Characteristics of soil salinity and water-salt transport in the vadose zone of salt-impacted regions with variable permeability.

Soil salinization poses a significant ecological challenge, emerging as a critical constraint to agricultural development in the arid and semi-arid regions of China, especially in southern Xinjiang. In particular, Yuepuhu County, situated in Kashgar, faces a distinctive issue. Impermeable thin clay layers within the vadose zone impede year-round leaching of salts, significantly impacting the growth of cotton. Through a combination of indoor testing, experiments, and statistical analyses, this study elucidated the varying permeability of soil layers at different depths and explored the forms and accumulation characteristics of soil salts in Yuepuhu County. It unveiled patterns of water and salt movement in soils with variable permeability layers, identifying key influencing factors. The research also proposed an irrigation regime suitable for cultivating vadose zone soils in the local context. The findings revealed a progression of increasing soil complexity and decreasing burial depth of clay layers from northwest to southeast, aligned with the direction of groundwater flow. With increasing depth, a noticeable reduction in soil saturated hydraulic conductivity was observed, indicating significant variability in permeability. Predominantly chloride-sulfate type saline soils in Yuepuhu County contained potassium (K+) and sodium (Na+) as the main cations in surface soils. Salinity strongly correlated with calcium (Ca2+) and magnesium (Mg2+). Chloride (Cl-), sulfate (SO42-), K+, Na+, and bicarbonate (HCO3-) reflected the degree of soil salinization in Yuepuhu County. The clay interlayers in variable permeability zones significantly impeded water and salt movement in the vadose zone. Moving from west to east, thicker and shallower clay interlayers hindered downward water movement, increasing the difficulty of salt leaching. Additionally, the irrigation regime influenced water and salt movement in the vadose zone. Under the same soil structure, flood irrigation with a higher water flux resulted in more significant salt leaching, and lower total dissolved solids (TDS) in irrigation water were more favorable for effective salt leaching. Collectively, our findings provided a theoretical foundation for improving and managing local saline soils, as well as guiding the implementation of rational agricultural irrigation practices.

Functional characterization of RFC and PCFT for antifolates accumulation in non-small cell lung cancer cells.

Antifolates are important for chemotherapy in non-small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH. In this study, we found RFC showed a slightly pH-dependent uptake of antifolates, with similar affinity values at pH 7.4 and 6.5. PCFT showed a highly pH-dependent uptake of antifolates with an optimum pH of 6.0 for pemetrexed and 5.5 for methotrexate. The Km value of PCFT for pemetrexed at pH 7.4 was more than 10 times higher than that at pH 6.5. Interestingly, we found antifolate accumulations mediated by PCFT at acidic pH were significantly affected by the efflux transporter, breast cancer resistance protein (BCRP). The highest pemetrexed concentration was observed at pH 7.0 - 7.4 after a 60-minute accumulation in PCFT-expressing cells, which was further evidenced by the cytotoxicity of pemetrexed, with the IC50 value of pemetrexed at pH 7.4 being one-third of that at pH 6.5. In addition, the in vivo study indicated increasing PCFT and RFC expression significantly enhanced the antitumor efficacy of pemetrexed despite the high expression of BCRP. These results suggest that both RFC and PCFT are important for antifolates accumulation in NSCLC, although there is an acidic microenvironment and high BCRP expression in tumors. Significance Statement Evaluating the role of RFC and PCFT on antifolates accumulation in NSCLC is necessary for new drug designs. By using RFC- or PCFT-expressing NSCLC cell models, we found that both RFC and PCFT were important for antifolates accumulation in NSCLC, rather than only PCFT playing a dominant role. BCRP significantly affected PCFT-mediated antifolates accumulation at acidic pH, but not RFC-mediated pemetrexed accumulation at physiological pH. High expression of PCFT or RFC enhanced the cytotoxicity and antitumor effect of pemetrexed.

A microfluidic-based chemiluminescence biosensor for sensitive multiplex detection of exosomal microRNAs based on hybridization chain reaction.

