miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database.

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

Combining Proximity Labeling and Cross-Linking Mass Spectrometry for Proteomic Dissection of Nuclear Envelope Interactome.

Proximity labeling (PL) and chemical cross-linking (XL) mass spectrometry are two powerful methods to dissect protein-protein interactions (PPIs) in cells. Although PL typically captures neighboring proteins within a range of 10-20 nm of a single bait protein, chemical XL defines direct protein-protein contacts within 1 nm in a systemic manner. Here, we develop a new method, named PL/XL-MS, to harness the advantages of both PL and XL. PL/XL-MS can enrich a subcellular compartment by PL and simultaneously identify PPIs of multiple proteins from XL data. We applied PL/XL-MS to dissect the human nuclear envelope interactome. PL/XL-MS successfully enriched the nuclear envelope proteins and identified most known inner nuclear membrane proteins. By searching the cross-linked peptides, we successfully observed 109 literature-curated PPIs of 14 nuclear envelope proteins. Based on the homoprotein XL data, we experimentally characterized a nuclear matrix protein, Matrin-3, and observed its preferential localization near the nuclear envelope. PL/XL-MS is a simple and general method for studying protein networks in a subproteome of interest.

Effect of Implementing Electronic Toll Collection in Reducing Highway Particulate Matter Pollution.

Highway vehicle emissions can result in adverse health problems to nearby residents and workers, especially during traffic congestion. In response, the policy to implement electronic toll collection (ETC) has helped alleviate traffic congestion, as compared to manual toll collection (MTC) and has led to reduced air pollution and improved public health. However, the effect of ETC in reducing particulate matter polluting the air is not well understood, especially in the ultrafine particle (UFP) range (particle diameter <100 nm). To the best of our knowledge, this is the first study to investigate how ETC affects the traffic pattern and air quality, especially UFP and PM2.5. We selected a site in Tainan, Taiwan, and measured UFP and PM2.5 concentrations before and after the construction of the ETC system. The computed traffic volumes during peak travel periods (7:00 AM to 9:00 AM and 4:00 PM to 6:00 PM) respectively, accounted for approximately 23-25% and 14-18% before and after the implementation of ETC, indicating that peak traffic volumes were more homogeneous after ETC. Moreover, the results indicate that the full implementation of ETC can help reduce UFP number concentrations and PM2.5 mass concentrations in the highway downwind area by 4 × 103 #/cm3 and 20.5 µg/m3, respectively. After the full implementation of the ETC, significant reductions in both the UFP number concentration and PM2.5 mass concentration were seen. Furthermore, excessive lifetime cancer risks (ELCR) from exposure to PM2.5 and UFP together were reduced 49.3% after the implementation of the ETC. Accordingly, ETC not only helps alleviate traffic congestion but also reduces traffic emissions and lifetime cancer risk for people living or working near highways.

The evaluation of BTEX and carbonyls emissions from recycled building materials.

Environmental friendly building materials (BMs) get more attention due to their potential to reduce carbon and air pollutant emissions. However, recycled building materials (RBMs) have no required standard of volatile organic compounds (VOCs) emissions. This study was mainly about the assessment of benzene, toluene, ethylbenzene, and xylene (BTEX), as well as carbonyls emissions from recycled building materials, including gypsum board (GB), calcium silicate board (CSB), fiber cement board (FCB), class I built wall tile (WT), and waterproof gypsum board (WGB). The highest initial and final levels of BTEX were observed on CSB, followed by GB and FCB, and no detectable BTEX were observed on WT and WGB. Benzene was with the highest level among all identified BTEX. Emissions of carbonyls were observed on all materials. The highest initial and final levels of carbonyls were observed on GB, followed by FCB and CSB, while the lowest ones were detected on WT and WGB. The final (96-h) steady-state emissions of BTEX from GB and CSB were 9 and 37 times those from conventional pairs and 27 and 41 times those from low-VOC pairs. Similarly, the final steady-state emissions of carbonyls from GB and CSB were 4.8 and 1.3 times those from conventional pairs and 16 and 2.5 times those from low-VOC pairs. The requirement of evaluation standard for VOC emissions from RBMs is highly recommended to protect consumers. Graphical abstract.

Dynamics of a Persistent Insulator-to-Metal Transition in Strained Manganite Films.

