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1.
J Clin Oncol ; : JCO2301889, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564700

RESUMO

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

2.
World J Gastroenterol ; 30(9): 1189-1212, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577195

RESUMO

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.


Assuntos
Glucuronosiltransferase , Fígado , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Fígado/metabolismo
3.
J Chem Phys ; 160(16)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38647303

RESUMO

An exciton-phonon (ex-ph) model based on our recently developed block interaction product basis framework is introduced to simulate the distal charge separation (CS) process in aggregated perylenediimide (PDI) trimer incorporating the quantum dynamic method, i.e., the time-dependent density matrix renormalization group. The electronic Hamiltonian in the ex-ph model is represented by nine constructed diabatic states, which include three local excited (LE) states and six charge transfer (CT) states from both the neighboring and distal chromophores. These diabatic states are automatically generated from the direct products of the leading localized neutral or ionic states of each chromophore's reduced density matrix, which are obtained from ab initio quantum chemical calculation of the subsystem consisting of the targeted chromophore and its nearest neighbors, thus considering the interaction of the adjacent environment. In order to quantum-dynamically simulate the distal CS process with massive coupled vibrational modes in molecular aggregates, we used our recently proposed hierarchical mapping approach to renormalize these modes and truncate those vibrational modes that are not effectively coupled with electronic states accordingly. The simulation result demonstrates that the formation of the distal CS process undergoes an intermediate state of adjacent CT, i.e., starts from the LE states, passes through an adjacent CT state to generate the intermediates (∼200 fs), and then formalizes the targeted distal CS via further charge transference (∼1 ps). This finding agrees well with the results observed in the experiment, indicating that our scheme is capable of quantitatively investigating the CS process in a realistic aggregated PDI trimer and can also be potentially applied to exploring CS and other photoinduced processes in larger systems.

4.
Angew Chem Int Ed Engl ; 63(18): e202401050, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38444397

RESUMO

Geminal bis(boronates) are versatile synthetic building blocks in organic chemistry. The fact that they predominantly serve as nucleophiles in the previous reports, however, has restrained their synthetic potential. Herein we disclose the ambiphilic reactivity of α-halogenated geminal bis(boronates), of which the first catalytic utilization was accomplished by merging a formal Heck cross-coupling with a highly diastereoselective allylboration of aldehydes or imines, providing a new avenue for rapid assembly of polyfunctionalized boron-containing compounds. We demonstrated that this cascade reaction is highly efficient and compatible with various functional groups, and a wide range of heterocycles. In contrast to a classical Pd(0/II) scenario, mechanistic experiments and DFT calculations have provided strong evidence for a catalytic cycle involving Pd(I)/diboryl carbon radical intermediates.

5.
J Phys Chem Lett ; 15(13): 3523-3530, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38522085

RESUMO

Singlet fission (SF) is a process where a singlet state splits into two triplet states, which is essential for enhancing optoelectronic devices. Macrocyclic structures allow for precise control of chromophore orientation and facilitate singlet fission in solutions. However, the behavior of these structures in thin films, crucial for solid-state device optimization, remains underexplored. This study examines the aggregation and singlet fission processes of bipentacene macrocycles (BPc) in thin films using molecular dynamics simulations and electronic structure calculations. Findings indicate that BPc aggregates more rapidly with less chloroform, aligning parallel to the substrate. Intramolecular singlet fission (iSF) rates are rarely changed during evaporation, but the efficiency of intermolecular singlet fission (xSF) improves due to the increase in packing domains, suggesting that orderly crystal domains are not necessary for device efficiency. This opens avenues for varied device designs and traditional solution-based methods for optimal device development.

