A novel and efficient four-component dicyclization strategy has been developed for one-step constructing diverse antibacterial 3-(1,3,4-oxadiazol-2-yl)isoindolin-1-ones under very mild base-free and metal-free conditions without other additives. This one-pot process underwent two consecutive cyclization reactions including tandem Ugi/aza-Wittig reaction and N-acylation by utilizing (N-isocyanimine)triphenylphosphorane, methyl 2-formylbenzoate, primary amines, and carboxylic acids. The method was conferred its favorable characteristics, including ambient temperature conditions, one-step synthesis, without any additives, facile gram-scale synthesis, and good yields.

The development of efficient and sustainable methods to obtain spirocyclic compounds is of significance as these structures are widely found in pharmaceuticals and agrochemicals. Herein, we disclose an electrochemical dearomative spirocyclization of N-acyl sulfonamides in a continuous-flow cell. The reaction is simple and efficient without external catalysts or supporting electrolytes, in-cluding a decagram-scale synthesis.

Advances in single-cell level analytical techniques, especially cytometric approaches, have led to profound innovation in biomedical research, particularly in the field of clinical immunology. This has resulted in an expansion of high-dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis is thus becoming untenable to handle these challenges. Furthermore, most newly developed computational methods lack flexibility and interoperability, hampering their accessibility and usability. Here, we adapted Seurat, an R package originally developed for single-cell RNA sequencing (scRNA-seq) analysis, for high-dimensional flow cytometric data analysis. Based on a 20-marker antibody panel and analyses of T cell profiles in both adult blood and cord blood, we showcased the robust capacity of Seurat in flow cytometric data analysis, which was further validated by Spectre, another high-dimensional cytometric data analysis package, and conventional manual analysis. Importantly, we identified a unique CD8 + T cell population defined as CD8 +CD45RA +CD27 +CD161 + T cell, that was predominantly present in cord blood. We characterized its IFN-γ-producing and potential cytotoxic properties using flow cytometry experiments and scRNA-seq analysis from a published dataset. Collectively, we identified a unique human cord blood CD8 +CD45RA +CD27 +CD161 + T cell subset and demonstrated that Seurat, a widely used package for scRNA-seq analysis, possesses great potential to be repurposed for cytometric data analysis. This facilitates an unbiased and thorough interpretation of complicated high-dimensional data using a single analytical pipeline and opens a novel avenue for data-driven investigation in clinical immunology.

Empathic accuracy is an ability to precisely understand someone else’s current thoughts and feelings during an interaction. EA has mostly been studied in adult populations, although intra-individual differences in EA could be explained by age and developmental changes during childhood. A systematic review was conducted to synthesize the existing literature on empathic accuracy (EA) in childhood and during parent-child interactions. Following PRISMA norms, five electronic databases were searched and yielded 22 references. Most studies were conducted in samples of adolescents. Besides, the operationalization of EA varied across studies. Few results support age variations in EA during childhood. Children’s and parents’ EA is linked to parental and children’s behaviors during interactions. Parents and children also hold beliefs that girls and mothers should have higher empathy than boys and fathers. Finally, this systematic review highlighted a lack of transparent methodologies and specific assessment of EA in children in the current literature.

This Article examines how it can be utilized and rationally utilized using a digital platform. Korea is reviewing the National Assembly Act and the Petition Act, and this research promotes political opinions and legislative efficiency through digital platforms. Also, in the election campaign, it is important the implementation of a new democracy process using a digital platform and its effects. In particular, this researches how are digital platforms, YouTube/political applications/metaverse, used in the 2022 presidential election in Korea and what effect they have had, how can a digital platform deal with the rational choice of voters or the side effects using big data combined with AI. This paper presents what role should digital platforms play in order to reflect public will, expand voters’ political participation. Therefore, this paper studied legal ways to provide political opinions and accept policies through digital platform systems such as of ‘electronic petitions’, Metaverse, AI.

A new species of Ixora (Rubiaceae), Ixora fernandoi C.B. Moran, from Dinagat Island, Philippines is formally described and illustrated. This species is easily recognized from other known Ixora species by its infloresceence that are erect to drooping, articulate throughout, flower bud with rounded apex, calyx tube not more than 2 mm long; corolla tube 6–8 mm long; corolla lobes elliptic oblong.

