Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload-induced heart failure mice.

Cardiac remodeling is a commonly observed pathophysiological phenomenon associated with the progression of heart failure in various cardiovascular disorders. Carnosol, a phenolic compound extracted from rosemary, possesses noteworthy pharmacological properties including anti-inflammatory, antioxidant, and anti-apoptotic activities. Considering the pivotal involvement of inflammation, oxidative stress, and apoptosis in cardiac remodeling, the present study aims to assess the effects of carnosol on cardiac remodeling and elucidate the underlying mechanisms. In an in vivo model, cardiac remodeling was induced by performing transverse aortic constriction (TAC) surgery on mice, while an in vitro model was established by treating neonatal rat cardiomyocytes (NRCMs) with Ang II. Our results revealed that carnosol treatment effectively ameliorated TAC-induced myocardial hypertrophy and fibrosis, thereby attenuating cardiac dysfunction in mice. Moreover, carnosol improved cardiac electrical remodeling and restored connexin 43 expression, thereby reducing the vulnerability to ventricular fibrillation (VF). Furthermore, carnosol significantly reduced Ang II-induced cardiomyocyte hypertrophy in NRCMs and alleviated the upregulation of hypertrophy and fibrosis markers. Both in vivo and in vitro models of cardiac remodeling exhibited the anti-inflammatory, anti-oxidative, and anti-apoptotic effects of carnosol. Mechanistically, these effects were mediated through the Sirt1/PI3K/AKT pathway, as the protective effects of carnosol were abrogated upon inhibition of Sirt1 or activation of the PI3K/AKT pathway. In summary, our study suggests that carnosol prevents cardiac structural and electrical remodeling by regulating the anti-inflammatory, anti-oxidative, and anti-apoptotic effects mediated by Sirt1/PI3K/AKT signaling pathways, thereby alleviating heart failure and VF.

Correction: Effect of the HXBM408 bacteria on rat intestinal bacterial diversity and the metabolism of soybean isoflavones.

[This corrects the article DOI: 10.1371/journal.pone.0253728.].

Ferrocene-Based Antioxidant Self-Healing Hydrogel via the Biginelli Reaction for Wound Healing.

The development of antioxidant wound dressings to remove excessive free radicals around wounds is essential for wound healing. In this study, we developed an efficient strategy to prepare antioxidant self-healing hydrogels as wound dressings by combining multicomponent reactions (MCRs) and postpolymerization modification. A polymer containing ferrocene and phenylboronic acid groups was developed via the Biginelli reaction, followed by efficient modification. This polymer is antioxidant due to its ferrocene moieties and can rapidly cross-link poly(vinyl alcohol) to realize an antioxidant self-healing hydrogel through dynamic borate ester linkages. This hydrogel has low cytotoxicity and is biocompatible. In in vivo experiments, this hydrogel is superior to existing clinical dressings in promoting wound healing. This study demonstrates the value of the Biginelli reaction in exploring biomaterials, potentially offering insights into the design of other multifunctional polymers and related materials using different MCRs.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

A comprehensive overview of graph neural network-based approaches to clustering for spatial transcriptomics.

Spatial transcriptomics technologies enable researchers to accurately quantify and localize messenger ribonucleic acid (mRNA) transcripts at a high resolution while preserving their spatial context. The identification of spatial domains, or the task of spatial clustering, plays a crucial role in investigating data on spatial transcriptomes. One promising approach for classifying spatial domains involves the use of graph neural networks (GNNs) by leveraging gene expressions, spatial locations, and histological images. This study provided a comprehensive overview of the most recent GNN-based methods of spatial clustering methods for the analysis of data on spatial transcriptomics. We extensively evaluated the performance of current methods on prevalent datasets of spatial transcriptomics by considering their accuracy of clustering, robustness, data stabilization, relevant requirements, computational efficiency, and memory use. To this end, we explored 60 clustering scenarios by extending the essential frameworks of spatial clustering for the selection of the GNNs, algorithms of downstream clustering, principal component analysis (PCA)-based reduction, and refined methods of correction. We comparatively analyzed the performance of the methods in terms of spatial clustering to identify their limitations and outline future directions of research in the field. Our survey yielded novel insights, and provided motivation for further investigating spatial transcriptomics.

Astilbin protects from sepsis-induced cardiac injury through the NRF2/HO-1 and TLR4/NF-κB pathway.

