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1.
Ecol Evol ; 14(7): e11627, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952653

RESUMO

Melanism, the process of heavier melanin deposition, can interact with climate variation at both micro and macro scales, ultimately influencing color evolution in organisms. While the ecological processes regulating melanin production in relation to climate have been extensively studied, intraspecific variations of melanism are seldom considered. Such scientific gap hampers our understanding of how species adapt to rapidly changing climates. For example, dark coloration may lead to higher heat absorption and be advantageous in cool climates, but also in hot environments as a UV or antimicrobial protection mechanism. To disentangle such opposing predictions, here we examined the effect of climate on shaping melanism variation in 150 barred grass snakes (Natrix helvetica) and 383 green whip snakes (Hierophis viridiflavus) across Italy. By utilizing melanistic morphs (charcoal and picturata in N. helvetica, charcoal and abundistic in H. viridiflavus) and compiling observations from 2002 to 2021, we predicted that charcoal morphs in H. viridiflavus would optimize heat absorption in cold environments, while offering protection from excessive UV radiation in N. helvetica within warm habitats; whereas picturata and abundistic morphs would thrive in humid environments, which naturally have a denser vegetation and wetter substrates producing darker ambient light, thus providing concealment advantages. While picturata and abundistic morphs did not align with our initial humidity expectations, the charcoal morph in N. helvetica is associated with UV environments, suggesting protection mechanisms against damaging solar radiation. H. viridiflavus is associated with high precipitations, which might offer antimicrobial protection. Overall, our results provide insights into the correlations between melanin-based color morphs and climate variables in snake populations. While suggestive of potential adaptive responses, future research should delve deeper into the underlying mechanisms regulating this relationship.

2.
Front Endocrinol (Lausanne) ; 15: 1289923, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978630

RESUMO

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear. Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference. Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference. Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment.


Assuntos
Autoanticorpos , Hipotireoidismo , Tireotropina , Humanos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Tireotropina/sangue , Tireotropina/imunologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Hipotireoidismo/diagnóstico , Hipotireoidismo/imunologia , Hipotireoidismo/sangue , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/sangue , Tireoidite Autoimune/diagnóstico , Testes de Função Tireóidea , Idoso , Imunoensaio/métodos , Ensaio de Radioimunoprecipitação
3.
J Environ Manage ; 366: 121722, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38991346

RESUMO

The breeding of livestock raises substantial environmental concerns, especially the efficient management of nutrients and pollution. This research is designed to assess the potency of char and modified char in diluting nutrient concentrations in livestock wastewater. The characteristics of graphene oxide, struvite, and calcium-modified char were inspected, defining their efficacy in both batch and bed-column investigations of nutrient sorption. Various factors, including sorption capacity, time of contact, ion levels, a decrease in ion levels over time, and sorption kinetics, have been considered, along with their appropriateness for respective models. The first evaluation of the options concluded that 600 °C char was better since it exhibited higher removal efficiency. Modified char sorption data at 600 °C was used to adjust the models "PSOM, Langmuir", and "Thomas". The models were applied to both batch and bed-column experiments. The maximum phosphate sorption was 110.8 mg/g, 85.73 mg/g, and 82.46 mg/g for B-GO, B-S, and B-C modified chars respectively, in the batch experiments. The highest phosphate sorption in column experiments, at a flow rate of 400 µl/min, was 51.23 mg per 10 g of sorbent. This corresponds to a sorption rate of 5.123 mg/g. B-GO and B-S modified chars showed higher sorption capacities; this was observed in both the batch and bed-column studies. This displayed the capability of graphene oxide and struvite-modified chars for efficient ion and nutrient uptake, whether in single or multi-ion environments, making them a very good candidate for nutrient filtration in livestock wastewater treatment. Additionally, B-GO char enhanced the sorption of phosphate, resulting in augmented seed germination and seedling growth. These results reveal that B-GO char can be used as a possible substitute for chemical fertilizers.

