Comprehensive analysis of the prognostic and immunological signature of TNFAIP8 family genes in human glioma.

TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.

Ethical requirements of instructions for authors of complementary and alternative medicine journals: a cross-sectional study.

BACKGROUND: Medical research in complementary and alternative medicine (CAM) has increased recently, raising ethical concerns about the moral status of CAM. Medical academic journals are responsible for conducting ethical review (ER) of manuscripts to protect the interests of human subjects and to make ethical results available before deciding to publish. However, there has been no systematic analysis of the ER in CAM journals. This study is aim to evaluate the current status of ethical requirements and compliance in CAM journals. METHODS: This is a cross-sectional study. We reviewed instructions for authors (IFAs) of CAM journals included in the Journal Citation Reports (2021) ( https://jcr.clarivate.com ) for general information and requirements for ER. We also browsed the manuscripts regarding randomized controlled trials published by CAM journals in Q1 and Q2 section from January to June, 2023, to check the actual situation of ethical requirement. Descriptive statistics and Fisher's exact test were used for statistical analysis. RESULTS: 27 journals and 68 manuscripts were ultimately included. 92.6% (25/27) IFAs included keywords of ER, indicating the presence of ethical considerations. However, no specific ER was required for CAM (n = 0). We categorized journals by Geographic origin, JCR section, Year of electronic JCR, Types of studies, % of OA Gold to explore the factors that could influence CAM journals to have certain ethical review policies. The results showed there was no statistical significance in certain ethical review policy in any classification of journals (p > 0.05). All RCT manuscripts included in the study generally met the requirements of the published journals for ethical review. CONCLUSIONS: All IFAs discussed ER, but the content was scattered, unfocused, and there were no specific ER requirements regarding CAM. Although the manuscripts basically met the requirements of the journal, it was not possible to get closer to the process of ER in the manuscript. To ensure full implementation of these policies in the future, CAM journals should require authors to provide more details, or to form a list of items necessary for CAM ethical review.

Reasons and experience for patients with amyotrophic lateral sclerosis using traditional Chinese medicine: a CARE-TCM based mixed method study.

BACKGROUND AND AIM: Traditional Chinese medicine (TCM) is widely used by patients with amyotrophic lateral sclerosis (ALS). However, their reasons and experience in using TCM have received insufficient attention. Therefore, we conducted a mixed method study to gain insights into this issue. MATERIALS AND METHODS: This study was conducted on the basis of the China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM). Data were collected from Dongzhimen Hospital through a mixed method approach, including a questionnaire and a semi-structured interview. Patients with ALS who were using TCM when they were initially registered with CARE-TCM and who had been followed-up for over six months were recruited. The questionnaires' outcomes were statistically outlined, and the interview transcripts were thematically analysed to identify themes and sub-themes. RESULTS: Fifty-two and sixteen patients were included in the questionnaire and semi-structured interview groups, respectively. Patients used TCM with the hope of regulating their body holistically to improve nonmotor symptoms and quality of life (QOL). Those who recognised TCM as ineffective tended to discontinue it after a three-month trial period. Although quality was a major concern, herbal medicine (HM) was the most frequently used modality among all participants (n = 52), with the majority (n = 44, 84.6%) continuing to use it. Patients emphasised in-person consultations as a crucial part of TCM treatment. However, the disability caused by disease often made this interaction unattainable. CONCLUSION: Nonmotor symptoms and QOL hold substantial importance for patients with ALS using TCM. HM is a more suitable modality than other TCM treatment modalities, but patients are facing challenges in seeking HM treatment. It is necessary to promote the implementation of hierarchical diagnosis and treatment, thus making TCM more accessible. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04885374 (registered on May 13, 2021).

Study on the differences and influencing factors of spatial distribution of population aging at township scale: a case study of township research units in Anshun City, China.

