Publications by authors named "Li Zhu"

2,182 Publications

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A novel nomogram for predicting locoregional recurrence risk in breast cancer patients treated with neoadjuvant chemotherapy and mastectomy.

Radiother Oncol 2021 Jun 10. Epub 2021 Jun 10.

Department of Radiation Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Background: This study aimed to establish a nomogram for predicting locoregional recurrence (LRR) in breast cancer patients treated with neoadjuvant chemotherapy (NAC) and mastectomy.

Methods: A total of 2368 patients who received NAC and mastectomy between 2000 and 2014 from 12 grade A tertiary hospitals in China were analyzed retrospectively. The nomogram was developed based on the patients treated in three cancer hospitals (training set, n=1629) and validated based on patients from the other nine general hospitals (validation set, n=739). Factors identified from Fine and Gray's competing risk analysis were used to establish the nomogram. The predictive performance of the nomogram model was compared with the cTNM stage, ypTNM stage, and the Neo-Bioscore model by using the area under the time dependent receiver operating characteristic curves (tAUC), calibration curve, and decision curve analysis (DCA).

Results: The nomogram incorporated six risk factors derived from multivariable analysis of the training set including age, ypT stage, ypN stage, lymph node ratio, postmastectomy radiotherapy, and endocrine therapy. In the training set, the AUC of the nomogram was 0.792, which was higher than the values of the cTNM stage (0.582), ypTNM stage (0.737), and the Neo-Bioscore prognosis model (0.658). In the validation set, the AUC of the cTNM (0.619); ypTNM (0.636); and Neo-Bioscore staging system (0.584) were also significantly lower than the AUC of the nomogram (0.705). Both in the training and validation sets, the calibration curve showed good agreement between the nomogram-based predictions and the actual observations CONCLUSION: The novel nomogram provides a more accurate evaluation of LRR for breast cancer patients treated with NAC and mastectomy.
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http://dx.doi.org/10.1016/j.radonc.2021.06.015DOI Listing
June 2021

Bulk Crystalline 4H-Silicon through a Metastable Allotropic Transition.

Phys Rev Lett 2021 May;126(21):215701

Earth and Planets Laboratory, Carnegie Institution for Science, Washington, DC 20015, USA.

We report the synthesis of bulk, highly oriented, crystalline 4H hexagonal silicon (4H-Si), through a metastable phase transformation upon heating the single-crystalline Si_{24} allotrope. Remarkably, the resulting 4H-Si crystallites exhibit an orientation relationship with the Si_{24} crystals, indicating a structural relationship between the two phases. Optical absorption measurements reveal that 4H-Si exhibits an indirect band gap near 1.2 eV, in agreement with first principles calculations. The metastable crystalline transition pathway provides a novel route to access bulk crystalline 4H-Si in contrast to previous transformation paths that yield only nanocrystalline-disordered materials.
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http://dx.doi.org/10.1103/PhysRevLett.126.215701DOI Listing
May 2021

Proteolysis and multimerization regulate signaling along the two-component regulatory system AdeRS.

iScience 2021 May 26;24(5):102476. Epub 2021 Apr 26.

Talent Highland and Center for Gut Microbiome Research of Med-X Institute, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.

Bacterial two-component regulatory systems are ubiquitous environment-sensing signal transducers involved in pathogenesis and antibiotic resistance. The two-component regulatory system AdeRS is made up of a sensor histidine kinase AdeS and a cognate response regulator AdeR, which together reduce repression of the multidrug-resistant efflux pump AdeABC. Herein we demonstrate that an N-terminal intrinsically disordered tail in AdeR is important for the upregulation of expression, although it greatly increases the susceptibility of AdeR to proteasome-mediated degradation. We also show that AdeS assembles into a hexameric state that is necessary for its full histidine kinase activity, which appears to occur via autophosphorylation. Taken together, this study demonstrates new structural mechanisms through which two-component systems can transduce environmental signals to impact gene expression and enlightens new potential antimicrobial approach by targeting two-component regulatory systems.
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http://dx.doi.org/10.1016/j.isci.2021.102476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169943PMC
May 2021

Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2α signaling pathway in IPEC-J2 cells.

J Anim Sci Biotechnol 2021 Jun 11;12(1):69. Epub 2021 Jun 11.

Institute of Animal Nutrition, Sichuan Agricultural University, Huimin Road 211#, Chengdu, Sichuan Province, 611130, P. R. China.

Background: Rotavirus (RV) is a major pathogen that causes severe gastroenteritis in infants and young animals. Endoplasmic reticulum (ER) stress and subsequent apoptosis play pivotal role in virus infection. However, the protective mechanisms of intestinal damage caused by RV are poorly defined, especially the molecular pathways related to enterocytes apoptosis. Thus, the aim of this study was to investigate the protective effect and mechanism of sodium butyrate (SB) on RV-induced apoptosis of IPEC-J2 cells.

Results: The RV infection led to significant cell apoptosis, increased the expression levels of ER stress (ERS) markers, phosphorylated protein kinase-like ER kinase (PERK), eukaryotic initiation factor 2 alpha (eIF2α), caspase9, and caspase3. Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis. The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78 (GRP78), PERK, and eIF2α. In addition, SB treatment restrained the ERS-mediated apoptotic pathway, as indicated by downregulation of C/EBP homologous protein (CHOP) mRNA level, as well as decreased cleaved caspase9 and caspase3 protein levels. Furthermore, siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis.

