Psychometric validation of the short version of the Information Needs in Cardiac Rehabilitation scale through a first global assessment.

AIMS: Tailored education is recommended for cardiac patients, yet little is known about information needs in areas of the world where it is most needed. This study aims to assess (i) the measurement properties of the Information Needs in Cardiac Rehabilitation short version (INCR-S) scale and (ii) patient's information needs globally. METHODS AND RESULTS: In this cross-sectional study, English, simplified Chinese, Portuguese, or Korean versions of the INCR-S were administered to in- or out-patients via Qualtrics (January 2022-November 2023). Members of the International Council of Cardiovascular Prevention and Rehabilitation community facilitated recruitment. Importance and knowledge sufficiency of 36 items were rated. Links to evidence-based lay education were provided where warranted. A total of 1601 patients from 19 middle- and high-income countries across the world participated. Structural validity was supported upon factor analysis, with five subscales extracted: symptom response/medication, heart diseases/diagnostic tests/treatments, exercise and return-to-life roles/programmes to support, risk factors, and healthy eating/psychosocial management. Cronbach's alpha was 0.97. Construct validity was supported through significantly higher knowledge sufficiency ratings for all items and information importance ratings for all subscales in cardiac rehabilitation (CR) enrolees vs. non-enrolees (all P < 0.001). All items were rated as very important-particularly regarding cardiac events, nutrition, exercise benefits, medications, symptom response, risk factor control, and CR-but more so in high-income countries in the Americas and Western Pacific. Knowledge sufficiency ranged from 30.0 to 67.4%, varying by region and income class. Ratings were highest for medications and lowest for support groups, resistance training, and alternative medicine. CONCLUSION: Identification of information needs using the valid and reliable INCR-S can inform educational approaches to optimize patients' health outcomes across the globe.

Patients need information to manage their heart diseases, such as what to do if they have chest pain, what a heart attack is, and how to take their medicine to lower the chances they will have another one, so a study of the information needs of over 1600 heart patients from around the globe was undertaken for the first time. Using the Information Needs in Cardiac Rehabilitation short version (INCR-S) scale­which was shown to be a good measurement tool through the study and hence may improve patient education­patients reported they most wanted information about heart events, heart-healthy eating, exercise benefits, their pills, symptom response, risk factor control, and cardiac rehabilitation­but more so in high-income countries in the Americas and Western Pacific. Knowledge sufficiency ratings for each item ranged from 30.0 to 67.4%, also varying by region and income class; perceived knowledge sufficiency ratings were highest for medications and lowest for support groups, resistance training, and alternative medicine.

Assessment of aortic dilatation in Chinese children and adolescents with Turner syndrome: a single center experience.

BACKGROUND: Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. METHODS: This study included TS patients admitted to Shenzhen Children's Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada's method). RESULTS: A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those < 10 years old (16.6% vs. 1.8%, P = 0.009), and the proportion of patients with CoA or BAV who additionally exhibited AD was higher than those without these conditions (31.6% vs. 5.2%, P < 0.001). The ASI, A/D ratio, TSZ-score, and CHTSZ-score of the 11 patients with AD were 2.27 ± 0.40 cm/m2, 1.90 ± 0.37, 1.28 ± 1.08, and 3.07 ± 2.20, respectively. Among the AD patients, only 3 cases had a TSZ-score ≥ 2, and 2 cases had a TSZ-score ≥ 1. However, based on the assessment using the CHTSZ-score, 6 patients scored ≥ 2, and 5 patients scored ≥ 1. In contrast, the TSZ-score generally underestimated the aortic Z-scores in Chinese children with TS compared to the CHTSZ-score. CONCLUSIONS: The applicability of ASI and A/D ratio to children with TS is questionable, and racial differences can affect the assessment of TSZ-score in the Chinese population. Therefore, establishing the CHTSZ-score specifically tailored for Chinese children and adolescents is of paramount importance.

Higher N-terminal pro-brain natriuretic peptide level at onset of peritoneal dialysis-related peritonitis is a risk factor for technique failure.

BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.

Characterization and pharmacokinetics of cinnamon and star anise compound essential oil pellets prepared via centrifugal granulation technology.

