Publications by authors named "Min Li"

5,782 Publications

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PEDOT:PSS/CuCl Composite Hole Transporting Layer for Enhancing the Performance of 2D Ruddlesden-Popper Perovskite Solar Cells.

J Phys Chem Lett 2022 Jun 27:6101-6109. Epub 2022 Jun 27.

State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.

Poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) is a popular hole transport layer (HTL) in 2D Ruddlesden-Popper (RP) perovskite solar cell (PSCs) due to its highly conductive, transparent, and solution-processable characteristics. However, fundamental questions such as its strong acidity or mismatched energy level with the 2D RP photoactive layer often restrict the performance and stability of devices. Herein, copper chloride (CuCl), a common direct band gap semiconductor, is doped into PEDOT:PSS, lowering the acidity and tuning the work function of PEDOT:PSS. Due to the improved wettability and the existing chloride in the PEDOT:PSS/CuCl composite substrate, the coated 2D perovskite films exhibit uniform morphology, vertically oriented crystal growth, and enhanced crystallinity. In comparison with controlled devices, the PEDOT:PSS/CuCl based inverted 2D RP PSCs show a maximum power conversion efficiency of 13.36% and long-term stability. The modified PEDOT:PSS overcomes intrinsic imperfections by doping CuCl, indicating that it has a lot of promise for mass production in electrical devices.
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http://dx.doi.org/10.1021/acs.jpclett.2c01399DOI Listing
June 2022

Predicting the loss to follow-up (LTFU) of HIV/AIDS patients in China using a recency-frequency (RF) model.

Authors:
Min Li Qunwei Wang

HIV Med 2022 Jun 27. Epub 2022 Jun 27.

College of Economics and Management, Nanjing University of Aeronautics and Astronautics, Nanjing, China.

Background: We constructed a recency-frequency (RF) model for predicting the loss to follow-up (LTFU) in HIV/AIDS patients in China.

Methods: Data on HIV/AIDS outpatients in the research unit from 1 August 2009 to 30 September 2020 and from 1 October to 31 December 2020 were exported as the observation and prediction datasets, respectively. The classic recency-frequency-monetary (RFM) model was expanded into RFm, RF, RFL and RFmL models. In the observation dataset, the best predictive model was obtained using k-means clustering and C5.0 verification. Then, two rounds of k-means modelling were performed on the best model: data with R ≤ 6 months were retained, randomly divided into a training set (70%) and a testing set (30%) and used to perform the second round of modelling to subdivide the churn and non-churn patients. Next, an ANN algorithm was used to predict LTFU, and the confusion matrix with prediction datasets was constructed.

Results: The observation and prediction datasets included 16 949 and 10 748 samples, respectively. The RF model with three clusters and a quality of 0.82 was the best predictive model. From the observation set, 13 799 samples were retained, and the model accuracy was 100% on the training and testing sets. These 13 799 samples were subdivided into 1563 samples of churn patients and 12 216 samples of non-churn patients. The accuracy of ANN prediction was 99.89%. The accuracy and precision of the confusion matrix were 85.41% and 99.76%, respectively.

Conclusion: The RF model is effective in predicting the LTFU of HIV/AIDS patients in China and preventing its occurrence.
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http://dx.doi.org/10.1111/hiv.13324DOI Listing
June 2022

Poria cocos polysaccharides rescue pyroptosis-driven gut vascular barrier disruption in orderv to alleviates non-alcoholic steatohepatitis.

J Ethnopharmacol 2022 Jun 23:115457. Epub 2022 Jun 23.

Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510000, Guangdong, China. Electronic address:

Ethnopharmacological Relevance: Poria cocos polysaccharides (PCP) are abundant in Poria cocos (Schw.) Wolf (Poria). This is a common traditional Chinese medicine used to treat gastrointestinal and liver diseases. Poria cocos dispel dampness and enhance gastrointestinal functions, strongly affecting the treatment of non-alcoholic fatty liver disease. Still, the mechanism is not yet clear.

Aim Of The Study: The latest research found that protecting the integrity of the intestinal barrier can slow down the progression of non-alcoholic fatty liver disease (NAFLD). Hence, our research ought to explore the protective mechanism of PCP on the intestinal barrier under a high-fat diet and to clarify the relationship between intestinal barrier damage and steatohepatitis.

Materials And Methods: H&E staining was done to evaluate pathological damage, whereas Nile red and oil red O staining was conducted to evaluate hepatic fat infiltration. Immunofluorescence staining and immunohistochemical staining were used to detect protein expression and locations. Bone marrow-derived macrophages were isolated for in vitro experiments. ONOO- and ROS fluorescent probes and MDA, SOD, and GSH kits assessed the levels of nitrogen and oxidative stress. LPS levels were detected with a Limulus Amebocyte Lysate assay. The Western blot analysis and reverse transcription-quantitative PCR detected the expression of related proteins and genes. The Elisa kit detected the level of the inflammatory factors in the cell supernatant. For the vivo NAFLD experiments, in briefly, mice were randomly chosen to receive either a High-fat diet or control diet for 12 weeks. Drug treatments started after 4 weeks of feeding. Zebrafish larvae were raised separately in fish water or 7 mM thioacetamide as the control or model group for approximately 72 h. In the therapy groups, different concentrations of PCP were added to the culture environment at the same time.

Results: In zebrafish, we determined the safe concentration of PCP and found that PCP could effectively reduce the pathological damage in the liver and intestines induced by the NAFLD model. In mice, PCP could slow down weight gain, hyperlipidemia, and liver steatosis caused by a high-fat diet. More importantly, PCP could reduce the destruction of the gut-vascular barrier and the translocation of endotoxins caused by a high-fat diet. Further, we found that PCP could inhibit intestinal pyroptosis by regulating PARP-1. Pyroptosis inhibitors, such as MCC950, could effectively protect the intestinal and liver damage induced by a high-fat diet. We also found that pyroptosis mainly occurred in intestinal macrophages. PCP could effectively improve the survival rate of bone marrow-derived macrophages in a high-fat environment and inhibit pyroptosis.

