Chidamide induces cell cycle arrest via NR4A3/P21 axis upregulation to suppress relapsed and refractory acute myeloid leukemia.

(1) Currently, the survival prognosis for patients with relapsed and refractory acute myeloid leukemia (R/R AML) is extremely poor. Therefore, the exploration of novel drugs is imperative to enhance the prognosis of patients with R/R AML. The therapeutic efficacy and mechanism of Chidamide, a novel epigenetic regulatory drug, in the treatment of R/R AML remain unclear. METHODS: The mechanism of action of Chidamide has been explored in various AML cell lines through various methods such as cell apoptosis, cell cycle analysis, high-throughput transcriptome sequencing, gene silencing, and xenograft models. RESULTS: Here, we have discovered that chidamide potently induces apoptosis, G0/G1 phase arrest, and mitochondrial membrane potential depolarization in R/R AML cells, encompassing both primary cells and cell lines. Through RNA-seq analysis, we further revealed that chidamide epigenetically regulates the upregulation of differentiation-related pathways while suppressing those associated with cell replication and cell cycle progression. Notably, our screening identified NR4A3 as a key suppressor gene whose upregulation by chidamide leads to P21-dependent cell cycle arrest in the G0/G1 phase. CONCLUSIONS: We have discovered a novel epigenetic regulatory mechanism of chidamide in the treatment of relapsed and refractory acute myeloid leukemia (R/R AML).

Extraction of Uranium by a Pyrazole-Based Porous Organic Polymer.

In this work, we report a pyrazole-based porous organic polymer (namely, ECUT-POP-2) for extraction of uranium. ECUT-POP-2 affords a high uranium extraction capacity of up to 1851 mg/g, excellent selectivity, and good reusability, suggesting its superior application in treating uranium-containing wastewater and acquring nuclear fuel.

Robust Six-Connected Self-Penetrating Net with Two-Fold Interpenetration for Trace SO2 Removal and UO22+ Detection.

We reported in this work a new metal-organic framework, ECUT-177, showing a highly rare six-connected net with both self-penetrating and interpenetrating features. More interestingly, ECUT-177 also enables promising applications in both trace SO2 capture and luminescence sensing of uranyl.

SEMA4D/PlexinB1 promotes AML progression via activation of PI3K/Akt signaling.

BACKGROUND: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. SEMA4D is a 150 kDa transmembrane protein that belongs to the IV class of the subfamily of semaphorin family. Previous studies have reported that SEMA4D is a multifunctional target in many solid tumors, involving multiple physiological systems, and there are emerging therapies to target these pathways. The role of SEMA4D in AML has not yet been explored. METHODS: The SEMA4D expression prolile, clinical data and potential prognostic analysis were acquired via the cBioPortal and GEPIA databases. SEMA4D expression was measured using real-time quantitative PCR and western blot. Cell counting kit-8 (CCK8) and flow cytometry were used to evaluate the malignant biological characteristics. RESULTS: We observed that SEMA4D was increased in AML patients and correlated with risk stratification and prognosis. Moreover, SEMA4D promotes the proliferation and inhibits apoptosis of AML cells by binding to its receptor, PlexinB1, and reduces the sensitivity of AML cells to daunorubicin. In addition, SEMA4D/PlexinB1 promotes the proliferation and survival of AML cells by activating the PI3K/Akt signaling pathway. VX15/2503, an anti-SEMA4D antibody, can inhibit the proliferation of AML cells in xenograft mouse models, thereby inhibiting the development of AML. CONCLUSION: SEMA4D will serve as a unique predictive biomarker and a possible therapeutic target in AML.

Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves' disease.

