Revisiting the antigen markers of vector-borne parasitic diseases identified by immunomics: identification and application to disease control.

INTRODUCTION: Protein microarray is a promising immunomic approach for identifying biomarkers. Based on our previous study that reviewed parasite antigens and recent parasitic omics research, this article expands to include information on vector-borne parasitic diseases (VBPDs), namely, malaria, schistosomiasis, leishmaniasis, babesiosis, trypanosomiasis, lymphatic filariasis, and onchocerciasis. AREAS COVERED: We revisit and systematically summarize antigen markers of vector-borne parasites identified by the immunomic approach and discuss the latest advances in identifying antigens for the rational development of diagnostics and vaccines. The applications and challenges of this approach for VBPD control are also discussed. EXPERT OPINION: The immunomic approach has enabled the identification and/or validation of antigen markers for vaccine development, diagnosis, disease surveillance, and treatment. However, this approach presents several challenges, including limited sample size, variability in antigen expression, false-positive results, complexity of omics data, validation and reproducibility, and heterogeneity of diseases. In addition, antigen involvement in host immune evasion and antigen sensitivity/specificity are major issues in its application. Despite these limitations, this approach remains promising for controlling VBPD. Advances in technology and data analysis methods should continue to improve candidate antigen identification, as well as the use of a multiantigen approach in diagnostic and vaccine development for VBPD control.

Renal Function in Aged C57BL/6J Mice Is Impaired by Deposition of Age-Related Apolipoprotein A-II Amyloid Independent of Kidney Aging.

Spontaneous and age-related amyloidosis has been reported in C57BL/6J mice. However, the biochemical characteristics of age-related amyloidosis remain unclear. Herein, the age-related prevalence of amyloidosis, the types of amyloid fibril proteins, and the effects of amyloid deposition were investigated in renal function in C57BL/6J mice. The results obtained revealed a high incidence of amyloidosis in C57BL/6J mice originating from The Jackson Laboratory as well as the deposition of large amounts of amyloid in the glomeruli of aged mice. The amyloid fibril protein was identified as wild-type apolipoprotein A-II (ApoA-II). Induction of amyloid deposition in 40-week-old mice, equivalent to that of spontaneous development in 80-week-old mice, to rule out the effects of aging, revealed subsequent damage to kidney function by amyloid deposits. Furthermore, amyloid deposition in the mesangial region decreased podocyte density, compromised foot processes, and led to the accumulation of fibroblast growth factor 2 in glomeruli. Collectively, these results suggest that ApoA-II deposition is a general pathology in aged C57BL/6J mice and is dependent on supplier colonies. Therefore, the effects of age-related amyloid deposition need to be considered in research on aging in mice.

Tunable-bias based optical neural network for reinforcement learning in path planning.

Owing to the high integration, reconfiguration and strong robustness, Mach-Zehnder interferometers (MZIs) based optical neural networks (ONNs) have been widely considered. However, there are few works adding bias, which is important for neural networks, into the ONNs and systematically studying its effect. In this article, we propose a tunable-bias based optical neural network (TBONN) with one unitary matrix layer, which can improve the utilization rate of the MZIs, increase the trainable weights of the network and has more powerful representational capacity than traditional ONNs. By systematically studying its underlying mechanism and characteristics, we demonstrate that TBONN can achieve higher performance by adding more optical biases to the same side beside the inputted signals. For the two-dimensional dataset, the average prediction accuracy of TBONN with 2 biases (97.1%) is 5% higher than that of TBONN with 0 biases (92.1%). Additionally, utilizing TBONN, we propose a novel optical deep Q network (ODQN) algorithm to complete path planning tasks. By implementing simulated experiments, our ODQN shows competitive performance compared with the conventional deep Q network, but accelerates the computation speed by 2.5 times and 4.5 times for 2D and 3D grid worlds, respectively. Further, a more noticeable acceleration will be obtained when applying TBONN to more complex tasks. Also, we demonstrate the strong robustness of TBONN and the imprecision elimination method by using on-chip training.

