A novel red-to-near-infrared AIE fluorescent probe for detection of Hg2+ with large Stokes shift in plant and living cells.

Due to the highly toxic nature of mercury ions to living organisms, accurately detecting Hg2+ in water samples and biological systems is of great significance. In this study, we designed and synthesized a novel red-to-near-infrared Aggregation-Induced Emission (AIE) fluorescent probe (named as DS) based Fluorene derivatives on specifically for Hg2+ detection. Probe DS can visually identify Hg2+ through an red-to-near-infrared fluorescence enhancement change, characterized by a large Stokes shift (130 nm) and AIE feature. This probe offers a fast response, high selectivity and sensitivity. The Hg2+-induced deprotection reaction of the thioketal mechanism was thoroughly investigated using nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) calculation. Additionly, dynamic light scattering (DLS) results indicated that the aggregation states changes of the molecular play a crucial role in the AIE fluorescence response of probe DS toward Hg2+. The red-to-near-infrared response with AIE feature not only avoids the interference of auto-fluorescence signals in complex environments, but also reduces the fluorescence quenching caused by probe molecular aggregation. This makes probe DS highly suitable for high-quality imaging detection of Hg2+ in aqueous environments. Furthermore, probe DS demonstrates the capability for visual fluorescence detection of Hg2+ concentrations in water sample, plant roots and living cells.

Novel Bioactive Natural Products from Marine-Derived Penicillium Fungi: A Review (2021-2023).

Marine-derived Penicillium fungi are productive sources of structurally unique and diverse bioactive secondary metabolites, representing a hot topic in natural product research. This review describes structural diversity, bioactivities and statistical research of 452 new natural products from marine-derived Penicillium fungi covering 2021 to 2023. Sediments are the main sources of marine-derived Penicillium fungi for producing nearly 56% new natural products. Polyketides, alkaloids, and terpenoids displayed diverse biological activities and are the major contributors to antibacterial activity, cytotoxicity, anti-inflammatory and enzyme inhibitory capacities. Polyketides had higher proportions of new bioactive compounds in new compounds than other chemical classes. The characteristics of studies in recent years are presented.

Ultrasensitive Detection of Prostate Specific Antigen by an Unlabeled Fluorescence Aptasensor Based on the AIE Effect.

The accurate and sensitive detection of prostate specific antigen (PSA) is vital for the early diagnosis and treatment of prostate cancer. To this end, an unlabeled fluorescent aptasensor was constructed by using a novel Compound B {1,1'-(1,4-phenylene) bis(3-ethyl-1H-imidazol-3-ium) iodide} with aggregation-induced emission (AIE) activity as a fluorescence signal and NH2-Fe3O4 particle as an adsorption platform. Compound B could combine with prostate specific antigen aptamers (PSA-Apt) to form a PSA-Apt/B complex, which further generated the AIE effect. Then, PSA was added to the PSA-Apt/B solution. PSA combined with PSA-Apt/B to form the PSA-Apt/B/PSA complex. Next, NH2-Fe3O4 magnetic particles were added to the solution. Given that PSA-Apt/B/PSA would no longer combine with NH2-Fe3O4 magnetic particles, the PSA-Apt/B/PSA complex remained in the supernate after magnet separation, and the supernate showed strong fluorescence (I). When no PSA was added to the PSA-Apt/B solution, PSA-Apt/B could combine with NH2-Fe3O4 magnetic particles and would be sucked into the bottom of the test tube by magnet, and the supernate would show weak fluorescence (I0). Result showed that the difference between the above-mentioned two fluorescence values (∆I = I - I0) had an excellent linear relationship with the PSA concentration within the concentration range of 0.01-10 ng/mL, and its limit of detection was 3 pg/mL (S/N = 3). In addition, the sensor has high accuracy and can be directly used to test PSA in actual serum samples.

Molybdesum selenide-based platelet-rich plasma containing carboxymethyl chitosan/polyvinyl pyrrolidone composite antioxidant hydrogels dressing promotes the wound healing.

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.

Triterpenoid saponins from Bupleurum marginatum and their anti-liver fibrotic activities.

A new triterpenoid saponin (1), along with five known compounds (2-6), was isolated from Bupleurum marginatum Wall. ex DC, of which compounds 2-4 were obtained for the first time from this plant. The structures were confirmed by the analysis of 1D, 2D NMR, and HR-ESIMS data, and comparison with previous spectral data. Anti-liver fibrotic activities of the isolates were determined as proliferation inhibition of LPS-induced activation of HSC-T6 in vitro.