Liver dysfunction is a common complication of Graves' disease (GD) that may be caused by excessive thyroid hormone (TH) or anti-thyroid drugs (ATDs). Radioactive iodine (RAI) therapy is one of the first-line treatments for GD, but it is unclear whether it is safe and effective in patients with liver dysfunction. 510 consecutive patients with GD receiving first RAI were enrolled in the study, and followed up at 3-, 6- and 12-month. Liver dysfunction was recorded in 222 (43.5%) patients. GD patients with liver dysfunction had higher serum levels of free triiodothyronine (FT3) (median 27.6 vs. 20.6 pmol/L, p < 0.001) and free thyroxine (FT4) (median 65.4 vs. 53.5 pmol/L, p < 0.001) levels than those with normal liver function. Binary logistic regression analysis showed that duration of disease (OR = 0.951, 95% CI: 0.992-0.980, p = 0.001) and male gender (OR = 1.106, 95% CI: 1.116-2.384; p = 0.011) were significant differential factors for liver dysfunction. Serum TSH levels were higher in patients with liver dysfunction at all 3 follow-up time points (p = 0.014, 0.008, and 0.025 respectively). FT3 level was lower in patients with liver dysfunction at 3-month follow-up (p = 0.047), but the difference disappeared at 6 and 12 months (p = 0.351 and 0.264 respectively). The rate of euthyroidism or hypothyroidism was higher in patients with liver dysfunction than in those with normal liver function at 3 months (74.5% vs 62.5%; p = 0.005) and 6 months (82.1% vs 69.1%; p = 0.002) after RAI treatment, but the difference did not persist at 12-month follow-up (89.6% vs 83.2%, p = 0.081).There were no statistically significant differences in treatment efficacy (94.48% vs 90.31%, p = 0.142), incidence of early-onset hypothyroidism (87.73% vs 83.67%, p = 0.277), and recurrence rate (4.91% vs 7.14%, p = 0.379) between the 2 groups at 12-month follow-up. In conclusion, the efficacy of RAI was comparable in GD patients with liver dysfunction and those with normal liver function.

SPAG1 promotes the development of AML by activating the ERK/MAPK signaling pathway and affects the chemotherapy sensitivity of venetoclax.

Sperm-associated antigen 1 (SPAG1) is considered to be associated with infertility and tumorigenesis. However, its function in acute myeloid leukemia (AML) remains unclear. In this study, we evaluated the expression level of SPAG1 and explored its clinical prognostic value in patients with AML, as well as its biological function in AML cells. SPAG1 is widely expressed in AML patients, resulting in a poor prognosis. However, its expression was not associated with Fms-related receptor tyrosine kinase 3 (FLT3) mutations. Utilizing the RNA interference knockdown tests, we found that SPAG1 could promote the proliferation and survival of AML cells and regulate the expression of structural maintenance of chromosomes protein 3 (SMC3), activating the ERK/MAPK signaling pathway. Furthermore, we discovered that inhibiting SPAG1 impacted AML cell susceptibility to venetoclax. In conclusion, SPAG1 may serve as a potential therapeutic target in AML.

A High-Precision Algorithm for DOA Estimation Using a Long-Baseline Array Based on the Hearing Mechanism of the Ormia Ochracea.

Inspired by the Ormia Ochracea hearing mechanism, a new direction of arrival estimation using multiple antenna arrays has been considered in spatially colored noise fields. This parasitoid insect can locate s cricket's position accurately using the small distance between its ears, far beyond the standard array with the same aperture. This phenomenon can be understood as a mechanical coupled structure existing between the Ormia ears. The amplitude and phase differences between the received signals are amplified by the mechanical coupling, which is functionally equivalent to a longer baseline. In this paper, we regard this coupled structure as a multi-input multi-output filter, where coupling exists between each pair of array elements. Then, an iterative direction-finding algorithm based on fourth-order cumulants with fully coupled array is presented. In this manner, the orientation of the mainlobe can direct at the incident angle. Hence, the direction-finding accuracy can be improved in all possible incident angles. We derive the Cramér-Rao lower bound for our proposed algorithm and validate its performance based on simulations. Our proposed DOA estimation algorithm is superior to the existing biologically inspired direction-finding and fourth-order cumulants-based estimation algorithms.

