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We introduce a novel approach that utilizes an ionic liquid-assisted synthesis method to synthesize BiOBr material. This material is then loaded onto Mo 2 CT x , facilitating the formation of a BiOBr/Bi 2 Se 3 heterostructure through selenization treatment. The doping of heteroatoms improves the hydrophilicity and electronegativity of the material. The introduced heterojunction adjusts the electronic structure at the interface, resulting in a lower OH–/H+ adsorption energy. Due to the above advantages, the sample has excellent performance in HER and supercapacitor. [Display omitted] Heteroatom doping and heterojunction formation are effective strategies to enhance electrochemical performance. In this study, we present a novel approach that utilizes an ionic liquid-assisted synthesis method to fabricate a BiOBr-based material, which is subsequently loaded onto Mo 2 CT x via a selenization treatment to create a BiOBr/Bi 2 Se 3 heterostructure, denoted as NBF-BiOBr/Bi 2 Se 3 /Mo 2 CT x. The incorporation of heteroatoms improves its hydrophilicity and electronegativity, while the formation of heterojunctions adjusts the electronic structure at the interface, resulting in lower OH–/H+ adsorption energy. The specific surface area of NBF-BiOBr/Bi 2 Se 3 /Mo 2 CT x is 193.1 m2/g. In hydrogen evolution reaction (HER) tests, NBF-BiOBr/Bi 2 Se 3 /Mo 2 CT x exhibits exceptional catalytic performance in acidic media, requiring only an overpotential of 109 mV to achieve a current density of 10 mA cm−2. Furthermore, NBF-BiOBr/Bi 2 Se 3 /Mo 2 CT x demonstrates superior electrochemical performance in an asymmetric supercapacitor, with an energy density as high as 55.6 Wh kg−1 at a power density of 749.9 Wh kg−1. This work provides a novel approach for heteroatom doping and heterojunction synthesis, offering promising prospects for further advancements in the field. [ABSTRACT FROM AUTHOR]

Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al–treatment–induced alternation in the volatilization rate of monoterpenes (α–pinene, β–pinene, limonene, α–terpinene, γ–terpinene and 3–carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO 2 assimilation, maximum quantum yield of primary PSII photochemistry (F v /F m), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α–pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus , and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species. [Display omitted] • The emission rate of volatile isoprenoids varied in C. grandis and C. sinensis. • Al treatment downregulated both MVA and MEP pathways in C. grandis leaves. • Al treatment upregulated MEP pathway in C. sinensis leaves. • Isoprenoid metabolism was involved in Al tolerance response in Citrus plants. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder defined as the presence of intrahepatic lipid deposition and steatosis as well as chronic inflammation without excessive alcohol consumption. Our previous studies found that inulin could dramatically improve lipid metabolism disorders in NAFLD murine models. In recent years, mounting evidence has approved that there are disproportionately increased bile acids (BAs) in patients with NAFLD while the hepatic bile acids signaling is suppressed. Meanwhile the primary function of bile acids is to promote the excretion of cholesterol and therefore keep the cholesterol metabolism balance. Hence, we investigate whether inulin exerts beneficial effects on lipid metabolism disorders by modulating bile acids signaling in our present study. And we found that inulin treatment significantly reversed the abnormal accumulation of bile acids in high-fat-induced NAFLD mice. Furthermore, our data confirmed that inulin supplementation attenuates NAFLD via restoring the activity of FXR accompanied by increasing hepatic bile acids de novo synthesis and further enhancing bile acids excretion in mice. • Inulin intervention activated the activity of FXR. • Inulin intervention increased the synthesis of bile acids. • Inulin intervention facilitated the excretion of bile acids. [ABSTRACT FROM AUTHOR]

Elderly women with clinically node-positive (cN+) breast cancer (BC) often have comorbidities that limit life expectancy and complicate treatment. We sought to determine whether the number of lymph nodes (LNs) retrieved among older women with node-positive BC was associated with overall survival (OS). Using the National Cancer Database (2010-2015), women 70-90 y with cN + BC and ≥1 LNs removed were categorized by treatment sequence: upfront surgery or neoadjuvant chemotherapy (NAC). Multivariable Cox proportional hazards models with restricted cubic splines characterized the functional association of LN retrieval with OS; threshold values of LN retrieval were estimated. Cox proportional hazards models were used to estimate the association of LN retrieval groups with OS. In the upfront surgery cohort, a nonlinear association was identified between LNs retrieved and OS. In the NAC cohort, no association was identified. For the upfront surgery cohort, the optimal threshold value of LN retrieval was 21 LNs (90% confidence interval 18-23). Based on this estimate, LN retrieval groups were created: <6, 6-11, 12-17, 18-23, and >23 LNs. After adjustment, retrieval of <12 LNs in the upfront surgery group was associated with a worse OS. No differences were observed in the NAC group. For elderly women receiving upfront surgery, there is no survival benefit to removing more than 12 LNs, and for those receiving NAC, there is no association between number of LNs removed and survival. In older women who present with cN + BC, aggressive surgery to remove more than 12 LNs may not be necessary. [ABSTRACT FROM AUTHOR]

Abstract Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 2 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERβ on the cognition, neurogenesis and apoptosis in high-fat diet and streptozocin-induced diabetic mice. We found that ERα and/or ERβ activation using their agonists (0.5 mg/kg E2, PPT or DPN) ameliorate memory impairment in the Morris water maze and Y-maze tests, increase hippocampal neurogenesis and prevent hippocampal apoptotic responses. Importantly, treatment with the pharmacologic ERs agonists caused significant increases in the membrane ERα and ERβ expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of type 2 diabetes mellitus mice. Our data indicate that ERα and ERβ are involved in the cognitive impairment in type 2 diabetes, and that activated ERs, such as application of ERs agonists, could be a novel and promising strategy for the treatment of diabetic cognitive impairment. Highlights • ERα and ERβ are involved in the cognitive impairment in type 2 diabetes mellitus mice. • ERα and/or ERβ activation ameliorate memory impairment, neurogenesis and apoptosis in type 2 diabetes mellitus mice. • ERα and/or ERβ activation enhance the PI3K/Akt, CREB and BDNF expression in the hippocampus of diabetic mice. [ABSTRACT FROM AUTHOR]

Highlights • We enhance the GO model by adding Type 9 operator, which make it convenient for analyst to comprehend and model a system with feedback loops. • This study creatively proposed the new Cyclic Bayesian Networks (CBNs) based on the existing theoretical research. • To improve GO model analyzing capability, we map enhanced cyclic GO model to its corresponding CBNs, and utilizing CBN's matured algorithm, system failure information and posterior probability distribution can be obtained easily. • Moreover, BNs are becoming widely used for dependability and uncertainty analysis, which ensures the CBNs with good adaptation for complex closed-loop system with complex dependence and uncertainty. Abstract GO methodology is a success-oriented method for reliability analysis of complex safety critical system, which existing in various fields, such as aircraft carrier, nuclear plant, petrochemical plant, etc. However, the traditional GO methodology is insufficient in modeling the system with feedback signals, which are common in those systems. The challenge lies in modeling the closed-loop feedback process and its algorithms. To address this issue, an approach based on Cyclic Bayesian Networks (CBNs) is presented in this paper to enhance its capability of feedback modeling. In the approach, Type 9 operator is the key element to be introduced to simulate a component with feedback signal, and then the GO model can be cyclic to represent a system with feedback loops; furthermore, we compare the decision capability of the GO and BN methodologies in dynamic structure and uncertainty handling. Considering the complexity of the analysis of the GO method, the cyclic GO model is mapped to its corresponding CBNs according to some mapping rules. And leveraging matured algorithms and toolkit of BNs, we can not only obtain the probability of each node in each state via failure propagation, but also identify critical events given the event occurrence via backward reasoning. Eventually, a case of chemical treatment tank liquid level controlling minus-feedback system is analyzed to demonstrate the approach’s feasibility, and by enhancing the capability with loop structured system modeling, the approach makes GO methodology more practical in more modern complex engineering systems with feedback loops. [ABSTRACT FROM AUTHOR]

