Publications by authors named "Jiahui Chen"

185 Publications

Impact of enhanced recovery nursing combined with limb training on knee joint function and neurological function after total knee arthroplasty in patients with knee osteoarthritis.

Am J Transl Res 2021 15;13(6):6864-6872. Epub 2021 Jun 15.

Department of Orthopedics, First Affiliated Hospital of Kunming Medical University Kunming, Yunnan Province, China.

Objective: To investigate the impact of enhanced recovery after surgery (ERAS) nursing combined with limb training on knee joint function and neurological function after total knee arthroplasty in patients with knee osteoarthritis (KOA).

Methods: Eighty-six patients with KOA after TKA were randomly divided into two groups, group A and group B, with 43 patients in each group. Group A was given ERAS nursing, and group B was given limb rehabilitation training combined with ERAS nursing. The changes in knee joint function and neurological function were observed.

Results: There was no significant difference in the time to get out of bed for the first time, first bowel movement time after the surgery, hospital stay and hospital costs between the two groups (P>0.05). There was no significant difference in VAS scores between the two groups before the operation and 1 d after the operation (P>0.05). Three days and seven days after the operation, the VAS scores in the two groups both decreased, and the VAS scores of group B were higher than those of group A (P<0.05). There was no significant difference in the excellent rate of Judet scores and Lysholm scores between the two groups (P>0.05), but the two indicators in the two groups all increased at three and six months after the operation, and the two indicators in group B were higher than those of group A (P<0.05). There was no significant difference in NIHSS scores between the two groups before the operation (P>0.05). Fifteen and thirty days after the operation, the NIHSS scores of the two groups both decreased, and the NIHSS scores of group B were lower than those of group A (P<0.05). After the nursing care, the scores of health knowledge level, self-care concept, self-care responsibility and self-care skills in group B were higher than those in group A (P<0.05). The incidence of complications in group B during nursing was lower than group A (P<0.05).

Conclusion: The enhanced recovery after surgery nursing combined with limb training has a better effect on KOA patients after TKA. It can significantly improve knee joint function, limb motor ability and neurological function, increase patients' cognition of disease and reduce the incidence of complications, compared with simple enhanced recovery after surgery nursing.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290758PMC
June 2021

Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis.

Front Immunol 2021 7;12:688674. Epub 2021 Jul 7.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Cell swelling and membrane blebbing are characteristic of pyroptosis. In the present study, we explored the role of intracellular tension activity in the deformation of pyroptotic astrocytes. Protein nanoparticle-induced osmotic pressure (PN-OP) was found to be involved in cell swelling and membrane blebbing in pyroptotic astrocytes, and was associated closely with inflammasome production and cytoskeleton depolymerization. However, accumulation of protein nanoparticles seemed not to be absolutely required for pyroptotic permeabilization in response to cytoskeleton depolymerization. Gasdermin D activation was observed to be involved in modification of typical pyroptotic features through inflammasome-induced OP upregulation and calcium increment. Blockage of nonselective ion pores can inhibit permeabilization, but not inflammasome production and ion influx in pyroptotic astrocytes. The results suggested that the inflammasomes, as protein nanoparticles, are involved in PN-OP upregulation and control the typical features of pyroptotic astrocytes.
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http://dx.doi.org/10.3389/fimmu.2021.688674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293990PMC
July 2021

Efficacy and safety of laser combination therapy and laser alone therapy for keloid: a systematic review and meta-analysis.

Lasers Med Sci 2021 Jul 20. Epub 2021 Jul 20.

Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China.

To evaluate the efficacy and safety of laser alone therapy and laser combination therapy (mainly combined with other kinds of laser or steroids) for keloid.PubMed, Embase and Web of Science were searched for relevant articles from inception to June 2020. Comprehensive Meta-Analysis software 2.0 (CMA) was used to perform the meta-analysis.A total of 29 articles were included in this meta-analysis. During the mean follow-up of 14 (1-84) months, the overall improvement rates of baseline Vancouver scar scale (VSS) score and itch were 0.454 (95%CI 0.351-0.561, I = 0) and 0.786 (95%CI 0.613-0.895, I = 0) in the laser combination therapy group. The improvement rates of scar height and flexibility in the laser combination therapy group were 0.629 (95%CI 0.519-0.727, I = 52.089) and 0.784 (95%CI 0.251-0.975, I = 89.420). The average improvement rate of the scar score in laser combination therapy was 0.338 (0.201-0.510); however, there were insufficient data for laser alone therapy comparison. The laser combination therapy had a greater pain improvement rate, 0.580 (0.389-0.750) versus 0.420 (0.224-0.645), compared to laser alone therapy, and a greater degree of good or excellent (> 50%) improvement in the overall scar, 0.636 (95%CI 0.347-0.852) versus 0.149 (95%CI 0.032-0.482), with laser alone therapy. Moreover, a lower regrowth rate of 0.187 (0.129-0.263) versus 0.249 (0.060-0.631), a lower post-treatment pigmentation rate of 0.125 (0.091-0.169) versus 0.135 (0.058-0.282), and a lower infection rate of 0.047 (0.009-0.209) versus 0.076 (0.012-0.351) were observed in the laser combination therapy compared with those rates in the laser alone therapy.The overall effect of laser combination therapy was better than that of laser alone therapy, and the incidence of adverse reactions was lower in laser combination therapy than in laser alone therapy.
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http://dx.doi.org/10.1007/s10103-021-03364-4DOI Listing
July 2021

gene mutations in a Chinese cohort with congenital ectopia lentis: spectrum and genotype-phenotype analysis.

Br J Ophthalmol 2021 Jul 19. Epub 2021 Jul 19.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China

Aims: To identify the mutation spectrum and genotype-phenotype correlations of () mutations in a Chinese cohort with congenital ectopia lentis (EL).

Methods: Patients clinically suspected of congenital zonulopathy were screened using panel-based next-generation sequencing followed by multiplex ligation-dependent probe amplification. All the probands were subjected to thorough ocular examinations. Molecular and clinical data were integrated in pursuit of genotype-phenotype correlation.

