Maize straw increases while its biochar decreases native organic carbon mineralization in a subtropical forest soil.

Organic soil amendments have been widely adopted to enhance soil organic carbon (SOC) stocks in agroforestry ecosystems. However, the contrasting impacts of pyrogenic and fresh organic matter on native SOC mineralization and the underlying mechanisms mediating those processes remain poorly understood. Here, an 80-day experiment was conducted to compare the effects of maize straw and its derived biochar on native SOC mineralization within a Moso bamboo (Phyllostachys edulis) forest soil. The quantity and quality of SOC, the expression of microbial functional genes concerning soil C cycling, and the activity of associated enzymes were determined. Maize straw enhanced while its biochar decreased the emissions of native SOC-derived CO2. The addition of maize straw (cf. control) enhanced the O-alkyl C proportion, activities of ß-glucosidase (BG), cellobiohydrolase (CBH) and dehydrogenase (DH), and abundances of GH48 and cbhI genes, while lowered aromatic C proportion, RubisCO enzyme activity, and cbbL abundance; the application of biochar induced the opposite effects. In all treatments, the cumulative native SOC-derived CO2 efflux increased with enhanced O-alkyl C proportion, activities of BG, CBH, and DH, and abundances of GH48 and cbhI genes, and with decreases in aromatic C, RubisCO enzyme activity and cbbL gene abundance. The enhanced emissions of native SOC-derived CO2 by the maize straw were associated with a higher O-alkyl C proportion, activities of BG and CBH, and abundance of GH48 and cbhI genes, as well as a lower aromatic C proportion and cbbL gene abundance, while biochar induced the opposite effects. We concluded that maize straw induced positive priming, while its biochar induced negative priming within a subtropical forest soil, due to the contrasting microbial responses resulted from changes in SOC speciation and compositions. Our findings highlight that biochar application is an effective approach for enhancing soil C stocks in subtropical forests.

Direct fabrication of NbS2 nanoflakes on carbon fibers by atomic layer deposition for ultrasensitive cardiac troponin I detection.

The sensitive detection of cardiac troponin I (cTnI) is of great significance for the early diagnosis of acute myocardial infarction (AMI). Herein, in order to fabricate an electrochemical biosensor for ultrasensitive cTnI detection, atomic layer deposition (ALD) was employed to directly deposit NbS2 nanoflakes (NFs) on carbon fiber paper (CFP). Due to the self-limiting reaction of ALD, NbS2NFs were deposited uniformly and accurately on the surface of carbon fibers by controlling the number of ALD cycles, which ensured ultrasensitive detection. Precise regulation of the nanoscale morphology and electrochemical performance of NbS2 nanoflakes via ALD cycles was observed in depth. Owing to the high surface area and conductivity, an anodic/cathodic current of ∼3.01 mA of NbS2NFs/CFP can be obtained. Subsequently, an electrochemical biosensor based on the excellent performance of NbS2NFs/CFP was fabricated. The ultrasensitive detection of cTnI in a linear range of 1 fM to 0.1 nM with a detection limit of 0.32 fM was achieved.

Atomic layer deposition (ALD)-constructed TaS2nanoflakes for cancer-related nucleolin detection.

Sensitive detection of nucleolin (NCL) is of great significance for the early diagnosis of cancer. In this work, as a new type of two-dimensional (2D) transition metal dichalcogenides (TMDCs), TaS2nanoflakes (NFs) were precisely constructed by atomic layer deposition (ALD) on carbon fiber paper (CFP) with high specific surface area.In situobservation showed that the nucleation and growth of TaS2nanoflakes were precisely controlled by the number of ALD cycles, thereby regulating their electrochemical properties. The electrochemical performance of TaS2NFs was observed in depth, and compared with that of traditional 2D TMDCs. Due to the high surface area and conductivity, anodic/cathodic current of ∼1570µA of TaS2NFs/CFP can be obtained. Subsequently, an electrochemical biosensor based on ALD-constructed TaS2NFs/CFP for cancer-related NCL detection was fabricated. Due to the excellent electrochemical performance of TaS2NFs/CFP, ultrasensitive detection of NCL in the linear range of 0.1 pM-10 nM with a detection limit of 0.034 pM was achieved.

