Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis.

Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90ß on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b were found to be novel clients of Hsp90ß in particular. Pharmacological inhibition of Hsp90 with 17-DMAG results in N protein proteasome-dependent degradation. Hsp90 depletion-induced N protein degradation is independent of CHIP, a ubiquitin E3 ligase previously identified for Hsp90 client proteins, but alleviated by FBXO10, an E3 ligase identified by subsequent siRNA screening. We also provide evidence that Hsp90 depletion may suppress SARS-CoV-2 assembly partially through induced M or N degradation. Additionally, we found that GSDMD-mediated pyroptotic cell death triggered by SARS-CoV-2 was mitigated by inhibition of Hsp90. These findings collectively highlight a beneficial role for targeting of Hsp90 during SARS-CoV-2 infection, directly inhibiting virion production and reducing inflammatory injury by preventing the pyroptosis that contributes to severe SARS-CoV-2 disease.

Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17.

Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, and sparrow DCoV HKU17 (Chinese strain), and PDCoV in the subgenera Buldecovirus are grouped together at whole-genome levels; however, the spike (S) glycoprotein and its S1 subunit of HKU17 are more closely related to night heron DCoV HKU19 in Herdecovirus. Nevertheless, the S1 protein of HKU11, HKU13, or HKU17 bound to or interacted with chicken APN (chAPN) or porcine APN (pAPN) by flow cytometry analysis of cell surface expression of APN and by coimmunoprecipitation in APN-overexpressing cells. Expression of chAPN or pAPN allowed entry of pseudotyped lentiviruses with the S proteins from HKU11, HKU13 and HKU17 into nonsusceptible cells and natural avian and porcine cells, which could be inhibited by the antibody against APN or anti-PDCoV-S1. APN knockdown by siRNA or knockout by CRISPR/Cas9 in chicken or swine cell lines significantly or almost completely blocked infection of these pseudoviruses. Hence, we demonstrate that HKU11, HKU13, and HKU17 with divergent S genes likely engage chAPN or pAPN to enter the cells, suggesting a potential interspecies transmission from wild birds to poultry and from birds to mammals by certain avian DCoVs. IMPORTANCE The receptor usage of avian deltacoronaviruses (DCoVs) has not been investigated thus far, though porcine deltacoronavirus (PDCoV) has been shown to utilize aminopeptidase N (APN) as a cell receptor. We report here that chicken or porcine APN also mediates cellular entry by three avian DCoV (HKU11, HKU13, and HKU17) spike pseudoviruses, and the S1 subunit of three avian DCoVs binds to APN in vitro and in the surface of avian and porcine cells. The results fill the gaps in knowledge about the avian DCoV receptor and elucidate important insights for the monitoring and prevention of potential interspecies transmission of certain avian DCoVs. In view of the diversity of DCoVs, whether this coronavirus genus will cause novel virus to emerge in other mammals from birds, are worthy of further surveillance and investigation.

Neurological complications during the Omicron COVID-19 wave in China: A cohort study.

BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.

Umbilical cord blood cell characteristics in very preterm neonates for autologous cell therapy of preterm-associated complications.

BACKGROUND: There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. METHODS: Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. RESULTS: Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 108. To infuse a dose of 5 × 107 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 107 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. CONCLUSION: UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 107 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

Facile synthesis of Ni3Se4/Ni0.6Zn0.4O/ZnO nanoparticle as high-performance electrode materials for electrochemical energy storage device.

To enhance the performance of transition metal chalcogenide composite electrode material, a key point is a composite design and preparation based on the synergistic effect between the oxide and selenide materials. With a facile 'one step template-annealing' step, Ni3Se4, Ni0.6Zn0.4O and ZnO are simultaneously synthesized, by 500 °C annealing. With the increase of annealing temperature from 350 °C to 600 °C, nickel selenides change from NiSe2to Ni3Se4to NiSe. The charge storage capacity increases first and then decreases with the increase of annealing temperature, and the 500 °C annealing obtained three compound composite Ni3Se4/Ni0.6Zn0.4O/ZnO (NNZ-500) nanoparticle material displayed a high specific capacitance of 1089.2 F g-1at 1 A g-1, and excellent cycle stability of 99.8% capacitance retention after 2000 cycles at 5 A g-1. Moreover, an asymmetric supercapacitor was assembled with NNZ-500 as the positive electrode material and activated carbon as the negative electrode material. This kind of asymmetric supercapacitor demonstrated a high energy density of 53.4 Wh kg-1at 819.0 W kg-1, and cycle stability with 98.6% capacitance retention after 2000 cycles. This material preparation approach provides great potential for the future development of high performance transition metal composite electrode materials in energy storage applications.

