Deficiency of smooth muscle cell ILF3 alleviates intimal hyperplasia via HMGB1 mRNA degradation-mediated regulation of the STAT3/DUSP16 axis.

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.

Transcriptome analysis of multiple tissues reveals the potential mechanism of death under acute heat stress in chicken.

BACKGROUND: Acute heat stress could induce high mortality and cause huge economic losses in the poultry industry. Although many studies have revealed heat stress-induced injuries of multiple tissues, the main target tissue and molecular mechanism of death under acute heat stress was largely unknown. This study systematically compared the transcriptome data of five main visceral tissues in chickens to reveal the response of multiple tissues to acute heat stress and determine the main target tissue of acute heat stress, further revealing the injuries of main target tissue and their potential mechanism by combing pathological section and qRT-PCR technologies. RESULTS: The transcriptome data of five visceral tissues revealed that acute heat stress broadly caused inflammatory response and damaged tissues metabolic homeostasis. Among the five tested visceral tissues, the number of differentially expressed genes in the lung was the highest, and their fold changes were the greatest, indicating that the lung was the main target tissue of acute heat stress. The results of pathological section revealed severe inflammation, emphysema and pulmonary hemorrhage in the lung under acute heat stress. Our study found that some pro-inflammatory genes, including CNTFR, FURIN, CCR6, LIFR and IL20RA, were significantly up-regulated both in the heat-stress and heat-death groups, and their fold changes in the heat-death group were significantly greater than that in the heat-stress group. We also found an anti-inflammatory gene, AvBD9, exhibiting an extremely high expression in the heat-stress group but a low expression in the heat-death group. CONCLUSIONS: Our study found that acute heat stress caused multiple tissue injuries broadly and the lung was the main target tissue of acute heat stress in chicken. Acute heat stress caused a severe inflammatory response, emphysema, and pulmonary haemorrhage, The severe inflammatory response in the heat-death group was related to the up-regulation of pro-inflammatory genes and down-regulation of anti-inflammatory genes.

A Carboxyl Group-Functionalized Ionic Liquid Hybrid Adsorbent for Solid-Phase Extraction and Determination of Trace Diclofenac Sodium in Milk Samples.

A simple and efficient sample pretreatment technology is very important for the accurate determination of trace drug residues in foods to ensure food safety. Herein, we report a new carboxyl group-functionalized ionic liquid hybrid solid- phase adsorbent (PS-IL-COOH) for the highly efficient extraction and quantitative determination of diclofenac sodium (DS) residue in milk samples. It was found that the adsorption efficiency of PS-IL-COOH for the ppb level of DS was greater than 93.0%, the adsorption capacity was 934.1 mg/g, and the enrichment factor was 620.0, which surpass most of the previously reported values for DS adsorbents. The high concentration of salts did not interfere with the adsorption of DS. Importantly, the recovery of DS was above 90% after 16 adsorption--regeneration cycles. The synergistic effect of the multiple interactions was found to be the main factor for the high efficiency of DS adsorption. The proposed method was applied to the extraction and detection of DS in milk samples, with the relative recovery ranging from 88.2 to 103.0%.

Predicting Heavy Metal Adsorption on Soil with Machine Learning and Mapping Global Distribution of Soil Adsorption Capacities.

Studying heavy metal adsorption on soil is important for understanding the fate of heavy metals and properly assessing the related environmental risks. Existing experimental methods and traditional models for quantifying adsorption, however, are time-consuming and ineffective. In this study, we developed machine learning models for the soil adsorption of six heavy metals (Cd(II), Cr(VI), Cu(II), Pb(II), Ni(II), and Zn(II)) using 4420 data points (1105 soils) extracted from 150 journal articles. After a comprehensive comparison, our results showed that the gradient boosting decision tree had the best performance for a combined model based on all the data. The Shapley additive explanation method was used to identify the feature importance and the effects of these features on the adsorption, based on which six independent models were developed for the six metals to achieve better model performance than the combined model. Using these independent models, the global distribution of heavy metal adsorption capacities on soils was predicted with known soil properties. Reversed models, including one combined model for all the six metals and six independent models, were also built using the same data sets to predict the heavy metal concentration in water when the adsorbed amount is known for a soil/sediment.

An improved weighted index for the assessment of heavy metal pollution in soils in Zhejiang, China.

