Rhizobial-induced phosphatase GmPP2C61A positively regulates soybean nodulation.

Symbiotic nitrogen fixation (SNF) is crucial for legumes, providing them with the nitrogen necessary for plant growth and development. Nodulation is the first step in the establishment of SNF. However, the determinant genes in soybean nodulation and the understanding of the underlying molecular mechanisms governing nodulation are still limited. Herein, we identified a phosphatase, GmPP2C61A, which was specifically induced by rhizobia inoculation. Using transgenic hairy roots harboring GmPP2C61A::GUS, we showed that GmPP2C61A was mainly induced in epidermal cells following rhizobia inoculation. Functional analysis revealed that knockdown or knock-out of GmPP2C61A significantly reduced the number of nodules, while overexpression of GmPP2C61A promoted nodule formation. Additionally, GmPP2C61A protein was mainly localized in the cytoplasm and exhibited conserved phosphatase activity in vitro. Our findings suggest that phosphatase GmPP2C61A serves as a critical regulator in soybean nodulation, highlighting its potential significance in enhancing symbiotic nitrogen fixation.

EPA and DHA Alleviated Chronic Dextran Sulfate Sodium Exposure-Induced Depressive-like Behaviors in Mice and Potential Mechanisms Involved.

Patients with ulcerative colitis (UC) have higher rates of depression. However, the mechanism of depression development remains unclear. The improvements of EPA and DHA on dextran sulfate sodium (DSS)-induced UC have been verified. Therefore, the present study mainly focused on the effects of EPA and DHA on UC-induced depression in C57BL/6 mice and the possible mechanisms involved. A forced swimming test and tail suspension experiment showed that EPA and DHA significantly improved DSS-induced depressive-like behavior. Further analysis demonstrated that EPA and DHA could significantly suppress the inflammation response of the gut and brain by regulating the NLRP3/ASC signal pathway. Moreover, intestine and brain barriers were maintained by enhancing ZO-1 and occludin expression. In addition, EPA and DHA also increased the serotonin (5-HT) concentration and synaptic proteins. Interestingly, EPA and DHA treatments increased the proportion of dominant bacteria, alpha diversity, and beta diversity. In conclusion, oral administration of EPA and DHA alleviated UC-induced depressive-like behavior in mice by modulating the inflammation, maintaining the mucosal and brain barriers, suppressing neuronal damage and reverting microbiota changes.

Overexpression of HbGRF4 or HbGRF4-HbGIF1 Chimera Improves the Efficiency of Somatic Embryogenesis in Hevea brasiliensis.

Transgenic technology is a crucial tool for gene functional analysis and targeted genetic modification in the para rubber tree (Hevea brasiliensis). However, low efficiency of plant regeneration via somatic embryogenesis remains a bottleneck of successful genetic transformation in H. brasiliensis. Enhancing expression of GROWTH-REGULATING FACTOR 4 (GRF4)-GRF-INTERACTING FACTOR 1 (GIF1) has been reported to significantly improve shoot and embryo regeneration in multiple crops. Here, we identified endogenous HbGRF4 and HbGIF1 from the rubber clone Reyan7-33-97, the expressions of which dramatically increased along with somatic embryo (SE) production. Intriguingly, overexpression of HbGRF4 or HbGRF4-HbGIF1 markedly enhanced the efficiency of embryogenesis in two H. brasiliensis callus lines with contrasting rates of SE production. Transcriptional profiling revealed that the genes involved in jasmonic acid response were up-regulated, whereas those in ethylene biosynthesis and response as well as the S-adenosylmethionine-dependent methyltransferase activity were down-regulated in HbGRF4- and HbGRF4-HbGIF1-overexpressing H. brasiliensis embryos. These findings open up a new avenue for improving SE production in rubber tree, and help to unravel the underlying mechanisms of HbGRF4-enhanced somatic embryogenesis.

Reappraising the role of chronic inflammatory burden in heart failure.

