pH/enzyme dual sensitive and nucleus-targeting dendrimer nanoparticles to enhance the antitumour activity of doxorubicin.

Direct delivery of drugs into the nucleus is a promising nanotechnology therapy, since the nucleus is one of the most important organelles controlling cell proliferation and apoptosis. Here, we report a nucleus-targeting nanocarrier for nuclear drug delivery using a pH/enzyme dual sensitive strategy. The specific ligand PGM (PKKKRKV-GFLG-Mp), composed of nuclear localization sequence (PKKKRKV), enzyme-sensitive tetrapeptide (Gly-Phe-Leu-Gly, GFLG), and pH-sensitive molecules morpholine (Mp), was modified on poly (amidoamine) (PAMAM) by maleimide active polyethylene glycol ester (NHS-PEG-MAL) to form PAMAM-PEG-PGM. Doxorubicin (DOX) was loaded into the cavity of PAMAM to prepare DOX/PAMAM-PEG-PGM. In vitro release study suggested DOX release from DOX/PAMAM-PEG-PGM nanoparticles followed pH and enzyme-triggered manner. In vitro studies showed DOX/PAMAM-PEG-PGM nanoparticles could not only promote cell internalization through the charge switching of morpholine, but also achieve nuclear internalization by the mediation of composite formed by NLS and importin α/ß receptor. Further, employing H22 tumour-bearing BALB/c mice as a model, the systemic distribution and anticancer effects of nanoparticles were studied in vivo. The results indicated the nanoparticles could preferentially accumulate in the tumour site in vivo, and the tumour inhibition rate was 88.47%. In short, the nanoparticles developed could be promising in application to nucleus-targeting therapy to enhance antitumour activity.

[Detection of Lead Chrome Green Illegally Added in Tea Based on Confocal Raman Spectroscopy].

In this paper, confocal Raman spectroscopy was applied to detect the contents of lead chrome green as a heavy-metal stain illegally added in tea. Firstly, Raman spectra of five different concentrations of lead chrome green in tea infusion were acquired based on specific concentration method. The qualitative analysis of sample added with lead chrome green was achieved with comparing the Raman spectra of sample and standard substance. Four main Raman characteristic wavenumbers, 1 341, 1 451, 1 527 and 1 593 cm(-1), were extracted for the qualitative identification of lead chrome green in tea. After spectral preprocessing of the raw Raman spectra, backward interval PLS (biPLS), competitive adaptive reweighted sampling (CARS) and successive projections algorithm (SPA) were combined to deeply mine the characteristic wavenumbers of lead chrome green in Raman spectra, and finally 14 characteristic wavenumbers were optimized. Partial least squares (PLS) and least square support vector machine (LS-SVM) were separately used to build the model based on the extracted 14 wavenumbers. As a result, these two models both had good robustness and high ability to predict and all the determination coefficient (R(2)) of calibration, validation and prediction were higher than 0.9, which proved the effectiveness of the extracted characteristic wavenumbers. Compared with the PLS model, the nonlinear model built by LS-SVM got a better result, R(2) of prediction was 0.964 and the root mean square error of prediction (RMSEP) was 0.535. This study indicated that it is feasible to detect the contents of lead chrome green illegally added in tea based on confocal Raman spectroscopy combined with specific sample treatment and chemometrics methods. This study helped the valid supervision of food safety problem on lead chrome green illegally added in tea.

Embryonic trophoblasts induce decidual regulatory T cell differentiation and maternal-fetal tolerance through thymic stromal lymphopoietin instructing dendritic cells.

Physiological pregnancy requires the maternal immune system to recognize and tolerate embryonic Ags. Although multiple mechanisms have been proposed, it is not yet clear how the fetus evades the maternal immune system. In this article, we demonstrate that trophoblast-derived thymic stromal lymphopoietin (TSLP) instructs decidual CD11c(+) dendritic cells (dDCs)with increased costimulatory molecules; MHC class II; and Th2/3-type, but not Th1-type, cytokines. TSLP-activated dDCs induce proliferation and differentiation of decidual CD4(+)CD25(-) T cells into CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) through TGF-ß1. TSLP-activated dDC-induced Tregs display immunosuppressive features and express Th2-type cytokines. In addition, decidual CD4(+)CD25(+)FOXP3(+) Tregs promote invasiveness and HLA-G expression of trophoblasts, resulting in preferential production of Th2 cytokines and reduced cytotoxicity in decidual CD56(bright)CD16(-) NK cells. Of interest, decreased TSLP expression and reduced numbers of Tregs were observed at the maternal-fetal interface during miscarriage. Our study identifies a novel feedback loop between embryo-derived trophoblasts and maternal decidual leukocytes, which induces a tolerogenic immune response to ensure a successful pregnancy.

