Canagliflozin alleviates pulmonary hypertension by activating PPARγ and inhibiting its S225 phosphorylation.

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.

A Hemoglobin Bionics-based System for Combating Antibiotic Resistance in Chronic Diabetic Wounds via Iron Homeostasis Regulation.

Owing to the increased tissue iron accumulation in patients with diabetes, microorganisms may activate high expression of iron-involved metabolic pathways, leading to the exacerbation of bacterial infections and disruption of systemic glucose metabolism. Therefore, an on-demand transdermal dosing approach that utilizes iron homeostasis regulation to combat antimicrobial resistance is a promising strategy to address the challenges associated with low administration bioavailability and high antibiotic resistance in treating infected diabetic wounds. Here, we aim to propose an effective therapy based on hemoglobin bionics to induce disturbances in bacterial iron homeostasis. The preferred "iron cargo" was synthesized by protoporphyrin IX chelated with dopamine and gallium (PDGa), and was delivered via a glucose/pH-responsive microneedle bandage (PDGa@GMB). The PDGa@GMB down-regulated the expression levels of the iron uptake regulator (Fur) and the peroxide response regulator (perR) in Staphylococcus aureus, leading to iron nutrient starvation and oxidative stress, ultimately suppressing iron-dependent bacterial activities. Consequently, PDGa@GMB demonstrated insusceptibility to genetic resistance while maintaining sustainable antimicrobial effects (> 90%) against resistant strains of both S. aureus and E. coli, and accelerated tissue recovery (< 20 d). Overall, PDGa@GMB not only counteracts antibiotic resistance but also holds tremendous potential in mediating microbial-host crosstalk, synergistically attenuating pathogen virulence and pathogenicity. This article is protected by copyright. All rights reserved.

Icariside II alleviates lipopolysaccharide-induced acute lung injury by inhibiting lung epithelial inflammatory and immune responses mediated by neutrophil extracellular traps.

AIMS: Acute lung injury (ALI) is a life-threatening lung disease characterized by inflammatory cell infiltration and lung epithelial injury. Icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exhibits anti-inflammatory and immunomodulatory effects. However, the effect and mechanism of ICS II in ALI remain unclear. The purpose of the current study was to investigate the pharmacological effect and underlying mechanism of ICS II in ALI. MAIN METHODS: Models of neutrophil-like cells, human peripheral blood neutrophils, and lipopolysaccharide (LPS)-induced ALI mouse model were utilized. RT-qPCR and Western blotting determined the gene and protein expression levels. Protein distribution and quantification were analyzed by immunofluorescence. KEY FINDINGS: ICS II significantly reduced lung histopathological damage, edema, and inflammatory cell infiltration, and it reduced pro-inflammatory cytokines in ALI. There is an excessive activation of neutrophils leading to a significant production of NETs in ALI mice, a process mitigated by the administration of ICS II. In vivo and in vitro studies found that ICS II could decrease NET formation by targeting neutrophil C-X-C chemokine receptor type 4 (CXCR4). Further data showed that ICS II reduces the overproduction of dsDNA, a NETs-related component, thereby suppressing cGAS/STING/NF-κB signalling pathway activation and inflammatory mediators release in lung epithelial cells. SIGNIFICANCE: This study suggested that ICS II may alleviate LPS-induced ALI by modulating the inflammatory response, indicating its potential as a therapeutic agent for ALI treatment.

I prefer what you can see: The role of visual perspective-taking on the gaze-liking effect.

Individuals' gaze on an object usually leads others to prefer that object, which is called the gaze-liking effect. However, it is still unclear whether this effect is driven by social factors (i.e., visual perspective-taking) or the domain-general processing (i.e., attention cueing). This research explored the mechanism of the gaze-liking effect by manipulating the objects' visibility to an avatar in six online one-shot experiments. The results showed that participants' affective evaluation for the object was modulated by the avatar's visual perspective. Specifically, the visible object to the avatar received a higher rating of liking degree. However, when the avatar was replaced with a non-social stimulus, the experimental effect was absent. Furthermore, the gaze-liking effect was robust while controlling for confounding factors such as the distance between the object and the avatar or type of stimuli. These findings provided convincing evidence that the gaze-liking effect involves a process of the other's visual experience and is not merely a by-product of the gaze-cueing effect.

