Biology subjects

Yang, C.

Publications and source records attributed to Yang, C..

At least 361 records · Page 20Linked to original sources

bioRxiv2021

Single-cell transcriptome lineage tracing of human pancreatic development identifies distinct developmental trajectories of alpha and beta cells

In comparison to mouse, the developmental process of human islets has not been properly elucidated. The advancement of single cell RNA-seq technology enables us to study the properties of alpha and beta cells at single cell resolution. By using mitochondrial genome variants as endogenous lineage-tracing markers, we found that human alpha and beta cells have different lineage features. This finding suggests specific endocrine progenitors for alpha and beta cells, which is different from mouse islet cells. This strategy was also applied to a study of chemically-induced islet cell reprogramming and was used to help identify artemether-induced alpha-to-beta trans-differentiation in human islets. The computational results of this study will inspire future studies to establish, maintain, and expand beta cell-specific progenitors in vitro and in vivo.

developmental biology↗

bioRxiv2020

Sequencing of clinical samples reveals that adaptation keeps establishing during H7N9 virus infection in humans

The H7 subtype avian influenza viruses (AIV) have a much longer history and their adaptation through evolution pose continuous threat to humans 1. Since 2013 March, the novel reasserted H7N9 subtype have transmitted to humans through their repeated assertion in the poultry market. Through repeated transmission, H7N9 gradually became the second AIV subtype posing greater public health risk after H5N1 2,3. After infection, how the virus tunes its genome to adapt and evolve in humans remains unknown. Through direct amplification of H7N9 and high throughput (HT) sequencing of full genomes from the swabs and lower respiratory tract samples collected from infected patients in Shenzhen, China, we have analyzed the in vivo H7N9 mutations at the level of whole genomes and have compared with the genomes derived by in vitro cultures. These comparisons and frequency analysis against the H7N9 genomes in the public database, 40 amino acids were identified that play potential roles in virus adaptation during H7N9 infection in humans. Various synonymous mutations were also identified that might be crucial to H7N9 adaptation in humans. The mechanism of these mutations occurred in a single infection are discussed in this study.

microbiology↗

bioRxiv2020

CRISPR knockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep

Identification of mechanisms which increase deep sleep could lead to novel treatments which promote the restorative effects of sleep. Here, knockdown of the 3 GABAA-receptor subunit from parvalbumin neurons in the thalamic reticular nucleus using CRISPR-Cas9 gene editing increased the thalamocortical delta oscillations implicated in many health-promoting effects of sleep. Inhibitory synaptic currents were strongly reduced in vitro. Effects were most pronounced in the mouse sleep (light) period. Further analysis identified a novel deep-sleep state in mice prior to NREM-REM transitions which was preferentially affected by deletion of 3 subunits. Our results identify a functional role for GABAA receptors on Thalamic Reticular Nucleus neurons and suggest antagonism of 3 subunits as a strategy to enhance deep sleep. One Sentence SummarySelective genetic knockdown of the major subunit of GABAA receptors present in the thalamic reticular nucleus enhanced deep sleep in mice.

neuroscience↗

bioRxiv2020

Oxidized LDL but not angiotensin II induces the interaction between LOX-1 and AT1 receptors

Oxidized low-density lipoprotein (Ox-LDL) can induce cardiac hypertrophy, but the mechanism is still unclear. Here we elucidate the role of angiotensin II (AngII) receptor (AT1-R) in Ox-LDL-induced cardiomycyte hypertrophy. Inhibition of Ox-LDL receptor LOX-1 and AT1-R rather than AngII abolished Ox-LDL-induced hypertrophic responses. Similar results were obtained from the heart of mice lacking endogenous Ang II and their cardiomyocytes. Ox-LDL but not AngII induced binding of LOX-1 to AT1-R, and the inhibition of LOX-1 or AT1-R rather than AngII abolished the association of these two receptors. Ox-LDL-induced ERKs phosphorylation in LOX-1 and AT1-R-overexpression cells and the binding of both receptors were suppressed by the mutants of LOX-1 (Lys266Ala/Lys267Ala) or AT1-R (Glu257Ala), however, the AT1-R mutant lacking Gq protein-coupling ability only abolished the ERKs phosphorylation. The phosphorylation of ERKs induced by Ox-LDL in LOX-1 and AT1-R-overexpression cells was abrogated by Gq protein inhibitor but not by Jak2, Rac1 and RhoA inhibitors. Therefore, the direct interaction between LOX-1 and AT1-R and the downstream Gq protein activation are important mechanisms for Ox-LDL-but not AngII-induced cardiomyocyte hypertrophy.