Conclusions: These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2α signaling pathway via GPR109a, which provide new ideas for the prevention and control of RV.
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http://dx.doi.org/10.1186/s40104-021-00592-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194137PMC
June 2021

MICAL2PV suppresses the formation of tunneling nanotubes and modulates mitochondrial trafficking.

EMBO Rep 2021 Jun 6:e52006. Epub 2021 Jun 6.

Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Tunneling nanotubes (TNTs) are actin-rich structures that connect two or more cells and mediate cargo exchange between spatially separated cells. TNTs transport signaling molecules, vesicles, organelles, and even pathogens. However, the molecular mechanisms regulating TNT formation remain unclear and little is known about the endogenous mechanisms suppressing TNT formation in lung cancer cells. Here, we report that MICAL2PV, a splicing isoform of the neuronal guidance gene MICAL2, is a novel TNT regulator that suppresses TNT formation and modulates mitochondrial distribution. MICAL2PV interacts with mitochondrial Rho GTPase Miro2 and regulates subcellular mitochondrial trafficking. Moreover, down-regulation of MICAL2PV enhances survival of cells treated with chemotherapeutical drugs. The monooxygenase (MO) domain of MICAL2PV is required for its activity to inhibit TNT formation by depolymerizing F-actin. Our data demonstrate a previously unrecognized function of MICAL2 in TNT formation and mitochondrial trafficking. Furthermore, our study uncovers a role of the MICAL2PV-Miro2 axis in mitochondrial trafficking, providing a mechanistic explanation for MICAL2PV activity in suppressing TNT formation and in modulating mitochondrial subcellular distribution.
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http://dx.doi.org/10.15252/embr.202052006DOI Listing
June 2021

Elemental Impurities in Pediatric Calcium Carbonate Preparations-High Throughput Quantification and Risk Assessment.

Front Chem 2021 17;9:682798. Epub 2021 May 17.

Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and drug Control, Beijing, China.

Calcium carbonate which is extracted from the Earth in combination with other mineral impurities, is largely used in preparations for pediatric supplements. Elemental impurities in drug products pose toxicological concerns without therapeutic benefits. Thus, it is very urgent to assess the safety of chronic exposure to elements that may be present in trace amounts. In the present study, we developed high throughput ICP-MS method for the quantitative determination of 62 elemental impurities in high matric calcium carbonate samples and validated according to USP 233. Calcium carbonate preparations which state clearly used for child (including neonates, infants, toddlers and children) from 9 manufactures and two types of raw materials (light calcium carbonate and ground calcium carbonate) were investigated in terms of the content and variability of 62 elemental impurities. According to the results, ground calcium carbonate was more suitable to be used in pediatric preparations concerning elemental impurities. Parts of elemental impurities in CaCO preparations which are derived from the raw materials and the preparation process, may cause potential risks for children. These results indicate that it is necessary to establish a modern instrumental analysis method to evaluate and control elemental impurities in CaCO raw materials and preparations.
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http://dx.doi.org/10.3389/fchem.2021.682798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173443PMC
May 2021

Study on the Immune Escape Mechanism of Acute Myeloid Leukemia With DNMT3A Mutation.

Front Immunol 2021 20;12:653030. Epub 2021 May 20.

Department of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mutated acute myeloid leukemia (AML) has a poor prognosis, but the exact mechanism is still unclear. Here, we aimed to explore the mechanism of immune escape in AML with DNMT3A mutation. We constructed a DNMT3A knockout clone and DNMT3A-R882H-mutated clones. RNA-seq results showed that transcription factors and macrophage inflammatory proteins were significantly downregulated in the DNMT3A mutant clones. KEGG enrichment and gene set enrichment analysis (GSEA) showed that a large number of genes were enriched in inflammatory immune-related pathways, such as the toll-like receptor signaling pathway. Therefore, we co-cultured AML cells with macrophages. The DNMT3A-mutated AML cells attenuated M1 macrophage polarization and resisted its killing effect and . In xenografts, the tumor volumes in the experimental group were significantly larger than those in the control group, and the proportion of M2 macrophages was significantly higher. After the co-culture, the increase in pro-inflammatory cytokine expression in the mutant cells was significantly lower than that in the control group, while that in immunosuppressive factors was not significantly different. In co-cultivated supernatants, the concentration of inflammatory factors in the experimental group was significantly lower than that in the control group, while that of immunosuppressive factors was significantly higher. Resistin significantly promoted the expression of inflammatory proteins in AML cells. It relieved the inhibitory effect of DNMT3A mutation, promoted the phenotypic recovery of the co-cultured macrophages, eliminated resistance, and regulated the immune microenvironment. Thus, resistin may serve as an ancillary drug for patients with DNMT3A-mutated AML.
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http://dx.doi.org/10.3389/fimmu.2021.653030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173207PMC
May 2021

In vitro digestion and fecal fermentation of highly resistant starch rice and its effect on the gut microbiota.