From degraded to deciphered: ATAC-seq's application potential in forensic diagnosis.

In recent years, molecular biology-based diagnostic techniques have made remarkable strides and are now extensively utilized in clinical practice, providing invaluable insights for disease diagnosis and treatment. However, forensic medicine, especially forensic pathology, has witnessed relatively limited progress in the application of molecular biology technologies. A significant challenge in employing molecular techniques for forensic diagnoses lies in the quantitative and qualitative changes observed in diagnostic markers due to sample degradation-a recognized and formidable obstacle. Inspired by the success of DNA sequencing in forensic practices, which enables accurate individual identification even in cases involving degraded and deteriorated tissues and organs, we propose the application of the assay for transposase-accessible chromatin with sequencing (ATAC-seq) to identify targets at the transcriptional onset, exploring chromatin and DNA-level alterations for injury and disease inference in forensic samples. This study employs ATAC-seq to explore alterations in chromatin accessibility post-injury and their subsequent changes over a 2-h degradation period, employing traumatic brain injury (TBI) as a representative model. Our findings reveal high sensitivity of chromatin accessibility sites to injury, evidenced by shifts in thousands of peak positions post-TBI. Remarkably, these alterations remain largely unaffected by early degradation. Our results robustly endorse the notion that integrating and incorporating these specific loci for injury and disease diagnosis in forensic samples holds tremendous promise for practical application. We further validated the above results using human cortical tissue, which supported that early degradation did not significantly affect chromatin accessibility. This pioneering advancement in molecular diagnostic techniques may revolutionize the field of forensic science, especially forensic pathology.

GNA15 facilitates the malignant development of thyroid carcinoma cells via the BTK-mediated MAPK signaling pathway.

G protein subunit alpha 15 (GNA15) is recognized as an oncogene for some cancers, however, its role in thyroid carcinoma (TC) is elusive and is investigated in this study. Concretely, bioinformatics was employed to analyze the GNA15 expression profile in TC. The effect of GNA15 on TC cell functions was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Transwell assays. Expressions of extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 were determined using Western blot. The involvement of Bruton tyrosine kinase (BTK) in the mechanism of GNA15 was investigated by BTK knockdown and rescue assay. GNA15 presented an overexpression pattern in TC samples, which facilitated the viability, proliferation, migration, and invasion of TC cells; GNA15 silencing led to converse results. Ratios of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 were upregulated by GNA15 overexpression. The BTK deficiency weakened the aforementioned behaviors of TC cells and blocked the MAPK signaling pathway, however, these effects were counteracted by GNA15 overexpression. Collectively, GNA15 contributes to the malignant development of TC cells by binding to BTK and thus activating the MAPK signaling pathway.

Undaria pinnatifida gel inks for food 3D printing are developed based on the colloidal properties of Undaria pinnatifida slurry and protein/colloidal/starch substances.

Currently, people eat Undaria pinnatifida (UP) in a single way, and processing homogeneity is serious. However, UP has not gained any traction in the 3D printing industry to date. This study explored the incorporation of soy protein isolate (SPI), pea protein (PP), xanthan gum (XG), guar gum (GG), corn starch (CS), and potato starch (PS) into UP slurry liquid, the primary component of the study, to formulate a UP gel ink. The UP gel 3D printing ink system based on UP paste was established and characterized. The results show that hydrogen bonds are formed, and three-dimensional gel network structure is formed in all UP gel inks. UP gel inks containing high concentrations of SPI and GG exhibited good texture and rheological qualities and good 3D printing effect, with storage modulus (G') values of 8440.405 ± 3.893 and 8111.730 ± 3.585 Pa. The loss of modulus (G″) values were 1409.107 ± 3.524 and 1071.673 ± 3.669 Pa. Unfortunately, the properties of other UP gel inks are not suitable, resulting in poor 3D printing results. The food 3D printing method developed in this study provides valuable insights for expanding food 3D printing material choices and achieving high-value applications of UP.

