Publications by authors named "Xinhua Chen"

307 Publications

Effects of Nanosecond Pulsed Electric Fields in Cell Vitality, Apoptosis, and Proliferation of TPC-1 Cells.

Anal Cell Pathol (Amst) 2021 13;2021:9913716. Epub 2021 Oct 13.

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Objective: To evaluate the effects of nanosecond pulsed electric fields (nsPEFs) with different pulse durations in cell vitality, apoptosis, and proliferation of TPC-1 cells, optimize pulse parameters and expand the application range of nsPEFs.

Methods: The pulse duration of 0, 300 ns, 500 ns, and 900 ns is generated with nsPEF generator. CCK-8 was used to investigate the effect of nsPEFs on the viability of TPC-1 cells. Flow cytometry was used to evaluate the apoptosis of TPC-1 after pulse treatment. The effect of nsPEFs on the proliferation ability of TPC-1 cells was detected by 5-ethy-nyl-2'-deoxyuridine. The morphological changes of TPC-1 cells after pulse treatment were observed by transmission electron microscopy.

Results: NsPEFs with 900 ns pulse duration can significantly affect the viability of TPC-1 cells and inhibit the proliferation ability of TPC-1 cells. In addition, nsPEFs can also induce apoptosis of TPC-1 cells.

Conclusion: NsPEFs with longer pulse duration can significantly affect the biological behavior of TPC-1 cells, such as cell viability and proliferation ability, and can also induce cell apoptosis, thereby inhibiting cell growth.
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http://dx.doi.org/10.1155/2021/9913716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528613PMC
October 2021

The anti-hyperuricemic effects of green alga Enteromorpha prolifera polysaccharide via regulation of the uric acid transporters in vivo.

Food Chem Toxicol 2021 Oct 20;158:112630. Epub 2021 Oct 20.

College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, 350002, China; Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. Electronic address:

A novel polysaccharide obtained from Enteromorpha prolifera (EPP) was purified through diethylaminoethyl cellulose-52 and Sephadex G-75 chromatography. Fourier transform infrared spectroscopy, high-performance liquid chromatography, and nuclear magnetic resonance (NMR) spectroscopy were employed to analyse the structure of EPP. It mainly comprised rhamnose, glucuronic acid, galactose, arabinose, and xylose at a molar ratio of 20.45:12.74:10.99:5.84:1.95, and its average molecular weight was 46.56 kDa. The seven major glycosidic residues identified by NMR were as follows: →2)-α-L-Araf-(1→, →2)-α-L-Rhap-(1→, →4)-α-L-Rhap-(1→, →2,6)-β-D-Galp-(1→, →4)-β-D-GlcpA-(1→, →3,4)-β-D-GlcpA-(1→, and →4)-β-Xylp-(1→. The effect of EPP on hyperuricemic mice was determined by analysing correlative general physical parameters, renal histopathology, renal gene expressions, and gut microbiome. EPP significantly reduced serum uric acid (UA), serum blood urea nitrogen, serum xanthine oxidase (XOD), and hepatic XOD as well as improved histological parameters in hyperuricemic mice. Furthermore, mRNA and protein expression analyses showed the upregulation of UA excretion genes such as ABCG2, OAT1, and NPT1 and downregulation of UA resorption gene URAT1. Moreover, EPP maintained the stability of the intestinal flora and confirmed that Parasutterella is closely related to the regulation of hyperuricemia. This study is the first to demonstrate the anti-hyperuricemic activity of EPP and highlight its therapeutic potential for hyperuricemia-related diseases.
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http://dx.doi.org/10.1016/j.fct.2021.112630DOI Listing
October 2021

ATG12 is involved in the antiviral immune response in large yellow croaker (Larimichthys crocea).

Fish Shellfish Immunol 2021 Oct 13;119:262-271. Epub 2021 Oct 13.

Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China. Electronic address:

ATG12, a core autophagy protein, forms a conjugate with ATG5 to promote the formation of autophagosome membrane, and plays an important role in antiviral immunity. However, little is known about the function of ATG12 in fish. Here, we cloned the open reading frame (ORF) of large yellow croaker (Larimichthys crocea) ATG12 (LcATG12), which is 354 nucleotides long and encodes a protein of 117 amino acids. The deduced LcATG12 possesses a conserved APG12 domain (residues 31 to 117), and shares 91.45% identities with ATG12 in orange-spotted grouper (Epinephelus coioides). LcATG12 was constitutively expressed in all examined tissues, with the highest level in intestine. Its transcript was also detected in primary head kidney granulocytes (PKG), primary head kidney macrophages (PKM), primary head kidney lymphocytes (PKL), and large yellow croaker head kidney (LYCK) cell line, and was significantly up-regulated by poly(I:C). LcATG12 was regularly distributed in both cytoplasm and nucleus of LYCK and epithelioma papulosum cyprinid (EPC) cells. Overexpression of LcATG12 in EPC cells significantly inhibited the replication of spring viremia of carp virus (SVCV). Further studies reveled that LcATG12 could induce the occurrence of autophagy in LYCK cells. Furthermore, overexpression of LcATG12 in LYCK cells increased the expression levels of large yellow croaker type I interferons (IFNs, IFNc, IFNd, and IFNh), IFN regulatory factors (IRF3 and IRF7), and IFN-stimulated genes (PKR, Mx, and Viperin). All these data indicated that LcATG12 plays a role in the antiviral immunity possibly by inducing both autophagy and type I IFN response in large yellow croaker.
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http://dx.doi.org/10.1016/j.fsi.2021.10.015DOI Listing
October 2021

[Progress in the Treatment of Tachyarrhythmia by Pulsed Electric Field Ablation Catheter Ablation].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Sep;45(5):517-523

Zhejiang Medical Laboratory of Pulsed Power Technology, Hangzhou, 310003.