Cardiac dysfunction and arrhythmia are severe complications of sepsis-induced cardiomyopathy and are associated with an increased risk of morbidity and mortality. Currently, the precise mechanism for sepsis-induced myocardial damage remains unclear. Astilbin, a flavonoid, is reported to have anti-inflammatory, antioxidative, and antiapoptotic properties. However, the effects of astilbin on sepsis-induced cardiomyopathy have not been studied so far. This study aims to investigate the effect of astilbin in sepsis-induced myocardial injury and elucidate the underlying mechanism. In vivo and in vitro sepsis models were created using lipopolysaccharide (LPS) as an inducer in H9C2 cardiomyocytes and C57BL/6 mice, respectively. Our results demonstrated that astilbin reduced myocardial injury and improved cardiac function. Moreover, astilbin prolonged the QT and corrected QT intervals, attenuated myocardial electrical remodeling, and promoted gap junction protein (Cx43) and ion channels expression, thereby reducing the susceptibility of ventricular fibrillation. In addition, astilbin alleviated LPS-induced inflammation, oxidative stress, and apoptosis. Astilbin suppressed the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in vivo and in vitro models. Astilbin remarkedly upregulated the nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1) expression. The in vitro treatment with an NRF2 inhibitor reversed the inhibition of the TLR4/NF-κB pathway and antioxidant properties of astilbin. Astilbin attenuated LPS-induced myocardial injury, cardiac dysfunction, susceptibility to VF, inflammation, oxidative stress, and apoptosis by activating the NRF2/HO-1 pathway and inhibiting TLR4/ NF-κB pathway. These results suggest that astilbin could be an effective and promising therapeutics target for the treatment of sepsis-induced cardiomyopathy.

The Impact of Parent-child Sports Games on Children's Psychological Development / El impacto de los juegos deportivos entre padres e hijos en el desarrollo psicológico de los niños

Childhood is a stage of rapid psychological development, movement and psychological development are inseparable. At this stage, games are the main form of activity for children which play a dominant role in promoting children's psychological development. By implementing parent-child sports game intervention activities, children can prevent psychological disorders or behavioural problems, help them better adapt to social life, and make more effective contributions to society and humanity. Therefore, current research aimed to check the impact of parent-child sports games on children's psychological development. For this purpose, survey subjects were 50 students from large class of kindergarten A and 50 students from the large class of kindergarten B. An experimental research design was applied by using control and experimental group. The findings that the experimental group showed significant improvements in cognitive ability, emotional stability, willpower, and personality shaping compared to the control group. Moreover, their social adaptability was notably higher, fostering smoother communication and harmonious interpersonal relationships. The findings highlight the importance of early engagement in sports game activities to promote psychological health and resilience in preschool children, emphasizing the need for integrating such activities into early childhood education and parental involvement programs. The research also explored a new research area for further research.(AU)

[Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining].

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

UGCG modulates heart hypertrophy through B4GalT5-mediated mitochondrial oxidative stress and the ERK signaling pathway.

Mechanical pressure overload and other stimuli often contribute to heart hypertrophy, a significant factor in the induction of heart failure. The UDP-glucose ceramide glycosyltransferase (UGCG) enzyme plays a crucial role in the metabolism of sphingolipids through the production of glucosylceramide. However, its role in heart hypertrophy remains unknown. In this study, UGCG was induced in response to pressure overload in vivo and phenylephrine stimulation in vitro. Additionally, UGCG downregulation ameliorated cardiomyocyte hypertrophy, improved cardiomyocyte mitochondrial oxidative stress, and reduced the ERK signaling pathway. Conversely, UGCG overexpression in cardiomyocytes promoted heart hypertrophy development, aggravated mitochondrial oxidative stress, and stimulated ERK signaling. Furthermore, the interaction between beta-1,4-galactosyltransferase 5 (B4GalT5), which catalyses the synthesis of lactosylceramide, and UGCG was identified, which also functions as a synergistic molecule of UGCG. Notably, limiting the expression of B4GalT5 impaired the capacity of UGCG to promote myocardial hypertrophy, suggesting that B4GalT5 acts as an intermediary for UGCG. Overall, this study highlights the potential of UGCG as a modulator of heart hypertrophy, rendering it a potential target for combating heart hypertrophy.

