Superspreading Surface with Hierarchical Porous Structure for Highly Efficient Vapor-Liquid Phase Change Heat Dissipation.

Superspreading surfaces with excellent water transport efficiency are highly desirable for addressing thermal failures through the liquid-vapor phase change of water in electronics thermal management applications. However, the trade-off between capillary pressure and viscous resistance in traditional superspreading surfaces with micro/ nanostructures poses a longstanding challenge in the development of superspreading surfaces with high cooling efficiency in confined spaces. Herein, a heat-treated hierarchical porous enhanced superspreading surface (HTHP) for highly efficient electronic cooling is proposed. Compared with the single porous structures in nanograss, nanosheets, and copper foam, HTHP with hierarchical honeycomb pores effectively resolves the trade-off effect by introducing large vertical through-pores to reduce viscous resistance, and connected small pores to provide sufficient capillary pressure synergistically. HTHP exhibits excellent capillary performance in both horizontal spreading and vertical rising. Despite a thickness of only 0.33 mm, the as-prepared ultrathin vapor chamber (UTVC) fabricated to exploit the superior capillary performance of HTHP achieved effective heat dissipation with outstanding thermal conductivity (12 121 Wm-1K-1), and low thermal resistance (0.1 KW-1) at a power of 5 W. This regulation strategy based on hierarchical honeycomb porous structures is expected to promote the development of high-performance superspreading surfaces with a wide range of applications in thermal management.

[A highly sensitive approach for the analysis of tyrosine phosphoproteome in primary T cells].

Tyrosine phosphorylation, a common post-translational modification process for proteins, is involved in a variety of biological processes. However, the abundance of tyrosine-phosphorylated proteins is very low, making their identification by mass spectrometry (MS) is difficult; thus, milligrams of the starting material are often required for their enrichment. For example, tyrosine phosphorylation plays an important role in T cell signal transduction. However, the number of primary T cells derived from biological tissue samples is very small, and these cells are difficult to culture and expand; thus, the study of T cell signal transduction is usually carried out on immortalized cell lines, which can be greatly expanded. However, the data from immortalized cell lines cannot fully mimic the signal transduction processes observed in the real physiological state, and they usually lead to conclusions that are quite different from those of primary T cells. Therefore, a highly sensitive proteomic method was developed for studying tyrosine phosphorylation modification signals in primary T cells. To address the issue of the limited T cells numbers, a comprehensive protocol was first optimized for the isolation, activation, and expansion of primary T cells from mouse spleen. CD3+ primary T cells were successfully sorted; more than 91% of the T cells collected were well activated on day 2, and the number of T cells expanded to over 7-fold on day 4. Next, to address the low abundance of tyrosine-phosphorylated proteins, we used SH2-superbinder affinity enrichment and immobilized Ti4+affinity chromatography (Ti4+-IMAC) to enrich the tyrosine-phosphorylated polypeptides of primary T cells that were co-stimulated with anti-CD3 and anti-CD28. These polypeptides were resolved using nanoscale liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). Finally, 282 tyrosine phosphorylation sites were successfully identified in 1 mg of protein, including many tyrosine phosphorylation sites on the immunoreceptor tyrosine-based activation motif (ITAM) in the intracellular region of the T cell receptor membrane protein CD3, as well as the phosphotyrosine sites of ZAP70, LAT, VAV1, and other proteins related to signal transduction under costimulatory conditions. In summary, to solve the technical problems of the limited number of primary cells, low abundance of tyrosine-phosphorylated proteins, and difficulty of detection by MS, we developed a comprehensive proteomic method for the in-depth analysis of tyrosine phosphorylation modification signals in primary T cells. This protocol may be applied to map signal transduction networks that are closely related to physiological states.

A combination of risk stratification systems for thyroid nodules and cervical lymph nodes may improve the diagnosis and management of thyroid nodules.