Abstract Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 1 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERβ on the memory impairment and apoptosis in streptozotocin-induced diabetic mice. We found that ERα and/or ERβ activation using their agonists (0.5 mg/kg E2, PPT or DPN) ameliorate memory impairment in the Morris water maze (MWM) and Y-maze tests and suppress apoptosis as evidenced by decreased caspase-3 activity and increased ratio of Bcl-2/Bax. Importantly, treatment with the pharmacologic ERs agonists caused significant increases in the membrane ERα and ERβ expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of diabetic mice. Our data indicate that ERα and ERβ are involved in the cognitive impairment of type 1 diabetes and that activation of ERs via administration of ERs agonists could be a novel and promising strategy for the treatment of diabetic cognitive impairment. Highlights • ERα and ERβ are involved in the cognitive impairment in type 1 diabetes mellitus mice. • ERα and/or ERβ activation ameliorate memory impairment and apoptosis in type 1 diabetes mellitus mice. • ERα and/or ERβ activation enhance the PI3K/Akt, CREB and BDNF expression in the hippocampus of diabetic mice. [ABSTRACT FROM AUTHOR]

Diabetes and obesity are commonly associated with Alzheimer's disease (AD). Accumulating evidence show that insulin signaling defects are protentional upstream driver of AD. However, the mechanism by which diabetes and insulin signaling defects contribute to AD remains unknown. Here we show that Fat mass and obesity-associated protein (FTO) is involved the insulin defects-associated AD. Defective insulin signaling in diabetes and obesity in human and mice activated Fto in the brain tissues. Lentivirus-mediated knockdown of Fto reduced the phosphorylation of Tau protein whereas overexpression of FTO promoted the level of phosphorylated Tau in neurons. Mechanism study demonstrated that FTO activated the phosphorylation of Tau in a mTOR-dependent manner because FTO activated mTOR and its downstream signaling and rapamycin blocked FTO-mediated phosphorylation of Tau. FTO promoted the activation of mTOR by increasing the mRNA level of TSC1 but not TSC2, the upstream inhibitor of mTOR. Finally, we found that conditional knockout of Fto in the neurons reduced the cognitive deficits in 3xTg AD mice. Collectively, our evidence demonstrated that FTO is critically involved in insulin defects-related AD. [ABSTRACT FROM AUTHOR]

• Social isolation and loneliness are increasing at an alarming rate. • Isolation and loneliness are risk factors for Alzheimer's Disease-related dementia. • Isolation and loneliness affect cognition differentially in women and men. • Understanding how loneliness leads to cognitive decline can inform treatment. • Animal models of social isolation can help reveal the underlying mechanisms. Alzheimer's Disease (AD) is the leading cause of dementia, observed at a higher incidence in women compared with men. Treatments aimed at improving pathology in AD remain ineffective to stop disease progression. This makes the detection of the early intervention strategies to reduce future disease risk extremely important. Isolation and loneliness have been identified among the major risk factors for AD. The increasing prevalence of both loneliness and AD emphasizes the urgent need to understand this association to inform treatment. Here we present a comprehensive review of both clinical and preclinical studies that investigated loneliness and social isolation as risk factors for AD. We discuss that understanding the mechanisms of how loneliness exacerbates cognitive impairment and AD with a focus on sex differences will shed the light for the underlying mechanisms regarding loneliness as a risk factor for AD and to develop effective prevention or treatment strategies. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is used to edit eukaryotic genomes. Here, we show that CRISPRi can also be used for fine-tuning prokaryotic gene expression while simultaneously regulating multiple essential gene expression with less labor and time consumption. As a case study, CRISPRi was used to control polyhydroxyalkanoate (PHA) biosynthesis pathway flux and to adjust PHA composition. A pathway was constructed in Escherichia coli for the production of poly(3-hydroxybutyrate- co -4-hydroxybutyrate) [P(3HB- co -4HB)] from glucose. The native gene sad encoding E. coli succinate semi-aldehyde dehydrogenase was expressed under the control of CRISPRi using five specially designed single guide RNAs (sgRNAs) for regulating carbon flux to 4-hydroxybutyrate (4HB) biosynthesis. The system allowed formation of P(3HB- co -4HB) consisting of 1–9 mol% 4HB. Additionally, succinate, generated by succinyl-coA synthetase and succinate dehydrogenase (respectively encoded by genes sucC , sucD and sdhA , sdhB ) was channeled preferentially to the 4HB precursor by using selected sgRNAs such as sucC2, sucD2, sdhB2 and sdhA1 via CRISPRi. The resulting 4HB content in P(3HB- co -4HB) was found to range from 1.4 to 18.4 mol% depending on the expression levels of down-regulated genes. The results show that CRISPRi is a feasible method to simultaneously manipulate multiple genes in E. coli . [ABSTRACT FROM AUTHOR]

Abstract: The fusellovirus SSV2 and the integrative plasmid pSSVi, which constitute a unique helper-satellite virus system, replicate in Sulfolobus solfataricus P2. In this study, we investigated the interplay among SSV2, pSSVi and their host by transcriptomic analysis. Following infection of S. solfataricus P2, SSV2 activated its promoters in a temporal and distributive fashion, starting from the transcription of ORF305. Expression of several host genes encoding DNA replication and transcription proteins was up-regulated, suggesting that SSV2 depended heavily on the host replication machinery for its replication. SSV2 gene expression appeared to follow a similar pattern in S. solfataricus P2 harboring pSSVi to that in S. solfataricus P2 lacking the plasmid. Several early genes of the virus were transcribed earlier and more efficiently in the presence of pSSVi than in its absence. These results provide valuable clues to the understanding of the three-way interactions among SSV2, pSSVi and the host. [Copyright &y& Elsevier]

Abstract: The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in Liposcelis paeta Pearman were investigated in three field populations collected from Nanyang city of Henan Province (NY), Wuzhou (WZ) and Hezhou (HZ) Cities of Guangxi Province, China. The result of bioassay showed that the LC50s of the NY (281.4802mg/m2) and the WZ (285.0655mg/m2) to dichlorvos were 1.156-fold and 1.171-fold higher than that of the HZ (243.5197mg/m2), respectively. Compared to NY population, the activity per insect and the specific activity of AChE in WZ and HZ populations were significantly higher, and significant kinetic differences among the three populations were also observed. The apparent Michaelis–Menten constant (K m) for acetylthiocholine iodide (ATChI) was obviously lower in NY than that in WZ and HZ populations, indicating a higher affinity to the substrate ATChI in the NY population. The affinity to the substrate ATChI between WZ and HZ population was also significantly different. As for V max, the values of WZ and HZ populations were significantly greater when compared to that for NY population, suggesting a possible over expression of AChE in the former two populations. The inhibition studies of AChE indicated that paraoxon-ethyl, demeton-S-methyl, carbaryl, and eserine all possessed some inhibitory effects on AChE in L. paeta. The results of I 50S suggested that when compared to the other two populations, while AChE from HZ population was less sensitive to paraoxon-ethyl and demeton-S-methyl. The contradiction with the result of the bioassay might be due to the different insecticides used in the bioassay. Although both carbaryl and eserine had excellent inhibitory effects, there was no significant difference among the three populations. The statistical analysis of the bimolecular rate constants (k i) was consistent with the above situation that carbamates expressed remarkable inhibitory effects. It was noticeable that NY population was most sensitive to carbaryl while least to eserine. The differences in AChE among three populations may attribute to the difference in control practices for psocids between Henan and Guangxi Provinces. [Copyright &y& Elsevier]