An aging population is one of the main features of China's current population structure, and it is a key area that needs attention to achieve high-quality population development. Because of its unique geographical environment, economic conditions, and sociocultural background, the study of population aging in the karst region of southwest China is particularly important. However, there is a lack of research exploring the regional differentiation of population aging and its influencing factors in the karst regions of southwest China. In light of this, we chose Anshun City, located in Guizhou Province's southwest area, as the case study area. We used the Lorenz curve and spatial autocorrelation to study the differences in the spatial distribution pattern of population aging and introduced multi-scale geographical weighted regression to explore its influencing factors. The results show that Anshun City's older people population proportion (OPP) is generally high with more than 7% of the older people there, making it part of an aging society. The OPP appeared high in the east and low in the west in spatial distribution; the older people population density (OPD) revealed a gradually increasing trend from south to north. At the township scale, both the OPP and the OPD showed significant spatial positive correlation, and the spatial agglomeration characteristics were obvious. OPD and OPP have a positive spatial correlation at the global level, and townships with similar OPP or OPD were spatially adjacent. The spatial distribution characteristics of population aging are the consequence of complex contributions such as natural, social, economic, and karst factors. Further, the spatial distribution pattern of aging is determined by a variety of influencing factors, which have different directions and intensities. Therefore, it is necessary to formulate and implement corresponding policies and strategies to deal with the aging problem in the future.

Alleviating Recombinant Tissue Plasminogen Activator-induced Hemorrhagic Transformation in Ischemic Stroke via Targeted Delivery of a Ferroptosis Inhibitor.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood-brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin-1 (Lip) is proposed to alleviate the side effects. A well-designed macrocyclic carrier, glucose-modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke.

Integrative Dissection of Lignin Composition in Tartary Buckwheat Seed Hulls for Enhanced Dehulling Efficiency.

The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome-wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O-methyltransferases (COMTs) and one ferulate 5-hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome-wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.

High-quality chromosome-level genome assembly and multi-omics analysis of rosemary (Salvia rosmarinus) reveals new insights into the environmental and genome adaptation.

High-quality genome of rosemary (Salvia rosmarinus) represents a valuable resource and tool for understanding genome evolution and environmental adaptation as well as its genetic improvement. However, the existing rosemary genome did not provide insights into the relationship between antioxidant components and environmental adaptability. In this study, by employing Nanopore sequencing and Hi-C technologies, a total of 1.17 Gb (97.96%) genome sequences were mapped to 12 chromosomes with 46 121 protein-coding genes and 1265 non-coding RNA genes. Comparative genome analysis reveals that rosemary had a closely genetic relationship with Salvia splendens and Salvia miltiorrhiza, and it diverged from them approximately 33.7 million years ago (MYA), and one whole-genome duplication occurred around 28.3 MYA in rosemary genome. Among all identified rosemary genes, 1918 gene families were expanded, 35 of which are involved in the biosynthesis of antioxidant components. These expanded gene families enhance the ability of rosemary adaptation to adverse environments. Multi-omics (integrated transcriptome and metabolome) analysis showed the tissue-specific distribution of antioxidant components related to environmental adaptation. During the drought, heat and salt stress treatments, 36 genes in the biosynthesis pathways of carnosic acid, rosmarinic acid and flavonoids were up-regulated, illustrating the important role of these antioxidant components in responding to abiotic stresses by adjusting ROS homeostasis. Moreover, cooperating with the photosynthesis, substance and energy metabolism, protein and ion balance, the collaborative system maintained cell stability and improved the ability of rosemary against harsh environment. This study provides a genomic data platform for gene discovery and precision breeding in rosemary. Our results also provide new insights into the adaptive evolution of rosemary and the contribution of antioxidant components in resistance to harsh environments.

Conducting and reporting the Delphi method in traditional Chinese medicine syndrome diagnosis research: A cross-sectional analysis.

