Publications by authors named "Nan Zheng"

435 Publications

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

Using Micro-Raman Spectroscopy to Investigate Chemical Composition, Mixing States, and Heterogeneous Reactions of Individual Atmospheric Particles.

Environ Sci Technol 2021 Jul 21. Epub 2021 Jul 21.

BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China.

Measuring the chemical composition of individual atmospheric aerosol particles can provide direct evidence of their heterogeneous reactions and mixing states in the atmosphere. In this study, micro-Raman spectroscopy was used to measure the chemical composition of 1200 individual atmospheric particles in 11 samples collected in Beijing air. (NH)SO, NHNO, various minerals, carbonaceous species (soot and organics), and NaNO were identified in the measured particles according to their characteristic Raman peaks. These species represented the main components of aerosol particles. In individual particles, NHNO and (NH)SO either existed separately or were internally mixed. Possible reaction pathways of CaCO particles in the atmosphere were proposed based on the results of this study and laboratory simulations on heterogeneous reactions in the literature. CaCO reacted with N- and S-containing (nitrogen- and sulfur-containing) acidic gases to produce Ca(NO) and CaSO. Ca(NO) further reacted with S-containing acidic gases and oxidants to produce CaSO. Of the soot-containing particles, 23% were internal mixtures of soot and inorganic material. Of the organics-containing particles, 57% were internal mixtures of organic and inorganic materials. Micro-Raman spectroscopy directly identified functional groups and molecules in individual atmospheric particles under normal ambient conditions, rendering it a powerful tool for measuring the chemical composition of individual atmospheric particles with a diameter of ≥1.0 μm.
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http://dx.doi.org/10.1021/acs.est.1c01242DOI Listing
July 2021

Lactoferrin could alleviate liver injury caused by Maillard reaction products with furan ring through regulating necroptosis pathway.

Food Sci Nutr 2021 Jul 6;9(7):3449-3459. Epub 2021 May 6.

Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs Institute of Animal Science Chinese Academy of Agricultural Sciences Beijing China.

As classical MRPs, the toxic effects of furosine, pyralline, and 5-hydroxymethylfurfural (5-HMF) in liver tissue are evaluated and the related mechanism is investigated here, and the protective effects of lactoferrin on liver injury caused by Maillard reaction products (MRPs) with furan ring are proved in vitro and in vivo. First, we detect the concentrations of furosine, pyralline, and 5-HMF in several foods using ultrahigh-performance liquid chromatography (UHPLC). Then, the effects of the three MRPs on liver cells (HL-7702) viability, as well as liver tissue, are performed and evaluated. Furthermore, the regulations of three MRPs on necroptosis-related pathway in liver cells are investigated. Additionally, the effects of lactoferrin in alleviating liver injury, as well as regulating necroptosis pathway, were evaluated. Results elucidate that lactoferrin protects liver injury caused by MRPs with furan ring structure through activating RIPK1/RIPK3/p-MLKL necroptosis pathway and downstream inflammatory reaction.
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http://dx.doi.org/10.1002/fsn3.2254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269604PMC
July 2021

Loss of Knee Flexion and Femoral Rollback of the Medial-Pivot and Posterior-Stabilized Total Knee Arthroplasty During Early-Stance of Walking in Chinese Patients.

Front Bioeng Biotechnol 2021 24;9:675093. Epub 2021 Jun 24.

Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

The medial-pivot (MP) prosthesis was developed to produce more physiological postoperative knee kinematics and better patient satisfaction than traditional prostheses, but outcomes are inconsistent in different studies of Caucasian patients. This study aimed to investigate the postoperative patient satisfaction and knee kinematics of the MP and posterior-stabilized (PS) prosthesis during gait activity in Chinese patients. A retrospective analysis of 12 patients was received for this study in each MP group and PS group. Patient-reported satisfaction level and Forgotten Joint Score (FJS) were evaluated with questionnaires. A dual fluoroscopic imaging system was used to investigate knee kinematics of MP and PS total knee arthroplasty (TKA) during treadmill walking at a speed of 0.4 m/s. Comparable promising patient satisfaction and overall FJS (MP 60.7 ± 15.35 vs. PS 51.3 ± 17.62, = 0.174) were found between the MP and PS groups. Peak flexion appeared at around 70% of gait cycle with values of 52.4 ± 7.4° for MP and 50.1 ± 3.6° for PS groups (no difference). Both groups maintained a stable position at the stance phase and began to translated anteriorly at toe-off with an amount of 4.5 ± 2.3 mm in the MP and 6.6 ± 2.7 mm in the PS ( = 0.08) group until late swing. The range of this external rotation motion was 5.9 ± 4.8 and 6.2 ± 4.1° ( = 0.79) for the MP and PS, respectively. A similar knee kinematics pattern characterized by a loss of early-stance knee flexion and femoral rollback during walking was observed in the MP and PS TKAs. Our study confirmed similar effectiveness of MP TKA compared to PS TKA in Chinese patients, while the change of knee kinematics of both implants during slow walking should be noted.
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http://dx.doi.org/10.3389/fbioe.2021.675093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264512PMC
June 2021

Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer.

Front Immunol 2021 24;12:678318. Epub 2021 Jun 24.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, China.

