Social Self-Sorting of Quasi-Racemates: A Unique Approach for Dual-Pore Molecular Crystals.

Despite recent advances in porous organic molecular crystals, the engineering of dual-pore systems within the intermolecular voids remains a significant challenge. In this study, we have achieved the crystallization-induced social self-sorting of "quasi-racemic" dialdehydes into a macrocyclic imine. X-ray crystallographic analysis unambiguously characterizes the resulting structure as incorporating two quasi-racemate pairs with four diamine molecules. Notably, different alkyl substituents on the quasi-racemates afford two types of one-dimensional pores within the macrocyclic imine crystal. The different adsorption properties of these pores were substantiated through adsorption experiments. An intriguing helical arrangement of guest molecules was observed within one of the pores. This study provides pioneering evidence that the social self-sorting of quasi-racemates offers a new methodology for creating dual-functional supramolecular materials.

Association of short-term changes in HbA1c with body composition and the importance of muscle maintenance in patients with Type 2 diabetes.

AIMS: This study aimed to investigate the relationship between changes in glucose metabolism and body composition in patients with diabetes. METHODS: We included 380 patients with type 2 diabetes, who underwent bioelectrical impedance analysis, in this longitudinal study. Changes in HbA1c (ΔHbA1c) levels and body composition indices were compared between baseline and 6 months. A multivariate analysis was performed to examine the relationship between ΔHbA1c and changes in body composition. RESULTS: HbA1c levels were significantly decreased at 6 months (P < 0.01), but there was no significant change in BMI. A linear multiple regression analysis showed that ΔHbA1c was negatively correlated with changes in muscle mass (ß = -0.18; P = 0.047) and bone mineral content (ß = -0.28; P < 0.001), but there was no significant association between ΔHbA1c levels and a change in body fat percentage. CONCLUSIONS: This study shows a limited association between short-term changes in glucose metabolism and changes in body composition in patients with type 2 diabetes. Therefore, interventions aimed at reducing adiposity may not affect glucose metabolism in the short term, while interventions focused on maintaining or enhancing muscle mass and bone mineral content may play an important role in diabetes management.

Modelling and Development of a Mechanical Eye for the Evaluation of Robotic Systems for Surgery.

Ophthalmic surgery, which addresses critical eye diseases such as retinal disorders, remains a formidable and arduous surgical pursuit. Nevertheless, with the advent of cutting-edge robotics and automation technology, significant advancement has been made in recent years to enhance the safety and efficacy of these procedures through meticulous research and development efforts. Ensuring the safe and effective execution of micro-surgical procedures requires stringent quality control measures, notably concerning evaluating and testing the devices utilized. During the development phase, these instruments must undergo extensive and continual evaluation by clinical practitioners to guarantee their safety and efficacy. Ideally, the test conditions should be identical to those of an actual operation. When testing robotic systems for ophthalmology, essential variables of the human eye, such as tissue properties and movement mechanisms, should be addressed. To minimize the discrepancy of tests and actual eye surgery conditions, in this paper, we propose a developed mechanical eye model to enable the realistic evaluation of ophthalmic surgical systems. After developing a virtual and physical model, the model was tested by an eye surgeon. The eye surgeon rated the model with four out of five possible points.Clinical relevance- This method ensures minimal discrepancy in verification of ophthalmic surgical devices by allowing the mechanical eye model to behave similar to the human eye, thus providing a realistic surgical procedure.

RCIT: A Robust Catadioptric-based Instrument 3D Tracking Method For Microsurgical Instruments In a Single-Camera System.

