Orientational transitions of discotic columnar liquid crystals in cylindrical pores.

Confined in a cylindrical pore with homeotropic anchoring condition, the hexagonal columnar phase of discotic liquid crystals can form a "log-pile" configuration, in which the columns are perpendicular to the long axis of the pore. However, the {100} planes of the hexagonal lattice can orient either parallel (termed (100)‖ orientation) or perpendicular ((100)⊥) to pore axis. Here we experimentally show that the (100)‖ orientation is found in narrower cylindrical pores, and the (100)‖-(100)⊥ transition can be controlled by engineering the structure of the molecules. The (100)‖ orientation is destroyed in asymmetric discotics hepta(heptenyloxy)triphenylene (SATO7); replacing the oxygen linkage in hexa(hexyloxy)triphenylene (HATO6) by sulphur (HATS6) improves the (100)‖ orientation in small pores; adding a perfluorooctyl end to each alkyl chain of HATO6 (HATO6F8) moves the (100)‖-(100)⊥ transition to larger pores. We have provided a semi-quantitative explanation of the experimental observations, and discussed them in the context of previous findings on related materials in a wider pore size range from 60 nm to 100 µm. This allows us to produce a comprehensive picture of confined columnar liquid crystals whose applications critically depend on our ability to align them.

Developmental dyslexia genes are selectively targeted by diverse environmental pollutants.

BACKGROUND: Developmental dyslexia, a complex neurodevelopmental disorder, not only affects children's academic performance but is also associated with increased healthcare costs, lower employment rates, and reduced productivity. The pathogenesis of dyslexia remains unclear and it is generally considered to be caused by the overlap of genetic and environmental factors. Systematically exploring the close relationship between exposure to environmental compounds and susceptibility genes in the development of dyslexia is currently lacking but high necessary. METHODS: In this study, we systematically compiled 131 publicly reported susceptibility genes for dyslexia sourced from DisGeNET, OMIM, and GeneCards databases. Comparative Toxicogenomics Database database was used to explore the overlap between susceptibility genes and 95 environmental compounds, including metals, persistent organic pollutants, polycyclic aromatic hydrocarbons, and pesticides. Chemical bias towards the dyslexia risk genes was taken into account in the observation/expectation ratios > 1 and the corresponding P value obtained by hypergeometric probability test. RESULTS: Our study found that the number of dyslexia risk genes targeted by each chemical varied from 1 to 109. A total of 35 chemicals were involved in chemical reactions with dyslexia-associated genes, with significant enrichment values (observed/expected dyslexia risk genes) ranging from 1.147 (Atrazine) to 66.901 (Dibenzo(a, h)pyrene). CONCLUSION: The results indicated that dyslexia-associated genes were implicated in certain chemical reactions. However, these findings are exploratory, and further research involving animal or cellular experiments is needed.

Thermotropic "Plumber's Nightmare" - A Tight Liquid Organic Double Framework.

Gyroid, double diamond and the body-centred "Plumber's nightmare" are the three most common bicontinuous cubic phases in lyotropic liquid crystals and block copolymers. While the first two are also present in solvent-free thermotropics, the latter had never been found. Containing six-fold junctions, it was unlikely to form in the more common phases with rod-like cores normal to the network columns, where a maximum of four branches can join at a junction. The solution has therefore been sought in side-branched mesogens that lie in axial bundles joined at their ends by flexible "hinges". But for the tightly packed double framework, geometric models predicted that the side-chains should be very short. The true Plumber's nightmare reported here, using fluorescent dithienofluorenone rod-like mesogen, has been achieved with, indeed, no side chains at all, but with 6 flexible end-chains. Such molecules normally form columnar phases, but the key to converting a complex helical column-forming mesogen into a framework-forming one was the addition of just one methyl group to each pendant chain. A geometry-based explanation is given.

Supertwisted Chiral Gyroid Mesophase in Chiral Rod-Like Compounds.

