Innovative Fusion: Natural Compound-Rhein and PROTACs Unleash Potent VEGFR-2 Degraders.

VEGFR-2 is a prominent therapeutic target in antitumor drug research to block tumor angiogenesis. This study focused on the synthesis and optimization of PROTACs based on the natural product rhein, resulting in the successful synthesis of 15 distinct molecules. In A549 cells, D9 exhibited remarkable antitumor efficacy with an IC50 of 5.88 ± 0.50 µM, which was 15-fold higher compared to rhein (IC50=88.45 ± 2.77 µM). An in-depth study of the effect of D9 on the degradation of VEGFR-2 revealed that D9 was able to induce the degradation of VEGFR-2 in A549 cells in a time-dependent manner. The observed effect was reversible, contingent upon the proteasome and ubiquitination system, and demonstrably linked to CRBN. Further experiments revealed that D9 induced apoptosis in A549 cells and led to cell cycle arrest in the G1 phase. Molecular docking simulations validated the binding mode of D9 to VEGFR, establishing the potential of D9 to bind to VEGFR-2 in its natural state. In summary, this study confirms the feasibility of natural product-bound PROTAC technology for the development of a new generation of VEGFR-2 degraders, offering a novel trajectory for the future development of pharmacological agents targeting VEGFR-2.

Effect and Mechanism of Rhein-praseodymium Complex on Intestinal Uric Acid Excretion in Rats with Renal Injury and Hyperuricemia.

BACKGROUND: Hyperuricemia (HUA) is a disease characterized by excessive uric acid production and/or insufficient uric acid excretion caused by abnormal purine metabolism in the human body. Uric acid deposition caused by hyperuricemia can cause complications, such as kidney damage. The current therapeutic drugs for HUA are not very targeted and usually have specific toxic side effects. OBJECTIVES: This study aimed to synthesize a compound using rhein and praseodymium, which can effectively help hyperuricemia patients with kidney injury to excrete uric acid through the intestine and preliminarily explore its intestinal excretion mechanism. METHODS: The natural active ingredient rhein and rare earth metal praseodymium were used to synthesize Rh-Pr. The possible chemical structure of Rh-Pr was deduced by UV, IR, 1H-NMR, conductivity method, and thermogravity analysis. Adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) were administered by gavage for three weeks to establish the hyperuricemia rat model of renal injury. Serum uric acid (UA), creatinine (Cr), urea nitrogen (BUN), and uric acid concentration in urine and feces were detected by biochemical methods. The protein expression levels of GLUT9, ABCG2, and MRP4 in the jejunum, ileum, and colon of rats were detected by Western Blotting. RESULTS: According to the characterization, the chemical composition formula of the complex is Pr(C15H7O6)3·2H2O. In vivo, activity tests showed that Rh-Pr could enhance the intestinal uric acid excretion level of rats, upregulate the expression of ABCG2 protein in the jejunum and ileum, down-regulate the expression of GLUT9 protein in the ileum and colon, and also had a good recovery effect on serum uric acid, creatinine, and urea nitrogen levels. CONCLUSION: Rh-Pr is different from other drugs in that it promotes intestinal uric acid excretion and has a renal recovery effect. It reduces the patient's kidney burden and is significant for hyperuricemia patients with kidney injury.

Application of a Remotely Controlled Artificial Intelligence Analgesic Pump Device in Painless Treatment of Children.

In order to effectively improve the application of analgesic pump devices in the treatment of children, a method based on remote control artificial intelligence is proposed. 100 children with dental pulpitis who were treated in a hospital from December 2018 to December 2020 were selected as the research subjects; they were randomly divided into control group and observation group by an equidistant sampling method, with 50 cases in each group. Children in the control group were given articaine and adrenaline anesthesia, and the observation group was treated with articaine and adrenaline combined with a computer-controlled anesthesia system, the anesthesia pain degree and satisfaction degree of the two groups of children were observed and compared. The results showed that the pain score in anesthesia and intraoperative pain score in the observation group was significantly lower than that in the control group, and the differences were statistically significant (P < 0.05). The total satisfaction of 96.6% patients in the observation group was significantly higher than that in the control group (84.7%) and the difference was statistically significant (P < 0.05). There were no serious complications in both groups. The application of the computer anesthesia system combined with articaine adrenaline in the painless treatment of children's dental pulp proved to have better effects, the treatment compliance is higher, and it is worthy of clinical promotion.

