Double-stranded DNA enhances platelet activation, thrombosis, and myocardial injury via cyclic GMP-AMP synthase.

AIMS: Elevated dsDNA levels in STEMI patients are associated with increased infarct size and worse clinical outcomes. However, the direct effect of dsDNA on platelet activation remains unclear. This study aims to investigate the direct influence of dsDNA on platelet activation, thrombosis, and the underlying mechanisms. METHODS AND RESULTS: Analysis of clinical samples revealed elevated plasma dsDNA levels in STEMI patients, which positively correlated with platelet aggregation and markers of neutrophil extracellular traps (NETs) such as MPO-DNA and CitH3. Platelet assays demonstrated the activation of the cGAS-STING pathway in platelets from STEMI patients. DsDNA directly potentiated platelet activation and thrombus formation. Mechanistic studies using G150 (cGAS inhibitor), H151 (STING inhibitor), and MCC950 (NLRP3 inhibitor), as well as cGAS-/-, STING-/- and NLRP3-/- mice showed that dsDNA activated cGAS, a previously unreported DNA sensor in platelets, and induced activation of the STING/NLRP3/caspase-1/IL-1ß axis. This cascade enhanced platelet activation and thrombus formation. Platelet cGAS depletion or Palbociclib, a cGAS-STING inhibitor, approved by the FDA for advanced breast cancer, ameliorated myocardial ischemia-reperfusion injury in ApoE-/- mice fed with a high-fat diet for 12 weeks. CONCLUSIONS: These results suggested that dsDNA is a novel driver of platelet activation and thrombus formation in STEMI patients. TRANSLATIONAL PERSPECTIVE: ST-elevated myocardial infarction (STEMI) patients exhibit high levels of plasma double-stranded DNA (dsDNA), which directly potentiates platelet activation through the platelet cGAS/STING/NLRP3/caspase-1/IL-1ß signaling pathway. STEMI patients may benefit from cGAS inhibition in the prevention of platelet hyperactivity and thrombus formation.

Unlocking the potential of methionine: a dietary supplement for preventing colitis.

The incidence rate of colitis and conversion of colitis into colorectal cancer is increasing. However, the results of drug treatments are inconsistent with variable side effects; therefore, it is necessary to find alternative ways of treating colitis, e.g. through dietary supplements. One such dietary supplement could be sulfur-containing amino acids, which are known to have anti-inflammatory, antioxidant, and gut microbiota homeostasis effects. Therefore, the aim of the present study was to explore the effect of methionine supplementation in the diet of mice on experimental dextran sulfate sodium (DSS)-induced colitis. Here, 24 male C57BL/6J mice were split into three experimental treatment groups in such a way that each treatment group had four replicates and each replicate had two mice. The control group was colitis-free, while colitis was induced by the administration of DSS in the DSS groups. In the DSS and DSS plus methionine (DSS + Met) groups, DSS was provided in drinking water containing 3% DSS on days 1-5 and later provided with purified water on days 6-7. It was found that supplementing with methionine could activate pathways like Nrf2, and inhibit pathways like TLR4 and Nlrp3 to realize anti-inflammatory and antioxidant effects. Moreover, methionine could alter the microbiota of the gut in the experimental mice, whereby exploration of the gut microbiota demonstrated that methionine supplementation in the diet increased the abundance of parabacteroides and the production of propionate and butyrate. The current study shows that the dietary prophylactic supplementation of methionine has a beneficial effect on resisting colitis, providing new insights for the prevention of colitis.

Regulatory role of lncMD1 in goat skeletal muscle satellite cell differentiation via miR-133a-3p and miR-361-3p targeting.