This study investigates how disclosure of different types of private information about self, others, and non-personal information may be influenced by privacy concerns and its impact on social media engagement. We propose that the privacy concerns for self and privacy for others have relationships with self-disclosure and disclosure of information about others. Additionally, we investigated the relationship between information disclosure (about self, others, and non-personal) with social media engagement. We focus on social media usage by the Iranian people. The Iranian government has many extreme restrictions on the use of Internet and social media by its citizens. The recent national protests in Iran provide a good opportunity to investigate social media usage by the Iranians. The survey data was collected from Iranian participants (n=379), and we empirically tested the proposed research model. We found non-personal sharing has a positive relationship with self-disclosure, disclosure about others, and engagement. Furthermore, results indicate significant negative relationships between privacy concern for self and self-disclosure and privacy concern for others and disclosure about others.

Sea-level fluctuations in the marginal seas of the northwestern Pacific Ocean during the Pleistonene have profoundly influenced the genetic structure of marine organisms. Previous phylogeographic studies have mainly focused on fish and molluscs; other taxonomic groups have been poorly studied, which restricts a comprehensive understanding of the geogenetic patterns of marine species in this area. To precisely understand how environmental factors and historical events shape the population structure of the sea pen Cavernularia obesa in the East China Sea, we determined partial nucleotide sequences of the mitochondrial cytochrome oxidase subunit I (COI) gene in 71 individuals from five sites. Results of population Genetic and demographic analyses revealed a low genetic diversity within each population. Moreover, the historical population size change showed that the populations experienced bottlenecks during the Pleistonene. The sea level of the East China Sea decreased by >100 m when the glacial advanced during the Pleistonene, which caused the shrinking of habitats for marine species and eventually resulted in low genetic diversity within the populations in this area.

Polymer mechanochemistry on reactive species has attracted more and more attentions over the past 20 years, as the mechanochemical generation of reactive species has a great potential in developing different polymeric materials for various proposes, such as stress detection, self-healing, self-strengthening, controllable degradation and release of small molecules. In this review, we first discuss the recent progress on polymer mechanochemistry of the reactive species that are generated from the mechanochemical reactions of mechanophores. Five types of reactive species, including radical, zwitterion, ionic, carbene and neutral intermediates, and their applications were reviewed in detail. Since mechanochemical reactions are sensitive to the mechanophore structure and polymer framework, we then discuss how mechanophore isomerism, polymer structure, polymer attachment point, and polymer architecture influence the mechanophore activation. At last, we provide our perspectives on the polymer mechanochemistry of reactive species.

Increases in blade size and mass necessitates the reexamination of modeling assumptions in various disciplines. The accuracy of the responses produced from a geometrically exact beam model largely depends on how well the cross-sectional analysis is handled. However, most cross-sectional meshing tools do not account for the adhesive bond lines or joints that typical wind blade manufacturing requires. Adhesives layers can reach 30 mm in thickness and generous amounts of adhesive “squeeze out” can introduce high uncertainty in the adhesive widths. In this work, not only are adhesive layers accounted for, but a sensitivity analysis is also performed on the aeroelastic response of a turbine with 100m-long blades. The cross-sectional meshing capabilities of a new code called pyNuMAD is established. Stiffness and mass matrices are found to be consistent with a validated cross-sectional tool called SONATA. Aeroelastic sensitives to adhesive thicknesses and widths at the webs and trailing edges are presented. Adhesives were found to reduce twist deformation by up to 5%. Loads along the blade span were found to be nonconservative in most cases. In general, the trailing edge adhesive tends to have greater impact on blade response when compared to web adhesives, but this observation seems less certain at higher wind speeds. Accounting for adhesives in aeroelastic simulations is recommended.

Background: autoimmune diseases (ADS) are associated with sepsis. This study aims to investigate the causalities between ADs and sepsis using Mendelian randomization (MR). Methods: we extracted single-nucleotide polymorphisms (SNPs) closely associated with 10 ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS), inflammatory bowel disease (IBD), celiac disease (CD), psoriasis (PsO), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and ulcerative colitis (UC) from the GWAS. Two-sample MR analysis was conducted using GWAS data from the UK Biobank to assess the association between the liability of each ad and sepsis and sepsis-related 28-day mortality. The inverse variance-weighted (IVW) method was used as the primary analysis. If sig-nificant causal relationships are found (considering multiple comparisons) in the univariate MR analysis, multivariate MR (MVMR) analysis is performed to adjust for body mass index (BMI) and smoking. A series of sensitivity analyses were conducted to validate the robustness of the results. Results: after adjusting for multiple testing, MR analysis revealed that PSC patients are responsible for increased susceptibility to sepsis using the IVW method (OR:1.033, 95%CI:1.007-1.060, PFDR = 0.020). Further sensitivity analyses validated the robustness of the above association. Even after adjusting for BMI and smoking, the MVMR-IVW still displayed a positive correlation（OR:1.043, 95%CI:1.022-1.064, P-value for IVW = 3.32E-05） between PSC patients and susceptibility to sepsis. However, no significant causal relationship was observed between SLE, RA, T1D, MS, IBD, CD, PsO, PBC, and UC with susceptibility to sepsis or short-term death risk. Conclusions: our MR analysis revealed a genetic susceptibility of PSC to sepsis. However, no causal relationship was observed between SLE, RA, T1D, MS, IBD, CD, PsO, PBC, and UC with suscep-tibility to sepsis or short-term death risk. Keywords: autoimmune diseases; sepsis; primary sclerosing cholangitis; Mendelian randomization