A functional variant of ALDH1A2 is associated with hand osteoarthritis in the Chinese population.

Genome-wide association study identified common variants within the ALDH1A2 gene as the susceptible loci of hand osteoarthritis (HOA) in UK and Iceland populations. Located in chromosome 15, ALDH1A2 encodes aldehyde dehydrogenase family 1 member A2, which is an enzyme that catalyses the synthesis of retinoic acid from retinaldehyde. Our purposes were to replicate the association of functional variant in ALDH1A2 with the development of HOA in the Chinese population. Variant rs12915901 of ALDH1A2 was genotyped in 872 HOA patients and 1223 healthy controls. Subchondral bone samples were collected from 40 patients who had undergone a trapeziectomy, and the tissue expression of ALDH1A2 was analysed. The chi-square analysis was used to compare the frequency of genotype and risk allele between the HOA cases and controls. The Student t test was used to compare the mRNA expression of ALDH1A2 between patients with genotype AA/AG and those with genotype GG. The frequency of genotype AA was significantly higher in HOA patients than in the controls (7.6% vs. 5.1%, p = .01). The frequency of allele A was significantly higher in the patients than in the controls (28.9% vs. 24.6%, p = .005). The mRNA expression of ALDH1A2 was 1.31-folds higher in patients with genotype GG than in the patients with genotype AA/AG (0.000617 ± 0.000231 vs. 0.000471 ± 0.000198, p = .04). Variant rs12915901 of ALDH1A2 contributed to the susceptibility of HOA in the Chinese population. Allele A of rs12915901 can add to the risk of HOA possibly via down-regulation of ALDH1A2 expression.

A radiomics nomogram based on multiparametric MRI for diagnosing focal cortical dysplasia and initially identifying laterality.

BACKGROUND: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. METHODS: Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. RESULTS: The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p < 0.05) with the duration of FCD. CONCLUSION: The radiomics nomogram generated by logistic regression model-based multiparametric MRI represents an important advancement in FCD diagnosis and treatment.

SN2 Reaction at the Amide Nitrogen Center Enables Hydrazide Synthesis.

Nucleophilic substitutions are fundamentally important transformations in synthetic organic chemistry. Despite the substantial advances in bimolecular nucleophilic substitutions (SN2) at saturated carbon centers, analogous SN2 reaction at the amide nitrogen atom remains extremely limited. Here we report an SN2 substitution method at the amide nitrogen atom with amine nucleophiles for nitrogen-nitrogen (N-N) bond formation that leads to a novel strategy toward biologically and medicinally important hydrazide derivatives. We found the use of sulfonate-leaving groups at the amide nitrogen atom played a pivotal role in the reaction. This new N-N coupling reaction allows the use of O-tosyl hydroxamates as electrophiles and readily available amines, including acyclic aliphatic amines and saturated N-heterocycles as nucleophiles. The reaction features mild conditions, broad substrate scope (>80 examples), excellent functional group tolerability, and scalability. The method is applicable to late-stage modification of various approved drug molecules, thus enabling complex hydrazide scaffold synthesis.

Ku-band analog photonic down-conversion link with coherent I/Q image rejection and digital linearization.

Analog photonic down-conversion links have been widely used in radar, electronic warfare, and satellite communication systems. Aiming at the optimization demands of the link performance, we demonstrate and experimentally verify a Ku-band photonic down-conversion link based on coherent in-phase/quadrature (I/Q) image rejection and digital nonlinear compensation. The image-rejection ratio at 17.5 GHz is measured to be 47 dB. After digital processing, the image intermodulation distortions (MMD) and the intermodulation distortions (IMD3) are suppressed by 18.1 dB and 10.9 dB, respectively. The corresponding spurious-free dynamic range (SFDR) reaches 108.83 dB·Hz2/3.

Hybrid inverse design scheme for nanophotonic devices based on encoder-aided unsupervised and supervised learning.

Machine learning methods have been regarded as practical tools for the inverse design of nanophotonic devices. However, for the devices with complex expected targets, such as the spectrum with multiple peaks and valleys, there are still many sufferings remaining for these data-driven approaches, such as overfitting. To resolve it, we firstly propose a hybrid inverse design scheme combining supervised and unsupervised learning. Compared with the previous inverse design schemes based on artificial neural networks (ANNs), clustering algorithms and an encoder model are introduced for data preprocessing. A typical metamaterial composed of multiple metal strips that can produce tunable dual plasmon-induced transparency phenomena is designed to verify the performance of our proposed hybrid scheme. Compared with the ANNs directly trained by the entire dataset, the loss functions (mean squared error) of the ANNs in our hybrid scheme can be effectively reduced by more than 51% for both training and test datasets under the same training conditions. Our hybrid scheme paves an efficient improvement for the inverse design tasks with complex targets.

Photonic Hopfield neural network for the Ising problem.

The Ising problem, a vital combinatorial optimization problem in various fields, is hard to solve by traditional Von Neumann computing architecture on a large scale. Thus, lots of application-specific physical architectures are reported, including quantum-based, electronics-based, and optical-based platforms. A Hopfield neural network combined with a simulated annealing algorithm is considered one of the effective approaches but is still limited by large resource consumption. Here, we propose to accelerate the Hopfield network on a photonic integrated circuit composed of the arrays of Mach-Zehnder interferometer. Our proposed Photonic Hopfield Neural Network (PHNN), utilizing the massively parallel operations and integrated circuit with ultrafast iteration rate, converges to a stable ground state solution with high probability. The average success probabilities for the MaxCut problem with a problem size of 100 and the Spin-glass problem with a problem size of 60 can both reach more than 80%. Moreover, our proposed architecture is inherently robust to the noise induced by the imperfect characteristics of components on chip.

A Machine Learning Framework for Diagnosing and Predicting the Severity of Coronary Artery Disease.

Background: Although machine learning (ML)-based prediction of coronary artery disease (CAD) has gained increasing attention, assessment of the severity of suspected CAD in symptomatic patients remains challenging. Methods: The training set for this study consisted of 284 retrospective participants, while the test set included 116 prospectively enrolled participants from whom we collected 53 baseline variables and coronary angiography results. The data was pre-processed with outlier processing and One-Hot coding. In the first stage, we constructed a ML model that used baseline information to predict the presence of CAD with a dichotomous model. In the second stage, baseline information was used to construct ML regression models for predicting the severity of CAD. The non-CAD population was included, and two different scores were used as output variables. Finally, statistical analysis and SHAP plot visualization methods were employed to explore the relationship between baseline information and CAD. Results: The study included 269 CAD patients and 131 healthy controls. The eXtreme Gradient Boosting (XGBoost) model exhibited the best performance amongst the different models for predicting CAD, with an area under the receiver operating characteristic curve of 0.728 (95% CI 0.623-0.824). The main correlates were left ventricular ejection fraction, homocysteine, and hemoglobin (p < 0.001). The XGBoost model performed best for predicting the SYNTAX score, with the main correlates being brain natriuretic peptide (BNP), left ventricular ejection fraction, and glycated hemoglobin (p < 0.001). The main relevant features in the model predictive for the GENSINI score were BNP, high density lipoprotein, and homocysteine (p < 0.001). Conclusions: This data-driven approach provides a foundation for the risk stratification and severity assessment of CAD. Clinical Trial Registration: The study was registered in www.clinicaltrials.gov protocol registration system (number NCT05018715).

Risk stratification and prognostic value of multi-modal MRI-based radiomics for extranodal nasal-type NK/T-cell lymphoma.