6.
Theriogenology ; 219: 75-85, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38402700

RESUMO

Endometritis is a disease caused by a postpartum bacterial infection with a poor prognosis that primarily affects dairy cows. Three-dimensional organoids have been used as a model for endometritis, because they exhibit a structure comparable to that of the endometrium, demonstrating both expansibility and hormone responsiveness. These characteristics render them an ideal platform for in vitro investigations of endometrial diseases. Estradiol (E2) is an endogenous steroid hormone with demonstrated anti-inflammatory properties, and the objective of this study was to determine the mechanism by which E2 modulates the inflammatory response and the Wnt signal transduction pathway in bovine endometrial epithelial cells and organoids following E. coli infection. We present the techniques for isolating and culturing primary bovine endometrial epithelial cells (BEECs), and producing endometrial organoids. For the experiments, the endometrial epithelial cells and organoids were infected with E. coli for 1 h, followed by incubation with E2 for 12 h. The mRNA and protein expressions of the inflammation-related genes, IL-1ß, IL-6, TLR4, and NF-κB, as well as the Wnt pathway-related genes, Wnt4, ß-catenin, c-Myc, and CyclinD1, were assessed using real-time quantitative-PCR and western blotting, respectively. The CCK8 viable cell counting assay was utilized to determine the optimal concentration of the Wnt inhibitor, IWR-1. The mRNA and protein expression of Wnt pathway-related genes was assessed following IWR-1 treatment, while the expression levels of proliferation-associated genes (Ki67, PCNA) and barrier repair genes (occludin, claudin, and Zo-1) in BEECs and organoids were evaluated after E2 treatment. The results of this study show that mRNA expression of the inflammatory genes, IL-1ß, TLR4, and NF-κB (P < 0.05) decreased in BEECs following E2 treatment compared to the E. coli group. The protein expression of the IL-1ß, IL-6, TLR4 and NF-κB genes was also inhibited (P < 0.05). Similar results were observed in tests on the organoids. Our findings demonstrate that E2 significantly upregulates the expression of Wnt-related genes, including ß-catenin and c-Myc, while concurrently downregulating the expression of GSK3ß (P < 0.05). Next, we treated E. coli-infected BEECs and organoids with the Wnt inhibitor, IWR-1. Compared with E. coli and E. coli + E2, the expression of mRNA and protein from Wnt 4, ß-catenin, and CyclinD1 in E. coli + E2 and E. coli + IWR-1 was down-regulated (P < 0.05). The expression of the proliferation genes, Ki67, PCNA, and the tight junction genes, occludin, claudin1, and Zo-1, in organoids was significantly higher than that in BEECs (P < 0.05). In summary, we found strong potential for E2 mitigation of the E. coli-induced inflammatory response in BEECs and organoids, through activation of the Wnt pathway. In addition, the proliferation and repair capacity of organoids was much higher than that of BEECs.


Assuntos
Doenças dos Bovinos , Endometrite , Infecções por Escherichia coli , Feminino , Bovinos , Animais , Endometrite/veterinária , NF-kappa B/metabolismo , Via de Sinalização Wnt , Interleucina-6/metabolismo , Escherichia coli/metabolismo , Estradiol/farmacologia , Estradiol/metabolismo , Receptor 4 Toll-Like/metabolismo , beta Catenina , Antígeno Ki-67/metabolismo , Ocludina/metabolismo , Ocludina/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Endométrio/metabolismo , Células Epiteliais/metabolismo , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/metabolismo , RNA Mensageiro/metabolismo , Doenças dos Bovinos/metabolismo
7.
J Chem Theory Comput ; 20(3): 1252-1262, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38305003

RESUMO

The optical, electronic, and (photo) catalytic properties of covalent organic frameworks (COFs) are largely determined by their electronic structure and, specifically, by their Frontier conduction and valence bands (VBs). In this work, we establish a transparent relationship between the periodic electronic structure of the COFs and the orbital characteristics of their individual molecular building units, a relationship that is challenging to unravel through conventional solid-state calculations. As a demonstration, we applied our method to five COFs with distinct framework topologies. Our approach successfully predicts their first-principles conduction and VBs by expressing them as a linear combination of the Frontier molecular orbitals localized on the COF fragments. We demonstrate that our method allows for the rapid exploration of the impact of chemical modifications on the band structures of COFs, making it highly suitable for further application in the quest to discover new functional materials.

