Biology subjects

Dong, H.

Publications and source records attributed to Dong, H..

At least 109 records · Page 6Linked to original sources

bioRxiv2022

Reduced ventral attention network connectivity is linked to the accelerated maturation of adult-like cortical organization in childhood

The human brain experiences functional changes through childhood and adolescence, shifting from an organizational framework anchored within sensorimotor and visual regions into one that is balanced through interactions with later-maturing aspects of association cortex. Here, we link this profile of functional reorganization to the development of ventral attention network connectivity across independent datasets. We demonstrate that maturational changes in cortical organization preferentially link to within-network connectivity and heightened degree centrality in the ventral attention network, while connectivity within network-linked vertices predicts cognitive ability. This connectivity is closely associated with maturational refinement of cortical organization. Children with low ventral attention network connectivity exhibit adolescent-like topographical profiles, suggesting that attentional systems may be relevant in understanding how brain functions are refined across development. These data suggest a role for attention networks in supporting age-dependent shifts in cortical organization and cognition across childhood and adolescence.

neuroscience↗

bioRxiv2022

Modulation of Receptor-like Trans-Membrane Kinase 1 nuclear localisation by DA1 peptidases in Arabidopsis.

The activities of proteins can depend on their cleavage, which influences their cellular location, stability and functions. The cleavage of intracellular domains of Receptor -Like Kinases (RLK) has an important functional role in the transduction of signals from the cell surface to the nucleus in many organisms. However, the peptidases that catalyse protein cleavage during signal transduction remain poorly understood despite their crucial roles in diverse signalling processes. Here we report in the flowering plant Arabidopsis thaliana that members of the DA1 family of ubiquitin-regulated Zn metallopeptidases cleave the cytoplasmic kinase domain of TransMembrane Kinase 1 (TMK1), releasing it for nuclear localisation where it represses auxin-responsive cell growth during apical hook formation by phosphorylation and stabilisation of the transcriptional repressors IAA32 and IAA34. Mutations in DA1 family members exhibited reduced apical hook formation, and DA1 family mediated cleavage of TMK1 was promoted by auxin treatment. Expression of the DA1 family - generated intracellular kinase domain of TMK1 by an auxin-responsive promoter fully restored apical hook formation in a tmk1 mutant, establishing the function of DA1 family peptidase activities in TMK1-mediated differential cell growth and apical hook formation. DA1 family peptidase activity therefore modulates TMK1 kinase activity between a membrane location where it stimulates acid cell growth and initiates an auxin-dependent kinase cascade controlling cell proliferation in lateral roots and a nuclear localisation where it represses auxin mediated gene expression and growth.

plant biology↗

bioRxiv2022

m6A RNA methylation impairs gene expression variability and reproductive thermotolerance in Arabidopsis

Plants are more susceptible to high temperature stress during reproductive development, which can cause drastic yield loss of fruit and seed crops. Unfortunately, the underlying mechanism remains largely unknown. Here we suggest that m6A RNA methylation level increases in the reproductive tissues of Arabidopsis and negatively regulates gene expression variability. It has been suggested that stochasticity of gene expression can be advantageous to fitness of living organisms under environmental challenges. Indeed, reduced gene expression variability in flowers was associated with compromised transcriptional activation of heat-responsive genes. Importantly, disruption of an RNA demethylase AtALKBH10B led to lower gene expression variability, hypo-responsiveness of heat-activated genes, and strong reduction of plant fertility. Overall, our work proposes a novel mechanism that m6A RNA modification mediates the bet-hedging strategy of plants challenged by heat stress.

