Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.

Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc-/-, il2rga-/- zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and visualized therapeutic responses using a four-color FUCCI cell-cycle fluorescent reporter. These experiments identified that combination treatment arrested rhabdomyosarcoma cells in the G2 cell cycle prior to induction of apoptosis. Finally, patient-derived xenografts could be engrafted into our model, opening new avenues for developing personalized therapeutic approaches in the future.

NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer.

Deregulation of oncogenic signals in cancer triggers replication stress. Immediate early genes (IEGs) are rapidly and transiently expressed following stressful signals, contributing to an integrated response. Here, we find that the orphan nuclear receptor NR4A1 localizes across the gene body and 3' UTR of IEGs, where it inhibits transcriptional elongation by RNA Pol II, generating R-loops and accessible chromatin domains. Acute replication stress causes immediate dissociation of NR4A1 and a burst of transcriptionally poised IEG expression. Ectopic expression of NR4A1 enhances tumorigenesis by breast cancer cells, while its deletion leads to massive chromosomal instability and proliferative failure, driven by deregulated expression of its IEG target, FOS. Approximately half of breast and other primary cancers exhibit accessible chromatin domains at IEG gene bodies, consistent with this stress-regulatory pathway. Cancers that have retained this mechanism in adapting to oncogenic replication stress may be dependent on NR4A1 for their proliferation.

Genetically Encoded Lizard Color Divergence for Camouflage and Thermoregulation.

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.

Iron-Catalyzed Asymmetric Imidation of Sulfides via Sterically Biased Nitrene Transfer.

Transition-metal-catalyzed enantioselective nitrene transfer to sulfides has emerged as one of the most powerful strategies for rapid construction of enantioenriched sulfimides. However, achieving stereocontrol over highly active earth-abundant transition-metal nitrenoid intermediates remains a formidable challenge compared with precious metals. Herein, we disclose a chiral iron(II)/N,N'-dioxide-catalyzed enantioselective imidation of dialkyl and alkyl aryl sulfides using iminoiodinanes as nitrene precursors. A series of chiral sulfimides were obtained in moderate-to-good yields with high enantioselectivities (56 examples, up to 99% yield, 98:2 e.r.). The utility of this methodology was demonstrated by late-stage modification of complex molecules and synthesis of the chiral insecticide sulfoxaflor and the intermediates of related bioactive compounds. Based on experimental studies and theoretical calculations, a water-bonded high-spin iron nitrenoid species was identified as the key intermediate. The observed stereoselectivity was original from the steric repulsion between the amide unit of the ligand in the chiral cave and the bulky substituent of sulfides. Additionally, dioxazolones proved to be suitable acylnitrene precursors in the presence of an iron(III)/N,N'-dioxide complex, resulting in the formation of enantioselectivity-reversed sulfimides (14 examples, up to 81% yield, 97:3 e.r.).

Divergent Synthesis of Scabrolide A and Havellockate via an exo-exo-endo Radical Cascade.

Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo-exo-endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6-endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.

Zirconaaziridine-Mediated Ni-Catalyzed Diastereoselective C(sp2)-Glycosylation.

In the realm of organic synthesis, the catalytic and stereoselective formation of C-glycosidic bonds is a pivotal process, bridging carbohydrates with aglycones. However, the inherent chirality of the saccharide scaffold often has a substantial impact on the stereoinduction imposed by a chiral ligand. In this study, we have established an unprecedented zirconaaziridine-mediated asymmetric nickel catalysis, enabling the diastereoselective coupling of bench-stable glycosyl phosphates with a range of (hetero)aromatic and glycal iodides as feasible coupling electrophiles. Our developed method showcases a broad scope and a high tolerance for various functional groups. More importantly, precise stereocontrol toward both anomeric configurations of forming C(sp2)-glycosides can be realized by simply utilizing the popular chiral bioxazoline (biOx) ligands in this reductive Ni catalysis. Regarding the operating mechanism, both experimental and computational studies support the occurrence of a redox transmetalation process, leading to the formation of a transient, bimetallic Ni-Zr species that acts as a potent and efficient single-electron reductant in the catalytic process.

Rhodium-Catalyzed Highly Enantioselective Hydroboration of Acyclic Tetrasubstituted Alkenes Directed by an Amide.