SERS-Temperature Dual-Mode T-type Lateral Flow Strip for Accurate Detection of Free and Total Prostate-Specific Antigens in Blood.

Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)-temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of T-type lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS-temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS-temperature synchronous dual-mode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer on-site by simultaneous POC detection of t-PSA and f-PSA in blood.

Six Undescribed Capnosane-Type Macrocyclic Diterpenoids from South China Sea Soft Coral Sarcophyton crassocaule: Structural Determination and Biological Evaluation.

Six undescribed capnosane-type macrocyclic diterpenes sarcocrassolins A-F (1-6) and one related known analog pavidolide D (7) were isolated from Sarcophyton crassocaule, a soft coral collected off the Nansha Islands, in the South China Sea. Their complete structures, relative configurations and absolute configurations were established through comprehensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance (QM-NMR) and single-crystal X-ray diffraction. Sarcocrassolins D (4) and E (5) showed inhibitory activity against lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW264.7 cells with IC50 values of 76.8 ± 8.0 µM and 93.0 ± 3.8 µM, respectively.

Fluorometric detection of alpha-fetoprotein based on the use of a novel organic compound with AIE activity and aptamer-modified magnetic microparticles.

BACKGROUND: Liver cancer is one of the most common cancers in the world, and it seriously threatens human life and health. Alpha-fetoprotein (AFP), as a carcinogenic glycoprotein, is an important serum marker for detecting liver cancer. Therefore, the accurate and sensitive determination of AFP is crucial for the early diagnosis and treatment of liver cancer. To this end, a label-free fluorescence aptasensor for detecting AFP based on the use of a novel organic Compound D with an aggregation-induced emission activity and aptamer-modified magnetic microparticles was constructed. RESULTS: Compound D could combine with the complementary short chain of the aptamer (CSC-Apt) of AFP to form the D/CSC-Apt complex and realize the fluorescence enhancement of Compound D. Then, magnetic particles modified by the Apt of AFP (Apt-Fe3O4) were prepared. When AFP (or nontarget substance) and D/CSC-Apt were successively added to the Apt-Fe3O4 solution, Apt-Fe3O4 selectively bound to AFP or the D/CSC-Apt complex. Magnetic separation technology showed the changes in the fluorescence intensity of the supernatant. The research results revealed a good linear relationship between the changes in the fluorescence intensity of the supernatant and concentration of AFP within the concentration range of 10-10000 pg mL-1. The proposed aptasensor could achieve high-sensitivity and high-specificity detection of AFP, and its limit of detection was 3 pg mL-1 (S/N = 3). SIGNIFICANCE AND NOVELTY: The sensor combines the advantages of high selectivity of Apt, high sensitivity of fluorescence analysis, AIE effect and good water solubility of Compound D, and rapid separation using magnetic separation technology. And it can be directly used for the detection of AFP in actual serum samples with high accuracy, whereas most of the methods reported in the literature can only detect AFP in spiked serum samples.

Corrigendum: Clostridium butyricum protects against pancreatic and intestinal injury after severe acute pancreatitis via downregulation of MMP9.

[This corrects the article DOI: 10.3389/fphar.2022.919010.].

Facial Preparation of Cyclometalated Iridium (III) Nanowires as Highly Efficient Electrochemiluminescence Luminophores for Biosensing.

In this study, highly efficient ECL luminophores composed of iridium complex-based nanowires (Ir-NCDs) were synthesized via covalently linking bis(2-phenylpyridine)-(4-carboxypropyl-2,2'-bipyridyl) iridium(III) hexafluorophosphate with nitrogen-doped carbon quantum dots (NCDs). The ECL intensity of the nanowires showed a five-fold increase in ECL intensity compared with the iridium complex monomer under the same experimental conditions. A label-free ECL biosensing platform based on Ir-NCDs was established for Salmonella enteritidis (SE) detection. The ECL signal was quenched linearly in the range of 102-108 CFU/mL for SE with a detection limit of 102 CFU/mL. Moreover, the relative standard deviations (RSD) of the stability within and between batches were 0.98% and 3.9%, respectively. In addition, the proposed sensor showed high sensitivity, selectivity and stability towards SE in sheep feces samples with satisfactory results. In summary, the excellent ECL efficiency of Ir-NCDs demonstrates the prospects for Ir(III) complexes in bioanalytical applications.

One-Step, On-Site Chemical Printing of a 3D Plasmon-Coupled Silver Nanocoral Substrate toward SERS-Based POCT.