cell biology↗

bioRxiv2020

Immunoglobulin A Antibody Composition Is Sculpted to Bind the Self Gut Microbiome

Despite being the most abundantly secreted immunoglobulin isotype, the reactivity of IgA antibodies towards each individuals own gut commensal bacteria still remains elusive. By colonizing germ-free mice with defined commensal bacteria, we found the binding specificity of bulk fecal and serum IgA towards resident gut bacteria resolves well at the species level and has modest strain level specificity. IgA hybridomas generated from lamina propria B cells of gnotobiotic mice showed that most IgA clones recognized a single bacterial species, while a small portion displayed polyreactivity. Species-specific IgAs had a range of strain specificities. Given the unique bacterial species and strain composition in each individuals gut, our findings suggest the IgA repertoire is uniquely shaped to bind our self gut bacteria.

immunology↗

bioRxiv2020

Convolutional neural network for automated mass segmentation in mammography

BackgroundAutomatic segmentation and localization of lesions in mammogram (MG) images are challenging even with employing advanced methods such as deep learning (DL) methods. We developed a new model based on the architecture of the semantic segmentation U-Net model to precisely segment mass lesions in MG images. The proposed end-to-end convolutional neural network (CNN) based model extracts contextual information by combining low-level and high-level features. We trained the proposed model using huge publicly available databases, (CBIS-DDSM, BCDR-01, and INbreast), and a private database from the University of Connecticut Health Center (UCHC). ResultsWe compared the performance of the proposed model with those of the state-of-the-art DL models including the fully convolutional network (FCN), SegNet, Dilated-Net, original U-Net, and Faster R-CNN models and the conventional region growing (RG) method. The proposed Vanilla U-Net model outperforms the Faster R-CNN model significantly in terms of the runtime and the Intersection over Union metric (IOU). Training with digitized film-based and fully digitized MG images, the proposed Vanilla U-Net model achieves a mean test accuracy of 92.6%. The proposed model achieves a mean Dice coefficient index (DI) of 0.951 and a mean IOU of 0.909 that show how close the output segments are to the corresponding lesions in the ground truth maps. Data augmentation has been very effective in our experiments resulting in an increase in the mean DI and the mean IOU from 0.922 to 0.951 and 0.856 to 0.909, respectively. ConclusionsThe proposed Vanilla U-Net based model can be used for precise segmentation of masses in MG images. This is because the segmentation process incorporates more multi-scale spatial context, and captures more local and global context to predict a precise pixel-wise segmentation map of an input full MG image. These detected maps can help radiologists in differentiating benign and malignant lesions depend on the lesion shapes. We show that using transfer learning, introducing augmentation, and modifying the architecture of the original model results in better performance in terms of the mean accuracy, the mean DI, and the mean IOU in detecting mass lesion compared to the other DL and the conventional models.