The three-phase enriched environment paradigm promotes neurovascular restorative and prevents learning impairment after ischemic stroke in rats.

Enriched environment (EE) with a complex combination of sensorimotor, cognitive and social stimulations has been shown to enhance brain plasticity and improve recovery of functions in animal models of stroke. The present study extended these findings by assessing whether the three-phase EE intervention paradigm would improve neurovascular remodeling following ischemic stroke. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). A three-phase EE intervention paradigm was designed in terms of the different periods of cerebral ischemia by periodically rearranging the EE cage. Morris water maze (MWM) tests were performed to evaluate the learning and memory function. Multimodal MRI was applied to examine alterations to brain structures, intracranial vessels, and cerebral perfusion on the 31st day after MCAO. The changes of capillaries ultrastructure were examined by transmission electron microscope. Double-immunofluorescent staining was used to evaluate neurogenesis and angiogenesis. The expression of angiogenesis-related factors and neurovascular remodeling related signaling pathways including Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/ß-catenin and the axon guidance molecules were detected by Western blot analysis. MRI measurements revealed that EE treatment significantly increased survival volume of cortex and striatum, improved cerebral blood flow (CBF), amplified anterior azygos cerebral artery (azACA), ipsilateral internal carotid artery (ICA) and anterior communicating artery (AComA) vessel signal compared with standard housed rats (IS). Consistent with these findings, EE reduced ischemic BBB damage of capillary, enhanced endogenous angiogenesis and modified the expression of VEGF, Ang-1 or Ang-2 in ischemic rats. Additionally, this proangiogenic effect was consistent with the increased progenitor cell proliferation and neuronal differentiation in the peri-infarct cortex and striatum after EE intervention. Specifically, EE intervention paradigm markedly increased expression of phosphorylated PI3K, AKT and GSK-3, but reduced phosphorylated ß-catenin. Moreover, the axon guidance proteins expression level was significant higher in EE group. In parallel to these findings, EE significantly enhanced recovery of lost spatial learning memory function in MCAO rats without affecting infarct size. Together, MRI findings along with histological results strongly supported that the three-phase EE paradigm benefited neurovascular reorganization and thereby improved poststroke cognitive function. Moreover, our findings suggest that this type of EE paradigm induced neurogenesis and angiogenesis, at least in part, via regulating PI3K/AKT/GSK-3/ß-catenin signaling pathway and activation of the intrinsic axonal guidance molecules in animal models of ischemic stroke.

Boosting Selective Adsorption of Xe over Kr by Double-Accessible Open-Metal Site in Metal-Organic Framework: Experimental and Theoretical Research.

Obtaining highly valuable Xe from air or other sources is highly important but still seriously restricted by its inherent inert nature and the great difficulty in separation from other inert gases, especially for Xe and Kr that show comparable size. In this work, we show both experimental and theoretical research of how to boost the selective adsorption of Xe over Kr by double-accessible open-metal site in metal-organic framework (MOF). The MOF, namely, UTSA-74, shows a high Xe uptake up to 2.7 mmol/g and a lower Kr uptake of 0.58 mmol/g at 298 K and 1 bar, leading to a high selectivity of 8.4. The effective Xe/Kr separation was further confirmed by both transient breakthrough simulation and experimental breakthrough. The separation mechanism, as unveiled by the grand canonical Monte Carlo simulation and dispersion-corrected density functional theory calculation, is due to the unique double-accessible open-metal site in UTSA-74 that affords stronger interaction toward Xe than Kr.

Multi-Sensor Passive Localization Using Direct Position Determination with Time-Varying Delay.

