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1.
Cell Signal ; : 111227, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744388

RESUMO

PURPOSE: Pancreatic cancer (PC) is a common tumor of the digestive tract with an insidious onset and high malignancy potential. Currently, surgery is the only effective treatment modality. Therefore, it is crucial to discover new targeted therapeutic modalities. We studied whether transgelin 2 (TAGLN2) targeted control of actin-related protein 2/3 complex subunit 5 (ARPC5)-mediated activation of the MEK/ERK signaling pathway to Influences the proliferation, invasion, and metastasis of pancreatic cancer cells. METHODS: The effects of TAGLN2 overexpression and knockdown on the proliferative viability and invasive metastatic ability of pancreatic cancer cells were verified through in vitro and in vivo assays via constructing a stable lentiviral transfection of human pancreatic cancer cell lines PANC-1 and SW1990. Bioinformatics analysis was used to predict the relationship between TAGLN2 and ARPC5. These findings were subsequently verified through protein profiling, immunofluorescence (IF), and coimmunoprecipitation (CO-IP) assays. In vitro experiments were also conducted to confirm the effect of TAGLN2 modulation on ARPC5 expression, which subsequently affects the proliferation and invasive metastatic ability of pancreatic cancer cells. The study analyzed the relationship between TAGLN2 and the MEK/ERK signaling pathway through bioinformatics and in vitro experiments with the MEK signaling pathway inhibitor U0126. RESULTS: TAGLN2 is expressed at high levels in pancreatic cancer cell lines, and its expression is positively correlated with poor prognosis of pancreatic cancer. ARPC5 is a direct target of TAGLN2 and is associated with the MEK/ERK signaling pathway. In vivo and ex vivo experiments confirmed that overexpression of TAGLN2 promoted the proliferation, invasion, and metastasis of pancreatic cancer cells, and silencing ARPC5 reversed these effect. CONCLUSION: Our research revealed that TAGLN2 protein binds to ARPC5 protein and contributes to increased ARPC5 expression and activation of the MEK/ERK signaling pathway. This activation promotes pancreatic cancer cell growth, infiltration, and spread. Hence, TAGLN2 is a potential viable therapeutic target in pancreatic cancer and represents a novel therapeutic approach.

2.
Biomater Sci ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747322

RESUMO

Considering the shortcomings of known medical hemostatic materials such as bone wax for bleeding bone management, it is essential to develop alternative bone materials capable of efficient hemostasis and bone regeneration and adaptable to clinical surgical needs. Thus, in the current work, a calcium sulfate hemihydrate and starch-based composite paste was developed and optimized. Firstly, it was found that the use of hydroxypropyl distarch phosphate (HDP) coupled with pregelatinization could generate an injectable, malleable and self-hardening paste with impressive anti-collapse ability in a dynamic aqueous environment, suggesting its potential applicability in both open and minimally invasive clinical practice. The as-hardened matrix exhibited a compressive strength of up to 61.68 ± 5.13 MPa compared to calcium sulfate cement with a compressive strength of 15.16 ± 2.42 MPa, making it a promising candidate for the temporary mechanical stabilization of bone defects. Secondly, the as-prepared paste revealed superior hemostasis and bone regenerative capabilities compared to calcium sulfate cement and bone wax, with greatly enhanced bleeding management and bone healing outcomes when subjected to testing in in vitro and in vivo models. In summary, our results confirmed that calcium sulfate bone cement reinforced with the selected starch can act as a reliable platform for bleeding bone treatment, overcoming the limitations of traditional bone hemostatic agents.