The analysis of microRNAs (miRNAs) in exosomes is of great importance for noninvasive early disease diagnosis. However, current techniques to detect exosomal miRNAs is hampered either by laborious exosome isolation or low abundance of miRNAs in exosomes. Here, we developed a microfluidic chemiluminescence (CL) analysis method for the multiplexed detection of exosomal miR-21 and miR-155. The microfluidic device contained three parts: a snake-shaped channel for fully mixing chemiluminescent reagents, a ship-shaped channel modified with CD63 protein aptamer for capturing exosomes, and another two parallel ship-shaped channels for hybridization chain reaction (HCR) amplification and CL detection. The multiple signal amplification was realized by Y-shaped arrays, HCR amplification, and poly-HRP catalyzed CL reaction. Using this multiple signal amplification method, our microfluidic CL biosensor achieves a limit of detection of miRNAs of 0.49 fM, with a linear range of 1 fM-10 pM, which is better or comparable to previously reported biosensors. What's more, the proposed microfluidic biosensor exhibits great specificity and selectivity to the target miRNA. Moreover, the microfluidic CL strategy exhibited excellent accuracy and could significantly distinguish different cancer subtypes as well as cancer patients and healthy people. These results suggest that this simple, high sensitive, and more accurate analytical strategy by analyzing different types of exosomal miRNAs has the potential applications in cancer diagnosis and stage monitoring.

Hepatitis B virus infection, infertility, and assisted reproduction. / ä¹™è‚ã€ä¸å­•ä¸è‚²ä¸Žè¾ åŠ©ç”Ÿæ®–.

BACKGROUND: Hepatitis B virus (HBV) is one of the most widespread viruses worldwide and a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma. Previous studies have revealed the impacts of HBV infection on fertility. An increasing number of infertile couples with chronic hepatitis B (CHB) virus infection choose assisted reproductive technology (ART) to meet their fertility needs. Despite the high prevalence of HBV, the effects of HBV infection on assisted reproduction treatment remain limited and contradictory. OBJECTIVE: The aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes, vertical transmission, pregnancy complications, and viral activity during ART treatment. METHODS: We conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to 2022. RESULTS: HBV infection negatively affected fertility in both males and females. Existing research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction treatment. The impact of HBV infection on the pregnancy outcomes of ART is still controversial. Current evidence does not support that ART increases the risk of vertical transmission of HBV, while relevant studies are limited. With the development of ART, the risk of HBV reactivation (HBVr) is increasing, especially due to the wide application of immunosuppressive therapy. CONCLUSIONS: Regular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during ART. The determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.

Sonoinduced Tumor Therapy and Metastasis Inhibition by a Ruthenium Complex with Dual Action: Superoxide Anion Sensitization and Ligand Fracture.

Photoresponsive ruthenium(II) complexes have recently emerged as a promising tool for synergistic photodynamic therapy and chemotherapy in oncology, as well as for antimicrobial applications. However, the limited penetration power of photons prevents the treatment of deep-seated lesions. In this study, we introduce a sonoresponsive ruthenium complex capable of generating superoxide anion (O2•-) via type I process and initiating a ligand fracture process upon ultrasound triggering. Attaching hydroxyflavone (HF) as an "electron reservoir" to the octahedral-polypyridyl-ruthenium complex resulted in decreased highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gaps and triplet-state metal to ligand charge transfer (3MLCT) state energy (0.89 eV). This modification enhanced the generation of O2•- under therapeutic ultrasound irradiation at a frequency of 1 MHz. The produced O2•- rapidly induced an intramolecular cascade reaction and HF ligand fracture. As a proof-of-concept, we engineered the Ru complex into a metallopolymer platform (PolyRuHF), which could be activated by low-power ultrasound (1.5 W cm-2, 1.0 MHz, 50% duty cycle) within a centimeter range of tissue. This activation led to O2•- generation and the release of cytotoxic ruthenium complexes. Consequently, PolyRuHF induced cellular apoptosis and ferroptosis by causing mitochondrial dysfunction and excessive toxic lipid peroxidation. Furthermore, PolyRuHF effectively inhibited subcutaneous and orthotopic breast tumors and prevented lung metastasis by downregulating metastasis-related proteins in mice. This study introduces the first sonoresponsive ruthenium complex for sonodynamic therapy/sonoactivated chemotherapy, offering new avenues for deep tumor treatment.

Spatial-frequency parallel subsampling for distributed compressive sensing in ultrasonic imaging inspection.