BACKGROUND: Heart failure (HF) is a clinical syndrome associated with poor quality of life, substantial utilization of health care resources, and premature mortality. It is now considered to be the most urgent unmet medical need in the field of cardiovascular disease. Accumulated evidence suggested that comorbidity-driven inflammation has emerged as a critical component of HF pathogenesis. Although anti-inflammatory therapies have increased in popularity, very few effective treatments are still available. A comprehensive understanding of the interplay between chronic inflammation and its impact on HF will facilitate the identification of future therapeutic targets. METHODS: A two-sample Mendelian randomization study was conducted to assess the association between genetic liability for chronic inflammation and HF. By analyzing functional annotations and enrichment data, we were able to identify common pathophysiological mechanisms. RESULTS: The present study did not provide evidence for chronic inflammation as the cause of HF and the reliability of the results was enhanced by the other three Mendelian randomization analysis methods. Functional annotations of genes and pathway enrichment analyses have indicated that chronic inflammation and HF share a common pathophysiology. CONCLUSIONS: The associations between chronic inflammation and cardiovascular disease from observational studies may be explained by shared risk factors and comorbidities rather than direct effects.

Two Birds One Stone: Graphene Assisted Reaction Kinetics and Ionic Conductivity in Phthalocyanine-Based Covalent Organic Framework Anodes for Lithium-ion Batteries.

This work reports a covalent organic framework composite structure (PMDA-NiPc-G), incorporating multiple-active carbonyls and graphene on the basis of the combination of phthalocyanine (NiPc(NH2 )4 ) containing a large π-conjugated system and pyromellitic dianhydride (PMDA) as the anode of lithium-ion batteries. Meanwhile, graphene is used as a dispersion medium to reduce the accumulation of bulk covalent organic frameworks (COFs) to obtain COFs with small-volume and few-layers, shortening the ion migration path and improving the diffusion rate of lithium ions in the two dimensional (2D) grid layered structure. PMDA-NiPc-G showed a lithium-ion diffusion coefficient (DLi + ) of 3.04 × 10-10 cm2 s-1 which is 3.6 times to that of its bulk form (0.84 × 10-10 cm2 s-1 ). Remarkably, this enables a large reversible capacity of 1290 mAh g-1 can be achieved after 300 cycles and almost no capacity fading in the next 300 cycles at 100 mA g-1 . At a high areal capacity loading of ≈3 mAh cm-2 , full batteries assembled with LiNi0.8 Co0.1 Mn0.1 O2 (NCM-811) and LiFePO4 (LFP) cathodes showed 60.2% and 74.7% capacity retention at 1 C for 200 cycles. Astonishingly, the PMDA-NiPc-G/NCM-811 full battery exhibits ≈100% capacity retention after cycling at 0.2 C. Aided by the analysis of kinetic behavior of lithium storage and theoretical calculations, the capacity-enhancing mechanism and lithium storage mechanism of covalent organic frameworks are revealed. This work may lead to more research on designable, multifunctional COFs for electrochemical energy storage.

Structure and Reactivity of a Seven-Coordinate Ruthenium Iodosylbenzene Complex.

Seven-coordinate (CN7) ruthenium-oxo species have attracted much attention as highly reactive intermediates in both organic and water oxidation. Apart from metal-oxo, other metal-oxidant adducts, such as metal-iodosylarenes, have also recently emerged as active oxidants. We reported herein the first example of a CN7 Ru-iodosylbenzene complex, [RuIV(bdpm)(pic)2(O)I(Cl)Ph]+ (H2bdpm = [2,2'-bipyridine]-6,6'-diylbis(diphenylmethanol); pic = 4-picoline). The X-ray crystal structure of this complex shows that it adopts a distorted pentagonal bipyramidal geometry with Ru-O(I) and O-I distances of 2.0451(39) and 1.9946(40) Å, respectively. This complex is highly reactive, and it readily undergoes O-atom transfer (OAT) and C-H bond activation reactions with various organic substrates. This work should provide insights for the development of new highly reactive oxidizing agents based on CN7 geometry.

Hyperhomocysteinemia lowers serum testosterone concentration via impairing testosterone production in Leydig cells.