3.
Alzheimers Dement ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747519

RESUMO

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

4.
Front Plant Sci ; 15: 1387575, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736453

RESUMO

Plants have evolved interconnected regulatory pathways which enable them to respond and adapt to their environments. In plants, stress memory enhances stress tolerance through the molecular retention of prior stressful experiences, fostering rapid and robust responses to subsequent challenges. Mounting evidence suggests a close link between the formation of stress memories and effective future stress responses. However, the mechanism by which environmental stressors trigger stress memory formation is poorly understood. Here, we review the current state of knowledge regarding the RNA-based regulation on stress memory formation in plants and discuss research challenges and future directions. Specifically, we focus on the involvement of microRNAs (miRNAs), small interfering RNAs (siRNAs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) in stress memory formation. miRNAs regulate target genes via post-transcriptional silencing, while siRNAs trigger stress memory formation through RNA-directed DNA methylation (RdDM). lncRNAs guide protein complexes for epigenetic regulation, and AS of pre-mRNAs is crucial to plant stress memory. Unraveling the mechanisms underpinning RNA-mediated stress memory formation not only advances our knowledge of plant biology but also aids in the development of improved stress tolerance in crops, enhancing crop performance and global food security.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38728178

RESUMO

A Gram-negative, facultative anaerobic, non-motile and rod-shaped bacterium, designated 10c7w1T, was isolated from a human gastrointestinal tract. Colonies on agar plates were small, circular, smooth and beige. The optimal growth conditions were determined to be 37 °C, pH 7.0-7.5 and 0 % (w/v) NaCl. Comparative analysis of complete 16S rRNA gene sequences revealed that strain 10c7w1T showed the highest sequence similarity of 95.8 % to Ottowia beijingensis MCCC 1A01410T, followed by Ottowia thiooxydans (95.2 %) JCM 11629T. The average amino acid identity values between 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were above 60 % (71.4 and 69.5 %). The average nucleotide identity values between strain 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were 76.9 and 72.5 %, respectively. The dominant fatty acids (≥10 %) were straight chain ones, with summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C16 : 00 being the most abundant. Q-8 was the only respiratory quinone. The major polar lipids of strain 10c7w1T were phosphatidylethanolamine, diphosphatidylglycerol and unknown lipids. The DNA G+C content of strain 10c7w1T was 63.6 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic data, strain 10c7w1T is considered to represent a novel species within the genus Ottowia, for which the name Ottowia cancrivicina sp. nov. is proposed. The type strain is 10c7w1T (=MCCC 1H01399T=KCTC 92200T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Estômago , RNA Ribossômico 16S/genética , Ácidos Graxos/química , Humanos , DNA Bacteriano/genética , Estômago/microbiologia , Hibridização de Ácido Nucleico , Ubiquinona , Fosfolipídeos/química
6.
Artigo em Inglês | MEDLINE | ID: mdl-38728664

RESUMO

Organic solar cells (OSCs) could benefit from the ternary bulk heterojunction (BHJ), a method that allows for fine-tuning of light capture, cascade energy levels, and film shape, in order to increase their power conversion efficiency (PCE). In this work, the third components of PM6:Y6 and PM6:BTP-eC9 BHJs are a set of four star-shaped unfused ring electron acceptors (SSUFREAs), i.e., BD-IC, BFD-IC, BD-2FIC, and BFD-2FIC, that are facilely synthesized by direct C-H arylation. The four SSUFREAs all show complete complementary absorption with PM6, Y6, and BTP-eC9, which facilitates light harvesting and exciton collection. When BFD-2FIC is added as a third component, the PCEs of PM6:Y6 and PM6:BTP-eC9 binary BHJs are able to be improved from 15.31% to 16.85%, and from 16.23% to 17.23%, respectively, showing that BFD-2FIC is useful for most effective ternary OSCs in general, and increasing short circuit current (JSC) and better film morphology are two additional benefits. The ternary PM6:Y6:BFD-2FIC exhibits a 9.7% percentage of increase in PCE compared to the PM6:Y6 binary BHJ, which is one of the highest percentage increases among the reported ternary BHJs, showing the huge potential of BFD-2FIC for ternary BHJ OSCs.

