Inhibition of XPR1-dependent phosphate efflux induces mitochondrial dysfunction: A potential molecular target therapy for hepatocellular carcinoma?

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.

Tunable Non-Markovianity for Bosonic Quantum Memristors.

We studied the tunable control of the non-Markovianity of a bosonic mode due to its coupling to a set of auxiliary qubits, both embedded in a thermal reservoir. Specifically, we considered a single cavity mode coupled to auxiliary qubits described by the Tavis-Cummings model. As a figure of merit, we define the dynamical non-Markovianity as the tendency of a system to return to its initial state, instead of evolving monotonically to its steady state. We studied how this dynamical non-Markovianity can be manipulated in terms of the qubit frequency. We found that the control of the auxiliary systems affects the cavity dynamics as an effective time-dependent decay rate. Finally, we show how this tunable time-dependent decay rate can be tuned to engineer bosonic quantum memristors, involving memory effects that are fundamental for developing neuromorphic quantum technologies.

Chiroptical Sensing of Amino Acid Derivatives by Host-Guest Complexation with Cyclo[6]aramide.

A hydrogen-bonded (H-bonded) amide macrocycle was found to serve as an effective component in the host-guest assembly for a supramolecular chirality transfer process. Circular dichroism (CD) spectroscopy studies showed that the near-planar macrocycle could produce a CD response when combined with three of the twelve L-α-amino acid esters (all cryptochiral molecules) tested as possible guests. The host-guest complexation between the macrocycle and cationic guests was explored using NMR, revealing the presence of a strong affinity involving the multi-point recognition of guests. This was further corroborated by density functional theory (DFT) calculations. The present work proposes a new strategy for amplifying the CD signals of cryptochiral molecules by means of H-bonded macrocycle-based host-guest association, and is expected to be useful in designing supramolecular chiroptical sensing materials.

Diversity of upper respiratory tract infections and prevalence of Streptococcus pneumoniae colonization among patients with fever and flu-like symptoms.

BACKGROUND: Many upper respiratory pathogens cause similar symptoms. In China, routine molecular tests for upper respiratory pathogens are not widely performed and antibiotics abuse in treating upper respiratory tract infections (URTIs) is a major public health concern. METHODS: We performed qualitative real-time PCR tests to detect common upper respiratory tract pathogens including 9 viruses and 3 bacteria in 1221 nasopharyngeal swabs from patients with fever and influenza-like symptoms in a Chinese city. A quantitative real-time PCR was also performed to measure the bacterial density of the colonizing Streptococcus pneumoniae in these samples. RESULTS: We found very diverse pathogens including 81.7% viruses, 11.6% bacteria and 6.7% mixed viruses and bacteria. S. pneumoniae colonization was found in 8.0% of the cases but most of them had low bacterial density (Mean = 3.9 log cfu/ml). We also discovered an increase of S. pneumoniae colonization frequency (but not the density) in patients with detectable upper respiratory tract pathogens, in a pathogen variety-dependent manner. CONCLUSIONS: Our study provided strong evidence against empiric antibiotic use for treating URTIs, and highlighted a strong need for improving the diagnostic capacity for URTIs by using more molecular testing in China.

Learning Student Network Under Universal Label Noise.

Data-free knowledge distillation aims to learn a small student network from a large pre-trained teacher network without the aid of original training data. Recent works propose to gather alternative data from the Internet for training student network. In a more realistic scenario, the data on the Internet contains two types of label noise, namely: 1) closed-set label noise, where some examples belong to the known categories but are mislabeled; and 2) open-set label noise, where the true labels of some mislabeled examples are outside the known categories. However, the latter is largely ignored by existing works, leading to limited student network performance. Therefore, this paper proposes a novel data-free knowledge distillation paradigm by utilizing a webly-collected dataset under universal label noise, which means both closed-set and open-set label noise should be tackled. Specifically, we first split the collected noisy dataset into clean set, closed noisy set, and open noisy set based on the prediction uncertainty of various data types. For the closed-set noisy examples, their labels are refined by teacher network. Meanwhile, a noise-robust hybrid contrastive learning is performed on the clean set and refined closed noisy set to encourage student network to learn the categorical and instance knowledge inherited by teacher network. For the open-set noisy examples unexplored by previous work, we regard them as unlabeled and conduct self-supervised learning on them to enrich the supervision signal for student network. Intensive experimental results on image classification tasks demonstrate that our approach can achieve superior performance to state-of-the-art data-free knowledge distillation methods.

