Unfolding Protein-Based Hapten Coupling via Thiol-Maleimide Click Chemistry: Enhanced Immunogenicity in Anti-Nicotine Vaccines Based on a Novel Conjugation Method and MPL/QS-21 Adjuvants.

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol-maleimide "click" chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine-BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

Harnessing the potential of de-sulfated heparin for targeted drug delivery: A three-component approach exemplified by conjugation with galactose and paclitaxel.

Heparin, an anticoagulant with a century-long history of use, has been investigated over the past decade as a potential drug delivery vehicle. Despite its safety and efficacy, its interactions with many proteins through specific sulfate patterns can complicate drug delivery by mediating diverse biological functions. Here, we present the synthesis of a three-component drug delivery system comprising de-sulfated heparin as the carrier, galactose as the targeting moiety, and paclitaxel as the therapeutic drug. Removal of sulfates eliminated most of its anticoagulant effects in all intermediates. Through coupling with galactose and paclitaxel, the system improved the solubility of the drug and achieved selective targeting and efficient drug delivery to HepG2 cells, a liver carcinoma cell line with high galactose receptor expression. While the three-component system exhibited a slightly higher IC50 value than native paclitaxel, demonstrating its efficacy as a drug carrier, the IC50 value for the normal human liver cell line QSG7701 was significantly higher, indicating its selectivity and safety. Our study introduces a novel approach utilizing desulfated heparin as a carrier, warranting further investigation to unlock its potential in targeted drug delivery strategies.

Strategic development of a self-adjuvanting SARS-CoV-2 RBD vaccine: From adjuvant screening to enhanced immunogenicity with a modified TLR7 agonist.

Adjuvants enhance the body's immune response to a vaccine, often leading to better protection against diseases. Monophosphoryl lipid A analogues (MPLA, TLR4 agonists), α-galactosylceramide analogues (NKT cell agonists), and imidazoquinoline compounds (TLR7/8 agonists) are emerging novel adjuvants on market or under clinical trials. Despite significant interest in these adjuvants, a direct comparison of their adjuvant activities remains unexplored. We initially assessed the activities of various adjuvants from three distinct categories using the SARS-CoV-2 RBD trimer antigen. TLR4 and TLR7/8 agonists are discovered to elicit robust IgG2a/2b antibodies, which is crucial for eliciting antibody dependent cytotoxicity. While α-galactosylceramide analogs induced mainly IgG1 antibody. Then, because of the flexibility of the TLR7/8 agonist, we designed and synthesized a tri-component self-adjuvanting SARS-CoV-2 RBD vaccine, featuring a covalent TLR7 agonist and targeting mannoside. Animal studies indicated that this vaccine generated antigen-specific humoral immunity. Yet, its immunogenicity seems compromised, indicating the complexity of the vaccine.

MoAti1 mediates mitophagy by facilitating recruitment of MoAtg8 to promote invasive growth in Magnaporthe oryzae.

Mitophagy is a selective autophagy for the degradation of damaged or excessive mitochondria to maintain intracellular homeostasis. In Magnaporthe oryzae, a filamentous ascomycetous fungus that causes rice blast, the most devastating disease of rice, mitophagy occurs in the invasive hyphae to promote infection. To date, only a few proteins are known to participate in mitophagy and the mechanisms of mitophagy are largely unknown in pathogenic fungi. Here, by a yeast two-hybrid screen with the core autophagy-related protein MoAtg8 as a bait, we obtained a MoAtg8 interactor MoAti1 (MoAtg8-interacting protein 1). Fluorescent observations and protease digestion analyses revealed that MoAti1 is primarily localized to the peripheral mitochondrial outer membrane and is responsible for recruiting MoAtg8 to mitochondria under mitophagy induction conditions. MoAti1 is specifically required for mitophagy, but not for macroautophagy and pexophagy. Infection assays suggested that MoAti1 is required for mitophagy in invasive hyphae during pathogenesis. Notably, no homologues of MoAti1 were found in rice and human protein databases, indicating that MoAti1 may be used as a potential target to control rice blast. By the host-induced gene silencing (HIGS) strategy, transgenic rice plants targeted to silencing MoATI1 showed enhanced resistance against M. oryzae with unchanged agronomic traits. Our results suggest that MoATI1 is required for mitophagy and pathogenicity in M. oryzae and can be used as a target for reducing rice blast.

MicroRNA-322-5p protects against myocardial infarction through targeting BTG2.

