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Enceladus is an icy world with potentially habitable conditions, as suggested by the coincident presence of a subsurface ocean, an active energy source due to water-rock interactions, and the basic chemical ingredients necessary for terrestrial life. Among all ocean worlds in our Solar System, Enceladus is the only active body that provides direct access to its ocean through the ongoing expulsion of subsurface material from erupting plumes. Here we present the Enceladus Touchdown aNalyzing Astrobiology (ETNA) mission, a concept designed during the 2019 Caltech Space Challenge. ETNA’s goals are to determine whether Enceladus provides habitable conditions and what (pre-) biotic signatures characterize Enceladus. ETNA would sample and analyze expelled plume materials at the South Polar Terrain (SPT) during plume fly-throughs and landed operations. An orbiter includes an ultraviolet imaging spectrometer, an optical camera, and radio science and a landed laboratory includes an ion microscope and mass spectrometer suite, temperature sensors, and an optical camera, plus three seismic geophones deployed during landing. The nominal mission timeline is 2 years in the Saturnian system and ∼1 year in Enceladus orbit with landed operations. The detailed exploration of Enceladus’ plumes and SPT would achieve broad and transformational Solar System science related to the building of habitable worlds and the presence of life elsewhere. The nature of such a mission is particularly timely and relevant given the recently released Origins, Worlds, and Life: A Decadal Strategy for Planetary Science and Astrobiology 2023–2032, which includes a priority recommendation for the dedicated exploration of Enceladus and its habitable potential.

Yeo Jin Choi,1,* Yong Won Choi,2,* Jung-woo Chae,3,* Hwi-yeol Yun,3 Sooyoung Shin4,5 1Department of Clinical Pharmacy, Graduate School of Clinical Pharmacy, CHA University, Seongnam, Gyeonggi-do, 13488, Republic of Korea; 2Department of Hematology-Oncology, School of Medicine, Ajou University, Suwon, Gyeonggi-do, 16499, Republic of Korea; 3College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea; 4College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, 16499, Republic of Korea; 5Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Gyeonggi-do, 16499, Republic of Korea*These authors contributed equally to this workCorrespondence: Sooyoung Shin; Hwi-yeol Yun Tel +82 31 219 3456; +82 42 821 5941Fax +82 31 219 3435; +82 42 823 6566Email syshin@ajou.ac.kr; hyyun@cnu.ac.krBackground: Cancer patients are at increased risk for venous thromboembolism (VTE) due to cancer-induced hypercoagulability. However, current guidelines do not routinely recommend prophylactic use of oral anticoagulants to prevent VTE in cancer patients.Objective: To evaluate the efficacy and safety of novel oral anticoagulants (NOACs) versus no anticoagulant use (no-use) and, additionally, differential effects between NOACs and warfarin, in VTE and adverse bleeding prevention among cancer patients, in consideration of risk stratification by gender, high-risk chemotherapy exposure, and Khorana index.Methods: This national health insurance data-based study with a 180-day follow-up enrolled cancer patients with or without oral anticoagulant use in 2017. The primary outcome was VTE risk in oral anticoagulant users vs non-users. Four propensity score-matched comparison pairs were designed: use vs no-use, NOAC vs no-use, warfarin vs no-use, and NOAC vs warfarin. A logistic regression model was used to investigate between-group differences in VTE and bleeding risk.Results: When compared to no-use, NOACs showed substantial effects in preventing VTE complications (OR=0.40, p< 0.001), primarily deep vein thrombosis (DVT) events (OR=0.38, p< 0.001), in both male and female cancer patients as well as those with a Khorana score ≥ 1. Adverse bleeding risk was comparable or lower in NOAC-receiving female patients (p=0.13) and male patients (p=0.04), respectively. In contrast, no protective effects were found with warfarin compared to no-use in controlling thrombosis and adverse bleeding risk. In a head-to-head comparison of NOACs versus warfarin, DVT risk in those patients exposed to high-risk chemotherapy was significantly decreased with NOAC use (OR=0.19, p=0.03).Conclusion: NOACs can be a promising thromboprophylactic option in both male and female cancer patients with VTE risk.Keywords: venous thromboembolism, cancer, oral anticoagulant, Khorana