Hyperhomocysteinemia (HHcy) plays a salient role in male infertility. However, whether HHcy interferes with testosterone production remains inconclusive. Here, we reported a lower serum testosterone level in HHcy mice. Single-cell RNA sequencing revealed that genes related to testosterone biosynthesis, together with nuclear receptor subfamily 5 group A member 1 (Nr5a1), a key transcription factor for steroidogenic genes, were downregulated in the Leydig cells (LCs) of HHcy mice. Mechanistically, Hcy lowered trimethylation of histone H3 on lysine 4 (H3K4me3), which was bound on the promoter region of Nr5a1, resulting in downregulation of Nr5a1. Intriguingly, we identified an unknown cell cluster annotated as Macrophage-like Leydig cells (McLCs), expressing both LCs and macrophages markers. In HHcy mice, McLCs were shifted toward pro-inflammatory phenotype and thus promoted inflammatory response in LC. Betaine supplementation rescued the downregulation of NR5A1 and restored the serum testosterone level in HHcy mice. Overall, our study highlights an etiological role of HHcy in LCs dysfunction.

Longitudinal relationships among career adaptability, resilience, and career commitment in chinese nursing undergraduates: testing differences in career interest between cross-lagged models.

PURPOSE: Various physiological and psychological negative situations experienced by nurses as a result of COVID-19 pandemic have been shown to increase their perception of organizational difficulty and decrease their career commitment, thereby accelerating the turnover rate of nurses. Resilience and career adaptability have important influences on career commitment, so there is a need to evaluate the relationships between them and the underlying mechanisms. PATIENTS AND METHODS: Using a cross-lagged design, the Career Adaptability Scale, the Chinese version of career commitment, and Davidson's Resilience Scale as research methods, we studied 692 nursing students for two consecutive years to evaluate the relationship among career adaptability, resilience, and career commitment. RESULTS: Career adaptability at T1 substantially and positively predicts the career commitment at T2. Career adaptability and resilience are mutually predictive. No interaction is found between resilience and career commitment over time. There is a substantial difference in the cross-lagged relationship among career adaptability, resilience, and career commitment for low- and high-career interest. CONCLUSION: Our results show the importance of developing career commitment early on. Developing career adaptability, enhancing resilience, and increasing career interest in nursing students might help to increase career commitment.

Sulforaphane protects myocardium from ischemia-reperfusion injury by regulating CaMKIIN2 and CaMKIIδ.

Myocardial ischemia/reperfusion (I/R) injury poses a significant threat to human health. High level of reactive oxygen species (ROS) and calcium overload are the foremost causes of myocardial damage in I/R. Sulforaphane (SFN) is known for its promising antioxidant effect. Whether or not SFN has myocardial protective effect against I/R is largely unknown. This study aimed to investigate if SFN can protect myocardium from I/R injury. We found that mice or cells pre-treated with SFN showed improved cardiac functions and cell survival. SFN treatment inhibited the production of inflammatory cytokines and the increase of intracellular calcium induced by hypoxia-reperfusion (H/R), while mitochondria membrane potential was effectively maintained. Transcriptome analysis showed that CaMKIIδ expression was down-regulated by SFN treatment in I/R myocardium, while CaMKIIN2, the inhibitor of CaMKII, was upregulated. Knockdown of CaMKIIN2 not only led to increased level of total CaMKIIδ and the phosphorylated CaMKIIδ but also blocked the pro-survival effect of SFN for H/R cells. Moreover, CaMKIIN2 overexpression was sufficient to suppress CaMKIIδ activation and improve cell survival under H/R. Taken together, this study demonstrated that SFN exerts cardioprotective effect toward I/R injury through upregulating CaMKIIN2 and down-regulating CaMKIIδ.

GmNAC181 promotes symbiotic nodulation and salt tolerance of nodulation by directly regulating GmNINa expression in soybean.