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, enantioselective hydroboration of tetrasubstituted alkenes with high diastereo- and enantioselectivities continues as an unmet challenge since the 1950s due to its extremely low reactivity and the difficulties to simultaneously control the regio- and stereoselectivity of a tetrasubstituted alkene. Here, we report highly regio-, diastereo-, and enantioselective catalytic hydroboration of diverse acyclic tetrasubstituted alkenes. The delicate interplay of an electron-rich rhodium complex and coordination-assistance forms a highly adaptive catalyst that effectively overcomes the low reactivity and controls the stereoselectivity. The generality of the catalyst system is exemplified by its efficacy across various tetrasubstituted alkenes with diverse steric and electronic properties.

Nickel-Catalyzed Atroposelective C-H Alkylation Enabled by Bimetallic Catalysis with Air-Stable Heteroatom-Substituted Secondary Phosphine Oxide Preligands.

The catalytic asymmetric construction of axially chiral C-N atropisomers remains a formidable challenge due to their low rotational barriers and is largely reliant on toxic, cost-intensive, and precious metal catalysts. In sharp contrast, we herein describe the first nickel-catalyzed atroposelective C-H alkylation for the construction of C-N axially chiral compounds with the aid of a chiral heteroatom-substituted secondary phosphine oxide (HASPO)-ligated Ni-Al bimetallic catalyst. A wide range of alkenes, including terminal and internal alkenes, were well compatible with the reaction, providing a variety of benzimidazole derivatives in high yields and enantioselectivities (up to 97:3 e.r.). The key to success was the identification of novel HASPOs as highly effective chiral preligands. Mechanistic studies revealed the catalyst mode of action, and in-depth data science analysis elucidated the key features of the responsible chiral preligands in controlling the enantioselectivity.

Photoactivatable CRISPR/Cas12a Sensors for Biomarkers Imaging and Point-of-Care Diagnostics.

In recent years, the CRISPR/Cas12a-based sensing strategy has shown significant potential for specific target detection due to its rapid and sensitive characteristics. However, the "always active" biosensors are often insufficient to manipulate nucleic acid sensing with high spatiotemporal control. It remains crucial to develop nucleic acid sensing devices that can be activated at the desired time and space by a remotely applied stimulus. Here, we integrated photoactivation with the CRISPR/Cas12a system for DNA and RNA detection, aiming to provide high spatiotemporal control for nucleic acid sensing. By rationally designing the target recognition sequence, this photoactivation CRISPR/Cas12a system could recognize HPV16 and survivin, respectively. We combined the lateral flow assay strip test with the CRISPR/Cas12a system to realize the visualization of nucleic acid cleavage signals, displaying potential instant test application capabilities. Additionally, we also successfully realized the temporary control of its fluorescent sensing activity for survivin by photoactivation in vivo, allowing rapid detection of target nucleic acids and avoiding the risk of contamination from premature leaks during storage. Our strategy suggests that the CRISPR/Cas12a platform can be triggered by photoactivation to sense various targets, expanding the technical toolbox for precise biological and medical analysis. This study represents a significant advancement in nucleic acid sensing and has potential applications in disease diagnosis and treatment.

Allosteric Activator-Regulated CRISPR/Cas12a System Enables Biosensing and Imaging of Intracellular Endogenous and Exogenous Targets.

Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

The selective sponging of miRNAs by OIP5-AS1 regulates metabolic reprogramming of pyruvate in adenoma-carcinoma transition of human colorectal cancer.

RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.

Dissection of the antitumor mechanism of tetrandrine based on metabolite profiling and network pharmacology.

RATIONALE: Tetrandrine, the Q-marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated. METHODS: The metabolites of tetrandrine in rats were profiled using ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology. RESULTS: A total of 30 metabolites were characterized in rats after ingestion of tetrandrine (10 mg/kg), including 0 in plasma, 7 in urine, 11 in feces, 9 in liver, 8 in spleen, 4 in lung, 5 in kidney, 5 in heart, and 4 in brain. This study was the first to show the metabolic processes demethylation, hydroxylation, and carbonylation in tetrandrine. The pharmacology network results showed that tetrandrine and its metabolites could regulate AKT1, TNF, MMP9, MMP2, PAK1, and so on by involving in proteoglycan tumor pathway, PI3K-Akt signaling pathway, tumor pathway, MAPK signaling pathway, and Rap1 signaling pathway. CONCLUSIONS: The metabolism features of tetrandrine and its potential antitumor mechanism were summarized, providing data for further pharmacological validation.

Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Drug-coated balloon in the treatment of coronary artery de-novo large lesions angiography.

