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Perilla leaf oil (PLO) is a global premium vegetable oil with abundant nutrients and substantial economic value, rendering it susceptible to potential adulteration by unscrupulous entrepreneurs. The addition of cinnamon oil (CO) is one of the main adulteration avenues for illegal PLOs. In this study, new and real-time ambient mass spectrometric methods were developed to detect CO adulteration in PLO. First, atmospheric solids analysis probe tandem mass spectrometry combined with principal component analysis and principal component analysis-linear discriminant analysis was employed to differentiate between authentic and adulterated PLO. Then, a spectral library was established for the instantaneous matching of cinnamaldehyde in the samples. Finally, the results were verified using the SRM mode of ASAP-MS/MS. Within 3 min, the three methods successfully identified CO adulteration in PLO at concentrations as low as 5% v/v with 100% accuracy. The proposed strategy was successfully applied to the fraud detection of CO in PLO.

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JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

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JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

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This study aimed to investigate the chemical structure and prebiotic activity of a Dictyophora indusiata polysaccharide fraction DIP0p. Our results indicated that DIP0p belongs to a heteropolysaccharide composed of glucose, galactose, mannose and xylose, accounting for 53.25 %, 24.18 %, 19.19 % and 3.37 %, respectively. Methylation and NMR results suggested that the main glycosidic bonds of DIP0p is →3)-Glcp-(1 â†’ with →4)-Glcp-(1→, →3,4)-Glcp-(1→, →3,4)-Galp-(1 â†’ and →6)-Manp-(1 â†’ branches. In addition, DIP0p increased the abundance of benificial bacteria during the in vitro fecal fermentation, including Phascolarctobacterium, Parabacteroides and Bifidobacterium. It is remarkable that DIP0p improved the level of acetic acid, propionic acid, and butyric acid of the fermentation system, which were 1.31, 1.52, and 2.64 folds higher than the Controls, respectively. In summary, this study comprehensively analyzed the structure and probiotic activity of DIP0p, which providing a theoretical basis for the development of the functional foods.

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Restoring submerged plants naturally has been a significant challenge in water ecology restoration programs. Some silicate-based mineral materials have shown promise in improving the substrate properties for plant growth. While it is well-established that silicate mineral materials enhance submerged plant growth by improving salt release and reducing salt stress, the influence of rhizosphere microorganisms on phytohormone synthesis and key enzyme activities has been underestimated. This study focused on two typical silicate mineral materials, bentonite and maifanite, to investigate their effects on Myriophyllum oguraense from both plant physiology and microbiome perspectives. The results demonstrated that both bentonite and maifanite regulated the synthesis of phytohormones such as gibberellin (GA) and methyl salicylate (MESA), leading to inhibition of cellular senescence and promotion of cell division. Moreover, these silicate mineral materials enhanced the activity of antioxidant enzymes, thereby reducing intracellular reactive oxygen species levels. They also optimized the structure of rhizosphere microbial communities, increasing the proportion of functional microorganisms like Nitrospirota and Sva0485, which indirectly influenced plant metabolism. Analysis of sediment physicochemical properties revealed increased rare earth elements, macronutrients, and oxygen content in pore water in the presence of silicate materials, creating favorable conditions for root growth. Overall, these findings shed light on the multifaceted mechanisms by which natural silicate mineral materials promote the growth of aquatic plants, offering a promising solution for restoring aquatic vegetation in eutrophic lake sediments.

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Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) activity, which shiftes intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases the proportion of interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.

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Marine organisms represent promising bioactive peptide resources with diverse biological activities such as antioxidant, antimicrobial, antihypertensive, anti-fatigue, and immunoregulatory activities. Despite many studies on marine bioactive peptides, there is a dearth of comprehensive review articles on the emerging trends that encompass the production techniques and the biological applications of marine bioactive peptides. In this review, we summarize the major research and findings related to marine bioactive peptides, encompassing aspects of their production, purification, biological activities, nanotechnology-based strategies, and their potential applications. Enzymatic hydrolysis currently stands out as the most commonly used method for producing marine bioactive peptides; the downstream purification process often includes a combination of multiple purification techniques. Due to their diverse biological properties, marine peptides have garnered considerable interest for industrial applications as active ingredients in the food, pharmaceutical, and cosmetics industries. Additionally, the incorporation of encapsulation strategies such as nano emulsion, nanoliposome, and microemulsions holds promise for significantly enhancing the bioavailability and bioactivity of marine peptides. Future research should also prioritize the systematic identification and validation of the potential health benefits of marine peptides by both in vitro and in vivo animal models, along with the conduct of human clinical trials.

