Satellite-Detected Contrasting Responses of Canopy Structure and Leaf Physiology to Drought

Disentangling drought impacts on plant photosynthesis is crucial for projecting future terrestrial carbon dynamics. We examined the separate responses of canopy structure and leaf physiology to an extreme summer drought that occurred in 2011 over Southwest China, where the weather was humid and radiation was the main growth-limiting factor. Canopy structure and leaf physiology were, respectively, represented by near-infrared reflectance of vegetation (NIRv) derived from MODIS data and leaf scale fluorescence yield (Φf) derived from both continuous SIF (CSIF) and global OCO-2 SIF (GOSIF). We detected contrasting responses of canopy structure and leaf physiology to drought with a 14.0% increase in NIRv, compared with 12.6 or 19.3% decreases in Φf from CSIF and GOSIF, respectively. The increase in structure resulted in a slight carbon change, due to water deficit-induced physiological constraints. The net ecosystem effect was a 7.5% (CSIF), 1.2% (GOSIF), and-2.96% (EC-LUE GPP) change in photosynthesis. Our study improves understanding of complex vegetation responses of plant photosynthesis to drought and may contribute to the reconciliation of contrasting observed directions in plant responses to drought in cloudy regions via remote sensing

Impact of automatic acquisition of key clinical information on the accuracy of electrocardiogram interpretation: a cross-sectional study

Background: The accuracy of electrocardiogram (ECG) interpretation by doctors are affected by the available clinical information. However, having a complete set of clinical details before making a diagnosis is very difficult in the clinical setting especially in the early stages of the admission process. Therefore, we developed an artificial intelligence-assisted ECG diagnostic system (AI-ECG) using natural language processing to provide screened key clinical information during ECG interpretation. Methods: Doctors with varying levels of training were asked to make diagnoses from 50 ECGs using a common ECG diagnosis system that does not contain clinical information. After a two-week-blanking period, the same set of ECGs was reinterpreted by the same doctors with AI-ECG containing clinical information. Two cardiologists independently provided diagnostic criteria for 50 ECGs, and discrepancies were resolved by consensus or, if necessary, by a third cardiologist. The accuracy of ECG interpretation was assessed, with each response scored as correct/partially correct = 1 or incorrect = 0. Results: The mean accuracy of ECG interpretation was 30.2% and 36.2% with the common ECG system and AI-ECG system, respectively. Compared to the unaided ECG system, the accuracy of interpretation was significantly improved with the AI-ECG system (P for paired t-test = 0.002). For senior doctors, no improvement was found in ECG interpretation accuracy, while an AI-ECG system was associated with 27% higher mean scores (24.3 ± 9.4% vs. 30.9 ± 10.6%, P = 0.005) for junior doctors. Conclusion: Intelligently screened key clinical information could improve the accuracy of ECG interpretation by doctors, especially for junior doctors

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease

Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6), CD14+ monocytes (P ≤ 2.74 × 10−4) and CD19+ B cells (P ≤ 2.00 × 10−6), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10−6). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE

Organelle-specific anchored delivery system stretching a reversal of tumor hypoxia microenvironment to a combinational chemo-photothermal therapy

Direct delivery to an organelle-specific point can boost the efficacy of therapy procedures to new heights. Among other subcellular organelles, mitochondria generate ATP as intracellular powerhouse, and are associated with multiple aspects of tumorigenesis and tumor development. Here, a mitochondrial anchored biomimetic nanoplatform (CZACN) is designed and its reversal of tumor hypoxia microenvironment underlying the mitochondria-located chemo-photothermal therapy is studied. After shuttling into cancer cells, therapeutic payloads including cisplatin (CDDP) and Au nanozymes are controllably released in the ATP-overexpressed mitochondria. CDDP generates O2â ¢â , forms H2O2 for a chemical fuel in the next reaction, and damages mitochondrial DNA. Meanwhile, the catalase-like Au nanozymes catalyze the produced hydrogen peroxide for oxygen supply to relieve hypoxic tumor microenvironment, offering cytotoxic singlet oxygen against cancer cells under NIR treatment. As a result of cancer-cell self-recognition, mitochondria-targeted therapy, and photothermal conversion ability, the fabricated CZACNs obtained 89.2 ± 3.70% of tumor growth inhibition under NIR irradiation and constrained the dose-limiting toxicity of CDDP, as well. These findings reinforce the synergistic effect of organelle-specific navigation and in situ oxygen self-sufficiency for combinational chemo-photothermal therapy.X.C., X.Y., and L.Z. contributed equally to this work. This work has been supported by the National Natural Science Foundation of China (22003038, 81922037, and 11575107), the Shanghai University-Universal Medical Imaging Diagnostic Research Foundation (19H00100), Shanghai Biomedical Science and Technology Support Project (19441903600), the Program for Changjiang Scholars and Innovative Research Team in University (IRT13078). The authors would like to thank the workers from Shiyanjia Lab (www.shiyanjia.com) for the ICP-OES analysis

Biomineralization of a calcifying ureolytic bacterium Microbacterium sp. GM-1

Background: Biomineralization is a significant process performed by living organisms in which minerals are produced through the hardening of biological tissues. Herein, we focus on calcium carbonate precipitation, as part of biomineralization, to be used in applications for environmental protection, material technology, and other fields. A strain GM-1, Microbacterium sp. GM-1, isolated from active sludge, was investigated for its ability to produce urease and induce calcium carbonate precipitation in a metabolic process. Results: It was discovered that Microbacterium sp. GM-1 resisted high concentrations of urea up to 60 g/L. In order to optimize the calcification process of Microbacterium sp. GM-1, the concentrations of Ni2+ and urea, pH value, and culture time were analyzed through orthogonal tests. The favored calcite precipitation culture conditions were as follows: the concentration of Ni2+ and urea were 50 \u3bcM and 60 g/L, respectively, pH of 10, and culture time of 96 h. Using X-ray diffraction analysis, the calcium carbonate polymorphs produced by Microbacterium sp. GM-1 were proven to be mainly calcite. Conclusions: The results of this research provide evidence that Microbacterium sp. GM-1 can biologically induce calcification and suggest that strain GM-1 may play a potential role in the synthesis of new biominerals and in bioremediation or biorecovery

