Variation of soil bacterial communities along a chronosequence of Eucalyptus plantation

Eucalyptus is harvested for wood and fiber production in many tropical and sub-tropical habitats globally. Plantation has been controversial because of its influence on the surrounding environment, however, the influence of massive Eucalyptus planting on soil microbial communities is unclear. Here we applied high-throughput sequencing of the 16S rRNA gene to assess the microbial community composition and diversity of planting chronosequences, involving two, five and ten years of Eucalyptus plantation, comparing to that of secondary-forest in South China. We found that significant changes in the composition of soil bacteria occurred when the forests were converted from secondary-forest to Eucalyptus. The bacterial community structure was clearly distinct from control and five year samples after Eucalyptus was grown for 2 and 10 years, highlighting the influence of this plantation on local soil microbial communities. These groupings indicated a cycle of impact (2 and 10 year plantations) and low impact (5-year plantations) in this chronosequence of Eucalyptus plantation. Community patterns were underpinned by shifts in soil properties such as pH and phosphorus concentration. Concurrently, key soil taxonomic groups such as Actinobacteria showed abundance shifts, increasing in impacted plantations and decreasing in low impacted samples. Shifts in taxonomy were reflected in a shift in metabolic potential, including pathways for nutrient cycles such as carbon fixation, which changed in abundance over time following Eucalyptus plantation. Combined these results confirm that Eucalyptus plantation can change the community structure and diversity of soil microorganisms with strong implications for land-management and maintaining the health of these ecosystems

Cardiorenal disease connection during post-menopause: The protective role of estrogen in uremic toxins induced microvascular dysfunction

Female gender, post-menopause, chronic kidney disease (CKD) and (CKD linked) microvascular disease are important risk factors for developing heart failure with preserved ejection fraction (HFpEF). Enhancing our understanding of the interrelation between these risk factors could greatly benefit the identification of new drug targets for future therapy. This review discusses the evidence for the protective role of estradiol (E2) in CKD-associated microvascular disease and related HFpEF. Elevated circulating levels of uremic toxins (UTs) during CKD may act in synergy with hormonal changes during post-menopause and could lead to coronary microvascular endothelial dysfunction in HFpEF. To elucidate the molecular mechanism involved, published transcriptome datasets of indoxyl sulfate (IS), high inorganic phosphate (HP) or E2 treated human derived endothelial cells from the NCBI Gene Expression Omnibus database were analyzed. In total, 36 genes overlapped in both IS- and HP-activated gene sets, 188 genes were increased by UTs (HP and/or IS) and decreased by E2, and 572 genes were decreased by UTs and increased by E2. Based on a comprehensive in silico analysis and literature studies of collected gene sets, we conclude that CKD-accumulated UTs could negatively impact renal and cardiac endothelial homeostasis by triggering extensive inflammatory responses and initiating dysregulation of angiogenesis. E2 may protect (myo)endothelium by inhibiting UTs-induced inflammation and ameliorating UTs-related uremic bleeding and thrombotic diathesis via restored coagulation capacity and hemostasis in injured vessels

Robust Multimodal Failure Detection for Microservice Systems

Proactive failure detection of instances is vitally essential to microservice systems because an instance failure can propagate to the whole system and degrade the system's performance. Over the years, many single-modal (i.e., metrics, logs, or traces) data-based nomaly detection methods have been proposed. However, they tend to miss a large number of failures and generate numerous false alarms because they ignore the correlation of multimodal data. In this work, we propose AnoFusion, an unsupervised failure detection approach, to proactively detect instance failures through multimodal data for microservice systems. It applies a Graph Transformer Network (GTN) to learn the correlation of the heterogeneous multimodal data and integrates a Graph Attention Network (GAT) with Gated Recurrent Unit (GRU) to address the challenges introduced by dynamically changing multimodal data. We evaluate the performance of AnoFusion through two datasets, demonstrating that it achieves the F1-score of 0.857 and 0.922, respectively, outperforming the state-of-the-art failure detection approaches

Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1

Aims: Formation of a functional vascular system is essential and its formation is a highly regulated process initiated during embryogenesis, which continues to play important roles throughout life in both health and disease. In previous studies, Fzd5 was shown to be critically involved in this process and here we investigated the molecular mechanism by which endothelial loss of this receptor attenuates angiogenesis. Methods and results: Using short interference RNA-mediated loss-of-function assays, the function and mechanism of signaling via Fzd5 was studied in human endothelial cells (ECs). Our findings indicate that Fzd5 signaling promotes neovessel formation in vitro in a collagen matrix-based 3D co-culture of primary vascular cells. Silencing of Fzd5 reduced EC proliferation, as a result of G0/G1 cell cycle arrest, and decreased cell migration. Furthermore, Fzd5 knockdown resulted in enhanced expression of the factors Angpt2 and Flt1, which are mainly known for their destabilizing effects on the vasculature. In Fzd5-silenced ECs, Angpt2 and Flt1 upregulation was induced by enhanced PKC signaling, without the involvement of canonical Wnt signaling, non-canonical Wnt/Ca2+-mediated activation of NFAT, and non-canonical Wnt/PCP-mediated activation of JNK. We demonstrated that PKC-induced transcription of Angpt2 and Flt1 involved the transcription factor Ets1. Conclusions: The current study demonstrates a pro-angiogenic role of Fzd5, which was shown to be involved in endothelial tubule formation, cell cycle progression and migration, and partly does so by repression of PKC/Ets1-mediated transcription of Flt1 and Angpt2

Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies

Inherited cardiomyopathies caused by pathological genetic variants include multiple subtypes of heart disease. Advances in next-generation sequencing (NGS) techniques have allowed for the identification of numerous genetic variants as pathological variants. However, the disease penetrance varies among mutated genes. Some can be associated with more than one disease subtype, leading to a complex genotype-phenotype relationship in inherited cardiomyopathies. Previous studies have demonstrated disrupted metabolism in inherited cardiomyopathies and the importance of metabolic adaptations in disease onset and progression. In addition, genotype- and phenotype-specific metabolic alterations, especially in lipid metabolism, have been revealed. In this mini-review, we describe the metabolic changes that are associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), which account for the largest proportion of inherited cardiomyopathies. We also summarize the affected expression of genes involved in fatty acid oxidation (FAO) in DCM and HCM, highlighting the potential of PPARA-targeting drugs as FAO modulators in treating patients with inherited cardiomyopathies

Quantum phase transition in magnetic nanographenes on a lead superconductor

Quantum spins, referred to the spin operator preserved by full SU(2) symmetry in the absence of the magnetic anistropy, have been proposed to host exotic interactions with superconductivity4. However, spin orbit coupling and crystal field splitting normally cause a significant magnetic anisotropy for d/f-shell spins on surfaces6,9, breaking SU(2) symmetry and fabricating the spins with Ising properties10. Recently, magnetic nanographenes have been proven to host intrinsic quantum magnetism due to their negligible spin orbital coupling and crystal field splitting. Here, we fabricate three atomically precise nanographenes with the same magnetic ground state of spin S=1/2 on Pb(111) through engineering sublattice imbalance in graphene honeycomb lattice. Scanning tunneling spectroscopy reveals the coexistence of magnetic bound states and Kondo screening in such hybridized system. Through engineering the magnetic exchange strength between the unpaired spin in nanographenes and cooper pairs, quantum phase transition from the singlet to the doublet state has been observed, in consistent with quantum models of spins on superconductors. Our work demonstrates delocalized graphene magnetism host highly tunable magnetic bound states with cooper pairs, which can be further developed to study the Majorana bound states and other rich quantum physics of low-dimensional quantum spins on superconductors.Comment: 13 pages, 4figure

The splicing factor DHX38 enables retinal development through safeguarding genome integrity

DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, wedemonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control

Advanced lung cancer inflammation index is associated with long-term cardiovascular death in hypertensive patients: national health and nutrition examination study, 1999–2018

Background: Hypertension is one of the main causes of cardiovascular death. Inflammation was considered influential factors of cardiovascular (CVD) death in patients with hypertension. Advanced lung cancer inflammation index (ALI) is an index to assess inflammation, few studies have investigated the relationship between advanced lung cancer inflammation index and cardiovascular death in hypertensive patients.Objective: The aim of this study was to investigate the association between advanced lung cancer inflammation index and long-term cardiovascular death in hypertensive patients.Method: Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 with mortality follow-up through 31 December 2019 were analyzed. Advanced lung cancer inflammation index was calculated as BMI (kg/㎡) × serum albumin level (g/dL)/neutrophil to lymphocyte ratio (NLR). A total of 20,517 participants were evaluated. Patients were divided into three groups based on tertiles of advanced lung cancer inflammation index as follows: T1 (n = 6,839), T2 (n = 6,839), and T3 (n = 6,839) groups. The relationship between advanced lung cancer inflammation index and long-term cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights.Results: The median advanced lung cancer inflammation index value in this study was 61.9 [44.4, 84.6]. After full adjustment, the T2 group (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50–0.69; p < 0.001) and T3 group (HR: 0.48, 95% CI: 0.39–0.58; p < 0.001) were found to have a significantly lower risk of cardiovascular death compared to the T1 group.Conclusion: High levels of advanced lung cancer inflammation index were associated with reduced risk of cardiovascular death in hypertensive patients

Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis

Background: Vitamin D deficiency is related to increased cancer risk and deaths. However, whether vitamin D supplementation reduces cancer mortality remains unclear, and several randomized controlled trials yield inconsistent results. Methods: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception until 28 June 2022, for randomized controlled trials investigating vitamin D supplementation. Pooled relative risks (RRs) and their 95% confidence intervals (CIs) were estimated. Trials with vitamin D supplementation combined with calcium supplementation versus placebo alone and recruiting participants with cancer at baseline were excluded in the present study. Results: This study included 12 trials with a total of 72,669 participants. Vitamin D supplementation did not reduce overall cancer mortality (RR 0.96, 95% CI 0.80-1.16). However, vitamin D supplementation was associated with a reduction in lung cancer mortality (RR 0.63, 95% CI 0.45-0.90). Conclusions: Vitamin D supplementation could not reduce cancer mortality in this highly purified meta-analysis. Further RCTs that evaluate the association between vitamin D supplementation and total cancer mortality are still needed

Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy

BACKGROUND: Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies. METHODS: We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs. RESULTS: Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis. CONCLUSIONS: Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically