Cross-Linking CdSO4-Type Nets with Hexafluorosilicate Anions to Form an Ultramicroporous Material for Efficient C2H2/CO2 and C2H2/C2H4 Separation.

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.

Cushioning mechanism of the metatarsals during landing for the skateboarding ollie maneuver.

Skateboarding is an Olympic event with frequent jumping and landing, where the cushioning effect by the foot structure (from the arch, metatarsals, etc.) and damping performance by sports equipment (shoes, insoles, etc.) can greatly affect an athlete's sports performance and lower the risk of limb injury. Skateboarding is characterized by the formation of a "man-shoe-skateboard system," which makes its foot cushioning mechanism different from those of other sports maneuvers, such as basketball vertical jump and gymnastics broad jump. Therefore, it is necessary to clarify the cushioning mechanism of the foot structure upon landing on a skateboard. To achieve this, a multibody finite element model of the right foot, shoe, and skateboard was created using Mimics, Geomagic, and ANSYS. Kinetic data from the ollie maneuver were used to determine the plantar pressure and Achilles tendon force at three characteristics (T1, T2, and T3). The stress and strain on the foot and metatarsals (MT1-5) were then simulated. The simulation results had an error of 6.98% compared to actual measurements. During landing, the force exerted on the internal soft tissues tends to increase. The stress and strain variations were highest on MT2, MT3, and MT4. Moreover, the torsion angle of MT1 was greater than those of the other metatarsals. Additionally, the displacements of MT2, MT3, and MT4 were higher than those of the other parts. This research shows that skateboarders need to absorb the ground reaction force through the movements of the MTs for ollie landing. The soft tissues, bones, and ligaments in the front foot may have high risks of injury. The developed model serves as a valuable tool for analyzing the foot mechanisms in skateboarding; furthermore, it is crucial to enhance cushioning for the front foot during the design of skateboard shoes to reduce potential injuries.

Glutamate rescues heat stress-induced apoptosis of Sertoli cells by enhancing the activity of antioxidant enzymes and activating the Trx1-Akt pathway in vitro.

Heat stress reduces the number of Sertoli cells, which is closely related to an imbalanced redox status. Glutamate functions to maintain the equilibrium of redox homeostasis. However, the role of glutamate in heat treated Sertoli cells remains unclear. Herein, Sertoli cells from 3-week-old piglets were treated at 44 °C for 30 min (heat stress). Glutamate levels increased significantly following heat stress treatment, followed by a gradual decrease during recovery, while glutathione (GSH) showed a gradual increase. The addition of exogenous glutamate (700 µM) to Sertoli cells before heat stress significantly reduced the heat stress-induced apoptosis rate, mediated by enhanced levels of antioxidant substances (superoxide dismutase (SOD), total antioxidant capacity (TAC), and GSH) and reduced levels of oxidative substances (reactive oxygen species (ROS) and malondialdehyde (MDA)). Glutamate addition to Sertoli cells before heat stress upregulated the levels of glutamate-cysteine ligase, modifier subunit (Gclm), glutathione synthetase (Gss), thioredoxin (Trx1) and B-cell leukemia/lymphoma 2 (Bcl-2), and the ratio of phosphorylated Akt (protein kinase B)/total Akt. However, it decreased the levels of Bcl2-associated X protein (Bax) and cleaved-caspase 3. Addition of the inhibitor of glutaminase (Gls1), Bptes (Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, 30 µM)to Sertoli cells before heat stress reversed these effects. These results inferred that glutamate rescued heat stress-induced apoptosis in Sertoli cells by enhancing activity of antioxidant enzymes and activating the Trx1-Akt pathway. Thus, glutamate supplementation might represent a novel strategy to alleviate the negative effect of heat stress.

A novel FK506-loading mesoporous silica nanoparticle homing to lymph nodes for transplant rejection treatment.