Soybean (Glycine max) is one of the most important crops world-wide. Under low nitrogen (N) condition, soybean can form a symbiotic relationship with rhizobia to acquire sufficient N for their growth and production. Nodulation signaling controls soybean symbiosis with rhizobia. The soybean Nodule Inception (GmNINa) gene is a central regulator of soybean nodulation. However, the transcriptional regulation of GmNINa remains largely unknown. Nodulation is sensitive to salt stress, but the underlying mechanisms are unclear. Here, we identified an NAC transcription factor designated GmNAC181 (also known as GmNAC11) as the interacting protein of GmNSP1a. GmNAC181 overexpression or knockdown in soybean resulted in increased or decreased numbers of nodules, respectively. Accordingly, the expression of GmNINa was greatly up- and downregulated, respectively. Furthermore, we showed that GmNAC181 can directly bind to the GmNINa promoter to activate its gene expression. Intriguingly, GmNAC181 was highly induced by salt stress during nodulation and promoted symbiotic nodulation under salt stress. We identified a new transcriptional activator of GmNINa in the nodulation pathway and revealed a mechanism by which GmNAC181 acts as a network node orchestrating the expression of GmNINa and symbiotic nodulation under salt stress conditions.

Multi-parameter influenced acquisition model with an in-orbit jitter for inter-satellite laser communication of the LCES system.

With the development of large low earth orbit (LEO) communication constellations, the efficiency of laser inter-satellite link (ISL) establishing become the bottleneck for subsequent large-scale launch and rapid networking applications of LEO communication constellations. Hence, we establish the pointing jitter error structure of LEO communication experiment satellites (LCES) system. The error structure can be used to trace the source of errors and evaluate the in-orbit jitter. And we derive an analytical expression of the acquisition probability density function (PDF) which comprehensively considering the influence of the scanning region, the pointing jitter error, the overlap factor and the in-orbit jitter error. The multi-parameter influenced acquisition model is validated by Monte Carlo (MC) simulations and semi-physical tests. The results reveals that the multi-parameter influenced acquisition model can be used to guide the in-orbit ISL establishing.

Trimethylamine-N-Oxide Aggravates Kidney Injury via Activation of p38/MAPK Signaling and Upregulation of HuR.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is an intestinal metabolic toxin, which is produced by gut flora via metabolizing high-choline foods. TMAO is known to increase the risk of atherosclerosis and cardiovascular events in chronic kidney disease (CKD) patients. OBJECTIVES: The objective of this study was to explore the role and mechanism of TMAO aggravating kidney injury. METHOD: We used the five-sixths nephrectomy (5/6 Nx)-induced CKD rats to investigate whether TMAO could aggravate kidney damage and its possible mechanisms. Six weeks after the operation, the two groups of 5/6 Nx rats were subjected to intraperitoneal injection with 2.5% glucose peritoneal dialysis fluid (2.5% PDF) and 2.5% PDF plus TMAO 20 mg/kg/day. RESULTS: In this study, we provided evidence showing TMAO significantly aggravated renal failure as well as inflammatory cell infiltration and in five-sixths nephrectomy-induced CKD rats. We found that TMAO could upregulate inflammatory factors including MCP-1, TNF-α, IL-6, IL-1ß, and IL-18 by activating p38 phosphorylation and upregulation of human antigen R. TMAO could aggravate oxidative stress by upregulating NOX4 and downregulating SOD. The result also confirmed that TMAO promoted NLRP3 inflammasome formation as well as cleaved caspase-1 and IL-1ß activation in the kidney tissue. CONCLUSIONS: Taken together, the present study validates TMAO as a pro-inflammatory factor that causes renal inflammatory injury and renal function impairment. Inhibition of TMAO synthesis or promoting its clearance may be a potential therapeutic approach of CKD in the future.

MicroRNA-10 negatively regulates inflammation in diabetic kidney via targeting activation of the NLRP3 inflammasome.