Asiaticoside Down-Regulates HIF-1α to Inhibit Proliferation, Migration, and Angiogenesis in Thyroid Cancer Cells

Background: Thyroid cancer (TC), the most prevalent endocrine malignancy, has been subjected to various treatment methods. However, the efficacy of asiaticoside (AC) for treating TC remains uncertain. Aims: To explore the impact of AC on TC and determine its potential mechanisms of action. Study Design: In vitro and in vivo cell line study. Methods: We evaluated the effects of AC on human TC cell lines, namely TPC-1 and FTC-133. Both in vitro and in vivo experimental validations were conducted. Results: AC significantly diminished the viability and proliferation of TC cells based on the CCK-8 assay and Edu staining findings. Migration and invasion assays revealed that AC effectively curtailed the migration and invasiveness of TC cells. The tube formation assay demonstrated that AC substantially impeded TC cell-induced angiogenesis. Western blot assay revealed that AC significantly reduced the expression levels of TRAF6, HIF-1α, and VEGFA, indicating that AC could potentially exert its anticancer effect by inhibiting the TRAF6/HIF1α pathway. Our in vivo experiments, which involved administering AC to BALB/c nude mice injected with TPC-1 cells, demonstrated significant inhibition of tumor growth and reduction in the expression of Ki-67, TRAF6, HIF-1α, and VEGFA. Conclusion: Our study highlights the significant inhibitory effect of AC on TC, offering fresh insights and potential drug candidates for TC treatment.

Trauma-informed Interventions in Early Childhood Education and Care Settings: A Scoping Review.

Trauma in early childhood is a significant public health concern. Early Childhood Education and Care (ECEC) services are uniquely positioned to buffer the negative impact of early childhood trauma on children. This scoping review synthesized studies evaluating trauma-informed interventions in ECEC settings through a systematic search of four relevant online databases (PsycINFO, Medline, ERIC, A+ Education). Fourteen studies met the inclusion criteria, with 12 ECEC center-based trauma-informed interventions evaluated. Types and components of trauma-informed interventions, outcomes, and measures are presented. Findings suggest that trauma-informed interventions in ECEC settings are nascent but growing. Increasingly, programs are adopting multi-tiered system of support to address early childhood trauma, with these models suggesting promising results. The predominant focus of ECEC center-based trauma-informed interventions was upskilling teachers through training and coaching, with studies focused on assessment of teacher-level outcomes. Child, organization, and caregiver-level outcomes are not explored to the same extent, with evaluation of organizational outcomes relying predominately on qualitative methods. Whilst the short-term outcomes of trauma-informed approaches in ECEC have been examined, longer-term impacts and the causal mechanistic pathways of such programs have yet to be explored.

Culture-Delivery Live Probiotics Dressing for Accelerated Infected Wound Healing.

Probiotic therapy in infected wound healing is hindered by its low viability and colonization efficiency during treatments. Developing dressings that maintain metabolic activity and prevent the potential leakage of probiotics is imperative. Herein, a culture-delivery live probiotics hydrogel dressing is designed and synthesized, formed by gelatin modified with norbornene (GelNB) and sulfhydryl (GelSH), distributing Lactobacillus reuteri (L. reuteri)-laden alginate microspheres (AlgMPs). GelNB-GelSH hydrogel (GelNBSH) incorporating AlgMPs embedding L. reuteri (GelNBSH-L) possesses bioprintability and efficient polymerization that can maintain the activity of L. reuteri in situ, promote its proliferation, and limit its leakage. Thereby, GelNBSH-L achieved a sustainable antimicrobial effect against both S. aureus and E. coli (>90%). Above all, the results show that GelNBSH-L could ensure propitious viability and efficient antibacterial properties of probiotics, effectively inhibit the further development of bacterial infectious wounds and shorten the repair cycle, aiding in ameliorating future clinical probiotic biotherapy.

Identification of Oxidative Stress-Related Biomarkers in Acute Myocardial Infarction.

Purpose: Acute Myocardial Infarction (AMI) is globally prevalent, with oxidative stress as a key contributor to its pathogenesis. This study aimed to explore oxidative stress-related genes as potential AMI biomarkers, elucidating their role in disease progression. Patients and Methods: Gene expression data from AMI samples in the Gene Expression Omnibus (GEO) database and oxidative stress-related genes (OSRGs) from the GeneCards database were extracted. Weighted Gene Co-expression Network Analysis (WGCNA) identified key module genes associated with AMI. Intersecting OSRGs, key module genes, and differentially expressed genes (DEGs) between AMI and normal samples led to the extraction of differentially expressed ORSGs (DE-ORSGs) related to AMI. Feature genes were mined using the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) algorithm, followed by potential diagnostic value assessment using receiver operating characteristic (ROC) curves. Gene Set Enrichment Analysis (GSEA) was executed on the identified key genes. Immune infiltration levels were explored using the CIBERSORT algorithm, and a Transcription Factor (TF) -mRNA regulatory network of key genes was created. The key genes were validated using qRT-PCR. Results: We authenticated three key genes (MMP9, TGFBR3, and S100A12) from 6 DE-ORSGs identified in AMI. GSEA revealed that these key genes were enriched in immune-related signaling pathways. Immune infiltration analysis identified three differential immune cell types (resting NK cells, Monocytes, and M0 Macrophages) between AMI and normal groups. Correlation analysis revealed positive associations of MMP9 with M0 Macrophages and S100A12 with Monocytes and M0 Macrophages, whereas TGFBR3 was negatively related to Monocytes. A TF-mRNA regulatory network was generated based on these key genes. qRT-PCR validation confirmed the differential expression of S100A12 and TGFBR3 between AMI and control samples. Conclusion: TGFBR3, and S100A12 were identified as potential oxidative stress-related biomarkers in AMI, providing new insights for AMI diagnosis and treatment.

Phycocyanin/lysozyme nanocomplexes to stabilize Pickering emulsions for fucoxanthin encapsulation.

Food-grade Pickering emulsions with plant proteins have attracted increasing interest in recent years. In this work, we report a type of phycocyanin (PC) electrostatic nanocomplex fabricated following a complexation between PC and lysozyme (Lys). The aim was to investigate toward investigating the performance of phycocyanin-Lysozyme (PC-Lys) nanocomplexes in stabilizing Pickering emulsions and protecting fucoxanthin (FX) from degradation. The properties of the PC-Lys nanocomplexes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy and three-phase contact angle. Using PC-Lys nanocomplexes as emulsifiers, Pickering emulsions were successfully prepared. Pickering emulsions stabilized by PC-Lys nanocomplexes generated a tight three-dimensional network structure, which increased the memory modulus and viscoelasticity of the emulsion. Furthermore, the produced Pickering emulsions considerably increased the chemical stability and bioavailability of FX. Overall, our study showed that PC-Lys nanocomplexes have the potential for use in Pickering emulsion construction with enhanced protective effects on loaded lipophilic ingredients.

The role of tumor-associated macrophages in the progression, prognosis and treatment of endometrial cancer.

Tumor-associated macrophages (TAMs) are the main immune cells in the tumor microenvironment (TME) of endometrial cancer (EC). TAMs recruitment and polarization in EC is regulated by the TME of EC, culminating in a predominantly M2-like macrophage infiltration. TAMs promote lymphatic angiogenesis through cytokine secretion, aid immune escape of EC cells by synergizing with other immune cells, and contribute to the development of EC through secretion of exosomes so as to promoting EC development. EC is a hormone- and metabolism-dependent cancer, and TAMs promote EC through interactions on estrogen receptor (ER) and metabolic factors such as the metabolism of glucose, lipids, and amino acids. In addition, we have explored the predictive significance of some TAM-related indicators for EC prognosis, and TAMs show remarkable promise as a target for EC immunotherapy.

Reanalysis of single-cell data reveals macrophage subsets associated with the immunotherapy response and prognosis of patients with endometrial cancer.