Dual inhibition of glycolysis and glutaminolysis as a therapeutic strategy in the treatment of ovarian cancer

Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production. As determined by MTT assay, glucose stimulated cell growth while the combination of glucose, glutamine and pyruvate resulted in the greatest stimulation of cell proliferation. Furthermore, 2-deoxy-glucose (2-DG) and 3-bromopyruvate (3-BP) induced apoptosis, caused G1 phase cell cycle arrest and reduced glycolytic activity. Moreover, 2-DG in combination with a low dose of aminooxyacetate (AOA) synergistically increased the sensitivity to 2-DG in the inhibition of cell growth in the ovarian cancer cell lines. These studies suggest that dual inhibition of glycolysis and glutaminolysis may be a promising therapeutic strategy for the treatment of ovarian cancer

Microglia Mediate Synaptic Material Clearance at the Early Stage of Rats With Retinitis Pigmentosa

Resident microglia are the main immune cells in the retina and play a key role in the pathogenesis of retinitis pigmentosa (RP). Many previous studies on the roles of microglia mainly focused on the neurotoxicity or neuroprotection of photoreceptors, while their contributions to synaptic remodeling of neuronal circuits in the retina of early RP remained unclarified. In the present study, we used Royal College of Surgeons (RCS) rats, a classic RP model characterized by progressive microglia activation and synapse loss, to investigate the constitutive effects of microglia on the synaptic lesions and ectopic neuritogenesis. Rod degeneration resulted in synapse disruption and loss in the outer plexiform layer (OPL) at the early stage of RP. Coincidentally, the resident microglia in the OPL increased phagocytosis and mainly engaged in phagocytic engulfment of postsynaptic mGluR6 of rod bipolar cells (RBCs). Complement pathway might be involved in clearance of postsynaptic elements of RBCs by microglia. We pharmacologically deleted microglia using a CSF1 receptor (CSF1R) inhibitor to confirm this finding, and found that it caused the accumulation of postsynaptic mGluR6 levels and increased the number and length of ectopic dendrites in the RBCs. Interestingly, the numbers of presynaptic sites expressing CtBP2 and colocalized puncta in the OPL of RCS rats were not affected by microglia elimination. However, sustained microglial depletion led to progressive functional deterioration in the retinal responses to light in RCS rats. Based on our results, microglia mediated the remodeling of RBCs by phagocytosing postsynaptic materials and inhibiting ectopic neuritogenesis, contributing to delay the deterioration of vision at the early stage of RP

NT1014, a novel biguanide, inhibits ovarian cancer growth in vitro and in vivo

Abstract Background NT1014 is a novel biguanide and AMPK activator with a high affinity for the organic cation-specific transporters, OCT1 and OCT3. We sought to determine the anti-tumorigenic effects of NT1014 in human ovarian cancer cell lines as well as in a genetically engineered mouse model of high-grade serous ovarian cancer. Methods The effects of NT1014 and metformin on cell proliferation were assessed by MTT assay using the human ovarian cancer cell lines, SKOV3 and IGROV1, as well as in primary cultures. In addition, the impact of NT1014 on cell cycle progression, apoptosis, cellular stress, adhesion, invasion, glycolysis, and AMPK activation/mTOR pathway inhibition was also explored. The effects of NT1014 treatment in vivo was evaluated using the K18 − gT121+/−; p53fl/fl; Brca1fl/fl (KpB) mouse model of high-grade serous ovarian cancer. Results NT1014 significantly inhibited cell proliferation in both ovarian cancer cell lines as well as in primary cultures. In addition, NT1014 activated AMPK, inhibited downstream targets of the mTOR pathway, induced G1 cell cycle arrest/apoptosis/cellular stress, altered glycolysis, and reduced invasion/adhesion. Similar to its anti-tumorigenic effects in vitro, NT1014 decreased ovarian cancer growth in the KpB mouse model of ovarian cancer. NT1014 appeared to be more potent than metformin in both our in vitro and in vivo studies. Conclusions NT1014 inhibited ovarian cancer cell growth in vitro and in vivo, with greater efficacy than the traditional biguanide, metformin. These results support further development of NT1014 as a useful therapeutic approach for the treatment of ovarian cancer

Orientation-dependent optic-fiber accelerometer based on excessively tilted fiber grating

An orientation-dependent optic-fiber accelerometer based on the excessively tilted fiber grating (ExTFG) inscribed in SM28 fiber is demonstrated, which is based on the optical power demodulation scheme. Without any complicated processing, the cladding mode resonances of the bare ExTFG show high sensitivity to slight perturbation of bending. Due to its excellent azimuth-related bending properties, such a bare ExTFG fixed on a simple cantilever beam has exhibited strong orientation-dependent vibration properties. The experimental results show that a TE mode of the sensor can provide a maximum acceleration sensitivity of 74.14 mV/g at 72 Hz and maximum orientation sensitivity of 9.1 mV/deg while, for a TM mode, a maximum acceleration sensitivity of 57.85 mV/g at 72 Hz and maximum orientation sensitivity of 7.4 mV/deg could be achieved. These unique properties enable the sensor to act as a vector accelerometer for applications in many vibration measurementfields