Conclusions: These results indicated that PCP inhibited the pyroptosis of small intestinal macrophages to protect the intestinal barrier integrity under a high-fat diet. This resulted in decreased endotoxin translocation and progression of steatohepatitis.
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http://dx.doi.org/10.1016/j.jep.2022.115457DOI Listing
June 2022

Efficient phosphorus recovery as struvite by microbial electrolysis cell with stainless steel cathode: Struvite purity and experimental factors.

Sci Total Environ 2022 Jun 23:156914. Epub 2022 Jun 23.

Beijing Key Lab for Source Control Technology of Water Pollution, College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, China; Engineering Research Center for Water Pollution Source Control & Eco-remediation, College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, China. Electronic address:

Phosphorus (P) recovery from waste streams is an essential choice due to the coming global P crisis. One promising solution is to recover P by microbial electrolysis cell (MEC). Both the P recovery effectiveness and product quality are of critical importance for application. In this study, a two-chamber MEC was constructed and the effects of applied voltage, NaAc concentration, Mg/P molar ratio, N/P molar ratio, and initial P concentration on P recovery and product purity were explored. The maximum P recovery efficiency of 99.64 % and crystal accumulation rate over 106.49 g/m-d were achieved. Struvite (MAP) was confirmed as the final recovered product and the purity obtained could reach up to 99.95 %. Besides, higher applied voltage, N/P molar ratio and initial P concentration could promote P recovery efficiency, while the purity of MAP showed correlation with applied voltage, Mg/P molar ratio, N/P molar ratio and initial P concentration. The correlation between NaAc concentration and both of the above was not very significant. A lower energy consumption of 4.1 kWh/kg P was observed at the maximum P recovery efficiency. In addition, the efficiency of P recovery from real wastewater also could reach nearly 88.25 %. These results highlight the promising potential of efficient phosphorus recovery from P-rich wastewater by MEC.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156914DOI Listing
June 2022

Can agricultural land use alter the responses of soil biota to antibiotic contamination?

J Hazard Mater 2022 Jun 11;437:129350. Epub 2022 Jun 11.

School of Ecology and Environmental Sciences, Yunnan University, Kunming 650500, China; State Key Laboratory of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Antibiotics accumulate in soils via various agricultural activities, endangering soil biota that play fundamental roles in maintaining agroecosystem function. However, the effects of land-use heterogeneity on soil biota tolerance to antibiotic stresses are not well understood. In this study, we explored the relationships between antibiotic residues, bacterial communities, and earthworm populations in areas with different land-use types (forest, maize, and peanut fields). The results showed that antibiotic levels were generally higher in maize and peanut fields than in forests. Furthermore, land use modulated the effects of antibiotics on soil bacterial communities and earthworm populations. Cumulative antibiotic concentrations in peanut fields were negatively correlated with bacterial diversity and earthworm abundance, whereas no significant correlations were detected in maize fields. In contrast, antibiotics improved bacterial diversity and richness in forest soils. Generally, earthworm populations showed stronger tolerance to antibiotics than did soil bacterial communities. Agricultural land use differentially modified the responses of the soil bacterial community and earthworm population to antibiotic contamination, and earthworms might provide an alternative for controlling antibiotic contamination.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129350DOI Listing
June 2022

Optical Fiber-Based Recording of Climbing Fiber Ca Signals in Freely Behaving Mice.

Biology (Basel) 2022 Jun 13;11(6). Epub 2022 Jun 13.

Center for Neurointelligence, School of Medicine, Chongqing University, Chongqing 400030, China.

The olivocerebellar circuitry is important to convey both motor and non-motor information from the inferior olive (IO) to the cerebellar cortex. Several methods are currently established to observe the dynamics of the olivocerebellar circuitry, largely by recording the complex spike activity of cerebellar Purkinje cells; however, these techniques can be technically challenging to apply in vivo and are not always possible in freely behaving animals. Here, we developed a method for the direct, accessible, and robust recording of climbing fiber (CF) Ca signals based on optical fiber photometry. We first verified the IO stereotactic coordinates and the organization of contralateral CF projections using tracing techniques and then injected Ca indicators optimized for axonal labeling, followed by optical fiber-based recordings. We demonstrated this method by recording CF Ca signals in lobule IV/V of the cerebellar vermis, comparing the resulting signals in freely moving mice. We found various movement-evoked CF Ca signals, but the onset of exploratory-like behaviors, including rearing and tiptoe standing, was highly synchronous with recorded CF activity. Thus, we have successfully established a robust and accessible method to record the CF Ca signals in freely behaving mice, which will extend the toolbox for studying cerebellar function and related disorders.
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http://dx.doi.org/10.3390/biology11060907DOI Listing
June 2022

Decipher the molecular descriptors and mechanisms controlling sulfonamide adsorption onto mesoporous carbon: Density functional theory calculation and partial least-squares path modeling.

J Hazard Mater 2022 Aug 6;436:129299. Epub 2022 Jun 6.

The Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871, China; College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China; International Joint Laboratory for Regional Pollution Control, Ministry of Education, Beijing 100871, China; State Environmental Protection Key Laboratory of All Material Fluxes in River Ecosystems, Beijing 100871, China. Electronic address:

Mesoporous carbons (MCs) exhibit excellent removal efficiencies to various organic chemicals. However, how the properties of chemicals influence the adsorption mechanisms and further determine their adsorption onto MCs are poorly understood. We investigated the adsorption of 22 sulfonamides (SAs) onto four MCs, and further uncovered the major molecular descriptors and adsorption mechanisms influencing the adsorption by density functional theory (DFT) and partial least-squares path modeling (PLS-PM). The results revealed that the excess molar refraction (E), McGowan's molar volume (V), energy of the highest occupied molecular orbital (E), hardness (H), and most positive net charge on carbon atom (Q) were identified as the indirect factors affecting the distribution coefficient (logK), by influencing the BE(π-π), BE(H), and logK. BE(π-π) and logK displayed significant direct impacts on logK (p < 0.05), while BE(H) showed insignificant direct influences on logK (p > 0.05). The PLS-PM results indicate the main driving forces for SAs adsorption including π-π interactions, hydrophobic effects, and hydrogen bonding. This study provides a new perspective on revealing the adsorption mechanisms, and the identified factors can be used to develop the quantitative model to further predict the adsorption of SAs onto MCs.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129299DOI Listing
August 2022

The pro-inflammatory effect of Staphylokinase contributes to community-associated Staphylococcus aureus pneumonia.

