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Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described. Conventional BS-Seq workflows may not be helpful because bisulfite conversion degrades larger DNA into smaller fragments, leading to erroneous categorization as uscfDNA. We describe the '5mCAdpBS-Seq' workflow in which pre-methylated 5mC (5-methylcytosine) single-stranded adapters are ligated to heat-denatured cfDNA before bisulfite conversion. This method retains only DNA fragments that are unaltered by bisulfite treatment, resulting in less biased uscfDNA methylation analysis. Using 5mCAdpBS-Seq, uscfDNA had lower levels of DNA methylation (∼15%) compared to mncfDNA and was enriched in promoters and CpG islands. Hypomethylated uscfDNA fragments were enriched in upstream transcription start sites (TSSs), and the intensity of enrichment was correlated with expressed genes of hemopoietic cells. Using tissue-of-origin deconvolution, we inferred that uscfDNA is derived primarily from eosinophils, neutrophils, and monocytes. As proof-of-principle, we show that characteristics of the methylation profile of uscfDNA can distinguish non-small cell lung carcinoma from non-cancer samples. The 5mCAdpBS-Seq workflow is recommended for any cfDNA methylation-based investigations.

ObjectivePrimary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.MethodsUsing a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.ResultsSaliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

The hot-rolled microstructure of medium Mn steel has coarse grains and severe elemental segregation, resulting in low strength and plasticity. Constructing a multiphase structure, refining the microstructure, and regulating elemental segregation enhance the mechanical properties. In this study, liquid nitrogen treatment created a layered distribution of austenite and martensite. Warm rolling was then used to reduce layer thickness and refine grain structure. After liquid nitrogen and warm rolling treatments, the strength and plasticity of medium Mn steel increased to 1270 MPa and 23.3%, respectively, far exceeding the hot-rolled state (724 MPa, 12.8%). Warm rolling also triggers austenite reverted transformation (ART) and introduces high-density dislocations, further improving austenite stability. This strengthening effect is higher than that from intercritical annealing alone. Improved austenite stability delays the transformation induced plasticity (TRIP) effect, preventing brittle fracture and enhancing deformation coordination between layers, significantly increasing the plastic deformation capacity of medium Mn steel.

Abstract Recent studies have identified a correlation between chronic viral hepatitis and cognitive impairment, yet the underlying mechanisms remain unclear. This study investigated the influence of TGFB1 genetic polymorphisms on cognitive function in individuals with and without hepatitis infections, hypothesizing that these polymorphisms and the viral hepatitis‐induced inflammatory environment interact to affect cognitive abilities. Participants (173 with viral hepatitis and 258 healthy controls) were recruited. Genotyping of TGFB1 SNPs was performed using the C2‐58 Axiom Genome‐Wide TWB 2.0 Array Plate. Cognitive function was assessed using the MMSE and MoCA tests. Our results showed that healthy individuals carrying the C allele of rs2241715 displayed better performance in sentence writing (p = 0.020) and language tasks (p = 0.022). Notably, viral hepatitis was found to moderate the impact of the rs2241715 genotype on language function (p = 0.002). Similarly, those carrying the T allele of rs10417924 demonstrated superior orientation to time (p = 0.002), with viral hepatitis modifying the influence of the SNP on this particular cognitive function (p = 0.010). Our findings underscore the significant role of TGFβ1 in cognitive function and the moderating impact of viral hepatitis on TGFB1 SNP effects. These findings illuminate the potential of TGFB1 as a therapeutic target for cognitive impairment induced by viral hepatitis, thus broadening our understanding of TGFβ1 functionality in the pathogenesis of neurodegeneration.

Abstract Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents. Graphic abstract

Abstract Background This study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years. Methods Comprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model. Results From 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender. Conclusions The global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and

Abstract Accurately interpreting past climate variability, especially distinguishing between forced and unforced changes, is challenging. Proxy data confirm the occurrence of large volcanic eruptions, but linking temperature patterns to specific events or origins is elusive. We present a method combining historical climate records with a machine learning model trained on climate simulations of various volcanic magnitudes and locations. This approach identifies volcanic events based solely on post-eruption temperature patterns. Validations with historical simulations and reanalysis products confirm the identification of significant volcanic events. Explainable artificial intelligence methods point to specific fingerprints in the temperature record that reveal key regions for classification and point to possible physical mechanisms behind climate disruption for major events. We detect unexpected climatic effects from smaller events and identify a northern extratropical footprint for the unidentified 1809 event. This provides an additional line of evidence for past volcanoes and refines our understanding of volcanic impacts on climate.