Results: A total of 131 probands of mutations from unrelated families were recruited. Around 65% of the probands were children younger than 9 years old. Overall, 110 distinct mutations were identified, including 39 novel ones. The most at-risk regions were exons 13, 2, 6, 15, 24 and 33 in descending order of mutation frequency. The most prevalent mutation was c.184C>T (seven, 5.34%) in the coding sequence and c.5788+5G>A (three, 2.29%) in introns. Missense mutations were the most frequent type (103, 78.63%); half of which were distributed in the N-terminal regions (53, 51.46%). The majority of missense mutations were detected in one of the calcium-binding epidermal growth factor-like domains (62, 60.19%), and 39 (62.90%) of them were substitutions of conserved cysteine residues. Microspherophakia (MSP) was found in 15 patients (11.45%). Mutations in the middle region (exons 22-42), especially exon 26, had higher risks of combined MSP (OR, 5.51 (95% CI 1.364 to 22.274), p=0.017).

Conclusions: This study extended the knowledge of the mutation spectrum and provided novel insights into its clinical correlation regarding EL and MSP in the Chinese population.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319084DOI Listing
July 2021

CRISPR-/Cas12a-Mediated Liposome-Amplified Strategy for the Surface-Enhanced Raman Scattering and Naked-Eye Detection of Nucleic Acid and Application to Food Authenticity Screening.

Anal Chem 2021 Jul 19;93(29):10167-10174. Epub 2021 Jul 19.

School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.

Surface-enhanced Raman scattering (SERS) has been recognized as a powerful tool for biosensors due to the ultrahigh sensitivity and unique fingerprint information. However, there are some limitations in trace target nucleic acid detection for the restricted signal-transducing and amplification strategies. Inspired by CRISPR/Cas12a with specific target DNA-activated collateral single-strand DNA (ssDNA) cleavage activity and liposome with signal molecule-loading properties, we first proposed a sensitive SERS-based on-site nucleic acid detection strategy mediated by CRISPR/Cas12a with -cleavage activity on ssDNA linkers utilized to capture liposomes. Liposomes loading two kinds of signal molecules, 4-nitrothiophenol (4-NTP) and cysteine, could achieve the dual-mode detection of target DNA with SERS and naked eye, respectively. The promptly amplified signals were initiated by the triggered breakdown of signal molecule-loaded liposomes. Emancipated 4-NTP, a biological-silent Raman reporter, would achieve highly selective and sensitive SERS measurement. Released cysteine induced the aggregation of plasmonic gold nanoparticles, leading to an obvious red to blue colorimetric shift to realize portable naked-eye detection. With this strategy, target nucleic acid concentration was dexterously converted into SERS and visualization signals and could be detected as low as 100 aM and 10 pM, respectively. The approach was also successfully applied to determine meat adulteration, achieving the detection of a low adulteration ratio in the complicated food matrix. We anticipate that this strategy will not only be regarded as a universal platform for the on-site detection of food authenticity but also broaden SERS application for the accurate determination of diverse biomarkers.
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http://dx.doi.org/10.1021/acs.analchem.1c01163DOI Listing
July 2021

Revealing the Threat of Emerging SARS-CoV-2 Mutations to Antibody Therapies.

J Mol Biol 2021 Jul 14;433(18):167155. Epub 2021 Jul 14.

Department of Mathematics, Michigan State University, MI 48824, USA; Department of Electrical and Computer Engineering, Michigan State University, MI 48824, USA; Department of Biochemistry and Molecular Biology, Michigan State University, MI 48824, USA. Electronic address:

The ongoing massive vaccination and the development of effective intervention offer the long-awaited hope to end the global rage of the COVID-19 pandemic. However, the rapidly growing SARS-CoV-2 variants might compromise existing vaccines and monoclonal antibody (mAb) therapies. Although there are valuable experimental studies about the potential threats from emerging variants, the results are limited to a handful of mutations and Eli Lilly and Regeneron mAbs. The potential threats from frequently occurring mutations on the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) to many mAbs in clinical trials are largely unknown. We fill the gap by developing a topology-based deep learning strategy that is validated with tens of thousands of experimental data points. We analyze 796,759 genome isolates from patients to identify 606 non-degenerate RBD mutations and investigate their impacts on 16 mAbs in clinical trials. Our findings, which are highly consistent with existing experimental results about Alpha, Beta, Gamma, Delta, Epsilon, and Kappa variants shed light on potential threats of 100 most observed mutations to mAbs not only from Eli Lilly and Regeneron but also from Celltrion and Rockefeller University that are in clinical trials. We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, F486L, F490L/S, Q493L, and S494P might compromise some of mAbs in clinical trials. Our study gives rise to a general perspective about how mutations will affect current vaccines.
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http://dx.doi.org/10.1016/j.jmb.2021.167155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277955PMC
July 2021

Camellia nitidissima Chi leaf as pancreatic lipase inhibitors: Inhibition potentials and mechanism.

J Food Biochem 2021 Jul 6:e13837. Epub 2021 Jul 6.

College of Food Science, South China Agricultural University, Guangzhou, China.

In this study, Camellia nitidissima Chi leaf extract was investigated for its compounds and pancreatic lipase inhibitory potentials. The interaction was determined using ultraviolet (UV) spectroscopy, circular dichroism (CD), fluorescence spectroscopy (FS), and molecular docking to understand the inhibiton, kinetic, and conformation of extraction-pancreatic lipase complex. C. nitidissima Chi leaf extraction inhibited the pancreatic lipase activity in a dose-dependent manner at the concentration of 1-12 mg/ml. The Lineweaver-Burk plots indicated that the inhibition on pancreatic lipase by extraction was noncompetitive. In addition, the decrease in α-helix contents, increase in β-sheet and β-turn, and decrease in fluorescence intensity after extraction treatment indicated that the conformation of pancreatic lipase was changed. This work revealed that C. nitidissima Chi leaf extraction played a significant role in inhibiting pancreatic lipase activity and brought out a solution of delay fat accumulation. PRACTICAL APPLICATIONS: This study reports the components in the extract of C. nitidissima Chi leaf and its inhibitory effect and mechanism of pancreatic lipase. C. nitidissima Chi leaf is a good source of bioactive components, including multiflorin B, kaempferol-3-O-rutinoside, vicenin-2, apigenin-6-C-pentosyl-8-C-hexosyl, vitexin, kaempferol, and other ingredients. It can inhibit pancreatic lipase and be used to control obesity and treat hyperlipidemia. This study also revealed the structure changes of C. nitidissima Chi leaf extract on pancreatic lipase, and further revealed the inhibitory mechanism of C. nitidissima Chi leaf extract on lipase, which provides a theoretical basis for C. nitidissima Chi leaf as a lipase inhibitor.
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http://dx.doi.org/10.1111/jfbc.13837DOI Listing
July 2021

Development of a highly-specific F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping.