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There is an increasing need for determining 3D structures of DNAs, e.g., for increasing the efficiency of DNA aptamer selection. Recently, we have proposed a computational method of 3D structure prediction of DNAs, called 3dDNA, which has been integrated into our original web server 3dRNA, now renamed 3dRNA/DNA (http://biophy.hust.edu.cn/new/3dRNA). Currently, 3dDNA can only output the predicted DNA 3D structures for users but cannot rank them as an energy function for assessing DNA 3D structures is still lacking. Here, we first provide a brief introduction to 3dDNA and then introduce a new energy function, 3dDNAscore, for the assessment of DNA 3D structures. 3dDNAscore is an all-atom knowledge-based potential by integrating 86 atomic types from nucleic acids. Benchmarks demonstrate that 3dDNAscore can effectively identify near-native structures from the decoys generated by 3dDNA, thus enhancing the completeness of 3dDNA.

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An unprecedented eco-friendly multi-component domino reaction for the synthesis of novel N,O-acetals is reported. The protocol involves sequential coupling, [1,5]-hydride transfer and hetero-Diels-Alder cyclization. This new strategy enables direct α,ß-difunctionalization of cyclic amines utilizing enamines generated in situ. The methodology features high atom and step economy, excellent regioselectivity, a simple work-up procedure and molecular diversity.

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INTRODUCTION: This study investigates the effects of varying nicotine doses and administration frequencies on mouse body weight, adipose tissues, and liver. METHODS: Male C57BL6/J mice received subcutaneous nicotine doses (0.5mg/kg, 1mg/kg, or 2mg/kg) once daily (qd), twice daily (bid), or four times daily (qid) for 4 weeks. Body weight, inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT), brown adipose tissue (BAT) weight and size, and UCP1 expression were assessed, along with liver fat deposition and morphology. RESULTS: Nicotine administration reduced body weight and decreased the weight and size of iWAT and eWAT compared to controls. The frequency of nicotine administration had a more significant impact on body weight and fat tissues than the dosage itself, with 2mg/kg bid being optimal for weight reduction. Nicotine increased BAT cell numbers and amplified UCP1 expression in iWAT and BAT. It had minor effects on eWAT UCP1 expression and no substantial impact on liver fat deposition or morphology, except for a reduction in liver weight with doses exceeding 4mg/kg. CONCLUSIONS: Nicotine-induced weight reduction is frequency-dependent, with 2mg/kg bid being the optimal regimen. The mechanisms may include reductions in iWAT and eWAT weights and cell sizes, induction of browning in iWAT, increased BAT quantity and UCP1 expression, and heightened energy expenditure in iWAT and BAT. Nicotine's ability to induce eWAT browning is relatively weak, indicating diverse mechanisms of action across different adipose tissue types. These findings provide a foundation for further exploration of nicotine's multifaceted functions and underlying mechanisms. IMPLICATIONS: This study examines how different nicotine doses and administration frequencies affect mouse body weight and adipose tissues. It finds that administering nicotine bid (twice daily) at 2mg/kg leads to optimal weight reduction. Nicotine induces browning in white adipose tissue, increases brown adipose tissue quantity and UCP1 expression, and affects energy expenditure. The findings underscore nicotine's nuanced effects across different adipose tissue types and lay groundwork for further exploration of its mechanisms and therapeutic potential in weight management.

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Spatial heterogeneity and plasticity of the mammalian liver are critical for systemic metabolic homeostasis in response to fluctuating nutritional conditions. Here, a spatially resolved transcriptomic landscape of mouse livers across fed, fasted and refed states using spatial transcriptomics is generated. This approach elucidated dynamic temporal-spatial gene cascades and how liver zonation-both expression levels and patterns-adapts to shifts in nutritional status. Importantly, the pericentral nuclear receptor Nr1i3 (CAR) as a pivotal regulator of triglyceride metabolism is pinpointed. It is showed that the activation of CAR in the pericentral region is transcriptionally governed by Pparα. During fasting, CAR activation enhances lipolysis by upregulating carboxylesterase 2a, playing a crucial role in maintaining triglyceride homeostasis. These findings lay the foundation for future mechanistic studies of liver metabolic heterogeneity and plasticity in response to nutritional status changes, offering insights into the zonated pathology that emerge during liver disease progression linked to nutritional imbalances.

