Lavandula is widely present in the Mediterranean region and its species, namely, those included in the section Stoechas, are valuable resources of active compounds with several biological assets. Since ancient times lavenders have been used in traditional medicine and for domestic purposes. These species are melliferous, decorative, and essential oil-producing plants with a high economic interest in the pharmaceutical, flavor, fragrance, and food industries. The essential oils of Lavandula section Stoechas are characterized by high amounts of 1,8-cineole, camphor, fenchone, and specifically for L. stoechas subsp. luisieri one of the major compounds is trans-α-necrodyl acetate. On the other hand, the diversity of non-volatile components like phenolic compounds, such as phenolic acids and flavonoids, make these species an important source of phytochemicals with pharmacological interest. Rosmarinic, caffeic, and salvianolic B acids are the major phenolic acids, and luteolin and eriodictyol-O-glucuronide are the main reported flavonoids. However, the concentration of these secondary metabolites is strongly affected by the plant’s phenological phase and varies in Lavandula sp. from different areas of origin. Indeed, lavender extracts have shown promising antioxidant, antimicrobial, anti-inflammatory, and anticancer properties as well as several other beneficial actions with potential for commercial applications. Despite several studies on the bioactive potential of lavenders from the section Stoechas, a systematized and updated review of their chemical profile is lacking. Therefore, we carried out the present review that gathers relevant information on the different types of secondary metabolites found in these species as well as their bioactive potential.Globally, climate change and wildfires are disrupting natural ecosystems, thus setting several endemic species at risk. The genus  Lavandula belongs to the Lamiaceae family and includes around 39 species distributed from the Mediterranean region to India, and North Atlantic Islands  Cav., Lavandula stoechas L. subsp. luisieri (Rozeira) Rozeira, Lavandula stoechas L. subsp. stoechas, and Lavandula viridis L’Hér., all endemic to the Mediterranean region. In most studies, the authors do not mention with which subspecies they work. For example, in L. pedunculata, only four studies referred to the subspecies sampaiana (Chaytor) Franco [L. stoechas subsp. stoechas, some authors only refer to L. stoechas L. These species grow in the semi-arid and rather inhospitable soils in this region, which reveals their strong resistance and suitability to cultivation with inexpensive maintenance of the soil. Only three Lavandula species are cultivated for the commercial production of their essential oils, namely, Lavandula angustifolia Mill. (fine lavender or English lavender), Lavandula x intermedia Emeric (lavandin), and Lavandula latifolia Medicus (spike lavender) [Stoechas is distinct from the others due to its large and colored apical bracts located at the apex of the flower spikes [Lavandula genus that only five species, two of them being hybrids, have ISO standards, or a standard chemical profile for the essential oils included in the European Pharmacopoeia [Subnudae . In the ) Franco ,6,7,8. Favender) . Accordir spikes ,10. Hower spikes . A chemor spikes . Regardir spikes . Importar spikes ,15. Aproacopoeia . TherefoStoechas are aromatic perennial shrubs that have been reported since ancient times due to their medicinal, fragrance, and culinary uses. These species are rich in valuable essential oils and other secondary metabolites, including phenolic compounds, with several beneficial properties. Indeed, ethnobotanical studies have shown the popular uses of some of these species for the treatment of digestion, headaches, heartburn, blood circulation, as a sedative, antidermatitis, nasal decongestive bronchitis, and asthma [Species from the section d asthma ,18. In rd asthma ,21,22,23Lavandula section Stoechas covers several topics including secondary metabolites found in essential oils and other extracts and their biological activities. This review was performed from several scientific databases, such as Google Scholar, Science Direct, Springer Link, Wiley Online Library, PubMed, and ResearchGate, and combined the following keywords: “Lavandula essential oil”, “Lavandula extracts”, “Lavandula chemical composition”, and “Lavandula biological activity”. The literature review on the chemical characterization of essential oils or other extracts was compiled for each species, as follows: L. pedunculata (9 articles), L. stoechas (30 articles), L. stoechas subsp. luisieri (16 articles), and L. viridis (6 articles). Regarding pharmacological and other biological activities, generally, the same article has more than one biological activity reported, and a few of them reported more than one species. From 163 consulted references, 95% correspond to scientific articles, 3% refer to books, and 2% are books chapter, all published between 2002 and 2021.The present literature review on Secondary metabolites can be obtained from fresh or dried plant parts and at different phenological stages. To preserve the chemical composition of the extracts and their metabolites, appropriate extraction methods should be considered. Currently, the extraction method recommended by the European Pharmacopoeia to obtain essential oils is through distillation, which can be divided into several types such as water or hydrodistillation (HD), steam distillation (SD), or by the expression for citrus fruits . The disStoechas, extracts from the aerial parts of L. stoechas subsp. luisieri were obtained with an average yield of 1.4% and 0.4%, for SFE (CO2) and HD extraction, respectively [L. viridis with values of 3.4% and 0.5% for SFE (CO2) and HD, respectively [Stoechas  is presented with a brief introduction regarding chemical composition and main compounds, relevant features, biosynthesis, and bioactive properties.Regarding the section ectively . The SFEectively . In bothTerpenes or terpenoids are the most important constituents of essential oils, with more than 40,000 individual compounds already identified in the Plant Kingdom. These secondary metabolites play an important role in the interactions of plants with the environment and ecosystem, namely, in plant defense and insect attraction for pollination. For example, some compounds are directly involved in pollinator attraction , act as mediators in plant defense against stress , or as insect repellents (necrodol) .The biosynthesis of terpene compounds starts with two interconvertible molecules with five-carbons units: isopentenyl diphosphate (IPP) and its allylic isomer dimethylallyl diphosphate (DMAPP). These precursors are synthesized from different pathways: the mevalonic acid (MVA) and the methylerythritol phosphate (MEP) pathways . MonoterLavandula species of the section Stoechas, the terpenoids, mainly mono- and sesquiterpenes are the most studied due to their abundance in essential oils. The oxygenated derivatives of terpenoids are also abundant, namely, several irregular monoterpenoids. Beyond their relevance in plant–environment, plant–plant, or plant–insect interactions, these compounds also present interesting fragrance and flavor features. The medicinal properties reported for Lavandula species are mainly due to their essential oils, which also contribute to the aroma of these species. Lavender essential oil is a colorless to pale yellow liquid with a characteristic sweet, fresh, floral-herbaceous with a slight balsamic-woody undertone odor [Rosmarinus [L. pedunculata, L. stoechas subsp. luisieri, and L. viridis. Furthermore, bifurcated trichomes were found in L. pedunculata and L. viridis [In one odor . In perfone odor . The speone odor . The essone odor . Lavendesmarinus . All typ viridis ,39.Stoechas are generally characterized by the presence of monoterpenes hydrocarbons, oxygenated monoterpenes, and sesquiterpenes. In some cases, non-terpenic compounds also occur, namely, phenylpropanoids. The first ones are light and very volatile molecules also called “top notes” by the perfumery industry, while the sesquiterpenes are less volatile, showing a high potential for stereochemical diversity and also responsible for stronger odors [The essential oils of section er odors . The quaer odors ,40,41. Eer odors ,41.Lavandula essential oils from the section Stoechas reported so far are summarized in L. pedunculata from the Mediterranean region reported camphor, fenchone, and 1,8-cineole, as the major compounds of its essential oil [L. pedunculata essential oils from the North and Center of Portugal and pointed out some differences in the chemical polymorphism with plants from the North being rich in 1,8-cineole/camphor (24%/32%) and plants from Central Portugal presenting high amounts of fenchone (49%) [Studies on the composition of tial oil ,42,43,44ne (49%) .L. stoechas essential oils, some studies reported the chemical composition of plants from Tunisia, Turkey, Iran, Morocco, Algeria, Greece, and Spain [L. stoechas essential oils from plants growing in the southeast of Spain, from the supra-Mediterranean and upper meso-Mediterranean bioclimatic zones. The authors revealed differences between essential oils concerning the presence and number of minor compounds, such as linalool, bornyl acetate, thymol, myrtenyl acetate, and viridiflorol [L. stoechas essential oil from Greece whose main compounds were thujone (32%) and myrtenyl acetate (8%) [L. stoechas essential oil [Concerning nd Spain ,59,60,61diflorol . In thisdiflorol . Karabagtial oil ,86.L. stoechas subsp. stoechas and L. stoechas subsp. luisieri are two subspecies of L. stoechas, with very similar morphological features; however, they are very distinctive in what concerns the chemical composition of their essential oils. Although the authors of the above-referred studies did not specify on which subspecies they were working, by observing the chemical profile reported in their studies, it seems that the characterization refers to L. stoechas subsp. stoechas essential oil, due to the presence of characteristic major compounds. Indeed, L. stoechas subsp. stoechas essential oil has been characterized by high concentrations of fenchone (40–71%), camphor (12–47%), and 1,8-cineole (15–18%) [L. stoechas subsp. stoechas with pulegone (40%), menthol (18%), and menthone (13%) being identified as major compounds, and common compounds such as fenchone, camphor, and 1,8-cineole not being detected [As previously mentioned, (15–18%) ,78,79. Ndetected .L. stoechas subsp. luisieri or L. luisieri  is only found in the Iberian Peninsula, namely, in the southwest of Spain and Portugal [L. stoechas subsp. luisieri refer to plants collected in Portugal, contrasting with a few studies from Spanish plants. Besides the very small morphological differences between subsp. stoechas and subsp. luisieri, the latter showed a very peculiar and distinctive chemical profile compared to other species of the section Stoechas and to plant species in general. Interestingly, in this species, irregular monoterpenoids with cyclopentenic structures, namely, necrodane derivatives, are present in their essential oils. García-Vallejo found these compounds for the first