[In Vivo Study of Chitin in Fungal Hyphae Based on Confocal Raman Microscopy].

Chitin is an important structural polysaccharide of fungal cell wall. In this paper, aerial hyphae of Colletotrichum camelliae Massee was first studied by confocal Raman microscopy in vivo. Firstly, the optimal experimental parameters of hyphae for collecting the Raman spectra were determined, and the typical Raman spectra of hyphae, chitin standard and background were acquired. By comparing analysis, characteristic peaks of chitin were found in hyphae. Then, a region of interesting on hyphae was selected for Raman scanning. Through principal component analysis, the Raman signal of hyphae and background in the scanning area can be separated clearly. Combined with loading weight plot, two main characteristic peaks of hyphae were obtained, 1 622 cm(-1) was belong to chitin and 1 368 cm(-1) was assigned to pectic polysaccharide. Finally, two and three dimension chemical images of fungal hyphae were realized based on Raman fingerprint spectra of chitin in a nondestructive way.

Poly(I:C) treatment leads to interferon-dependent clearance of hepatitis B virus in a hydrodynamic injection mouse model.

UNLABELLED: We have previously shown that poly(I:C) activates murine hepatic cells to produce interferon (IFN) and suppresses hepatitis B virus (HBV) replication in vitro. Therefore, we addressed whether poly(I:C) is able to induce the clearance of HBV in vivo. The chronic HBV replication mouse model was established by the hydrodynamic injection (HI) of pAAV-HBV1.2 into the tail veins of wild-type and IFN-α/ßR-, IFN-γ-, and CXCR3-deficient C57BL/6 mice. Fourteen days post-HI of pAAV-HBV1.2, mice were administered poly(I:C) by intraperitoneal injection, intramuscular injection, or HI. Only treatment of poly(I:C) by HI led to HBV clearance in wild-type C57BL/6 mice. Serum HBsAg disappeared within 40 days postinfection (dpi) in mice that received poly(I:C) by HI, and this was accompanied by the appearance of anti-HBs antibodies. HBV-specific T-cell and antibody responses were significantly enhanced by HI of poly(I:C). HBV replication intermediates and HBcAg-positive hepatocytes were eliminated in the liver. HI of poly(I:C) induced the production of IFNs in mice and enhanced the levels of cytokines, IFN-stimulated genes, and T-cell markers in the liver. Importantly, poly(I:C)-induced HBV clearance was impaired in IFN-α/ßR-, IFN-γ-, and CXCR3-deficient mice, indicating that the induction of type I IFN and the stimulation and recruitment of T cells into the liver are essential for HBV clearance in this model. Taken together, the application of poly(I:C) by HI into the liver enhances innate and adaptive immune responses and leads to HBV clearance in an HBV mouse model, implicating the potential of intrahepatic Toll-like receptor 3 (TLR3) activation for the treatment of chronic hepatitis B patients. IMPORTANCE: It has become well accepted that immunomodulation is a potentially useful approach to treat chronic viral infection. Recently, combinations of antiviral treatment and therapeutic vaccinations were evaluated for therapies of chronic hepatitis B virus (HBV) infection. Activation of the innate immune branch may also be important for viral control and contributes to HBV clearance. Our present study demonstrated that hepatic TLR3 activation led to clearance of hepatitis B virus in an HBV mouse model. For the first time, we showed that HBV clearance in this model is dependent not only on type I interferon (IFN) but also on type II IFN, indicating a coordinated action of innate and adaptive immune responses. T-cell recruitment appeared to be critical for the success of TLR3-mediated antiviral action. These findings implicate the potential of intrahepatic TLR3 activation for the treatment of chronic HBV infection.

Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion.