7.
Phys Med Biol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729205

RESUMO

OBJECTIVE: Electron paramagnetic resonance (EPR) imaging is an advanced in vivo oxygen imaging modality. The main drawback of EPR imaging is the long scanning time. Sparse-view projections collection is an effective fast scanning pattern. However, the commonly-used filtered backprojection (FBP) algorithm is not competent to accurately reconstruct images from sparse-view projections because of the severe streak artifacts. The aim of this work is to develop an advanced algorithm for sparse reconstruction of 3D EPR imaging. METHODS: The optimization based algorithms including the total variation (TV) algorithm have proven to be effective in sparse reconstruction in EPR imaging. To further improve the reconstruction accuracy, we propose the directional TV (DTV) model and derive its Chambolle-Pock (CP) solving algorithm. RESULTS: After the algorithm correctness validation on simulation data, we explore the sparse reconstruction capability of the DTV algorithm via a simulated six-sphere phantom and two real bottle phantoms filled with OX063 trityl solution and scanned by an EPR imager with a magnetic field strength of 250G. CONCLUSION: Both the simulated and real data experiments show that the DTV algorithm is superior to the existing FBP and TV-type algorithms and a deep learning based method according to visual inspection and quantitative evaluations in sparse reconstruction of EPR imaging. SIGNIFICANCE: These insights gained in this work may be used in the development of fast EPR imaging workflow of practical significance.

8.
Br J Radiol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730550

RESUMO

OBJECTIVES: To evaluate the performance of machine learning models in predicting treatment response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer using computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for studies published before January 2023. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to assess the methodological quality of the included studies, random-effects models were used to calculate sensitivity and specificity, I2 values were used for heterogeneity measurements, and subgroup analyses were carried out to detect potential sources of heterogeneity. RESULTS: A total of 1690 patients from 24 studies were included. The meta-analysis calculated a pooled area under the curve (AUC) of 0.92 (95%CI-0.89-0.94), pooled sensitivity of 0.81 (95%CI-0.73-0.88), and pooled specificity of 0.88 (95%CI-0.82-0.92). We investigated 4 studies that mainly contributed to heterogeneity. After performing meta-analysis again excluding these 4 studies, the heterogeneity was significantly reduced. In subgroup analysis, the pooled AUC of the deep learning model was 0.95 and was 0.88 for the traditional statistical model; the pooled AUC of studies that used diffusion-weighted imaging (DWI) was 0.90, and was 0.92 in studies that did not use DWI; the pooled AUC of studies conducted in China was 0.94, and was 0.83 in studies conducted in other countries. CONCLUSIONS: Machine learning has promising potential in predicting tumor response to nCRT in patients with locally advanced rectal cancer. Together with clinical information, machine-learning based models may bring us closer toward precision medicine. ADVANCES IN KNOWLEDGE: Compared to traditional machine learning models, deep learning-based studies are able to obtain higher AUC, although they are less predominant and more heterogeneous. Together with clinical information, machine-learning based models may bring us closer toward precision medicine.

9.
Cancer Lett ; : 216951, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734159

RESUMO

Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK+ effector memory T cells were relatively enriched and CXCL13+ exhausted T cells and regulator T cells decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B+ memory B cells suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK+ Tem and TNFRSF13B+ Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.