A novel technique for lymphadenectomy along the left recurrent laryngeal nerve during minimally invasive esophagectomy: a retrospective cohort study.

BACKGROUND: In the context of esophageal cancers, lymph nodes located along the left recurrent laryngeal nerve (RLN) exhibit significant involvement, posing significant challenges for lymphadenectomy. The objective of this study is to assess the safety and efficacy of a novel technique for lymphadenectomy called "elastic suspension of left RLN" method, comparing it with the conventional approach. METHODS: Between January 2016 and June 2020, a total of 393 patients who underwent minimally invasive esophagectomy with gastroplasty and cervical esophagogastric anastomosis were enrolled in the study. Among them, 291 patients underwent the "elastic suspension of left RLN" method, while 102 patients underwent the conventional method. We compared the number of harvested lymph nodes along the left RLN and assessed postoperative complications between these two groups. Additionally, the overall survival (OS) rate was calculated and analyzed for the entire cohort. RESULTS: In comparison to the conventional group, the elastic suspension group exhibited a higher yield of harvested lymph nodes along the left RLN (5.36 vs 3.07, P < 0.001). Moreover, the incidence of postoperative hoarseness was lower in the elastic suspension group (10.65% vs 18.63%, P = 0.038). The average duration of lymphadenectomy along the left RLN was 11.85 min in the elastic suspension group and 11.51 min in the conventional group, although this difference was not statistically significant (P = 0.091). Notably, the overall 5-year OS was markedly higher in the elastic suspension group compared to the conventional group (64.1% vs. 50.1%, P = 0.020). CONCLUSIONS: The findings suggest that the novel "elastic suspension of left RLN" method for lymphadenectomy along the left RLN in minimally invasive esophagectomy is both safe and effective. This technique holds promise for widespread adoption in esophagectomy procedures.

Reusable SERS Substrates Based on Gold Nanoparticles for Peptide Detection.

Raman spectroscopy is a powerful analytical technique widely used for quantitative and qualitative analysis. However, the development of inexpensive, reproducible, and reusable enhancing substrates remains a challenge for material scientists and analytical chemists. In this study, we address this challenge by demonstrating the deposition of core-shell nanoparticles consisting of a gold core and a thin inert SiO2 shell within a confined space, resulting in the formation of a highly efficient Raman-enhancing structure. Nanoparticles were characterized by UV-vis spectroscopy, dynamic light scattering, and total reflectance X-ray fluorescence spectroscopy, whereas the prepared substrates were characterized by scanning electron microscopy and Raman spectroscopy with a model molecule, malachite green. The relationship between Raman intensity and the loading of malachite green dye exhibited linearity, indicating the uniform spatial distribution of hotspots across the substrate. The limit of detection was determined as 2.9 µM of malachite green when 10 uL was distributed over a ca. 25 mm2 surface area. Moreover, the same substrate, after thorough washing in ethanol, was successfully employed for the detection of bovine serum albumin at a concentration level of 55 µg mL-1, demonstrating its reusability and versatility. Our findings highlight the potential of these substrates for various applications in biomedical research, clinical diagnosis, and beyond.

Roles of Two Major Domains of the Porcine Deltacoronavirus S1 Subunit in Receptor Binding and Neutralization.

