Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Simulations of thermal conductance across tilt grain boundaries in graphene

Non-equilibrium molecular dynamics （MD） method was performed to simulate the thermal transporta- tion process in graphene nanoribbons （GNRs）. A convenient way was conceived to introduce tilt grain boundaries （GBs） into the graphene lattice by repetitive removing C atom rows along certain directions. Comprehensive MD simulations reveal that larger-angle GBs are effective thermal barriers and substantially reduce the average thermal conductivity of GNRs. The GB thermal conductivity is ~ 10 W-m-1 .K-l for a bicrystal GNR with a misorientation of 21.8%, which is -97 % less than that of a prefect GNR with the same size. The total thermal resistance has a monotonic dependence on the den- sity of the 5-7 defects along the GBs. A theoretical model is proposed to capture this relation and resolve the contribu- tions by both the reduction in the phonon mean free path and the defect-induced thermal resistance.

Comparison of Image Reconstruction Algorithms in EIT Imaging

Electrical Impedance Tomography (EIT) is a medical imaging technique which can be used to monitor the regional ventilation in patients utilizing voltage measurements made at the thorax. Several reconstruction algorithms have been developed during the last few years. In this manuscript we compare a well-established algorithm and a re-cently developed method for image reconstruction regarding EIT indices derived from the differently reconstructed images.

MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways

AIM:To determine how the oncogene mi R-21 regulates the RAS signaling pathways and affects colon cancer cell behaviors.METHODS:RAS p21 GTPase activating protein 1(RASA1) protein expression in six colon cancer cell lines was assessed by Western blot.Colon cancer RKO cells were chosen for transfection because they are KRAS wild type colon cancer cells whose RASA1 expression is significantly decreased.RKO cells were transfected with vectors overexpressing or downregulating either mi R-21 or RASA1.Furthermore,a luciferase reporter assay was used to determine whether RASA1 is a gene target of mi R-21.Then,changes in m RNA and protein levels of RASA1,RASGTP,and other components of the RAS signaling pathways were assessed in transfected RKO cells by real-time quantitative reverse transcription-polymerase chain reaction,Western blot and immunoprecipitation.Finally,cell proliferation,apoptosis,invasion,and tumorformation ability w ere assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay,flow cytometry,transwell assay,and animal experiment,respectively.RESULTS:RASA1 protein levels were significantly decreased in RKO cells compared with the other 5 colon cancer cell lines,and RASA1 was confirmed as a target gene of mi R-21.Interestingly,RASA1 m RNA and protein levels in pre-mi R-21-LV(up-regulation of mi R-21) cells were lower than those in anti-mi R-21-LV(down-regulation of mi R-21) cells(P < 0.05).In addition,pre-mi R-21-LV or si RASA1(down-regulation of RASA1) cells showed higher cell proliferation,reduced apoptosis,increased expression of RAS-GTP,p-AKT,Raf-1,KRAS,and p-ERK1/2,and higher invasion and tumor formation ability,compared with control,antimi R-21-LV or pc DNA3.1-RASA1(up-regulation of RASA1) cells(P < 0.05).CONCLUSION:RASA1 is a target gene of mi R-21,which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.

Growing actin networks regulated by obstacle size and shape

Growing actin networks provide the driving force for the motility of cells and intracellular pathogens. Based on the molecular-level processes of actin polymerization, branching, capping, and depolymerization, we have developed a modeling framework to simulate the stochastic and cooperative behaviors of growing actin networks in propelling obstacles, with an emphasis on the size and shape effects on work capacity and filament orientation in the growing process. Our results show that the characteristic size of obstacles changes the protrusion power per unit length, without influencing the orientation distribution of actin filaments in growing networks. In contrast, the geometry of obstacles has a profound effect on filament patterning, which influences the orientation of filaments differently when the drag coefficient of environment is small, intermediate, or large. We also discuss the role of various parameters, such as the aspect ratio of obstacles, branching rate, and capping rate, in affecting the protrusion power of network growth.

Genetic association of COL1A1 polymorphisms with high myopia in Asian population: a Meta-analysis

AIM: To comprehensively evaluate the potential association of COL1A1 polymorphisms with high myopia by a systematic review and Meta-analysis. METHODS: All association studies on COL1A1 and high myopia reported up to June 10, 2014 in PubMed, Embase, Web of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed for single-nucleotide polymorphisms (SNPs) using fixed- and random - effects models according to between-study heterogeneity. Publication bias analyses were conducted by Eggers test. RESULTS: A total of four studies from reported papers were included in this analysis. The Meta-analyses for COL1A1 rs2075555, composed of 2304 high myopia patients and 2272 controls, failed to detect any significant association with high myopia. A total of 971 cases and 649 controls were tested for COL1A1 rs2269336. The association of COL1A1 rs2269336 with high myopia was observed in recessive model (CC vs CG+GG, P = 0.03) and in heterozygous model (CG vsGG, P = 0.04), but not in other models. CONCLUSION: This Meta-analysis shows that COL fill rs2269336 (CC vs CG +GG) affects individual susceptibility to high myopia, whereas there is no association detected between SNPs rs2075555 and high myopia. Given the limited sample size, further investigations including more ethnic groups are required to validate the association.