bioinformatics↗

bioRxiv2020

Chemoproteomics Maps Glycolytic Targetome in Cancer Cells

Hyperactivated glycolysis, favoring uncontrolled growth and metastasis by producing essential metabolic intermediates engaging bioenergetics and biosynthesis, is a metabolic hallmark of most cancer cells. Although sporadic information has revealed glycolytic metabolites also possess non-metabolic function as signaling molecules, it remains largely elusive how these metabolites interact with and functionally regulate their binding targets. Here we introduce a Target Responsive Accessibility Profiling (TRAP) approach that measures ligand binding-induced steric hindrance in protein targets via global profiling accessibility changes in reactive lysines, and mapped 913 target candidates and 2,487 interactions for 10 major glycolytic metabolites in cancer cells via TRAP. The elucidated targetome uncovers diverse regulatory modalities of glycolytic metabolites involving the direct perturbation of carbohydrate metabolism enzymes, intervention of transcriptional control, modulation of proteome-level acetylation and protein complex assemblies. The advantages gained from glycolysis by cancer cells are expanded by discovering lactate as a ligand for an orphan transcriptional regulator TRIM 28 that promotes p53 degradation, and by identifying pyruvate acting against a cell apoptosis inducer trichostatin A via attenuating protein acetylation. Lastly, the inhibition of glycolytic key enzymes led to identify an intrinsically active glycolytic intermediate glyceraldehyde 3-phosphate that elicits its cytotoxicity by engaging with ENO1 and MTHFD1. Collectively, the glycolytic targetome depicted by TRAP constitutes a fertile resource for understanding how glycolysis finely tunes metabolism and signaling in support of cancer cells, and fostering the exploitation of glycolytic targetome as promising nodes for anti-cancer therapeutics development.

cancer biology↗

bioRxiv2020

Social transmission of egg rejection in a cuckoo host

Social learning can enable the rapid dissemination of behaviors throughout a population. Rejection of foreign eggs is a key defense in hosts of avian brood parasites; however, whether social cues can inform whether a host rejects an egg remains unknown. Here, we aimed to determine whether access to social information can influence egg rejection behavior in semi-colonial barn swallows (Hirundo rustica). By manipulating the social information available from a neighboring nest, we found that swallows that had access to social information (i.e. neighbor recently rejected an egg) were more likely to reject a foreign egg compared to those that did not have access to social information (i.e. neighbor did not reject an egg). This result provides the first empirical evidence that egg rejection behavior can solely be informed by social information, and in doing so highlights the dynamic nature of defenses that hosts can deploy against brood parasitism.

animal behavior and cognition↗

bioRxiv2020

Nav1.3 and fibroblast growth factor homologous factor 14 are primary determinants of the TTX-sensitive sodium current in mouse adrenal chromaffin cells

Adrenal chromaffin cells (CCs) in rodents express a rapidly inactivating, TTX-sensitive sodium current. The current has generally been attributed to Nav1.7, although a possible role for Nav1.3 has also been suggested. Nav channels in rat CCs rapidly inactivate into two separable pathways, which differ in their time course of recovery from inactivation. One population recovers with time constants similar to traditional fast inactivation and the other about 10-fold slower. Inactivation properties suggest that the two pathways result from a single homogenous population of channels. Here we probe the properties and molecular components of the Nav current present in mouse CCs. We first confirm that functional properties of Nav current in rat and mouse cells are generally similar in terms of activation range, steady-state inactivation, and dual pathway fast inactivation. The results then show that all inward Nav current is absent in CCs from Nav1.3 KO mice. Subsequently, in a mouse with KO of fibroblast growth factor homology factor 14 (FGF14), we find that the slow component of recovery from fast inactivation is completely absent in most CCs, with no change in the time constant of fast recovery. Experiments probing the use-dependence of Nav current diminution between WT and FGF14 KO mice directly demonstrate a role of slow recovery from inactivation in determination of Nav current availability. Overall, the results indicate that the FGF14-mediated inactivation is the major determinant in defining use-dependent changes in Nav availability in CCs. We also consider the potential impact that inactivating FGFs with different recovery kinetics can exert on differential use-dependent changes in Nav availability.

biophysics↗

bioRxiv2020

Plant endophytic bacteria: a potential resource pool of electroactive microorganisms