Pulsed electric field(PEF) provides high-energy instantaneous pulse and release energy to myocardial cell membrane, resulting in irreversible electroporation and causes myocardial cell contents leakage, destruction of intracellular homeostasis, cell death, and slight inflammatory response. PEF as non-thermal energy promotes the design and application of arrhythmia ablation catheter to enter a new stage. There are currently limited clinical studies that have proved the safety and effectieness of Farawave PEF catheter, PVAC GOLD PEF catheter, Lattice-tip Sphere-9 PEF and radiofrequency (RF) catheter used for atrial fibrillation ablation, but still need further discussion. The research of atrial fibrillation ablation with PEF is under study in China. In this paper, the design and application of PEF ablation for tachyarrhythmia are reviewed.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.05.010DOI Listing
September 2021

Long-slit polarization-insensitive imaging spectrometer for wide-swath hyperspectral remote sensing from a geostationary orbit.

Opt Express 2021 Aug;29(17):26851-26864

To improve the swath width and quantitative accuracy of hyperspectral payloads on a geostationary orbit, a long-slit polarization-insensitive imaging spectrometer is designed and demonstrated in this paper. For the wide swath, several long-slit spectrometers with the same specification have been designed and compared. The result shows that the Wynne-Offner spectrometer has advantages in increasing slit length and reducing volume, and it is suitable for being spliced for ultra-wide swath. To solve the problem of inaccurate radiation measuring caused by the polarization of imaging spectrometers, the requirement for linear polarization sensitivity (LPS) is theoretically analyzed and assessed. As diffraction grating is the main polarization-sensitive element in an imaging spectrometer, we propose to increase the apical angle of the grating groove to reduce its LPS and compensate its residual polarization by specially polarized optical films coated on lens surfaces, thus the polarization-insensitive system is achieved. At last, a VNIR spectrometer with superior spatial and spectral performance is developed, and its slit is 61.44 mm long. The maximum LPS of this system is reduced from 10.0% to 2.3% (test 2.5%) after the depolarization design, which greatly reduces the uncertainty of the measuring radiation caused by polarization. The developed imaging spectrometer can play a role in quantitative hyperspectral remote sensing, especially in wide-swath applications on geostationary orbit.
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http://dx.doi.org/10.1364/OE.432972DOI Listing
August 2021

Global landscape of SARS-CoV-2 genomic surveillance, public availability extent of genomic data, and epidemic shaped by variants.

Res Sq 2021 Sep 29. Epub 2021 Sep 29.

Genomic surveillance has shaped our understanding of SARS-CoV-2 variants, which have proliferated globally in 2021.We collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data from multiple public repositories, and aggregated publicly available variant data. Then, different proxies were used to estimate the sequencing coverage and public availability extent of genomic data, in addition to describing the global dissemination of variants. We found that the COVID-19 global epidemic clearly featured increasing circulation of Alpha since the start of 2021, which was rapidly replaced by the Delta variant starting around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 63 countries performing routine genomic surveillance and 79 countries with high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequenced coverage across regions and countries. Across different variants, 21-46% of countries with explicit reporting on variants shared less than half of their variant sequences in public repositories. Our findings indicated an urgent need to expand sequencing capacity of virus isolates, enhance the sharing of sequences, the standardization of metadata files, and supportive networks for countries with no sequencing capability.
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http://dx.doi.org/10.21203/rs.3.rs-927070/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491853PMC
September 2021

Ultrasensitive and quantitative toxin measurement correlates with baseline severity, severe outcomes, and recurrence among hospitalized patients with Clostridioides difficile infection.

Clin Infect Dis 2021 Sep 19. Epub 2021 Sep 19.

Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: Stool toxin concentrations may impact Clostridioides difficile infection (CDI) severity and outcomes. We correlated fecal C. difficile toxin concentrations, measured by an ultrasensitive and quantitative assay, with CDI baseline severity, attributable outcomes, and recurrence.

Methods: We enrolled 615 hospitalized adults (≥ 18y) with CDI (acute diarrhea, positive stool NAAT, and decision to treat). Baseline stool toxin A and B concentrations were measured by Single Molecule Array. Subjects were classified by baseline CDI severity (four scoring methods) and outcomes within 40 days (death, ICU stay, colectomy, and recurrence).

Results: Among 615 patients (median 68.0 years), in all scoring systems, subjects with severe baseline disease had higher stool toxin A+B concentrations than those without (P<0.01). Nineteen subjects (3.1%) had a severe outcome primarily-attributed to CDI (group 1). This group had higher median toxin A+B [14,303 pg/mL (IQR 416.0, 141,967)] than subjects in whom CDI only contributed to the outcome [group 2, 163.2 pg/mL(0.0, 8423.3)], subjects with severe outcome unrelated to CDI [group 3, 158.6 pg/mL (0.0, 1795.2)], or no severe outcome [group 4, 209.5 pg/mL (0.0, 8566.3)](P=0.003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5-66.1%)(P=0.02). Individuals with recurrence had higher toxin A+B [2266.8 pg/mL(188.8, 29411)] than those without [154.0 pg/mL(0.0, 5864.3)](P<0.001) and higher rates of detectable toxin (85.7% versus 64.0%, P=0.004).

