Post-COVID-19 persistent olfactory,gustatory,and trigeminal chemosensory disorders:Definitions,mechanisms,and potential treatments

The nose and the oral cavities are the main sites for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into the body.Smell and taste deficits are the most common acute viral manifestations.Persistent smell disorders are the most common and bothersome complications after SARS-CoV-2 infection,lasting for months to years.The mechanisms and treatment of persistent post-coronavirus disease 2019(COVID-19)smell and taste disorders are still challenges.Information sources for the review are PubMed,Centers for Disease Control and Prevention,Ovid Medline,Embase,Scopus,Web of Science,International Prospective Register of Systematic Reviews,Cumulative Index to Nursing and Allied Health Literature,Elton Bryson Stephens Company,Cochrane Effective Practice and Organization of Care,Cooperation in Science and Technology,International Clinical Trials Registry Platform,World Health Organization,Randomized Controlled Trial Number Registry,and MediFind.This review summarizes the up-to-date information about the prevalence,patterns at onset,and prognoses of post-COVID-19 smell and taste disorders,evidence for the neurotropism of SARS-CoV-2 and the overlap between SARSCoV-1,Middle East respiratory syndrome coronavirus,and SARS-CoV-2 in structure,molecular biology,mode of replication,and host pathogenicity,the suggested cellular and molecular mechanisms for these post-COVID19 chemosensory disorders,and the applied pharmacotherapies and interventions as trials to treat these disorders,and the recommendations for future research to improve understanding of predictors and mechanisms of these disorders.These are crucial for hopeful proper treatment strategies.

GUSTATORY RESPONSES OF NEURONS IN THE PARABRACHIAL NUCLEUS OF RATS

Objective To investigate the gustatory neural response of the neurons to five basic taste stimuli in the parabrachial nucleus (PBN). Methods Evoked responses from PBN taste neurons to tastants were recorded using standard extracellular microelectrode technique. Results 46 taste neurons were recorded in PBN, and most of them were broadly responsive. On the basis of their most effective taste stimuli, these taste neurons were classified into five types. Those are NaCl-, HCl-, quinine-, sucrose-, and monosodium glutamate (MSG)-best neurons. Except for the quinine-best neurons, the responses of each best-stimulus category to its best stimulus were significantly stronger than those of others (P<0.01). The results of correlation analysis showed that the correlations between sucrose and each of the other 4 tastants were smaller than those among others. Conclusion The results suggest that PBN taste neurons probably play an important role in discriminating for hedonic taste.

Marcus-Gunn Jaw Winking Syndrome and Gustatory Sweating in Long Standing Poorly Controlled Diabetes: A Case Report

Introduction: Marcus Gunn jaw winking syndrome (MGJWS) is a rare congenital disorder belonging to the synkinetic eye movement group of disorders observed in children. It occurrence in adults and patients with diabetes has not been reported. Material and Methods: A 64 year man with poorly controlled diabetes of 18 years presented with 3 month history of jaw winking on the left side along with gustatory sweating, which was managed conservatively. There was spontaneous improvement in jaw wink at 4 months of follow up. Conclusions: Acquired causes of MGJWS are not known. This is probably the first report of this syndrome occurring at such a late age. Long standing poorly controlled diabetes may have had some role in the development of jaw winking in this patient.

The temporal-spatial expression and functional analysis of three gustatory receptor genes in Solenopsis invicta using sweet and bitter compounds