There are few accurate prognostic indications of the illness’s development and severity for COVID-19, despite certain biomarkers having been investigated. The unexpected nature of COVID-19’s course, which can quickly progress from asymptomatic to severe disease, lies at the heart of the disease’s intricacy. Predicting SARS-CoV-2 pathogenicity through laboratory biomarkers and as such, identifying the patients’ illness severity at the time of initial admission would be crucial in aiding patient care. In this study, we sought to evaluate hematological, biochemical and inflammatory biomarkers in COVID-19 patients. This was a cross-sectional research with 48 COVID-19 patients (16 asymptomatic/mild, 16 moderate, and 16 severe) and 48 age-sex matched COVID-19-negative clients from Moi Teaching and Referral Hospital in Kenya. On admission, demographic information, symptoms, and laboratory test results were collected. Significantly, COVID-19 severity was associated with hemoglobin (p<0.0001), white blood cells (p=0.0022), hematocrit (p<0.0001), blood urea nitrogen (p=0.01), blood sodium (p=0.0002), potassium (p=0.0483), C-reactive protein (p=0.0002), and Lactate Dehydrogenase (p<0.0001). CRP showed a high positive connection (0.5433; p=0.0006) with COVID-19 severity, but LDH showed a mild positive correlation (0.2484; p<0.0001). When comparing asymptomatic/mild COVID-19 to severe COVID-19, discriminative accuracy for CRP and LDH was greatest (AUC:0.8867, 95% CI:0.7532-1.000) and (AUC:1.000, 95% CI:1.000-1.000), respectively. Inflammatory biomarkers, hematological and biochemical indices have the potential to complement SARS-CoV-2 testing and predict the course of COVID-19. This will be useful in designing appropriate care for COVID-19 patients through targeted therapy.

Background: Autoimmune diseases (ADs) have serious impacts on the quality of life of patients and for which with no ideal treatment. The plasma proteome represents a major source of druggable targets. We aimed to identify plasma proteins as potential therapeutic targets for ADs. Methods: We performed two-sample Mendelian Randomization (MR) to explore the causal relationship between 4,907 plasma proteins (N=35,559) and six ADs (N ranged from 23,210 to 173,981) and further validated using another independent plasma proteomic dataset (N=10,708). Five methods were used to evaluate the causal effects, including inverse variance weighted, MR egger, weighted median, simple mode and weighted mode. Sensitivity analysis and reverse MR analysis were conducted to evaluate the robustness of MR results and druggability analysis was used to identify potential drug targets. Results: A total of 24 plasma proteins associated with ADs were identified in the discovery dataset, of which 11 were successfully validated in replication sample. The genetically predicted ARC1B, FcRIIIa, MAPK2 and Collagen II were associated with type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease and celiac disease, respectively. The genetically predicted TBPL1 and DEFI6 were associated with systemic lupus erythematosus. IL-2 sRa, MICB, FTMT, FCAMR and SLAF1 were associated with multiple sclerosis. No reverse causation existed. The druggability analysis showed that IL-2 sRa has become an approved drug target and FcRIIIa and MAPK2 are in clinical trials. Conclusions: The identified proteins might be promising drug targets for ADs and warrant further mechanistic studies.

The selective adsorption of DMSO vapor on calixarene scaffold from a mixture consisting of either DMSO and water or DMSO and methanol was studied. Two calixarene-type scaffolds based on 4-chlorobenzaldehyde were obtained by reacting the aldehyde with either resorcinol or pyrogallol and characterized by various techniques including NMR, FTIR, thermal, and XRD. These materials were then used as sorbent materials for separating vapors. Results from this investigation indicate the scaffolds show selectivity towards DMSO. The resorcinol-based scaffold showed a higher selectivity for DMSO compared to the pyrogallol counterpart. The influence of synthesis solvent on the conformation and structural changes resulting from the interaction of the guest molecules with the host was also investigated.