Introduction: To assess the performance of the European Thyroid Association Thyroid Imaging and Reporting Data System (EU-TIRADS) and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), which combine risk stratification systems for thyroid nodules (TN-RSS) and cervical lymph nodes (LN-RSS) in diagnosing malignant and metastatic thyroid cancer in a single referral center. Methods: We retrospectively analyzed 2,055 consecutive patients who underwent thyroidectomy or fine-needle aspiration (FNA) from January 2021 to December 2022. TNs and LNs were categorized according to the ultrasonography (US) features of EU-TIRADS and K-TIRADS, respectively. The diagnostic performance and postponed malignancy rate (PMR) were compared with those of EU-TIRADS and K-TIRADS. PMR was defined as the number of patients with malignant nodules not recommended for biopsy among patients with cervical LN metastasis. Results: According to the EU-TIRADS and K-TIRADS, for TN-RSS alone, there were no significant differences in sensitivity, specificity, accuracy, unnecessary FNA rate (UFR), missed malignancy rate (MMR), and PMR between the two TIRADSs (29.0% vs. 28.8%, 50.5% vs. 51.1%, 32.3% vs. 32.2%, 23.6% vs. 23.5%, 88.6% vs. 88.5%, and 54.2% vs. 54.5%, P > 0.05 for all). Combining the LN-RSS increased the diagnostic accuracy (42.7% vs. 32.3% in EU-TIRADS; 38.8% vs. 32.2% in K-TIRADS) and decreased the PMR (54.2% vs. 33.9% in EU-TIRADS; 54.5% vs. 39.3% in K-TIRADS). EU-TIRADS had higher sensitivity and accuracy and lower PMR than K-TIRADS (41.3% vs. 36.7%, 42.7% vs. 38.8%,33.9% vs. 39.3%, P < 0.05 for all). Conclusions: A combination of TN-RSS and LN-RSS for the management of thyroid nodules may be associated with a reduction in PMR, with enhanced sensitivity and accuracy for thyroid cancers in EU-TIRADS and K-TIRADS. These results may offer a new direction for the detection of aggressive thyroid cancers.

Effect of osmanthus hydrolat on the aroma quality and volatile components of osmanthus black tea.

Osmanthus fragrans is an evergreen shrub with a pleasant fragrance and a wide range of applications in many fields. The condensed hydrolat obtained during the drying process of its fresh flowers was collected in a low-temperature vacuum environment and its sensory evaluation and volatile components were studied. The main aroma compounds in Osmanthus fragrans were dihydro-ß-ionone, nonanal, ß-cyclocitral, ß-ionone, benzaldehyde, α-ionone, and 6-methyl-5-hepten-2-one, whose contents were used as the main evaluation criteria, and the hydrolats obtained under different scenting and drying times were compared. This process can effectively collect the aroma components in Osmanthus fragrans and the optimal drying conditions were 50 °C for 5 h. The hydrolat was used to provide the scent of osmanthus black tea, which had a fresher and mellower taste, while the fragrance of osmanthus was abundant. These results show that osmanthus hydrolat can be used to provide the scent of floral black tea. Chemical compounds studied in this article: (-)-Catechin (PubChem CID: 1203); (-)-epigallocatechin gallate (PubChem CID: 65064); (-)-epicatechin gallate (PubChem CID: 367141); (-)-epigallocatechin (PubChem CID: 72277); (-)-epicatechin (PubChem CID: 72276); (-)-gallocatechin gallate (PubChem CID: 199472); (-)-catechin gallate (PubChem CID: 6419835); (-)-gallocatechin (PubChem CID: 9882981).

Relationship between first trimester physical activity and premature rupture of membranes: a birth cohort study in Chinese women.

OBJECTIVE: This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. METHODS: A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. RESULTS: Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58-0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59-0.81, OR = 0.70, 95% CI 0.60-0.82, OR = 0.62, 95% CI 0.53-0.73 and OR = 0.82, 95% CI 0.70-0.97, respectively). CONCLUSIONS: High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. TRIAL REGISTRATION: The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.

Evolution of ferromagnetic cluster in perovskite La0.88Sr0.12MnO3 nanocrystalline detected by EPR spectrum.

Electron paramagnetic resonance (EPR) studies were performed on La0.88Sr0.12MnO3 (LSMO) nanocrystalline together with the measurement of its magnetization. Various spectrum parameters including line width, effective g-value and double-integrated intensities have been analyzed in detail. We found nonlinear behavior occurred in the inverse susceptibility far above the Curie temperature TC, indicating short-range ferromagnetic (FM) clusters and Griffiths-like phase behavior in the paramagnetic (PM) phase. Based on the variation of EPR spectra, except for a typical PM resonance peak, an extra resonance signal was observed in the lower field region and developed as temperature decreased from 320 K to 110 K, which gave a direct evidence of the existence of FM cluster in the PM region of LSMO nanocrystalline. We proposed that the appearance of the Griffiths phase was due to the short FM correlation in the PM regime enhanced by surface spin ordering.