BACKGROUND: Numerous studies have explored the therapeutic potential of microRNA (miR) in myocardial infarction (MI) treatment. This study focuses on the role of miR-322-5p in MI, particularly in its regulatory interaction with B-cell translocation gene 2 (BTG2). MATERIALS AND METHODS: Expression levels of miR-322-5p and BTG2 were assessed in a rat MI model. Adenovirus altering miR-322-5p or BTG2 expression were administered to MI rats. Evaluation included cardiac function, inflammation, myocardial injury, pathological changes, apoptosis, and NF-κB pathway-related genes in MI rats post-targeted treatment. The miR-322-5p and BTG2 targeting relationship was investigated. RESULTS: MI rats exhibited low miR-322-5p and high BTG2 expression in the myocardial tissues. Restoration of miR-322-5p enhanced cardiac function, alleviated inflammation and myocardial injury, mitigated pathological changes and apoptosis, and deactivated the NF-κB pathway in MI rats. BTG2 expression was negatively-regulated by miR-322-5p. Overexpressed BTG2 counteracted miR-322-5p-induced cardioprotection on MI rats. CONCLUSION: This study provides evidence that miR-322-5p protects against MI by suppressing BTG2 expression.

Iodosylbenzene-Promoted Glycosylation with Selenoglycosides: Application in One-Pot Glycosylation.

A novel method for the glycosylation of selenoglycosides activated by iodosylbenzene was developed. The glycosylation reaction conditions were mild, fast, and efficient, with a high tolerance to diverse protecting groups and a wide substrate scope, which is advantageous for synthesizing complex glycosides. In addition, selenoglycosides were shown to be orthogonal to thioglycosides under the promotion of iodosylbenzene. Notably, a high yield of the poorly reactive glucuronidation reaction product was obtained by acetyl-protected selenoglycoside. Finally, the orthogonal one-pot synthesis of ß-(1→6) oligoglucans demonstrated the usefulness of this method in oligosaccharide synthesis.

Analysis of surgical site infection and tumour-specific survival rate in patients with renal cell carcinoma after laparoscopic radical nephrectomy.

Surgical site infections (SSIs) may pose a significant risk to patients undergoing surgery. This study aims to explore the risk factors for SSIs in patients undergoing laparoscopic radical nephrectomy for renal cell carcinoma and the impact of infection on tumour-specific survival (CSS) after nephrectomy for renal cell carcinoma. To explore the risk factors for SSIs in patients undergoing laparoscopic radical nephrectomy for renal cell carcinoma and the impact of infection on tumour-specific survival (CSS) after nephrectomy for renal cell carcinoma. A retrospective analysis was conducted on 400 patients in our hospital from June 2021 to June 2023. This study divided patients into two groups: those with SSI and those without SSI. Collect general data and information related to the operating room. Clearly defined inclusion and exclusion criteria. Select surgical time, laminar mobile operating room use, and intraoperative hypothermia as observation indicators. Perform statistical analysis using SPSS 25.0 software, including univariate, multivariate, and survival analyses of wound-infected and uninfected patients. Out of 400 patients, 328 had no SSIs, 166 died during follow-up, 72 had SSIs, and 30 died during follow-up. There was no statistically significant difference (p > 0.05) in comparing primary data between individuals without SSIs and those with SSIs. There were statistically significant differences (p < 0.05) in surgical time, nonlaminar flow operating room use, and intraoperative hypothermia. The postoperative survival time of SSI patients with a tumour diameter of 7.0-9.9 cm was significantly longer than that of SSI patients, and the difference was statistically significant (p < 0.05). The occurrence of severe infection in patients with other tumour diameters did not affect postoperative survival, and the difference was not statistically significant (p > 0.05). After multiple factor analysis, it was found that severe infection can prolong the postoperative survival of patients with tumour diameter exceeding 7 cm (HR = 0.749, p < 0.05). This study identified nonlaminar flow operating rooms, prolonged surgical time, and intraoperative hypothermia as significant risk factors for SSIs. After nephrectomy for renal cell carcinoma patients with a tumour diameter of 7-9.9 µ m, perioperative infection can prolong their survival. However, it has no significant effect on patients with other tumour diameters.

Direct in Situ Fabrication of Multicolor Afterglow Carbon Dot Patterns with Transparent and Traceless Features via Laser Direct Writing.