Spontaneous abortion is the most common complication of pregnancy. Immune activation and the subsequent inflammation-induced tissue injury are often observed at the maternal-fetal interface as the final pathological assault in recurrent spontaneous abortion. However, the precise mechanisms responsible for spontaneous abortion involving inflammation are not fully understood. Chemokine CCL28 and its receptors CCR3 and CCR10 are important regulators in inflammatory process. Here, we examined the expression of CCL28 and its receptors in decidual stromal cells (DSCs) by immunochemistry and flow cytometry (FCM), and compared their expression level in DSCs from normal pregnancy versus spontaneous abortion, and their relationship to inflammatory cytokines production by DSCs. We further analyzed regulation of the pro-inflammatory cytokines on CCL28 expression in DSCs by real-time polymerase chain reaction, In-cell Western and FCM. The effects of CCL28-CCR3/CCR10 interaction on DSC apoptosis was investigated by Annexin V staining and FCM analysis or DAPI staining and nuclear morphology. Higher levels of the inflammatory cytokines interleukin (IL)-1ß, IL-17A and tumor necrosis factor-α, and increased CCR3/CCR10 expression were observed in DSCs from spontaneous abortion compared with normal pregnancy. Treatment with inflammatory cytokines differently affected CCL28 and CCR3/CCR10 expression in DSCs. Human recombinant CCL28 promoted DSC apoptosis, which was eliminated by pretreatment with neutralizing antibodies against CCR3/CCR10 and CCL28. However, CCL28 did not affect DSC growth. These results suggest that the inflammation-promoted up-regulation of CCL28 and its receptors interaction in DSCs is involved in human spontaneous abortion via inducing DSC apoptosis.

Sphingomonas ginsengisoli sp. nov. and Sphingomonas sediminicola sp. nov.

Two novel bacteria, designated strains Gsoil 634(T) and Dae 20(T), were isolated in South Korea from soil of a ginseng field and freshwater sediment, respectively and were characterized by a polyphasic approach to clarify their taxonomic positions. Phylogenetic analysis based on 16S rRNA gene sequences indicated that, although they probably represented two distinct species (indicated by a sequence similarity of 96.6 %), both strain Gsoil 634(T) and strain Dae 20(T) belonged to the genus Sphingomonas and were most closely related to 'Sphingomonas humi' PB323 (97.8 % and 96.7 % sequence similarity, respectively), Sphingomonas kaistensis PB56(T) (96.8 % and 96.7 %), Sphingomonas astaxanthinifaciens TDMA-17(T) (96.6 % and 95.4 %) and Sphingomonas jaspsi TDMA-16(T) (95.6 % and 95.8 %). For both novel strains, the major ubiquinone was Q-10, the major polyamine was homospermidine, the major cellular fatty acids included summed feature 7 (C(18 : 1)ω7c, C(18 : 1)ω9t and/or C(18 : 1)ω12t), C(17 : 1)ω6c and C(16 : 0), and the polar lipids included sphingoglycolipid. These chemotaxonomic data supported the affiliation of both strains to the genus Sphingomonas. However, the DNA-DNA relatedness value between strain Gsoil 634(T) and 'Sphingomonas humi' PB323(T) was 31 %. Moreover, the results of physiological and biochemical tests allowed the phenotypic differentiation of strains Gsoil 634(T) and Dae 20(T) from established members of the genus Sphingomonas. Based on these data, the two isolates represent two novel species in the genus Sphingomonas, for which the names Sphingomonas ginsengisoli sp. nov. (type strain Gsoil 634(T) = KCTC 12630(T) = DSM 18094(T) = LMG 23739(T)) and Sphingomonas sediminicola sp. nov. (type strain Dae 20(T)  = KCTC 12629(T) = DSM 18106(T) = LMG 23592(T)) are proposed.

Establishment and application of hepatitis B virus persistent replication model in IFNAR(-/-) mouse.