Transition metal oxides possess complex free-energy surfaces with competing degrees of freedom. Photoexcitation allows shaping of such rich energy landscapes. In epitaxially strained La_{0.67}Ca_{0.33}MnO_{3}, optical excitation with a sub-100-fs pulse above 2 mJ/cm^{2} leads to a persistent metallic phase below 100 K. Using single-shot optical and terahertz spectroscopy, we show that this phase transition is a multistep process. We conclude that the phase transition is driven by partial charge-order melting, followed by growth of the persistent metallic phase on longer timescales. A time-dependent Ginzburg-Landau model can describe the fast dynamics of the reflectivity, followed by longer timescale in-growth of the metallic phase.

Nonlinear photoacoustic microscopy via a loss modulation technique: from detection to imaging.

In order to achieve high-resolution deep-tissue imaging, multi-photon fluorescence microscopy and photoacoustic tomography had been proposed in the past two decades. However, combining the advantages of these two imaging systems to achieve optical-spatial resolution with an ultrasonic-penetration depth is still a field with challenges. In this paper, we investigate the detection of the two-photon photoacoustic ultrasound, and first demonstrate background-free two-photon photoacoustic imaging in a phantom sample. To generate the background-free two-photon photoacoustic signals, we used a high-repetition rate femtosecond laser to induce narrowband excitation. Combining a loss modulation technique, we successfully created a beating on the light intensity, which not only provides pure sinusoidal modulation, but also ensures the spectrum sensitivity and frequency selectivity. By using the lock-in detection, the power dependency experiment validates our methodology to frequency-select the source of the nonlinearity. This ensures our capability of measuring the background-free two-photon photoacoustic waves by detecting the 2nd order beating signal directly. Furthermore, by mixing the nanoparticles and fluorescence dyes as contrast agents, the two-photon photoacoustic signal was found to be enhanced and detected. In the end, we demonstrate subsurface two-photon photoacoustic bio-imaging based on the optical scanning mechanism inside phantom samples.

Insight into the diurnal variations and potential sources of ambient PM2.5-bound polycyclic aromatic hydrocarbons during spring in Northern Taiwan.

In recent decades, polycyclic aromatic hydrocarbons (PAHs), the primary organic pollutants associated with particulate matter (PM), have attracted significant attention due to their carcinogenic and mutagenic potential. However, past studies have lacked exploration into the diurnal variation characteristics of PAHs, primarily due to limited analytical technical capabilities. This study utilized a thermal-desorption device coupled with gas chromatography/mass spectrometry (TD-GC/MS) to identify the levels of PAHs in PM2.5 during short periods (3-hr) and aimed to investigate the diurnal variations, possible sources, and potential health risks associated with PM2.5-bound PAHs in northern Taiwan. The mean concentration of total PAHs in PM2.5 was 1.22 ± 0.69 ng m-3 during the sampling period, with high molecular weight PAHs dominating. Source apportionment by the positive matrix factorization (PMF) model indicated that industrial emissions and traffic emissions (57.7 %) were the predominant sources of PAHs, with petroleum volatilization and coal/biomass combustion (42.3 %) making a lesser contribution. Diurnal variations of industrial and traffic emissions showed higher concentrations during traffic rush hours, while petroleum volatilization and coal/biomass combustion displayed higher concentrations at noon. Results from the potential source contribution function (PSCF) and the concentration weighted trajectory (CWT) model suggested that industrial emissions and traffic emissions mostly originated from local sources and were concentrated in the vicinity of the sampling site and the coastal area of western Taiwan. Source-attributed excess cancer risk (ECR) showed that industrial and traffic emissions had the highest cancer risks during morning traffic peak hours (1.69 ×10-5), while petroleum volatilization and coal/biomass combustion reached the maximum at noon (4.75 ×10-6). As a result, efforts to reduce PAH emissions from industrial and vehicle exhaust sources, especially during morning traffic hours, can help mitigate their adverse impact on human health.

Applying the total carbon-black carbon approach method to investigate the characteristics of primary and secondary carbonaceous aerosols in ambient PM2.5 in northern Taiwan.