Electroactive microorganisms play a significant role in microbial fuel cells (MFCs). These devices, which are based on a wide microbial diversity, can convert a large array of organic matter components into sustainable and renewable energy. At present, electricity-producing microorganisms are mostly isolated from sewage, anaerobic sediments and soil, however, the sources are very limited. For a more comprehensive understanding of the electron transfer mechanism of the electricity-producing microorganisms and the interaction with the environment, it is necessary to obtain a thorough understanding of their resource distribution and discover potential resources. In this study, plant tissues were selected to isolate endophytic bacteria, and the electrochemical activity potential of those bacteria was evaluated by high-throughput screening with a WO3 nanoprobe. Twenty-six strains of endophytic bacteria were isolated from plant tissues belonging to Angelica and Sweet Potato, of which 17 strains from 6 genera had electrochemical activity, including Bacillus sp., Pleomorphomonas sp., Rahnella sp., Shinella sp., Paenibacillus sp. and Staphylococcus sp.. Moreover, the electricity-producing microorganisms in the plant tissue are enriched. Microbial community analysis by high-throughput sequence indicated that Pseudomonas and Clostridioides are the dominant genera of MFC anode inoculated with angelica tissue.Staphylococcus and Lachnoclostridium 5 are the dominant genera in MFC anode inoculated with sweet potato tissue. And the most representative Gram-positive strain Staphylococcus succinus subsp. succinus H6 and plant tissue-inoculated MFC were further analyzed for electrochemical activity. After nearly 1500 h of voltage monitoring and cyclic voltammetry analysis, the results showed that a strain numbered H6 and plant tissue-inoculated MFC had a good electrogenerating activity. ImportanceSome biological characteristics of microorganisms are inextricably linked to their living environment. For plant endophytes, some of their biological characteristics have a profound impact on the host. The discovery of the production of electrobacteria in plants helps us to understand the interaction between microorganisms and plants more deeply. For example, there may be intercellular electron transfer between the internally producing bacteria and nitrogen-fixing bacteria to improve the efficiency of nitrogen fixation. In addition, there may be a connection between the weak electrical signal of the plant and the the endophytic electricity-producing microorganismsThe discovery of electricity-producing bacteria in plants also brings a more comprehensive understanding of the distribution of electricity-producing microbial resources and the mechanism of origin.

microbiology↗

bioRxiv2020

Kidney injury molecule-1 is a potential receptor for SARS-CoV-2

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and high mortality. Identification of SARS-CoV-2 in kidney of COVID-19 patients suggests renal tropism and direct infection. Presently, it is generally recognized that SARS-CoV-2 initiates invasion through binding of receptor-binding domain (RBD) of spike protein to host cell-membrane receptor ACE2, however, whether there is additional target of SARS-CoV-2 in kidney remains unclear. Kidney injury molecule-1 (KIM1) is a transmembrane protein that drastically up-regulated after renal injury. Here, binding between SARS-CoV2-RBD and the extracellular Ig V domain of KIM1 was identified by molecular simulations and co-immunoprecipitation, which was comparable in affinity to that of ACE2 to SARS-CoV-2. Moreover, KIM1 facilitated cell entry of SARS-CoV2-RBD, which was potently blockaded by a rationally designed KIM1-derived polypeptide. Together, the findings suggest KIM1 may mediate and exacerbate SARS-CoV-2 infection in a vicious cycle, and KIM1 could be further explored as a therapeutic target.

cell biology↗

bioRxiv2020

exosome-LncPICALM-AU1 regulates endothelial-mesenchymal transition in hepatopulmonary syndrome