To address the problem of the high hardware requirements and insufficient data storage capacity in current ultrasonic imaging testing, a novel approach is developed using a programmable device, which combines spatial-frequency parallel subsampling with the distributed compressive sensing simultaneous orthogonal matching pursuit (DCS-SOMP) algorithm to achieve fast and high-quality ultrasonic imaging inspection with a small amount of subsampled data. The spatial sparse measurement method was employed to achieve spatial subsampling and minimize the count of signals. Additionally, frequency subsampling was utilized to significantly reduce the data volume of time-domain signals while ensuring signal quality by truncating the primary testing frequency components. The subsampled data was then reconstructed using distributed compressive sensing (DCS) for multi-channel data reconstruction. The experiment of ultrasonic scanning imaging was conducted on a carbon steel specimen containing six transverse through-holes with a diameter of Ф1.5 mm at different depths. The ultrasonic signals were acquired using the spatial-frequency parallel subsampling method, and subsequently reconstructed using the DCS-SOMP algorithm. The results show that the proposed method achieves comparable image quality to that obtained with complete data, using only 1/8 of the complete data, while accurately locating and quantifying defects.

An artificial metabzyme for tumour-cell-specific metabolic therapy.

Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO4 nanocatalyst, dubbed 'artificial metabzyme'. It showcases dual active centres, namely, Fe2+ and tetrahedral Mo4+, that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO4 metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy.

Effects of an essential oil blend rich in cinnamaldehyde and carvacrol on rumen biohydrogenation and fatty acid profile in the longissimus lumborum of growing lambs.

BACKGROUND: Essential oils extracted from cinnamon bark and oregano are rich in cinnamaldehyde and carvacrol and show potential for promoting animal performance. However, their impact on rumen biohydrogenation and the fatty acid composition of meat has not been reported. The hypothesis of this study was that a blend of essential oils rich in cinnamaldehyde and carvacrol would inhibit rumen biohydrogenation and promote the accumulation of polyunsaturated fatty acids (PUFAs) in lamb meat. The present study evaluated the effect of a blend essential oil (EO) rich in cinnamaldehyde and carvacrol on the nutrient digestibility, rumen biohydrogenation, growth performance, and fatty acid profile of the longissimus lumborum of lambs. RESULTS: Sixty male lambs with an average age of 84 ± 0.98 days and initial body mass of 25.4 ± 0.29 kg (mean ± standard deviation) were assigned randomly to four diets, and supplemented with 0 (EO0), 30 (EO30), 60 (EO60), and 120 (EO120) mg kg-1 dry matter of EO for 60 days. Although dry matter and neutral detergent fiber digestibility all showed a linear decrease (P ≤ 0.02) with increasing quantities of EO, final body mass and average daily gain increased linearly (P = 0.04), and average daily weight gain (ADG)/dry matter intake (DMI) tended to increase linearly (P = 0.07). Increasing EO supplementation resulted in a linear decrease in total volatile fatty acid concentration, acetate molar percentage, and acetate-to-propionate ratio (P ≤ 0.03), with the EO120 treatment being lower than the other EO treatments (P ≤ 0.05). Seven lambs from the EO120 treatment and seven lambs from the EO0 treatment were randomly slaughtered. It was observed that the proportions of C18:2n6c and PUFA in longissimus lumborum were higher in the EO120 treatment than the EO0 treatment (P ≤ 0.05). The relative abundance of Firmicutes in the rumen was decreased by the EO120 treatment in comparison with the EO0 treatment (P ≤ 0.05). Furthermore, the predicted relative abundances of genes encoding for conjugated linoleic acid reductase tended to decrease with the EO120 treatment (P = 0.06). CONCLUSIONS: We demonstrated that supplementation of the EO blend rich in cinnamaldehyde and carvacrol can enhance lamb growth performance and promote the deposition of desirable PUFAs in meat. © 2024 Society of Chemical Industry.

Rapid species discrimination of similar insects using hyperspectral imaging and lightweight edge artificial intelligence.