Food Chem 2021 Nov 13;361:130095. Epub 2021 May 13.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address:

Highly resistant starch rice (HRSR) is of particular interest in terms of its capacity to deliver short-chain fatty acids (SCFAs) to the colon in the prevention of diabetes mellitus and obesity. In this study, HRSR was processed into cooked rice, rice milk, rice cake, and rice popcorn, and the in vitro digestion and fermentation processes were monitored. The results showed that the starch digestibility of the four samples conformed to a first-order two-phase equation, and the resistant starch content of rice cake was the highest (11.98%). Compared with inulin, rice cake had a slower fermentation rate, and the butyrate concentration increased by 67.85%. The abundances of Prevotellaceae, which promotes the synthesis of SCFAs, and anti-inflammatory Faecalibacterium increased. The abundances of Proteobacteria and Megamonas, markers of gut microbiota imbalance, decreased. The results might facilitate the design and production of functional food products for type 2 diabetic and obese patients and improving colonic health.
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http://dx.doi.org/10.1016/j.foodchem.2021.130095DOI Listing
November 2021

Near-infrared light-controllable MXene hydrogel for tunable on-demand release of therapeutic proteins.

Acta Biomater 2021 May 31. Epub 2021 May 31.

State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082 P.R. China. Electronic address:

Precise delivery of therapeutic protein drugs that specifically modulate desired cellular responses is critical in clinical practice. However, the spatiotemporal regulation of protein drugs release to manipulate the target cell population in vivo remains a huge challenge. Herein, we have rationally developed an injectable and Near-infrared (NIR) light-responsive MXene-hydrogel composed of TiC, agarose, and protein that enables flexibly and precisely control the release profile of protein drugs to modulate cellular behaviors with high spatiotemporal precision remotely. As a proof-of-concept study, we preloaded hepatic growth factor (HGF) into the [email protected] ([email protected]/HGF) to activate the c-Met-mediated signaling by NIR light. We demonstrated NIR light-instructed cell diffusion, migration, and proliferation at the user-defined localization, further promoting angiogenesis and wound healing in vivo. Our approach's versatility was validated by preloading tumor necrotic factor-α (TNF-α) into the composite hydrogel ([email protected]/TNF-α) to promote the pro-apoptotic signaling pathway, achieving the NIR light-induced programmed cell deaths (PCD) of tumor spheroids. Taking advantage of the deep-tissue penetrative NIR light, we could eradicate the deep-seated tumors in a xenograft model exogenously. Therefore, the proposed MXene-hydrogel provides the impetus for developing therapeutic synthetic materials for light-controlled drug release under thick tissue, which will find promising applications in regenerative medicine and tumor therapy. STATEMENT OF SIGNIFICANCE: Current stimuli-responsive hydrogels for therapeutic proteins delivery mainly depend on self-degradation, passive diffusion, or the responsiveness to cues relevant to diseases. However, it remains challenging to spatiotemporally deliver protein-based drugs to manipulate the target cell population in vivo in an "on-demand" manner. Therefore, we have rationally constructed an injectable and Near-infrared (NIR) light-responsive composite hydrogel by embedding TiC MXene and protein drugs within an agarose hydrogel to enable the remote control of protein drugs delivery with high spatiotemporal precision. The NIR light-controlled release of the growth factor or cytokine has been carried out to regulate receptor-mediated cellular behaviors under deep tissue for skin wound healing or cancer therapy. This system will provide the potential for precision medicine through the development of intelligent drug delivery systems.
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http://dx.doi.org/10.1016/j.actbio.2021.05.027DOI Listing
May 2021

Expression Characteristics of microRNA in Pig Umbilical Venous Blood and Umbilical Arterial Blood.

Animals (Basel) 2021 May 27;11(6). Epub 2021 May 27.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

As the medium of material exchange between mother and fetus, umbilical cord blood is closely connected with fetal development. microRNA (miRNA) has a wide range of biological functions and has high flow characteristics. Small RNA sequencing of pig umbilical venous blood (UVB) and umbilical arterial blood (UAB) revealed that a total of 302 miRNAs were identified, and 106 and 22 miRNAs were specifically expressed in the UVB and UAB, respectively. Using the two methods of differential expression multiple and differential expression percentage, it is found that only 35% of the highly expressed miRNAs in the UVB by the two analysis modes overlap, but 56.25% of the enriched signal pathways are the same. Only 20% of the highly expressed miRNAs in the UAB overlap, but 62.07% of the signal pathways are the same. Further analysis revealed that miR-423 can be used as a characteristic miRNA of UVB and has the potential to treat muscle-related diseases. miR-122-5p can be used as a characteristic miRNA of UAB and may help to improve liver- and brain-related diseases. In summary, these results enrich understanding of miRNA in mother-fetal communication and provide a reference for the development and application of porcine cord blood products.
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http://dx.doi.org/10.3390/ani11061563DOI Listing
May 2021

Obtaining Specific Sequence Tags for and Visually Detecting Them Using the CRISPR-Cas12a System.

Pathogens 2021 May 6;10(5). Epub 2021 May 6.

State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijng 100071, China.