• A conservative sharp interface method is developed to simulate displacements of and collisions among particle clouds. • A hard sphere model is proposed to handle multi-body collisions among a number of particles. • Simulations are performed for the interaction between shocks and 2D/3D particles. • Results are verified against experimental data and benchmark solutions. In this paper we present a second-order accurate conservative sharp interface method capable of simulating displacements and collisions of many particles in compressible inviscid flows. We implement a cut cell algorithm to resolve moving particles of arbitrary shape on a Cartesian mesh, thereby generating unstructured body-fitted meshes near the particle surfaces and structured meshes away from the particles. A second-order finite volume method in the arbitrary Lagrange-Eulerian framework is used for the discretization of the Euler equations, so that exact conservation of mass, momentum and energy is enforced for the flow computations, even in the presence of moving particles. The boundary condition at the particle surfaces is enforced by solving a local Riemann problem, which is constructed in the direction normal to the solid surface. The movement of a particle is affected by the forces exerted by the surrounding fluid and its collisions with other particles. A hard sphere model is proposed to deal with the particle collisions; in particular, it is capable of handling multi-body collisions occurring in no-dilute particle clouds, regardless of the number of particles involved. Furthermore, the model ensures the conservation of momentum and energy during the collision process. The method is validated by comparing against benchmark solutions or experimental data available in the literature, for test cases such as supersonic flows past a stationary cylinder and lift-off of rigid cylinders after shock impact. Good agreement has been achieved qualitatively and quantitatively. The method is also used to investigate the complicated flow phenomena, e.g. transport of particle clouds in supersonic flows through a confined channel and the interaction between shocks and three-dimensional particles. [ABSTRACT FROM AUTHOR]

• Multi-point monitoring based on FBG sensor arrays has been proposed and implemented. • Evolution process of clay layer weakening has been detected and demonstrated. • Survival rate of FBG is illustrated and suggestions to ensure which is also provided. A large area of thick unconsolidated stratum layer overlying the coal seam of eastern China, which brought the regional disaster prevention issue under the circumstance of unconsolidated layer settlement triggered by mining activities. In this paper, the multi-point monitoring system based on fiber Bragg grating (FBG) sensors array was implemented into the deep unconsolidated layer to realize a long-term ground monitoring, which investigated the compression process of ground rock layers at different burial depths and revealed the mechanical weakening characteristics of clay. The deformation characteristics of the aquifers were analyzed, including a sand layer, gravel layer, and clay water barrier, as well as the weakening characteristics of the clay layer aquifer. The monitoring results of the FBG sensing system show that unconsolidated layer settlement usually occurs in thick and stable aquifers and adjacent clay layers, and the peripheral part of the deep clay layer in contact with the aquifer will become a weakened zone. The clay layer at such locations should also be a key monitoring layer with increasing depth. The survival rate of FBG sensors were discussed to propose the suggestions of system installation. These findings could provide important guidance for predicting the unconsolidated layer settlement process and for the timely implementation of governance measures. [ABSTRACT FROM AUTHOR]

• Plastomes of Rhodiola are conserved with respect to size, structure, and gene content. • Rhodiola is divided into two clades: dioecious and hermaphrodite. • Four chloroplast genes of Rhodiola may be involved in alpine adaptation. The amount of plastome sequence data available has soared in the last decade, but the nature of plastome evolution during rapid radiations is largely unknown. Moreover, although there is increasing evidence showing that plastomes may have undergone adaptive evolution in order to allow adaptation to various environments, few studies have systematically investigated the role of the plastome in alpine adaptation. To address these questions, we sequenced and analyzed 12 representative species of Rhodiola , a genus which includes ca. 70 perennial herbs mainly growing in alpine habitats in the Qinghai-Tibet Plateau and the Hengduan Mountains. Rapid radiation in this genus was triggered by the uplift of the Qinghai-Tibet Plateau. We also included nine species of Crassulaceae as the outgroups. All plastomes were conserved with respect to size, structure, and gene content and order, with few variations: each contained 134 genes, including 85 protein-coding genes, 37 tRNAs, 8 rRNAs, and 4 potential pseudogenes. Four types of repeat sequence were detected. Slight contraction and expansion of the inverted repeats were also revealed. Both the genome-wide alignment and sequence polymorphism analyses showed that the inverted repeats and coding regions were more conserved than the single-copy regions and the non-coding regions. Positive selection analyses identified three genes containing sites of positive selection (rpl16 , ndhA , ndhH), and one gene with a faster than average rate of evolution (psaA). The products of these genes may be involved in the adaptation of Rhodiola to alpine environments such as low CO 2 concentration and high-intensity light. [ABSTRACT FROM AUTHOR]

• 3D sharp interface method for compressible flows with topology change of interface. • Cell-splitting configurations decrease from 288 configurations to 12 basic ones. • Conservation laws are well maintained, even at interfaces with topology changes. • Numerical results are validated against various experimental ones. A three-dimensional (3D) conservative sharp interface (CSI) method, which combines 3D cut-cell methods and finite volume methods in the arbitrary Lagrangian-Eulerian framework, is proposed to simulate compressible inviscid two-phase flows. The 3D cut-cell method allows to reconstruct interfaces on a Cartesian mesh and update unstructured interface cells in the vicinity of the interface, making the reconstructed interface always coinciding with the cell faces of the interface cells. The complexity in generating 3D interface cells is significantly reduced by exploiting the symmetry and rotational symmetry of fluid positions in a cut cell. Compared to our previous two-dimensional work (Lin et al. (2017) [17]), the occurrence of large interface cells is also avoided by using the new strategy of cell assembly. With the help of the 3D cut-cell method, a second-order finite volume method in the arbitrary Lagrangian-Eulerian framework can be used nearly in the whole domain, except for the interface cells with under-resolved interfaces or topology changes, at which a first-order finite volume method is used instead. The convergence of the 3D CSI method is examined by studying the Rayleigh collapse of a gas bubble in water, and second-order accuracy has been obtained for the interface evolution. Simulation of shock-induced bubble collapse demonstrates that the axisymmetricity of the interface is well preserved in the 3D computation. Moreover, the 3D CSI methods are also given experimental validation, including the interaction of a shock with 3D curved gas-gas interface and droplet deformation after shock impact. In all cases, a good agreement has been achieved with the experimental data, with respect to the interface evolution and flow features. [ABSTRACT FROM AUTHOR]

Our study proposed to investigate the function of potassium voltage-gated channel sub-family Q member 1 opposite strand 1 (KCNQ1OT1) in cerebral ischemia-reperfusion (I/R) injury and the underlying mechanism. We constructed an oxygen-glucose-deprivation/reoxygenation (OGD/R) model using the primary cortical neurons to mimic the cerebral I/R injury in vitro. Small inference RNA (siRNA) was used to silencing KCNQ1OT1. Dual luciferase assay was conducted to verify the interaction between KCNQ1OT1 and miR-9 and interaction between miR-9 and MMP8. CCK8 assay and flow cytometry analysis were applied for determing the viability and apoptosis of neurons, accordingly. QPCR and Western blot were performed to determine the RNA and protein expression. Our outcomes revealed that the expression of KCNQ1OT1 in cultured neurons was notably enhanced after suffered to OGD/R. Knockdown of KCNQ1OT1 weakened OGD/R-induced injury in neurons. Moreover, depletion of KCNQ1OT1 lead to the up-regulation of miR-9 and down-regulation of MMP8. Dual luciferase target validation assays demonstrated that KCNQ1OT1 directly interact with miR-9 and MMP8 is a direct target of miR-9, suggesting that KCNQ1OT1/miR-9/MMP8 might constitute the competing endogenous RNA (ceRNA) mechanism. Knockdown of MMP8 or up-regulation of miR-9 also could weaken OGD/R-induced injury. Furthermore, cells co-transfected with si-KCNQ1OT1, miR-9 mimic and si-MMP8 could significantly abolish the injury on neurons caused by OGD/R. Taken together, our data manifested that KCNQ1OT1 possibly acts as a facilitator in cerebral I/R injury through modulating miR-9/MMP8 axis as a ceRNA. [ABSTRACT FROM AUTHOR]