Soil heavy metal pollution assessment is an important procedure in soil quality and ecological risk management, for which different mathematical models have been developed. However, these models have often failed to consider the characteristics of both heavy metals and the polluted sites. In this study, we analyzed the concentrations of seven heavy metals in soils in Zhejiang Province, China, and developed an improved weighted index (IWI) model to evaluate pollution levels. In contrast to traditional models, weights were assigned to different heavy metals using statistical tools, including hierarchical cluster analysis and principal component analysis. Of the 89 sites, 61.8% were considered unpolluted with IWI values < 1; 32.58% were slighted polluted with IWI values from 1 to 2, and only 2.25% of the sites were seriously polluted with IWI values > 3. The IWI results agree well with two traditional integrated index models, but can be also applied to much wider heavy metal concentration ranges. Possible pollution sources were then proposed based on the IWI model. The IWI overcame several shortcomings of the traditional indices and could be very beneficial for assessing heavy metal pollution in soil. Overall, this study developed a new model for soil pollution assessment and soil ecological risk management and comprehensively evaluated the current pollution status of soil surrounding potable surface water sources in Zhejiang Province, China.

Spatial-Temporal Pattern of Sulfate-Dependent Anaerobic Methane Oxidation in an Intertidal Zone of the East China Sea.

Methane is a primary greenhouse gas which is responsible for global warming. The sulfate-dependent anaerobic methane oxidation (S-AOM) process catalyzed by anaerobic methanotrophic (ANME) archaea and sulfate-reducing bacteria (SRB) is a vital link connecting the global carbon and sulfur cycles, and it is considered to be the overriding methane sink in marine ecosystem. However, there have been few studies regarding the role of S-AOM process and the distribution of ANME archaea in intertidal ecosystem. The intertidal zone is a buffer zone between sea and land and plays an important role in global geochemical cycle. In the present study, the abundance, potential methane oxidation rate, and community structure of ANME archaea in the intertidal zone were studied by quantitative PCR, stable isotope tracing method and high-throughput sequencing. The results showed that the potential S-AOM activity ranged from 0 to 0.77 nmol 13CO2 g-1 (dry sediment) day-1 The copy number of 16S rRNA gene of ANME archaea reached 106 ∼ 107 copies g-1 (dry sediment). The average contribution of S-AOM to total anaerobic methane oxidation was up to 34.5%, while denitrifying anaerobic methane oxidation accounted for the rest, which implied that S-AOM process was an essential methane sink that cannot be overlooked in intertidal ecosystem. The simulated column experiments also indicated that ANME archaea were sensitive to oxygen and preferred anaerobic environmental conditions. This study will help us gain a better understanding of the global carbon-sulfur cycle and greenhouse gas emission reduction and introduce a new perspective into the enrichment of ANME archaea.IMPORTANCE The sulfate-dependent anaerobic methane oxidation (S-AOM) process catalyzed by anaerobic methanotrophic (ANME) archaea and sulfate-reducing bacteria (SRB) is a vital link connecting the global carbon and sulfur cycles. We conducted a research into the spatial-temporal pattern of S-AOM process and the distribution of ANME archaea in coastal sediments collected from the intertidal zone. The results implied that S-AOM process was a methane sink that cannot be overlooked in the intertidal ecosystem. We also found that ANME archaea were sensitive to oxygen and preferred anaerobic environmental conditions. This study will help us gain a better understanding of the global carbon-sulfur cycle and greenhouse gas emission reduction and introduce a new perspective into the enrichment of ANME archaea.

Denitrifying Anaerobic Methane Oxidation: A Previously Overlooked Methane Sink in Intertidal Zone.

The intertidal zone is an open ecosystem rich in organic matter and plays an important role in global biogeochemical cycles. It was previously considered that methane was mainly removed by sulfate-dependent anaerobic methane oxidation (sulfate-AOM) process in marine ecosystems while other anaerobic methane oxidation processes were ignored. Recent researches have demonstrated that denitrifying anaerobic methane oxidation (DAMO), consisting of nitrite-dependent anaerobic methane oxidation (nitrite-AOM) and nitrate-dependent anaerobic methane oxidation (nitrate-AOM), can also oxidize methane. In this work, the community structure, quantity and potential methane oxidizing rate of DAMO archaea and bacteria in the intertidal zone were studied by high-throughput sequencing, qPCR and stable isotope tracing method. The results showed that nitrate-AOM and nitrite-AOM were both active in the intertidal zone and showed approximate methane oxidation rates. The copy number of 16S rRNA gene of DAMO archaea and DAMO bacteria were 104 ∼ 105 copies g-1 (dry sediment), whereas NC10 bacteria were slightly higher. The contribution rate of DAMO process to total anaerobic methane removal in the intertidal zone reached 65.6% ∼ 100%, which indicates that DAMO process is an important methane sink in intertidal ecosystem. Laboratory incubations also indicated that DAMO archaea were more sensitive to oxygen and preferred a more anoxic environment. These results help us draw a more complete picture of methane and nitrogen cycles in natural habitats.