plant biology↗

bioRxiv2022

Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses

As the SARS-CoV-2 pandemic enters its third year, vaccines that not only prevent disease, but also prevent transmission are needed to help reduce global disease burden. Currently approved parenteral vaccines induce robust systemic immunity, but poor immunity at the respiratory mucosa. Here we describe the development of a novel vaccine strategy, Prime and Spike, based on unadjuvanted intranasal spike boosting that leverages existing immunity generated by primary vaccination to elicit mucosal immune memory within the respiratory tract. We show that Prime and Spike induces robust T resident memory cells, B resident memory cells and IgA at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, Prime and Spike enables induction of cross-reactive immunity against sarbecoviruses without invoking original antigenic sin. One-sentence summaryBroad sarbecovirus protective mucosal immunity is generated by unadjuvanted intranasal spike boost in preclinical model.

immunology↗

bioRxiv2021

SARS-CoV-2 RdRp is a versatile enzyme with proofreading activity and ability to incorporate NHC into RNA by using diphosphate form molnupiravir as a substrate

The coronavirus disease 2019 (COVID-19) has been ravaging throughout the world for more than two years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the viral RNA-dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Here, we reveal that RdRp can recognize and utilize nucleoside diphosphates (NDPs) as a substrate to synthesize RNAs with an efficiency of about two thirds of using nucleoside triphosphates (NTPs) as a substrate. NDPs incorporation is also template-specific and has high fidelity. Moreover, RdRp can incorporate {beta}-d-N4-hydroxycytidine (NHC) into RNA while using diphosphate form molnupiravir (MDP) as a substrate. We also observed that MDP is a better substrate for RdRp than the triphosphate form molnupiravir (MTP).

molecular biology↗

bioRxiv2021

Chitin and cuticle proteins form the cuticular layer in the spinning duct of silk-spinning arthropods

Chitin is found in the exoskeleton and peritrophic matrix of arthropods, but recent studies have also identified chitin in the spinning duct of silk-spinning arthropods. Here, we report the presence and function of chitin and cuticle proteins ASSCP1 and ASSCP2 in the spinning duct of silkworms. We show that chitin and these proteins are co-located in the cuticular layer of the spinning duct. Ultrastructural analysis indicates that the cuticular layer has a multilayer structure by layered stacking of the chitin laminae. After knocking down ASSCP1 and ASSCP2, the fine structure of this layer was disrupted, which had negative impacts on the mechanical properties of silk. This work clarifies the function of chitin in the spinning duct of silk-spinning arthropods. Chitin and cuticle proteins are the main components of the hard and rigid cuticular layer, providing the shearing stress during silk fibrillogenesis and regulating the final mechanical properties of silk.

molecular biology↗

bioRxiv2021

Inhibition of SAR S-CoV-2 infection and replication by lactoferrin, MUC1 and α-lactalbumin identified in human breastmilk

The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to the public health. Human breastmilk is an extremely complex with nutritional composition to nourish infants and protect them from different kinds of infection diseases and also SARS-CoV-2 infection. Previous studies have found that breastmilk exhibited potent antiviral activity against SARS-CoV-2 infection. However, it is still unknown which component(s) in the breastmilk is responsible for its antiviral activity. Here, we identified Lactoferrin (LF), MUC1 and -Lactalbumin (-LA) from human breastmilk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and in vitro confirmation that inhibited SARS-CoV-2 infection and analyzed their antiviral activity using the SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP) in the Huh7.5, Vero E6 and Caco-2-N cell lines. Additionally, we found that LF and MUC1 could inhibit viral attachment, entry and post-entry replication, while -LA just inhibit viral attachment and entry. Importantly, LF, MUC1 and -LA possess potent antiviral activities towards not only wild-type but also variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.1 (kappa). Moreover, LF from other species (e.g., bovine and goat) is still capable of blocking viral attachment to cellular heparan sulfate. Taken together, our study provided the first line of evidence that human breastmilk components (LF, MUC1 and -LA) are promising therapeutic candidates warranting further development or treatingVID-19 given their exceedingly safety levels.

microbiology↗

bioRxiv2021

Natural variation further increases resilience of sorghum bred for chronically drought-prone environments