Determination of the mechanisms of interspecies transmission is of great significance for the prevention of epidemic diseases caused by emerging coronaviruses (CoVs). Recently, porcine deltacoronavirus (PDCoV) was shown to exhibit broad host cell range mediated by surface expression of aminopeptidase N (APN), and humans have been reported to be at risk of PDCoV infection. In the present study, we first demonstrated overexpression of APN orthologues from various species, including mice and felines, in the APN-deficient swine small intestine epithelial cells permitted PDCoV infection, confirming that APN broadly facilitates PDCoV cellular entry and perhaps subsequent interspecies transmission. PDCoV was able to limitedly infect mice in vivo, distributing mainly in enteric and lymphoid tissues, suggesting that mice may serve as a susceptible reservoir of PDCoV. Furthermore, elements (two glycosylation sites and four aromatic amino acids) on the surface of domain B (S1B) of the PDCoV spike glycoprotein S1 subunit were identified to be critical for cellular surface binding of APN orthologues. However, both domain A (S1A) and domain B (S1B) were able to elicit potent neutralizing antibodies against PDCoV infection. The antibodies against S1A inhibited the hemagglutination activity of PDCoV using erythrocytes from various species, which might account for the neutralizing capacity of S1A antibodies partially through a blockage of sialic acid binding. The study reveals the tremendous potential of PDCoV for interspecies transmission and the role of two major PDCoV S1 domains in receptor binding and neutralization, providing a theoretical basis for development of intervention strategies. IMPORTANCE Coronaviruses exhibit a tendency for recombination and mutation, which enables them to quickly adapt to various novel hosts. Previously, orthologues of aminopeptidase N (APN) from mammalian and avian species were found to be associated with porcine deltacoronavirus (PDCoV) cellular entry in vitro. Here, we provide in vivo evidence that mice are susceptible to PDCoV limited infection. We also show that two major domains (S1A and S1B) of the PDCoV spike glycoprotein involved in APN receptor binding can elicit neutralizing antibodies, identifying two glycosylation sites and four aromatic amino acids on the surface of the S1B domain critical for APN binding and demonstrating that the neutralization activity of S1A antibodies is partially attributed to blockage of sugar binding activity. Our findings further implicate PDCoV's great potential for interspecies transmission, and the data of receptor binding and neutralization may provide a basis for development of future intervention strategies.

Prediction model of poorly differentiated colorectal cancer (CRC) based on gut bacteria.

BACKGROUND: The mortality of colorectal cancer is high, the malignant degree of poorly differentiated colorectal cancer is high, and the prognosis is poor. OBJECTIVE: To screen the characteristic intestinal microbiota of poorly differentiated intestinal cancer. METHODS: Fecal samples were collected from 124 patients with moderately differentiated CRC and 123 patients with poorly differentiated CRC, and the bacterial 16S rRNA V1-V4 region of the fecal samples was sequenced. Alpha diversity analysis was performed on fecal samples to assess the diversity and abundance of flora. The RDP classifier Bayesian algorithm was used to analyze the community structure. Linear discriminant analysis and Student's t test were used to screen the differences in flora. The PICRUSt1 method was used to predict the bacterial function, and six machine learning models, including logistic regression, random forest, neural network, support vector machine, CatBoost and gradient boosting decision tree, were used to construct a prediction model for the poor differentiation of colorectal cancer. RESULTS: There was no significant difference in fecal flora alpha diversity between moderately and poorly differentiated colorectal cancer (P > 0.05). The bacteria that accounted for a large proportion of patients with poorly differentiated and moderately differentiated colorectal cancer were Blautia, Escherichia-Shigella, Streptococcus, Lactobacillus, and Bacteroides. At the genus level, there were nine bacteria with high abundance in the poorly differentiated group, including Bifidobacterium, norank_f__Oscillospiraceae, Eisenbergiella, etc. There were six bacteria with high abundance in the moderately differentiated group, including Megamonas, Erysipelotrichaceae_UCG-003, Actinomyces, etc. The RF model had the highest prediction accuracy (100.00% correct). The bacteria that had the greatest variable importance in the model were Pseudoramibacter, Megamonas and Bifidobacterium. CONCLUSION: The degree of pathological differentiation of colorectal cancer was related to gut flora, and poorly differentiated colorectal cancer had some different bacterial flora, and intestinal bacteria can be used as biomarkers for predicting poorly differentiated CRC.

Recent status of sesaminol and its glucosides: Synthesis, metabolism, and biological activities.

