Synthesis, structure and photophysical properties of truxene and truxene-triindole compounds.

Multi-branched π-conjugated organic molecules, due to their fascinating structures and unique optical properties, exhibit potential applications in optoelectronics. Herein, series of 4-N,N-diphenylaminostyryl substituted multi-branched truxene compounds (namely TN1, TN2 and TN3) and a truxene-triindole compound (namely N3T3) were synthesized. These compounds are characterized by effective π-extension and remarkably enhanced two-photon absorption (TPA) compared to their less π-conjugated analogues. For truxene compounds, the more the number of the branch, the large the TPA efficiency, and the C3-symmetric three-branched TN3 exhibit the largest TPA. The aromatic triindole unit proves to be a better two-photon fluorophore compared with truxene. The results conclude that the influence of π-conjugation, molecular planarity and intramolecular charge-transfer (ICT) to TPA is far more pronounced than to linear optical properties.

Three new flavonoid glycosides from the herbaceous stems of Ephedra intermedia.

Phytochemical investigation of the n-butanol extracts of the herbaceous stems of Epheda intermedia led to the isolation of eight flavonoids that included three new flavonoid glycosides (1-3) and five previously reported analogues (4-8). Their structures have been identified on the basis of various spectral data. Besides, all the flavonoids were tested in vitro for their ability to inhibit α-glucosidase under the positive control of acarbose, and the results indicated that none of them exhibited significant inhibitory effect on α-glucosidase at 100 µM.

Amine-Borane-Mediated, Nickel/Photoredox-Catalyzed Cross-Electrophile Coupling between Alkyl and Aryl Bromides.

Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp3)-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.

Prediction of laser printers and cartridges based on three-dimensional profiles via discrimination analysis.

Printer source prediction is an important task when examining questioned documents. While some research has provided methods to predict the source printer of documents, with the advent of compatible consumables, printer prediction could become more complex and difficult. Predicting the source printer after replacing cartridges and identifying the source of printer cartridges are unresolved issues that are rarely addressed in current research. Herein, we introduce a novel technique to predict the manufacturer, model, and cartridges of laser printers (i.e., compatible, and original cartridges) used to produce a given document. Document samples produced using eight laser printers and 247 cartridges were collected to establish a dataset. Common manufacturers included HP, Canon, Lenovo, and Epson. After obtaining white-light images and three-dimensional profile images of printed characters, a morphological analysis was conducted by questioned document examiners (QDEs) using microscopy. Microscopic image features across a series of images were also extracted and analyzed using algorithms. Then, six high-dimensional reduction algorithms were used to obtain between- and within-printer variations as well as between- and within-cartridge variations. Finally, we conducted principal component analysis (PCA) and discriminant analysis. For 40 % of the samples, mixed discrimination analysis (MDA) and fixed discrimination analysis (FDA) were employed to predict the manufacturer, model and cartridge of laser printers used to produce the questioned printed document; the remaining 60 % samples comprised the training dataset. In the prediction of manufacturer, model and cartridge, our method achieved mean accuracies of 95.5 %, 97.5 %, and 90.2 %, respectively. Hence, this technique could reasonably aid in predicting the manufacturer, model, and cartridge of a laser printer, even if different cartridges are loaded into printers.

[Effect of 2-phenylethyl-beta-glucopyranoside isolated from Huaizhong No. 1 Rehmannia glutinosa on hypoxic pulmonary hypertension by regulating PI3K/Akt/m TOR/HIF-1α pathway].

The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.

Visible Light-Induced, Nickel-Catalyzed Late-Stage 4-Alkylation of Hantzsch Esters with Alkyl Bromide.

Herein, visible light-induced, nickel-catalyzed direct functionalization of the Hantzsch esters (HEs) with readily accessible alkyl bromides has been successfully achieved by taking advantage of HE as the reductant and substrate through an aromatization-dearomatization process. In this strategy, the single electron reduction of alkyl bromides by reactive Ni(I) species is essential for the success of this late-stage transformation. A wide range of 4-alkyl-1,4-dihydropyridines were rapidly assembled in moderate to good yields under mild conditions, rendering this photoinduced approach attractive for synthetic and medicinal chemistry.

Real-time monitoring of intracellular biochemical response in locally stretched single cell by a nanosensor.

Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level.

Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis.

Inkjet printer prediction under complicated printing conditions based on microscopic image features.