time in the essential oil of L. stoechas subsp. luisieri, with α-necrodol and α-necrodyl acetate reported as the main compounds [Necrodes surinamensis [L. stoechas subsp. luisieri and Evolvulus alsinoides L. essential oils [trans-necrodol and its isomers. Figadère et al. suggested that the necrodol skeleton could be generated from geranyl diphosphate from the typical head-to-tail 1′-4-linkage of DMAPP and IPP via the isocamphane skeleton [Delottococcus aberiae , which are mainly composed of irregular terpenoids that show non-head-to-tail 1′-2 linkages between the isoprene units. The authors suggested an alternative biosynthetic pathway to the necrodol skeleton via a lavandulyl cation [L. stoechas subsp. luisieri essential oil from the Iberian Peninsula, camphor (1.1–74.4%), trans-α-necrodyl acetate (1.8–48.2%), 2,3,4,4-tetramethyl-5-methylcyclopenten-2-enone (2–38%), fenchone (0.1–22%), and 1,8-cineole (1.3–21%) have been reported as the major constituents [L. stoechas subsp. luisieri are trans-α-necrodyl acetate followed by 1,8-cineole, fenchone, and camphor [trans-α-necrodyl acetate [trans-α-necrodyl acetate (17%), followed by trans-α-necrodol (7%) and 1,8-cineole (6%), while the main compounds of the essential oils from southern plants were 1,8-cineole (34%) and fenchone (18%), and the concentration of necrodane compounds was very low (around 3% of trans-α-necrodyl acetate) [trans-α-necrodyl acetate (27%), trans-α-necrodol (13%), lavandulyl acetate (7%), and linalool (6%) in the flowering phenological stage, while the essential oil of the dormancy phase had a lower necrodane content; however, 5-methylene-2,3,4,4-tetramethylcyclopenten-2-enone (11%), fenchone (6%), 1,8-cineole (5%), and camphor (3%) concentrations were higher than those observed in the essential oil obtained from the flowering stage [According to Upson and Andrews, Portugal . Most ofompounds . These knamensis  and, recial oils . The necial oils ,36. As fskeleton . Vacas el cation . Concerntituents ,74,75,76 camphor ,74,75,76 acetate ,74,75,76ng stage . Regarding stage ,36,72.L. stoechas in Portugal, the taxonomy of the genus Lavandula has undergone several taxonomic changes. Specifically for L. stoechas subspecies, the variability found between the concentrations of the main components suggests the presence of several chemotypes [Due to the morphological variability and hybridization capacity of emotypes . An inteemotypes .L. viridis essential oil from the south of Portugal, similar chemical profiles have been reported in different studies, suggesting a high homogeneity of this volatile extract, with the main compounds being 1,8-cineole (21–74%) and camphor (3–32%), followed by α-pinene (0.3–9%) and camphene (0.1–8%) [Stoechas and their respective main compounds.Regarding (0.1–8%) ,84. In cStoechas present in their essential oil composition considerable concentrations of camphor and 1,8-cineole. Camphor is a monoterpenoid ketone with two enantiomeric forms: (1S)-(-)- and (1R)-(+)-camphor. Both forms have a similar camphoraceous fragrance; however, the stereochemistry effects on the biological properties are still unknown. In plants, camphor is produced by the cyclization of geranyl diphosphate by the enzyme (+)-bornyl diphosphate synthase generating (+)-bornyl diphosphate. The hydrolysis of (+)-bornyl diphosphate then originates (+)-borneol by the action of bornyl-diphosphate diphosphatase and the (+)-borneol dehydrogenase oxidates (+)-borneol to (+)-camphor [Cinnamomum camphora. Several pharmacological properties are reported for camphor, namely, antimicrobial, antiviral, antitussive, antimutagenic, and antinociceptive effects [As a unifying feature, all species from the section -camphor . Camphor effects ,94. More effects ; a herba effects ; and preStoechas, mainly in L. viridis. This compound is a monoterpenoid oxide and has been mostly extracted from the Lamiaceae, Zingiberaceae, and Myrtaceae families, namely, from Eucalyptus sp. essential oil, which contains high concentrations (above 90%) of this compound. Moreover, 1,8-cineole can be available in a standardized type for clinical uses [Eucalyptol or 1,8-cineole is also always present in species of the section cal uses . AlthougAnother way to achieve chemical compound synthesis is the development of microbial metabolic engineering strategies. Owing to its pleasant aroma, 1,8-cineole is often used as a flavoring agent in cosmetics, fragrance, and food products, and as an insect repellant. 1,8-Cineole is frequently reported for the treatment of respiratory diseases applied in drug formulations as a decongestant and antitussive stimulator, being the anti-inflammatory, antioxidant, anticancer, antimicrobial, antiviral, sedative, and analgesic effects of some of the main pharmacological properties . For exaLavandula section Stoechas species, except in L. viridis essential oils. It is one of the main compounds reported in L. pedunculata and L. stoechas subsp. stoechas. The most important members of the fenchane group of bicyclic monoterpenes are the secondary alcohol fenchol and the corresponding ketone fenchone. Fenchone is a substituted norbornane with a ketone functional group and three additional methyl groups and is derived via the rearrangement of a bicyclic precursor structurally. Norbornanes are known for their strained bonds and angles, as they are constrained to have the cyclohexane ring in an envelope configuration, which gives rise to high reactivity [Fenchone is also present at considerable concentrations in activity . FenchonLavandula essential oils, the non-volatile fraction  remains poorly described, with only a few studies reporting their chemical composition. Moreover, some studies are often qualitative, reporting only the presence or absence of phenolic compounds, and the equipment used for analytical identification and quantification is not always the same, thus compromising comparisons between reported chemical contents. Indeed, in In comparison to the large number of studies that characterize Lavandula species from section Stoechas, phenolic acids, and flavonoids are the most reported phenolic compounds. Furthermore, other non-volatile metabolites such as triterpenes can be found, as detailed in the following sections, and shown in In plants, phenolic compounds can be present in their free form and/or linked to sugars or proteins. In recent years, the biological activity of these compounds has been reported, namely, their antioxidant, antimicrobial, anti-inflammatory, and insecticidal effects, and others. Phenolic compounds are widely used in the food industry as a natural preservative , as a natural pigment, or as a functional additive . In the Phenolic acids are a diverse class of the main phenolic compounds produced in plants via the shikimate pathway, through L-phenylalanine or L-tyrosine as the precursor agents . These cLavandula species, some studies that compare the aqueous and hydroethanolic/ethanolic extracts report that the aqueous extract has a higher concentration of total phenolic compounds than the more non-polar ones [Stoechas as pointed out in In lar ones ,8. PhenoL. pedunculata aqueous extracts, 73 mg/g in subsp. luisieri, 74 mg/g in subsp. stoechas, and 38.8 mg/g in L.viridis hydroethanolic extracts [L. pedunculata aqueous extract and chlorogenic acid (18.5 mg/g) in L. stoechas subsp. stoechas methanolic extract [Stoechas section. The occurrence of this type of caffeic acid tetramer, mainly present in the genus Salvia, was reported for the first time in L. stoechas by Algieri et al. [L. pedunculata and L. stoechas [For example, rosmarinic acid, which is the main compound present in all compiled species, has a maximum value of 550 mg/g in extracts ,108,109.extracts ,116,117. extract ,108. Sali et al. . Other cstoechas ,107.Flavonoids are plant pigments, mainly responsible for the color of flowers. They are characterized by a 15-carbon skeleton, arranged as C6-C3-C6, with diverse substitutions, arrangements of the base skeleton, or unsaturation degrees, thus giving rise to different subclasses. Their structures consist of two aromatic rings linked to a 3-carbon bridge, containing a heterocyclic ring . They arLavandula include flavones, flavonols, flavanones, and anthocyanidins. These can occur in a free form (aglycones) or conjugated with O- or C-glycosides. In the conjugated form, the glycoside moiety is usually a glucoside, glucuronide, or rutinoside. Some flavonoids from the Lavandula species, especially anthocyanidins, are also subjected to acylation with malonic and coumaric acids. Regarding flavonoids, Upson and Andrews [Lavandula. In addition to 7-O-monoglycoside flavones, the most common type of flavonoids found in the Lamiaceae family, are di-O-glycoside flavones that are present exclusively in the section Stoechas, which can be a chemical marker of this section. Contreras et al. also corroborated these findings by showing the absence of the C-glycosides and hydroxylated flavones in L. stoechas, contrasting with the presence of these types of flavones in L. dentata that belong to the section Dentatae [O-glucuronide, methylluteolin-O-glucuronide, eriodictyol-O-glucuronide, and luteolin 7-O-glucoside are the most representative in L. pedunculata, L. stoechas subsp. stoechas and L. viridis [Euphorbia, Eucalyptus, or Pinus species, was also reported in L. viridis hydroethanolic and ethanolic extracts [Stoechas and, therefore, the absence of flavonoids in L. stoechas subsp. luisieri does not necessarily mean that they are not present in these extracts.In plants, flavonoids are involved in diverse processes such as UV protection, pigmentation, stimulation of nitrogen-fixing nodules, and disease resistance . Flavono Andrews  revealedDentatae . Compoun viridis ,108,109.extracts ,120. As L. stoechas subsp. luisieri ethanolic extract [L. stoechas extract two new copaane sesquiterpenoids, the stoechanones A and B, were identified by spectroscopic techniques (NMR and HRESIMS). These compounds have shown a high herbicidal potential [L. stoechas subsp. luisieri SFE extract. Typically, this type of compound has been also reported in the essential oil of L. stoechas subsp. luisieri [Low molecular terpenes are mainly found in essential oils, while in most non-polar extracts, high molecular terpenes such as triterpenoids can occur. Triterpenoids are widely distributed in plants, either in the free form (aglycone) or as glycosides, or in other combined forms. Structurally, they are composed of 30 carbon atoms consisting of six isoprene units, and they are biosynthesized by the cyclization of the squalene subproduct of the IPP and DMAPP pathways ,122. Acc extract . The las extract ,124. Due extract . Recentlotential . Moreoveluisieri ,72,75,76Lavandula species have been used in traditional medicine to treat many diseases, which indicates that aromatic and medicinal plants play an important role in human health, due to their biological properties. In the literature reviewed, terpenes, phenolic acids, and flavonoids are always present as the main chemical constituents in Lavandula extracts including volatile, polar, and non-polar extracts. These phytochemical substances are responsible for most of the reported biological activities. Essential oils and non-volatile extracts of species from the