Cinnamon and star anise essential oils are extracted from natural plants and provide a theoretical basis for the development and clinical application of compound essential oil pellets. However, cinnamon oil and star anise oil have the characteristics of a pungent taste, extreme volatility, poor palatability, and unstable physical and chemical properties, which limit their clinical use in veterinary medicine. In this study, the inhibitory effects of cinnamon oil and star anise oil on Escherichia coli and Salmonella were measured. Compound essential oil pellets were successfully prepared by centrifugal granulation technology. Subsequently, the in vitro dissolution of the pellets and their pharmacokinetics in pigs were investigated. The results showd that, cinnamon and star anise oils showed synergistic or additive inhibitiory effects on Escherichia coli and Salmonella. The oil pellets had enteric characteristics in vitro and high dissolution in vitro. The pharmacokinetic results showed that the pharmacokinetic parameters Cmax and AUC were directly correlated with the dosage and showed linear pharmacokinetic characteristics, which provided a theoretical basis for the development and clinical application of compound essential oil pellets.

Function and mechanism of action of the TRPV1 channel in the development of triple-negative breast cancer.

Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.

Unveiling convergent and divergent intrinsic brain network alternations in depressed adolescents engaged in non-suicidal self-injurious behaviors with and without suicide attempts.

AIMS: Limited understanding exists regarding the neurobiological mechanisms underlying non-suicidal self-injury (NSSI) and suicide attempts (SA) in depressed adolescents. The maturation of brain network is crucial during adolescence, yet the abnormal alternations in depressed adolescents with NSSI or NSSI+SA remain poorly understood. METHODS: Resting-state functional magnetic resonance imaging data were collected from 114 depressed adolescents, classified into three groups: clinical control (non-self-harm), NSSI only, and NSSI+SA based on self-harm history. The alternations of resting-state functional connectivity (RSFC) were identified through support vector machine-based classification. RESULTS: Convergent alterations in NSSI and NSSI+SA predominantly centered on the inter-network RSFC between the Limbic network and the three core neurocognitive networks (SalVAttn, Control, and Default networks). Divergent alterations in the NSSI+SA group primarily focused on the Visual, Limbic, and Subcortical networks. Additionally, the severity of depressive symptoms only showed a significant correlation with altered RSFCs between Limbic and DorsAttn or Visual networks, strengthening the fact that increased depression severity alone does not fully explain observed FC alternations in the NSSI+SA group. CONCLUSION: Convergent alterations suggest a shared neurobiological mechanism along the self-destructiveness continuum. Divergent alterations may indicate biomarkers differentiating risk for SA, informing neurobiologically guided interventions.

Analysis of landscape pattern vulnerability in Dasi river basin at the optimal scale.

Since the reform and opening up in 1978, the Dasi River Basin within Jinan's startup area from replacing old growth drivers with new ones (startup area) has experienced rapid urbanization and industrialization, and the landscape pattern has changed significantly, resulting in a series of eco-environmental problems. In order to more accurately identify the vulnerable areas of landscape pattern, understand their cause mechanism and changing laws, and provide a theoretical basis for the implementation of sustainable landscape pattern planning and management in the region. Four Landsat images of 2002, 2009, 2015 and 2020 were taken as data sources, and the optimal granularity of landscape pattern analysis was determined from the perspective of landscape level and class level by using the coefficient of variation method, granularity effect curve and information loss model, and the optimal amplitude was determined by using the grid method and semi-variance function. Then, the landscape vulnerability assessment model was constructed based on the optimal scale, and its spatiotemporal evolution characteristics and spatial autocorrelation were analyzed. The result showed that: (1) The optimal granularity of landscape pattern analysis in this study area was 80 m, and the optimal amplitude was 350 × 350 m. (2) During 2002-2020, the overall vulnerability of landscape pattern in the southern part of the study area showed an increasing trend, while that in the middle and northern parts showed a decreasing trend. (3) The mean values of the vulnerability index of the overall landscape pattern in 2002, 2009, 2015 and 2020 were 0.1479, 0.1483, 0.1562 and 0.1625, respectively, showing an increasing trend year by year. In terms of land use, during 2002-2020, the average vulnerability indices of forestland and built up land increased by 23.18% and 21.43%, respectively, followed by water body and bare land, increased by 12.18% and 9.52%, respectively, while the changes of cropland and grassland were relatively small, increasing by 5.36% and 5.65%, respectively. (4) During 2002-2020, the landscape pattern vulnerability showed a significant spatial positive correlation in terms of spatial distribution. The Low-Low areas were generally transferred from the southeastern and midwestern to the middle and northern, and the High-High areas were mainly transferred from the middle to the southern. Overall, the degree of the spatial agglomeration of the landscape pattern vulnerability showed an increasing trend.