4.
Artigo em Francês | MEDLINE | ID: mdl-38997852

RESUMO

Macro-amputations are extremely serious traumas and represent one of the rare extreme emergencies in hand and upper limb surgery. Their rarity, especially in our developed countries, makes their treatment relatively unknown by surgical and anesthetic teams. However, the action plan to use during a macro-reimplantation, the decisive elements of pre- and post-operative management, and the key stages of the surgery, must be perfectly known, because they determine the success of a major reimplantation, for the limb survival and the future functional result. After a brief historical overview, the literature review proposed here provides an opportunity for an update on these formidable injuries and propose a treatment algorithm to guide the medical team in the management of these complex patients.

5.
J Exp Clin Cancer Res ; 43(1): 198, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39020414

RESUMO

Pancreatic cancer (PC) is a clinically challenging tumor to combat due to its advanced stage at diagnosis as well as its resistance to currently available therapies. The absence of early symptoms and known detectable biomarkers renders this disease incredibly difficult to detect/manage. Recent advances in the understanding of PC biology have highlighted the importance of cancer-immune cell interactions, not only in the tumor micro-environment but also in distant systemic sites, like the bone marrow, spleen and circulating immune cells, the so-called macro-environment. The response of the macro-environment is emerging as a determining factor in tumor development by contributing to the formation of an increasingly immunogenic micro-environment promoting tumor homeostasis and progression. We will summarize the key events associated with the feedback loop between the tumor immune micro-environment (TIME) and the tumor immune macroenvironment (TIMaE) in pancreatic precancerous lesions along with how it regulates disease development and progression. In addition, liquid biopsy biomarkers capable of diagnosing PC at an early stage of onset will also be discussed. A clearer understanding of the early crosstalk between micro-environment and macro-environment could contribute to identifying new molecular therapeutic targets and biomarkers, consequently improving early PC diagnosis and treatment.


Assuntos
Biomarcadores Tumorais , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/metabolismo , Biomarcadores Tumorais/sangue , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/sangue , Progressão da Doença
6.
New Solut ; : 10482911241260404, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042914

RESUMO

In 1987 Landrigan and Markowitz co-authored a report entitled "Occupational Disease in New York State." They found that death and illness from occupational disease were common and that the costs of exposure to hazardous conditions warranted public funding for new occupational health infrastructure in New York State. A recent confirmatory report recognized a wider spectrum of contemporary hazards and emphasized how public health problems connect to work. These reports provide factual snapshots at 2 points in time, but they do not explain nor analyze the changing conditions they describe. Including macro-contexts such as globalization, financialization, and neoliberalism, this article demonstrates several unique occupational safety and health implications by clarifying key themes related to the state's role, especially regulation and healthcare delivery systems. Conclusions directly tie the trajectory of occupational disease to workers' collective ability to confront and roll back neoliberalism while pushing occupational disease out of its medical/science silo.

8.
Materials (Basel) ; 17(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998246

RESUMO

Steel slag is an industrial solid waste, which can provide a new calcium source for microbial mineralization as it contains abundant calcium elements. This study treated cemented backfill material with microorganisms and steel slag to enhance its performance. The influence of microbial treatment on the strength, microstructure, and pore characteristics of the backfill was assessed using a strength test, nuclear magnetic resonance, scanning electron microscopy, and X-ray diffraction. The results indicate that (1) the microbial mineralization and the hydration reaction take place at the same time; (2) when the proportion of bacterial solution exceeded 50%, microorganisms excessively consumed Ca2+, which hindered the following hydration reaction; (3) the additional amount of bacterial solution added into the steel-slag-based cemented backfill material should be less than 50%, which increases the strength by up to 22.10%; (4) the excessive bacterial solution sharply reduces the strength of the backfill even by 21.41%; and (5) the addition of bacterial solution affects the pore characteristics. A 50% bacterial solution can make backfill reach its lowest porosity. The strength has an inversely proportional relationship with porosity, diameter, and roundness (σ = ax + b, a < 0).