Background: The Delphi method has been extensively used to reach a consensus in traditional Chinese medicine (TCM) syndrome diagnosis research when subjective judgment is not uniform and objective evidence is lacking. The conduct and reporting of the Delphi method in TCM syndrome diagnosis research have never been critiqued. Our study aims to explore the consistency of using this technique and assess the reporting quality. Methods: A cross-sectional study was employed to scope articles reporting the conduct of the Delphi method in TCM syndrome diagnosis research. We searched the PubMed, Web of Science, CNKI, VIP, Wanfang and SinoMed databases with the restriction of Chinese and English language from their inception to March 25, 2023. A standardized extraction form was designed to collect demographics and methodological processes reflecting the rigor and transparency in TCM syndrome diagnosis research. Results: A total of 1832 studies were screened, and 50 were included. The median number of panels was 30 (IQR 20-34.5) and only 12 (24.0 %) studies were with a heterogeneous sample of panels. Two rounds was most common (37/50; 74.0 %), followed by three (7/50; 14.0 %), and only 13 (26.0 %) studies determined the number of rounds a priori. The reporting quality varied, with 18.0 % (9/50) reporting anonymity, 30.0 % (15/50) describing the controlled feedback, 20.0 % (10/50) reporting the procedure duration (7.14 ± 3.29 months) and 26.0 % (13/50) predefining the consensus. Conclusion: The Delphi method is inconsistently conducted and nontransparently reported in TCM syndrome diagnosis research. Standardized criteria are urgently needed for best practices in future research.

Na2CO3-responsive mechanism insight from quantitative proteomics and SlRUB gene function in Salix linearistipularis seedlings.

Mongolian willow (Salix linearistipularis) is a naturally occurring woody dioecious plant in the saline soils of north-eastern China, which has a high tolerance to alkaline salts. Although transcriptomics studies have identified a large number of salinity-responsive genes, the mechanism of salt tolerance in Mongolian willow is not clear. Here, we found that in response to Na2CO3 stress, Mongolian willow regulates osmotic homeostasis by accumulating proline and soluble sugars and scavenges reactive oxygen species (ROS) by antioxidant enzymes and non-enzymatic antioxidants. Our quantitative proteomics study identified 154 salt-sensitive proteins mainly involved in maintaining the stability of the photosynthetic system and ROS homeostasis to cope with Na2CO3 stress. Among them, Na2CO3-induced rubredoxin (RUB) was predicted to be associated with 122 proteins for the modulation of these processes. The chloroplast-localized S. linearistipularis rubredoxin (SlRUB) was highly expressed in leaves and was significantly induced under Na2CO3 stress. Phenotypic analysis of overexpression, mutation and complementation materials of RUB in Arabidopsis suggests that SlRUB is critical for the regulation of photosynthesis, ROS scavenging and other metabolisms in the seedlings of Mongolian willow to cope with Na2CO3 stress. This provides more clues to better understand the alkali-responsive mechanism and RUB functions in the woody Mongolian willow.

A study on matching supply and demand of ecosystem services in the Hexi region of China based on multi-source data.

To achieve the best management of the ecosystem and sustainable socioeconomic development, it is crucial to clarify the matching relationship between the supply and demand of ecosystem services (ESs). Four types of ESs were chosen for the Hexi region in this study: food supply, carbon sequestration, water yield, wind erosion control and sediment retention. We assessed the supply-demand and matching relationships of different ESs using the Integrated Valuation of Ecosystem Service and Tradeoffs (InVEST) model, the ESs supply-demand ratio and the four-quadrant model. Moreover, we also analyzed the supply-demand ratio of integrated ESs and their cold spots. The findings suggest that (1) from 2000 to 2020, the average supply of food supply, carbon sequestration, water yield, wind erosion control and sediment retention increased by 44.31 t/km2, 128.44 t/hm2, 14,545.94 m3/km2 and 0.14 kg/m2 respectively, which showed a spatial pattern of "high in the southeast and low in the northwest". The average demand for food supply and carbon sequestration increased by 1.33 t/km2 and 0.32 t/hm2 respectively, while the average demand for water yield and wind erosion control and sediment retention decreased by 2997.25 m3/km2 and 1.19 kg/km2 respectively. The spatial distribution is consistent with the layout of population density, production and residential areas, and fragile ecological areas. (2) The supply-demand ratio of food supply, carbon sequestration and water yield is greater than 0.095, which is in a state of oversupply, and the supply-demand ratio of wind erosion control and sediment retention is less than 0, which is in a state of shortage; all ESs are mainly in low-low spatial matching areas, mainly concentrated in the desert areas of the northwest in the Hexi region. (3) The supply-demand ratio of integrated ESs increased by 0.024, and the proportion of cold spots and sub-cold spots was more than 50% and concentrated in the northwest, while hot spots and sub-hot spots accounted for only about 16%, mainly distributed in the southern Qilian Mountains and some oasis areas.