Effect of Nitrogen on Microbial Communities of Purple Mudstone Weathering Products in Southwest China: A Column Experiment.

Nitrogen application significantly affects microorganisms in agricultural ecosystems. However, it is still unclear how nitrogen application affects soil chemical properties and microbial communities in purple mudstone weathering products. In this study, a field soil column experiment was conducted in a typical purple soil area with four nitrogen fertilizer application gradients of 0 [CK], 280 [N1], 560 [N2], and 840 [N3] N kg ha-1. Nitrogen addition decreased the bacterial chao1 value and increased the bacterial evenness index. For both α- and ß-diversity, the effect of nitrogen addition on bacteria was much greater than that on fungi. Nitrogen addition significantly increased the relative abundance of Proteobacteria, Gemmatimonadetes, Bacteroidetes, and Ascomycota and decreased the relative abundance of Actinobacteria, Cyanobacteria, and Basidiomycota. Both pH and TC are the most important soil chemical properties influencing the bacterial and fungal communities. With the increases in the nitrogen application rate, the co-occurrence network complexity increased and then decreased. In summary, nitrogen fertilizer application could significantly change the soil chemical properties, microbial community diversity, composition, and co-occurrence network of purple mudstone weathering products. Among them, the N2 treatment (560 N kg∙ha-1) can more effectively stimulate the soil nutrients, enhance microbial network complexity, and promote further weathering of purple mudstone.

Knowledge distillation based on multi-layer fusion features.

Knowledge distillation improves the performance of a small student network by promoting it to learn the knowledge from a pre-trained high-performance but bulky teacher network. Generally, most of the current knowledge distillation methods extract relatively simple features from the middle or bottom layer of teacher network for knowledge transmission. However, the above methods ignore the fusion of features, and the fused features contain richer information. We believe that the richer and better information contained in the knowledge delivered by teachers to students, the easier it is for students to perform better. In this paper, we propose a new method called Multi-feature Fusion Knowledge Distillation (MFKD) to extract and utilize the expressive fusion features of teacher network. Specifically, we extract feature maps from different positions of the network, i.e., the middle layer, the bottom layer, and even the front layer of the network. To properly utilize these features, this method designs a multi-feature fusion scheme to integrate them together. Compared to features extracted from single location of teacher network, the final fusion feature map contains meaningful information. Extensive experiments on image classification tasks demonstrate that the student network trained by our MFKD can learn from the fusion features, leading to superior performance. The results show that MFKD can improve the Top-1 accuracy of ResNet20 and VGG8 by 1.82% and 3.35% respectively on the CIFAR-100 dataset, which is better than state-of-the-art many existing methods.

A preliminary study on the inorganic carbon sink function of mineral weathering during sediment transport in the Yangtze River mainstream.

This study proposed that the dissolution of calcium and magnesium minerals in river sediment could sequester CO2 and function as a carbon sink. Based on the published study, "the contents and chemical and mineral compositions of the suspended particulate materials in the Yangtze River and their geological environmental implications" by Ding Tiping, the contents of CaO, MgO, calcite and dolomite in suspended sediment collected from 25 sampling points in the mainstream and 13 sampling points in the tributaries of the Yangtze River in 4 sampling campaigns during 2003-2007 were used to calculate the total inorganic carbon sink (TCS) capacity and nonsubstantial and substantial inorganic carbon sink (NSCS and SCS) capacities of suspended sediment along the river. Due to the reduction in the sediment yield, the TCS, NSCS and SCS of the Cuntan-Datong section during 2006-2019 decreased by 18.52 × 106 tons, 12.24 × 106 tons and 8.72 × 106 tons, respectively, compared to the period before 2002. The average annual sedimentation of the Three Gorges Reservoir (TGR) was 114.5 × 106 tons, and the related TCS and SCS losses were 6.76 × 106 tons and 2.29 × 106 tons, respectively, which were equivalent to 7.9 and 2.7 percent of the 85.8 × 106 tons of CO2 emissions reduced by the clean energy production of the Three Gorges Hydropower Station. The TCS of global rivers was estimated as 757 × 106 tons (the SCS was more than one quarter of the TCS), which is equivalent to 71.6% of the TCS by global rock weathering with 1.06 × 109 tons of sequestered CO2. The collision and erosion of river sediment caused by turbulence in the processes of sediment transport (off-site rock weathering) could promote the dissolution of minerals. Therefore, it is reasonable that the dissolution rate of calcium and magnesium minerals for offsite rock weathering was much higher than that for in situ rock weathering.