The type I interferon and IFNAR play an important role in hepatitis B virus (HBV) infection and anti-HBV therapy. However, its mechanism of action is still poorly understood. To gain more insights into the role of type I interferon and type I interferon receptor (IFNAR) in HBV infection, we established an HBV persistent replication IFNAR knockout (IFNAR(-/-)) mouse model and preliminarily applied this model. At first, the progeny of IFNAR(-/-) mouse was reproduced. Then hydrodynamic injection with pAAV/HBV1.2 plasmid was conducted to establish the persistent HBV replication IFNAR(-/-) mouse model. At last, we applied this model to evaluate the effect of nucleoside analogues entecavir (ETV) on HBV replication. It was found that there was no difference in the serum HBsAg and HBeAg levels and HBcAg expression in the liver tissue between the ETV treated groups and normal saline (NS) treated group, but the serum HBV DNA levels were significantly suppressed 10, 25, 40 and 55 days after the ETV treatment [P=0.035, P=0.00, P=0.149 and P=0.084, IFNAR knockout (KO) control group vs. C57BL/6 ETV groups, respectively; P=0.081, P=0.001, P=0.243 and P=0.147, IFNAR KO control group vs. IFNAR KO ETV groups, respectively]. Interestingly, there was no difference in serum HBV DNA levels between the ETV treated IFNAR(-/-) and C57BL/6 mice. This result suggests that HBV suppression during ETV treatments doesn't depend on type I interferon and IFNAR. Collectively, persistent HBV replication IFNAR(-/-) mouse model that we established is a useful and convenient tool to detect the function of the type I interferon and IFNAR in HBV infection and anti-HBV treatments.

Influences of environmental factors on the dissipation of green tides in the Yellow Sea, China.

Green tides attack the Yellow Sea every year since 2007 and have caused substantial financial loss. Based on Haiyang-1C/Coastal zone imager (HY-1C/CZI) and Terra/MODIS satellite images, the temporal and spatial distribution of green tides floating in the Yellow Sea during 2019 was extracted. The relationships between the growth rate of the green tides and the environmental factors including sea surface temperature (SST), photosynthetically active radiation (PAR), sea surface salinity (SSS), nitrate and phosphate during the green tides' dissipation phase has been detected. Based on the maximum likelihood estimation, a regression model that includes SST, PAR and phosphate was recommended to predict the growth rate of the green tides in the dissipation phase (R2 = 0.63), and this model was also examined using Bayesian information criterion and Akaike information criterion. When the average SST in the study area was above 23.6 °C, the coverage of green tides began to decrease with the increase in temperature under the influence of PAR. The growth rate of the green tides was related to SST (R = -0.38), PAR (R = -0.67) and phosphate (R = 0.40) in the dissipation phase. Compared with HY-1C/CZI, the green tide area extracted using Terra/MODIS tended to be underestimated when the green tide patches were smaller than 11.2 km2. Otherwise, the lower spatial resolution of MODIS resulted in larger mixed pixels of water and algae, which would overestimate the total area of the green tides.

A Randomized, Single-dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers.

The test drug, a recombinant humanized monoclonal antibody, is a biosimilar candidate for the reference drug. The purpose of this study was to evaluate the bioequivalence of these two drugs. The study was divided into two parts, a pre-study and a formal trial. The pre-study included two subjects who were each given a single intravenous infusion of 6 mg/kg test drug. The formal trial was designed to be a randomized, double-blind, parallel controlled trial in which 70 subjects were randomly assigned 1:1 to receive either test or reference drug as a single 6 mg/kg intravenous infusion. In the pre-study, the immunogenicity was negative in both subjects and the safety of the test drug was considered to be good. The two groups in the formal trial had similar demographic characteristics. The 90% confidence interval of geometric mean ratios of area under the serum concentration-time curve from the time 0 to the time of last quantifiable concentration, area under the serum concentration-curve from time 0 to infinity, and maximum observed serum concentration between the test group and the reference group fell between 80% and 125% and the bioequivalence was recognized. There was no significant difference in the positive rate of antidrug antibodies. The treatment-emergent adverse events in the test group were similar to those in the reference group. This study showed that the test drug has similar pharmacokinetics, immunogenicity, and safety to the reference drug in healthy male subjects.

Ambulatory atrioventricular synchronous pacing over time using a leadless ventricular pacemaker: Primary results from the AccelAV study.

