Assessment of Acute Mountain Sickness: Comparing the Chinese AMS Score to the Lake Louise Score.

Wu, Yu, Wenqi Zhao, Bao Liu, Jianyang Zhang, Zhifeng Zhong, Simin Zhou, Jiaxin Xie, Yuqi Gao, Peng Li, and Jian Chen. Assessment of Acute Mountain Sickness: Comparing the Chinese Ams Score to the Lake Louise Score. High Alt Med Biol 00:000-000, 2024. Objective: To compare the ability of the Chinese AMS Score (CAS) to detect acute mountain sickness (AMS) using the 2018 version of the Lake Louise Score (LLS) as reference. Methods: After flying from Chengdu (altitude: 500 m) to Lhasa (3,658 m), 2,486 young men completed a questionnaire. The questionnaire contained LLS and CAS items. An LLS ≥3 and/or a CAS ≥cutoff were used as the criteria for AMS. Hierarchical cluster analysis and two-step cluster analysis were used to investigate relationships between the symptoms. Results: AMS incidence rates were 33.8% (n = 840) with the LLS and 59.3% (n = 1,473) with the CAS (χ2 = 872.5, p < 0.001). The LLS and CAS had a linear relationship (orthogonal regression, Pearson r = 0.91, p < 0.001). With the LLS as the standard, the CAS had high diagnostic accuracy (area under the curve = 0.95, 95% confidence interval: 0.94-0.96). However, with the CAS, 25.5% (n = 633) more participants were labeled as having AMS than with the LLS (false positives). Two clusters were identified: one with headache only (419 participants, 66.2%) and one without headache but with other symptoms (214 participants, 33.8%). Reducing the weight of headache in the CAS allowed to align CAS and LLS. Conclusion: In comparison to the LLS, the CAS has a sensitivity close to 100% but lacks specificity given the high rate of false positives. The different weight of headaches may be the main reason for the discrepancy.

Interactions between nanoparticles and lymphatic systems: Mechanisms and applications in drug delivery.

The lymphatic system has garnered significant attention in drug delivery research due to the advantages it offers, such as enhancing systemic exposure and enabling lymph node targeting for nanomedicines via the lymphatic delivery route. The journey of drug carriers involves transport from the administration site to the lymphatic vessels, traversing the lymph before entering the bloodstream or targeting specific lymph nodes. However, the anatomical and physiological barriers of the lymphatic system play a pivotal role in influencing the behavior and efficiency of carriers. To expedite research and subsequent clinical translation, this review begins by introducing the composition and classification of the lymphatic system. Subsequently, we explore the routes and mechanisms through which nanoparticles enter lymphatic vessels and lymph nodes. The review further delves into the interactions between nanomedicine and body fluids at the administration site or within lymphatic vessels. Finally, we provide a comprehensive overview of recent advancements in lymphatic delivery systems, addressing the challenges and opportunities inherent in current systems for delivering macromolecules and vaccines.

[Water-soluble Inorganic Ion Content of PM2.5 and Its Change Characteristics in Urban Area of Beijing in 2022].

To explore the content and variation characteristics of water-soluble ions of atmospheric fine particles (PM2.5) in a Beijing urban area and put forward the pollution prevention and control scheme, the water-soluble ions, gaseous precursors (SO2, NO2), and meteorological factors (temperature, RH) of PM2.5 in 2022 were analyzed and determined. The results showed that the water-soluble ions with the highest proportion in PM2.5 in the Beijing City urban area were NO3-, NH4+, and SO42-, accounting for 52.7% of PM2.5. The mass concentrations of PM2.5 and SNA were lower than the historical results, whereas the proportion of SNA, SOR, and NOR was higher than the historical results. This showed that the fine particulate matter pollution in Beijing has been significantly improved, but it still has strong secondary pollution characteristics. NO3-/SO42-(2.2) was higher than those of historical and nearby provinces and cities, reflecting the expanding influence of mobile sources. In terms of seasonal variation, PM2.5 showed the characteristic of high in autumn and low in summer. The proportion of NO3- was the highest in autumn, spring, and winter; the proportion of SO42- was the highest in summer; and the proportion of NH4+ changed little in each season. The seasonal variation rules of NOR and SOR were almost opposite, which reflected the difference in transformation factors between NOR and SOR. The main forms of SNA in the Beijing urban area were NH4NO3 and (NH4)2SO4. The neutralization degree of cations and anions was the highest in winter, the cation NH4+ was slightly insufficient in summer, and NH4+ was in excess in spring and autumn. The Beijing urban area was an ammonia-rich environment. In terms of pollution level, RH, particulate matter moisture, and water-soluble ions mass concentration all increased with the increase in pollution level, and SNA increased fastest, with its proportion in PM2.5 increasing first and then stabilizing, whereas the contribution rate of other water-soluble ions decreased gradually. In terms of spatial distribution, the mass concentration relationship of SNA at the central urban area and suburbs was NO3- > SO42- > NH4+, which reflected the pollution characteristics dominated by NO3-. The highest contribution rate of SNA to PM2.5 occurred in the eastern region, the central urban area, and the transmission point, indicating that the secondary reaction was relatively active in the central urban area and the eastern region, and the regional transport was also an important source of secondary ions.

