Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

An environmentally insensitive fluorescent probe for G4 DNA detection: Design, synthesis, and mechanism studies.

G4 DNA structure highly localized to functionally important sites within the human genome, has been identified as a biomarker for regulation of multiple biological processes. Identification G4-responsive fluorescence probes has broad application prospects for addressing G4 biological functions, as well as developing of new families of anticancer drugs. However, some currently designed G4 DNA probes may suffer from serious solvent-dependent effect, and cause unspecific fluorescence that masks the specific signal from G4 DNA. Herein, with a bulky imidazole-cored molecular rotor fusing in D-A building block of carbazole-pyridinium, we constructed a new probe ACPS. This new probe with desirable environmentally insensitive property exhibited a "fluorescence-off" state in various polarity solvents. In the presence of G4 DNA, the intra-molecular rotations would be restricted, triggering intense fluorescence enhancement. Especially, probe ACPS bound to G4 DNA structures with superior selectivity, exhibiting much weaker fluorescence response in the presence of non-G4 DNA structures. This probe was also able to realize fluorescence visualization in cell imaging. Collectively, the probe design strategy eliminates the background fluorescence caused by uncontrollable environmental polarity change, thereby achieving high-fidelity sensing G4 DNA structures in complicated systems.

Selective c-MYC G4 DNA recognition based on a fluorescent light-up probe with disaggregation-induced emission characteristics.

The c-MYC promoter is well-known as an important oncogene, the overexpression of which leads to ∼80% of all solid tumors. The four-stranded G4 present in the c-MYC promoter has been shown to play a pivotal role in the regulation of c-MYC transcription. Accordingly, strategies employed for c-MYC G4 DNA sensing have implications for the detection of many human pathologies. However, achieving specificity toward c-MYC G4 over other structurally similar G4s is a challenging task. Here, a supramolecular strategy that relies on the recognition-driven disaggregation of a novel BODIPY probe is outlined. The synthesized probe remained almost non-fluorescent in aqueous media in the aggregation state. Of all the tested G4 and non-G4 DNAs, only c-MYC triggered probe disaggregation and induced a significant increase in fluorescence intensity. The binding details discussed here suggest the basis for the recognition of a particular G4 structure, thus opening up a new way for the design and development of sequence-selective supramolecular G4 probes with desired properties.

Sesamol Protects Testis from Ischemia-Reperfusion Injury through Scavenging Reactive Oxygen Species and Upregulating CREMτ Expression.

Testicular torsion/detorsion-induced damage is considered as a typical ischemia-reperfusion injury attributed to excessive reactive oxygen species (ROS) production. ROS may regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The cAMP-responsive element modulator-τ (CREMτ) gene expression in the testis is essential for normal germ cell differentiation. The present study was aimed at investigating the effect of sesamol, a powerful antioxidant, on testicular ischemia-reperfusion injury and related mechanisms in an experimental testicular torsion-detorsion rat model. The type of our study was a randomized controlled trial. Sixty rats were randomly divided into the following 3 groups: (1) sham-operated control group (n = 20), (2) testicular ischemia-reperfusion group (n = 20), and (3) testicular ischemia-reperfusion+sesamol-treated group (n = 20). Testicular ischemia-reperfusion was induced by left testicular torsion (720° rotation in a counterclockwise direction) for 2 hours, followed by detorsion. Orchiectomy was performed at 4 hours or 3 months after detorsion. The testis was obtained for the analysis of the following parameters, including malondialdehyde level (a sensitive indicator of ROS), CREMτ expression, and spermatogenesis. In the testicular ischemia-reperfusion group, the malondialdehyde level was significantly increased with a concomitant significant decrease in CREMτ expression and spermatogenesis in ipsilateral testis. These results suggest that overproduction of ROS after testicular ischemia-reperfusion may downregulate CREMτ expression, which causes spermatogenic injury. Sesamol treatment resulted in a significant reduction in the malondialdehyde level and significant increase in CREMτ expression and spermatogenesis in ipsilateral testis. These data support the above suggestion. Our study shows that sesamol can attenuate testicular ischemia-reperfusion injury through scavenging ROS and upregulating CREMτ expression.