The ZmbHLH47-ZmSnRK2.9 Module Promotes Drought Tolerance in Maize.

Drought stress globally poses a significant threat to maize (Zea mays L.) productivity and the underlying molecular mechanisms of drought tolerance remain elusive. In this study, we characterized ZmbHLH47, a basic helix-loop-helix (bHLH) transcription factor, as a positive regulator of drought tolerance in maize. ZmbHLH47 expression was notably induced by both drought stress and abscisic acid (ABA). Transgenic plants overexpressing ZmbHLH47 displayed elevated drought tolerance and ABA responsiveness, while the zmbhlh47 mutant exhibited increased drought sensitivity and reduced ABA sensitivity. Mechanistically, it was revealed that ZmbHLH47 could directly bind to the promoter of ZmSnRK2.9 gene, a member of the subgroup III SnRK2 kinases, activating its expression. Furthermore, ZmSnRK2.9-overexpressing plants exhibited enhanced ABA sensitivity and drought tolerance, whereas the zmsnrk2.9 mutant displayed a decreased sensitivity to both. Notably, overexpressing ZmbHLH47 in the zmsnrk2.9 mutant closely resembled the zmsnrk2.9 mutant, indicating the importance of the ZmbHLH47-ZmSnRK2.9 module in ABA response and drought tolerance. These findings provided valuable insights and a potential genetic resource for enhancing the environmental adaptability of maize.

Cr(VI) removal during cotransport of nano-iron-particles combined with iron sulfides in groundwater: Effects of D. vulgaris and S. putrefaciens.

Iron-based materials such as nanoscale zerovalent iron (nZVI) are effective candidates to in situ remediate hexachromium (Cr(VI))-contaminated groundwater. The anaerobic bacteria could influence the remediation efficiency of Cr(VI) during its cotransport with nZVI in porous media. To address this issue, the present study investigated the adsorption and reduction of Cr(VI) during its cotransport with green tea (GT) modified nZVI (nZVI@GT) and iron sulfides (FeS and FeS2) in the presence of D. vulgaris or S. putrefaciens in water-saturated sand columns. Experimental results showed that the nZVI@GT preferred to heteroaggregate with FeS2 rather than FeS, forming nZVI@GT-FeS2 heteroaggregates. Although the presence of D. vulgaris further induced nZVI@GT-FeS2 heteroaggregates to form larger clusters, it pronouncedly improved the dissolution of FeS and FeS2 for more Cr(VI) reduction associated with lower Cr(VI) flux through sand. In contrast, S. putrefaciens could promote the dispersion of the heteroaggregates of nZVI@GT-FeS2 and the homoaggregates of nZVI@GT or FeS by adsorption on the extracellular polymeric substances, leading to the improved transport of Fe-based materials for a much higher Cr(VI) immobilization in sand media. Overall, our study provides the essential perspectives into a chem-biological remediation technique through the synergistic removal of Cr(VI) by nZVI@GT and FeS in contaminated groundwater. ENVIRONMENTAL IMPLICATION: The green-synthesized nano-zero-valent iron particles (nZVI@GT) using plant extracts (or iron sulfides) have been used for in situ remediation of Cr(VI) contaminated groundwater. Nevertheless, the removal of Cr(VI) (including Cr(VI) adsorption and Cr(III) generation) could be influenced by the anaerobic bacteria governing the transport of engineered nanoparticles in groundwater. This study aims to reveal the inherent mechanisms of D. vulgaris and S. putrefaciens governing the cotransport of nZVI@GT combined with FeS (or FeS2) to further influence the Cr(VI) removal in simulated complex groundwater media. Our findings provides a chemical and biological synergistic remediation strategy for nZVI@GT application in Cr(VI)-contaminated groundwater.

Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination.