Skeletal muscle satellite cells (SMSCs) are pivotal in skeletal muscle development and are influenced by numerous regulatory factors. This study focuses on the regulatory and functional mechanism roles of lncMD1, a muscle-specific long non-coding RNA, in the proliferation and differentiation of goat SMSCs. Employing in vitro cultured goat SMSCs, this study demonstrated that lncMD1, functions as a decoy for miR-133a-3p and miR-361-3p. This interaction competitively binds these microRNAs to modulate the expression of dynactin subunit 2 (DCTN2) and dynactin subunit 1 (DCTN1), thereby affects SMSCs proliferation and differentiation. These findings enhance the understanding of non-coding RNAs in goat SMSCs growth cycles and offer a theoretical foundation for exploring the molecular processes of goat skeletal muscle myogenic development.

The risk of treatment-related toxicities with PD-1/PD-L1 inhibitors in patients with lung cancer.

The risk of treatment-related toxicities with programmed cell death 1 and its ligand (PD-1/PD-L1) inhibitors in patients with lung cancer is unclear and inconclusive. PubMed, EMBASE, and the Cochrane Library databases were systematically searched without language restrictions from inception to May 31, 2024 to identify Phase 3 randomized controlled trials of lung cancer comparing PD-1/PD-L1 inhibitors versus placebo/best supportive care (alone or in combination with nontargeted chemotherapy) that had available data regarding treatment-related adverse events (TRAEs) or incidence and sample size. Random-effect models were employed to study the pooled relative risk (RR) and 95% confidence intervals (CIs). Finally, 36 trials, involving 19,693 participants, fulfilled the inclusion criteria. PD-1/PD-L1 inhibitors significantly augmented the likelihood of developing all-grade (RR, 1.03; 95% CI, 1.01-1.04, p < .01) and grade ≥3 TRAEs (RR, 1.16; 95% CI, 1.10 to 1.23, p < .01). PD-1/PD-L1 inhibitors substantially augmented the odds of developing treatment-related serious adverse events (SAEs) (RR, 1.48; 95% CI, 1.27-1.71, p < .01) and fatal adverse events (FAEs) (RR, 1.42; 95% CI, 1.11-1.82, p < .01). Subgroup analyses indicated that the RR of SAEs and FAEs were generally consistent, regardless of treatment type, tumor type, treatment setting, PD-1/PD-L1 inhibitors type and study design. The most common causes of FAEs were respiratory failure/insufficiency (33.3%), cardiac events (16.1%), and hematological disorders (10.1%). We demonstrated that PD-1/PD-L1 inhibitors were significantly correlated with higher possibility of developing treatment-related toxicities, especially SAEs and FAEs, compared with placebo/best supportive care controls.

Exploring the genome-wide transcriptomic responses of Bulinus truncatus to Schistosoma haematobium infection: An important host-parasite system involved in the transmission of human urogenital schistosomiasis.

Freshwater snails of the genus Bulinus are critical hosts for Schistosoma haematobium, the causative agent of urogenital schistosomiasis. Among the 37 recognized Bulinus species, B. truncatus is a key vector. Using RNA sequencing (RNAseq), we investigated the genome-wide transcriptional responses of B. truncatus to S. haematobium infection. Our findings suggest that snails employ a complex defense strategy against the parasites by up-regulating genes involved in immune response, stress reaction, structural integrity, metabolism, and detoxification. In response, schistosome parasites appear to manipulate the snail's defense system, as evidenced by the suppression of immune-related genes such as ficolin, peptidoglycan recognition protein, and C-type lectin domain-containing protein genes. The down-regulation of biomphalysin 9, compared to its function in Biomphalaria glabrata, indicates divergent immune strategies among snail hosts. Additionally, we compared transcriptome profiles between embryos and juveniles, providing insights into developmental processes. This study offers valuable genomic data for Bulinus snails, illuminating the molecular interactions between bulinids and schistosomes, and advancing our understanding of their developmental biology.

Therapeutic approaches to CNS diseases via the meningeal lymphatic and glymphatic system: prospects and challenges.

