Characteristics of drug resistance mutations in ART-experienced HIV-1 patients with low-level viremia in Zhengzhou City, China.

Although most people living with HIV (PLWH) receiving antiretroviral therapy (ART) achieve continuous viral suppression, some show detectable HIV RNA as low-level viremia (LLV) (50-999 copies/mL). Drug resistance mutations (DRMs) in PLWH with LLV is of particular concern as which may lead to treatment failure. In this study, we investigated the prevalence of LLV and LLV-associated DRMs in PLWH in Zhengzhou City, China. Of 3616 ART-experienced PLWH in a long-term follow-up cohort from Jan 2022 to Aug 2023, 120 were identified as having LLV. Of these PLWH with LLV, we obtained partial pol and integrase sequences from 104 (70 from HIV-1 RNA and 34 from proviral DNA) individuals. DRMs were identified in 44 individuals. Subtyping analysis indicated that the top three subtypes were B (48.08%, 50/104), CRF07_BC (31.73%, 33/104), and CRF01_AE (15.38%, 16/104). The proportions of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) associated DRMs were 23.83% (24/104), 35.58% (37/104), 5.77% (6/104), and 3.85% (4/104), respectively, which contributed to an overall prevalence of 42.31% (44/104). When analyzed by individual DRMs, the most common mutation(s) were V184 (18.27%, 19/104), followed by V179 (11.54%, 12/104), K103 (9.62%, 10/104), Y181 (9.62%, 10/104), M41 (7.69%, 8/104), and K65R (7.69%, 8/104). The prevalence of DRMs in ART-experienced PLWH with LLV is high in Zhengzhou City and continuous surveillance can facilitate early intervention and provision of effective treatment.

Accelerated stability modeling of recrystallization from amorphous solid Dispersions: A Griseofulvin/HPMC-AS case study.

Amorphous solid dispersions (ASDs) represent an important approach for enhancing oral bioavailability for poorly water soluble compounds; however, assuring that these ASDs do not recrystallize to a significant extent during storage can be time-consuming. Therefore, various efforts have been undertaken to predict ASD crystallization levels with kinetic models. However, only limited success has been achieved due to limits on crystal content quantification methods and the complexity of crystallization kinetics. To increase the prediction accuracy, the accelerated stability assessment program (ASAP), employing isoconversion (time to hit a specification limit) and a modified Arrhenius approach, are employed here for predictive shelf-life modeling. In the current study, a model ASD was prepared by spray drying griseofulvin and HPMC-AS-LF. This ASD was stressed under a designed combinations of temperature, relative humidity and time with the conditions set to ensure stressing was carried out below the glass transition temperature (Tg) of the ASD. Crystal content quantification method by X-ray powder diffraction (XRPD) with sufficient sensitivity was developed and employed for stressed ASD. Crystallization modeling of the griseofulvin ASD using ASAPprime® demonstrated good agreement with long-term (40 °C/75 %RH) crystallinity levels and support the use of this type of accelerated stability studies for further improving ASD shelf-life prediction accuracy.

Single center clinical analysis of macrophage activation syndrome complicating juvenile rheumatic diseases.

BACKGROUND: Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis. METHODS: Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference. RESULTS: Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred. CONCLUSIONS: Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.

Fasting and Glucose Metabolism Differentially Impact Peripheral Inflammation in Human Type 2 Diabetes.

Cytokines produced by peripheral T-helper 1/17 cells disproportionately contribute to the inflammation (i.e., metaflammation) that fuels type 2 diabetes (T2D) pathogenesis. Shifts in the nutrient milieu could influence inflammation through changes in T-cell metabolism. We aimed to determine whether changes in glucose utilization alter cytokine profiles in T2D. Peripheral blood mononuclear cells (PBMCs), CD4+ T-cells, and CD4+CD25- T-effector (Teff) cells were isolated from age-matched humans classified by glycemic control and BMI. Cytokines secreted by CD3/CD28-stimulated PBMCs and Teff were measured in supernatants with multiplex cytokine assays and a FLEXMAP-3D. Metabolic activity of stimulated CD4+ T-cells was measured by a Seahorse XFe96 analyzer. In this study, we demonstrated that T-cell stimulated PBMCs from non-fasted people with T2D produced higher amounts of cytokines compared to fasting. Although dysglycemia characterizes T2D, cytokine production by PBMCs or CD4+ T-cells in T2D was unaltered by hyperglycemic media. Moreover, pharmacological suppression of mitochondrial glucose oxidation did not change T-cell metabolism in T2D, yet enhanced cytokine competency. In conclusion, fasting and glucose metabolism differentially impact peripheral inflammation in human T2D, suggesting that glucose, along with fatty acid metabolites per our previous work, partner to regulate metaflammation. These data expose a major disconnect in the use of glycemic control drugs to target T2D-associated metaflammation.