Commun Biol 2022 Jun 23;5(1):618. Epub 2022 Jun 23.

Department of Laboratory Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pneumonia caused by community-associated Staphylococcus aureus (CA-SA) has high morbidity and mortality, but its pathogenic mechanism remains to be further investigated. Herein, we identify that staphylokinase (SAK) is significantly induced in CA-SA and inhibits biofilm formation in a plasminogen-dependent manner. Importantly, SAK can enhance CA-SA-mediated pneumonia in both wild-type and cathelicidins-related antimicrobial peptide knockout (CRAMP) mice, suggesting that SAK exacerbates pneumonia in a CRAMP-independent manner. Mechanistically, SAK induces pro-inflammatory effects, especially in the priming step of NLRP3 inflammasome activation. Moreover, we demonstrate that SAK can increase K efflux, production of reactive oxygen species production, and activation of NF-κB signaling. Furthermore, the NLRP3 inflammasome inhibitor can counteract the effective of SAK induced CA-SA lung infection in mice. Taken together, we speculate that SAK exacerbates CA-SA-induced pneumonia by promoting NLRP3 inflammasome activation, providing new insights into the pathogenesis of highly virulent CA-SA and emphasizes the importance of controlling inflammation in acute pneumonia.
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http://dx.doi.org/10.1038/s42003-022-03571-xDOI Listing
June 2022

Engineering the hydroxyl content on aluminum oxyhydroxide nanorod for elucidating the antigen adsorption behavior.

NPJ Vaccines 2022 Jun 23;7(1):62. Epub 2022 Jun 23.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024, Dalian, China.

The interaction between the aluminum salt-based adjuvants and the antigen in the vaccine formulation is one of the determining factors affecting the immuno-potentiation effect of vaccines. However, it is not clear how the intrinsic properties of the adjuvants could affect this interaction, which limits to benefit the improvement of existing adjuvants and further formulation of new vaccines. Here, we engineered aluminum oxyhydroxide (AlOOH) nanorods and used a variety of antigens including hepatitis B surface antigen (HBsAg), SARS-CoV-2 spike protein receptor-binding domain (RBD), bovine serum albumin (BSA) and ovalbumin (OVA) to identify the key physicochemical properties of adjuvant that determine the antigen adsorption at the nano-bio interface between selected antigen and AlOOH nanorod adjuvant. By using various physicochemical and biophysical characterization methods, it was demonstrated that the surface hydroxyl contents of AlOOH nanorods affected the adsorptive strength of the antigen and their specific surface area determined the adsorptive capacity of the antigen. In addition, surface hydroxyl contents had an impact on the stability of the adsorbed antigen. By engineering the key intrinsic characteristics of aluminum-based adjuvants, the antigen adsorption behavior with the aluminum adjuvant could be regulated. This will facilitate the design of vaccine formulations to optimize the adsorption and stability of the antigen in vaccine.
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http://dx.doi.org/10.1038/s41541-022-00495-9DOI Listing
June 2022

Asparagine synthetase regulates lung-cancer metastasis by stabilizing the β-catenin complex and modulating mitochondrial response.

Cell Death Dis 2022 Jun 23;13(6):566. Epub 2022 Jun 23.

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China.

The availability of asparagine is the limitation of cell growth and metastasis. Asparagine synthetase (ASNS) was an essential enzyme for endogenous asparagine products. In our study, ASNS-induced asparagine products were essential to maintain tumor growth and colony formations in vitro. But mutated ASNS which defected endogenous asparagine products still upregulated cell invasiveness, which indicated that ASNS promoted invasiveness by alternative pathways. Mechanically, ASNS modulated Wnt signal transduction by promoting GSK3β phosphorylation on ser9 and stabilizing the β-catenin complex, as result, ASNS could promote more β-catenin translocation into nucleus independent of endogenous asparagine. At the same time, ASNS modulated mitochondrial response to Wnt stimuli with increased mitochondrial potential and membrane fusion. In summary, ASNS promoted metastasis depending on Wnt pathway and mitochondrial functions even without endogenous asparagine products.
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http://dx.doi.org/10.1038/s41419-022-05015-0DOI Listing
June 2022

Structural elucidation of two novel degradants of lurasidone and their formation mechanisms under free radical-mediated oxidative and photolytic conditions via liquid chromatography-photodiode array/ultraviolet-tandem mass spectrometry and one-dimensional/two-dimensional nuclear magnetic resonance spectroscopy.

J Mass Spectrom 2022 Jul;57(7):e4871

Center of Excellence for Modern Analytical Technologies (CEMAT), Huahai Pharmaceutical Co., Ltd., Linhai, Zhejiang, China.

Lurasidone is an antipsychotic drug clinically used for the treatment of schizophrenia and bipolar disorder. During a mechanism-based forced degradation study of lurasidone, two novel degradation products were observed under free radical-mediated oxidative (via AIBN) and solution photolytic conditions. The structures of the two novel degradants were identified through an approach combining HPLC, LC-MS (n = 1, 2), preparative HPLC purification and NMR spectroscopy. The degradant formed under the free radical-mediated condition is an oxidative degradant with half of the piperazine ring cleaved to form two formamides; a mechanism is proposed for the formation of the novel N,N'-diformyl degradant, which should be readily applicable to other drugs that contain a piperazine moiety that is widely present in drug molecules. The degradant observed under the solution photolytic condition is identified as the photo-induced isomer of lurasidone with the benzisothiazole ring altered into a benzothiazole ring.
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http://dx.doi.org/10.1002/jms.4871DOI Listing
July 2022

Dietary α-lipoic acid alleviates deltamethrin-induced immunosuppression and oxidative stress in northern snakehead (Channa argus) via Nrf2/NF-κB signaling pathway.

Fish Shellfish Immunol 2022 Jun 20;127:228-237. Epub 2022 Jun 20.

Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Provincial Key Laboratory of Animal Nutrition and Feed Science, College of Animal Science and Technology, Jilin Agriculture University, Changchun, 130118, China. Electronic address:

The goal of the study was to determine the ameliorative effects of dietary alpha-lipoic acid (α-LA) on deltamethrin (DEL)-induced immunosuppression and oxidative stress in northern snakehead (Channa argus). The northern snakeheads (15.38 ± 0.09 g) were exposed to DEL (0.242 μg/L) and fed with diets supplemented α-LA at 300, 600, and 900 mg/kg. After the 28-day exposure test, we obtained the following results: i) α-LA alleviates DEL-induced liver injury by reversing the increase of the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver cytochrome P450 enzymes (Cytochrome P450 (cyp)1a and cyp1b) expression levels. ii) α-LA can reverse the DEL-induced reduction of serum complement 4 (C4), C3, immunoglobulin M (IgM), and lysozyme (LYS) levels and the increase of liver and intestine nuclear factor kappa B (nf-κb) p65, tumor necrosis factor (tnf)-α, interleukin (il)-1β, il-8, and il-6 gene expressions, while il-10 expression levels showed the opposite result. iii) α-LA reversed the reduction of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione-S-transferase (GST) and glutathione peroxidase (GSH-Px) levels in the liver and intestine induced by DEL, while malondialdehyde (MDA) showed the opposite result. iv) α-LA reversed the reduction of Cu/Zn sod, nuclear factor erythroid 2-related factor 2 (nrf2), NAD (P)H: quinone oxidoreductase (nqo)1, and heme oxygenase (ho)-1 antioxidant gene expression levels in the liver and intestine induced by DEL. Therefore, our study indicated that optimal α-LA (600 mg/kg) could attenuate DEL-induced toxicity (including liver damage, immunotoxicity, and oxidative stress) in northern snakehead via Nrf2/NF-κB signaling pathway. This is the first research that explores the alleviated effects of α-LA on DEL-induced toxicity damage in fish. This study provides a positive measure to reduce the toxicity damage caused by DEL to aquatic animals, and provides a theoretical basis for exploring the regulation mechanism of α-LA in toxic substances.
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http://dx.doi.org/10.1016/j.fsi.2022.06.029DOI Listing
June 2022

Noval porous phosphate-solubilizing bacteria beads loaded with BC/nZVI enhanced the transformation of lead fractions and its microecological regulation mechanism in soil.

J Hazard Mater 2022 Jun 17;437:129402. Epub 2022 Jun 17.

Innovation Academy for Green Manufacture, Key Laboratory of Green Process and Engineering, Beijing Engineering Research Centre of Process Pollution Control, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address:

Soil lead pollution becomes a serious environmental problem. Microbial remediation has received widespread attentions due to high efficiency and no secondary pollution. In this research, a noval porous spherical phosphate-solubilizing bacteria bead loaded with biochar/nZVI (Bio-bead) was used to passivate lead in soil, and the effects and microecological regulation mechanisms of this process were also investigated. The results showed that the pH, OM, and AP of soil in the Bio-bead group were increased and the ORP was decreased over time compared with the blank group. The proportion of stable (oxidizable and residue) fractions of lead in Bio-bead group (45%) was much higher than that of the blank group (35%). In addition, the result of microbial community structure showed that Bio-beads did not change the species of dominant bacterial, excepting the abundance of Pseudomonas increased significantly and the abundance of Sphingomonas reduced during remediation. Redundancy analysis showed that pH, OM, AP and the ratio of residual and oxidizable fractions lead in soil were positively correlated with the abundance of Pseudomonas, while ORP was negatively correlated with the abundance of Pseudomonas. These findings have proved that Bio-bead is a potential strategy for remediation of lead-contaminated soil even in complexed soils.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129402DOI Listing
June 2022

Codelivery of SARS-CoV-2 Prefusion-Spike Protein with CBLB502 by a Dual-Chambered Ferritin Nanocarrier Potentiates Systemic and Mucosal Immunity.

ACS Appl Bio Mater 2022 Jun 23. Epub 2022 Jun 23.

Shanghai Public Health Clinical Center, Fudan University, 201058 Shanghai, China.

Thousands of breakthrough infections are confirmed after intramuscular (i.m.) injection of the approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two major factors might contribute to breakthrough infections. One is the emergence of mutant variants of SARS-CoV-2, and the other is that i.m. injection has an inefficient ability to activate mucosal immunity in the upper respiratory tract. Here, we devised a dual-chambered nanocarrier that can codeliver the adjuvant CBLB502 with prefusion-spike (pre-S) onto a ferritin nanoparticle. This vaccine enabled enhanced systemic and local mucosal immunity in the upper and lower respiratory tract. Further, codelivery of CBLB502 with pre-S induced a Th1/Th2-balanced immunoglobulin G response. Moreover, the codelivery nanoparticle showed a Th1-biased cellular immune response as the release of splenic INF-γ was significantly heightened while the level of IL-4 was elevated to a moderate extent. In general, the developed dual-chambered nanoparticle can trigger multifaceted immune responses and shows great potential for mucosal vaccine development.
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http://dx.doi.org/10.1021/acsabm.2c00328DOI Listing
June 2022

Matrix Effect of Diverse Biological Samples Extracted with Different Extraction Ratios on the Detection of β--Methylamino-L-Alanine by Two Common LC-MS/MS Analysis Methods.

Toxins (Basel) 2022 Jun 2;14(6). Epub 2022 Jun 2.

College of Environmental Science and Engineering, Ocean University of China, Qingdao 266100, China.