section Stoechas have been studied by several authors and their biological effects have shown promising potential to be used in pharmaceutical, cosmetic, or food applications. Properties such as antioxidant, antimicrobial, anti-inflammatory, antitumor, immune system protector, insecticide, and other effects have been described to these species, as systematized next.Since ancient times Recently, the interest in the role and use of natural antioxidants has increased as a strategy to prevent oxidative damage in several health disorders, in which oxidative stress plays a relevant role. Regarding the assessment of free radicals, oxidative stress, and antioxidant activity, although several methods have been developed, no single method is truly adequate for estimating the total antioxidant capacity of the extracts due to different mechanisms of action. Indeed, according to the mechanism of action, hydrogen atom transfer and single electron transfer techniques are generally used. The first technique measures the capacity of an antioxidant to catch free radicals by hydrogen donation and includes the oxygen radical absorbance capacity (ORAC), total radical-trapping antioxidant (TRAP), thiobarbituric acid reactive substances (TBARS), and chemiluminescence (CL) methods. The second mechanism is based on the electron transfer reduction capacity of an antioxidant compound, such as ferric antioxidant power (FRAP) or cupric reducing antioxidant capacity (CUPRAC). Additional methods, such as the DPPH  and Trolox equivalent antioxidant capacity (TEAC), are based on both hydrogen and single electron transfer. In these cases, the radicals can be scavenged by electron reduction or radical quenching that involves hydrogen transfer. Generally, these methods are applied in vitro, while the lipid and glutathione peroxidase and catalase activity assays (the enzymatic antioxidant methodology) are used in vivo . PhenoliLavandula have been addressed using several model systems, such as DPPH, TEAC, ORAC, FRAP, and CUPRAC. Stoechas. Considering the importance of phenolic compounds, it is relevant to correlate their content with the antioxidant potential of each plant extract. Indeed, several studies have reported a positive correlation between the phenolic and flavonoid content and antioxidant potential in these species [L. pedunculata and L. stoechas subsp. luisieri, showed high antioxidant activity (greater for the last species) [The antioxidant activities of  species ,127,128.L. stoechas essential oil [L. stoechas subsp. luisieri than L. pedunculata [Lavandula spp. essential oils with greater antioxidant power was reported by Matos et al., who revealed that L. stoechas subsp. luisieri essential oil was the most active, followed by L. viridis and lastly L. pedunculata [As expected, essential oils showed the lowest values for phenolic and flavonoid contents in comparison to methanolic and water extracts, thus revealing that terpenes also have some antioxidant power, mainly responsible for the antioxidant activity of essential oils. Carrasco et al. confirmed that linalool and thymol are responsible for the antioxidant activity of tial oil . Similarunculata . Caffeicunculata . The ranunculata .Some methodologies have been developed to evaluate the antimicrobial activity of plant products, with diffusion methods widely applied. For example, the agar disk-diffusion assay which is the official method for antimicrobial susceptibility tests was accepted and approved for publication in the Clinical and Laboratory Standards Institute (CLSI). Nevertheless, other diffusion methods are also widely used such as the agar well diffusion, agar plug diffusion, the antimicrobial gradient method, or the Etest commercial version . Likewise, dilution methods are frequently reported for the determination of the minimum inhibitory concentration (MIC). Both agar or broth dilution assays are used, being the micro- or macro-dilution the most used for antimicrobial susceptibility testing .Lavandula species have also been reported due to their antimicrobial action. The great effectiveness of essential oils does not seem to be related only to the presence of their major compounds, but many times to the synergistic effect between several components. Due to the complex mixture of essential oils, they do not act on specific targets in the cells, so no adaptation or resistance to the essential oils has been reported [Lavandula essential oils and also that of their major compounds, such as linalool, camphor, and 1,8-cineole. Importantly, these results corroborate that the activity of the volatile extracts is not due to just one constituent [L. pedunculata and L. stoechas subsp. luisieri, was evaluated for the same microorganisms. Both species showed high antimicrobial effects, but the latter species was more effective, presenting lower MIC values [Terpenes and phenolic compounds present in essential oils and non-volatile extracts of reported ,136. Somstituent ,82,85. FC values ,128.Stoechas are presented in Escherichia coli, Klebsiella pneumonia, Salmonella enterica, Haemophilus influenzae, and Pseudomonas aeruginosa, with the essential oils and extracts of Lavandula species of section Stoechas inhibiting their growth. In addition, Gram-positive bacteria such as Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus were susceptible to essential oils and extracts. The Lavandula extracts revealed inhibitory action against Candida spp., some dermatophytes strains, Aspergillus spp., food spoilage species (Rhizopus stolonifer and Penicillium spp.), and some pathogenic fungi of plants .Concerning the effect of extracts, the solvent used in the extraction process seems to influence the antimicrobial activity observed, being the non-polar extracts and essential oils, in general, more active than the polar extracts ,21,128. Leishmania spp. have also been reported. The antileishmanial activity of L. stoechas essential oil was evaluated against Leishmania infantum, L. tropica, and L. major. The concentration of L. stoechas essential oil that reduced 50% of the parasite cell (IC50) was found for L. major (0.9 µg/mL) and L. infantum (7 µg/mL). However, against L. tropia, the inhibition effect was not found in concentrations up to 10 µg/mL, and these results showed more activity than the positive control (glucantime) [L. stoechas essential oil against Leishmania spp. [Interestingly results against the protozoa cantime) . Moreovenia spp. .Stoechas has been reported. The essential oil of L. stoechas, rich in 1,8-cineole, showed an anti-inflammatory effect able to reduce carrageenan-induced paw edema with an effect similar to that of the positive control (indomethacin). Dermal application of the oil, at doses of 82 and 410 mg/kg, considerably reduced the acute paw edema in mice [L. stoechas is mainly composed of fenchone, camphor, and 1,8-cineole, of which the first two revealed a slight inhibition of lipoxygenase (LOX), which can contribute to the moderate anti-inflammatory activity revealed by the essential oil [L. stoechas subsp. luisieri essential oil (200 mg/kg) showed anti-inflammatory activity through the inhibition of carrageenan-induced rat paw edema (83%) and analgesic effects (67%), with a stronger action compared to the positive control [Inflammation is recognized as a biological process in response to tissue injury. There are several methods for determining the anti-inflammatory activity of plant extracts or their constituents, which vary according to what is intended to be inhibited at the level of the inflammatory cascade. In vitro studies, mainly aim to assess the inhibition of the activity of enzymes and/or mediators of inflammation, such as nitric oxide (NO), arachidonate 5-lipoxygenase (5-LOX), human leukocyte elastase, and interleukin-6, and elucidate the mechanisms of action involved. Normally the evaluation of the inhibition of inflammatory enzymes or mediators is carried out spectrophotometrically or by molecular biology methods, such as Western blot analysis ,145,146. in mice . As has tial oil . L. stoetial oil 0 mg/kg sL. stoechas as an herbal remedy for gastrointestinal disorders is justified by the results of its methanolic extracts, rich in rosmarinic acid, which showed a potent anti-inflammatory action, presenting an intestinal anti-inflammatory effect in a murine epithelial cell line (CMT-93) [L. dentata extract, only L. stoechas extract exhibited an anti-inflammatory effect by appreciably inhibiting carrageenan-induced paw edema in mice [L. stoechas inhibited the inflammation induced by carrageenan in rats [L. stoechas also showed a significant reduction in edema of about 85% and 62%, respectively, demonstrating that these compounds in L. stoechas extracts seem to be responsible for the anti-inflammatory activity observed [L. stoechas showed inhibition of the lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages [L. stoechas methanolic extract revealed anti-inflammatory activity in vivo (10 and 25 mg/kg), with values comparable to those registered for glucocorticoid dexamethasone, a steroidal anti-inflammatory drug. This anti-inflammatory effect was explained by the regulation of inflammatory precursors, such as inducible nitric oxide synthase, pro-inflammatory cytokines, and cyclooxygenase 2 [L. pedunculata extracts through an in vitro model of lipopolysaccharide (LPS)-stimulated macrophages, showing the inhibition of nitric oxide (NO) production, an important inflammatory marker [50  between aqueous and hydroethanolic extracts, which revealed values of IC50 of 140 µg/mL for aqueous extract and 124 µg/mL for hydroethanolic extract. Zuzarte et al. also reported the inhibition of NO production by L. stoechas essential oil at 0.16 to 0.32 µL/mL, without affecting cell viability [L. stoechas subsp. luisieri, at non-cytotoxic concentrations (up to 200 µg/mL), the essential oil showed significant inhibition of inflammatory markers (iNOS expression and NF-ƙB activation) in intestinal C2BBe1 and human chondrocytes [The potential use of (CMT-93) . In comp in mice ,107. In  in rats ,149. The in rats . Flavonoobserved . Moreoverophages . In anotgenase 2 . Signifidrocytes .The usual aspects of neurodegenerative diseases include loss of cholinergic neurons and an increase in the activity of cholinesterase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE). These enzymes are responsible for the rapid hydrolysis of acetylcholine in cholinergic synapses . AnotherL. stoechas subsp. luisieri were reported as showing a promising effect on the treatment of Alzheimer’s disease. The essential oil (90 µg/mL) and, namely, 2,3,4,4-tetramethyl-5-methylene-cyclopent-2-enone (45 µg/mL) inhibited BACE-1 activity by enzymatic and cellular assays [L. stoechas methanolic extract showed appreciably reduced levels of AChE and malondialdehyde in the brain of mice. Further, it was demonstrated that L. stoechas can be useful in attenuating the dementia process, reducing the oxidative process of neurons, and decreasing the neurodegradation of cholinergic transmission in the brain of mice [L. pedunculata polar extracts and essential oil (at a concentration of 2.5 mg/mL) were active against AChE and BChE, with the essential oil revealing the most effective inhibitor action for AChE (57%) compared to polar extracts (45%); however, for BChE, no significant differences were observed between the essential oil and non-volatile extracts [L. pedunculata essential oil compared with the ethanolic extract, thus suggesting the potential of terpenes in the inhibition of cholinesterases [L. viridis methanolic extract showed a strong inhibitory effect of AChE and BChE activities in vitro and in vivo [L. viridis essential oil and supercritical fluid extract revealed AChE inhibition, with the essential oil being the most effective AChE inhibitor, while the supercritical extract was the most effective BChE inhibitor. The inhibition of AChE and BChE was evaluated for the main compounds of the L. viridis essential oil, with 1,8-cineole being the most active compound [Medicinal plants have been widely used as memory enhancers and in dementia therapy, mainly as β-secretase (BACE-1), AChE, and BChE inhibitors. Due to the low molecular weight and high hydrophobicity of terpenoids, they have a good chance of crossing cell membranes and the blood–brain barrier. The essential oil and necrodane components of r assays . Concern of mice . L. peduextracts . Ferreirsterases . Further in vivo . L. viricompound . Studiescompound .Cytotoxicity assays are extensively used in in vitro cytotoxic studies and are generally performed against normal and tumor cell lines. The methodologies mostly applied to quantify cell viability resort to 3--2,5-diphenyltetrazolium bromide (MTT), Alamar blue, or neutral red (NR), through spectrophotometric measurement. In addition, a protein method is reported, the lactate dehydrogenase leakage (LDH) assay .L. stoechas subsp. luisieri on the viability of normal and cancer cells has been investigated. The hydroethanolic extracts and essential oil of this species did not affect the viability of normal cells, namely, adherent human skin fibroblasts (BJ) and mouse macrophages (RAW264.7) at low concentrations  [L. pedunculata [L. stoechas subsp. stoechas, the hydromethanolic extract showed a low cytotoxic effect (up 62.5 µg/mL) on RAW264.7 [Stoechas section. Lopes et al. reported that L. pedunculata extracts were effective in inhibiting the growth of breast adenocarcinoma (MCF-7), lung cancer (NCI-H460), cervical carcinoma (HeLa), and hepatocellular carcinoma (HepG2) [L. stoechas subsp. luisieri also showed cytotoxic effects in hepatocellular carcinoma (HepG2) [L. stoechas were also evaluated concerning the cell viability of macrophages (RAW264.7), preadipocytes (3T3L1), and rat H4IIE hepatoma. It was observed that both extracts did not affect the viability of the cells (up to 200 µg/mL for the first type of cells and up to 50 µg/mL for the last two) [L. stoechas extracts. In the RAW 264.7 cell line, the viability was not affected by L. stoechas essential oil at concentrations up to 0.32 µL/mL, which seems to reveal a safer potential of the essential oil compared to polar extracts [L. stoechas and L. stoechas subsp. stoechas were highly effective in cancer cells, showing very low IC50 values (0.035–18 µg/mL), in human gastric adenocarcinoma (AGS), melanoma (MV3), breast carcinoma (MDA-MB-231) for L. stoechas, and in human colon cancer (COL-2) and hormone-dependent human prostate cancer (LNCaP) for L. stoechas subsp. stoechas, thus confirming a potent in vitro antitumor effect of these volatile extracts [L. stoechas subsp. stoechas chloroform extract against P-388 (mouse leukemia) cells [L. viridis methanolic and hydroethanolic extracts (500 µg/mL) and their main compound, rosmarinic acid (125 and 250 µg/mL), did not show any toxic effect on colon adenocarcinoma (CaCo-2) cell viability [The effect of ctively) ,36. Simis RAW264. at low cRAW264.7 . Concern (HepG2) . Ethyl aast two) . The samffect up .5 µg/mL extracts ,80. Beyoiability .Lavandula sp. section Stoechas can be observed in A summary of the cytotoxic effects in non-tumor and tumor cells of the essential oils and extracts of the Lavandula section Stoechas, other biological activities, namely, the anti-hyperglycemic, anticonvulsant, hepatic, renoprotective, reproprotective, and spasmolytic effects were also reported. The anti-hyperglycemic potential of L. stoechas hydroethanolic extract and essential oil in alloxan-induced diabetic mice was demonstrated by significant effects on the reduction in blood glucose levels compared to pioglitazone, the reference drug [L. stoechas showed potential hepatic, renoprotective, and reproprotective effects against malathion-induced oxidative stress injury in the liver and kidney, and steroidogenesis disruptions in mice. This beneficial effect of the essential oil appears to be related to its antioxidant properties and ability to eliminate free radicals [L. stoechas (600 mg/kg) possesses an anticonvulsant activity, reducing the severity of convulsions and lethality induced by pentylenetetrazole (PTZ) in mice. At this concentration, although no hypnotic effect in mice was observed, the animals were considered calm and relaxed, revealing a sedative effect. A spasmolytic effect of hydromethanolic extract has also been reported in rabbits at concentrations of 0.1–1 mg/mL, causing inhibition of spontaneous fasting contractions. According to the authors, these activities seem to be mediated by the same mechanism, namely, through the calcium channel blockade [L. stoechas subsp. stoechas methanolic extract, the phenolic and flavonoid content was not affected by the digestion process. Concerning the major compounds, chlorogenic acid showed better bioavailability when compared to flavone glycosides. Regarding the antioxidant activity, a slight reduction was observed after digestion [L. viridis extracts by gastric fluid contrasting with the pancreatic fluid. This work showed that the antioxidant activity of the methanol extract and rosmarinic acid was maintained after in vitro gastrointestinal processes [For nce drug ,53. The radicals ,59. It wblockade . These bigestion . Costa erocesses .L. stoechas and L. pedunculata essential oils and showed high activity against the wheat pest Tribolium castaneum, causing the mortality of the individuals after 2 days of treatment. In this study, L. stoechas essential oil showed more marked insecticidal effects [L. pedunculata and L. stoechas, respectively. The essential oil of L. stoechas showed a high insecticidal effect with low lethal concentrations (LC50) for cigarette beetle Lasioderma serricorne (3.84 μL/L), lesser grain borer Rhyzopertha dominica (5.66 μL/L), and Tribolium castaneum (39.69 μL/L) [L. stoechas essential oil showed active effects against Anopheles labranchiae  with LC50 of 112.5 mg/L [Sitophilus granarius and S. oryzae was revealed for L. stoechas essential oil [L. stoechas subsp. luisieri, González-Coloma et al. reported antifeedant effects caused by the main compounds  and by the essential oil against Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. Only M. persicae was considerably affected by the action of these two chemical compounds, while the essential oil also revealed a feeding inhibition in S. littoralis and L. decemlineata. According to these results, antifeedant properties cannot be attributed to the major compounds individually, which, once again, supports the existence of synergistic effects among the essential oil components [L. stoechas subsp. luisieri essential oil and a methanolic extract, from wild and cultivated plants, against Rhopalosiphum padi, S. littoralis, and M. persicae. As in the previous study, a significant antifeedant effect was reported for the essential oils and methanolic extract, but the latter was less effective. Moreover, the ethanolic extract was inactive against M. persicae; however, a supercritical fluid extract with a high concentration of necrodane-type ketones showed strong S. littoralis antifeedant effects [L. stoechas subsp. luisieri, such as 2,3,4,4-tetramethyl-5-methylidenecyclopent-2-en-1-one, hydroxymethyl-2,3,4,4-tetramethylcyclopent-2-en-1-one, and 3-oxo-cadinol, showed antifeedant effects against S. littoralis [The use of chemical insecticides is presently the most popular practice for controlling insects. However, the exhaustive use of these chemical products is responsible for the emergence of resistant insects, has negative impacts on the environment, and is involved in food chain contamination. Thus, the search for new alternatives to avoid such damage is imperative, and the use of molecules with natural origins, such as essential oils, seems to be a promising alternative to control insects and larvae. The insecticidal activity varies with the concentration of essential oil used, species of insects tested, and time of exposure ,158. Bac effects . Similar69 μL/L) . L. stoe2.5 mg/L . Furthermponents . Afterwa effects . Some ofttoralis .Meloydogine javanica, in contrast to the aqueous extract [L. stoechas subsp. luisieri against Hyalomma lusitanicum [Beyond the antifeedant activity, also, nematicidal effects were reported for the necrodane derivatives against  extract . Julio eitanicum . This prL. stoechas subsp. luisieri against Lactuca sativa and Lolium perenne, with the latter showing more sensibility [L. stoechas showed phytotoxic effects against seed germination and seedling growth of Amaranthus retroflexus, with a strong inhibition in the seed germination and radical and hypocotyl lengths of seedlings, suggesting a potential herbicide activity [L. stoechas on the development of two mycorrhizal species (Septoglomus deserticola and Rhizophagus intraradices) in a host plant, Allium porrum. It was verified that a small number of leaves–flowers (up to 2 g/L of soil) or essential oil (up to 25 mg/L of soil) were beneficial for fungi infection and the effects of allelopathy were also confirmed; however, it was revealed that higher concentrations induced the inhibition of these mycorrhizal species [Phytotoxic effects were reported for the necrodane derivative compounds of sibility . Masi etactivity . On the  species .L. pedunculata growing in soils with multi-elemental contamination under Mediterranean conditions were studied by Santos et al. Their phytostabilization potential was confirmed by the accumulation of elements in roots, avoiding their translocation to the aerial parts, and no phytotoxic effects on plants were observed [L. stoechas in mercury-rich soil, in which it was observed that the roots act as a barrier, revealing very low concentrations of mercury in the leaves that could contribute to the phyto-immobilization of this element in the soil [Phytostabilization involves the reduction in the mobility of heavy metals in soils. Populations of observed . Similarthe soil .Stoechas mainly present in Mediterranean areas. The remarkable diversity of chemical compounds found in these species is systematized for the first time. This qualitative and quantitative chemical diversity is mainly due to genetic differences and diverse environmental conditions that influence the plant’s biological properties. Therefore, a proper chemical characterization is imperative to distinguish different species, which are sometimes very similar morphologically. Indeed, due to the similar morphology, these species are sometimes mistaken and undifferentiated, which can lead to incorrect labeling and, consequent, misuse. Bearing in mind that this difficulty does not arise only in these species, and given the insufficient regulation and control by official organisms, we believe that studies on plant phytochemistry and pharmacology are extremely important and useful for future decisions and the definition of control standards. The biological properties of these plants can be applied in several areas, from pharmaceutical to food additives, cosmetics, and hygienic and vegetal sanitary industries (Stoechas has a broad spectrum of antimicrobial activity, acting on several classes of microorganisms. Furthermore, the anticancer activity of essential oils and other non-volatile extracts in several cancer lines points out promising opportunities in the clinic. Thus, these extracts/compounds can be considered as an alternative and economical source of natural products that can be employed in numerous industries. Moreover, the knowledge of phytochemistry will also contribute to the cultivation of more valuable species, a sustainable way to increase the progress in less-favored areas, promoting species preservation and, consequently, biodiversity.The present review focused on the phytochemical characterization and biological properties of the section dustries . It was