The superiority of drug-coated balloon (DCB) in treating small vessels, branching lesions, and high-risk bleeding lesions in coronary heart disease patients has been confirmed. However, its safety and efficacy in large vessels are still unclear. We aimed to investigate whether the efficacy of DCB in large vessels is not inferior to that of drug-eluting stent (DES). From November 2019 to April 2022, a total of 88 patients in our hospital who underwent coronary angiography for the first time and decided to receive DCB or DES treatment were selected. Indicators including late lumen loss (LLL), major adverse cardiovascular event (MACE) rate, major bleeding and all-cause mortality were evaluated at 9 months and 1-year post percutaneous coronary intervention (PCI) therapy. The primary endpoint of 9-month LLL was -0.07 in the DCB group and 0.19 mm in the DES group (p value＜0.001). 1-year cumulative MACE rates were similar in the DCB and DES groups (3.03% vs. 7.23%, P=0.519), TLR rates were similar (3.03% vs. 7.23%, P=0.519), Major bleeding was similar (3.03% vs. 5.45%, P=0.580), and 1 case of Cardiac death in DES group. For LLL, the DCB-only strategy was non-inferior to DES in treating de novo large lesions in the coronary arteries. Furthermore, the efficacy of DCB was comparable to DES at 1 year of follow-up for secondary clinical endpoints.

Correlation between triglyceride glucose-body mass index and hypertension risk: evidence from a cross-sectional study with 60,283 adults in eastern China.

BACKGROUND: Insulin resistance (IR) and obesity are established risk factors for hypertension, with triglyceride-glucose (TyG) serving as a recognized surrogate marker for IR. The aim of this study was to investigate the association between TyG-BMI and hypertension in the general population. METHODS: A total of 60,283 adults aged ≥18 years who underwent face-to-face questionnaires, anthropometric measurements, and laboratory examination were included in this study. Multivariable logistic regression models and receiver operating characteristic curve (ROC) were used to determine the association between TyG-BMI and hypertension. The restricted cubic spline model was used for the dose-response analysis. RESULTS: After fully adjusting for confounding variables, multivariate logistic regression model showed a stable positive association between TyG-BMI and hypertension (OR: 1.61 per SD increase; 95% CI: 1.55-1.67; P-trend < 0.001). The multivariate adjusted OR and 95% CI for the highest TyG-BMI quartile compared with the lowest quartile were 2.52 (95% CI 2.28-2.78). Dose-response analysis using restricted cubic spline confirmed that the association between TyG-BMI index and hypertension was linear. Subgroup analyses showed that stronger associations between TyG-BMI index and hypertension were detected in young and middle-aged individuals (P for interaction < 0.05). ROC analysis showed that TyG-BMI index could better predict the risk of hypertension than other parameters (TyG-BMI cut-off value: 207.105, AUC: 0.719, sensitivity 65.5%, specificity 66.8%), particularly among young and middle-aged people. CONCLUSION: The TyG-BMI index was independently associated with hypertension in the study population. Further studies are required to confirm this relationship.

Blockade of the ADAM8-Fra-1 complex attenuates neuroinflammation by suppressing the Map3k4/MAPKs axis after spinal cord injury.

BACKGROUND: Mechanical spinal cord injury (SCI) is a deteriorative neurological disorder, causing secondary neuroinflammation and neuropathy. ADAM8 is thought to be an extracellular metalloproteinase, which regulates proteolysis and cell adherence, but whether its intracellular region is involved in regulating neuroinflammation in microglia after SCI is unclear. METHODS: Using animal tissue RNA-Seq and clinical blood sample examinations, we found that a specific up-regulation of ADAM8 in microglia was associated with inflammation after SCI. In vitro, microglia stimulated by HMGB1, the tail region of ADAM8, promoted microglial inflammation, migration and proliferation by directly interacting with ERKs and Fra-1 to promote activation, then further activated Map3k4/JNKs/p38. Using SCI mice, we used BK-1361, a specific inhibitor of ADAM8, to treat these mice. RESULTS: The results showed that administration of BK-1361 attenuated the level of neuroinflammation and reduced microglial activation and recruitment by inhibiting the ADAM8/Fra-1 axis. Furthermore, treatment with BK-1361 alleviated glial scar formation, and also preserved myelin and axonal structures. The locomotor recovery of SCI mice treated with BK-1361 was therefore better than those without treatment. CONCLUSIONS: Taken together, the results showed that ADAM8 was a critical molecule, which positively regulated neuroinflammatory development and secondary pathogenesis by promoting microglial activation and migration. Mechanically, ADAM8 formed a complex with ERK and Fra-1 to further activate the Map3k4/JNK/p38 axis in microglia. Inhibition of ADAM8 by treatment with BK-1361 decreased the levels of neuroinflammation, glial formation, and neurohistological loss, leading to favorable improvement in locomotor functional recovery in SCI mice.

The Safety and Efficacy of ZelanteDVT™ Catheter Rheolytic Thrombectomy in the Treatment of Patients with Iliac Vein Stent Thrombosis.

BACKGROUND: To examine the safety and efficacy of ZelanteDVT™ catheter rheolytic thrombectomy in the treatment of patients with iliac vein stent thrombosis. METHODS: A retrospective analysis method was conducted by means of collecting the data of 32 patients who had completed the treatment of iliac vein stent thrombosis with ZelanteDVT catheter rheolytic thrombectomy from March 2019 to March 2023. Data on clinical characteristics, technical success, clinical success, complications, and early follow-up were analyzed. RESULTS: The technical success rates were 100%, intraoperatively, in which 22 cases were improved to thrombus clearance Grade II (50-90%), 10 were Grade III (>90%). There were 21 cases treated with subsequent catheter-directed thrombolysis, and the average urokinase administration of (120.90 ± 29.63)∗10ˆ4 units. The clinical success rates were 100% and the swelling of the affected limbs were significantly improved, a significant difference in the pre/postoperative between-thigh circumference difference [(5.16 ± 1.08) vs. (1.75 ± 0.84), P < 0.000]. The pre/postoperative Venous Clinical Severity Score was [(12.94 ± 1.70) vs. (7.44 ± 1.31), P < 0.000]. No serious complications occurred during the perioperative period. The postoperative and 12-month stent patency rate was 100.00% (32/32) and 71.88% (23/32), respectively. CONCLUSIONS: The ZelanteDVT catheter rheolytic thrombectomy seems to have a promising application prospect for the treatment of patients with iliac vein stent thrombosis.

Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis.

Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.

Association between movement behavior patterns and cardiovascular risk among Chinese adults aged 40-75: a sex-specific latent class analysis.

BACKGROUND: Cardiovascular disease (CVD) is a major global health threat, particularly in China, contributing to over 40% of deaths. While sleep behaviors, sedentary behaviors, and physical activities are recognized as independent lifestyle risk factors for CVD, there remains limited understanding of specific movement behavior patterns and their CVD risks, especially considering sex-specific differences. This study examines movement behavior patterns among Chinese adults (40-75) and their associations with cardiovascular risk, with a focus on sleep, physical activity (PA), and sedentary behavior (SB). METHODS: Data pertaining to 13,465 male participants and 15,613 female participants, collected from the Chronic Disease and Risk Factor Surveillance Survey in Nanjing from February 2020 to December 2022. The latent class analysis method was employed to identify underlying movement patterns across sexes. Multinomial logistic regression models assessed CVD risk, and the China-PAR model calculated 10-year risk. RESULTS: Three male and four female movement patterns emerged. Active Movers (17.10% males, 5.93% females) adhered to PA recommendations but had poorer sleep quality. Moderate Achievers (61.42% males, 45.32% females) demonstrated moderate behavior. Sedentary Sleepers (21.48% males, 10.20% females) exhibited minimal PA but good sleep. Female Moderate Physical Activity (MPA) Dominant Movers demonstrated a prevalent adherence to recommended MPA levels. Active movers had the lowest CVD risk. After adjusting for potential confounders, moderate achievers (OR = 1.462, 95% CI 1.212, 1.764) and sedentary sleepers (OR = 1.504, 95% CI 1.211, 1.868) were both identified as being associated with a high-risk of cardiovascular diseases (CVDs) compared to active movers in males, demonstrating a similar trend for intermediate risk. Such associations were not statistically significant among females. CONCLUSIONS: Our study revealed sex-specific movement patterns associated with CVD risks among middle-aged Chinese adults. We suggest that adopting an active movement behavior pattern, characterized by meeting or exceeding recommended levels of vigorous physical activity (VPA) and reducing sedentary behavior, is beneficial for all middle-aged adults, particularly males. An active lifestyle could help counteract the adverse effects of relatively poor sleep quality on the risk of developing CVD in this population. Integrating sleep, PA, and SB information provides a holistic framework for understanding and mitigating CVD risks.