Construction of a mitochondria-targeted probe to monitor cysteine levels in cancer cells and zebrafish.

Cysteine (Cys) plays an indispensable role as an antioxidant in the maintenance of bioredox homeostasis. We have constructed an efficient fluorescent probe Mito-Cys based on the binding of indole and naphthol. The acrylic ester group serves as a recognition switch for specific detection of Cys, which undergoes Michael addition and intramolecular cyclization reactions, thereby ensuring the chemical kinetics priority of Cys compared to other biothiols. The probe has good water solubility, large Stokes shift (137 nm), with a detection limit of 21.81 nM. In addition, cell imaging experiments have shown that the probe has excellent mitochondrial targeting ability (R = 0.902). The probe can distinguish between Cys, homocysteine (Hcy) and glutathione (GSH), and can detect Cys specifically and quickly (100 s) to ensure accurate quantitative analysis of Cys changes in cells. More importantly, the probe confirms that ferroptosis inducing factors trigger thiol starvation in mitochondria, which helps to gain a deeper understanding of the physiological and pathological functions related to Cys and ferroptosis.

Effects of Multi-Dimensional Nursing Based on HAPA Theory on Self-Care Ability and Cardiac Function in Patients with Coronary Heart Failure and Heart Failure.

Objective: This study aimed to investigate the effects of multi-dimensional nursing based on the Health Action Process Approach (HAPA) theory on self-care ability and cardiac function in patients with coronary heart disease (CHD) and heart failure. To explore the effects of multi-dimensional nursing based on the health action process approach (HAPA) theory on self-care ability and cardiac function in patients with coronary heart disease (CHD) and heart failure. Methods: A total of 94 patients with CHD and heart failure admitted to the hospital were enrolled between January 2021 and October 2022. The random number table method divided them into a control group (47 cases, routine nursing in cardiology department) and observation group (47 cases, multi-dimensional nursing based on HAPA theory, which is a mental model used to explain and predict the health behavior of individuals). Before and after the intervention, self-care ability, negative emotions, cardiac function and quality of life in both groups were evaluated by the exercise of self-care agency scale (ESCA), self-rating anxiety scale (SAS), self-rating depression scale (SDS), 6-minute walking test, left ventricular ejection fraction (LVEF) and Minnesota living with heart failure questionnaire (MLWHFQ). Results: During the study period, at discharge, self-care ability in both groups was improved, which was better in the observation group than the control group (P < .05). At discharge, SAS and SDS scores in both groups were decreased, which were lower in the observation group than control group (P < .05). At 6 weeks after discharge, cardiac function (LVEF, 6 min walking distance) in both groups was improved, and the improvement effect was better in the observation group than control group (P < .05). There was no significant difference in the quality of life at discharge and 6 weeks after discharge in the observation group (P > .05), but it was worse in the control group at 6 weeks after discharge (P < .05). Conclusions: Multi-dimensional nursing based on HAPA theory can significantly improve self-care ability, improve cardiac function, and quality of life in patients with CHD and heart failure.

Simple and sensitive electrochemical sensing of amethopterin by using carbon nanobowl/cyclodextrin electrode.

Resulted from the severe side effects, the development of inexpensive, simple and sensitive method for amethopterin (ATP, an antineoplastic drug) is very important but it still remains a challenge. In this work, low cost nanohybrid composed of carbon nanobowl (CNB) and ß-cyclodextrins (ß-CD) (CNB-CD) was prepared with a simple autopolymerization way and applied as electrode material to develop a novel electrochemical sensor of ATP. Scanning-/transmission-electron microscopy, Fourier transform infrared spectrum, photographic image and electrochemical technologies were utilized to characterize morphologies and structure of the as-prepared CNB and CNB-CD materials. On the basic of the coordination advantages from CNB (prominent electrical property and surface area) and ß-CD (superior molecule-recognition and solubility capabilities), the CNB-CD nanohybrid modified electrode exhibits superior sensing performances toward ATP, and a low detection limit of 0.002 µM coupled with larger linearity of 0.005-12.0 µM are obtained. In addition, the as-prepared sensor offers desirable repeatability, stability, selectivity and practical application property, confirming that this proposal may have important applications in the determination of ATP.