To examine the factors associated with ovarian failure (OF) and assess the effectiveness of ovarian transposition (OT) before pelvic irradiation for preserving ovarian function in patients with cervical cancer (CC) undergoing hysterectomy. During 2003 to 2017, patients who underwent hysterectomy with preservation of one or both ovaries were retrospectively enrolled. Patients were divided into 4 groups, depending on whether radiotherapy (RT) and OT were performed: group 1, RT(+) and OT(+); group 2, RT(+) and OT(−); group 3, RT(−) and OT(+); group 4, RT(−) and OT(−). OF was defined as serum follicle-stimulating hormone levels of ≥30 mIU/mL. Sixty-six patients (59 [89.4%] invasive CC and 7 [10.6%] cervical intraepithelial neoplasia) were included. The 2-year OF-free survival rate was 61.4% (95% confidence interval [CI] 37.8-86.0), 0%, 91.7% (95% CI 76.0-100), and 75.8% (95% CI 58.2-93.4) for groups 1, 2, 3, and 4, respectively. In groups 1 and 2 receiving RT, OT, and combination of external beam radiotherapy and vaginal brachytherapy were associated with OF on multivariate analysis (MVA) ( P -value = .002 and .046, respectively). In groups 3 and 4 without RT, older age (40 years old) and OT did not affect OF; however, the number of remaining ovaries was independently associated with OF in MVA ( P = .035). OT could effectively preserve ovarian function in patients treated with adjuvant RT, while OT procedure itself did not affect ovarian failure. OT should be considered in the management of premenopausal cervical cancer patients.

The quantification of the UV characteristics of smoke aerosols is valuable to UV Index forecasting, air quality studies, air chemistry studies, and assessments of the impacts on regional and global environmental changes. The wavelength dependence of the light absorption by smoke aerosol has been researched throughout the UV and visible spectral region and varies with fire type and aerosol composition. An objective of this study is to investigate the spectral optical properties (eg, extinction coefficient, single-scattering albedo, and asymmetry parameter), UV actinic fluxes, and radiative forcing of smoke of different fire regimes. The smoke aerosol information (eg, simulated smoke fields from biomass burning emission and vertical distribution of the mass concentration of smoke components) from WRF-Chem is used to distinguish 2 smoke types: flaming and smoldering. To compute the spectral optical properties for the fire regimes, the representative size distribution and spectral refractive index have been implemented into the Mie code, and the optical properties are used to run the tropospheric ultraviolet and visible radiative transfer model. We make comparisons between simulated model and measured actinic flux in the UV and visible spectra under smoke aerosol laden conditions. The WRF-Chem-SMOKE model simulates the smoke plume matched with fire locations and comparable aerosol optical depth (AOD) with satellite measurements. However, the correlation between the simulated and observed AOD is small, which implies that adjusting the fire size for the emission inputs and improving meteorological fields are required for further research. The smoke at selected locations reduces the UV actinic flux and increases the visible actinic flux above the plume at small solar zenith angles. The specific spectral response is dependent on the smoke type. Overall, the results of this investigation show that this approach is valuable to estimate the impact of smoke on UV and visible radiative fluxes.

Traditionally, chemical agents such as formalin (FA) and β-propiolactone (BPL) have long been used for the preparation of inactivated vaccines or toxoids. It has been shown that FA extensively modifies vaccine antigens and thus affects immunogenicity profiles, sometimes compromising the protective efficacy of the vaccines or even exacerbating the disease upon infection. In this study, we show that natural catechins from green tea extracts (GT) can be used as an inactivating agent to prepare inactivated viral vaccines. GT treatment resulted in complete and irreversible inactivation of influenza virus as well as dengue virus. In contrast to FA that reacted extensively with multiple amino acids including lysine, a major anchor residue for epitope binding to MHC molecules, GT catechin epigallocatechin-3-gallate (EGCG) crosslinked primarily with cysteine residues and thus preserved the major epitopes of the influenza hemagglutinin. In a mouse model, vaccination with GT-inactivated influenza virus (GTi virus) elicited higher levels of viral neutralizing antibodies than FA-inactivated virus (FAi virus). The vaccination completely protected the mice from a lethal challenge and restricted the challenge viral replication in the lungs. Of note, the quality of antibody responses of GTi virus was superior to that with FAi virus, in terms of the magnitude of antibody titer, cross-reactivity to hetero-subtypes of influenza viruses, and the avidity to viral antigens. As the first report of using non-toxic natural compounds for the preparation of inactivated viral vaccines, the present results could be translated into a clinically relevant vaccine platform with improved efficacy, safety, productivity, and public acceptance.

Platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a potent phospholipid mediator and has been reported to be localized in atherosclerotic plaque. However, its role in the progression of atherosclerosis remains unclear. In the present study, we investigated the role of PAF in the production of matrix metalloproteinase (MMP) in primary vascular smooth muscle cells (VSMCs). When rat aortic primary VSMCs were stimulated with PAF (1 nmol/l), the expressions of MMP-2 mRNA and protein, but not of MMP-9, were significantly increased, and these upregulations were markedly attenuated by inhibiting extracellular signal-regulated kinases (ERKs) using molecular and pharmacological inhibitors, but not by using inhibitors of p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. Likewise, ERK phosphorylation was markedly enhanced in PAF-stimulated VSMCs, and this was attenuated by WEB2086, but not by EGF receptor inhibitor, demonstrating the specificity of PAF receptor (PAFR) in PAF-induced ERK phosphorylation. In immunofluorescence studies, β-arrestin2 in PAF-stimulated VSMCs colocalized with PAFR and phosphorylated ERK (P-ERK). Coimmunoprecipitation results suggest that β-arrestin2-bound PAFRs existed as a complex with P-ERK. In addition, PAF-induced ERK phosphorylation and MMP-2 production were significantly attenuated by β-arrestin2 depletion. Taken together, the study shows that PAF enhances MMP-2 production in VSMCs via a β-arrestin2-dependent ERK signaling pathway.

This study investigates the impact of green trade exports (GTE) on green total factor productivity (GTFP) and environmental sustainability in OECD countries using panel data from 2003 to 2016. We employ linear regression models, polynomial models, and threshold regression techniques to analyze this relationship. Our findings reveal an inverted N-shaped curve between GTE and GTFP, with two turning points. The threshold regression results indicate that when clean energy is below 8.660%, a 1 unit increase in GTE decreases GTFP by 1.518 units. However, when clean energy exceeds this threshold, a 1 unit increase in GTE increases GTFP by 1.056 units. For R&D, the effect of GTE on GTFP changes from −3.165 to 1.193 as R&D exceeds the threshold of 0.664%. Additionally, we find that GTE has a lagged effect on increasing CO2 emissions, with coefficients of 0.0234 and 0.0278 for 1-year and 2-year lags, respectively. The interaction between clean energy and GTE reduces CO2 emissions by 0.00234 units and PM2.5 by 0.0145 units. These results provide important insights for policymakers in developing countries seeking to participate effectively in the global industrial chain while promoting sustainable development. [ABSTRACT FROM AUTHOR]

In this paper, an effective equivalent modeling technique has been proposed to describe small-signal characteristics of InP-based high electron mobility transistors (HEMTs) after proton radiation, which is composed of an artificial neural network and equivalent-circuit models. Small-signal intrinsic parameters of InP-based HEMTs are extracted from S-parameters before and after 2 MeV proton radiation as modeling objects. The deep learning model of a generative adversarial network has been explored to expand the measured finite data samples. Four feedforward neural networks are incorporated to equivalent-circuit topology to form the equivalent model, which are trained to accurately predict the radiation-induced variations of Cgs, Cgd, Rds, and gm, respectively. The prediction accuracy of the developed equivalent model has been well verified in terms of the broad-band S-parameters under radiation fluence of 1 × 1014 and 5 × 1013 H+/cm2. This equivalent modeling method with characterization of radiation damage effects could provide significant guidance for the aerospace monolithic millimeter-wave integrated circuit design. [ABSTRACT FROM AUTHOR]