8.
Talanta ; 271: 125674, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38245960

RESUMO

Abnormal levels of dopamine (DA) and uric acid (UA) in the human body are valuable indicators for monitoring human health, as they are associated with certain diseases. Therefore, it is crucial to develop sensitive and simultaneous analytical techniques for DA and UA in diagnosing the related diseases. Herein, the Co- and Mo- doped carbon nanofibers (Co, Mo@CNFs) electrochemical biosensor was developed successfully for the sensitive and accurate simultaneous detection of DA and UA. A straightforward electrospinning technique followed by a carbonization process was employed for the synthesis of Co, Mo@CNFs, and the encapsulation of Co and Mo within CNFs served to not only prevent nanoparticle agglomeration, thus providing more active sites, but also to facilitate rapid electron transfer. By incorporating Co and Mo into CNFs, the electrocatalytic activity of the modified electrode was greatly improved due to the beneficial conductivity and synergistic effects of transition metals. This enhancement effectively addressed issues such as the overlapping anodic peaks that occur when DA and UA are oxidized concurrently. Due to the mentioned synergistic contributions, the modified Co, Mo@CNFs electrode (Co, Mo@CNFs/GCE) achieved remarkable sensitivity for the simultaneous detection of DA and UA, while also exhibiting strong anti-interference ability. The detection limits for DA and UA were 2.35 nmol L-1 and 0.16 µmol L-1, respectively. We applied the developed Co, Mo@CNFs/GCE electrochemical biosensor to detect DA and UA in 50-fold diluted serum and urine samples. The results affirm the biosensor's reliability and precision. Moreover, the developed Co, Mo@CNFs/GCE biosensor demonstrated excellent performance in simultaneously detecting DA and UA, providing an efficient and dependable detection approach for clinical diagnosis and bioanalysis.


Assuntos
Dopamina , Nanofibras , Humanos , Ácido Úrico , Reprodutibilidade dos Testes , Carbono , Eletrodos , Ácido Ascórbico , Técnicas Eletroquímicas
9.
J Mol Med (Berl) ; 102(2): 257-272, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141114

RESUMO

Liver injury is closely associated with macrophage activation following HBV infection. Our previous study showed that only HBeAg, but not HBsAg and HBcAg, stably enhances inflammatory cytokine production in macrophages. And we also indicated that HBeAg could induce macrophage activation via TLR2 and thus aggravate the progression of liver fibrosis. However, the specific molecular mechanism of HBeAg in macrophage activation is not clear. We screened significantly overexpressed RGS16 from RNASeq results of HBeAg-stimulated macrophages and validated them with cellular assays, GSE83148 microarray dataset, and in clinical samples. Meanwhile, small interference, plasmid, and lentivirus transfection assays were used to establish cell models for knockdown and overexpression of RGS16, and q-PCR, ELISA, Transwell, and CCK-8 assays were used to analyze the role of RGS16 in HBeAg-induced macrophage activation. In addition, the upstream and downstream mechanisms of RGS16 in HBeAg-treated macrophage activation were explored using inhibitors, phostag gels, and RGS16 phosphorylation mutant plasmids. Finally, the effect of RGS16 on hepatic inflammation in murine tissues was evaluated by H&E staining, liver enzyme assay and immunofluorescence. RGS16 was significantly upregulated in HBeAg-induced macrophage activation, and its expression was enhanced with increasing HBeAg content and treatment time. Functional experiments showed that overexpression of RGS16 promoted the production of inflammatory factors TNF-α and IL-6 and boosted macrophage proliferation and migration, while knockdown of RGS16 exhibited the opposite effect. Mechanistically, we discovered that RGS16 is regulated by the TLR2/P38/STAT5 signaling pathway. Meanwhile, RGS16 enhanced ERK phosphorylation via its own Tyr168 phosphorylation to contribute to macrophage activation, thereby accelerating liver injury. Finally, in mice, overexpression of RGS16 markedly strengthened liver inflammation. HBeAg upregulates RGS16 expression through the TLR2-P38-STAT5 axis, and the upregulated expression of RGS16 enhances macrophage activation and accelerates liver injury by promoting ERK phosphorylation. In this process, phosphorylation of Tyr168 is necessary for RGS16 to function. KEY MESSAGES: RGS16 boosted HBeAg-induced macrophage inflammation, proliferation, and migration. Tyr168 phosphorylation of RGS16 affected by ERK promoted macrophage activation. HBeAg upregulated the expression of RGS16 through TLR2/P38/STAT5 signal pathway. RGS16 promoted liver injury by regulating macrophage functions in mouse model.