10.
ACS Appl Mater Interfaces ; 16(19): 25498-25510, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701230

RESUMO

Clean, energy-free methods of cooling are an effective way to respond to the global energy crisis. To date, cooling materials using passive daytime radiative cooling (RC) technology have been applied in the fields of energy-efficient buildings, solar photovoltaic cooling, and insulating textiles. However, RC materials frequently suffer from comprehensive damage to their microstructure, resulting in the loss of their initial cooling effect in complex outdoor environments. Here, a superhydrophobic daytime passive RC porous film with environmental tolerance (SRCP film) was fabricated, which integrated strong solar reflectivity (approximately 90%), mid-infrared emissivity (approximately 0.97), and superhydrophobicity (water contact angle (WCA) of 160° and sliding angle of 3°). This study revealed that SRCP film had an average reflectivity of 14.3% higher than SiO2 particles in the 0.3-2.5 µm wavelength region, achieving a cooling effect of 13.2 °C in ambient conditions with a solar irradiance of 946 W·m-2 and a relative humidity of 74% due to the synergistic effect of effective solar reflection and thermal infrared emission. In addition, empirical results showed that the attained films possessed outstanding environmental tolerance, maintaining high WCA (156°), stable cooling effect (8.3 °C), and low SiO2 loss (less than 5.1%) after 30 consecutive days of UV irradiation and 14 days of corrosion with acidic and alkaline solutions. More importantly, this work could be flexibly prepared by various methods without the use of any fluorine-containing reagents, which greatly widens the practical application scope.

11.
Int J Biol Macromol ; 269(Pt 2): 132167, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729479

RESUMO

The Japanese puffer, Takifugu rubripes, is a commercially important fish species in China that is under serious threat from white spot disease (cyptocaryoniasis), which leads to heavy economic losses. We previously found that interleukin-1ß (IL-1ß), an important cytokine with a potential role in resistance against pathogens, was one of the most significantly differentially up-regulated proteins in the gills and spleen of T. rubripes infected by the protozoan parasite Cryptocaryon irritans. In this study, we assessed the potential function of T. rubripes IL-1ß (TrIL-1ß) in fish infected with C. irritans. Phylogenetic analysis indicated that the TrIL-1ß protein sequence was most closely related to that of Atlantic salmon (Salmo salar) (67.2 %). The incubation experiments revealed that TrIL-1ß may reduce trophont activity by destroying membranes. Immunofluorescence experiments showed that recombinant TrIL-1ß promoted the expression of endogenous IL-1ß, which penetrated and disrupted the cell membranes of trophonts. Transmission electron microscopy showed that the IL-1ß group had less tissue damage compared with control groups of fish. IL-1ß-small interfering RNA and IL-1ß overexpression experiments were performed in head kidney primary cells, and challenge experiments were performed in vitro. Quantitative RT-PCR results showed that TrIL-1ß regulated and activated MyD88/NF-κB and MyD88/MAPK/p38 signaling pathways during C. irritans infection. TrIL-1ß also promoted the differential expression of IgM, showing that it was involved in humoral immunity of T. rubripes. The cumulative mortality experiment show that TrIL-1ß could protect fish against C. irritans infection. These results enrich current knowledge about the molecular structure of TrIL-1ß. They also suggested that recombinant TrIL-1ß could be used as an adjuvant in a subunit vaccine against C. irritans infection, which is of profound importance for the prevention and control of parasitic diseases in T. rubripes.

12.
Environ Sci Technol ; 58(19): 8182-8193, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38691136

RESUMO

As an alternative plasticizer to conventional phthalates, di(2-ethylhexyl) terephthalate (DEHTP) has attracted considerable concerns, given its widespread detection in the environment and humans. However, the potential toxicity, especially liver toxicity, posed by DEHTP remains unclear. In this study, based on the 2017-2018 National Health and Nutrition Examination Survey, two metabolites of DEHTP, i.e., mono(2-ethyl-5-hydroxyhexyl) terephthalate (MEHHTP) and mono(2-ethyl-5-carboxypentyl) terephthalate (MECPTP), were found to be present in the urine samples of nearly all representative U.S. adults. Moreover, a positive linear correlation was observed between the concentrations of the two metabolites and the risk of nonalcoholic fatty liver disease (NAFLD) in the population. Results of weighted quantile sum and Bayesian kernel machine regression indicated that MEHHTP contributed a greater weight to the risk of NAFLD in comparison with 12 conventional phthalate metabolites. In vitro experiments with hepatocyte HepG2 revealed that MEHHTP exposure could increase lipogenic gene programs, thereby promoting a dose-dependent hepatic lipid accumulation. Activation of liver X receptor α may be an important regulator of MEHHTP-induced hepatic lipid disorders. These findings provide new insights into the liver lipid metabolism toxicity potential of DEHTP exposure in the population.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Ácidos Ftálicos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Humanos , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Masculino , Adulto , Feminino
14.
Adv Healthc Mater ; : e2400623, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691766

RESUMO

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.

