Different dietary carbohydrate component intakes and long-term outcomes in patients with NAFLD: results of longitudinal analysis from the UK Biobank.

BACKGROUND: This study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD). METHODS: We used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars. RESULTS: During a median of 10.5 (IQR: 10.2-11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14-2.39) for free sugars, 0.51 (0.35-0.74) for non-free sugars, and 0.55 (0.36-0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04-1.39) for free sugars, 0.79 (0.68-0.92) for non-free sugars, and 0.79 (0.67-0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality. CONCLUSIONS: A lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients.

Highly Ion-Permselective Porous Organic Cage Membranes with Hierarchical Channels.

Membranes of high ion permselectivity are significant for the separation of ion species at the subnanometer scale. Here, we report porous organic cage (i.e., CC3) membranes with hierarchical channels including discrete internal cavities and cage-aligned external cavities connected by subnanometer-sized windows. The windows of CC3 sieve monovalent ions from divalent ones and the dual nanometer-sized cavities provide pathways for fast ion transport with a flux of 1.0 mol m-2 h-1 and a mono-/divalent ion selectivity (e.g., K+/Mg2+) up to 103, several orders of magnitude higher than the permselectivities of reported membranes. Molecular dynamics simulations illustrate the ion transport trajectory from the external to internal cavity via the CC3 window, where ions migrate in diverse hydration states following the energy barrier sequence of K+ < Na+ < Li+ ≪ Mg2+. This work sheds light on ion transport properties in porous organic cage channels of discrete frameworks and offers guidelines for developing membranes with hierarchical channels for efficient ion separation.

Highly Stable Single Crystals of Three-Dimensional Porous Oligomer Frameworks Synthesized under Kinetic Conditions.

Various robust, crystalline, and porous organic frameworks based on in situ-formed imine-linked oligomers were investigated. These oligomers self-assembled through collaborative intermolecular hydrogen bonding interactions via liquid-liquid interfacial reactions. The soluble oligomers were kinetic products with multiple unreacted aldehyde groups that acted as hydrogen bond donors and acceptors and directed the assembly of the resulting oligomers into 3D frameworks. The sequential formation of robust covalent linkages and highly reversible hydrogen bonds enforced long-range symmetry and facilitated the production of large single crystals, with structures that were unambiguously determined by single-crystal X-ray diffraction. The unique hierarchical arrangements increased the steric hindrance of the imine bond, which prevented attacks from water molecules, greatly improving the stability. The multiple binding sites in the frameworks enabled rapid sequestration of micropollutant in water.

Estimated small dense low-density lipoprotein cholesterol and nonalcoholic fatty liver disease in nonobese populations.

AIMS/INTRODUCTION: To explore the association between estimated small dense low-density lipoprotein cholesterol (sdLDL-C) and the risk of incident nonalcoholic fatty liver disease (NAFLD) in nonobese populations. MATERIALS AND METHODS: This study included participants who underwent health checkups in 2014 and were followed up until 2019. We carried out Cox proportional hazards regression analyses to evaluate the association of estimated sdLDL-C with NAFLD. Discordance analyses were carried out to estimate the relative NAFLD risk in estimated sdLDL-C versus low-density lipoprotein cholesterol (LDL-C) discordant/concordant groups. Estimated sdLDL-C was calculated by equations based on LDL-C and triglycerides. The diagnosis of NAFLD was based on the presence of abdominal ultrasonography after excluding other causes of chronic liver disease. RESULTS: Over a mean follow-up period of 26,694 person-years, 844 incident NAFLD cases were recorded. Compared with the first quartile of estimated sdLDL-C, the fourth quartile was associated with a 2.933-fold increased risk of NAFLD (95% confidence interval 2.095-4.107). With the increase in estimated sdLDL-C, the risk of NAFLD gradually increased both in participants within the normal range of LDL-C (hazard ratio 2.854, 95% confidence interval 1.650-5.617) and beyond the normal range of LDL-C (hazard ratio 2.636, 95% confidence interval 1.263-5.502). In addition, the inconsistent high estimated sdLDL-C/low LDL-C group was associated with an increased risk of NAFLD, but not the low estimated sdLDL-C/high LDL-C group. CONCLUSIONS: Estimated sdLDL-C was positively associated with the risk of incident NAFLD in a nonobese population, independent of LDL-C.

Remnant cholesterol and severity of nonalcoholic fatty liver disease.

BACKGROUND: Serum remnant cholesterol levels are being increasingly acknowledged as a causal risk factor for atherosclerotic disease, regardless of conventional lipid parameters. The positive association between remnant cholesterol and nonalcoholic fatty liver disease (NAFLD) has been revealed in previous studies. However, whether remnant cholesterol is associated with the severity of NAFLD remains unknown. This study aimed to explore the association between serum remnant cholesterol and the risk of NAFLD severity. METHODS: This cross-sectional study included a total of 6,053 participants who attended health checkups. The severity of hepatic steatosis was evaluated by liver ultrasound transient elastography. Univariable and multivariable logistic regression analyses were performed to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between remnant cholesterol and the severity of hepatic steatosis. To explore whether the association between remnant cholesterol and NAFLD severity was independent of conventional lipid parameters, we further investigated this association in individuals with normal values of low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides. RESULTS: In total, 36.9% of individuals had mild steatosis, and 5.9% had moderate-to-severe steatosis. The serum level of remnant cholesterol in nonsteatosis, mild steatosis and moderate-to-severe steatosis gradually increased (0.71 ± 0.33, 0.97 ± 0.52 and 1.07 ± 0.63 mmol/L, respectively). In the multivariable mode, remnant cholesterol was positively associated with mild hepatic steatosis (OR: 1.730, 95% CI: 1.541 - 1.941, P < 0.001) and moderate-to-severe steatosis (OR: 2.342, 95% CI: 1.765 - 3.109, P < 0.001). These associations were not significantly altered in individuals with normal triglycerides, HDL-C and LDL-C (OR: 1.664, 95% CI: 1.448 - 1.911, P < 0.001; OR: 2.269, 95% CI: 1.619 - 3.180, P < 0.001, respectively). CONCLUSIONS: Higher levels of serum remnant cholesterol were associated with more severe hepatic steatosis, regardless of conventional lipid parameters. Individuals with higher remnant cholesterol may need more attention in regular surveillance of NAFLD.

Covalent organic framework nanofluidic membrane as a platform for highly sensitive bionic thermosensation.

Thermal sensation, which is the conversion of a temperature stimulus into a biological response, is the basis of the fundamental physiological processes that occur ubiquitously in all organisms from bacteria to mammals. Significant efforts have been devoted to fabricating artificial membranes that can mimic the delicate functions of nature; however, the design of a bionic thermometer remains in its infancy. Herein, we report a nanofluidic membrane based on an ionic covalent organic framework (COF) that is capable of intelligently monitoring temperature variations and expressing it in the form of continuous potential differences. The high density of the charged sites present in the sub-nanochannels renders superior permselectivity to the resulting nanofluidic system, leading to a high thermosensation sensitivity of 1.27 mV K-1, thereby outperforming any known natural system. The potential applicability of the developed system is illustrated by its excellent tolerance toward a broad range of salt concentrations, wide working temperatures, synchronous response to temperature stimulation, and long-term ultrastability. Therefore, our study pioneers a way to explore COFs for mimicking the sophisticated signaling system observed in the nature.

Hollow nanosphere construction of covalent organic frameworks for catalysis: (Pd/C)@TpPa COFs in Suzuki coupling reaction.

A novel catalyst with a yolk-shell structure was designed to overcome the leaching of noble metals in heterogeneous catalysis. Through a template method, palladium (Pd) nanoparticles were encapsulated by hollow spherical covalent organic frameworks (COFs) consisting of 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (Tp) and p-phenylenediamine (Pa). The final catalyst with a yolk-shell structure was denoted as (Pd/C)@TpPa COFs. The unique morphology and chemical structure of this novel composite (Pd/C)@TpPa COFs were confirmed by a transmission electron microscope (TEM), a laser particle analyzer, X-ray diffraction (XRD), and N2 adsorption and desorption. Subsequently, to demonstrate its catalytic performance brought by structural design, this novel catalyst was applied to catalyze the Suzuki reaction. Interestingly, this catalyst exhibited a brilliant size cutoff efficiency for aryl benzene amounting to 100% and achieved a high conversion with only 0.05 mol% Pd loading. Besides, this catalyst could be readily recovered via filtration and reused for at least five consecutive cycles without any significant loss in its activity.

Cell cycle heterogeneity directs spontaneous 2C state entry and exit in mouse embryonic stem cells.

Mouse embryonic stem cells (ESCs) show cell-to-cell heterogeneity. A small number of two-cell-like cells (2CLCs) marked by endogenous retrovirus activation emerge spontaneously. The 2CLCs are unstable and they are prone to transiting back to the pluripotent state without extrinsic stimulus. To understand how this bidirectional transition takes place, we performed single-cell RNA sequencing on isolated 2CLCs that underwent 2C-like state exit and re-entry, and revealed a step-by-step transitional process between 2C-like and pluripotent states. Mechanistically, we found that cell cycle played an important role in mediating these transitions by regulating assembly of the nucleolus and peri-nucleolar heterochromatin to influence 2C gene Dux expression. Collectively, our findings provide a roadmap of the 2C-like state entry and exit in ESCs and also a causal role of the cell cycle in promoting these transitions.

Generation of the human induced pluripotent stem cell line (ZJUi005-A) from a patient with Pelizaeus-Merzbacher disease (PMD) carrying a novel hemizygous mutation in PLP1 gene.

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked leukodystrophy caused by mutations in the proteolipid protein 1 gene (PLP1) which is specifically expressed on the myelin sheath of oligodendrocytes. We established an induced pluripotent stem cell (iPSC) line (ZJUi005-A) from peripheral blood mononuclear cells of an 18-year-old male PMD patient with a novel hemizygous c.437T>C mutation in PLP1 gene using episomal reprogramming plasmids. The ZJUi005-A iPSC line carried the PLP1 mutation, expressed pluripotency markers, exhibited normal karyotype and showed differentiation potential in vitro.