FTIR spectroscopy for assessment of hair from lung cancer patients and its application in monitoring the chemotherapy treatment effect.

Lung cancer is the most common cancer and the leading cause of death in China. The current gold standard for clinical lung cancer diagnosis is based on histopathological examination of tumors, but it has the limitation for easy operation and convenient applications. Therefore, researchers are still striving to develop other tools and methods for non-invasive and rapid assessment of the health conditions of lung cancer patients. Hair, as a reflection of the metabolism of the body, is closely related to human health conditions. In principle, Fourier-transform infrared (FTIR) spectroscopy can probe the major chemical compositions in the hair. However, as indicated by previous studies, there is still the challenge to make good use of FTIR spectroscopy for achieving reliable analysis of hair from cancer patients. In this study, hair samples from 82 lung cancer patients were collected and subjected to FTIR measurements and analysis, which showed the protein content in the hair is closely related to the protein content in the blood serum of patients, and the contents of protein and lipid are statistically lower in the lung cancer patients. Furthermore, we demonstrated that FTIR spectroscopy could be employed to monitor the hair of lung cancer patients undergoing chemotherapy, and confirmed that the FTIR spectra of the hair may reflect the resultant effect of the chemotherapy. As such, this work validates the way of using FTIR spectroscopy in hair analysis for the assistance of medical diagnosis of lung cancer as well as monitoring the conditions of the patients under the medical treatment.

Frailty and Health-Related Quality of Life in Elderly Patients Undergoing Esophageal Cancer Surgery: A Longitudinal Study.

PURPOSE: This study aims to elucidate the longitudinal alterations in frailty and health-related quality of life experienced by elderly patients undergoing surgical treatment for esophageal cancer. Additionally, it seeks to ascertain the impact of preoperative frailty on postoperative health-related quality of life over time. METHODS: 131 patients were included in the prospective study. Patients' frailty and health-related quality-of-life were assessed utilizing the Tilburg and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at preoperative, 1 week, 1 month, and 3 months, postoperatively. Statistical analyses were performed using generalized estimating equations, repeated-measures analysis of variance, and linear mixed models (LMMs). RESULTS: Out of 131 patients, 28.2% had frailty before surgery, and the prevalence of frailty consistently higher after surgery compared with baseline (67.9%, 51.9%, and 39.7%). There was no significant change in frailty scores in preoperative frail patients within 3 months following surgery (p = .496, p < .999, p < .999); whereas in preoperative non-frail patients, the frailty scores increased at 1 week (p < .001) and then decreased at 1 month (p = .014), followed by no change at 3 months. In addition, preoperative frail patients had significantly worse global quality-of-life (ß = -4.24 (-8.31; -.18), p = .041), physical functioning (ß = -9.87 (-14.59; -5.16), p < .001), role functioning (ß = -10.04 (-15.76; -4.33), p = .001), and social functioning (ß = -8.58 (-15.49; -1.68), p = .015), compared with non-frail patients. CONCLUSIONS: A significant proportion of participants exhibited a high prevalence of preoperative frailty. These patients, who were preoperatively frail, exhibited a marked reduction in health-related quality-of-life, a more gradual recovery across various functional domains, and an increased symptom burden during the follow-up period. Therefore, it is crucial to meticulously identify and closely monitor patients with preoperative frailty for any changes in their postoperative physiology, role, and social functioning.

Knockdown of IRF8 alleviates neuroinflammation through regulating microglial activation in Parkinson's disease.