• BMDMϕ engulf spinal cord debris, transform into proinflammatory foamy Mϕ in SCI. • Foamy Mϕ contribute to neuroinflammation and SCI progression. • ABCA1 deficiency in foamy Mϕ increases lipid accumulation and inflammation in SCI. • Enhancing ABCA1 inhibits the inflammation and rescues phagocytotic ability of Mϕ. • Enhancement of ABCA1 expression promotes lipid efflux and functional recovery. Spinal cord injury (SCI) triggers a complex cascade of events, including myelin loss, neuronal damage, neuroinflammation, and the accumulation of damaged cells and debris at the injury site. Infiltrating bone marrow derived macrophages (BMDMϕ) migrate to the epicenter of the SCI lesion, where they engulf cell debris including abundant myelin debris to become pro-inflammatory foamy macrophages (foamy Mϕ), participate neuroinflammation, and facilitate the progression of SCI. This study aimed to elucidate the cellular and molecular mechanisms underlying the functional changes in foamy Mϕ and their potential implications for SCI. Contusion at T10 level of the spinal cord was induced using a New York University (NYU) impactor (5 g rod from a height of 6.25 mm) in male mice. ABCA1, an ATP-binding cassette transporter expressed by Mϕ, plays a crucial role in lipid efflux from foamy cells. We observed that foamy Mϕ lacking ABCA1 exhibited increased lipid accumulation and a higher presence of lipid-accumulated foamy Mϕ as well as elevated pro-inflammatory response in vitro and in injured spinal cord. We also found that both genetic and pharmacological enhancement of ABCA1 expression accelerated lipid efflux from foamy Mϕ, reduced lipid accumulation and inhibited the pro-inflammatory response of foamy Mϕ, and accelerated clearance of cell debris and necrotic cells, which resulted in functional recovery. Our study highlights the importance of understanding the pathologic role of foamy Mϕ in SCI progression and the potential of ABCA1 as a therapeutic target for modulating the inflammatory response, promoting lipid metabolism, and facilitating functional recovery in SCI. [ABSTRACT FROM AUTHOR]

Arabinoxylan (AX) is an important component of dietary fiber, and exerts significant effects on the processing quality and nutritional value of flour. Feruloyl arabinoxylan (FAX) is a major factor influencing the functional properties of AX. Here, a genome-wide association study (GWAS) was conducted for FAX content using a high-density SNP platform. FAX content was evaluated in 256 wheat varieties (two populations) in four environments. Results showed that 83 and 33 marker-trait associations (MTAs) for FAX content were identified, explaining 6.7–9.2% and 10.2–21.2% phenotypic variation in the two populations. Two and three MTAs were repeatedly detected in at least two environments. Five MTAs were detected in both populations. Linear regression indicated a clear dependence of FAX content on the number of favorable alleles, indicating that QTL pyramiding would be an effective approach to modify FAX content. Associated with these significant MTAs, five candidate genes: isoflavone reductase, carnitine dehydrogenase, acylamino acid releasing enzyme, glucose isomerase, and GMP synthase were found to be involved in FAX biosynthesis. Lastly, our study contributes important information for genetic improvement of wheat quality and contributes to developing marker-assisted selection. • 83 and 33 marker-trait associations (MTAs) for FAX content were identified by GWAS. • 5 MTAs were detected in both populations. • 5 varieties in each of 2 populations had more favorable alleles and higher FAX content. • 5 candidate genes were found to be involved in FAX biosynthesis. [ABSTRACT FROM AUTHOR]

With economic development and overnutrition, including high-fat diets (HFD) and high-glucose diets (HGD), the incidence of obesity in children is increasing, and thus, the incidence of precocious puberty is increasing. Therefore, it is of great importance to construct a suitable animal model of overnutrition-induced precocious puberty for further in-depth study. Here, we fed a HFD, HGD, or HFD combined with a HGD to pups after P-21 weaning, while weaned pups fed a normal diet served as the control group. The results showed that HFD combined with a HGD increased the body weight (BW) of weaned rat pups. In addition, a HFD, HGD, and HFD combined with a HGD lowered the age at which vaginal opening occurred and accelerated the vaginal cell cycle. Furthermore, a HFD combined with a HGD increased the weight of the uterus and ovaries of weaned rat pups. Additionally, a HFD combined with a HGD promoted the development of reproductive organs in weaned female rat pups. Ultimately, a HFD combined with a HGD was found to elevate the serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), leptin, adiponectin, and oestradiol (E2) and increase hypothalamic GnRH, Kiss-1, and GPR54 expression levels in weaned female rat pups. The current study found that overnutrition, such as that through a HFD combined with HGD, could induce precocious puberty in weaned female rat pups. In addition, a rat model of overnutrition-induced precocious puberty was established. • Overnutrition, such as through an HFD or HGD, could induce precocious puberty in weaned female rat pups. • A rat model of overnutrition-induced precocious puberty was established. • With economic development, overnutrition, including HFD and HGD, leads to an increasing number of obese children, thus increasing the incidence of precocious puberty. • We established a new rat model of overnutrition-induced precocious puberty by HFD and HGD for further in-depth study. [ABSTRACT FROM AUTHOR]

Diabetes is associated with cardiac inflammation and impaired endothelium-dependent coronary vasodilation, but molecular mechanisms involved in this dysfunction remain unclear. We examined contributions of inflammatory molecules lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), stress-activated kinases (c-Jun N-terminal kinase [JNK] and p38), arginase, and reactive oxygen species to coronary arteriolar dysfunction in a porcine model of type 1 diabetes. Coronary arterioles were isolated from streptozocin-induced diabetic pigs and control pigs for vasoreactivity and molecular/biochemical studies. Endothelium-dependent nitric oxide (NO)-mediated vasodilation to serotonin was diminished after 2 weeks of diabetes, without altering endothelium-independent vasodilation to sodium nitroprusside. Superoxide scavenger TEMPOL, NO precursor L-arginine, arginase inhibitor nor-NOHA, anti-LOX-1 antibody or JNK inhibitors SP600125 and BI-78D3 improved dilation of diabetic vessels to serotonin. However, hydrogen peroxide scavenger catalase, anti-IgG antibody or p38 kinase inhibitor SB203580 had no effect. Combined inhibition of arginase and superoxide levels did not further improve vasodilation. Arginase-I mRNA expression, LOX-1 and JNK protein expression, and superoxide levels were elevated in diabetic arterioles. In conclusion, sequential activation of LOX-1, JNK, and L-arginine consuming enzyme arginase-I in diabetes elicits superoxide-dependent oxidative stress and impairs endothelial NO-mediated dilation in coronary arterioles. Therapeutic targeting of these adverse vascular molecules may improve coronary arteriolar function during diabetes. • Diabetes impairs endothelial NO vasodilator function of porcine coronary arterioles • Blockade of LOX-1, JNK, or arginase improves dilation of diabetic vessels • NO precursor L-arginine or superoxide scavenger improves vasodilation • Arginase-I mRNA expression and superoxide levels are elevated in diabetic vessels • LOX-1 and JNK protein expressions are elevated in diabetic vessels [ABSTRACT FROM AUTHOR]