Water pollution scenarios and response options for China.

China has formulated several policies to alleviate the water pollution load, but few studies have quantitatively analyzed their impacts on future water pollution loads in China. Based on grey water footprint (GWF) assessment and scenario simulation, we analyze the water pollution (including COD, NH3-N, TN and TP) in China from 2021 to 2035 under different scenarios for three areas: consumption-side, production-side and terminal treatment. We find that under the current policy scenario, the GWF of COD, NH3-N, TN, and TP in China could be reduced by 15.0 % to 39.9 %; the most effective measures for GWF reduction are diet structure change (in the consumption-side area), and the wastewater treatment rate and livestock manure utilization improvement (in the terminal treatment area). However, the GWF will still increase in 8 provinces, indicating that the current implemented policy is not universally effective in reducing GWF across all provinces. Under the technical improvement scenario, the GWF of the four pollutants will decrease by 54.9 %-71.1 % via improvements in the current measures related to current policies and new measures in the production-side area and the terminal treatment area; thus, GWF reduction is possible in all 31 provinces. However, some policies face significant challenges in achieving full implementation, and certain policies are only applicable to a subset of provinces. Our detailed analysis of future water pollution scenarios and response options to reduce pollution loads can help to inform the protection of freshwater resources in China and quantitatively assess the effectiveness of policies in other fields.

Mitochondrial VOLTAGE-DEPENDENT ANION CHANNEL 3 regulates stomatal closure by abscisic acid signaling.

In Arabidopsis (Arabidopsis thaliana), stomatal closure mediated by abscisic acid (ABA) is redundantly controlled by ABA receptor family proteins (PYRABACTIN RESISTANCE 1 [PYR1]/PYR1-LIKE [PYLs]) and subclass III SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2 (SnRK2s). Among these proteins, the roles of PYR1, PYL2, and SnRK2.6 are more dominant. A recent discovery showed that ABA-induced accumulation of reactive oxygen species (ROS) in mitochondria promotes stomatal closure. By analyzing stomatal movements in an array of single and higher order mutants, we revealed that the mitochondrial protein VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3) jointly regulates ABA-mediated stomatal closure with a specialized set of PYLs and SnRK2s by affecting cellular and mitochondrial ROS accumulation. VDAC3 interacted with 9 PYLs and all 3 subclass III SnRK2s. Single mutation in VDAC3, PYLs (except PYR1 and PYL2), or SnRK2.2/2.3 had little effect on ABA-mediated stomatal closure. However, knocking out PYR1, PYL1/2/4/8, or SnRK2.2/2.3 in vdac3 mutants resulted in significantly delayed or attenuated ABA-mediated stomatal closure, despite the presence of other PYLs or SnRK2s conferring redundant functions. We found that cellular and mitochondrial accumulation of ROS induced by ABA was altered in vdac3pyl1 mutants. Moreover, H2O2 treatment restored ABA-induced stomatal closure in mutants with decreased stomatal sensitivity to ABA. Our work reveals that VDAC3 ensures redundant control of ABA-mediated stomatal closure by canonical ABA signaling components.

Qualified placebo for trials of herbal medicine treatment in rare diseases? A cross-sectional analysis.