Stabilizing the Catalyst Layer for Durable and High Performance Alkaline Membrane Fuel Cells and Water Electrolyzers.

Anion exchange membrane (AEM) fuel cells (AEMFCs) and water electrolyzers (AEMWEs) suffer from insufficient performance and durability compared with commercialized energy conversion systems. Great efforts have been devoted to designing high-quality AEMs and catalysts. However, the significance of the stability of the catalyst layer has been largely disregarded. Here, an in situ cross-linking strategy was developed to promote the interactions within the catalyst layer and the interactions between catalyst layer and AEM. The adhesion strength of the catalyst layer after cross-linking was improved 7 times compared with the uncross-linked catalyst layer due to the formation of covalent bonds between the catalyst layer and AEM. The AEMFC can be operated under 0.6 A cm-2 for 1000 h with a voltage decay rate of 20 µV h-1. The related AEMWE achieved an unprecedented current density of 15.17 A cm-2 at 2.0 V and was operated at 0.5, 1.0, and 1.5 A cm-2 for 1000 h.

NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin.

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

The Characterization of G-Quadruplexes in Tobacco Genome and Their Function under Abiotic Stress.

Tobacco is an ideal model plant in scientific research. G-quadruplex is a guanine-rich DNA structure, which regulates transcription and translation. In this study, the prevalence and potential function of G-quadruplexes in tobacco were systematically analyzed. In tobacco genomes, there were 2,924,271,002 G-quadruplexes in the nuclear genome, 430,597 in the mitochondrial genome, and 155,943 in the chloroplast genome. The density of the G-quadruplex in the organelle genome was higher than that in the nuclear genome. G-quadruplexes were abundant in the transcription regulatory region of the genome, and a difference in G-quadruplex density in two DNA strands was also observed. The promoter of 60.4% genes contained at least one G-quadruplex. Compared with up-regulated differentially expressed genes (DEGs), the G-quadruplex density in down-regulated DEGs was generally higher under drought stress and salt stress. The G-quadruplex formed by simple sequence repeat (SSR) and its flanking sequence in the promoter region of the NtBBX (Nitab4.5_0002943g0010) gene might enhance the drought tolerance of tobacco. This study lays a solid foundation for further research on G-quadruplex function in tobacco and other plants.

Layered Hydride LiH4 with a Pressure-Insensitive Superconductivity.

For hydride superconductors, each significant advance is built upon the discovery of novel H-based structural units, which in turn push the understanding of the superconducting mechanism to new heights. Based on first-principles calculations, we propose a metastable LiH4 with a wavy H layer composed of the edge-sharing pea-like H18 rings at high pressures. Unexpectedly, it exhibits pressure-insensitive superconductivity manifested by an extremely small pressure coefficient (dTc/dP) of 0.04 K/GPa. This feature is attributed to the slightly weakened electron-phonon coupling with pressure, caused by the reduced charge transfer from Li atoms to wavy H layers, significantly suppressing the substantial increase in the contribution of phonons to Tc. Its superconductivity originates from the strong coupling between the H 1s electrons and the high-frequency phonons associated with the H layer. Our study extends the list of H-based structural units and enhances the in-depth understanding of pressure-related superconductivity.

Enhancement of zinc-ion storage capability by synergistic effects on dual-ion adsorption in hierarchical porous carbon for high-performance aqueous zinc-ion hybrid capacitors.