The field of robotic microsurgery and micro-manipulation has undergone a profound evolution in recent years, particularly with regard to the accuracy, precision, versatility, and dexterity. These advancements have the potential to revolutionize high-precision biomedical procedures, such as neurosurgery, vitreoretinal surgery, and cell micro-manipulation. However, a critical challenge in developing micron-precision robotic systems is accurately verifying the end-effector motion in 3D. Such verification is complicated due to environmental vibrations, inaccuracy of mechanical assembly, and other physical uncertainties. To overcome these challenges, this paper proposes a novel single-camera framework that utilizes mirrors with known geometric parameters to estimate the 3D position of the microsurgical instrument. Euclidean distance between reconstructed points by the algorithm and the robot movement recorded by the highly accurate encoders is considered an error. Our method exhibits an accurate estimation with the mean absolute error of 0.044 mm when tested on a 23G surgical cannula with a diameter of 0.640 mm and operates at a resolution of 4024 × 3036 at 30 frames per second.

Determinants of phase angle in Japanese patients with diabetes.

Phase angle, obtained using bioelectrical impedance analysis, non-invasively reflects the whole-body cellular condition and nutritional status and may be helpful as a prognostic factor. Patients with diabetes had a smaller phase angle than healthy subjects. However, the clinical significance of phase angle has not yet been elucidated. Therefore, the purpose of this study was to clarify the relationship between phase angle and HbA1c in patients with diabetes and the clinical relevance of phase angle. A retrospective, multicenter, cross-sectional study was conducted with Japanese patients with diabetes. Body composition was determined with bioelectrical impedance analysis, and this was used to obtain phase angle. Phase angle was assessed in relation to clinical parameters, body composition parameters, and HbA1c levels. A total of 655 patients were enrolled (400 men and 255 women, aged 57.1 ± 14.8 years, body mass index 25.6 ± 5.2 kg/m2, HbA1c 8.1 ± 1.9%). Even in patients with diabetes, the phase angle was higher in men than in women and did not differ between the types of diabetes. Multiple regression analysis, performed with phase angle as the objective variable, and age, sex, diabetes type, HbA1c, albumin level, and body mass index as explanatory variables, revealed that phase angle was negatively affected by HbA1c (B = - 0.043, 95% Confidence interval: - 0.07 to - 0.02, p < 0.001). HbA1c, age, sex, albumin level, and body mass index were independent determinants of phase angle in participants with diabetes.

CO2-Induced Gate-Opening Adsorption on a Chabazite/Phillipsite Composite Zeolite Transformed from a Faujasite Zeolite Using Organic Structure-Directing Agent-Free Steam-Assisted Conversion.

Organic structure-directing agent-free steam-assisted conversion and Cs+ ion exchange were used to transform the faujasite (FAU)-type zeolite to the Cs+-type chabazite/phillipsite (CHA/PHI) composite zeolite. Compared with the pure PHI-type zeolite, the Cs+-type CHA/PHI zeolite showed gate-opening CO2 adsorption behavior and good thermal stability. In situ powder X-ray diffraction (PXRD) of the CO2 adsorption was measured to elucidate the mechanism for the gate-opening adsorption on the CHA/PHI zeolite. The Na+-type CHA/PHI zeolite did not show such adsorption behavior, and the PXRD pattern of the Na+-type CHA/PHI zeolite did not change with increasing CO2 partial pressure, which suggests that this unique adsorption behavior was caused by the PHI framework transition or Cs+ ions moving in both the CHA and PHI frameworks. Furthermore, in situ Fourier-transform infrared spectra of CO2 adsorption and CO2 breakthrough measurement on the Cs+-type CHA/PHI zeolite suggest that the CHA and PHI frameworks in the CHA/PHI zeolite shared eight-membered-ring windows and that CO2 molecules could easily diffuse from a CHA cage to a PHI framework. The ideal adsorbed solution theory was used to calculate the CO2/N2 separation selectivity for the Cs+-type CHA/PHI zeolite. At 298 and 318 K, the Cs+-type CHA/PHI composite zeolite showed a high CO2/N2 separation coefficient of >10,000 compared with other zeolites with high CO2 adsorption capacity. Furthermore, the CO2 working capacity was calculated for the Cs+-type CHA/PHI zeolite in both the pressure- and temperature-swing processes, and the results showed that the CHA/PHI composite zeolite could selectively separate CO2 from the CO2/N2 gas mixtures released from power generation plants operating using these processes.