BACKGROUND: Magnetic resonance imaging (MRI) performs well in the locoregional assessment of extranodal nasal-type NK/T-cell lymphoma (ENKTCL). It's important to assess the value of multi-modal MRI-based radiomics for estimating overall survival (OS) in patients with ENKTCL. METHODS: Patients with ENKTCL in a prospectively cohort were systemically reviewed and all the pretreatment MRI were acquisitioned. An unsupervised spectral clustering method was used to identify risk groups of patients and radiomic features. A nomogram-revised risk index (NRI) plus MRI radiomics signature (NRI-M) was developed, and compared with the NRI. RESULTS: The 2 distinct type I and II groups of the MRI radiomics signatures were identified. The 5-year OS rates between the type I and type II groups were 87.2% versus 67.3% (P = 0.002) in all patients, and 88.8% versus 69.2% (P = 0.003) in early-stage patients. The discrimination and calibration of the NRI-M for OS prediction demonstrated a better performance than that of either MRI radiomics or NRI, with a mean area under curve (AUC) of 0.748 and 0.717 for predicting the 5-year OS in all-stages and early-stage patients. CONCLUSIONS: The NRI-M model has good performance for predicting the prognosis of ENKTCL and may help design clinical trials and improve clinical decision making.

MiR-107-3p Knockdown Alleviates Endothelial Injury in Sepsis via Kallikrein-Related Peptidase 5.

INTRODUCTION: Endothelial injury is a major characteristic of sepsis and contributes to sepsis-induced multiple-organ dysfunction. In this study, we investigated the role of miR-107-3p in sepsis-induced endothelial injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 20 µg/mL of lipopolysaccharide (LPS) for 6-48 h. The levels of miR-107-3p and kallikrein-related peptidase 5 (KLK5) were examined. HUVECs were treated with LPS for 12 h and subsequently transfected with miR-107-3p inhibitor, KLK5 siRNA, or cotransfected with KLK5 siRNA and miR-107-3p inhibitor/negative control inhibitor. Cell survival, apoptosis, invasion, cell permeability, inflammatory response, and the Toll-like receptor 4/nuclear factor κB signaling were evaluated. In addition, the relationship between miR-107-3p and KLK5 expression was predicted and verified. RESULTS: LPS significantly elevated miR-107-3p levels, which peaked at 12 h. Conversely, the KLK5 level was lower in the LPS group than in the control group and was lowest at 12 h. MiR-107-3p knockdown significantly attenuated reductions in cell survival and invasion, apoptosis promotion, hyperpermeability and inflammation induction, and activation of the NF-κB signaling caused by LPS. KLK5 knockdown had the opposite effect. Additionally, KLK5 was demonstrated as a target of miR-107-3p. MiR-107-3p knockdown partially reversed the effects of KLK5 depletion in LPS-activated HUVECs. CONCLUSIONS: Our findings indicate that miR-107-3p knockdown may protect against sepsis-induced endothelial cell injury by targeting KLK5. This study identified a novel therapeutic target for sepsis-induced endothelial injury.

Photo-Triggered, Copper(II) Chloride-Catalyzed Radical Hydroalkylation and Hydrosilylation of Vinylboronic Esters To Access Alkylboronic Esters.

Alkyl boronic acids and their derivatives constitute vital building blocks in organic synthesis and are important motifs identified in medicinal chemistry. Herein, we present a phototriggered, CuCl2-catalyzed radical hydroalkylation and hydrosilylation of vinylboronic esters to alkylboronic esters. This approach exhibits mild reaction conditions, utilization of easily accessible reagents, and scalability up to a gram scale. Further synthetic transformations of the hydrosilylation products and mechanistic studies are also demonstrated.

Polarization-tunable interfacial properties in monolayer-MoS2 transistors integrated with ferroelectric BiAlO3(0001) polar surfaces.