Alpha7 nicotinic acetylcholine receptor agonist PHA-543613 improves memory deficits in presenilin 1 and presenilin 2 conditional double knockout mice.

Cholinergic system dysfunction has been considered as a critical feature of neurodegenerative progression in Alzheimer's disease (AD). The α7 nicotinic acetylcholine receptors (α7-nAChRs) are widely expressed in the hippocampus cortex and play an important role in memory formation, considered as potential therapeutic agents targets. However, underlying mechanisms have not been fully elucidated. Here, we combine behavioral, molecular biological methods with in vitro slice and in vivo multichannel electrophysiological recording techniques to investigate the molecular, cellular synaptic and neuronal mechanisms of activating α7-nAChR by PHA-543613 (a selective α7-nAChR agonist), which influences the impaired cognitive function using presenilin 1 (PS1) and presenilin 2 (PS2) conditional double knockout (cDKO) mice. Our results demonstrated that PHA-543613 treatment significantly improved the impaired hippocampus-related memory via recovering the reduced the hippocampal synaptic protein levels of α7-nAChR, NMADAR and AMPAR, thereby restoring the impaired post-tetanic potentiation (PTP), long-term potentiation (LTP), activation of molecular signaling pathway for neuronal protection, theta power and strength of theta-gamma phase-amplitude coupling (PAC) at hippocampus in 6-month-old cDKO mice. For the first time, we systematically reveal the mechanisms by which PHA-543613 improves memory deficits at different levels. Therefore, our findings may be significant for the development of therapeutic strategies for AD.

Exogenous Aß1-42 monomers improve synaptic and cognitive function in Alzheimer's disease model mice.

Growing evidence has suggested the poor correlation between brain amyloid plaque and Alzheimer's disease (AD). Presenilin1 (PS1) and presenilin2 (PS2) conditional double knockout (cDKO) mice exhibited the reduced 42-amino acid amyloid-ß peptide (Aß1-42) level and AD-like symptoms, indicating a different pathological mechanism from the amyloid cascade hypothesis for AD. Here we found that exogenous synthetic Aß1-42 monomers could improve the impaired memory not only in cDKO mice without Aß1-42 deposition but also in the APP/PS1/Tau triple transgenic 3 × Tg-AD mice with Aß1-42 deposition, which were mediated by α7-nAChR. Our findings demonstrate for the first time that reduced soluble Aß1-42 level is the main cause of cognitive dysfunction in cDKO mice, and support the opinions that low soluble Aß1-42 level due to Aß1-42 deposition may also cause cognitive deficits in 3 × Tg-AD mice. Therefore, "loss-of-function" of Aß1-42 should be avoided when designing therapies aimed at reducing Aß1-42 burden in AD.

BMP9-ID1 Signaling Activates HIF-1α and VEGFA Expression to Promote Tumor Angiogenesis in Hepatocellular Carcinoma.

Since hepatocellular carcinoma (HCC) is a typical hypervascular malignant tumor with poor prognosis, targeting angiogenesis is an important therapeutic strategy for advanced HCC. Involvement of bone morphologic protein 9 (BMP9), a transforming growth factor-beta superfamily member, has recently been reported in the development of liver diseases and angiogenesis. Here, we aimed to elucidate the role of BMP9 signaling in promoting HCC angiogenesis and to assess the antiangiogenic effect of BMP receptor inhibitors in HCC. By analyzing HCC tissue gene expression profiles, we found that BMP9 expression was significantly correlated with angiogenesis-associated genes, including HIF-1α and VEGFR2. In vitro, BMP9 induced HCC cell HIF-1α/VEGFA expression and VEGFA secretion. Silencing of the inhibitor of DNA-binding protein 1 (ID1), a transcription factor targeted by BMP9 signaling, suppressed BMP9-induced HIF-1α/VEGFA expression and VEGFA secretion, resulting in decreased human umbilical vein endothelial cell (HUVEC) lumen formation. BMP receptor inhibitors, which inhibit BMP9-ID1 signaling, suppressed BMP9-induced HIF-1α/VEGFA expression, VEGFA secretion, and HUVEC lumen formation. In vivo, the BMP receptor inhibitor LDN-212854 successfully inhibited HCC tumor growth and angiogenesis by inhibiting BMP9-ID1 signaling. In summary, BMP9-ID1 signaling promotes HCC angiogenesis by activating HIF-1α/VEGFA expression. Thus, targeting BMP9-ID1 signaling could be a pivotal therapeutic option for advanced HCC.