Abstract Background Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. Methods The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People’s Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. Results The overall HPV infection rate at the First People’s Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20–29 age group and 13.84% in the 30–39 age group, followed by a gradual increase to 14.64% in the 40–49 age group, 16.65% in the 50–59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. Conclusion There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Abstract Background Combining pemetrexed with bevacizumab may have some potential in improving the efficacy in patients with non-small-cell lung cancer (NSCLC), and this meta-analysis aims to explore the impact of pemetrexed addition to bevacizumab on treatment efficacy for NSCLC. Methods PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of pemetrexed addition to bevacizumab on treatment efficacy in patients with NSCLC. Overall survival and progression-free survival were included in this meta-analysis. Results Four RCTs were finally included in the meta-analysis. Overall, compared with bevacizumab for NSCLC, pemetrexed addition showed significantly improved overall survival (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.76 to 0.99; P = 0.03), survival rate (odd ratio [OR] = 1.41; 95% CI = 1.06 to 1.86; P = 0.02), progression-free survival (HR = 0.63; 95% CI = 0.55 to 0.72; P

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

BackgroundUsing broad range cell-free DNA sequencing (BRcfDNA-Seq), a nontargeted next-generation sequencing (NGS) methodology, we previously identified a novel class of approximately 50 nt ultrashort single-stranded cell-free DNA (uscfDNA) in plasma that is distinctly different from 167 bp mononucleosomal cell-free DNA (mncfDNA). We hypothesize that uscfDNA possesses characteristics that are useful for disease detection.MethodsUsing BRcfDNA-Seq, we examined both cfDNA populations in the plasma of 18 noncancer controls and 14 patients with late-stage nonsmall cell lung carcinoma (NSCLC). In comparison to mncfDNA, we assessed whether functional element (FE) peaks, fragmentomics, end-motifs, and G-Quadruplex (G-Quad) signatures could be useful features of uscfDNA for NSCLC determination.ResultsIn noncancer participants, compared to mncfDNA, uscfDNA fragments showed a 45.2-fold increased tendency to form FE peaks (enriched in promoter, intronic, and exonic regions), demonstrated a distinct end-motif-frequency profile, and presented with a 4.9-fold increase in G-Quad signatures. Within NSCLC participants, only the uscfDNA population had discoverable FE peak candidates. Additionally, uscfDNA showcased different end-motif-frequency candidates distinct from mncfDNA. Although both cfDNA populations showed increased fragmentation in NSCLC, the G-Quad signatures were more discriminatory in uscfDNA. Compilation of cfDNA features using principal component analysis revealed that the first 5 principal components of both cfDNA subtypes had a cumulative explained variance of >80%.ConclusionsThese observations indicate that the distinct biological processes of uscfDNA and that FE peaks, fragmentomics, end-motifs, and G-Quad signatures are uscfDNA features with promising biomarker potential. These findings further justify its exploration as a distinct class of biomarker to augment pre-existing liquid biopsy approaches.

Abstract Background Metabolic abnormalities and immune inflammation are deeply involved in pulmonary vascular remodelling and the development of pulmonary hypertension (PH). However, the regulatory mechanisms of glycolysis in macrophages are still elusive. Cumulative evidence indicates that β-catenin plays a crucial role in metabolic reprogramming. This study aimed to investigate the effect of β-catenin on macrophage glycolysis in PH. Methods LPS-induced BMDMs were generated via in vitro experiments. A monocrotaline (MCT)-induced PH rat model was established, and the β-catenin inhibitor XAV939 was administered in vivo. The role of β-catenin in glycolysis was analysed. The degree of pulmonary vascular remodelling was measured. Results β-catenin was significantly increased in both in vitro and in vivo models. In LPS-induced BMDMs, β-catenin increased the levels of hexokinase 2 (HK2), phosphofructokinase (PFK), M2-pyruvate kinase (PKM2), lactate dehydrogenase (LDH), and lactate (LA) and the expression of inflammatory cytokines and promoted PASMC proliferation and migration in vitro. XAV939 decreased the level of glycolysis and downregulated the expression of inflammatory cytokines in vivo. MCT promoted pulmonary arterial structural remodelling and right ventricular hypertrophy, and XAV939 alleviated these changes. Conclusions Our findings suggest that β-catenin is involved in the development of PH by promoting glycolysis and the inflammatory response in macrophages. Inhibition of β-catenin could improve the progression of PH.