Conclusions: In CDI patients, ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course.
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http://dx.doi.org/10.1093/cid/ciab826DOI Listing
September 2021

Prediction of vaccine efficacy of the Delta variant.

medRxiv 2021 Aug 31. Epub 2021 Aug 31.

The emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.
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http://dx.doi.org/10.1101/2021.08.26.21262699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423227PMC
August 2021

Transcriptome analysis revealed multiple immune processes and energy metabolism pathways involved in the defense response of the large yellow croaker Larimichthys crocea against Pseudomonas plecoglossicida.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Jul 24;40:100886. Epub 2021 Jul 24.

Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. Electronic address:

The large yellow croaker (Larimichthys crocea) aquaculture industry is suffering substantial financial losses caused by visceral white nodules disease resulting from Pseudomonas plecoglossicida infection. However, how L. crocea responds to P. plecoglossicida infection remains largely unknown. Here, we characterized the changes in the mRNA profile in the spleen of L. crocea upon P. plecoglossicida infection and explored the related defensive strategies. Sample clustering analysis and qRT-PCR indicated that P. plecoglossicida induced profound and reproducible transcriptome remodeling in the L. crocea spleen. Many innate immune-related genes, such as IL-17 signaling molecules, chemokines and chemokine receptors, complement components, TLR5 signaling molecules, and antimicrobial peptide hepcidins (Hamps), were upregulated by P. plecoglossicida and may play important roles in the L. crocea defense against P. plecoglossicida. The antibacterial activity of Hamp2-5 against P. plecoglossicida was further confirmed by using synthetic mature peptide of Hamp2-5. Additionally, significant enrichment of "Glycolysis/Gluconeogenesis", "Citrate cycle" and "Oxidative phosphorylation" pathways and a significant upregulation of all 6 rate-limiting enzyme genes (HK1, PFK, PKM, CS, IDH2, DLST) in the Glycolysis and Citrate cycle pathways in P. plecoglossicida-infected fish suggested that ATP synthesis may be accelerated to ensure energy supply in response to pathogenic infection. Altogether, our results not only identified the key immune-related genes and immune pathways that participated in the defense response of L. crocea against P. plecoglossicida, but also revealed a novel defensive strategy involving ATP synthesis in this species.
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http://dx.doi.org/10.1016/j.cbd.2021.100886DOI Listing
July 2021

Cancer-fighting potentials of algal polysaccharides as nutraceuticals.

Food Res Int 2021 09 13;147:110522. Epub 2021 Jun 13.

Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, China. Electronic address:

Cancer has been listed as one of the world's five incurable diseases by the World Health Organization and causes tens of thousands of deaths every year. Unfortunately, anticancer agents either show limited efficacy or show serious side effects. The algae possess high nutritional value and their polysaccharides have a variety of biological activities, especially anti-cancer and immunomodulatory properties. Algal polysaccharides exert anti-cancer effects by inducing apoptosis, cell cycle arrest, anti-angiogenesis, and regulating intestinal flora and immune function. Algal polysaccharides can be combined with nanoparticles and other drugs to reduce the side effects caused by chemotherapy and increase the anticancer effects. This review shows the signal pathways related to the anti-cancer mechanisms of algal polysaccharides, including their influence on intestinal flora and immune regulation, the application of nanoparticles, and the effects on combination therapy and clinical trials of cancer treatments.
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http://dx.doi.org/10.1016/j.foodres.2021.110522DOI Listing
September 2021

Neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination: a systematic review and pooled meta-analysis.

Clin Infect Dis 2021 Jul 24. Epub 2021 Jul 24.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Recently emerged SARS-CoV-2 variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) significantly escaped natural-infection-mediated neutralization, with an average of 4.1-fold (95% CI: 3.6-4.7), 1.8-fold (1.4-2.4), and 3.2-fold (2.4-4.1) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 decreased slightly (1.4-fold, 95%CI: 1.2-1.6). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (5.5-9.0) for non-replicating vector platform, 4.1-fold (3.7-4.4) for mRNA platform, and 2.5-fold (1.7-2.9) for protein subunit platform. Neutralizing antibodies levels induced by mRNA vaccines against SARS-CoV-2 variants were similar, or higher, than that derived from naturally-infected individuals.
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http://dx.doi.org/10.1093/cid/ciab646DOI Listing
July 2021

Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota.

Front Microbiol 2021 2;12:649091. Epub 2021 Jul 2.

Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, China.

Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS)-based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.
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http://dx.doi.org/10.3389/fmicb.2021.649091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283677PMC
July 2021

Design and manufacture of miniaturized immersed imaging spectrometer for remote sensing.

Opt Express 2021 Jul;29(14):22603-22613

A miniaturized immersed imaging spectrometer possessing long slit and large relative aperture is proposed. It is integrated monolithically with three concentric optical components. Through the chief ray tracing, we analyzed its astigmatism characteristic and then deduced the anastigmatic condition for long slit. Meanwhile, it is athermal by matching the suitable lens materials to compensate thermal defocus. Based on the anastigmatic and athermal conditions, we have designed a miniaturized VNIR immersed imaging spectrometer and developed the prototype. Its slit is 48 mm long and it is optically fast with an F-number of 2.5. The new form shows about 12 times smaller in volume than the classic Offner-Chrisp imaging spectrometer and weighs only 2 kg, and has excellent thermal adaptability while temperature changes between -40 °C and 60 °C. Meanwhile, fabrication of core elements and gluing process of the immersed imaging spectrometer are presented. Test results of the prototype show superior performance with high imaging quality and small smile and keystone distortions. Such miniaturized immersed imaging spectrometer will greatly improve the performance and reduce the costs of wide swath hyperspectral remote sensing, and is desirable for usage on small plane or satellite platforms.
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http://dx.doi.org/10.1364/OE.433805DOI Listing
July 2021

Humoral Immune Response to Toxins A and B in Hospitalized Immunocompromised Patients With Infection.