Three worldwide historical plague pandemics resulted in millions of deaths. , the etiologic agent of plague, is also a potential bioterrorist weapon. Simple, rapid, and specific detection of is important to prevent and control plague. However, the high similarity between and its sister species within the same genus makes detection work problematic. Here, the genome sequence from the CO92 strain was electronically separated into millions of fragments. These fragments were analyzed and compared with the genome sequences of 539 strains and 572 strains of 20 species within the genus. Altogether, 97 -specific tags containing two or more single nucleotide polymorphism sites were screened out. These 97 tags efficiently distinguished from all other closely related species. We chose four of these tags to design a Cas12a-based detection system. PCR-fluorescence methodology was used to test the specificity of these tags, and the results showed that the fluorescence intensity produced by was significantly higher than that of non- ( < 0.0001). We then employed recombinase polymerase amplification and lateral flow dipsticks to visualize the results. Our newly developed plasmid-independent, species-specific library of tags completely and effectively screened chromosomal sequences. The detection limit of our four-tag Cas12a system reached picogram levels.
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http://dx.doi.org/10.3390/pathogens10050562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148545PMC
May 2021

Expression of Antigens Fused to Different Vectors and Their Effectiveness as Vaccines.

Vaccines (Basel) 2021 May 21;9(6). Epub 2021 May 21.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.

Pertussis is an acute respiratory tract infection caused by . Even though its current vaccine coverage is relatively broad, they still have some shortcomings such as short protection time and might be incapable of blocking the spread of the disease. In this study, we developed new pertussis vaccine candidates by separately fusing three pertussis antigens ( fimbriae 2 "Fim2", pertussis toxin S1 subunit "PtxS1", and filamentous hemagglutinin "FHA") to each of two immune-boosting carrier proteins (B subunits of AB5 toxin family: cholera toxin B subunit "CTB" and shiga toxin B subunit "StxB"). We then immunized mice with these fusion antigens and found that they significantly increased the serum antibody titers and elicited high bactericidal activity against . After CTB-or StxB-fused antigen-immunized mice were challenged with a non-lethal dose of , the bacterial loads in different tissues of these mice were significantly reduced, and their lung damage was nearly invisible. Furthermore, we also demonstrated that these candidate vaccines could provide strong prophylactic effects against a lethal challenge with . Overall, our candidate vaccines conferred better immune protection to mice compared with pertussis antigen alone. This B5 subunit-based vaccine strategy provides a promising option for vaccine design.
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http://dx.doi.org/10.3390/vaccines9060542DOI Listing
May 2021

The impacts of health insurance on financial strain for people with chronic diseases.

Authors:
Zixuan Peng Li Zhu

BMC Public Health 2021 05 29;21(1):1012. Epub 2021 May 29.

School of Political Science and Public Administration, Guangxi University for Nationalities, Nanning, China.

Background: Due to ongoing expenses for both short-term and long-term needs for health services, people with chronic diseases tend to struggle with financial hardship. Health insurance is employed as a useful tool in aiding people to solve such financial strain. This study aims to examine and compare the impacts of public and private health insurance on solving financial barriers for people with chronic diseases.

Methods: This research obtained an outpatient sample consisted of 1739 individuals and an inpatient sample consisted of 1034 individuals. We employed a Chi-square test and a two-sample T-test to explore differences in financial strain and insurance status between people with chronic diseases and those without. Then we adopted binary logistic regression technique to assess the impacts of different types of health insurance on outpatient and inpatient financial strain for people with chronic diseases.

Results: Our research has five key findings: first, people with chronic diseases were more likely to experience both the outpatient and inpatient financial strain (P < 0.01); second, public health insurance was found to reduce the outpatient financial strain; third, private health insurance was found to positively associate with inpatient financial barriers; fourth, Urban Employment Insurance (UEI) was expected to reduce both the outpatient and inpatient financial barriers, while self-paid private insurance (SPI) was positively associated with inpatient financial barriers; and fifth, income was identified as a positive predictor of having outpatient and inpatient financial strain.

Conclusions: Public health insurance has the potential to reduce the outpatient financial strain for people with chronic diseases. Private health insurance was identified as a positive predictor of inpatient financial strain for people with chronic diseases. Policy should be proposed to promote the capacity of public health insurance and explore the potential effects of private health insurance on solving the inpatient financial barriers faced by people with chronic diseases in China.
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http://dx.doi.org/10.1186/s12889-021-11075-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164330PMC
May 2021

An Aptamer-Based Antagonist against the Receptor for Advanced Glycation End-Products (RAGE) Blocks Development of Colorectal Cancer.

Mediators Inflamm 2021 5;2021:9958051. Epub 2021 May 5.

College of Biology, Hunan University, Changsha, China.

Tumor angiogenesis plays a crucial role in colorectal cancer development. Dysregulation of the receptor for the advanced glycation end-products (RAGE) transmembrane signaling mediates inflammation, resulting in various cancers. However, the mechanism of the RAGE signaling pathway in modulating development of colorectal cancer has not been explored. In this study, an aptamer-based RAGE antagonist (Apt-RAGE) was used to inhibit interaction between RAGE and S100B, thus blocking downstream NFB-mediated signal transduction. results showed that Apt-RAGE effectively inhibited S100B-dependent and S100B-independent RAGE/NFB activation in colorectal HCT116 cancer cells, thus decreasing proliferation and migration of cells. Notably, expression and secretion of VEGF-A were inhibited, implying that Apt-RAGE can be used as an antiangiogenesis agent in tumor therapy. Moreover, Apt-RAGE inhibited tumor growth and microvasculature formation in colorectal tumor-bearing mice. Inhibition of angiogenesis by Apt-RAGE was positively correlated with suppression of the RAGE/NFB/VEGF-A signaling. The findings of this study show that Apt-RAGE antagonist is a potential therapeutic agent for treatment of colorectal cancer.
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http://dx.doi.org/10.1155/2021/9958051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116144PMC
May 2021

Arbuscular mycorrhizal trees influence the latitudinal beta-diversity gradient of tree communities in forests worldwide.