This paper focuses on passive emitter localization using moving sensors. The increase in observation time is beneficial to improve the localization accuracy, but it could cause deterioration of the relative motion between the emitter and the sensors, especially the nonlinear motion. The common localization algorithms typically have two steps: (1) parameter estimation and (2) position determination, where the parameters are assumed to be constant, and it is not applicable for long observation times. We proposed the time-varying delay-based direct position determination (DPD-TVD) method, regarding the variation in the propagation time delay during the observation time. Using one step, the proposed algorithm can obtain the emitter's position directly from the received signals by calculating the cost function corresponding to the map grid. By better adapting to highly dynamic scenarios, the proposed algorithm can achieve better localization accuracy than that of constant parameters using one-step or two-step procedures, which is demonstrated by the simulation results.

[Morphological and microscopical identification of Genkwa Ramulus and its adulterants].

The purpose of this article is to identify Daphne genkwa and its adulterants, Wikstroemia chamaedaphne, according to the morphological and microstructure characteristics of their stem and foliage. The root of D.genkwa was studied simultaneously. The results indicated that the crude drug and processed pieces of Genkwa Ramulus were mainly composed of stems and branches where obvious opposite petiole scars and branch marks were able to be seen on their nodes. Otherwise, foliage or peduncles generally couldn't be found. Moreover, the fine silver flocculent fibers could be observed in the bark of fracture surface. The adulterants were the plant segments which were composed of stems, foliage and peduncles with spikelet-pedicel scars. There existed microstructures differences between Genkwa Ramulus and its adulterants. In the former, single thick lignified phloem fibers were interspersed in the stem phloem of the transverse section with very thick wall and unicellular non-glandular hairs could be observed on the lower epidermis of foliage. Nevertheless, in the latter, there was no thick lignified phloem fibers in cross section of stem phloem, the outer wall of epidermal cells of foliage hadthick cuticles and no non-glandular hairs in lower epidermis of foliage. The results can be used for the identification and the quality standard of the crude drug and processed pieces of D.genkwa.The characteristics of the microstructures and the transverse section can be used to identify the radix D.genkwa.

Role of Beclin-1-Mediated Autophagy in the Survival of Pediatric Leukemia Cells.

BACKGROUND/AIMS: Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined. In the current study, we addressed these questions. METHODS: We analyzed the effects of oxidative stress on the cell viability of PL cells in vitro, using a CCK-8 assay. We analyzed the effects of oxidative stress on the apoptosis and autophagy of PL cells. We analyzed the levels of Beclin-1 and microRNA-93 (miR-93) in PL cells. Prediction of binding between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The relationship between levels of miR-93 and patients' survival was analyzed in PL patients. RESULTS: We found that oxidative stress dose-dependently increased autophagy in PL cells. While low-level oxidative stress did not increase apoptosis, high-level oxidative stress increased apoptosis, seemingly from failure of autophagy-mediated cell survival. High-level oxidative stress appeared to suppress the protein levels of an autophagy protein Beclin-1 in PL cells, possibly through induction of miR-93, which inhibited the translation of Beclin-1 mRNA via 3'-UTR binding. CONCLUSION: Beclin-1-mediated autophagy plays a key role in the survival of PL cells against oxidative stress. Induction of miR-93 may increase the sensitivity of PL cells to oxidative stress during chemotherapy to improve therapeutic outcome.

Prognostic significance of FLT3-ITD in pediatric acute myeloid leukemia: a meta-analysis of cohort studies.

The purpose of the study was to assess the effect of the internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) on the outcome in pediatric acute myeloid leukemia (AML) patients. We identified eligible studies from several databases including PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) (from January 1995 to July 2015). Ten studies of 1661 pediatric patients with AML were included in exploring the relationship between the FLT3-ITD and overall survival (OS)/event free survival (EFS). Pediatric patients with AML with FLT3-ITD had worse OS [HR = 2.19 (1.60-3.01)]/EFS [HR = 1.70 (1.37-2.11)] than those patients without FLT3-ITD. Furthermore, FLT3-ITD had unfavorable effect on OS/EFS in the subgroups of NOS, uni/multivariate model, number of patients, the length of following-up, and patient source. The findings of this meta-analysis indicated that FLT3-ITD had negative impact on pediatric patients with AML.