Climate-change-associated shifts in rainfall distribution together with a looming worldwide water crisis make drought resilience of central importance to food security. Even for relatively drought resilient crops such as sorghum, moisture stress is nonetheless one of the major constraints for production. Here, we explore the potential to use natural genetic variation to build on the inherent drought tolerance of an elite cultivar (Teshale) bred for Ethiopian conditions including chronic drought, evaluating a backcross nested-association mapping (BC-NAM) population using 12 diverse founder lines crossed with Teshale under three drought-prone environments in Ethiopia. All twelve populations averaged higher head exsertion and lower leaf senescence than the recurrent parent in the two highest-stress environments, reflecting new drought resilience mechanisms from the donors. A total of 154 QTLs were detected for eight drought responsive traits - the validity of these were supported in that 100 (64.9%) overlapped with QTLs previously detected for the same traits, concentrated in regions previously associated with stay-green traits as well as the flowering regulator Ma6 and drought resistant gene P5CS2. Allele effects show that some favorable alleles are already present in the Ethiopian cultivar, however the exotic donors offer rich scope for increasing drought resilience. Using model-selected SNPs associated with eight traits in this study and three in a companion study, phenotypic prediction accuracies for grain yield were equivalent to genome-wide SNPs and were significantly better than random SNPs, indicating that these studied traits are predictive of sorghum grain yield. Rich scope for improving drought resilience even in cultivars bred for drought-prone regions, together with phenotypic prediction accuracy for grain yield, provides a foundation to enhance food security in drought-prone areas like the African Sahel.

genetics↗

bioRxiv2021

New adaptive peaks for crops - an example from improvement of drought-resilience of sorghum in Ethiopia

O_LIAs the center of diversity for sorghum [Sorghum bicolor (L.) Moench], elite cultivars selected in Ethiopia are of central importance to sub-Saharan food security. Despite being presumably well adapted to their center of diversity, elite Ethiopian sorghums nonetheless experience constraints to productivity, for example associated with shifting rainfall patterns associated with climate change. C_LIO_LIA sorghum backcross nested association mapping (BC-NAM) population developed by crossing thirteen diverse lines pre-identified to have various drought resilience mechanisms, with an Ethiopian elite cultivar, Teshale, was tested under three rain-fed environments in Ethiopia. C_LIO_LI27, 15, and 15 QTLs with predominantly small additive effects were identified for days to flowering, days to maturity, and plant height, respectively. Many associations detected in this study corresponded closely to known or candidate genes or previously mapped QTLs, supporting their validity. Field tests show drought resilience to be improved by incorporation of adaptations from the diverse donor lines. C_LIO_LIThe expectation that genotypes such as Teshale from near the center of diversity tend to have a history of strong balancing selection, with novel variations more likely to persist in small marginal populations, was strongly supported in that for these three traits, nearly equal numbers of alleles from the donor lines conferred increases and decreases in phenotype relative to the Teshale allele. Such rich variation provides a foundation for selection to traverse a valley of reduced yield and arrive at a new adaptive peak, exemplifying the nature of efforts that may be necessary to adapt many crops to new climate extremes. C_LI Societal Impact StatementIn Ethiopia, agriculture is the largest economic sector and contributes 48% of the nations GDP, and sorghum provides more than one third of the cereal diet and is widely grown for food, feed, brewing, and construction purposes. With a worldwide water crisis looming, developing drought tolerant sorghum is vital in rain-fed environments, particularly in sub-Saharan Africa. Addressing such issues often requires a far-reaching approach to identify and incorporate new traits into a gene pool, followed by a period of selection to re-establish an overall adaptive phenotype. This study revealed that with the enormous altitudinal variation of a country such as Ethiopia, somewhat different lines may be needed for different locales.

genetics↗

bioRxiv2021

BMSC-Derived Exosomal MiRNAs Can Modulate Bone Restoration in Diabetic Rats with Femoral Defects