High-fat diet-induced atherosclerosis promotes neurodegeneration in the triple transgenic (3 × Tg) mouse model of Alzheimer's disease associated with chronic platelet activation.

BACKGROUND: Epidemiological studies link vascular disease risk factors such as atherosclerosis, hypertension, and diabetes mellitus with Alzheimer's disease (AD). Whether there are direct links between these conditions to ß-amyloid (Aß) aggregation and tau pathology is uncertain. METHODS: To investigate the possible link between atherosclerosis and AD pathology, we subjected triple transgenic (3 × Tg) AD mice to a high-fat diet (HFD) at 3 months of age, which corresponds to early adulthood in humans. RESULTS: After 9 months of treatment, HFD-treated 3 × Tg mice exhibited worse memory deficits accompanied by blood hypercoagulation, thrombocytosis, and chronic platelet activation. Procoagulant platelets from HFD-treated 3 × Tg mice actively induced the conversion of soluble Aß40 into fibrillar Aß aggregates, associated with increased expression of integrin αIIbß3 and clusterin. At 9 months and older, platelet-associated fibrillar Aß aggregates were observed to obstruct the cerebral blood vessels in HFD-treated 3 × Tg mice. HFD-treated 3 × Tg mice exhibited a greater cerebral amyloid angiopathy (CAA) burden and increased cerebral vascular permeability, as well as more extensive neuroinflammation, tau hyperphosphorylation, and neuron loss. Disaggregation of preexisting platelet micro-clots with humanized GPIIIa49-66 scFv Ab (A11) significantly reduced platelet-associated fibrillar Aß aggregates in vitro and improved vascular permeability in vivo. CONCLUSIONS: These findings suggest that a major contribution of atherosclerosis to AD pathology is via its effects on blood coagulation and the formation of platelet-mediated Aß aggregates that compromise cerebral blood flow and therefore neuronal function. This leads to cognitive decline.

αCaMKII in the lateral amygdala mediates PTSD-Like behaviors and NMDAR-Dependent LTD.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that afflicts many individuals. However, its molecular and cellular mechanisms remain largely unexplored. Here, we found PTSD susceptible mice exhibited significant up-regulation of alpha-Ca2+/calmodulin-dependent kinase II (αCaMKII) in the lateral amygdala (LA). Consistently, increasing αCaMKII in the LA not only caused PTSD-like behaviors such as impaired fear extinction and anxiety-like behaviors, but also attenuated N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) at thalamo-lateral amygdala (T-LA) synapses, and reduced GluA1-Ser845/Ser831 dephosphorylation and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization. Suppressing the elevated αCaMKII to normal levels completely rescued both PTSD-like behaviors and the impairments in LTD, GluA1-Ser845/Ser831 dephosphorylation, and AMPAR internalization. Intriguingly, deficits in GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization were detected not only after impaired fear extinction, but also after attenuated LTD. Our results suggest that αCaMKII in the LA may be a potential molecular determinant of PTSD. We further demonstrate for the first time that GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization are molecular links between fear extinction and LTD.

Nanocrystalline NiSe2/MoS2 heterostructures for electrochemical hydrogen evolution reaction.