Cervical cancer caused by human papillomavirus (HPV) infections is the fourth most common cancer in women worldwide. Current prophylactic HPV vaccines have achieved promising success in preventing HPV infection. However, still 570,000 new cases were reported in 2018. The current primary treatment for the patient with cervical cancer is either surgery or chemoradiotherapy. Cervical cancer still lacks standard medical therapy. HPV18 induced cervical cancer has the worst prognosis and high mortality compared to other HPV infections. The development of HPV18 related with cervical malignancy requires the persistent infection of cervical-vaginal epithelium by HPV18 subtype, which can take years to transform the epithelium. This period of repeated infection provides a window for therapeutic intervention. Neutralizing antibodies formulated as topical agents that inhibit HPV18 infection should reduce the chance of cervical malignancy. We previously demonstrated that potent neutralizing anti-sera against HPV18 infection were induced by HPV18 viral like particle (VLP) generated in mammalian cells. We, therefore, isolated two potent neutralizing antibodies, 2A12 and 8H4, from over 3,810 hybridomas prepared from mice immunized with HPV18 VLP. 2A12 and 8H4 exhibited excellent potency, with 50% virus-inhibitory concentrations (IC) of 0.4 and 0.9 ng/ml, respectively. Furthermore, 2A12 and 8H4 recognized distinct and non-overlapping quaternary epitopes and bound specifically with HPV18. Humanized 2A12 (Hu2A12) retained comparable neutralizing activity against HPV18 infection in various acidic pH settings and in hydrogel formulation with IC values of 0.04 to 0.77 ng/ml, indicating that Hu2A12 will be a promising candidate for clinical development as a topical vaginal biopharmaceutical agent against HPV18 infection.
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http://dx.doi.org/10.3389/fimmu.2021.678318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264373PMC
June 2021

Nonstructural Protein NSs Hampers Cellular Antiviral Response through LSm14A during Severe Fever with Thrombocytopenia Syndrome Virus Infection.

J Immunol 2021 Jul 9. Epub 2021 Jul 9.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China;

The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome virus (SFTSV) plays multiple functions in the virus life cycle. Proteomic screening for host proteins interacting with NSs identified the cellular protein LSm14A. LSm14A, a member of the LSm family involved in RNA processing in the processing bodies, binds to viral RNA or synthetic homolog and mediates IFN regulatory factor 3 activation and IFN-β induction. NSs interacted with and colocalized with LSm14A, and this interaction effectively inhibited downstream phosphorylation and dimerization of IFN regulatory factor 3, resulting in the suppression of antiviral signaling and IFN induction in several cell types of human origin. Knockdown of NSs resulted in the suppression of SFTSV replication in host cells. Viral RNA bound to LSm14A-NSs protein complex during the interaction. A newly discovered motif of NSs functioned to interact with LSm14A. Altogether, our data demonstrated a mechanism used by SFTSV to inhibit host innate immune response.
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http://dx.doi.org/10.4049/jimmunol.2100148DOI Listing
July 2021

Multifunctional room-temperature phosphorescent carbon dots for relative humidity determination and information encryption.

Talanta 2021 Oct 26;233:122541. Epub 2021 May 26.

Key Laboratory of Modern Analytical Science and Separation Technology, College of Chemistry, Chemical Engineering and Environment, Minnan Normal University, Zhangzhou, 363000, PR China.

The relative humidity (RH) determination is crucial in many fields. Based on the phosphorescent properties of room-temperature phosphorescent (RTP) carbon dots, the RTP carbon dots as a probe are expected to be used to rapidly detect relative humidity. In this study, matrix-free room-temperature phosphorescent N-doped carbon dots (N-CDs) were successfully prepared from urea, succinic acid, and acrylamide using a hydrothermal method. The as-synthesized N-CDs had good biocompatibility and water solubility. The N-CDs emitted blue fluorescence and green phosphorescence. Moreover, the N-CD powder exhibited stable phosphorescence with a phosphorescence lifetime of 158 ms (afterglow time to the naked eye for ~7 s). Because HO molecules affected the afterglow time, the as-prepared N-CD test paper for the first time could be applied as a probe to monitor RH, the afterglow time of the N-CD test paper is linearly related to the RH (y = -0.0729x+7.042, R = 0.998) and the RH detection range is 0%-85%. And the results were consistent with those obtained using a hygrometer. In addition, the N-CD solution could also be used as an encryption ink in the advanced information security field.
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http://dx.doi.org/10.1016/j.talanta.2021.122541DOI Listing
October 2021

Linear and high-molecular-weight poly-porphyrins for efficient photodynamic therapy.

Biomater Sci 2021 Jun;9(13):4630-4638

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. China.

Photodynamic therapy (PDT) holds great potential in cancer treatment due to the advantages of non-invasiveness, negligible side-effect, and high spatiotemporal selectivity. Porphyrin is the most widely used photosensitizer in clinical treatment. However, its PDT efficacy is always limited by the undesired aggregation caused quenching (ACQ) effect originating from the planar and rigid structure. In this work, a linear polymeric porphyrin with "structure defects" was developed to overcome the ACQ effect for most of the photosensitizers with conjugated macrocycles. Compared to porphyrin monomers, poly-porphyrins could improve singlet oxygen generation ability, and the singlet oxygen quantum yield enhanced with increasing molecular weight of poly-porphyrins. To achieve efficient in vivo PDT, PEG and acetazolamide were conjugated to the optimized poly-porphyrins to afford pP-PEG-AZ nanoparticles (pP-PEG-AZ NPs) with excellent stability, efficient in vitro intracellular internalization, negligible dark-toxicity, notable photo-toxicity, and in vivo anti-cancer efficacy based on combined PDT and anti-angiogenesis therapy.
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http://dx.doi.org/10.1039/d1bm00117eDOI Listing
June 2021

Well-Placed Acetabular Component Oriented Outside the Safe Zone During Weight-Bearing Daily Activities.

Front Bioeng Biotechnol 2021 10;9:664907. Epub 2021 Jun 10.

Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

A comprehensive and thorough understanding of functional acetabular component orientation is essential for optimizing the clinical outcome after total hip arthroplasty (THA). This study aimed to quantify the functional acetabular anteversion and inclination of unilateral THA patients during walking and static standing and to determine whether the functional acetabular orientation falls within the Lewinnek safe zone. Seventeen patients with unilateral THA received a CT scan and dual fluoroscopic imaging during level walking and static standing to evaluate hip kinematics. The pelvic functional coordinate system of the 3D CT-based computer model was defined by the line of gravity and anterior pelvic plane (APP) to measure functional acetabular anteversion and inclination in different postures. The Lewinnek safe zone was used to determine the acetabular malposition during functional activities. The THA side demonstrated an average of 10.1° (± 9.6°, range -7.5° to 29.9°) larger functional anteversion and 16.0° (± 9.2°, range -7.2° to 29.9°) smaller inclination than native hips during level walking. Functional acetabular anteversion in the THA side during level walking and static standing was significantly larger than anatomical measurements ( < 0.05). Acetabular orientation of most well-placed THA components anatomically in the Lewinnek safe zone fell outside the safe zone during more than half of the gait cycle and static standing. The current study revealed that an anatomically well-placed acetabular cup does not guarantee a well-functional orientation during daily activities. The mechanical performance and loading conditions of the THA component during other weight-bearing activities should be investigated in further studies.
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http://dx.doi.org/10.3389/fbioe.2021.664907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222599PMC
June 2021

Polymorphisms in the GCK gene increase the risk of clopidogrel resistance in stable coronary artery disease (SCAD) patients.

Hematology 2021 Dec;26(1):447-452

Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, People's Republic of China.

Background: Diabetes mellitus is a major factor in clopidogrel resistance (CR), and the glucokinase (GCK) gene plays a pivotal role in glucose homeostasis. This study investigated the contribution of GCK polymorphisms to CR risk.

Methods: Two hundred SCAD patients were recruited, and their platelet functions were detected by the Verify-Now P2Y12 assay. The polymorphisms of GCK were tested based on the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We investigated the associations of GCK polymorphisms and CR. Multivariate logistic regression was performed to analyse the correlations between GCK polymorphisms and clinical values.

Results: Our study found that the SNPs rs4607517 and rs6975024 were associated with CR. Additionally, patients with the G allele of rs4607517had a greater CR risk, but the C allele of rs6975024 might be a protective factor. Finally, logistic regression revealed that CC + TC (rs6975024) as well as the values of albumin were correlated with a decreased risk of CR, and higher levels of uric acid (UA) may be positively associated with CR.

Conclusion: The GCK gene polymorphisms might increase the CR risk in SCAD patients. Meanwhile, higher albumin levels and lower UA values might decrease the risk.
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http://dx.doi.org/10.1080/16078454.2021.1945789DOI Listing
December 2021

Electrocatalytic redox neutral [3 + 2] annulation of -cyclopropylanilines and alkenes.

Chem Sci 2020 Nov 9;12(3):969-975. Epub 2020 Nov 9.

Department of Chemistry & Environmental Science, New Jersey Institute of Technology Newark New Jersey 07102 USA

Although synthetic organic electrochemistry (EC) has advanced significantly, net redox neutral electrosynthesis is quite rare. Two approaches have been employed to achieve this type of electrosynthesis. One relies on turnover of the product by the reactant in a chain mechanism. The other involves both oxidation on the anode and reduction on the cathode in which the radical cation or the radical anion of the product has to migrate between two electrodes. Herein, a home-built electrochemistry/mass spectrometry (EC/MS) platform was used to generate an -cyclopropylaniline radical cation electrochemically and to monitor its reactivity toward alkenes by mass spectrometry (MS), which led to the discovery of a new redox neutral reaction of intermolecular [3 + 2] annulation of -cyclopropylanilines and alkenes to provide an aniline-substituted 5-membered carbocycle direct electrolysis (yield up to 81%). A chain mechanism, involving the regeneration of the substrate radical cation and the formation of the neutral product, is shown to be responsible for promoting such a redox neutral annulation reaction, as supported by experimental evidence of EC/MS.
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http://dx.doi.org/10.1039/d0sc05665kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179209PMC
November 2020

Discovery of Methylene Thioacetal-Incorporated α-RgIA Analogues as Potent and Stable Antagonists of the Human α9α10 Nicotinic Acetylcholine Receptor for the Treatment of Neuropathic Pain.

J Med Chem 2021 Jul 23;64(13):9513-9524. Epub 2021 Jun 23.

Department of Pediatrics, Division of Endocrinology and Diabetes, Stanford University, Stanford, California 94305, United States.

α9-Containing nicotinic acetylcholine receptors (nAChRs) are key targets for the treatment of neuropathic pain. α-Conotoxin RgIA4 is a peptide antagonist of human α9α10 nAChRs with high selectivity. However, structural rearrangement reveals a potential liability for clinical applications. We herein report our designer RgIA analogues stabilized by methylene thioacetal as nonopioid analgesic agents. We demonstrate that replacing disulfide loop I [Cys-Cys] with methylene thioacetal in the RgIA skeleton results in activity loss, whereas substitution of loop II [Cys-Cys] can be accommodated. The lead molecule, RgIA-5524, exhibits highly selective inhibition of α9α10 nAChRs with an IC of 0.9 nM and much reduced degradation in human serum. studies showed that RgIA-5524 relieves chemotherapy-induced neuropathic pain in wild type but not α9 knockout mouse models, demonstrating that α9-containing nAChRs are necessary for the therapeutic effects. This work highlights the application of methylene thioacetal as a disulfide surrogate in conotoxin-based, disulfide-rich peptide drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00802DOI Listing
July 2021

The combination of lactoferrin and linolenic acid inhibits colorectal tumor growth through activating AMPK/JNK-related apoptosis pathway.

PeerJ 2021 31;9:e11072. Epub 2021 May 31.

Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

Colorectal cancer is a common cause of death with few available therapeutic strategies, and the preventative complexes in adjunctive therapy are urgently needed. Increasing evidences have shown that natural ingredients, including lactoferrin, oleic acid, docosahexaenoic acid (DHA) and linolenic acid, possess anti-inflammatory and anti-tumor activities. However, investigations and comparisons of their combinations in colorectal tumor model have not been reported, and the mechanism is still unrevealed. In the study, we examined the viability, migration, invasion and apoptosis of HT29 cells to choose the proper doses of these components and to select the effective combination in vitro. BALB/c nude mice bearing colorectal tumor were used to explore the role of selected combination in inhibiting tumor development in vivo. Additionally, metabonomic detection was performed to screen out the specific changed metabolitesand related pathway. The results demonstrated that lactoferrin at 6.25 μM, oleic acid at 0.18 mM, DHA at 0.18 mM, and linolenic acid at 0.15 mM significantly inhibited the viabilities of HT29 cells ( < 0.05). The combination of lactoferrin (6.25 μM) + linolenic acid (0.15 mM) exhibited the strongest activity in inhibiting the migration and invasion of HT29 cells in vivo and suppressing tumor development in vitro ( < 0.05). Furthermore, the lactoferrin + linolenic acid combination activated p-AMPK and p-JNK, thereby inducing apoptosis of HT29 cells ( < 0.05). The present study was the first to show that lactoferrin + linolenic acid combination inhibited HT29 tumor formation by activating AMPK/JNK related pathway.
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http://dx.doi.org/10.7717/peerj.11072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174148PMC
May 2021

End-Group Modifications with Bromine and Methyl in Nonfullerene Acceptors: The Effect of Isomerism.

ACS Appl Mater Interfaces 2021 Jun 15;13(25):29737-29745. Epub 2021 Jun 15.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

The development of isomeric molecules has been widely exploited in molecular structures associated with organic solar cells (OSC) and is an effective pathway to finely tune the photoelectric properties and device performance. The molecular properties of nonfullerene acceptors and the morphology of blend films can be effectively controlled by manipulating isomeric substituent positions on benzene-fused end-capping groups (EG) in acceptors. Here, three isomeric EGs were designed and synthesized which simultaneously possess an electron-withdrawing bromine and an electron-donating methyl substituent. By linking three isomeric EGs, , , and each with the BTP-CHO core, three isomeric small-molecule acceptors (SMA) were obtained. The power conversion efficiency (PCE) of PM6:-based OSCs is 13.43%, is much higher than that of PM6:- (11.92%) and PM6:- (11.08%) based devices. Our results show that isomeric EGs can provide strategies to tune the absorption spectra of SMAs, intramolecular charge transfer (ICT) and electron mobility of organic semiconductor device, and ultimately increase the performance of nonfullerene acceptors.
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http://dx.doi.org/10.1021/acsami.1c08060DOI Listing
June 2021

Metabolomics analysis underlay mechanisms in the renal impairment of mice caused by combination of aflatoxin M1 and ochratoxin A.

Toxicology 2021 Jun 11;458:152835. Epub 2021 Jun 11.

Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China. Electronic address:

Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are pernicious mycotoxins widely co-existing in the environment. However, nephrotoxicity and underlying mechanism induced by AFM1 coupled with OTA still remain to be explored. In this study, CD-1 mice were treated with 3.5 mg/kg b.w. AFM1, OTA, and AFM1 + OTA for 35 days, and UPLC-MS-based metabolomics method was effectuated to investigate metabolomic profiles of mice kidney. Subsequent experiments on human renal proximal tubular (HK-2) cells were performed to dig out the causal connections between distinguished differential metabolites and nephrotoxicity. Compared with DMSO vehicle group, all three toxin treatments (AFM1 and OTA alone, and in combination) significantly reduced final body weight, and remarkably elevated the concentration of serum creatinine (SCr) and caused abnormal histological phenotypes (shown by histopathological slices). OTA, AFM1 + OTA but not AFM1 reduced the relative weight index of kidney. These phenotypic results indicated that AFM1 and OTA were both toxic to the body, and it seemed that OTA exhibited a notable impairment to kidney while AFM1 had similar but limited effect compared with OTA. Further metabolomics analysis showed that when AFM1 and OTA were combined together, OTA exerted dominant effect on the alteration of metabolic processes. There were few differences in the number of changed metabolites between OTA and AFM1 + OTA group. Among the differentially expressed metabolites affected by OTA, and AFM1 + OTA, lysophosphatidylcholines (LysoPCs) were identified as the main type with significant upregulation, in which LysoPC (16:0) accounted for the most prime proportion. Western blotting results of HK-2 cells showed that single OTA and AFM1 + OTA increased the apoptotic protein expressions of Bax, caspase 3 and PARP, and decreased the expression of Bcl-2; while AFM1 only raised the expression of caspase 3. LysoPC (16:0) but not LysoPC (18:1) lifted the protein level of caspase 3 and PARP in HK-2 cells, and reduced the level of Bcl-2. Taken together, this study is the first effort trying to assess nephrotoxicity of AFM1 with OTA, and we guessed that OTA had a more pronounced toxicity to kidney in contrast to AFM1. No obvious synergism between AFM1 and OTA was found to contribute to the occurrence or development of nephropathy. LysoPC (16:0) might be the pivotal metabolite in response to single OTA and combined AFM1 + OTA engendering renal injury.
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http://dx.doi.org/10.1016/j.tox.2021.152835DOI Listing
June 2021

The association of polymorphisms in related circadian rhythm genes and clopidogrel resistance susceptibility.

Basic Clin Pharmacol Toxicol 2021 Jun 12. Epub 2021 Jun 12.

Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, China.