The insect gustatory system participates in identifying potential food sources and avoiding toxic compounds.During this process,gustatory receptors(GRs)recognize feeding stimulant and deterrent compounds.However,the GRs involved in recognizing stimulant and deterrent compounds in the red imported fire ant,Solenopsis invicta,remain unknown.Therefore,we conducted a study on the genes SinvGR1,SinvGR32b,and SinvGR28a to investigate the roles of GRs in detecting feeding stimulant and deterrent compounds.In this current study,we found that sucrose and fructose are feeding stimulants and the bitter compound quinine is a feeding deterrent.The fire ant workers showed significant behavior changes to avoid the bitter taste in feeding stimulant compounds.Reverse transcription quantitative real-time polymerase chain reaction results from developmental stages showed that the SinvGR1,SinvGR32b,and SinvGR28a genes were highly expressed in fire ant workers.Tissue-specific expression profiles indicated that SinvGR1,SinvGR32b,and SinvGR28a were specifically expressed in the antennae and foreleg tarsi of workers,whereas SinvGR32b gene transcripts were also highly accumulated in the male antennae.Furthermore,the silencing of SinvGRI or SinvGR32b alone and the co-silencing of both genes disrupted worker stimulation and feeding on sucrose and fructose.The results also showed that SinvGR28a is required for avoiding quinine,as workers with knockdown of the SinvGR28a gene failed to avoid and fed on quinine.This study first identified stimulant and deterrent compounds of fire ant workers and then the GRs involved in the taste recognition of these compounds.This study could provide potential target gustatory genes for the control of the fire ant.

Ligand dose-dependent activation of signaling pathways through the gustatory receptor NlGr11 linked to feeding efficacy in Nilaparvata lugens

Insects often face both conditions with sufficient nutrients and conditions of undernutrition in the field.Through gustatory receptors,insects sense nutrients and regulate their physiological functions such as feeding and reproduction.However,it remains unclear whether signaling pathways activated by gustatory receptors depend on the concentration of nutrients and whether the difference in signaling pathways directly affects insects’physiological functions.Herein,we found that a sugar gustatory receptor,NlGr11,from the brown planthopper(BPH),Nilaparvata lugens,activated G protein-coupled signaling and ionotropic pathways when bound to high galactose concentration.BPHs subsequently demonstrated longer feeding times,feeding loads,and higher vitellogenin(NlVg)expression than BPHs exposed to high galactose concentrations,which only activated the ionotropic pathway.For the first time,our findings link plant nutrient conditions,signaling pathways activated by nutrients,and their gustatory receptors,and nutrient dose-dependent feeding efficacy and vitellogenin(Vg)expression in an insect.This will help us to better understand the molecular mechanism for insect feeding strategies on plants at different stages of nutritional conditions.

Identification of a sugar gustatory receptor and its effect on fecundity of the brown planthopper Nilaparvata lugens

In insects, the gustatory system plays a crucial role in multiple physiological behaviors, including feeding, toxin avoidance, courtship, mating and oviposition. Gustatory stimuli from the environment are recognized by gustatory receptors. To date, little is known about the function of gustatory receptors in agricultural pest insects. In this study, we cloned a sugar gustatory receptor gene, N/Gr11, from the brown planthopper (BPH), Nilaparvata lugens (Stal), a serious pest of rice in Asia;we then identified its ligands, namely, fructose, galactose and arabinose, by calcium imaging assay. After injection of N/Gr11 doublestranded RNA, we found that the number of eggs laid by BPH decreased. Moreover, we found that N/Gr11 inhibited the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and promoted the phosphorylation of protein kinase B (AKT). These findings demonstrated that N/Gr11 could accelerate the fecundity of BPH through AMPK- and AKT-mediated signaling pathways. This is the first report to indicate that a gustatory receptor modulates the fecundity of insects and that the receptor could be a potential target for pest control.

Olfactory and gustatory dysfunctions of COVID-19 patients in China:A multicenter study

Introduction:With the spread of the epidemic worldwide,an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019(COVID-19):olfactory or taste disorders.Therefore,clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID-19 patients is of great significance and urgency.Materials and Methods:A retrospective study was conducted,which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients,through face-to-face interviews and telephone follow-up.Following the completion of questionnaires,the patients participating in the study,were categorized according to the degree of olfactory and taste disorders experienced,and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded.Results:Among the 229 patients,31(13.54%)had olfactory dysfunction,and 44(19.21%)had gustatory dysfunction.For the patients with olfactory dysfunction,6(19.35%)developed severe disease and became critically ill.Olfactory dysfunction appeared before the other symptoms in 21.43%of cases.The proportion of females with olfactory and gustatory dysfunction was higher than that of males(P<0.001).Conclusions:The incidence of olfactory and gustatory dysfunction was much lower than that reported abroad;the prognosis of patients with olfactory dysfunction is relatively favorable;olfactory and gustatory dysfunction can be used as a sign for early screening;females are more prone to olfactory and gustatory dysfunction.