Surface-enhanced Raman scattering (SERS) with the advantages of high sensitivity, nondestructive analysis, and a unique fingerprint effect shows great potential in point-of-care testing (POCT). However, SERS faces challenges in rapidly constructing a substrate with high repeatability, homogeneity, and sensitivity, which are the key factors that restrict its practical applications. In this study, we propose a one-step chemical printing strategy for synthesizing a three-dimensional (3D) plasmon-coupled silver nanocoral (AgNC) substrate (only need about 5 min) without any pretreatments and complex instruments. The galvanic replacement between AgNO3 and Cu sheets will provide both Ag0 for the formation of silver nanostructures and Cu2+ for the polymerization of fish sperm DNA (FSDNA). The protection of AgNCs is facilitated by the crosslinked FSDNA, which can improve the stability of the substrate and promote the control of its coral-like morphology. The obtained substrate displays excellent capacity of signal enhancement due to the 3D plasmon coupling both between nanocoral tentacles and between nanocorals and Cu sheets as well. Therefore, the AgNC substrates display high activity (enhancement factor = 1.96 × 108) and uniformity (RSD < 6%). Food colorants have been widely used in various foods to improve their color, but the inevitable toxicity of colorants seriously threatens food safety. Therefore, the proposed AgNC substrates were used to directly quantify three kinds of weak-affinity food colorant molecules including Brilliant Blue, Allura Red, and Sunset Yellow assisted by the capture by cysteamine hydrochloride (CA), showing the detection limits (S/N = 3) of 0.053, 0.087, and 0.089 ppm, respectively. The SERS method has been further applied in the detection of the three kinds of food colorants in both complex food samples and urine with recoveries of 91-119%. The satisfactory detection results suggest that the facile preparation strategy of AgNC substrates will be widely used in SERS-based POCT to promote the development of food safety and on-site healthcare.

Chitosan-based multifunctional hydrogel for sequential wound inflammation elimination, infection inhibition, and wound healing.

In this study, a composite hydrogel (QMPD hydrogel) composed of methacrylate anhydride (MA) grafted quaternary ammonium chitosan (QCS-MA), polyvinylpyrrolidone (PVP), and dopamine (DA) was designed for the sequential wound inflammation elimination, infection inhibition, and wound healing. The QMPD hydrogel formation was initiated by the ultraviolet light-triggered polymerization of QCS-MA. Furthermore, hydrogen bonds, electrostatic interactions, and "π-π" stacking between QCS-MA, PVP, and DA were involved in the hydrogel formation. In this hydrogel, the quaternary ammonium groups of quaternary ammonium chitosan and the photothermal conversion of polydopamine are capable of killing bacteria on wounds, which showed the bacteriostatic ratios of 85.6 % and 92.5 % toward Escherichia coli and Staphylococcus aureus, respectively. Moreover, the oxidation of DA sufficiently scavenged free radicals and introduced the QMPD hydrogel with good anti-oxidant and anti-inflammatory abilities. Together with the extracellular matrix-mimic tropical structure, the QMPD hydrogel significantly promoted the wound management of mice. Therefore, the QMPD hydrogel is expected to provide a new method for the design of wound healing dressings.

[Cembranoids and their bioactivities in soft coral Sarcophyton glaucum].

Chemical constituents in soft coral Sarcophyton glaucum were separated and purified by various chromatographic methods. Based on the spectral data, physicochemical properties, and comparison with the data reported in the literature, nine cembranoids, including a new cembranoid named sefsarcophinolide(1) together with eight known cembranoids, namely(+)-isosarcophine(2), sarcomilitatin D(3), sarcophytonolide J(4),(1S,3E,7E,13S)-11,12-epoxycembra-3,7,15-triene-13-ol(5), sarcophytonin B(6),(-)-eunicenone(7), lobophytin B(8), and arbolide C(9), were identified. As revealed by biological activity experiment results, compounds 2-6 had weak acetylcholinesterase inhibitory activity, and compound 5 displayed weak cytotoxicity against K562 tumor cell line.

Potential α-Glucosidase Inhibitors from the Deep-Sea Sediment-Derived Fungus Aspergillus insulicola.