Assuntos
Antígenos E da Hepatite B , Sistema de Sinalização das MAP Quinases , Animais , Camundongos , Antígenos E da Hepatite B/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Ativação de Macrófagos , Fosforilação , Fator de Transcrição STAT5/metabolismo , Receptor 2 Toll-Like
10.
J Phys Chem Lett ; 14(49): 11190-11199, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38055859

RESUMO

Introducing the two-dimensional (2D) hexagonal boron nitride (hBN) between 2D transition metal dichalcogenide (TMD) layers promises convenient manipulation of the interlayer exciton (IX) and interlayer charge transfer in TMD/hBN/TMD heterostructures, while the role of inserted hBN layers during IX formation is controversial. Employing ab initio nonadiabatic molecular dynamics (NAMD) simulations and the electron-phonon coupling model, we systematically investigate interlayer hole transfer in MoSe2/WSe2 bilayers intercalated by hBN layers with various thicknesses. The conventional direct hole transfer from MoSe2 to WSe2 is decelerated by 2-3 orders of magnitude after the hBN insertion. Meanwhile, a novel channel intermediated by a deeper hole of WSe2 becomes dominant, where the intralayer shear mode of hBN plays a crucial role by reducing the energy barriers for this new channel. The unique role of hBN layers is revealed for the first time, enriching the knowledge of the underlying microscopic mechanisms and providing instructive guidance to practical van der Waals optoelectronic devices.

11.
Food Chem X ; 20: 100933, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38144804

RESUMO

Dipeptides have been shown to be an important taste substance in alcoholic beverages. However, the characterization of dipeptides in Chinese liquors was poor. Here, dansylation combined with liquid chromatography - mass spectrometry was employed to analyze dipeptides in eight liquors of two flavors. Consequently, 35 dipeptides were identified from liquors and 32 of them were quantified. Dipeptide quantification showed LODs smaller than 2.5 ng/mL. The calibration curves showed concentration spans from two to three orders of magnitude with satisfactory linearity. The matrix effects in low and high concentrations were from -25.71 % to 24.19 % and -14.82 % to 20.73 %, respectively. Intra- and inter-day precision is lower than 15 % for both low and high concentrations. The dipeptide contents in sauce flavor liquors were higher than those in strong flavor liquors. Ala- and -Phe dipeptides showed their unique trends between sauce and strong flavor liquors. This study provides new clues to evaluate taste of liquors.