Previous studies have confirmed that a dynamic change in circadian rhythm will affect platelet activity, resulting in clopidogrel resistance (CR). We attempted to evaluate whether polymorphisms of related circadian rhythm genes are involved in CR in stable coronary artery disease (SCAD) patients. A sum of 204 SCAD patients met our requirements and were recruited, and 96 patients were considered to have CR. After clinical data collection and platelet function evaluation, genomic DNA was isolated from human peripheral blood, and 23 tagSNPs from related circadian rhythm genes were genotyped by GenomeLab SNPstream Genotyping System. After RNA isolation, relative expression of related gene mRNAs (CLOCK, CRY1, CACNA1C and PRKCG) was measured by real-time PCR. The results showed that polymorphisms in CRY1, CACNA1C and PRKCG changed the response to clopidogrel. And then, the rs1801260 polymorphism might lead to higher mRNA expression in CLOCK and potentially induce the occurrence of CR. Additionally, the TC genotype of rs3745406 might lower mRNA expression of PRKCG, resulting in CR. These findings support the hypothesized role of circadian rhythm genes in CR and indicate probable biomarkers for CR susceptibility, providing new insight into individualized medicine for coronary heart disease.
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http://dx.doi.org/10.1111/bcpt.13622DOI Listing
June 2021

Nanographene-Osmapentalyne Complexes as a Cathode Interlayer in Organic Solar Cells Enhance Efficiency over 18.

Adv Mater 2021 Jul 12;33(30):e2101279. Epub 2021 Jun 12.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.

Interface engineering is a critical method by which to efficiently enhance the photovoltaic performance of nonfullerene solar cells (NFSC). Herein, a series of metal-nanographene-containing large transition metal involving d -p conjugated systems by way of the addition reactions of osmapentalynes and p-diethynyl-hexabenzocoronenes is reported. Conjugated extensions are engineered to optimize the π-conjugation of these metal-nanographene molecules, which serve as alcohol-soluble cathode interlayer (CIL) materials. Upon extension of the π-conjugation, the power conversion efficiency (PCE) of PM6:BTP-eC9-based NFSCs increases from 16% to over 18%, giving the highest recorded PCE. It is deduced by X-ray crystallographic analysis, interfacial contact methods, morphology characterization, and carrier dynamics that modification of hexabenzocoronenes-styryl can effectively improve the short-circuit current density (J ) and fill factor of organic solar cells (OSCs), mainly due to the strong and ordered charge transfer, more matching energy level alignments, better interfacial contacts between the active layer and the electrodes, and regulated morphology. Consequently, the carrier transport is largely facilitated, and the carrier recombination is simultaneously impeded. These new CIL materials are broadly able to enhance the photovoltaic properties of OSCs in other systems, which provides a promising potential to serve as CILs for higher-quality OSCs.
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http://dx.doi.org/10.1002/adma.202101279DOI Listing
July 2021

More Anterior Contact Position in Patients With Fixed-Bearing Unicompartmental Knee Arthroplasty During Daily Activities Than Wear Simulator.

Front Bioeng Biotechnol 2021 20;9:666435. Epub 2021 May 20.

Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: While wear simulation of unicompartmental knee arthroplasty (UKA) showed outstanding long-term wear performance, studies reported that polyethylene (PE) wear was responsible for 12% fixed-bearing (FB) UKA failure. This paper aimed to quantify the 6-degrees-of-freedom (6-DOF) knee kinematics and contact positions of FB UKA during daily activities and compare with the previous results of wear simulator.

Methods: Fourteen patients following unilateral medial FB UKA received a CT scan and dual fluoroscopic imaging during level walking, single-leg deep lunge, and sit-to-stand motion for evaluating 6-DOF FB UKA kinematics. The closest point between surface models of the femoral condyle and PE insert was determined to locate the medial compartmental articular contact positions, which were normalized relative to the PE insert length. The contact area was compared with the wear region in previous simulator studies.

Results: The contact positions during daily activities were more anterior than those in the previous wear simulator studies ( < 0.001). Significant differences in the femoral anteroposterior translation and tibial internal rotation during the stance phase were observed and compared with those in lunge and sit-to-stand motions ( < 0.05). The contact position located anteriorly and medially by 5.2 ± 2.7 and 1.8 ± 1.6 mm on average for the stance phase, 1.0 ± 2.4 and 0.9 ± 1.5 mm for the lunge, and 2.1 ± 3.3 and 1.4 ± 1.4 mm for sit-to-stand motion. The contact position was in the more anterior part during the stance phase ( < 0.05).

Conclusion: The current study revealed that the contact position of FB UKA was located anteriorly and medially on the PE insert during weight-bearing activities and different from previous findings of the wear simulator. We should take 6-DOF knee kinematics and contact patterns of FB UKA into account to reproduce realistic wear performance for wear simulator and to improve implant design.
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http://dx.doi.org/10.3389/fbioe.2021.666435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173134PMC
May 2021

Cationic Polyporphyrins as siRNA Delivery Vectors for Photodynamic and Gene Synergistic Anticancer Therapy.

ACS Appl Mater Interfaces 2021 Jun 4;13(23):27513-27521. Epub 2021 Jun 4.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, P. R. China.