Abstract Background Cancer creates an immunosuppressive environment that hampers immune responses, allowing tumors to grow and resist therapy. One way the immune system fights back is by inducing ferroptosis, a type of cell death, in tumor cells through CD8 + T cells. This involves lipid peroxidation and enzymes like lysophosphatidylcholine acyltransferase 3 (Lpcat3), which makes cells more prone to ferroptosis. However, the mechanisms by which cancer cells avoid immunotherapy-mediated ferroptosis are unclear. Our study reveals how cancer cells evade ferroptosis and anti-tumor immunity through the upregulation of fatty acid-binding protein 7 (Fabp7). Methods To explore how cancer cells resist immune cell-mediated ferroptosis, we used a comprehensive range of techniques. We worked with cell lines including PD1-sensitive, PD1-resistant, B16F10, and QPP7 glioblastoma cells, and conducted in vivo studies in syngeneic 129 Sv/Ev, C57BL/6, and conditional knockout mice with Rora deletion specifically in CD8+ T cells, Cd8 cre;Rora fl mice. Methods included mass spectrometry-based lipidomics, targeted lipidomics, Oil Red O staining, Seahorse analysis, quantitative PCR, immunohistochemistry, PPARγ transcription factor assays, ChIP-seq, untargeted lipidomic analysis, ROS assay, ex vivo co-culture of CD8+ T cells with cancer cells, ATAC-seq, RNA-seq, Western blotting, co-immunoprecipitation assay, flow cytometry and Imaging Mass Cytometry. Results PD1-resistant tumors upregulate Fabp7, driving protective metabolic changes that shield cells from ferroptosis and evade anti-tumor immunity. Fabp7 decreases the transcription of ferroptosis-inducing genes like Lpcat3 and increases the transcription of ferroptosis-protective genes such as Bmal1 through epigenetic reprogramming. Lipidomic profiling revealed that Fabp7 increases triglycerides and monounsaturated fatty acids (MUFAs), which impede lipid peroxidation and ROS generation. Fabp7 also improves mitochondrial function and fatty acid oxidation (FAO), enhancing cancer cell survival. Furthermore, cancer cells increase Fabp7 expression in CD8+ T cells, disrupting circadian clock gene expression and triggering apoptosis through p53 stabilization. Clinical trial data revealed that higher FABP7 expression correlates with poorer overall survival and progression-free survival in patients undergoing immunotherapy. Conclusions Our study uncovers a novel mechanism by which cancer cells evade immune-mediated ferroptosis through Fabp7 upregulation. This protein reprograms lipid metabolism and disrupts circadian regulation in immune cells, promoting tumor survival and resistance to immunotherapy. Targeting Fabp7 could enhance immunotherapy effectiveness by re-sensitizing resistant tumors to ferroptosis.

Abstract As technology advances, rangeland management is rapidly transitioning toward intelligent systems. To optimize grassland resources and implement scientific grazing practices, livestock grazing monitoring has become a pivotal area of research. Traditional methods, such as manual tracking and wearable monitoring, often disrupt the natural movement and feeding behaviors of grazing livestock, posing significant challenges for in-depth studies of grazing patterns. In this paper, we propose a machine vision-based grazing goat herd detection algorithm that enhances the streamlined ELAN module in YOLOv7-tiny, incorporates an optimized CBAM attention mechanism, refines the SPPCSPC module to reduce the parameter count, and improves the anchor boxes in YOLOv7-tiny to enhance target detection accuracy. The BiAF-YOLOv7 algorithm achieves precision, recall, F1 score, and mAP values of 94.5, 96.7, 94.8, and 96.0%, respectively, on the goat herd dataset. Combined with DeepSORT, our system successfully tracks goat herds, demonstrating the effectiveness of the BiAF-YOLOv7 algorithm as a tool for livestock grazing monitoring. This study not only validates the practicality of the proposed algorithm but also highlights the broader applicability of machine vision-based monitoring in large-scale environments. It provides innovative approaches to achieve grass-animal balance through information-driven methods, such as monitoring and tracking.

