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The Journal of Physical Chemistry... Jul 2024Most nonrelativistic electron correlation methods can be adapted to account for relativistic effects, as long as the relativistic molecular spinor integrals are...
Most nonrelativistic electron correlation methods can be adapted to account for relativistic effects, as long as the relativistic molecular spinor integrals are available, from either a four-, two-, or one-component mean-field calculation. However, relativistic multireference correlation methods remain a relatively unexplored area, with mixed evidence regarding the improvements brought by perturbative treatments. We report, for the first time, the implementation of state-averaged four-component relativistic multireference perturbation theories to second and third order based on the driven similarity renormalization group (DSRG). With our methods, named 4c-SA-DSRG-MRPT2 and 3, we find that the dynamical correlation included on top of 4c-CASSCF references can significantly improve the spin-orbit splittings in p-block elements and potential energy surfaces when compared to 4c-CASSCF and 4c-CASPT2 results. We further show that 4c-DSRG-MRPT2 and 3 are applicable to these systems over a wide range of the flow parameter, with systematic improvement from second to third order in terms of both improved error statistics and reduced sensitivity with respect to the flow parameter.
PubMed: 38954768
DOI: 10.1021/acs.jpclett.4c01372 -
Chemistry & Biodiversity Jul 2024α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase...
α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-vis, FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4c (IC50= 3.8 µM), 4g (IC50= 14.5 µM), and 4f (IC50= 17.1 µM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4f and 4h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.
PubMed: 38954767
DOI: 10.1002/cbdv.202401021 -
CNS Neuroscience & Therapeutics Jul 2024Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary...
AIMS
Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion.
METHODS
We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI).
RESULTS
rtPA increased neutrophil infiltration into the brain microvessels and worsened blood-brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI.
CONCLUSION
Neutrophils play a crucial role in promoting ischemic injury and blood-brain barrier disruption, making them potential therapeutic targets.
Topics: Tissue Plasminogen Activator; Animals; Humans; Male; Neutrophils; Rats; Recombinant Proteins; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Rats, Sprague-Dawley; Aged; Blood-Brain Barrier; Cell Movement; Female; Neutrophil Infiltration; Middle Aged; Brain Ischemia; Disease Models, Animal
PubMed: 38954749
DOI: 10.1111/cns.14825 -
Anatomical Sciences Education Jul 2024This study assesses the acceptability, appropriateness, feasibility, and efficacy of a novel asynchronous video-based intervention for teaching respiratory physiology...
This study assesses the acceptability, appropriateness, feasibility, and efficacy of a novel asynchronous video-based intervention for teaching respiratory physiology and anatomy to medical students in resource-limited settings. A series of short video lectures on pleural anatomy, pulmonary physiology, and pathophysiology was created using Lightboard and screen capture technology. These were uploaded to YouTube and Google Drive and made available to 1st-3rd year medical students at two Latin American universities for 1 week. Employing a parallel-convergent mixed methods design, we conducted surveys, focus groups, interviews, and pre/post testing for qualitative and quantitative data. Thematic Analysis was used to analyze qualitative data and McNemar's test for quantitative analysis. Seventy-six students participated. The videos' short format, interactivity, and Lightboard style were highly valued for their flexibility, time efficiency, and educational impact. Students recognized their clinical relevance and trusted their content, suggesting potential applicability in similar settings. Despite infrastructure and connectivity challenges, the use of flexible streaming and downloadable options facilitated learning. Survey results indicated high levels of feasibility (99%), appropriateness (95%), and acceptability (95%), with significant knowledge gains observed (37% correct pre-test answers vs. 56% post-test, p < 0.0001). Our findings demonstrate high acceptability, appropriateness, feasibility, and efficacy of a targeted asynchronous education centered on short-format videos in resource-limited settings, enabling robust learning despite local barriers. Flexible access is key for overcoming localized barriers. Taking an adaptive, learner-centered approach to content creation and delivery to address constraints was pivotal to success. Our modular videos could serve as versatile models for flexible education in resource-constrained settings.
PubMed: 38954744
DOI: 10.1002/ase.2474 -
Journal of the American Chemical Society Jul 2024Polymers possessing saturated fused polycycles in the main chain repeating unit have been underexplored despite their potential utility based on their expected...