12.
Artigo em Inglês | MEDLINE | ID: mdl-37933874

RESUMO

Cell membrane coating strategies have been increasingly researched due to their unique capabilities of biomimicry and biointerfacing, which can mimic the functionality of the original source cells in vivo but fail to provide customized nanoparticle surfaces with new or enhanced capabilities beyond natural cells. However, the field of drug lead discovery necessitates the acquisition of sufficient surface density of specific target membrane receptors, presenting a heightened demand for this technology. In this study, we developed a novel approach to fabricate high density of fibroblast growth factor receptor 4 (FGFR4) cell membrane-coated nanoparticles through covalent site-specific immobilization between genetically engineered FGFR4 with HaloTag anchor on cell membrane and chloroalkane-functionalized magnetic nanoparticles. This technique enables efficient screening of tyrosine kinase inhibitors from natural products. And the enhanced density of FGFR4 on the surface of nanoparticles were successfully confirmed by Western blot assay and confocal laser scanning microscopy. Further, the customized nanoparticles demonstrated exceptional sensitivity (limit of detection = 0.3 × 10-3 µg mL-1). Overall, the proposed design of a high density of membrane receptors, achieved through covalent site-specific immobilization with a HaloTag anchor, demonstrates a promising strategy for the development of cell membrane surface engineering. This approach highlights the potential of cell membrane coating technology for facilitating the advanced extraction of small molecules for drug discovery.

14.
Quant Imaging Med Surg ; 13(9): 5664-5675, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37711817

RESUMO

Background: Although transverse colon ptosis (TCP) is commonly diagnosed in patients with constipation, it has not attracted significant attention in the evaluation of constipation. Herein, we assessed the correlation between TCP-related radiological parameters and the severity of slow transit constipation (STC). Methods: This study was a single-center retrospective cohort study, with participants enrolled between 2012 and 2020 in Zhongnan Hospital of Wuhan University, China. STC was diagnosed according to Rome IV criteria and results of colonic transit test (CTT); healthy volunteers were also recruited as controls. All participants were examined using abdominal X-rays (AXRs) to acquire the radiological parameters related to TCP. Among these parameters, the degree of TCP (DTCP) was defined as the vertical distance from the top of the splenic flexure to the lowest point of the reverse colon. The Wexner Constipation Score and Hospital Anxiety and Depression Scale were used to assess clinical severity. After multivariable linear regression, the correlations between radiological parameters and severity of STC were investigated. We also explored the differences in radiological parameters between the operation and the conservative group. Results: The study included 139 patients with STC and 125 healthy people in as the normal control (NC). Patients with STC probably had larger DTCPs than those in the NC group (242.27±25.86 vs. 93.00±32.57 mm; P<0.001). Pearson correlation analysis showed that TCP-related parameters were consistent with the symptom severity of STC [e.g., parameter DTCP was strongly correlated with Wexner Constipation Score, with a ß coefficient (95% CI) of 8.63 (8.24-9.02), P<0.001]. Multivariable linear regression models showed that patients with a larger DTCP were more likely to undergo surgery (23.67; 95% CI: 1.40-45.94; P=0.04). Conclusions: TCP-related parameters, especially the DTCP, may serve as novel and feasible alternative indices for the assessment of STC. However, the potential value of DTCP in assisting the evaluation of STC needs to be confirmed in study with a larger sample size.

15.
Commun Chem ; 6(1): 202, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37775528

RESUMO

Precisely controlling macromolecular stereochemistry and sequences is a powerful strategy for manipulating polymer properties. Controlled synthetic routes to prepare degradable polyester, polycarbonate, and polyether are of recent interest due to the need for sustainable materials as alternatives to petrochemical-based polyolefins. Enantioselective ring-opening polymerization and ring-opening copolymerization of racemic monomers offer access to stereoregular polymers, specifically enantiopure polymers that form stereocomplexes with improved physicochemical and mechanical properties. Here, we highlight the state-of-the-art of this polymerization chemistry that can produce microstructure-defined polymers. In particular, the structures and performances of various homogeneous enantioselective catalysts are presented. Trends and future challenges of such chemistry are discussed.