Aqueous zinc-ion capacitors (AZICs) are considered potential energy storage devices thanks to their ultrahigh power density, high safety, and extended cycling life. Carbon-based materials widely used as cathodes in AZICs face challenges, such as inappropriate pore sizes, poor electrolyte-electrode wettability, and insufficient vacancy defects and active sites. These limitations hinder efficient energy storage capacity and long-term stability. To address these issues, the B and F co-doped hierarchical porous carbon cathode materials (BFPC) are constructed through a facile annealing treatment process. The BFPC-2//Zn device exhibited high capacities of 222.4 and 118.3 mAh g-1 at current densities of 0.2 and 10 A g-1, respectively. Notably, the BFPC-2//Zn device demonstrated long-term cycling stability with a high capacity retention of 96.9 % after 20,000 cycles at 10 A g-1. Additionally, the assembled BFPC-2 based AZICs displayed a maximum energy density of 175.8 Wh kg-1 and an ultrahigh power density of 17.3 kW kg-1. Mechanism studies revealed that the exceptional energy storage ability and charge-transfer process of the BFPC cathode are attributed to the synergistic effect of B and F heteroatoms and the coupling effect between vacancy defects and pore size. This work presents a novel design strategy by incorporating B and F active sites into hierarchical porous carbon materials, providing enhanced energy storage capabilities for practical application in AZICs.

Metallic Re3O2 with mixed-valence states.

Rhenium (Re) shows the richest valence states from +2 to +7 in compounds, but its mixed-valence states are still missing thus far. In this work, we have explored the Re-O phase diagram with a wide range of stoichiometric compositions under high pressure through first-principles structural search calculations. Besides identifying two novel high-pressure phases of ReO2 and ReO3, we reveal two hitherto unknown Re-rich Re3O2 and O-rich ReO4 compounds. Re atoms in Re3O2 show mixed-valence states due to their inequivalent coordination environments, the first example in Re-based compounds. Electronic structure calculations demonstrate that the four discovered Re-O phases exhibit metallicity contributed by Re 5d electrons. Among them, ReO3 has a predicted critical temperature of up to 12 K at 50 GPa, derived from the interaction between Re 5d electrons and Re-derived low-frequency phonons. Our study points to new opportunities to disclose novel transition metal compounds with mixed-valence states.

Formulation analysis of functional fragrance via polar-gradient extraction method and chemometrics pattern recognition.

In this study, characteristic components of 15 natural flavors was analyzed by the polar-gradient extraction (PGE) technique in combination with GC-MS and chemometrics pattern recognition. The obtained results were utilized for the traceability of 4 functional fragrance formulations. The optimal PGE system consisting of 5 different polar solvents, was developed based on similarity-intermiscibility theory. Four chemometrics pattern recognition models including PCA, HCA, PLS-DA, and OPLS-DA were constructed based on the characteristic component database constituting 15 natural flavors. These models were used to trace 4 functional fragrance formulations. The experimental results obtained were found to be satisfactory and accurate. The combination of PGE technique and chemometric pattern recognition methods provides theoretical guidance for the analysis of characteristic components of natural flavors and the traceability of functional fragrance formulations. This approach can be promoted in various fields such as food, traditional Chinese medicine, and cosmetics.

A unique subseafloor microbiosphere in the Mariana Trench driven by episodic sedimentation.

Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor microbiosphere. Currently, the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is unknown. Here, analyses of carbon isotope composition in a ~ 750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition, with anomalous 14C ages likely caused by seismically driven mass transport and the funneling effect of trench geomorphology. Microbial community composition and diverse enzyme activities in the upper ~ 27 cm differed from those at lower depths, probably due to sudden sediment deposition and differences in redox condition and organic matter availability. At lower depths, microbial population numbers, and composition remained relatively constant, except at some discrete depths with altered enzyme activity and microbial phyla abundance, possibly due to additional sudden sedimentation events of different magnitude. Evidence is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth's deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic populations. Such depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00212-y.

Genome-wide identification and expression analysis of NF-Y gene family in tobacco (Nicotiana tabacum L.).

Nuclear factor Y (NF-Y) gene family is an important transcription factor composed of three subfamilies of NF-YA, NF-YB and NF-YC, which is involved in plant growth, development and stress response. In this study, 63 tobacco NF-Y genes (NtNF-Ys) were identified in Nicotiana tabacum L., including 17 NtNF-YAs, 30 NtNF-YBs and 16 NtNF-YCs. Phylogenetic analysis revealed ten pairs of orthologues from tomato and tobacco and 25 pairs of paralogues from tobacco. The gene structure of NtNF-YAs exhibited similarities, whereas the gene structure of NtNF-YBs and NtNF-YCs displayed significant differences. The NtNF-Ys of the same subfamily exhibited a consistent distribution of motifs and protein 3D structure. The protein interaction network revealed that NtNF-YC12 and NtNF-YC5 exhibited the highest connectivity. Many cis-acting elements related to light, stress and hormone response were found in the promoter of NtNF-Ys. Transcriptome analysis showed that more than half of the NtNF-Y genes were expressed in all tissues, and NtNF-YB9/B14/B15/B16/B17/B29 were specifically expressed in roots. A total of 15, 12, 5, and 6 NtNF-Y genes were found to respond to cold, drought, salt, and alkali stresses, respectively. The results of this study will lay a foundation for further study of NF-Y genes in tobacco and other Solanaceae plants.