Introduction. Psychotic disorders are associated with academic difficulties. Supported Employment Program (SEP) guidelines have become the gold standard to improve occupational functioning in psychotic disorders. More recently, these guidelines have been adapted to education. In Canada, several community organizations and hospital programs offer supported education to young people with psychotic disorders. However, SEP guidelines are not systematically used. The objective of this study was to assess the fidelity of 6 Canadian (Quebec) organizations offering supported education services to young people with psychotic disorders to the SEP guidelines adapted to education. Methods. Six sites offering educational services to young people with psychotic disorders were recruited. Semi-structured interviews were conducted with one supported education professional and one manager of each site, using the Quality of Supported Education Implementation Scale (QSEDIS). This new scale has been developed from the Quality of Supported Employment Implementation Scale. The QSEDIS assesses the fidelity of the quality of the implementation of supported education programs, using three subscales (Employees, Organization and Services). Results. Acceptable fidelity scores were observed in the three QSEDIS subscales for all six sites combined. The Services subscale received the highest score of fidelity (4.4./5), followed by the Supported Education Employee (4.1/5) and the Organization (3.7/5). Conclusion. The results suggest that supported education services offered to young people with psychotic disorders in the six sites are generally consistent with SEP guidelines adapted to education. Further research is warranted to validate whether acceptable SEP guidelines fidelity according to the QSEDIS translates into educational outcomes.

Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response particularly precedes microvascular alteration, considered the primary factor of diabetic retinopathy. Actived microglia express many pro-inflammatory cytokines exacerbates retina inflammation and disruption. In the present study, we investigated that MSCs alleviated blood–retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSCs-treated retinal microglia in the diabetic rats exhibited reduced expression of M1-phenotype markers, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. Meanwhile, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSCs treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Knocking down HMGB1 or TLR4 in microglia had comparable effects as with MSCs treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs’ regulatory effects on microglia polarization. Collectively, MSCs exert a beneficial effect on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway.

Organic difluoroboron complexes is a kind of potential platforms for a wide range of applications owing to their excellent photo-physical properties. Herein, we have explored a simple and direct synthesis methodologies for a library of N,O-Bidentate difluoroboron complexes from quinoxalin-2(1H)-ones and ketones in one shot. The photophysical properties of the generated com-plexes were evaluated and the application potential of these compound on subcellular was also explored.

The experiment was conducted to find out the effect of different preservative solutions to extend the vase life of blue water lily (Nymphaea stellata). Experimentation was arranged in a complete randomized design (CRD) with eight treatments along with distilled water used as the control treatment and each treatments replicated thrice. A preliminary trial was conducted to find out the best chemical solution/s and experiment 2, best concentrations using Al2 (SO3)4 200ppm, Clorox 0.5%, and Sugar 2.0% under laboratory conditions (23 ⁰C) with continuous light intensity of two florescent bulbs. The best concentration/s selected in the preliminary trail was used for next experiment. Non-parametric data, such as wilting of petals and sepal, sepal color, petiole rigidity, petiole color, were recorded based on the visual observations and the data were analyzed using statistical analysis system (SAS). Results reveled, cut flowers treated with combination treatment under laboratory condition, Al2(SO3)4 200ppm and Clorox 0.5% + sugar 2.0% of distilled water at 23⁰C were the best solutions to lengthen the vase life of blue water lily flowers up to seven days from harvest.

A disposable monolithic column mass spectrometry kit was developed based on monolithic column for microsampling, purification, storage, transportation and direct MS analysis of whole blood. The kit mainly consists of a capillary for quantitative microsampling of very small amount of blood (2 μL), a cation exchange monolithic column for purification and storage, and a syringe for loading sample. The cost of the kit is estimated to only one dollar. This MS kit is very friendly to various users that one can easily siphon small amount blood in the kit followed by rapid sample clean-up in 30s. We established a rapid quantitative method using the kit with a limit detection as low as 0.33 nM, achieved more than five orders of magnitude enhancement in MS analysis sensitivity compared to nanoelectrospray ionization MS analysis. The kit can avoid analyte exposure to oxygen, moisture and sunlight, which helps the storage of the sample. The relative standard deviation within 10 days were less than 10%. This method has been successfully applied to the quantitative analysis of procainamide hydrochloride in 2 μL rat blood. These results indicate that this kit does have the potential to achieve low-cost, highly sensitive quantitative MS analysis of biological sample.