Neurotoxin β--methylamino-L-alanine (BMAA) is hypothesized as an important pathogenic factor for neurodegenerative diseases such as amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC). Comparative study on the accuracy of BMAA analyzed by the regular LC-MS/MS methods is still limited for different biological matrices. In this study, a free-BMAA sample of cyanobacterium and BMAA-containing positive samples of diatom, mussel, scallop, and oyster were extracted with varied extraction ratios (ER) ranging from 1:20 to 1:2000. These extracts were then purified by MCX cartridges. After SPE purification, these different biological samples were analyzed by two common LC-MS/MS analysis methods, a direct analysis without derivatization by a hydrophilic interaction liquid chromatography (HILIC)-MS/MS and pre-column 6-aminoquinolyl--hydroxysuccinimidyl carbamate (AQC) derivatization combined with a C18 column. The results suggested that the recoveries of BMAA spiked in the cyanobacterial sample were close to 100% in the total soluble form extracts with the ER of 1:100 (g/mL) and the precipitated bound form extracts with the ER of 1:500. The recommended ER for the precipitated bound form of BMAA in diatoms and the total soluble form of BMAA in mollusks are 1:500 and 1:50, respectively. The quantitative results determined by the AQC derivatization method were lower than those determined by the direct analysis of the HILIC method in diatom and mollusk samples. The results of the HILIC method without the derivatization process were closer to the true value of BMAA in cyanobacteria. This work contributes to the performance of the solid-phase extraction (SPE) purification protocol and the accuracy of BMAA analysis by LC-MS/MS in diverse biological samples.
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http://dx.doi.org/10.3390/toxins14060387DOI Listing
June 2022

Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells.

Mol Cancer 2022 Jun 22;21(1):133. Epub 2022 Jun 22.

Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, Jiangsu, China.

Background: Undifferentiated carcinoma with osteoclast-like giant cells (OGCs) of pancreas (UCOGCP) is a rare subtype of pancreatic ductal adenocarcinoma (PDAC), which had poorly described histopathological and clinical features.

Methods: In this study, single-cell RNA sequencing (scRNA-seq) was used to profile the distinct tumor microenvironment of UCOGCP using samples obtained from one UCOGCP patient and three PDAC patients. Bioinformatic analysis was carried out and immunohistochemical (IHC) staining was used to support the findings of bioinformatic analysis. After quality control of the raw data, a total of 18,376 cells were obtained from these four samples for subsequent analysis. These cells were divided into ten main cell types following the Seurat analysis pipeline. Among them, the UCOGCP sample displayed distinct distribution patterns from the rest samples in the epithelial cell, myeloid cell, fibroblast, and endothelial cell clusters. Further analysis supported that the OGCs were generated from stem-cell-like mesenchymal epithelial cells (SMECs).

Results: Functional analysis showed that the OGCs cluster was enriched in antigen presentation, immune response, and stem cell differentiation. Gene markers such as LOX, SPERINE1, CD44, and TGFBI were highly expressed in this SMECs cluster which signified poor prognosis. Interestingly, in myeloid cell, fibroblasts, and endothelial cell clusters, UCOGCP contained higher percentage of these cells and unique subclusters, compared with the rest of PDAC samples.

Conclusions: Analysis of cell communication depicted that CD74 plays important roles in the formation of the microenvironment of UCOGCP. Our findings illustrated the genesis and function of OGCs, and the tumor microenvironment (TME) of UCOGCP, providing insights for prognosis and treatment strategy for this rare type of pancreatic cancer.
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http://dx.doi.org/10.1186/s12943-022-01596-8DOI Listing
June 2022

Nuclear receptor estrogen-related receptor gamma suppresses colorectal cancer aggressiveness by regulating Wnt/β-catenin signalling.

Carcinogenesis 2022 Jun 21. Epub 2022 Jun 21.

Department of Pathology, The First Affiliated Hospital, Shandong First Medical University& Shandong Qianfoshan Hospital, Jinan, Shandong, China.

Colorectal cancer is the predominant cause of cancer-related death worldwide, because of lack of effective therapeutic targets. Estrogen-related receptor gamma (ESRRG), which belongs to the family of nuclear receptors, functions as an important element regulating gene transcription. In our report, we identified ESRRG as a potential tumor suppressor. The decreased level of ESRRG was initially observed in CRC and was highly associated with poor prognosis. ESRRG overexpression abrogated cell growth and metastasis in vitro and in vivo. Mechanistically, ESRRG repressed the epithelial-to-mesenchymal transition (EMT) process and antagonized Wnt signaling by regulating β-catenin degradation. In addition, significant ESRRG hypermethylation was found in CRC and inversely correlated with its expression. Consistently, the expression of ESRRG was induced after treatment with DNA demethylating agent 5-AZA. Taken together, these findings define a tumor-suppressive role of ESRRG in CRC, providing a potential novel therapeutic approach for this cancer.
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http://dx.doi.org/10.1093/carcin/bgac054DOI Listing
June 2022

miR-564: A potential regulator of vascular smooth muscle cells and therapeutic target for aortic dissection.

J Mol Cell Cardiol 2022 Jun 18;170:100-114. Epub 2022 Jun 18.

Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China; Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, 266021, People's Republic of China. Electronic address:

Background: Aortic dissection (AD) is a lethal cardiac disorder and one of the most concerning cardiovascular diseases (CVDs). Increasing evidence indicates that human aortic vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AD, especially related to phenotypic transformation. And notablely, the development of AD is also accompanied by inflammation.

Methods: By using quantitative real-time PCR and fluorescence in situ hybridization (FISH), we detected the expression levels of miR-564 in vitro and in vivo. The effects of miR-564 proliferation and migration were investigated in VSMCs. The downstream targets of miR-564 were found by bioinformatics analyse, and verified in the regulation on VSMCs. An AD murine model was constructed and clinical evaluation was performed to explore the critical roles of miR-564 in vivo. At the same time, the level of inflammation was detected using quantitative real-time PCR and immunofluorescence.