Sesamum indicum is a major and important oilseed crop that is believed to promote human health in many countries, especially in China. Sesame seeds contain two types of lignans: lipid-soluble lignans and water-soluble glucosylated lignans. The major glucosylated lignans are sesaminol glucosides (SGs). So far, four sesaminol isomers and four SGs are identified. During the naturally occurring process of SGs production, sesaminol is generated first from two molecules of E-coniferyl alcohol, and then the sugar is added to the sesaminol one by one, leading to production of SGs. Sesaminol can be prepared from SGs, from sesamolin, and through artificial synthesis. SGs are metabolized in the liver and intestine and are then transported to other tissues. They exhibit several biological activities, most of which are based on their antioxidant and anti-inflammatory activities. In this paper, we present an overview of the current status of research on sesaminol and SGs. We have also discussed their synthesis, preparation, metabolism, and biological activities. It has been suggested that sesaminol and SGs are important biological substances with strong antioxidant properties in vitro and in vivo and are widely used in the food industry, medicine, and cosmetic products. The recovery and utilization of SGs from sesame seed cake after oil processing will generate massive economic benefits.

Capabilities and mechanisms of microalgae on nutrients and florfenicol removing from marine aquaculture wastewater.

The regulations governing the discharge of marine aquaculture wastewater are becoming increasingly stringent, and the problems of nitrogen and phosphorus pollution and antibiotic residues in wastewater are serious. Microalgae-based treatment with the dual benefits of wastewater purification and microalgae resource recycling was regarded as the most promising technology in aquaculture wastewater treatment. Isochrysis galbana and Chlorella sp. were chosen to investigate antibiotic and nutrient removal mechanisms from aquaculture wastewater. FLO addition stimulated microalgae growth at low FLO concentrations (0.1 and 1 mg/L) but inhibited growth at 10 mg/L. The removal efficiency of DIN by Chlorella sp. and I. galbana after 7 days of cultivation was 66.4% and 25.8%, respectively. Linear curves were obtained between DIN concentration and cultivation duration, remove constant (k) increased as FLO concentration increased from 0 to 10 mg/L, and the highest value of k was obtained in both the Chlorella sp. and I. galbana groups at 10 mg/L. DIP concentrations in FLO-contained simulated aquaculture wastewater decreased sharply with the cultivation of Chlorella sp. and I. galbana, and DIP removal rate increased as FLO concentration increased. When the initial concentration of FLO was 0.1 mg/L, biodegradation by I. galbana accounted for 86.67% of FLO removal. In contrast, FLO removal with biodegradation and biosorption by Chlorella sp. was 89.74% and 3.72%, respectively. Furthermore, Chlorella sp. grown in MPBR demonstrated superior capability for antibiotic-containing marine aquaculture wastewater purification, with average removal rates of DIN and DIP of 81.2% and 100%, respectively. The high removal rate is related to membranes which can improve microalgae performance by decoupling SRT and HRT. For microalgae-based aquaculture wastewater, ammonia was the most crucial nitrogen source, followed by nitrate. These findings serve as a theoretical foundation for developing microalgae-based aquaculture wastewater treatment technology and eliminating antibiotics in aquaculture.

Global imaging with high resolution region of interest using fusion data based on dual-field of view detection system.

X-ray micro-computed tomography (CT) is an important tool for high-resolution three-dimensional imaging. But one limitation of micro-CT is the compromise between resolution and fields of view (FOV). In this paper, we develop an x-rays dual-FOV optical coupling detection (DFOCD) system for global imaging with high-resolution region of interest (ROI). In DFOCD system, the beam splitter separates lights to form two sub-optical paths, two objectives with different FOV and magnification are used in the two sub-optical paths for dual-FOV imaging. Then a data fusion method is proposed to register and fuse dual-FOV data. Reconstructed images are obtained based on back projection filtering algorithm using fusion data. Dual-FOV data are collected simultaneously in DFOCD system, which precludes artifacts in fusion images from phantom movement or changes in two acquisitions on common micro-CT, and also saves scanning time. Simulation and experimental results show that details in ROI and global morphology of phantoms are correctly reconstructed. Bright ring artifacts of ROI caused by truncated data are corrected in reconstruction images. Therefore, global imaging with high-resolution ROI of samples can be obtained by single scan experiment using DFOCD system and data fusion method, which is expected to expand the application of micro-CT.

Transurethral laser versus open simple prostatectomy for large volume prostates: a systematic review and meta-analysis of randomized controlled trials.