The exosomal miRNAs of BMSCs participate in hyperglycemia induced poor healing of bone defects. Here, we demonstrate that exosomes derived from BMSCs harvested from diabetes mellitus(DM) rats suppressed bone formation when administered to normal rats with bone defects. Using high-throughput sequencing analysis of microRNA molecules, high miR-140-3p levels were expressed in exosomes released by N-BMSCs. Using TargetScan software and luciferase activity assays, plxnb1 was identified as the downstream molecular target of exosomal miR-140-3p that regulated osteogenesis. Transplantation of exosomes that overexpressed miR-140-3p into DM rats promoted the restoration of bone defects. Furthermore, miR-140-3p significantly promoted the differentiation of DM-BMSCs into osteoblasts and inhibited the expression p-RohA and p-ROCK in the plexin B1 signaling pathway. Taken together, these observations suggest that DM decreases the levels of exosomal miR-140-3p, which impedes bone formation and the differentiation of BMSCs. MiR-140-3p may represent a potential therapeutic target for DM related to abnormal bone metabolism.

cell biology↗

bioRxiv2021

Engineering site-selective incorporation of fluorine into natural product analogs

While bioactive compounds are commonly derived both by human design as well as from living organisms, man-made and natural products typically display very different structural characteristics. As such, a longstanding goal in the discovery of new molecular function is to develop approaches to incorporate the advantageous elements of both groups of molecules, thereby expanding the molecular space accessible for this purpose. In this work, we report the engineering a fluorine-selective enzyme that can complement mutated acyltransferase (AT) domains of a modular polyketide synthase, which are the main determinants of the identity and location of substituents on polyketides, to produce different fluorinated regioisomers of the erythromycin precursor in vitro. We further show that by engineering cell uptake of fluorinated building blocks, we can control fluorine selectivity in vivo to produce selectively fluorinated polyketides using engineered E. coli. These results demonstrate that it is possible to introduce fluorine, a key synthetic design element for drug development, selectively into the scaffold of a complex natural product and produce these analogs by microbial fermentation.

synthetic biology↗

bioRxiv2021

The obesity-linked human lncRNA AATBC regulates adipocyte plasticity by stimulating mitochondrial dynamics and respiration

Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, the activation of thermogenic brown and beige adipocytes is linked to improved cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this adipocyte plasticity could help improving energy balance and weight loss. Here, we show that the long non-coding RNA (lncRNA) Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Searching for new human lncRNAs implicated in adipocyte biology we compared transcriptional profiles of human adipose tissues and cultured adipocytes and discovered that AATBC was enriched in thermogenic conditions. Using primary human adipocytes and immortalized human adipocytes we found that gain-of-function of AATBC enhanced the thermogenic phenotype whereas loss-of-function diminished this effect. The AATBC-mediated increase in mitochondrial respiration was linked to a more fragmented mitochondrial network and vice versa. While we found that AATBC is predominantly located in the nucleus, its effect on global transcription was only marginal. As AATBC is specific to humans, we expressed AATBC in adipose tissue of mice to study its systemic impact, which led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, body mass index and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.

molecular biology↗

bioRxiv2021

Selection and evaluation of qPCR reference genes for expression analysis in the tiny egg parasitoid wasp, Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae)