Endometrial cancer (EC) is an aggressive gynecological malignancy with an increased incidence rate. The immune landscape crucially affects immunotherapy efficacy and prognosis in EC patients. Here, we characterized the distinct tumor microenvironment signatures of EC tumors by analyzing single-cell RNA sequencing data from Gene Expression Omnibus and bulk RNA sequencing data from The Cancer Genome Atlas, which were compared with normal endometrium. Three macrophage subsets were identified, and two of them showed tissue-specific distribution. One of the macrophage subsets was dominant in macrophages derived from EC and exhibited characteristic behaviors such as promoting tumor growth and metastasis. One of the other macrophage subsets was mainly found in normal endometrium and served functions related to antigen presentation. We also identified a macrophage subset that was found in both EC and normal endometrial tissue. However, the pathway and cellular cross-talk of this subset were completely different based on the respective origin, suggesting a tumor-related differentiation mechanism of macrophages. Additionally, the tumor-enriched macrophage subset was found to predict immunotherapy responses in EC. Notably, we selected six genes from macrophage subset markers that could predict the survival of EC patients, SCL8A1, TXN, ANXA5, CST3, CD74 and NANS, and constructed a prognostic signature. To verify the signature, we identified immunohistochemistry for the tumor samples of 83 EC patients based on the selected genes and further followed up with the survival of the patients. Our results provide strong evidence that the signature can effectively predict the prognosis of EC patients.

Novel PVAMA/GelMA aerogels prepared by liquid-phase collection of photoinitiated polymerisation: injectable and flowable low-density 3D scaffolds for bone regeneration.

Nanofibrous scaffolds, which are morphologically/structurally similar to native extracellular matrix, are ideal biomaterials for tissue engineering and regenerative medicine. However, the use of traditional electrospinning techniques to produce three-dimensional (3D) nanofibrous scaffolds with desired structural properties presents difficulty. To address this challenge, we prepared a novel liquid-phase-collected photoinitiated polymerised aerogel 3D scaffold (LPPI-AG) using the thermally induced (nanofiber) self-aggregation method after liquid-phase electrospinning of the hydroxyapatite-doped methacrylated polyvinyl alcohol/methacrylated gelatine solution obtained by photoinitiated polymerisation. The fabricated aerogel scaffolds had a high porosity of approximately 99.01% ± 0.40% and an interconnected network structure with pore sizes ranging from submicron to ∼300 µm. The new aerogel rapidly became flowable when exposed to a solution, and it can fill gaps and repair gap edges effectively and be loaded with nutrients and growth factors that promote bone growth for bone tissue engineering. LPPI-AG scaffolds can considerably promote osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Furthermore, in vivo studies showed that the LPPI-AG scaffold significantly promoted bone formation in a mouse model of critical-size calvarial defects.

Lignans from the seed shells of Cerasus humilis (Bge.) Sok and their bioactivities.

The exploration of Cerasus humilis (Bge.) Sok seed shells yielded the identification of six previously uncharacterized compounds, in addition to twelve known compounds. Structure elucidation of these compounds relied on spectroscopic data analysis, and their absolute configurations were established by comparing calculated and experimental electronic circular dichroic (ECD) spectra, supplemented by interpretation of optical rotation data. Notably, none of these compounds exhibited cytotoxicity against HepG2 and A549 cell lines. Remarkably, a majority of the compounds displayed potent antioxidant activity.

Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch.

Autologous skin flap transplantation is a common method for repairing complex soft tissue defects caused by cancer, trauma, and congenital malformations. Limited blood supply range and post-transplantation ischemia-reperfusion injury can lead to distal necrosis of the flap and long-term functional loss, which severely restricts the decision-making regarding the optimal surgical plan. To address this issue, we develop a hydrogel patch that releases carbon monoxide and nitric oxide gases on demand, to afford a timely blood supply for skin flap transplantation during surgery. Using an ischemia-reperfusion dorsal skin flap model in rats, we show that the hydrogel patch maintains the immediate opening of blood flow channels in transplanted tissue and effective blood perfusion throughout the perioperative period, activating perfusion of the hemodynamic donor site. We demonstrate that the hydrogel patch promotes distal vascularization and long-term functional reconstruction of transplanted tissues by inhibiting inflammatory damage and accelerating blood vessel formation.