Abstract Background The triglyceride-glucose (TyG) index has been validated as a novel biomarker for cardiovascular disease (CVD) risk. However, the prospective relationship between baseline and long-term trajectories of the TyG index and CVD risk in people living with HIV (PLWH) remains unexplored. Methods This cohort study included 16,122 treatment-naive PLWH who initiated antiretroviral therapy (ART) at the Third People's Hospital of Shenzhen from 2005 to 2022. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Group-based trajectory modeling was used to identify distinct TyG index trajectories over the follow-up period. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using multivariate Cox proportional hazards models to assess the association between TyG index trajectories and CVD risk. Nonlinear relationships were investigated using a restricted cubic spline plot. Results During a median follow-up of 70 months, 214 PLWH developed CVD. Each 1-standard deviation (SD) increase in the baseline TyG index was associated with a 39% higher risk of CVD (HR 1.39, 95% CI 1.22, 1.59) after adjusting for covariates. Participants were categorized into four distinct TyG trajectory groups: low-stable, low-moderate-stable, high-moderate-stable, and high-increasing. After multivariate adjustment, the high-increasing trajectory group had a 2.92-fold (95% CI 1.68, 5.05) increased risk of CVD compared to the low-stable group. The restricted cubic spline plot showed an upward trend between the baseline TyG index and the CVD occurrence (P

Abstract Objective This study aimed to evaluate the effectiveness and safety of everolimus in treating seizures associated with focal cortical dysplasia type 2 (FCD 2). Methods A prospective, crossover, placebo‐controlled clinical trial (ClinicalTrials.gov: NCT03198949) enrolled patients aged 4–40 years with pathologically confirmed FCD 2 and a history of ≥3 seizures per month for two out of the 3 months prior to screening. The trial included a 4‐week baseline phase, two 12‐week core phases, and a 29‐week extension phase. Patients received everolimus or placebo in a blinded manner during core phase I, with crossover to the alternate treatment in core phase II. Everolimus dosage started at 4.5 mg/m2/day, targeting a serum level of 5–15 ng/mL. The primary outcome was the proportion of patients achieving ≥50% seizure reduction from baseline in the last month of each core phase. Safety profiles were compared between groups. Results Between May 11, 2017, and June 19, 2020, 21 patients completed the core phases. There was no significant difference in the primary outcome between everolimus and placebo groups (24% vs. 19%, p = 0.66). The patients showed varied responses. Three patients with a pathogenic variant in the MTOR gene or no genetic abnormalities achieved seizure freedom with everolimus in the last month of the core phase, while none of the patients with variants in other genes did. Adverse events, such as mucositis or skin ulceration, were more common with everolimus (19/21 vs. 7/21, p

Objective This study investigated the effects of circRNA18_46222157_46248185 (named circRNA18) on goat melanogenesis, which differs significantly in goat skins isolated from white and brown coat-colored skins. Methods Expression patterns of circRNA18 in goat skin and melanocytes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. The circRNA18 interference vector was designed and synthesized to transfect melanocytes and detect the effect of circRNA18 interference on melanin production. Bioinformatics software was used to predict the targeted adsorption miRNAs of circRNA18, verified by luciferase assay. A miRNA expression vector was constructed and transfected into melanocytes to detect the effect of miRNA on melanin production, and the targeted regulatory genes were detected by luciferase assay. Target gene interference vector was constructed to detect the influence of target gene interference on melanin production. Results qRT-PCR results unveiled distinct expression patterns of circRNA18 in diverse tissues of male and female goats, while in situ hybridization assays showed that circRNA18 is expressed in the cytoplasm of melanocytes. Functional analysis demonstrated that the downregulation of circRNA18 in melanocytes leads to a significant increase (p

Abstract Premature frailty is a critical challenge for young breast cancer survivors (YBCSs), impacting their health and perpetuating gender inequality through heightened vulnerability and marginalization. While digital health shows promise in frailty screening, its effectiveness for comprehensively managing frailty remains inconclusive. This randomized controlled trial, registered at the Chinese Clinical Trial Registry (ChiCTR2200058823), tests the “AI-TA” program’s efficacy on premature frailty and quality of life in YBCSs. The intervention group received a gender- and generation-sensitive program combining artificial intelligence interactions and humanities skills. The control group received 12 weeks of online information support. Both groups improved in frailty dimensions (P

In order to solve the problems that the decomposition results of current similar data decomposition methods are inconsistent with the actual text quantity, the increase of sensitive data is not significant, and the absolute error mean and normalized root mean square error are high, a large-scale real text corpus similar data decomposition method is proposed. Dividing into a plurality of minority sub-clusters, determining the probability distribution of the minority sub-clusters in the similar data set of the text corpus, and sampling the data in the similar data set of the text corpus. On the basis of data ontology structure mapping model and text big data analysis model, tag semantics are generated to realize similar data decomposition of text corpus. The experimental results show that this method improves the category imbalance of the original data set, can decompose the text accurately, and the decomposition results are basically consistent with the actual text quantity, with lower absolute error mean and normalized root mean square error, and have better similar data decomposition ability.