Acta Pharm Sin B 2021 Jun 1;11(6):1686-1695. Epub 2021 Apr 1.

Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified as a lead compound, which was then radiolabeled with fluorine-18 a facile SAr reaction to form 2-[F]fluoropyridine scaffold. Good blood-brain barrier permeability and high specific binding was demonstrated for radioligand [F] (also named as [F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent F-labeled MAGL PET tracers.
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http://dx.doi.org/10.1016/j.apsb.2021.01.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245801PMC
June 2021

Ultrasound-assisted covalent reaction of myofibrillar protein: The improvement of functional properties and its potential mechanism.

Ultrason Sonochem 2021 Aug 24;76:105652. Epub 2021 Jun 24.

Key Laboratory of Meat Processing, Ministry of Agriculture, Key Lab of Meat Processing and Quality Control, Ministry of Education, Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

The effects of the different combined manner of ultrasound and covalent reaction between polyphenol and myofibrillar protein (MP) from chicken were studied. More so, antioxidant activities, digestive properties, and potential mechanism of ultrasound-assisted oxidation system of hydrophilic ((-)-Epicatechin gallate, ECG) and hydrophobic (Baicalein, BN) polyphenols was also analyzed in this study. Among all the combined treatments, surface hydrophobicity (SUH), active sulfhydryl contents (ASC), and specific surface area (SSA) of ultrasonic assisted ECG oxidation group (T6) was relatively apparent, indicating that a more unfolding MP structure was obtained. Furthermore, ultrasonic assisted ECG oxidation group showed the highest antioxidant activities compared with other combined treatments on the basis of the results of DPPH free radical scavenging activities, metal ion chelating activities, and hydroxyl radicals (OH·) scavenging activities. The results of simulated digestion system and kinetic analysis also verified that ultrasonic assisted ECG oxidation had higher MP bio-accessibility than the control group. In contrast, a lower digestibility was displayed in ultrasonic assisted BN oxidation group. In summary, the ultrasound-assisted covalent reaction of MP and ECG might be a desirable approach for industrial production of MP from chicken with better antioxidant activities and digestive properties.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251511PMC
August 2021

Surgical treatment of gastric cancer: Current status and future directions.

Chin J Cancer Res 2021 Apr;33(2):159-167

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Surgery is the most important and effective method for the treatment of gastric cancer. Since the first gastrectomy in the early 19th century, surgical treatment of gastric cancer has undergone more than 100 years of development. With the increasing understanding of gastric cancer and the promotion of a series of clinical trials, the concept of gastric cancer surgery has evolved from the initial "bigger is better" to today's "standardized surgery" and is developing towards individualized surgery focusing on accurate resection and quality of life. This trend has had a tremendous impact on the development of surgical treatments, such as minimally invasive surgeries, function-preserving surgeries, and the optimal extent of lymph node dissection. Understanding the development and current status of gastric cancer surgery and exploring the remaining academic controversies are goals that every gastric surgeon should constantly pursue. However, how should gastric cancer surgery develop in the future? What opportunities and challenges will we encounter? In this review, we elaborate on the development and current status of gastric cancer surgery based on a series of clinical studies and discuss the controversy in the development of gastric cancer surgery.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.02.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181878PMC
April 2021

Candidate Gene Analysis for Nitrogen Absorption and Utilization in Japonica Rice at the Seedling Stage Based on a Genome-Wide Association Study.

Front Plant Sci 2021 4;12:670861. Epub 2021 Jun 4.

Key Laboratory of Germplasm Enhancement, Physiology and Ecology of Food Crops in Cold Region, Ministry of Education, Northeast Agricultural University, Harbin, China.

Over-application of nitrogen (N) fertilizer in fields has had a negative impact on both environment and human health. Domesticated rice varieties with high N use efficiency (NUE) reduce fertilizer requirements, enabling sustainable agriculture. Genome-wide association study (GWAS) analysis of N absorption and utilization traits under low and high N conditions was performed to obtain 12 quantitative trait loci (QTLs) based on genotypic data including 151,202 single-nucleotide polymorphisms (SNPs) developed by re-sequencing 267 japonica rice varieties. Eighteen candidate genes were obtained by integrating GWAS and transcriptome analyses; among them, the functions of , , and genes in N transport and assimilation have been identified, and OsJAZ12 and OsJAZ13 also play important roles in rice adaptation to abiotic stresses. A NUE-related candidate gene, , was identified by quantitative real-time PCR (qRT-PCR) analyses. encodes a NAC transcription factor and has been shown to be a positive regulator of the drought stress response in rice. Overexpression of significantly increased rice NUE and grain yield under deficient N conditions, but the difference was not significant under sufficient N conditions. NUE and grain yield significantly decreased under both N supply conditions in the mutant. This study provides crucial insights into the genetic basis of N absorption and utilization in rice, and a NUE-related gene, , was cloned to provide important resources for rice breeding with high NUE and grain yield.
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http://dx.doi.org/10.3389/fpls.2021.670861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212024PMC
June 2021

Effects of cinnamon essential oil on the physical, mechanical, structural and thermal properties of cassava starch-based edible films.

Int J Biol Macromol 2021 Aug 16;184:574-583. Epub 2021 Jun 16.

College of Food Science, South China Agricultural University, Guangzhou, Guangdong 510642, China.

The edible films were mainly made from oxidized hydroxypropyl cassava starch incorporated with cinnamon essential oil (CEO). The effects of CEO amount on the physical and mechanical properties of films were studied, and the structures of films with and without CEO were characterized. The results showed that the elongation at break, water resistance, water vapor transmission coefficient, as well as oxygen and ultraviolet barrier properties of the films (p < 0.05) significantly increased with addition of CEO, while the tensile strength of the films decreased. The field emission scanning electron microscopic (FE-SEM) images and infrared (IR) spectra showed that the CEO had good compatibility with other components and could be evenly dispersed in the film, which was conducive to the stable release of the active components. X-ray diffraction (XRD) patterns showed that the addition of CEO increased the crystallinity of the film, indicating that the compatibility and structural stability of the crystal structure of the film were improved. The thermogravimetric analysis results showed that CEO was beneficial to improve the thermal stability of the films. This study provided a potential to develop edible films from modified cassava starch with CEO.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.067DOI Listing
August 2021

A randomized, double-blind, single-dose, two-way, parallel phase I clinical study comparing the pharmacokinetics and safety of adalimumab injecta and Humira® in healthy Chinese male volunteers.