Open Forum Infect Dis 2021 Jul 1;8(7):ofab286. Epub 2021 Jun 1.

Harvard Medical School, Boston, Massachusetts, USA.

Background: The humoral immune response to toxins in infection (CDI) is incompletely characterized in immunocompromised hosts (ICHs).

Methods: We conducted a prospective study of hospitalized adults with CDI, with and without immunosuppression (hematologic malignancy, active solid tumor, solid organ or stem cell transplant, inflammatory bowel disease, autoimmune disease, congenital or acquired immunodeficiency, asplenia, chronic receipt of high-dose steroids, or receipt of immunosuppressing medications within 12 months). Serum and stool antibody concentrations of immunoglobulin (Ig)M, IgG, and IgA to toxins A and B at treatment days 0, 3, and 10-14 were compared.

Results: Ninety-eight subjects (47 ICH; 51 non-ICH) were enrolled. Baseline serum antitoxin A and B antibody levels were similar. At day 3, ICHs demonstrated lower serum levels of antitoxin A IgG, antitoxin A IgA, and antitoxin B IgA (all < .05). At day 10-14, lower antitoxin A IgG concentrations were observed in ICHs (ICH, 21 enzyme-linked immunosorbent assay [ELISA] units; interquartile range [IQR], 16.4-44.6) compared with non-ICH subjects (49.0 ELISA units; IQR, 21.5-103; = .045). In stool, we observed lower concentrations of antitoxin B IgA antibodies at baseline and at day 3 for ICH subjects, with a notable difference in concentrations of antitoxin B IgA at day 3 (ICH, 6.7 ELISA units [IQR, 1.9-13.9] compared with non-ICH, 18.1 ELISA units [IQR, 4.9-31.7]; = .003).

Conclusions: The ICHs with CDI demonstrated lower levels of antitoxin antibodies in serum and stool during early CDI therapy compared with non-ICHs. These data provide insight into the humoral response to CDI in ICHs.
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http://dx.doi.org/10.1093/ofid/ofab286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271131PMC
July 2021

Syntheses, Structures and Luminescent Properties of Eu- and Tb-MOFs with 3,5-Pyridinedicarboxylate and 1,2-Benzenedicarboxylate.

J Fluoresc 2021 Sep 5;31(5):1393-1399. Epub 2021 Jul 5.

Key Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province, College of Chemical and Materials Engineering, Institute of Surface Micro and Nano Materials, Xuchang University, Henan, 461000, P. R. China.

Two lanthanide-based MOFs (Ln-MOFs) were synthesized by reaction of Eu(III) or Tb(III) perchlorates with mixed dicarboxylates of 3,5-pdc and 1,2-bdc (3,5-Hpdc = 3,5-pyridinedicarboxylic acid; 1,2-Hbdc = 1,2-benzenedicarboxylic acid) by hydrothermal method. The chemical formulas of the two complexes were [Eu(3,5-pdc)(1,2-bdc)(HO)] (1) and {[Tb(3,5-pdc)(1,2-bdc)(HO)]·2HO} (2). IR spectra and element analyses were tested to characterize the two compounds. The crystal structures were determined by X-ray single crystal diffraction. MOF 1 was 3D porous network structure but MOF 2 was 2D layered structure. The two MOFs emitted the characteristic fluorescence of Eu(III) or Tb(III) ion with the excitations of UV-rays. Their lifetimes of excited states for Eu(III) (D) and Tb(III) (D) were 0.31 and 0.82 ms. The absolute quantum yields (Ф) of MOF1 and 2 were also tested and the Ф(1) (λ = 320 nm) and Ф(2) (λ = 296 nm) were 15% and 48%, respectively.
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http://dx.doi.org/10.1007/s10895-021-02763-8DOI Listing
September 2021

Molecular characterization and role in virus infection of Beclin-1 in large yellow croaker (Larimichthys crocea).

Fish Shellfish Immunol 2021 Sep 17;116:30-41. Epub 2021 Jun 17.

Key Laboratory of Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China. Electronic address:

Beclin-1, the ortholog of yeast autophagy-related gene 6 (Atg6), has a central role in autophagy, which has been linked to diverse biological processes including immunity, development, tumor suppression, and lifespan extension. However, understanding of function of fish Beclin-1 is limited now. In this study, the complete Beclin-1 cDNA of large yellow croaker Larimichthys crocea (LcBeclin-1) was cloned, whose open reading frame (ORF) is 1344 bp long and encodes a protein of 447 amino acids (aa). The deduced LcBeclin-1 possesses a typical Bcl-2 homology domain 3(BH3) and an APG6 domain that contains a central coiled-coil domain (CCD, residues 174 to 231) and a C-terminal evolutionarily conserved domain (ECD, residues 241 to 334). LcBeclin-1 shared a high amino acid identity of 81.66-98.66% with reported Beclin-1 molecules from other vertebrate species. LcBeclin-1 gene was constitutively expressed in all tissues tested, with the highest levels in heart. LcBeclin-1 transcripts were also detected in primary head kidney granulocytes (PKGs), primary head kidney macrophages (PKMs), primary head kidney leukocytes (PKLs), and large yellow croaker head kidney cell line (LYCK), and were significantly upregulated by poly (I:C) in PKMs and LYCK cells. Subcellular localization showed that LcBeclin-1 was evenly distributed in the cytoplasm and nucleus of LYCK cells. Overexpression of LcBeclin-1 significantly increased the replication of SVCV, as evidenced by increased severity of the cytopathic effects, enhanced viral titre, and upregulated transcriptional levels of viral genes. Further studies showed that LcBeclin-1 induced the occurrence of autophagy in LYCK cells. Additionally, LcBeclin-1 also decreased the expression levels of large yellow croaker interferons (IFNs; IFNc, IFNd, and IFNh), interferon regulatory factor 3 (IRF3) and IRF7, IFN-stimulated genes (ISGs; Mx, PKR, and Viperin) in LYCK cells. All these data suggest that LcBeclin-1 promoted the viral replication possibly by inducing autophagy or negatively modulating IFN response, which will help us to further understand the function of fish Beclin-1.
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http://dx.doi.org/10.1016/j.fsi.2021.06.006DOI Listing
September 2021