Successful gene therapy is highly dependent on the efficiency of gene delivery, which is mostly achieved by the carrier. Current gene carriers are generally nontherapeutic and take over most of the proportion in the delivery systems. Therefore, a library of polymerized and cationic photosensitive drugs (polyphotosensitizers, pPSs) with HIF-1α siRNA delivery capability is constructed to realize using "drug" to deliver "gene". The pPS component acts as both a therapeutic carrier for intracellular HIF-1α siRNA delivery and a photosensitive drug with photodynamic therapy (PDT). A reactive oxygen species (ROS)-cleavable linker is used to polymerize PS, allowing the successful segregation of PS monomers in space, avoiding the undesired aggregation-caused quenching (ACQ) effect and enhancing the and PDT effect. The complexes formed by pPSs and HIF-1α siRNA exhibited desired siRNA condensation and serum stability at the optimal conditions (pPSs with guanidines/siRNA weight ratio of 15), efficient intracellular internalization, and gene-silencing efficiency (60%) compared with commercial available transfection reagents (40%), as well as synergistic and phototoxicity for the combination PDT-gene therapy toward cancer treatment. This study provides a promising paradigm for the design of both the gene delivery carrier and the photosensitizer, as well as for broad utilities in the combination therapy toward cancer treatment.
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http://dx.doi.org/10.1021/acsami.1c07662DOI Listing
June 2021

Change in Susceptibility Values in Knee Cartilage After Marathon Running Measured Using Quantitative Susceptibility Mapping.

J Magn Reson Imaging 2021 May 24. Epub 2021 May 24.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Background: Quantitative susceptibility mapping (QSM) has been used to study the magnetic susceptibility properties of collagen fibers in articular cartilage; however, it is unclear whether QSM is sensitive to changes due to degradation caused by long-distance running. It is clinically important to understand the link between long-distance running and microstructural changes in knee cartilage.

Purpose: To investigate the ability of QSM to assess microstructural changes within cartilage after repetitive loading.

Study Type: Prospective.

Population: Thirteen recreational, male long-distance runners.

Field Strength/sequence: Three-dimensional gradient recalled echo acquired at 3 T.

Assessment: Magnetic resonance imaging (MRI) and 3D kinematics (translations and rotations during treadmill walking and running) of the knee joint were collected before and after marathon running. The compartments for analysis included the patella, trochlea, and subregions of femoral and tibial cartilage. Changes in regional susceptibility and cartilage thickness were calculated after marathon running. A susceptibility profile was obtained by fitting susceptibility as a function of the normalized depth of cartilage from the superficial to deep layers.

Statistical Tests: Paired t-test or Wilcoxon signed-rank test, 95% confidence interval (CI) of the depth-wise susceptibility profile, Pearson correlation or Spearman correlation.

Results: There was a statistically significant increase in susceptibility value in the weight-bearing region of central medial femoral cartilage (cMF-c) after marathon running (pre-marathon: -0.0219 ± 0.0151 ppm, post-marathon: -0.0070 ± 0.0213 ppm, P < 0.05), while the cartilage thickness did not show significant changes in any regions (P-value range: 0.068-0.963). Significant susceptibility elevations occurred in the middle and deep layers of cMF-c (95% CIs did not overlap). A trend toward a positive correlation was found between the changes in susceptibility value in cMF-c and proximal-distal translation of the knee joint during walking (r = 0.55, P = 0.101) and running (r = 0.57, P = 0.089).

Data Conclusion: Localized magnetic susceptibility alterations were observed within knee cartilage in the weight-bearing area after repetitive loading without any morphologic changes.

Level Of Evidence: 2 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27745DOI Listing
May 2021

Ruminal microbiota-host interaction and its effect on nutrient metabolism.

Anim Nutr 2021 Mar 15;7(1):49-55. Epub 2020 Dec 15.

State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Rumen microbiota has a close and intensive interaction with the ruminants. Microbiota residing in the rumen digests and ferments plant organic matters into nutrients that are subsequently utilized by the host, making ruminants a unique group of animals that can convert plant materials indigestible by humans into high-quality animal protein as meat and milk. Many studies using meta-omics technologies have demonstrated the relationships between rumen microbiome and animal phenotypes associated with nutrient metabolism. Recently, the causality and physiological mechanisms underpinning the host-microbiota interactions have attracted tremendous research interest among researchers. This review discusses the host-microbiota interactions and the factors affecting these interactions in ruminants and provides a summary of the advances in research on animal husbandry. Understanding the microbiota composition, the functions of key bacteria, and the host-microbiota interaction is crucial for the development of knowledge-based strategies to enhance animal productivity and host health.
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http://dx.doi.org/10.1016/j.aninu.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110878PMC
March 2021

Push or Pull Electrons: Acetoxy and Carbomethoxy-Substituted Isomerisms in Organic Solar Cell Acceptors.

J Phys Chem Lett 2021 May 12;12(19):4666-4673. Epub 2021 May 12.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

Isomerism is a major factor affecting the properties of materials. Herein, two isomeric acceptors based on acetoxy and methyl ester end group substituents, and are reported. When blended with PBDB-TF, devices based on achieve an inferior (8.32%) power conversion efficiency (PCE) while the material has a superior PCE of 13.25%. We investigated the reasons why these two devices, which differ only in the isomeric substituents on the terminal site, have such a large difference in photovoltaic performance. Our investigation conducted theoretical calculations and examined UV-vis absorption, energy levels, exciton dissociation and bimolecular recombination, mobilities tests, photoluminescence, and packing modes. It is found that the energy levels of the materials are fine-tuned, the absorption spectra are adjusted, and the energy loss is regulated. Our studies explored the reasons for the properties of materials differing, and the acetoxy and carbomethoxy substitutions provided some useful information concerning high-performance acceptor materials.
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http://dx.doi.org/10.1021/acs.jpclett.1c01077DOI Listing
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.

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

Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms.

Mycopathologia 2021 Jun 6;186(3):387-397. Epub 2021 May 6.

Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing, 210042, Jiangsu, China.

Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A. fumigatus. During the past decades, A. fumigatus azole resistance has become prevalent due to the medical and agricultural use of antifungal drugs and fungicides. Until now, the role of fungal biofilms in azole resistance of A. fumigatus remains unclear. In the present study, we compared biofilm drug susceptibility and biofilm formation under itraconazole of azole-resistant strains, sensitive strains, and standard strains, separately. The biofilm viability and matrix thickness at the early and the late stage were measured by XTT assay and Calcofluor white. Our results showed that the sessile minimum inhibitory concentration of itraconazole, which describing the inhibition of drugs on fungi sessile with biofilm, was much higher than the traditional minimal inhibitory concentration of itraconazole. Additionally, low concentrations of itraconazole inhibited biofilm formation of A. fumigatus strains. Notably, biofilm formation by azole-resistant strains could not be inhibited by high concentrations of itraconazole but could be effectively restrained by low concentrations of micafungin, revealing the efficacy of a cell-wall inhibitor to disrupt A. fumigatus biofilm formation. However, late-stage biofilms of both azole-resistant strains and standard strains were hard to disrupt using itraconazole. We found that itraconazole was effective to prevent A. fumigatus biofilm formation at the early stage. For the treatment of A. fumigatus biofilm, our findings suggest that an early-stage preventive strategy is preferred and micafungin is effective to control the azole-resistant strain infection.
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http://dx.doi.org/10.1007/s11046-021-00534-4DOI Listing
June 2021

Association of the Geriatric Nutritional Risk Index with incident hypertension in the older Chinese population: a 6-year cohort study.

J Int Med Res 2021 May;49(5):3000605211010051

Department of Cardiovascular Medicine, Kunming Children's Hospital, Kunming, Yunnan Province, China.

Background: We examined the association of the Geriatric Nutritional Risk Index (GNRI) with the incidence of hypertension.

Methods: We used data of the China Health and Nutrition Survey in this study. Participants aged ≥60 years were eligible. The GNRI was defined as follows: GNRI = [1.489 × albumin (ALB; g/L)] + [41.7 × (actual weight/ideal weight)]. Participants with systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication were defined as having hypertension.

Results: This study included 4853 participants, comprising 3612 control participants and 1241 participants with hypertension. The GNRI, ALB, and body mass index (BMI) were significantly associated with higher incidence of hypertension (HR: 1.030, 1.026, and 1.088; 95% CI: 1.020-1.041, 1.008-1.044, and 1.069-1.107, respectively). The GNRI, ALB, and BMI were associated with an earlier age of hypertension onset (β = -0.403, -0.613, and -0.321; 95% CI: -0.493 to -0.314, -0.767 to -0.459, and -0.484 to -0.159, respectively).

Conclusions: A higher GNRI was associated with increased incidence of hypertension. An elevated GNRI was associated with earlier age of hypertension onset.
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http://dx.doi.org/10.1177/03000605211010051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113967PMC
May 2021

Effect of Food Endotoxin on Infant Health.

Toxins (Basel) 2021 04 22;13(5). Epub 2021 Apr 22.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

Endotoxin is a complex molecule derived from the outer membrane of Gram-negative bacteria, and it has strong thermal stability. The processing of infant food can kill pathogenic bacteria but cannot remove endotoxin. Because the intestinal structure of infants is not fully developed, residual endotoxin poses a threat to their health by damaging the intestinal flora and inducing intestinal inflammation, obesity, and sepsis, among others. This paper discusses the sources and contents of endotoxin in infant food and methods for preventing endotoxin from harming infants. However, there is no clear evidence that endotoxin levels in infant food cause significant immune symptoms or even diseases in infants. However, in order to improve the safety level of infant food and reduce the endotoxin content, this issue should not be ignored. The purpose of this review is to provide a theoretical basis for manufacturers and consumers to understand the possible harm of endotoxin content in infant formula milk powder and to explore how to reduce its level in infant formula milk powder. Generally, producers should focus on cleaning the milk source, securing the cold chain, avoiding long-distance transportation, and shortening the storage time of raw milk to reduce the level of bacteria and endotoxin. After production and processing, the endotoxin content should be measured as an important index to test the quality of infant formula milk powder so as to provide high-quality infant products for the healthy growth of newborns.
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http://dx.doi.org/10.3390/toxins13050298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143472PMC
April 2021

Transformed Carbon Fibers/Al₂O₃ Nanocomposites Using Cao-MgO-SiO₂ Sintering Agent.

J Nanosci Nanotechnol 2021 Oct;21(10):5235-5240

State Key Laboratory of New Ceramic and Fine Processing, Tsinghua University, Beijing 100084, China.

transformed carbon fibers/Al₂O₃ ceramic matrix nanocomposites with Cao-MgO-SiO₂ sintering agent were prepared by hot-pressed sintering technology in vacuum. In the sintering process, pre-oxidized polyacrylonitrile fibers (below named as pre-oxidized PAN fibers) were used as the precursors of transformed carbon fibers. The micro/nanostructure of composites and interface between transformed carbon fibers and matrix were investigated, as well as the properties of composites. The results showed that the composites could be sintered well at a relatively low temperature of 1650 °C. During the sintering, the precursors, pre-oxidized PAN fibers, were transformed into carbon fibers, and the transformed carbon fibers had the graphitelike structure along the fiber axial direction. The carbon atoms arrangement in the surface layer of the fiber was more orderly than the core. A typical diffraction peak of carbon fiber at 26°, which corresponded to the (002) crystal plane, was observed, and the inter-planar spacing was approximately 0.34 nm. The CaO-MgO-SiO₂ sintering agent formed MgAl₂O₄ and CaAl₂Si₂O phases in the interface between transformed carbon fibers and matrix, therefore improving the interface bonding, and thereby modifying the mechanical properties of the composites.
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http://dx.doi.org/10.1166/jnn.2021.19354DOI Listing
October 2021

Optimizing the Femoral Offset for Restoring Physiological Hip Muscle Function in Patients With Total Hip Arthroplasty.