Expert Opin Biol Ther 2021 Jun 30:1-10. Epub 2021 Jun 30.

Phase I Clinical Trial Laboratory, Affiliated Hospital of Changchun University of Chinese Medicine, Jilin, China.

: Humira® is a fully humanized anti-tumor necrosis factor (TNF-α) monoclonal antibody that has been marketed and approved in the United States for the clinical treatment of rheumatoid arthritis (RA), ankylosing spondylitis, psoriasis and other immune-mediated diseases. This study compared the bioequivalence, immunogenicity and safety of adalimumab injecta (a biosimilar of Humira® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Humira® in healthy Chinese male subjects in a phase I clinical study.: Healthy Chinese male subjects (N = 164) were randomly given a subcutaneous injection of 40 mg adalimumab or Humira® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and primary pharmacokinetic (PK) parameters were statistically analyzed. To evaluate drug immunogenicity, anti-drug antibody (ADA) and neutralizing antibody (nAb) levels were detected. To evaluate the safety of the drugs, the subjects' physical indicators, such as multiple vital signs and routine blood tests, were continuously monitored.: The similarity ratios of adalimumab and Humira® PK parameters were all within 80%-125%, meeting the bioequivalence standards. Drug-induced ADA and nAb levels were similar, and the drug safety in subjects was also similar.: All study drugs showed similar bioequivalence, immunogenicity and safety.: CTR20182070 (Chinese Clinical Trial Registry).
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http://dx.doi.org/10.1080/14712598.2021.1944097DOI Listing
June 2021

Early Goal-Directed Renal Replacement Therapy in Acute Decompensated Heart Failure Patients with Cardiorenal Syndrome.

Blood Purif 2021 Jun 15:1-9. Epub 2021 Jun 15.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Introduction: The aim of this study was to clarify the efficacy of early goal-directed renal replacement therapy (GDRRT) for treatment of cardiorenal syndrome (CRS) patients after acute decompensated heart failure (ADHF).

Methods: In the retrospective, observational study, we enrolled 54 patients in the early GDRRT group and 63 patients in the late GDRRT group. Baseline characteristics, clinical data at initiation renal replacement therapy time, and the clinical outcome were collected and several parameters were compared and analyzed between 2 groups.

Results: The urine volume at GDRRT initiation time in the early group was higher than that in the late GDRRT group (1,060.3 ± 332.1 vs. 300.5 ± 148.3 mL, p < 0.001). Hemodynamic parameters such as mean artery pressure were higher (70.06 ± 32.99 vs. 54.34 ± 40.88 mm Hg, p = 0.012), the heart rate was slower (80.17 ± 15.26 vs. 99.21 ± 25.45 bpm, p = 0.002), and the diameter of inferior vena cava was narrower (22.00 ± 1.91 vs. 25.77 ± 5.5 mm, p = 0.04) in early GDRRT. Primary end point was inhospital all-cause mortality and cardiovascular mortality, which was obviously lower in the early GDRRT group (respectively 24.1 vs. 60.3%, p = 0.002 and 20.3 vs. 50.8%, p = 0.005). The second end point of kidney recovery in the early GDRRT group was much better than that in the latter GDRRT group (p = 0.018). Moreover, urine volume after GDRRT of the early group was more significant than that of the late group (1,432 ± 172 vs. 702 ± 183 mL, p = 0.005).

Conclusion: This study clarified the effectiveness of the early GDRRT strategy in ADHF patients suffered from CRS, which reduced inhospital mortality and improved the urine output and clinical kidney recovery outcome.
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http://dx.doi.org/10.1159/000515826DOI Listing
June 2021

Prediction and mitigation of mutation threats to COVID-19 vaccines and antibody therapies.

Chem Sci 2021 Apr 13;12(20):6929-6948. Epub 2021 Apr 13.

Department of Mathematics, Michigan State University MI 48824 USA

Antibody therapeutics and vaccines are among our last resort to end the raging COVID-19 pandemic. They, however, are prone to over 5000 mutations on the spike (S) protein uncovered by a Mutation Tracker based on over 200 000 genome isolates. It is imperative to understand how mutations will impact vaccines and antibodies in development. In this work, we first study the mechanism, frequency, and ratio of mutations on the S protein which is the common target of most COVID-19 vaccines and antibody therapies. Additionally, we build a library of 56 antibody structures and analyze their 2D and 3D characteristics. Moreover, we predict the mutation-induced binding free energy (BFE) changes for the complexes of S protein and antibodies or ACE2. By integrating genetics, biophysics, deep learning, and algebraic topology, we reveal that most of the 462 mutations on the receptor-binding domain (RBD) will weaken the binding of S protein and antibodies and disrupt the efficacy and reliability of antibody therapies and vaccines. A list of 31 antibody disrupting mutants is identified, while many other disruptive mutations are detailed as well. We also unveil that about 65% of the existing RBD mutations, including those variants recently found in the United Kingdom (UK) and South Africa, will strengthen the binding between the S protein and human angiotensin-converting enzyme 2 (ACE2), resulting in more infectious COVID-19 variants. We discover the disparity between the extreme values of RBD mutation-induced BFE strengthening and weakening of the bindings with antibodies and angiotensin-converting enzyme 2 (ACE2), suggesting that SARS-CoV-2 is at an advanced stage of evolution for human infection, while the human immune system is able to produce optimized antibodies. This discovery, unfortunately, implies the vulnerability of current vaccines and antibody drugs to new mutations. Our predictions were validated by comparison with more than 1400 deep mutations on the S protein RBD. Our results show the urgent need to develop new mutation-resistant vaccines and antibodies and to prepare for seasonal vaccinations.
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http://dx.doi.org/10.1039/d1sc01203gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153213PMC
April 2021

Unveiling the molecular mechanism of SARS-CoV-2 main protease inhibition from 137 crystal structures using algebraic topology and deep learning.

Chem Sci 2020 Sep 30;11(44):12036-12046. Epub 2020 Sep 30.

