Data_Sheet_1_Association between the triglyceride glucose index and cognitive impairment and dementia: a meta-analysis.docx

BackgroundThe triglyceride and glucose (TyG) index is an alternative index of insulin resistance (IR). We aimed to clarify the relationship between the TyG index and cognitive impairment and dementia.MethodsWe conducted a comprehensive search of the PubMed, Cochrane Library, and Embase databases until February 2023 to identify relevant studies. Random-effects models were used to pool effect sizes, and the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to assess the quality of the evidence.ResultsTen studies were included, with seven of which investigated the relationship between the TyG index and cognitive impairment and three exploring the association between the TyG index and dementia. When the TyG index was described as a categorical variable, it was positively associated with the risk of cognitive impairment (OR = 2.32; 95% CI 1.39–3.87) and dementia (OR = 1.14, 95% CI 1.12–1.16). The association of the TyG index with the risk of cognitive impairment (OR = 3.39, 95% CI 1.67–6.84) and dementia (OR = 1.37, 95% CI 1.03–1.83) remained significant for per 1 unit increment in the TyG index. The GRADE assessment indicated a very low certainty for cognitive impairment. Low certainty and moderate certainty were observed for dementia when the TyG index was analyzed as a categorical variable and as a continuous variable, respectively.ConclusionThe TyG index is associated with an increased risk of cognitive impairment and dementia. Further prospective research is warranted to confirm these findings.Systematic review registration: https://www.crd.york.ac.uk/, Protocol registration number: CRD42023388028.</p

Additional file 2 of What is the postoperative nutrition intake in children with congenital heart disease? A single-center analysis in China

Additional file 2. Use of blood and its biological products after surgery

Additional file 1 of What is the postoperative nutrition intake in children with congenital heart disease? A single-center analysis in China

Additional file 1. Patient diagnosis and surgical procedure

Creating Conformational Entropy by Increasing Interdomain Mobility in Ligand Binding Regulation: A Revisit to N-Terminal Tandem PDZ Domains of PSD-95

The two N-terminal PDZ domains of postsynaptic density protein-95 (PDS-95 PDZ1 and PDZ2) are closely connected in tandem by a conserved peptide linker of five amino acids. The interdomain orientation between PDZ1 and PDZ2 of the ligand-free PDZ12 tandem is restrained, and this conformational arrangement facilitates the synergistic binding of PDZ12 to multimeric targets. The interdomain orientation of the target-bound state of PDZ12 is not known. Here, we have solved the structure of PDZ12 in complex with its binding domain from cypin. Both chemical shift data and residual dipolar coupling measurements showed that the restrained interdomain orientation disappeared upon cypin peptide binding. NMR-based relaxation experiments revealed slow interdomain motions in the PDZ12/cypin peptide complex. Molecular dynamics simulations also showed that the PDZ12/cypin complex has larger conformational flexibility than the ligand-free PDZ12. This dramatic change of protein dynamics provides extra conformational entropy upon ligand binding, thus enhancing the ligand binding affinity of the PDZ12 tandem. Modulation of ligand binding affinity through concerted interdomain structural and dynamic rearrangements may represent a general property of multidomain scaffold proteins

Site Selective Azo Coupling for Peptide Cyclization and Affinity Labeling of an SH3 Protein

A key challenge in bioconjugation is to control the site selectivity of the reaction. Chemical reagents often react with proteineous chemical groups without showing preference to their location or microenvironment in the protein; to confine the reaction to an amino acid at a specific site, one needs to distinguish this residue from others despite their identical chemical properties. Here, we report a strategy that utilizes proximity-driven reactivity to achieve site selective azo coupling between tyrosine and aryldiazonium. A phenylalanine analogue with an aryldiazonium moiety at its side chain was incorporated into a synthetic peptide and was found to react only with tyrosine in its vicinity but also to remain inert to others that are not immediately adjacent, a property attained by fine regulation of the electronic effect of the substituent on the aryl ring. Proximity-driven intramolecular azo coupling was showcased in cyclization of a β-hairpin peptide, structural features of the azo linked cyclic peptide was elucidated by NMR, and intermolecular azo coupling was achieved between an SH3 protein Abl-SH3 and its polyproline peptide ligands at specific tyrosine residues. This approach is generally applicable to develop covalent affinity labels for SH3 proteins because of the high occurrence rate of tyrosine at the peptide-binding site of SH3 proteins

Betti Base as an Efficient Ligand for Copper-Catalyzed Ullmann Coupling of Phenol with Aryl Halides

<div><p></p><p>A simple, general, and highly efficient Betti base ligand has been developed for copper-catalyzed Ullmann coupling of phenol with aryl halides without the protection of an inert atmosphere. The reaction proceeds smoothly in the presence of K₂CO₃ as the base and dimethylsulfoxide as the solvent. The catalyst was reused several times with no evident loss of catalytic activity and is environmentally friendly.</p> </div

Table_1_High-Energy Enteral Nutrition in Infants After Complex Congenital Heart Surgery.pdf