The benefit of transurethral laser prostatectomy over open simple prostatectomy (OSP) is controversial in aged symptomatic benign prostatic hyperplasia (BPH) patients with large volume prostates, and the aim of this study is to compare the safety and efficiency of these two methods. Meta-analysis was applied using the Review Manager V5.3 software and the retrieved randomized controlled clinical trials (RCTs) comparing transurethral laser prostatectomy with OSP were analyzed for the treatment of large volume prostates from 2000 to 2019 in PubMed, Web of Science, Cochrane, and EMBASE datasets. Five RCTs assessing transurethral laser prostatectomy versus OSP were considered suitable for this meta-analysis, which included a total of 448 patients, with 232 patients undergoing laser and 216 patients undergoing OSP. Compared with OSP, although transurethral laser prostatectomy required a longer operative time (weighted mean difference (WMD) 27.49 mins; 95% confidence interval (CI) 16.54-38.44; P < 0.00001) and obtained a less resected prostate weight (WMD - 11.72 g; 95% CI - 21.75 to - 1.70; P = 0.02), patients undergoing laser prostatectomy benefited from significantly less hemoglobin decline (- 0.97 g/dL; 95% CI - 1.31 to - 0.64; P < 0.00001), shorter time of catheterization (WMD - 3.67 days; 95% CI - 5.60 to - 1.75; P = 0.0002), shorter length of hospital stay (WMD - 4.75 days; 95% CI - 6.57 to - 2.93; P < 0.00001), and less blood transfusion (odds ratio 0.10; 95% CI 0.03 to 0.35; P = 0.0003). During postoperative follow-up, no significant difference was observed between the two groups in IPSS, QoL, Qmax, and PVR. Both transurethral laser prostatectomy and OSP are safe and effective for large prostates that require prostate resection. Taking into account of less blood loss, shorter catheterization time and hospital stay, and less blood transfusion, transurethral laser prostatectomy may be a better treatment for patients with large prostates.

Worldwide aflatoxin contamination of agricultural products and foods: From occurrence to control.

Aflatoxins represent a global public health and economic concern as they are responsible for significant adverse health and economic issues affecting consumers and farmers worldwide. Produced by fungal species from the Aspergillus genus, aflatoxins are a toxic, mutagenic, and carcinogenic group of fungal metabolites that routinely contaminate food and agricultural products. Climate and diet are essential factors in the aflatoxin contamination of food and subsequent human exposure process. Countri es with warmer climates and staple foods that are aflatoxin-susceptible shoulder a substantial portion of the global aflatoxins burden. Enactment of regulations, prevention of pre- and postharvest contamination, decontamination, and detoxification have been used to prevent human dietary exposure to aflatoxin. Exploiting their chemical and structural properties, means are devised to detect and quantify aflatoxin presence in foods. Herein, recent developments in several important aspects impacting aflatoxin contamination of the food supply, including: fungal producers of the toxin, occurrence in food, worldwide regulations, detection methods, preventive strategies, and removal and degradation methods were reviewed and presented. In conclusion, aflatoxin continues to be a major food safety problem, especially in developing countries where regulatory limits do not exist or are not adequately enforced. Finally, knowledge gaps and current challenges in each discussed aspect were identified, and new solutions were proposed.

Development of mesh-type Fenton-like Cu/Fex/γ-Al2O3/Al catalysts and application for catalytic degradation of dyes.

The application of nanoparticle heterogeneous Fenton-like catalysts is limited due to the requirement of filtration after reaction and possible secondary pollution. In this work, a novel mesh-type monolithic Fenton-like Cu/Fex/γ-Al2O3/Al catalyst was developed for the degradation of dyes. The Cu and Fe species are uniformly dispersed on the mesh-type anodic monolithic γ-Al2O3 supports, and the results of scanning electron microscopy and X-ray diffractometry analysis show that Fe can reduce the particle size of Cu over γ-Al2O3. The activity results show that the degradation rate of rhodamine B (RhB) reached 99.5% within 1 h using 4 × 6 cm Cu12.0/Fe2.0/γ-Al2O3/Al catalyst with 1,200 ppm H2O2 at 50 °C. The important role of •OH as a reactive oxidant was confirmed through electron spin-resonance spectroscopy and radical scavenging experiment. The hydrogen temperature programmed reduction suggests the high redox ability of Cu/Fe bimetallic catalyst is beneficial to the production of •OH. The Cu/Fe bimetallic catalyst shows excellent recyclability in a 10-cycle experiment, the degradation rate of RhB was maintained at 98% and the leaching amount of metals was lower than 0.7 mg/L. The mesh-type catalyst will be easily applied for the continuous wastewater treatment because it does not need filtration for recovery.