[Comparative study on identification of Clematidis Radix et Rhizoma from different origins based on microstructure and NIRS method].

Microscopic identification and NIRS methods were applied to identify Clematidis Radix et Rhizoma of two different origins. The results showed that both methods could identify the samples. NIRS could identify the two samples nondestructively, and provides a basis for establishment of a standard herbs radix clematidis NIRS fingerprint in the future.

[Research on quality standards of Euonymus fortunei].

To establish quality standards of Euonymus fortunei, and supply scientific evidence for the quality control of Euonymus fortunei. Empirical and microscopic identification methods were adopted to observe morphological and histological characters. The contents of water, total ash, acid-insoluble ash and alcohol-soluble extractive were analysed according to the methods of Chinese Pharmaco- poeia (2010). Dulcitol and reference herbs were used to identify materia medica of Euonymus fortunei by TLC method. The total flavonol glycosides contents were analysed by HPLC method, using quercetin and kaempferol as reference substances. Quercetin and kaempferol were separated on a C18 column (4.6 mm x 250 mm, 5 µm) with methanol-0.1% formic acid(51:49) as the mobile phase and detected at 366 nm. The flavonoid aglycones content was then multiplied by a conversion coefficient, and the result was the total flavonol glycosides content. The macroscopical identification, microscopic features and TLC methods were proper. The average contents of water, total ash, acid-insoluble ash, alcohol-soluble extractive and total flavonol glycosides were 8.76%, 6.48%, 0.31%, 17.48% and 0.211% , respectively. The quality standards established on the basis of the research results were suitable for the quality evaluation of Euonymus fortunei.

MDL: Industrial carbon emission prediction method based on meta-learning and diff long short-term memory networks.

Greenhouse gas emissions, as one of the primary contributors to global warming, present an urgent environmental challenge that requires attention. Accurate prediction of carbon dioxide (CO2) emissions from the industrial sector is crucial for the development of low-carbon industries. However, existing time series models often suffer from severe overfitting when data volume is insufficient. In this paper, we propose a carbon emission prediction method based on meta-learning and differential long- and short-term memory (MDL) to address this issue. Specifically, MDL leverages Long Short-Term Memory (LSTM) to capture long-term dependencies in time series data and employs a meta-learning framework to transfer knowledge from multiple source task datasets for initializing the carbon emission prediction model for the target task. Additionally, the combination of differential LSTM and the meta-learning framework reduces the dependency of the differential long- and short-term memory network on data volume. The smoothed difference method, included in this approach, mitigates the randomness of carbon emission sequences, consequently benefiting the fit of the LSTM model to the data. To evaluate the effectiveness of our proposed method, we validate it using carbon emission datasets from 30 provinces in China and the industrial sector in Xinjiang. The results show that the average absolute error (MAE), Coefficient of Determination (R2) and root mean square error (RMSE) of the method have been reduced by 61.8% and 63.8% on average compared with the current mainstream algorithms. The method provides an efficient and accurate solution to the task of industrial carbon emission prediction, and helps environmental policy makers to formulate environmental policies and energy consumption plans.

An imidazole-based covalent-organic framework enabling a super-efficiency in sunlight-driven uranium extraction from seawater.

Uranium extraction from seawater represents an effective way to solve the difficulty of the insufficient uranium supply chain. However, this route is still restricted by the low extraction efficiency of reported adsorbents. Here, we find that reversing the donor-acceptor in imidazole-based COFs (covalent-organic frameworks) would be effective for enhancing the extraction efficiency of uranium. As a result, the TI-COF is found to enable a uranium extraction efficiency up to 8.8 mg g-1 day-1 from seawater under visible light irradiation, exceeding all established adsorbents for such use, and an unprecedented uranium extraction efficiency up to 6.9 mg g-1 day-1 from seawater under natural sunlight.

Long non-coding RNA small nucleolar RNA host gene 29 drives chronic myeloid leukemia progression via microRNA-483-3p/Casitas B-lineage Lymphoma axis-mediated activation of the phosphoinositide 3-kinase/Akt pathway.