BACKGROUND: Previous studies demonstrated that accelerometer-based, mechanically timed atrioventricular synchrony (AVS) is feasible using a leadless ventricular pacemaker. OBJECTIVE: The purpose of this study was to determine the performance of a leadless ventricular pacemaker with accelerometer-based algorithms that provide AVS pacing. METHODS: AccelAV was a prospective, single-arm study to characterize AVS in patients implanted with a Micra AV, which uses the device accelerometer to mechanically detect atrial contractions and promote VDD pacing. The primary objective was to characterize resting AVS at 1 month in patients with complete atrioventricular block (AVB) and normal sinus function. RESULTS: A total of 152 patients (age 77 ± 11 years; 48% female) from 20 centers were enrolled and implanted with a leadless pacemaker. Among patients with normal sinus function and complete AVB (n = 54), mean resting AVS was 85.4% at 1 month, and ambulatory AVS was 74.8%. In the subset of patients (n = 20) with programming optimization, mean ambulatory AVS was 82.6%, representing a 10.5% improvement (P <.001). Quality of life as measured by the EQ-5D-3L (EuroQol Five-Dimensions Three-Level questionnaire) improved significantly from preimplant to 3 months (P = .031). In 37 patients with AVB at both 1 and 3 months, mean AVS during rest did not differ (86.1% vs 84.1%; P = .43). There were no upgrades to dual-chamber devices or cardiac resynchronization therapy through 3 months. CONCLUSION: Accelerometer-based mechanical atrial sensing provided by a leadless pacemaker implanted in the right ventricle significantly improves quality of life in a select cohort of patients with AV block and normal sinus function. AVS remained stable through 3 months, and there were no system upgrades to dual-chamber pacemakers.

Spallation ultracold neutron source of superfluid helium below 1 K.

For the production of high-density ultracold neutrons (UCNs), we placed 0.8 K superfluid helium in a cold neutron moderator. We resolved previous heat-load problems in the spallation neutron source that were particularly serious below 1 K. With a proton-beam power of 400 MeV×1 µA, a UCN production rate of 4 UCN cm(-3) s(-1) at the maximum UCN energy of E(c)=210 neV and a storage lifetime of 81 s were obtained. A cryogenic test showed that the production rate can be increased by a factor of 10 with the same storage lifetime by increasing the proton-beam power as well as (3)He pumping speed.

Effect of suppressor of cytokine signaling 2 (SOCS2) on fat metabolism induced by growth hormone (GH) in porcine primary adipocyte.

SOCS2, a member of suppressor of cytokine signaling (SOCS) family, is a negative regulator of the signal pathway Janus kinase/signal transducers and activators of transcription (JAK/STAT). Growth hormone (GH) could stimulate lipolysis in adipose tissue. To demonstrate the specific influence of SOCS2 on porcine adipocytes differentiation and lipid metabolism induced by GH, we induced porcine primary adipocytes with 500 ng/ml GH and then tested the triglyceride (TG) accumulation and mRNA expressions of crucial genes in lipid metabolism like peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), SOCS2 and SOCS3. Then we retested these genes expressions in different time point after further treatment that over expressed SOCS2 in primary adipocytes and treated with 500 ng/ml GH. Results showed 500 ng/ml GH significantly restrained the porcine primary adipocytes differentiation. Specifically, 0.5 h after the induction with GH, accumulation of TG began to increase, and turned down since 8 h after. GH could promote PPARγ and FAS expressions during earlier stage (0-1 h), restrain from 4 h. However, ATGL and HSL mRNA expressions were stabile increasing. The expression of SOCS2 increased steadily after GH stimulation while SOCS3 expression was instantaneous rise. Overexpression of SOCS2 significantly decreased GH-induced the increase of PPARγ, FAS, ATGL and HSL mRNA expressions in earlier stage (0-1 h), as well as FAS and ATGL protein expression. Otherwise SOCS2 overexpression significantly decreased signal transducers and activators of transcription 3 (STAT3), signal transducers and activators of transcription 5 (STAT5) mRNA expressions and tyrosine phosphorylation levels with GH stimulation. At the same time SOCS3 mRNA kept in a lower level in Ad-SOCS2 transfected adipocytes. In conclusion, SOCS2 might be an important negative regulator of GH signaling in porcine adipocytes, which would provide the ground work for the mechanism of SOCS2 regulation fat metabolism.

Comprehensive effects of interdecadal change of sea surface temperature increase in the Indo-Pacific Ocean on the warming-wetting of the Qinghai-Tibet Plateau.