Three new phenolic compounds, epicocconigrones C-D (1-2) and flavimycin C (3), together with six known phenolic compounds: epicocconigrone A (4); 2-(10-formyl-11,13-dihydroxy-12-methoxy-14-methyl)-6,7-dihydroxy-5-methyl-4-benzofurancarboxaldehyde (5); epicoccolide B (6); eleganketal A (7); 1,3-dihydro-5-methoxy-7-methylisobenzofuran (8); and 2,3,4-trihydroxy-6-(hydroxymethyl)-5-methylbenzyl-alcohol (9), were isolated from fermentation cultures of a deep-sea sediment-derived fungus, Aspergillus insulicola. Their planar structures were elucidated based on the 1D and 2D NMR spectra and HRESIMS data. The absolute configurations of compounds 1-3 were determined by ECD calculations. Compound 3 represented a rare fully symmetrical isobenzofuran dimer. All compounds were evaluated for their α-glucosidase inhibitory activity, and compounds 1, 4-7, and 9 exhibited more potent α-glucosidase inhibitory effect with IC50 values ranging from 17.04 to 292.47 µM than positive control acarbose with IC50 value of 822.97 µM, indicating that these phenolic compounds could be promising lead compounds of new hypoglycemic drugs.

A novel core-shell composite of PCN-222@MIPIL for ultrasensitive electrochemical sensing 4-nonylphenol.

A novel core-shell composite of PCN-222 and molecularly imprinted poly (ionic liquid) (PCN-222@MIPIL) with high conductivity and selectivity was prepared for electrochemical sensing 4-nonylphenol (4-NP). The electrical conductivities of some MOFs including PCN-222, ZIF-8, NH2-UIO-66, ZIF-67, and HKUST-1 were explored. The results indicated that PCN-222 had the highest conductivity and was then used as a novel imprinted support. PCN-222@MIPIL with core-shell and porous structure was synthesized using PCN-222 as support and 4-NP as template. The average pore volume of PCN-222@MIPIL was 0.085 m3 g-1. In addition, the average pore width of PCN-222@MIPIL was from 1.1 to 2.7 nm. The electrochemical response for PCN-222@MIPIL sensor for 4-NP was 2.54, 2.14, and 4.24 times that of non-molecularly imprinted poly (ionic liquid) (PCN-222@NIPIL), PCN-222, and MIPIL sensors, respectively, which result from superior conductivity and imprinted recognition sites of PCN-222@MIPIL. The current response of PCN-222@MIPIL sensor to 4-NP concentration from 1 × 10-4 to 10 µM presented an excellent linear relationship. The detection limit of 4-NP was 0.03 nM. The synergistic effect between the PCN-222 supporter with high conductivity, specific surface area and shell layer of surface MIPIL results in the outstanding performance of PCN-222@MIPIL. PCN-222@MIPIL sensor was adopted for detecting 4-NP in real samples and presented to be a reliable approach for determining 4-NP.

Chitosan-Based Hemostatic Hydrogels: The Concept, Mechanism, Application, and Prospects.

The design of new hemostatic materials to mitigate uncontrolled bleeding in emergencies is challenging. Chitosan-based hemostatic hydrogels have frequently been used for hemostasis due to their unique biocompatibility, tunable mechanical properties, injectability, and ease of handling. Moreover, chitosan (CS) absorbs red blood cells and activates platelets to promote hemostasis. Benefiting from these desired properties, the hemostatic application of CS hydrogels is attracting ever-increasing research attention. This paper reviews the recent research progress of CS-based hemostatic hydrogels and their advantageous characteristics compared to traditional hemostatic materials. The effects of the hemostatic mechanism, effects of deacetylation degree, relative molecular mass, and chemical modification on the hemostatic performance of CS hydrogels are summarized. Meanwhile, some typical applications of CS hydrogels are introduced to provide references for the preparation of efficient hemostatic hydrogels. Finally, the future perspectives of CS-based hemostatic hydrogels are presented.

New Azaphilones from the Marine-Derived Fungus Penicillium sclerotiorum E23Y-1A with Their Anti-Inflammatory and Antitumor Activities.

Nine new azaphilones, including penicilazaphilones I-N (1, 2 and 6-9), epi-geumsanol D (3) and penidioxolanes C (4) and D (5) were isolated from the culture of the marine-derived fungus Penicillium sclerotiorum E23Y-1A. The structures of the isolates were deduced from extensive spectroscopic data (1D and 2D NMR), high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. All the azaphilones from P. sclerotiorum E23Y-1A were tested for their anti-inflammatory and antitumor activities. Penicilazaphilone N (9) showed moderate anti-inflammatory activity with an IC50 value of 22.63 ± 2.95 µM, whereas penidioxolane C (4) exhibited moderate inhibition against human myeloid leukemia cells (K562), human liver cancer cells (BEL-7402), human gastric cancer cells (SGC-7901), human non-small cell lung cancer cells (A549), and human hela cervical cancer cells, with IC50 values of 23.94 ± 0.11, 60.66 ± 0.13, 46.17 ± 0.17, 60.16 ± 0.26, and 59.30 ± 0.60 µM, respectively.