"Adjusting Internal Organs and Dredging Channel" Electroacupuncture Ameliorates Insulin Resistance in Type 2 Diabetes Mellitus by Regulating the Intestinal Flora and Inhibiting Inflammation.

Diabetes Metab Syndr Obes 2021 9;14:2595-2607. Epub 2021 Jun 9.

Northeast Asia Institute of Chinese Medicine, Changchun University of Chinese Medicine, Jilin, 130117, People's Republic of China.

Introduction: Traditional Chinese acupuncture has been demonstrated to be beneficial for treatment of type 2 diabetes mellitus (T2DM). The mechanism of acupuncture on T2DM is crucial for their biological activity as well as their usefulness as tools in biology and medicine. However, its mechanism is poorly understood.

Methods: In an effort to explore the mechanism, eight db/db mice (a type of spontaneous T2DM mouse) were treated with adjusting internal organs and dredging channel electroacupuncture (AODCEA) for 2 weeks. Another eight db/db mice were fed as T2DM group (T2DMG), and eight db/m mice were set as normal control group (NCG). Lipopolysaccharide (LPS), interleukin-6 (IL-6), and diabetes-related indicators, such as fasting blood glucose (FBG) and triglyceride (TG), were detected by enzyme-linked immune sorbent assay (ELISA). The V4 region of 16S rRNA gene was analyzed by Illumina sequencing to evaluate the effect of AODCEA on intestinal flora. The amount of short-chain fatty acids (SCFAs) in the feces were determined by gas chromatography-mass spectrometry (GC-MS).

Results: Our results indicate that AODCEA treatment can reduce diabetes-related indicators. We observed the increased probiotics such as Blautia and Lactobacillus and decreased opportunist pathogens (Alistipes, Helicobacter, Prevotella) by AODCEA interventions. Importantly, the total amount of SCFAs in the feces of T2DM mice was promoted by AODCEA. Finally, obviously alleviated systemic inflammation was exhibited through AODCEA treatment by detection of lipopolysaccharide (LPS) and interleukin-6 (IL-6) in serum.

Conclusion: AODCEA can reshape the structure of intestinal flora, which can increase intestinal SCFAs, affect the circulating LPS level, and reduce the inflammatory response.
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http://dx.doi.org/10.2147/DMSO.S306861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200173PMC
June 2021

Integrating gut microbiome and host immune markers to understand the pathogenesis of infection.

Gut Microbes 2021 Jan-Dec;13(1):1-18

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts USA.

( ) infection is the most common cause of healthcare-associated infection and an important cause of morbidity and mortality among hospitalized patients. A comprehensive understanding of infection (CDI) pathogenesis is crucial for disease diagnosis, treatment, and prevention. Here, we characterized gut microbial compositions and a broad panel of innate and adaptive immunological markers in 243 well-characterized human subjects (including 187 subjects with both microbiota and immune marker data), who were divided into four phenotype groups: CDI, Asymptomatic Carriage, Non-CDI Diarrhea, and Control. We found that the interactions between gut microbiota and host immune markers are very sensitive to the status of colonization and infection. We demonstrated that incorporating both gut microbiome and host immune marker data into classification models can better distinguish CDI from other groups than can either type of data alone. Our classification models display robust diagnostic performance to differentiate CDI from Asymptomatic carriage (AUC~0.916), Non-CDI Diarrhea (AUC~0.917), or Non-CDI that combines all other three groups (AUC~0.929). Finally, we performed symbolic classification using selected features to derive simple mathematic formulas that explicitly quantify the interactions between the gut microbiome and host immune markers. These findings support the potential roles of gut microbiota and host immune markers in the pathogenesis of CDI. Our study provides new insights for a microbiome-immune marker-derived signature to diagnose CDI and design therapeutic strategies for CDI.
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http://dx.doi.org/10.1080/19490976.2021.1935186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210874PMC
June 2021

α-Tocopherol Stereoisomer Profiles in Matched Human Maternal and Umbilical Cord Plasma.

Curr Dev Nutr 2021 Jun 3;5(6):nzab073. Epub 2021 May 3.

Department of Obstetrics/Gynecology, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA.

Background: α-Tocopherol (αT) is essential for fetal development. One study has shown that the human placenta preferentially transfers the natural stereoisomer, -αT. But prenatal supplements generally contain synthetic αT (S-αT).

Objectives: We aimed to determine if umbilical cord plasma is enriched for -αT in racially diverse neonates from both uncomplicated and complicated pregnancies and if cord -αT enrichment is impacted by maternal αT stereoisomer profile.

Methods: We measured αT and αT stereoisomers in plasma from a randomly selected subset of 66 predominantly black and Hispanic maternal-fetal pairs from the Camden Study involving control (= 28) and complicated pregnancies (= 38). We collected maternal plasma at study entry (week 16 gestation; w16) and week 28 gestation (w28) and cord plasma at birth.

Results: -αT was the predominant stereoisomer in all maternal and cord plasma samples, but S-αT stereoisomers were found in most samples and comprised a high percentage of αT in some maternal-neonate pairs. Cord plasma had a higher percentage -αT (< 0.05) and lower percentage S-αT (< 0.0001) than w28 plasma. Pregnancy status did not impact maternal or cord plasma concentrations of αT, -αT, or S-αT; except plasma from complicated pregnancies was higher in S-αT at w28 than at w16 (< 0.05). Maternal w28 αT did not correlate with cord αT. However, both maternal w28 αT and S-αT positively correlated with both cord S-αT ( = 0.340, = 0.0049;  = 0.538, < 0.00001) and percentage S-αT ( = 0.399, = 0.001;  = 0.786, < 0.00001) but negatively correlated with cord percentage -αT ( = -0.399, = 0.0009; = -0.786, < 0.00001).

Conclusions: The proportion of -αT was higher in cord compared with maternal plasma in both uncomplicated and complicated pregnancies. Our data suggest that maternal S-αT raises cord S-αT and decreases the proportion of -αT in the neonatal circulation. Because the bioactivities of -αT and S-αT differ, this warrants future research to determine the importance of our observations to neonatal αT status.
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http://dx.doi.org/10.1093/cdn/nzab073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178107PMC
June 2021

Metabolizable Near-Infrared-II Nanoprobes for Dynamic Imaging of Deep-Seated Tumor-Associated Macrophages in Pancreatic Cancer.

ACS Nano 2021 06 1;15(6):10010-10024. Epub 2021 Jun 1.

Paul C. Lauterbur Research Center for Biomedical Imaging, Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Key Laboratory of Ultrasound Imaging and Therapy, CAS Key Laboratory of Health Informatics, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China.

Tumor-associated macrophages (TAMs) play a crucial part in cancer evolution. Dynamic imaging of TAMs is of great significance for treatment outcome evaluation and precision tumor therapy. Currently, most fluorescence nanoprobes tend to accumulate in the liver and are difficult to metabolize, which leads to strong background signals and inadequate imaging quality of TAMs nearby the liver such as pancreatic cancer. Herein, we aim to develop metabolizable dextran-indocyanine green (DN-ICG) nanoprobes in the second near-infrared window (NIR-II, 1 000-1 700 nm) for dynamic imaging of TAMs in pancreatic cancer. Compared to free ICG, the NIR-II fluorescence intensity of DN-ICG nanoprobes increased by 279% with significantly improved stability. We demonstrated that DN-ICG nanoprobes could specifically target TAMs through the interaction of dextran with specific ICAM-3-grabbing nonintegrin related 1 (SIGN-R1), which were highly expressed in TAMs. Subsequently, DN-ICG nanoprobes gradually metabolized in the liver yet remained in pancreatic tumor stroma in mouse models, achieving a high signal-to-background ratio (SBR = 7) in deep tissue (∼0.5 cm) NIR-II imaging of TAMs. Moreover, DN-ICG nanoprobes could detect dynamic changes of TAMs induced by low-dose radiotherapy and zoledronic acid. Therefore, the highly biocompatible and biodegradable DN-ICG nanoprobes harbor great potential for precision therapy in pancreatic cancer.
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http://dx.doi.org/10.1021/acsnano.1c01608DOI Listing
June 2021

Acupuncture therapy and cognitive dysfunction in patients with type 2 diabetes: A protocol for systematic review.

Medicine (Baltimore) 2021 May;100(21):e26115

Department of Acupuncture and Tuina, Changchun University of Chinese Medicine.

Background: With the aging of society, the incidence of type 2 diabetes (T2DM) is increasing every year, and there is a clear correlation between T2DM and cognitive dysfunction. Acupuncture therapy has been widely used in the treatment of T2DM, but there is no systematic review on the treatment of T2DM associated with cognitive impairment. Therefore, this study aimed to conduct a meta-analysis of acupuncture in the treatment of T2DM with cognitive impairment to clarify its efficacy.

Methods: A structured and systematic literature search will be conducted in the following databases up to April 26, 2021: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (WOS), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific and Journal Database (VIP), and Wan Fang database (Wanfang). We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures.

Results: This meta-analysis further determined the beneficial effects of acupuncture on T2DM with cognitive impairment.

Conclusion: The purpose of this meta-analysis was to explore the effect of acupuncture on patients T2DM with and cognitive impairment patients, and provide more options for clinicians and patients to treat T2DM with cognitive impairment.

Ethics And Dissemination: This systematics review will evaluate the efficacy and safety of acupuncture in the treatment of T2DM with cognitive impairment. Since all the data included were published, the systematic review did not require ethical approval.

Registration Number: CRD42021245681.
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http://dx.doi.org/10.1097/MD.0000000000026115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154404PMC
May 2021

Prognosis prediction model for a special entity of gastric cancer, linitis plastica.

J Gastrointest Oncol 2021 Apr;12(2):307-327

Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Gastric linitis plastica (GLP) is characteristic by its poor prognosis and highly aggressive characteristics compared with other types of gastric cancer (GC). However, the guidelines have not yet been distinguished between GLP and non-GLP.