BACKGROUND: While substantial placebos have been used in herbal medicine (HM) clinical trials for rare diseases, the use and quality of reporting of HM-placebo remain unclear. We aim to describe the use of HM-placebo in clinical trials for rare diseases and determine the quality of reporting in these trials. METHODS: This is a cross-sectional study. We searched PubMed, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, WanFang database, China Science and Technology Journal Database, National Institute of Informatics Support Academic Information Services, ClinicalTrials.gov and Chinese Clinical Trials Registry from their inception date to 14 February 2023 to identify registered and published trials that use placebos as a comparator in rare diseases. We collected data on placebo use reporting and the efficacy and safety of placebo. Descriptive statistics, the Chi-square test, and Binary multivariable logistic regression analysis were used to determine the placebo characteristics of the HM trial and its effect on reporting. RESULTS: Among the 55 studies, we included that with a median administration time of placebo of 84 days (IQR 42-180) and a median placebo sample size of 30 (IQR 24-54). About half of the trials (27, 49.1%) did not provide their ethical approvals, and one trial had details of informed consent. None of the studies were fully reported and more than half of the items reported less than 50%. A total of 10 trials (18.2%) of placebo has active ingredients even though none of them performed pharmacological inert tests. Of the 29 studies with available data on adverse events, 5 (17.2%) trials did not show a better safety profile in the placebo group. Under the context that a relatively high-quality report is defined as a report with more than 9 items, there was a statistically significant difference between the two groups in the rate of relatively high-quality reports of the administration time (p = 0.047, OR 0.10, 95% CI 0.01 to 0.90), but the results are not representative. CONCLUSION: The overall situation of HM-placebo in the field of rare diseases was poor. In particular, the placebo is tied to the quality of trials, and poor placebo hinders the generation of high-quality evidence for herbal clinical trials in the field of rare diseases. We summarize the current methods of assessment involved in the use of placebos and propose various considerations for placebos in different contexts. Our study can greatly promote rare disease researchers to review the quality of their placebo and clinical trials. It is imperative to guarantee that meticulously conducted research generates clinical evidence of the highest caliber. We also expect that in the future, more rigorous relevant standards about the reporting and design of HM-placebo will be developed. High-quality clinical trials are the prerequisite for the wide clinical application of herbal medicines for rare diseases.

Transcriptome profiling of Bergenia purpurascens under cold stress.

Bergenia purpurascens is an important medicinal, edible and ornamental plant. It generally grows in high-altitude areas with complex climates. There have been no reports about how B. purpurascens survives under cold stress. Here, the B. purpurascens under low temperature were subjected to transcriptomics analysis to explore the candidate genes and pathways that involved in the cold tolerance of B. purpurascens. Compared with the control treatment, we found 9,600 up-regulated differentially expressed genes (DEGs) and 7,055 down-regulated DEGs. A significant number of DEGs were involved in the Ca2+ signaling pathway, mitogen-activated protein kinase (MAPK) cascade, plant hormone signaling pathway, and lipid metabolism. A total of 400 transcription factors were found to respond to cold stress, most of which belonged to the MYB and AP2/ERF families. Five novel genes were found to be potential candidate genes involved in the cold tolerance of B. purpurascens. The study provide insights into further investigation of the molecular mechanism of how B. purpurascens survives under cold stress.

Adipsin inhibits Irak2 mitochondrial translocation and improves fatty acid ß-oxidation to alleviate diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid ß-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism. METHODS: A high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC-MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator. RESULTS: The expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC-MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin. CONCLUSIONS: Adipsin improves fatty acid ß-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.

Active DHEA uptake in the prostate gland correlates with aggressive prostate cancer.

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3ßHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3ßHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3ßHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3ßHSD1 inhibitors as early intervention.

Efficacy and safety of Panax notoginseng saponins (Xuesaitong) for patients with acute ischemic stroke: a systematic review and meta-analysis of randomized controlled trials.

