Since 2019, Coronavirus Disease 2019(COVID-19) has affected millions of people worldwide. Except for acute respiratory distress syndrome, dysgeusis is also a common symptom of COVID-19 that burdens patients for weeks or permanently. However, the mechanisms underlying taste dysfunctions remain unclear. Here, we performed complete autopsies of five patients who died of COVID-19. Integrated tongue samples, including numerous taste buds, salivary glands, vessels, and nerves were collected to map the pathology, distribution, cell tropism, and receptor distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the tongue. Our results revealed that all patients had moderate lymphocyte infiltration around the salivary glands and in the lamina propria adjacent to the mucosa, and pyknosis in the epithelia of taste buds and salivary glands. This may be because the serous acini, salivary gland ducts, and taste buds are the primary sites of SARS-CoV-2 infection. Multicolor immunofluorescence showed that SARS-CoV-2 readily infects Keratin (KRT)7+ taste receptor cells in taste buds, secretory cells in serous acini, and inner epithelial cells in the ducts. The major receptors, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), were both abundantly expressed in these cells. Viral antigens and receptor were both rarely detected in vessels and nerves. This indicates that SARS-CoV-2 infection triggers pathological injury in the tongue, and that dysgeusis may be directly related to viral infection and cellular damage.

N-Succinyl amino acids (N-Suc-AAs) are garnering attention for their potential as taste-active compounds. The intricate variety of N-Suc-AAs presented considerable challenges in identifying those with taste-active properties. Consequently, we employed structure-based virtual screening to pinpoint taste-active N-Suc-AAs, revealing N-succinyl-L-tryptophan (ST) as a compound with high affinity for different taste receptors. Following this discovery, ST was synthesized through an enzymatic process, achieving a yield of 40.2%, with its structure verified via NMR spectroscopy. Sensory evaluation alongside electronic tongue assessments indicated that ST at a concentration of 1 mg/L significantly enhances umami, kokumi, and saltiness intensities, while concurrently mitigating bitterness from various bitter compounds, whilst itself remaining tasteless. Additionally, time-intensity (TI) results elucidated a marked augmentation in umami duration and a notable diminution in bitterness duration for solutions imbued with 1 mg/L ST. Molecular docking study suggested ST interacted with diverse taste receptors as an agonist or antagonist, primarily through hydrogen bonds and hydrophobic interactions. This study marked the inaugural report on the enzymatic synthesis of ST and its efficacy in improving taste characteristics, underscoring the importance of ST in improving sensory qualities of food products and fostering innovation within the seasoning industry.

Gustation is one of the most important human senses. Taste dysfunctions, which may be due to aging, tongue cancer surgery, radiotherapy and chemotherapy, affect life quality. That is why the need for taste bud regeneration has received more attention. At present, research on development and renewal of taste cells provides a basis for taste bud regeneration; molecular mechanisms related to taste bud regeneration are being continuously uncoverd, aiding in the identification of more accurate targets for therapy. New methods such as nerve regeneration, tissue engineering, and cytokine therapy have emerged. The author reviews the mechanism and the latest methods of taste bud regeneration of lingual epithelium, aiming to open new horizions for the prevention and treatment of gustatory diseases, and provide theoretical references for its regeneration.
味觉是人类重要感官，由增龄变化、舌癌手术、放化疗等引起的味觉功能障碍可影响人生活质量，味蕾再生需求逐渐得到关注。目前，关于味觉细胞发育及更新的基础研究为味蕾再生提供了理论基础；了解味蕾再生的分子机制有助于获悉准确的作用靶点；神经再生、组织工程、细胞因子疗法等新方法试图实现味蕾的功能性再生并加速其临床转化。本文围绕舌上皮味蕾再生机制及最新的组织工程学方法进行综述，以期为味觉损伤疾病的预防和治疗提供参考，为味蕾再生提供依据。.

Taste sensor, a useful tool which could detect and identify thousands of different chemical substances in liquid environments, has attracted continuous concern from beverage and foodstuff industry and its consumers. Although many taste sensing methods have been extensively developed, the assessment of tastant content remains challenging due to the limitations of sensor selectivity and sensitivity. Here we present a novel biomimetic electrochemical taste-biosensor based on bioactive sensing elements and immune amplification with nanomaterials carrier to address above concerns, while taking sweet taste perception as a model. The proposed biosensor based on ligand binding domain (T1R2 VFT) of human sweet taste receptor protein showed human mimicking character and initiated the application of immune recognition in gustation biosensor, which can precisely and sensitively distinguish sweet substances against other related gustation substances with detection limit of 5.1 pM, far less than that of taste sensors without immune amplification whose detection limit was 0.48 nM. The performance test demonstrated the biosensor has the capacity of monitoring the response of sweet substances in real food environments, which is crucial in practical. This biomimetic electrochemical taste-biosensor can work as a new screening platform for newly developed tastants and disclose sweet perception mechanism.