15.
World J Diabetes ; 15(5): 1011-1020, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38766432

RESUMO

BACKGROUND: Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM: To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS: The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION: This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

16.
Pulm Circ ; 14(2): e12370, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38774814

RESUMO

To explore the genetic causal association between pulmonary artery hypertension (PAH) and iron status through Mendelian randomization (MR), we conducted MR analysis using publicly available genome-wide association study (GWAS) summary data. Five indicators related to iron status (serum iron, ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (sTfR), and transferrin saturation) served as exposures, while PAH was the outcome. The genetic causal association between these iron status indicators and PAH was assessed using the inverse variance weighted (IVW) method. Cochran's Q statistic was employed to evaluate heterogeneity. We assessed pleiotropy using MR-Egger regression and MR-Presso test. Additionally, we validated our results using the Weighted median, Simple mode, and Weighted mode methods. Based on the IVW method, we found no causal association between iron status (serum iron, ferritin, TIBC, sTfR, and transferrin saturation) and PAH (p ß > 0.05). The Weighted median, Simple mode, and Weighted mode methods showed no potential genetic causal association (p ß > 0.05 in the three analyses). Additionally, no heterogeneity or horizontal pleiotropy was detected in any of the analyses. Our results show that there are no genetic causal association between iron status and PAH.

17.
J Am Chem Soc ; 146(20): 13733-13740, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38723265

RESUMO

A highly enantioselective formal hydroformylation of vinyl arenes enabled by copper hydride (CuH) catalysis is reported. Key to the success of the method was the use of the mild Lewis acid zinc triflate to promote the formation of oxocarbenium electrophiles through the activation of diethoxymethyl acetate. Using the newly developed protocol, a broad range of vinyl arene substrates underwent efficient hydroacetalization reactions to provide access to highly enantioenriched α-aryl acetal products in good yields with exclusively branched regioselectivity. The acetal products could be converted to the corresponding aldehydes, alcohols, and amines with full preservation of the enantiomeric purity. Density functional theory studies support that the key C-C bond-forming event between the alkyl copper intermediate and the oxocarbenium electrophile takes place with inversion of configuration of the Cu-C bond in a backside SE2-type mechanism.

18.
Luminescence ; 39(5): e4773, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38757733

RESUMO

Two Schiff base probes (S1 and S2) were prepared and synthesized by incorporating thienopyrimidine into salicylaldehyde or 3-ethoxysalicylaldehyde individually, with the aim of detecting Ga3+ and Pd2+ sequentially. Upon chelation with Ga3+, S1 and S2 exhibited fluorescence enhancement in DMSO/H2O buffer. Both S1-Ga3+ and S2-Ga3+ were quenched by Pd2+. The limit of detection for S1 in response to Ga3+ and Pd2+ was 2.86 × 10-7 and 4.4 × 10-9 M, respectively. For S2, the limit of detection for Ga3+ and Pd2+ was 4.15 × 10-8 and 3.0 × 10-9 M, respectively. Furthermore, the complexation ratios of both S1 and S2 with Ga3+ and Pd2+ were determined to be 1:2 through Job's plots, ESI-MS analysis, and theoretical calculations. Two molecular logic gates were constructed, leveraging the response behaviors of S1 and S2. Moreover, the potential utility of S1 and S2 for monitoring Ga3+ and Pd2+ in domestic water was verified.


