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Two novel phosphodiesterase 5 (PDE-5) inhibitors were detected in pressed candy using high-performance liquid chromatography (HPLC)-diode array detection. Following extraction with acetonitrile and sonication, the compounds were isolated and purified via semi-preparative liquid chromatography. Structural characterisation was achieved through high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy. The results indicate that both compounds possess identical UV absorption spectra. The molecular formulas of compounds 1 and 2 are C 23 H 32 N 4 O 4 and C 22 H 30 N 4 O 4 , respectively, each featuring a pyrimidinone benzene structure with a single methylene group (-CH 2 ) variation. As studies on these illicit compounds in functional foods have not been conducted, regulatory agencies must take note and incorporate them for the assessment of illicit additives in functional and healthcare foods.

In this work, we developed a ratiometric fluorescent probe (NT) based on ICT framework in near-infrared (NIR) which could detect pH and viscosity simultaneously. Long emission wavelength in NIR could protect the probe from interference of background fluorescence and improve the accuracy of the test. Due to the presence of thiazole-salt, the probe possessed good water solubility and could respond immediately to pH in water system. The pH values measured by NT in the actual samples were not much different from that measured by the pH meter, therefore, NT could give excellent accuracy. NT realized the reversible detection of pH by protonation and deprotonation. NT was used successfully to detect the pH of actual water samples, human serum and meat, as well as the viscosity variation caused by thickeners. Additionally, NT could monitor the changes of pH and viscosity in living cells. Therefore, the novel probe exhibited potential application in the fields of the environment, human health and food safety evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fluoride ion is not only important for dental health, but also a contributing factor in a variety of diseases. At the same time, fluoride ions and cell viscosity are both important to the physiological environment of mitochondria. We developed a dual-response ratiometric fluorescent probe BDF based on Förster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) mechanism for the detection of F - and viscosity. BDF has an outstanding intramolecular energy transfer efficiency of 97.7% and shows excellent performance for fluorine ion detection. In addition, when the system viscosity increases, the fluorescence emission intensity of BDF is greatly heightened, indicating the possibility of viscosity detection. Finally, based on the fluorescence properties of BDF, we used the probe to detect F - in the toothpaste sample and image exogenous fluoride ions in HeLa cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Thyroid cancer (TC) has increased globally, with a prominent increase in small, papillary thyroid cancers. PEST-containing nuclear protein (PCNP), a nuclear protein, has been found to be associated with human cancers in recent years. However, the role and molecular mechanism of PCNP in thyroid cancer remain underexplored. In the present study, the results showed that the expression levels of PCNP in human thyroid tissues were higher than those in adjacent non-tumor tissues. Overexpression of PCNP reduced the proliferation, migration, and invasion of human thyroid cancer cells and down-regulation of PCNP showed reverse effects. In addition, PCNP regulated cell cycle arrest through modifications in the expression of cell cycle regulating genes and PCNP affected apoptosis via activation of ERK/JNK/p38 pathway in thyroid cancer cells. Moreover, PCNP overexpression promoted autophagy by reducing the expression levels of Wnt/β-catenin pathway in TC cells, however, PCNP knockdown had opposite effects. Furthermore, PCNP overexpression reduced the growth of xenografted human thyroid cancer, whereas PCNP knockdown showed opposite trends. In conclusion, in vitro and in vivo data demonstrate that PCNP as a tumor suppressor gene may serve as a novel prognostic and potential therapeutic marker in human thyroid cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Brønsted acid-catalyzed direct C(sp 2 )-H alkylation of N -heteroaromatics with cyclic ethers via a cross-dehydrogenative coupling reaction in the presence of benzoyl peroxide was developed. This methodology successfully provided an easy access to a variety of alkyl-substituted quinoxaline, benzoimidazole, pyrazine, pyrimidine, quinoline, isoquinoline, and pyridine derivatives in up to 94% yield under metal-free conditions.

A new tadalafil analogue was detected via high-performance liquid chromatography (HPLC)-diode array detection (DAD) during routine screening of health foods suspected of adulteration with erectile dysfunction drugs. The UV absorption spectrum of the unknown was almost identical to that of tadalafil. The analogue was purified by preparative HPLC and structural elucidation carried out by mass spectrometric and NMR spectroscopic experiments. The spectral data revealed that this tadalafil analogue bears a benzyl group instead of the methyl group. The isolated compound was identified as N-benzyl tadalafil. Considering the risk it poses to public health, this new PDE-5 analogues for ED should be included on the inspection list for illegal products.