Approximately 40% of patients with lung adenocarcinoma (LUAD) often develop bone metastases during the course of their disease. However, scarcely any in vivo model of LUAD bone metastasis has been established, leading to a poor understanding of the mechanisms underlying LUAD bone metastasis. Here, we established a multiorgan metastasis model via the left ventricular injection of luciferase-labeled LUAD cells into nude mice and then screened out lung metastasis (LuM) and bone metastasis (BoM) cell subpopulations. BoM cells exhibited greater stemness and epithelial-mesenchymal transition (EMT) plasticity than LuM cells and initially colonized the bone and subsequently disseminated to distant organs after being reinjected into mice. Moreover, a CD74-ROS1 fusion mutation (C6; R34) was detected in BoM cells but not in LuM cells. Mechanistically, BoM cells bearing the CD74-ROS1 fusion highly secrete the C-C motif chemokine ligand 5 (CCL5) protein by activating STAT3 signaling, recruiting macrophages in tumor microenvironment and strongly inducing M2 polarization of macrophages. BoM cell-activated macrophages produce a high level of TGF-ß1, thereby facilitating EMT and invasion of LUAD cells via TGF-ß/SMAD2/3 signaling. Targeting the CD74-ROS1/CCL5 axis with Crizotinib (a ROS1 inhibitor) and Maraviroc (a CCL5 receptor inhibitor) in vivo strongly impeded bone metastasis and secondary metastasis of BoM cells. Our findings reveal the critical role of the CD74-ROS1/STAT3/CCL5 axis in the interaction between LUAD bone metastasis cells and macrophages for controlling LUAD cell dissemination, highlighting the significance of the bone microenvironment in LUAD bone metastasis and multiorgan secondary metastasis, and suggesting that targeting CD74-ROS1 and CCL5 is a promising therapeutic strategy for LUAD bone metastasis.

MicroRNA-451 Regulates Angiogenesis in Intracerebral Hemorrhage by Targeting Macrophage Migration Inhibitory Factor.

Intracerebral hemorrhage (ICH) is a subtype of stroke with the highest fatality and disability rate. Up to now, commonly used first-line therapies have limited value in improving prognosis. Angiogenesis is essential to neurological recovery after ICH. Recent studies have shown that microRNA-451(miR-451) plays an important role in angiogenesis by regulating the function of vascular endothelial cells. We found miR-451 was significantly decreased in the peripheral blood of ICH patients in the acute stage. Based on the clinical findings, we conducted this study to investigate the potential regulatory effect of miR-451 on angiogenesis after ICH. The expression of miR-451 in ICH mouse model and in a hemin toxicity model of human brain microvascular endothelial cells (hBMECs) was decreased the same as in ICH patients. MiR-451 negatively regulated the proliferation, migration, and tube formation of hBMECs in vitro. MiR-451 negatively regulated the microvessel density in the perihematoma tissue and affected neural functional recovery of ICH mouse model. Knockdown of miR-451 could recovered tight junction and protect the integrity of blood-brain barrier after ICH. Based on bioinformatic programs, macrophage migration inhibitory factor (MIF) was predicted to be the target gene and identified to be regulated by miR-451 inhibiting the protein translation. And p-AKT and p-ERK were verified to be downstream of MIF in angiogenesis. These results all suggest that miR-451 will be a potential target for regulating angiogenesis in ICH.

Glycopeptide-based multifunctional nanofibrous hydrogel that facilitates the healing of diabetic wounds infected with methicillin-resistant Staphylococcus aureus.

Diabetic wound management remains a significant challenge in clinical care due to bacterial infections, excessive inflammation, presence of excessive reactive oxygen species (ROS), and impaired angiogenesis. The use of multifunctional wound dressings has several advantages in diabetic wound healing. Moreover, the balance of macrophage polarization plays a crucial role in promoting skin regeneration. However, few studies have focused on the development of multifunctional wound dressings that can regulate the inflammatory microenvironment and promote diabetic wound healing. In this study, an extracellular matrix-inspired glycopeptide hydrogel composed of glucomannan and polypeptide was proposed for regulating the local microenvironment of diabetic wound sites. The hydrogel network, which was formed via Schiff base and hydrogen bonding interactions, effectively inhibited inflammation and promoted angiogenesis during wound healing. The hydrogels exhibited sufficient self-healing ability and had the potential to scavenge ROS and to activate the mannose receptor (MR), thereby inducing macrophage polarization toward the M2 phenotype. The experimental results confirm that the glycopeptide hydrogel is an effective tool for managing diabetic wounds by showing antibacterial, ROS scavenging, and anti-inflammatory effects, and promoting angiogenesis to facilitate wound repair and skin regeneration in vivo. STATEMENT OF SIGNIFICANCE: •The designed wound dressing combines the advantage of natural polysaccharide and polypeptide. •The hydrogel promotes M2-polarized macrophages, antibacterial, scavenges ROS, and angiogenesis. •The multifunctional glycopeptide hydrogel dressing could accelerating diabetic wound healing in vivo.