Neuroinflammation associated with microglial activation plays a role in the development of Parkinson's disease (PD). The upregulation of interferon regulatory factor 8 (IRF8) in microglia following peripheral nerve injury has been observed to induce microglial activation. This suggests the potential therapeutic significance of IRF8 in PD. This research aims to explore the effects of IRF8 on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and lipopolysaccharide (LPS)-induced neuroinflammation, along with its underlying mechanisms. The study examines the differential expression of IRF8 and its effects on neuropathological changes using a PD mouse model and a PD model established from BV2 cells in vitro. IRF8 was found to be prominently expressed in the substantia nigra pars compacta (SNpc) region of PD mice and LPS-stimulated BV2 cells, while the expression of tyrosine hydroxylase (TH) and dopamine (DA) content in the SNpc region of PD mice was notably reduced. MPTP treatment and LPS stimulation intensified microglial activation, inflammation, and activation of the AMPK/mTOR signaling pathway in vivo and in vitro, respectively. Upon IRF8 silencing in the PD mouse and cell models, the knockdown of IRF8 ameliorated MPTP-induced behavioral deficits, increased the counts of TH and Nissl-positive neurons and DA content, reduced the number of Iba-1-positive microglia, and reduced the content of inflammatory factors, possibly by inhibiting the AMPK/mTOR signaling pathway. Similar outcomes were observed in the PD cell model. In conclusion, the suppression of IRF8 alleviates neuroinflammation through regulating microglial activation in PD models in vivo and in vitro by the AMPK/mTOR signaling pathway.

Symptom cluster trajectories and sentinel symptoms during the first cycle of chemotherapy in patients with lung cancer.

PURPOSE: To investigate symptom severity, symptom cluster trajectories and sentinel symptoms during chemotherapy cycle 1 in patients with lung cancer. METHODS: Patients with lung cancer were recruited to complete the MD Anderson Symptom Inventory (MDASI) and First Appearance of Symptoms Time Sheet daily during the first week of chemotherapy cycle 1. Latent class growth analysis was performed to examine symptom cluster trajectories. The Apriori algorithm combined with the time of the first appearance of symptoms after chemotherapy was used to determine the sentinel symptoms of each symptom cluster. RESULTS: A total of 175 lung cancer patients participated in the study. Five symptom clusters were identified: class 1 (difficulty remembering-numbness-hemoptysis-weight loss), class 2 (cough-expectoration-chest tightness-shortness of breath), class 3 (nausea-sleep disturbance-drowsiness-constipation), class 4 (pain-distress-dry mouth-sadness-vomiting), class 5 (fatigue-lack of appetite). Sentinel symptoms were found to be cough (class 2) and fatigue (class 5), while none were found for other symptom clusters. CONCLUSION: The trajectories of five symptom clusters were observed during the first week of chemotherapy cycle 1 and the sentinel symptoms of each cluster were explored. The study has important significance for the effective management of symptoms and the quality of nursing care for patients. At the same time, alleviating sentinel symptoms may reduce the severity of the whole symptom cluster, reducing medical resources and improving quality of life for lung cancer patients.

A New Antibody Binding Test for Potency Assessment of the Human Rabies Vaccine.

This study established a new protocol of the antibody binding test to evaluate the potency of the rabies vaccine containing the final bulk and the product. The principle of this experiment is to combine rabies vaccine with quantitative anti-rabies virus neutralizing antibody. After combination, the remaining rabies vaccine is combined with the quantitative fluorescent labeled rabies virus. After this, observe the remaining fluorescent labeled rabies virus, calculate the fluorescence area with fluorescence observation equipment, then calculate the potency of rabies vaccine by Reed and Muench method. The test results of many batches of rabies vaccine final bulk and finished products showed that the potency detected by this method was consistent with that of National Institute of Health method.

Efficient Synthesis and Biological Evaluation of 6-Trifluoroethoxy Functionalized Pteridine Derivatives as EGFR Inhibitors.