Identification and expression profiles of gustatory receptor genes in Bactrocera minax larvae(Diptera:Tephritidae):Role of BminGR59f in larval growth

Insects employ various types of gustatory receptors(GRs)to identify nutrient-rich food and avoid toxic substances.The larval gustatory system is the critical checkpoint for food acceptance or rejection.As a specialist herbivore,the larvae of Bactrocera minax feed only on unripe citrus fruits.However,how larvae use GRs to check and adapt to the secondary metabolites in unripe citrus fruits remains unknown.In this study,we first performed developmental expression profiles showing that most BminGRs genes were highly expressed in 1st and 2nd instar larvae and that tissue-specific expression indicated high expression of most BminGRs genes in the mouthparts of 2nd instar larvae.Furthermore,we found that silencing BminGR59f by RNA interference(RNAi)affected the growth of 2nd instar B.minax larvae.Hesperidin and naringin were screened as ligands of BminGR59f via RNAi and cell calcium imaging,and the combination of these two flavones increased the body weight of larvae.In summary,we identified a novel gustatory perception pattern in B.minax for detecting hesperidin and naringin,which boosted the growth of B.minax larvae.These results shed light on how specialist herbivores detect and adapt to host metbolites in adverse environments depending on larval GRs.

保留腮腺咬肌筋膜在预防Frey综合征中的应用

腮腺良性肿瘤目前仍以手术治疗为主,经典手术方法是保留面神经的腮腺浅叶或全叶加肿瘤切除术,但术后Frey综合征发生率较高,会造成严重后果,常给患者造成较大的精神痛苦,影响患者的生活质量。为探讨如何预防、减少腮腺肿瘤术后Frey综合征的发生,本研究采用保留腮腺咬肌筋膜关闭腺体创面,预防Frey综合征,效果满意。

Sweet and Bitter Tastes Evoked Different Neuronal Activation in the Rostral Portion of the Nucleus of the Solitary Tract of Developing Rats

The impact of the gustatory stimuli on the rostral portion of the nucleus of the solitary tract (rNST) was investigated in developing rats, by using c-fos immunohistochemical staining. Wistar male rats of 5, 15, and 25 days of age were isolated from the mother for 12 h, then stimulated via the intraoral route with quinine, sucrose, or NaCl, and sacrificed 90 min later. The water-stimulated group showed minimal c-fos-like immunoreactivity (FLI) compared with taste-stimulated groups that exhibited different FLI in the rNST at the different ages. At all ages the quinine-stimulated group induced FLI in the medial subfield, while sucrose induced FLI in the lateral subfield of the rNST. The intensity of FLI was highest at P15, and it declined at P25. These findings provide detailed insight into the anatomical basis of rNST activation that is involved in early food intake and the learning capacity of the newborn.

Analysis of the Sensory and Hedonic Impacts of Sweet and Bitter Tastes in Perinatally Underfed Rats

Newborn rats discriminate tastes and generate gustofacial response (GFR) because the neuronal substrate is already operating. The oral application of sucrose or quinine hydrochloride produces a specific GFR. We analyzed the effects of perinatal undernutrition on the GFR development of rats at two cue concentrations. In the undernourished group, pregnant dams received different percentages of a balance diet. After birth, prenatally underfed pups continue the undernourishment by remaining for 12 h with a foster dam, and for 12 h with a nipple-ligated mother. Cues were presented as a single droplet of sucrose, sodium chloride, or quinine at low or high concentrations onto the lips at postnatal days (PDs) 1 and 3, and mouth-opening (MOF) and lip-licking frequencies (LLF) were noted. On PD 1 the undernourished group showed smaller MOF increases in response to low salt and quinine stimuli than the controls but no differences at high concentrations. On PD 3, both low and high concentrations of the sucrose and quinine cues significantly increased the MOF in the underfed compared to the control group. Low but not high salt decreased LLF on PD1 in the underfed compared to the control group. On PD 3 the undernourished pups showed significant increases of LLF with low quinine compared with the control rats, but the reverse was observed with high quinine. These data suggest that perinatal undernutrition affects the development of the sensory and hedonic aspects of taste causing changes in GFR expression.

