Biology subjects

Zhao, R.

Publications and source records attributed to Zhao, R..

At least 145 records · Page 8Linked to original sources

bioRxiv2021

SSR1 is a vital regulator in plant mitochondrial iron-sulfur biosynthesis

The Arabidopsis SHORT AND SWOLLEN ROOT1 (SSR1) gene encodes a mitochondrial TPR domain-containing protein and was previously reported to function in maintaining mitochondria function. In a screen for suppressors of the short-root phenotype of the loss-of-function mutant ssr1-2, two mutations, sus1 and sus2 (suppressor of ssr1-2), were isolated. sus1 and sus2 result from G87D and T55M single amino acid substitution in HSCA2 (At5g09590) and ISU1 (At4g22220), both of which are core components in iron-sulfur cluster biosynthesis pathway in mitochondria (ISC). We here demonstrated that SSR1 displayed a strong chaperone-like activity and was able to enhance the binding of HSCA2 to ISU1, an essential step for the normal operation of ISC machinery. Accordingly, the enzymatic activities of several iron-sulfur proteins, the mitochondrial membrane potential and ATP content are reduced in ssr1-2. Interestingly, SSR1 appears to exist only in plant lineages, possibly conferring adaptive advantages on plant ISC machinery to environment.

plant biology↗

bioRxiv2021

LncRNA XIST knockdown suppresses cell proliferation and promotes apoptosis in diabetic cataract via miR-34a/SMAD2 axis

Emerging evidence has manifested that long non-coding RNAs (lncRNAs) played critical roles in diabetes. The present research aimed to investigate the role and mechanism of XIST on proliferation, migration and apoptosis in diabetic cataract (DC). In the present study, lens epithelial cells (SRA01/04) were treated by high glucose (HG). The levels of XIST, miR-34a and SMAD2 were examined by RT-qPCR. MTT, transwell, wound healing and TUNEL assays were employed to examine cell proliferation, invasion, migration and apoptosis. The interaction between miR-34a and XIST or SMAD2 was verified by luciferase reporter assay. It was found that XIST expression was increased and miR-34a level was decreased in DC tissues and HG-induced SRA01/04 cells. XIST knockdown or miR-34a addition attenuated cell proliferation and migration, and induced apoptosis in SRA01/04 cells under HG. XIST targeted miR-34a and regulated DC progression via miR-34a. SMAD2 was a target gene of miR-34a and was positively modulated by XIST. SMAD2 addition accelerated cell proliferation, migration and inhibited the apoptosis in HG-stimulated SRA01/04 cells, which were abrogated by XIST depletion. In conclusion, XIST facilitated the proliferation, migration and invasion, and inhibited the apoptosis via miR-34a/SMAD2 axis in DC.

microbiology↗

bioRxiv2021

Hydroxide ions amplified by water entanglement underly the mechanism of general anesthesia

It is believed that inhaled anesthetics occupy hydrophobic pockets within target proteins, but how inhaled anesthetics with diverse shapes and sizes fit into highly structurally selective pockets is unknown. For hydroxide ions are hydrophobic, we determined whether hydroxide ions could bridge inhaled anesthetics and protein pockets. We found that small additional load of cerebral hydroxide ions decreases anesthetic potency. Multiple-water entanglement network, derived from Ising model, has a great ability to amplify ultralow changes in the cerebral hydroxide ion concentration, and consequently, amplified hydroxide ions account for neural excitability. Molecular dynamics simulations showed that inhaled anesthetics produce anesthesia by attenuating the formation of multiple-water entanglement network. This work suggests amplified hydroxide ions underlying a unified mechanism for the anesthetic action of inhaled anesthetics.

animal behavior and cognition↗

bioRxiv2021

Helarchaeota and Co-occurring Sulfate-Reducing Bacteria in Subseafloor Sediments from the Costa Rica Margin

Deep sediments host many archaeal lineages, including those of the Asgard superphylum that may depend on/require syntrophic partnerships. Our knowledge about sedimentary archaeal diversity and their metabolic pathways and syntrophic partners is still very limited. We present here new genomes of Helarchaeota and co-occurring sulfate-reducing bacteria (SRB) recovered from organic-rich sediments off Costa Rica Margin. Our molecular analyses revealed three new metagenome-assembled genomes (MAGs) affiliating with Helarchaeota, each of which has three variants of the methyl-CoM reductase-like (MCR-like) complex that may enable them to oxidize short-chain alkanes anaerobically. These Helarchaeota have no multi-heme cytochromes (MHCs) but have Group 3b and Group 3c [NiFe] hydrogenases, and formate dehydrogenase, and therefore could transfer the reducing equivalents generated from alkane oxidation to external partners via the transfer of these substances. We also recovered five MAGs of SRB affiliated with the class of Desulfobacteria, two of which showed relative abundances (represented by genome coverages) positively correlated with those of the three Helarchaeota. Genome analysis suggested that these SRB bacteria have the capacity of H2 and formate utilizations and may facilitate electron transfers from other organisms by means of these reduced substances. Our findings suggest that Helarchaeota may metabolize synergistically with SRB in marine anoxic sediments, and exert an important influence on the carbon cycle by mitigating the hydrocarbon emission from sediments to the overlying ocean.

microbiology↗

bioRxiv2020

Bovine serum albumin as an immunogenic carrier facilitating the development of hapten-specific monoclonal antibodies

There is a common misconception that the generation of hapten-specific monoclonal antibodies (mAbs) requires the use of a heterologous conjugate to ensure carrier-specific antibodies not being detected. In this study, salbutamol (SAL) was used as a model hapten to exhibit the benefits of bovine serum albumin (BSA) as a carrier for developing hapten-specific mAbs. SAL-BSA conjugate would serve as both an immune antigen and a screening antigen during the preparation of SAL-specific mAbs. Six hybridomas were identified to secret mAbs specific for free SAL with minor or negligible cross-reactivity with other {beta}-agonists. Meanwhile, none of hybrodomas secreting anti-BSA antibodies were screened out even though the fetal bovine serum (FBS) added to the medium decreased from 10% to 1% (v/v). Based on one of the six mAbs, 3F12, a direct competitive enzyme-linked immunosorbent assay (dcELISA) was developed for meausring SAL. Under the optimized assay, the quantitative working range was from 312.5 to 20,000 pg/mL (R2 = 0.9959), with a limit of detection (LOD) of 142.9 pg/mL. The results showed that BSA is an efficient and suitable protein carrier for facilitating the development of hapten-specific mAbs.

biochemistry↗

bioRxiv2020

Fast 3D printing of large-scale biocompatible hydrogel models

Large scale cell-laden hydrogel models hold great promise for tissue repair and organ transplantation, but their fabrication is faced with challenges in achieving clinically-relevant size and hierarchical structures. 3D bioprinting is an emerging technology, but its application in large, solid hydrogel fabrication has been limited by the slow printing speed that can affect the part quality and the biological activity of the encapsulated cells. Here we present a Fast hydrogeL prOjection stereolithogrAphy Technology (FLOAT) that allows the creation of a centimeter-sized, multiscale solid hydrogel model within minutes. Through precisely controlling the photopolymerization condition, we established low suction force-driven, high-velocity flow of the hydrogel prepolymer that supports the continuous replenishment of the prepolymer solution below the curing part and the nonstop part growth. We showed that this process is unique to the hydrogel prepolymer without externally supplemented oxygen. The rapid printing of centimeter-sized hydrogel models using FLOAT was shown to significantly reduce the part deformation and cellular injury caused by the prolonged exposure to the environmental stresses in layer-by-layer based printing methods. Media perfusion in the printed vessel network was shown to promote cell survival and metabolic function in the deep core of the large-sized hydrogel model over long term. The FLOAT is compatible with multiple photocurable hydrogel materials and the printed scaffold supports the endothelialization of prefabricated vascular channels. Together, these studies demonstrate a rapid 3D hydrogel printing method and highlight the potential of this method in the fabrication of large-sized engineered tissue models.

bioengineering↗

bioRxiv2020

Sifarchaeota a novel Asgard phylum capable of polysaccharide degradation and anaerobic methylotrophy