Co-culture system of human skin equivalents with mouse neural spheroids.

This study describes a co-culture system of human skin equivalents (HSEs) and dorsal root ganglion (DRG) neurons. We prepared spheroids of mouse DRG neurons with or without Schwann cells (SCs). Spheroids comprising DRG neurons and SCs showed longer neurite extensions than those comprising DRG neurons alone. Neurite extension of more than 1 mm was observed from spheroids cultured inside HSEs, whereas neurite extension was primarily observed on the surface of HSEs from spheroids cultured on HSEs. We propose that our model may be a useful tool for studying neurite extension in the human skin.

VGF nerve growth factor inducible has the potential to protect pancreatic ß-cells.

VGF nerve growth factor inducible (VGF) is a secreted polypeptide involved in metabolic regulation. VGF-derived peptides have been reported to regulate insulin secretion in the plasma of patients with type 2 diabetes and model mice. However, the protective effects of VGF on pancreatic ß-cells in diabetic model are not well understood. In this study, we aimed to elucidate the ß-cell protective effect of VGF on a streptozotocin (STZ)-induced diabetic model using VGF-overexpressing (OE) mice and also examined the therapeutic effect by a small molecule, SUN N8075 which is an inducer of VGF. VGF-OE mice improved blood glucose levels and maintained ß-cell mass compared to wild-type (WT) mice on STZ-induced diabetic model. In addition, VGF-OE mice showed better glucose tolerance than WT mice. In culture, AQEE-30, a VGF-derived peptide, suppressed STZ-induced ß-cell death in vitro and attenuated the decrease in the phosphorylation of Akt and GSK3ß. Furthermore, SUN N8075 suppressed the blood glucose levels and increased VGF expression in the pancreatic islet. SUN N8075 also protected STZ-induced ß-cell death in vitro. These findings indicate that VGF plays a hypoglycemic role in response to blood glucose levels in diabetes and protects ß-cells from STZ-induced cell death. Therefore, VGF and its inducer have the therapeutic potential by preserving ß-cells in diabetes.

ALK5 inhibitor acts on trabecular meshwork cell and reduces intraocular pressure.

Intraocular pressure (IOP) is the most important risk factor for the onset and progression of glaucoma. IOP reduction has been proven effective in the treatment of glaucoma. IOP is controlled by the production and outflow of the aqueous humor (AH), and the trabecular meshwork (TM) is the main pathway for AH drainage from the eye. However, there are few conventional IOP-lowering treatments that target TM, and there is a need for such treatments. In this study, we screened for the expression level of fibronectin as an indicator and identified an activin receptor-like kinase (ALK) 5 inhibitor. Western blot analysis showed that SB431542, an ALK 5 inhibitor, reduced fibronectin and α-SMA expression. Moreover, a single dose of the ALK5 inhibitor SB431542 reduced IOP in mice, and the IOP-lowering effect of the ALK5 inhibitor was greater than that of a Rho-associated coiled-coil-containing protein kinase inhibitor (Y-27632). Repeated dosing with ALK5 inhibitor eye drops (once daily) enhanced the murine IOP-lowering effect. Furthermore, ALK5 inhibition decreased the expression of extracellular matrix (ECM) mRNA and suppressed ECM production. These findings suggest that ALK5 inhibitors may contribute to the development of new treatments for glaucoma that target the TM.

Direct TEM Observation of Vacancy-Mediated Heteroatom Incorporation into a Zeolite Framework: Towards Microscopic Design of Zeolite Catalysts.