Cordyceps militaris is a famous traditional edible and medicinal fungus in Asia, and its fruiting body has rich medicinal value. The molecular mechanism of fruiting body development is still not well understood in C. militaris. In this study, phylogenetically analysis and protein domains prediction of the 14 putative chitinases were performed. The transcription level and enzyme activity of chitinase were significant increased during fruiting body development of C. militaris. Then, two chitinase genes (Chi1 and Chi4) were selected to construct gene silencing strain by RNA interference. When Chi1 and Chi4 genes were knockdown, the differentiation of the primordium was blocked, and the number of fruiting body was significantly decreased approximately by 50% compared to wild-type (WT) strain. The length of the single mature fruiting body was shortened by 27% and 38% in Chi1- and Chi4-silenced strains, respectively. In addition, the chitin content and cell wall thickness were significantly increased in Chi1- and Chi4-silenced strains. These results provide new insights into the biological functions of chitinase in fruiting body development of C. militaris. Cordyceps militaris is a well-known traditional edible and medicinal mushroom in Asia. Its fruiting body has the functions of anti-tumor /[A405standard × time × Venz × Total protein]. A405sample: absorbance of the sample at 405 nm; A405blank: absorbance of the blank at 405 nm; 0.05: mmole/mL of p-nitrophenol in the standard solution; 0.3: final volume of the 96 well plate reaction after addition of the stop solution (mL); DF: dilution factor; A405standard: absorbance of the standard solution at 405 nm; time: minutes; Venz: volume of the sample (mL). Asterisks indicate significant differences  compared to the control according to two-way analysis of variance (ANOVA) using GraphPad Prism. The values were expressed as the mean ± SD, and p < 0.05 was defined as statistically significant.The facturer . Unit deC. militaris mycelium powder was collected and resuspended in 3 mol/L KOH in a water bath at 80 °C for 90 min, and then pre-cooled 75% ethanol was added in advance and then the powder was placed in an ice bath for 15 min on an ice box. Then 545 diatomite (mass to volume ratio 13.3%) was added and mixed, and the precipitation was collected by centrifugation. The precipitate was washed with pre-cooled 40% ethanol and then washed twice with pre-cooled ddH2O. The precipitate was resuspended in water, 5% KHSO4 and 5% (w/v) NaNO2. The supernatant was centrifuged and mixed with ddH2O and 12.5% (w/v) (NH4)2SO4. Next, 5 mg/mL 3-methyl-2-benzothiazolinone hydrazone hydrochloride was added, boiled for 5 min, 0.83% (w/v) FeCl3 was added, and the reaction was carried out at room temperature for 25 min. The absorbance value was measured by microplate reader at 650 nm. Standard curves were drawn using glucosamine as a standard.The determination of chitin content is as previously described . BrieflyC. militaris cDNA as the template and the primers listed in Chi1 and Chi4 were designed. The obtained PCR product was added to the agarose gel with dye solution. A gel imager was used for testing and the DNA gel recovery kit was used to recover it. T-A cloning vector was connected for 12 h, and inhaled the vector connected to the silent DNA segment for Escherichia coli DH5α, stranded for 25–30 min, heat shocked for 60 s, and the sterile LB medium without antibiotics was added to mixed evenly and cultured for 1 h. The supernatant was then centrifuged for 30 s and discarded. After the suspended cells were suspended, they were coated on LB solid medium containing kanamycin (50 mg/mL), and inverted at 37 °C to culture. The plasmid of the silent vector was extracted and the plasmid DNA of Chi1 and Chi4 was digested by BamHI and SalI to obtain the double digested products, then they were contected with T4 DNA ligase and transform the enzyme linked products into E. coli DH5α. PCR detection was performed in PCAMBIA1300 plasmid. Inoculated EHA105 Agrobacterium in YEB, and incubated in a shaking table for 12–16 h. Inoculated recovered Agrobacterium tumefaciens into YEB, and continued to culture until OD600 is 0.4–0.5. Agrobacterium EHA105 was inoculated in YEB to prepare Agrobacterium competent cells, the successfully constructed pCAMBIA1300 plasmid (RNAi: pGPD-CmChitinase-p35S) was transferred into Agrobacterium EHA105. Then prepared pupae grassland protoplasts, and 100 μL Agrobacterium and 100 μL protoplasm whose concentration was up to standard were fully mixed, then coated them on IM solid medium covered with cellophane, and co-cultured in dark for 2 days. The plasmid RNAi: pGPD-CmChitinase-p35S was transformed into C. militaris by Agrobacterium tumefaciens-mediated transformation (ATMT). After the co-culture, dozens of transformants were randomly selected after growth on M-100 medium containing 50 mg/mL carbenicillin and 100 mg/mL hygromycin B. qRT-PCR analyses were performed to determine the silencing efficiency of the transformants. Gene expression was evaluated by calculating the difference between the threshold cycle (CT) value of the gene analyzed and the CT value of the housekeeping gene tubulin (TUB). qRT-PCR calculations analyzing the relative gene expression levels were performed according to the 2−ΔΔCT method with paired primes listed in Construction of RNA interference cassette targeting chitinase using fungal RNAi vector pCAMBIA1300. Inhibition of chitinase expression by glyceraldehyde-3-phosphate dehydrogenase promoter and 35S promoter. The chitinase gene was amplified by PCR using The detection of cell wall thickness by transmission electron microscopy is a reference to previously reported methods with some modifications . MyceliaC. militaris, the sequences of the chitinase gene of Metarhizium robertsii , Beauveria bassiana  and Neurospora crassa  were used as input in the BLAST search of the C. militaris genome database. Fourteen putative chitinase genes (named as Chi1–14) were obtained. Then, 13 chitinases from M. robertsii, 5 chitinases from N. crassa and 3 chitinases from B. bassiana were used for phylogenetic analysis with Chi1–14 , the chitinase activity of mature fruiting body (MFB) was significantly increased approximately by 2.1-fold. These results hint that chitinase play a role in fruiting body development in C. militaris. Then, the significantly upregulated chitinase genes Chi1 and Chi4, which containing GH18 and chitin binding domains, were selected for follow-up study.Next, real-time quantitative PCR was used to detect the expression of 14 chitinase genes in six fruiting body development stages of Chi1 and Chi4 were selected to construct the gene silencing strains. The gene-silenced transformants were screened phenotypically on PDA supplemented with hygromycin B, and the results were confirmed by PCR (Chi1i and Chi4i), but not in the wild-type (WT) strain. The parallel PCR amplification experiment with plasmid DNA (P) as template was set as positive control  were expressed mainly in the cap during fruiting body maturation, and the expression of these two chitinases increased with the maturation of the fruiting body [Chi1, Chi4, Chi6, and Chi11 transcription in mature fruiting bodies mature fruiting body of C. militaris. In addition, we found that silencing of Chi1 and Chi4 genes resulted in blocked primordial differentiation and defective fruiting body development, and the chitin content and cell wall thickness were increased. These studies showed that chitinase plays a role in the fruiting body development of different mushroom.Chitinase plays a role in chitin catabolism and cell wall remodeling . Some stectively . In Aspeilitaris . In Copring body , which wIsaria fumosorosea, knockout chitinase gene Ifchit1 which contain LysM domain led to the average lethal dose (LT50) of killing insect Plutella xylostella increased by about three times compared with wild-type strains, indicating that Ifchit1 mutant’s ability to penetrate or destroy insect cuticle was reduced [B. bassiana, knockout two chitinases Blys2 and Blys5, which containing conservative LysM domain, significantly prolonged the killing time and inhibited the immune response ability to insect wax moth larvae [BbSir2 of B. bassiana, which containing two LysM domains, decreased the budding spore number by about 10–12% and increased the LT50 by 30% of insect Galleria mellonella larvae by 30%, showing that BbSir2 mutant reduced the virulence of B. bassiana [C. militaris, the live insect tussah pupa or grain culture medium which added with insect silkworm pupa powder were used to culture fruiting body [Chi4 and Chi5 of C. militaris also contain LysM domain. Therefore, chitinase of C. militaris has the potential to decompose insect chitin which needs further study.In addition to cell wall remodeling and fruiting bodies development, fungal chitinase participates in the decomposition of chitin in insect cell wall . The mai reduced . In inseh larvae . Knockoubassiana . In C. ming body ,39. In tC. militaris. We found primordial differentiation and fruiting body development were defected, and the chitin content and cell wall thickness were increased in Chi1 and Chi4 silenced strain. Our results hint that chitinase is involved in the fruiting body development by regulating chitin content in C. militaris.In summary, 14 putative chitinase genes were characterized and formed preliminary studies on the function of chitinase in


Background and Objectives: Hyperuricemia is associated with a variety of comorbidities. The objective of this study was to investigate the association between hyperuricemia and hearing impairment in Korean adults. Materials and Methods: Audiometric and laboratory test data from the 2019 to 2020 Korean National Health and Nutrition Examination Survey (KNHANES) were used for analysis. Hearing impairment was defined as a pure-tone average  threshold level ≥ 41 decibels. The definition of hyperuricemia was different for males and females: >7 mg/dL for males vs. >6 mg/dL for females. Results: A total of 4857  subjects were analyzed. The mean age was 56.8 years old. The weighted prevalence was 12.1% for hyperuricemia and 2.5% for gout. The prevalence of hearing impairment was 13.4%. In the univariable analysis, hyperuricemia was significantly associated with hearing impairment. However, the diagnosis of gout was not associated with hearing impairment. In the multivariable analysis, hyperuricemia (odds ratios (OR): 1.41, 95% confidence interval [CI]: 1.03–1.92, p = 0.030) was associated with hearing impairment along with age , female sex , education , and occupational noise exposure . In the subgroup analysis, hyperuricemia was associated with hearing impairment in females  and the elderly aged 60 years or more . Conclusions: Hyperuricemia was independently associated with hearing impairment, especially in females and the elderly aged 60 years or more. Hearing loss is one of the most prevalent health conditions that people experience today. According to the World Health Organization (WHO), as of 2021, 430 million people had some degree of impaired hearing requiring hearing rehabilitation. It has been estimated that over 700 million people will have disabling hearing loss by 2050. Hearing impairment can have a significant impact on social interaction and the overall quality of life. Age-related hearing loss is associated with cognitive decline, cognitive impairment, and dementia [Uric acid is a metabolic product of purine nucleotides. Several components can affect serum uric acid levels, including dietary or lifestyle factors, drugs, and kidney function.Gout is regarded as an arthritic condition resulting from the deposition of monosodium urate crystals in joints following chronic elevation of the uric acid level. Hyperuricemia and gout are associated with a variety of comorbidities, including chronic kidney disease, hypertension, obesity, heart failure, diabetes, myocardial infarction, and stroke . Moon etThe Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide survey assessing the general health and nutrition status of the South Korean population through interviews about health and nutrition and basic health assessments. In 2019–2020, the survey was conducted with a basic assessment of gout and serum uric acid levels. The aim of the present study was to evaluate the association between hyperuricemia/gout and hearing impairment by adjusting for various possible factors associated with hearing impairment in the Korean adult population using data from the 2019–2020 KNHANES. n = 17,990,725) participants were selected for analysis.Audiometric and laboratory test data from the 2019 to 2020 Korean National Health and Nutrition Examination Survey (KNHANES) were used for analysis. The methodology of KNHANES has been described in a previous study . In brieHeavy alcohol use was defined as the consumption of alcohol more than two or three times per week in the year prior to the interview. Occupational noise exposure was defined as a history of more than three years of exposure to loud noises such as machines or generators in the workplace. Loud noise means that the noise in the workplace is so loud that conversation is impossible. Gout was defined in the questionnaire as “Gout diagnosed by a physician (yes/no) through a standardized interview”. The question was, “Was your gout diagnosed by a physician?” Hypertension was defined as a systolic blood pressure of 140 mmHg or higher or a diastolic blood pressure of 90 mmHg or higher. Participants taking antihypertensive medication were also included in this group. Pre-hypertension was defined as a systolic blood pressure of 120–139 mmHg and a diastolic blood pressure of 80–89 mmHg. Diabetes was defined as a fasting blood glucose level of 126 mg/dL or higher, a diagnosis of diabetes by a physician, the use of hypoglycemic drugs or insulin injections, or a HbA1c level of 6.5% or higher. Pre-diabetes was defined as a fasting blood glucose level of 100–125 mg/dL or an HbA1c of 5.7–6.4%. Dyslipidemia was defined as a total cholesterol level greater than 240 mg/dL or the use of cholesterol-lowering drugs. The definition of hyperuricemia was different for males and females: >7 mg/dL for males and >6 mg/dL for females. Obesity was defined as a BMI of 25 or higher. Blood samples were collected in the morning after fasting for at least 8 h. Blood samples were immediately refrigerated and transported in cold storage to the central testing facility. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) study equation: eGFR (mL/min/1.73 m2) = 175 × (serum creatinine) − 1.154 × (age) − 0.203 ×  [To collect information on demographic variables, a standardized interview was performed individually by a professional investigator using an established questionnaire that consisted of demographic and socioeconomic characteristics. In detail, the questionnaire included data on age, sex, smoking status, alcohol consumption, body mass index (BMI), educational level, and occupational noise exposure. A pure-tone air-conduction threshold was obtained in a soundproof booth using an automatic audiometer . The soundproof booth and audiometer were installed in the mobile vehicles, and the maximum permissible noise of the soundproof booth was strictly controlled under the regulation of ANSI-ASA S3.1. Trained professional investigators collected data independently for each ear at the following five frequencies: 0.5, 1.0, 2.0, 4.0, and 8.0 kHz. Hearing impairment was determined according to three categories of frequency . Average-frequency pure-tone threshold was defined as the average of 0.5, 1.0, 2.0, and 4.0 kHz. Low/mid-frequency pure-tone threshold was defined as the average of air-conduction hearing thresholds measured at 0.5, 1.0, and 2.0 kHz. High-frequency pure-tone threshold was defined as the average of air-conduction hearing thresholds measured at 4.0 and 8.0 kHz. Hearing impairment was defined as a pure-tone average  threshold level ≥41 decibels for the superior ear.< 60 mL/min/1.73 m2, were evaluated using a univariable analysis. Only variables with a p-value ≤ 0.2 were selected for the multivariable analysis with the logistic regression model. In the logistic regression analysis, we calculated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for hearing impairment. A subgroup analysis with stratification according to sex and age was also performed. Using the Bonferroni method, p-values were corrected. Statistical analyses were performed using SAS version 9.4 . All p-values were two-sided, and p-values < 0.05 were considered statistically significant.Owing to sex differences in serum uric acid levels, analyses were stratified by sex. Potential factors associated with hyperuricemia, including age, sex, education level, current smoking, heavy alcohol use, occupational noise exposure, BMI, hypertension, diabetes, dyslipidemia, and eGFR n = 17,990,725) were analyzed for this study. The weighted demographic and clinical characteristics of the study population are presented in A total of 4857 adults aged ≥ 40 years (weighted p = 0.554), whereas hyperuricemia did . When subjects were divided into subgroups by age and sex, gout did not show any significant association in any subgroup analysis. Hyperuricemia showed a significant association with hearing impairment in females  and the elderly aged ≥ 60 years . Based on these results, we performed a multivariate analysis by selecting hyperuricemia as an independent variable associated with hearing impairment. To evaluate whether hyperuricemia and gout were associated with hearing impairment, a univariable logistic analysis was performed . Gout diClinical characteristics were analyzed according to the presence of hyperuricemia . HyperurFemale subjects with hyperuricemia were older than those with normal uric acid levels. The ratio of education level according to the presence of hyperuricemia was significantly different among female subjects but not among male subjects. In addition, the weighted prevalence rates of diabetes and hypertension were higher in female subjects with hyperuricemia than in subjects with normal uric acid levels.2, and hyperuricemia were associated with hearing impairment , female sex , university-level education , occupational noise exposure , and hyperuricemia  were significantly associated with hearing impairment (p < 0.001), university-level education , and occupational noise exposure  were significantly associated with hearing impairment in male participants. Hyperuricemia was not significantly associated with hearing impairment in male participants. In the female subgroup analysis, hyperuricemia remained a significant factor associated with hearing impairment , age , and university-level education . Hyperuricemia was also significantly associated with hearing impairment in participants aged ≥ 60 years .In the multivariable-adjusted analysis, age , female sex , university-level education , occupational noise exposure , and diabetes  were associated with high-frequency hearing impairment (p = 0.018).In the multivariable logistic regression analysis for high-frequency hearing impairment, age , female sex , university-level education , and occupational noise exposure  were associated with low/mid-frequency hearing impairment  production . ROS areIn this study, hypruricemia was associated with high-frequency hearing impairment in older adults. It corresponded well with a previous study reporting significant abnormalities in otoacoustic emissions at higher frequencies (4 and 5 kHz) in participants with hyperuricemia . High-frIn the subgroup analysis, hyperuricemia showed a significant association with the female gender. In females, serum uric acid levels are lower than in males. However, uric acid levels increase after menopause . EstrogeA number of studies have demonstrated that hyperuricemia is linked to cardiovascular and neurologic diseases, including hypertension, coronary heart disease, metabolic syndrome, stroke, and neurodegenerative diseases . It has This study has several limitations. First, this study was unable to obtain information on uric acid-lowering agents or diuretics that might have an impact on serum uric acid levels. Second, the diagnosis of gout was dependent on the information provided by the participants in the interview. In this study, specific criteria were not applied for the definition of gout. Third, audiometric measurements were only performed for participants aged 40 years or older in this survey. Considering age is an important factor associated with hearing impairment, the results of the study should be interpreted only for individuals aged 40 years or older. Finally, it was not possible to establish causality due to the cross-sectional design of this study. Despite all these limitations, the strength of this study lies in the fact that we analyzed the relationship between uric acid and hearing impairment in a nationwide representative sample of the general adult population. An audiometric test was conducted, and analyses were performed to determine whether gout or uric acid levels were associated with hearing.In conclusion, the current study highlights that hyperuricemia is independently associated with hearing impairment, especially in females and older adults (≥60 years). Further investigations are required to clarify the relationship between serum uric acid levels and hearing impairment.


