Extreme Resonant Eccentricity Excitation of Stars around Merging Black-Hole Binary.

We study the dynamics of a star orbiting a merging black-hole binary (BHB) in a coplanar triple configuration. During the BHB's orbital decay, the system can be driven across the apsidal precession resonance, where the apsidal precession rate of the stellar orbit matches that of the inner BHB. As a result, the system gets captured into a state of resonance advection until the merger of the BHB, leading to extreme eccentricity growth of the stellar orbit. This resonance advection occurs when the inner binary has a nonzero eccentricity and unequal masses. The resonant driving of the stellar eccentricity can significantly alter the hardening rate of the inner BHB and produce observational signatures to uncover the presence of nearby merging or merged BHBs.

Mutation of Disulfide Bond Sites Reduces the Immunoreactivity of Cra a 4 by Changing the Structural Characteristics.

Sarcoplasmic calcium-binding protein (Cra a 4) from Crassostrea angulata belongs to the EF-hand superfamily, and understanding of its structure-allergenicity relationship is still insufficient. In this study, chemical denaturants were used to destroy the structure of Cra a 4, showing that disruption of the structure reduced its IgG-/IgE-binding activity. To explore which critical amino acid site affects the allergenicity of Cra a 4, the mutants were obtained by site-directed mutations in the disulfide bonds site (C97), conformational epitopes (I105, D114), or Ca2+-binding region (D106, D110) and their IgG-/IgE-binding activity was reduced significantly using serological tests. Notably, C97A had the lowest immunoreactivity. In addition, two conformational epitopes of Cra 4 were verified. Meanwhile, the increase of the α-helical content, surface hydrophobicity, and surface electrostatic potential of C97A affected its allergenicity. Overall, the understanding of the structure-allergenicity relationship of Cra a 4 allowed the development of a hypoallergenic mutant.

Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

IXPE detection of polarized X-rays from magnetars and photon mode conversion at QED vacuum resonance.

The recent observations of the anomalous X-ray pulsars 4U 0142+61 and 1RXS J170849.0-400910 by the Imaging X-ray Polarimetry Explorer (IXPE) opened up a new avenue to study magnetars, neutron stars endowed with superstrong magnetic fields (B ≳ 1014 G). The detected polarized X-rays from 4U 0142+61 exhibit a 90° linear polarization swing from low photon energies (E ≲ 4 keV) to high energies (E ≳ 5.5 keV). We show that this swing can be explained by photon polarization mode conversion at the vacuum resonance in the magnetar atmosphere; the resonance arises from the combined effects of plasma-induced birefringence and Quantum electrodynamics (QED)-induced vacuum birefringence in strong magnetic fields. This explanation suggests that the atmosphere of 4U 0142 is composed of partially ionized heavy elements and that the surface magnetic field is comparable to or less than 1014 G, consistent with the dipole field inferred from the measured spindown. It also implies that the spin axis of 4U 0142+61 is aligned with its velocity direction. The polarized X-rays from 1RXS J170849.0-400910 do not show such 90° swing, consistent with magnetar atmospheric emission with B ≳ 5 × 1014 G.

Comprehensive Proteomics Analysis Identifies CD38-Mediated NAD+ Decline Orchestrating Renal Fibrosis in Pediatric Patients With Obstructive Nephropathy.

Obstructive nephropathy is one of the leading causes of kidney injury and renal fibrosis in pediatric patients. Although considerable advances have been made in understanding the pathophysiology of obstructive nephropathy, most of them were based on animal experiments and a comprehensive understanding of obstructive nephropathy in pediatric patients at the molecular level remains limited. Here, we performed a comparative proteomics analysis of obstructed kidneys from pediatric patients with ureteropelvic junction obstruction and healthy kidney tissues. Intriguingly, the proteomics revealed extensive metabolic reprogramming in kidneys from individuals with ureteropelvic junction obstruction. Moreover, we uncovered the dysregulation of NAD+ metabolism and NAD+-related metabolic pathways, including mitochondrial dysfunction, the Krebs cycle, and tryptophan metabolism, which led to decreased NAD+ levels in obstructed kidneys. Importantly, the major NADase CD38 was strongly induced in human and experimental obstructive nephropathy. Genetic deletion or pharmacological inhibition of CD38 as well as NAD+ supplementation significantly recovered NAD+ levels in obstructed kidneys and reduced obstruction-induced renal fibrosis, partially through the mechanisms of blunting the recruitment of immune cells and NF-κB signaling. Thus, our work not only provides an enriched resource for future investigations of obstructive nephropathy but also establishes CD38-mediated NAD+ decline as a potential therapeutic target for obstruction-induced renal fibrosis.