Polymers possessing saturated fused polycycles in the main chain repeating unit have been underexplored despite their potential utility based on their expected properties such as high rigidity, chemical resistance, transparency, and thermal stability. In this regard, herein, we developed a radical stitching polymerization of styryl vinyl ketones for the synthesis of polyketones possessing saturated fused bicyclic repeating units. The polymerization proceeded smoothly with a high degree of stitching efficiency in a chain-growth manner under free radical conditions. This method was further extended to the alternating copolymerization of styryl vinyl ketones and 1-styryl-2-vinylbenzenes, representing the first alternating stitching copolymerization of two different monomers. The obtained polymers were found to show promising thermal properties and high transparency in the visible light region.
PubMed: 38954742
DOI: 10.1021/jacs.4c05094 -
ACS Chemical Biology Jul 2024Hepatitis C virus (HCV) is a positive-stranded RNA virus that mainly causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Recently we confirmed m5C...
Hepatitis C virus (HCV) is a positive-stranded RNA virus that mainly causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Recently we confirmed m5C modifications within NS5A gene of HCV RNA genome. However, the roles of the m5C modification and its interaction with host proteins in regulating HCV's life cycle, remain unexplored. Here, we demonstrate that HCV infection enhances the expression of the host m5C reader YBX1 through the transcription factor MAX. YBX1 acts as an m5C reader, recognizing the m5C-modified NS5A C7525 site in the HCV RNA genome and significantly enhancing HCV RNA stability. This m5C-modification is also required for YBX1 colocalization with lipid droplets and HCV Core protein. Moreover, YBX1 facilitates HCV RNA replication, as well as viral assembly/budding. The tryptophan residue at position 65 (W65) of YBX1 is critical for these functions. Knockout of YBX1 or the application of YBX1 inhibitor SU056 suppresses HCV RNA replication and viral protein translation. To our knowledge, this is the first report demonstrating that the interaction between host m5C reader YBX1 and HCV RNA m5C methylation facilitates viral replication. Therefore, hepatic-YBX1 knockdown holds promise as a potential host-directed strategy for HCV therapy.
PubMed: 38954741
DOI: 10.1021/acschembio.4c00322 -
Bioconjugate Chemistry Jul 2024Fibroblast activation protein (FAP) has recently gained significant attention as a promising tumor biomarker for both diagnosis and therapeutic applications. A series of...
Fibroblast activation protein (FAP) has recently gained significant attention as a promising tumor biomarker for both diagnosis and therapeutic applications. A series of radiopharmaceuticals based on fibroblast activation protein inhibitors (FAPIs) have been developed and translated into the clinic. Though some of them such as radiolabeled FAPI-04 probes have achieved favorable in vivo imaging performance, further improvement is still highly desired for obtaining radiopharmaceuticals with a high theranostics potential. In this study, we innovatively designed an FAPI ligand SMIC-3002 by changing the core quinoline motif of FAPI-04 to the quinolinium scaffold. The engineered molecule was further radiolabeled with Ga to generate a positron emission tomography (PET) probe, [Ga]Ga-SMIC-3002, which was then evaluated in vitro and in vivo. [Ga]Ga-SMIC-3002 demonstrated high in vitro stability, nanomolar affinity for FAP (8 nM for protein, 23 nM for U87MG cells), and specific uptake in FAP-expressing tumors, with a tumor/muscle ratio of 19.1 and a tumor uptake of 1.48 ± 0.03 ID/g% at 0.5 h in U87MG tumor-bearing mice. In summary, the quinolinium scaffold can be successfully used for the development of the FAP-targeted tracer. [Ga]Ga-SMIC-3002 not only shows high potential for clinical translation but also offers insights into designing a new generation of FAPI tracers.
PubMed: 38954733
DOI: 10.1021/acs.bioconjchem.4c00214 -
PLoS Neglected Tropical Diseases Jul 2024When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To date, the extent of the transcriptomic...
When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To date, the extent of the transcriptomic changes in first hybrid generations, along with their functional outcome constitute an important knowledge gap, especially in parasite species. Here we explored the molecular and functional outcomes of hybridization in first-generation hybrids between the blood fluke parasites Schistosoma haematobium and S. bovis. Through a transcriptomic approach, we measured gene expression in both parental species and hybrids. We described and quantified expression profiles encountered in hybrids along with the main biological processes impacted. Up to 7,100 genes fell into a particular hybrid expression profile (intermediate between the parental expression levels, over-expressed, under-expressed, or expressed like one of the parental lines). Most of these genes were different depending on the direction of the parental cross (S. bovis mother and S. haematobium father or the reverse) and depending on the sex. For a given sex and cross direction, the vast majority of genes were hence unassigned to a hybrid expression profile: either they were differentially expressed genes but not typical of any hybrid expression profiles or they were not differentially expressed neither between hybrids and parental lines nor between parental lines. The most prevalent profile of gene expression in hybrids was the intermediate one (24% of genes assigned to a hybrid expression profile). These results suggest that transcriptomic compatibility between S. haematobium and S. bovis remains quite high. We also found support for an over-dominance model (over- and under-expressed genes in hybrids compared to parental lines) potentially associated with heterosis. In females in particular, processes such as reproductive processes, metabolism and cell interactions as well as signaling pathways were indeed affected. Our study hence provides new insight on the biology of Schistosoma hybrids with evidences supporting compatibility and heterosis.