Activation of Human Prefrontal Cortex to Pleasant and Aversive Taste Using Functional Near-Infrared Spectroscopy

The aim of the study was to investigate the representation of taste in human prefrontal cortex (PFC), in particular, to compare the representation of a pleasant and an aversive taste using functional near-infrared spectroscopy (fNIRS), so as to obtain further understanding of the taste preference mechanism. The pleasant stimulus used was sweet taste (10% sucrose), and the unpleasant stimulus was sour taste (1% critic acid). Based on event-related design, the experiments were performed with 16 healthy volunteers using the OEG-16 fNIRS sensor. A general linear model was used to analyze the collected data. For the concentration change of oxygenated hemoglobin (ΔoxyHb), we found that significant deactivation was induced by sweetness and sourness in parts of the frontopolar area, orbitofrontal area and dorsolateral prefrontal cortex in bilateral hemisphere of human brain. And the right PFC showed different levels of activation between sweetness and sourness. In addition, brain activities were more sensitive to sourness than sweetness. Finally, we confirmed that the PFC was involved in sweet and sour taste processing, and fNIRS provided an alternative way for studying taste-related brain function under more natural conditions.

A Neurobiological Examination of Environmental, Subjective, Peripheral and Central Taste Sensation Processing Variances Associated with Taste Alterations: A Case Study Method

This study examines a common phenomenon that is greatly ignored by the clinical community for numerous reasons. Many people for a multitude of reasons experience taste alterations. The supertaster phenomenon is an alteration of taste that requires more investigation. In this study, a proband was examined for subjective reports of a taste alteration to determine its nature through a medical history examination and interview as well as any recollections of the taste disorder in her life. Through this examination, it was found that medical history examination and interview of the proband that many members of her nuclear family showed traits of the same taste disorder or in the case of one family member being a suspect for the taste alteration and one member not showing any signs because of genetic diversity as a half-sibling. Taste disorders are heritable, have multiple health and mental health consequences, influence life choices including mate choice, avoidance behaviors, social choices, alcohol use/abuse, smoking, food choices, and more. More awareness is needed in the research and clinical community into taste alterations as well as calls for future research from neuroscience, biomedical science, life science, and allied science community to investigate taste alterations.

The genome sequence of a spider mite,Tetranychustruncatus, provides insights into interspecific host rangevariation and the genetic basis of adaptation to a low-qualityhost plant

The phytophagous miteTetranychus truncatusis a serious pest in East Asiabut has a relatively narrower host range than the pest miteTetranychus urticae,which canfeed on over 1200 plant species.Here,we generated a high-quality chromosomal levelgenome ofT.truncatusand compared it with that ofT.urticae,with an emphasis on thegenes related to detoxification and chemoreception,to explore the genomic basis under-lying the evolution of host range.We also conducted population genetics analyses(in 86females from 10 populations)and host transfer experiments(in 4 populations)to investi-gate transcription changes following transfer to a low-quality host(Solanum melongena,eggplant),and we established possible connections between fitness on eggplant and genesrelated to detoxification and chemoreception.We found thatT.truncatushas fewer genesrelated to detoxification,transport,and chemoreception thanT.urticae,with a particularlystrong reduction in gustatory receptor(GR)genes.We also found widespread transcrip-tional variation amongT.truncatuspopulations,which varied in fitness on eggplant.Wecharacterized selection on detoxification-related genes throughωvalues and found a nega-tive correlation between expression levels andωvalues.Based on the transcription results,as well as the fitness and genetic differences among populations,we identified genes po-tentially involved in adaptation to eggplant inT.truncatus.Our work provides a genomicresource for this pest mite and new insights into mechanisms underlying the adaptation ofherbivorous mites to host plants.