Accumulation, regional distribution, and environmental effects of Sb in the largest Hg-Sb mine area in Qinling Orogen, China.

In this study, knowledge gaps on Sb concentration in rocks, ores, tailings, soil, river water, sediments, and crops of mine areas were identified and discussed in terms of contamination levels, spatial distribution, and environmental effects. Accordingly, Xunyang Hg-Sb mine, the largest Hg-Sb deposit in China as research region in this study, field sampling and laboratory analysis were conducted. The results showed elevated concentrations of Sb in the soil, sediment, and river water. The X-ray diffraction analysis indicated that the main minerals of the rocks were quartz, dolomite, calcite, and margarite. Based on the TESCAN integrated mineral analyzer analysis, the main ore minerals in the Gongguan mine were dolomite (93.97%), cinnabar (2.50%), stibnite (2.48%), calcite (0.38%), and quartz (0.38%). The µ-XRF analysis indicated that Sb distribution was similar to those of S and O, instead of those of Hg and As. The clear spatial variation of Sb concentration in environmental media, mines, tailings, and settling ponds affected Sb accumulation. Actinobacteriota, Proteobacteria, Acidobacteriota, and Chloroflexi were the dominant phyla in the soil. Patescibacteria, Proteobacteria, and Bdellovibrionota were negatively correlated with Sb in the soil (p < 0.05). Exposure to Sb through maize grain and cabbage consumption poses serious non-carcinogenic health risk for residents. This work provides a scientific basis for the environmental quality assessment of Sb mine areas and development of applicable guidelines.

Promoting Ethylene Selectivity from CO2 Electroreduction on CuO Supported onto CO2 Capture Materials.

Cu is a unique catalyst for CO2 electroreduction, since it can catalyze CO2 reduction to a series of hydrocarbons, alcohols, and carboxylic acids. Nevertheless, such Cu catalysts suffer from poor selectivity. High pressure of CO2 is considered to facilitate the activity and selectivity of CO2 reduction. Herein, a new strategy is presented for CO2 reduction with improved C2 H4 selectivity on a Cu catalyst by using CO2 capture materials as the support at ambient pressure. N-doped carbon (Nx C) was synthesized through high-temperature carbonization of melamine and l-lysine. We observed that the CO2 uptake capacity of Nx C depends on both the microporous area and the content of pyridinic N species, which can be controlled by the carbonization temperature (600-800 °C). The as-prepared CuO/Nx C catalysts exhibit a considerably higher C2 H4 faradaic efficiency (36 %) than CuO supported on XC-72 carbon black (19 %), or unsupported CuO (20 %). Moreover, there is a good linear relationship between the C2 H4 faradaic efficiency and CO2 uptake capacity of the supports for CuO. The local high CO2 concentration near Cu catalysts, created by CO2 capture materials, was proposed to increase the coverage of CO intermediate, which is favorable for the coupling of two CO units in the formation of C2 H4 . This study demonstrates that pairing Cu catalysts with CO2 capture supports is a promising approach for designing highly effective CO2 reduction electrocatalysts.

Tunable coupling of spin ensembles.

Spin ensembles are promising candidates for quantum memory units because they have long coherence time. Controlling the coupling between spin ensembles is necessary and important in quantum information processing. In this Letter, we propose a method to realize tunable coupling between spin ensembles by a superconducting flux qubit acting as a coupler. The resulting coupling can be used to high-fidelity speed up the adiabatic transfer of quantum information.

Cu overlayers on tetrahexahedral Pd nanocrystals with high-index facets for CO2 electroreduction to alcohols.

We investigated CO2 electroreduction on Cu overlayers on tetrahexahedral Pd nanocrystals with {310} high-index facets, which exhibited a high Faradaic efficiency towards alcohols. The selectivity to ethanol or methanol can be readily tuned by changing the Cu coverage.