Abstract Objectives To develop ultrasound-based radiomics models and a clinical model associated with inflammatory markers for predicting intrahepatic cholangiocarcinoma (ICC) lymph node (LN) metastasis. Both are integrated for enhanced preoperative prediction. Methods This study retrospectively enrolled 156 surgically diagnosed ICC patients. A region of interest (ROI) was manually identified on the ultrasound image of the tumor to extract radiomics features. In the training cohort, we performed a Wilcoxon test to screen for differentially expressed features, and then we used 12 machine learning algorithms to develop 107 models within the cross-validation framework and determine the optimal radiomics model through receiver operating characteristic (ROC) curve analysis. Multivariable logistic regression analysis was used to identify independent risk factors to construct a clinical model. The combined model was established by combining ultrasound-based radiomics and clinical parameters. The Delong test and decision curve analysis (DCA) were used to compare the diagnostic efficacy and clinical utility of different models. Results A total of 1239 radiomics features were extracted from the ROIs of tumors. Among the 107 prediction models, the model (Stepglm + LASSO) utilizing 10 radiomics features ultimately yielded the highest average area under the receiver operating characteristic curve (AUC) of 0.872, with an AUC of 0.916 in the training cohort and 0.827 in the validation cohort. The combined model, which incorporates the optimal radiomics score, clinical N stage, and platelet-to-lymphocyte ratio (PLR), achieved an AUC of 0.882 in the validation cohort, significantly outperforming the clinical model with an AUC of 0.687 (P = 0.009). According to the DCA analysis, the combined model also showed better clinical benefits. Conclusions The combined model incorporating ultrasound-based radiomics features and the PLR marker offers an effective, noninvasive intelligence-assisted tool for preoperative LN metastasis prediction in ICC patients. Clinical trial number Not applicable.

Abstract This retrospective study aimed to stress the advantages of autologous hematopoietic stem cell transplantation (auto-HSCT) in treating primary MM. Ninety-four MM patients who underwent initial parallel sequential auto-HSCT were selected. Data on efficacy (efficacy evaluation, renal function and hemoglobin recovery), immune reconstitution (B-cell subsets, immunoglobulin levels, T-cell subsets, NK cells, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR)) and hematopoietic reconstitution times were collected and analyzed. Whether in all selected patients or in groups R-ISS II-III, there was a notable increase in the proportion of patients achieving in a very good partial response (VGPR) or better (P

Abstract Early antiretroviral therapy (ART) initiation is known to limit the establishment of the HIV reservoir, with studies suggesting benefits such as a reduced number of infected cells and a smaller latent reservoir. However, the long-term impact of early ART initiation on the dynamics of the infected cell pool remains unclear, and clinical evidence directly comparing proviral integration site counts between early and late ART initiation is limited. In this study, we used Linear Target Amplification-PCR (LTA-PCR) and Next Generation Sequencing to compare unique integration site (UIS) clonal counts between individuals who initiated ART during acute HIV infection stage (Acute-ART group) and those in the AIDS stage (AIDS-ART group). Our analysis revealed distinct clonal distribution patterns, with greater UIS heterogeneity in Acute-ART group and more homogeneity in AIDS-ART group. Monoclonal UIS accumulation, predominantly in-gene regions, was influenced by ART timing and duration, with early treatment delaying this process. Host cell genes integrated by HIV provirus as monoclonal types were enriched in cell cycle and lymphocyte activation pathways. Tumor suppressor genes (TSGs) were more frequently integrated as monoclonal types in AIDS-ART group, suggesting potential risk factors. Overall, we introduced a sequencing method to assess provirus size in human peripheral blood and identified the widespread presence of monoclonal distribution of UIS in AIDS-ART group after long-term treatment. The early intervention helps slow the progress of clonal expansion of infected cells, reducing the formation of stable and persistent reservoirs, and ultimately posing fewer barriers to achieving a functional cure.