A novel technique is introduced to predict the printer model used to produce a given document. Samples containing only a few letters printed under varying conditions (i.e., different printing modes, letter types, fonts) were collected to establish a dataset of 41 inkjet printer models from common manufacturers, such as HP, Canon, and Epson. Morphological features were analyzed by extraction of image features using several algorithms in a series of microscopic images and a Wilcoxon test was used to measure the significance of variations between printed samples. Significant differences between various printing conditions might post potential challenge to questioned document examination. Discriminant analysis and the k-nearest neighbor (KNN) algorithm were also employed for source printer prediction under varying printing condition on 30% images with the rest images as training dataset. The results of a validation experiment demonstrated that while quadratic discriminant analysis (QDA) achieved an accuracy of 96.3%, a combination of KNN and QDA reached 98.6%. As such, this technique could aid in the forensic examination of printed documents.

Callicarpayongshunensis (Lamiaceae): A new species from Hunan, China.

This study provides detailed description of a newly-discovered Callicarpayongshunensis Wen B. Xu, Xiao D. Li & Yan Ling Liu (Lamiaceae) species from Hunan, China. The species shares similarities in the inflorescence, glandular colour and leaf shape features with C.luteopunctata H. T. Chang and C.giraldii Hesse ex Rehd., while its white fruits are similar to those of C.longifolia Lamk. However, its procumbent, evergreen shrub and white fruits are distinctly different from those of C.luteopunctata and C.giraldii, while its procumbent, scarless nodes and stellate pubescence free fruits distinguishes it from C.longifolia. Images, distribution, morphological features, molecular phylogenetic classification and conservation assessment of this new Callicarpa species are explored.

Five new eremophilane-type sesquiterpenes from the fresh roots of Rehmannia glutinosa.

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

Chemical constituents from stipes of Lentinus edodes and their protective effects against Aß25-35-induced N9 microglia cells injury.

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.

Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients.

BACKGROUND: The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC-apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). METHODS: Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. RESULTS: The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators. CONCLUSION: PYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA.

Photoredox/Nickel Dual Catalysis-Enabled Aryl Formylation with 2,2-Dimethoxy-N,N-dimethylethan-1-amine as CO Source.

Herein, a dual photoredox/nickel catalyzed formylation of aryl bromide with commercially available 2,2-dimethoxy-N,N-dimethylethan-1-amine as an effective CO source has been successfully achieved, delivering a series of aromatic aldehydes in moderate to good yields. Compared with the traditional reductive carbonylation process, this newly designed synthetic protocol provides a straightforward toolbox to access aromatic aldehydes, obviating the use of carbon monoxide and stoichiometric reductants. Finally, the utility of this direct formylation reaction was demonstrated in the pharmaceutical analogue synthesis.

Real-Time Quantification of Nanoplastics-Induced Oxidative Stress in Stretching Alveolar Cells.

Nanoplastics from air pollutants can be directly inhaled into the alveoli in the lungs and further enter blood circulation, and numerous studies have revealed the close relation between internalized nanoplastics with many physiological disorders via intracellular oxidative stress. However, the dynamic process of nanoplastics-induced oxidative stress in lung cells under breath-mimicked conditions is still unclear, due to the lack of methods that can reproduce the mechanical stretching of the alveolar and simultaneously monitor the oxidative stress response. Here, we describe a biomimetic platform by culturing alveoli epithelial cells on a stretchable electrochemical sensor and integrating them into a microfluidic device. This allows reproducing the respiration of alveoli by cyclic stretching of the alveoli epithelial cells and monitoring the nanoplastics-induced oxidative stress by the built-in sensor. By this device, we prove that cyclic stretches can greatly enhance the cellular uptake of nanoplastics with the dependencies of strain amplitude. Importantly, oxidative stress evoked by internalized nanoplastics can be quantitatively monitored in real time. This work will promote the deep understanding about the cytotoxicity of inhaled nanoplastics in the pulmonary mechanical microenvironment.

Nanosensor detection of reactive oxygen and nitrogen species leakage in frustrated phagocytosis of nanofibres.

Exposure to widely used inert fibrous nanomaterials (for example, glass fibres or carbon nanotubes) may result in asbestos-like lung pathologies, becoming an important environmental and health concern. However, the origin of the pathogenesis of such fibres has not yet been clearly established. Here we report an electrochemical nanosensor that is used to monitor and quantitatively characterize the flux and dynamics of reactive species release during the frustrated phagocytosis of glass nanofibres by single macrophages. We show the existence of an intense prolonged release of reactive oxygen and nitrogen species by single macrophages near their phagocytic cups. This continued massive leakage of reactive oxygen and nitrogen species damages peripheral cells and eventually translates into chronic inflammation and lung injury, as seen during in vitro co-culture and in vivo experiments.