[Characteristics of Microplastic Pollution in Sediment of Silty Coast in Culture Bay].

Microplastic pollution is a central issue of great concern in the current environmental field. Microplastic pollution in marine environmental media is widely reported, but the characteristics of microplastic pollution in deep sediments are rarely reported. Based on this, three sampling points were set up on the muddy coast near the Haizhou Bay, a typical aquaculture sea area, to analyze the characteristics of microplastic pollution in sediment column samples. The study showed that the abundance of microplastics in the sediments of the study area was(0.12 ± 0.07)n·g-1, which was at the medium pollution level. The total amount of microplastics in the sediment column was 3.43-6.00 times the abundance of microplastics in the surface sediment (5 cm). The abundance of microplastics in the sediment column samples showed regional differences. There was no significant difference in the abundance of microplastics in the sediment at different depths, but the index decreased with the increase in depth. The relationship between sediment moisture content, depth, and microplastics indicated that the abundance of microplastics in sediment was related to the physical properties of the sediment. Transparent and black microplastics accounted for the highest proportion in each station. Fiber was the most common form of microplastics in the sediment, and microplastics with small particle size accounted for the majority. The density of microplastics did not prevent its appearance in the sediment. The pollution characteristics of microplastics varied greatly in different depths of sediments.

Two IFNa3s mediate the regulation of IRF9 in the process of infection with Streptococcus iniae in yellowfin seabream, Acanthopagrus latus (Hottuyn, 1782).

IRF9 can play an antibacterial role by regulating the type I interferon (IFN) pathway. Streptococcus iniae can cause many deaths of yellowfin seabream, Acanthopagrus latus in pond farming. Nevertheless, the regulatory mechanism of type I IFN signalling by A. latus IRF9 (AlIRF9) against S. iniae remains elucidated. In our study, AlIRF9 has a total cDNA length of 3200 bp and contains a 1311 bp ORF encoding a presumed 436 amino acids (aa). The genomic DNA sequence of AlIRF9 has nine exons and eight introns, and AlIRF9 was expressed in various tissues, containing the stomach, spleen, brain, skin, and liver, among which the highest expression was in the spleen. Moreover, AlIRF9 transcriptions in the spleen, liver, kidney, and brain were increased by S. iniae infection. By overexpression of AlIRF9, AlIRF9 is shown as a whole-cell distribution, mainly concentrated in the nucleus. Moreover, the promoter fragments of -415 to +192 bp and -311 to +196 bp were regarded as core sequences from two AlIFNa3s. The point mutation analyses verified that AlIFNa3 and AlIFNa3-like transcriptions are dependent on both M3 sites with AlIRF9. In addition, AlIRF9 could greatly reduce two AlIFNa3s and interferon signalling factors expressions. These results showed that in A. latus, both AlIFNa3 and AlIFNa3-like can mediate the regulation of AlIRF9 in the process of infection with S. iniae.

Explaining how childhood physical abuse and physical neglect influence adult depression: An analysis with multiple sequential mediators.

