Data_Sheet_1_Genetically predicted chronic rhinosinusitis and the risk of stroke: a two-sample Mendelian randomization study.xlsx

ObjectiveThe causal association between chronic rhinosinusitis (CRS) and stroke remains uncertain due to the susceptibility of observational studies to confounding and the possibility of reverse causality. This study aims to examine the potential causal relationship between CRS and the risk of stroke, encompassing various subtypes.MethodsIn this research, we utilized genome-wide association study (GWAS) data for CRS from FinnGen. We identified significant single-nucleotide polymorphisms (SNPs) associated with CRS and used them as instrumental variables (IVs). GWAS data for any ischemic stroke (AIS), ischemic stroke (IS), large-artery atherosclerotic stroke (LAS), small-vessel strokes (SVS), cardioembolic strokes (CES), intracerebral hemorrhage (ICH), lobar ICH, and non-lobar ICH came from multi-ancestry GWAS datasets. We conducted two-sample Mendelian randomization (MR) analyses using inverse variance weighting (IVW), weighted median, and MR-Egger regression methods to investigate potential causal relationships between CRS and stroke. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses.ResultThe IVW analysis revealed no significant associations between CRS and AIS (OR = 0.99, 95% CI [0.93–1.05], p = 0.73), IS (OR = 0.97, 95% CI [0.81–1.17], p = 0.09), SVS (OR = 0.96, 95% CI [0.82–1.12], p = 0.58), LAS (OR = 0.91, 95% CI [0.77–1.08], p = 0.09), CES (OR = 0.97, 95% CI [0.81–1.17], p = 0.79), ICH (OR = 1.28, 95% CI [0.74–2.22], p = 0.28), lobar ICH (OR = 1.22, 95% CI [0.60–2.50], p = 0.28), and non-lobar ICH (OR = 1.25, 95% CI [0.65–2.40], p = 0.79). Sensitivity analysis found no evidence of horizontal pleiotropy.ConclusionAccording to genetic evidence, this Mendelian randomization (MR) study does not indicate a causal relationship between CRS and stroke in European populations. However, further studies are necessary to comprehensively evaluate the potential association between CRS and stroke.</p

Data_Sheet_2_Genetically predicted chronic rhinosinusitis and the risk of stroke: a two-sample Mendelian randomization study.docx

ObjectiveThe causal association between chronic rhinosinusitis (CRS) and stroke remains uncertain due to the susceptibility of observational studies to confounding and the possibility of reverse causality. This study aims to examine the potential causal relationship between CRS and the risk of stroke, encompassing various subtypes.MethodsIn this research, we utilized genome-wide association study (GWAS) data for CRS from FinnGen. We identified significant single-nucleotide polymorphisms (SNPs) associated with CRS and used them as instrumental variables (IVs). GWAS data for any ischemic stroke (AIS), ischemic stroke (IS), large-artery atherosclerotic stroke (LAS), small-vessel strokes (SVS), cardioembolic strokes (CES), intracerebral hemorrhage (ICH), lobar ICH, and non-lobar ICH came from multi-ancestry GWAS datasets. We conducted two-sample Mendelian randomization (MR) analyses using inverse variance weighting (IVW), weighted median, and MR-Egger regression methods to investigate potential causal relationships between CRS and stroke. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses.ResultThe IVW analysis revealed no significant associations between CRS and AIS (OR = 0.99, 95% CI [0.93–1.05], p = 0.73), IS (OR = 0.97, 95% CI [0.81–1.17], p = 0.09), SVS (OR = 0.96, 95% CI [0.82–1.12], p = 0.58), LAS (OR = 0.91, 95% CI [0.77–1.08], p = 0.09), CES (OR = 0.97, 95% CI [0.81–1.17], p = 0.79), ICH (OR = 1.28, 95% CI [0.74–2.22], p = 0.28), lobar ICH (OR = 1.22, 95% CI [0.60–2.50], p = 0.28), and non-lobar ICH (OR = 1.25, 95% CI [0.65–2.40], p = 0.79). Sensitivity analysis found no evidence of horizontal pleiotropy.ConclusionAccording to genetic evidence, this Mendelian randomization (MR) study does not indicate a causal relationship between CRS and stroke in European populations. However, further studies are necessary to comprehensively evaluate the potential association between CRS and stroke.</p

Being Two Is Better than Being One: A Facile Strategy to Fabricate Multicomponent Nanoparticles for Efficient Gene Delivery