Multicolor afterglow patterns with transparent and traceless features are important for the exploration of new functionalities and applications. Herein, we report a direct in situ patterning technique for fabricating afterglow carbon dots (CDs) based on laser direct writing (LDW) for the first time. We explore a facile step-scanning method that reduces the heat-affected zone and avoids uneven heating, thus producing a fine-resolution afterglow CD pattern with a minimum line width of 80 µm. Unlike previous LDW-induced luminescence patterns, the patterned CD films are traceless and transparent, which is mainly attributed to a uniform heat distribution and gentle temperature rise process. Interestingly, by regulating the laser parameters and CD precursors, an increased carbonization and oxidation degree of CDs could be obtained, thus enabling time-dependent, tunable afterglow colors from blue to red. In addition, we demonstrate their potential applications in the in situ fabrication of flexible and stretchable optoelectronics.

Transformation of crystal structure induced by the temperatures in carbon dots (CDs)-based composites with multicolor fluorescence for white Light-Emitting-Diode (WLED).

Regulation of the fluorescence through crystalizing from the matrix in the Carbon dots (CDs)-based solid-state materials has been verified to be one of the effective methods, yet there are not only challenges in preparing such materials efficiently, but also insufficient insight into their regulation mechanisms. Here, a one-pot solvothermal route to synthesize a series of CDs-based composites with crystalline matrix is reported. These crystals exhibited multicolor fluorescence with the feature of multi-peaks emissions with increasing temperatures from 140 ℃ to 220 ℃, in which the orange emitting O-CDs@PA and the yellow emitting Y-CDs@PA crystals obtained the FLQYs of 22% and 68% respectively due to relatively stable crystalline structures. After comparative analysis to both crystals in detail, the core and the groups associated with them on the interface between CDs and matrix were adjusted in size and species during structural transformation of the crystal matrix, which changes radically the energy band structures to influence fluorescent emitting of both crystals ultimately. In addition, the reasons resulting in higher FLQY for Y-CDs@PA were provided leveraging the schematic illustration presumed based on the PL properties of both crystals. Because of the optimal optical performances, these fluorescent materials promised to fabricate WLED devices and obtained a number of photometric parameters endowed these WLED devices with the feature of warm-white light.

Stereocontrolled Synthesis of α-3-Deoxy-d-manno-oct-2-ulosonic Acid (α-Kdo) Glycosides Using C3-p-Tolylthio-Substituted Kdo Donors: Access to Highly Branched Kdo Oligosaccharides.

3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) is an eight-carbon monosaccharide found widely in bacterial lipopolysaccharides (LPSs) and capsule polysaccharides (CPSs). We developed an indirect method for the stereoselective synthesis of α-Kdo glycosides with a C3-p-tolylthio-substituted Kdo phosphite donor. The presence of the p-tolylthio group enhanced the reactivity, suppressed the formation of elimination by-products (2,3-enes), and provided complete α-stereocontrol. A variety of Kdo α-glycosides were synthesized by our method in excellent yields (up to 98 %). After glycosylation, the p-tolylthio group can be efficiently removed by free-radical reduction. Subsequently, the orthogonality of the phosphite donor and thioglycoside donor was demonstrated by the one-pot synthesis of a trisaccharide in Helicobacter pylori and Neisseria meningitidis LPS. Moreover, an efficient total synthesis route to the challenging 4,5-branched Kdo trisaccharide in LPSs from several A. baumannii strains was highlighted. To demonstrate the high reactivity of our approach further, the highly crowded 4,5,7,8-branched Kdo pentasaccharide was synthesized as a model molecule for the first time. Additionally, the reaction mechanism was investigated by DFT calculations.

Systematic analysis reveals distinct roles of USF family proteins in various cancer types.

BACKGROUND: Upstream stimulatory factors (USFs) are members of the basic helix-loop-helix leucine zipper transcription factor family, including USF1, USF2, and USF3. The first two members have been well studied compared to the third member, USF3, which has received scarce attention in cancer research to date. Despite a recently reported association of its alteration with thyroid carcinoma, its expression has not been previously analyzed. METHODS: We comprehensively analyzed differential levels of USFs expression, genomic alteration, DNA methylation, and their prognostic value across different cancer types and the possible correlation with tumor-infiltrating immune cells and drug response by using different bioinformatics tools. RESULTS: Our findings established that USFs play an important role in cancers related to the urinary system and justify the necessity for further investigation. We implemented and offer a useful ShinyApp to facilitate researchers' efforts to inquire about any other gene of interest and to perform the analysis of drug response in a user-friendly fashion at http://zzdlab.com:3838/Drugdiscovery/.

Comparing the clinical outcomes of single vs. systematic dual stenting strategies for unprotected left main bifurcation lesion: a systematic review and meta-analysis.