BACKGROUND: Substantial evidence indicates that experiencing physical abuse and neglect during childhood significantly elevates the likelihood of developing depression in adulthood. Nevertheless, there remains a dearth of understanding regarding the mechanisms underpinning this correlation. OBJECTIVE: In this study, we aimed to examine the associations of childhood physical abuse and physical neglect with depression using follow-up data from UK Biobank and quantified the contribution of smoking, insomnia, and BMI in these associations. PARTICIPANTS AND SETTINGS: This study included 144,704 participants (64,168 men and 80,536 women) from UK Biobank, most of whom were white (97 %). METHODS: Physical abuse and physical neglect were measured using two items of Childhood Trauma Screener (CTS). Data on the incidence of depression were obtained from primary care, hospital inpatient records, self-reported medical conditions, and death registries. We used a sequential mediation analysis based on the "g-formula" approach to explore the individual and joint effects of potential mediators. RESULTS: The depression incidence rate was 1.85 per 1000 person-years for men and 2.83 per 1000 person-years for women, respectively. Results of Cox proportional risk regression showed that physical abuse (HRs: 1.39-1.53, P < 0.001) and physical neglect (HRs: 1.43-1.60, P < 0.001) are associated with depression. Smoking, insomnia, and BMI together mediated 3 %-26 % of the associations. CONCLUSIONS: These findings contribute to our understanding of how physical abuse and physical neglect influence depression. Furthermore, a more effective reduction in the burden of depression can be achieved by managing modifiable mediators.

Association and biological pathways between lung function and incident depression: a prospective cohort study of 280,032 participants.

BACKGROUND: Lung health is increasingly recognized as an essential factor in mental health. However, prospective evidence on lung function with incident depression remains to be determined. The study aimed to examine the prospective association between impaired lung function and incident depression and the underlying biological mechanisms. METHODS: This prospective cohort study comprised 280,032 non-depressed individuals with valid lung function measurements from the UK Biobank. Lung function was assessed through the forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1). Cox proportional hazard models were applied to estimate the associations between lung function and incident depression. Mediation analyses were fitted to investigate the potential mediating role of biomarkers and metabolites in the association. RESULTS: A total of 9514 participants (3.4%) developed depression during a median follow-up of 13.91 years. Individuals in the highest quartile had a lower risk of depression (FVC % predicted: HR = 0.880, 95% CI = 0.830-0.933; FEV1% predicted: HR = 0.854, 95% CI = 0.805-0.905) compared with those in the lowest quartile of the lung function indices. Additionally, the restricted cubic splines suggested lung function indices had reversed J-shaped associations with incident depression (nonlinear P < 0.05 for FVC % predicted and FEV1% predicted). Impaired lung function yielded similar risk estimates (HR = 1.124, 95% CI = 1.074-1.176). Biomarkers involving systemic inflammation, erythrocytes, and liver and renal function may be potential mediators in the lung function-depression association. CONCLUSIONS: This study revealed that the higher risk of developing depression was associated with impaired lung function. Also, the association might be partially mediated by biomarkers including systemic inflammation, erythrocytes, and liver and renal function, though these mediation findings should be interpreted with caution due to potential temporal ambiguity.

Prediction on the changes in potential suitable areas for mangroves along the coast of Guangxi and the threat from Spartina alterniflora invasion.

As one of the important blue carbon pools in tropical and subtropical intertidal zones, mangroves are widely distributed along the coast of Guangxi in China. To deeply explore the variations of potential suitable habitats for mangroves in China under the background of climate change, based on remote sensing interpretation data of coastal wetlands in Guangxi, global marine environment and bioclimatic environment data in 2021, we constructed a maximum entropy habitat distribution model to simulate the spatial distribution of potential suitable areas for mangroves and the invasive species, Spartina alterniflora, along the coast of Guangxi, and predicted the patterns under extreme climate change scenarios (SSP5-8.5). The results showed that the interpreted area of mangrove forests along the coastline of Guangxi was 9136.7 hm2 in 2021, while the predicted area of potential suitable habitat area was 55955.9 hm2. Current distribution area of mangroves had basically covered its potential high suitability area and nearly 10% of the moderate suitability area. The current area of S. alterniflora was 1320.4 hm2, and the predicted area of potential high suitability area was twice of current area, indicating that there was still a large proportion of high suitability area that was not occupied by S. alterniflora. The most important environmental factors driving the distribution of potential habitats in mangroves were offshore Euclidean distance (62.2%), terrain deviation index (8.7%), average sea surface temperature in the hottest season (6.1%), and seabed terrain elevation (5.6%). The contribution of geographical conditions on mangrove distribution was predominant. Under the climate change scenario (SSP5-8.5), potential suitable area for mangroves would increase by 5.3%, while that for S. alterniflora would decrease by 3.1%. The overlapping proportion of the potential suitable area for mangroves and S. alterniflora was similar under current and SSP5-8.5 scenarios, being 15.2% and 14.5%, respectively. In the future, it is necessary to strengthen the protection and ecological restoration of mangroves along the coast of Guangxi and there is great challenge for preventing further invasion of S. alterniflora.