Large wind turbines experience amplified asymmetrical loads at particular harmonics of the rotational frequency. Individual pitch control (IPC) has emerged as a potential controls solution to this problem. H ∞ control, which facilitates robust, multivariable controller synthesis in the frequency domain, is a candidate approach to IPC design for several reasons. Firstly, the objectives of asymmetrical load attenuation are best described in the frequency domain. Secondly, the IPC control signals and loads in orthogonal directions are coupled, which necessitates a multivariable controller approach. Thirdly, H ∞ synthesis is a method that can explicitly impose constraints on the robustness of the closed-loop system. A downside of IPC is the significant increase in blade-pitch travel incurred, which introduces additional loading on the blade-pitch bearings over time. We investigate strategies to constrain the blade-pitch travel in the controller tuning procedure. A comprehensive study is thus presented for a range of H ∞ -synthesized IPCs to attenuate asymmetrical loads on large rotors at harmonics of the rotational frequency while mitigating blade-pitch travel. All developed controllers are validated and compared using a 25 MW fixed-bottom offshore wind turbine model via linear analysis of the robustness of the closed-loop system to input and output disturbances and nonlinear analysis via the study of structural load power spectra, damage-equivalent loads (DEL), and the actuator duty cycle (ADC) of the blade-pitch actuator.

Low level jets (LLJs) describe conditions in which the wind speed reaches a local maximum with respect to altitude near the surface, and have been observed intermittently in the US Mid-Atlantic offshore environment. LLJs pose unique operating conditions for future wind turbines operating in the region, presenting negative shear and locally strong veer, but they are not typically considered in existing turbine standards. This work builds upon recent research that explains the formation and evolution of U.S. Mid-Atlantic LLJs through a simple analytical governing equation. We generate several LLJ inflow conditions with varying jet characteristics based on this analytical model and create monotonically-sheared (MS) analogues with constant veer in order to assess the impacts of the LLJ on turbine performance and loading. Using aeroelastic simulations with these inflow conditions on the IEA 15MW reference turbine, we find that the LLJ leads to a greater range of tower top pitching and yawing moments, which could contribute to larger accumulated structural fatigue in components compared to monotonically-sheared inflow. These preliminary results demonstrate a path toward a unified set of test cases for low-level wind maxima that can inform International Electrotechnical Commission standards related to offshore wind turbine design.

Primulina guarouba, a new species from the limestone area of northern Guangxi, China, is described and illustrated. According to the maximum likelihood (ML) and Bayesian inference (BI) analysis, it nests in a strongly supported clade (BP = 99%) that includes P. cordifolia, P. repanda and P. huangii. Of these, P. guarouba is similar to the P. cordifolia in morphology, but it is easily distinguished from the latter by some of the distinct characters in leaf blade, peduncles, bracts, calyx, corolla, pistil.

Stability against oxygen is an important factor affecting the performance of organic semiconductor devices. Improving photooxidation stability can prolong the service life of the device and maintain the mechanical and photoelectric properties of the device. Generally, various encapsulation methods from molecular structure to macroscopic device level are used to improve photooxidation stability. Here, we adopted a crystallization strategy to allow 14H-spiro[dibenzo[c,h]a-cridine-7,9′-uorene] (SFDBA) to pack tightly to resist fluo-rescence decay caused by oxidation. In this case, the inert group of SFDBA acts as a “steric armor”, protecting the photosensitive group from being attacked by oxygen. Therefore, compared with the fluorescence quenching of SFDBA powder under two hours of sunlight, SFDBA crystal can maintain its fluorescence emission for more than eight hours under the same conditions. Furthermore, the photolu-minescence quantum yields (PLQYs) of the crystalline film is 327.37 % higher than that of the amorphous film. It shows that the crystal-lization strategy is an effective method to resist oxidation.

The SARS-CoV-2 immune response is crucial for disease management, although diminishing immunity raises the possibility of reinfection. In matched samples collected at one month and six to eight months after infection, we examined the immunological response to SARS-CoV-2 in a group of convalescent critically ill COVID-19 patients. The PBMCs were isolated from enrolled study participants and flow cytometry analysis was done to assess the lymphocyte subsets of naive, effector, central memory, and effector memory CD4+ or CD8+ T cells in COVID-19 patients at one month and six to eight months after infection. Immunophenotypic characterization of immune cell subsets was performed on individuals who were followed longitudinally for one month (n=44) and up to 6-8 months (n=25) after recovery from COVID infection. We observed that CD4+ T cells in hospitalized SARS-CoV-2 patients tended to decrease, whereas CD8+ T cells steadily recovered after one month, while there was a sustained increase in the population of effector T cells and effector memory T cells. Furthermore, COVID-19 patients showed persistently low B cells and a small increase in the NK cell population. In conclusion, our findings show that T cell responses were maintained at 6-8 months after infection. This opens new pathways for further research into the long-term effects in COVID-19 immunopathogenesis.