Wasp-stung rat model translationally expresses the coagulopathy manifestations of human wasp patients.

Two over 80 wasp stings male victims appeared severe abnormal coagulation were consecutively examined by thromboelastography (TEG) guided with heparinase during hospitalization. However, the cause of coagulopathy remains unsolved. Rats were applied to establish a wasp-stung animal model highly resembled the manifestations of wasp-stung patients. According body surface area conversion, Sprague-Dawley rats were stung based on wasp sting numbers (0, 4, 8, 12 stings; n = 6 each) with various exposure times (0, 1, 3, 6 h) to determine the simulation of coagulopathy. The blood R, K values, and angle degree of wasp-stung rats were measured by TEG. The TEG profiles of stung rats were found to be concomitant with that of wasp-stung patients. Data showed that the endogenous heparinization of rats was time-dependent. Compared to the TEG profile of eight stings given rat, the coagulation time of 2 mm clot formation at 3 h (R value) was longer than that at 0 h. The coagulation time was prolonged with increasing sting numbers when compared to the various stings at 1, 3, and 6 h exposed. Interestingly, there was observed the peak coagulation at 3 h of eight stings. The Ck-standard and Ck-heparinase at 3 h after 8 stings given were R: 9.6-4.4 min; K: 3.8-1.8 min; angle degree: 49.8-68.0, respectively. The original data of R, K values and angle degree in two wasp-stung victims were 11.7-13.6 min, 4.3-5.5 min, and 41.2-32.8° in CK-standard, respectively; whereas those of the CK-heparinase groups were 5.6-6.7 min, 2.4-2.5 min, and 59.5-58.8°, correspondingly. Conclusively, this massive wasp-stung animal model can be applied to the investigations of pathogenesis and provides a clinical strategy or guideline for clinical intervention.

Construction and application of tuberculosis medical and nursing integration cooperation model.

OBJECTIVE: To explore the clinical effect of the tuberculosis (TB) doctor-nurse integration management model METHODS: This study is a retrospective historical cohort study. The clinical data of 180 patients with TB in our hospital from 2019 to 2020 were analyzed retrospectively. In a control group, 90 cases were treated with the traditional medical care model. An observation group of 90 cases received clinical diagnoses, treatments, and nursing under a doctor-nurse integration management model. Comparative analyses between the two groups were conducted on various aspects, including the awareness level of TB prevention and control, medication compliance and patient satisfaction. Comparisons between the two groups were evaluated using independent-sample t-tests or Chi-squared tests RESULTS: Compared with the control group, the knowledge awareness levels of TB prevention and medication compliance in the observation group were significantly higher (p < .05). The appointment waiting times and hospitalization times in the observation group were significantly lower than in the control group (p < .05). The total average satisfaction score of the patients in the observation group was significantly higher than in the control group (p < .05). Compared with the control group, the patients in the observation group were significantly more satisfied with their nursing methods, operating techniques, psychological techniques, service attitudes, and ward management (p < .05). In addition, in the observation group, medical-nursing relationships and doctor-patient communication were better than in the control group; additionally, the satisfaction of doctors with nursing work was also higher than in the control group, which was a statistically significant difference (p < .05) CONCLUSION: The implementation of an integrated medical-nursing cooperation model for TB will help increase the awareness of health knowledge in patients with TB, improve patient medication compliance and enhance patient satisfaction.

SPI1 is a prognostic biomarker of immune infiltration and immunotherapy efficacy in clear cell renal cell carcinoma.