Incorporating hetero-metal-atom, e.g., titanium, into zeolite frameworks can enhance the catalytic activity and selectivity in oxidation reactions. However, the rational design of zeolites containing titanium at specific sites is difficult because the precise atomic structure during synthesis process remained unclear. Here, a titanosilicate with predictable titanium distribution was synthesized by mediating vacancies in a defective MSE-type zeolite precursor, based on a pre-designed synthetic route including modification of vacancies followed by titanium insertion, where electron microscopy (EM) plays a key role at each step resolving the atomic structure. Point defects including vacancies in the precursor and titanium incorporated into the vacancy-related positions have been directly observed. The results provide insights into the role of point defects in zeolites towards the rational synthesis of zeolites with desired microscopic arrangement of catalytically active sites.

Effects of an ethics education program on nurses' moral efficacy in an acute health care facility.

AIM: This study aimed to evaluate an ethics education program developed to increase moral efficacy among nurses in an acute health care facility. BACKGROUND: Moral distress among nurses can cause serious problems in terms of hospital organisations and patient safety. To reduce moral distress and promote professional confidence in nursing practice, a strategic intervention program is needed. METHODS: An ethics education program introduced methods to increase self-efficacy in accordance with Bandura's social cognitive theory. Eight nurses were recruited from 2017 to 2019, and all conversations and discussions regarding the ethics consultation were recorded on IC recorders and analysed qualitatively. RESULTS: Four core categories-Convinced to take an active role in ethical issues; Progressed in nursing practice with ethical agency; Experienced professional transformation; and Empowered by the presence of colleagues-emerged as outcomes of the ethics education program that related to moral efficacy. CONCLUSIONS: The four core outcome categories suggested that the participants had gained confidence after taking part in the ethical education program. IMPLICATIONS FOR NURSING MANAGEMENT: The results of the participants' described behaviours and actions suggested that they would be proactive in contributing to reductions in moral distress in the future.

Piezo1 activation induces fibronectin reduction and PGF2α secretion via arachidonic acid cascade.

Glaucoma is a neurodegenerative disease that leads to blindness, and lowering intraocular pressure (IOP) is very important in glaucoma treatment. The trabecular meshwork is responsible for aqueous humor outflow, and the accumulation of fibronectin in trabecular meshwork is known to cause ocular hypertension. We have already shown that Piezo1 activation has an IOP lowering effect in mice and suppresses fibronectin expression level in human trabecular meshwork cells (HTMC). In this study, we report the mechanism of the reduction of fibronectin caused by Piezo1 activation. Activation of Piezo1 in HTMC showed increased expression of matrix metalloproteinase-2 (MMP-2) and cyclooxygenase (COX)-2, and decreased fibronectin expression. In addition, Piezo1 activation enhanced phosphorylation of cytosolic phospholipase A2 (cPLA2), and inhibitors targeting cPLA2 and COX-2 suppressed Yoda 1, a Piezo1 agonist, induced fibronectin reduction. These results indicate that the arachidonic acid cascade underlies this reaction, and, in support of this hypothesis, activation of Piezo1 promoted secretion of prostaglandin F2α (PGF2α) in HTMC. These results indicate that the activation of Piezo1 in HTMC promotes the degrading of fibronectin by promoting the arachidonic acid cascade and increasing the expression of PGF2α and MMP-2.

Diabetes-related shame among people with type 2 diabetes: an internet-based cross-sectional study.

INTRODUCTION: Emerging evidence suggests that diabetes stigma and negative emotions associated with it may impair the quality of life of people with diabetes. Among these psychological distresses, shame is considered the most distressing of all human emotional experiences and may be a condition to which diabetes clinicians should pay attention. This epidemiological study focused on diabetes-related shame and aimed to determine the prevalence of diabetes-related shame, its factors, and its association with psychological indicators. RESEARCH DESIGN AND METHODS: A cross-sectional online survey was conducted among people with type 2 diabetes preregistered with a research firm. The questionnaire included experience of diabetes-related shame and demographic data such as age, clinical characteristic measures such as hemoglobin A1c (HbA1c), and psychological indicators, including the WHO Five Well-Being Index (WHO-5) and Problem Areas In Diabetes-5 (PAID-5). Differences in each indicator between people with diabetes who experienced shame and those who did not were analyzed with the unpaired t-test. As supplemental analysis, binomial logistic regression analysis was used to identify factors associated with the prevalence of diabetes-related shame. RESULTS: Of the 510 participants, 32.9% experienced diabetes-related shame and 17.5% concealed their disease from colleagues or friends. Those who had experienced diabetes-related shame showed significantly lower WHO-5 and higher PAID-5 scores (p<0.001). However, no significant difference was found in HbA1c (p=0.36). Binomial logistic regression revealed that women, young adults, those without a college degree, those with low self-efficacy, and those with a strong sense of financial burden or external pressure were at higher risk of experiencing diabetes-related shame. CONCLUSIONS: Among people with type 2 diabetes mellitus, diabetes-related shame was associated with diabetes-specific emotional distress and low psychological well-being. Further research and care development are needed to address diabetes-related shame and improve the quality of life of people with diabetes.