Abstract Background With the popularization of robotic surgical systems in the field of surgery, robotic gastric cancer surgery has also been fully applied and promoted in China. The Chinese Guidelines for Robotic Gastric Cancer Surgery was published in the Chinese Journal of General Surgery in August 2021. Methods We have made a detailed interpretation of the process of robotic gastric cancer surgery regarding the indications, contraindications, perioperative preparation, surgical steps, complication, and postoperative management based on the recommendations of China’s Guidelines for Robotic Gastric Cancer Surgery and supplemented by other surgical guidelines, consensus, and single-center experience. Results Twenty experiences of perioperative clinical management of robotic gastric cancer surgery were described in detail. Conclusion We hope to bring some clinical reference values to the front-line clinicians in treating robotic gastric cancer surgery. Trial registration The guidelines were registered on the International Practice Guideline Registration Platform ( http://www.guidelines-registry.cn ) (registration number: IPGRP-2020CN199).

Water is a vital resource on the earth, serving as the foundation of life and playing a crucial role in our daily activities. Perfluorooctanoic acid (PFOA) is an organic compound, which poses a significant threat to the environment due to its persistence and bioaccumulation. PFOA exhibits various toxicities, including neurotoxicity, immunotoxicity, and carcinogenicity. It has been detected in worldwide of air and water samples, as it can easily move through different environmental media such as water, soil, and the atmosphere. The widespread distribution of PFOA in these media poses potential risks to both ecosystems and human health over the long term. Therefore, it is of utmost importance to develop a rapid detection method for accurately monitoring PFOA levels in water. In this study, the electrospray extraction ionization-tandem mass spectrometry (EESI-MS/MS) technique was utilized to directly and rapidly detect PFOA in tap water and river water. To achieve the highest ionization efficiency of PFOA in EESI-MS/MS across different water samples, the experimental parameters such as ion transfer tube temperature, spray voltage, electrospray solvent flow rate, and sample flow rate were optimized. The optimal conditions were temperature of 200 °C for the ion transfer tube, spray voltage of 2 kV, electrospray solvent flow rate of 4 µL/min, and sample flow rate of 6 µL/min. The experiments were conducted under negative ion mode with a mass scan range of m/z 50-500. Methanol solution was used as the electrospray solvent, and collision-induced dissociation (CID) was employed. The secondary characteristic fragment ion m/z 369 of m/z 413 for qualitative and quantitative analysis, enabling direct and rapid detection of PFOA in various water samples. The experimental results demonstrated good linearity of PFOA in the concentration range of 1-500 ng/L, with a linear correlation coefficient (R2) of 0.9976. The detection limit (LOD) of the proposed method is 0.57 ng/L, and the limit of quantification (LOQ) is 1.73 ng/L. The recovery rate ranges from 92.1% to 105.2%, with a relative standard deviation (RSD, n=6) of 1.89%-5.45%. In summary, this method has the advantages of high sensitivity, accuracy, and fast analysis speed, without the need of sample pretreatment. The established EESI-MS/MS method can be effectively applied for direct and rapid detection of PFOA in different water samples, showing promising prospects for monitoring environmental water pollutants. Moreover, it provides valuable references and technical means for the detection of other pollutants.

Abstract The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.

Societal Impact Statement Rice wild relatives (RWR) provide valuable genetic resources for modern rice breeding, yet knowledge gaps constrain their conservation and further utilization. To address these gaps, the potential distributions of 22 RWR taxa were modeled, and their conservation statuses were assessed. Most taxa were identified as medium priority for further conservation. Further ex‐situ collecting hotspots are in Southeast and South Asia, Northern Australia, West Africa, and tropical Americas, while habitat protection lies in Southeast and South Asia, Northern Australia, and West Africa. Climate change may shift equatorial habitats to higher latitudes and mountain habitats to higher altitudes. Summary Rice wild relatives (RWR) provide valuable genetic resources for modern rice breeding. However, knowledge gaps on their geographic distributions and conservation status constrain their conservation and further utilization. To fill these critical gaps, we modeled the potential distributions of 22 RWR taxa under current climate scenarios, assessed their conservation status, both ex situ (in genebanks or botanical gardens) and in situ (in protected areas), and examined changes in taxa richness of RWR in predicted areas under future climate scenarios. The RWR were primarily distributed in tropical Asia to tropical Australia, tropical Africa, and South and Central America. We identified 4 out of 22 taxa as high priority (HP) for further conservation action and 18 taxa as medium priority (MP). Hotspots requiring further collecting for ex situ conservation are concentrated in Southeast and South Asia, Northern Australia, West Africa, and tropical Americas. Meanwhile, habitat protection should be enhanced in Southeast and South Asia, Northern Australia, and West Africa. Under future climate change, suitable habitats near the equator are expected to shift toward higher latitudes and some in lower‐latitude basins may become unsuitable due to excessive heat, resulting in decreased taxa richness in these areas. Additionally, suitable habitats in high mountain areas may shift to higher altitudes, potentially augmenting taxa richness in the highlands. Our findings provide vital insights to guide future rescue conservation efforts for RWR.