Colorectal cancer is the second most commonly diagnosed cancer worldwide, and may develop sporadically or due to chronic colitis. Macrophages are a major component of the colorectal tumour microenvironment and may be broadly classified as classically-activated (CAM) ‘inflammatory’ or alternatively-activated (AAM) ‘pro-angiogenic’ macrophages. Hematopoietic Cell Kinase (Hck) is a myeloid-specific Src family kinase involved in alternative macrophage polarisation, which correlates with a poor prognosis in human colorectal cancer. To investigate the role of Hck in colorectal tumourigenesis, Hck mutant mice that express a constitutively active form of Hck (HckCA) were subjected to models of sporadic and colitis-associated colorectal cancer. In both models, HckCA mice demonstrated increased tumour size and multiplicity compared to wild-type animals. FACS analysis of tumour immune-cell infiltrates did not reveal a difference in the number of tumour-associated macrophages (TAMs) between genotypes; however, CD206+ alternatively-activated TAMs were significantly greater in HckCA mice compared to wild-type. Furthermore, qPCR analysis highlighted a significant increase in genes associated with alternative-macrophage activation in HckCA TAMs. To confirm the role of macrophages in HckCA-driven tumourigenesis, wild-type mice were reconstituted with HckCA bone-marrow, and subjected to sporadic or colitis-associated colon cancer induction, after which we observed an increased tumour burden and an AAM phenotype compared to wild-type bone-marrow recipients. Finally, we have shown that the inhibition of Hck using a small molecule inhibitor reduces alternative macrophage polarisation. Collectively, our results suggest that excessive Hck activation enhances colorectal tumourigenesis by facilitating alternative macrophage polarisation, which may be alleviated through the therapeutic targeting of this kinase. [ABSTRACT FROM AUTHOR]

Elevated levels of endothelin-1 (ET-1), a potent vasoactive peptide, are implicated as a risk factor for cardiovascular diseases by exerting vasoconstriction. The aim of this study was to address whether ET-1, at sub-vasomotor concentrations, elicits adverse effects on coronary microvascular function. Porcine coronary arterioles (50–100 μm) were isolated, cannulated and pressurized without flow for in vitro study. Diameter changes were recorded using a videomicrometer. Arterioles developed basal tone (60 ± 3 μm) and dilated to the endothelium-dependent nitric oxide (NO)-mediated vasodilators serotonin (1 nmol/L to 0.1 μmol/L) and adenosine (1 nmol/L to 10 μmol/L). Treating the vessels with a clinically relevant sub-vasomotor concentration of ET-1 (10 pmol/L, 60 min) significantly attenuated arteriolar dilations to adenosine and serotonin but not to endothelium-independent vasodilator sodium nitroprusside. The arteriolar wall contains ET A receptors and the adverse effect of ET-1 was prevented by ET A receptor antagonist BQ123, the superoxide scavenger Tempol, the NADPH oxidase inhibitors apocynin and VAS2870, the NOX2-based NADPH oxidase inhibitor gp91 ds-tat, or the p38 kinase inhibitor SB203580. However, ET B receptor antagonist BQ788, H 2 O 2 scavenger catalase, scrambled gp91 ds-tat, or inhibitors of xanthine oxidase (allopurinol), PKC (Gö 6983), Rho kinase (Y27632), and c-Jun N-terminal kinase (SP600125) did not protect the vessel. Immunohistochemical staining showed that ET-1 elicited Tempol-, apocynin- and SB203580-sensitive superoxide productions in the arteriolar wall. Our results indicate that exposure of coronary arterioles to a pathophysiological, sub-vasomotor concentration of ET-1 leads to vascular dysfunction by impairing endothelium-dependent NO-mediated dilation via p38 kinase-mediated production of superoxide from NADPH oxidase following ET A receptor activation. [ABSTRACT FROM AUTHOR]

Nitrogen pollutants such as ammonia and nitrates cause soil and groundwater contamination at municipal solid waste landfill (MSWL) sites due to leachate leakage. Here, the migration of nitrogen pollutants in the vadose zone of the red bed (VZRB) at a MSWL site was studied by static adsorption batch experiments and one-dimensional simulated migration experiments. The results indicated that the soil in the red bed did not adsorb nitrates. Chemical adsorption and monolayer adsorption of the soil played dominant roles during ammonia adsorption in the VZRB, which was best fitted by the pseudo-second-order kinetic equation (R N H 4 + 2 = 0.99) and the Langmuir model. The ammonia adsorption capacity of the soil was the highest (Q m = 2.041 mg·g−1) at 318 K. It was due to the endothermic and non-spontaneous chemical adsorption of ammonia, whose enthalpy change (ΔH) reached 20.995 kJ·mol−1 and Gibbs free energy ranged from 8.469 to 8.706 kJ·mol−1. Chloride penetration tests indicated that the diffusion coefficient and migration speed reached 0.0515 cm2·h−1 and 0.0833 cm·h−1, respectively, in the clay layer under the MSWL sites. The average hysteresis diffusion coefficients of ammonia in the simulated soil columns leached by ammonium chloride solution (SSCAC) and by the leachate from MSWL (SSCL) were 1.129 and 1.400, respectively. After the leaching experiments, the clay pore structure was saturated, and the specific surface area decreased. The absorption peak intensities of clay functional groups, including carboxyl, alkyne, and hydroxyl groups, were reduced. The ammonia content in the soil of SSCAC decreased from the top (14.51 mg·kg−1) to the bottom (3.14 mg·kg−1) and in the SSCL from 24.96 mg·kg−1 to 5.05 mg·kg−1, respectively. Thus, the impermeable clay layer and VZRB helped in retardation of ammonia leakage from MSWL sites. This was due to the blockage of seepage, ammonia mechanical filtration, ammonia monolayer chemical adsorption, and the reaction between the functional groups and ammonia in the VZRB underneath the MSWL sites. [Display omitted] • The loamy soil in the VZRB had high ammonia adsorption capacity. • The ammonia adsorption and desorption were followed the pseudo-second-order kinetic. • The ammonia adsorption was endothermic, non-spontaneous chemical process. • Mechanical filtration, adsorption and biofilms blocked the nitrogen migration. [ABSTRACT FROM AUTHOR]

Abstract: The goal of this study is to investigate whether different types of structures and lexical tones of Chinese characters cause different processing fluency. In Experiment 1, participants’ explicit affective assessments of Chinese characters with different structures, frequencies, and lexical tones were analyzed. Results indicated that participants showed explicit preferences and dispreferences to different structures and lexical tones. In Experiment 2, participants’ implicit responses to different structures and lexical tones were investigated using a metaphor experimental paradigm. Results were consistent with the major findings of Experiment 1. In Experiments 3 and 4, participants’ recognition of words of different structures and lexical tones were analyzed. Results revealed that participants had a better memory for Surround structure characters when stimuli were visually presented and for Tone 3 when stimuli were auditorily presented. Finally, the significance and implications of this study are discussed. [Copyright &y& Elsevier]