PubMed: 38954732
DOI: 10.1371/journal.pntd.0012267 -
PloS One 2024Brain tumors pose a significant threat to health, and their early detection and classification are crucial. Currently, the diagnosis heavily relies on pathologists...
Brain tumors pose a significant threat to health, and their early detection and classification are crucial. Currently, the diagnosis heavily relies on pathologists conducting time-consuming morphological examinations of brain images, leading to subjective outcomes and potential misdiagnoses. In response to these challenges, this study proposes an improved Vision Transformer-based algorithm for human brain tumor classification. To overcome the limitations of small existing datasets, Homomorphic Filtering, Channels Contrast Limited Adaptive Histogram Equalization, and Unsharp Masking techniques are applied to enrich dataset images, enhancing information and improving model generalization. Addressing the limitation of the Vision Transformer's self-attention structure in capturing input token sequences, a novel relative position encoding method is employed to enhance the overall predictive capabilities of the model. Furthermore, the introduction of residual structures in the Multi-Layer Perceptron tackles convergence degradation during training, leading to faster convergence and enhanced algorithm accuracy. Finally, this study comprehensively analyzes the network model's performance on validation sets in terms of accuracy, precision, and recall. Experimental results demonstrate that the proposed model achieves a classification accuracy of 91.36% on an augmented open-source brain tumor dataset, surpassing the original VIT-B/16 accuracy by 5.54%. This validates the effectiveness of the proposed approach in brain tumor classification, offering potential reference for clinical diagnoses by medical practitioners.
Topics: Humans; Brain Neoplasms; Algorithms; Neural Networks, Computer
PubMed: 38954731
DOI: 10.1371/journal.pone.0298102 -
PloS One 2024Rice wine, well known for its unique flavor, rich nutritional value, and health benefits, has potential for extensive market development. Rhizopus and Aspergillus are...
Rice wine, well known for its unique flavor, rich nutritional value, and health benefits, has potential for extensive market development. Rhizopus and Aspergillus are among several microorganisms used in rice wine brewing and are crucial for determining rice wine quality. The strains were isolated via Rose Bengal and starch as a combined separation medium, followed by oenological property and sensory evaluation screening. The strain exhibiting the best performance can be screened using the traditional rice wine Qu. The strains YM-8, YM-10, and YM-16, which exhibited strong saccharification and fermentation performance along with good flavor and taste, were obtained from traditional rice wine Qu. Based on ITS genetic sequence analysis, the YM-8, YM-10, and YM-16 strains were identified as Rhizopus microsporus, Rhizopus arrhizus, and Aspergillus oryzae. The optimum growth temperature of each of the three strains was 30°C, 32°C, and 30°C, and the optimum initial pH was 6.0, 6.5, and 6.5, respectively. The activities of α-amylase, glucoamylase, and protease of YM-16 were highest at 220.23±1.88, 1,269.04±30.32, and 175.16±1.81 U/g, respectively. The amino acid content of rice wine fermented in a 20-L bioreactor with the three mold strains was higher than that of the control group, except for arginine, which was significantly lower than that of the control group. The total amino acid content and the total content of each type of amino acid were ranked as YM-16 > YM-8 > YM-10 > control group, and the amino acid content varied greatly among the strains. The control group had a higher content, whereas YM-8 and YM-16 had lower contents of volatile aroma components than the control group and had the basic flavor substances needed for rice wine, which is conducive to the formation of rice wine aroma. This selected strain, YM-16, has strong saccharification and fermentation ability, is a rich enzyme system, and improves the flavor of rice wine, thereby demonstrating its suitability as a production strain for brewing.
Topics: Wine; Oryza; Bioreactors; Fermentation; Rhizopus; Taste; Aspergillus oryzae; Hydrogen-Ion Concentration
PubMed: 38954729
DOI: 10.1371/journal.pone.0300213