Department of Mathematics, Michigan State University MI 48824 USA

Currently, there is neither effective antiviral drugs nor vaccine for coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to its high conservativeness and low similarity with human genes, SARS-CoV-2 main protease (M) is one of the most favorable drug targets. However, the current understanding of the molecular mechanism of M inhibition is limited by the lack of reliable binding affinity ranking and prediction of existing structures of M-inhibitor complexes. This work integrates mathematics (, algebraic topology) and deep learning (MathDL) to provide a reliable ranking of the binding affinities of 137 SARS-CoV-2 M inhibitor structures. We reveal that Gly143 residue in M is the most attractive site to form hydrogen bonds, followed by Glu166, Cys145, and His163. We also identify 71 targeted covalent bonding inhibitors. MathDL was validated on the PDBbind v2016 core set benchmark and a carefully curated SARS-CoV-2 inhibitor dataset to ensure the reliability of the present binding affinity prediction. The present binding affinity ranking, interaction analysis, and fragment decomposition offer a foundation for future drug discovery efforts.
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http://dx.doi.org/10.1039/d0sc04641hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162568PMC
September 2020

Clinical Ocular Diagnostic Model of Marfan Syndrome in Patients With Congenital Ectopia Lentis by Pentacam AXL System.

Transl Vis Sci Technol 2021 06;10(7)

Department of Ophthalmology and Vision Science, Eye and ENT Hospital of Fudan University, Shanghai, China.

Purpose: To construct an ocular diagnostic model of Marfan syndrome (MFS) distinguishing MFS from congenital ectopia lentis by the Pentacam AXL system.

Methods: Multivariable logistic regression was performed for the MFS ocular model. Furthermore, discrimination and calibration were validated externally. Data for 96 patients with ectopia lentis were assigned to the training cohort. Eighty patients with ectopia lentis were assigned to the test cohort. Diagnosis of MFS was based on the Ghent-2 criteria and diagnosis of congenital ectopia lentis in the control did not comply with the Ghent-2 criteria.

Results: The clinical model was based on the axial length/total corneal refractive power ratio. In the training cohort, the area under the receiver operating characteristic curve was 0.816 (95% confidence interval, 0.754-0.878) in the final model, which showed better performance than the previous minor criteria for diagnosis MFS of myopia of more than 3 diopters. In the test cohort, the area under the receiver operating characteristic curve was 0.818 (95% confidence interval, 0.718-0.918). In decision curve analysis, the net benefit of the model was better between threshold probabilities of 40% to 80%.

Conclusions: We demonstrated the value of the axial length/total corneal refractive power ratio as a potential diagnostic marker of MFS and clinical performance of diagnostic models, which may assist ophthalmologists in rapid identification of the patients at high risk of MFS.

Translational Relevance: This clinical ocular diagnostic model can be easily applied using the Pentacam AXL system. This model aids in the early differential diagnosis of MFS from other forms of congenital ectopia lentis, which may decrease the risk of developing severe ocular symptoms.
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http://dx.doi.org/10.1167/tvst.10.7.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185401PMC
June 2021

Size selection of the Ambu AuraOnce laryngeal mask in Chinese men weighing >70 kg: a pilot study.

J Int Med Res 2021 May;49(5):3000605211016689

Department of Anesthesiology, Jinshan Hospital of Fudan University, Shanghai, China.

Objective: To collect computed tomography data of the laryngeal anatomy of Chinese men and to determine the feasibility of using the size 4 Ambu AuraOnce laryngeal mask (Ambu A/S, Copenhagen, Denmark) in Chinese men weighing >70 kg.

Methods: This prospective study involved men who underwent surgery from May 2018 to January 2019 at Jinshan Hospital. Pharyngeal and laryngeal parameters were measured by computed tomography. The laryngeal mask insertion success rate, requirement for tracheal tube insertion, laryngeal mask insertion time, fiberoptic bronchoscopy grading, air leakage pressure, and pharyngeal complications were analyzed.

Results: In a comparison of the size 4 and 5 Ambu AuraOnce devices, the first insertion success rate was 100% and 87% and the three-times insertion success rate was 100% and 93%, respectively, with no significant differences. However, the insertion time was significantly different at 19.6 ± 5.9 versus 31.1 ± 11.2 s, respectively, and the proportions of fiberoptic grading levels were also significantly different. There were no significant differences in the air leakage pressure or pharyngeal complications.

Conclusion: The size 4 Ambu AuraOnce is more adequate than the size 5 for Chinese men weighing >70 kg, with a shorter insertion time and higher fiberoptic bronchoscopic grading.
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http://dx.doi.org/10.1177/03000605211016689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142532PMC
May 2021

Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries.

Genomics 2021 07 15;113(4):2158-2170. Epub 2021 May 15.

Department of Mathematics, Michigan State University, MI 48824, USA; Department of Electrical and Computer Engineering, Michigan State University, MI 48824, USA; Department of Biochemistry and Molecular Biology, Michigan State University, MI 48824, USA. Electronic address:

Recently, the SARS-CoV-2 variants from the United Kingdom (UK), South Africa, and Brazil have received much attention for their increased infectivity, potentially high virulence, and possible threats to existing vaccines and antibody therapies. The question remains if there are other more infectious variants transmitted around the world. We carry out a large-scale study of 506,768 SARS-CoV-2 genome isolates from patients to identify many other rapidly growing mutations on the spike (S) protein receptor-binding domain (RBD). We reveal that essentially all 100 most observed mutations strengthen the binding between the RBD and the host angiotensin-converting enzyme 2 (ACE2), indicating the virus evolves toward more infectious variants. In particular, we discover new fast-growing RBD mutations N439K, S477N, S477R, and N501T that also enhance the RBD and ACE2 binding. We further unveil that mutation N501Y involved in United Kingdom (UK), South Africa, and Brazil variants may moderately weaken the binding between the RBD and many known antibodies, while mutations E484K and K417N found in South Africa and Brazilian variants, L452R and E484Q found in India variants, can potentially disrupt the binding between the RBD and many known antibodies. Among these RBD mutations, L452R is also now known as part of the California variant B.1.427. Finally, we hypothesize that RBD mutations that can simultaneously make SARS-CoV-2 more infectious and disrupt the existing antibodies, called vaccine escape mutations, will pose an imminent threat to the current crop of vaccines. A list of most likely vaccine escape mutations is given, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S. Mutation T478K appears to make the Mexico variant B.1.1.222 the most infectious one. Our comprehensive genetic analysis and protein-protein binding study show that the genetic evolution of SARS-CoV-2 on the RBD, which may be regulated by host gene editing, viral proofreading, random genetic drift, and natural selection, gives rise to more infectious variants that will potentially compromise existing vaccines and antibody therapies.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123493PMC
July 2021

Transcriptome profile analysis reveals KLHL30 as an essential regulator for myoblast differentiation.