BACKGROUND: Pteridine-based scaffolds have been widely prevalent in pharmaceuticals, such as kinase inhibitors targeting EGFR, FLT3 and PI3K/mTOR which are attractive targets for the anticancer therapy. OBJECTIVE: This work aimed at designing and synthesizing 6-2,2,2-trifluoroethoxy functionalized pteridine-based derivatives for investigation of their anti-cancer activities as EGFR inhibitor. METHODS: Pteridine-based derivatives were synthesized in 6 steps involving amination, bromination, cyclization, alkoxylation, chlorination and coupling reactions. Cellular anti-proliferative activities and inhibition activities on EGFR signaling of these pteridine derivatives in vitro were determined by the MTT assay and western blot analysis, respectively. Molecular docking simulation studies were carried out by the crystallographic structure of the erlotinib/EGFR kinase domain [Protein Data Bank (PDB) code: 1M17]. RESULTS: The compound 7m, with IC50 values of 27.40 µM on A549 cell line, exhibited comparable anti-proliferative activity relative to the positive control. Besides, western blots showed its obvious down-regulation of p-EGFR and p-ERK expression at 0.8 µM. The molecular docking model displayed a hydrogen bond between Met-769 amide nitrogen and N-1 in pteridine motif of 7m which lied at the ATP binding site of EGFR kinase domain. CONCLUSION: The inhibition of 7m on cellular growth was comparable to that of the positive control. The inhibitory activities of 7m on EGFR phosphorylation and ERK phosphorylation in A549 cell line were relatively superior to that of the positive control. Both results suggested that the antiproliferative activity of 7m against A549 cell line was caused by inhibition of EGFR signaling pathway, providing a new perspective for the modification of pteridine-based derivatives as EGFR inhibitor.

Poly[dibromidobis[µ-1-(pyridin-4-ylmeth-yl)-1H-1,2,4-triazole-κN:N']cadmium].

The title coordination polymer, [CdBr(2)(C(8)H(8)N(4))(2)](n), arose from a layer-separated diffusion synthesis at room temperature. The title compound is isotypic with the I and Cl analogues. The Cd atom, located on an inversion center, is coordinated by two bromide ions and four N atoms (two from triazole rings and two from pyridyl rings) in a distorted trans-CdBr(2)N(4) octa-hedral arrangement. The bridging 1-(4-pyridyl-meth-yl)-1H-1,2,4-triazole ligands are twisted [dihedral angle between the triazole and pyridine rings = 72.56 (13)°], affording a two-dimensional 4(4) sheet structure in the crystal.

Real-time lane detection model based on non bottleneck skip residual connections and attention pyramids.

The security of car driving is of interest due to the growing number of motor vehicles and frequent occurrence of road traffic accidents, and the combination of advanced driving assistance system (ADAS) and vehicle-road cooperation can prevent more than 90% of traffic accidents. Lane detection, as a vital part of ADAS, has poor real-time performance and accuracy in multiple scenarios, such as road damage, light changes, and traffic jams. Moreover, the sparse pixels of lane lines on the road pose a tremendous challenge to the task of lane line detection. In this study, we propose a model that fuses non bottleneck skip residual connections and an improved attention pyramid (IAP) to effectively obtain contextual information about real-time scenes and improve the robustness and real-time performance of current lane detection models. The proposed model modifies the efficient residual factorized pyramid scene parsing network (ERF-PSPNet) and utilizes skip residual connections in non bottleneck-1D modules. A decoder with an IAP provides high-level feature maps with pixel-level attention. We add an auxiliary segmenter and a lane predictor side-by-side after the encoder, the former for lane prediction and the latter to assist with semantic segmentation for classification purposes, as well as to solve the gradient disappearance problem. On the CULane dataset, the F1 metric reaches 92.20% in the normal scenario, and the F1 metric of the model is higher than the F1 metrics of other existing models, such as ERFNet-HESA, ENet_LGAD, and DSB+LDCDI, in normal, crowded, night, dazzling light and no line scenarios; in addition, the mean F1 of the nine scenarios reached 74.10%, the runtime (time taken to test 100 images) of the model was 5.88 ms, and the number of parameters was 2.31M, which means that the model achieves a good trade-off between real-time performance and accuracy compared to the current best results (i.e., a running time of 13.4 ms and 0.98M parameters).