Separating the effects of early and later life body mass index on liver diseases: A Mendelian randomization study.

BACKGROUND AND AIM: The independent effects of childhood and adult body mass index (BMI) on non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC) are lacking assessment. We aimed to separate the effects of childhood and adult BMI on NAFLD, cirrhosis, and HCC. METHODS: Genetic variants associated with childhood and adult BMI were selected as instrumental variables. Two-sample univariable and multivariable MR estimated the total and direct effect of childhood and adult BMI on NAFLD, cirrhosis, and HCC. RESULTS: Genetically predicted each 1-SD increased childhood BMI (OR = 1.30, 95 % CI = 1.12 to 1.51, P = 0.001) and adult BMI (OR = 1.57 95 % CI = 1.33 to 1.84, P = 5.49E-08) was associated with an increased risk of NAFLD. The association between childhood BMI (OR = 0.97, 95 % CI = 0.77 to 1.24, P = 0.825) and NAFLD did not remain significant after adjusting for adult BMI (OR = 1.64, 95 % CI = 1.23 to 2.20, P = 0.001). The direct effects of childhood and adult BMI on cirrhosis and HCC were insignificant after considering their relationship. CONCLUSION: Maintaining a normal BMI in adulthood significantly reduces the adverse effect of a higher childhood BMI on NAFLD. Further investigation is required to clarify the presence of this effect in cirrhosis and HCC.

Dimensions of family stress and repetitive nonsuicidal self-injury in adolescence: Examining the interactive effects of impulsivity and emotion dysregulation.

BACKGROUND: Repetitive non-suicidal self-injury (R-NSSI) in adolescence represents a significant risk factor for suicide. Although exposure to family stress is robustly associated with the risk of non-suicidal self-injury (NSSI), studies have not examined the potential mechanisms linking different forms of family stress and R-NSSI. OBJECTIVE: This study examined how unique dimensions of family stress (threat and deprivation) relate to R-NSSI via interactions between impulsivity and emotion dysregulation. PARTICIPANTS AND SETTING: The current sample included 3801 middle-school adolescents (42.2 % girls, Mage = 13.21 years). METHODS: We conducted a two-wave study with 6-month intervals. Participants completed self-report measures assessing family stress, impulsivity, emotion dysregulation, and NSSI. RESULTS: Moderate mediation analyses showed that threat was indirectly associated with NSSI frequency through the interaction of impulsivity and emotion dysregulation in the R-NSSI group and indirectly through impulsivity in the occasional NSSI (O-NSSI) group. Deprivation did not predict subsequent NSSI frequency in either group. CONCLUSIONS: These findings lend empirical support to dimensional models of adversity and suggest that adolescents who experience threat-related family stress may have greater impulsivity and are more likely to report R-NSSI in the context of emotion dysregulation.

Kuntai capsule for the treatment of diminished ovarian reserve: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) results in reduced fertility. Kuntai capsule, a Chinese patent medicine, which can nourish the heart and kidneys, has shown promising efficacy in its treatment. However, there is no enough clinical evidence to confirm the efficacy and safety of Kuntai capsule. AIM OF THE STUDY: This review aims to evaluate Kuntai capsule's potential benefits and detriments for diminished ovarian reserve. MATERIALS AND METHODS: Databases namely China National Knowledge Infrastructure, WANFANG Database, Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, and Embase were searched from their inception to July 2023. We included randomized controlled trials (RCTs) comparing Kuntai capsule to hormone therapy (HT) and Kuntai capsule in combination with HT to HT alone for DOR treatment. The risk of bias was evaluated using RoB 1.0. A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were antral follicle count (AFC) and serum anti-Müllerian hormone (AMH), secondary outcomes were follicle-stimulating hormone (FSH) and adverse reactions. RESULTS: A Meta-analysis of 12 randomized controlled trials (RCTs), encompassing a total of 905 DOR patients was conducted. The results indicated that the combination of Kuntai capsule with HT exhibited superior efficacy in enhancing AFC (MD = 1.34, 95% CI [0.96,1.72]) and AMH levels (MD = 1.09 (ng/mL) 95% CI[0.80,1.38]), Kuntai capsule demonstrated improvements in AFC (MD = 0.65, 95% CI [0.48,0.83]) in DOR patients compared to HT alone. CONCLUSIONS: Based on the available results, the combination of Kuntai capsule with HT appears to improve the AFC, AMH and FSH levels of DOR patients. Kuntai capsule alone appears to improve the AFC and FSH levels of DOR patients. However, included trials had methodological quality issues, further standardized research is required.

Pre-eclamptic foetal programming predisposes offspring to hepatic steatosis via DNA methylation.

OBJECTIVES: Gamete and embryo-foetal origins of adult diseases hypothesis proposes that adulthood chronic disorders are associated with adverse foetal and early life traits. Our study aimed to characterise developmental changes and underlying mechanisms of metabolic disorders in offspring of pre-eclampsia (PE) programmed pregnancy. METHODS: Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME) induced pre-eclampsia-like C57BL/6J mouse model was used. Lipid profiling, histological morphology, indirect calorimetry, mRNA sequencing, and pyrosequencing were performed on PE offspring of both young and elderly ages. RESULTS: PE offspring exhibited increased postnatal weight gain, hepatic lipid accumulation, enlarged adipocytes, and impaired energy balance that continued to adulthood. Integrated RNA sequencing of foetal and 52-week-old livers revealed that the differentially expressed genes were mainly enriched in lipid metabolism, including glycerol-3-phosphate acyl-transferase 3 (Gpat3), a key enzyme for de novo synthesis of triglycerides (TG), and carnitine palmitoyltransferase-1a (Cpt1a), a key transmembrane enzyme that mediates fatty acid degradation. Pyrosequencing of livers from PE offspring identified hypomethylated and hypermethylated regions in Gpat3 and Cpt1a promoters, which were associated with upregulated and downregulated expressions of Gpat3 and Cpt1a, respectively. These epigenetic alterations are persistent and consistent from the foetal stage to adulthood in PE offspring. CONCLUSION: These findings suggest a methylation-mediated epigenetic mechanism for PE-induced intergenerational lipid accumulation, impaired energy balance and obesity in offspring, and indicate the potential benefits of early interventions in offspring exposed to maternal PE to reduce their susceptibility to metabolic disorder in their later life.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer.

BACKGROUND: Previous neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. METHODS: Thirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. RESULTS: The voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LIMITATIONS: This study is based on cross-sectional data and the sample size is limited. CONCLUSION: These findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Blocking senescence and tolerogenic function of dendritic cells induced by γδ Treg cells enhances tumor-specific immunity for cancer immunotherapy.

BACKGROUND: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy. METHODS: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence and dysfunction induced by Treg cells. Impaired tumor antigen HER2-specific recognition and immune response of senescent DCs induced by γδ Treg cells were explored in vitro and in vivo in humanized mouse models. In addition, the DC-based HER2 tumor vaccine immunotherapy in breast cancer models was performed to explore the enhanced antitumor immunity via prevention of DC senescence through blockages of STAT3 and programmed death-ligand 1 (PD-L1) signaling. RESULTS: We showed that tumor-derived γδ Treg cells promote the development of senescence in DCs with tolerogenic functions in breast cancer. Senescent DCs induced by γδ Treg cells suppress Th1 and Th17 cell differentiation but promote the development of Treg cells. In addition, we demonstrated that PD-L1 and STAT3 signaling pathways are critical and involved in senescence induction in DCs mediated by tumor-derived γδ Treg cells. Importantly, our complementary in vivo studies further demonstrated that blockages of PD-L1 and/or STAT3 signaling can prevent γδ Treg-induced senescence and reverse tolerogenic functions in DCs, resulting in enhanced HER2 tumor-specific immune responses and immunotherapy efficacy in human breast cancer models. CONCLUSIONS: These studies not only dissect the suppressive mechanism mediated by tumor-derived γδ Treg cells on DCs in the tumor microenvironment but also provide novel strategies to prevent senescence and dysfunction in DCs and enhance antitumor efficacy mediated by tumor-specific T cells for cancer immunotherapy.