Biochem Biophys Res Commun 2021 Jun 29;559:84-91. Epub 2021 Apr 29.

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong Province, China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, and Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Skeletal muscle development is a sophisticated multistep process orchestrated by diverse myogenic transcription factors. Recent studies have suggested that Kelch-like genes play vital roles in muscle disease and myogenesis. However, it is still unclear how Kelch-like genes impact myoblast physiology. Here, through integrative analysis of the mRNA expression profile during chicken primary myoblast and C2C12 differentiation, many differentially expressed genes were found and suggested to be enriched in myoblast differentiation and muscle development. Interestingly, a little-known Kelch-like gene KLHL30 was screened as skeletal muscle-specific gene with essential roles in myogenic differentiation. Transcriptomic data and quantitative PCR analysis indicated that the expression of KLHL30 is upregulated under myoblast differentiation state. KLHL30 overexpression upregulated the protein expression of myogenic transcription factors (MYOD, MYOG, MEF2C) and induced myoblast differentiation and myotube formation, while knockdown of KLHL30 caused the opposite effect. Furthermore, KLHL30 was found to significantly decrease the numbers of cells in the S stage and thereby depress myoblast proliferation. Collectively, this study highlights that KLHL30 as a muscle-specific regulator plays essential roles in myoblast proliferation and differentiation.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.086DOI Listing
June 2021

Grade of Membership models reveal geographical and environmental correlates of floristic structure in a temperate biodiversity hotspot.

New Phytol 2021 May 1. Epub 2021 May 1.

Department of Science and Education, Field Museum, Chicago, IL, 60605, USA.

Identifying the contours and correlates of species turnover is central to understanding the nature of biogeographical regions. The Hengduan Mountains region of south-central China (HMR) is well known for its high diversity of plants, but its boundaries and internal floristic structure are poorly understood, especially in relation to geographical and environmental factors. With data on occurrences and elevational ranges of seed plants across the HMR and adjacent areas of the greater Qinghai-Tibet Plateau, we identified motifs (distinct species assemblages) by Grade of Membership models, and characterized relative contributions of geography, elevation, and climate to their spatial patterns. Motifs segregate primarily by latitude, elevation, and correlated environmental variables, most sharply across the tropical-temperate divide. Secondarily, they segregate by longitude and geographical features, and reveal a novel divide across the Jinsha River. A core set of motifs corresponds to previous delineations of the HMR. The HMR biodiversity hotspot is more a mosaic of floristic elements than a cohesive entity. Grade of Membership models effectively reveal the geographical contours of biotic structure, and are a valuable new tool for biogeographical analysis.
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http://dx.doi.org/10.1111/nph.17443DOI Listing
May 2021

Nebula: A Coordinating Grammar of Graphics.

IEEE Trans Vis Comput Graph 2021 Apr 28;PP. Epub 2021 Apr 28.

In multiple coordinated views (MCVs), visualizations across views update their content in response to users interactions in other views. Interactive systems provide direct manipulation to create coordination between views, but are restricted to limited types of predefined templates. By contrast, textual specification languages enable flexible coordination but expose technical burden. To bridge the gap, we contribute Nebula, a grammar based on natural language for coordinating visualizations in MCVs. The grammar design is informed by a novel framework based on a systematic review of 176 coordinations from existing theories and applications, which describes coordination by demonstration, i.e., how coordination is performed by users. With the framework, Nebula specification formalizes coordination as a composition of user- and coordination-triggered interactions in origin and destination views, respectively, along with potential data transformation between the interactions. We evaluate Nebula by demonstrating its expressiveness with a gallery of diverse examples and analyzing its usability on cognitive dimensions.
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http://dx.doi.org/10.1109/TVCG.2021.3076222DOI Listing
April 2021

Modeling the Effects of Calcium Overload on Mitochondrial Ultrastructural Remodeling.

Appl Sci (Basel) 2021 Mar 26;11(5). Epub 2021 Feb 26.

Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.

Mitochondrial cristae are dynamic invaginations of the inner membrane and play a key role in its metabolic capacity to produce ATP. Structural alterations caused by either genetic abnormalities or detrimental environmental factors impede mitochondrial metabolic fluxes and lead to a decrease in their ability to meet metabolic energy requirements. While some of the key proteins associated with mitochondrial cristae are known, very little is known about how the inner membrane dynamics are involved in energy metabolism. In this study, we present a computational strategy to understand how cristae are formed using a phase-based separation approach of both the inner membrane space and matrix space, which are explicitly modeled using the Cahn-Hilliard equation. We show that cristae are formed as a consequence of minimizing an energy function associated with phase interactions which are subject to geometric boundary constraints. We then extended the model to explore how the presence of calcium phosphate granules, entities that form in calcium overload conditions, exert a devastating inner membrane remodeling response that reduces the capacity for mitochondria to produce ATP. This modeling approach can be extended to include arbitrary geometrical constraints, the spatial heterogeneity of enzymes, and electrostatic effects to mechanize the impact of ultrastructural changes on energy metabolism.
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http://dx.doi.org/10.3390/app11052071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067326PMC
March 2021

Biomimetic Nanotheranostics Camouflaged with Cancer Cell Membranes Integrating Persistent Oxygen Supply and Homotypic Targeting for Hypoxic Tumor Elimination.

ACS Appl Mater Interfaces 2021 May 23;13(17):19710-19725. Epub 2021 Apr 23.

Institute of Orthopedics, Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P. R. China.

Treatment resistance of the tumors to photodynamic therapy (PDT) owing to O deficiency largely compromised the therapeutic efficacy, which could be addressed modulating oxygen levels by using O self-enriched nanosystems. Here, we report on augmenting the O-evolving strategy based on a biomimetic, catalytic nanovehicle (named as N/[email protected]), constructed by the catalase-immobilized hollow mesoporous nanospheres by enveloping a cancer cell membrane (CCM), which acts as an efficient nanocontainer to accommodate nitrogen-doped graphene quantum dots (N-GQDs) and protoporphyrin IX (PpIX). Inheriting the virtues of biomimetic CCM cloaking, the CCM-derived shell conferred N/[email protected] nanovehicles with highly specific self-recognition and homotypic targeting toward cancerous cells, ensuring tumor-specific accumulation and superior circulation durations. N-GQDs, for the first time, have been evidenced as a new dual-functional nanoagents with PTT and PDT capacities, enabling the generation of O for PDT and inducing local low-temperature hyperthermia for thermally ablating cancer cells and infrared thermal imaging (IRT). Leveraging the intrinsic catalytic features of catalase, such N/[email protected] nanovehicles effectively scavenged the excessive HO to sustainably evolve oxygen for a synchronous O self-supply and hypoxia alleviation, with an additional benefit because the resulting O bubbles could function as an echo amplifier, leading to the sufficient echogenic reflectivity for ultrasound imaging. Concurrently, the elevated O reacted with N-GQDs and PpIX to elicit a maximally increased O output for augmented PDT. Significantly, the ultrasound imaging coupled with fluorescence imaging, IRT, performs a tumor-modulated trimodal bioimaging effect. Overall, this offers a paradigm to rationally explore O self-supply strategies focused on versatile nanotheranostics for hypoxic tumor elimination.
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http://dx.doi.org/10.1021/acsami.1c03010DOI Listing
May 2021

Surgical outcomes of modified capsular tension ring and intraocular lens implantation in Marfan syndrome with ectopia lentis.

Eur J Ophthalmol 2021 Apr 22:11206721211012868. Epub 2021 Apr 22.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Objective: To evaluate surgical outcomes of modified capsular tension ring (MCTR) and intraocular lens (IOL) implantation in eyes of Marfan syndrome (MFS).

Methods: This retrospective case series included MFS patients receiving MCTR transscleral fixation and IOL in-the-bag implantation. The MCTR was sutured to the sclera through a sulcus by 9-0 polypropylene with the modified knotless Z-suture technique. Main outcomes were visual acuity and postoperative complications.

Results: A total of 109 MFS patients (187 eyes) had the surgery. Patients were 15.47 ± 14.36 years old and followed up for 10.07 ± 8.99 months. MCTR and IOL implantations were performed in 174 eyes (93.05%). The postoperative BCVA (LogMAR) was 0.24 ± 0.24 (1 month), 0.26 ± 0.20 (3 months), 0.22 ± 0.20 (6 months), 0.20 ± 0.19 (12 months) and 0.25 ± 0.32 (over 12 months), which was significantly better than preoperatively (0.63 ± 0.35) ( < 0.001). Major complications included posterior capsular opacification (PCO) in 41 eyes (23.56%) and decentered anterior capsular opacification (ACO) in 15 eyes (8.62%). The mean occurrence time was 9.44 ± 7.08 and 8.87 ± 15.08 months respectively. Other complications included transient intraocular pressure elevation in seven eyes (4.02%), retinal detachment in two eyes (1.15%), cystoid macula edema in one eye (0.57%), and endophthalmitis in one eye (0.57%). No eye had suture breakage or IOL dislocation.

Conclusions: The visual improvement is significant in eyes of MFS undergoing MCTR transscleral fixation and IOL in-the-bag implantation. The long-term monitoring of complications is warranted, especially in the first-two years.
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http://dx.doi.org/10.1177/11206721211012868DOI Listing
April 2021

Surgical outcomes of modified capsular tension ring and intraocular lens implantation in Marfan syndrome with ectopia lentis.

Eur J Ophthalmol 2021 Apr 22:11206721211012868. Epub 2021 Apr 22.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Objective: To evaluate surgical outcomes of modified capsular tension ring (MCTR) and intraocular lens (IOL) implantation in eyes of Marfan syndrome (MFS).

Methods: This retrospective case series included MFS patients receiving MCTR transscleral fixation and IOL in-the-bag implantation. The MCTR was sutured to the sclera through a sulcus by 9-0 polypropylene with the modified knotless Z-suture technique. Main outcomes were visual acuity and postoperative complications.

Results: A total of 109 MFS patients (187 eyes) had the surgery. Patients were 15.47 ± 14.36 years old and followed up for 10.07 ± 8.99 months. MCTR and IOL implantations were performed in 174 eyes (93.05%). The postoperative BCVA (LogMAR) was 0.24 ± 0.24 (1 month), 0.26 ± 0.20 (3 months), 0.22 ± 0.20 (6 months), 0.20 ± 0.19 (12 months) and 0.25 ± 0.32 (over 12 months), which was significantly better than preoperatively (0.63 ± 0.35) ( < 0.001). Major complications included posterior capsular opacification (PCO) in 41 eyes (23.56%) and decentered anterior capsular opacification (ACO) in 15 eyes (8.62%). The mean occurrence time was 9.44 ± 7.08 and 8.87 ± 15.08 months respectively. Other complications included transient intraocular pressure elevation in seven eyes (4.02%), retinal detachment in two eyes (1.15%), cystoid macula edema in one eye (0.57%), and endophthalmitis in one eye (0.57%). No eye had suture breakage or IOL dislocation.

Conclusions: The visual improvement is significant in eyes of MFS undergoing MCTR transscleral fixation and IOL in-the-bag implantation. The long-term monitoring of complications is warranted, especially in the first-two years.
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http://dx.doi.org/10.1177/11206721211012868DOI Listing
April 2021

Revealing the threat of emerging SARS-CoV-2 mutations to antibody therapies.

bioRxiv 2021 Apr 12. Epub 2021 Apr 12.

The ongoing massive vaccination and the development of effective intervention offer the long-awaited hope to end the global rage of the COVID-19 pandemic. However, the rapidly growing SARS-CoV-2 variants might compromise existing vaccines and monoclonal antibody (mAb) therapies. Although there are valuable experimental studies about the potential threats from emerging variants, the results are limited to a handful of mutations and Eli Lilly and Regeneron mAbs. The potential threats from frequently occurring mutations on the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) to many mAbs in clinical trials are largely unknown. We fill the gap by developing a topology-based deep learning strategy that is validated with tens of thousands of experimental data points. We analyze 261,348 genome isolates from patients to identify 514 non-degenerate RBD mutations and investigate their impacts on 16 mAbs in clinical trials. Our findings, which are highly consistent with existing experimental results about variants from the UK, South Africa, Brazil, US-California, and Mexico shed light on potential threats of 95 high-frequency mutations to mAbs not only from Eli Lilly and Regeneron but also from Celltrion and Rockefeller University that are in clinical trials. We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, E484Q/V/A/G/D, F486L, F490L/V/S, Q493L, and S494P/L might compromise some of mAbs in clinical trials. Our study gives rise to a general perspective about how mutations will affect current vaccines.
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http://dx.doi.org/10.1101/2021.04.12.439473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057235PMC
April 2021

Clinical and Genetic Characteristics of Atypical Hemolytic Uremic Syndrome in Children: A Chinese Cohort Study.

