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Six new prenylated flavonoids, named visconaeas A-F (1-6), and eleven known isopentenyl flavonoids (7-17) were isolated from Dodonaea viscosa (L.) Jacq. The structures of the separated compounds were determined through comprehensive spectral analysis and quantum chemical calculations. These compounds were tested for their anti-Zika virus and cytotoxicity activities. The results indicated that compound 4 showed low cytotoxicity and strong anti-Zika virus potential with EC 50 16.34 μM., 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. Published by Elsevier B.V.)

Three new lanostane triterpenoids ( 1-3 ) along with two new amides fatty compounds ( 4-5 ) were isolated from the ethyl acetate extract of a culture of the endophytic fungus Alternaria sp. gx-2. Their structures were identified by 1D and 2D NMR spectral data and HRESIMS. Compounds 1-12 were evaluated for their anti-inflammatory and tyrosinase inhibition activities. The isolated compounds did not show inhibitory activities at a concentration of 100 μM against tyrosinase, while under the concentration of 10 μM, the release of lactate dehydrogenase (LDH) inhibition rate of compound 1 was 54.45%, indicating that compound 1 had moderate anti-inflammatory activity on the activation of NLRP3 inflammasome.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC 50 value of 2.830 μM and compound 12 with the IC 50 value of 0.682 μM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1β was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity 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 Ltd. All rights reserved.)

We present an advancement in synthesizing organophosphorus compounds via chemoselective phosphorylation achieved by a palladium and SelectPhos ligand system (Pd/ L1 ). This catalysis system exhibits remarkable chemoselectivity, even in poly(pseudo)halide substrates and overcoming toxicity and substrate scope limitations. The catalytic system is robust, which is demonstrated across diverse substrates such as chloroaryl and bromoaryl triflates. Furthermore, we present a one-pot sequential strategy combining phosphorylation with Suzuki-Miyaura coupling, providing a versatile platform for the efficient synthesis of complex organophosphorus compounds, challenging conventional reactivity paradigms.

In this study, a novel and efficient Pd-catalyzed chemoselective deuterodehalogenation reaction of halogenated aryl triflates was developed using isopropanol- d 8 as the deuterium source. This chemoselective reaction afforded an unconventional chemoselectivity order of C-Br > C-Cl > C-OTf. This catalytic system was successfully applied to chemoselective hydrodehalogenation of chloroaryl triflates, providing excellent C-Cl chemoselectivity over C-OTf.

Two new compounds, including a norsesquiterpenoid, annuionone H ( 1 ), and a quassinoid, picraqualide G ( 2 ), along with eleven known compounds ( 3-13 ), were isolated from the twigs and leaves of Picrasma quassioides . Comprehensive spectroscopic analyses and NMR calculation with DP4+ analysis were used to identify their structures. Moreover, of all these compounds, compound 4 showed a week inhibition rate in the anti-inflammatory screening results against mouse macrophage J774A.1 cell.

Four new diterpenoids (1-4) and sixteen known diterpenoids (5-20) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were rhamofolane diterpenoids with a 5/7/6 tricyclic systems, compound 3 was a lathyranes diterpenoid, and compound 4 was a jathophanes diterpenoid. The isolated compounds were tested for their cytotoxicity and anti-Zika virus properties, and compounds 9 and 15 showed low cytotoxicity and strong anti-Zika virus properties with EC 50 2.63 and 5.94 μM, respectively. Further, the inhibitory effects of compounds on protein levels were determined using Western blotting and immunofluorescence assays., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The adsorption performances of ammonia nitrogen (NH + 4 -N) in water by unmodified biochar are ineffective. In this study, nano zero-valent iron-modified biochar (nZVI@BC) was prepared to remove NH + 4 -N from water. The NH + 4 -N adsorption characteristics of nZVI@BC were investigated through adsorption batch experiments. The composition and structure characteristics of nZVI@BC were analyzed using scanning electron microscopy, energy spectrum analysis, BET-N 2 surface area (SSA), X-ray diffraction, and FTIR spectra to explore the main adsorption mechanism of NH + 4 -N by nZVI@BC. The results showed that the composite synthesized at the iron to biochar mass ratio of 1:30 (nZVI@BC1/30) performed well in NH + 4 -N adsorption at 298 K. The maximum adsorption amount of nZVI@BC1/30 at 298 K was remarkably increased by 45.96% and reached 16.60 mg·g -1 . The pseudo-second-order model and Langmuir model fitted well with the adsorption process of NH + 4 -N by nZVI@BC1/30. There was competitive adsorption between coexisting cations and NH + 4 -N, and the sequence of coexisting cations to the adsorption of NH + 4 -N by nZVI@BC1/30 was Ca 2+ > Mg 2+ > K + > Na + . The adsorption mechanism of NH + 4 -N by nZVI@BC1/30 could be mainly attributed to ion exchange and hydrogen bonding. In conclusion, nano zero-valent iron-modified biochar can improve the adsorption performance of NH + 4 -N and enhance the application potential of biochar in the field of nitrogen removal from water.