Correlations between ecosystem service value and landscape ecological risk and its spatial heterogeneity in Jilin Province, China.

Exploring the correlations between ecosystem service value (ESV) and landscape ecological risk and the driving factors of their spatial variations is crucial for maintaining regional ecological security and promoting sustainable human well-being. We carried out a grid resampling size of 5 km×5 km assessment units of Jilin Pro-vince based on the remote sensing monitoring data of land use in 2000, 2005, 2010, 2015, and 2020. We quantitatively evaluated the landscape ecological risk and ESV, and analyzed their spatial-temporal variations. Employing bivariate spatial autocorrelation analysis and the geographical detector models, we examined the correlation between the landscape ecological risk and ESV and explored the driving factors for their spatial variations. The results showed that ESV in Jilin Province decreased from 385.895 billion yuan to 378.211 billion yuan during 2000-2020. The eastern region was dominated by extremely low risk, medium risk, and low risk areas. In contrast, the western region was mainly composed of extremely high risk and high risk areas. There was a significant negative correlation and spatial negative correlation between landscape ecological risk and ESV in Jilin Province. Human activity and land use type were the important driving factors for spatial differentiation in both landscape ecological risk and ESV. Our findings suggested that scientific land use regulation and appropriate control of human activities are critically needed to optimize Jilin Province's ecological environment.

Ling-Gui-Zhu-Gan decoction ameliorates nonalcoholic fatty liver disease via modulating the gut microbiota.

Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis. Metagenomics, metabolomics, and transcriptomics were used to explore the structure and metabolism of the gut microbiota. LG significantly improved hepatic function and decreased lipid droplet accumulation in HD-induced NAFLD mice. LG reversed the structure of the gut microbiota that is damaged by HD and improved intestinal barrier function. Meanwhile, the LG group showed a lower total blood bile acids (BAs) concentration, a shifted BAs composition, and a higher fecal short-chain fatty acids (SCFAs) concentration. Furthermore, LG could regulate the hepatic expression of genes associated with the primary BAs biosynthesis pathway and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study suggested that LG could ameliorate NAFLD by altering the structure and metabolism of gut microbiota, while BAs and SCFAs are considered possible mediating substances. IMPORTANCE: Until now, there has still been no study on the gut microbiota and metabolomics of Ling-Gui-Zhu-Gan decoction (LG) in nonalcoholic fatty liver disease (NAFLD) mouse models. Our study is the first to report on the reshaping of the structure and metabolism of the gut microbiota by LG, as well as explore the potential mechanism underlying the improvement of NAFLD. Specifically, our study demonstrates the potential of gut microbial-derived short-chain fatty acids (SCFAs) and blood bile acids (BAs) as mediators of LG therapy for NAFLD in animal models. Based on the results of transcriptomics, we further verified that LG attenuates NAFLD by restoring the metabolic disorder of BAs via the up-regulation of Fgf15/FXR in the ileum and down-regulation of CYP7A1/FXR in the liver. LG also reduces lipogenesis in NAFLD mice by mediating the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which then contributes to reducing hepatic inflammation and improving intestinal barrier function to treat NAFLD.

High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen.

High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

Visible-light-promoted regioselective hydrocarboxylation of allenes with formate salt and CO2.

Visible-light-promoted hydrocarboxylation of allenes with formate salt and CO2 was developed for the first time using commercially available [Ir(ppy)2(dtbbpy)]PF6 as a photocatalyst. This strategy provides an efficient and practical method to access ß,γ-unsaturated linear carboxylic acids in moderate yields with complete regioselectivity.

Clean-up of divalent cobalt ions by massive sequestration in a low-cost calcium silicate hydrate material.