Abstract: Endothelium-derived vasodilators, i.e., nitric oxide (NO), prostacyclin (PGI2) and prostaglandin E2 (PGE2), play important roles in maintaining cardiovascular homeostasis. C-reactive protein (CRP), a biomarker of inflammation and cardiovascular disease, has been shown to inhibit NO-mediated vasodilation. The goal of this study was to determine whether CRP also affects endothelial arachidonic acid (AA)-prostanoid pathways for vasomotor regulation. Porcine coronary arterioles were isolated and pressurized for vasomotor study, as well as for molecular and biochemical analysis. AA elicited endothelium-dependent vasodilation and PGI2 release. PGI2 synthase (PGI2-S) inhibitor trans-2-phenyl cyclopropylamine blocked vasodilation to AA but not to serotonin (endothelium-dependent NO-mediated vasodilator). Intraluminal administration of a pathophysiological level of CRP (7 μg/mL, 60 min) attenuated vasodilations to serotonin and AA but not to nitroprusside, exogenous PGI2, or hydrogen peroxide (endothelium-dependent PGE2 activator). CRP also reduced basal NO production, caused tyrosine nitration of endothelial PGI2-S, and inhibited AA-stimulated PGI2 release from arterioles. Peroxynitrite scavenger urate failed to restore serotonin dilation, but preserved AA-stimulated PGI2 release/dilation and prevented PGI2-S nitration. NO synthase inhibitor L-NAME and superoxide scavenger TEMPOL also protected AA-induced vasodilation. Collectively, our results suggest that CRP stimulates superoxide production and the subsequent formation of peroxynitrite from basal released NO compromises PGI2 synthesis, and thus endothelium-dependent PGI2-mediated dilation, by inhibiting PGI2-S activity through tyrosine nitration. By impairing PGI2-S function, and thus PGI2 release, CRP could promote endothelial dysfunction and participate in the development of coronary artery disease. [Copyright &y& Elsevier]

The inflammation and immune hypothesis of major depressive disorder (MDD) explains the mechanism of neuroinflammatory response to promote depression-like behaviors and provides targets for immunotherapy. Previous studies revealed that the neuronal function of the entorhinal cortex (EC) was relative to the depression symptoms in MDD. However, it remains largely unknown what role of neuroinflammation plays in the EC. Hence, we used immunofluorescence to determine c-Fos expression in the EC of lipopolysaccharide (LPS)-treated mice. Mice model was constructed of 10-day LPS treatment, and depression-related behaviors were assessed. We used gene expression microarray to determine differentially expressed genes (DEGs) in the EC of LPS group comparing to control group, and molecular verification was performed by quantitative real-time PCR and Western blot. We found that c-Fos expression was significant reduced in the two layers (Lateral 3.25 mm and 3.00 mm) of the EC in LPS-treated mice compared to saline-treated mice. Mice in LPS group exhibited depression- and anxiety-like behaviors in chronic model. Gene expression analyses identified 339 DEGs in the EC between LPS and control group. The molecular verification showed activation of IL-1R1/NF-κB/CCL5 signaling and upregulation of markers of astrocyte (GFAP) and microglia (AIF1 and CD86) in the EC. Our results suggested that LPS-induced neuroinflammation inhibited neuronal activity in the EC of mice, and that activation of IL-1R1/NF-κB/CCL5 signaling could be involved in the neuroinflammation in the EC of LPS-treated depression model. • Lipopolysaccharide (LPS) treatment reduced c-Fos expression in the entorhinal cortex (EC) of mice. • LPS-treated mice showed depression- and anxiety-like behaviors. • Gene expression analyses revealed neuroinflammatory alterations in the EC. • IL-1R1/NF-κB/CCL5 signaling could be involved in inflammatory response in the EC. [ABSTRACT FROM AUTHOR]

Accumulating evidence revealed the abnormal expression of KLF5 in human cancers while its role in melanoma remains uncharacterized. This study aimed to explore the role of KLF5 in the proliferation and metastasis of melanoma. Bioinformatics analysis was performed to detect WWP1, BAP1 and KLF5 expression in melanoma, followed by expression determination on clinical tissues from melanoma patients and cancer cells. The cancer cells were infected with lentivirus expressing KLF5 or BAP1 while PI3K, AKT and mTOR expression was detected and autophagy was observed. Treated cells were injected to mice when tumor growth was measured and autophagy-related protein was detected. Plasmids expressing WWP1 and Ub-K48 were co-transfected into treated melanoma cells while immunoprecipitation assay was performed to determine the interaction among KLF5, WWP1, and BAP1. WWP1 was poorly expressed in melanoma cells and tissues whereas KLF5 was highly expressed and was positively correlated to poor prognosis. KLF5 promoted melanoma cell malignant phenotypes as well as inhibited autophagy. Interestingly, KLF5 contributed to activation of PI3K-AKT-mTOR signaling pathway, thereby inhibiting autophagy in melanoma cells. WWP1 mediated K48-linked ubiquitination of KLF5 to promote its degradation, and BAP1 antagonized this modification and stabilized KLF5 protein expression. Besides, BAP1 promoted KLF5-mediated growth of melanoma in vivo. Taken altogether, BAP1 antagonized WWP1-mediated ubiquitination of KLF5 to inhibit autophagy and promote melanoma development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel GNA derivatives were synthesized and screened for their antitumor activities. • Introduction of sulfoximines increased the antitumor activity of GNA derivatives. • 12 k with CF 3 group displayed the most pronounced anti-cancer efficacy. • 12 k triggered pyroptosis in cancer cells via the caspase-3/GSDME pathway. Gambogenic acid (GNA), a caged xanthone derived from Garcinia hanburyi , exhibits a wide range of anti-cancer properties. The caged skeleton of GNA serves as the fundamental pharmacophore responsible for its antitumor effects. However, limited exploration has focused on the structural modifications of GNA. This study endeavors to diversify the structure of GNA and enhance its anti-cancer efficacy. Sulfoximines, recognized as pivotal motifs in medicinal chemistry due to their outstanding properties, have featured in several anti-cancer drugs undergoing clinical trials. Accordingly, a series of 33 GNA derivatives combined with sulfoximines were synthesized and evaluated for their anti-cancer effects against MIAPaCa2, MDA-MB-231, and A549 cells in vitro. The activity screening led to the identification of compound 12 k , which exhibited the most potent anti-cancer effect. Mechanistic studies revealed that 12 k primarily induced pyroptosis in MIAPaCa2 and MDA-MB-231 cells by activating the caspase-3/gasdermin E (GSDME) pathway. These findings suggested that 12 k is a promising drug candidate in cancer therapy and highlighted the potential of sulfoximines as a valuable functional group in drug discovery. [ABSTRACT FROM AUTHOR]

Influenza A virus nucleoprotein (NP) is a structural component that encapsulates the viral genome into the form of ribonucleoprotein complexes (vRNPs). Efficient assembly of vRNPs is critical for the virus life cycle. The assembly route from RNA-free NP to the NP-RNA polymer in vRNPs has been suggested to require a cellular factor UAP56, but the mechanism is poorly understood. Here, we characterized the interaction between NP and UAP56 using recombinant proteins and showed that UAP56 features two NP binding sites. In addition to the UAP56 core comprised of two RecA domains, we identified the N-terminal extension (NTE) of UAP56 as a previously unknown NP binding site. In particular, UAP56-NTE recognizes the nucleic acid binding region of NP. This corroborates our observation that binding of UAP56-NTE and RNA to NP is mutually exclusive. Collectively, our results reveal the molecular basis for how UAP56 acts on RNA-free NP, and provide new insights into NP-mediated influenza genome packaging. • Cellular factor UAP56 features multiple binding sites for influenza A virus NP. • N-terminal extension (NTE) of UAP56 recognizes nucleic acid binding site of NP. • Binding of UAP56-NTE and RNA to NP is mutually exclusive. [ABSTRACT FROM AUTHOR]