With the explosion of data-centric applications, new in-memory computing technologies, based on nonvolatile memory devices, have become competitive due to their merged logic-memory functionalities. Herein, employing first-principles quantum transport simulation, we theoretically investigate for the first time the electronic and contact properties of two types of monolayer (ML)-MoS2 ferroelectric field-effect transistors (FeFETs) integrated with ferroelectric BiAlO3(0001) (BAO(0001)) polar surfaces. Our study finds that the interfacial properties of the investigated partial FeFET devices are highly tunable by switching the electric polarization of the ferroelectric BAO(0001) dielectric. Specifically, the transition from quasi-Ohmic to the Schottky contact, as well as opposite contact polarity of respective n-type and p-type Schottky contact under two polarization states can be obtained, suggesting their superior performance metrics in terms of nonvolatile information storage. In addition, due to the feature of (quasi-)Ohmic contact in some polarization states, the explored FeFET devices, even when operating in the regular field-effect transistor (FET) mode, can be extremely significant in realizing a desirable low threshold voltage and interfacial contact resistance. In conjunction with the formed van der Waals (vdW) interfaces in ML-MoS2/ferroelectric systems with an interlayer, the proposed FeFETs are expected to provide excellent device performance with regard to cycling endurance and memory density.

The tunneling electroresistance effect in a van der Waals ferroelectric tunnel junction based on a graphene/In2Se3/MoS2/graphene heterostructure.

In recent years, α-In2Se3 has attracted great attention in miniaturizing nonvolatile random memory devices because of its room temperature ferroelectricity and atomic thickness. In this work, we construct two-dimensional (2D) van der Waals (vdW) heterostructures α-In2Se3/MoS2 with different ferroelectric polarization and design a 2D graphene (Gr)/In2Se3/MoS2/Gr ferroelectric tunnel junction (FTJ) with the symmetric electrodes. Our calculations show that the band alignment of the heterostructures can be changed from type-I to type-II accompanied by the reversal of the ferroelectric polarization of In2Se3. Furthermore, the ferroelectricity persists in Gr/In2Se3/MoS2/Gr vdW FTJs, and the presence of dielectric layer MoS2 in the FTJs enables the effective modulation of the tunneling barrier by altering the ferroelectric polarization of α-In2Se3, which results in two distinct conducting states denoted as "ON" and "OFF" with a large tunneling electroresistance (TER) ratio exceeding 105%. These findings suggest the importance of ferroelectric vdW heterostructures in the design of FTJs and propose a promising route for applying the 2D ferroelectric/semiconductor heterostructures with out-of-plane polarization in high-density ferroelectric memory devices.

Polygenic control of the wavy coat of the NCT mouse: involvement of an intracisternal A particle insertional mutation of the protease, serine 53 (Prss53) gene, and a modifier gene.

The Nakano cataract mouse (NCT) manifests a wavy coat for their first hair as a genetic trait. In this study, we explored the molecular genetic basis of the wavy coat. We revealed by crossing experiments that the wavy coat is controlled by a major gene on chromosome 7 of NCT, homozygosity of which is a prerequisite for developing the wavy coat, and by a gene on chromosome 9 with a minor effect to reinforce the manifestation of the trait. In humans, a polymorphism of the protease, serine 53 (PRSS53) gene on the homologous chromosome is known to be associated with curly scalp hair. We then investigated the Prss53 gene and discovered that NCT has an insertion of an intracisternal A particle element in the first intron of the gene. Nevertheless, the expression of the Prss53 is not altered in the NCT skin both in transcript and protein levels. Subsequently, we created C57BL/6J-Prss53em1 knockout mice and found that these mice manifest vague wavy coats. A portion of backcross and intercross mice between the C57BL/6J-Prss53em1 and NCT manifested intense or vague wavy coats. These findings demonstrate the polygenic nature of the wavy coat of NCT and Prss53 knockout mice and highlight the similarity of the trait to the curly hair of humans associated with the PRSS53 alteration.

Polarization-insensitive coupled optoelectronic oscillator with low spurious tones and phase noise.