The aberrant expression of the long non-coding RNA (lncRNA) Small Nucleolar RNA Host Gene 29 (SNHG29) has been associated with various human cancers. However, the role of SNHG29 in chronic myeloid leukemia (CML) remains elusive. Therefore, this study aimed to investigate the function of SNHG29 in CML and unveil its potential underlying mechanisms. Herein, peripheral blood samples from 44 CML patients and 17 healthy subjects were collected. The expressions of SNHG29, microRNA-483-3p (miR-483-3p), and Casitas B-lineage Lymphoma (CBL) were measured using quantitative polymerase chain reaction (qPCR) or Western Blot. Cell viability, apoptosis, and cell cycle progression were evaluated using the Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine incorporation, and flow cytometry, respectively. Western Blot analysis was employed to assess protein expressions related to cellular proliferation, apoptosis, and oncogenesis. RNA immunoprecipitation and dual-luciferase reporter assays were utilized to verify the interactions among SNHG29, miR-483-3p, and CBL. SNHG29 was significantly overexpressed in both blood samples of CML patients and CML cell lines. In CML, increased expression of SNHG29 was positively correlated with clinical staging, and patients with high SNHG29 expression had poorer survival outcomes. Functionally, knocking down SNHG29 effectively inhibited CML cell proliferation and promoted apoptosis. Mechanistically, SNHG29 acted as a competing endogenous RNA for miR-483-3p to modulate CBL expression, thereby activating the Phosphoinositide 3-Kinase/Akt signaling pathway and mediating CML progression. In summary, these findings reveal that SNHG29 promotes tumorigenesis in CML, offering a potential therapeutic strategy for CML treatment.

Treating ischemic stroke by improving vascular structure and promoting angiogenesis using Taohong Siwu Decoction: An integrative pharmacology strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Neovessels represent a crucial therapeutic target and strategy for repairing ischemic tissue. Taohong Siwu Decoction (THSWD) exhibits potential in promoting angiogenesis to address ischemic stroke (IS). However, its impact on neovessel structure and function, alongside the underlying molecular mechanisms, remains elusive. AIM OF THE STUDY: Our aim is to investigate the protective effects of THSWD on neovessel structure and function, as well as the associated molecular mechanisms, utilizing an integrative pharmacological approach. MATERIALS AND METHODS: We initially employed behavioral tests, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Haematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), Laser Doppler flowmetry (LDF), Evans blue staining, and immunofluorescence to evaluate the protective effects of THSWD on neovascular structure and function in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Subsequently, we utilized network pharmacology, metabolomics, and experimental validation to elucidate the underlying molecular mechanisms of THSWD in enhancing neovascular structure and function. RESULT: In addition to significantly reducing neurological deficits and cerebral infarct volume, THSWD mitigated pathological damage, blood-brain barrier (BBB) leakage, and cerebral blood flow disruption. Moreover, it preserved neovascular structure and stimulated angiogenesis. THSWD demonstrated potential in ameliorating cerebral microvascular metabolic disturbances including lipoic acid metabolism, fructose and mannose metabolism, purine metabolism, and ether lipid metabolism. Consequently, it exhibited multifaceted therapeutic effects, encompassing anti-inflammatory, antioxidant, energy metabolism modulation, and antiplatelet aggregation properties. CONCLUSION: THSWD exhibited protective effects on cerebral vascular structure and function and facilitated angiogenesis by rectifying cerebral microvascular metabolic disturbances in MCAO/R rats. Furthermore, integrated pharmacology offers a promising approach for studying the intricate traditional Chinese medicine (TCM) system in IS treatment.

Identification of drug targets for Sjögren's syndrome: multi-omics Mendelian randomization and colocalization analyses.

Background: Targeted therapy for Sjögren's syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets. Methods: We conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets. Results: Upon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56-3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04-3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins. Conclusion: Our study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.