• Chloroplast (cp) genomes of 35 species representing 31 genera of the 14 tribes of the Ranunculaceae were sequenced, based on which well-resolved phylogenetic trees were obtained. • Two waves of radiation within the core Ranunculaceae were identified, through which most of the extant tribes and genera were generated. • Many of the characters that were once widely used for systematic considerations were actually results of parallel, convergent or reversal evolution. • Frequent inversions, duplications, or losses of fragments have contributed to cp genome evolution. The family Ranunculaceae, a member of early-diverging eudicots that is increasingly being used as a model for the study of plant developmental evolution, has been the focus of systematic studies for centuries. Recent studies showed that the family can be divided into 14 tribes, with Glaucideae, Hydrastideae, and Coptideae being the successive basal-most lineages. The relationships among the remaining 11 tribes, however, remain controversial, so that a clear picture of character evolution within the family is still lacking. In this study, by sequencing, assembling and analyzing the chloroplast (cp) genomes of 35 species representing 31 genera of the 14 tribes, we resolved the relationships among the tribes and genera of the Ranunculaceae and clarified several long-standing controversies. We found that many of the characters that were once widely used for taxonomic and systematic considerations were actually results of parallel, convergent or even reversal evolution, suggestive of unreliability. We also found that the family has likely experienced two waves of radiative evolution, through which most of the extant tribes and genera were generated. Notably, both waves of radiation were correlated with the increase in the temperature of the earth, suggesting that global warming may have been the driving force of the radiation events. Based on these observations, we hypothesize that global warming and the associated decrease in the type and number of animal pollinators may have been the main reason why taxa with highly elaborate petals as well as those without petal were generated during each of the two waves of radiation. [ABSTRACT FROM AUTHOR]

There is an urgent demand to investigate mechanisms for the improvement of denitrification in carbon-deficient environment, which will effectively reduce the eutrophication in water bodies polluted by nitrate. In this study, denitrifying bacterium Comamonas sp. YSF15 was used to explore the differences in different carbon source concentrations, with the complete genome, metabolomics, and other detecting methods. Results showed that strain YSF15 was able to achieve efficient denitrification, with complete pathways for denitrification and central carbon metabolism. The carbon deficiency prompted the bacteria to use extracellular amino acid-like metabolites initially, to alleviate inhibition and maintain bioactivity, which also facilitated glycogen storage. The biogenic inhibitors (tautomycin, navitoclax, and glufosinate) at extremely low level potentially favored the competitiveness and intraspecific utilization of extracellular polysaccharides (PS). Optimal solutions for bioaggregation in carbon-deficient condition are achieved by regulating the hydrophobicity, and hydrogen bond in extracellular metabolites. The strategy contributes to the maintenance of bioactivity and adaptation to carbon deficiency. Overall, this study provides a new perspective on understanding the denitrification strategies in carbon-deficient environment, and helps to improve the nitrate removal in low-carbon wastewater treatment. [Display omitted] • The coupled carbon and nitrogen metabolism in strain YSF15 for denitrification. • The bioactivity maintenance and metabolic regulation provoked by carbon deficiency. • Enhanced bioaggregation as an effective strategy to improve denitrification. [ABSTRACT FROM AUTHOR]

Quaternary climatic oscillations have had tremendous effects on current distribution of species. Previous studies unraveled multiple microrefugia on the Qinghai-Tibetan Plateau (QTP) in two woody plants. Still we know little whether herbs growing in forests responded to climatic oscillations similarly. We herein conducted a phylogeographic study on Rhodiola sect. Trifida , an herbaceous group endemic to the QTP, which mainly growing on the forest floors, using plastid and ITS sequences as well as ecological niche modeling. The origin and divergence of major clades of sect. Trifida were in accordance with the last phase of the QTP uplifts. Mismatch distribution analysis indicated a range expansion dated to ca. 135 thousand years ago. A high frequency and an even distribution of private haplotypes in both plastid and ITS data sets throughout the distribution of sect. Trifida were detected. The ecological niche modeling results showed that there were suitable habitats on the QTP platform during the LGM. Our results found that multiple microrefugia existed on the QTP platform, supporting the hypothesis that species with similar geographic distribution and inhabiting the same community had similar responses to the Quaternary climatic oscillations. Furthermore, species delimitations in sect. Trifida need to be tested based on integrative evidence from morphological, ecological and genetic data. [ABSTRACT FROM AUTHOR]

Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes were detected by using RNA-sequencing. The anterior cingulate cortex (ACC) tissues were collected for biochemical experiments. The Golgi-Cox staining and virus labeling were used to evaluate the dendritic spines. We applied fluoxetine (FLX) and amodiaquine dihydrochloride (AQ, a highly selective agonist of Nr4a2) in mice. Overexpression experiments were performed by injecting with AAV-Nr4a2-EGFP into ACC. Chemogenetic activation of CamkII neurons via injecting the hM3Dq virus. Mice treated with LPS displayed depressive- and anxiety-like behaviors. The reduction of Nr4a2 and FosB induced by LPS were rescued by pretreatment with FLX or AQ. More importantly, LPS-induced behavior deficits in mice were also alleviated via fluoxetine treatment and pharmacological activation the expression of Nr4a2. Meanwhile, enhancing the level of Nr4a2 could improve dendritic spines loss of neuron and morphological changes in microglia. Overexpression of Nr4a2 in ACC reversed the depressive- and anxiety-like behaviors caused by LPS administration. Activation of CamkII neurons in ACC could robustly increase the expression of Nr4a2 and improve LPS-induced behavior deficits. Our findings demonstrate that the Nr4a2 may regulate depressive-like behaviors via alleviating the impairment of morphology and function on microglia and CamkII neurons induced by chronic neuroinflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

• Phagocytosis of debris generated from myelin sheath damage in CNS disease and injury is proving to be a novel source of pathologic consequences. • Both professional and semi-professional phagocytes participate in the clearance of myelin debris in the CNS. • Myelin debris clearance is a prerequisite for healing and neurodegeneration, however, the myelin debris engulfed by different cells can result in different pathological consequences. Central nervous system (CNS) disorders and trauma involving changes to the neuronal myelin sheath have long been a topic of great interest. One common pathological change in these diseases is the generation of myelin debris resulting from the breakdown of the myelin sheath. Myelin debris contains many inflammatory and neurotoxic factors that inhibit remyelination and make its clearance a prerequisite for healing in CNS disorders. Many professional and semiprofessional phagocytes participate in the clearance of myelin debris in the CNS. These cells use various mechanisms for the uptake of myelin debris, and each cell type produces its own unique set of pathologic consequences resulting from the debris uptake. Examining these cells' phagocytosis of myelin debris will contribute to a more complete understanding of CNS disease pathogenesis and help us conceptualize how the necessary clearance of myelin debris must be balanced with the detrimental consequences brought about by its clearance. [ABSTRACT FROM AUTHOR]

Abstract: The Xiaogushan cave site is one of the most important prehistoric sites in North China. The stone and bone artifacts found in the cave are similar to European contemporaneous artifacts. Cave deposits consist of five layers that have been dated from 46,353±1179 to 4229±135 cal. yr BP, using radiocarbon dating techniques on charcoal and bone samples collected from Layers 2–5. In this paper, optically stimulated luminescence (OSL) techniques were applied to date six samples taken from Layers 1–3. The luminescence properties of the fine-grained and coarse-grained quartz extracts indicate that the materials are suitable for OSL dating using a single-aliquot regeneration-dose (SAR) protocol. The OSL ages obtained are broadly consistent with the stratigraphy and the associated calibrated radiocarbon ages. The dating results show that the cave was first occupied by humans about 70ka. The human occupation of the cave may be related to climate change. An occupation hiatus is inferred to between ∼17 to ∼10ka. The stone and bone artifacts found in Layers 2 and 3 may indicate the Middle to Upper Paleolithic transitions in the region. [ABSTRACT FROM AUTHOR]

Abstract: It has been reported that the plasma levels of VEGF in tumor patients decreased during dendritic cell (DC)-based immunotherapy, but the underlying mechanism remains unclear. Our current report demonstrates that VEGF levels were significantly decreased in the supernatants of DCs incubated with rhVEGF or tumor conditioned medium (TCM) while the intracellular VEGF in DCs was increased. The increased intracellular VEGF was not due to the de novo VEGF synthesis by DCs because exogenous VEGF inhibited the mRNA expression of VEGF in DCs. More direct evidence was provided to demonstrate that Cy3-labeled VEGF could be internalized by DCs specifically and efficiently. In addition, the activity of DCs to internalize VEGF was abolished by neutralizing antibody against VEGF receptor-1 (Flt-1) and inhibitors of endocytosis such as carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and genistein. This study highlights a novel function of DCs and allows a better understanding of the DC–VEGF interaction. [Copyright &y& Elsevier]