As important mediators of intercellular communication, exosome have can modulate various cellular functions by transferring a variety of intracellular components to target cells. However, little is known about the role of exosome-mediated communication between distant organs. Hepatopulmonary syndrome (HPS) is a severe lung injury caused by chronic liver disease. A new long noncoding RNA (lncRNA) PICALM-AU1 was found and upregulated in the liver of HPS. It was located in the cholangiocytes of liver and then, secreted as exosome into the serum. PICALM-AU1 carrying serum exosomes induced endothelial-mesenchymal transition (EndMT) of PMVECs and promoted lung injury in vivo and in vitro. Furthermore, overexpression of PICALM-AU1 significantly suppressed miR144-3p and subsequently induced ZEB1 expression. Taken together, our findings identified cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the EndMT of HPS lung. And PICALM-AU1 represents a noninvasive biomarker and potential therapeutic target for HPS.

pathology↗

bioRxiv2020

New evidence concerning the genome designations of the AC(DC) tetraploid Avena species

The tetraploid Avena species in the section Pachycarpa Baum, including A. insularis, A. maroccana, and A. murphyi, are thought to be involved in the evolution of hexaploid oats; however, their genome designations are still being debated. Repetitive DNA sequences play an important role in genome structuring and evolution, so understanding the chromosomal organization and distribution of these sequences in Avena species could provide valuable information concerning genome evolution in this genus. In this study, the chromosomal organizations and distributions of six repetitive DNA sequences (including three SSR motifs (TTC, AAC, CAG), one 5S rRNA gene fragment, and two oat A and C genome specific repeats) were investigated using non-denaturing fluorescence in situ hybridization (ND-FISH) in the three tetraploid species mentioned above and in two hexaploid oat species. Preferential distribution of the SSRs in centromeric regions was seen in the A and D genomes, whereas few signals were detected in the C genomes. Some intergenomic translocations were observed in the tetraploids; such translocations were also detected between the C and D genomes in the hexaploids. These results provide robust evidence for the presence of the D genome in all three tetraploids, strongly suggesting that the genomic constitution of these species is DC and not AC, as had been thought previously.

genetics↗

bioRxiv2020

Prime-boost vaccination of mice and Rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

COVID-19 vaccines are being developed urgently worldwide, among which single-shot adenovirus vectored vaccines represent a major approach. Here, we constructed two novel adenovirus vectored COVID-19 vaccine candidates on simian adenovirus serotype 23 (Sad23L) and human adenovirus serotype 49 vectors (Ad49L) carrying the full-length gene of SARS-CoV-2 spike protein (S), designated Sad23L-nCoV-S and Ad49L-nCoV-S vaccines, respectively. The immunogenicity elicited by these two vaccine strains was individually evaluated in mice. Specific humoral and cellular immune responses were proportionally observed in a dose-dependent manner, and stronger response was obtained by boosting. Furthermore, five rhesus macaques were intramuscularly injected with a dose of 5x109 PFU Sad23L-nCoV-S vaccine for prime vaccination, followed by boosting with 5x109 PFU of Ad49L-nCoV-S vaccine at 4-week interval. Three macaques were injected with Sad23L-GFP and Ad49L-GFP vectorial viruses as negative controls. Both mice and macaques tolerated well the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost vaccination regimen induced high titers of 103.16 S-binding antibody (S-BAb), 102.75 cell receptor binding domain (RBD)-BAb and 102.38 neutralizing antibody (NAb) to pseudovirus a week after boosting injection, followed by sustained high levels over 10 weeks of observation. Robust IFN-{gamma} secreting T-cell response (712.6 SFCs/106 cells), IL-2 secreting T-cell response (334 SFCs/106 cells) and intracellular IFN-{gamma} expressing CD4+/CD8+ T cell response (0.39%/0.55%) to S peptides were detected in the vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S vaccines can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

immunology↗

bioRxiv2020

Coordination of two enhancers drives expression of olfactory trace amine-associated receptors

Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.

neuroscience↗

bioRxiv2020

Quantification of discrete gut bacterial strains following fecal transplantation for recurrent Clostridioides difficile infection demonstrates long-term stable engraftment in non-relapsing recipients