A coupled optoelectronic oscillator (COEO) based on σ-shaped fiber ring structure and intra-cavity semiconductor optical amplifier (SOA) is proposed and experimentally demonstrated. The σ-shaped fiber ring structure is skillfully utilized in COEO to eliminate the harmful influence of polarization disturbance. The SOA is embedded for super-mode suppression due to the fast gain saturation effect. The eximious phase noise performance of COEO could be maintained by operating the SOA at the unitary gain regime. The stable operation of COEO is guaranteed by the immunity to polarization fluctuation and the greatly suppressed spurious-mode competition. As a result, a 10-GHz signal is generated featuring high spectral purity and ultra-low spurious tones as soon as the system is power-on, and can hold steady even if the polarization changes dramatically. The single sideband phase noise of the proposed COEO is about -133 dBc/Hz at 10-kHz offset frequency, and the spurious suppression ratio reaches more than 95 dB, which is 60-dB superior than the conventional COEO.

Coexistence of multiple microcombs in monochromatically pumped Si3N4 microresonators.

We experimentally demonstrate that multiple microcombs can coexist in monochromatically pumped Si3N4 microresonators. By pumping around the mode crossing using a CW laser with mixed polarization, three types of coherent microcombs are generated simultaneously: (i) TE-polarized soliton microcomb; (ii) TM-polarized Turing rolls microcomb; and (iii) cross-phase-modulation-induced TM-polarized microcomb. It is proved that the type-(iii) microcomb shares the same comb line spacing with the type-(i) microcomb although the free spectral ranges of TE and TM modes are different. In addition, a 22.95-GHz signal is extracted from a ∼100-GHz microresonator by heterodyning the TE and TM comb lines, and phase noise analysis reveals their coherence characteristics.

Involvement of increased endoplasmic reticulum stress in the development of cataracts in BALB.NCT-Cpoxnct mice.

The BALB.NCT-Cpoxnct is a mutant mouse model for hereditary cataracts. We previously uncovered that the primary cause of the cataracts of BALB.NCT-Cpoxnct is a mutation in the coproporphyrinogen oxidase (Cpox) gene. Because of the mutation, excessive coproporphyrin is accumulated in the BALB.NCT-Cpoxnct lens. In this study, we analyzed the changes in transcriptome and proteins in the lenses of 4- and 12-week-old BALB.NCT-Cpoxnct to further elucidate the molecular etiology of cataracts in this mouse strain. Transcriptome analysis revealed that endoplasmic reticulum (ER) stress was increased in the BALB.NCT-Cpoxnct lens that induced persistent activation of the PERK signaling pathway of the ER stress response. Also, levels of crystallin transcripts and proteins were reduced in the BALB.NCT-Cpoxnct lens. Analysis of proteins disclosed aggregation of crystallins and keratins prior to the manifestation of cataracts in 4-week-old BALB.NCT-Cpoxnct mice. At 12 weeks of age, insoluble crystallins were accumulated in the cataractous BALB.NCT-Cpoxnct lens. Overall, our data suggest the following sequence of events in the BALB.NCT-Cpoxnct lens: accumulated coproporphyrin induces the aggregation of proteins including crystallins. Aggregated proteins increase ER stress that, in turn, leads to the repression of global translation of proteins including crystallins. The decline in the molecular chaperone crystallin aggravates aggregation and insolubilization of proteins. This vicious cycle would eventually lead to cataracts in BALB.NCT-Cpoxnct.

Serum CTRP9 and high-molecular weight adiponectin are associated with ischemic stroke.

BACKGROUND: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke. METHODS: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured. RESULTS: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke and increased during stage III (11th day to one month) and stage IV (1 month after), compared to control. In the non-hyperlipidemia group, serum CTRP9, tAPN, and HMW were decreased in ischemic stroke patients compared to control (P < 0.05). Serum CTRP9 is closely related to serum tAPN and HMW (r = 0.992, 0.991). Serum CTRP9 are protective against ischemic stroke (OR = 0.400, 95% CI 0.197-0.810, P < 0.05). CONCLUSIONS: Lower serum CTRP9, tAPN, LMW, and HMW are significantly associated with increased ischemic stroke risk in non-hyperlipidemia subjects. CTRP9, tAPN, and HMW isoforms may be valuable clinical indicators for patients with ischemic stroke.