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation has emerged as a central mediator of kidney inflammation in diabetic kidney disease (DKD). However, the mechanism underlying this activation in DKD remains poorly defined. In this study, we found that kidney-enriched microRNA-10a and -10b (miR-10a/b), predominantly expressed in podocytes and tubular epithelial cells, were downregulated in kidney from diabetic mice and patients with DKD. High glucose decreased miR-10a/b expression in vitro in an osmolarity-independent manner. miR-10a/b functioned as negative regulators of the NLRP3 inflammasome through targeting the 3'untranslated region of NLRP3 mRNA, inhibiting assembly of the NLRP3 inflammasome and decreasing caspase-1-dependent release of pro-inflammatory cytokines. Delivery of miR-10a/b into kidney prevented NLRP3 inflammasome activation and renal inflammation, and it reduced albuminuria in streptozotocin (STZ)-treated mice, whereas knocking down miR-10a/b increased NLRP3 inflammasome activation. Restoration of miR-10a/b expression in established DKD ameliorated kidney inflammation and mitigated albuminuria in both db/db and STZ-treated mice. These results suggest a novel intervention strategy for inhibiting kidney inflammation in DKD by targeting the NLRP3 inflammasome.

De novo Nanopore Genome Sequencing of the Clinical Diutina catenulata Type-strain CBS565.

Diutina catenulata is an ascomycetous yeast, that is regularly fluconazole-resistant and increasingly reported as the cause of invasive infection in humans. Here, we describe the de novo genome assembly of the clinical D. catenulata type-strain CBS565 and provide insights into the genome and compared it to an Illumina-sequenced environmental strain.

Towards BioMnOx-mediated intra/extracellular electron shuttling for doxycycline hydrochloride metabolism in Bacillus thuringiensis.

Doxycycline hydrochloride (DCH) could be continuously removed by Bacillus thuringiensis S622 with the in-situ biogenic manganese oxide (BioMnOx) via oxidizing/regenerating. The DCH removal rate was significantly increased by 3.01-fold/1.47-fold at high/low Mn loaded via the integration of biological (intracellular/extracellular electron transfer (IET/EET)) and abiotic process (BioMnOx, Mn(III) and •OH). BioMnOx accelerated IET via activating coenzyme Q to enhance electrons transfer (ET) from complex I to complex III, and as an alternative electron acceptor for respiration and provide another electron transfer transmission channel. Additionally, EET was also accelerated by stimulating to secrete flavins, cytochrome c (c-Cyt) and flavin bounded with c-Cyt (Flavins & Cyts). To our best knowledge, this is the first report about the role of BioMnOx on IET/EET during antibiotic biodegradation. These results suggested that Bacillus thuringiensis S622 incorporated with BioMnOx could adopt an alternative strategy to enhance DCH degradation, which may be of biogeochemical and technological significance.

Properties and regulation of Gly-Sar uptake and transport in bovine intestinal epithelial cells.

Intestinal absorption of peptides is vital for the overall health and productivity of dairy cows. This study investigated the regulation, uptake and transport of dipeptides in bovine intestinal epithelial cells (BIECs). We also evaluated the effects of time, pH, concentration of the dipeptides, temperature, presence of diethylpyrocarbonate (DEPC)-an inhibitor of PepT1, and other dipeptides (Met-Met, Lys-Lys or Met-Lys), on the uptake and transport of Gly-Sar-FITC, which was a common fluorophore-labelled dipeptide. Under controlled experiments, BIECs were treated with 25 µM LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor) and 25 µM Perifosine (a protein kinase B (AKT) inhibitor). The subsequent expression of PepT1 in the BIECs was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. It was found that the uptake and transport of Gly-Sar-FITC were significant high at 37℃ than that at 4℃. The optimal pH for transport and uptake of Gly-Sar-FITC was 6.0-6.5, whereas the two properties decreased significantly in the presence of DEPC, Met-Met, Lys-Lys and Met-Lys (p < 0.05). The apical-to-basolateral transport was also found to be significantly higher than the reverse transport (p < 0.05). PI3K and AKT inhibitors were found to significantly suppress the expression of PepT1, thus impairing uptake and transport of Gly-Sar-FITC. Findings of this study thus suggest that the uptake and transport of Gly-Sar-FITC in BIECs are mediated by PepT1, and the PI3K/AKT signalling pathway regulates the absorption of small peptides.