BACKGROUND: Spi-1 proto-oncogene (SPI1), which encodes an ETS-domain transcription factor, can activate gene expression in myeloid and lymphoid lineages. The role of SPI1 in the tumor immune microenvironment in clear cell renal cell carcinoma (ccRCC) remains unknown. In this study, we investigated the possible role of SPI1 in ccRCC using an independent cohort and a comprehensive bioinformatics analysis. MATERIALS AND METHODS: Quantitative real-time PCR, western blot and immunohistochemistry assays were used to compare the SPI1 expression levels between ccRCC tissues and normal tissues, analyze the relationships between SPI1 and CD68, CD8, CD4 expression levels, and explore the link between SPI1 and the efficacy of immunotherapy in our cohort. Tumor Immune Estimation Resource, UALCAN, cBioPortal, TISIDB database, and LinkedOmics database were used in our study. RESULTS: SPI1 expression level was higher in ccRCC bulk tissues than in normal bulk tissues. SPI1 was an independent prognostic factor for poor overall survival and progression-free survival in patients with ccRCC. SPI1 expression was strongly related to the infiltration of immune cells and immune-related molecules. SPI1 was more highly expressed in tumor-infiltrating immune cells rather than in cancer cells. Non-responders to immunotherapy against ccRCC were more likely to express higher SPI1 levels than responders. Genes co-expressed with SPI1 primarily correlated with immune-related pathways. CONCLUSIONS: SPI1 expression in tumor bulk tissues is associated with disease progression and poor prognosis, as well as high expression levels of immune markers and infiltration of immune cells. SPI1 can be used as a prognostic biomarker to monitor and evaluate immunotherapy efficacy.

Identification of the Immunoglobulin E Epitope of Arginine Kinase, an Important Allergen from Crassostrea angulata.

Arginine kinase (AK) was identified as an allergen in Crassostrea angulata. However, little information is available about its epitopes. In this study, AK from C. angulata was registered to the World Health Organization/International Union of Immunological Societies allergen nomenclature committee to be named as Cra a 2. The immunoglobulin G/immunoglobulin E-binding capacity of Cra a 2 was significantly reduced after chemical denaturation treatment. Further, eight linear mimotopes and five conformational mimotopes of Cra a 2 were obtained using phage panning. In addition to six linear epitopes that have been identified, two linear epitopes were verified by a synthetic peptide, of which L-Cra a 2-2 was conserved in shellfish. Four conformational epitopes were verified by site-directed mutation, among which mutation of C-Cra a 2-1 affected the structure and reduced the immunoreactivity of Cra a 2 most significantly. Overall, the identified epitopes may lay a foundation for the development of hypoallergenic oyster products through food processing.

Corrigendum: Transcriptional progressive patterns from mild to severe renal ischemia/reperfusion-induced kidney injury in mice.

[This corrects the article DOI: 10.3389/fgene.2022.874189.].

Transcriptional progressive patterns from mild to severe renal ischemia/reperfusion-induced kidney injury in mice.

The renal ischemia/reperfusion (I/R)-induced acute kidney injury incidence after nephron-sparing surgery for localized renal tumors is 20%, but the biological determinant process of postoperative acute kidney injury remains unclear. Using Gene Expression Omnibus database (GSE192883) and several bioinformatics analyses (discrete time points analysis, gene set enrichment analysis, dynamic network biomarker analysis, etc), combined with the establishment of the I/R model for verification, we identified three progressive patterns involving five core pathways confirmed using gene set enrichment analysis and six key genes (S100a10, Pcna, Abat, Kmo, Acadm, and Adhfe1) verified using quantitative polymerase chain reaction The dynamic network biomarker (DNB) subnetwork composite index value is the highest in the 22-min ischemia group, suggesting the transcriptome expression level fluctuated sharply in this group, which means 22-min ischemia is an critical warning point. This study illustrates the core molecular progressive patterns from mild to severe I/R kidney injury, laying the foundation for precautionary biomarkers and molecular intervention targets for exploration. In addition, the safe renal artery blocking time of nephron-sparing surgery that we currently accept may not be safe anymore.

FBP1 /miR-24-1/enhancer axis activation blocks renal cell carcinoma progression via Warburg effect.

Warburg effect is a pivotal hallmark of cancers and appears prevalently in renal cell carcinoma (RCC). FBP1 plays a negative role in Warburg effect as a rate-limiting enzyme in gluconeogenesis, yet its mechanism in RCC remains to be further characterized. Herein, we revealed that FBP1 was downregulated in RCC tissue samples and was related to the poor survival rate of RCC. Strikingly, miR-24-1 whose DNA locus is overlapped with enhancer region chr9:95084940-95087024 was closely linked with the depletion of FBP1 in RCC. Of note, miRNAs like miR-24-1 whose DNA loci are enriched with H3K27ac and H3K4me1 modifications are belonging to nuclear activating miRNAs (NamiRNAs), which surprisingly upregulate target genes in RCC through enhancer beyond the conventional role of repressing target gene expression. Moreover, miR-24-1 reactivated the expression of FBP1 to suppress Warburg effect in RCC cells, and subsequently inhibited proliferation and metastasis of RCC cells. In mechanism, the activating role of miR-24-1 was dependent on enhancer integrity by dual luciferase reporter assay and CRISPR/Cas9 system. Ultimately, animal assay in vivo validated the suppressive function of FBP1 on 786-O and ACHN cells. Collectively, the current study highlighted that activation of FBP1 by enhancer-overlapped miR-24-1 is capable of contributing to Warburg effect repression through which RCC progression is robustly blocked, providing an alternative mechanism for RCC development and as well implying a potential clue for RCC treatment strategy.

Characterization, Epitope Identification, and Cross-reactivity Analysis of Tropomyosin: An Important Allergen of Crassostrea angulata.

Oyster is a common shellfish product in China, which is associated with food allergy. However, there is still lack of research on allergens in oysters. In this study, tropomyosin (TM), an important allergen of Crassostrea angulata, was purified and identified by mass spectrometry. Subsequently, TM was cloned and expressed, with a sequence of size 852 bp, encoding 284 amino acid residues. The results of circular dichroism, digestion assay, inhibition enzyme-linked immunosorbent assay, and basophil activation test showed that recombinant TM had similar physicochemical properties and immunological properties to native TM. Furthermore, two conformational mimotopes were obtained and 10 IgE linear epitopes were verified. Meanwhile, different degrees of cross-reactivity were observed between C. angulata TM and the other 8 shellfish TMs using antibodies and serological analysis, which may relate to the 3 conserved epitope regions. These findings are expected to provide a theoretical basis for the molecular diagnosis of oyster allergy and cross-reactivity among shellfish.

A narrative review: The pharmaceutical evolution of phenolic syringaldehyde.

To better understand the pharmacological characters of syringaldehyde (SA), which is a key-odorant compound of whisky and brandy, this review article is the first to compile the published literature for molecular docking that were subsequently validated by in vitro and in vivo assays to predict and develop insights into the medicinal properties of SA in terms of anti-oxidation, anti-inflammation, and anti-diabetes. The molecular docking displayed significantly binding affinity for SA towards tumor necrosis factor-α, interleukin-6, and antioxidant enzymes when inflammation from myocardial infarction and spinal cord ischemia. Moreover, SA nicely docked with dipeptidyl peptidase-IV, glucagon-like peptide 1 receptor, peroxisome proliferator-activated receptor, acetylcholine M2 receptor, and acetylcholinesterase in anti-diabetes investigations. These are associated with (1) an increase glucose utilization and insulin sensitivity to an anti-hyperglycemic effect; and (2) to potentiate intestinal contractility to abolish the α-amylase reaction when concurrently reducing retention time and glucose absorption of the intestinal tract to achieve a glucose-lowering effect. In silico screening of multi-targets concomitantly with preclinical tests could provide a potential exploration for new indications for drug discovery and development.

GTSE1 promotes tumor growth and metastasis by attenuating of KLF4 expression in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors and is characterized by a poor prognosis. Although G2- and S -phase expressed-1 (GTSE1) is known to be involved in the progression and metastasis of various cancers, its significance and mechanism in ccRCC remain unknown. In the present study, we found that GTSE1 was overexpressed in ccRCC tissues, especially in metastatic samples. Moreover, high GTSE1 expression was positively correlated with higher pT stage, tumor size, clinical stage, and WHO/ISUP grade and worse prognosis. And GTSE1 expression served as an independent prognostic factor for overall survival (OS). In addition, GTSE1 knockdown inhibited ccRCC cell proliferation, migration, and invasion, and enhanced cell apoptosis in vitro and in vivo. GTSE1 was crucial for epithelial-mesenchymal transition (EMT) in ccRCC. Mechanistically, GTSE1 depletion could upregulate the expression of Krüppel-like factor 4 (KLF4), which acts as a tumor suppressor in ccRCC. Downregulation of KLF4 effectively rescued the inhibitory effect induced by GTSE1 knockdown and reversed the EMT process. Overall, our results revealed that GTSE1 served as an oncogene regulating EMT through KLF4 in ccRCC, and that GTSE1 could also serve as a novel prognostic biomarker and may represent a promising therapeutic target for ccRCC.