Fecal Microbiota Transplantation (FMT), while successful for the treatment of recurrent Clostridioides difficile (rCDI) infection, lacks a quantitative identification of the discrete bacterial strains that transmit and stably engraft in recipients, and their association with clinical outcomes. Using >1,000 unique bacterial strains isolated and sequenced from a combination of 22 FMT donors and recipients, we develop a statistical approach Strainer to detect and track sequenced bacterial strains from low depth metagenomic sequencing data. On application to 14 FMT interventions, we detect stable and high engraftment of [~]71% of gut microbiota strains in recipients at even 5-years post-transplant, a remarkably durable therapeutic from a single administration. We found differential transmission and engraftment efficacy across bacterial taxonomic groups over short and long-time scales. Although [~]80% of the original pre-FMT recipient strains were eliminated by the FMT, those strains that remain persist even 5 years later, along with newer strains acquired from the environment. The precise quantification of donor bacterial strains in recipients independently explained the clinical outcomes of early and late relapse. Our framework identifies the consistently engrafting discrete bacterial strains for use in Live Biotherapeutic Products (LBP) as a safer, scalable alternative to FMT and enables systematic evaluation of different FMT and LBP study designs.

immunology↗

bioRxiv2020

Neuroendocrine and behavioral measures of negative valence in male sign-tracker and goal-tracker rats

Environmental cues attain the ability to guide behavior via learned associations. As predictors, cues can elicit adaptive behavior and lead to valuable resources (e.g., food). For some individuals, however, cues are transformed into incentive stimuli and elicit motivational states that can be maladaptive. The goal-tracker/sign-tracker animal model captures individual differences in cue-motivated behaviors, with reward-associated cues serving as predictors of reward for both phenotypes but becoming incentive stimuli to a greater degree for sign-trackers. While these distinct phenotypes are characterized based on Pavlovian conditioned approach behavior, they exhibit differences on a number of behaviors relevant to psychopathology. To further characterize the neurobehavioral endophenotype associated with individual differences in cue-reward learning, neuroendocrine and behavioral profiles associated with stress and anxiety were investigated in male goal-tracker, sign-tracker, and intermediate responder rats. It was revealed that baseline corticosterone increases with Pavlovian learning, but to the same degree, regardless of phenotype. No significant differences in behavior were observed between goaltrackers and sign-trackers during an elevated plus maze or open field test, nor were there differences in corticosterone response to the open field test or physiological restraint. Upon examination of central markers associated with stress-reactivity, we found that sign-trackers have greater glucocorticoid receptor mRNA expression in the ventral hippocampus, with no phenotypic differences in the dorsal hippocampus or prelimbic cortex. These findings demonstrate that goal-trackers and sign-trackers do not differ on stress- and anxiety-related behaviors, and suggest that differences in neuroendocrine measures between these phenotypes can be attributed to distinct cue-reward learning styles. Significance StatementWhile the goal-tracker/ sign-tracker animal model derives from individual differences in Pavlovian conditioned approach behavior, other traits, including some of relevance to addiction and post-traumatic stress disorder, have been shown to co-exist with the propensity to sign-track. The extent to which this model encompasses differences in aversive arousal and associated neuroendocrine measures, however, remains largely unexplored. Here we show that behavioral and corticosterone response to stress-related paradigms do not differ between goal-trackers and sign-trackers. However, glucocorticoid receptor expression in the ventral hippocampus does differ between phenotypes, suggesting that this central marker that is typically associated with stress-responsivity, may, in fact, play an important role in appetitive motivation.

animal behavior and cognition↗

bioRxiv2020

ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas

Diabetes is associated with increased mortality from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq pancreas datasets and performed fluorescence in situ hybridization, Western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) patients. These in silico and ex vivo analyses demonstrated pancreatic expression of ACE2 is prominent in pancreatic ductal epithelium and the microvasculature, with rare endocrine cell expression of this molecule. Pancreata from COVID-19 patients demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression primarily limited to ducts. SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, appears an unlikely central pathogenic feature of COVID-19 as it relates to diabetes.

pathology↗