The brain has traditionally been considered an "immune-privileged" organ lacking a lymphatic system. However, recent studies have challenged this view by identifying the presence of the glymphatic system and meningeal lymphatic vessels (MLVs). These discoveries offer new opportunities for waste clearance and treatment of central nervous system (CNS) diseases. Various strategies have been developed based on these pathways, including modulation of glymphatic system function, enhancement of meningeal lymphatic drainage, and utilization of these routes for drug delivery. Consequently, this review explores the developmental features and physiological roles of the cerebral lymphatic system as well as its significance in various CNS disorders. Notably, strategies for ameliorating CNS diseases have been discussed with a focus on enhancing glymphatic system and MLVs functionality through modulation of physiological factors along with implementing pharmacological and physical treatments. Additionally, emphasis is placed on the potential use of the CNS lymphatic system in drug delivery while envisioning future directions in terms of mechanisms, applications, and translational research.

Arsenic Reduces Methane Emissions from Paddy Soils: Insights from Continental Investigation and Laboratory Incubations.

Arsenic (As) contamination and methane (CH4) emissions co-occur in rice paddies. However, how As impacts CH4 production, oxidation, and emission dynamics is unknown. Here, we investigated the abundances and activities of CH4-cycling microbes from 132 paddy soils with different As concentrations across continental China using metagenomics and the reverse transcription polymerase chain reaction. Our results revealed that As was a crucial factor affecting the abundance and distribution patterns of the mcrA gene, which is responsible for CH4 production and anaerobic CH4 oxidation. Laboratory incubation experiments showed that adding 30 mg kg-1 arsenate increased 13CO2 production by 10-fold, ultimately decreasing CH4 emissions by 68.5%. The inhibition of CH4 emissions by As was induced through three aspects: (1) the toxicity of As decreased the abundance and activity of the methanogens; (2) the adaptability and response of methanotrophs to As is beneficial for CH4 oxidation under As stress; and (3) the more robust arsenate reduction would anaerobically consume more CH4 in paddies. Additionally, significant positive correlations were observed between arsC and pmoA gene abundance in both the observational study and incubation experiment. These findings enhance our understanding of the mechanisms underlying the interactions between As and CH4 cycling in soils.

Synergetic effects of chlorinated paraffins and microplastics on microbial communities and nitrogen cycling in deep-sea cold seep sediments.

Chlorinated paraffins (CPs) and microplastics (MPs) are commonly found in deep-sea cold seep sediments, where nitrogen cycling processes frequently occur. However, little is known about their combined effects on sedimentary microbial communities and nitrogen cycling in these environments. This study aimed to investigate the synergistic impacts of CPs and MPs on microbial communities and nitrogen cycling in deep-sea cold seep sediments through microcosm experiments. Our results demonstrated that the presence of CPs and MPs induced significant alterations in microbial community composition, promoting the growth of Halomonas. Furthermore, CPs and MPs were found to enhance nitrification, denitrification and anammox processes, which was evidenced by the higher abundance of genes associated with nitrification and denitrification, as well as increased activity of denitrification and anammox in the CPs and MPs-treatment groups compared to the control group. Additionally, the enhanced influence of CPs and MPs on denitrification was expected to promote nitrate-dependent and sulfate-dependent anaerobic oxidation of methane, thereby resulting in less methane released into the environment. These findings shed light on the potential consequences of simultaneous exposure to CPs and MPs on biogeochemical nitrogen cycling in deep-sea cold seep sediments.

Prognostic Value of Plasma Immunoglobulin G N-Glycome Traits in Pulmonary Arterial Hypertension.