Next-Generation Sequencing-Based Analysis of Urine Cell-Free mtDNA Reveals Aberrant Fragmentation and Mutation Profile in Cancer Patients.

BACKGROUND: Many studies have demonstrated the high efficacy of cell-free nuclear DNA in cancer diagnostics. Compared to nuclear DNA, mitochondrial DNA (mtDNA) exhibits distinct characteristics, including multiple copies per cell and higher mutation frequency. However, the potential applicability of cell-free mtDNA (cf-mtDNA) in plasma and urine remains poorly investigated. METHODS: Here, we comprehensively analyzed the fragmentomic and mutational characteristics of cf-mtDNA in urine and plasma samples from controls and cancer patients using next-generation sequencing. RESULTS: Compared to plasma cf-mtDNA, urine cf-mtDNA exhibited increased copy numbers and wider spread in fragment size distributions. Based on 2 independent animal models, urine cf-mtDNA originated predominantly from local shedding and transrenal excretion. Further analysis indicated an enhanced fragmentation of urine cf-mtDNA in renal cell carcinoma (RCC) and colorectal cancer (CRC) patients. Using the mtDNA sequence of peripheral blood mononuclear cells for reference, the mutant fragments were shorter than wild-type fragments in urine cf-mtDNA. Size selection of short urine cf-mtDNA fragments (<150 bp) significantly enhanced the somatic mutation detection. Our data revealed remarkably different base proportions of fragment ends between urine and plasma cf-mtDNA that also were associated with fragment size. Moreover, both RCC and CRC patients exhibited significantly higher T-end and lower A-end proportions in urine cf-mtDNA than controls. By integrating the fragmentomic and mutational features of urine cf-mtDNA, our nomogram model exhibited a robust efficacy for cancer diagnosis. CONCLUSIONS: Our proof-of-concept findings revealed aberrant fragmentation and mutation profiles of urine cf-mtDNA in cancer patients that have diagnostic potential.

Analysis of Immunoreactivity of α/α2-Tropomyosin from Haliotis discus hannai, Based on IgE Epitopes and Structural Characteristics.

Tropomyosin (TM) was reported to be a supercoil allergen of shellfish. However, little information is available about its link between structure and allergenicity. In this study, the subunit of TM (α-TM) and supercoil of TM (α2-TM) were identified from Haliotis discus hannai. α2-TM showed higher immunoreactivity than α-TM. Meanwhile, seven linear epitopes in α-TM and α2-TM were verified, and two conformational epitopes in α2-TM were predicted. The physicochemical properties and chemical bond assays confirmed the existence of the disulfide bond in α2-TM. According to spectroscopy and hydrophobicity analysis, α-TM showed higher α-helix features and blueshift of the fluorescence intensity peak compared with those of α2-TM. The structure analysis revealed the possibility of conformational epitopes in α2-TM, which could explain the immunoreactivity differences between α-TM and α2-TM further. These results improved the understanding of Haliotis discus hannai TM, which lay the foundation for the food processing of abalone.

Identification and characterization of Crassostrea angulata arginine kinase, a novel allergen that causes cross-reactivity among shellfish.