Results: Overexpression of miR-564 inhibited cell proliferation and migration, as well as phenotype switch, with or without platelet-derived growth factor BB (PDGF-BB) treatment, whereas downregulation of miR-564 led to opposite results. Mechanistically, miR-564 directly interacted with the target genes proto-oncogene (SKI) and neurogranin (NRGN) to regulate the biological functions of VSMCs. In particular, animal experiments demonstrated that miR-564 can alleviate the progression of AD mainly through mediating phenotypic swithing and inflammation which was consistent with clinical evaluation.

Conclusions: Our study identified miR-564 as a significant molecule that attenuates AD progression by inhibiting inflammation and VSMCs proliferation, migration and phenotypic transformation, suggesting that it may be a potential therapeutic target for AD.
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http://dx.doi.org/10.1016/j.yjmcc.2022.06.003DOI Listing
June 2022

Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates.

mSphere 2022 Jun 21:e0026022. Epub 2022 Jun 21.

Shanghai Institute of Infectious Disease and Biosecurity, Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan Universitygrid.8547.e, Shanghai, China.

The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual species. In this study, we analyzed the ploidy states of 500 clinical isolates of C. glabrata from four Chinese hospitals and found that approximately 4% of the isolates were in or able to spontaneously switch to an aneuploid (genomic DNA, 1N-2N), diploid (2N), or hyperdiploid (>2N) form under or conditions. Stable diploid cells were identified in 3% of the isolates (15/500). Of particular interest, one clinical strain existed only in the diploid form. Multilocus sequence typing (MLST) assays revealed two major genetic clusters (A and B) of C. glabrata isolates. Most of the isolates (70%) from China belonged to the A cluster, whereas most of the isolates from other countries (such as Iran, Japan, United States, and European countries) belonged to the B cluster. Further investigation indicated that C. glabrata cells of different ploidy forms differed in a number of respects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Additionally, C. glabrata could undergo spontaneous switching between the diploid and haploid forms under both and conditions. Given the absence of an apparent sexual phase, one would expect that the ploidy shifts could function as an alternative strategy that promotes genetic diversity and benefits the ability of the fungus to rapidly adapt to the changing environment. The human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here, we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. To our surprise, we found that the ploidy of a subset of clinical isolates varied dramatically. Some isolates were in or able to switch to an aneuploid, diploid, or hyperdiploid form. C. glabrata cells with different ploidy differed in a number of biological respects, including morphology, antifungal susceptibility, virulence, and global gene expression profile. Given the absence of an apparent sexual phase in this fungus, we propose that ploidy switching could be a strategy for rapid adaptation to environmental changes and could function as an alternative to sexual reproduction.
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http://dx.doi.org/10.1128/msphere.00260-22DOI Listing
June 2022

Preconception reproductive tract infections status and adverse pregnancy outcomes: a population-based retrospective cohort study.

BMC Pregnancy Childbirth 2022 Jun 20;22(1):501. Epub 2022 Jun 20.

NHC Key Lab. of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, 400020, Shanghai, China.

Background: Reproductive tract infections can cause serious adverse outcomes for pregnant women such as spontaneous abortion and preterm birth. However, it is unclear whether maternal reproductive tract infection before pregnancy would also be related to any adverse pregnancy outcomes. This study aims to investigate the association of maternal preconception reproductive tract infections with subsequent adverse pregnancy outcomes.

Methods: A retrospective cohort study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. A total of 57,586 women (57,708 pregnancies) from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project were included. They all took preconception examinations for gonorrhea, chlamydia, trichomoniasis, syphilis, bacterial vaginosis and candidiasis before pregnancy within one year. Primary outcomes included spontaneous abortion (< 28 weeks gestation), preterm birth (< 37 weeks gestation), macrosomia and low birthweight.

Results: Of the 57,708 pregnancies, 2438 (4.22%) had at least one type of reproductive tract infections. Compared with women who were not infected with any reproductive tract infection before pregnancy, women with reproductive tract infections had a higher rate of spontaneous abortion (7.88% vs. 5.62%, p < 0.001). After analyzing by each infection, there were few significant associations between pre-pregnancy infections and adverse outcomes. Preconception syphilis infection was significantly associated with increased odds of spontaneous abortion (aOR = 2.07, 95%CI 1.50-2.85), induced abortion/labour due to medical reasons (aOR = 1.60, 95%CI 1.01-2.54) and preterm birth (aOR = 1.60, 95%CI 1.12-2.30) after adjusting for potential confounders. Preconception trichomoniasis was intended to relate to a higher risk of spontaneous abortion (aOR = 1.65, 95%CI 1.01-2.71), but its impact seemed to be attributed to its co-infection with other RTIs. Women who were chlamydia or bacterial vaginosis positive before pregnancy showed higher odds of macrosomia (aOR = 2.00, 95% CI 1.07-3.74 for chlamydia; aOR = 1.58, 95% CI 1.06-2.34 for bacterial vaginosis). Preconception bacterial vaginosis might also be associated with higher risks of very preterm birth (aOR = 2.16, 95%CI 1.23-3.78) and large for gestational age (aOR = 1.36, 95%CI 1.02-1.81).

Conclusions: Women with infections of the genital tract before pregnancy might also have increased risks of subsequent adverse outcomes including spontaneous abortion, preterm birth and macrosomia.
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http://dx.doi.org/10.1186/s12884-022-04836-3DOI Listing
June 2022

A lymphatic route for a hyperbranched heteroglycan from Radix Astragali to trigger immune responses after oral dosing.

Carbohydr Polym 2022 Sep 27;292:119653. Epub 2022 May 27.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.