[Research progress on chemical constituents and pharmacological activities of Hovenia].

The medicinal parts of Hovenia include the branches, leaves, seeds and fruits with inflorescence axis. This plant has been used with a long history as traditional herbal medicine for the treatment of alcoholism and liver protection. Modern pharmacological research shows that the crude extracts or pure compounds from Hovenia have anti-alcoholism, hepatoprotective, anti-hyperuricemia, anti-viral and anti-tumor activities, etc. Previous phytochemical studies have indicated that flavonoids, triterpenoid saponins, phenylpropanoids and polysaccharides are the major constituents in this plant. In this paper, we systematically summarized and analyzed the chemical constituents and pharmacological activities of Hovenia, providing the scientific evidences for the rational use and comprehensive development of Hovenia.

Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in RAW264.7 cells.

Ganoderma lucidum immunomodulatory protein (FIP-glu) is an active ingredient with potential immunoregulatory functions. The study was conducted to explore the immunomodulatory activities of recombinant FIP-glu (rFIP-glu) and its possible mechanism in macrophage RAW264.7 cells. In vitro assays of biological activity indicated that rFIP-glu significantly activated RAW264.7 cells and possessed proinflammatory and anti-inflammatory abilities. RNA sequencing analysis and Western blot analysis showed that macrophage activation involved PI3K/Akt and MAPK pathways. Furthermore, real-time quantitative polymerase chain reaction indicated that the PI3K inhibitor LY294002 blocked the messenger RNA (mRNA) levels of MCP-1 (CCL-2), the MEK1/2 inhibitor U0126 reduced the mRNA levels of TNF-α and MCP-1 (CCL-2), and the JNK1/2/3 inhibitor SP600125 prevented the upregulation of inducible nitric oxide synthase mRNA in rFIP-glu-induced cells. rFIP-glu did not mediate these inflammatory effects through a general pathway but rather through a different pathway for a different inflammatory mediator. These data imply that rFIP-glu possessed immunomodulatory activity in macrophages, which was mediated through PI3K/Akt and MAPK pathways.

Porcine Deltacoronavirus Engages the Transmissible Gastroenteritis Virus Functional Receptor Porcine Aminopeptidase N for Infectious Cellular Entry.

Identification of cellular receptors used by coronavirus (CoV) entry into the host cells is critical to an understanding of pathogenesis and to development of intervention strategies. The fourth CoV genus, Deltacoronavirus, evolutionarily related to the Gammacoronavirus, has just been defined recently. In the current study, we demonstrate that porcine aminopeptidase N (pAPN) acts as a cross-genus CoV functional receptor for both enteropathogenic porcine deltacoronovirus (PDCoV) and alphacoronovirus (AlphaCoV) (transmissible gastroenteritis virus [TGEV]) based upon three lines of evidence. First, the soluble S1 protein of PDCoV bound to the surface of target porcine cell lines known to express pAPN as efficiently as TGEV-S1, which could be blocked by soluble pAPN pretreatment. Second, both PDCoV-S1 and TGEV-S1 physically recognized and interacted with pAPN by coimmunoprecipitation in pAPN cDNA-transfected cells and by dot blot hybridization assay. Finally, exogenous expression of pAPN in refractory cells conferred susceptibility to PDCoV-S1 binding and to PDCoV entry and productive infection. PDCoV-S1 appeared to have a lower pAPN-binding affinity and likely consequent lower infection efficiency in pAPN-expressing refractory cells than TGEV-S1, suggesting that there may be differences between these two viruses in the virus-binding regions in pAPN. This study paves the way for dissecting the molecular mechanisms of PDCoV-host interactions and pathogenesis as well as facilitates future vaccine development and intervention strategies against PDCoV infection.IMPORTANCE The emergence of new human and animal coronaviruses is believed to have occurred through interspecies transmission that is mainly mediated by a species-specific receptor of the host. Among the four genera of the Coronavirinae, a couple of functional receptors for the representative members in the genera Alphacoronavirus and Betacoronavirus have been identified, whereas receptors for Gammacoronavirus and Deltacoronavirus, which are believed to originate from birds, are still unknown. Porcine coronaviruses, including the newly discovered porcine deltacoronavirus (PDCoV) associated with diarrhea in newborn piglets, have posed a serious threat to the pork industry in Asia and North America. Here, we report that PDCoV employs the alphacoronavirus TGEV functional receptor porcine aminopeptidase N (pAPN) for cellular entry, demonstrating the usage of pAPN as a cross-genus CoV functional receptor. The identification of the PDCoV receptor provides another example of the expanded host range of CoV and paves the way for further investigation of PDCoV-host interaction and pathogenesis.