Nat Commun 2021 05 25;12(1):3137. Epub 2021 May 25.

School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.

Arbuscular mycorrhizal (AM) and ectomycorrhizal (EcM) associations are critical for host-tree performance. However, how mycorrhizal associations correlate with the latitudinal tree beta-diversity remains untested. Using a global dataset of 45 forest plots representing 2,804,270 trees across 3840 species, we test how AM and EcM trees contribute to total beta-diversity and its components (turnover and nestedness) of all trees. We find AM rather than EcM trees predominantly contribute to decreasing total beta-diversity and turnover and increasing nestedness with increasing latitude, probably because wide distributions of EcM trees do not generate strong compositional differences among localities. Environmental variables, especially temperature and precipitation, are strongly correlated with beta-diversity patterns for both AM trees and all trees rather than EcM trees. Results support our hypotheses that latitudinal beta-diversity patterns and environmental effects on these patterns are highly dependent on mycorrhizal types. Our findings highlight the importance of AM-dominated forests for conserving global forest biodiversity.
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http://dx.doi.org/10.1038/s41467-021-23236-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149669PMC
May 2021

Toxic effects of norfloxacin in soil on fed and unfed Folsomia candida (Isotomidae: Collembola) and on gut and soil microbiota.

Sci Total Environ 2021 Sep 15;788:147793. Epub 2021 May 15.

CAS Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China.

Soils contaminated with antibiotics may exert effects on soil-dwelling animals. A systematic ecological toxicity assessment of norfloxacin on the soil collembolan Folsomia candida (F. candida) was therefore conducted in soil and Petri dish systems with and without feeding at the population, individual and cellular levels. The indicators survival, reproduction, antioxidant enzyme activities peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD), malondialdehyde (MDA) contents and gut microbiota were studied. The surrounding soil microbiota were also investigated because F. candida can ingest soil microbiota that may have effects on the gut microbiota. In general, the toxicity of norfloxacin to F. candida in contaminated soil without food addition was higher than in contaminated soil with food addition. Norfloxacin had little effect at population and individual levels but antioxidant enzyme activities changed significantly in treatments with longer exposure times or higher norfloxacin concentrations. CAT was more sensitive than SOD or POD. The diversity indices and composition at phylum level of the gut microbiota showed little change. However, the operational taxonomic units in the gut decreased in the presence of norfloxacin. The relative abundance of Wolbachia, the predominant bacterial genus in the gut, decreased significantly with increasing soil norfloxacin concentration. Wolbachia may therefore be a promising bioindicator in the assessment of norfloxacin pollution of soils at environmental concentrations.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147793DOI Listing
September 2021

Production of a Promising Biosynthetic Self-Assembled Nanoconjugate Vaccine against Klebsiella Pneumoniae Serotype O2 in a General Escherichia Coli Host.

Adv Sci (Weinh) 2021 May 24:e2100549. Epub 2021 May 24.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, No. 20, Dongda Street, Fengtai District, Beijing, 100071, P. R. China.

Klebsiella pneumoniae has emerged as a severe opportunistic pathogen with multiple drug resistances. Finding effective vaccines against this pathogen is urgent. Although O-polysaccharides (OPS) of K. pneumoniae are suitable antigens for the preparation of vaccines given their low levels of diversity, the low immunogenicity (especially serotype O2) limit their application. In this study, a general Escherichia coli host system is developed to produce a nanoscale conjugate vaccine against K. pneumoniae using the Nano-B5 self-assembly platform. The experimental data illustrate that this nanoconjugate vaccine can induce an efficient humoral immune response in draining lymph nodes (dLNs) and elicit high titers of the IgG antibody against bacterial lipopolysaccharide (LPS). The ideal prophylactic effects of these nanoconjugate vaccines are further demonstrated in mouse models of both systemic and pulmonary infection. These results demonstrate that OPS with low immunogenicity can be changed into an effective antigen, indicating that other haptens may be applicable to this strategy in the future. To the knowledge, this is the first study to produce biosynthetic nanoconjugate vaccines against K. pneumoniae in E. coli, and this strategy can be applied to the development of other vaccines against pathogenic bacteria.
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http://dx.doi.org/10.1002/advs.202100549DOI Listing
May 2021

-Induced lncRNA Enhanced Resistance of Ovarian Cancer Cells to Cisplatin by Regulating Axis.

DNA Cell Biol 2021 Jun 24;40(6):821-832. Epub 2021 May 24.

Department of Gynecology, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.