Association Between Different Types of Physical Activity and Hepatic Steatosis and Liver Fibrosis: A Cross-Sectional Study Based on NHANES.

BACKGROUND AND AIMS: Many studies have shown a link between physical activity (PA) and nonalcoholic fatty liver disease (NAFLD). However, more research is needed to investigate the relationship between different types of PA and NAFLD. This study aimed to explore the potential link between different types of PA, hepatic steatosis, and liver fibrosis. STUDY: A cross-sectional study was conducted using the data set from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. A multiple linear regression model was used to examine the linear relationship between different types of PA, the controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). In addition, smoothing curve fitting and threshold effect analysis were used to depict their nonlinear relationship. RESULTS: This study involved 5933 adults. Multiple linear regression analysis revealed a significantly negative correlation between leisure-time PA and CAP, while the relationship between occupation-related PA, transportation-related PA, and CAP was not significant. Subgroup analysis further revealed that leisure-time PA was significantly negatively correlated with CAP in women and younger age groups (under 60 y old), while the relationship was not significant in men and older age groups. In addition, there was a significant negative correlation between leisure-time PA and liver fibrosis in men. CONCLUSIONS: Leisure-time PA can prevent hepatic steatosis, and women and young people benefit more. Occupation-related PA is not associated with hepatic steatosis and cannot replace leisure-time PA. In men, increasing leisure-time PA is more effective in preventing liver fibrosis.

Erratum: Subclavian Vein Blood Sampling in Conscious Rats.

This corrects the article 10.3791/66075.

Porous and graphitic carbon nanosheets with controllable structure for zinc-ion hybrid capacitor.

The imbalances of storage capacity and reaction kinetics between carbonaceous cathodes and zinc (Zn) anodes restrict the widespread application of Zn-ion hybrid capacitor (ZIHC). Structure optimization is a promising strategy for carbon materials to achieve sufficient Zn2+ storage sites and satisfied ion-electron kinetics. Herein, porous graphitic carbon nanosheets (PGCN) were simply synthesized using a K3[Fe(C2O4)3]- and urea-assisted foaming strategy with polyvinylpyrrolidone as carbon precursor, followed by activation and graphitization. Sufficient pores with well-matched pore sizes (0.80-1.94 nm) distributed across the carbon nanosheets can effectively shorten mass-transfer distance, promoting accessibility to active sites. A partially graphitic carbon structure with high graphitization degree can accelerate electron transfer. Furthermore, high nitrogen doping (7.2 at.%) provides additional Zn2+ storage sites to increase storage capacity. Consequently, a PGCN-based ZIHC has an exceptional specific capacity of 181 mAh g-1 at 0.5 A g-1, superb energy density of 145 Wh kg-1, and excellent cycling ability without capacity decay over 10,000 cycles. In addition, the flexible solid-state device assembled with PGCN exhibits excellent electrochemical performances even when bent at various angles. This study proposes a straightforward and economical strategy to construct porous graphitic carbon nanosheets with enhanced storage capacity and fast reaction kinetics for the high performance of ZIHC.

Essential spectral pixels-based improvement of UMAP classifying hyperspectral imaging data to identify minor compounds in food matrix.