Long-distance quantum information transfer with strong coupling hybrid solid system.

In this paper, we demonstrate how information can be transferred among the long-distance memory units in a hybrid solid architecture, which consists the nitrogen-vacancy (NV) ensemble acting as the memory unit, the LC circuit acting as the transmitter (receiver), and the flux qubit acting as the interface. Numerical simulation demonstrates that the high-fidelity quantum information transfer between memory unit and transmitter (receiver) can be implemented, and this process is robust to both the LC circuit decay and NV ensemble spontaneous emission.

Direct measurement on the geometric phase of a double quantum dot qubit via quantum point contact device.

We propose a direct measurement scheme to read out the geometric phase of a coupled double quantum dot system via a quantum point contact(QPC) device. An effective expression of the geometric phase has been derived, which relates the geometric phase of the double quantum dot qubit to the current through QPC device. All the parameters in our expression are measurable or tunable in experiment. Moreover, since the measurement process affects the state of the qubit slightly, the geometric phase can be protected. The feasibility of the scheme has been analyzed. Further, as an example, we simulate the geometrical phase of a qubit when the QPC device is replaced by a single electron transistor(SET).

Single-step implementation of a multiple-target-qubit controlled phase gate without need of classical pulses.

We propose a simple method for achieving a multiqubit phase gate of one qubit simultaneously controlling n target qubits, by using three-level quantum systems (i.e., qutrits) coupled to a cavity or resonator. The gate can be realized via one operational step, without need of classical pulses, and by a virtual photon process. Thus, the gate operation is greatly simplified and decoherence from the cavity decay is much reduced, when compared with previous proposals. In addition, the operation time is independent of the number of qubits and no adjustment of the qutrit level spacings or the cavity frequency is needed during the operation.

Stability and cytotoxicity of angiotensin-I-converting enzyme inhibitory peptides derived from bovine casein.

This study investigated the effect of heat treatment combined with acid and alkali on the angiotensin-I-converting enzyme (ACE) inhibitory activity of peptides derived from bovine casein. The free amino group content, color, and cytotoxicity of the peptides were measured under different conditions. When heated at 100 °C in the pH range from 9.0 to 12.0, ACE inhibitory activity was reduced and the appearance of the peptides was significantly darkened. After thermal treatment in the presence of acid and alkali, the free amino group content of ACE inhibitory peptides decreased markedly. High temperature and prolonged heating also resulted in the loss of ACE inhibitory activity, the loss of free amino groups, and the darker coloration of bovine casein-derived peptides. However, ACE inhibitory peptides, within a concentration range of from 0.01 to 0.2 mg/ml, showed no cytotoxicity to Caco-2 and ECV-304 cell lines after heat treatment. This indicated that high temperature and alkaline heat treatment impaired the stability of bovine casein-derived ACE inhibitory peptides.

Iridium oxide nanomonitors: clinical diagnostic devices for health monitoring systems.

The objective of this research is to demonstrate the potential of iridium oxide (IrOx) nanowires based device towards detection of proteins that are disease biomarkers. This device is based on electrical detection of protein biomarkers wherein an immunoassay is built onto the iridium oxide nanowires that in turn undergoes specific electrical parameter perturbations during each binding event associated with the immunoassay. Detection of two inflammatory proteins C-reactive protein (CRP) and Myeloperoxidase (MPO) that are biomarkers of cardiovascular diseases is demonstrated. The performance metrics of the device in response to the two biomarkers in pure form and in serum samples were evaluated and compared to standard ELISA assays. The methodology that has been adopted is based on measuring impedance and calibrating its change in magnitude with concentration of proteins. We demonstrate the following performance metrics: limits of detection up to 1 ng/ml for CRP and 500 pg/ml for MPO in pure and serum samples; linear dynamic range of detection from 10 ng/ml to 100 microg/ml for CRP and 1 ng/ml to 1 microg/ml for MPO and cross-reactivity contained at less than 10% of selective binding for both the inflammatory proteins. Iridium oxide has an ability to detect very small changes to the surface charge and this capability is utilized for achieving the performance metrics and forms the basis of the key innovations of this technology, which are, improving the selectivity and sensitivity of detection.