Species discrimination of insects is an important aspect of ecology and biodiversity research. The traditional methods based on human visual experience and biochemical analysis cannot strike a balance between accuracy and timeliness. Morphological identification using computer vision and machine learning is expected to solve this problem, but image features have poor accuracy for very similar species and usually require complicated networks that are unfriendly to portable edge devices. In this work, we propose a fast and accurate species discrimination method of similar insects using hyperspectral features and lightweight machine learning algorithm. Feature regions selection, feature spectra selection and model quantification are used for the optimization of discriminating network. The experimental results of six similar butterfly species in the genus of Graphium show that, compared with morphological recognition with machine vision, our work achieves a higher accuracy of 92.36 ± 3.04% and a shorter inference time of 0.6 ms, with the tiny-size convolutional neural network deployed on a neural network chip. This study provides a rapid and high-accuracy species discrimination method for insects with high appearance similarity and paves the way for field discriminations using intelligent micro-spectrometer based on on-chip microstructure and artificial intelligence chip.

Mitigating Zn Dendrite Growth and Enhancing the Utilization of Zn Electrode in Aqueous Zn-Ion Batteries.

In spite of extensive research and appreciable progress, in aqueous zinc-ion batteries, Zn metal anode is struggling with low Zn utility and poor cycling stability. In this study, a 3D "electrochemical welding" composite electrode is designed by introduction of ZnO/C nanofibers film to copper foils as an anode according to pre-electrodeposition active Zn (Zn@ZnO/C-Cu). The flow of Zn2+ through carbon fiber layer is regulated by zincophilic ZnO, promoting homogeneous diffusion of Zn2+ to Cu foil. In subsequent Zn deposition/stripping processes, the hydrophobicity of ZnO/C fiber layer reduces water at the interface of Zn@ZnO/C-Cu and results in uniform electric field significant suppressing growth of Zn dendritic and side reactions. Thus, pre-electrodeposition active Zn electrochemical welds ZnO/C nanofibers and Cu foil collectively provide stable charge/electron transfer and stripping/plating of Zn with low polarization and excellent cycling performance. The assembled symmetrical batteries exhibit stable cycling performance for over 470 h under 20% utilization of Zn at 5 mA cm-2, and an average coulombic efficiency of 99.9% at low negative/positive capacity ratio (N/P = 1) after 1000 cycles in the Zn@ZnO/C-Cu||Na2V6O16·1.5H2O full cell.

Optimizing gelation properties of mixed meat myofibrillar proteins: investigating the effects of different proportions of beef, pork and chicken on physicochemical, structural and gelation properties.

BACKGROUND: The gelation properties of myofibrillar protein (MP) directly affect the texture, taste and water-holding capacity (WHC) of meat products. To enhance the gelation properties of single-species meat MP, the present study investigated the influence of different proportions of beef, pork and chicken MP on the physicochemical properties, structure and gelation properties of the MP. RESULTS: The results revealed that, when the proportion reached 5:2:3, the particle size decreases, leading to the maximum decomposition and unfolding of MPs, which exposes a greater number of hydrophobic amino acid residues. These changes promote interactions between protein molecules, especially the unfolding of α-helices and the formation of ß-sheets during the heating process, which provides favorable conditions for the formation of protein gels and improves the gel strength and WHC of MP gels. Additionally, scanning electron microscopy revealed that the mixed MP gels are more compact and have more uniform gel networks and pores compared to single-species MP gels. CONCLUSION: Based on these results, the synergistic effect is induced by the interactions between proteins from different. This research provides a method for the subsequent development of new meat products and improvement of meat product quality, and also lays a theoretical foundation for composite research of proteins from different sources. © 2024 Society of Chemical Industry.

One-Step Realization of Layered/Spinel Heterostructures and Na Doping by Sodium Dodecyl Sulfate-Assisted Sol-Gel Method for Li-Ion Batteries.

Li-rich layered oxide cathodes have attracted extensive attention due to their high energy density. However, due to the low initial Coulombic efficiency and the capacity fading and voltage fading during cycling, its practical application is still a great challenge. Here, we report the one-step realization of layered/spinel heterostructures and Na doping by the sodium dodecyl sulfate (SDS)-assisted sol-gel method. The spinel phase provides 3D diffusion channels for Li-ions, and sodium doping changes the layered lattice constant and expands the layer spacing. Therefore, the designed Li1.15Mn0.54Ni0.13Co0.13Na0.05O2 (SDS-2) cathode possesses excellent electrochemical performance such as higher initial Coulombic efficiency and rate capacity and also alleviates voltage decay. The initial discharge-specific capacity of SDS-2 is 298.8 mAh g-1 at 0.1 C, and the discharge-specific capacity can reach 111.7 mAh g-1 at 10 C. This strategy can provide new insights into the design and synthesis of high-performance Li-rich layered oxide cathode materials.

Droplet digital molecular beacon-LAMP assay via pico-injection for ultrasensitive detection of pathogens.

A pico-injection-aided digital droplet detection platform is presented that integrates loop-mediated isothermal amplification (LAMP) with molecular beacons (MBs) for the ultrasensitive and quantitative identification of pathogens, leveraging the sequence-specific detection capabilities of MBs. The microfluidic device contained three distinct functional units including droplet generation, pico-injection, and droplet counting. Utilizing a pico-injector, MBs are introduced into each droplet to specifically identify LAMP amplification products, thereby overcoming issues related to temperature incompatibility. Our methodology has been validated through the quantitative detection of Escherichia coli, achieving a detection limit as low as 9 copies/µL in a model plasmid containing the malB gene and 3 CFU/µL in a spiked milk sample. The total analysis time was less than 1.5 h. The sensitivity and robustness of this platform further demonstrated the potential for rapid pathogen detection and diagnosis, particularly when integrated with cutting-edge microfluidic technologies.

Ginseng extract improves pancreatic islet injury and promotes ß-cell regeneration in T2DM mice.

Introduction: Panax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting ß-cell regeneration. Methods: The T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet ß-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind ß-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses. Results and Discussion: The present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1ß decreased. Ginseng extract preserved normal islet morphology, increased nascent ß-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing ß-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to ß-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance ß-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

Ferroptosis-inducing photosensitizers alleviate hypoxia tumor microenvironment for enhanced fluorescence imaging-guided photodynamic therapy.

This study describes H2O2-activated photosensitizer nanoparticles (ICyHD NPs), which inhibit histone deacetylase via binding Zn2+ to induce ferroptosis and upregulate the intracellular O2, thus resulting in enhanced photodynamic therapeutic effect. ICyHD NPs exert strong antitumor effects on mice and have improved the therapeutic precision via observing the increase in cellular fluorescence.

Comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers.

In recent years, attention has been directed towards cost-effective and compact freeform Schwarzschild imaging spectrometers with plane gratings. The utilization of tolerance analysis serves as a potent approach to facilitate the development of prototypes. Conventional tolerance analysis methods often rely solely on the modulation transfer function (MTF) criterion. However, for a spectrometer system, factors such as the keystone/smile distortion and spectral resolution performance also require consideration. In this study, a tailored comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers was developed, considering vital aspects such as the MTF, keystone/smile distortion, and spectral resolution. Through this approach, meticulous tolerance analysis was conducted for a freeform Schwarzschild imaging spectrometer, providing valuable insights for the prototype machining and assembly processes. Emphasis was placed on the necessity of precise control over the tilt and decenter between the first and third mirrors, whereas the other fabrication and assembly tolerances adhered to the standard requirements. Finally, an alignment computer-generated hologram (CGH) was employed for the preassembly of the first and third mirrors, enabling successful prototype development. The congruence observed between the measured results and tolerance analysis outcomes demonstrates the effectiveness of the proposed method.

FFT-Based Probability Density Imaging of Euler Solutions.

When using traditional Euler deconvolution optimization strategies, it is difficult to distinguish between anomalies and their corresponding Euler tails (those solutions are often distributed outside the anomaly source, forming "tail"-shaped spurious solutions, i.e., misplaced Euler solutions, which must be removed or marked) with only the structural index. The nonparametric estimation method based on the normalized B-spline probability density (BSS) is used to separate the Euler solution clusters and mark different anomaly sources according to the similarity and density characteristics of the Euler solutions. For display purposes, the BSS needs to map the samples onto the estimation grid at the points where density will be estimated in order to obtain the probability density distribution. However, if the size of the samples or the estimation grid is too large, this process can lead to high levels of memory consumption and excessive computation times. To address this issue, a fast linear binning approximation algorithm is introduced in the BSS to speed up the computation process and save time. Subsequently, the sample data are quickly projected onto the estimation grid to facilitate the discrete convolution between the grid and the density function using a fast Fourier transform. A method involving multivariate B-spline probability density estimation based on the FFT (BSSFFT), in conjunction with fast linear binning appropriation, is proposed in this paper. The results of two random normal distributions show the correctness of the BSS and BSSFFT algorithms, which is verified via a comparison with the true probability density function (pdf) and Gaussian kernel smoothing estimation algorithms. Then, the Euler solutions of the two synthetic models are analyzed using the BSS and BSSFFT algorithms. The results are consistent with their theoretical values, which verify their correctness regarding Euler solutions. Finally, the BSSFFT is applied to Bishop 5X data, and the numerical results show that the comprehensive analysis of the 3D probability density distributions using the BSSFFT algorithm, derived from the Euler solution subset of x0,y0,z0, can effectively separate and locate adjacent anomaly sources, demonstrating strong adaptability.