Iridium-catalyzed asymmetric allylation of sodium triisopropylsilanethiolate: a new way to form chiral thiols.

The iridium phosphoramidite complex-promoted regio- and enantioselective reaction of allylic carbonates with sodium triisopropylsilanethiolate produced allylic sulfides in 40-77% yields with up to 97 : 3 (branched : linear) and 89% ee, which were readily transformed into chiral thiol in 68% yield with 87% ee or disulfides with two chiral C-S bond centers in 40-73% yields with up to 90 : 10 dr and 99% ee.

Soil type affects not only magnitude but also thermal sensitivity of N2O emissions in subtropical mountain area.

It is a concern whether the effect of soil type on N2O emissions has to be considered for regional mitigation strategies and emission estimates in mountainous areas with inherent spatial heterogeneities of soil type. To date, there were few field experiments which investigated soil type effects on N2O emissions. Thus a 2-year field study was conducted to measure N2O emissions and soil environmental variables from three different soils that were formed from similar parental rock under the same climate. Seasonal N2O fluxes ranged from 0.18 to 0.40 kg N ha-1 for wheat seasons and 0.40 to 1.50 kg N ha-1 for maize seasons across different experimental soils. The intra- and inter-annual variations in N2O emissions were mainly triggered by temporal dynamics of soil temperature and moisture conditions. On average, seasonal N2O fluxes for acidic soils were significantly lower than for neutral and alkaline soils in cold-dry wheat seasons while significantly greater than for neutral and alkaline soils in warm-wet maize seasons. These determined differences of N2O emissions were mainly caused by differences of initial soil properties across different soils. Moreover, seasonal N2O fluxes were positively correlated with soil pH in wheat seasons, but negatively correlated in maize seasons. The temperature sensitivity coefficient (Q10) of soil N2O emissions for acidic soil (4.06) were significantly greater than those for neutral (1.82) and alkaline (1.15) soils. Overall, N2O emissions for acidic soils were not only higher than those for neutral and alkaline soils but also more sensitive to changing temperature. The present study highlights that soil type is needed to be carefully considered for regional estimate and proposing mitigation strategy of N2O emissions especially in subtropical mountain regions with inherent great heterogeneity of soil type.

Bioavailable phosphorus transport from a hillslope cropland of purple soil under natural and simulated rainfall.

To further understand the mechanism of bioavailable total P (BAP) and bioavailable dissolved P (BDP) transport by overland and subsurface flow, we exposed a runoff plot 4.5 m long × 1.5 m wide × 0.6 m deep to simulated and natural rainfall in order to study the effects of rainfall type, rainfall intensity, and vegetation cover on BAP and BDP transport. The results showed that vegetation cover could alleviate the discharge of overland flow and sediment transport and enhance subsurface flow. BAP transport significantly increased with elevated rainfall intensity. Vegetation cover reduced the BAP transport by overland flow and increased it by subsurface flow. BDP transport showed no significant relationship with vegetation cover and rainfall type. The bioavailable particulate P (BPP) transport by overland flow contributed to no less than 90% by weight of total BAP, and the BPP transport by subsurface flow contributed to no less than 60% by weight of total BAP. Short-time heavy rainfall caused more BAP transport and accelerated non-point source pollution.

Epidemiological and Genomic Analysis of SARS-CoV-2 in 10 Patients From a Mid-Sized City Outside of Hubei, China in the Early Phase of the COVID-19 Outbreak.

A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from 10 patients in Shaoxing (Zhejiang Province), a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with >99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values <28. We found that a cluster of four patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium, and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of two family members living together without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs. average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 and offers a glimpse into the early phase of this viral infection outside of Hubei, China.

Cobalt Nanoparticles Chemically Bonded to Porous Carbon Nanosheets: A Stable High-Capacity Anode for Fast-Charging Lithium-Ion Batteries.