Nephron 2021 19;145(4):415-427. Epub 2021 Apr 19.

Department of Nephrology, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare but critical illness. To this date, few studies have reported on the disease in Chinese children.

Methods: We studied a Chinese pediatric cohort to delineate the clinical characteristics, genotypes, and prognosis. Ninety-one patients with aHUS were enrolled in this study.

Results: Fifty-nine children (64.8%) had anti-complement-factor-H autoantibody-associated aHUS (anti-CFH aHUS). Of these children, 21 (46.7%) had complement factor-H-related protein 1 (CFHR1) homozygous deletion, and most patients with CFHR1 homozygous deletion also had complement factor-H-related protein 3 (CFHR3) homozygous deletions (76.2%). Using gene sequencing of 15 candidate genes, we identified 14 genetic variants in 46 aHUS patients, including 5 pathogenic or like pathogenic variants and 9 variants of uncertain significance. The average follow-up time was 46.1 ± 28 months. Among patients with anti-CFH aHUS, there was a correlation between CFHR1 homozygous deletion and patients with persistent proteinuria (odds ratio [OR] 6.954, 95% confidence interval [CI] 1.033-46.821, p = 0.046). As of the last follow-up, ESRD or deaths occurred in 3.6% of the children with anti-CFH aHUS and 26.7% of children with aHUS who were negative for anti-CFH.

Conclusions: Anti-complement-factor-H antibody positivity is the main cause of morbidity in Chinese children with aHUS. There may be a correlation between CFHR1 homozygous deletion and persistent proteinuria. Comprehensive assessment of anti-CFH antibodies and genetic variants is essential for the management of aHUS children.
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http://dx.doi.org/10.1159/000513009DOI Listing
April 2021

Identification of Candidate Genes Conferring Cold Tolerance to Rice ( L.) at the Bud-Bursting Stage Using Bulk Segregant Analysis Sequencing and Linkage Mapping.

Front Plant Sci 2021 11;12:647239. Epub 2021 Mar 11.

Key Laboratory of Germplasm Enhancement, Physiology and Ecology of Food Crops in Cold Region, Ministry of Education, Northeast Agricultural University, Harbin, China.

Low-temperature tolerance during the bud-bursting stage is an important characteristic of direct-seeded rice. The identification of cold-tolerance quantitative trait loci (QTL) in species that can stably tolerate cold environments is crucial for the molecular breeding of rice with such traits. In our study, high-throughput QTL-sequencing analyses were performed in a 460-individual F mapping population to identify the major QTL genomic regions governing cold tolerance at the bud-bursting (CTBB) stage in rice. A novel major QTL, , which controls seed survival rate (SR) under low-temperature conditions of 5°C/9 days, was mapped on the 5.40-Mb interval on chromosome 9. Twenty-six non-synonymous single-nucleotide polymorphism (nSNP) markers were designed for the region based on re-sequencing data and local QTL mapping conducted using traditional linkage analysis. We mapped to a 483.87-kb region containing 58 annotated genes, among which six predicted genes contained nine nSNP loci. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed that only Os09g0444200 was strongly induced by cold stress. Haplotype analysis further confirmed that the SNP 1,654,225 bp in the Os09g0444200 coding region plays a key role in regulating the cold tolerance of rice. These results suggest that Os09g0444200 is a potential candidate for . Our results are of great significance to explore the genetic mechanism of rice CTBB and to improve the cold tolerance of rice varieties by marker-assisted selection.
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http://dx.doi.org/10.3389/fpls.2021.647239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006307PMC
March 2021

A novel tp53-associated nomogram to predict the overall survival in patients with pancreatic cancer.

BMC Cancer 2021 Mar 31;21(1):335. Epub 2021 Mar 31.

Department of Pancreas and Endocrine Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China.

Background: Gene mutations play critical roles in tumorigenesis and cancer development. Our study aimed to screen survival-related mutations and explore a novel gene signature to predict the overall survival in pancreatic cancer.

Methods: Somatic mutation data from three cohorts were used to identify the common survival-related gene mutation with Kaplan-Meier curves. RNA-sequencing data were used to explore the signature for survival prediction. First, Weighted Gene Co-expression Network Analysis was conducted to identify candidate genes. Then, the ICGC-PACA-CA cohort was applied as the training set and the TCGA-PAAD cohort was used as the external validation set. A TP53-associated signature calculating the risk score of every patient was developed with univariate Cox, least absolute shrinkage and selection operator, and stepwise regression analysis. Kaplan-Meier and receiver operating characteristic curves were plotted to verify the accuracy. The independence of the signature was confirmed by the multivariate Cox regression analysis. Finally, a prognostic nomogram including 359 patients was constructed based on the combined expression data and the risk scores.

Results: TP53 mutation was screened to be the robust and survival-related mutation type, and was associated with immune cell infiltration. Two thousand, four hundred fifty-five genes included in the six modules generated in the WGCNA were screened as candidate survival related TP53-associated genes. A seven-gene signature was constructed: Risk score = (0.1254 × ERRFI1) - (0.1365 × IL6R) - (0.4400 × PPP1R10) - (0.3397 × PTOV1-AS2) + (0.1544 × SCEL) - (0.4412 × SSX2IP) - (0.2231 × TXNL4A). Area Under Curves of 1-, 3-, and 5-year ROC curves were 0.731, 0.808, and 0.873 in the training set and 0.703, 0.677, and 0.737 in the validation set. A prognostic nomogram including 359 patients was constructed and well-calibrated, with the Area Under Curves of 1-, 3-, and 5-year ROC curves as 0.713, 0.753, and 0.823.

Conclusions: The TP53-associated signature exhibited good prognostic efficacy in predicting the overall survival of PC patients.
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http://dx.doi.org/10.1186/s12885-021-08066-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011162PMC
March 2021
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