The component and structure of interpersonal trust.

Prior research has identified trust trait, trust expectation, trust risk and trust behavior as integral components of interpersonal trust. However, there still lack an in-depth exploration of the structural relationships among these integral components-how these integral components collectively constitute interpersonal trust. The current study innovatively proposed that interpersonal trust is anchored by individual trust trait, mediated by the dynamic equilibrium between trust risk and trust expectation, and culminates in trust behavior as the outcome. Interpersonal trust results from the synergistic interplay of individual and environmental factors. We called such structural relationships as the pyramid structure model of interpersonal trust, and proved its rationality by empirical evidence.

Genome-wide association study for seedling heat tolerance under two temperature conditions in bread wheat (Triticum aestivum L.).

BACKGROUND: As the greenhouse effect intensifies, global temperatures are steadily increasing, posing a challenge to bread wheat (Triticum aestivum L.) production. It is imperative to comprehend the mechanism of high temperature tolerance in wheat and implement breeding programs to identify and develop heat-tolerant wheat germplasm and cultivars. RESULTS: To identify quantitative trait loci (QTL) related to heat stress tolerance (HST) at seedling stage in wheat, a panel of 253 wheat accessions which were re-sequenced used to conduct genome-wide association studies (GWAS) using the factored spectrally transformed linear mixed models (FaST-LMM). For most accessions, the growth of seedlings was found to be inhibited under heat stress. Analysis of the phenotypic data revealed that under heat stress conditions, the main root length, total root length, and shoot length of seedlings decreased by 47.46%, 49.29%, and 15.19%, respectively, compared to those in normal conditions. However, 17 varieties were identified as heat stress tolerant germplasm. Through GWAS analysis, a total of 115 QTLs were detected under both heat stress and normal conditions. Furthermore, 15 stable QTL-clusters associated with heat response were identified. By combining gene expression, haplotype analysis, and gene annotation information within the physical intervals of the 15 QTL-clusters, two novel candidate genes, TraesCS4B03G0152700/TaWRKY74-B and TraesCS4B03G0501400/TaSnRK3.15-B, were responsive to temperature and identified as potential regulators of HST in wheat at the seedling stage. CONCLUSIONS: This study conducted a detailed genetic analysis and successfully identified two genes potentially associated with HST in wheat at the seedling stage, laying a foundation to further dissect the regulatory mechanism underlying HST in wheat under high temperature conditions. Our finding could serve as genomic landmarks for wheat breeding aimed at improving adaptation to heat stress in the face of climate change.

Effect of ultrasound-assisted L-lysine treatment on pork meat quality and myofibrillar protein properties during postmortem aging.

This paper aimed to investigate the effects of ultrasound-assisted L-lysine treatment on meat quality and myofibrillar proteins (MPs) properties of pork longissimus dorsi during postmortem aging. The results revealed that the L-lysine (Lys) and/or ultrasound treatment significantly increased (p < 0.05) the water-holding capacity and tenderness of the pork during postmortem aging, while the ultrasound-assisted Lys treatment had the lowest cooking loss, pressurization loss, Warner-Bratzler shear force, and hardness. In addition, L-lysine and/or ultrasound treatment increased (p < 0.05) pH value, T21, and myofibrillar fragmentation index, while the ultrasound-assisted Lys treatment had the highest value. Meanwhile, the protein solubility was increased with Lys and/or ultrasound treatment during postmortem aging, and ultrasound-assisted Lys treatment had the highest solubility, reaching 88.19%, 92.98%, and 91.73% at 0, 1, and 3 days, respectively. The result of protein conformational characteristics showed that Lys and/or ultrasound treatment caused the unfolding of the α-helix structure, resulting in the exposure of more hydrophobic amino acids and buried sulfhydryl groups, ultimately enhancing MPs solubility. In summary, ultrasound-assisted Lys treatment altered the structure of MPs, resulting in the enhancement of the water-holding capacity and tenderness of the pork. PRACTICAL APPLICATION: This study showed that ultrasound-assisted L-lysine (Lys) treatment could enhance the water-holding capacity and tenderness of pork during postmortem aging. The results might provide a reference for the application of ultrasound-assisted Lys treatment on the improvement of pork meat quality. To facilitate practical applications in production, the development of medium and large-sized ultrasound equipment for conducting small-scale and pilot experiments is crucial for future research.

The correlation study between the length and angle of ascending aortic and the incidence risk of acute type A aortic dissection.