BACKGROUND: Bitter taste receptors (Tas2rs) are generally considered to sense various bitter compounds to escape the intake of toxic substances. Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.
METHODS: To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues, multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique. A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes. Then, T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds. Perception to taste substance was also studied using two-bottle preference tests.
RESULTS: We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique. Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice. But qRT-PCR results revealed the changed expression profile of mTas2rs gene in taste buds of these mutant mice. With two-bottle preference tests, these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105. In addition, these mutant mice showed a loss of taste perception to quinine dihydrochloride, denatonium benzoate, and cucurbitacin B (CuB). Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.
CONCLUSIONS: These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

COVID-19, mainly manifested as acute respiratory distress syndrome, has afflicted millions of people worldwide since 2019. Taste dysfunction is a common early-stage symptom of COVID-19 infection that burdens patients for weeks or even permanently in some cases. Owing to its subjectivity and complexity, the mechanism of taste disorder is poorly studied. Previous studies have reported that the COVID-19 entry receptors are highly expressed in taste buds, thereby intensifying the cytocidal effect. Taste receptor cells are vulnerable to inflammation, and the COVID-19-induced cytokine storm causes secondary damage to taste function. Interferon and various proinflammatory cytokines can trigger cell apoptosis and disrupt the renewal of taste bud stem cells. This immune response can be further enhanced by the accumulation of Angiotensin II (Ang II) caused by an unbalanced local renin-angiotensin system (RAS) system. In addition, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is neurotropic and can invade the brain through the olfactory bulb, affecting the nervous system. Other factors, such as host zinc deficiency, genetic susceptibility, sialic acid, and some neurotransmitters, also contribute to the pathogenesis process. Although several medical interventions have displayed effectiveness, only a few strategies exist for the treatment of postinfectious dysgeusia. Stem cell-based taste regeneration offers promise for long-term taste disorders. Clinical studies have demonstrated that stem cells can treat long COVID-19 through immune regulation. In dysgeusia, the differentiation of taste bud stem cells can be stimulated through exogenous epithelial-derived and neural-derived factors to regenerate taste buds. Tongue organoids are also emerging as functional taste buds, offering new insights into the study of taste regeneration. This review presents the current evidence of the pathogenesis of COVID-19-related dysgeusia, summarizes currently available treatments, and suggests future directions of taste regeneration therapy.

Long-term consumption of a high-sugar diet may contribute to the pathogenesis of several chronic diseases, such as obesity and type 2 diabetes. Sweet peptides derived from a wide range of food sources can enhance sweet taste without compromising the sensory properties. Therefore, the research and application of sweet peptides are promising strategies for reducing sugar consumption. This work first outlined the necessity for global sugar reduction, followed by the introduction of sweet taste receptors and their associated transduction mechanisms. Subsequently, recent research progress in sweet peptides from different protein sources was summarized. Furthermore, the main methods for the preparation and evaluation of sweet peptides were presented. In addition, the current challenges and potential applications are also discussed. Sweet peptides can stimulate sweetness perception by binding sweet taste receptors T1R2 and T1R3 in taste buds, which is an effective strategy for reducing sugar consumption. At present, sweet peptides are mainly prepared artificially by synthesis, hydrolysis, microbial fermentation, and bioengineering strategies. Furthermore, sensory evaluation, electronic tongues, and cell models have been used to assess the sweet taste intensity. The present review can provide a theoretical reference for reducing sugar consumption with the aid of sweet peptides in the food industry.

Bioelectronic tongues based on umami taste receptors have recently been reported for versatile applications such as food analyses. However, their practical applications are still limited, partly due to their limited stability and non-specific responses in real sample environments. Herein, we have developed a hydrogel-based bioelectronic tongue for the sensitive assessment of umami intensity in fish extract samples. In this study, the T1R1 venus flytrap of an umami taste receptor was immobilized on the gold floating electrodes of a carbon nanotube-based field-effect transistor. A polyacrylamide conducting hydrogel film was further hybridized on the sensor surface via physical adsorption, which could provide a good physiological environment to maintain the activity of receptors due to its excellent hydrophilicity and biocompatibility. The bioelectronic tongue with a receptor-embedded hydrogel structure showed a sensitive detection of umami substances down to 1 fM, and it also had a wide detection range of 10-15-10-2 M for monosodium glutamate and disodium inosinate, which covers the human taste threshold. More importantly, the proposed sensor could significantly reduce the non-specific binding of non-target molecules to a carbon nanotube channel as well as exhibit long-term stability, enabling sensitive detection of umami substances even in fish extract samples. Our hydrogel-based bioelectronic tongue provides a promising platform for future applications such as the flavor evaluation of foods and beverages.

Rationale: Gustation is important to several biological functions in mammals. However, chemotherapy drugs often harm taste perception in cancer patients, while the underlying mechanism is still unclear for most drugs and there is no effective way to restore taste function. This study investigated the effects of cisplatin on the taste cell homeostasis and gustatory function. Methods: We used both mice and taste organoid models to study the effect of cisplatin on taste buds. Gustometer assay, gustatory nerve recording, RNA-Sequencing, quantitative PCR, and immunohistochemistry was performed to analyze the cisplatin-induced alteration in taste behavior and function, transcriptome, apoptosis, cell proliferation and taste cell generation. Results: Cisplatin inhibited proliferation and promoted apoptosis in the circumvallate papilla, leading to significant impairment in taste function and receptor cell generation. The transcriptional profile of genes associated with cell cycle, metabolic process and inflammatory response was significantly altered after cisplatin treatment. Cisplatin inhibited growth, promoted apoptosis, and deferred taste receptor cell differentiation in taste organoids. LY411575, a γ-secretase inhibitor, reduced the number of apoptotic cells and increased the number of proliferative cells and taste receptor cells, potentially suggesting as a taste tissue protective agent against chemotherapy. LY411575 treatment could offset the increased number of Pax1+ or Pycr1+ cells induced by cisplatin in the circumvallate papilla and taste organoids. Conclusion: This study highlights the inhibitory effects of cisplatin on taste cell homeostasis and function, identifies critical genes and biological processes regulated by chemotherapy, and proposes potential therapeutic targets and strategy for taste dysfunction in cancer patients.

The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients\' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders.