Three novel umami peptides derived from the alcohol extract of the Pacific oyster(Crassostrea gigas):identification,characterizations and interactions with T1R1/T1R3 taste receptors

Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.

Role of bitter contributors and bitter taste receptors:a comprehensive review of their sources,functions and future development

Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.

Studies of the Variability of Primary Metabolites in the Epicarp, Mesocarp and Seed of Dacryodes edulis Fruit at Taste Maturity

The fruits of Dacryodes edulis are rich in biologically active substances, which makes them of great interest in terms of validation. In this study, we targeted the primary metabolites in the epicarp, the mesocarp and the seed of the fruit of Dacryodes edulis at taste maturity, which were selected for their nutritional quality and its appreciation throughout the Gulf of Guinea area, which is very popular because of its large size, texture and special taste. The evaluation of total carbohydrates, total lipids and soluble proteins in the epicarp, mesocarp and seed of the fruit at taste maturity was made from spectrophotometer measurements. The overall analysis of the results of the present study shows that total carbohydrates, total lipids and proteins accumulate more in the seed with respectively 251.33 ± 1.15 mg/g DM;9.92 ± 0.201 mg/g DM and 55.075 ± 0.024 mg/g DM. Likewise, the results indicate low concentrations of total carbohydrates and total lipids in the epicarp with respectively 245 ± 1 mg/g DM and 4.77 ± 0.047 mg/g DM, on the other hand, it is the mesocarp which presents the lowest content of soluble proteins: 28.075 ± 3.231 mg/g DM. This variation could be linked to the nature of the compartment, more particularly to the storage location. This comparative study could lead to the valorization of the seed of the fruit of Dacryodes edulis for its richness in metabolites and arouse significant interest in nutrition.

First report of the histopathological effect of electrocautery using on the urethral taste rosea during glans penis injury by incision in rabbits

Objective:Currently,electrocautery devices have frequently been used in penile surgical procedures.We hypothesized that electrocautery using during penile surgical procedures may harm the taste rosea and the dorsal nerve of the penis or clitoris.Methods:Eighteen young age male New Zealand rabbits were studied:five in the control(Group I,n=5),five in the penile surgery without using electrocautery(sham group,Group II,n=5),eight in the monopolar cautery(study group,Group III,n=8)groups under general anesthesia.The animals were followed for 3 weeks and sacrificed.Penile tissue—pudendal nerve root complexes and dorsal root ganglion of sacral 3 level were examined using stereological methods.The results were compared statistically.Results:The live and degenerated taste bud-like structures and degenerated neuron densities of pudendal ganglia(mean±standard deviation,n/mm^(3))were estimated as 198±24/mm^(3),4±1/mm^(3),and 5±1/mm^(3) in Group I;8±3/mm^(3),174±21/mm^(3),and 24±7/mm^(3) in Group II;and 21±5/mm^(3),137±14/mm^(3),and 95±12/mm^(3) in Group III,respectively.Neurodegeneration of taste buds and pudendal ganglia was significantly different between groups.Conclusion:Intact spinal cord and normal parasympathetic and thoracolumbar sympathetic networks are crucial for human sexual function.The present study indicates that the glans penis injury by using electrocautery may lead to pudendal ganglia degeneration.Iatrogenic damage to taste rosea and retrograde degeneration of the pudendal nerve may be the cause of sexual dysfunction responsible mechanism.

Comparison between Care Strategies for Patients with Osteoarthritis of the Hands Based on the Use of Joint Protection, Assistive Technology and Exercises

Background: Osteoarthritis (OA) is a disabling disease that can affect 6% to 12% of the adult population and more than a third of people over 65 years of age. Purpose: To assess whether a group of people with hand osteoarthritis (hOA) who received different types of treatment improved their function after two years of follow-up. Method: The entire sample (n = 97) underwent three follow-up assessments regarding anthropometric parameters of the upper limbs and ability to perform functional activities. Subsequently, the sample was divided into two groups for the intervention periods, called the First Period (n = 73) and the Second Period (n = 24);the First Period kept the same protocol with orientations, and the Second Period went to an intervention with orientation strength exercises and use of orthosis. Findings: In the separate analysis of the three questions of the DASH pain module, no differences were found between the assessment moments for groups of guidelines, treatment, or symptoms. Significant effects were observed for F(2, 162) = 3.5, p = 0.033, η2 = 0.04, and interaction for moments and intervention F(2, 162) = 4.3, p = 0.016, η2 = 0.05. Implications: It can be concluded that only guidance treatment does not benefit patients with hand osteoarthritis. In contrast, guidance, exercise, and orthosis treatment can significantly improve the disease.

Epidemiology of Hand Injuries That Presented to the Emergency Department of a Tertiary Care Facility in Suburban Mumbai, India: A Study Including 489 Patients

Background: Hand injuries are very common and responsible for a significant number of emergency department (ED) visits, most of which are not to hand specialists [1]. The functionality and outcome of hand injuries can vary significantly depending on the mechanism and pattern of injuries, which is why it is imperative for emergency physicians to recognize the complexities, and the potential repercussion of missed injuries in such cases. Objective: The aim of this study is to provide epidemiological information on hand injuries and their patterns. The objective is 1) to assess whether most hand injuries are superficial (simple), or involve underlying deeper structures (complex) and 2) to assess whether most hand injuries presented to the emergency department were managed by the emergency physician or plastic/orthopaedic surgeon. Methods: This retrospective single-centre observational study conducted at an emergency department in a tertiary care hospital in Mumbai, India collected data from hand trauma patients using a standardized documentation form. Demographic data, trauma-related data, and disposition plans were analysed. Results: A total of 489 cases sustained hand injuries over a period of one year. The patients were predominantly males in the 20 - 30 year age group and injuries were mainly sustained over the right hand. Most of the injuries were sustained at home (42%). The most common mechanism (34%) was sharp object injury (including needle-stick and other sharps in hospital), followed by blunt injury (30%). Among grievous hand injuries, door jamb was a mechanism noted in 11% of patients, accounting for 50% of all crush injuries. Lacerations were the most common pattern (24.7%) noticed, followed closely by fractures (23.3%). Digits II - IV were injured most commonly (54%), followed by carpals (14%) and the thumb (10%). Nearly 80% of the hand injuries were managed by emergency physicians alone, with 61% of cases involving superficial structures. Though 14% of the cases required plastic surgery intervention, the initial evaluation of all these patients was performed by the emergency physician. Conclusions: Our study highlights the burden of hand injuries on the emergency physician, as well as the odds of missed injuries, directly indicating the necessity of a thorough anatomical knowledge of the structures of the hand, and in turn, a proper physical examination. A dedicated registry for hand trauma would help quantify the mechanism and pattern of injuries, and formulate preventive strategies.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

Novel umami peptides from two Termitomyces mushrooms and molecular docking to the taste receptor T1R1/T1R3

Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces aff.bulborhizus.Ten umami peptides from aqueous extracts were separated using a Sephadex G-15 gel filtration chromatography.The intense umami fraction was evaluated by both sensory evaluation and electronic tongue.They were identified as KLNDAQAPK,DSTDEKFLR,VGKGAHLSGEH,MLKKKKLA,SLGFGGPPGY,TVATFSSSTKPDD,AMDDDEADLLLLAM,VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK.Seven peptides,except VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK were selectively synthesized to verify their taste characteristics.All these 10 peptides had umami or salt taste.The 10 peptides were conducted by molecular docking to study their interaction with identified peptides and the umami taste receptor T1R1/T1R3.All these 10 peptides perfectly docked the active residues in the T1R3 subunit.Our results provide theoretical basis for the umami taste and address the umami mechanism of two wild edible Termitomyces mushrooms.

Effects of prebiotics on the fermentation of traditional suancai of Northeast China

Suancai is a traditional fermented vegetable widely consumed in Northeast China.In this study,different prebiotics were used to improve the quality of suancai.Four prebiotics(inulin(INU),xylooligosaccharide(XO S),galactooligosaccharide(GOS),and stachyose(STA))were shown to reduce the pH value and increase the content of total titratable acidity(TTA)in suancai,while the contents of most organic acids were also increased.The addition of prebiotics had significant effects on the bacterial microbiota during the suancai fermentation process.All prebiotics were shown to contribute to the growth of Lactobacillus.The suancai sample with fructooligosaccharides(FOS)had the highest relative abundance of Lactobacillus.Besides,INU and XOS could increase the abundance of Weissella.To evaluate the quality of suancai fermented with prebiotics,profiles of volatile flavor compounds(VOCs)and free amino acids(FAA)were analyzed.The prebiotics affected the VOCs and FAA profiles via transforming the bacterial microbiota.In addition,the addition of prebiotics also changed the taste profiles of the suancai samples.This study is among the first attempts to reveal the effects of different prebiotics on suancai fermentation,and the findings provide a foundation to develop new ways for improving the quality of suancai.

Umami taste components in chicken-spices blends and potential effect of aroma on umami taste intensity

In this study,umami taste intensity(UTI)and umami taste components in chicken breast(CB)and chickenspices blends were characterized using sensory and instrumental analysis.Our main objective was to assess the aroma-umami taste interactions in different food matrices and reconcile the aroma-taste perception to assist future product development.The impact of key aroma,including vegetable-note"2-pentylfuran",meaty"methional",green"hexanal",and spicy-note-estragole and caryophyllene"on UTI was evaluated in monosodium glutamate and chicken extract.We found that spices significantly decreased UTI and umami taste components in CB.Interestingly,the perceptually similar odorants and tastants exhibited the potential to enhance UTI in food matrices.Methional was able to increase the UTI,whereas spicy and green-note components could reduce the UTI significantly.This information would be valuable to food engineers and formulators in aroma selection to control the UTI perceived by consumers,thus,improving the quality and acceptability of the chicken products.

Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

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

Molecular mechanisms of bitterness and astringency in the oral cavity induced by soyasaponin

The interaction mechanism between soyasaponin(Ssa)and bitter receptors/mucin,as well as the saliva interface behavior of Ssa,were investigated to explore the presentation mechanism of Ssa bitterness and astringency(BA).Strong bitterness arising from high Ssa concentrations(0.5–1.5 mg/mL)had a masking effect on astringency.At Ssa concentrations of 1.0–1.5 mg/mL,Ssa micelles altered the structure of mucin,exposing its internal tryptophan to a more polar environment.At Ssa concentrations of 0.05–1.50 mg/mL,its reaction with mucin increased the aggregation of particles in artificial saliva,which reduced the frictional lubricating properties of oral saliva.Ssa-mucin interactions affected the salivary interfacial adsorption layer,and their complexes synergistically reduced the interfacial tension.Ssa monomers and soyasapogenols bind to bitter receptors/mucin via hydrogen bonding and hydrophobic interactions.Class A Ssa binds more strongly than class B Ssa,and thus likely presents a higher BA.In conclusion,Ssa interacts with bitter receptors/mucin causing conformational changes and aggregation of salivary mucin,resulting in diminished frictional lubricating properties of oral saliva.This,in turn,affects taste perception and gustatory transmission.

Hand Cooling Enhances the Proprioceptive Drift during Rubber Hand Illusion

Background: The neural representation of the body is easily altered by integrating multiple sensory signals in the brain. The “Rubber Hand Illusion” (RHI) is one of the most popular experimental paradigms to investigate this phenomenon. During this illusion, ownership of a rubber hand is temporarily induced. It was shown that external and continuous cooling of the palm enhanced the RHI, suggesting an association between altered the autonomic nervous system regulation and altered the sense of ownership of a specific limb. Purpose: To investigate whether artificially cooling the entire hand for a short period affects the magnitude of the illusion. Methods: Participants immersed their entire hand in cool, cold, or warm water for 1 min before the RHI procedure. Results: We found that cooling the entire hand enhanced the proprioceptive drift during the RHI but not the subjective feeling of ownership. In contrast, warming and intense cooling of the entire hand did not affect the RHI strength. Conclusion: Our results suggest that transient and moderate cooling of the entire hand was sufficient in enhancing the illusory disembodiment of one’s own hand.

Tenosynovitis of hand: Causes and complications

Tenosynovitis represents a common clinical condition characterized by inflam-mation of the synovium that encases the tendon sheath.Although tenosynovities may be noted in any tendon in the body,extremities such as hand,and foot remain the sites of high predilection to acquire this condition.The predominant cause of this predilection rests in the intricate tendon arrangements in these extremities that permit fine motor actions.This editorial explores the common causes and the complications associated with this condition to improve the understanding of the readers of this common condition encountered in our everyday clinical practice.

Surgical management of adult hand macrodactyly in a 49-year-old patient:A case report

BACKGROUND Macrodactyly is a rare congenital malformation characterized by an increase in the size of all structures of a digit,accounting for less than 1%of all congenital upper extremity conditions.CASE SUMMARY We report a case involving a 49-year-old woman who presented for the first time with untreated,radial-sided hand macrodactyly.We performed soft tissue debulking,amputation,median nerve neurotomy and coaptation,and carpal tunnel release.At the 6-year follow-up,no significant growth was observed in the bone or soft tissue of the affected area.CONCLUSION Tissue overgrowth in patients with progressive macrodactyly can continue and progress excessively with age.Median nerve neurotomy and coaptation play a crucial role in preventing recurrence of the deformity.

Epidemiology and Clonal Spread Evidence of Carbapenem-Resistant Organisms in the Center of Care and Protection of Orphaned Children, Vietnam

Objective: To determine the prevalence of colonization and transmission of carbapenem-resistant Gram-negative organisms in order to develop of an effective infection prevention program. Design: Cross-sectional study with carbapenem-resistant organisms (CRO) colonization detection from the fecal specimens of 20 Health Care Workers (HCWs) and 67 residents and 175 random environment specimens from September 2022 to September 2023. Setting: A Care and Protection Centre of Orphaned Children in South of HCM City. Participants: It included 20 HCWs, 67 residents, and 175 randomly collected environmental specimens. Method: Rectal and environmental swabs were collected from 20 HCWs, 67 residents (most of them were children), and 175 environmental specimens. MELAB Chromogenic CARBA agar plates, Card NID, and NMIC-500 CPO of the BD Phoenix TM Automated Microbiology System and whole genome sequencing (WGS) were the tests to screen, confirm CROs, respectively and determine CRO colonization and transmission between HCWs, residents, and the environment. Result: We detected 36 CRO isolates, including 6, 11 and 19 CROs found in 6 HCWs, 10 residents and 19 environments. The prevalence of detectable CRO was 30% (6/20) in HCWs, 14.92% (10/67) in residents, and 10.86% (19/175) in environmental swabs in our study. WGS demonstrated CRO colonization and transmission with the clonal spread of E. coli and A. nosocomialis, among HCWs and residents (children). Conclusion: Significant CRO colonization and transmission was evident in HCWs, residents, and the center environment. Cleaning and disinfection of the environment and performing regular hand hygiene are priorities to reduce the risk of CRO colonization and transmission.

Epidemiology of work-related hand and wrist injuries in a referral center: A descriptive study

BACKGROUND Occupational hand and wrist injuries(OHWIs)account for 25%of work-related accidents in low-and middle-income countries.In Colombia,more than 500000 occupational accidents occurred in 2021,and although the rate declined to less than 5%in 2020 and 2021,at least one in four accidents involved a hand or wrist injury.AIM To describe the OHWIs in workers seen at the emergency room at a second-level hospital in Colombia.METHODS An observational study was performed using data from workers who experienced OHWIs and attended a second-level hospital,between June,2020 and May,2021.The overall frequency of OHWIs,as well as their distribution by sociodemo-graphic,clinical,and occupational variables,are described.Furthermore,association patterns between sex,anatomical area(fingers,hand,wrist),and type of job were analyzed by correspondence analysis(CA).RESULTS There were 2.101 workers treated for occupational accidents,423(20.3%)were cases of OHWIs,which mainly affected men(93.9%)with a median age of 31 years and who worked mainly in mining(75.9%).OHWIs were more common in the right upper extremity(55.3%)and comprised different types of injuries,such as contusion(42.1%),laceration(27.9%),fracture(18.7%),and crush injury(15.6%).They primarily affected the phalanges(95.2%),especially those of the first finger(25.7%).The CAs showed associations between the injured anatomical area and the worker’s job that differed in men and women(explained variance>90%).CONCLUSION One out of five workers who suffered occupational accidents in Cundinamarca,Columbia had an OHWI,affecting mainly males employed in mining.This occupational profile is likely to lead to prolonged rehabilitation,and permanent functional limitations.Our results might be useful for adjusting preventive measures in cluster risk groups.

Non-steroidal anti-inflammatory drugs in postoperative hand fracture management:Do they positively or negatively impact recovery?

This editorial explores the impact of non-steroidal anti-inflammatory drugs(NSAIDs)on postoperative recovery in hand fracture patients,amidst shifting pain management strategies away from opioids due to their adverse effects.With hand fractures being significantly common and postoperative pain management crucial for recovery,the potential of NSAIDs offers a non-addictive pain control alternative.However,the controversy over NSAIDs'effects on bone healing—stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union—necessitates further investigation.Despite a comprehensive literature search,the study finds a lack of specific research on NSAIDs in postoperative hand fracture management,highlighting an urgent need for future studies to balance their benefits against possible risks.

Discovery of the relationship between bitter taste and bitter flavor (efficacy) based on hTAS2Rs

Objective:To explore the relationship between bitter taste and bitter flavor(efficacy),their character-istics were analyzed at the target and pharmacodynamic points.Methods:Compounds with bitter receptor activity were obtained by high-throughput screening models of the human bitter taste receptors(hTAS2Rs),which were used to analyze bitter taste.The efficacy of anti-asthma medications was used as an example to research bitter flavor(efficacy).The pharmacological effects of bitter taste and bitter flavor(efficacy)were classified according to the functional modules.The coverage for the same targets or pharmacological effects in the overall protein interaction network(PIN)of bitter taste and bitter flavor(efficacy)was analyzed to reveal their relationship.The effect of the compound polydatin with anti-asthma activation on hTAS2R14 was studied to verify the reliability of the aforementioned idea.Results:A total of 121 Chinese materia medica(CMM)compounds that activate hTAS2R10,hTAS2R14,and hTAS2R49 were obtained.The analysis results indicated that 108 same targets for bitter taste and bitter flavor(efficacy)were obtained,accounting for 13.9%in the PIN of bitter taste and 72.5%in the PIN of bitter flavor(efficacy).The pharmacological effects shared by bitter taste and bitter flavor(efficacy)accounted for 79%of the PIN of bitter taste and 81%of the PIN of bitter flavor(efficacy).The activating effect of the anti-asthma compound polydatin on hTAS2R14 was dose-dependent with EC 50 of 4.3 m M.Conclusion:In this study,the relationship between bitter taste and bitter flavor(efficacy)has been demonstrated from the target and pharmacodynamic points,which are based on hTAS2Rs and anti-asthma effect.Bitter taste and bitter flavor(efficacy)exhibited a high correlation.This study provides a theoretical and scientific basis for the hypothesis that“the property theory of CMM is the clinical pharmacodynamics of CMM.”

Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease

Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.