Germacrone mitigates cardiac remodeling by regulating PI3K/AKT-mediated oxidative stress, inflammation, and apoptosis.

Cardiac remodeling is a common consequence of cardiovascular diseases and is closely associated with oxidative stress, inflammation, and apoptosis. Germacrone, a bioactive compound present in Rhizoma curcuma, has been shown to possess anti-oxidative, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the protective effect of germacrone against cardiac remodeling. Here, C57BL/6 mice were subcutaneous injection with isoproterenol (ISO) once daily for two weeks and were concurrent intragastric injection of germacrone. In vitro, neonatal rat cardiomyocytes (NRCMs) were used to verify the protective effect of germacrone on ISO-induced cardiac injury. Our findings indicated that ISO induce oxidative stress, inflammation, and apoptosis in vivo and in vitro, while germacrone treatment significantly attenuates these effects, thereby attenuating myocardium remodeling and cardiac dysfunction. Mechanistically, germacrone reduced cardiac remodeling-induced activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and the cardioprotective effects of germacrone were abrogated by a PI3K agonist. In conclusion, our results suggest that germacrone attenuates oxidative stress, inflammation, and apoptosis in cardiac remodeling by inhibiting the PI3K/AKT pathway, and may therefore represent a promising therapeutic approach for the treatment of cardiac remodeling.

[Activation of Hippo Pathway Proteins in Thrombin-Stimulated Platelets and Regutates Platelets Activation in Vitro].

OBJECTIVE: To investigate the phosphorylation levels of Hippo pathway proteins in thrombin stimulated platelets and to explore its effects on platelet activation. METHODS: The phosphorylation levels of Hippo pathway proteins - Mammalian STE20-like kinase 1/2 (MST1/2), Nuclear Dbf2 related kinase 1/2 (NDR1/2) and Mps one binder 1(MOB1) in human thrombin stimulated platelets was detected by Western blot. The effect of MST1/2 inhibitor XMU-MP-1 on platelet aggregation was detected by Platelet Aggregometer. The effect of XMU-MP-1 on platelet integrin αIIbß3 activation and CD62p expression was detected by flow cytometry. The effect of XMU-MP-1 on the "outside-in" signal of platelet integrin was detected by blood clot retraction test. The effects of XMU-MP-1 on platelet Hippo pathway proteins and p38 phosphorylation levels was detected by Western blot. RESULTS: The phosphorylation levels of MST1/2, NDR1/2 and MOB1 were significantly increased in thrombin activated platelets; XMU-MP-1 inhibited thrombin-induced platelet aggregation and αIIbß3 activation, but did not affect α-granules release and clot retraction. In addition, thrombin induced phosphorylation of the Hippo proteins were decreased in XMU-MP-1 treated platelets, while the phosphorylation of p38 was not affected. CONCLUSION: In thrombin stimulated platelets, Hippo pathway proteins were activated and contributed to platelets activation.

Effect of C7-T1 Extensional Posterior Transpedicle Osteotomy on Mobility and Quality of Life in Patients with Ankylosing Spondylitis Complicated with Lumbar Kyphosis and Related Factors.

Objective: To analyze the effect of C7-T1 extensional posterior transpedicular vertebral osteotomy (PSO) on mobility and quality of life in patients with ankylosing spondylitis (AS) and lumbar kyphosis. Methods: This study was conducted from February 2019 to February 2021 and a total of 38 patients with AS combined with kyphosis from Tianjin Union Medical Center, Tianjin, China, were selected for the study. After performing all preoperative examinations, all patients were treated with C7-T1 extensional posterior PSO osteotomy. The patients' operation and follow-up, pain degree as a Visual analogue scale (VAS) score and sagittal balance index changes before and after surgery, spinal function measured as; Bath Ankylosing Spondylitis Functional Index (BASFI) score and quality of life by Scoliosis Research Society-22 (SRS-22) score, were observed before and after surgery. Pearson correlation coefficient was used to analyze the correlation between patients' quality of life and BASFI score. Results: After surgery, the pain of the patients' back was significantly relieved, the patients' appearance and trunk balance function were significantly improved, and the symptoms related to nerve function were not significantly aggravated. No complications such as infection, internal fixation failure or spinal decompensation occurred in all patients. VAS score, kyphosis Cobb Angle and Sagittal Vertical Axis (SVA) of all patients showed P < .05 before and 1 year after surgery. BASFI score 1 year after surgery decreased significantly than that before surgery (P < .05). 1 year after surgery, body function, pain symptoms, self-image and psychological state of the patients were significantly improved, and the SRS-22 total score of the patients 1 year after surgery increased significantly than before surgery (P < 0.05). BASFI score was negatively correlated with SRS-22 score by Pearson correlation coefficient analysis (P < .05). Conclusion: C7-T1 extensional posterior PSO osteotomy has a good effect in the treatment of AS patients with lumbar kyphosis. The sagittal balance was well-restored with improvement in patients' quality of life after surgery, which makes C7-T1 osteotomy worthy of clinical application to treat patients suffering from AS combined with lumbar kyphosis.

The in vivo drug delivery pattern of the organelle-targeting small molecules.

Eukaryotic cell organelles sustain the life of cells. Their structural changes and dysfunctions can cause abnormal physiological activities and lead to various diseases. Molecular imaging technology enables the visualization of subcellular structures, cells, organs, and the whole living body's structure and metabolism dynamic changes. This could help to reveal the pharmacology mechanisms and drug delivery pathway in vivo. This article discusses the relationship between organelles and human disease, reviews recent probes targeting organelles and their behavior in vivo. We found that mitochondria-targeting probes prefer accumulation in the intestine, heart, and tumor. The lysosome-targeting probe accumulates in the intestine and tumor. Few studies on endoplasmic reticulum- or Golgi apparatus-targeting probes have been reported for in vivo imaging. We hope this review could provide new insights for developing and applying organelle-targeting probes.

Poly(vinyl alcohol) Modified via the Hantzsch Reaction for Biosafe Antioxidant Self-Healing Hydrogel.

Efficient routes for the preparation of functional self-healing hydrogels from functional polymers are needed. In this study, we developed a strategy to effectively produce a vanillin-modified poly(vinyl alcohol) (PVA-vanillin) through the Hantzsch reaction. This polymer was cross-linked with a phenylboronic acid-containing polymer (PB) that was also prepared using the Hantzsch reaction to fabricate a hydrogel through borate ester linkages under mild conditions (25 °C, pH ∼ 7.4). This hydrogel had excellent antioxidant abilities due to the 1,4-dihydropyridine (DHP) rings and the vanillin moieties in the hydrogel structures; it was also self-healable and injectable owing to the dynamic borate ester linkages. Furthermore, the antioxidant self-healing hydrogel had low cytotoxicity and exhibited favorable safety in animal experiments, indicating its potential as a safe implantable cell or drug carrier. This study developed a method for preparing functional polymers and related self-healing hydrogels in a facile manner; it demonstrated the value of the Hantzsch reaction in exploiting antioxidant self-healing hydrogels for biomedical applications, which may provide insight into the design of other functional self-healing hydrogels through different multicomponent reactions.

Curcumol alleviates cardiac remodeling via the AKT/NF-κB pathway.

Cardiac remodeling is the final stage of almost all cardiovascular diseases, leading to heart failure and arrhythmias. However, the pathogenesis of cardiac remodeling is not fully understood, and specific treatment schemes are currently unavailable. Curcumol is a bioactive sesquiterpenoid that has anti-inflammatory, anti-apoptotic, and anti-fibrotic properties. This study aimed to investigate the protective effect of curcumol on cardiac remodeling and elucidate its relevant underlying mechanism. Curcumol significantly attenuated cardiac dysfunction, myocardial fibrosis, and hypertrophy in the animal model of isoproterenol (ISO)-induced cardiac remodeling. Curcumol also alleviated cardiac electrical remodeling, thereby reducing the risk of ventricular fibrillation (VF) after heart failure. Inflammation and apoptosis are critical pathological processes involved in cardiac remodeling. Curcumol inhibited the inflammation and apoptosis induced by ISO and TGF-ß1 in mouse myocardium and neonatal rat cardiomyocytes (NRCMs). Furthermore, the protective effects of curcumol were found to be mediated through the inhibition of the protein kinase B (AKT)/nuclear factor-kappa B (NF-κB) pathway. The administration of an AKT agonist reversed the anti-fibrotic, anti-inflammatory, and anti-apoptotic effects of curcumol and restored the inhibition of NF-κB nuclear translocation in TGF-ß1-induced NRCMs. Our study suggests that curcumol is a potential therapeutic agent for the treatment of cardiac remodeling.