The correlation characteristics between anomalous changes in summer precipitation on the Qinghai-Tibet Plateau (QTP) and the high-impact areas of global sea-surface temperature (SST) are mainly studied in this paper. The results show that the interdecadal change of the regional "warming-wetting" in China is especially prominent in the northern part of the main body of the QTP, which is therefore identified as the high-value area of precipitation variability. Investigations have revealed that the high-value areas of summer precipitation variability in the northern QTP are significantly correlated with four high-value areas of SST variability, namely the western North Pacific, the western Central Pacific, the Southwest Pacific, and the central Indian Ocean. In these four high-impact areas, a synchronous tendency is found in the SST increase and sea-surface specific humidity. Through the tracking analysis of the correlated vectors of the water vapor source for the warming-wetting of the QTP, it further confirms that the four high-value areas of SST variability in the Indo-Pacific Ocean are the major impact sources of water vapor transport for the warming-wetting of the QTP. Moreover, the comparison of the characteristics of various interdecadal global water vapor transport circulations show that from 1991 to 2020, the trans-equatorial water vapor transport from the Southern Hemisphere witnessed a notable increase, which furthermore suggests that the interdecadal change of SST increase in the Southwest Pacific and central Indian Ocean is the key reason for the warming-wetting of the QTP. In addition, a comprehensive image of high-impact marine water vapor sources for modulating the warming-wetting tendency in the QTP is proposed.

Distinct impacts of vapor transport from the tropical oceans on the regional glacier retreat over the Qinghai-Tibet Plateau.

An influence of precipitation on the glacier changes over the Qinghai-Tibet Plateau (QTP) is investigated in this paper. The results show that the glacial loss rates of glaciers in the QTP are significantly correlated with the interannual changes of precipitation and low cloud cover. The water vapor, importing with the warm and wet airflows from the Asian Monsoon regions, significantly influence the precipitation in the southern and northern glacier areas of the QTP in the summer monsoon season. The three-dimensional changes of water vapor transport can lead to the difference of water balance between different glacier areas. Under global warming, the northwest QTP is in the ascending branch of the vertical water driven thermally by the tropical Indian Ocean. The warm water vapor from the tropical ocean climbs to the QTP, forming a significant supply effect of precipitation in the northwestern glacier area, which makes the glacier retreat at a relatively slow rate. Meanwhile, the southern and southeastern QTP regions are in the descending branch of vapor transport with the declining trend in the lower troposphere, which lead to the shortage water supply aggravating the glacier loss in the southern and southeastern QTP.

[Toll-like receptor dependent innate immune responses by primary mouse hepatocytes and its control of HBV replication].

OBJECTIVE: This report aims to investigate the Toll-like receptor (TLR) signaling pathways and induced antiviral activity in hepatocytes. METHODS: We isolated primary hepatocytes from wild-type C57BL/6 mice and examined the expression of TLR by realtime RT-PCR. Hepatocytes were stimulated with TLR 1-9 agonists and the supernatants were harvested. The secretion of cytokines were tested by ELISA. The antiviral effectors in supernatants were assayed via virus protection assay (in EMCV system) and the control of HBV replication were assessed via Southern blotting (in HBV system). RESULTS: We demonstrated that hepatocytes expressed TLR1-9. In accordance with these TLR expression profiles, hepatocytes responded to all TLR ligands by producing inflammatory cytokines (TNF-α or IL-6), to TLR -1,-3,-7 and -9 ligands by producing type I IFN (IFN-α or IFN-ß). Only TLR 3 and TLR 7 agonists could stimulate the production of high amounts of antiviral mediators by hepatocytes in virus protection assay. By contrast, supernatants from TLR1, -3 and -4 directly stimulated hepatocytes and TLR 3, -7 and -9 transfected hepatocytes were able to potently suppress HBV replication. CONCLUSION: Primary hepatocytes display a unique TLR signaling pathway and can control HBV replication after stimulation by TLR agonists in mice. It may be helpful for the development of TLR-based therapeutic approaches against hepatotropic virus.

Retrospective cohort study comparing the epidemiological and clinical characteristics between imported and local COVID-19 inpatients in Nanyang, China.

China has experienced an outbreak of COVID-19 since December 2019. This study investigated the differences between the imported and local cases of COVID-19 in Nanyang, China. In this study, a total of 129 COVID-19 confirmed cases with a clear epidemiological history admitted to hospitals in Nanyang from January 24 to February 26, 2020 were enrolled. Patients who had a travel history to or a residence history in Wuhan or in the surrounding areas in Hubei Province within 14 days before the illness onset were assigned to the imported group (n=70), and the others were assigned to the local group (n=59). The differences in epidemiological characteristics, clinical features, laboratory and imaging results, and prognosis were compared between the 2 groups. The early diagnosed cases were mainly imported cases, and the later diagnosed ones were mainly local cases. The most common first symptom was fever; moderate fever was commonly seen in imported cases whereas low fever was commonly seen in local cases. Lymphocyte counts in the imported group were lower than those in the local group. The imported group showed more advanced and severe abnormalities in the CT scan whereas the local group showed milder pulmonary abnormalities. The proportion of severe and critically severe patients in the imported group was higher than that in the local group. In conclusion, the imported cases have more severe or critically severe patients with a higher mortality rate than the local cases.