The Asgard superphylum is a deeply branching monophyletic group of Archaea, recently described as some of the closest relatives of the eukaryotic ancestor. The wide application of genomic analyses from metagenome sequencing has established six distinct phyla, whose genomes encode for diverse metabolic capacities and play important biogeochemical and ecological roles in marine sediments. Here, we describe two metagenome-assembled genomes (MAGs) recovered from deep marine sediments off Costa Rica margin, defining a novel lineage phylogenetically married to Thorarchaeota, as such we propose the name "Sifarchaeota" for this phylum. The two "Sifarchaeota" MAGs encode for an anaerobic methylotrophy pathway enabling the utilization of C1-C3 compounds (methanol and methylamines) to synthesize acetyl CoA. Also, the MAGs showed a remarkable saccharolytic capabilities compared to other Asgard lineages and encoded for diverse classes of carbohydrate active enzymes (CAZymes) targeting different mono-, di- and oligosaccharides. Comparative genomic analysis based on the full metabolic profiles of Asgard lineages revealed the close relation between "Sifarchaeota" and Odinarchaeota MAGs, which suggested a similar metabolic potentials and ecological roles. Furthermore, we identified multiple potential horizontal gene transfer (HGT) events from different bacterial donors within "Sifarchaetoa" MAGs, which hypothetically expanded "Sifarchaeota" capacities for substrate utilization, energy production and niche adaptation. ImportanceDeep marine sediments are the home of multiple poorly described archaeal lineages, many of which have ecological and evolutionary importance. We recovered metagenome-assembled genomes (MAGs) belonging to a novel Asgard phylum from the deep sediment of the Costa Rica margin. We proposed the name "Sifarchaeota" to describe the members of this phylum. Representative genomes of the "Sifarchaeota" showed remarkable saccharolytic capacities extending the known metabolic features encoded by the Asgard lineages. We attribute its ability to survive under the deep sediment conditions to its putative capacities to utilize different (C1-C3) compounds commonly encountered in deep sediment environments via anaerobic methylotrophy pathway. Also, we showed the importance of horizontal gene transfer in enhancing the "Sifarchaeota" collective adaptation strategies.

microbiology↗

bioRxiv2020

Diversity and biogeography of Woesearchaeota: A comprehensive analysis of multi-environment data

Woesearchaeota is a newly proposed archaeal phylum frequently detected in various environments. Due to the limited systematical study, little is known about their distribution, taxonomy, and metabolism. Here, we conducted a comprehensive study for Woesearchaeota with 16S ribosomal RNA (rRNA) gene sequencing data of 27,709 samples and metagenomic whole genome sequencing (WGS) data of 1,266 samples. We find that apart from free-living environments, Woesearchaeota also widely distribute in host-associated environments. And host-associated environmental parameters greatly affect their distribution. 81 Woesearchaeota genomes, including 33 genomes firstly reconstructed in this project, were assigned to 59 Woesearchaeota species, suggesting their high taxonomic diversity. Comparative analysis indicated that Woesearchaeota have an open pan-genome with small core genome. Metabolic reconstruction showed that particular metabolic pathway absence in specific environments, demonstrated the metabolic diversity of Woesearchaeota varies in differences environments. These results have placed host-associated environments into the global biogeography of Woesearchaeota and have demonstrated their genomic diversity for future investigation of adaptive evolution.