Contribution of Solvents to Geometrical Preference in the Z/E Equilibrium of N-Phenylthioacetamide.

We studied the Z/E preference of N-phenylthioacetamide (thioacetanilide) derivatives in various solvents by means of 1H NMR spectroscopy, as well as molecular dynamics (MD) and other computational analyses. Our experimental results indicate that the Z/E isomer preference of secondary (NH)thioamides of N-phenylthioacetamides shows substantial solvent dependency, whereas the corresponding amides do not show solvent dependency of the Z/E isomer ratios. Detailed study of the solvent effects based on molecular dynamics simulations revealed that there are two main modes of hydrogen (H)-bond formation between solvent and (NH)thioacetamide, which influence the Z/E isomer preference of (NH)thioamides. DFT calculations of NH-thioamide in the presence of one or two explicit solvent molecules in the continuum solvent model can effectively mimic the solvation by multiple solvent molecules surrounding the thioamide in MD simulations and shed light on the precise nature of the interactions between thioamide and solvent. Orbital interaction analysis showed that, counterintuitively, the Z/E preference of NH-thioacetamides is mainly determined by steric repulsion, while that of sterically congested N-methylthioacetamides is mainly determined by thioamide conjugation.

Defect Formation, T-Atom Substitution and Adsorption of Guest Molecules in MSE-Type Zeolite Framework-DFT Modeling.

We used computational modeling, based on Density Functional Theory, to help understand the preference for the formation of silanol nests and the substitution of Si by Ti or Al in different crystallographic positions of the MSE-type framework. All these processes were found to be energetically favorable by more than 100 kJ/mol. We suggested an approach for experimental identification of the T atom position in Ti-MCM-68 zeolite via simulation of infrared spectra of pyridine and acetonitrile adsorption at Ti. The modeling of adsorption of hydrogen peroxide at Ti center in the framework has shown that the molecular adsorption was preferred over the dissociative adsorption by 20 to 40 kJ/mol in the presence or absence of neighboring T-atom vacancy, respectively.

Aggregation of Cystatin C Changes Its Inhibitory Functions on Protease Activities and Amyloid ß Fibril Formation.

Cystatin C (CST3) is an endogenous cysteine protease inhibitor, which is implicated in cerebral amyloid angiopathy (CAA). In CAA, CST3 is found to be aggregated. The purpose of this study is to investigate whether this aggregation could alter the activity of the protein relevant to the molecular pathology of CAA. A system of CST3 protein aggregation was established, and the aggregated protein was characterized. The results showed that CST3 aggregated both at 80 °C without agitation, and at 37 °C with agitation in a time-dependent manner. However, the levels of aggregation were high and appeared earlier at 80 °C. Dot-blot immunoassay for oligomers revealed that CST3 could make oligomeric aggregates at the 37 °C condition. Electron microscopy showed that CST3 could make short fibrillary aggregates at 37 °C. Cathepsin B activity assay demonstrated that aggregated CST3 inhibited the enzyme activity less efficiently at pH 5.5. At 7.4 pH, it lost the inhibitory properties almost completely. In addition, aggregated CST3 did not inhibit Aß1-40 fibril formation, rather, it slightly increased it. CST3 immunocytochemistry showed that the protein was positive both in monomeric and aggregated CST3-treated neuronal culture. However, His6 immunocytochemistry revealed that the internalization of exogenous recombinant CST3 by an astrocytoma cell culture was higher when the protein was aggregated compared to its monomeric form. Finally, MTT cell viability assay showed that the aggregated form of CST3 was more toxic than the monomeric form. Thus, our results suggest that aggregation may result in a loss-of-function phenotype of CST3, which is toxic and responsible for cellular degeneration.