Ambient fine particulate matter (PM2.5) comprises a diverse array of carbonaceous species, and the impact of carbonaceous aerosols (CA) extends to both long-term and short-term effects on human health and the environment. Understanding the distinctive composition of CA is crucial for gaining insights into the origins of airborne particulate matter. Due to their diverse physicochemical properties and intricate heterogeneous reactions, CA often exhibits temporal and spatial variations. Ground-based and highly time-resolved apportionment methods play a vital role in discerning CA emissions. This study utilized high-time resolution data of total carbon (TC) and black carbon (BC) for CA apportionment in northern Taiwan. The advanced numerical model (TC-BC(λ)), coupled with continuous measurement data, facilitated CA allocation based on optical absorption characteristics, organic or elemental carbon composition, and the distinction between primary and secondary origins. Primary carbonaceous aerosols dominated the monitoring site, accounting for 67.5 % compared to the 32.5 % contribution from secondary forms of CA. The summer season exhibited a maximum increase in secondary organic aerosols (SOA) at 41.5 %. Diurnal variations for primary emissions, such as BCc and primary organic aerosols (POA), showed marked peaks for BCff and POAnon-abs during morning rush hours. In contrast, BCbb and POABrC displayed bimodal peaks with increased concentrations during evening hours. Conversely, SOA exhibited significantly different diurnal trends, with SOABrC peaking late at night due to aqueous phased reactions and a noontime peak of SOAnon-abs observed due to photo-oxidation processes. Furthermore, the study employed backward trajectory analysis and concentration-weighted trajectories (CWTs) to examine the long-range transport of CA, identifying potential sources, origins, and transport patterns of CA components to the receptor site in Taiwan during different seasons.

Chemical characteristics and formation mechanism of secondary inorganic aerosols: The decisive role of aerosol acidity and meteorological conditions.

In recent years, there has been a growing concern about air pollution and its impact on the air quality and human health, especially for fine particulate matter (PM2.5) and its associated secondary aerosols in urban areas. This study conducted a year-long field campaign to collect PM2.5 samples day and night in an urban area of central Taiwan. Higher PM2.5 mass concentrations were observed in winter (27.7 ± 9.7 µg/m3), followed by autumn (22.5 ± 8.3 µg/m3), spring (19.2 ± 6.4 µg/m3), and summer (11.0 ± 3.1 µg/m3). The dominant formation mechanism of secondary inorganic aerosols was heterogeneous reactions of NO3- at night and homogeneous reactions of SO42- during the day. Additionally, significant correlations were observed between aerosol liquid water content (ALWC) and NO3- during nighttime, indicating the importance of aqueous-phase NO3- formation. The role of aerosol acidity was explored and a unique alkaline condition was found in spring and summer, which showed lower PM2.5 concentrations than the neutralized condition. Under the neutralized condition, higher PM2.5 concentrations were commonly found when combining the ammonium-rich regime with molar ratios of [NO3-]/[SO42-] exceeding 1.6, suggesting the importance of reducing both NH3 and NOx. Furthermore, the results showed that reducing NH3 should be prioritized under high temperature conditions, while reducing NOx became important under low temperature conditions. Clustering of backward trajectories showed that long-range transport could enhance the formation of secondary aerosols, but local emissions emerged as the main factor driving high PM2.5 concentrations. This study provides insights for policymakers to improve air quality, suggesting that different mitigation strategies should be formulated based on meteorological variables and that using clean energy for vehicles and electricity generation is important to alleviate air pollution.

Virtual spatial overlap modulation microscopy for resolution improvement.

High spatial and temporal resolutions are important advantages of optical imaging over other modalities. The recently developed spatial overlap modulation (SPOM) microscopy enables high resolution imaging by spatial modulation of double-beam overlap. However, SPOM suffers from bad temporal resolution and high system complexity. In this paper, we re-formulate the SPOM resolution theory and develop Virtual SPOM (vSPOM) microscopy. By one-way oversampling and convolution with differential filters, vSPOM not only realizes the same factor of spatial resolution improvement as SPOM, but overcome SPOM's major drawbacks. We demonstrated vSPOM on in vivo clinical images and find that the Gabor filter, which represents two-beam vSPOM, is the most effective among all vSPOM filters. The development of vSPOM enables easy incorporation of SPOM into any imaging system, and extends the use of SPOM to real-time in vivo applications.

Blu-ray disk lens as the objective of a miniaturized two-photon fluorescence microscope.

In this paper, we examine the performance of a Blu-ray disk (BD) aspheric lens as the objective of a miniaturized scanning nonlinear optical microscope. By combining a single 2D micro-electro mechanical system (MEMS) mirror as the scanner and with different tube lens pairs, the field of view (FOV) of the studied microscope varies from 59 µm × 93 µm up to 178 µm × 280 µm, while the corresponding lateral resolution varies from 0.6 µm to 2 µm for two-photon fluorescence (2PF) signals. With a 34/s video frame rate, in vivo dynamic observation of zebrafish heartbeat through 2PF of the excited green fluorescence protein (GFP) is demonstrated.