Assuntos
Corantes Fluorescentes , Gálio , Paládio , Pirimidinas , Bases de Schiff , Bases de Schiff/química , Paládio/química , Pirimidinas/química , Pirimidinas/análise , Gálio/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Espectrometria de Fluorescência , Estrutura Molecular
19.
Nature ; 629(8010): 98-104, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693411

RESUMO

Photobiocatalysis-where light is used to expand the reactivity of an enzyme-has recently emerged as a powerful strategy to develop chemistries that are new to nature. These systems have shown potential in asymmetric radical reactions that have long eluded small-molecule catalysts1. So far, unnatural photobiocatalytic reactions are limited to overall reductive and redox-neutral processes2-9. Here we report photobiocatalytic asymmetric sp3-sp3 oxidative cross-coupling between organoboron reagents and amino acids. This reaction requires the cooperative use of engineered pyridoxal biocatalysts, photoredox catalysts and an oxidizing agent. We repurpose a family of pyridoxal-5'-phosphate-dependent enzymes, threonine aldolases10-12, for the α-C-H functionalization of glycine and α-branched amino acid substrates by a radical mechanism, giving rise to a range of α-tri- and tetrasubstituted non-canonical amino acids 13-15 possessing up to two contiguous stereocentres. Directed evolution of pyridoxal radical enzymes allowed primary and secondary radical precursors, including benzyl, allyl and alkylboron reagents, to be coupled in an enantio- and diastereocontrolled fashion. Cooperative photoredox-pyridoxal biocatalysis provides a platform for sp3-sp3 oxidative coupling16, permitting the stereoselective, intermolecular free-radical transformations that are unknown to chemistry or biology.


Assuntos
Aminoácidos , Biocatálise , Acoplamento Oxidativo , Processos Fotoquímicos , Aminoácidos/biossíntese , Aminoácidos/química , Aminoácidos/metabolismo , Biocatálise/efeitos da radiação , Evolução Molecular Direcionada , Radicais Livres/química , Radicais Livres/metabolismo , Glicina/química , Glicina/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Glicina Hidroximetiltransferase/química , Indicadores e Reagentes , Luz , Acoplamento Oxidativo/efeitos da radiação , Fosfato de Piridoxal/metabolismo , Estereoisomerismo , Aminoácidos de Cadeia Ramificada/química , Aminoácidos de Cadeia Ramificada/metabolismo
20.
J Int Med Res ; 52(5): 3000605241247696, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698505

RESUMO

OBJECTIVE: To compare an Extreme Gradient Boosting (XGboost) model with a multivariable logistic regression (LR) model for their ability to predict sepsis after extremely severe burns. METHODS: For this observational study, patient demographic and clinical information were collected from medical records. The two models were evaluated using area under curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: Of the 103 eligible patients with extremely severe burns, 20 (19%) were in the sepsis group, and 83 (81%) in the non-sepsis group. The LR model showed that age, admission time, body index (BI), fibrinogen, and neutrophil to lymphocyte ratio (NLR) were risk factors for sepsis. Comparing AUC of the ROC curves, the XGboost model had a higher predictive performance (0.91) than the LR model (0.88). The SHAP visualization tool indicated fibrinogen, NLR, BI, and age were important features of sepsis in patients with extremely severe burns. CONCLUSIONS: The XGboost model was superior to the LR model in predictive efficacy. Results suggest that, fibrinogen, NLR, BI, and age were correlated with sepsis after extremely severe burns.


Assuntos
Queimaduras , Curva ROC , Sepse , Humanos , Sepse/etiologia , Sepse/sangue , Sepse/complicações , Sepse/diagnóstico , Masculino , Feminino , Queimaduras/complicações , Modelos Logísticos , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Neutrófilos/imunologia , Fibrinogênio/metabolismo , Fibrinogênio/análise , Prognóstico , Estudos Retrospectivos , Área Sob a Curva , Idoso
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