Promotive role of microRNA­150 in hippocampal neurons apoptosis in vascular dementia model rats.

Cognitive impairment is one of the primary features of vascular dementia (VD). However, the specific mechanism underlying the regulation of cognition function in VD is not completely understood. The present study aimed to explore the effects of microRNA (miR)­150 on VD. To determine the effects of miR­150 on cognitive function and hippocampal neurons in VD model rats, rats were subjected to intracerebroventricular injections of miR­150 antagomiR. The Morris water maze test results demonstrated that spatial learning ability was impaired in VD model rats compared with control rats. Moreover, compared with antagomiR negative control (NC), miR­150 antagomiR alleviated cognitive impairment and enhanced memory ability in VD model rats. The triphenyltetrazolium chloride, Nissl staining and immunohistochemistry results further demonstrated that miR­150 knockdown improved the activity of hippocampal neurons in VD model rats compared with the antagomiR NC group. To validate the role of miR­150 in neurons in vitro, the PC12 cell line was used. The flow cytometry and Hoechst 33342/PI double staining results indicated that miR­150 overexpression significantly increased cell apoptosis compared with the mimic NC group. Moreover, the dual­luciferase reporter gene assay results indicated that miR­150 targeted HOXA1 and negatively regulated HOXA1 expression. Therefore, the present study indicated that miR­150 knockdown ameliorated VD symptoms by upregulating HOXA1 expression in vivo and in vitro.

Electrochemical synthesis of quinazolinone via I2-catalyzed tandem oxidation in aqueous solution.

The development of protocols for synthesizing quinazolinones using biocompatible catalysts in aqueous medium will help to resolve the difficulties of using green and sustainable chemistry for their synthesis. Herein, using I2 in coordination with electrochemical synthesis induced a C-H oxidation reaction which is reported when using water as the environmentally friendly solvent to access a broad range of quinazolinones at room temperature. The reaction mechanism strongly showed that I2 cooperates electrochemically promoted the oxidation of alcohols, then effectively cyclizing amides to various quinazolinones.

A two-dimensional manganese(II) complex: poly[bis-(µ(2)-4,4'-bipyrid-yl)tetra-kis-(µ(2)-3,5-dinitro-benzoato)dimanganese(II)].

The Mn atom in the title compound, [Mn(2)(C(7)H(3)N(2)O(6))(4)(C(10)H(8)N(2))(2)](n), is six-coordinated by two N atoms and four O atoms, forming a distorted octa-hedral geometry. The Mn-O bond lengths are in the range 2.1281 (13)-2.2011 (12) Šand the Mn-N bond lengths are 2.269 (2) and 2.278 (2) Å. Mn(II) atoms are double-bridged along the a axis by two pairs of bi-monodentate carboxyl groups, forming a double-stranded chain, while the bidentate 4,4'-bipyridine ligand bridges the Mn atom along the b axis. This results in a two-dimensional structure constructed of oblong grids with the sides of length 11.634 and 5.075 Å

Poly[dichloridobis[µ-1-(4-pyridyl-meth-yl)-1,2,4-triazole]cadmium(II)].

In the title coordination polymer, [CdCl(2)(C(8)H(8)N(4))(2)](n), the Cd(II) atom, lying on an inversion center, is coordinated by two Cl atoms and two triazole N atoms and two pyridyl N atoms from four 1-(4-pyridyl-meth-yl)-1,2,4-triazole (pmta) ligands in a distorted trans-CdCl(2)N(4) octa-hedral arrangement. The bridg-ing pmta ligands, with a dihedral angle between the triazole and pyridyl rings of 71.86 (8)°, link the Cd atoms into a 4(4) sheet parallel to (02). π-π inter-actions between the triazole rings [centroid-centroid distance = 3.428 (2) Å] connect the sheets.

From Bacteria to Cancer: A Benzothiazole-Based DNA Gyrase B Inhibitor Redesigned for Hsp90 C-Terminal Inhibition.

Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for the folding and maturation of client proteins that are associated with all ten hallmarks of cancer. Hsp90 N-terminal pan inhibitors have experienced unfavorable results in clinical trials due to induction of the heat shock response (HSR), among other concerns. Novobiocin, a well characterized DNA gyrase B inhibitor, was identified as the first Hsp90 C-terminal inhibitor that manifested anticancer effects without induction of the HSR. In this letter, a library of Hsp90 C-terminal inhibitors derived from a benzothiazole-based scaffold, known to inhibit DNA gyrase B, was designed, synthesized, and evaluated. Several compounds were found to manifest low micromolar activity against both MCF-7 and SKBr3 breast cancer cell lines via Hsp90 C-terminal inhibition.

Poly[dichloridobis[µ-1-(4-pyridylmeth-yl)-1H-1,2,4-triazole]copper(II)].

The title coordination polymer, [CuCl(2)(C(8)H(8)N(4))(2)](n), arose from a layer-separated diffusion synthesis at room temperature. The Cu atom (site symmetry ) is coordinated by two chloride ions and four N atoms (two from triazole rings and two from pyridyl rings) in a distorted trans-CuCl(2)N(4) octa-hedral arrangement. The bridging 1-(4-pyridylmeth-yl)-1H-1,2,4-triazole ligands [dihedral angle between the triazole and pyridine rings = 68.08 (8)°] result in a two-dimensional 4(4) sheet structure in the crystal.

[Synthesis and photophysical properties of two kinds of substituted phthalocyaninatozinc].

Two kinds of substituted phthalocyaninatozinc, tetra-beta-phthalimidobutoxy phthalocyaninatozinc (1) and tetra-beta-phthalimidomethyl phthalocyaninatozinc (2), were synthesized by mix melting method, which bear the same phthalimide substituents but the linking of the substituents to the phthalocyanine ring is different. The substituent linking to the phthalocyanine ring is one methylene in ZnPc (2), while the substituents linking to the phthalocyanine ring is four methylenes and one ather in ZnPc (1), in which ather is near by phthalocyanine ring. The absorption and fluorescence spectra and the abilities of singlet oxygen generation of these two phthalocyanines were compared with respect to the effect of different linked fashions. The magnitude of the redshift of absorption and fluorescence spectra relative to unsubstituded ZnPc is greater for tetra-beta-phthalimidobutoxy phthalocyaninatozinc (1) than for tetra-beta-phthalimidomethyl phthalocyaninatozinc (2). This result is related to the presence of stronger electron donating peripheral substituents of ZnPc (1), with phiF of (1) is larger than that of (2) and the abilities of singlet oxygen generation of (1) is smaller than that of (2).

[Fluorescence spectra and photo-generating rate of singlet oxygen of phthalocyaninatopalladium].

The absorption spectral properties, fluorescence spectral properties and the abilities of photo-generating singlet oxygen of four phthalocyanines, namely tetra-alpha-(2,2,4-trimethyl-3-pentoxy) phthalocyaninatopalladium (zinc) and tetra-alpha-(2,4-diterbutylphenoxy) phthalocyaninatopalladium (zinc), were determined. Experimental results show that the ability of photo-generating singlet oxygen of phthalocyaninatopalladium is similar to that of phthalocyaninatozincx, though palladium(II) is an open shell electron structure and zinc( II ) is a closed shell structure. This may be concerned with a weak flourescence intensity and a strong inter-crossing transition of phthalocyaninatopalladium.

[Synthesis and UV/Vis spectra of a dialkyloxy substituted phthalocyanine].

A dialkyloxy substituted metal-free phthalocyanine was synthesized by using 3-(2',2',4'-trimethyl-3'-pentoxy)-1,3-diiminoisoindoles and 1,3,3-trichloroisoindolenine as starting materials, and characterized by element analysis, 1H NMR, IR and UV/Vis spectra. The dependences of wavelength of UV/Vis spectra and its split of Q band absorption on the number of substituents and, dielectric constant of solvents are discussed based on the comparison with tetraalkyloxy substituted metal-free phthalocyanine.