Tacrolimus (FK506) is an effective therapeutic for transplant rejection in clinical practice, primarily inhibiting rejection by suppressing the activation and proliferation of allogeneic T cells in the lymph nodes (LNs). However, conventional administration methods face challenges in directly delivering free FK506 to the LNs. In this study, we introduce a novel LN-targeted delivery system based on mesoporous silica nanoparticles (MSNs-FK506-MECA79). These particles were designed to selectively target high endothelial venules in LNs; this was achieved through surface modification with MECA79 antibodies. Their mean size and zeta potential were 201.18 ± 5.98 nm and - 16.12 ± 0.36 mV, respectively. Our findings showed that MSNs-FK506-MECA79 could accumulate in LNs and increase the local concentration of FK506 from 28.02 ± 7.71 ng/g to 123.81 ± 76.76 ng/g compared with the free FK506 treatment group. Subsequently, the therapeutic efficacy of MSNs-FK506-MECA79 was evaluated in a skin transplantation model. The treatment with MSNs-FK506-MECA79 could lead to a decrease in the infiltration of T cells in the grafts, a reduction in the grade of rejection, and a significant prolongation of survival. Consequently, this study presents a promising strategy for the active LN-targeted delivery of FK506 and improving the immunotherapeutic effects on transplant rejection.

Multi-Relational Deep Hashing for Cross-Modal Search.

Deep cross-modal hashing retrieval has recently made significant progress. However, existing methods generally learn hash functions with pairwise or triplet supervisions, which involves learning the relevant information by splicing partial similarity between data pairs; notably, this approach only captures the data similarity locally and incompletely, resulting in sub-optimal retrieval performance. In this paper, we propose a novel Multi-Relational Deep Hashing (MRDH) approach, which can fully bridge the modality gap by comprehensively modeling the similarity relationship between data in different modalities. In more detail, to investigate the inter-modal relationships, we constrain the consistency of cross-modal pairwise similarities to maintain the semantic similarity across modalities. Moreover, to further capture complete similarity information, we design a new similarity metric, which we term cross-modal global similarity, by encouraging hash codes of similar data pairs from different modalities to approach a common center and hash codes for dissimilar pairs to converge to different centers. Adopting this approach enables our model to generate more discriminative hash codes. Extensive experiments on three benchmark datasets demonstrate the superiority of our method on cross-modal hashing retrieval.

The role of TGF-ß signaling in muscle atrophy, sarcopenia and cancer cachexia.

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.

Asynchronous Parallel Large-Scale Gaussian Process Regression.

Gaussian process regression (GPR) is an important nonparametric learning method in machine learning research with many real-world applications. It is well known that training large-scale GPR is a challenging task due to the required heavy computational cost and large volume memory. To address this challenging problem, in this article, we propose an asynchronous doubly stochastic gradient algorithm to handle the large-scale training of GPR. We formulate the GPR to a convex optimization problem, i.e., kernel ridge regression. After that, in order to efficiently solve this convex kernel problem, we first use the random feature mapping method to approximate the kernel model and then utilize two unbiased stochastic approximations, i.e., stochastic variance reduced gradient and stochastic coordinate descent, to update the solution asynchronously and in parallel. In this way, our algorithm scales well in both sample size and dimensionality, and speeds up the training computation. More importantly, we prove that our algorithm has a global linear convergence rate. Our experimental results on eight large-scale benchmark datasets with both regression and classification tasks show that the proposed algorithm outperforms the existing state-of-the-art GPR methods.

[Multi-index evaluation of different parts of Amomum villosum].

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.

Unsupervised Out-of-Distribution Object Detection via PCA-Driven Dynamic Prototype Enhancement.

To promote the application of object detectors in real scenes, out-of-distribution object detection (OOD-OD) is proposed to distinguish whether detected objects belong to the ones that are unseen during training or not. One of the key challenges is that detectors lack unknown data for supervision, and as a result, can produce overconfident detection results on OOD data. Thus, this task requires to synthesize OOD data for training, which achieves the goal of enhancing the ability of localizing and discriminating OOD objects. In this paper, we propose a novel method, i.e., PCA-Driven dynamic prototype enhancement, to explore exploiting Principal Component Analysis (PCA) to extract simulative OOD data for training and obtain dynamic prototypes that are related to the current input and are helpful for boosting the discrimination ability. Concretely, the last few principal components of the backbone features are utilized to calculate an OOD map that involves plentiful information that deviates from the correlation distribution of the input. The OOD map is further used to extract simulative OOD data for training, which alleviates the impact of lacking unknown data. Besides, for in-distribution (ID) data, the category-level semantic information of objects between the backbone features and the high-level features should be kept consistent. To this end, we utilize the residual principal components to extract dynamic prototypes that reflect the semantic information of the current backbone features. Next, we define a contrastive loss to leverage these prototypes to enlarge the semantic gap between the simulative OOD data and the features from the residual principal components, which improves the ability of discriminating OOD objects. In the experiments, we separately verify our method on OOD-OD and incremental object detection. The significant performance gains demonstrate the superiorities of our method.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening.

