Symmetry in Asymmetric Catalysis and Hydrogen Bond-Based Self-Assembly : Synthesis and Investigations

The thesis elaborates on four different projects focusing on synthesizing symmetry-related molecules and investigating their performance as catalysts for asymmetric catalysis or as monomers for hydrogen bond-based self-assembly.Chapter 2 describes a new method to desymmetrize a meso-ligand. Two pseudo-Cs-symmetric bissalen complexes from a meso bissalen ligand and two different pairs of metal ions were designed and synthesized. The resulting complexes catalyzed asymmetric ring-opening of meso-epoxides with up to 76% ee of the product, indicating a new approach to applying meso-ligand in asymmetric catalysis. Chapters 3 and 4 deal with the synthesis of a C3-symmetric tricyclic trilactam and its derivatives as monomers for hydrogen bond-based self-assembly. In Chapter 3, we have accomplished the racemic and enantiomeric syntheses of the unfunctionalized trilactam that had been attempted for a long time. Solid-state hydrogen bond-based self-assembly of the two trilactams was revealed by single-crystal X-ray diffraction. Due to the poor solubility of the unsubstituted trilactams in non-polar solvents, the studies on their self-assembly in solution were hindered. In Chapter 4, we turned our efforts towards the synthesis of a more lipophilic trilactam, aiming to study its self-assembly in non-polar solvents. Many functionalizations of different intermediates involved in the synthesis of the unfunctionalized trilactam were attempted but failed to result in the lipophilic trilactam. An unexpected oxidative rearrangement of an α,β-unsaturated-γ-lactam was discovered during the attempts towards the lipophilic trilactam. Substrate scope screening of the reaction and DFT calculation of the possible transition state of the rearrangement step indicated an important role played by the β-substituent of the unsaturated γ-lactam.Chapter 5 presents two different approaches aiming at increasing the biocompatibility of a C2-symmetric molecule as a monomer for hydrogen bond-based self-assembly, i.e., increasing the hydrophilicity of the monomer while keeping its lipophilicity. The approach where we tried to improve the hydrophilicity of the monomer by complexing it with cyclodextrins did not work well. The effect of cyclodextrin complexation on the hydrophilicity of the monomer was limited. The other approach, where PEG groups were installed on the side chain of the monomer, worked very well. The resulting monomer could get dissolved in water and extracted back to organic solvents. 1H NMR spectra of the PEGylated monomer in toluene-d6 and C6D6 indicated the formation of a self-assembled aggregate

Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis

Inflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxidative stress. The aim of this study was to investigate the role of KAL in AAA through studies in experimental mouse models and patients. Serum KAL concentration was negatively associated with the diagnosis and growth of human AAA. Transgenic overexpression of the human KAL gene (KS-Tg) or administration of recombinant human KAL (rhKAL) inhibited AAA in the calcium phosphate (CaPO4) and subcutaneous angiotensin II (AngII) infusion mouse models. Upregulation of KAL in both models resulted in reduction in the severity of aortic elastin degradation, reduced markers of oxidative stress and less vascular smooth muscle apoptosis within the aorta. Administration of rhKAL to vascular smooth muscle cells incubated in the presence of AngII or in human AAA thrombus-conditioned media reduced apoptosis and downregulated markers of oxidative stress. These effects of KAL were associated with upregulation of Sirtuin 1 activity within the aortas of both KS-Tg mice and rodents receiving rhKAL. These results suggest KAL-Sirtuin 1 signalling limits aortic wall remodelling and aneurysm development through reductions in oxidative stress and vascular smooth muscle cell apoptosis. Upregulating KAL may be a novel therapeutic strategy for AAA. © 2021, The Author(s)

A physics-based defects model and inspection algorithm for automatic visual inspection

AbstractThe representation of physical characteristics is the most essential feature of mathematical models used for the detection of defects in automatic inspection systems. However, the feature of defects and formation of the defect image are not considered enough in traditional algorithms. This paper presents a mathematical model for defect inspection, denoted as the localized defects image model (LDIM), is different because it modeling the features of manual inspection, using a local defect merit function to quantify the cost that a pixel is defective. This function comprises two components: color deviation and color fluctuation. Parameters related to statistical data of the background region of images are also taken into consideration. Test results demonstrate that the model matches the definition of defects, as defined by international industrial standards IPC-A-610D and IPC-A-600G. Furthermore, the proposed approach enhances small defects to improve detection rates. Evaluation using a defects images database returned a 100% defect inspection rate with 0% false detection. Proving that this method could be practically applied in manufacture to quantify inspection standards and minimize false alarms resulting from human error

Hub genes identification and validation of ferroptosis in SARS-CoV-2 induced ARDS: perspective from transcriptome analysis

IntroductionAcute Respiratory Distress Syndrome (ARDS) poses a significant health challenge due to its high incidence and mortality rates. The emergence of SARS-CoV-2 has added complexity, with evidence suggesting a correlation between COVID-19 induced ARDS and post-COVID symptoms. Understanding the underlying mechanisms of ARDS in COVID-19 patients is crucial for effective clinical treatment.MethodTo investigate the potential role of ferroptosis in SARS-CoV-2 induced ARDS, we conducted a comprehensive analysis using bioinformatics methods. Datasets from the Gene Expression Omnibus (GEO) were utilized, focusing on COVID-19 patients with varying ARDS severity. We employed weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and single-cell sequencing to identify key genes associated with ferroptosis in ARDS. Hub genes were validated using additional GEO datasets and cell experiment.ResultThe analysis discerned 916 differentially expressed genes in moderate/severe ARDS patients compared to non-critical individuals. Weighted Gene Co-expression Network Analysis (WGCNA) unveiled two modules that exhibited a positive correlation with ARDS, subsequently leading to the identification of 15 hub genes associated with ferroptosis. Among the noteworthy hub genes were MTF1, SAT1, and TXN. Protein-protein interaction analysis, and pathway analysis further elucidated their roles. Immune infiltrating analysis highlighted associations between hub genes and immune cells. Validation in additional datasets confirmed the upregulation of MTF1, SAT1, and TXN in SARS-CoV-2-induced ARDS. This was also demonstrated by qRT-PCR results in the BEAS-2B cells vitro model, suggesting their potential as diagnostic indicators.DiscussionThis study identifies MTF1, SAT1, and TXN as hub genes associated with ferroptosis in SARS-CoV-2-induced ARDS. These findings provide novel insights into the molecular mechanisms underlying ARDS in COVID-19 patients and offer potential targets for immune therapy and targeted treatment. Further experimental validation is warranted to solidify these findings and explore therapeutic interventions for ARDS in the context of COVID-19

IPDreamer: Appearance-Controllable 3D Object Generation with Image Prompts

Recent advances in text-to-3D generation have been remarkable, with methods such as DreamFusion leveraging large-scale text-to-image diffusion-based models to supervise 3D generation. These methods, including the variational score distillation proposed by ProlificDreamer, enable the synthesis of detailed and photorealistic textured meshes. However, the appearance of 3D objects generated by these methods is often random and uncontrollable, posing a challenge in achieving appearance-controllable 3D objects. To address this challenge, we introduce IPDreamer, a novel approach that incorporates image prompts to provide specific and comprehensive appearance information for 3D object generation. Our results demonstrate that IPDreamer effectively generates high-quality 3D objects that are consistent with both the provided text and image prompts, demonstrating its promising capability in appearance-controllable 3D object generation.Comment: 11 pages, 7 figure

A Design Of Taper-Like Etched Multicore Fiber Refractive Index-Insensitive A Temperature Highly Sensitive Mach-Zehnder Interferometer

We propose and demonstrate Mach-Zehnder interferometer (MZI), which is the refractive index (RI) insensitive and temperature highly sensitive based on etched multi-core fiber (MCF) structure. The MCF and Fiber Bragg Grating (FBG) are used as hybrid sensing elements. The fabrication of the interferometer is provided a new taper-like structure by etching the MCF to further expose the side cores to the surroundings. The interferometer has produced a sensitivity of 103.2pm/°C within the ambient temperature up-to 70°C. Moreover, the superior temperature sensitivity is 89.19pm/°C, 66.64pm/°C, 56.42pm/°C in the range of 24°C to 130°C, and RI-insensitive in the range of 1.34 to 1.38, for different waists of etched seven-core fiber interferometers (E7CFIs) \sim ~84.70\mu \text{m} , 93.10\mu \text{m} , 108.67\mu \text{m} , respectively. Compared with the conventional FBGs, the sensitivity of the interferometer is significantly improved by 8 times. E7CFI\u27s novel and advantageous features can easily be distinguished other devices. Besides, the proposed sensing architecture is compact, easy to fabricate, highly sensitive, easy to reproduce, and makes it an inexpensive fiber optic device

The association between serum uric acid and blood pressure in different age groups in a healthy Chinese cohort

High serum uric acid (sUA) has been reported to be a risk factor for hypertension however, whether this is the case for all age groups is not clear. We examined the association between sUA concentrations and systolic and diastolic blood pressure (SBP and DBP) in different age groups in a cohort of healthy Chinese participants. A total of 1082 healthy participants aged from 41 to 70 years were included. sUA concentration was measured by the uricaseperoxidase method. SBP and DBP were assessed using mercury sphygmomanometry. Hypertension was defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Hyperuricemia (HUA) was defined as sUA concentration of >7mg/dL in men and >6mg/dL in women. The association between sUA concentration and SBP and DBP was examined using Pearson's correlation test, multivariate linear regression, and logistic regression analysis. The prevalence of hypertension and HUA increased with age (P<.001). Hypertension was more common in participants that had HUA than in those that did not (38.95% vs 30.16%, P=.02). Higher sUA was significantly associated with higher SBP and DBP in the 41- to 50-year-old participants (SBP, b=0.35, P<.001; DBP, b=.29, P<.001; after adjustment for age, sex, total cholesterol, estimated glomerular filtration rate, and fasting plasma glucose). HUA was also a risk factor for hypertension in this age group (odds ratio 1.425, 95% confidence interval, 1.217–1.668, P<.001). There was no association between sUA concentration and SBP and DBP in the other age groups. In this population of healthy Chinese participants, sUA concentration was positively associated with hypertension only in the 41- to 50-year-old group. Lowering uric acid in this age group may help to reduce the incidence of hypertension

Major Traditional Probiotics: Comparative Genomic Analyses and Roles in Gut Microbiome of Eight Cohorts

Modulating gut microbiota to promote host health is well recognized. Therefore, people consume dietary products containing traditional probiotics in wishing to improve their health, and they need more research-based advices on how to select products with suitable probiotic species. Probiotic designers are sometimes confused about how to design precision products for different consumers by taking advantages of different probiotic species’ strengths. Additionally, large-scale analyses on traditional probiotic complementarity potentials and their roles in gut microbiome related to common diseases are not well understood. Here, we comprehensively analyzed 444 genomes of major traditional probiotic (sub) species (MTPS, n = 15) by combining one newly sequenced genome with all of the public NCBI-available MTPS-related genomes. The public human fecal metagenomic data (n = 1,815) of eight cohorts were used to evaluate the roles of MTPS, compared to other main gut bacteria, in disease association by examining the species enrichment direction in disease group or the control group. Our work provided a comprehensive genetic landscape and complementarity relations for MTPS and shed light on personalized probiotic supplements for consumers with different health status and the necessity that researchers and manufactures could explore novel probiotics as well as traditional ones

Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis

Aims: Inflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxidative stress.The aim of this study was to investigate the role of KAL in AAA through studies in experimental mouse models and patients. Methods and results: Serum KAL concentration was negatively associated with the diagnosis and growth of human AAA. Transgenic overexpression of the human KAL gene (KS-Tg) or administration of recombinant human KAL (rhKAL) inhibited AAA in the calcium phosphate (CaPO4) and subcutaneous angiotensin II (AngII) infusion mouse models, respectively. Upregulation of KAL in both models resulted in reduction in the severity of aortic elastin degradation, reduced markers of oxidative stress and less vascular smooth muscle apoptosis within the aorta. Administration of rhKAL to vascular smooth muscle cells incubated in the presence of AngII or in human AAA thrombus-conditioned media reduced apoptosis and downregulated markers of oxidative stress. These effects of KAL were associated with upregulation of Sirtuin 1 activity within the aortas of both KS-Tg mice and rodents receiving rhKAL. Conclusions: These results suggest KAL-Sirtuin 1 signalling limits aortic wall remodelling and aneurysm development through reductions in oxidative stress and vascular smooth muscle cell apoptosis. Upregulating KAL may be a novel therapeutic strategy for AAA

Sound-localization-related activation and functional connectivity of dorsal auditory pathway in relation to demographic, cognitive, and behavioral characteristics in age-related hearing loss

BackgroundPatients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains unclear.Materials and methodsUsing a passive listening task with stimuli from five different horizontal directions in functional magnetic resonance imaging, we defined functional regions of interest (ROIs) of the auditory “where” pathway based on the data of previous literatures and young normal hearing listeners (n = 20). Then, we investigated associations of the demographic, cognitive, and behavioral features of sound localization with task-based activation and connectivity of the ROIs in ARHL patients (n = 22).ResultsWe found that the increased high-level region activation, such as the premotor cortex and inferior parietal lobule, was associated with increased localization accuracy and cognitive function. Moreover, increased connectivity between the left planum temporale and left superior frontal gyrus was associated with increased localization accuracy in ARHL. Increased connectivity between right primary auditory cortex and right middle temporal gyrus, right premotor cortex and left anterior cingulate cortex, and right planum temporale and left lingual gyrus in ARHL was associated with decreased localization accuracy. Among the ARHL patients, the task-dependent brain activation and connectivity of certain ROIs were associated with education, hearing loss duration, and cognitive function.ConclusionConsistent with the sensory deprivation hypothesis, in ARHL, sound source identification, which requires advanced processing in the high-level cortex, is impaired, whereas the right–left discrimination, which relies on the primary sensory cortex, is compensated with a tendency to recruit more resources concerning cognition and attention to the auditory sensory cortex. Overall, this study expanded our understanding of the neural mechanisms contributing to sound localization deficits associated with ARHL and may serve as a potential imaging biomarker for investigating and predicting anomalous sound localization