Methods: A total of 342 eligible patients with GLP identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training set (n=298) and validation set (n=153). A nomogram would be developed with the constructed predicting model based on the training cohort's data, and the validation cohort would be used to validate the model. Principal component analysis (PCA) was used to evaluate the differences between groups. Cox regression and LASSO (least absolute shrinkage and selection operator) were used to construct the models. Calibration curve, time-dependent receiver operating characteristic (ROC) curve, concordance index (C-index) and decision curve analysis (DCA) were used to evaluate the predicting performance. Restricted mean survival time (RMST) was used to analyze the curative effect of adjuvant therapy.

Results: For patients in training cohort, univariable and multivariable Cox analyses showed that age, examined lymph nodes (LN.E), positive lymph nodes (LN.P), lesion size, combined resection, and radiotherapy are independent prognostic factors for overall survival (OS), while chemotherapy can not meet the proportional hazards (PHs) assumption; age, race, lesion size, LN.E, LN.P, combined resection and marital status are independent prognostic factors for cancer-specific survival (CSS). The C-index of the nomogram was 0.678 [95% confidence interval (CI), 0.660-0.696] and 0.673 (95% CI, 0.630-0.716) in the training and validation cohort, respectively. Meanwhile, the C-index of the CSS nomogram was 0.671 (95% CI, 0.653-0.699) and 0.650 (95% CI, 0.601-0.691) in the training and validation cohort for CSS, respectively. Furthermore, the nomogram was well calibrated with satisfactory consistency. RMST analysis further determined that chemotherapy and radiotherapy might be beneficial for improving 1- and 3-year OS and CSS, but not the 5-year CSS.

Conclusions: We developed nomograms to help predict individualized prognosis for GLP patients. The new model might help guide treatment strategies for patients with GLP.
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http://dx.doi.org/10.21037/jgo-20-264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107584PMC
April 2021

Whole genome sequencing of a snailfish from the Yap Trench (~7,000 m) clarifies the molecular mechanisms underlying adaptation to the deep sea.

PLoS Genet 2021 05 13;17(5):e1009530. Epub 2021 May 13.

Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.

Hadal environments (depths below 6,000 m) are characterized by extremely high hydrostatic pressures, low temperatures, a scarce food supply, and little light. The evolutionary adaptations that allow vertebrates to survive in this extreme environment are poorly understood. Here, we constructed a high-quality reference genome for Yap hadal snailfish (YHS), which was captured at a depth of ~7,000 m in the Yap Trench. The final YHS genome assembly was 731.75 Mb, with a contig N50 of 0.75 Mb and a scaffold N50 of 1.26 Mb. We predicted 24,329 protein-coding genes in the YHS genome, and 24,265 of these genes were successfully functionally annotated. Phylogenetic analyses suggested that YHS diverged from a Mariana Trench snailfish approximately 0.92 million years ago. Many genes associated with DNA repair show evidence of positive selection and have expanded copy numbers in the YHS genome, possibly helping to maintain the integrity of DNA under increased hydrostatic pressure. The levels of trimethylamine N-oxide (TMAO), a potent protein stabilizer, are much higher in the muscles of YHS than in those of shallow-water fish. This difference is perhaps due to the five copies of the TMAO-generating enzyme flavin-containing monooxygenase-3 gene (fmo3) in the YHS genome and the abundance of trimethylamine (TMA)-generating bacteria in the YHS gut. Thus, the high TMAO content might help YHS adapt to high hydrostatic pressure by improving protein stability. Additionally, the evolutionary features of the YHS genes encoding sensory-related proteins are consistent with the scarce food supply and darkness in the hadal environments. These results clarify the molecular mechanisms underlying the adaptation of hadal organisms to the deep-sea environment and provide valuable genomic resources for in-depth investigations of hadal biology.
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http://dx.doi.org/10.1371/journal.pgen.1009530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118300PMC
May 2021

Comprehensive mapping of neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination.

medRxiv 2021 May 5. Epub 2021 May 5.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Background: Immunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed.

Methods: We systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays.

Findings: We identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non-replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9).

Interpretation: Our findings indicate that the antibody response established by natural infection or vaccination might be able to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed.

Funding: Chinese National Science Fund for Distinguished Young Scholars.

Research In Context: Several newly emerged SARS-CoV-2 variants have raised significant concerns globally, and there is concern that SARS-CoV-2 variants can evade immune responses that are based on the prototype strain. It is not known to what extent do emerging SARS-CoV-2 variants escape the immune response induced by previous infection or vaccination. However, existing studies of neutralizing potency against SARS-CoV-2 variants are based on limited numbers of samples and lack comparability between different laboratory methods. Furthermore, there are no studies providing whole picture of neutralizing antibodies induced by prior infections or vaccination against emerging variants. Therefore, we systematically reviewed and quantitively synthesized evidence on the degree to which antibodies from previous SARS-CoV-2 infection or vaccination effectively neutralize variants. In this study, 56 studies, including 2,483 individuals and 8,590 neutralization tests, were identified. Antibodies from natural infection or vaccination are likely to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Lineage B.1.351 escaped natural-infection-mediated neutralization the most, with GMT of 79.2 (95% CI: 68.5-91.6), while neutralizing antibody titers against the B.1.1.7 variant were largely preserved (254.6, 95% CI: 214.1-302.8). Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The neutralizing antibody response after vaccinating with non-replicating vector vaccines against lineage B.1.351 was worse than responses elicited by vaccines on other platforms, with levels lower than that of individuals who were previously infected. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Our findings indicate that antibodies from natural infection of the parent lineage of SARS-CoV-2 or vaccination may be less able to neutralize some emerging variants, and antibody-based therapies may need to be updated. Furthermore, standardized protocols for neutralizing antibody testing against SARS-CoV-2 are needed to reduce lab-to-lab variations, thus facilitating comparability and interpretability across studies.
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http://dx.doi.org/10.1101/2021.05.03.21256506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109187PMC
May 2021

Alterations in the human oral and gut microbiomes and lipidomics in COVID-19.