9.
Molecules ; 29(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38999018

RESUMO

After the period of halogenated compounds, the period of nano-structured systems, and that of phosphorus (and nitrogen)-based additives (still in progress), following the increasingly demanding circular economy concept, about ten years ago the textile flame retardant world started experiencing the design and exploitation of bio-sourced products. Indeed, since the demonstration of the potential of such bio(macro)molecules as whey proteins, milk proteins (i.e., caseins), and nucleic acids as effective flame retardants, both natural and synthetic fibers and fabrics can take advantage of the availability of several low-environmental impact/"green" compounds, often recovered from wastes or by-products, which contain all the elements that typically compose standard flame-retardant recipes. The so-treated textiles often exhibit flame-retardant features that are similar to those provided by conventional fireproof treatments. Further, the possibility of using the same deposition techniques already available in the textile industry makes these products very appealing, considering that the application methods usually do not require hazardous or toxic chemicals. This review aims to present an overview of the development of bio-sourced flame retardants, focusing attention on the latest research outcomes, and finally discussing some current challenging issues related to their efficient application, paving the way toward further future implementations.

10.
PeerJ ; 12: e17511, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006019

RESUMO

Background: Capsicum chinense Jacq. (Ghost Pepper) is well-known for its high pungency and pleasant aroma. The recent years witnessed a significant decline in popularity of this important crop due to the use of inferior planting material and lack of elite lines. To maintain constant performance across a variety of settings, it is crucial to choose stable lines with high yield and capsaicin content, as these are the most promising traits of Ghost Pepper. Method: In this study, 120 high-capsaicin genotypes were subjected to a 3-year (kharif 2017, 2018 and 2019) stability investigation utilizing two well-known stability methods: Eberhart-Russell (ER) and additive main effects and multiple interaction (AMMI). Three replications were used following Randomized Complete Block Design for 11 traits. The experiment soil was sandy loam with pH 4.9. Minimum and maximum temperature of 18.5 °C, 17.5 °C, 17.4 °C and 32.2 °C, 31.3 °C, 32.7 °C and rainfall of 1,781, 2,099, 1,972 mm respectively was recorded for the study period. Result: The genotype-environment linear interaction (G×E Lin.) was highly significant for days to 50% flowering, capsaicin content, fruit length and girth, fruit yield per plant and number of fruits per plant at p < 0.005. G×E interaction for fruit yield and capsaicin content in AMMI-analysis of variance reported 67.07% and 71.51% contribution by IPCA-1 (interactive principal component axis) and 32.76% and 28.49% by IPCA-2, respectively. Eight genotypes were identified to be stable with high yield and capsaicin content. The identified stable lines can be opted for cultivation to reduce the impact of crop failure when grown in different macro-environments. Moreover, the pharmaceutical and spice sectors will also be benefitted from the lines with high capsaicin content. Further research assessing the lines' performance across various regions of India can provide a solid foundation for the crop's evaluation at national level.


Assuntos
Capsaicina , Capsicum , Frutas , Genótipo , Capsicum/crescimento & desenvolvimento , Capsicum/genética , Capsicum/química , Capsicum/metabolismo , Capsaicina/metabolismo , Capsaicina/análise , Frutas/crescimento & desenvolvimento , Frutas/química , Frutas/genética , Frutas/metabolismo , Interação Gene-Ambiente
11.
ISA Trans ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39034232

RESUMO

In this paper, for macro-micro composite motion platform with piezoelectric hysteresis, an finite-time adaptive robust control method based on extended hysteresis observer is proposed. The dynamic model of macro-micro system is constructed at first. An extended hysteresis observer was designed to estimate the actual displacement and speed of motion system. Then, an adaptive robust control law is designed to eliminate the uncertain hysteresis model parameters. After this, exponential convergence result of the proposed control method is given and proved. By setting the expected bandwidth of macro-micro system, the gain adjustment process of the control method can be reduced in computation. The effectiveness of the proposed control method is demonstrated by comparison with other control methods in simulation, and the proposed control method has more stable tracking effect and smaller tracking error.