Although it suffers from a heavy dependence on the noble platinum catalyst, the electrochemical hydrogen evolution reaction (HER) is one of the most promising methods for the production of hydrogen. After numerous efforts, it is found that MoS2-based heterostructure may replace platinum as the electrochemical HER catalyst. In this work, the nanocrystalline NiSe2/MoS2 heterostructures were successfully prepared on the carbon fiber paper (CFP) substrate through electrochemical deposition and hydrothermal process. According to a series of electrochemical HER tests and a comparison with other MoS2-based heterostructure catalysts, the CFP/NiSe2/MoS2 catalyst with an overpotential η 10 of 143 mV and a Tafel slope of 45 mV dec-1 exhibited an excellent electrochemical HER catalytic performance and durability. In addition, CFP/NiSe2/MoS2 catalyst was treated by plasma to further improve the catalytic performance of the catalyst.

Association between homocysteine and obesity: A meta-analysis.

According to previous studies of obesity, we found that the association between homocysteine concentrations and obesity was reported controversially. Thus, we carried out this meta-analysis to investigate this association. We searched PubMed, The Cochrane library, and EMBASE database for studies that evaluate the relationship between homocysteine concentrations and obesity from inception to March, 2019. The quality of all included studies was assessed by the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research Quality (AHRQ). The RevMan5.3 software and Stata12.0 software were used for conducting all data analyses. Standardized mean differences (SMD) with the corresponding 95% confidence intervals (95% CIs) were used as a measure of effect size to assess the relationship between homocysteine concentrations and obesity through a meta-analysis. The level of significance was set at P < .05. A total of 14 studies were ultimately included in our meta-analysis. Meta-analysis of the 14 studies found remarkable lower homocysteine concentrations in controls than in obese patients (SMD = 0.76, 95% CI = 0.25-1.27, P < .01; I2  = 94% and P < .01 for heterogeneity), regardless of nutritional status, dietary habit, insulin resistance (IR) status, special disease history, history of medicine taken, genetic background, and so on. Homocysteine concentrations in nonobese patients with polycystic ovarian syndrome (PCOS) were lower than obese patients with PCOS (SMD = 0.48, 95% CI = 0.20-0.77, P < .01; I2  = 39% and P = .18 for heterogeneity). The result of our meta-analysis showed that homocysteine concentrations were significantly elevated among obese patients.

Co-activation of Akt, Nrf2, and NF-κB signals under UPRER in torpid Myotis ricketti bats for survival.

Bats hibernate to survive stressful conditions. Examination of whole cell and mitochondrial proteomes of the liver of Myotis ricketti revealed that torpid bats had endoplasmic reticulum unfolded protein response (UPRER), global reduction in glycolysis, enhancement of lipolysis, and selective amino acid metabolism. Compared to active bats, torpid bats had higher amounts of phosphorylated serine/threonine kinase (p-Akt) and UPRER markers such as PKR-like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4). Torpid bats also had lower amounts of the complex of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65)/I-κBα. Cellular redistribution of 78 kDa glucose-regulated protein (GRP78) and reduced binding between PERK and GRP78 were also seen in torpid bats. Evidence of such was not observed in fasted, cold-treated, or normal mice. These data indicated that bats activate Akt, Nrf2, and NF-κB via the PERK-ATF4 regulatory axis against endoplasmic reticulum stresses during hibernation.

MicroRNA-30b regulates insulin sensitivity by targeting SERCA2b in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Insulin resistance is strongly associated with non-alcoholic fatty liver disease, a chronic, obesity-related liver disease. Increased endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity. METHODS: We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR-30b or inhibit miR-30b rats were injected with lentivirus particles containing PGLV3-miR-30b or PGLV3-miR-30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects. RESULTS: Our data showed that miR-30b was markedly up-regulated in the liver of HFD-treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+ -ATPase 2b (SERCA2b), as a novel target of miR-30b. Overexpression of miR-30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR-30b by miR-30b antimiR suppressed ER stress and insulin resistance in HFD-treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR-30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA-IR) in human subjects. CONCLUSIONS: Our findings suggest that miR-30b represents not only a potential target for the treatment of insulin resistance, but also a non-invasive disease biomarker of NAFLD.