Characterization of the sources and health risks of polycyclic aromatic hydrocarbons in PM2.5 and their relationship with black carbon: A case study in northern Taiwan.

Polycyclic aromatic hydrocarbons (PAHs) and black carbon (BC) often coexist in PM2.5 because both form during the incomplete combustion of organic matter. These compounds are regarded as hazardous air pollutants with potential health effects, including respiratory and cardiovascular effects. In this study, to evaluate the health risks of PAHs and BC at an urban site in northern Taiwan, 16 priority PAHs and BC, identified by the United States Environmental Protection Agency, were analyzed and quantified in PM2.5 to determine their concentrations, their relationship with each other, and their likely sources. The results indicated that the mean concentrations of total PAHs and BC were 0.91 ng m-3 and 0.97 µg m-3, respectively, with a significant positive correlation between them, indicating the same emission sources. The results also indicated that fossil fuel combustion and traffic emissions were primary contributors to PAHs, with wood and biomass combustion playing a less prominent role. Among these 16 priority PAHs, benzo[a]pyrene, dibenz[a,h]anthracene, benzo[b]fluoranthene, and indeno[1,2,3-cd]pyrene served as major carcinogenic compounds, accounting for 89.0% of the total carcinogenic toxicity. Thus, the lifetime excess cancer risk resulting from PAH exposure was estimated as 8.03 × 10-6, indicating a potential carcinogenic risk to human health at the sampling site. Overall, this study highlights the need for future mitigation policies for traffic emissions and fossil fuel combustion for reducing the local emissions of BC and co-produced PAHs in northern Taiwan.

Spatial distributions of PM10-bound metal elements in the central part of western Taiwan and their potential emission sources and the carcinogenic health risks.

This study aimed to investigate the spatial distribution of metal elements in PM10 and their potential sources and associated health risks over a period of two years in eight locations in the central part of western Taiwan. The study revealed that the mass concentration of PM10 and the total mass concentration of 20 metal elements in PM10 were 39.0 µg m-3 and 4.74 µg m-3, respectively, with total metal elements accounting for approximately 13.0% of PM10. Of the total metal elements, 95.6% were crustal elements (Al, Ca, Fe, K, Mg, and Na), with trace elements (As, Ba, Cd, Cr, Co, Cu, Ga, Mn, Ni, Pb, Sb, Se, V, and Zn) contributing only 4.4%. Spatially, the inland areas exhibited higher PM10 concentrations due to lee-side topography and low wind speeds. In contrast, the coastal regions exhibited higher total metal concentrations because of the dominance of crustal elements from sea salt and crustal soil. Four primary sources of metal elements in PM10 were identified as sea salt (58%), re-suspended dust (32%), vehicle emissions and waste incineration (8%), and industrial emissions and power plants (2%). The positive matrix factorization (PMF) analysis results indicated that natural sources like sea salt and road dust contributed up to 90% of the total metal elements in PM10, while only 10% was attributed to human activities. The excess cancer risks (ECRs) associated with As, Co, and Cr(VI) were greater than 1 × 10-6, and the total ECR was 6.42 × 10-5. Although only 10% of total metal elements in PM10 came from human activities, they contributed to 82% of the total ECR.

Multielectron redox chemistry of a neutral, NIR-active, indigo-pillared Re(I)-based triangular metalloprism.