A two-dimensional electrode architecture of ∼25 nm sized Co nanoparticles chemically bonded to ∼100 nm thick amorphous porous carbon nanosheets (Co@PCNS) through interfacial Co-C bonds is reported for the first time. This unique 2D hybrid architecture incorporating multiple Li-ion storage mechanisms exhibited outstanding specific capacity, rate performance, and cycling stabilities compared to nanostructured Co3O4 electrodes and Co-based composites reported earlier. A high discharge capacity of 900 mAh/g is achieved at a charge-discharge rate of 0.1C (50 mA/g). Even at high rates of 8C (4 A/g) and 16C (8 A/g), Co@PCNS demonstrated specific capacities of 620 and 510 mAh/g, respectively. Integrity of interfacial Co-C bonds, Co nanoparticles, and 90% of the initial capacity are preserved after 1000 charge-discharge cycles. Implementation of Co nanoparticles instead of Co3O4 restricted Li2O formation during the charge-discharge process. In situ formed Co-C bonds during the pyrolysis steps improve interfacial charge transfer, and eliminate particle agglomeration, identified as the key factors responsible for the exceptional electrochemical performance of Co@PCNS. Moreover, the nanoporous microstructure and 2D morphology of carbon nanosheets facilitate superior contact with the electrolyte solution and improved strain relaxation. This study summarizes design principles for fabricating high-performance transition-metal-based Li-ion battery hybrid anodes.

A process-oriented hydro-biogeochemical model enabling simulation of gaseous carbon and nitrogen emissions and hydrologic nitrogen losses from a subtropical catchment.

Quantification of nitrogen losses and net greenhouse gas (GHG) emissions from catchments is essential for evaluating the sustainability of ecosystems. However, the hydrologic processes without lateral flows hinder the application of biogeochemical models to this challenging task. To solve this issue, we developed a coupled hydrological and biogeochemical model, Catchment Nutrients Management Model - DeNitrification-DeComposition Model (CNMM-DNDC), to include both vertical and lateral mass flows. By incorporating the core biogeochemical processes (including decomposition, nitrification, denitrification and fermentation) of the DNDC into the spatially distributed hydrologic framework of the CNMM, the simulation of lateral water flows and their influences on nitrogen transportation can be realized. The CNMM-DNDC was then calibrated and validated in a small subtropical catchment belonged to Yanting station with comprehensive field observations. Except for the calibration of water flows (surface runoff and leaching water) in 2005, stream discharges of water and nitrate in 2007, the model validations of soil temperature, soil moisture, crop yield, water flows in 2006 and associated nitrate loss, fluxes of methane, ammonia, nitric oxide and nitrous oxide, and stream discharges of water and nitrate in 2008 were statistically in good agreement with the observations. Meanwhile, our initial simulation of the catchment showed scientific predictions. For instance, it revealed the following: (i) dominant ammonia volatilization among the losses of nitrogenous gases (accounting for 11-21% of the applied annual fertilizer nitrogen in croplands); (ii) hotspots of nitrate leaching near the main stream; and (iii) a net GHG sink function of the catchment. These results implicate the model's promising capability of predicting ecosystem productivity, hydrologic nitrogen loads, losses of gaseous nitrogen and emissions of GHGs, which could be used to provide strategies for establishing sustainable catchments. In addition, the model's capability would be further proved by applying in other catchments with different backgrounds.

Regioselective Fluorination of 1-(2,2-Dibromovinyl)benzene Derivatives with Wet Tetra-n-butylammonium Fluoride: One-Pot Synthesis of (Z)-1-(2-Bromo-1-fluorovinyl)benzenes.

A direct fluorination of 1-(2,2-dibromovinyl)benzene derivatives using wet tetra-n-butylammonium fluoride (TBAF·3H2O) as either a base or a fluorine source in toluene was accomplished, which provided (Z)-1-(2-bromo-1-fluorovinyl)benzene compounds in up to 81% yields with high regioselectivities. This reaction results strongly depend upon the reaction conditions. The mechanism of this reaction was investigated as well.

From Allergens to Battery Anodes: Nature-Inspired, Pollen Derived Carbon Architectures for Room- and Elevated-Temperature Li-ion Storage.

The conversion of allergic pollen grains into carbon microstructures was carried out through a facile, one-step, solid-state pyrolysis process in an inert atmosphere. The as-prepared carbonaceous particles were further air activated at 300 °C and then evaluated as lithium ion battery anodes at room (25 °C) and elevated (50 °C) temperatures. The distinct morphologies of bee pollens and cattail pollens are resembled on the final architecture of produced carbons. Scanning Electron Microscopy images shows that activated bee pollen carbon (ABP) is comprised of spiky, brain-like, and tiny spheres; while activated cattail pollen carbon (ACP) resembles deflated spheres. Structural analysis through X-ray diffraction and Raman spectroscopy confirmed their amorphous nature. X-ray photoelectron spectroscopy analysis of ABP and ACP confirmed that both samples contain high levels of oxygen and small amount of nitrogen contents. At C/10 rate, ACP electrode delivered high specific lithium storage reversible capacities (590 mAh/g at 50 °C and 382 mAh/g at 25 °C) and also exhibited excellent high rate capabilities. Through electrochemical impedance spectroscopy studies, improved performance of ACP is attributed to its lower charge transfer resistance than ABP. Current studies demonstrate that morphologically distinct renewable pollens could produce carbon architectures for anode applications in energy storage devices.