Lung cancer is the leading cause of cancer-related mortality worldwide. PEST-containing nuclear protein (PCNP) has been found in the nucleus of cancer cells. Whether PCNP plays a role in the growth of lung adenocarcinoma is still unknown. In the present study, the results indicated that the level of PCNP in lung adenocarcinoma tissue was significantly higher than that in corresponding adjacent non-tumor tissue. Over-expression of PCNP promoted the proliferation, migration, and invasion of lung adenocarcinoma cells, while down-regulation of PCNP exhibited opposite effects. PCNP over-expression decreased apoptosis through up-regulating the expression levels of phospho (p)-signal transducers and activators of transcription (STAT) 3 and p-STAT5 in lung adenocarcinoma cells, whereas PCNP knockdown showed opposite trends. PCNP overexpression enhanced autophagy by increasing the expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) in lung adenocarcinoma cells, however an opposite trend was observed in the sh-PCNP group. In addition, overexpression of PCNP showed the tumor-promoting effect on xenografted lung adenocarcinoma, while PCNP knockdown reduced the growth of lung adenocarcinoma via regulating angiogenesis. Our study elucidates that PCNP can regulate the procession of human lung adenocarcinoma cells via STAT3/5 and PI3K/Akt/mTOR signaling pathways. PCNP may be considered as a promising biomarker for the diagnosis and prognosis in patients with lung adenocarcinoma. Furthermore, PCNP can be a novel therapeutic target and potent PCNP inhibitors can be designed and developed in the treatment of lung adenocarcinoma.

Tumour necrosis factor-α-induced protein 8-like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non-tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down-regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down-regulating the expression levels of Wnt3a, phospho (p)-β-Catenin, and p-glycogen synthase kinase-3β in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p-Smad2, p-Smad3, and transforming growth factor-beta (TGF-β) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/β-Catenin and TGF-β/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Diaphragm dysfunction is an important clinical problem worldwide. Hydrogen sulfide (H 2 S) is involved in many physiological and pathological processes in mammals. However, the effect and mechanism of H 2 S in diaphragm dysfunction have not been fully elucidated. In this study, we detected that the level of H 2 S was decreased in lipopolysaccharide- (LPS-) treated L6 cells. Treatment with H 2 S increased the proliferation and viability of LPS-treated L6 cells. We found that H 2 S decreased reactive oxygen species- (ROS-) induced apoptosis through the mitogen-activated protein kinase (MAPK) signaling pathway in LPS-treated L6 cells. Administration of H 2 S alleviated LPS-induced inflammation by mediating the toll-like receptor-4 (TLR-4)/nuclear factor-kappa B (NF- κ B) signaling pathway in L6 cells. Furthermore, H 2 S improved diaphragmatic function and structure through the reduction of inflammation and apoptosis in the diaphragm of septic rats. In conclusion, these findings indicate that H 2 S ameliorates LPS-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF- κ B signaling pathways. Novel slow-releasing H 2 S donors can be designed and applied for the treatment of diaphragm dysfunction.

A novel sesquiterpene with an unprecedented epoxy lactone skeleton, named tatarinolactone, together with two new amides, a new biphenylpropanoid and two known lignans were isolated from the rhizomes of Acorus tatarinowii Schott. Their structures were identified as 6,7,8-trihydroxy-4α-isobutyl-4,7-dimethylhexahydro-6,8α-epoxychromen-2(3H)-one (1), (E)-methyl 4-[3-(4-hydroxy-3-methoxyphenyl)acrylamido]butanoate (2), (Z)-methyl 4-[3-(4-hydroxy-3-methoxyphenyl)acrylamido]butanoate enol isomer (3), (R)-4-hydroxy-3-[1-hydroxy-3-(4-hydroxy-3-methoxyphenyl)propan-2-yl]-5-methoxybenzoic acid (4), (2S,3R)-ceplignan (5), and (2R,3S)-ceplignan (6), respectively, based on extensive spectroscopic analysis and by comparison to the known compounds. To test their effects on serotonin transporters, a high content assay using hSERT-HEK293 cell line was adopted. Results indicated that compounds 1 and 4 significantly inhibited SERT activity, while compounds 2, 3, 5, and 6 significantly enhanced SERT activity, which partly explain the traditional uses of the rhizomes of Acorus tatarinowii Schott in treatments of neuropsychiatric and digestive disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To quantitatively evaluate mutual relations of 4 component drugs in anti-HIV action., Methods: The effect of TCM four components on cell growth was detected using MTT assay. The antiviral effects of 4 components were observed at the maximal nonvenomous dose. The combination index (CI) value of combined two or four components were calculated using median-effect principle. The mutual relations of two or four components for antiviral actions were assessed using CI., Results: Synergism was dominant in combination of A and B, and the effect was dose-dependent. Antagonism was dominant in combination of C and D, and the effect was dose-dependent. But the combination of A, B, C, and D was synergistic when the inhibition rate was over 10%., Conclusion: Median-effect principle can be used to quantitatively assess the anti-HIV effect of four components.