Gut barrier makes a huge research gap between in vivo and in vitro studies of orally bioactive polysaccharides: whether/how they contact the related cells in vivo. A hyperbranched heteroglycan RAP from Radix Astragali, exerting antitumor and immunomodulatory effects in vitro and in vivo, is right an example. Here, we determined first that RAP's antitumor activity is immune-dependent. Being undegraded and non-absorbing, RAP quickly entered Peyer's patches (PPs) in 1 h where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was further delivered to mesenteric lymph node, bone marrow, and tumor. By contrast, the control Dendrobium officinale polysaccharide did not enter PPs. These findings revealed a blood/microbiota-independent and selective lymphatic route for orally administrated RAP to directly contact immune cells and trigger antitumor immune responses. This route bridges the research gap between the in vitro and in vivo studies and might apply to many other bioactive polysaccharides.
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http://dx.doi.org/10.1016/j.carbpol.2022.119653DOI Listing
September 2022

PGM3 regulates beta-catenin activity to promote colorectal cancer cell progression.

Exp Biol Med (Maywood) 2022 Jun 20:15353702221101810. Epub 2022 Jun 20.

Department of Gastroenterology, Beijing Friendship Hospital, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Capital Medical University, Beijing 100050, P.R. China.

The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. Mechanistically, we demonstrated that the activity of β-catenin in CRC was maintained by PGM3-mediated O-GlcNAcylation. PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC.
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http://dx.doi.org/10.1177/15353702221101810DOI Listing
June 2022

Can retail investors induce corporate green innovation? -Evidence from Baidu Search Index.

Heliyon 2022 Jun 7;8(6):e09663. Epub 2022 Jun 7.

Graduate School of Economics and Management, Ural Federal University, Mira 19, 620002 Ekaterinburg, Russia.

China's rapid economic development has caused some environmental damage in recent years. The popularity of the Internet has enriched the ways for investors to obtain information, which would exert an impact on corporate environmental behavior. Focusing on micro-enterprise green innovation from the perspective of informal regulation, this paper investigates the impact of investor attention on corporate green innovation. This study takes Chinese A-share listed companies from 2011 to 2018 as samples, constructs panel fixed-effects models and adopts multiple linear, Logistic and Tobit regressions. This article finds that investor attention, measured by the web search index, can significantly improve corporate green innovation. The conclusion is still valid after a series of robust tests. Besides, mechanism tests reveal that investor attention can promote corporate green innovation by improving the implementation efficiency of punitive environmental regulation, the use efficiency of environmental subsidies, and by increasing the reputation cost of enterprises. In additional tests, this paper further clarifies that investors' attention to negative public opinion can play a better role in environmental governance, and reveals the reason why investors are motivated to improve corporate green innovation. This research puts forward a unique perspective, which extends the understanding of informal environmental regulation and enriches research on green innovation at the micro-enterprise level, promoting the cross research of finance and environmental protection.
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http://dx.doi.org/10.1016/j.heliyon.2022.e09663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201017PMC
June 2022

Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism.

Front Pharmacol 2022 3;13:870407. Epub 2022 Jun 3.

Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group). Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including ( < 0.01), ( < 0.01) and ( < 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine ( < 0.01), phenylalanine ( < 0.05), and arbutin ( < 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., and ) ( < 0.05) Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., ) enriched in the BER group were negatively associated with the above-mentioned clinical indices ( < 0.05). Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.
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http://dx.doi.org/10.3389/fphar.2022.870407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204213PMC
June 2022

Research on Infant Health Diagnosis and Intelligence Development Based on Machine Learning and Health Information Statistics.

Front Public Health 2022 2;10:846598. Epub 2022 Jun 2.

SEGI University, Petaling Jaya, Malaysia.

Intelligent health diagnosis for young children aims at maintaining and promoting the healthy development of young children, aiming to make young children have a healthy state and provide a better future for their physical and mental health development. The biological basis of intelligence is the structure and function of human brain and the key to improve the intelligence level of infants is to improve the quality of brain development, especially the early development of brain. Based on machine learning and health information statistics, this paper studies the development of infant health diagnosis and intelligence, physical and mental health. Pre-process the sample data, and use the filtering method based on machine learning and health information statistics for feature screening. Compared with traditional statistical methods, machine learning and health information statistical methods can better obtain the hidden information in the big data of children's physical and mental health development, and have better learning ability and generalization ability. The machine learning theory is used to analyze and mine the infant's health diagnosis and intelligence development, establish a health state model, and intuitively show people the health status of their infant's physical and mental health development by means of data. Moreover, the accumulation of these big data is very important in the field of medical and health research driven by big data.
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http://dx.doi.org/10.3389/fpubh.2022.846598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201248PMC
June 2022

[Vitamin A nutrition status of Chinese urban adults aged 18 to 60 years old in 2015].

Wei Sheng Yan Jiu 2022 May;51(3):381-385

NHC Key Laboratory of Trace Element Nutrition, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To investigate the vitamin A nutritional status and its related influencing factors of Chinese 18-60 urban adults by analyzing serum retinol level in 2015.

Methods: Serum samples of 42 people, half male and half female, were randomly selected in each point, from the 302 monitoring sites of Chinese adult chronic diseases and nutrition surveillance in 2015. The serum retinol levels were determined by high pressure liquid chromatography(HPLC).

Results: A total of 2571 serum samples were detected. The serum retinol level of Chinese urban adults of 18-60 years old was 1.98(1.56-2.53)μmol/L, the deficiency rate was 0.25%, and the marginal deficiency rate was 4.45%. The serum retinol level of male was 2.19(1.75-2.78)μmol/L, the deficiency rate was 0.05%, and the marginal deficiency rate was 2.48%; The serum retinol level of female was 1.80(1.42-2.25)μmol/L, the deficiency rate was 0.46%, and the marginal deficiency rate was 6.51%. The significant differences in serum retinol was observed deficiency rate and marginal deficiency rate between males and females(P<0.01), the nutritional status of males was better than the females. The deficiency rate and marginal deficiency rate of 18-29 years old were the highest, which were 0.34% and 5.81% respectively. The deficiency rate and marginal deficiency rate of over 50 years old were the lowest, which were 0.15% and 2.60% respectively. The vitamin A deficiency rate and marginal deficiency rate of people with body mass index(BMI)<18.5 were 0.95% and 7.24%, 0.33% and 5.85% for BMI=18.5-23.9, 0.13% and 3.27% for BMI=24.0-27.9, respectively. The differences of vitamin A deficiency rate and marginal deficiency rate among different BMI were significant.