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Rhizosphere is a vital area for substance exchange and energy transfer between roots and soil microorganisms. Therefore, diazotrophs in the rhizosphere play a pivotal role in facilitating plant nitrogen acquisition. We investigated the variability in the abundance and community structure of soil diazotrophs and the influencing factors across rhizosphere soils of Cunninghamia lanceolata in three locations: Baisha State-owned Forest Farm in Longyan City (BS), Sanming Forest Ecosystem and Global Change Research Station (SM), and Wuyishan National Forest Park in Nanping City (WYS), located in the western region of Fujian Province, quantified the diazotrophic abundance by using real-time quantitative PCR, and assessed the community structure by high-throughput sequencing. The results showed that soil pH, C:N ratio, and C:(N:P) stoichiometry in SM were notably lower compared to those in BS and WYS. In SM, the abundance of the nifH gene was 6.38×108 copies·g-1, significantly lower than 1.35×109 copies·g-1 in BS and 1.10×109 copies·g-1 in WYS. Additionally, α diversity index of diazotrophs was lower in SM compared to BS and WYS, while the community structure of diazotrophs in rhizosphere soils of BS and WYS was similar, which differed significantly from that in SM. The diazotrophic sequences in the three forest farms could be divided into 5 phylum, 8 classes, 15 orders, 23 families and 33 genera, with Proteobacteria, α-proteobacteria, and Bradyrhizobium as the dominant phylotypes. Soil pH, available phosphorus, NO3--N and C:(N:P) ratio were identified as significant factors influencing both the abundance and community structure of nifH genes, with soil pH performing the greatest. Taken together, there were spatial variations in the distribution of diazotrophic abundance and community structure in C. lanceolata rhizosphere soils, with soil pH as the primary driving factor.

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Wilms tumor (WT) is the most common malignant tumor of the urinary system in children. Though the traditional treatment of surgery plus radiotherapy and chemotherapy achieves exciting clinical efficacy, in relapsed and refractory cases, the long-term overall survival rates are poor. Besides, chemotherapy and radiation have serious long-term toxic side effects on children. Cancer immunotherapy is a new tumor therapy that works by activating the body's immune system to allow immune cells to kill tumor cells more efficiently. Currently, cancer immunotherapy has been tested in clinical trials or basic studies in WT. This article reviews the current status of clinical trials and basic research of cancer immunotherapy in WT to promote the application of cancer immunotherapy in WT patients.

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Background: Several existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK. Methods: Single nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Based on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P<0.0007), whereas the other four biomarkers could only provide some evidence of predisposition. Conclusion: Our two-sample Mendelian randomization study supports the existence of a causal relationship between these five blood and urine biomarkers and the occurrence of oral leukoplakia, and provides evidence for a number of risk and protective factors for the development of oral leukoplakia; however, the definitive mechanisms for the occurrence and development of oral leukoplakia still remain to be elucidated, and further studies on these relevant mechanisms are still needed.

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Rationale: Mechanical force plays crucial roles in extracellular vesicle biogenesis, release, composition and activity. However, it is unknown whether mechanical force regulates apoptotic vesicle (apoV) production. Methods: The effects of mechanical unloading on extracellular vesicles of bone marrow were evaluated through morphology, size distribution, yield, and protein mass spectrometry analysis using hindlimb unloading (HU) mouse model. Apoptosis resistance and aging related phenotype were assessed using HU mouse model in vivo and cell microgravity model in vitro. The therapeutic effects of apoVs on HU mouse model were assessed by using microcomputed tomography, histochemical and immunohistochemical, as well as histomorphometry analyses. SiRNA and chemicals were used for gain and loss-of-function assay. Results: In this study, we show that loss of mechanical force led to cellular apoptotic resistance and aging related phenotype, thus reducing the number of apoVs in the circulation due to down-regulated expression of Piezo1 and reduced calcium influx. And systemic infusion of apoVs was able to rescue Piezo1 expression and calcium influx, thereby, rescuing mechanical unloading-induced cellular apoptotic resistance, senescent cell accumulation. Conclusions: This study identified a previously unknown role of mechanical force in maintaining apoptotic homeostasis and eliminating senescent cells. Systemic infusion of mesenchymal stem cell-derived apoVs can effectively rescue apoptotic resistance and eliminate senescent cells in mechanical unloading mice.

