Oral Synergism of Egg-White-Derived Peptides (EWDP) and Curcumin for Colitis Mitigation via Polysaccharide/Cyclodextrin Metal-Organic Framework-Based Assemblies.

Recently, oral deliverable strategies of multiple nutraceuticals for ulcerative colitis (UC) mitigation have attracted increasing attention. This study aimed to fabricate facile oral assemblies loaded with egg-white-derived peptides (EWDP) and curcumin based on carboxymethyl chitosan (CMCS) and an γ-cyclodextrin metal-organic framework (MOF). Herein, outer CMCS could coassemble with EWDP (both nutraceuticals and building blocks) into cobweb-like fibrils to promote bridging with inner MOF via coordinative noncovalent interactions (hydrogen bonding, hydrophobic interaction, and electrostatic interaction). Compared with conventional γ-cyclodextrin/MOF-based composites, the above coassembly could also endow the biocompatible assemblies with superior nanoscale colloidal properties, processing applicability (curcumin storage stability, bioaccessibility, and aqueous solubility), and bioactivity. Moreover, the oral synergism of EWDP and curcumin (initially nonsynergistic) for UC mitigation was achieved by alleviating inflammatory damage and gut microbiota imbalance. Overall, the novel assemblies could be a promising amplifier and platform to facilitate oral formulations of various nutraceuticals for food processing and UC relief.

High expression of SRSF1 facilitates osteosarcoma progression and unveils its potential mechanisms.

BACKGROUND: SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. METHODS: SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. RESULTS: SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. CONCLUSIONS: Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.

Casein-quaternary chitosan complexes induced the soft assembly of egg white peptide and curcumin for ulcerative colitis alleviation.

Soft assembly of peptide and curcumin (Cur) molecules enables functional integration by finding dynamic equilibrium states through non-covalent interactions. Herein, we developed two soft assembly systems, curcumin-egg white peptides (Cur-EWP) aggregations (AGs) and Cur-EWP-casein-quaternary chitosan (Cur-EWP-CA-QC) nanoparticles (NPs) to comparatively investigate their therapeutic effects on ulcerative colitis in mice and elucidate their underlying mechanism. Results revealed that Cur-EWP AGs, despite gastrointestinal tract instability, exhibited a propensity for swift accumulation within the colorectal region, enriching mucus-associated and short-chain fatty acid (SCAF)-producing bacteria, restoring the intestinal barrier damage. Whereas, Cur-EWP-CA-QC NPs, benefiting from their remarkable stability and exceptional mucosal adsorption properties, not only enhanced permeability of Cur and EWP in the small intestine to activate the immune response and boost tight junction protein expression but also, in their unabsorbed state, regulated the intestinal flora, exerting potent anti-inflammatory activity. Soft assembly of peptides and hydrophobic nutraceuticals could synergize biological activities to modulate chronic diseases.

Design, synthesis and bioactivity evaluation of 4-hydroxycoumarin derivatives as potential anti-inflammatory agents against acute lung injury and colitis.

Acute lung injury (ALI) and inflammatory bowel disease (IBD) are common inflammatory illnesses that seriously affect people's health. Herein, a series of 4-hydroxylcoumarin (4-HC) derivatives were designed and synthesized. The inhibitory effects of these compounds on LPS-induced interleukin-6 (IL-6) release from J774A.1 cells were then screened via ELISA assay, compound B8 showed 3 times more active than the lead compound 4-HC. The most active compound B8 had the IC50 values of 4.57 µM and 6.51 µM for IL-6 release on mouse cells J774A.1 and human cells THP-1, respectively. Furthermore, we also found that B8 could act on the MAPK pathway. Based on the target prediction results of computer virtual docking, kinase inhibitory assay was carried out, and it revealed that targeting IRAK1 was a key mechanism for B8 to exert anti-inflammatory activity. Moreover, B8 exerted a good therapeutic effect on the dextran sulfate sodium (DSS)-induced colitis model and liposaccharide (LPS)-induced ALI mouse models. The acute toxicity experiments indicated that high-dose B8 caused no adverse reactions in mice, confirming its safety in vivo. Additionally, the preliminary pharmacokinetic (PK) parameters of B8 in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, B8 is a potential candidate of drug for the treatment of ALI and colitis.

Dual-comb spectroscopy of ammonia formation in non-thermal plasmas.

Plasma-activated chemical transformations promise the efficient synthesis of salient chemical products. However, the reaction pathways that lead to desirable products are often unknown, and key quantum-state-resolved information regarding the involved molecular species is lacking. Here we use quantum cascade laser dual-comb spectroscopy (QCL-DCS) to probe plasma-activated NH3 generation with rotational and vibrational state resolution, quantifying state-specific number densities via broadband spectral analysis. The measurements reveal unique translational, rotational and vibrational temperatures for NH3 products, indicative of a highly reactive, non-thermal environment. Ultimately, we postulate on the energy transfer mechanisms that explain trends in temperatures and number densities observed for NH3 generated in low-pressure nitrogen-hydrogen (N2-H2) plasmas.

Structural basis for dimerization of a paramyxovirus polymerase complex.

The transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.7 Å cryo-EM structure of human parainfluenza virus type 3 (hPIV3) L-P complex with the connector domain (CD') of a second L built, while reconstruction of the rest of the second L-P obtains a low-resolution map of the ring-like L core region. This study reveals detailed atomic features of nsNSV polymerase active site and distinct conformation of hPIV3 L with a unique ß-strand latch. Furthermore, we report the structural basis of L-L dimerization, with CD' located at the putative template entry of the adjoining L. Disruption of the L-L interface causes a defect in RNA replication that can be overcome by complementation, demonstrating that L dimerization is necessary for hPIV3 genome replication. These findings provide further insight into how nsNSV polymerases perform their functions, and suggest a new avenue for rational drug design.

Fates and models for exposure pathways of pyrethroid pesticide residues: A review.

Pyrethroids (PYs) are widely applied pesticides whose residues pose potential health risks. This review describes current knowledge on PY chemical properties, usage patterns, environmental and food contamination, and human exposure models. It evaluates life cycle assessment (LCA), chemical alternatives assessment (CAA), and high-throughput screening (HTS) as tools for pesticide policy. Despite efforts to mitigate PY presence, their pervasive residues in the environment and food persist. And the highest concentrations ranged from 54,360 to 80,500 ng/L in water samples from agricultural fields. Food processing techniques variably reduce PY levels, yet no method guarantees complete elimination. This review provides insights into the fates and exposure pathways of PY residues in agriculture and food, and highlights the necessity for improved PY management and alternative practices to safeguard health and environment.

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Linking Periodontitis with Inflammatory Bowel Disease through the Oral-Gut Axis: The Potential Role of Porphyromonas gingivalis.

Periodontitis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases that are characterized by abnormal host immune responses and microbiota dysbiosis. Emerging evidence implies potential associations between periodontitis and IBD. Porphyromonas gingivalis (P. gingivalis), a primary cause of periodontitis, is thought to play a role in the development of IBD through the oral-gut disease axis. However, the precise mechanisms of its involvement remain enigmatic. In this narrative review, we begin with a discussion of the bidirectional relationship between periodontitis and IBD and the involvement of P. gingivalis in each of the two diseases. Further, we summarize the possible routes by which P. gingivalis links periodontitis and IBD through the oral-gut axis, as well as the underlying mechanisms of its involvement in the pathogenesis of IBD. Collectively, P. gingivalis participates in the progression of IBD through gut dysbiosis, impairment of the intestinal barrier, release of inflammatory mediators, and disturbance of the immune response. The above findings may provide new insights for exploring novel biomarkers and potential therapeutic approaches for IBD.

Design, synthesis and antitumor activity of 2-substituted quinazoline-4-amine derivatives.

Werner (WRN) syndrome protein is a multifunctional enzyme with helicase, ATPase, and exonuclease activities that are necessary for numerous DNA-related transactions in the human cell. Recent studies identified WRN as a synthetic lethal target in cancers. In this study, a series of new N-arylquinazoline-4-amine analogs were designed and synthesized based on structure optimization of quinazoline. The structures of the thirty-two newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The anticancer activity in vitro against chronic myeloid leukemia cells (K562), non-small cell lung cancer cells (A549), human prostate cancer cells (PC3), and cervical cancer cells (HeLa) of the target compounds was evaluated. Among them, the inhibition ratio of compounds 17d, 18a, 18b, 11 and 23a against four cancer cells at 5 µM concentration were more than 50 %. The IC50 values of compounds 18a and 18b were 0.3 ± 0.01 µM and 0.05 ± 0.02 µM in K562 cells respectively, compared with HeLa and A549 cells, 18a and 18b were more sensitive to K562 cells. In addition, the PC3 cells with WRN overexpression (PC3-WRN) was constructed, 18a and 18b and 23a were more sensitive to PC3-WRN cells compared with the control group cells (PC3-NC). Then, the cell viability of the novel WRN inhibitors were further assessed by colony formation assay. Compared with PC3-NC cells, 18b and 23a had obvious inhibitory effect on PC3-WRN cell at 1000 nM. In summary, these results indicated that the compounds 18b and 23a could be WRN protein inhibitor with potent anticancer properties in vitro.

Parental Autonomy Granting, Peer Attachment and Problematic Internet Use Among Chinese Adolescents: The Moderating Effect of School Climate.

While the correlation between parental autonomy granting and adolescents' problematic Internet use (PIU) has been confirmed, the processes underlying this connection have not been thoroughly investigated. Drawing on the ecological systems theory, this study sought to investigate the mediating mechanism of peer attachment and the moderating mechanism of school climate that link parental autonomy granting to PIU. A two-wave longitudinal design was employed with a time interval of six months. The participants were 852 adolescents who attended three middle schools located in Guangdong Province, China. Self-report questionnaires were used to obtain data on demographics, parental autonomy granting, peer attachment, school climate, and PIU. The findings indicated that peer attachment significantly mediated the link between parental autonomy granting and adolescent PIU. A positive school climate significantly moderated the influence of parental autonomy granting on peer attachment and the influence of peer attachment on PIU. Specifically, the association between parental autonomy granting and peer attachment and the association between peer attachment and PIU were more pronounced when the school climate was perceived to be positive. This research underscores the possible significance of peer attachment in the association between parental autonomy granting and PIU and offers valuable insights for mitigating the negative outcomes of PIU.

Effective separation of maslinic acid and oleanolic acid from olive pomace using high-speed shear off-line coupled with high-speed countercurrent chromatography and their antibacterial activity test.

In this work, a high-speed shear extraction off-line coupling high-speed countercurrent chromatography method was developed to separate maslinic acid and oleanolic acid from olive pomace. To improve extraction efficiency, the polar disparity between maslinic acid and oleanolic acid necessitated the concurrent utilization of both polar and non-polar solvents during high-speed shear extraction. Then, the high-speed shear extraction was directly feed to high-speed countercurrent chromatography for subsequently separation. A total of 250 min were needed to complete the extraction and separation process. This yielded two molecules from 3.3 g of defatted olive pomace: 7.2 mg of 93.8 % pure maslinic acid and 2.3 mg of 90.1 % pure oleanolic acid, both determined by HPLC at 210 nm. Furthermore, the compounds exhibited inhibitory activity against Escherichia coli and Staphylococcus aureus. At a concentration of 100 µg/mL, its efficacy in inhibiting hyaluronidase was comparable to that of the standard drug indomethacin. Compared with the conventional separation method, this coupled technique reduced the whole time due to the direct injection of sample extraction solution. This technique provides a useful approach for the separation of natural products with significant polarity differences.

Body image and physical activity in Latinas.

Women with negative body image engage in less physical activity. The purpose of this study is to examine the relationship between body image and physical activity in Latinas participating in a lifestyle program. Participants (age 43.8 ± 10.1 years and BMI 30.4 ± 5.2 kg/m2) were enrolled in a 12-month culturally and linguistically adapted, individually tailored, intervention focused on increasing moderate-to-vigorous intensity physical activity (MVPA). Longitudinal assessments were conducted on body image dissatisfaction (BID) using the Figure Rating Scale, MVPA using the 7-day PAR interview, and objectively measured body weight. Pre-intervention BID did not significantly predict MVPA change. Participants experienced considerable reduction in BID. Greater MVPA engagement and weight loss were independently related to BID reduction. Acculturation did not moderate these relationships. Body image improved in Latinas participating in a cognitive and behavioral physical activity intervention regardless of weight loss and acculturation level.

Cardiac magnetic resonance-derived mitral annular plane systolic excursion: a robust indicator for risk stratification after myocardial infarction.

To explore the predictive value of mitral annular plane systolic excursion (MAPSE) derived by cardiac magnetic resonance (CMR) for major adverse cardiovascular events (MACE) in postmyocardial infarction (MI) patients. Patients with MI who underwent 3.0 T CMR (Chinese Clinical Trial Registry, ChiCTR2200055158) were recruited retrospectively. CMR parameters included MAPSE and LVEF. Patients were followed up for MACE for more than 6 months and were separated into a No-MACE group and a MACE group. A total of 165 post-MI patients were included, and 103 patients were finally analyzed (61 patients belonged to the No-MACE group, and 42 patients belonged to the MACE group). The LVEF and MAPSE of the patients belonging to the No-MACE group were considerably higher than those of the patients belonging to the MACE group. Both LVEF and MAPSE were effective indicators of the occurrence of MACE after MI. The risk of MACE decreased as LVEF and MAPSE increased. For the risk prediction of MACE after MI, compared with model I (chi-square value 4.0 vs. 31.4, P < 0.001) and model II (chi-square value 22.7 vs. 31.4, P = 0.003), model III had a significant incremental predictive value. Moreover, the cutoff value of MAPSE was 9.70 mm. CMR-derived MAPSE is an effective predictor of MACE occurrence in patients with MI, and MAPSE provided a significant incremental predictive value. Moreover, MAPSE could complement LVEF for superior risk stratification of MI patients.

Recent trends in multidimensional countercurrent chromatography.

Countercurrent chromatography (CCC) is a potent separation approach known for its remarkable efficiency and capacity in preparation. It's applied as a substitute or combined with different chromatographic techniques, resulting in its rebranding as multidimensional CCC (MDCCC). Numerous essential mixtures from natural products contain hundreds or thousands of distinct components of importance. These mix types are too complicated to separate in any reasonable time using a single CCC dimension. However, if a multidimensional technique is utilized, where a complex mixture is separated by an initial dimension, smaller fractions of that separation are gathered. Each fraction is studied individually; complex mixes can be resolved relatively quickly. Thus, several MDCCC separation features have been studied to demonstrate their advantages, limitations, and prospective capacity to separate exceedingly complex mixtures. In this review, MDCCC aspects, including principles, multiple columns system, multilayer coil J-type, on-line monitoring system, and applications, have been thoroughly_explored.

Uptake and cellular responses of Microcystis aeruginosa to PFOS in various environmental conditions.

Although PFOS has been banned as a persistent organic pollutant, it still exists in large quantities within the environment, thus impacting the health of aquatic ecosystems. Previous studies focused solely on high PFOS concentrations, disregarding the connection with environmental factors. To gain a more comprehensive understanding of the PFOS effects on aquatic ecosystems amidst changing environmental conditions, this study investigated the cellular responses of Microcystis aeruginosa to varying PFOS concentrations under heatwave and nutrient stress conditions. The results showed that PFOS concentrations exceeding 5.0 µg/L had obvious effects on multiple physiological responses of M. aeruginosa, resulting in the suppression of algal cell growth and the induction of oxidative damage. However, PFOS concentration at levels below 20.0 µg/L has been found to enhance the growth of algal cells and trigger significant oxidative damage under heatwave conditions. Heatwave conditions could enhance the uptake of PFOS in algal cells, potentially leading to heightened algal growth when PFOS concentration was equal to or less than 5.0 µg/L. Conversely, deficiency or limitation of nitrogen and phosphorus significantly decreased algal abundance and chlorophyll content, inducing severe oxidative stress that could be mitigated by exposure to PFOS. This study holds significance in managing the impact of PFOS on algal growth across diverse environmental conditions.

Genomic surveillance and evolutionary dynamics of type 2 porcine reproductive and respiratory syndrome virus in China spanning the African swine fever outbreak.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a serious threat to the pig industry in China. Our previous study demonstrated that PRRSV persists with local circulations and overseas imports in China and has formed a relatively stable epidemic pattern. However, the sudden African swine fever (ASF) outbreak in 2018 caused serious damage to China's pig industry structure, which resulted in about 40 per cent of pigs being slaughtered. The pig yields recovered by the end of 2019. Thus, whether the ASF outbreak reframed PRRSV evolution with changes in pig populations and further posed new threats to the pig industry becomes a matter of concern. For this purpose, we conducted genomic surveillance and recombination, NSP2 polymorphism, population dynamics, and geographical spread analysis of PRRSV-2, which is dominant in China. The results showed that the prevalence of ASF had no significant effects on genetic diversities like lineage composition, recombination patterns, and NSP2 insertion and deletion patterns but was likely to lead to changes in PRRSV-2 recombination frequency. As for circulation of the two major sub-lineages of Lineage 1, there was no apparent transmission of NADC30-like among provinces, while NADC34-like had obvious signs of inter-provincial transmission and foreign importation during the ASF epidemic. In addition, two suspected vaccine recombinant epidemic strains suggest a slight safety issue of vaccine use. Herein, the interference of ASF to the PRRSV-2 evolutionary pattern was evaluated and vaccine safety was analyzed, in order to monitor the potential threat of PRRSV-2 to China's pig industry in the post-epidemic era of ASF.

Semantic Segmentation of Remote Sensing Data Based on Channel Attention and Feature Information Entropy.

The common channel attention mechanism maps feature statistics to feature weights. However, the effectiveness of this mechanism may not be assured in remotely sensing images due to statistical differences across multiple bands. This paper proposes a novel channel attention mechanism based on feature information called the feature information entropy attention mechanism (FEM). The FEM constructs a relationship between features based on feature information entropy and then maps this relationship to their importance. The Vaihingen dataset and OpenEarthMap dataset are selected for experiments. The proposed method was compared with the squeeze-and-excitation mechanism (SEM), the convolutional block attention mechanism (CBAM), and the frequency channel attention mechanism (FCA). Compared with these three channel attention mechanisms, the mIoU of the FEM in the Vaihingen dataset is improved by 0.90%, 1.10%, and 0.40%, and in the OpenEarthMap dataset, it is improved by 2.30%, 2.20%, and 2.10%, respectively. The proposed channel attention mechanism in this paper shows better performance in remote sensing land use classification.

Comparison of two different multiple dual-mode counter-current chromatograph for separation of ketoconazole enantiomers.

In this work, two different multiple dual-mode (MDM) counter-current chromatography methods, conventional MDM and modified MDM elution modes, were compared for the chiral separation of the ketoconazole enantiomers. The biphasic solvent system which consisted of n-hexane: isobutyl acetate: 0.1 mol/L phosphate buffer (2:4:6, v/v) (pH = 8.5) was employed as stationary phase and mobile phase. And the hydroxypropyl-ß-cyclodextrin (HP-ß-CD) with a concentration of 100 mmol/L was dissolved in the phosphate buffer, as the chiral selector. Under two different methods, dual-mode (DM) elution was performed to determine the time of the transformed phase roles and multiple cycles were performed to isolate ketoconazole, respectively. The result indicated that the modified MDM elution had a significant improvement on the separation, increasing the resolution from 0.51 to 1.19, while the resolution was increased from 0.40 to 0.79 by the conventional MDM elution. Ultimately, baseline separation of ketoconazole enantiomers was essentially achieved by high-speed counter-current chromatography under optimized modified MDM separation conditions. The final recoveries of the two enantiomers, R-(K) and S-(K), were 92.5 % and 83.3 %, respectively, corresponding to enantiomeric excess values of 99.0 % and 97.0 %, as determined by HPLC.