Multifunctionality is necessary in the design of efficient gene vectors due to the existence of multiple barriers during gene delivery. Traditional methods in the design of polyfunctional materials for this purpose are associated with sophisticated syntheses and high costs. Here, we proposed a facile coassembly approach to fabricate multicomponent nanoparticles for efficient gene delivery. The resulting particles contain different functional dendrimers and show favorable physicochemical characteristics. All the combinations in the fabrication of multicomponent nanoparticles show a synergistic effect in improving transfection efficacy. The prepared nanoparticles successfully address two or more barriers in the gene delivery process and show minimal toxicity on the transfected cells. The combination of high transfection efficacy and low cytotoxicity suggests that the prepared multicomponent nanoparticles as promising carriers in gene delivery

DataSheet1_Prediction of the tetramer protein complex interaction based on CNN and SVM.PDF

Protein-protein interactions play an important role in life activities. The study of protein-protein interactions helps to better understand the mechanism of protein complex interaction, which is crucial for drug design, protein function annotation and three-dimensional structure prediction of protein complexes. In this paper, we study the tetramer protein complex interaction. The research has two parts: The first part is to predict the interaction between chains of the tetramer protein complex. In this part, we proposed a feature map to represent a sample generated by two chains of the tetramer protein complex, and constructed a Convolutional Neural Network (CNN) model to predict the interaction between chains of the tetramer protein complex. The AUC value of testing set is 0.6263, which indicates that our model can be used to predict the interaction between chains of the tetramer protein complex. The second part is to predict the tetramer protein complex interface residue pairs. In this part, we proposed a Support Vector Machine (SVM) ensemble method based on under-sampling and ensemble method to predict the tetramer protein complex interface residue pairs. In the top 10 predictions, when at least one protein-protein interaction interface is correctly predicted, the accuracy of our method is 82.14%. The result shows that our method is effective for the prediction of the tetramer protein complex interface residue pairs.</p

Insights into the Interactions between Dendrimers and Bioactive Surfactants: 3. Size-Dependent and Hydrophobic Property-Dependent Encapsulation of Bile Salts

The supramolecular structures of dendrimer−bile salt complexes have been investigated by multidimensional and multinuclear NMR techniques, such as 1H NMR, COSY, TOCSY, NOESY, and DOSY. 2D-NOESY analysis indicated the localization of bile salt in the interior pockets of dendrimers. The orientation of the guest in the pockets was predicted by the NOE cross-peaks based on NOESY spectrum. 1H NMR experiments suggested that no electrostatic interactions between the amine groups of dendrimers and the negatively charged group of bile salts occur in the complexes. DOSY studies further confirmed the inclusion structures based on the diffusion coefficient information. The supramolecular structures of dendrimer−bile salt complexes were mainly formed by hydrophobic interactions/hydrogen-bond interactions in the interior pockets of dendrimers. In addition, size- and hydrophobic property-dependent encapsulation of bile salts and bile derivates in the cavities was observed. These results suggest a new interaction model of dendrimer−surfactant aggregates and provide new insight into the interactions between dendrimers and bioactive surfactants

Host−Guest Chemistry and Physicochemical Properties of the Dendrimer−Mycophenolic Acid Complex

The nature of the dendrimer−mycophenolic acid (MPA) complex was investigated by 1H NMR and 2D NOESY spectroscopy. The 1H NMR analysis proved that the water-soluble supramolecular structure of the complex was formed based on ionic interactions between dendrimers and MPA molecules on the surface as well as hydrophobic interactions/hydrogen-bond interactions in the interior pockets of dendrimers. The 2D NOESY analysis predicted the localization of MPA molecules in the pockets of dendrimers and gave information on the detailed interactions between dendrimer scaffolds and MPA molecules in the interior. Further solubility and release studies investigated the physicochemical properties of the dendrimer−MPA complexes. These results showed that the host−guest chemistry of dendrimer−MPA complexes proposed by NMR techniques explains the solubilization and release behavior of MPA in the presence of PAMAM dendrimers well. The general host−guest chemistry of the dendrimer−drug complex is promising for the development of new drug delivery systems

Data_Sheet_1_Higher ultra processed foods intake is associated with low muscle mass in young to middle-aged adults: a cross-sectional NHANES study.docx