Mapping and ultrastructure of antennal chemosensilla of the wheat bug Eurygaster maura

Antennae of the wheat stink bug Eurygaster maura L. （Hemiptera： Scutelleridae） were investigated to elucidate structure and distribution of antennal chemosensilla in females. Five type of sensilla were identified and characterized using a scanning electron microscope （SEM） and a transmission electron microscope （TEM）. Type 1 sensilla are mechanical and contact chemoreceptors with a single apical pore. Types 2 and 3 sensilla are multiporous chemoreceptors both with typical features of olfactory sensilla. Type 4 are multiporous peg-like sensilla, short and with a grooved surface. Type 5 are sensilla coeloconica with a smooth and aporous peg completely inserted in a sub-cuticular chamber. All types are distributed on the two flagellar segments, but we considered only the apical flagellomere in which the largest number of sensilla are located. The most abundant sensilla are type 3, while the less numerous are type 5. All types, except type 2, decreased in number from the tip to the base of the segment. The lower density of sensilla was recorded on the dorsal-internal part of the apical antennomere, while the higher density was recorded on the opposite side （external-ventral）.

Effects of DIMBOA on impulse discharges of maxillary lateral sensillum styloconicum of armyworm larvae

THE DIMBOA (2, 4-dihydroxy-7-methoxy-1, 4-benzoxazin-3-one), a secondary product present in corn plants, plays an important role in protecting the plant against the pest attack. DIMBOA is rich in seedlings of cereal crops, especially in maize. Many investigators demonstrated a linear relationship between the DIMBOA content in plant and the resistance of the plant to pest. Feng et al. (1992) summarized that the toxicity of DIMBOA is associated

Galactose-N/Gr11 inhibits AMPK phosphorylation byactivating the PI3K-AKT-PKF-ATPsignaling cascade viainsulin receptor and Gβγ

As ligands of the sugar gustatory receptors,sugars have been known to activatethe insulin/insulin-like growth factor signaling pathway;however,the precise pathways thatare activated by the sugar-bound gustatory receptors in insects remain unclear.In this study,we aimed to investigate the signaling cascades activated by NlGr11,a sugar gustatory re-ceptor in the brown planthopper Nilaparvata lugens(Stal),and its ligand.Galactose-boundNGrl1(galactose-NIGr11)activated the-phosphatidylinositol 3-kinase(PI3K)-AKT signaling cascade via insulin receptor(InR)and Gβγin vitro.In addition,galactose-NlGr11inhibited the adenosine monophosphate-activated protein kinase(AMPK)phosphorylationby activating the AKT-phosphofructokinase(PFK)-ATP signaling cascade in vitro.Impor-tantly,the InR-PI3K-AKT-PFK-AKT signaling cascade was activated and the AMPKphosphorylation was inhibited after feeding the brown planthoppers with galactose solu-tion.Collectively,these findings confirm that NIGr1l can inhibit AMPK phosphorylationby activating the PI3K-AKT-PFK-ATP signaling cascades via both InR and GBy whenbound to galactose.Thus,our study provides novel insights into the signaling pathwaysregulated by the sugar gustatory receptors in insects.

A fructose receptor gene influences development and feed intake in Helicoverpa armigera

Gustatory receptors(GRs)are critical for multiple life activities of insects.Owing to the rapid development of genome and transcriptome sequencing,numerous insect GRs have been identified.However,the expression patterns and functions of these receptors are poorly understood.In this study,we analyzed the expression pattern of GRs in Helicoverpa armigera and found that the fructose receptor HarmGR9 was highly expressed in the foregut and abdomen.The function of HarmGR9 was identified using the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system.Knockout of the HarmGR9 gene shortened the developmental period of the larval stages and increased food consumption in both larvae and adults.This study revealed the tissue distribution of sugar-sense-related receptors in H.armigera and thereby expanded the understanding of insect feeding regulation.