Sensitive determination of prostate-specific antigen with graphene quantum dot-based fluorescence aptasensor using few-layer V2CTx MXene as quencher.

A novel fluorescence aptasensor of prostate-specific antigen (PSA) was established using few-layer vanadium carbide (FL-V2CTx) nanosheet as a quencher. First, FL-V2CTx was prepared by the delamination of multi-layer V2CTx (ML-V2CTx) with tetramethylammonium hydroxide. The aptamer-carboxyl graphene quantum dots (CGQDs) probe was prepared by combining the aminated PSA aptamer and CGQDs. Then, the aptamer-CGQDs were absorbed onto the surface of FL-V2CTx by hydrogen bond interaction, which led to the decrease in fluorescence of aptamer-CGQDs due to photoinduced energy transfer. After addition of PSA, PSA-aptamer-CGQDs complex was released from FL-V2CTx. The fluorescence intensity of aptamer-CGQDs-FL-V2CTx with PSA was higher than that without PSA. The FL-V2CTx-based fluorescence aptasensor provided a PSA detection linear range from 0.1 to 20 ng mL-1 with detection limit of 0.03 ng mL-1. The ΔF value of fluorescence intensities for aptamer-CGQDs-FL-V2CTx with and without PSA was 5.6, 3.7, 7.7, and 5.4 times of ML-V2CTx, few-layer titanium carbide (FL-Ti3C2Tx), ML-Ti3C2Tx and graphene oxide aptasensors, respectively, indicating the advantage of FL-V2CTx. The aptasensor had high selectivity for PSA detection compared with some proteins and tumor markers. This proposed method had convenience and high sensitivity for PSA determination. The determination results of PSA in human serum samples using the aptasensor were consistent with those by chemiluminescent immunoanalysis. The fluorescence aptasensor can be successfully applied for PSA determination in serum samples of prostate cancer patients.

A novel fluorescence aptasensor based on PCN-223 as an efficient quencher for sensitive determination of prostate-specific antigen.

A novel fluorescence aptasensor based on PCN-223 as an efficient quencher was developed to sensitively detect prostate-specific antigen (PSA). The 5-carboxytetramethylrhodamine (TAMRA)-labeled PSA aptamer was adsorbed on PCN-223 by π-π stacking and hydrogen-bonding interactions, which contributed to fluorescence quenching because of the photoinduced electron transfer from TAMRA to PCN-223. In addition, the amount of quenched fluorescence of the PSA-binding aptamer complex-PCN-223 was lower than that of TAMRA aptamer-PCN-223 without PSA (at excitation/emission peaks of 545/582 nm), which can be explained by the fact that the PSA-binding aptamer complexes contributed to the separation of the aptamer from PCN-223. ∆F value of fluorescence intensities for TAMRA aptamer-PCN-223 with and without PSA showed a good linear relationship with PSA concentration over a range of 0.1 to 24 ng mL-1, with a detection limit of 0.05 ng mL-1. Compared with three metal-organic frameworks (MOFs) of UiO-66-NH2, ZIF-67, and Ni3(HITP)2 as quenchers, PCN-223 as a Zr-MOF exhibited the highest ∆F value for PSA detection. The advantage of PCN-223 could be attributed to its carboxyl, benzene, and porphyrin groups, the large specific surface area and good biocompatibility. This proposed aptasensor can be successfully used to detect PSA in sera of prostate cancer patients. The PSA detection results of this aptasensor were consistent with those which were obtained from hospital by Archtecti2000sr automatic chemiluminescence immunoanalyzer. The proposed aptasensor has potential clinical detection application.

Two new triterpenoid saponins from Bupleurum marginatum Wall. ex DC.

Two new triterpenoid saponins (1 and 2), together with two known saponins (3 and 4) were isolated from Bupleurum marginatum Wall. ex DC. Their structures were elucidated by the comprehensive spectroscopic analysis. Compounds 1 and 2 represented the rare example of an oleanane-type triterpenoid with two sugar moieties at C-3 and C-28. The cytotoxic activity of four compounds was evaluated against normal heptocell BRL-3A in vitro.