Oyster is a common food that causes allergy. However, little information is available about its allergens and cross-reactivity. In this study, arginine kinase (AK) was identified as a novel allergen in Crassostrea angulata. The primary sequence of AK was cloned which encoded 350 amino acids, and recombinant AK (rAK) was obtained. The immunodot results, secondary structure and digestive stability showed that native AK and rAK had similar IgG/IgE-binding activity and physicochemical properties. Serological analysis of 14 oyster-sensitive individuals demonstrated that AK exhibited cross-reactivity among oysters, shrimps, and crabs. Furthermore, nine epitopes in oyster AK were verified using inhibition dot blots and inhibition enzyme linked immunosorbent assay, six of which were similar to the epitopes of shrimp/crab AK. The most conserved epitopes were P5 (121-133) and P6 (133-146), which may be responsible for the cross-reactivity caused by AK. These findings will provide a deeper understanding of oyster allergens and cross-reactivity among shellfish.

Linear Epitopes Play an Important Role in the Immunoglobulin G (IgG)/Immunoglobulin E (IgE)-Binding Capacity of Scy p 4.

Sarcoplasmic calcium-binding protein is a stable allergen in Scylla paramamosain and named Scy p 4. To explore the importance of linear epitopes in the immunoglobulin G (IgG)/immunoglobulin E (IgE)-binding capacity of Scy p 4, chemical denaturants were used to destroy the structure. Scy p 4 was reduced with dithiothreitol and subsequently alkylated with iodoacetamide (IAA). Furthermore, the structural analysis indicated that IAA-Scy p 4 was an unstructured protein. The inhibition enzyme-linked immunosorbent assay showed that IAA-Scy p 4 could inhibit the binding of Scy p 4 to sensitize serum, with inhibition rates reached 55%. Moreover, the linear mimotopes of Scy p 4 were predicted in silico. Three linear epitopes were verified by serological tests and named L-Scy p 4-1 (AA76-91), L-Scy p 4-2 (AA111-125), and L-Scy p 4-3 (AA137-146). Overall, these data provide an understanding of the relationship between the structure and allergenicity about Scy p 4, and the identified linear epitopes can be used for diagnosis and food processing of shellfish allergy.

A nutraceutical combination of cinnamon, purple onion, and tea linked with key enzymes on treatment of type 2 diabetes.

Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause adverse effects. This study was to explore the efficacy of polyherbal dietary supplement cinnamon, purple onion, and tea on the mediation of postprandial hyperglycemia in the search of combinations with a maximal response. A starch solution (3 g/kg Bwt) of oral starch tolerance test (OSTT) and glucose solution (4 g/kg Bwt) of oral glucose tolerance test (OGTT) with and without cinnamon, purple onion, tea extract (15 mg/kg Bwt), and mixture (each 5 mg/kg Bwt, 1:1:1), metformin (14 mg/kg Bwt), or acarbose (50 mg/kg Bwt) was administered to high fat plus high fructose-induced diabetic mice after an overnight fast. Postprandial plasma glucose levels were measured and changed areas under the response curve were calculated to find out the maximal efficacy of optimal polyherbal combinations. Compared with acarbose, the mixture of extracts (purple onion, cinnamon, and tea) indicated the decreasing blood glucose in OSTT. In OGTT, the mixture of extracts showed greater efficacy for hypoglycemia when compared with metformin. The molecular docking of α-amylase, α-glucosidase, and AMPK was further confirmed the putatively acting molecules from the extracts of purple onion, cinnamon, and tea. Overall, this investigation evidenced a beneficial mediation for the progression of lowering blood glucose with a combinatory extract of cinnamon, dietary onion, and tea, implicating their prospective as nutraceuticals that might ameliorate hyperglycemia in diabetes. PRACTICAL APPLICATIONS: Diabetes mellitus (DM), one of metabolic syndrome, attributes to risk factors like obesity, physical inactivity, ageing, life style, and genetic predisposition even with significant morbidity and mortality. DM is increasing and accounts for an estimated annual medical expenditure of US$ 827 billion worldwide. Therefore, maintaining blood glucose levels within the normal range is critical for preventing diabetes and its co-morbidities. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; nevertheless, they may also cause adverse or side effects. In an effort to design novel and well-tolerated solutions to halt the progression of DM, however evidence-base is extremely limited regarding the efficacy of polyherbal dietary supplement individual herbs for the management of glycemia. In this investigation evidenced a beneficial mediation for the progression of lowering blood glucose with a combinatory extract of cinnamon, dietary onion, and tea, implicating their prospective as nutraceuticals that might ameliorate hyperglycemia in diabetes.