BackgroundMalnutrition is common in complex congenital heart disease (CCHD). The purpose of this study was to compare the safety and efficacy of early initiation of high-energy enteral nutrition (EN) with regular energy EN in infants after surgery for CCHD.MethodsThis is a subgroup analysis of a randomized controlled trial (RCT) which was conducted in the cardiac intensive care unit (CICU) of the largest pediatric heart center in China. Eighty children with CCHD after surgery were from two groups, the intervention group (n = 40) was given high-energy EN and the control group (n = 40) was given regular energy EN. We analyzed the effects of the two interventions on outcomes such as caloric attainment rate, gastrointestinal intolerance, duration of mechanical ventilation, and anthropometry at discharge.ResultsThere was no difference in the daily milk intake between the two groups, but the calorie intake (50.2 vs. 33.4, P ConclusionsEarly initiation of high-energy EN may be safe and effective in infants after complex cardiac surgery. Low doses high-energy EN did not increase gastrointestinal intolerance or glycemic fluctuations and also improved post-operative nutrition by increasing caloric and protein intake without increasing fluid intake.</p

MOESM1 of IFN-γ down-regulates the PD-1 expression and assist nivolumab in PD-1-blockade effect on CD8+ T-lymphocytes in pancreatic cancer

Additional file 1: Figure S1. The average tumor sizes of 0.1 μg/ml mAb-IFN-γ, IFN-γ, 0.1 μg/ml mAb and Ctrl groups on 31 days after the injection of BxPC-3 cells

Data_Sheet_1_Returning ryegrass to continuous cropping soil improves soil nutrients and soil microbiome, producing good-quality flue-cured tobacco.docx

The widespread and continuous cultivation of tobacco has led to soil degradation and reduced crop yields and quality. Green manure is an essential organic fertilizer that alleviates obstacles to continuous cultivation. However, the plant–soil microecological effects of green manure on flue-cured tobacco cultivation remain unclear. Thus, a positioning trail including two treatments, chemical fertilizer application only (treatment NPK) and chemical fertilizer application with turning ryegrass (treatment NPKG) was conducted, and the effect of ryegrass returning on the soil physicochemical properties, soil microbiome, crop yield, and quality of flue-cured tobacco in continuous cropping soil were investigated. Results showed that returning ryegrass to the field increased the thickness of soil humus layer from 13 cm to 15 cm, reduced the humus layer soil bulk density to 1.29 cm3/g. Ryegrass tilled and returned to the field increased soil organic matter content by 6.89–7.92%, increased rhizosphere soil available phosphorus content by 2.22–17.96%, and converted the soil non-exchangeable potassium into potassium that was available for plant absorption and utilization. Ryegrass tilling and returning to the field increased the potassium content of middle leaves of flue-cured tobacco by 7.69–10.07%, the increased potassium content in flue-cured tobacco was accompanied by increased total sugar, reducing sugar, and the ratio of reducing sugar to nicotine, which facilitated the harmonization of the chemical composition of cured tobacco leaves. Moreover, the increased number of markedly improved operational taxonomic units enhanced the complexity of the soil bacterial community and its compactness after ryegrass tillage and their return to the field. The available potassium, available phosphorus, total potassium content, pH, and sampling period of the rhizosphere soil had considerable effects on the rhizosphere microbial. Ryegrass tilling and returning to the field changed the soil microbiome, which increased the abundance of bulk soil Proteobacteria, rhizosphere soil Fibrobacterota, and microbes with anti-pathogen activity (Lysobacteria, Sphingomonas, Chaetomium, and Minimedusa); and reduced the abundance of pathogenic fungi Neocosmospore genus in the soil. In brief, ryegrass returned to the field, improved soil microecology and restored soil nutrients, and established a new dynamic balance of soil ecology, thereby improving the quality of cultivated land and the quality of flue-cured tobacco.</p

Effects of Cosolvents and Crowding Agents on the Stability and Phase Transition Kinetics of the SynGAP/PSD-95 Condensate Model of Postsynaptic Densities

The SynGAP/PSD-95 binary protein system serves as a simple mimicry of postsynaptic densities (PSDs), which are protein assemblies based largely on liquid–liquid phase separation (LLPS), that are located underneath the plasma membrane of excitatory synapses. Surprisingly, the LLPS of the SynGAP/PSD-95 system is much more pressure sensitive than typical folded states of proteins or nucleic acids. It was found that phase-separated SynGAP/PSD-95 droplets dissolve into a homogeneous solution at a pressure of tens to hundred bar. Since organisms in the deep sea are exposed to pressures of up to ∼1000 bar, this observation suggests that deep-sea organisms must counteract the high pressure sensitivity of PSDs to avoid neurological impairment. We demonstrate here that the compatible osmolyte trimethylamine-N-oxide (TMAO) as well as macromolecular crowding agents at moderate concentrations can mitigate the deleterious effect of pressure on SynGAP/PSD-95 droplet stability, extending stable LLPS up to almost a kbar level. Moreover, the formation of SynGAP/PSD-95 droplets is a very rapid process that can be switched on and off in seconds. In contrast with the marked effects of the cosolutes on droplet stability, at the cosolutes’ respective biologically relevant concentrations, their impact on the phase transformation kinetics is rather small. Only a high TMAO concentration results in a significant kinetic retardation of LLPS. Taken together, these findings offer new biophysical insights into the neurological effects of hydrostatic pressure. In particular, our results indicate how pressure-induced neurological disorders might be alleviated by upregulating certain cosolutes in the cellular milieu