Background: Stroke is the major cause of mortality and permanent disability and is associated with an astonishing economic burden worldwide. In the past few decades, accumulated evidence has indicated that Xuesaitong (XST) has therapeutic benefits in cases of acute ischemic stroke (AIS). Our study aimed to provide the best current body of evidence of the efficacy and safety of XST for patients with AIS. Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched eight electronic databases from inception to 17 July 2023 for relevant RCTs. The investigators independently screened trials, extracted data, and assessed the risk of bias. A meta-analysis was conducted using RevMan 5.3 and STATA 16.0 software. Results: In total, 46 RCTs involving 7,957 patients were included. The results showed that XST improved the long-term functional outcomes with lower modified Rankin Scale (mRS) scores (MD = -0.67; 95% CI [-0.92 to -0.42]; p < 0.00001) and a higher proportion of functional independence (mRS ≤2) (RR = 1.08; 95% CI [1.05 to 1.12]; p < 0.00001). Low-quality evidence indicated that XST improved the activities of daily living (MD = 10.17; 95% CI [7.28 to 13.06]; p < 0.00001), improved the neurological impairment (MD = -3.39; 95% CI [-3.94 to -2.84]; p < 0.00001), and enhanced the total efficiency rate (RR = 1.19; 95% CI [1.15 to 1.23]; p < 0.00001). No significant difference was found in the all-cause mortality or incidence of adverse events between the XST and control groups. The certainty of evidence was estimated as moderate to very low. Conclusion: Presently, the administration of XST within 14 days of AIS is associated with favorable long-term functional outcomes. In addition, XST can improve activities of daily living, alleviate neurological deficits, and has shown good tolerability. However, the current evidence is too weak, and the confidence of evidence synthesis was restricted by the high risk of bias. Given the insufficient evidence, appropriately sized and powered RCTs investigating the efficacy and safety of XST for patients with AIS are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=446208, CRD42023446208.

Relationship between Bladder Cancer, Nutritional Supply, and Treatment Strategies: A Comprehensive Review.

Bladder cancer (BC) is the predominant neoplasm affecting the urinary system and ranks among the most widespread malignancies globally. The causes of bladder cancer include genetic factors; age; sex; and lifestyle factors, such as imbalanced nutrition, obesity, and metabolic disorders. The lack of proper nutrient intake leads to the development of bladder cancer because insufficient nutrients are consumed to prevent this disease. The purpose of this review was to analyze the nutrients closely linked to the onset and advancement of bladder cancer and to explore the relationship between dietary nutrients and bladder cancer. Particular emphasis was placed on nutrients that are frequently ingested in daily life, including sugar, fat, protein, and others. The focus of this research was to analyze how nutritional intake before and after surgery affects the recovery process of patients who have been diagnosed with bladder cancer. This article seeks to increase awareness among both society and the medical community about the significance of implementing appropriate dietary nutrition to reduce the chances of developing bladder cancer, enhance perioperative care for patients with bladder cancer, and aid in their recuperation.

Rnd3 suppresses endothelial cell pyroptosis in atherosclerosis through regulation of ubiquitination of TRAF6.

BACKGROUND: As the main pathological basis for various cardiovascular and cerebrovascular diseases, atherosclerosis has become one of the leading causes of death and disability worldwide. Emerging evidence has suggested that Rho GTPase Rnd3 plays an indisputable role in cardiovascular diseases, although its function in atherosclerosis remains unclear. Here, we found a significant correlation between Rnd3 and pyroptosis of aortic endothelial cells (ECs). METHODS: ApoeKO mice were utilized as a model for atherosclerosis. Endothelium-specific transgenic mice were employed to disrupt the expression level of Rnd3 in vivo. Mechanistic investigation of the impact of Rnd3 on endothelial cell pyroptosis was carried out using liquid chromatography tandem mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP) assays, and molecular docking. RESULTS: Evidence from gain-of-function and loss-of-function studies denoted a protective role for Rnd3 against ECs pyroptosis. Downregulation of Rnd3 sensitized ECs to pyroptosis under oxidized low density lipoprotein (oxLDL) challenge and exacerbated atherosclerosis, while overexpression of Rnd3 effectively prevented these effects. LC-MS/MS, Co-IP assay, and molecular docking revealed that Rnd3 negatively regulated pyroptosis signaling by direct interaction with the ring finger domain of tumor necrosis factor receptor-associated factor 6 (TRAF6). This leads to the suppression of K63-linked TRAF6 ubiquitination and the promotion of K48-linked TRAF6 ubiquitination, inhibiting the activation of NF-κB and promoting the degradation of TRAF6. Moreover, TRAF6 knockdown countered Rnd3 knockout-evoked exacerbation of EC pyroptosis in vivo and vitro. CONCLUSIONS: These findings establish a critical functional connection between Rnd3 and the TRAF6/NF-κB/NLRP3 signaling pathway in ECs, indicating the essential role of Rnd3 in preventing pyroptosis of ECs.