Objective: This study utilized computed tomography angiography (CTA) to assess the risk of acute type A aortic dissection (ATAAD) by analyzing the imaging morphology indicators of the ascending aorta, along with the relevant risk factors associated with aortic dissection. Methods: The study utilized a retrospective observational research design. The population consisted of 172 patients who received treatment in the Department of Cardiothoracic Surgery at Qilu Hospital, Shandong University, from January 2018 to December 2022. The patients were divided into two groups: the ATAAD group (n = 97) and the thoracic aortic aneurysm group (TAA, n = 75). Demographic data and ascending aorta CTA measurements were collected from all patients. Single factor and multivariate logistic regression were employed to analyze the statistical differences in clinical data and ascending aorta CTA imaging morphology indicators between the two groups. Results: The variables were included in logistic multivariate analysis for further screening, indicating that the length of the ascending aorta (LAA) before ATAAD (OR = 3.365; 95% CI :1.742-6.500, P<0.001), ascending arch angle (asc-arch angle, OR = 0.902; 95% CI: 0.816-0.996, P = 0.042) and the maximum aortic diameter (MAD) before ATAAD, (OR = 0.614; 95% CI: 0.507-0.743, P<0.001) showed statistically significant differences. Conclusions: This study suggests that increased LAA and MAD, as well as a smaller asc-arch angle may be high-risk factors for the onset of ATAAD.

Comparison of ultrasound risk stratification systems for pediatric thyroid nodules.

Background: There is currently insufficient data to validate adult-based US risk stratification systems (RSSs) for the identification of malignant thyroid nodules in a pediatric population. Methods: From October 2016 and May 2023, 173 thyroid nodules of pediatric patients (age ≤ 18 years) with definitive pathology results and ultrasound (US) examination within 1 month before surgery or fine-needle aspiration (FNA) biopsy in our institution were enrolled in this study. The clinical and US characteristics of these nodules were retrospectively reviewed and categorized according to the ACR-TIRADS, C-TIRADS, and ATA guidelines. The diagnostic performance of US-based FNA criteria (original and simulating) of the three guidelines in thyroid cancer detection was estimated. Results: The three RSSs had similar AUC according to the categories(0.849-0.852, all P > 0.05). When combined with the original FNA criteria of the three RSSs to manage the nodules, the FNA rate of ACR-TIRADS and C-TIRADS were significantly less than ATA guidelines (53.18% vs. 64.63%, P < 0.05, and 52.60% vs. 64.63%, P < 0.05). The missed malignancy rate (MMR) and unnecessary FNA rate (UFR) of ATA guidelines (50.00%, 35.85%) was highest among the three RSSs, followed by the C-TIRADS (37.80%, 19.57%) and the ACR-TIRADS (37.04%, 19.57%). When nodules < 1 cm with the highest category in each RSS biopsied, that is when using the simulating FNA thresholds, the MMR was reduced overall (all P < 0.001), without a change in the UFR (all P > 0.05). All the three RSSs showed a substantial improvement in accuracy and malignant detection rate (all P < 0.05). Conclusion: The ACR-TIRADS, C-TIRADS, and ATA guidelines showed high missed malignancy rates when using their original recommended FNA criteria. When nodules < 1 cm with the highest category in each RSS biopsied, the missed malignancy rate of each RSS was decreased. Decreasing the FNA thresholds for highly suspicious malignant nodules may therefore be an effective means of managing malignant thyroid nodules in pediatric patients.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Corilagin Inhibits Neutrophil Extracellular Trap Formation and Protects against Hydrochloric Acid/Lipopolysaccharide-Induced Acute Lung Injury in Mice by Suppressing the STAT3 and NOX2 Signaling Pathways.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are characterized by uncontrolled inflammatory responses, neutrophil activation and infiltration, damage to the alveolar capillary membrane, and diffuse alveolar injury. Neutrophil extracellular traps (NETs), formed by activated neutrophils, contribute significantly to various inflammatory disorders and can lead to tissue damage and organ dysfunction. Corilagin, a compound found in Phyllanthus urinaria, possesses antioxidative and anti-inflammatory properties. In this study, we investigated the protective effects and underlying mechanisms of corilagin in hydrochloric acid (HCl)/lipopolysaccharide (LPS)-induced lung injury. Mice received intraperitoneal administration of corilagin (2.5, 5, or 10 mg/kg) or an equal volume of saline 30 min after intratracheal HCl/LPS administration. After 20 h, lung tissues were collected for analysis. Corilagin treatment significantly mitigated lung injury, as evidenced by reduced inflammatory cell infiltration, decreased production of proinflammatory cytokines, and alleviated oxidative stress. Furthermore, corilagin treatment suppressed neutrophil elastase expression, reduced NET formation, and inhibited the expression of ERK, p38, AKT, STAT3, and NOX2. Our findings suggest that corilagin inhibits NET formation and protects against HCl/LPS-induced ALI in mice by modulating the STAT3 and NOX2 signaling pathways.

Investigation of Microstructure, Oxides, Cracks, and Mechanical Properties of Ti-4Al-2V Joints Prepared Using Underwater Wet Laser Welding.

Developing advanced underwater welding technology for titanium, which is the key structural material for underwater applications, is of great significance for the design, fabrication, and maintenance of submarine equipment. In this study, in order to investigate the underwater welding microstructure and mechanical properties of Ti-4Al-2V alloy, underwater wet laser welding was conducted on Ti-4Al-2V alloy using varying laser power. The microstructure and properties of the welding joints were characterized and analyzed. The microstructure of the heat-affected zone and fusion zone in the welding joints are not significantly different from those of welding in air, but a mixed oxide layer composed of Al2O3 and TiO2 is formed on the surface of the fusion zone. Due to internal stress, a large number of cracks initiate on the oxide layer and propagate to the joints. In the 4 kW and 5 kW joints, a penetrating crack formed due to the excessive accumulation of internal stress breaking up the α phase. The mechanical properties of the joints are significantly affected by the laser power. The tensile strength of the 3 kW and 4 kW joints is comparable to that of the base metal, which is about 600 MPa, while the 5 kW joint shows brittle fracture with no plastic deformation and 228 MPa strength. This research lays a solid foundation for understanding the underwater wet laser welding behavior of titanium alloys.

Resting state functional connectome in breast cancer patients with fear of cancer recurrence.

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.

Associations of physical activity intensity, frequency, duration, and volume with the incidence of sarcopenia in middle-aged and older adults: a 4-year longitudinal study in China.

BACKGROUND: Physical activity (PA) plays an important role in the process of several chronic diseases. It may be also associated with the incidence of sarcopenia. This study aimed to determine the association of PA from different components including frequency, duration, intensity, and volume with the incidence of sarcopenia in middle-aged and older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study in 2011 and 2015. A total of 3,760 individuals aged ≥ 40 years were involved in this study. Sarcopenia was diagnosed using muscle mass, strength and physical performance according to the Asian Working Group for Sarcopenia. PA information including frequency, duration, intensity, and volume was obtained by a self-reported questionnaire. Logistic regression analysis was employed to examine the association between PA and the incidence of sarcopenia at 4-year follow-up. RESULTS: The incidence of sarcopenia was 5.9% during the 4-year follow-up. Compared to sedentary individuals, those taking 1-2 days or more per week, or a minimum of 10 min each time on vigorous-intensity PA (VPA) had a lower incidence of sarcopenia. Adults spending 3 days or more each week, a minimum of 30 min each time, or 150 min or more per week on moderate-intensity PA (MPA) had a lower presence of sarcopenia than sedentary adults. Adults taking 3 days or more per week, at least 30 min each time, or 150 min or more each week on light-intensity PA (LPA) tended to have a lower incidence of sarcopenia than sedentary individuals. Sensitivity analyses confirmed the robustness of the findings after removing persons with hypertension, dyslipidemia, or diabetes. CONCLUSIONS: These findings suggest that the frequency, duration, and volume of VPA or MPA are negatively associated with the presence of sarcopenia. Participation in LPA tends to have a lower incidence of sarcopenia in middle-aged and older adults.

The Modulation of Phospho-Extracellular Signal-Regulated Kinase and Phospho-Protein Kinase B Signaling Pathways plus Activity of Macrophage-Stimulating Protein Contribute to the Protective Effect of Stachydrine on Acetaminophen-Induced Liver Injury.