Self-assembled, hexarhenium(I), triangular metalloprism compound [{(CO)(3)Re(µ-2)Re(CO)(3)}(3)(µ(3)-1)(2)] (3) featuring three bis-chelating pillarlike indigo dianions (µ-2), each of which connects two fac-Re(CO)(3) cores, which are interconnected by a tritopic N donor, that is, a 2,4,6-tris(4-pyridyl)-1,3,5-triazine (µ(3)-1, tPyTz) ligand, has been synthesized in high yield and characterized. Metalloprism 3 exhibits a strong absorption in the near-infrared (NIR) region. The reversible, multielectron redox properties of the electrogenerated 3(n) species, where n=3+, 0, 3-, 4-, 5-, 8-, in the visible and especially in the NIR region were investigated in THF solution by cyclic voltammetry (CV), chronocoulometry, EPR spectroscopy, and thin-layer UV/Vis/NIR spectroelectrochemistry (SEC). Stepwise, site-specific electrochemical reductions lead to the formation of a series of highly stable ion (radical) species in which electrons associated with µ-2 or µ(3)-1 components of the molecule can be clearly distinguished. An EPR investigation revealed interaction of unpaired electrons with the metal nuclei ((185,187)Re, I=5/2) in the reduced intermediates. The framework has C(2) symmetry, and accidental degeneracies suffice. Detailed theoretical calculations by structure-based DFT confirm that the triply degenerate HOMO has ≥70% indigo character with a sizable dπ-Re character, while the LUMO is dominated by the triply degenerate indigo ligands, and the LUMO+1 by doubly degenerate tPyTz ligands. A comparison of 3 and previously reported 2,2'-bis-benzimidazolate- (BiBzlm) or alkoxy-pillared Re(I) metalloprisms indicates a very low switching potential with a potential window of less than 1 V and reversibly accessible optical properties with higher stability of the intermediates. The properties exhibited by 3 appear to be due to the slight tuning of the bridging ligand from N,N(-) to N,O(-).

Proteomic analysis of salt-responsive ubiquitin-related proteins in rice roots.

RATIONALE: Ubiquitination of proteins plays an important role in regulating a myriad of physiological functions in plants such as xylogenesis, senescence, cell cycle control, and stress response. However, only a limited number of proteins in plants have been identified as being ubiquitinated in response to salt stress. The relationships between ubiquitination and salt-stress responses in plants are not clear. METHODS: Rice (Oryza sativa) seedlings from the same genetic background with various salt tolerances exposed to salt stress were studied. The proteins of roots were extracted then analyzed using western blotting against ubiquitin. Differentially expressed ubiquitinated proteins were identified by nanospray liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) and quantified by label-free methods based on the Exponentially Modified Protein Abundance Index (emPAI) and on the peak areas of XIC spectra derived from ubiquitinated peptides. In addition, we performed a gel-based shotgun proteomic analysis to detect the ubiquitinated proteome that may be involved in response to salt stress. RESULTS: The expressions of ubiquitination on pyruvate phosphate dikinase 1, heat shock protein 81-1, probable aldehyde oxidase 3, plasma membrane ATPase, cellulose synthase A catalytic subunit 4 [UDP-forming] and cyclin-C1-1 were identified and compared before and after salt treatment. The functions of those ubiquitinated proteins were further discussed for defence against salt stress. In addition, a large number of ubiquitinated proteins were successfully identified as well in this study. CONCLUSIONS: The ubiquitination of proteins affected the protective mechanisms in rice seedlings to resist the salt stress during the initial phase. The findings in the present study also demonstrate that the regulated mechanisms through protein ubiquitination are important for rice seedlings against salt stress.

The effects of Davallic acid from Davallia divaricata Blume on apoptosis induction in A549 lung cancer cells.

Traditional or folk medicinal herbs continue to be prescribed in the treatment of various diseases and conditions in many cultures. Recent scientific efforts have focused on the potential roles of extracts of traditional herbs as alternative and complementary medications for cancer treatment. In Taiwan, Davallia divaricata Blume has been traditionally employed in folk medicine for therapy of lung cancer, davallic acid being the major active compound of D. divaricata Blume. In this study, we investigated the inhibitory activity of davallic acid on the proliferation of A549 lung cancer cells. Davallic acid was extracted from D. divaricata Blume, and its effects on cell viability, cell cycle distribution, ROS level, and apoptotic protein expression in A549 cells were determined. Davallic acid significantly induced reactive oxygen species (ROS) generation as well as caspase-3, -8, and -9 activation, thereby repressing A549 cell growth and elevating apoptotic activity. Since lung cancer has a high incidence of recurrence, these results indicate that davallic acid may have the potential to be a natural anti-lung cancer compound, and may provide a basis for further study of its use in combating cancer.

A THz Waveguide Bandpass Filter Design Using an Artificial Neural Network.

This paper presents a 300 GHz waveguide bandpass filter based on asymmetric inductive irises. The coupling matrix synthesis technique is used to design a 6-pole Chebyshev filter. In addition, an artificial neural network is applied to provide the filter geometries using the desired frequency response. The optimized filter is fabricated by the computer numeric controlled milling process. The measurement results show that the insertion loss is less than 3 dB and the return loss is better than 17 dB in the range 276-310 GHz.

Snapshots of a light-induced metastable hidden phase driven by the collapse of charge order.