Conclusion: The vitamin A nutritional status of urban adults in China is good, the vitamin A deficiency rate is very low, and the incidence of vitamin A deficiency is also low. It is basically not a public health problem according the WHO standard.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2022.03.006DOI Listing
May 2022

Corrigendum to: "Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis" [Biomed. Pharmacother. 112 (2019) 108607].

Biomed Pharmacother 2022 Jun 17:113294. Epub 2022 Jun 17.

Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China; Post-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. Electronic address:

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http://dx.doi.org/10.1016/j.biopha.2022.113294DOI Listing
June 2022

Danhong injection combined with tPA protects the BBB through Notch-VEGF signaling pathway on long-term outcomes of thrombolytic therapy.

Biomed Pharmacother 2022 Jun 16;153:113288. Epub 2022 Jun 16.

College of Life Science, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou 310053, China. Electronic address:

Current therapy for ischemic stroke primarily relies on tissue plasminogen activator (tPA), but it is limited by narrow treatment time window, bleeding complications and neurotoxicity. The preliminary study of tPA plus Danhong injection (DHI) shows that it can significantly reduce the side effects of tPA and improve its thrombolytic effect, but the mechanism of this action has not been further studied. In this study, the rats were randomly divided into sham group, vehicle group, DHI group (4 mL/kg), tPA group (5 mg/kg) and DHI+tPA group (4 mL/kg+ 2.5 mg/kg), administered intravenously 4.5 h since focal embolic stroke modeling. After 3 days and 7 days of cerebral ischemia, the neurological function of each treatment group was significantly improved compared with the vehicle group. The combination of DHI and tPA significantly reduced Evans blue (EB) penetration as well as the expressions of the proteins MMP-9, PAI-1 and P-selectin, while upregulating the expressions of claudin-5, occludin, and ZO-1 mRNA. Furthermore, the effect of continuous 7-day treatment was more conspicuous than 3-day treatment. Then, it significantly reduced the expressions of the proteins DLL-4 and VEGFR-2, increased the expressions of Notch-1, HIF-1α and HES-1 mRNA, and promoted the expressions of VEGF/HIF-1α-positive cells at 14 days following stroke. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) also showed that it improved pathological changes of ischemic brain tissue and the cerebral cortex micro-structure. These indicate that DHI combined with tPA may significantly ameliorate blood-brain barrier (BBB) disruption by activating Notch-VEGF signaling pathway to promote angiogenesis for long-term outcomes.
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http://dx.doi.org/10.1016/j.biopha.2022.113288DOI Listing
June 2022

The Safety, Toleration, and Pharmacokinetics of Two Intravenous Voriconazole Formulations in Healthy Chinese Volunteers After Increasing Dose Administrations.

Clin Pharmacol Drug Dev 2022 Jun 16. Epub 2022 Jun 16.

Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, China.

Sulfobutyl ether-beta-cyclodextrin sodium salt contained in the marketed intravenous voriconazole injection as a solubilizer may cause harmful accumulations. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of two intravenous voriconazole formulations containing excipients from different manufacturers using increasing dose administrations in healthy Chinese volunteers. A randomized, double-blind, placebo-controlled trial was conducted in three cohorts with 42 healthy Chinese volunteers. Each cohort of 14 volunteers was allocated in proportion (8:4:2) to test the formulation, reference voriconazole, or placebo successively by single-dose then multiple-dose administrations of 3, 4, and 6 mg/kg. Forty-one volunteers completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability (coefficient of variance of C up to 68.0%, AUC up to 70.2%, and nonlinear PKs with a regression coefficient of C  = 1.31 and AUC  = 1.75 in a single dose). In the steady state, R of the test drug versus reference drug of the 3, 4, and 6 mg/kg dose group were 5.2 and 5.3, 5.6 and 6.3, and 5.8 and 5.5, respectively, and Rc were 2.5 and 2.7, 2.6 and 3.1, and 2.8 and 2.6, respectively. Eighty-three adverse events with 37 transient visual disturbances were mild. PKs with high interindividual variability, nonlinear characteristics, and significant dose-dependent accumulation were comparable between the two formulations. Overall, the safety of the test formulation was acceptable.
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http://dx.doi.org/10.1002/cpdd.1126DOI Listing
June 2022

Design of a multi-epitope vaccine candidate against Brucella melitensis.

Sci Rep 2022 Jun 16;12(1):10146. Epub 2022 Jun 16.

Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, No. 393, Xinyi Road, Urumqi, 830011, Xinjiang, China.

Brucella is a typical facultative intracellular bacterium that can cause zoonotic infections. For Brucella, it is difficult to eliminate with current medical treatment. Therefore, a multi-epitope vaccine (MEV) should be designed to prevent Brucella infection. For this purpose, we applied the reverse vaccinology approach from Omp10, Omp25, Omp31 and BtpB. Finally, we obtained 13 cytotoxic T lymphocyte (CTL) epitopes, 17 helper T lymphocyte (HTL) epitopes, 9 linear B cell epitopes, and 2 conformational B cell epitopes for further study. To keep the protein folded normally, we linked AAY, GPGPG, and KK to CTL epitopes, HTL epitopes, and B cell epitopes, respectively. The N-terminal of the vaccine peptide is supplemented with appropriate adjuvants to enhance immunogenicity. To evaluate its immunogenicity, stability, safety, and feasibility, a final MEV containing 806 amino acids was constructed by linking linkers and adjuvants. In addition, molecular docking and molecular dynamics simulations were performed to verify the affinity and stability of the MEV-TLR4. Then, codon adaptation and in silico cloning studies were carried out to identify the possible codons for expressing the MEV. In animal experiments, the results demonstrated that the MEV had high immunogenicity. Collectively, this study provided a theoretical basis for the development of a Brucella vaccine.
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http://dx.doi.org/10.1038/s41598-022-14427-zDOI Listing
June 2022
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