In recent years, with rising concerns over food quality and safety, computer vision technology has gradually attracted attention and begun to be widely used in the field of food quality evaluation. Machine learning technologies such as artificial neural networks (ANN), convolutional neural networks (CNN), and support vector machines (SVM) allow automatic assessment and monitoring of food quality by training on large amounts of food images and related data. Particularly, with the development of deep learning, the computer is now able to more accurately recognize food features such as appearance, shape, and color, thereby allowing food classification, prediction and quality monitoring. In addition to its conventional application in food quality assessment, learning technologies also find application in more complex tasks such as defect detection, foreign object detection, and freshness assessment. These technologies not only improve the efficiency of food production and processing but also reduce errors caused by human factors, thereby ensuring food quality and safety. However, despite the significant progress in the application of learning technologies in food quality assessment, there are still challenges that need to be overcome. For instance, the high cost of acquiring and annotating food image datasets, as well as insufficient data quality and quantity, may affect the performance and generalization ability of models. Furthermore, the interpretability and transparency of models are important issues, especially when explaining or making decisions on food quality assessment results. Therefore, further research is needed to explore how to improve the quality and scale of datasets, optimize the robustness and interpretability of models, and develop more efficient and sustainable food quality assessment systems.

Ichthyosaurs, an iconic lineage of Mesozoic marine reptiles, were an important component of recovering ecosystems after the Permo-Triassic Mass Extinction event. Mixosauridae, a clade of small, early-diverging ichthyosaurs, were of particular significance for this process, being abundant predators in Middle Triassic shallow seas. Despite the abundance of well-preserved mixosaurid specimens from South China, Mixosaurus panxianensis remains the only comprehensively described species, hindering our understanding of the variability, taxonomy and diversity of mixosaurids from this re-gion. Here, we report a new species of Mixosaurus, Mixosaurus luxiensis, from Luxi County, Yunnan Province, South China. The wider postorbital skull portion differentiates the new species from Mixosaurus cornalianus and Mixosaurus kuhnschnyderi from central Europe. The non-durophagous dentition, composed of tiny piercing mesial teeth and robust but pointed distal teeth, resembles the dentition of M. cornalianus. However, the distal teeth of M. luxiensis sp. nov. are twice the size of the mesial ones, in contrast to M. cornalianus, in which the mesial and distal teeth are approximately equal in size. The forelimb exhibits a unique morphology, including a proportionally narrow radius, the presence of a peripheral notch on the ulna, and a large metacarpal V. A preliminary phylogenetic analysis suggests a close affinity of the new taxon with M. cornalianus from Western Tethys. Our study introduces important, new anatomical information on Mixosaurus from South China, useful for future studies of mixosaurid diversity.

Abstract Background The Triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in the risk of ischemic stroke. However, the interplay between TyG levels, lifestyle factors, and their collective impact on stroke risk in non-diabetic populations remains inadequately explored. This study aims to evaluate the association of ischemic stroke with the joint development of the TyG index and lifestyle in the non-diabetic population. Methods In this prospective cohort study, data was collected across three consecutive biennial surveys of the Kailuan Study from 2006 to 2011. The dual-trajectory model was used to determine the temporal development of TyG levels and lifestyle scores. Statistical analysis involved Cox regression models to evaluate the association between TyG-lifestyle trajectories and ischemic stroke risk, adjusting for potential confounders. Results A total of 44,403 participants were included, with five distinct TyG levels and lifestyle scores trajectory subtypes identified. In the multivariable-adjusted analyses, significant differences in ischemic stroke risk among the trajectory subtypes. Group 5, characterized by the highest TyG levels and moderate lifestyle scores, exhibited the greatest ischemic stroke risk (HR = 1.81, 95% CI: 1.51–2.18), while group 4, with moderate TyG levels and higher lifestyle scores, demonstrated the lowest risk (HR = 1.19, 95% CI: 1.04–1.37), compared with group 3. Participants with elevated TyG levels were at an increased risk of ischemic stroke in cases of pronounced insulin resistance, even with a healthy lifestyle. Conclusions This study reveals the significant associations between the identified TyG and lifestyle trajectories and the stratification of ischemic stroke risk among non-diabetics. The TyG index is a valuable indicator for assessing insulin resistance. However, the potential benefits of lifestyle changes for those with significantly high TyG levels need to be clarified by more research to develop more effective stroke prevention strategies.