The egg parasitoid Trichogramma spp. is an important biological control agent used against multiple species of Lepidopteran pest in forestry and agriculture. Due to the importance of Trichogramma spp. in biocontrol programs, its biological characteristics have been studied in detail, and current investigations should focus on the molecular biology of these tiny parasitoids. Real-time quantitative PCR (qPCR) is considered as the standard method for quantifying the gene expression of organisms. Surprisingly, the appropriate reference genes to ensure robust qPCR have not been documented at all for the Trichogramma genus. This study aimed to identify suitable reference genes for use in qPCR procedure of Trichogramma dendrolimi. Nine candidate housekeeping genes, namely glyceraldehyde-3-phosphate dehydrogenase (GAPDH), forkhead box O (FOXO), superoxide dismutase (SOD), beta-actin (ACTIN), ribosomal protein L10a (RPL10a), L18 (RPL18), L28 (RPL28), S13 (RPS13), and S15 (RPS15), were tested for their suitability as reference genes for developmental stage (3rd, 4th, 5th, 6th, 7th, 8th, 9th, and 10th day after parasitization), tissue (head, thorax, and abdomen of adults), sex of adults (male and female), and temperature (17 {degrees}C, 25 {degrees}C, and 32 {degrees}C). According to the GeNorm analysis, robust analysis should involve using an appropriate combination of reference genes, namely, at least three genes for different development stages, two genes for different tissues, two genes for different sex, and two genes for different temperature, respectively. According to the RelFinder method and by assessing the integrated values from using the {Delta}Ct method, GeNorm, NormFinder, and BestKeeper, we identified the developmental stage-specific reference genes SOD, GAPDH, and ACTIN; tissue-specific reference genes RPL18 and RPS15; sex-specific reference genes SOD and RPL18; and temperature-specific reference genes RPL18 and RPL10. When testing the use of stable vs. unstable reference genes, the substantial differences were observed in the estimation expression of a hypothetical target gene, HSP90, in response to temperature. The present study provides a robust method for the measurement of gene expression in T. dendrolimi and will be helpful for future biological control programs using Trichogramma wasps.

zoology↗

bioRxiv2021

The tetrameric assembly of 2-aminomuconic acid dehydrogenase is a functional requirement of cofactor NAD+ binding

The bacterium Pseudomonas sp. AP-3 is able to use the environmental pollutant 2-aminophenol as its sole source of carbon, nitrogen, and energy. Eight genes (amnA, B, C, D, E, F, G, and H) encoding 2-aminophenol metabolizing enzymes are clustered into a single operon. 2-aminomuconic 6-semialdehyde dehydrogenase (AmnC), a member of the aldehyde dehydrogenase (ALDH) superfamily, is responsible for oxidizing 2-aminomuconic 6-semialdehyde to 2-aminomuconate. In contrast to many other members of the ALDH superfamily, the structural basis of the catalytic activity of AmnC remains elusive. Here, we present the crystal structure of AmnC, which displays a homotetrameric quaternary assembly that is directly involved in its enzymatic activity. The tetrameric state of AmnC in solution was also presented using small-angle X-ray scattering. The tetramerization of AmnC is mediated by the assembly of a protruding hydrophobic beta-strand motif and residues V121 and S123 located in the NAD+-binding domain of each subunit. Dimeric mutants of AmnC dramatically lose NAD+ binding affinity and enzyme activity, indicating that tetrameric assembly of AmnC is required for oxidizing the unstable metabolic intermediate 2-aminomuconic 6-semialdehyde to 2-aminomuconic acid in the 2-aminophenol metabolism pathway.

microbiology↗

bioRxiv2021

A stem-loop RNA RIG-I agonist confers prophylactic and therapeutic protection against acute and chronic SARS-CoV-2 infection in mice

As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral replication in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I) dependent manner. SLR14 demonstrated remarkable protective capacity against lethal SARS-CoV-2 infection when used prophylactically and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity by inducing IFN-I responses in the absence of the adaptive immune system. In the context of infection with variants of concern (VOC), SLR14 conferred broad protection and uncovered an IFN-I resistance gradient across emerging VOC. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and for treatment of chronically infected immunosuppressed patients.

immunology↗

bioRxiv2021

CBX4 regulates long-form thymic stromal lymphopoietin-mediated airway inflammation through SUMOylation in HDM-induced asthma