Involvement of endoplasmic reticulum stress in rotenone-induced leber hereditary optic neuropathy model and the discovery of new therapeutic agents.

Leber hereditary optic neuropathy (LHON) is caused by mitochondrial DNA mutations and is the most common inherited mitochondrial disease. It is responsible for central vision loss in young adulthood. However, the precise mechanisms of onset are unknown. This study aimed to elucidate the mechanisms underlying LHON pathology and to discover new therapeutic agents. First, we assessed whether rotenone, a mitochondrial complex Ⅰ inhibitor, induced retinal degeneration such as that in LHON in a mouse model. Rotenone decreased the thickness of the inner retina and increased the expression levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and immunoglobulin heavy-chain binding protein (BiP). Second, we assessed whether rotenone reproduces LHON pathologies on RGC-5, a neural progenitor cell derived from the retina. Rotenone increased the cell death rate, ROS production and the expression levels of ER stress markers. During chemical compounds screening, we used anti-oxidative compounds, ER stress inhibitors and anti-inflammatory compounds in a rotenone-induced in vitro model. We found that SUN N8075, an ER stress inhibitor, reduced mitochondrial ROS production and improved the mitochondrial membrane potential. Consequently, the ER stress response is strongly related to the pathologies of LHON, and ER stress inhibitors may have a protective effect against LHON.

Piezo 1 is involved in intraocular pressure regulation.

Trabecular meshwork (TM) regulates the intraocular pressure (IOP) through the control of aqueous humor outflow. Previous reports show that TM cells express 11 types of mechanosensitive molecules, including Piezo 1, which sense mechanical stimuli. However, the role of Piezo 1 on TM remains unclear. Thus, in this study, we focused on the Piezo 1 and examined its role in TM cells. Immunostaining showed that Piezo 1 was expressed in mouse TM and human TM cells. Moreover, the eye drops containing Piezo 1 agonist Yoda 1 reduced the IOP in mice, and also reduced fibronectin expression level around the TM. In addition, Piezo 1 activation suppressed human TM cells migration/proliferation, and decreased fibronectin expression level. On the other hand, Piezo 1 activation increased matrix metalloproteinase (MMP)-2 expression responsible for fibronectin degradation. These findings could contribute to the development of new treatments for glaucoma.

Highly efficient titanosilicate catalyst Ti-MCM-68 prepared using a liquid-phase titanium source for the phenol oxidation.

A highly efficient Ti-MCM-68 catalyst for phenol oxidation with H2O2 was prepared by a mild liquid-phase treatment for the first time. The key preparation procedures to excellent catalytic activity and high para-selectivity were the use of aqueous solutions of the Ti source and calcination at 650 °C prior to catalytic use.

Asymptomatic Immune Checkpoint Inhibitor-associated Myocarditis.

We herein report the case of a 75-year-old man with asymptomatic immune checkpoint inhibitor (ICI)-associated myocarditis diagnosed on the basis of elevated levels of creatine kinase (CK), CK-myocardial band and troponin I (TNI). He was suspected of being complicated with myasthenia gravis (MG). High-dose prednisolone (PSL) is associated with a risk of MG exacerbation; therefore, PSL therapy was gradually increased from 5 mg/day to 20 mg/day, which resulted in the normalization of the TNI level, and no PSL-related side effects occurred. MG easily complicates myocarditis as an immune-related adverse event; thus, the treatment plan should be carefully considered.