[Characteristics of Deposited Sediment and Assessment of Heavy Metals in Typical Tributaries Bay Riparian Zone of the Three Gorges Reservoir].

In order to analyze the spatial variation characteristics of grain diameter, nutrient elements and heavy metal pollution with deposition sediment in tributaries bay of the Three Gorges Reservoir, we selected 9 typical tributaries bay, 54 deposited sediment samples were collected from the riparian zone for analyzing grain diameter distribution, capacity, organic matter, nutrient elements of TN, TP and K, heavy metal elements of Cr, Cu, Ni, Pb, and Zn. The results indicated that particle size distribution from Wujiang River in Fuling to the Modao stream in Yunyang presented a trend of fluctuation, deposited sediment at 160-165 m elevation was coarser than that at 165-175 m elevation,volume percent of sand and clay presented a moderate variation at both altitudes, while silt had small variation. Independent sample t test showed that characteristics difference between the upper and lower sediments in riparian zone was not significant. The geo-accumulation index of heavy metal pollutants in the sediment from riparian zone of the Three Gorges Reservoir tributaries bay indicated that, only Zn element in Zhenxi River, Longdong River and Long River, Pb element in the Modao Stream belonged to non-moderate pollution levels, whereas there were no pollution of all other elements in tributaries.

Tempo-spatial analysis of water quality in tributary bays of the Three Gorges Reservoir region (China).

As a giant newly built man-made canyon-shaped reservoir, the Three Gorges Reservoir (TGR) receives much attention around China and other parts of the world. Bays were deemed to be the most critical zone for water management of TGR; thus, a 3.5-year temporal and spatial investigation was performed to disclose water quality variation in TGR bays and to elucidate the potential affecting factors based on an integrated hydrographical analysis. The results showed that TGR bays had been moderately polluted with averaged nitrogen (N) concentration over 2 mg L(-1) and phosphorus (P) concentration less than 0.1 mg L(-1) in dry season and while high P over 0.2 mg L(-1) and low N of 1.54 mg L(-1) in average in flooding season. The interaction of dam regulation and flooding events influenced the temporal pattern of water quality in the TGR bays, in which particulate nutrients dynamic played an important role. Urban effluents and agricultural catchment area also influenced water quality in the bays, showing local spatial distribution characteristics via diffusion mechanism. Backwater ends might be the most critical areas of water quality degradation. Alleviation measures had been proposed for sustainable development of TGR region.

A highly sensitive and selective fluorescent probe for trivalent aluminum ion based on rhodamine derivative in living cells.

A rhodamine spirolactam derivative (1) is developed as a colormetric and fluorescent probe for trivalent aluminum ions (Al(3+)). It exhibits a highly sensitive "turn-on" fluorescent response toward Al(3+) with a 70-fold fluorescence intensity enhancement under 2 equiv. of Al(3+) added. The probe can be applied to the quantification of Al(3+) with a linear range covering from 5.0 × 10(-7) to 2.0 × 10(-5) M and a detection limit of 4.0 × 10(-8) M. Most importantly, the fluorescence changes of the probe are remarkably specific for Al(3+) in the presence of other metal ions, which meet the selective requirements for practical application. Moreover, the experiment results show that the response behavior of 1 towards Al(3+) is pH independent in neutral condition (pH 6.0-8.0) and the response of the probe is fast (response time less than 3 min). In addition, the proposed probe has been used to detect Al(3+) in water samples and image Al(3+) in living cells with satisfying results.

A ratiometric fluorescent probe with unexpected high selectivity for ATP and its application in cell imaging.

Naphthalimide-rhodamine compound (NR) is developed as a ratiometric fluorescent probe for ATP detection based on the FRET mechanism. It shows an unexpected high selectivity for ATP over other anions, especially organic phosphate anions, due to simultaneous interactions of two recognition sites, which benefits fluorescence imaging in living cells.