RationaleThymic stromal lymphopoietin (TSLP) is present in two distinct isoforms, short-form (sfTSLP) and long-form (lfTSLP). lfTSLP promotes inflammation while sfTSLP inhibits inflammation in allergic asthma. However, little is known about the regulation of lfTSLP and sfTSLP during allergic attack in asthma airway epithelium. Methods and ResultsHere, we report that SUMOylation was enhanced in HDM-induced allergic asthma airway epithelium. Inhibition of SUMOylation significantly alleviated airway Th2 inflammation and lfTSLP expression. Mechanistically, CBX4, a SUMOylation E3 ligase, enhanced lfTSLP, but not sfTSLP, mRNA translation through the RNA binding protein, MEX-3B. MEX-3B promoted lfTSLP translation through binding of its KH domains to the lfTSLP mRNA. Furthermore, CBX4 regulated MEX-3B transcription in HBE through enhancing SUMOylation levels of the transcription factor, TFII-I. ConclusionWe demonstrate an important mechanism whereby CBX4 promotes MEX-3B transcription through enhancing TFII-I SUMOylation, and MEX-3B enhances the expression of lfTSLP through binding to the lfTSLP mRNA and promoting its translation. Our findings uncover a novel target of CBX4 for therapeutic agents to lfTSLP-mediated asthma.

molecular biology↗

bioRxiv2021

ESD1 Affects Seed Setting Rate in Rice by Controlling Embryo Sac Development

Seed setting rate is one of the critical factors that determine rice yield. Grain formation is a complex biological process, whose molecular mechanism is yet to be improved. Here we investigated the function of an OVATE family protein, Embryo Sac Development 1 (ESD1), in the regulation of seed setting rate in rice (Oryza sativa) by examining its loss-of-function mutants generated via CRISPR/Cas9 technology. ESD1 was predominantly expressed at stage 6 of panicle development, especially in the ovules. esd1 mutants displayed reduced seed setting rates with normal stamen development and pollen tube growth but abnormal pistil group. Investigation of embryo sacs revealed that during the mitosis of functional megaspores, some egg cells degraded during differentiation in esd1 mutants, thereby hindering subsequent fertilization process and reducing seed setting rate. In addition, the transcriptional level of OsAPC6, a reported embryo sac developing gene, was found to be significantly reduced in esd1 mutants. These results support that ESD1 is an important modulator of embryo sac development and seed setting rate in rice. Together, this finding demonstrates that ESD1 positively regulates the seed setting rate by controlling embryo sac development in rice, and has implications for the improvement of rice yield.

plant biology↗

bioRxiv2021

Genetic diversity, population structure and selection signature in Ethiopian Sorghum (Sorghum bicolor L. ) germplasm

Ethiopia, the probable center of origin and diversity for sorghum (Sorghum bicolor L. [Moench]) and with unique eco-geographic features, possesses a large number of sorghum landraces that have not been well studied. Increased knowledge of this diverse germplasm through large-scale genomic characterization may contribute for understanding of evolutionary biology, and adequate use of these valuable resources from the center of origin. In this study, we characterized genetic diversity, population structure and selection signature in 304 sorghum accessions collected from diverse sorghum growing regions of Ethiopia using genotyping-by-sequencing (GBS). We identified a total of 108,107 high-quality single nucleotide polymorphism (SNPs) markers that were evenly distributed across the sorghum genome. The average gene diversity among accessions was high (He = 0.29). We detected a relatively low frequency of rare alleles (26%), highlighting the potential of this germplasm for subsequent allele mining studies through genome wide association studies (GWAS). While we found no evidence of genetic differentiation among administrative regions (FST = 0.02, p = 0.12), population structure and cluster analyses showed clear differentiation among six Ethiopian sorghum populations (FST = 0.28, p = 0.01) adapting to different environments. Analysis of SNP differentiation between the identified genetic groups revealed a total of 40 genomic regions carrying signatures of selection. These regions harbored candidate genes potentially involved in a variety of biological processes, including abiotic stress tolerance, pathogen defense and reproduction. Overall, a high level of untapped diversity for sorghum improvement remains available in Ethiopia, with patterns of diversity consistent with divergent selection on a range of adaptive characteristics.

genetics↗