12.
Adv Mater ; : e2407138, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38887139

RESUMO

MXene aerogels, known for good electrical properties, offer immense potential for the development of high-sensitivity pressure sensors. However, the intrinsic challenges stemming from the poor self-assembly capability and high hydrophilicity of MXene impedes the natural drying process of MXene-based hydrogels, thereby constraining their application on a large-sacle in sensor technology. Herein, we propose a graphene-assisted approach aimed at modulating the hydrophobicity and enhancing framework strength of MXene through a well-designed prefreezing technique incorporating three-dimensional (3D) spherical macro-porous structures. This synergistic strategy enables the fabrication of naturally dried MXene aerogels across various size scales. Moreover, the integration of 3D spherical macro-porous structures improves elasticity and electrical responsiveness of aerogels. Consequently, the aerogel sensor exhibits great performances, including high sensitivity (1250 KPa-1), low detection limit (0.4 Pa), wide frequency response range (0.1-8 Hz), and excellent stability (1000 cycles). This sensor proves adept at monitoring pressure signals ranging from lightweight paper to human motion. Additionally, the application of customized laser engraving endows aerogels with unique functionalities, such as compressibility and immunity to strain, stretchability and resistance to compression, as well as wind detection. Thus, our proposed approach holds significant promise as a scalable method for the mass production of aerogels with versatile applications. This article is protected by copyright. All rights reserved.

13.
Biol Trace Elem Res ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877165

RESUMO

In the presented study, 15 tropical and subtropical fruits were studied for their mineral composition ranging from trace to major elements by ICP-OES after microwave digestion. The moisture amounts were assigned to be between 21.90 (tamarind) and 95.66% (pepino). The differences between the macroelement quantities of the fruits were established to be statistically significant (p<0.01). P and K quantities of fruits were displayed to be between 53.40 (pepino) and 927.74 mg/kg (tamarind) to 720.27 (pepino) and 13441.12 mg/kg (tamarind), respectively. While Ca quantities of fruits vary between 123.71 (pineapple) and 1519.76 mg/kg (blood orange), Mg quantities of fruits were established to be between 78.66 (pepino) and 875.02 mg/kg (tamarind). In general, the lowest macroelement quantities were determined in pepino fruit, but the highest P and K contents were determined in Gooseberry and Tamarind fruits, respectively. The microelement amounts of the fruits were established to be at very low levels compared to the macroelement contents. In general, the most abundant element in fruits was Fe, followed by Zn, Cu, Mn and B in decreasing order. In general, heavy metal quantities of fruits were detected at very low levels (except As and Ba). As and Ba quantities of fruits were assigned to be between 0.972 µg/g (mandarin) and 5.86 (kiwi) to 0.103 (pineapple) and 4.08 (avocado), respectively. As with macro and microelements, results regarding heavy metal concentrations varied depending on fruit types.

14.
Nutrients ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892644

RESUMO

This scoping review aims to investigate longitudinal changes in minerals and vitamins concentrations in human milk among the Chinese population. Following the PRISMA-ScR guidelines, a comprehensive and systematic literature search was conducted using both English and Chinese databases. Data were extracted and categorized into six defined lactation stages. We found that the concentration of most minerals decreased throughout the lactation period, although calcium (Ca) and magnesium (Mg) fluctuated slightly across lactation periods. Fat-soluble vitamins also showed a decline throughout the lactation period, while water-soluble vitamins exhibited an increasing trend. However, folic acid, biotin, and pantothenic acid demonstrated a downward trend. Overall, this review has identified the longitudinal changes in minerals and vitamins concentrations in human milk among the Chinese population. In order to conduct a more in-depth examination of maternal characteristics and nutritional factors of the composition of human milk, it is recommended to utilize standardized protocols for the collection and analysis of human milk samples.


Assuntos
Lactação , Leite Humano , Minerais , Vitaminas , Humanos , Leite Humano/química , Feminino , Minerais/análise , Vitaminas/análise , China , Estudos Longitudinais , Povo Asiático , Adulto , População do Leste Asiático
15.
Int J Med Robot ; 20(4): e2654, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38941214

RESUMO

BACKGROUND: The method of stem cell transfer to narrow cochlear canals in vivo to generate hair cells is still an unclear operation. Thus, the development of any possible method that will ensure the usage of medical microrobots in small cochlear workspaces is a challenging procedure. METHODS: The current study tries to introduce a macro-micro manipulator system composed of a 6-DoF industrial serial manipulator as a macro manipulator and a proposed 5-DoF parallel manipulator with dual end effectors as a micro manipulator carrying permanent magnets for tetherless microrobot actuation inside the cochlea. RESULTS: Throughout the study, structural synthesis and kinematic analysis of the proposed micro manipulator were introduced. A prototype of the manipulator was manufactured and its hardware verification procedures were carried out using motion capture cameras and surgical navigation registration methodologies. CONCLUSIONS: Following motion training, the assembled macro-micro manipulator was successfully utilised to actuate a microrobot placed inside a manufactured cochlea mockup model.