Frequency spectrum might act as communication code between retina and visual cortex Ⅰ

AIM: To explore changes and possible communication relationship of local potential signals recorded simultaneously from retina and visual cortex I(V1).·METHODS: Fourteen C57BL/6J mice were measured with pattern electroretinogram(PERG) and pattern visually evoked potential(PVEP) and fast Fourier transform has been used to analyze the frequency components of those signals.· RESULTS: The amplitude of PERG and PVEP was measured at about 36.7 μV and 112.5 μV respectively and the dominant frequency of PERG and PVEP, however,stay unchanged and both signals do not have second, or otherwise, harmonic generation.· CONCLUSION: The results suggested that retina encodes visual information in the way of frequency spectrum and then transfers it to primary visual cortex.The primary visual cortex accepts and deciphers the input visual information coded from retina. Frequency spectrum may act as communication code between retina and V1.

Association of n3 and n6 polyunsaturated fatty acids in red blood cell membrane and plasma with severity of normal tension glaucoma

AIM: To determine whether red blood cell(RBC)membrane and plasma lipids, particularly long-chain polyunsaturated fatty acids such as eicosapentaenoic acid(EPA), docosahexaenoic acid(DHA), arachidonic acid(AA) are significantly correlated with severity of normal tension glaucoma(NTG).METHODS: This study included 35 patients with NTG and 12 healthy normal control subjects, matched for age and sex with the study group. The stage of glaucoma was determined according to the Hodapp-Parrish-Anderson classification. Lipids were extracted from RBC membranes and plasma, and fatty acid methyl esters prepared and analyzed by gas chromatography-mass spectrometry(GC-MS).RESULTS: When RBC lipids were analyzed, the levels of EPA, the levels of DHA and the ratio of n3 to n6 were positively associated with the Humphrey Perimetry mean Deviation(MD) score(r =0.617, P 【0.001; r =0.727, P 【0.001 and r =0.720, P 【0.001, respectively), while the level of AA was negatively associated with the MD score(r =-0.427, P =0.001). When plasma lipids were analyzed,there was a significant positive relationship between the levels of EPA and the MD score(r =0.648, P 【0.001), and the levels of AA were inversely correlated with the MD score(r =-0.638, P 【0.001). CONCLUSION: The levels of n3 and n6 polyunsaturated fatty acids in RBC membrane and plasma lipids were associated with severity of NTG.

Effects of dexamethasone and HA1077 on actin cytoskeleton and β-catenin in cultured human trabecular meshwork cells

AIM：To investigate the effects of dexamethasone（DEX） and 1-（5-isoquinolinesulfonyl）-homopiperazine（HA1077） on actin cytoskeleton and β-catenin in cultured human trabecular meshwork（HTM） cells.METHODS： The HTM cells were separated from human eyeball and cultured in vitro.They were divided into control group,DEX（1×10^-6mol/L） group,HA1077（3×10^-5mol/L）group,and DEX（1×10^-6mol/L） and HA1077（3×10^-5mol/L）group.Actin cytoskeleton and β-catenin in HTM cells of the four groups were examined by immunofluorescence and Western blot analyses.RESULTS： In DEX group,there were reorganization of actin cytoskeleton and formation of cross linked actin networks（CLANs）,which were partially reversed in DEX and HA1077 group.DEX treatment also induced an increased expression of β-catenin,which was obviously reduced in DEX and HA1077 group.Meanwhile,the cultured HTM cells in HA1077 group had lower expression of β-catenin than that in the control group. CONCLUSION： Our results show that HA1077 can reverse the changes of actin organization and expression of β-catenin induced by DEX in cultured HTM cells,suggesting that HA1077 may play an important role in increasing outflow and reducing intraocular pressure.