Front Bioeng Biotechnol 2021 30;9:645019. Epub 2021 Mar 30.

School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Objective: Femoral offset (FO) restoration is significantly correlated with functional recovery following total hip arthroplasty (THA). Accurately assessing the effects of FO changes on hip muscles following THA would help improve function and optimize functional outcomes. The present study aimed to (1) identify the impact of FO side difference on the hip muscle moment arms following unilateral THA during gait and (2) propose the optimal FO for a physiological hip muscle function.

Methods: hip kinematics from eighteen unilateral THA patients during gait were measured with a dual-fluoroscopic imaging system. The moment arms of thirteen hip muscles were calculated using CT-based 3D musculoskeletal models with the hip muscles' lines of actions. The correlation coefficient (R) between FO and hip muscle moment arm changes compared with the non-implanted hip was calculated. We considered that the FO reconstruction was satisfactory when the abductor moment arms increased, while the extensor, adductor, and flexor moment arms decreased less than 5%.

Results: A decreased FO following THA was significantly correlated with a decrease of the abductor and external rotator moment arms during the whole gait ( > 0.5) and a decrease of extensor moment arms during the stance phase ( > 0.4). An increased FO following THA was significantly associated with shorter flexor moment arms throughout the gait ( < -0.5) and shorter adductor moment arms in the stance phase ( < -0.4). An increase in FO of 2.3-2.9 mm resulted in increased abductor moment arms while maintaining the maximum decrease of the hip muscles at less than 5.0%.

Conclusion: An increase of 2-3 mm in FO could improve the abductor and external rotator function following a THA. Accurate surgical planning with optimal FO reconstruction is essential to restoring normal hip muscle function in THA patients.
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http://dx.doi.org/10.3389/fbioe.2021.645019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045972PMC
March 2021

The morphology, biomechanics, and physiological function of the suboccipital myodural connections.

Sci Rep 2021 Apr 13;11(1):8064. Epub 2021 Apr 13.

Department of Anatomy, College of Basic Medical Science, Dalian Medical University, 9 West Section, Lushun South Road, Dalian, 116044, People's Republic of China.

The myodural bridge (MDB) connects the suboccipital musculature to the spinal dura mater (SDM) as it passed through the posterior atlanto-occipital and the atlanto-axial interspaces. Although the actual function of the MDB is not understood at this time, it has recently been proposed that head movement may assist in powering the movement of cerebrospinal fluid (CSF) via muscular tension transmitted to the SDM via the MDB. But there is little information about it. The present study utilized dogs as the experimental model to explore the MDB's effects on the CSF pressure (CSFP) during stimulated contractions of the suboccipital muscles as well as during manipulated movements of the atlanto-occiptal and atlanto-axial joints. The morphology of MDB was investigated by gross anatomic dissection and by histological observation utilizing both light microscopy and scanning electron microscopy. Additionally biomechanical tensile strength tests were conducted. Functionally, the CSFP was analyzed during passive head movements and electrical stimulation of the suboccipital muscles, respectively. The MDB was observed passing through both the dorsal atlanto-occipital and the atlanto-axial interspaces of the canine and consisted of collagenous fibers. The tensile strength of the collagenous fibers passing through the dorsal atlanto-occipital and atlanto-axial interspaces were 0.16 ± 0.04 MPa and 0.82 ± 0.57 MPa, respectively. Passive head movement, including lateral flexion, rotation, as well as flexion-extension, all significantly increased CSFP. Furthermore, the CSFP was significantly raised from 12.41 ± 4.58 to 13.45 ± 5.16 mmHg when the obliques capitis inferior (OCI) muscles of the examined specimens were electrically stimulated. This stimulatory effect was completely eliminated by severing the myodural bridge attachments to the OCI muscle. Head movements appeared to be an important factor affecting CSF pressure, with the MDB of the suboccipital muscles playing a key role this process. The present study provides direct evidence to support the hypothesis that the MDB may be a previously unappreciated significant power source (pump) for CSF circulation.
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http://dx.doi.org/10.1038/s41598-021-86934-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044117PMC
April 2021

Aptamer-Based Fluorescence Quenching Approach for Detection of Aflatoxin M in Milk.

Front Chem 2021 24;9:653869. Epub 2021 Mar 24.

Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Aflatoxin M (AFM), one of the most toxic mycotoxins, is a feed and food contaminant of global concern. In this study, we developed a fast and simple method for detection of AFM based on a structure-switching signaling aptamer. This aptasensor is based on the change in fluorescence signal due to formation of an AFM/aptamer complex. To generate the aptasensor, the specific aptamer was modified with FAM (carboxyfluorescein), and their complementary DNAs (cDNA) were modified with a carboxytetramethylrhodamine (TAMRA) quenching group. In the absence of AFM, the aptamers were hybridized with cDNA, resulting in quenching of the aptamer fluorescence due to the proximity of the aptamer's fluorophore to the quenching group on the cDNA. On the other hand, in the presence of AFM, a structural switch in the aptamer was induced by formation of an AFM/aptamer complex. Changes in the structure of the aptamer led to the release of the cDNA, causing the generation of a fluorescence signal. Thus, AFM concentrations could be quantitatively monitored based on the changes in fluorescences. Under optimized conditions, this assay exhibited a linear response to AFM in the range of 1-100 ng/mL and a limit of detection of 0.5 ng/mL was calculated. This proposed aptasensor was applied to milk samples spiked with a dilution series of AFM, yielding satisfactory recoveries from 93.4 to 101.3%. These results demonstrated that this detection technique could be useful for high-throughput and quantitative determination of mycotoxin levels in milk and dairy products.
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http://dx.doi.org/10.3389/fchem.2021.653869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024576PMC
March 2021
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