Introduction: The optimal percutaneous coronary intervention (PCI) strategy for coronary left main (LM) bifurcation lesions remains controversial. This meta-analysis compared the medium and long-term follow-up clinical outcomes of single vs. systematic dual stenting strategies of LM bifurcation lesions. Methods: We systematically identified studies published within 5 years comparing single vs. systematic double stenting strategies for LM bifurcation lesions. The primary endpoint was medium-term (1 year) and long-term (at least 3 years) all-cause death. Secondary outcomes included major adverse cardiovascular events (MACEs), target lesion revascularization (TLR), overall occurrence of stent thrombosis (ST), cardiovascular (CV) mortality, and myocardial infarction (MI). Results: Two randomized controlled trials and nine observational studies with 7,318 patients were included in this meta-analysis. In terms of the medium-term follow-up clinical outcomes, our pooled analysis showed that use of the systematic dual stenting strategy was associated with a lower ST risk (odds ratio [OR] = 0.43, 95% confidence interval [CI]: 0.20-0.89, P = 0.02) and cardiac death risk (OR = 0.43, 95% CI: 0.21-0.89, P = 0.02) compared to the single stenting strategy; there was no significant difference between the two strategies regarding rates of all-cause death, MACE, TLR, and MI. Patients with long-term follow-up showed comparable observed clinical outcomes between the two strategies. Most importantly, for patients with true LM bifurcation, the risk of all-cause death, ST, and CV mortality following the systematic dual stenting strategy was significantly lower than the single stenting strategy. Conclusions: For patients with LM bifurcation lesions, both the systematic dual stenting strategy and single stenting strategy demonstrated comparable results in terms of all-cause mortality during medium-term and long-term follow-up. However, the systematic dual stenting strategy showed a tendency towards lower incidence of ST and CV mortality compared to the single stenting strategy during medium-term follow-up. Consequently, the systematic dual stenting strategy yielded superior clinical outcomes for patients with LM bifurcation lesions.

Sucrose non-fermenting protein kinase gene UvSnf1 is required for virulence in Ustilaginoidea virens.

Rice false smut caused by Ustilaginoidea virens is becoming one of the most devastating diseases in rice production areas in the world. Revealing U. virens potential pathogenic mechanisms provides ideas for formulating more effective prevention and control strategies. Sucrose non-fermenting 1 (Snf1) protein kinase plays a critical role in activating transcription and suppressing gene expression, as well as in cellular response to various stresses, such as nutrient limitation. In our study, we identified the Snf1 homolog UvSnf1 and analyzed its biological functions in U. virens. The expression level of UvSnf1 was dramatically up-regulated during invasion, indicating that UvSnf1 may participate in infection. Phenotypic analyses of UvSnf1 deletion mutants revealed that UvSnf1 is necessary for hyphae growth, spore production, and virulence in U. virens. Moreover, UvSnf1 promotes U. virens to use unfavorable carbon sources when the sucrose is insufficient. In addition, deletion of UvSnf1 down-regulates the expression of the cell wall-degrading enzymes (CWDEs) genes under sucrose limitation conditions in U. virens. Further analyses showed that CWDEs (UvCut1 and UvXyp1) are not only involved in growth, spore production, and virulence but are also required for the utilization of carbon sources. In conclusion, this study demonstrates that UvSnf1 plays vital roles in virulence and carbon source utilization in U. virens, and one of the possible mechanisms is playing a role in regulating the expression of CWDE genes.

Clinical Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Meta-analysis.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat type 2 diabetes mellitus (T2DM), which have been considered at the same treatment pattern point as basal insulin (BI). Thus, comprehensively comparing these drugs is conducive to informing the treatment decisions. In this context, this work was developed to evaluate the clinical efficacy and safety of GLP-1 RAs by comparing them with basal insulin. GLP-1 RAs were compared with basal insulin in adults with T2DM with inadequate oral anti-hyperglycemic drug control by searching related literature from MEDLINE, EMBASE, CENTRAL, and PubMed databases, which were published from established the datasets to October 2022. Data on hemoglobin A1c, body weight, and blood glucose were extracted and analyzed. The MD values of HbA1C, weight, and fasting blood glucose (FBG) change were -0.02, -1.37, and -1.68, respectively. Meanwhile, the OR of the hypoglycemia ratio was 0.33. In conclusion, GLP-1 RAs exhibited a great effect on blood glucose and weight control and a better effect on FBG control.