16.
bioRxiv ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37645974

RESUMO

SNARE and Sec/Munc18 proteins are essential in synaptic vesicle exocytosis. Open form t-SNARE syntaxin and UNC-18 P334A are well-studied exocytosis-enhancing mutants. Here we investigate the interrelationship between the two mutations by generating double mutants in various genetic backgrounds in C. elegans. While each single mutation rescued the motility of CAPS/unc-31 and synaptotagmin/snt-1 mutants significantly, double mutations unexpectedly worsened motility or lost their rescuing effects. Electrophysiological analyses revealed that simultaneous mutations of open syntaxin and gain-of-function P334A UNC-18 induces a strong imbalance of excitatory over inhibitory transmission. In liposome fusion assays performed with mammalian proteins, the enhancement of fusion caused by the two mutations individually was abolished when the two mutations were introduced simultaneously, consistent with what we observed in C. elegans. We conclude that open syntaxin and P334A UNC-18 do not have additive beneficial effects, and this extends to C. elegans' characteristics such as motility, growth, offspring bared, body size, and exocytosis, as well as liposome fusion in vitro. Our results also reveal unexpected differences between the regulation of exocytosis in excitatory versus inhibitory synapses.

17.
J Am Chem Soc ; 145(36): 19790-19799, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37639703

RESUMO

Molecules where the energy of the lowest excited singlet state is found below the energy of the lowest triplet state (inverted singlet-triplet molecules) are extremely rare. It is particularly challenging to discover new ones through virtual screening because the required wavefunction-based methods are expensive and unsuitable for high-throughput calculations. Here, we devised a virtual screening approach where the molecules to be considered with advanced methods are pre-selected with increasingly more sophisticated filters that include the evaluation of the HOMO-LUMO exchange integral and approximate CASSCF calculations. A final set of 7 candidates (0.05% of the initial 15 000) were verified to possess inversion between singlet and triplet states with state-of-the-art multireference methods (MS-CASPT2). One of them is deemed of particular interest because it is unrelated to other proposals made in the literature.

18.
Front Microbiol ; 14: 1217966, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37533822

RESUMO

This study was conducted to investigate the capability of the microbial community characteristics and soil variables to promote carbon and nitrogen cycles in maize fields under straw mulch. We covered the surface soil of the maize field with different amounts of wheat straw (0 kg/ha, 2,250 kg/ha, and 4,500 kg/ha) and used 16S rRNA and ITS sequencing, Biology ECO-plate, traditional enzymology, TOC analyzer, and HPLC to measure bacterial and fungal community composition and functions, characteristics of microbial carbon source metabolism, carbon and nitrogen fraction, enzyme activity, and organic acid content in the maize rhizosphere and non-rhizosphere. The results indicated that short-term straw mulch insignificantly affected the alpha diversity of bacterial and fungal communities whereas significantly influenced their beta diversity. The results of functional prediction revealed that straw mulch considerably boosted the relative abundances of bacteria belonging to chemoheterotrophy, aerobic chemoheterotrophy, ureolysis, and nitrogen fixation and inhibited fermentation and nitrate reduction in maize rhizosphere soil. These processes primarily drove the C and N cycles in soil. Straw mulch also improved fungal saprotrophs by raising the proportion of Chaetomiaceae and Chaetosphaeriaceae. The Biology ECO-plate results illustrated that straw mulch weakened the metabolism capacity of microbial labile carbon resources. As a result, the labile C and N fractions were raised under straw mulch. Our results also showed that straw mulch primarily regulated the microbial community structure in rhizosphere soil by significantly decreasing Firmicutes and Ascomycota relative abundance while increasing Basidiomycota. The fungal community structure is more than bacterial for affecting soil microbial biomass carbon, readily oxidizable organic carbon, dissolved organic carbon, available nitrogen, ammonium, and nitrate directly and indirectly through malic acid content and cellulase, protease, and amylase activity. Overall, our findings imply that straw mulch might influence the bacterial and fungal community structures, thereby boosting the production of labile C and N components and accelerating the C and N cycle in maize fields.