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

Earliest Prepared core technology in Eurasia from Nihewan (China): Implications for early human abilities and dispersals in East Asia.

Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.

Causality-Invariant Interactive Mining for Cross-Modal Similarity Learning.

In the real world, how to effectively learn consistent similarity measurement across different modalities is essential. Most of the existing similarity learning methods cannot deal well with cross-modal data due to the modality gap and have obvious performance degeneration when applied to cross-modal data. To tackle this problem, we propose a novel cross-modal similarity learning method, called Causality-Invariant Interactive Mining (CIIM), that can effectively capture informative relationships among different samples and modalities to derive the modality-consistent feature embeddings in the unified metric space. Our CIIM tackles the modality gap from two aspects, i.e., sample-wise and feature-wise. Specifically, we start from the sample-wise view and learn the single-modality and hybrid-modality proxies for exploring the cross-modal similarity with the elaborate metric losses. In this way, sample-to-sample and sample-to-proxy correlations are both taken into consideration. Furthermore, we conduct the causal intervention to eliminate the modality bias and reconstruct the invariant causal embedding in the feature-wise aspect. To this end, we force the learned embeddings to satisfy the specific properties of our causal mechanism and derive the causality-invariant feature embeddings in the unified metric space. Extensive experiments on two cross-modality tasks demonstrate the superiority of our proposed method over the state-of-the-art methods.

Nanoparticle-based T cell immunoimaging and immunomodulatory for diagnosing and treating transplant rejection.

T cells serve a pivotal role in the rejection of transplants, both by directly attacking the graft and by recruiting other immune cells, which intensifies the rejection process. Therefore, monitoring T cells becomes crucial for early detection of transplant rejection, while targeted drug delivery specifically to T cells can significantly enhance the effectiveness of rejection therapy. However, regulating the activity of T cells within transplanted organs is challenging, and the prolonged use of immunosuppressive drugs is associated with notable side effects and complications. Functionalized nanoparticles offer a potential solution by targeting T cells within transplants or lymph nodes, thereby reducing the off-target effects and improving the long-term survival of the graft. In this review, we will provide an overview of recent advancements in T cell-targeted imaging molecular probes for diagnosing transplant rejection and the progress of T cell-regulating nanomedicines for treating transplant rejection. Additionally, we will discuss future directions and the challenges in clinical translation.

Long-term survival of ischemic cardiomyopathy patients with severe left ventricular dysfunction after CABG vs heart transplantation: A single center retrospective analysis.

BACKGROUND: There are no guidelines on the surgical management for ischemic cardiomyopathy (ICM) patients with severe left ventricular dysfunction. The present study aims to assess the long-term survival of these patients treated with two different surgical techniques, coronary artery bypass grafting (CABG) and heart transplantation (HTx). METHODS: This retrospective study included 218 ICM patients with left ventricular ejection fraction (LVEF) ≤35% who underwent CABG (n = 106) and HTx (n = 112) from 2011 to 2021 in a single center. After propensity adjustment analysis each group consisted of 51 patients. Clinical characteristics were evaluated for all-cause follow-up mortality by the Cox proportional hazards regression model. A risk prediction model was generated from multivariable-adjusted Cox regression analysis and applied to stratify patients with different clinical risks. The long-term survival was estimated by Kaplan-Meier analysis for different surgery groups. RESULTS: Long-term survival was comparable between CABG and HTx groups. After being stratified into different risk subgroups according to risk predictors, the HTx group exhibited superior survival outcomes compared to the CABG group among the high-risk patients (67.8% vs 44.4%, 64.1% vs 38.9%, and 64.1% vs 33.3%, p = 0.047) at 12, 36, and 60 months respectively, while the survival was comparable between HTx and CABG groups among low-risk patients (87.0% vs 97.0%, 82.4% vs 97.0%, and 70.2% vs 91.6%, p = 0.11) at 12, 36, and 60 months respectively in the PSM cohort. CONCLUSION: Long-term survival in ICM patients with severe left ventricular dysfunction who received CABG or HTx was comparable in general. Nonetheless, a favorable outcome of HTx surgery compared to CABG was observed among high-risk patients.

Class-Incremental Unsupervised Domain Adaptation via Pseudo-Label Distillation.