Characterization of gut microbial and metabolite alterations in faeces of Goto Kakizaki rats using metagenomic and untargeted metabolomic approach.

BACKGROUND: In recent years, the incidence of type 2 diabetes (T2DM) has shown a rapid growth trend. Goto Kakizaki (GK) rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients. A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites. We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance. AIM: To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics. METHODS: Ten GK rats (model group) and Wistar rats (control group) were observed for 10 wk, and various glucose-related indexes, mainly including weight, fasting blood glucose (FBG) and insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß cell (HOMA-ß) were assessed. The faecal gut microbiota was sequenced by metagenomics, and faecal metabolites were analysed by untargeted metabolomics. Multiple metabolic pathways were evaluated based on the differential metabolites identified, and the correlations between blood glucose and the gut microbiota and metabolites were analysed. RESULTS: The model group displayed significant differences in weight, FBG and insulin levels, HOMA-IR and HOMA-ß indexes (P < 0.05, P < 0.01) and a shift in the gut microbiota structure compared with the control group. The results demonstrated significantly decreased abundances of Prevotella sp. CAG:604 and Lactobacillus murinus (P < 0.05) and a significantly increased abundance of Allobaculum stercoricanis (P < 0.01) in the model group. A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus. An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups. Fourteen potential metabolic biomarkers, including glycochenodeoxycholic acid, uric acid, 13(S)-hydroxyoctadecadienoic acid (HODE), N-acetylaspartate, ß-sitostenone, sphinganine, 4-pyridoxic acid, and linoleic acid, were identified. Moreover, FBG and HOMA-IR were found to be positively correlated with glutathione, 13(S)-HODE, uric acid, 4-pyridoxic acid and allantoic acid and ne-gatively correlated with 3-α, 7-α, chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-ß-cholestane (P < 0.05, P < 0.01). Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine (P < 0.01), and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp. CAG:604 (P < 0.01). The metabolic pathways showing the largest differences were arginine biosynthesis; primary bile acid biosynthesis; purine metabolism; linoleic acid metabolism; alanine, aspartate and glutamate metabolism; and nitrogen metabolism. CONCLUSION: Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.

Graph deep learning enabled spatial domains identification for spatial transcriptomics.

Advancing spatially resolved transcriptomics (ST) technologies help biologists comprehensively understand organ function and tissue microenvironment. Accurate spatial domain identification is the foundation for delineating genome heterogeneity and cellular interaction. Motivated by this perspective, a graph deep learning (GDL) based spatial clustering approach is constructed in this paper. First, the deep graph infomax module embedded with residual gated graph convolutional neural network is leveraged to address the gene expression profiles and spatial positions in ST. Then, the Bayesian Gaussian mixture model is applied to handle the latent embeddings to generate spatial domains. Designed experiments certify that the presented method is superior to other state-of-the-art GDL-enabled techniques on multiple ST datasets. The codes and dataset used in this manuscript are summarized at https://github.com/narutoten520/SCGDL.

Long-term phosphorus addition alters plant community composition but not ecosystem stability of a nitrogen-enriched desert steppe.

Under ongoing global change, whether grassland ecosystems can maintain their functions and services depends largely on their stability. However, how ecosystem stability responds to increasing phosphorus (P) inputs under nitrogen (N) loading remains unclear. We conducted a 7-year field experiment to examine the influence of elevated P inputs (ranging from 0 to 16 g P m-2 yr-1) on the temporal stability of aboveground net primary productivity (ANPP) under N addition of 5 g N·m-2·yr-1 in a desert steppe. We found that under N loading, P addition altered plant community composition but did not significantly affect ecosystem stability. Specifically, with the increase in the P addition rate, declines in the relative ANPP of legume could be compensated for by an increase in the relative ANPP of grass and forb species, yet community ANPP and diversity remained unchanged. Notably, the stability and asynchrony of dominant species tended to decrease with increasing P addition, and a significant decrease in legume stability was observed at high P rates (>8 g P m-2 yr-1). Moreover, P addition indirectly affected ecosystem stability by multiple pathways (e.g., species diversity, species asynchrony, dominant species asynchrony, and dominant species stability), as revealed by structural equation modeling results. Our results suggest that multiple mechanisms work concurrently in stabilizing the ecosystem stability of desert steppes and that increasing P inputs may not alter desert steppe ecosystem stability under future N-enriched scenarios. Our results will help improve the accuracy of vegetation dynamics assessments in arid ecosystems under future global change.