Association of MTHFR C677T polymorphism with primary open angle glaucoma:a Meta-analysis based on 18 case-control studies

AIM:To systematically understand the genetic association between methylenetetrahydrofolate reductase(MTHFR)C677 T polymorphism and primary open angle glaucoma(POAG).METHODS:A comprehensive literature search in Google Scholar,Pub Med,Science Citation Index,Foreign Medical Literature Retrieval Service,Chinese National Knowledge Infrastructure and Wanfang Databases was performed to collect all eligible studies up to August 2019.Study selection,data abstraction and study quality evaluation were performed by two independent investigators.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated to assess the association.RESULTS:Eighteen case-control studies including 2156 cases and 2201 controls were identified.There was no significant difference in the terms of MTHFR C677 T polymorphism and POAG in the Caucasian population(for T vs C OR=1.11,95%CI:0.88 to 1.39;for TT vs CC OR=1.01,95%CI:0.76 to 1.36;for TT+TC vs CC OR=1.15,95%CI:0.84 to 1.58 and for TT vs TC+CC OR=1.02,95%CI:0.78 to 1.33).However,a significant effect was revealed in the Asian population(for T vs C OR=1.34,95%CI:1.12 to 1.59;for TT+TC vs CC OR=1.41,95%CI:1.14 to 1.76).CONCLUSION:Based on 18 eligible studies,we provide a correlation between MTHFR C677 T polymorphism and POAG among the Asians subgroup indicating that the T allele or TT+TC genotype may play a critical role in POAG development in Asians.

A Noise-Robust Pulse for Excitation Transfer in a Multi-Mode Quantum Memory

Multi-mode quantum memory is a basic element required for long-distance quantum communication,as well as scalable quantum computation.For on-demand readout and long storage times,control pulses are crucial in order to transfer atomic excitations back and forth into spin excitations.Here,we introduce noise-robust composite pulse sequences for high-fidelity excitation transfer in multi-mode quantum memory.These pulses are robust to the deviations in amplitude and the detuning parameters of realistic conditions.We show the efficiency of these composite pulses with a typical rare-earth ion-doped system.This approach could be applied to a variety of quantum memory schemes.

Photoreduction adjusted surface oxygen vacancy of Bi_(2)MoO_(6) for boosting photocatalytic redox performance

In this study, Bi_(2)MoO_(6) with adjustable rich oxygen vacancies was prepared by a novel and simple solvothermal-photoreduction method which might be suitable for a large-scale production. The experiment results show that Bi_(2)MoO_(6) with rich oxygen vacancies is an excellent photocatalyst. The photocatalytic ability of BMO-10 is 0.3 and 3.5 times higher than that of the pristine Bi_(2)MoO_(6) for Rhodamine B degradation and Cr(VI) reduction, respectively. The results display that the band energy of the samples with oxygen vacancies was narrowed and the light absorption was broadened. Meanwhile, the efficiency of photogenerated electron-holes was increased and the separation and transfer speed of photogenerated carriers were improved. Therefore, this work provides a convenient and efficient method to prepare potential adjustable oxygen vacancy based photocatalysts to eliminate the pollution of dyes and Cr(VI) in water.

ERRATUM TO:Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival

Erratum to:SCIENCE CHINA Life Sciences,Volume 66,Issue 2:211-225(2022),https://doi.org/10.1007/s11427-021-2126-2 This paper contains an error in Figure 4C,where the representative images of filipin staining of retinal sections from 6-month-old mice were misused.We provide the correct picture for Figure 4C as follows.The statistical result in Figure 4D was corrected as well.This new Figure 4 does not affect the conclusion of this article.

Association analysis of genetic variants in critical patients with COVID-19 and validation in a Chinese population

Dear Editor,Genome-wide association studies(GWASs)have reported a genetic association between certain populations and the severity of COVID-19.In severe patients,changes in the locus 3p21.31(including SLC6A20,LZTFL1,CCR9,FYCO1,CXCR6,and XCR1)are associated with COVID-19 hospitalization(Ellinghaus et al.,2020).Moreover,variations in 9p34.2 region(including genes related to the ABO blood grouping)can affect both susceptibility and severity of COVID-19;in particular,individuals with blood group A may have an increased risk of COVID-19 infection,while those with blood group O may have a protective effect(Ellinghaus et al.,2020;Shelton et al.,2021).

Raman spectroscopy monitors adverse bone sequelae of cancer radiotherapy

Raman spectroscopy provides information on bone chemical composition and structure via widely used metrics including mineral to matrix ratio, mineral crystallinity and carbonate content, collagen cross- linking ratio and depolarization ratios. These metrics are correlated with bone material properties, such as hardness, plasticity and Young＇s modulus. We review application of Raman spectroscopy to two important irradiated animal models： the mouse tibia, a model for damage to cortical bone sites including the rib （breast cancer） and to healthy tissue adjacent to extremity sarcomas, and the rat mandible, a model for radiation damage in head and neck cancer radiotherapy. Longitudinal studies of irradiated mouse tibia demonstrate that radiation-induced matrix abnormalities can persist even 26 weeks post- radiation. Polarized Raman spectroscopy shows formation of more ordered orientation of both mineral and collagen. At 8 weeks post-radiation, irradiated rat hemimandible exhibits transient hyperminer- alization, increased collagen cross-linking and decreased depolarization ratios of mineral and collagen. A standard radioprotectant, amifostine, mitigates rat mandible radiation damage, with none remaining detectable 18 weeks post-radiation. Already a powerful tool to monitor radiation damage, Raman spectroscopy may be important in development of new radiotherapy protocols and radioprotective agents. Further in vfvo studies of radiation effects on the rodent models are underway, as are development of methodologies for eventual use in human subjects.

Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival

Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells(RGCs) by using an artificial intelligence(AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing(scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/-retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/-mice using atorvastatin reduced the cholesterol level in the retina,thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/-retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.

Epigenetic and transcriptional activation of the secretory kinase FAM20C as an oncogene in glioma

Gliomas are the most prevalent and aggressive malignancies of the nervous system.Previous bioinformatic studies have revealed the crucial role of the secretory pathway kinase FAM20C in the prediction of glioma invasion and malignancy.However,little is known about the pathogenesis of FAM20C in the regulation of glioma.Here,we construct the full-length transcriptome atlas in paired gliomas and observe that 22 genes are upregulated by full-length transcriptome and differential APA analysis.Analysis of ATAC-seq data reveals that both FAM20C and NPTN are the hub genes with chromatin openness and differential expression.Further,in vitro and in vivo studies suggest that FAM20C stimulates the proliferation and metastasis of glioma cells.Meanwhile,NPTN,a novel cancer suppressor gene,counteracts the function of FAM20C by inhibiting both the proliferation and migration of glioma.The blockade of FAM20C by neutralizing antibodies results in the regression of xenograft tumors.Moreover,MAX,BRD4,MYC,and REST are found to be the potential trans-active factors for the regulation of FAM20C.Taken together,our results uncover the oncogenic role of FAM20C in glioma and shed new light on the treatment of glioma by abolishing FAM20C.

Dynamic human retinal pigment epithelium(RPE)and choroid architecture based on single-cell transcriptomic landscape analysis

The retinal pigment epithelium(RPE)and choroid are located behind the human retina and have multiple functions in the human visual system.Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies.Here,we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages,revealing regional and age differences within the human RPE and choroid.Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types.Moreover,the transcription factors and their target genes change during aging.The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level.Moreover,we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging.The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

Nuclear transport proteins: structure, function, and disease relevance

Proper subcellular localization is crucial for the functioning of biomacromolecules,including proteins and RNAs.Nuclear transport is a fundamental cellular process that regulates the localization of many macromolecules within the nuclear or cytoplasmic compartments.In humans,approximately 60 proteins are involved in nuclear transport,including nucleoporins that form membrane-embedded nuclear pore complexes,karyopherins that transport cargoes through these complexes,and Ran system proteins that ensure directed and rapid transport.Many of these nuclear transport proteins play additional and essential roles in mitosis,biomolecular condensation,and gene transcription.Dysregulation of nuclear transport is linked to major human diseases such as cancer,neurodegenerative diseases,and viral infections.Selinexor(KPT-330),an inhibitor targeting the nuclear export factor XPO1(also known as CRM1),was approved in 2019 to treat two types of blood cancers,and dozens of clinical trials of are ongoing.This review summarizes approximately three decades of research data in this field but focuses on the structure and function of individual nuclear transport proteins from recent studies,providing a cutting-edge and holistic view on the role of nuclear transport proteins in health and disease.In-depth knowledge of this rapidly evolving field has the potential to bring new insights into fundamental biology,pathogenic mechanisms,and therapeutic approaches.

Band Structure Calculations of Dispersive Photonic Crystals in 3D using Holomorphic Operator Functions

We propose a finite element method to compute the band structures of dispersive photonic crystals in 3D.The nonlinear Maxwell’s eigenvalue problem is formulated as the eigenvalue problem of a holomorphic operator function.The N´ed´elec edge elements are employed to discretize the operators,where the divergence free condition for the electric field is realized by a mixed form using a Lagrange multiplier.The convergence of the eigenvalues is proved using the abstract approximation theory for holomorphic operator functions with the regular approximation of the edge elements.The spectral indicator method is then applied to compute the discrete eigenvalues.Numerical examples are presented demonstrating the effectiveness of the proposed method.