Class-Incremental Unsupervised Domain Adaptation (CI-UDA) requires the model can continually learn several steps containing unlabeled target domain samples, while the source-labeled dataset is available all the time. The key to tackling CI-UDA problem is to transfer domain-invariant knowledge from the source domain to the target domain, and preserve the knowledge of the previous steps in the continual adaptation process. However, existing methods introduce much biased source knowledge for the current step, causing negative transfer and unsatisfying performance. To tackle these problems, we propose a novel CI-UDA method named Pseudo-Label Distillation Continual Adaptation (PLDCA). We design Pseudo-Label Distillation module to leverage the discriminative information of the target domain to filter the biased knowledge at the class- and instance-level. In addition, Contrastive Alignment is proposed to reduce domain discrepancy by aligning the class-level feature representation of the confident target samples and the source domain, and exploit the robust feature representation of the unconfident target samples at the instance-level. Extensive experiments demonstrate the effectiveness and superiority of PLDCA. Code is available at code.

Initial Upper Palaeolithic material culture by 45,000 years ago at Shiyu in northern China.

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka.

A Chimeric Classical Insect-Specific Flavivirus Provides Complete Protection Against West Nile Virus Lethal Challenge in Mice.

West Nile virus (WNV), an arthropod-borne flavivirus, can cause severe symptoms, including encephalitis, and death, posing a threat to public health and the economy. However, there is still no approved treatment or vaccine available for humans. Here, we developed a novel vaccine platform based on a classical insect-specific flavivirus (cISF) YN15-283-02, which was derived from Culicoides. The cISF-WNV chimera was constructed by replacing prME structural genes of the infectious YN15-283-02 cDNA clone with those of WNV and successfully rescued in Aedes albopictus cells. cISF-WNV was nonreplicable in vertebrate cells and nonpathogenic in type I interferon receptor (IFNAR)-deficient mice. A single-dose immunization of cISF-WNV elicited considerable Th1-biased antibody responses in C57BL/6 mice, which was sufficient to offer complete protection against lethal WNV challenge with no symptoms. Our studies demonstrated the potential of the insect-specific cISF-WNV as a prophylactic vaccine candidate to prevent infection with WNV.

The cognitive appraisal path of stroke knowledge, coping traits, family functioning and stigma among stroke patients: A moderated parallel mediation model.

AIMS: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. BACKGROUND: Stroke-related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. DESIGN: A cross-sectional design. METHODS: The cross-sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. RESULTS: All 144 samples reported stigma symptoms with a moderate-to-high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co-mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. CONCLUSION: Among the cognitive appraisal factors affecting stroke-related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. RELEVANCE TO CLINICAL PRACTICE: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. PATIENT OR PUBLIC CONTRIBUTION: None.

Pro-osteogenic role of interleukin-22 in calcific aortic valve disease.

BACKGROUND AND AIMS: Although calcific aortic valve disease (CAVD) is a common valvular disease among elderly populations and its incidence has markedly increased in recent decades, the pathogenesis of CAVD remains unclear. In this study, we explored the potential role of interleukin (IL)-22 and the underlying molecular mechanism in CAVD. METHODS AND RESULTS: Our results showed that IL-22 was upregulated in calcific aortic valves from CAVD patients, and its main sources were CD3+ T cells and CD68+ macrophages. Human aortic valve interstitial cells (VICs) expressed the IL-22-specific receptor IL-22R1, and IL-22R1 expression also was elevated in calcified valves. Treatment of cultured human VICs with recombinant human IL-22 resulted in markedly increased expression of osteogenic proteins Runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP), as well as increased matrix calcium deposition. Moreover, siRNA silencing of IL-22R1 blocked the pro-osteogenic effect of IL-22 in VICs. In IL-22-treated VICs, we also observed increased phosphorylation of JAK3 and STAT3 and nuclear translocation of STAT3. Pretreatment with a specific JAK3 inhibitor, WHIP-154, or siRNA knockout of STAT3 effectively mitigated the IL-22-induced osteoblastic trans-differentiation of human VICs. CONCLUSIONS: Together, these data indicate that IL-22 promotes osteogenic differentiation of VICs by activating JAK3/STAT3 signaling. Based on our results demonstrating a pro-osteogenic role of IL-22 in human aortic valves, pharmacological inhibition of IL-22 signaling may represent a potential strategy for alleviating CAVD.