ecology↗

bioRxiv2020

Mechanism of duplex unwinding by coronavirus nsp13 helicases

The current COVID-19 pandemic urges in-depth investigation into proteins encoded with coronavirus (CoV), especially conserved CoV replicases. The nsp13 of highly pathogenic MERS-CoV, SARS-CoV-2, and SARS-CoV exhibit the most conserved CoV replicases. Using single-molecule FRET, we observed that MERS-CoV nsp13 unwound DNA in discrete steps of approximately 9 bp when ATP was used. If another NTP was used, then the steps were only 4 to 5 bp. In dwell time analysis, we detected 3 or 4 hidden steps in each unwinding process, which indicated the hydrolysis of 3 or 4 dTTP. Based on crystallographic and biochemical studies of CoV nsp13 helicases, we modeled an unwinding mechanism similar to the spring-loaded mechanism of HCV NS3 helicase, although our model proposes that flexible 1B and stalk domains, by allowing a lag greater than 4 bp during unwinding, cause the accumulated tension on the nsp13-DNA complex. The hinge region between two RecA-like domains in SARS-CoV-2 nsp13 is intrinsically more flexible than in MERS-CoV nsp13 due to the difference of a single amino acid, which causes the former to induce significantly greater NTP hydrolysis. Our findings thus establish a blueprint for determining the unwinding mechanism of a unique helicase family. O_LIWhen dTTP was used as the energy source, 4 hidden steps in each individual unwinding step after 3 - 4 NTP hydrolysis were observed. C_LIO_LIAn unwinding model of MERS-CoV-nsp13 which is similar to the spring-loaded mechanism of HCV NS3 helicase, except the accumulation of tension on nsp13/DNA complex is caused by the flexible 1B and stalk domains that allow a lag of 4-bp in unwinding. C_LIO_LIComparing to MERS-CoV nsp13, the hinge region between two RecA-like domains in SARS-CoV-2 nsp13 is intrinsically more flexible due to a single amino acid difference, which contributes to the significantly higher NTP hydrolysis by SARS-CoV-2 nsp13. C_LI

biophysics↗

bioRxiv2020

Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo

Some cancer patients treated with Atezolizumab, PD-L1 antibody drug launched by Genentech, quickly developed anti-drug antibody (ADA), led to loss of efficacy. This was likely due to the heavy aggregation of Atezolizumab, caused by mutation of N297A for removing unwanted antibody-dependent cytotoxicity (ADCC) of IgG1 antibody drug. Here, we developed a new version of Atezolizumab (Maxatezo), which was demonstrated better anti-tumor efficacy in vivo. In Atezolizumab, we mutated 297A to 297N back to bring back the glycosylation, and inserted a short sequence GGGS between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Moreover, the insertion of GGGS, without altering the glycosylation profile of IgG1, increased the yields of anti-PD-L1 antibody considerately. Additionally, glycosylation improved the stability yet reduced the amounts of aggregations in the antibody solutions. In turn, the level of ADA in animals treated with Maxatezo was 70% lower than the ones treated with Atezolizumab. Most importantly, at the same 10mg/kg dose, the anti-tumor activity of Maxatezo had attained 98% compared to that of Atezolizumab at 68%.Competing Interest StatementThe authors declare that they are affiliated with four commercial entities with stakes in the data. Patent of De-ADCC pending.View Full Text

bioengineering↗

bioRxiv2020

Changes to zonular tension alters the subcellular distribution of AQP5 in regions of influx and efflux of water in the rat lens.

PurposeThe lens utilizes circulating fluxes of ions and water that enter the lens at both poles and exit at the equator to maintain its optical properties. We have mapped the subcellular distribution of the lens aquaporins (AQP0, 1, & 5) in these water influx and efflux zones and investigated how their membrane location is affected by changes in tension applied to the lens by the zonules. MethodsImmunohistochemistry using AQP antibodies was performed on axial sections obtained from rat lenses that had been removed from the eye and then fixed, or were fixed in situ to maintain zonular tension. Zonular tension was pharmacologically modulated by applying either tropicamide (increased), or pilocarpine (decreased). AQP labelling was visualized using confocal microscopy. ResultsModulation of zonular tension had no effect on AQP1 or AQP0 labelling in either the water efflux, or influx zones. In contrast, AQP5 labelling changed from membranous to cytoplasmic in response to both mechanical and pharmacologically induced reductions in zonular tension in both the efflux zone, and anterior (but not posterior) influx zone associated with the lens sutures. ConclusionsAltering zonular tension dynamically regulates the membrane trafficking of AQP5 in the efflux and anterior influx zones to potentially change the magnitude of circulating water fluxes in the lens.

physiology↗

bioRxiv2020

Genomes of Thaumarchaeota from deep sea sediments reveal specific adaptations of three independently evolved lineages