[Role and mechanism of non-coding RNA in the pathogenesis of acute kidney injury].

Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.

Cellular and synaptic mechanisms for Parkinson's disease-related chronic pain.

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Chronic pain is experienced by the vast majority of patients living with Parkinson's disease. The degeneration of dopaminergic neuron acts as the essential mechanism of Parkinson's disease in the midbrain dopaminergic pathway. The impairment of dopaminergic neurons leads to dysfunctions of the nociceptive system. Key cortical areas, such as the anterior cingulate cortex (ACC) and insular cortex (IC) that receive the dopaminergic projections are involved in pain transmission. Dopamine changes synaptic transmission via several pathway, for example the D2-adenly cyclase (AC)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway and D1-G protein-coupled receptor kinase 2 (GRK2)-fragile X mental retardation protein (FMRP) pathway. The management of Parkinson's disease-related pain implicates maintenance of stable level of dopaminergic drugs and analgesics, however a more selective drug targeting at key molecules in Parkinson's disease-related pain remains to be investigated.

Association of ADAM10 gene variants with sporadic Parkinson's disease in Chinese Han population.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Genetic factors play important roles in PD risk. rs653765 and rs514049 of ADAM10 were reported to be associated with Alzheimer's disease (AD) in Caucasian population; however, the association of the two variants with PD in Chinese Han population remains unknown. The present investigation aimed to explore the possible association of ADAM10 variants with PD in Chinese Han population. METHODS: We enrolled 565 PD patients and 518 healthy controls to conduct a case-control study. DNA samples were extracted from peripheral blood leukocytes, and the genotypes were determined by utilization of MassARRAY platform. Plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found CC genotype of rs514049 was associated with an increased risk of PD (OR (95% CI) = 3.776 (1.127-11.217), p = 0.018). The C allele frequency of rs514049 was significantly higher in PD group (OR (95% CI) = 1.328 (1.031-1.709), p = 0.028), especially in male subgroup (OR (95% CI) = 1.484 (1.053-2.092), p = 0.024). However, there was no significant difference in the genotype or allele frequencies for rs653765 within the groups. Plasma levels were significantly decreased in PD patients compared with controls (p < 0.001). CONCLUSIONS: Our data suggested that C allele of rs514049 in ADAM10 may increase the risk of PD in Chinese Han population, especially in males. The decreased plasma levels are probably involved in PD development.

Association of CLU gene polymorphism with Parkinson's disease in the Chinese Han population.

BACKGROUND: Clusterin (CLU) plays important role in the pathology of neurodegenerative disorders. Recently, a genetic variant of CLU rs9331896 has been reported as a risk estimate for Alzheimer's disease (AD). However, the association between this variant and the risk of Parkinson's disease (PD) in the Chinese Han population remains elusive. METHODS: We sequenced CLU rs9331896 in 353 PD patients and 326 healthy-matched individuals of the Chinese Han population. The genotypes of rs9331896 were analyzed using MassArray (Agena Bioscience, San Diego, CA, USA) in accordance with the manufacturer's instructions. The distribution of genotypes and allelic frequencies was analyzed by a chi-squared test. Additionally, the expression of CLU protein in plasma was evaluated by an enzyme-linked immunosorbent assay and analysed with a t-test. RESULTS: The TT genotype in rs9331896 in a recessive model was found to be associated with the increased risk of PD (odds ratio = 1.408, 95% confidence interval = 1.034-1.916, p = 0.029). Subgroup analysis indicated that TT genotype carriers showed a significantly higher risk in male PD patients compared to male healthy controls (odds ratio = 1.611, 95% confidence interval = 1.046-2.483, p = 0.030). In addition, CLU levels in the plasma of PD patients were significantly higher than controls (p = 0.024). CONCLUSIONS: The CLU-rs9331896-TT genotype was a risk factor for PD, particularly in males. PD patients also expressed a high level of CLU in plasma.