Engeletin mediates antiarrhythmic effects in mice with isoproterenol-induced cardiac remodeling.

OBJECTIVE: Engeletin is a potent natural compound with antioxidant and anti-inflammatory properties. However, its role in cardiac remodeling remains unclear. Herein, the aim of the present study was to explore the effects of engeletin on cardiac structural and electrical remodeling and its underlying mechanism. METHODS: and results: A cardiac remodeling mice model using isoproterenol (ISO)-induced myocardial fibrosis was constructed and divided into the following four groups: control group; engeletin group; ISO group; engeletin + ISO group. Our results demonstrated that engeletin alleviated ISO-induced myocardial fibrosis and dysfunction. Moreover, engeletin significantly prolonged the QT and corrected QT (QTc) intervals, effective refractory period (ERP), and action potential duration (APD), and enhanced connexin protein 43 (Cx43) and ion channel expressions, thereby decreasing ventricular fibrillation (VF) susceptibility. Additionally, dihydroethidium staining illustrated that engeletin decreased reactive oxygen species (ROS) production. Of note, engeletin also increased the levels of superoxide dismutase and glutathione and decreased the activity of malondialdehyde and L-Glutathione oxidized. Moreover, engeletin significantly increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Furthermore, in vitro administration of an Nrf2 inhibitor abolished the anti-oxidant properties of engeletin. CONCLUSION: Engeletin ameliorated cardiac structural and electrical remodeling, ion channel remodeling, and oxidative stress induced by ISO in mice, thereby reducing VF susceptibility. These effects may be attributed to the anti-oxidant properties of engeletin associated with the Nrf2/HO-1 pathway.

Evaluation of enlarged laminectomy with lateral mass screw fixation in relieving nerve root symptoms and correcting kyphosis for cervical myelopathy and radiculopathy.

Purpose: This study aimed to compare the surgical efficacy of enlarged laminectomy with lateral mass screw fixation (EL-LMSF) and anterior cervical decompression and fusion (ACDF) for multilevel cervical myelopathy and radiculopathy (CMR) related to kyphosis. Methods: 75 patients were retrospectively reviewed and divided into ACDF and EL-LMSF group. Clinical results including operative time, blood loss, and postoperative complications were compared. The JOA scoring system was used to evaluate spinal cord function and the VAS score evaluate nerve root pain severity. Cervical alignment a C2-C7 was measured with Cobb method and compared to confirm the reconstruction effect. Results: Data on 75 patients (M/F: 41:34; EL-LMSF/ACDF:42/33) with the mean age of 57.5 years (range 43-72 year old) were reviewed retrospectively. Discectomy and/or sub-toal corpectomy in ACDF group was performed with a mean of 3.24 levels (range, 3-4). Enlarged laminectomy in EL-LMSF group was performed with a mean of 3.89 enlarged levels (range, 3-5). The procedure of ACDF group showed a shorter operation time (103 ± 22 min vs. 125 ± 37 min, P = 0.000) and less blood loss (78 ± 15 ml vs. 226 ± 31 ml, P = 0.000) compared than that of the EL-LMSF group. Patients treated with EL-LMSF indicated lower VAS for upper extremity (1.3 ± 1.7 vs. 3.3 ± 1.3, P = 0.003) and better curvature corrected (10.7 ± 4.2° vs. 8.5 ± 3.5°, P = 0.013). The difference were of statistical significance. No statistical difference was found after surgery in the JOA score (14.1 ± 1.7 vs. 13.5 ± 2.1, P = 0.222). During the follow-up period, 15.2% of patients in the ACDF group had complications including 2 cases with transient dysphagia, 1 case with C5 palsy, 1 case with axial pain, and 1 case with screw pullout 3 month after surgery. However, only 9.5% of cases in the EL-LMSF group experienced complications, including 3 cases of axial pain and 1 case of epidural hematoma. Conclusion: The EL-LMSF procedure requires a longer operation time and more blood loss because of the incision of the stenosed foramen. However, the procedure has obvious advantages in relieving nerve root symptoms and correcting cervical curvature with fewer postoperative complications.