Marine sediments represent a vast habitat for complex microbiomes. Among these, ammonia oxidizing archaea (AOA) of the phylum Thaumarchaeota are one of the most common, yet little explored inhabitants, that seem extraordinarily well adapted to the harsh conditions of the subsurface biosphere. We present 11 metagenome-assembled genomes of the most abundant AOA clades from sediment cores obtained from the Atlantic Mid-Ocean ridge flanks and Pacific abyssal plains. Their phylogenomic placement reveals three independently evolved clades within the order Ca. Nitrosopumilales, of which no cultured representative is known yet. In addition to the gene sets for ammonia oxidation and carbon fixation known from other AOA, all genomes encode an extended capacity for the conversion of fermentation products that can be channeled into the central carbon metabolism, as well as uptake of amino acids probably for protein maintenance or as an ammonia source. Two lineages encode an additional (V-type) ATPase and a large repertoire of gene repair systems that may allow to overcome challenges of high hydrostatic pressure. We suggest that the adaptive radiation of AOA into marine sediments occurred more than once in evolution and resulted in three distinct lineages with particular adaptations to this extremely energy limiting and high-pressure environment.

microbiology↗

bioRxiv2020

Evidence for an expanded repertoire of electron acceptors for the anaerobic oxidation of methane in authigenic carbonates in the Atlantic and Pacific Ocean

Authigenic carbonates represent a significant microbial sink for methane, yet little is known about the microbiome responsible for the methane removal. We identify carbonate microbiomes distributed over 21 locations hosted by 7 different cold seeps in the Pacific and Atlantic Oceans by carrying out a gene-based survey using 16S rRNA- and mcrA gene sequencing coupled with metagenomic analyses. These sites were dominated by bacteria affiliated to the Firmicutes, Alpha- and Gammaproteobacteria. ANME-1 and -2 clades were abundant in the carbonates yet their typical syntrophic partners, sulfate reducing bacteria, were not significantly present. Our analysis indicated that methane oxidizers affiliated to the ANME-1 and -2 as well as to the Candidatus Methanoperedens clades, are capable of performing complete methane- and potentially short-chain alkane oxidations independently using oxidized sulfur and nitrogen compounds as terminal electron acceptors. Gammaproteobacteria are hypothetically capable of utilizing oxidized nitrogen compounds in potential syntrophy with methane oxidizing archaea. Carbonate structures represent a window for a more diverse utilization of electron acceptors for anaerobic methane oxidation along the Atlantic and Pacific Margin.

microbiology↗

bioRxiv2020

Molecular mechanism of SARS-Cov-2 components caused ARDS in murine model

COVID-19 has become a major challenge to global health, and until now, no efficient antiviral agents have been developed. The SARS-CoV-2 infection is characterized by pulmonary and systemic inflammation in severe patients, and acute respiratory distress syndrome (ARDS) caused respiratory failure contributes to most mortalities. There is an urgent need for developing effective drugs and vaccines against SARS-CoV-2 and COVID-19 caused ARDS. However, most researchers cannot perform SARS-CoV-2 related researches due to lacking P3 or P4 facility. We developed a non-infectious, highly safety, time-saving SARS-CoV-2 components induced murine model to study the SARS-CoV-2 caused ARDS and cytokine storm syndrome (CSS). We also investigated mAbs and inhibitors which potentially neutralize the pro-inflammatory phenotype of COVID-19, and found that anti-IL-1, anti-IL-6, anti-TNF, anti-GM-CSF mAbs, p38 inhibitor, and JAK inhibitor partially relieved CSS. Besides, anti-IL-6, anti-TNF, anti-GM-CSF mAbs and inhibitors of p38, ERK, and MPO somewhat reduced neutrophilic alveolitis in the lung. In all, we established the murine model mimic of COVID-19, opening a biosafety and less time-consuming avenue for clarifying the mechanism of ARDS and CSS in COVID-19 and developing the therapeutic drugs.