Among the intriguing bicontinuous self-assembled structures, the gyroid cubic is the most ubiquitous. It is found in block and star polymers, surfactants with or without solvent, in thermotropic liquid crystals with end- or side-chains, and in biosystems providing structural color and modelling cell mitosis. It contains two interpenetrating networks of opposite chirality and is thus achiral if, as usual, the content of the two nets is the same. However, we now find that this is not the case for strongly chiral compounds. While achiral molecules follow the opposite twists of nets 1 and 2, molecules with a chiral center in their rod-like core fail to follow the 70° twist between junctions in net 2 and instead wind against it by -110° to still match the junction orientation. The metastable chiral gyroid is a high-entropy high-heat-capacity mesophase. The homochirality of its nets makes the CD signal of the thienofluorenone compounds close to that in the stable I23 phase with 3 isochiral nets.

Association of Beta-2 Microglobulin with Stroke and All-Cause Mortality in Adults Aged ≥40 in U.S.: NHANES III.

Background: Stroke is the predominant cause of death worldwide. We aimed to investigate the association of serum beta-2 microglobulin ( ß 2M) concentrations with risk of stroke and all-cause mortalities in a cohort study. Methods: Overall, 4914 U.S. adults (mean age = 63.0 years, 44.3% male) were recruited from the National Health and Nutrition Examination Survey (NHANES Ⅲ). During a median follow-up of 19.4 years, 254 stroke deaths and 3415 all-cause deaths were identified by the National Center for Health Statistics. The associations of ß 2M with stroke and all-cause mortalities were investigated by using weighted Cox proportional hazard regression models. Results: ß 2M was positively associated with stroke and all-cause mortality in unadjusted models and multivariable-adjusted models. The multivariable HR (95% CI) for stroke mortality in Q5 VS Q1 of serum ß 2M concentrations was 3.45 (1.33-8.91; p for trend = 0.001) and that for all-cause mortality was 3.95 (3.05-5.12; p for trend < 0.001). In subgroup analyses, the association of ß 2M and stroke mortality did not vary by different levels of sociodemographic and general stroke risk factors (p interaction > 0.05). In addition, the magnitude of positive association between ß 2M with all-cause mortality did vary by age, ratio of family income to poverty, smoking status, and history of hypertensive (p interaction < 0.05). Conclusions: Our findings suggest that support that ß 2M may be a marker of stroke and all-cause mortality, which provides a new perspective for the study of cerebrovascular health and long-term survival in the future.

Single-cell transcriptome analysis reveals the regulatory functions of islet exocrine cells after short-time obesogenic diet.

PURPOSE: This study aims to investigate the functions of exocrine islet cell subtypes in the early stage of obesity induced by high-fat diet (HFD), which is accompanied with deterioration of the systemic insulin response and islet subpopulation abnormalities. METHODS: In this study, we analyzed published islet single-cell RNA sequencing (scRNA-seq) datasets from the early stage induced by HFD feeding. Bioinformatics tools such as findMarkers, Cellchat, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology (GO) terms were applied to identify the different functions of exocrine cell clusters. RESULTS: A total of 26 cell clusters were obtained were identified from this dietary intervention model. Most proportions of cell subtypes were consistent between high-fat diet (HFD) and low-fat diet (LFD) groups, except for partial endocrine islet clusters and exocrine clusters. Most differentiated expression of genes in the HFD group was found in exocrine cluster. And we also found that the cell-cell interactions between ductal and endothelial cells were reduced in the HFD group, with the significant alteration in C17 (ductal) cluster. By further analyzing the co-expression regulatory network of transcription in the C17 cluster, we speculate that differentially expressed transcription factors affected the function of duct cells by affecting the expression of related genes in intercellular interaction networks, thereby promoting insulin resistance (IR) development. CONCLUSION: Our results provide a reference for the function and regulatory mechanisms of exocrine cells in the obesity induced by HFD and probably influence the process of following insulin resistance.

The association between closed-eye unipedal standing and the risk of cognitive impairment in the elderly: a 7-year community-based cohort study in Wuhan, China.