Electro-acupuncture regulates glucose metabolism in chronic stress model rats.

Studies have shown that acupuncture is very effective in treating chronic stress depression. However, little is known about the therapeutic mechanism of electro-acupuncture. Metabolomics, on the other hand, is a technology that determines the metabolic changes of organisms caused by various interventions as a whole and is related to the overall effect of electro-acupuncture (EA). 1HNMR, serum sample analysis, and histopathology and molecular biology analysis were used to evaluate the effects of EA. The results show that electro-acupuncture points can regulate the heat pain threshold of chronic stress model rats and change the morphology of adrenal cortex cells Structure, and regulate the contents of corticotropin-releasing hormone, Corticosterone (CORT), glucose, alanine and valine in the samples. These findings help to clarify the therapeutic mechanism of electro-acupuncture on heterologous chronic stress model rats. The effect of electro-acupuncture on improving chronic stress is likely to be achieved by regulating glucose metabolism, which can provide a reference for clinical acupuncture treatment of chronic stress depression.

Investigation of Citrinin and Pigment Biosynthesis Mechanisms in Monascus purpureus by Transcriptomic Analysis.

Monascus purpureus YY-1 is widely used in food colorant production in China. Our previous study clearly illustrated the whole-genome data for YY-1 and provided useful insight into evolutionary research and industrial applications. However, the presence of citrinin, which has nephrotoxic, hepatotoxic, and carcinogenic activities, has attracted attention to the safety of Monascus products. In an effort to reduce the harmful effects of citrinin in Monascus-related products, a random mutant of M. purpureus YY-1 with low citrinin production (designated as "winter") was obtained in this study. To analyze the biosynthesis and regulation mechanisms of pigment and citrinin, a transcriptomic analysis of the M. purpureus YY-1 and winter strains was performed. Comparative transcriptomic analysis reveals pksCT, the essential gene for citrinin synthesis, showed a low expression level in M. purpureus YY-1 and winter, which suggested there might be isoenzymes in M. purpureus YY-1 that were responsible for the citrinin synthesis during evolution. In addition, changes in transcription factor expression may also influence the network regulating the citrinin synthesis pathway in M. purpureus. Moreover, the yields of pigments produced by the winter mutant were significantly increased. Repressing the central carbon metabolism and improving the acetyl-CoA pool can contribute to a high pigment yield, and enhanced NADPH regeneration can also lead to the metabolic flux of pigment production in M. purpureus. Investigations into the biosynthesis and regulation of citrinin and pigment production in M. purpureus will enhance our knowledge of the mechanisms behind the biosynthesis of fungal secondary metabolites.

LSECs express functional NOD1 receptors: A role for NOD1 in LSEC maturation-induced T cell immunity in vitro.

Liver sinusoidal endothelial cells (LSECs) are organ resident APCs capable of antigen presentation and subsequent tolerization of T cells under physiological conditions. In this study, we investigated whether LSEC pretreatment with NOD-like receptor (NLR) agonists can switch the cells from a tolerogenic to an immunogenic state and promote the development of T cell immunity. LSECs constitutively express NOD1, NOD2 and RIPK2. Stimulation of LSECs with DAP induced the activation of NF-κB and MAP kinases and upregulated the expression of chemokines (CXCL2/9, CCL2/7/8) and cytokines (IFN-γ, TNF-α and IL-2). Pretreatment of LSECs with DAP induced significantly increased IFN-γ and IL-2-production by HBV-stimulated CD8+ T cells primed by DAP-treated LSECs. Consistently, a significant reduction in the HBV DNA and HBsAg level occurred in mice receiving T cells primed by DAP-treated LSECs. MDP stimulation had no impact on LSECs or HBV-stimulated CD8+ T cells primed with MDP-treated LSECs except for the upregulation of PD-L1. DAP stimulation in vitro could promote LSEC maturation and activate HBV-specific T cell responses. These results are of particular relevance for the regulation of the local innate immune response against HBV infections.