pathology↗

bioRxiv2020

Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19. HighlightsO_LICHO-expressed S1-Fc protein is very immunogenic in various animals and can rapidly induce strong antibody production C_LIO_LIS1-Fc protein solicits strong neutralizing activities against live virus C_LIO_LIStable CHO cell line expressing 50 mg/L of S1-Fc and a 3,000 L Bioreactor can produce 3 million doses of human COVID-19 vaccine every 10 days, making it an accessible and affordable option for worldwide vaccination C_LI

immunology↗

bioRxiv2020

Customizable high-throughput platform for profiling cofactor recruitment to DNA to characterize cis-regulatory elements and screen non-coding single-nucleotide polymorphisms

Determining how DNA variants affect the binding of regulatory complexes to cis-regulatory elements (CREs) and non-coding single-nucleotide polymorphisms (ncSNPs) is a challenge in genomics. To address this challenge, we have developed CASCADE (Comprehensive ASsessment of Complex Assembly at DNA Elements), which is a protein-binding microarray (PBM)-based approach that allows for the high-throughput profiling of cofactor (COF) recruitment to DNA sequence variants. The method also enables one to infer the identity of the transcription factor-cofactor (TF-COF) complexes involved in COF recruitment. We use CASCADE to characterize regulatory complexes binding to CREs and SNP quantitative trait loci (SNP-QTLs) in resting and stimulated human macrophages. By profiling the recruitment of the acetyltransferase p300 and MLL methyltransferase component RBBP5, we identify key regulators of the chemokine CXCL10, and by profiling a set of five functionally diverse COFs we identify a prevalence of ETS sites mediating COF recruitment at SNP-QTLs in macrophages. Our results demonstrate that CASCADE is a customizable, high-throughput platform to link DNA variants with the biophysical complexes that mediate functions such as chromatin modification or remodeling in a cell state-specific manner.

genomics↗

bioRxiv2020

RefKA: A fast and efficient long-read genome assembly approach for large and complex genomes

Recent advances in long-read sequencing have the potential to produce more complete genome assemblies using sequence reads which can span repetitive regions. However, overlap based assembly methods routinely used for this data require significant computing time and resources. Here, we have developed RefKA, a reference-based approach for long read genome assembly. This approach relies on breaking up a closely related reference genome into bins, aligning k-mers unique to each bin with PacBio reads, and then assembling each bin in parallel followed by a final bin-stitching step. During benchmarking, we assembled the wheat Chinese Spring (CS) genome using publicly available PacBio reads in parallel in 168 wall hours on a 250 CPU system. The maximum RAM used was 300 Gb and the computing time was 42,000 CPU hours. The approach opens applications for the assembly of other large and complex genomes with much-reduced computing requirements. The RefKA pipeline is available at https://github.com/AppliedBioinformatics/RefKA

bioinformatics↗

bioRxiv2020

High glucose attenuates Ca2+ influx in cytotoxic T lymphocytes upon target recognition

The killing efficiency of cytotoxic T lymphocytes (CTLs) is tightly regulated by intracellular Ca2+ concentration. Glucose is the key energy source for CTLs, lack of which significantly impairs CTL activation, proliferation and effector functions. The impact of high glucose on Ca2+ influx in CTLs remains largely elusive. In this work, we stimulated primary human CD8+ T cells in medium containing either 25 mM (high glucose, HG) or 5.6 mM glucose (normal glucose, NG). We found that store-operated calcium entry (SOCE) induced by thapsigargin (Tg) is elevated in HG-cultured CTLs compared to their counterparts in NG. Unexpectedly, the Ca2+ influx elicited by recognition of target cells is reduced in HG-cultured CTLs. Under HG condition, STIM1 and STIM2, the calcium sensors in the endoplasmic reticulum (ER), were down-regulated; ORAI1, the main structural component of calcium-release activated channels, remained unchanged, whereas ORAI2 and ORAI3 were up-regulated. The fraction of necrosis of HG-cultured CTLs was enhanced after killing without affecting glucose uptake. Thus, our findings reveal that HG has a distinctive impact on Tg-evoked SOCE and target recognition-induced Ca2+ influx in CTLs and causes more CTL death after killing, suggesting a novel regulatory role of high glucose on modulating CTL functions.

immunology↗