Assuntos
Cóclea , Desenho de Equipamento , Procedimentos Cirúrgicos Robóticos , Cóclea/cirurgia , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Movimento (Física) , Implante Coclear/métodos , Implante Coclear/instrumentação , Cirurgia Assistida por Computador/instrumentação , Cirurgia Assistida por Computador/métodos , Fenômenos Biomecânicos
16.
Materials (Basel) ; 17(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38930401

RESUMO

In nature, lakes and water channels offer abundant underwater energy sources. However, effectively harnessing these green and sustainable underwater energy sources is challenging due to their low flow velocities. Here, we propose an underwater energy-harvesting system based on a cylindrical bluff body and a cantilever beam composed of a macro fiber composite (MFC), taking advantage of the MFC's low-frequency, lightweight, and high piezoelectric properties to achieve energy harvesting in low-frequency and low-speed water flows. When a water flow impacts the cylindrical bluff body, it generates vibration-enhanced and low-frequency vortices behind the bluff body. The optimized diameter of the bluff body and the distance between the bluff body and the MFC were determined using finite element analysis software, specifically COMSOL. According to the simulation results, an energy-harvesting system based on an MFC cantilever beam applied in a low-frequency and low-speed water flow was designed and prepared. When the diameter of the bluff body was 25 mm, and the distance between the bluff body and MFC was 10 mm and the maximum output voltage was 22.73 V; the power density could reach 0.55 mW/cm2 after matching the appropriate load. The simulation results and experimental findings of this study provide valuable references for designing and investigating energy-harvesting systems applied in low-frequency and low-speed water flows.

17.
Water Res ; 259: 121850, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38851109

RESUMO

Iron (Fe0, Fe (II), and Fe (III)) has been previously documented to upregulate the expression of key genes, enhancing the production of volatile fatty acids (VFAs) to achieve waste/wastewater resource recovery. However, the precise mechanism by why iron influences gene expression remains unclear. This study applied iron-assisted fermentation systems to explore the behind enhancing mechanism by constructing regulon networks among genes, microbes, and transcription factors. In iron-conditioned systems, a significant enhancement in VFAs production and upregulation of genes expression (1.19-3.92 folds) related to organic conversion and the electron transfer chain was observed. Besides, gene co-expression network and Procrustes analysis identified ten hub transcription factors (e.g., arsR, crp, iscR, perR) and their major contributors (genus) (e.g., Paludibacter, Acinetobacter, Tolumonas). Further analysis suggested that most of hub transcription factors were implicated in iron homeostasis regulation, which speculated that the induced iron homeostasis transcription factors probably effectively regulated the expression of genes encoding enzymes involving in VFAs production and electron transfer of functional microbes, in the case of Paludibacter, Acinetobacter, and Tolumonas while regulating the iron homeostasis, resulting in the efficient production of VFAs in iron-conditioned systems. This study might contribute to an enhanced understanding of the underlying genetic mechanisms by why iron influences gene expression regulation of microbes, which also provides a genetic theoretical basis for improving system VFAs production and resource recovery.