Cellular internalization and trafficking of 20 KDa human growth hormone.

Twenty kilodalton human growth hormone (20K-GH) is the second most abundant GH isoform after the twenty-two kilodalton human growth hormone (22 K-GH) isoform. 20K-GH exhibits similar but not identical physiological activities as that of 22K-GH. The cell behaviour of 22K-GH has been extensively studied, but little or no information has been reported regarding 20K-GH. Here, we focussed on the internalization of 20K-GH. We found that the internalization of 20K-GH is rapid and occurs in a time- and dose-dependent manner. 20K-GH internalization is mediated by GHR. It appears that the internalization of 20K-GH and GHR into the cytoplasm is mediated by clathrin and/or caveolin. The current study indicates that 20K-GH can internalize into the cytoplasm and suggests that the internalized 20K-GH may exhibit different functions from those of 22K-GH.

Retrospective analysis of risk factors of slide positivity among febrile patients in the Salween river valley of Shan Special Region II, northern Myanmar.

BACKGROUND: In Myanmar, epidemiological conditions have been unclear due to a lack of accurate data. In 2014 and 2016, malaria outbreaks occurred in the Shan Special Region II (SSR2). It was reported that these outbreaks were caused by malaria patients from the Salween River Valley (SRV), but further research is needed to confirm these reports. To examine the risks of malaria infection in the SSR2 section of the SRV, this paper offers a retrospective analysis based on the data we collected in 2009. METHODS: A multivariate logistic model was utilized to analyze risk factors associated with the slide positivity of 2009. Results of the investigation in 2009 were compared with updated data. RESULTS: The number of slide positivity was 91 (24.7%, 95% confidence interval [CI], 20.3-29.4%) among 369 people who had fever 2 weeks ago of the survey, including 74 (20.1%; 95%CI, 16.1-24.5%) cases of P. falciparum, 13 (3.5%; 95%CI, 1.9-5.9%) of P.vivax and 4 (1.1%, 95%CI, 0.3-2.8%) of P. malariae. The adjusted odds ratio (OR) was 99.8 (95% CI, 24.7-887.7) for patients' age < 15 years, 6.61 (95%CI, 3.57-10.49) for people living at an altitude of < 800 m, 6.35 (95%CI, 2.45-23.27) for people lacking knowledge on malaria transmission and knowledge on symptoms, 2.10 (95%CI, 1.22-5.11) for people taking no measures against mosquito bites and 5.55 (95%CI, 2.65-13.05) for people delaying treatment. Compared with annual parasitic incidences 13.80 per 10,000 person-years (422/305733) in 2014, 2.36 per 10,000 person-years (73/309004) in 2015 and 5.25 per 10,000 person-years (164/312310) in 2015, malaria burden is reduced. CONCLUSION: Age, lower altitude, a lack of knowledge about malaria transmission and symptoms, inaction of measures against mosquito bites and delayed treatment-seeking were independent risk factors for slide positivity. These results indicate that malaria transmission was likely within housing settlements in the SRV, and that the transmission rates within the SRV are higher than in other areas. In order to eliminate malaria, it is important for people to obtain qualified treatment to contain artemisinin resistance. TRIAL REGISTRATION: Trial registration number: ChiCTR-COC-17012522 . Retrospectively registered 31 August 2017.