DesignUltra-processed foods (UPFs) have become a pressing global health concern, prompting investigations into their potential association with low muscle mass in adults.MethodsThis cross-sectional study analyzed data from 10,255 adults aged 20−59 years who participated in the National Health and Nutritional Examination Survey (NHANES) during cycles spanning from 2011 to 2018. The primary outcome, low muscle mass, was assessed using the Foundation for the National Institutes of Health (FNIH) definition, employing restricted cubic splines and weighted multivariate regression for analysis. Sensitivity analysis incorporated three other prevalent definitions to explore optimal cut points for muscle quality in the context of sarcopenia.ResultsThe weighted prevalence of low muscle mass was 7.65%. Comparing the percentage of UPFs calories intake between individuals with normal and low muscle mass, the values were found to be similar (55.70 vs. 54.62%). Significantly linear associations were observed between UPFs consumption and low muscle mass (P for non-linear = 0.7915, P for total = 0.0117). Upon full adjustment for potential confounding factors, participants with the highest UPFs intake exhibited a 60% increased risk of low muscle mass (OR = 1.60, 95% CI: 1.13 to 2.26, P for trend = 0.003) and a decrease in ALM/BMI (β = −0.0176, 95% CI: −0.0274 to −0.0077, P for trend = 0.003). Sensitivity analysis confirmed the consistency of these associations, except for the International Working Group on Sarcopenia (IWGS) definition, where the observed association between the highest quartiles of UPFs (%Kcal) and low muscle mass did not attain statistical significance (OR = 1.35, 95% CI: 0.97 to 1.87, P for trend = 0.082).ConclusionOur study underscores a significant linear association between higher UPFs consumption and an elevated risk of low muscle mass in adults. These findings emphasize the potential adverse impact of UPFs on muscle health and emphasize the need to address UPFs consumption as a modifiable risk factor in the context of sarcopenia.</p

Host−Guest Chemistry of Dendrimer-Drug Complexes. 2. Effects of Molecular Properties of Guests and Surface Functionalities of Dendrimers

The host−guest chemistry of dendrimer−drug complexes is investigated by NMR techniques, including 1H NMR and 2D-NOESY studies. The effects of molecular properties of drug molecules (protonation ability and spatial steric hindrance of charged groups) and surface functionalities of dendrimers (positively charged amine groups and negatively charged carboxylate groups) on the host−guest interactions are discussed. Different interaction mechanisms between dendrimers and drug molecules are proposed on the basis of NMR results. Primary amine- and secondary amine-containing drugs preferentially bind to negatively charged dendrimers by strong electrostatic interactions, whereas tertiary amine and quaternary ammonium-containing drugs have weak binding ability with dendrimers due to relatively low protonation ability of the tertiary amine group and serious steric hindrance of the quaternary ammonium group. Positively charged drugs locate only on the surface of negatively charged dendrimers, whereas negatively charged drugs locate both on the surface and in the interior cavities of positively charged dendrimers. The host−guest chemistry of dendrimer−drug complexes is promising for the development of new drug delivery systems

Host−Guest Chemistry of Dendrimer−Drug Complexes. 4. An In-Depth Look into the Binding/Encapsulation of Guanosine Monophosphate by Dendrimers

In the present study, we investigated the host−guest chemistry of dendrimer/guanosine monophosphate (GMP) and present an in-depth look into the binding/encapsulation of GMP by dendrimers using NMR studies. 1H NMR spectra showed a significant downfield shift of methylene protons in the outmost layer of the G5 dendrimer, indicating the formation of ion pairs between cationic amine groups of dendrimer and anionic phosphate groups of GMP. Chemical shift titration results showed that the binding constant between G5 dendrimer and GMP is 17 400 M−1 and each G5 dendrimer has 107 binding sites. The binding of GMP to dendrimers prevents its aggregation in aqueous solutions and thereby enhances its stability. Nuclear Overhauser effect measurements indicated that a GMP binding and encapsulation balance occurs on the surface and in the interior of dendrimer. The binding/encapsulation transitions can be easily tailored by altering the surface and interior charge densities of the dendrimer. All these findings provide a new insight into the host−guest chemistry of dendrimer/guest complexes and may play important roles in the study of dendrimer/DNA aggregates by a “bottom-up” strategy

Understanding the Binding Interactions between Dendrimer and 18 Common Amino Acids by NMR Techniques

In the present study, we focus on the interactions between poly(propylene imine) (PPI) dendrimer and 18 of the 20 common amino acids by several NMR techniques, including NMR titrations and NOESY analysis. Surface ionic interactions and interior encapsulations were observed, and the binding behavior of amino acids with PPI dendrimer depends much on the side-chain properties of the amino acid, such as charge and hydrophobic/hydrophilic properties. The 1H NMR titration results show that the formation of PPI dendrimer–amino acid complexes are driven mainly by ionic interactions for all the amino acids except tryptophan, which is involved in strong hydrophobic interactions with the interior pockets of PPI. The hydrophobic encapsulation of tryptophan in PPI pockets is confirmed by NOESY analysis. Amino acids with negatively charged residues much more easily saturate the surface charges on PPI than amino acids with uncharged residues, whereas amino acids with positively charged residues are the most difficult to bind with the surface amine groups on the PPI dendrimer. A simultaneous occurrence of interior encapsulation (hydrophobic, hydrogen bond, or ionic interactions) and surface binding (ionic interactions) was observed for tryptophan, phenylalanine, arginine, lysine, histidine, cysteine, and asparagine, and a preferential surface ionic binding on the PPI surface rather than encapsulations in the interior was obtained for the other amino acids