Cobalt is a critical resource in industrial economies for the manufacture of electric-vehicle batteries, alloys, magnets, and catalysts, but has acute supply-chain risks and poses a threat to the environment. Large-scale sequestration of cobalt in low-cost materials under mild conditions opens a path to cobalt recycling, recovery and environmental clean-up. We describe such sequestration of cobalt by a widely available commercial calcium silicate material containing the mineral xonotlite. Xonotlite rapidly and spontaneously takes up 40 percent of its weight of cobalt under ambient conditions of temperature and pressure and reduces dissolved cobalt concentrations to low parts per million. A new Sharp Front experimental design is used to obtain kinetic and chemical information. Sequestration occurs by a coupled dissolution-precipitation replacement mechanism. The cobalt silicate reaction product is largely amorphous but has phyllosilicate features.

Healthcare-associated carbapenem-resistant Klebsiella pneumoniae infections are associated with higher mortality compared to carbapenem-sensitive K. pneumoniae infections in the ICU: a retrospective cohort study.

BACKGROUND: We aimed to investigate the association between carbapenem resistance and the mortality rate, length of stay, and hospital cost in patients with Klebsiella pneumoniae infection. METHODS: The retrospective cohort study was conducted in the intensive care units of a large teaching tertiary hospital in southwest China between 1st January 2020 and 31st December 2022. To examine the impact of carbapenem resistance on mortality rates and economic burden, multivariate COX regression and generalised linear models were constructed. RESULTS: The study included 282 adult patients with KP infection (135 carbapenem-sensitive KP [CSKP]; 147 carbapenem-resistant KP [CRKP] infection). CRKP-infected patients demonstrated a higher mortality risk (unadjusted hazard ratio = 1.980; 95% CI 1.206-3.248; P 0.007; adjusted hazard ratio = 1.767; 95% CI 1.038-3.005; P 0.036) compared to CSKP-infected patients. Stratified analysis, according to the type of KP infection, revealed that patients with healthcare-associated CRKP infection showed a significantly higher risk of mortality compared to those with CSKP infection (Log-rank P=0.015). Moreover, patients with CRKP infection had longer hospital stays than those infected with CSKP (adjusted mean 38.74 days vs. 29.71 days; P 0.003), and the hospital-related expenses were notably higher among CRKP patients than CSKP patients (adjusted cost: GBP 40,126.73 vs. 25,713.74; P <0.001). CONCLUSIONS: CRKP infections increase mortality rates, prolong hospital stays, and raise healthcare costs. Consequently, it would be prudent for healthcare facilities to adopt targeted strategies, including curtailing pre-infection hospitalisation periods and managing medications more judiciously.

Analysis of risk factors for post-operative recurrence or progression of intravenous leiomyomatosis.

OBJECTIVE: To analyse the risk factors for post-operative recurrence or progression of intravenous leiomyomatosis and explore the impact of different treatment strategies on patient prognosis. METHODS: Patients with intravenous leiomyomatosis who underwent surgery from January 2011 to December 2020 and who were followed for ≥3 months were included. The primary endpoint was recurrence (for patients with complete resection) or progression (for patients with incomplete resection). Kaplan-Meier survival analysis was used to analyse the factors affecting recurrence. RESULTS: A total of 114 patients were included. The median age was 45 years old (range 24-58). The tumors were confined to the uterus and para-uterine vessels in 48 cases (42.1%), while in 66 cases (57.9%) it involved large vessels (iliac vein or genital vein and/or proximal large veins). The median follow-up time was 24 months (range 3-132). Twenty-nine patients (25.4%) had recurrence or progression. The median recurrence or progression time was 16 months (range 3-60). Incomplete tumor resection (p=0.019), involvement of the iliac vein or genital vein (p=0.042), involvement of the inferior vena cava (p=0.025), and size of the pelvic tumor ≥15 cm (p=0.034) were risk factors for recurrence and progression. For intravenous leiomyomatosis confined to the uterus or para-uterine vessels, no post-operative recurrence after hysterectomy and bilateral oophorectomy occurred in this cohort. Compared with hysterectomy and bilateral oophorectomy, the risk of recurrence after tumorectomy (with the uterus and ovaries retained) was significantly greater (p=0.009), while the risk of recurrence after hysterectomy was not significantly increased (p=0.058). For intravenous leiomyomatosis involving the iliac vein/genital vein and the proximal veins, post-operative aromatase inhibitor treatment (p=0.89) and two-stage surgery (p=0.86) were not related to recurrence in patients with complete tumor resection. CONCLUSION: Incomplete tumor resection, extent of tumor lesions and size of the pelvic tumor were risk factors for post-operative recurrence and progression of intravenous leiomyomatosis.

