with chain length N as D ~ N(-α), where the exponent α increases with ɛ(pf). Whereas in the regime 2R(G0) < d ≪ Nl0 with l0 the mean bond length of polymer, normal diffusion is observed only at ɛ(pf) < 2, but the polymer will be adsorbed on the fillers and cannot diffuse at ɛ(pf) > 2. In addition, we find that there is a critical interaction strength ɛ*(pf) = 2 in our model system.

Study on in-vivo anti-tumor activity of Verbena officinalis extract.

We investigated the anti-tumor effects of Verbena officinalis extract on H22 tumor-bearing mice and its effect on immune function. Mice model of H22 solid tumor was established, the mice were divided into five groups and administered the extract, later, tumors were removed and inhibition rates were calculated; spleens were removed and spleen indices were calculated, and the sheep red blood cell-delayed-type hypersensitivity (SRBC-DTH) and the serum hemolysin level were determined. The Verbena officinalis extract had anti-tumor effect, with the inhibition rate reaching 38.78%, it also increased the spleen index to a certain extent, in addition, the changes in DTA and HA were not obvious compared with the model group. The Verbena officinalis extract had in vivo anti-tumor effect, while causing no damage on the immune function.

Study on in vitro anti-tumor activity of Bidens bipinnata L. extract.

We studied the in vitro anti-tumor activity of Bidens Bipinnata L. extract. MTT assay was used to investigate the inhibitory effect of different concentrations of the extracts on human hepatocellular carcinoma (HepG2) cell lines and human cervical carcinoma (Hela) cell lines, and the IC50 values were calculated. The Bidens Bipinnata L. extract had different degrees of inhibitory effects on these two cells, and when exposure time was 48 h, the inhibition rate reached its peak, with IC50 values of 14.80 µg/mL and 13.50 µg/mL respectively. The Bidens Bipinnata L. extract had a good inhibitory effect on human HepG2 cell lines and Hela cell lines, and thus has certain development prospects.

Clinical and genetic characteristics of Chinese patients with hereditary haemorrhagic telangiectasia-associated pulmonary hypertension.

BACKGROUND: Mutations in activin receptor-like kinase-1 (ACVRL-1) or endoglin (ENG) are mostly identified in patients with hereditary haemorrhagic telangiectasia (HHT) associated with pulmonary hypertension (PH), but have not yet been studied in Chinese patients. MATERIAL AND METHODS: In this study, we investigated the clinical and molecular genetic features of Chinese patients with HHT-associated PH and analysed genotype/phenotype correlations in 14 probands and their relatives. Mutation analyses in ACVRL-1, bone morphogenetic protein receptor type 2 (BMPR2) and ENG were performed in 14 Chinese Han patients with HHT-associated PH. RESULTS: The overall mutation rate was 71·4%, including 8 ACVRL-1 mutations and 2 ENG mutations, 6 of which were novel. Six patients were identified with arteriovenous malformations (AVMs), including four patients with pulmonary AVMs and two patients with liver AVMs. Five of the patients with AVMs were identified with mutations. Most patients received targeted therapy for PH. CONCLUSIONS: Our findings have revealed the clinical phenotype and molecular genetic features of HHT-associated PH in Chinese Han patients and indicate that mutations of ACVRL-1 and ENG are genetic predisposing factors in Chinese patients. Our data further addressed clinical management and have provided limited experience in treating this group of disorders.