Stachydrine, a prominent bioactive alkaloid derived from Leonurus heterophyllus, is a significant herb in traditional medicine. It has been noted for its anti-inflammatory and antioxidant characteristics. Consequently, we conducted a study of its hepatoprotective effect and the fundamental mechanisms involved in acetaminophen (APAP)-induced liver injury, utilizing a mouse model. Mice were intraperitoneally administered a hepatotoxic dose of APAP (300 mg/kg). Thirty minutes after APAP administration, mice were treated with different concentrations of stachydrine (0, 2.5, 5, and 10 mg/kg). Animals were sacrificed 16 h after APAP injection for serum and liver tissue assays. APAP overdose significantly elevated the serum alanine transferase levels, hepatic pro-inflammatory cytokines, malondialdehyde activity, phospho-extracellular signal-regulated kinase (ERK), phospho-protein kinase B (AKT), and macrophage-stimulating protein expression. Stachydrine treatment significantly decreased these parameters in mice with APAP-induced liver damage. Our results suggest that stachydrine may be a promising beneficial target in the prevention of APAP-induced liver damage through attenuation of the inflammatory response, inhibition of the ERK and AKT pathways, and expression of macrophage-stimulating proteins.

Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis.

BACKGROUND: It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. METHODS: In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. RESULTS: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors. CONCLUSIONS: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.

Phase I, first-in-human study of XTR004, a novel 18F-labeled tracer for myocardial perfusion PET: Biodistribution, radiation dosimetry, pharmacokinetics, and safety after a single injection at rest.

OBJECTIVES: This study assessed the imaging characteristics, pharmacokinetics and safety of XTR004, a novel 18F-labeled Positron Emission Tomography (PET) myocardial perfusion imaging tracer, after a single injection at rest in humans. METHODS: Eleven healthy subjects (eight men and three women) received intravenous XTR004 (239-290 megabecquerel [MBq]). Safety profiles were monitored on the dosing day and three follow-up visits. Multiple whole-body PET scans were conducted over 4.7 h to evaluate biodistribution and radiation dosimetry. Blood and urine samples collected for 7.25 h were metabolically corrected to characterize pharmacokinetics. RESULTS: In the first 0-12 min PET images of ten subjects, liver (26.81 ± 4.01), kidney (11.43 ± 2.49), lung (6.75 ± 1.76), myocardium (4.72 ± 0.67) and spleen (3.1 ± 0.84) exhibited the highest percentage of the injected dose (%ID). Myocardial uptake of XTR004 in the myocardium initially reached 4.72 %ID and 7.06 g/mL, and negligibly changed within an hour (Δ: 7.20%, 5.95%). The metabolically corrected plasma peaked at 2.5 min (0.0013896 %ID/g) and halved at 45.2 min. Whole-body effective dose was 0.0165 millisievert (mSv)/MBq. Cumulative urine excretion was 8.18%. Treatment-related adverse events occurred in seven out of eleven subjects (63.6%), but no severe adverse event was reported. CONCLUSIONS: XTR004 demonstrated a favorable safety profile, rapid, high, and stable myocardial uptake and excellent potential for PET myocardial perfusion imaging (MPI). Further exploration of XTR004 PET MPI for detecting myocardial ischemia is warranted.

Combined analysis of transcriptomics and metabolomics provide insights into the antibacterial mechanism of bacteriocin XJS01 against multidrug-resistant Staphylococcus aureus.

Multidrug-resistant (MDR) bacteria are widespread in the environment and pose a serious threat to public health. It has been shown that bacteriocins have a great potential in controlling MDR pathogens, including Staphylococcus aureus. A previously reported Lactobacillus salivarius bacteriocin XJS01 exhibited good antibacterial activity against MDR S. aureus 2612:1606BL1486 (henceforth referred to as S. aureus_26), but its molecular mechanism remains unknown. Herein, we investigated the antibacterial mechanism of XJS01 on S. aureus_26 using an approach combining transcriptomics and metabolomics. The results showed that XJS01 induced significant changes at both transcriptional and metabolic levels in S. aureus_26. In total, 231 differentially expressed genes (DEGs) and 206 differentially abundance metabolites (DAMs) were identified in S. aureus_26 treated with 1 × MIC (minimum inhibition concentration) XJS01 compared with untreated (XJS01-free) cells (control). Functional analysis revealed that these DEGs and DAMs, alone with the related pathways and biological processes, were typically involved in stress response, being primarily related to metal uptake, cell virulence, self-help mechanism, amino acid and energy metabolism, bacterial stress response (e.g., two-component system), and membrane transport (e.g., phosphotransferase system). Overall, this study uncovered the multi-target effects of bacteriocins against MDR S. aureus at the genome-wide transcriptional and metabolic levels. These findings might be useful in the development of bacteriocins for the control of MDR S. aureus and other drug-resistant bacteria.