BACKGROUND: B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide is the only blood biomarker in established risk calculators for pulmonary arterial hypertension (PAH). Profiling systemic-originated plasma immunoglobulin G (IgG) N-glycans, which reflect different components of the pathophysiology of PAH including immune dysregulation and inflammation, may improve PAH risk assessment. OBJECTIVES: This study sought to identify plasma IgG N-glycan biomarkers that predict survival in PAH to improve risk assessment. METHODS: This cohort study examined 622 PAH patients from 2 national centers (Beijing [discovery] cohort: n = 273; Shanghai [validation] cohort: n = 349). Plasma IgG N-glycomes were profiled by a robust mass spectrometry-based method. Prognostic IgG N-glycan traits were identified and validated in the 2 cohorts using Cox regression and Kaplan-Meier survival analyses. The added value of IgG N-glycan traits to previously established risk models was assessed using Harrell C-indexes and survival analysis. RESULTS: Plasma IgG fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377; 95% CI: 0.168-0.845; P = 0.018) with confirmation in the validation cohort (HR: 0.445; 95% CI: 0.264-0.751; P = 0.005). IgG fucosylation remained a robust predictor of mortality in combined cohorts after full adjustment and in subgroup analyses. Integrating IgG fucosylation into previously established risk models improved their predictive capacity, marked by an overall elevation in Harrell C-indexes. IgG fucosylation was useful in further stratifying the intermediate-risk patients classified by a previously established model. CONCLUSIONS: Plasma IgG fucosylation informs PAH prognosis independent of established factors, offering additional value for predicting PAH outcomes.

Comparison of Subjective and Biomechanical Outcomes Between Proprioceptive Training and Modified Broström-Gould Surgery for Chronic Ankle Instability: A Randomized Controlled Trial.

Background: Both proprioceptive training and modified Broström-Gould surgery can improve ankle stability in patients with chronic ankle instability (CAI), but further biomechanical evaluation is necessary to determine the optimal treatment. Purpose: To compare the clinical outcomes and biomechanical changes after proprioceptive training versus modified Broström-Gould surgery in patients with CAI. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 56 patients with CAI were assigned randomly to either a nonoperative group (n = 28) who underwent 3 months of proprioceptive training or an operative group (n = 28) who underwent modified Broström-Gould surgery. Foot and Ankle Ability Measure (FAAM) scores, foot pressure during walking, center of pressure (COP) velocity, and time for the COP to reach the balance boundary (time to boundary [TTB]) during single-leg standing were collected before the intervention (baseline) and at 3, 6, and 12 months after the intervention. Two-way repeated-measures analysis of variance was used to compare group differences and changes over time. Results: The nonoperative group had significant improvements from baseline in FAAM-Sports score and significantly decreased TTB in both the anterior-posterior and medial-lateral directions at all timepoints, while the operative group showed significant improvements only in FAAM-Sports scores and TTB and COP velocity in the anterior-posterior direction at 6 and 12 months postintervention. During walking, the nonoperative group had significantly increased peak force under the medial foot at 3 months, which dropped back to baseline levels at 12 months, while the operative group had significantly increased peak force under the medial midfoot and hindfoot that persisted until 12 months (P < .05). Conclusion: In this study, both proprioceptive training and modified Broström-Gould surgery led to improved subjective functional scores, foot pressure distribution during walking, and postural stability during standing for patients with CAI but with different biomechanical patterns. Proprioceptive training led to an earlier recovery of sports function and better medial-lateral stability recovery, while surgery provided more persistent results. Registration: ChiCTR1900023999 (Chinese Clinical Trial Registry).

Research Progress on the Microstructure Evolution Mechanisms of Al-Mg Alloys by Severe Plastic Deformation.

Al-Mg alloys are widely used as important engineering structural materials in aerospace engineering, transportation systems, and structural constructions due to their low density, high specific strength, corrosion resistance, welding capability, fatigue strength, and cost-effectiveness. However, the conventional Al-Mg alloys can no longer fully satisfy the demands of practical production due to difficulties caused by many defects. The high strength of Al-Mg alloys as non-heat treatment precipitation-strengthened alloys is achieved primarily by solid solution strengthening along with work hardening rather than precipitation strengthening. Therefore, severe plastic deformation (SPD) techniques can be often used to produce ultrafine-grained structures to fabricate ultra-high strength aluminum alloys. However, this approach often achieves the strengthening of material at the cost of reduced ductility. This paper comprehensively summarizes the various approaches of ultrafine/nanocrystalline materials for enhancing their plasticity, elaborates on the creation of a bimodal microstructure within the alloy, and discusses the formation of a nanotwin microstructure within the alloy and the incorporation of dispersed nanoparticles. The mechanisms underlying both the strengthening and toughening during large plastic deformation in aluminum alloys are summarized, and the future research direction of high-performance ultrafine crystalline and nanocrystalline Al-Mg aluminum alloys is prospected.

Characterization of larval gut microbiota of two endoparasitoid wasps associated with their common host, Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae).

Insect gut microbes play important roles in digestion, metabolism, development, and environmental adaptation. Parasitoid wasps are one of the most important biological control agents in pest control, while the gut microbial species compositions and the associated functions have been poorly investigated. Two endoparasitoid wasps, Cotesia vestalis and Diadromus collaris, parasitize the larval stage and pupal stage of the diamondback moth, Plutella xylostella, respectively. Using whole-genome shotgun metagenomic sequencing, we characterized the gut microbial composition, diversity, and potential functional roles associated with the two parasitoid wasp larvae. The results reveal that Proteobacteria and Firmicutes are the dominant phyla in the gut of C. vestalis and D. collaris larvae, with Rhizobium and Enterococcus being the dominant genera. The putative microbial functions associated with the two parasitoid wasps might play a virtual role in assisting in consuming the host's nutritional composition. The enriched CAZymes family genes are primarily involved in the degradation and synthesis of chitin. Despite the richness of microbial species and communities, the microbes species and the microbial community structure exhibit significant similarity between the two parasitoid wasps and between the parasitoid wasp and the host P. xylostella. Notably, the prevalence of the genus Enterococcus shared among them suggests a possible link of gut microbes between the host and their associated parasitoids. Our study offers insights into the gut microbe-based interactions between the host and parasitoid wasps for the first time, potentially paving the way for the development of an ecologically friendly biocontrol strategy against the pest P. xylostella.IMPORTANCEEndoparasitoid wasps spend the majority of their lifespan within their host and heavily rely on the host's nutrition for survival. There is limited understanding regarding the composition and physiological impacts of gut microbial communities in parasitoid wasps, particularly during the larval stage, which is directly linked to the host. Based on a thorough characterization of the gut microbe and comprehensive comparative analysis, we found the microbial species of the larval parasitoid wasp Cotesia vestalis and the pupal parasitoid wasp Diadromus collaris were similar, sharing 159 genera and 277 species, as were the microbial community structure. Certain of the dominant microbial strains of the two parasitoid wasps were similar to that of their host Plutella xylostella larvae, revealing host insect may affect the microbial community of the parasitoid wasps. The putative microbial functions associated with the parasitoid wasp larvae play an important role in dietary consumption.

Effects of alligator weed invasion on wetlands in protected areas: A case study of Lishui Jiulong National Wetland Park.

Wetlands are one of the ecosystems most easily and severely invaded by alien species. Biological invasions can have significant impacts on local plant communities and ecosystem functioning. While numerous studies have assessed the impacts of biological invasions on wetlands, relatively few have been conducted in protected areas such as national wetland parks. We conducted a field survey to investigate the effects of the invasive herb Alternanthera philoxeroides (alligator weed) on the productivity and structure of plant communities and soil microbial communities in the Lishui Jiulong National Wetland Park in Zhejiang, China. We also examined the potential influence of the distance to the river edge on the impact of the alligator weed invasion. The alligator weed invasion significantly altered the plant community structure. It reduced the coverage of co-occurring plant species, including native (-31.2 %), invasive (-70.1 %), and non-invasive alien plants (-58.4 %). However, it increased species richness by 50 %, Pielou's evenness by 20 %, and Simpson's diversity index by 29.1 % for the overall plant community. Furthermore, within the community not invaded by alligator weed, increasing the distance to the river edge decreased the number of native plants by 57.0 % and the aboveground biomass of other invasive plants by 78.6 %. Contrary to expectations, no effects of the alligator weed invasion were observed on soil fungal and bacterial communities. Therefore, the impacts of the alligator weed invasion varied with spatial context and plant category, emphasizing the need to consider multiple scales and environmental factors when assessing the effects of invasive species on plant biodiversity. These insights enhance our understanding of plant invasions in wetlands and can guide the development of effective management strategies for these important ecosystems.

The Role of Microvascular Variations in the Process of Intervertebral Disk Degeneration and Its Regulatory Mechanisms: A Literature Review.

Microvascular changes are considered key factors in the process of intervertebral disk degeneration (IDD). Microvascular invasion and growth into the nucleus pulposus (NP) and cartilaginous endplates are unfavorable factors that trigger IDD. In contrast, the rich distribution of microvessels in the bony endplates and outer layers of the annulus fibrosus is an important safeguard for the nutrient supply and metabolism of the intervertebral disk (IVD). In particular, the adequate supply of microvessels in the bony endplates is the main source of the nutritional supply for the entire IVD. Microvessels can affect the progression of IDD through a variety of pathways. Many studies have explored the effects of microvessel alterations in the NP, annulus fibrosus, cartilaginous endplates, and bony endplates on the local microenvironment through inflammation, apoptosis, and senescence. Studies also elucidated the important roles of microvessel alterations in the process of IDD, as well as conducted in-depth explorations of cytokines and biologics that can inhibit or promote the ingrowth of microvessels. Therefore, the present manuscript reviews the published literature on the effects of microvascular changes on IVD to summarize the roles of microvessels in IVD and elaborate on the mechanisms of action that promote or inhibit de novo microvessel formation in IVD.

Probing the capacity of a spatiotemporal deep learning model for short-term PM2.5 forecasts in a coastal urban area.

Accurate forecast of fine particulate matter (PM2.5) is crucial for city air pollution control, yet remains challenging due to the complex urban atmospheric chemical and physical processes. Recently deep learning has been routinely applied for better urban PM2.5 forecasts. However, their capacity to represent the spatiotemporal urban atmospheric processes remains underexplored, especially compared with traditional approaches such as chemistry-transport models (CTMs) and shallow statistical methods other than deep learning. Here we probe such urban-scale representation capacity of a spatiotemporal deep learning (STDL) model for 24-hour short-term PM2.5 forecasts at six urban stations in Rizhao, a coastal city in China. Compared with two operational CTMs and three statistical models, the STDL model shows its superiority with improvements in all five evaluation metrics, notably in root mean square error (RMSE) for forecasts at lead times within 12 h with reductions of 49.8 % and 47.8 % respectively. This demonstrates the STDL model's capacity to represent nonlinear small-scale phenomena such as street-level emissions and urban meteorology that are in general not well represented in either CTMs or shallow statistical models. This gain of small-scale representation in forecast performance decreases at increasing lead times, leading to similar RMSEs to the statistical methods (linear shallow representations) at about 12 h and to the CTMs (mesoscale representations) at 24 h. The STDL model performs especially well in winter, when complex urban physical and chemical processes dominate the frequent severe air pollution, and in moisture conditions fostering hygroscopic growth of particles. The DL-based PM2.5 forecasts align with observed trends under various humidity and wind conditions. Such investigation into the potential and limitations of deep learning representation for urban PM2.5 forecasting could hopefully inspire further fusion of distinct representations from CTMs and deep networks to break the conventional limits of short-term PM2.5 forecasts.

The impact of vitamin E, vitamin B6, and niacin intake on cataract incidence based on NHANES 2005-2008 data.

Objective: This investigation aims to elucidate the correlations between dietary intakes of vitamin E, B6, and niacin and the incidence of cataracts, utilizing the comprehensive NHANES 2005-2008 dataset to affirm the prophylactic roles of these nutrients against cataract formation. Methods: Using data from the NHANES 2005-2008 cycles, this analysis concentrated on 7,247 subjects after exclusion based on incomplete dietary or cataract data. The identification of cataracts was determined through participants' self-reported ophthalmic surgical history. Nutritional intake was gauged using the automated multiple pass method, and the data were analyzed using logistic and quantile regression analyses to investigate the relationship between vitamin consumption and cataract prevalence. Results: Our analysis identified significant inverse associations between the intake of vitamins E, B6, and niacin and the risk of cataract development. Specifically, higher intakes of vitamin B6 (OR = 0.85, 95% CI = 0.76-0.96, p = 0.0073) and niacin (OR = 0.98, 95% CI = 0.97-1.00, p = 0.0067) in the top quartile were significantly associated with a reduced likelihood of cataract occurrence. Vitamin E intake showed a consistent reduction in cataract risk across different intake levels (OR = 0.96, 95% CI = 0.94-0.99, p = 0.0087), demonstrating a nonlinear inverse correlation. Conclusion: The outcomes indicate that elevated consumption of vitamin B6 and niacin, in conjunction with regular vitamin E intake, may have the potential to delay or prevent cataract genesis. These results suggest a novel nutritional strategy for cataract prevention and management, advocating that focused nutrient supplementation could be instrumental in preserving eye health and reducing the risk of cataracts. Further research is recommended to validate these findings and establish optimal dosages for maximum benefit.

Discovery of cycloheptapeptides phakefusins A-E from the marine sponge Phakellia fusca based on molecular networking.

Guided by a probe-based molecular networking strategy, five undescribed cycloheptapeptides, phakefusins A-E (1-5), were isolated from the marine sponge Phakellia fusca. Compounds 1 and 2 contain the nonproteinogenic amino acid residues of dioxindolyalanine (Dioia) and ß-3-oxindolylalanine (Oia), respectively. Compound 3 possesses a unique methionine sulfoxide, whereas compound 5 includes a glutamic acid ethyl ester unit. Their structures were elucidated through NMR spectroscopy, HR-MS/MS analysis, and the advanced Marfey's method. By synthesizing the (S, S/R)-Oia standard through tryptophan oxidation, we determined the configuration of this amino acid in compound 2 using the advanced Marfey's method. These cycloheptapeptides were evaluated for their antitumor, antibacterial, and antioxidant activities. Compound 1 showed moderate cytotoxicity against MCF-7 and PC9 cells, with IC50 values of 6.8 and 9.6 µM, respectively, while compounds 2-5 demonstrated potential antioxidant effects by upregulating HO-1, NQO1, and SOD2 levels, as well as inducing Nrf2 activation.

Dye-doped cellulose nanocrystals as novel dusting powders for visualizing latent fingerprints.

Powder-dusting method based on the visual contrast between the background surface and powder-covered ridges of a fingerprint is widely used to develop the invisible latent fingerprints (LFPs) left at crime scenes. Recently, the development of nano-sized powders with excellent optical performances has been extensively explored. In this work, we employed environmentally friendly and low-toxicity cellulose nanocrystals as the novel support. Using dye-doped cellulose nanocrystals as novel dusting powders, two dyes (phenylfluorone and curcumin) were adsorbed on the cellulose nanocrystals by a simple batch adsorption method. The dye-doped cellulose nanocrystals (namely, phenylfluorone-doped cellulose nanocrystals (PDCN) and curcumin-doped cellulose nanocrystals (CDCN)) containing 2% of the loaded mass of both the dyes with bright green fluorescence were developed to visualize LFPs on the surfaces of various substrates (such as glass slide, printing paper, orange plastic card, tile, stainless steel, compact disc, red plastic packing, copper foil and aluminum foil). Images of the LFPs can been obtained by both the dye-doped cellulose nanocrystals with sufficient affinity to the ridges of LFPs. High-quality ridge details with features at the second and third level can be detected by CDCN, whereas PDCN only display the secondary-level features of ridge details. Compared with PDCN, CDCN illustrate higher sensitivity, higher selectivity, and better contrast, especially for detecting fresh and non-fresh LFPs on porous and non-porous substrates, and has the potential for practical use in forensic science.

Structural characterization and immune activity evaluation of a polysaccharide from Lyophyllum Decastes.

An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1-6-linked ß-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.

Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. AIM OF THE STUDY: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. MATERIALS AND METHODS: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. RESULTS: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. CONCLUSIONS: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.