Assuntos
Ácidos Graxos Voláteis , Fermentação , Ferro , Fatores de Transcrição , Ferro/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Ácidos Graxos Voláteis/metabolismo , Homeostase , Regulação Bacteriana da Expressão Gênica , Bactérias/metabolismo , Bactérias/genética
18.
Ann Clin Biochem ; : 45632241262920, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906861

RESUMO

Immunoassays are widely used for laboratory assessment of endocrine functions including thyroid hormones. While usually adequate for patient evaluation, they are known to potentially suffer from interference from a variety of factors. We report the case of a 44 year-old male patient without clinical symptoms of thyroid disease who presented for specialist evaluation after pathological thyroid function tests prompted a transferal by his primary care practitioner. Thyroid function tests showed discrepant results across immunoassays and platforms of different manufacturers. Polyethylene glycol precipitation prompted the diagnosis of macro-thyroid-stimulating hormone, while heterophilic and non-specific antibody blocking reagents proved ineffective in eliminating the interference in thyroid-stimulating hormone, free triiodothyronine and free thyroxine measurements. Further assessment ruled out a diagnosis of familial dysalbuminemic hyperthyroxinemia, leaving an exclusion diagnosis of manufacturer-specific interference in free triiodothyronine and free thyroxine assays due to unknown factors. Both clinicians and laboratory specialists must be aware of potential interference in immunoassays which otherwise might be misleading, potentially triggering unnecessary (invasive) follow-up procedures or therapeutic interventions. Close communication is required for successful troubleshooting. To our knowledge, no other case of both macro-thyroid-stimulating hormone and manufacturer-specific interference in a single patient has been documented thus far.

20.
Phytomedicine ; 132: 155329, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38853123

RESUMO

BACKGROUND: Currently, there are many drugs available for the treatment of type 2 diabetes mellitus (T2DM), but most of them cause various side effects due to the need for long-term use. As a traditional Chinese medicine, Gegen Qinlian Decoction (GQD) has shown good efficacy and low side effects in the treatment of T2DM in both clinical and basic research. Based on relevant traditional Chinese medicine theories, dried ginger is innovatively added the formula of traditional GQD to create a modified GQD. This modification reduces the side effects of traditional GQD while exerting its therapeutic effect on T2DM. Previous studies have found that the modified GQD can regulate endoplasmic reticulum stress in the liver, inhibit hepatic gluconeogenesis, protect pancreatic islet ß cells, and control blood sugar levels by inhibiting the FXR/neuronal ceramide signaling pathway. GQD can also regulate the intestinal microbiota to achieve therapeutic and protective effects in various gastrointestinal diseases. However, there is no research exploring whether the modified GQD achieves its therapeutic mechanism for T2DM by regulating the intestinal microbiota. PURPOSE: To explore the mechanism of modified GQD in the treatment of T2DM based on multi-omics, focusing on its effect on the "intestinal flora bile acid TGR5'' axis. METHODS: The T2DM model was established using db/db mice, which were randomly divided into a model group, metformin group, high-dose GQD group, medium-dose GQD group, low-dose GQD group, while m/m mice were used as blank control. The drug intervention lasted for 12 weeks, during which the general conditions, oral glucose tolerance (OGT), blood glucose, and lipid-related indexes were recorded. Additionally, the fasting insulin (FINS), c-peptide, GLP-1 in serum, and cAMP in the ileum were measured by ELISA assay. Furthermore, the composition, abundance, and function of the intestinal microbiota were determined by macro genome sequencing, while bile acid was detected by targeted metabonomics. For histological evaluation, HE staining was used to observe the pathological changes of the ileum and pancreas, and the ultrastructure of the ileum and pancreas was observed by transmission electron microscopy. Apoptosis in the ileum tissue was detected by Tunel staining. Moreover, the mRNA and protein expressions of TGR5, PKA, CREB, PC1/3, GLP-1, and their phosphorylation levels in the ileum were detected by qPCR, immunohistochemistry, and Western blot; The expression of INS in the pancreas was also evaluated using immunohistochemistry. Finally, double immunofluorescence staining was used to detect the co-localization expression of TGR5 and GLP-1, NeuroD1, and GLP-1 in the ileum. RESULTS: The modified GQD was found to significantly reduce blood glucose, improve oral glucose tolerance, and blood lipid levels, as well as alleviate the injury of the ileum and pancreas in T2DM mice. Furthermore, modified GQD was found to effectively regulate intestinal flora, improve bile acid metabolism, activate the TRG5/cAMP/PKA/CREB signal pathway, and stimulate GLP-1 secretion. CONCLUSION: GQD can regulate the "intestinal flora-bile acid-TGR5" axis and has a therapeutic effect on T2DM in mice.

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