Gut 2021 07 31;70(7):1253-1265. Epub 2021 Mar 31.

State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Objective: To characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile.

Design: We collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity.

Results: Oral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery.

Conclusion: This study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.
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http://dx.doi.org/10.1136/gutjnl-2020-323826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042598PMC
July 2021

Infectivity, susceptibility, and risk factors associated with SARS-CoV-2 transmission under intensive contact tracing in Hunan, China.

Nat Commun 2021 03 9;12(1):1533. Epub 2021 Mar 9.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1178 potential SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts.
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http://dx.doi.org/10.1038/s41467-021-21710-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943579PMC
March 2021

Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis.

Lancet Glob Health 2021 05 8;9(5):e598-e609. Epub 2021 Mar 8.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China; Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China; Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: A rapidly increasing number of serological surveys for antibodies to SARS-CoV-2 have been reported worldwide. We aimed to synthesise, combine, and assess this large corpus of data.

Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and five preprint servers for articles published in English between Dec 1, 2019, and Dec 22, 2020. Studies evaluating SARS-CoV-2 seroprevalence in humans after the first identified case in the area were included. Studies that only reported serological responses among patients with COVID-19, those using known infection status samples, or any animal experiments were all excluded. All data used for analysis were extracted from included papers. Study quality was assessed using a standardised scale. We estimated age-specific, sex-specific, and race-specific seroprevalence by WHO regions and subpopulations with different levels of exposures, and the ratio of serology-identified infections to virologically confirmed cases. This study is registered with PROSPERO, CRD42020198253.

Findings: 16 506 studies were identified in the initial search, 2523 were assessed for eligibility after removal of duplicates and inappropriate titles and abstracts, and 404 serological studies (representing tests in 5 168 360 individuals) were included in the meta-analysis. In the 82 studies of higher quality, close contacts (18·0%, 95% CI 15·7-20·3) and high-risk health-care workers (17·1%, 9·9-24·4) had higher seroprevalence than did low-risk health-care workers (4·2%, 1·5-6·9) and the general population (8·0%, 6·8-9·2). The heterogeneity between included studies was high, with an overall I of 99·9% (p<0·0001). Seroprevalence varied greatly across WHO regions, with the lowest seroprevalence of general populations in the Western Pacific region (1·7%, 95% CI 0·0-5·0). The pooled infection-to-case ratio was similar between the region of the Americas (6·9, 95% CI 2·7-17·3) and the European region (8·4, 6·5-10·7), but higher in India (56·5, 28·5-112·0), the only country in the South-East Asia region with data.

Interpretation: Antibody-mediated herd immunity is far from being reached in most settings. Estimates of the ratio of serologically detected infections per virologically confirmed cases across WHO regions can help provide insights into the true proportion of the population infected from routine confirmation data.

Funding: National Science Fund for Distinguished Young Scholars, Key Emergency Project of Shanghai Science and Technology Committee, Program of Shanghai Academic/Technology Research Leader, National Science and Technology Major project of China, the US National Institutes of Health.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2214-109X(21)00026-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049592PMC
May 2021

Fecal Mycobiota Combined With Host Immune Factors Distinguish Clostridioides difficile Infection From Asymptomatic Carriage.

Gastroenterology 2021 Jun 5;160(7):2328-2339.e6. Epub 2021 Mar 5.

Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background & Aims: Although the role of gut microbiota in Clostridioides difficile infection (CDI) has been well established, little is known about the role of mycobiota in CDI. Here, we performed mycobiome data analysis in a well-characterized human cohort to evaluate the potential of using gut mycobiota features for CDI diagnosis.

Methods: Stool samples were collected from 118 hospital patients, divided into 3 groups: CDI (n = 58), asymptomatic carriers (Carrier, n = 28), and Control (n = 32). The nuclear ribosomal DNA internal transcribed spacer 2 was sequenced using the Illumina HiSeq platform to assess the fungal composition. Downstream statistical analyses (including Alpha diversity analysis, ordination analysis, differential abundance analysis, fungal correlation network analysis, and classification analysis) were then performed.

Results: Significant differences were observed in alpha and beta diversity between patients with CDI and Carrier (P < .05). Differential abundance analysis identified 2 genera (Cladosporium and Aspergillus) enriched in Carrier. The ratio of Ascomycota to Basidiomycota was dramatically higher in patients with CDI than in Carrier and Control (P < .05). Correlations between host immune factors and mycobiota features were weaker in patients with CDI than in Carrier. Using 4 fungal operational taxonomic units combined with 6 host immune markers in the random forest classifier can achieve very high performance (area under the curve ∼92.38%) in distinguishing patients with CDI from Carrier.

Conclusions: Our study provides specific markers of stool fungi combined with host immune factors to distinguish patients with CDI from Carrier. It highlights the importance of gut mycobiome in CDI, which may have been underestimated. Further studies on the diagnostic applications and therapeutic potentials of these findings are warranted.
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http://dx.doi.org/10.1053/j.gastro.2021.02.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169571PMC
June 2021
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