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Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, thrombocytopenia, and bleeding, however, its treatment options are limited. In this study, a kind of active component, chlorogenic acid compounds (CGAs) from sweetpotato leaves was extracted out to explore its medicinal value and provide novel therapeutic strategies for the treatment of ITP. CGAs was isolated by ionic liquids-ultrasound (IL-UAE), which contains six isomers of chlorogenic acid with total purity of 95.69%. The thrombopoietic effect and mechanism of CGAs were investigated using in silico prediction and experimental validation. The changes of HEL cells morphology in volume and the increase in the total cell percentage of polyploid cells indicated that CGAs could promote megakaryocyte differentiation. Meanwhile, CGAs could promote platelet formation in a murine model of ITP, which was established by injection of antiplatelet antibody. Further quantitative proteomics analysis and Western blot verification revealed that CGAs could activate PI3K/AKT signaling pathway, which confirmed the mechanism prediction. It suggested that CGAs may provide a novel therapeutic strategy that relies on the PI3K/AKT pathway to facilitate megakaryocyte differentiation and platelet production.

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BACKGROUND: Perioperative reflux aspiration presents a grave concern during sedation or general anesthesia, particularly when solid gastric contents prompt acute upper respiratory obstruction, potentially resulting in fatal consequences for patients. Currently, there are limited means for promptly assessing solid gastric contents in clinical settings. Therefore, this study examined the efficacy of ultrasound assessment for solid gastric contents, offering a rapid and non-invasive approach for early detection and decision-making regarding interventions. METHODS: The study included 400 patients scheduled for upper endoscopy procedures, which encompassed both gastroscope and gastroscope combined colonoscopy examinations with sedation. Ultrasound scanning of the antrum was performed while patients were positioned semi-sitting or in the right lateral decubitus (RLD) posture. The evaluation of solid gastric contents relied on direct visual observation during endoscopy. Gastric volume measurement occurred subsequent to endoscopic suction of gastric contents. Receiver operating characteristic curves were utilized to assess the effectiveness of ultrasonography in discerning solid contents. RESULT: Seven patients undergoing gastroscope with sedation were found to have solid gastric contents. The sensitivity, specificity, positive predictive value, and negative predictive value of the ultrasound qualitative evaluation of solid contents were 85.7%, 99%, 60%, and 99.7%, respectively. CONCLUSION: Solid stomach contents can be evaluated qualitatively with reasonable accuracy using ultrasonography. Additionally, in patients undergoing upper endoscopy and assessed to have solid gastric contents with ultrasound, administration of mild sedation is recommended. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR2100048994); registered 19/07/2021.

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Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism.

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Background: Diabetes mellitus and hypertension often coexist and share common risk factors. This study investigated the correlation between glycemic management and the prevalence of hypertension among Chinese adults diagnosed with type 2 diabetes mellitus (T2DM). Methods: This study included 1715 patients with T2DM from four cities in Anhui Province, China. Sociodemographic characteristics of the sample participants were collected via questionnaires. A univariate analysis of variance (ANOVA) was utilized for continuous variables, and chi-square testing was used for categorical variables. Binary logistic regression was utilized to examine the relationship between blood pressure and variables including fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), physical activity, dyslipidemia, and family history of hypertension. Results: FPG levels did not increase the risk of hypertension, while HbA1c was significantly and negatively associated with hypertension risk. HbA1c levels ranged from 7.2 to 8.6%, with odds ratios (OR) of 0.68 and 95% confidence intervals (CI) of 0.48 to 0.97 and a significant p value of less than 0.05. For the HbA1c levels above 8.6%, the OR was 0.58 with a 95% CI of 0.39 to 0.87 and a significant p value of less than 0.01. Furthermore, advanced age, higher BMI, greater waist circumference, presence of dyslipidemia, and positive family history of hypertension were all found to be significantly and independently linked to a heightened risk of developing hypertension. These associations remain significant after further adjustment. Conclusion: There was a negative association between HbA1c and the risk of hypertension, and the association remained significant after adjustment for antihypertensive drug use.