Constructing 3D Zincophilic Skeleton in Nitrogen-Doped Carbon Hybrid Fibers for Dendrite-Free Zn Anodes.

The Zn dendrite growth and side reactions are two major issues for the practical use of Zn metal anodes (ZMAs). Herein, an N-doped carbon-based hybrid fiber with the 3D porous skeleton and the zincophilic Cu nanoparticles (denoted as Cu@HLCF) is developed for stable ZMAs. The zincophilic Cu particles in the skeleton work as the active sites to facilitate uniform Zn nucleation. Meanwhile, the abundant pores in the framework of the hybrid fibers provide a large space to relieve the structural stress and suppress the dendrite growth. Moreover, the good mechanical characteristics of the hybrid fiber ensure its high potential applications for flexible electronics. Theoretical analysis results disclose the strong interaction between Zn and Cu sites, and experimental results demonstrate the low voltage hysteresis, high reversibility, and dendrite-free behavior of the Cu@HLCF host for Zn plating/stripping. Moreover, the solid-state Zn-ion battery (ZIB) assembled with a Cu@HLCF/Zn anode shows the prominent flexibility, impressively reliability, and outstanding cycling capability. Therefore, this work not only provides a novel design for the efficient and stable Zn metal anode but also promotes the development of flexible power sources for flexible electronics.

Sacubitril/valsartan reversal of left ventricular remodeling is associated with improved hemodynamics in resistant hypertension.

BACKGROUND: Sacubitril/valsartan (S/V) has been shown to be an effective antihypertensive drug combination. However, its therapeutic effects on blood pressure (BP), hemodynamics, and left ventricular (LV) remodeling in resistant hypertension (RHTN) remain unclear. METHODS: Eighty-six patients completed this self-control study, during which olmesartan was administered within the first 8 weeks (phase 1), followed by S/V within the second 8 weeks (phase 2), with nifedipine and hydrochlorothiazide taken as background medications. Office BP, echocardiography, and hemodynamics assessment using impedance cardiography were performed at baseline and at the eighth and sixteenth weeks. RESULTS: The reduction in office BP was larger in phase 2 than in phase 1 (19.59/11.66 mmHg vs. 2.88/1.15 mmHg). Furthermore, the treatment in phase 2 provided greater reductions in systemic vascular resistance index (SVRI) and thoracic blood saturation ratio (TBR), with differences between the two phases of -226.59 (-1212.80 to 509.55) dyn·s/cm5/m2 and -0.02 (-0.04 to 0.02). Switching from olmesartan to S/V also significantly reduced E/E', LV mass index, LV end-diastolic volume index, and LV end-systolic volume index (all P < 0.05). Decreases in arterial stiffness, SVRI, and TBR were correlated with changes in indicators of LV remodeling (all P < 0.05). This correlation persisted even after adjusting for confounders including changes in BP. CONCLUSIONS: Switching from olmesartan to S/V effectively lowered BP and reversed ventricular remodeling in RHTN. In addition, hemodynamic improvement was also observed. Changes in hemodynamics played an important role in reversing LV remodeling of S/V, and were independent of its antihypertensive effect.

BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

Ecological risk assessment based on soil adsorption capacity for heavy metals in Taihu basin, China.

Due to the toxicity, bioaccumulation, non-biodegradability and perseverance of heavy metals, their risk assessment is essential for soil quality management. The Hakanson potential ecological risk index (RI), which considers the effects of heavy metal concentration and toxicity, has been widely used in soil ecological risk assessment. However, RI overlooks the influence of soil properties on the mobility and availability of heavy metals in risk assessment. To fill this gap, this study sought to develop an improved ecological risk index (IRI), which incorporates soil adsorption into RI, and applied it to evaluate the ecological risk of heavy metals in the soil of the Taihu basin, China. The soil adsorption models based on the Gradient Boosting Decision Tree (GBDT) was used to predict the soil adsorption capacity of five heavy metals (i.e. cadmium, chromium, copper, lead, zinc). The soil adsorption capacity in 1446 sites in the Taihu basin was predicted by the GBDT models and was assigned as the weight of IRI. The risk assessment results of the five metals in the Taihu basin showed that 40% of the sites were at a moderate risk level and 60% of the sites were at a slight risk level based on the RI. The value of IRI in the basin ranged from 11.1 to 75.5, with a mean value of 28.1. IRI differed from RI in spatial distribution due to the influence of soil adsorption. The comparative analysis between the metal contents in sediments and surrounding soils confirmed the tremendous influence of soil adsorption on ecological risks, indicating that soil adsorption should be taken into consideration in soil risk assessment.

Gray Model Study of Strength and Pore Structure of Recycled Concrete Powder (RCP) Concrete Based on Low-Field NMR Technology.

In order to improve the resource utilization of recycled concrete powder (RCP), this study aimed to investigate the effect of RCP admixture, curing age, and alkali excitation on the strength of RCP concrete. In addition, the pore structure characteristics of RCP concrete were analyzed in combination with low-field NMR. Furthermore, a gray predictive GM (1, 4) model was established to predict the mechanical properties of the concrete based on the pore structure parameters, especially the compressive and flexural tensile strengths. The results of the study indicate that the mechanical properties, namely compressive strength and flexural strength, of RCP concrete exhibit an initial increase followed by a subsequent decrease with increasing RCP content at 3 d, 7 d, and 28 d curing ages. In particular, the concrete exhibits the highest mechanical properties when the RCP content reaches 10%. As the curing age increases, the RCP gradually achieves full hydration, resulting in further refinement of the concrete pores and a denser structure, which subsequently improves the mechanical properties. In addition, the strength growth rate of alkali-excited recycled concrete (ARC) showed a continuous increase, indicating that alkali excitation increasingly improved the mechanical properties of the concrete. Furthermore, the study accurately predicted the mechanical properties of RCP concrete by using GM (1, 4) prediction models for its compressive strength and flexural tensile strength using pore characteristic parameters.

A green extraction strategy for the detection of antioxidants in food simulants and beverages migrated from plastic packaging materials.

Antioxidants, widely utilized in the food packaging field, have a risk of migrating into foodstuffs and eventually entering the human body. In this work, a novel method was established for green extraction and determination of antioxidants in food simulants migrated from plastic packaging materials. It was found that the antioxidants could be extracted directly from food simulants by in-situ formation of hydrophobic deep eutectic solvents with low toxic medium-chain fatty alcohols. Under the optimal conditions, the limit of detection was 0.15 to 0.25 µg/L, and the limit of quantification was 0.5 to 1.0 µg/L for the antioxidants. The extraction reaches equilibrium in 2 min. Importantly, butylated hydroxytoluene was detected in two types of the surveyed food contact materials. The established method shows high sensitivity, high enrichment factor, and strong anti-interference ability, and can be used for the separation and enrichment of ultra-trace antioxidants in foodstuffs.

Melatonin alleviates early brain injury by inhibiting the NRF2-mediated ferroptosis pathway after subarachnoid hemorrhage.

Ferroptosis is a novel form of cell death that plays a critical role in the pathological and physiological processes of early brain injury following subarachnoid hemorrhage. Melatonin, as the most potent endogenous antioxidant, has shown strong protective effects against pathological changes following subarachnoid hemorrhage, but its impact on ferroptosis induced by subarachnoid hemorrhage remains unexplored. In our study, we established a subarachnoid hemorrhage model in male SD rats. We found that subarachnoid hemorrhage induced changes in ferroptosis-related indicators such as lipid peroxidation and iron metabolism, while intraperitoneal injection of melatonin (40 mg/kg) effectively ameliorated these changes to a certain degree. Moreover, in a subset of rats with subarachnoid hemorrhage who received pre-treatment via intravenous injection of the melatonin receptor antagonist Luzindole (1 mg/kg) and 4P-PDOT (1 mg/kg), we found that the protective effect of melatonin against subarachnoid hemorrhage includes inhibition of lipid peroxidation and reduction of iron accumulation depended on melatonin receptor 1B (MT2). Furthermore, our study demonstrated that melatonin inhibited neuronal ferroptosis by activating the NRF2 signaling pathway, as evidenced by in vivo inhibition of NRF2. In summary, melatonin acts through MT2 and activates NRF2 and downstream genes such as HO-1/NQO1 to inhibit ferroptosis in subarachnoid hemorrhage-induced neuronal injury, thereby improving neurological function in rats. These results suggest that melatonin is a promising therapeutic target for subarachnoid hemorrhage.

A Sustainable Strategy for Solid-Phase Extraction of Antiviral Drug from Environmental Waters by Immobilized Hydrogen Bond Acceptor.