Abstract: Shigella strains are human pathogens and normally identified based on their O antigens. The chemical structure and gene cluster of Shigella boydii type 17 O antigen were studied. As judged by sugar and methylation analyses along with NMR spectroscopy data, the O antigen of S. boydii type 17 has a linear trisaccharide O unit, which consists of two residues of N-acetylgalactosamine (GalNAc) and a 4-O-[(R)-1-carboxyethyl]-d-glucose (glucolactilic acid). The O antigen gene cluster of S. boydii type 17 was sequenced and genes encoding UDP-N-acetylglucosamine C4 epimerase for GalNAc synthesis, O unit flippase, O antigen polymerase, and glycosyltransferases were putatively identified based on sequence similarities and the presence of conserved motifs. Two genes, whose functions could not be clearly indicated by homology search, were confirmed to be involved in the synthesis of glucolactilic acid by mutation and structural verification of the O antigens from the mutants. To our knowledge, this is the first time that genes involved in the synthesis of glucolactilic acid have been reported. Two genes specific to S. boydii type 17 were also identified. [Copyright &y& Elsevier]

Abstract: Elevated levels of tumor necrosis factor-α (TNF), a proinflammatory cytokine, are associated with coronary artery disease. However, it is unclear whether vasodilator function of coronary resistance arterioles is susceptible to TNF. Herein, we examined whether TNF can affect endothelium-dependent nitric oxide (NO)-mediated dilation of coronary arterioles to adenosine and whether inflammatory signaling pathways such as mitogen-activated protein kinases, ceramide sphingolipids, and oxidative stress are involved in the TNF-mediated effect. To eliminate confounding influences associated with in vivo preparations, coronary arterioles from porcine heart were isolated and pressurized without flow for in vitro study. Intraluminal treatment with TNF (1 ng/ml, 90 min) significantly attenuated the NO release and vasodilation to adenosine. This inhibitory effect was not observed in denuded vessels or in the presence of NO synthase inhibitor l-NMMA. Histochemical data showed that superoxide production and JNK phosphorylation in arteriolar endothelial cells was enhanced by TNF. Administration of superoxide scavenger or inhibitors of ceramide-activated protein kinase (dimethylaminopurine), JNK (SP600125 and dicumarol), and xanthine oxidase (allopurinol) reduced superoxide production as well as restored NO release and vasodilation to adenosine. Conversely, the effects of TNF were insensitive to inhibitors of p38 (SB203580), ERK (PD98059), NAD(P)H oxidase (apocynin), or mitochondrial respiratory chain (rotenone). These data indicate that TNF inhibits endothelium-dependent NO-mediated dilation of coronary arterioles by ceramide-induced activation of JNK and subsequent production of superoxide via xanthine oxidase. Because myocardial ischemia augments adenosine production and elevates TNF level, inhibiting adenosine-stimulated endothelial release of NO by TNF could contribute to inadequate regulation of coronary blood flow during the development of ischemic heart disease. [Copyright &y& Elsevier]

Père David's deer (Elaphurus davidianus) is an emblematic endangered species and regarded as a national treasure, toxoplasmosis is a serious zoonotic parasitic disease for wild animals. Little is known about the prevalence of antibodies to this parasite in Père David's deer. In this study, sera from 43 wild Père David's deer, from Dafeng nature reserve China were tested for antibodies to Toxoplasma gondii by MAT. The investigation showed that antibodies to toxoplasma were detected in 8 of 43 (18.60%, 95% CI 6.97–30.24) samples. Seroprevalence ranged from 15.00% to 21.74% between the different genders, but the difference was not significant according to SPSS analysis (P > 0.05). This report of seroprevalence of antibodies to T. gondii in Père David's deer provides basic data of T. gondii infection data, which is important for controlling and preventing toxoplasmosis in Père David's deer. • Firstly reported T. gondii infection in the Père David's deer in Dafeng reserve. • The prevalence of T. gondii in serum samples from Père David's deer was 18.6%. • This result is an alert about the potential risk in Père David's deer. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear. In the present study, changes in the expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E6/E7 in CaSki cells. The dysregulated expression of KDM5A was identified, and its function in cervical cancer was investigated in vitro and in vivo. E7 oncoprotein-induced upregulation of KDM5A promoted cervical cancer cell proliferation and invasiveness in vitro and in vivo , which was correlated with poor prognosis in patients with cervical cancer. KDM5A was found to physically interact with the promoter region of miR-424–5p, and to suppress its expression by removing the tri- and di-methyl groups from H3K4 at the miR-424–5p locus. Furthermore, miR-424–5p repressed cancer cell proliferation and invasiveness by targeting suppressor of zeste 12 (Suz12). KDM5A upregulation promoted cervical cancer progression by repressing miR-424–5p, which resulted in a decrease in Suz12. Therefore, KDM5A functions as a tumor activator in cervical cancer pathogenesis by binding to the miR-424–5p promoter and inhibiting its tumor-suppressive function. These results indicate a function for KDM5A in cervical cancer progression and suggest its candidacy as a novel prognostic biomarker and target for the clinical management of this malignancy. • KDM5A promotes tumor growth and metastasis and represses miR-424–5p expression. • KDM5A directly represses miR-424–5p expression by removing tri- and dimethyl marks from H3K4. • miR-424–5p inhibits tumor cell proliferation and invasion by repressing Suz12. • KDM5A regulates Suz12 expression in miR-424-5p-dependent manner. [ABSTRACT FROM AUTHOR]

• Bashania species nested within Fargesia (s.l.) and divided into two groups. • We detected hybridization events in the evolution of Fargesia (s.l.) and its allies. • The Fargesia spathe clade may have a hybrid origin based on multi-faceted evidences. Reticulate evolution resulting from hybridization and introgression has been recognized as a creative source of species and diversification in bamboos. Previous phylogenetic studies revealed that Fargesia (s.l.) (Fargesia and Yushania) was divided into the Fargesia spathe clade and the non-spathe clade. Interestingly, the Fargesia spathe clade may have originated from hybridization among other clades within Fargesia (s.l.). Understanding the hybrid origin of this clade requires a robust phylogenetic framework in which major clades within Fargesia (s.l.) are resolved. Here, we used three nuclear genes to reconstruct the evolutionary history of Fargesia (s.l.) and its allies to identify putative patterns in the origin of the Fargesia spathe clade and to examine the extent to which reticulate evolution has occurred at the interspecific level in bamboos. Bashania species form a clade with Fargesia (s.l.), which is further divided into Group I and Group II. The Fargesia spathe clade, the Alpine Bashania clade, and Fargesia yajiangensis comprise Group I, while the Bashania fargesii clade and the remaining Fargesia (s.l.) species form Group II. Incongruence between the current nuclear-based and previous plastid phylogenies demonstrate several possible hybridization events among Fargesia (s.l.) species and related taxa, which have given rise to the Fargesia spathe clade, the Phyllostachys clade, and the Ampelocalamus clade. We also detected several putative hybrid species of Fargesia (s.l.). Our results show that reticulate evolution has played a prominent role in Fargesia (s.l.) evolution, which could, in part, account for the taxonomic difficulty associated with Fargesia (s.l.) and the alpine bamboos. The study also underscores the importance of hybridization in the evolution of bamboos, at both intergeneric and intrageneric levels. [ABSTRACT FROM AUTHOR]