Research progress of proanthocyanidins and anthocyanidins.

Proanthocyanidins (PA) are polyphenol compounds that are widely distributed in the bark, fruit core, skin, or seeds of various plants. Anthocyanidins are water-soluble natural pigments widely found in plants. They are all flavonoids, a major coloring substance in plants and fruits. In recent years, research into PA and anthocyanins has become increasingly popular because of their excellent anti-oxidation, scavenging of reactive oxygen free radicals and other physical and chemical activities, and their anti-cancer, vision protection, aging prevention, skin beauty pharmacological, and nutraceutical effects. Especially, recent systematic reviews and meta-analyses indicate their value, safety, and efficacy in the prevention, adjuvant therapy, and management of cardiometabolic disease. Here, we summarize their research progress from the aspects of chemical structure, biosynthetic pathways, distribution, extraction and separation, coloration, efficacy, and potential. The comparison between them might provide a reference for their development and efficient utilization. However, more large-sample-size randomized controlled trials and high-quality studies are needed to firmly establish their clinical efficacy.

An Advanced Strategy to Enhance TENG Output: Reducing Triboelectric Charge Decay.

The Internet of Things (IoT) is poised to accelerate the construction of smart cities. However, it requires more than 30 billion sensors to realize the IoT vision, posing great challenges and opportunities for industries of self-powered sensors. Triboelectric nanogenerator (TENG), an emerging new technology, is capable of easily converting energy from surrounding environment into electricity, thus TENG has tremendous application potential in self-powered IoT sensors. At present, TENG encounters a bottleneck to boost output for large-scale commercial use if just by promoting triboelectric charge generation, because the output is decided by the triboelectric charge dynamic equilibrium between generation and decay. To break this bottleneck, the strategy of reducing triboelectric charge decay to enhance TENG output is focused. First, multiple mechanisms of triboelectric charge decay are summarized in detail with basic theoretical principles for future research. Furthermore, recent advances in reducing triboelectric charge decay are thoroughly reviewed and outlined in three aspects: inhibition and application of air breakdown, simultaneous inhibition of air breakdown and triboelectric charge drift/diffusion, and inhibition of triboelectric charge drift/diffusion. Finally, challenges and future research focus are proposed. This review provides reference and guidance for enhancing TENG output.

Association between residual islet beta-cell function and achieving the target of time in range in inpatients with type 2 diabetes undergoing antidiabetic treatment: An observation study.

AIM: To assess whether the beta-cell function of inpatients undergoing antidiabetic treatment influences achieving time in range (TIR) and time above range (TAR) targets. MATERIALS AND METHODS: This cross-sectional study included 180 inpatients with type 2 diabetes. TIR and TAR were assessed by a continuous glucose monitoring system, with target achievement defined as TIR more than 70% and TAR less than 25%. Beta-cell function was assessed by the insulin secretion-sensitivity index-2 (ISSI2). RESULTS: Following antidiabetic treatment, logistic regression analysis showed that lower ISSI2 was associated with a decreased number of inpatients achieving TIR (OR = 3.10, 95% CI: 1.19-8.06) and TAR (OR = 3.40, 95% CI: 1.35-8.55) targets after adjusting for potential confounders. Similar associations still existed in those participants treated with insulin secretagogues (TIR: OR = 2.91, 95% CI: 0.90-9.36, P = .07; TAR, OR = 3.14, 95% CI: 1.01-9.80) or adequate insulin therapy (TIR: OR = 2.84, 95% CI: 0.91-8.81, P = .07; TAR, OR = 3.24, 95% CI: 1.08-9.67). Furthermore, receiver operating characteristic curves showed that the diagnostic value of the ISSI2 for achieving TIR and TAR targets was 0.73 (95% CI: 0.66-0.80) and 0.71 (95% CI: 0.63-0.79), respectively. CONCLUSIONS: Beta-cell function was associated with achieving TIR and TAR targets. Stimulating insulin secretion or exogenous insulin treatment could not overcome the disadvantage of lower beta-cell function on glycaemic control.