GAS5 promotes cytarabine induced myelosuppression via inhibition of hematopoietic stem cell differentiation.

Cytarabine (Ara-C) is widely used in the induction chemotherapy for acute myeloid leukemia (AML). Association between LncRNA GAS5 genetic polymorphism and the recovery of hematopoietic function after Ara-C-based chemotherapy is observed. This study aimed to identify whether intervention of GAS5 expression and GAS5 genotype affect Ara-C-induced inhibition of hematopoietic stem cells (HSCs) differentiation. In this study, cord blood-derived CD34+ cells were cultured in vitro, and a cell model of myelosuppression was established by treatment of CD34+ cells with Ara-C. The effect of GAS5 overexpression, Ara-C treatment, and GAS5 rs55829688 genotype on the hematopoietic colony-forming ability of CD34+ cells was assessed using methylcellulose-based colony forming unit assay. GAS5 overexpression slowed down the proliferation of cord blood-derived CD34+ cells significantly (p < 0.05) and decreased their ability to form hematopoietic colonies in vitro. Ara-C significantly reduced the hematopoietic colony-forming ability of CD34+ cells in vitro (p < 0.0001), and overexpressing GAS5 further decreased the number of hematopoietic colonies. GAS5 expression was higher in CD34+ cells than in CD34- cells, and positively correlated with GATA1 mRNA expression in CD34+ cells in vitro culture. However, GAS5 genotype had no effect on the total number of hematopoietic colonies formed from cord blood-derived CD34+ cells. In conclusion, our study highlights that GAS5 inhibited the in vitro proliferation and reduced the hematopoietic colony-forming ability of cord blood-derived CD34+ cells, with the most pronounced effect observed on CFU-GEMM formation. GAS5 also enhanced the inhibitory effect of Ara-C on the in vitro hematopoietic ability of CD34+ HSCs.

Geniposide promotes wound healing of skin ulcers in diabetic rats through PI3K/Akt pathway.

Continuously hyperglycation-induced lesion and poor blood flow contributed to the wound incurable and susceptible to infection. About fifteen percent of people with diabetes would develop ulcers during their lifetime, especially on the feet, which could lead to severe tissue destruction and eventual amputation. Various strategies were limited to accelerate wound healing in diabetic patients for high cost and unsatisfied effects. Geniposide is well-known for its anti-inflammation and anti-apoptosis in several pathological tissues. This study is to explore the protective effect of geniposide on wound healing rate, inflammatory response, nutritional function and cellular apoptosis in diabetic rats. Diabetic rats was induced by streptozotocin and defined as plasma glucose >300 mg/dl. Western blot and immunostaining technologies were performed to mark and quantify the target proteins. The oral administration of geniposide (200 mg/kg and 500 mg/kg) could significantly promote wound healing by the increment of lesion retraction in diabetic rats compared to model group. In the apoptotic study of skin wound in diabetic rats, the TUNEL-positive cells were greatly decreased in geniposide subgroups (P < 0.05). The levels of TNF-α, IL-1ß and IL-6 were significantly inhibited by geniposide with the IC50 value of 470 mg/kg, 464 mg/kg and 370 mg/kg body weight respectively, which might be related to the enhancement of the phosphorylation of PI3K and Akt proteins. Geniposide enhanced the repairment of skin wound in diabetic rats by inhibiting inflammatory response and apoptosis.

Visible-Light-Induced Nickel-Catalyzed Cross-Coupling of Aryl Bromides with Nitriles.

Herein, a visible-light-induced nickel-catalyzed cross-coupling of aryl bromide with nitrile has been reported. By utilization of readily available nitriles as carbonyl precursors, a range of structurally diverse aryl ketones were facilely constructed. The synthetic simplicity, mild reaction conditions, and acidic functional group tolerance would broaden the synthetic utilities of this developed protocol as an expedient alternative to Grignard/organolithium protocols.

Photoredox/Nickel Dual Catalysis-Enabled Cross-Dehydrogenative C-H Amination of Indoles with Unactivated Amine.

Herein, a direct cross-dehydrogenative C-H amination of indoles has been successfully achieved, enabled by the merger of photocatalysis with nickel catalysis. This developed process does not require stoichiometric oxidants and prefunctionalization of amine partners, providing a concise platform for C-N bond formation. Moreover, the synthetic practicality of this transformation was well revealed by its high step- and atom-economy, high reaction efficiency, and broad functional group tolerance.