Objectives: The prevention of cognitive impairment in the elderly is one of the public health priority areas. However, the relationship between closed-eye unipedal standing and cognitive impairment remains unclear. Methods: This study was conducted on a group of elderly individuals from a community, using a prospective cohort study design. Participants were monitored for 7 years and were diagnosed with new-onset cognitive impairment. Logistic regression models and restricted cubic spline (RCS) were used to investigate the relationship between closed-eye unipedal standing and cognitive impairment. Stratified analysis by baseline characteristics were also performed. Results: At baseline, 1,652 people aged 65 years or older were enrolled. Ultimately, 880 participants completed the follow-up and 155 (17.61%) of them satisfied the diagnostic criteria for cognitive impairment at follow-up. Compared to the closed-eye unipedal standing low group as the reference, the middle (OR = 0.601, 95% CI: 0.396-0.911) and high (OR = 0.508, 95% CI: 0.329-0.785) groups had significantly lower cognitive impairment risks. RCS analysis indicated a linear relationship (Pnon - linear = 0.177), with a reduced risk of developing cognitive impairment when the duration of closed-eye unipedal standing was exceeded ~2.920 s. Stratified analysis showed that for female, aged 70 years or younger, with 3 or more years of education, without lack of exercise and without falls within 1 year subgroup, the elderly in the high group of closed-eye unipedal standing had significantly reduced cognitive impairment risks. Conclusion: Among the elderly population, closed-eye unipedal standing duration was linearly and negatively associated with the cognitive impairment risk. The closed-eye unipedal standing duration might be a predictive index for cognitive impairment in the elderly.

4'-O-methylbavachalcone alleviates ischemic stroke injury by inhibiting parthanatos and promoting SIRT3.

Cerebral ischemia-reperfusion injury (CIRI) can induce massive death of ischemic penumbra neurons via oxygen burst, exacerbating brain damage. Parthanatos is a form of caspase-independent cell death involving excessive activation of PARP-1, closely associated with intense oxidative stress following CIRI. 4'-O-methylbavachalcone (MeBavaC), an isoprenylated chalcone component in Fructus Psoraleae, has potential neuroprotective effects. This study primarily investigates whether MeBavaC can act on SIRT3 to alleviate parthanatos of ischemic penumbra neurons induced by CIRI. MeBavaC was oral gavaged to the middle cerebral artery occlusion-reperfusion (MCAO/R) rats after occlusion. The effects of MeBavaC on cerebral injury were detected by the neurological deficit score and cerebral infarct volume. In vitro, PC-12 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R), and assessed cell viability and cell injury. Also, the levels of ROS, mitochondrial membrane potential (MMP), and intracellular Ca2+ levels were detected to reflect mitochondrial function. We conducted western blotting analyses of proteins involved in parthanatos and related signaling pathways. Finally, the exact mechanism between the neuroprotection of MeBavaC and parthanatos was explored. Our results indicate that MeBavaC reduces the cerebral infarct volume and neurological deficit scores in MCAO/R rats, and inhibits the decreased viability of PC-12 cells induced by OGD/R. MeBavaC also downregulates the expression of parthanatos-related death proteins PARP-1, PAR, and AIF. However, this inhibitory effect is weakened after the use of a SIRT3 inhibitor. In conclusion, the protective effect of MeBavaC against CIRI may be achieved by inhibiting parthanatos of ischemic penumbra neurons through the SIRT3-PARP-1 axis.

Chidamide represses MYC expression and might improve survival for patients with double expressor lymphoma.

Double expressor lymphoma (DEL), characterized by high expressions of both MYC and BCL-2, displays poor prognosis after current therapies. The HDAC inhibitor chidamide has been approved for treatment of T cell lymphoma, but its efficacy on B cell lymphoma is unclear. Here, by combining inhibition screening and transcriptomic analyses, we found that the sensitivity of B lymphoma cells to chidamide was positively correlated with the expression levels of MYC. Chidamide treatment reduced MYC protein levels and repressed MYC pathway in B lymphoma cells with high MYC expressions. Ectopic expression of MYC in chidamide-insensitive B lymphoma cells increased their response to chidamide. Thus, we proposed that adding chidamide into R-CHOP (CR-CHOP) might be effective for DEL, and retrospectively analyzed 185 DEL patients treated in West China Hospital. 80% of patients showed response to CR-CHOP treatment. In the median follow-up of 42 months, CR-CHOP significantly improve the survival for DEL patients with R-IPI ≤2. Totally 35 patients underwent autologous stem cell transplantation (ASCT) in remission and demonstrated a trend for better survival. Combining CR-CHOP with ASCT resulted in the most superior PFS and OS above all. For response patients, CR-CHOP reduced relapse with better PFS than R-CHOP-like regimens with or without ASCT. Taken together, our data indicated that chidamide repressed the MYC pathway in B lymphoma and is potentially efficacious to treat DEL.