Comparison of Different Systemic Inflammatory Markers in Predicting Clinical Outcomes with Syntax Score in Patients with Non-ST Segment Elevation Myocardial Infarction: A Retrospective Study.

Background: The clinical value of the Syntax score in patients with non-ST segment elevation myocardial infarction (NSTEMI) has been well established. The neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the high sensitivity C-reactive protein (hsCRP)-albumin ratio (hsCAR), and systemic immune-inflammatory (SII) index are promising systemic inflammation (SI) biomarkers in coronary artery diseases. However, studies which compare the predicting value of these SI indicators with the Syntax score in NSTEMI patients are limited. Material and Methods: NSTEMI patients who underwent coronary angiography (CAG) in our department were retrospectively enrolled. Both univariable and multivariable logistic regression analyses were performed to evaluate the clinical value between SI biomarkers and Syntax score in these patients. The area under the receiver operating characteristic curve (ROC) was used to compare the clinical values of these parameters in predicting 6-month major cardiovascular events (MACE) and over-all mortality. Results: A total of 429 NSTEMI patients were finally enrolled in this study. The level of NLR, PLR, as well as hsCAR, and SII in patients with high Syntax scores, are significantly higher than patients with the low Syntax score. Multivariable logistic regression analysis demonstrated that all of the SI indicators but not the Syntax score were the independent risk factors of 6-month MACE in NSTEMI patients. ROC showed that all of the SI indicators had better predictive value than the Syntax score in these patients (0.637, 0.592, 0.631, 0.590, 0.559, respectively) in predicting MACE and similar predictive value in over-all mortality (0.530, 0.524, 0.761, 0.553, 0.620, respectively). Conclusion: Novel SI biomarkers including NLR, PLR, hsCAR, and SII have better predictive value in MACE and similar predictive value in over-all mortality compared with Syntax score in NSTEMI patients.

Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo.

For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 µM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.

Mechanical Force-Induced Color-Variable Luminescence of Carbon Dots in Boric Acid Matrix.

Mechano-luminescent materials that exhibit distinct luminescence responses to force stimuli are urgently anticipated in view of application needs in the fields of sensing, anti-counterfeiting, optoelectronic devices, etc. However, most of the reported materials normally exhibit force-induced changes in luminescent intensity, whereas materials that possess force-induced color-variable luminescence remain rarely reported. Herein, for the first time, a novel mechanical force-induced color-variable luminescence material from carbon dots (CDs) in boric acid (CD@BA) is reported. At low CDs concentration, the luminescence of CD@BA exhibits a grinding-induced color variable from white to blue. This grinding-induced color variable can be switched to yellow-to-white changing by increasing the CDs concentration in BA. The grinding-induced color-variable luminescence originates from dynamic variation in emission ratio of fluorescence and room temperature phosphorescence, due to the influence of oxygen and water vapor in the air. At high CDs concentration, short-wavelength fluorescence undergoes more severe reabsorption compared to room temperature phosphorescence, leading to grinding-induced color-variable switching from white-to-blue to yellow-to-white. Based on the unique properties of CD@BA powder, the applications of recognizing and visualizing fingerprints on the surfaces of various of materials are demonstrated.

Self-strengthen luminescent hydrogel.

For typical synthetic materials, continue mechanical loading usually cause damage and even failure, because they are closed systems, without substance exchange with surroundings and structural reconstruction after damage. Double-network (DN) hydrogels have recently been demonstrated to generate radicals under mechanical loading. In this work, DN hydrogel provided with sustained monomer and lanthanide complex supply undergo self-growth, and thus simultaneous self-strengthen in both mechanical performance and luminescence intensity are realized through bond rupture-initiated mechanoradical polymerization. This strategy proves the feasibility of imparting desired functions to the DN hydrogel by mechanical stamping, and provides a new strategy for the design of luminescent soft materials with high fatigue resistance.

Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer.

Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine's immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-BlueTM hTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant.

Efficient synthesis of α-galactosylceramide and its C-6 modified analogs.

The synthesis of α-galactosylceramide (KRN7000) and its C-6 modified analogs remains a challenge due to the difficult α-1,2-cis-glycosidic bond. A non-participating benzyl (Bn) protecting group has been commonly used to favor the α-glycosylation product. Here, we report the α-selective glycosylation by using a bulky 4,6-O-di-tert-butylsilylene (DTBS) galactosyl donor, regardless of the 2-benzoyl (Bz) participating group. Compared with Bn, Bz groups can be selectively removed in basic conditions without impacting the C-6 azide modification. The azide has the potential for clicking with alkyne or being easily transformed to other functional groups.