Nearly one in four (24.4%) U.S. adults aged 20–69 years show evidence of noise-induced hearing loss . Panel members were recruited by mail, using probability-based sampling by address to reach respondents regardless of whether they had landline telephones or Internet access.* If needed, households were provided a laptop or tablet computer and Internet access. Personal identifiers were not included in the data file. Panelists who completed the survey received cash-equivalent rewards worth approximately $5.†Respondents were asked three questions about sound levels at both indoor and outdoor recreational venues and events at which enjoyment of amplified music was a central purpose of attendance. Respondents were asked how much they agreed or disagreed with each of the following statements: “Sound levels at venues or events should be limited to reduce risk of hearing loss”; “Warning signs should be posted if sound at a venue or event could exceed safe levels”; and “I would wear hearing protection if it was provided when sound at a venue or event could exceed safe levels.” Participants indicated their responses on a 5-point Likert scale . Answers were combined into three categories: 1) strongly agree or agree (agree), 2) neither agree nor disagree, and 3) disagree or strongly disagree (disagree). Multinomial logistic regression was used to calculate adjusted odds ratios (aORs), 95% CIs, and p-values. The following covariates were all included in the model: sex , age, race and ethnicity, educational attainment, household income, U.S. Census Bureau region of residence, and metropolitan residency status. This analysis was conducted using SAS statistical software ; p-values <0.05 were considered statistically significant. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.Most respondents were female (50.9%), and 62.8% were non-Hispanic White (White) . More thAfter adjusting for multiple covariates, women agreed significantly more often than did men that sound levels should be limited and that warning signs should be posted  . RespondAgreement with both limiting sound levels and wearing hearing protection progressively increased with the respondent’s level of educational attainment. Compared with those with less than a high school education, adults with a high school diploma, with some college or associate degree, and with a bachelor’s degree or higher agreed significantly more often with limiting sound levels  and wearing hearing protection . Only adults with some college and those with at least a bachelor’s degree agreed significantly more often than did those with less education that warning signs should be posted in venues and events where sound could exceed safe levels .Compared with respondents who reported an annual household income of <$25,000, those with an income of >$150,000 agreed significantly more often (aOR = 1.4) that warning signs should be posted. U.S. Census Bureau region and metropolitan residency status made little difference in perceptions regarding safe listening to amplified music at venues and events, with the exception of adults in metropolitan areas who agreed significantly that warning signs should be posted (1.5).The results from this survey indicate that U.S. adults are largely aware of the hazard posed by high sound levels at concerts and other events. More importantly, results indicate an encouraging openness to protective actions, such as limiting sound levels, posting warning signs, and use of hearing protection. More than one half of the respondents agreed that sound levels at venues or events should be limited to reduce risk for hearing loss, approximately three quarters of respondents agreed that warning signs should be posted if sound at a venue or event could exceed safe levels, and approximately three in five respondents agreed they would wear hearing protection if it was provided when sound at a venue or event could exceed safe levels. Survey results suggest targeting educational efforts for the use of hearing protection toward respondents aged <63 years. Raising the awareness among certain demographic groups  about limiting sound levels and displaying of warning signs might be warranted.However, stated intent to take protective action does not always result in the action being taken. In an earlier Porter Novelli Styles survey, approximately 80% of U.S. adults aged ≥18 years reported never or seldom using hearing protection at loud athletic or entertainment events. An additional 10% reported using hearing protection only some or about one half the time  equivalent continuous sound levelThe findings in this report are subject to at least four limitations. First, the data obtained in this survey were self-reported. Second, the survey relied on respondents’ perceptions of loudness and the risk for hearing loss. Third, respondents’ perceptions might be influenced by their experience of attending such events, but data on these experiences  were not collected. Finally, although survey responses were weighted by the U.S. demographic characteristics, how accurately this weighting has corrected any bias in this internet panel sample remains unknown.https://www.who.int/activities/making-listening-safe), CDC (https://www.cdc.gov/nceh/hearing_loss/toolkit), and a variety of professional organizations  to raise awareness of noise-related risks and promote protective behaviors, such as lowering the volume, using hearing protection, and taking breaks from noisy activities. Interventions should focus on helping persons understand the risks of high sound levels and managing their exposures so they can enjoy music for a lifetime without the debilitating effects of hearing loss.Music-induced hearing loss is entirely preventable. Hearing and other health professionals can make use of existing materials available from WHO (Exposure to loud music from personal listening devices and entertainment venues can pose a risk to hearing; nearly 25% of U.S. adults aged 20–69 years show evidence of noise-induced hearing loss.More than one half of U.S. adults aged ≥18 years are open to actions being taken at events and venues with amplified music to protect their hearing, such as limiting sound levels, posting of warning signs, and using hearing protection when provided.Health care practitioners can help persons understand their risks from high sound levels and manage their exposures. Resources are available to help raise awareness of noise risks and promote protective behaviors.


In recent years, antibiotics have been listed as a new class of environmental pollutants. Tetracycline antibiotics (TCs) used in human medical treatment, animal husbandry and agricultural production are the most widely used antibiotics. Due to their wide range of activities and low cost, their annual consumption is increasing. TCs cannot be completely metabolized by humans and animals. They can be abused or overused, causing the continuous accumulation of TCs in the ecological environment and potential negative effects on non-target organisms. These TCs may spread into the food chain and pose a serious threat to human health and the ecology. Based on the Chinese environment, the residues of TCs in feces, sewage, sludge, soil and water were comprehensively summarized, as well as the potential transmission capacity of air. This paper collected the concentrations of TCs in different media in the Chinese environment, contributing to the collection of a TC pollutant database in China, and facilitating the monitoring and treatment of pollutants in the future. Antibiotics are secondary metabolites produced by microorganisms  or higher plants with antipathogenic properties ,2. CurreThe first mention of TCs in the scientific literature dates back to 1948, and they started to be commercialized with good clinical results before long . TCs areWith the rapid development of the global economy, people tend to ignore the importance of the ecology, causing great pollution to the environment. The unprecedented use of TCs in treating and preventing diseases in humans and in aquaculture and agriculture has resulted in the continuous influx and accumulation of TCs. They can disrupt the safety and diversity of organisms in the environment and pose a serious threat to human security. This review summarizes the distribution characteristics of TCs in various environmental media and assesses the residual situation of their environment. In addition, this paper focuses on the exposure and danger levels of TCs in China’s ecological environment and provides valuable reference information for protecting the ecological environment.https://www.webofscience.com, accessed on 16 May 2022) and China academic journal network publishing database  for information retrieval, the two databases almost covered all the scientific literature in both Chinese and English. All search terms within a string were checked for a “title, abstract, and keyword”. The search algorithms were “tetracycline antibiotics”, “environment”  and “China”. Considering the adequacy of the amount of data and the consistency of data accuracy, the relevant literature in the past ten years (2012–2022) was selected. According to the results of the investigation in the past 10 years, the environment in all parts of the country has been polluted by antibiotics to varying degrees. Although the use of antibiotics has a history of nearly a hundred years, the research on its environmental risk is still under exploration.Using the Web of Science  or farms (antibiotics for veterinary use). Sewage generated from the pharmaceutical process enters the sewage plant for treatment, and some solid waste (leftovers or expired medicines) enters garbage plants for landfill treatment. A sewage treatment plant will treat wastewater and domestic sewage from hospitals and breeding plants. However, the plant cannot absolutely eliminate the TCs, and the sludge produced contains high concentrations of TCs. This is used as organic fertilizer and animal husbandry manure for returning to the field and is directly discharged into rivers for the fish farming industry. In the natural environment, TC pollution is mainly due to waste, sewage and organic fertilizers generated by the social environment.The rapid development of livestock and poultry farming has become an important industry in China, and TCs have become the most widely used veterinary antibiotics in China . AccordiThe output of manure around the farm is large, and this manure is directly applied to the surrounding soil without comprehensive treatment, resulting in the pollution of antibiotics in the soil. In China, antibiotics are added to feed in excess of 8000 t annually, while the annual maximum production of livestock waste is predicted to reach 3.19 billion tons ,34. In CResidue levels of TCs are in the order pig manure > poultry manure > cow manure and are generally higher in manure from industrial farms compared to manure from farm households. Northeast China is composed of Heilongjiang, Jilin and Liaoning provinces. CTC is the most commonly used, while OTC is the most used; the utilization of TC in pig feeding farms was more common than in chicken and cow feedlots . The TCsWWTPs are the last line of defense against harmful substances in domestic and industrial wastewater entering the environment. The removal efficiency of antibiotics depends on the physicochemical characteristics . The treSewage sludge is an inevitable waste produced by urban sewage treatment facilities. The treated wastewater containing antibiotics in WWTPs is used for irrigation or discharged into natural water bodies, resulting in a concentrated source of typical antibiotics in rivers. With potential agricultural nutritional value, sludge is a complex heterogeneous mixture of microorganisms and undigested organics such as paper, plant leftovers, oils, fecal waste and inorganic components . In totaAntibiotic-contaminated manure is frequently used as a soil amendment or land fertilizer in China, Europe, the Americas and other regions of the world . Manure 2+, Cd2+, Mg2+ and Al3+ or form ternary complexes as a bridge between organic matter and TCs [Detectable concentrations of TCs in soil range from μg/kg to mg/kg , and TCs and TCs ,66,67. T and TCs .The pH, texture, metal ions, clay content, organic matter, rainfall duration and pH of the rain all have a substantial impact on the adsorption and migration of antibiotics in the soil ,69,70. LResearch shows that bacteria in feces may not be well adapted to the soil environment because bacterial communities in feces and soil are largely different. . After aRivers around cities play a vital role in social and economic development. In addition to serving as a significant source of drinking water for both urban and rural inhabitants, they also provide water for aquaculture, ecological landscapes and agricultural irrigation. The temporal and spatial distributions of antibiotics in water sources in different regions of China are quite different. On the one hand, this difference is closely related to the local industrial structure; the method of antibiotic disposal in the pharmaceutical industry; the use of antibiotics in livestock, poultry and aquaculture; and the flood season of rivers. Sewage, surface runoff and direct discharge from animal husbandry resulted in high TC content in some surface water samples in China, and the residual content of TCs in surface water was collected . The ranOn the other hand, this is also related to the physical and chemical properties of TCs (adsorption and transformation), distance from the source, water environment temperature, pH, salt concentration and bioavailability . The degThe fugacity differential between water and surface sediment drives the exchange of surface water and sediment . Water sThe degree of adsorption of TCs is related to the content of organic carbon and clay: the more organic carbon present, the higher the amount of antibiotics adsorbed in the sediment. Sand’s limited capacity for adsorption is caused by its low organic matter concentration, and the variation in antibiotic concentrations in sandy sediments can be explained by the variation in dynamics and contamination load . Since TThe world’s largest supply of freshwater is groundwater, which is made up of 97% available freshwater and 3% mostly surface water . The mosDue to technical limitations, the presence of antibiotics and transport mechanisms in the air is rarely considered. It is generally considered that the air may contain detectable concentrations of antibiotics in pharmaceutical plants, hospitals, laboratories, livestock farms and feed mills. Airborne particulate matter is a complex biologically active particle that further exacerbates health and environmental hazards as it is loaded with fungi, bacteria and viruses as well as many other components of endotoxins, disinfectants, antibiotics (TCs) and antibiotic resistance genes ,127. TCsGenerally speaking, the residue of TCs in manure in China is in the order of mg/kg. Affected by factors such as culture scale, quantity and species preference of TCs, sampling time and place, the residual concentration of TCs in manure varies greatly in different production areas and different research reports. The performance and cost of different treatment units of sewage treatment plants in China are different due to the situation. The residual antibiotics in the effluent and excess sludge are usually in the order of ng/L.TCs are generally detected in the Chinese environment, and their distribution is irregular. There are large differences in the types and concentrations of TCs in Chinese watersheds, mainly due to the large area of China and the different industrial and agricultural conditions in different places, with the highest emission densities concentrated in the economically developed and densely populated areas of Beijing, Tianjin and Hebei, the Yangtze River Delta and the Pearl River Delta. Antibiotics enter the environment through different forms, and more and more TCs are exposed to the ecological environment in China, such as the detected amount, storage and long-distance transport of antibiotics in the environment. The concentration of TCs in most areas is close to or even above the ecological risk trigger value, which indicates a certain potential environmental risk and therefore requires an environmental risk assessment.The amount of TCs added to feed to encourage animal growth is far above the amount actually demanded. We need to change the concept of antibiotic use, scientifically regulate its use, establish relevant policies and establish antibiotic supervision and discharge standards. The research and development of alternatives needs to be strengthened, and degradation methods  need to be developed for severely polluted areas, especially in the field of biodegradation. These methods can be developed into promising removal techniques for TCs. However, there are still some problems that keep relevant research in the laboratory stage.The presence of exogenous antibiotics in air, soil and water environments allows TCs to enter organisms. TCs can be stored in vegetables, crops, animals, by-products and aquatic plants and animals. Although TCs can be stored in vegetables, crops, animals, by-products and aquatic animals and plants, it is unclear whether TCs will disappear in vegetables, fruits and food processing. It is recommended to develop tools for evaluating how the presence of TCs affects human health and to model the migration pathways of TCs from pharmaceutical factories to the environment.At present, the degradation mechanism and influencing factors of TCs are still unclear. Physical, chemical and biological degradation methods are mostly laboratory-based, with varying degradation capacities and products, and subject to environmental factors . Methods for the determination and extraction of tetracycline and related metabolites also need to be further optimized. At present, most studies only examine the extent to which TCs are reduced, but the degradation products are not studied in detail. Therefore, it is necessary to further understand the potential ecological risks of TCs, TC transformation products and tetracycline resistance genes to the environment. In addition, pollutants such as heavy metal ions, microplastics, chemicals, disinfectants and other types of antibiotics present in the environment have a responsive relationship , effects on beneficial bacteria in the environment  and ecological effects .