Chemoresistance is one of the major obstacles encountered in ovarian cancer (OC) therapy. Long noncoding RNA has been reported to be involved in the tumorigenesis of several types of cancers. However, the biological role of in the chemoresistance of OC is still unclear. In this study, it was found that the expression levels of and were increased and expression was decreased in cisplatin (DDP)-resistant OC cell lines. The depletion of enhanced the DDP sensitivity of DDP-resistant OC cells, as indicated by the inhibition of cell proliferation, migration, and invasion, and promotion of cell apoptosis. In the upstream mechanism exploration, we discovered that was induced by transcription factor. Moreover, it was identified that was a target of , and regulated the DDP resistance of OC through In addition, we screened the candidate genes of , and confirmed that was the downstream gene of Furthermore, the knockdown of inhibited proliferation, migration, and invasion, and accelerated apoptosis of DDP-resistant OC cells, which was counteracted after the inhibition of Finally, we observed that regulated the expression of through In conclusion, we demonstrated that -induced accelerated DDP resistance of OC through axis, suggesting may be a promising therapeutic target for DDP-resistant OC patients.
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http://dx.doi.org/10.1089/dna.2021.0059DOI Listing
June 2021

Staphylococcus aureus N-terminus formylated δ-toxin tends to form amyloid fibrils, while the deformylated δ-toxin tends to form functional oligomer complexes.

Virulence 2021 Dec;12(1):1418-1437

State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Beijing, China.

The community-associated Methicillin-resistant strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many strains. In addition, δ-toxin exists in the culture supernatant as both N-terminus formylated δ-toxin (fδ-toxin) and deformylated δ-toxin (dfδ-toxin) groups. Although δ-toxin has been studied for more than 70 years, its functions remain unclear. We isolated and purified PSMs from the supernatant of MW2, and found fibrils and oligomers aggregates by Size Exclusion Chromatography. After analyzing PSM aggregates and using peptide simulations, we found that the difference in the monomer structure of fδ-toxin and dfδ-toxin might ultimately lead to differences in the aggregation ability: fδ-toxin and dfδ-toxin tend to form fibrils and oligomers respectively. Of note, we found that fδ-toxin fibrils enhanced the stability of biofilms, while dfδ-toxin oligomers promoted their dispersal. Additionally, oligomeric dfδ-toxin combined with PSMα to form a complex with enhanced functionality. Due to the different aggregation capabilities and functions of fδ-toxin and dfδ-toxin, we speculate that they may be involved in the regulation of physiological activities of . Moreover, the dfδ-toxin oligomer not only provides a new form of complex in the study of PSMα, but also has significance as a reference in oligomer research pertaining to some human amyloid diseases.
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http://dx.doi.org/10.1080/21505594.2021.1928395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158037PMC
December 2021

Occurrence and ecotoxicological risk assessment of perfluoroalkyl substances in water of lakes along the middle reach of Yangtze River, China.

Sci Total Environ 2021 Sep 15;788:147765. Epub 2021 May 15.

Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China; Institute of Eco-Environmental Research, Guangxi Academy of Sciences, Nanning 530007, China. Electronic address:

Polyfluoroalkyl substances (PFASs) are widely distributed in aquatic environment, and the potential ecological risk of PFASs has become a new challenge in recent years. But there were few integrated studies about the distribution, source appointment and risk assessment of PFASs in water of lakes along the middle reach of Yangtze River, China. Hence, this study investigated the pollution characteristics, source apportionment, ecological risks assessment of eleven PFASs from the surface water in this region. The total concentrations of PFASs (∑PFASs) ranged from 12.43 to 77.44 ng L in this region. The ∑PFASs in Hong and Poyang Lakes were higher than those in Dongting Lake and middle reach of Yangtze River (p < 0.05). The compositions of PFASs in the middle reach of Yangtze River and along three lakes were similar, being with a larger proportion of short-chain PFACs. The food packaging and metal plating sources were identified as the main sources by two models. The total risk quotients (∑RQs) showed the ecological risk for algae in the middle reach of Yangtze River, Dongting and Poyang Lakes were negligible, but the low risk in some sites of Hong Lake. The EDIs of ∑PFASs were much lower than the tolerable daily intake recommended by the European Food Safety Authority. The results of this study were significant for developing effective strategies (e.g. short-chain substitution and restriction) of controlling PFASs pollution in the middle reach of Yangtze River and along lakes.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147765DOI Listing
September 2021

One-step production of functional branched oligoglucosides with coupled fermentation of Pichia pastoris GS115 and Sclerotium rolfsii WSH-G01.

Bioresour Technol 2021 Sep 15;335:125286. Epub 2021 May 15.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, PR China. Electronic address:

Endo-β-1,3-glucanase with high specific activity is a prerequisite for enzymatic preparation of valuable β-oligoglucosides. Heterologous expression in Pichia pastoris GS115 with error-prone PCR technology was implemented, and the mutant strain 7 N12 was obtained. The mutant endo-β-1,3-glucanase showed efficient specific activities for degrading curdlan (366 U mg) and scleroglucan (274.5 U mg). Thereafter, one-step production of functional branched oligoglucosides was established with coupled fermentation of Pichia pastoris and Sclerotium rolfsii. During the fermentation process, the endo-β-1,3-glucanase secreted by Pichia pastoris GS115 can efficiently hydrolyse scleroglucan metabolized by Sclerotium rolfsii WSH-G01. The maximum yields of β-oligoglucosides in the shake flasks and 7-L bioreactor reached 1.73 g L and 12.71 g L, respectively, with polymerization degrees of 2-17. The successful implementation of heterologous expression with error-prone PCR and the coupled fermentation simplified the multi-step enzymatic β-oligoglucoside preparation procedures, which makes it a potential strategy for industrial production of functional oligosaccharides.
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http://dx.doi.org/10.1016/j.biortech.2021.125286DOI Listing
September 2021

Prevalence of acne in Chinese college students and its associations with social determinants and quality of life: a population-based cross-sectional study.

Chin Med J (Engl) 2021 Jan 11;134(10):1239-1241. Epub 2021 Jan 11.

Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.

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http://dx.doi.org/10.1097/CM9.0000000000001292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143762PMC
January 2021

A medium-range structure motif linking amorphous and crystalline states.

Nat Mater 2021 May 20. Epub 2021 May 20.

Department of Physics, City University of Hong Kong, Kowloon, Hong Kong, China.

Amorphous materials have no long-range order, but there are ordered structures at short range (2-5 Å), medium range (5-20 Å) and even longer length scales. While regular and semiregular polyhedra are often found as short-range ordering in amorphous materials, the nature of medium-range order has remained elusive. Consequently, it is difficult to determine whether there exists any structural link at medium range or longer length scales between the amorphous material and its crystalline counterparts. Moreover, an amorphous material often crystallizes into a phase of different composition, with very different underlying structural building blocks, further compounding the issue. Here, we capture an intermediate crystalline cubic phase in a Pd-Ni-P amorphous alloy and reveal the structure of the medium-range order, a six-membered tricapped trigonal prism cluster (6M-TTP) with a length scale of 12.5 Å. We find that the 6M-TTP can pack periodically to several tens of nanometres to form the cube phase. Our experimental observations provide evidence of a structural link between the amorphous and crystalline phases in a Pd-Ni-P alloy at the medium-range length scale and suggest that it is the connectivity of the 6M-TTP clusters that distinguishes the crystalline and amorphous phases. These findings will shed light on the structure of amorphous materials at extended length scales beyond that of short-range order.
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http://dx.doi.org/10.1038/s41563-021-01011-5DOI Listing
May 2021

Upper Critical Solution Temperature-Type Responsive Cyclodextrins with Characteristic Inclusion Abilities.

Chemistry 2021 May 18. Epub 2021 May 18.

International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Materials Building Room 801, Nanchen Street 380, Shanghai, 200444, P. R. China.

Water-soluble and thermoresponsive macrocycles with stable inclusion toward guests are highly valuable to construct stimuli-responsive supramolecular materials for versatile applications. Here, we develop such macrocycles - ureido-substituted cyclodextrins (CDs) which exhibit unprecedented upper critical solution temperature (UCST) behavior in aqueous media. These novel CD derivatives showed good solubility in water at elevated temperature, but collapsed from water to form large coacervates upon cooling to low temperature. Their cloud points are greatly dependent on concentration and can be mediated through oxidation and chelation with silver ions. Significantly, the amphiphilicity of these CD derivatives is supportive to host-guest binding, which affords them inclusion abilities to guest dyes. The inclusion complexation remained nearly intact during thermally induced phase transitions, which is in contrast to the switchable inclusion behavior of lower critical solution temperature (LCST)-type CDs. Moreover, ureido-substituted CDs were exploited to co-encapsulate a pair of guest dyes whose fluorescence resonance energy transfer process can be switched by the UCST phase transition. We therefore believe these novel thermoresponsive CDs may form a new strategy for developing smart macrocycles and allow for exploring smart supramolecular materials.
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http://dx.doi.org/10.1002/chem.202101283DOI Listing
May 2021

Rice Ferredoxins localize to chloroplasts/plastids and may function in different tissues.

Plant Signal Behav 2021 May 14:1926813. Epub 2021 May 14.

State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou, China.

Ferredoxins (Fds) play a unique and important role in photosynthetic electron transport. Recently, we characterized the function of Fd1 in rice ( L.), showing that Fd1 is the primary photosynthetic electron transport protein and that Fd1 participates in carbon assimilation. However, the subcellular localization and specific functions of other Fds in rice are not yet fully understood. Here, our subcellular localization analysis of the seven Fds in rice showed that they are located in the chloroplasts of photosynthetic tissues and the plastids of non-photosynthetic tissues. Moreover, qRT-PCR indicated that transcript levels were highest in photosynthetic tissues, while transcript levels were highest in non-photosynthetic tissues. Collectively, our results suggest that rice Fds are located in chloroplasts/plastids, but may function in different tissues, and Fd4 may be a non-photosynthetic type Fd.
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http://dx.doi.org/10.1080/15592324.2021.1926813DOI Listing
May 2021

CFP is a prognostic biomarker and correlated with immune infiltrates in Gastric Cancer and Lung Cancer.

J Cancer 2021 12;12(11):3378-3390. Epub 2021 Apr 12.

Department of Physiology, School of medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China.

Complement factor properdin (), encodes plasma glycoprotein, is a critical gene that regulates the complement pathway of the innate immune system. However, correlations of in cancers remain unclear. In this study, the expression pattern and prognostic value of in pan-cancer were analyzed via the Oncomine, PrognoScan, GEPIA and Kaplan-Meier plotters. In addition, we used immunohistochemical staining to validate CFP expression in clinical tissue samples. Finally, we evaluated the correlations between and cancer immune infiltrates particularly in stomach adenocarcinoma (STAD) and lung adenocarcinoma (LUAD) by using GEPIA and TIMER databases. The results of database analysis and immunohistochemistry showed that the expression level of CFP in STAD and LUAD was lower than that in normal tissues. Low expression level of was associated with poorer overall survival (OS), first progression (FP), post progression survival (PPS) and was detrimental to the prognosis of STAD and LUAD, specifically in stage 3, stage T3, stage N2 and N3 of STAD (0.05). Moreover, expression of had significant positive correlations with the infiltration levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells (DCs) in STAD and LUAD. Furthermore, gene markers of infiltrating immune cells exhibited different -related immune infiltration patterns such as tumor-associated-macrophages (TAMs). These results suggest that can serve as a prognostic biomarker for determining prognosis and immune infiltration in STAD and LUAD.
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http://dx.doi.org/10.7150/jca.50832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100816PMC
April 2021

Severe secondary hyperkalemia and arrhythmia from drug interactions between calcium-channel blocker and voriconazole: a case presentation.

BMC Nephrol 2021 May 10;22(1):172. Epub 2021 May 10.

Department of Nephrology, Peking University People's Hospital, Beijing, China.

Background: Patients with kidney disease may have concurrent hypertension and infection. Dihydropyridine calcium-channel blockers (CCB) are the most popular class of antihypertensive drugs used in clinical settings and can be metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4). Voriconazole is a commonly used antifungal treatment and a CYP3A4-inhibitor. Insufficient attention to drug interactions from the concomitant use of CCB and voriconazole may result in serious adverse reactions.

Case Presentation: Here, we report a patient with acute kidney injury on stable anti-neutrophil cytoplasm antibody associated vasculitis who developed hyperkalemia resulting in sinus arrest with junctional escape rhythm attributed to drug interactions of CCB with voriconazole. This is a very rarely reported case and may be an under-recognized complication. After continuous renal replacement therapy and changing the anti-hypertensive drugs, symptoms, and laboratory abnormalities of the patient fully recovered.

Conclusions: This case warns us of severe consequences of drug interactions. Co-prescription of CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury, which may further induce hyperkalemia and arrhythmia.
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http://dx.doi.org/10.1186/s12882-021-02370-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108408PMC
May 2021

Strategies for optimizing acetyl-CoA formation from glucose in bacteria.

Trends Biotechnol 2021 May 5. Epub 2021 May 5.

Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; Huzhou Center of Industrial Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Huzhou 313000, China. Electronic address:

Acetyl CoA is an important precursor for various chemicals. We provide a metabolic engineering guideline for the production of acetyl-CoA and other end products from a bacterial chassis. Among 13 pathways that produce acetyl-CoA from glucose, 11 lose carbon in the process, and two do not. The first 11 use the Embden-Meyerhof-Parnas (EMP) pathway to produce redox cofactors and gain or lose ATP. The other two pathways function via phosphoketolase with net consumption of ATP, so they must therefore be combined with one of the 11 glycolytic pathways or auxiliary pathways. Optimization of these pathways can maximize the theoretical acetyl-CoA yield, thereby minimizing the overall cost of subsequent acetyl-CoA-derived molecules. Other strategies for generating hyper-producer strains are also addressed.
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http://dx.doi.org/10.1016/j.tibtech.2021.04.004DOI Listing
May 2021

Current diagnosis and treatment of acute pancreatitis in China: a real-world, multicenter study.

BMC Gastroenterol 2021 May 8;21(1):210. Epub 2021 May 8.

Department of Surgery, The First Hospital of China Medical University, No. 155 Najing North Street, Heping District, Shenyang, Liaoning Province, People's Republic of China.

Background: Efficacy of pancreatic enzyme inhibitors in acute pancreatitis (AP) is unclear in China.

Aims: We aimed to present the current status of AP and evaluate the efficacy of pancreatic enzyme inhibitors in a larger population in China.

Method: A retrospective, cross-sectional, real-world, multicenter analysis of a large dataset of patients presenting with AP from four hospitals of China over a two-year period was performed. Data were collected from the existing clinical records and the patients were grouped into medication group (somatostatin or octreotide or somatostatin and octreotide) and no medication group. Pair wise propensity score matching was performed for comparing somatostatin, octreotide and somatostatin/octreotide. The end points were incidence of disease complications, organ failure, hospitalization duration, and recovery time taken (hours) for serum amylase/serum lipase to normalcy.

Results: A total of 3900 patients were recruited and 2775 patients were included for analysis. A total of 1100, 661, 676 and 338 patients received either somatostatin or octreotide or somatostatin and octreotide or no medication, respectively. The incidence of complications (7.6% vs 13.6%), organ failure (4.5% vs 7.4%), and the instances of entering ICU (9.3% vs 13.3%) were higher in unmedicated group. Complications at discharge (2.91 times), organ failure (2.53 times), and hospitalization stay were higher in octreotide-treated patients compared with somatostatin-treated patients. In comparison to the octreotide group, the serum amylase/lipase recovery time was shorter in the somatostatin group.

Conclusion: This real-world study suggested that the use of pancreatic enzyme inhibitors was positively associated with greater clinical efficacy in AP patients and somatostatin might be more effective than octreotide in real-world settings in China.
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http://dx.doi.org/10.1186/s12876-021-01799-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105912PMC
May 2021