Classifying big data in hyperspectral imaging (HSI) can be challenging when minor (low-concentrated) compounds are present in actual samples, as for chemical additives and adulterants in food matrix. Herein, we propose a new strategy to classify HSI data for the identification of adulterants in food material for the first time. This strategy is based on the selection of essential spectral pixels of full HSI data followed by the feature space construction using uniform manifold approximation and projection as well as the data clustering utilizing hierarchical clustering analysis on the reduced data (named ESPs-UMAP-HCA). We apply our approach to analyze two real NIR datasets and four new Raman datasets. Compared with non-ESPs UMAP-HCA and t-distributed stochastic neighbor embedding combined with ESPs and HCA (ESPs-t-SNE-HCA), the developed strategy provides well-separated clusters for major and minor compounds in food matrix. Finally, the adulterants as minor compounds are accurately identified, which is confirmed by the fact that the extracted spectra of them perfectly match with their pure spectra. In addition, their locations are found in the contribution map even though they are present in a few pixels. What's more, the proposed strategy does not need any a priori knowledge of the data structure and the class memberships and therefore reduced the studied difficulty and confirmation bias in the analysis of big HSI datasets. Overall, the proposed ESPs-UMAP-HCA method could be a potential approach for food adulteration detection.

A Solar Evaporator Based on Polypyrrole Coated 3D Carbon Nanotube Materials for Efficient Solar-Driven Vapor Generation.

Highly porous light absorbers are fabricated based on polypyrrole (PPy)-coated carbon nanotube (CNT). Carbon nanotube sponge (CNTS) or carbon nanotube array (CNTA) with three-dimensional (3D) network structure is the framework of porous light absorbers. Both PPy@CNTS and PPy@CNTA composites exhibit excellent light absorption of the full solar spectrum. The CNTS and CNTA with porous structures have extremely large effective surface area for light absorption and for water evaporation that has great practical benefit to the solar-driven vapor generation. The PPy layer on CNT sidewalls significantly improves the hydrophilicity of porous CNTS and CNTA. The good wettability of water on CNT sidewalls makes water transport in porous CNT materials highly efficient. The PPy@CNTS and PPy@CNTA light absorbers achieve high water evaporation rates of 3.35 and 3.41 kg m-2 h-1 , respectively, under 1-sun radiation. The orientation of nano channels in CNTA-based light absorbers also plays an important role in the solar-driven vapor generation. The water transport and vapor escape are more efficient in CNTA-based light absorbers as compared to the CNTS-based light absorbers due to the relatively short path for the water transport and the vapor escape in CNTA-based light absorbers.

Relationship between glycated hemoglobin levels and three-month outcomes in acute ischemic stroke patients with or without diabetes: a prospective Korean cohort study.

OBJECTIVE: In patients experiencing acute ischemic stroke, there is ongoing debate surrounding the connection between chronic hyperglycemic status and their initial clinical outcomes. Our objective was to examine the connection between glycated hemoglobin (HbA1c) levels and adverse clinical outcomes at both 3-months adverse clinical outcomes in individuals with acute ischemic stroke (AIS) with and without diabetes. METHODS: The present prospective cohort study involved 896 AIS patients without diabetes and 628 with diabetes treated at a South Korean hospital from January 2010 to December 2016. The target independent variable is HbA1c. The outcome variable is a modified Rankin scale score ≥ 3. A binary logistic regression model was applied to assess the connection between HbA1c levels and 3-month poor clinical outcomes in AIS patients with and without diabetes. Additionally, a generalized additive model and smoothed curve fitting were utilized to explore potential nonlinear associations between HbA1c levels and 3-month adverse clinical outcomes in AIS patients with and without diabetes. RESULTS: The binary logistic regression model could not identify any statistically significant connection between HbA1c and 3-month adverse clinical outcomes in AIS patients, both those with and without diabetes, after correcting for various factors. However, a nonlinear relationship emerged between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. The inflection point for HbA1c was determined to be 6.1%. For HbA1c values ≤ 6.1%, an inverse association was observed between HbA1c and 3-month adverse clinical outcomes in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with an 87% reduction in 3-month adverse clinical outcomes (OR = 0.13, 95% CI: 0.02-0.81). Conversely, when HbA1c exceeded 6.1%, a positive association between HbA1c and 3-month adverse clinical outcomes became apparent in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with a 23% increase in 3-month adverse clinical outcomes (OR = 1.23, 95%CI: 1.03-1.47). However, it's important to note that no significant linear or nonlinear relationships were observed between HbA1c levels and 3-month adverse clinical outcomes in AIS patients without diabetes. CONCLUSION: Our findings suggest a nonlinear connection and threshold effect between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. AIS patients with diabetes had a lower risk of 3-month adverse clinical outcomes when their HbA1c control was close to 6.1%. Our findings may aid treatment decision-making and potentially guide interventions to optimize glycemic control in AIS patients.