Evaluation of transport mechanisms of methotrexate in human choriocarcinoma cell lines by LC-MS/MS.

Methotrexate (MTX) is commonly prescribed as the initial treatment for gestational trophoblastic neoplasia (GTN), but MTX monotherapy may not be effective for high-risk GTN and choriocarcinoma. The cellular uptake of MTX is essential for its pharmacological activity. Thus, our study aimed to investigate the cellular pharmacokinetics and transport mechanisms of MTX in choriocarcinoma cells. For the quantification of MTX concentrations in cellular matrix, a liquid chromatography-tandem mass spectrometry method was created and confirmed initially. MTX accumulation in BeWo, JEG-3, and JAR cells was minimal. Additionally, the mRNA levels of folate receptor α (FRα) and breast cancer resistance protein (BCRP) were relatively high in the three choriocarcinoma cell lines, whereas proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and organic anion transporter (OAT) 4 were low. Furthermore, the expression of other transporters was either very low or undetectable. Notably, the application of inhibitors and small interfering RNAs (siRNAs) targeting FRα, RFC, and PCFT led to a notable decrease in the accumulation of MTX in BeWo cells. Conversely, the co-administration of multidrug resistance protein 1 (MDR1) and BCRP inhibitors increased MTX accumulation. In addition, inhibitors of OATs and organic-anion transporting polypeptides (OATPs) reduced MTX accumulation, while peptide transporter inhibitors had no effect. Results from siRNA knockdown experiments and transporter overexpression cell models indicated that MTX was not a substrate of nucleoside transporters. In conclusion, the results indicate that FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of MTX, whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells. These results have implications for predicting transporter-mediated drug interactions and offer potential directions for further research on enhancing MTX sensitivity.

Non-chest pain symptoms and likelihood of coronary occlusion in emergency department patients with ST segment elevation undergoing emergent coronary angiography.

OBJECTIVES: Patients presenting with suspected ST segment elevation myocardial infarction frequently have symptoms in addition to chest pain, including dyspnea, nausea or vomiting, diaphoresis, and lightheadedness or syncope. These symptoms are often regarded as supporting the diagnosis of infarction. We sought to determine the prevalence of the non-chest pain symptoms among patients who were confirmed as having a critically diseased coronary vessel as opposed to those with no angiographic culprit lesion. METHODS: Data from 1393 consecutive patients with ST segment elevation who underwent emergent coronary angiography were analyzed. Records were reviewed in detail for symptoms, ECG findings, prior history, angiographic findings, and in-hospital outcomes. RESULTS: Dyspnea was present in 50.8% of patients, nausea or vomiting in 36.5%, diaphoresis in 51.2%, and lightheadedness/syncope in 16.8%. On angiography, 1239 (88.9%) patients had a culprit lesion and 154 (11.1%) were found not to have a culprit. Only diaphoresis had a higher prevalence among the patients with, as compared with those without a culprit, with an odds ratio of 2.64 ( P  < 0.001). The highest occurrence of diaphoresis was among patients with a totally occluded artery, with an intermediate frequency among patients with a subtotal stenosis, and the lowest prevalence among those with no culprit. These findings were consistent regardless of ECG infarct location, affected vessel, patient age, or sex. Among the subset of patients who presented without chest discomfort, none of the symptoms were associated with the presence of a culprit. CONCLUSION: The presence of diaphoresis, but not dyspnea, nausea, or lightheadedness is associated with an increased likelihood that patients presenting with ST elevation will prove to have a culprit lesion. In patients who present with ST elevation but without chest discomfort, these symptoms should not be regarded as 'chest pain equivalents'. Further objective data among patients with angiographic confirmation of culprit lesion status is warranted.