This resulted in 22 articles included within the collection. They examined a range of important topics related to hearing healthcare and research, including noise-induced hearing loss, health service quality and safety, psychological and psychosocial consequences of hearing loss and co-morbidities of hearing loss. All articles reported on hearing loss; there were no published articles with a primary focus on other hearing conditions such as tinnitus or hyperacusis, on the health of older people from the Deaf community or on users of Cochlear implants, suggesting key gaps in knowledge and targets for future research. This New Horizons article highlights novel directions in research and practice and takes a forward look at how research into hearing conditions may develop in years to come. It highlights opportunities for the growth of patient-centred research and hearing healthcare supported by the better integration of health and care services as well as cross-speciality working to include common co-morbid health conditions.Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life. Hearing is affected by multiple factors, including heredity, noise exposure, age, sex, ear disorders and lifestyle factors. Globally, hearing loss affects over 80% of adults aged 80 years and older, is often experienced in combination with other long-term health conditions and is a mid-life risk factor for dementia. To form a  Hearing conditions are highly prevalent in the population and affect communication and quality of life.Hearing loss affects over 80% of adults aged 80 years and older, often in combination with other long-term health conditions.For older adults, cochlear implants, the Deaf community, tinnitus and hyperacusis are underrepresented within published research.Opportunities for the growth of patient-centred research and care exist, supported by better integration of services.Hearing is our social sense, on which we rely to connect us with others. However, hearing conditions such as hearing loss, tinnitus and hyperacusis compromise our ability to communicate, and can often co-occur. Hearing conditions are often long-term conditions without cure. They affect a substantial proportion of the global population: with estimates for hearing loss ~20.3% , tinnituHearing conditions increase in both prevalence and severity as people age. For example, tinnitus affects approximately 10% of younger adults, rising to 24% of older adults . WorldwiHearing conditions, in particular hearing loss, are associated with a range of negative health conditions including vision loss, cognitive impairment, psychosocial health problems, diabetes, cardiovascular disease, stroke, arthritis and cancer  as well Estimates from 2019 show that nearly 1 trillion international dollars (Intl$) are lost each year due to unaddressed hearing loss .themed collection’ of articles published with Age and Ageing that are focused on hearing conditions. Second, it presents a forward-focused discussion of opportunities that exist (a ‘New Horizon’) in research and evidence-based care for older adults with hearing conditions.This publication is divided into two parts. First, it describes a ‘themed collection, we searched Age and Ageing for articles about hearing conditions that were published from 2000 onwards. Our search identified 22 articles eligible for inclusion within the collection. There were no articles identified that had a primary focus on tinnitus, hyperacusis or the Deaf community.To collate the et al. [Hearing loss is associated with several long-term health conditions, such as diabetes and vascular disease. What is less clear is the mechanism by which this occurs, which could be due directly to vascular disease or else mediated by various processes, including chronic inflammation (often referred to as inflammageing). Verschuur et al.  found anet al. [Another recognised risk factor associated with age-related hearing decline is noise exposure. Hoffs et al.  found thet al. [et al. [Along with increased co-morbidity, the association between hearing loss and increased mortality is well established, with the risks increasing with more severe hearing loss. For example, Fisher et al.  found si [et al.  also exaet al. [People living in the community with hearing loss may require additional support to manage their overall health. A longitudinal study by Schneider et al.  investiget al. [Older adults living with sensory impairment may face difficulties managing their medication stemming from barriers to communication. In a community-based study, Smith et al.  reportedThe quality of care that older people with hearing loss experience in social care settings is also negatively impacted by communication difficulties. An ethnographic study of two residential care homes in the UK found that social and environmental factors influenced residents’ access to social opportunities . Social et al. [Furthermore, healthcare professionals may be ill-equipped to address the communication challenges posed by hearing loss, thus influencing the quality of care that patients receive. Smith et al.  exploredet al. [n = 686) and without (n = 886) hearing loss, from the 1997–2004 Australian Blue Mountains Hearing Study. A significantly higher proportion of adults with hearing loss, compared with those without, experienced difficulties with three out of seven basic activities  and six out of seven instrumental activities . Additionally, greater hearing loss severity was associated with impaired ADL, following adjustments for key factors .The psychological and psychosocial impact of hearing loss is profound, persistent and increases with hearing loss severity. Gopinath et al.  examinedet al. [Gopinath et al.  also useet al. [n = 3,928) from the Three-City study in France. Baseline hearing loss was associated with self-reported anxiety symptoms but not incident GAD. In contrast, GAD at baseline was associated with an increased risk of self-reported hearing loss at follow-up. Therefore, perhaps managing anxiety may reduce the psychosocial impact of hearing loss.Cosh et al.  exploredet al. [Dobrota et al.  studied et al. [Finally, Heffernan et al.  used a qet al. [n = 4,926) and found that older adults with dual-sensory impairments had higher rates of depression, cognitive impairments and diabetes compared with those without impairments. Overall, dual sensory impairments were associated with an increased risk of all-cause mortality compared with those with hearing or vision loss alone. Using data collected from three international surveys of ageing , Maharani et al. [et al. [Dual sensory impairment (e.g. experiencing both vision and hearing loss) is common in older adults, and with an ageing population the prevalence is expected to increase . Dual seet al.  examinedi et al.  found th [et al.  examinedet al. [et al. [Due to the complexity of dual sensory impairments, more comprehensive environmental adaptations, management and assessments are required than for vision or hearing loss alone. In a study exploring healthcare professionals’ perceptions of the assessment and service provision for dual sensory impairments and cognition, Leroi et al.  identifi [et al.  identifiet al. [Untreated hearing loss in mid-life is a potentially modifiable risk factor for dementia, accounting for approximately 8% of dementia cases globally . Proposeet al.  found thet al. , 29 repoet al. [For people living with dementia, poor hearing is known to exacerbate the effects of cognitive decline. Naylor et al.  analysedet al. , 31 partet al. [et al. [An important consideration is that screening tools designed to identify cognitive impairment frequently rely on auditory-based assessment methods, raising concerns about the over-diagnosis of dementia in people with hearing loss . DeSilvaet al.  found no [et al.  exploredThe number of people living with hearing conditions is increasing, placing a greater burden on health and social care services and impacting the quality of care that individuals receive . Older pGovernment policies, such as the UK Accessible Information Standard provide a legal requirement to ensure that the needs of people who have hearing loss, are Deaf or blind, or experience dual sensory loss are met when using health and social care services . In 2015Hearing loss is the 3rd leading cause of YLD, and the leading cause of YLD for those over 70 years of age . Yet, fuMoving forward, hearing research is on a trajectory from a single- to multiple-condition foci. This will enable health and care professionals to deliver future evidence-based care informed by the experiences of those who live with (often co-morbid) hearing conditions alongside other  long-term health conditions. Hearing healthcare professionals recognise the potential benefits of addressing common co-morbidities of hearing (such as dementia) via integrated care pathways , 56. An themed collection on hearing conditions that offers a broad overview of key topics related to the consequences, diagnosis, management and common co-morbidities of hearing loss. There was a complete absence of articles reporting on older members of the Deaf community. Articles on the use of cochlear implants and on hearing conditions other than hearing loss are lacking within the journal’s themed collection, highlighting gaps in knowledge and key targets for future research.This publication summarises a Clinicians should be aware of the high prevalence of hearing conditions in older adults to aid the effective diagnosis, assessment and management of hearing conditions as well as assess risks for, and management of, associated chronic co-morbid conditions. A new horizon of opportunities for the growth of patient-centred evidence-based care exists, supported by targeted priority research and the integration of health and care services, using an interprofessional approach.Finally, what might we include when writing a similar article in 10 years’ time? We will know more about the role of hearing rehabilitation in dementia prevention, patients will have greater choice in hearing intervention and self-management support, the use of cochlear implants will be more widespread, audiology and other health and care services will have worked out how to work best together and basic science will have delivered some major advances, for example the regeneration of cochlear hair cells.Hearing_conditions_collection_afad150Click here for additional data file.