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. AIM: To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. METHODS: Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. RESULTS: General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. CONCLUSION: Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Coordination between two cis-elements of WRKY33, bound by the same transcription factor, confers humid adaption in Arabidopsis thaliana.

To cope with flooding-induced hypoxia, plants have evolved different strategies. Molecular strategies, such as the N-degron pathway and transcriptional regulation, are known to be crucial for Arabidopsis thaliana's hypoxia response. Our study uncovered a novel molecular strategy that involves a single transcription factor interacting with two identical cis-elements, one located in the promoter region and the other within the intron. This unique double-element adjustment mechanism has seldom been reported in previous studies. In humid areas, WRKY70 plays a crucial role in A. thaliana's adaptation to submergence-induced hypoxia by binding to identical cis-elements in both the promoter and intron regions of WRKY33. This dual binding enhances WRKY33 expression and the activation of hypoxia-related genes. Conversely, in arid regions lacking the promoter cis-element, WRKY70 only binds to the intron cis-element, resulting in limited WRKY33 expression during submergence stress. The presence of a critical promoter cis-element in humid accessions, but not in dry accessions, indicates a coordinated regulation enabling A. thaliana to adapt and thrive in humid habitats.

OsGADD45a1: a multifaceted regulator of rice architecture, grain yield, and blast resistance.

KEY MESSAGE: The homolog gene of the Growth Arrest and DNA Damage-inducible 45 (GADD45) in rice functions in the regulation of plant architecture, grain yield, and blast resistance. The Growth Arrest and DNA Damage-inducible 45 (GADD45) family proteins, well-established stress sensors and tumor suppressors in mammals, serve as pivotal regulators of genotoxic stress responses and tumorigenesis. In contrast, the homolog and role of GADD45 in plants have remained unclear. Herein, using forward genetics, we identified an activation tagging mutant AC13 exhibited dwarf characteristics resulting from the loss-of-function of the rice GADD45α homolog, denoted as OsGADD45a1. osgadd45a1 mutants displayed reduced plant height, shortened panicle length, and decreased grain yield compared to the wild-type Kitaake. Conversely, no obvious differences in plant height, panicle length, or grain yield were observed between wild-type and OsGADD45a1 overexpression plants. OsGADD45a1 displayed relatively high expression in germinated seeds and panicles, with localization in both the nucleus and cytoplasm. RNA-sequencing analysis suggested a potential role for OsGADD45a1 in the regulation of photosynthesis, and binding partner identification indicates OsGADD45a1 interacts with OsRML1 to regulate rice growth. Intriguingly, our study unveiled a novel role for OsGADD45a1 in rice blast resistance, as osgadd45a1 mutant showed enhanced resistance to Magnaporthe oryzae, and the expression of OsGADD45a1 was diminished upon blast fungus treatment. The involvement of OsGADD45a1 in rice blast fungus resistance presents a groundbreaking finding. In summary, our results shed light on the multifaceted role of OsGADD45a1 in rice, encompassing biotic stress response and the modulation of several agricultural traits, including plant height, panicle length, and grain yield.

The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry.

BACKGROUND: Currently, noninvasive imaging techniques and circulating biomarkers are still insufficient to accurately assess carotid plaque stability, and an in-depth understanding of the molecular mechanisms that contribute to plaque instability is still lacking. METHODS: We established a clinical study cohort containing 182 patients with carotid artery stenosis. After screening, 39 stable and 49 unstable plaques were included in the discovery group, and quantitative proteomics analysis based on data independent acquisition was performed for these plaque samples. Additionally, 35 plaques were included in the validation group to validate the proteomics results by immunohistochemistry analysis. RESULTS: A total of 397 differentially expressed proteins were identified in stable and unstable plaques. These proteins are primarily involved in ferroptosis and lipid metabolism-related functions and pathways. Plaque validation results showed that ferroptosis- and lipid metabolism-related proteins had different expression trends in stable plaques versus unstable fibrous cap regions and lipid core regions. Ferroptosis- and lipid metabolism-related mechanisms in plaque stability were discussed. CONCLUSIONS: Our results may provide a valuable strategy for revealing the mechanisms affecting plaque stability and will facilitate the discovery of specific biomarkers to broaden the therapeutic scope.