Autonomous drone hunter operating by deep learning and all-onboard computations in GPS-denied environments.

This paper proposes a UAV platform that autonomously detects, hunts, and takes down other small UAVs in GPS-denied environments. The platform detects, tracks, and follows another drone within its sensor range using a pre-trained machine learning model. We collect and generate a 58,647-image dataset and use it to train a Tiny YOLO detection algorithm. This algorithm combined with a simple visual-servoing approach was validated on a physical platform. Our platform was able to successfully track and follow a target drone at an estimated speed of 1.5 m/s. Performance was limited by the detection algorithm's 77% accuracy in cluttered environments and the frame rate of eight frames per second along with the field of view of the camera.

Heavy metals translocation and accumulation from the rhizosphere soils to the edible parts of the medicinal plant Fengdan (Paeonia ostii) grown on a metal mining area, China.

Fengdan (Paeonia ostii) is one of Chinese 34 famous medicinal materials. This study investigated the concentrations of Arsenic (As), Chromium (Cr), Cadmium (Cd), Copper (Cu), Lead (Pb), Iron (Fe), Manganese (Mn), and Zinc (Zn) in rhizosphere soils, cortex mouton and seeds of Fengdan planted in a metal mining area, China. The mean concentrations of As, Cd, Cu, and Zn in the rhizosphere soils were above the limits set by the Chinese Soil Environmental Quality Standard (GB 15618-1995). The contamination factor (CF) of Cd was >5, while it was >2for As, Cu, Pb, and Zn in all the soils. The integrated pollution index for all the soils was >3 and ˂ 5. Metal concentrations in the edible parts of Fengdan were in the following decreasing order: Mn>Fe>Zn>Cu>Pb>As>Cr≥Cd. The transfer factor mean values for As, Cu, Cd and Fe in the cortex moutan of old Fengdan (over 6 years) were significantly higher than in young Fengdan. Available metal concentrations, pH and soil organic matter content influenced the metal concentrations of the cortex moutan. The results indicated that mining and smelting operations have led to heavy metals contamination of soils and medicinal parts of Fengdan. The major metal pollutants were elemental Cd, Cu, Pb, and Zn. Heavy metals mainly accumulated in the cortex moutan of Fengdan. The mean concentrations of Cd, Cu, and Pb in the old cortex moutan (over 6 years) were above those of the Chinese Green Trade Standards for Medicinal Plants and Preparations in Foreign Trade (WM/T2-2004).

[Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

OBJECTIVE: To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. METHODS: A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. RESULTS: First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. CONCLUSIONS: Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

[Clinical research of AFP variant with microcentrifugalcolumn method and crossed affinity immunoelectrophoresis autoradiography method].

OBJECTIVE: To compare the clinical value of microcentrifugalcolumn method with crossed affinity immunoelectrophoresis autoradiography method for the measurement of alpha-fetoprotein variant (AFP-L3) in differentiation of benign and malignant liver. METHODS: Serum AFP-L3 variants in 102 primary hepatocellular carcinoma patients and 41 chronic and cirrhosis patients were separated by microcentrifugalcolumn method and crossed affinity immunoelectrophoresis autoradiography method and the clinical value of both method were compared. RESULTS: In 102 primary hepatocellular carcinoma patients, the sensitivity of AFP-L3 was 79.4% and 91.2% respectively, in 41 chronic and cirrhosis patients. The specificity of AFP-L3 was 70.7% and 29.3% respectively. The diagnostic accuracy was 76.9% and 73.4% respectively. The area in the ROC curve was 0.791 and 0.758 respectively. In the 4 primary hepatocellular carcinoma patients with lower AFP-L3, the AFP-L3 was positive by useing microcentrifugalcolumn method, but none of AFP-L3 were found by useing crossed affinity immunoelectrophoresis autoradiography method. CONCLUSION: The micro centrifugalcolumn method is more simple and rapid, it may be more useful in differentiation of benign and malignant liver than traditional crossed affinity immunoelectrophoresis autoradiography method.