19.
Clin Imaging ; 102: 1-8, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37437466

RESUMO

AIMS: To evaluate the value of four indices of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance as a potential imaging marker of liver functional reserve. METHODS: PubMed/Medline, Embase, Cochrane Library, and Web of Science were searched for studies concerning the relationship between Gd-EOB-DTPA-enhanced MRI and liver functional reserve estimated by ICG-R15, Pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated, Meanwhile, Sensitivity and subgroup analyses were performed along with Egger's test for the estimation of publication bias and potential heterogeneity. RESULTS: 14 publications with 1285 patients were included. The pooled r between relative liver enhancement (RLE), reduction rate of T1 relaxation time of the liver (rrT1), liver-to-spleen ratio (LSR), liver-to-muscle ratio (LMR), and ICG-R15 were -0.49 (95% CI, -0.56 to -0.41, p < 0.05), -0.47 (95% CI, -0.57 to -0.36, p < 0.05), -0.45 (95% CI, -0.55 to -0.34, p < 0.05), -0.50 (95% CI, -0.61 to -0.38, p < 0.05). moderate heterogeneity was observed between studies on rrT1, LSR, LMR, and ICG-R15 (p ≤ 0.05), but no significant heterogeneity was observed between RLE and ICG-R15. Further analysis shows that there was a notable heterogeneity between subgroup analysis of LSR and ICG-R15 stratified by years of publication, as well as rrT1 and LMR stratified by total patients and study design, the distribution funnel plots and the results of Egger's test showed no evidence of publication bias. CONCLUSIONS: RLE, LSR, LMR, and rrT1 all correlated significantly with ICG-R15-estimated hepatic functional reserve. The four indices represent a promising imaging biomarker in the prediction of liver functional reserve.


Assuntos
Meios de Contraste , Neoplasias Hepáticas , Humanos , Testes de Função Hepática , Fígado/diagnóstico por imagem , Fígado/patologia , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Neoplasias Hepáticas/patologia , Estudos Retrospectivos
20.
J Chromatogr A ; 1703: 464110, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37262933

RESUMO

Carbonyl compounds are among the most important flavor substances that affect the taste of Baijiu. However, high coverage analysis of carbonyl compounds is obstructed due to the poor ionization efficiency of these compounds. Here we report a chlorine isotope labeling-assisted ultrahigh-performance liquid chromatography-high resolution mass spectrometry-based method (CIL-UHPLCHRMS) for profiling and annotation of carbonyl compounds in sauce flavored-Baijiu Daqu. 4-Chloro-2-hydrazinylpyridine was demonstrated to be a good labeling reagent that could achieve highly sensitive profiling and high-coverage screening of carbonyl compounds in the absence of heavy isotope labeling reagents. In the analysis of eight carbonyl standards representing different carbonyl categories, l-(-)-fucose, 2-carboxybenzaldehyde, 2-hydroxyacetophenone and heptan-2-one could be ionized only after labeling and MS signals were significantly increased for other 4 standards with an enhancement factor ranging from 181-fold for 3-methoxysalicylaldehyde to 3141-fold for tridecan-2-one. The annotation was achieved based on multidimensional information including MS1, predicted tR, in silico MS/MS and manually annotated fragments. In total, 487 carbonyl compounds were detected in Baijiu Daqu, among which, 314 (64.5%) of them were positively or putatively identified. The outcome of the linearity (with a linear range of 2, 3 orders of magnitude), precision (less than 10%), and limit of detection (varied from 0.07 to 0.10 nM) indicated that the method was adequate for profiling carbonyl compounds in complex biological samples. The established method was successfully applied to study carbonyl compounds in Baijiu Daqu with different colors and different seasons. Taken collectively, the present work provides an effective, simple and economic strategy for comprehensive analysis of carbonyl compounds in complex matrix samples.


Assuntos
Cloro , Espectrometria de Massas em Tandem , Marcação por Isótopo , Cromatografia Líquida , Compostos Orgânicos , Isótopos , Halogênios
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