Deep eutectic solvents are a new generation of green solvents composed of hydrogen bond acceptors and donors. However, when used as extractants in liquid-liquid separation, they are difficult to recycle and easy to lose. In order to solve these problems, herein, immobilized hydrogen bond acceptor adsorbent material was prepared for the separation and enrichment of antiviral drug arbidol from seven kinds of environmental water samples by in situ formation of hydrophobic deep eutectic solvents. The structure, morphology and thermal stability of the adsorbents were characterized, the separation and enrichment conditions for the targeted analyte were optimized, and the adsorption thermodynamics and kinetics were investigated. It was found that the adsorbent material could effectively enrich trace arbidol with the recovery more than 95% at the concentration above 7.5 ng/mL, and the enrichment factor was as high as 634.7. Coexisting substances, such as NaCl, KCl, CaCl2 and MgCl2, did not interfere with the adsorption of arbidol, even if their concentration was high, up to 1.0 mol/L, and the relative recovery for real samples was in the range from 92.5% to 100.3%. Furthermore, the immobilized hydrogen bond acceptor could be recycled and reused, and the recovery of arbidol was still above 95% after 12 adsorption-desorption cycles. The mechanism study demonstrates that the synergistic effect of hydrogen bonding and π-π stacking is the primary factor for the high adsorption efficiency.

Novel recyclable acidic hydrophobic deep eutectic solvents for highly efficient extraction of calcium dobesilate in water and urine samples.

Deep eutectic solvents (DESs) have been considered to be one of the most promising green alternatives of conventional volatile solvents for liquid-liquid separation. However, acidic hydrophobic DESs have been less studied although they are of great importance for the extraction of compounds which are unstable in alkaline conditions. In this study, a novel family of acidic hydrophobic deep eutectic solvents was designed and prepared from methyl trioctyl ammonium chloride and a series of haloacetic acids. For the first time, the obtained DESs were used for extraction and determination of calcium dobesilate, which is an extensively used medicine for treating vascular diseases, but it can be easily oxidized under alkaline and neutral conditions. The factors influencing extraction process including pH, temperature, extract time, inorganic salts and organic coexistence were systematically investigated. It is found that these DESs exhibited outstanding extraction performance towards calcium dobesilate. The extraction equilibrium time was only 3 min in a wide range of pH (1.2-9.2) at room temperature and the extraction capacity was up to 504 mg/g. The detection limit of calcium dobesilate extracting from water samples was 0.05 µg/L and the limit of quantification was 0.5 µg/L. A variety of inorganic salts with the concentration up to 1.0 mol/L and common coexisting organic compounds, such as glucose and starch, with the concentration more than 1000 times higher than the target analyte had no obvious impact on the extraction efficiency. The relative recovery for real samples ranged from 93.2% to 108.6%. Furthermore, the DESs could be recycled and regenerated through back extraction. After fifteen cycles, the extraction efficiency was still up to 99%. Finally, the extraction and back extraction mechanism was discussed in detail.

CD22-Binding Synthetic Sialosides Regulate B Lymphocyte Proliferation Through CD22 Ligand-Dependent and Independent Pathways, and Enhance Antibody Production in Mice.

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed in various immune cells and most of them carry signaling functions. High-affinity synthetic sialoside ligands have been developed for various Siglecs. Therapeutic potentials of the nanoparticles and compounds that contain multiple numbers of these sialosides and other reagents such as toxins and antigens have been demonstrated. However, whether immune responses can be regulated by monomeric sialoside ligands has not yet been known. CD22 (also known as Siglec-2) is an inhibitory molecule preferentially expressed in B lymphocytes (B cells) and is constitutively bound and functionally regulated by α2,6 sialic acids expressed on the same cell (cis-ligands). Here, we developed synthetic sialosides GSC718 and GSC839 that bind to CD22 with high affinity (IC50 ~100 nM), and inhibit ligand binding of CD22. When B cells are activated by B cell antigen receptor (BCR) ligation, both GSC718 and GSC839 downregulate proliferation of B cells, and this regulation requires both CD22 and α2,6 sialic acids. This result suggests that these sialosides regulate BCR ligation-induced B cell activation by reversing endogenous ligand-mediated regulation of CD22. By contrast, GSC718 and GSC839 augment B cell proliferation induced by TLR ligands or CD40 ligation, and this augmentation requires CD22 but not α2,6 sialic acids. Thus, these sialosides appear to enhance B cell activation by directly suppressing the inhibitory function of CD22 independently of endogenous ligand-mediated regulation. Moreover, GSC839 augments B cell proliferation that depends on both BCR ligation and CD40 ligation as is the case for in vivo B cell responses to antigens, and enhanced antibody production to the extent comparable to CpG oligonuleotides or a small amount of alum. Although these known adjuvants induce production of the inflammatory cytokines or accumulation of inflammatory cells, CD22-binding sialosides do not. Thus, synthetic sialosides that bind to CD22 with high-affinity modulate B cell activation through endogenous ligand-dependent and independent pathways, and carry an adjuvant activity without inducing inflammation.