A Strategy for Accessing Trifluoromethyl Carbinol-Containing Chromones from o-Hydroxyaryl Enaminones and Trifluoroacetaldehyde/Ketone Derivatives.

Herein, we present a practical strategy for the direct construction of structurally diverse trifluoromethyl carbinol-containing compounds, especially CF3-substituted tertiary alcohol with chromone derivatives from easily available o-hydroxyaryl enaminones and trifluoroacetaldehyde/ketone derivatives under metal-free conditions. This reaction features a broad substrate scope with good yields and is easily scaled up. Notably, a one-pot in two-steps reaction of obtained products with amidines is also developed to provide a series of multi-substituted pyrimidine derivatives bearing two unique hydroxyls and one trifluoromethyl containing functional units.

Essential roles of matrix metalloproteinases in axolotl digit regeneration.

Among vertebrates, urodele amphibians possess a unique ability to regenerate various body parts including limbs. However, reports of their digit regeneration remain scarce, especially information about the related genes. In this study, it was evident that matrix metalloproteinases (mmps) including mmp9, mmp3/10a, and mmp3/10b, which play a crucial role in tissue remodeling, are highly expressed during early stages of digit regeneration in axolotl. Using in situ hybridization, we revealed that wound epidermis and blastema are two major origins of the MMPs during the regeneration process. Additionally, we found that the inhibition of MMPs with GM6001 (a wide-spectrum inhibitor of MMPs) in vivo after amputation disturbed normal digit regeneration process and resulted in malformed regenerates. Furthermore, inhibition of MMPs hindered blastema formation and decreased cell apoptosis at early stages in the digit regenerates. All these points suggest that MMPs are required for digit regeneration, as they play a significant role in the regulation of blastema formation.

Alpha 2 macroglobulin is a maternally-derived immune factor in amphioxus embryos: New evidence for defense roles of maternal immune components in invertebrate chordate.

In fish, a series of maternal derived immune components have been identified in their eggs or embryos at very early stages, which are proposed to provide protections to themselves against pathogenic attacks from hostile environment. The phenomenon of maternal immunity has been also recorded in several invertebrate species, however, so far, very limited information about the maternal immune molecules are available. In this study, it was demonstrated maternal alpha2 macroglobulin (A2m) protein, an important innate immune factor, exists in the fertilized eggs of amphioxus Branchiostoma japonicum, an invertebrate chordate. Maternal mRNA of A2m was also detected in amphioxus embryos at very early developing stages. In addition, it was recorded that the egg lysate prepared from the newly fertilized eggs can inhibit the growth of both Gram-negative bacterium Escherichia coli and Gram-positive bacterium Staphylococcus aureus in a concentration dependent manner. The bacteriostatic activity can be reduced notably after precipitated A2m with anti-A2m antibody. Thus maternal A2m is partly attributed to the bacteriostatic activity. It was further demonstrated that recombinant A2m can bind to E. coli cells directly. All these points come to a result that A2m is a maternal immune factor existing in eggs of invertebrate chordate, which may be involved in defense their embryos against harmful microbes' attacks.

[Influence of Postoperative Diet Type and Regimen on Hospital Comfort
and Rehabilitation of Lung Cancer Patients].

BACKGROUND: A reasonable and standardized dietary plan and procedure can help patients recovering quickly from lung cancer surgery. The aim of this study is to optimize the diet plan and procedure mainly based on medium chain triglyceride (MCT) diet and explore its clinical advantages for postoperative lung cancer patients. METHODS: From October 2023 to December 2023, a total of 156 patients were collected, who underwent lung cancer surgery in Lung Cancer Center, West China Hospital of Sichuan University. The patients were randomized into MCT group (76 cases) and routine diet (RD) group (80 cases). Clinical symptoms, biochemical index, postoperative hospitalization time and cost, dietary satisfaction and hospitalization comfort between the two groups were analyzed. RESULTS: The mean anus exhausting time in MCT group [24.00 (9.75, 36.97) h] was significantly shorter than that in RD group [28.50 (24.00, 48.00) h] (P<0.001). And the incidence of dizziness (18.42%), nausea and vomiting (6.58%) in MCT group were remarkably lower than those in RD group (51.25%, 31.25%) (P<0.001). Hospitalization comfort score in MCT group [(16.74±1.70)] was significantly higher than that in RD group [(14.83±2.34)] (P=0.016). Meanwhile, the average hospitalization cost in MCT group [(39,701.82±8105.47)¥] showed an obvious decrease compared with RD group [(44,511.79±9593.19)¥] (P=0.007). CONCLUSIONS: Optimizing the dietary plan and procedure mainly based on MCT diet for postoperative lung cancer patients can help the recovery of gastrointestinal function and improve hospitalization comfort, which promoted overall postoperative rehabilitation of patients with lung cancer surgery.

Inward motion of diamond nanoparticles inside an iron crystal.

In the absence of externally applied mechanical loading, it would seem counterintuitive that a solid particle sitting on the surface of another solid could not only sink into the latter, but also continue its rigid-body motion towards the interior, reaching a depth as distant as thousands of times the particle diameter. Here, we demonstrate such a case using in situ microscopic as well as bulk experiments, in which diamond nanoparticles ~100 nm in size move into iron up to millimeter depth, at a temperature about half of the melting point of iron. Each diamond nanoparticle is nudged as a whole, in a displacive motion towards the iron interior, due to a local stress induced by the accumulation of iron atoms diffusing around the particle via a short and easy interfacial channel. Our discovery underscores an unusual mass transport mode in solids, in addition to the familiar diffusion of individual atoms.

Radical-Polar Crossover Enabled Triple Cleavage of CF2Br2: A Multicomponent Tandem Cyclization to 3-Fluoropyrazoles.

The elaboration of step-economy and catalytic approaches for accessing diverse fluorinated heterocyclics is highly desirable. Described herein is a radical-polar crossover enabled three-component cyclization to polysubstituted fluoropyrazoles by using CF2Br2 as a novel C1F1 synthon. Mechanistic experiments revealed that the in situ generation of the reactive intermediate gem-difluorovinylimine ion is the key to this transformation. This protocol unlocks the novel reactivity of CF2Br2 and adds significant synthetic values to fluorine chemistry.

Green-Biased Technical Change and Its Influencing Factors of Agriculture Industry: Empirical Evidence at the Provincial Level in China.

The continued expansion of agriculture must contend with the dual pressures of changing factor endowment structure and constrained resources and environments. The main purpose of this paper is to provide feasible ideas for high-quality agricultural development in the transition period through the research on the green-biased technical change in Chinese agriculture. This paper selects China's provincial panel data of the agriculture industry from 1997 to 2017, combining the DEA-SBM model and Malmquist-Luenberger index decomposition method to calculate the green-biased technical change (BTC) index; second, the influence mechanism of BTC is empirically investigated by using the panel data regression analysis approach. The results show that: (1) in China's agriculture industry, BTC is the driving force behind long-term and steady improvement of technological advancement. Specifically, input-biased technical change (IBTC) has a substantial enhancing effect on agricultural green total factor productivity (GTFP), whereas output-biased technical change (OBTC) has a certain inhibiting effect. (2) On the whole, the tendency of capital substituting for labor and land is very evident, whereas the biased advantage of desirable output is not particularly prominent. (3) The BTC index in Chinese agriculture varies regionally. The eastern region has the highest IBTC index but the lowest OBTC index. (4) The degree of marketization, urbanization, capital deepening, financial support for agriculture, and other factors have a promoting effect on IBTC, whereas most of them have a restraining effect on OBTC. There is evident regional heterogeneity in the effect of environmental regulation intensity on BTC. The following are the primary contributions of this paper: based on national conditions in China, this paper empirically explores the changes and internal rules of green-biased technical change in China's agriculture industry from various regional viewpoints. It provides an empirical foundation for the regional diversification of agricultural green transformation.

Characterization of the protein structure of soymilk fermented by Lactobacillus and evaluation of its potential allergenicity based on the sensitized-cell model.

This study aimed to investigate the effects of fermented soymilk (FSM) with Lactobacillus brevis CICC 23,474 and L. brevis CICC 23,470 on the structural changes and allergenicity of major allergenic proteins in soymilk (SM). Spectroscopy and liquid chromatograph-tandem mass spectrometer (LC-MS/MS) were used to characterize changes in protein spatial structure and epitopes. The antigenicity and potential allergenicity were evaluated by immunoblotting, enzyme-linked immunosorbent assay (ELISA) and KU812 cell degranulation assay. Results suggested that the advanced structure of proteins was destroyed. Antigenicity was also significantly reduced, and five human IgE-binding linear epitopes (i.e., E5-E33, R27-S41, D414-A437, G253-I265 and V449-S471) were destroyed by fermentation. Furthermore, after in vitro simulated gastrointestinal digestion, FSM showed lower IgG/IgE-binding capacity and weaker degranulation ability of KU812 cells. All these findings demonstrated that fermentation with Lactobacillus can destroy the conformational and linear epitopes of proteins and reduce the potential allergenicity of SM.

LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC.

OBJECTIVES: Increasing researches emphasize the importance of long non-coding RNAs (lncRNAs) in the development of endometrial cancer (EC). There is wide recognition that LINC00470 is a critical participant in the tumorigenesis of cancers such as gastric cancer and glioblastoma, but its possible effects on EC progression remain to be explored. METHODS: We collected EC tissues and cells, where the expression of LINC00470 was determined, and followed by the Kaplan-Meier analysis of EC patient survival. We next examined the effect of LINC00470 and phosphatase and tensin homolog (PTEN) on EC cell migration, invasion, tube formation in vitro, and angiogenesis in mice xenografted with tumor after gain- or loss-of-function treatments. RNA pull-down, Co-IP, and ChIP experiments were performed to analyze the targeting relationships among LINC00470, MYC and DNMT3a. RESULTS: LINC00470 was aberrantly upregulated in EC and its high expression correlated to prognosis of EC patients. LINC00470 promoted invasiveness, migration, and angiogenesis of EC cells, and facilitated tumorigenesis and metastasis in vivo, but those effects were reversed by up-regulating PTEN. Functionally, LINC00470 bound to MYC in EC and that LINC00470 stimulated the binding of MYC to DNMT3a, and thus recruited DNMT3a through MYC to promote PTEN methylation. CONCLUSIONS: Our findings revealed that LINC00470 stimulated PTEN methylation to inhibit its expression by MYC-induced recruitment of DNMT3a, thus aggravating EC.

Investigation of eluted characteristics of fulvic acids using differential spectroscopy combined with Gaussian deconvolution and spectral indices.

The characteristics of subfractions of soil fulvic acid (FA3, FA5, FA7, FA9, and FA13) using stepwise elution from XAD-8 resin with pyrophosphate buffers were investigated by differential absorption spectroscopy (DAS) and differential fluorescence spectroscopy (DFS) combined with mathematical deconvolution and spectral indices. The log-transformed absorbance spectra (LTAS) exhibited three regions for both acidic-buffer-eluted subfractions (AESF) and neutral-buffer-eluted subfraction (NESF) and four regions for basic-buffer-eluted subfractions (BESF) according to the differences in spectral slopes. The DAS spectra of FA subfractions were closely fitted with seven Gaussian bands with maxima location at 199.66, 216.18 ± 1.50, 246.20 ± 3.85, 285.22 ± 7.26, 345.64 ± 5.30, 389.27, and 307.37 nm, respectively (R2 > 0.993). The content of salicylic-like and carboxyl groups in FA subfractions decreased, while the phenolic chromophore increased with elution sequence. From the 11 spectral indices, AESF had greater molecular weight, condensation, polymerization, hydroxyl radical production, humification degree, and terrigenous contribution, as well as contained more conjugated aromatic structures and less N-containing groups than NESF and BESF. The humification degree and humic characters of FA subfractions were closely associated to the aromaticity, molecular condensation, and DOM-metal-bound functional groups. The proper separation of FA into subfractions is beneficial for reducing its complexity and heterogeneity, which helps us to further explore its chemical properties and interactions with various contaminants in soil environments. Graphical abstract.

Mycoplasma lipoproteins and Toll-like receptors.

Mycoplasmas, the smallest free-living, self-replicating bacteria with diameters of 200 to 800 nm, have been reported to be associated with human diseases. It is well known that the mycoplasma lipoprotein/peptide is able to modulate the host immune system, whose N-terminal structure is an important factor in inducing immunity and distinguishing Toll-like receptors (TLRs). However, there is still no clear elucidation about the pathogenic mechanism of mycoplasma lipoprotein/peptide and the signaling pathway. Some researchers have focused on understanding the structures of these proteins and the relationships between their structure and biological function. This review provides an update on the research in this field.

Degradation of major allergens and allergenicity reduction of soybean meal through solid-state fermentation with microorganisms.

In this study, we determined whether solid-state fermentation could degrade major allergens and reduce potential allergenicity of soybean meal (SBM). Solid-state fermentation was realized through a mixture of Lactobacillus casei, yeast, and Bacillus subtilis. High-performance liquid chromatography, size exclusion-high-performance liquid chromatography, and capillary liquid chromatography/tandem mass spectrometry coupled with electrospray ionization were used to examine the total amino acids and molecular weight distribution of the fermented soybean meal (FSBM). In addition, the potential allergenicity of FSBM was assessed by conducting in vitro competitive inhibition ELISA and oral sensitization and challenge of a BALB/c mice model. The results indicated that the total amino acid content increased and soy protein was degraded into polypeptides with low molecular weights that were derived from the hydrolysis of the allergen sequences N232-D383, G253-I265, E169-S215, G68-G98, A365-I375, and V153-A167. Moreover, the FSBM group exhibited a lower in vitro immunoglobulin E (IgE)-binding capacity than the SBM group. The BALB/c model indicated that the FSBM group manifested milder damage to the intestine, lower mMCP-1 and IgE levels, and higher IFN-γ levels as compared to the SBM group. These findings suggested that the potential allergenicity of SBM was reduced by the solid-state fermentation induced by the mixture of Lactobacillus casei, yeast, and Bacillus subtilis.

Mycoplasma genitalium-derived lipid-associated membrane proteins activate NF-kappaB through toll-like receptors 1, 2, and 6 and CD14 in a MyD88-dependent pathway.

Mycoplasma genitalium is a leading pathogen of nongonoccocal chlamydia-negative urethritis, which has been implicated directly in numerous other genitourinary and extragenitourinary tract pathologies. The pathogenesis of infection is attributed in part to excessive immune responses. M. genitalium-derived lipid-associated membrane proteins (LAMPs) are a mixture of bacterial lipoproteins, exposed at the surface of mycoplasma, that are potent inducers of the host innate immune system. However, the interaction of M. genitalium-derived LAMPs as pathogenic agents with Toll-like receptors (TLRs) and the signaling pathways responsible for active inflammation and NF-kappaB activation have not been fully elucidated. In this study, LAMPs induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in a dose-dependent manner. Blocking assays showed that TLR2- and CD14-neutralizing antibodies reduced the expression of TNF-alpha and IL-6 in THP-1 cells. Furthermore, LAMP-induced NF-kappaB activation was increased in 293T cells transfected with TLR2 plasmid. The activity of NF-kappaB was synergically augmented by cotransfected TLR1, TLR6, and CD14. Additionally, LAMPs were shown to inhibit NF-kappaB expression by cotransfection with dominant-negative MyD88 and TLR2 plasmids. These results suggest that M. genitalium-derived LAMPs activate NF-kappaB via TLR1, TLR2, TLR6, and CD14 in a MyD88-dependent pathway.