Nonequilibrium hidden states provide a unique window into thermally inaccessible regimes of strong coupling between microscopic degrees of freedom in quantum materials. Understanding the origin of these states allows the exploration of far-from-equilibrium thermodynamics and the development of optoelectronic devices with on-demand photoresponses. However, mapping the ultrafast formation of a long-lived hidden phase remains a longstanding challenge since the initial state is not recovered rapidly. Here, using state-of-the-art single-shot spectroscopy techniques, we present a direct ultrafast visualization of the photoinduced phase transition to both transient and long-lived hidden states in an electronic crystal, 1T-TaS2, and demonstrate a commonality in their microscopic pathways, driven by the collapse of charge order. We present a theory of fluctuation-dominated process that helps explain the nature of the metastable state. Our results shed light on the origin of this elusive state and pave the way for the discovery of other exotic phases of matter.

A computer-assisted model for predicting probability of dying within 7 days of hospice admission in patients with terminal cancer.

OBJECTIVE: The aim of the present study is to compare the accuracy in using laboratory data or clinical factors, or both, in predicting probability of dying within 7 days of hospice admission in terminal cancer patients. METHODS: We conducted a prospective cohort study of 727 patients with terminal cancer. Three models for predicting the probability of dying within 7 days of hospice admission were developed: (i) demographic data and laboratory data (Model 1); (ii) demographic data and clinical symptoms (Model 2); and (iii) combination of demographic data, laboratory data and clinical symptoms (Model 3). We compared the models by using the area under the receiver operator curve using stepwise multiple logistic regression. RESULTS: We estimated the probability dying within 7 days of hospice admission using the logistic function, P = Exp(betax)/[1 + Exp(betax)]. The highest prediction accuracy was observed in Model 3 (82.3%), followed by Model 2 (77.8%) and Model 1 (75.5%). The log[probability of dying within 7 days/(1 - probability of dying within 7 days)] = -6.52 + 0.77 x (male = 1, female = 0) + 0.59 x (cancer, liver = 1, others = 0) + 0.82 x (ECOG score) + 0.59 x (jaundice, yes = 1, no = 0) + 0.54 x (Grade 3 edema = 1, others = 0) + 0.95 x (fever, yes = 1, no = 0) + 0.07 x (respiratory rate, as per minute) + 0.01 x (heart rate, as per minute) - 0.92 x (intervention tube = 1, no = 0) - 0.37 x (mean muscle power). CONCLUSIONS: We proposed a computer-assisted estimated probability formula for predicting dying within 7 days of hospice admission in terminal cancer patients.

SLC38A2 Overexpression Induces a Cancer-like Metabolic Profile and Cooperates with SLC1A5 in Pan-cancer Prognosis.

Cancer cells have dramatically increased demands for energy as well as biosynthetic precursors to fuel their restless growth. Enhanced glutaminolysis is a hallmark of cancer metabolism which fulfills these needs. Two glutamine transporters, SLC1A5 and SLC38A2, have been previously reported to promote glutaminolysis in cancer with controversial perspectives. In this study, we harnessed the proximity labeling reaction to map the protein interactome using mass spectrometry-based proteomics and discovered a potential protein-protein interaction between SLC1A5 and SLC38A2. The SLC1A5/SLC38A2 interaction was further confirmed by bimolecular fluorescence complementation assay. We further investigated the metabolic influence of SLC1A5 and SLC38A2 overexpression in human cells, respectively, and found that only SLC38A2, but not SLC1A5, resulted in a cancer-like metabolic profile, where the intracellular concentrations of essential amino acids and lactate were significantly increased as quantified by nuclear magnetic resonance spectroscopy. Finally, we analyzed the 5-year survival rates in a large pan-cancer cohort and found that the SLC1A5hi /SLC38A2lo group did not relate to a poor survival rate, whereas the SLC1A5lo /SLC38A2hi group significantly aggravated the lethality. Intriguingly, the SLC1A5hi /SLC38A2hi group resulted in an even worse prognosis, suggesting a cooperative effect between SLC1A5 and SCL38A2. Our data suggest that SLC38A2 plays a dominant role in reprogramming the cancer-like metabolism and promoting the cancer progression, whereas SLC1A5 may augment this effect when co-overexpressed with SLC38A2. We propose a model to explain the relationship between SLC1A5, SLC38A2 and SCL7A5, and discuss their impact on glutaminolysis and mTOR signaling.