One new alkaloid, picrasine A, two new quassinoids, picralactones A-B, together with eleven known compounds were isolated from Picrasma chinensis P.Y. Chen. The structures of these compounds were determined using 1D and 2D NMR, HR-ESI-MS, and IR spectroscopic data, and by comparison with published data. Some compounds were tested for tyrosinase inhibiting activity, however, none of them exhibited strong inhibitory effects., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Twelve new clerodane diterpenoids named callicarpanes A-L (1-12), together with eight known compounds (13-20), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1, 3, 5, 9, 10, 12, 15, 16, and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC 50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 μM. Further study revealed that compound 10 repressed IL-1β secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Callintegers A ( 1 ) and B ( 2 ), unprecedented clerodane norditerpenoids based on a novel carbon skeleton, were isolated from Callicarpa integerrima . Compounds 1 and 2 possess a novel 6/6/6-fused tricyclic ring system. Their structures and absolute configurations were determined by quantum chemical calculations, spectroscopic analysis, and single-crystal X-ray diffraction methods. Biological evaluation showed that compound 2 inhibited IL-1β secretion in a dose-dependent manner with an IC 50 value of 5.5 ± 3.2 μM. Caspase-1 maturation and IL-1β secretion were also reduced, indicating that compound 2 impaired NLRP3 inflammasome activation.

Background: Canadian sodium intakes remain high despite population-wide sodium reduction initiatives, highlighting the need for personal action in reducing dietary sodium. eHealth interventions support patients in dietary change and assist clinicians in decision-making and delivering care, including provision of advice. To date, impact of diet-focused eHealth tools, like the Sodium Calculator (SC) dietary screening tool, on clinical outcomes has received minimal examination. This study assessed feasibility of a randomized controlled trial (RCT) protocol to examine the impact of the SC, a physician-focused intervention, on the quality of dietary sodium reduction advice provided by physicians to their patients with hypertension., Methods: Primary care physicians from community-based primary care clinics were randomized to one of two groups: (1) 'usual care' for dietary sodium counselling or (2) dietary sodium counselling using the SC ('experimental group'). The primary endpoint was protocol feasibility defined by the following outcomes: process (e.g. recruitment, retention, protocol adherence, acceptability of intervention), resources (e.g. needs, impact on workflow), and management (e.g. staff requirements). Outcomes were assessed using direct observation, interviews, and questionnaires with patients, physicians, and clinic staff., Results: Seven physicians (n = 4 in experimental group, n = 3 in usual care group) and 65 patients with hypertension (48.5% men, 69.8 ± 10.1 years) successfully participated. The main challenges identified is related to recruitment rate (48% for patients, 20% for physicians) and physician protocol adherence (76%). These improved with minor protocol modifications. There were several areas of protocol success such as no disruption to physician workflow, hiring clinic nurses as research staff, having a physician site lead to support physician recruitment, and a 'Protocol Prompt Form' to increase physician protocol adherence. Importantly, there was a high degree of acceptability of the SC intervention among experimental group physicians [n = 3 (75%)]., Conclusions: The modified RCT protocol was considered feasible. The identified successes can be leveraged, and the risks can be mitigated, during implementation of a full-scale RCT. Assessment of this RCT protocol is an important step in understanding the effectiveness of diet-focused eHealth tools to supporting physician self-efficacy in assessing, monitoring, and implementing dietary advice in routine clinical practice and supporting patients in effective behaviour change., (© 2022. The Author(s).)

As a cell-penetrating peptide, polyarginine is widely used in drug delivery systems based on its membrane permeation ability. Previously, we developed the mPEG-PLA- b -polyarginine(R15) triblock copolymer, which exhibited a high siRNA delivery efficiency both in vitro and in vivo . As a continued effort, here the amphiphilic diblock polymer PCL-R15 was synthesized as a simplified model to further elucidate the structure-activity relationship of arginine-based amphiphilic polymers as siRNA delivery systems, and the cellular trafficking mechanisms of the PCL-R15/siRNA nanoplexes were investigated to understand the interaction patterns between the nanoplexes and cells. Compared to the R15/siRNA complexes, the introduction of PCL moiety was found to result in the stronger interactions with cells and the enhanced transfection efficiency after the formation of condensed nanoplexes. Caveolae-mediated endocytosis and clathrin-mediated endocytosis were major routes for the internalization of PCL-R15/siRNA nanoplexes. The intracellular release of siRNA from nanoplexes was confirmed by fluorescence resonance energy transfer assay. It was also noticed that the internalized PCL-R15/siRNA nanoplexes were transported through digestive routes and trapped in lysosomes, which may be the bottleneck for efficient siRNA delivery of PCL-R15/siRNA nanoplexes. This study investigated the relationship between the polymer structure of PCL-R15 and the cellular interaction patterns, which may render implications on the rational design of polyarginine-based siRNA delivery systems.

The impact of secondary metabolites on fruit quality, plant growth and human health has led to an increased demand for analytical methods to characterize and quantify these metabolites in recent years. A versatile, sensitive and rapid method based on UHPLC-QqQ-MS/MS was developed for simultaneous qualitation and quantitation of coumarins, furocoumarins, flavonoids and phenolic acids. The chromatographic elution and multiple reaction monitoring mode transitions were optimized to achieve good separation and accurate quantitation of 47 analytes, including 13 groups of isomers, during a single 13 min chromatographic run. This method was validated with good precision and recoveries, wide linear ranges and low limits of detection and quantitation (0.014-1.50 μg L -1 ). The validated method was further applied to quantify the analytes in flavedo, albedo and pulp from two pummelo varieties, C. grandis 'Shatianyu' and C. grandis 'Guanximiyu'. This method combines high sensitivity, good selectivity, and short chromatographic run time., 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 © 2020 Elsevier Ltd. All rights reserved.)

A safe and efficient delivery system is critical for clinical application of siRNA. However, the conventional electrostatic interaction-based siRNA nanoplexes with bulk mixing preparation were always unsatisfactory for its stability and safety. In this study, the new core-shell lipid/PCL-PEI/siRNA nanoparticles (LPS NPs) endowing holonomic constraint of siRNA in the inner core were prepared by microfluidic technology. On the microfluidic chip, siRNAs were completely compressed into the inner hydrophilic core of reverse PCL-PEI micelles at a low N/P ratio of 5, followed by coating a neutral lipid membrane to form core-shell nanoparticles, which had a uniform size (120.2 ± 1.4 nm) and a negative charge (-8.8 ± 1.6 mV). Compared to bulk mixing-based LMS NPs, the lower usage of cationic PCL-PEI materials and stronger protection of siRNA in serum were found in the microfluidic-based LPS NPs. Furthermore, it was demonstrated that the LPS NPs exhibited significant downregulation of EGFR mRNA and protein expression level both in vitro and in vivo, and showed significant inhibition of tumor growth following systemic administration along with no obvious systemic toxicity. These findings demonstrated that the microfluidic-based lipid/polymer hybrid nanoassemblies would offer a promising siRNA delivery system for clinical application.

Objective: To explore the clinical features and therapeutic efficacy of nasal endoscopic optic nerve decompression for traumatic optic neuropathy (TON)treatment. Method: Two hundred and twelve cases (217 eyes) with TON were retrospectively analyzed in our study, who were treated with nasal endoscopic optic nerve decompression in our institution from 1999 to 2016. χ ² -test was used to explore the potential prognostic factors on visual acuity. Result: All patients were followed up from 6 months to 2 years postoperatively, and the effective rate was 54.38%(118/217).In the 166 eyes with no light perception (NLP), the effective rate was 46.39% (77/166), while in the 51 eyes with light perception (LP), the effective rate was 80.39% (41/51).The therapeutic efficacy of patients with LP or above LP was better than that of NLP, and the difference was statistically significant(χ ²=18.186, P < 0.01).Moreover, the therapeutic efficacy of patients without an optic canal fracture was better than that with an optic canal fracture，and the difference had statistical significance (χ ²=10.096, P <0.01). Conclusion: The efficacy of nasal endoscopic optic nerve decompression on TON was positive, and even for the patients with NLP or a long history also should have a try., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Systemic delivery of siRNA is the most challenging step to transfer RNAi to clinical application for breast cancer therapy. In this study, the tumor targeted, T7 peptide modified core-shell nanoparticles (named as T7-LPC/siRNA NPs) were constructed to achieve effective systemic delivery of siRNA. The core-shell structure of T7-LPC/siRNA NPs enables them to encapsulate siRNA in the core and protect it from RNase degradation during circulation. In vitro cellular uptake and gene silencing experiments demonstrated that T7-LPC/siEGFR NPs could deliver EGFR siRNA into breast cancer cells through receptor mediated endocytosis and effectively down-regulate the EGFR expression. In vivo distribution study proved the T7-LPC/siRNA NPs could deliver fluorescence labeled siRNA to the tumor site more efficiently than the non-targeted PEG-LPC/siRNA NPs after intravenous administration. Furthermore, the experiments of in vivo tumor therapy confirmed that intravenous administration of T7-LPC/siEGFR NPs led to an effective EGFR down-regulation and an obvious inhibition of breast tumor growth, with little activation of immune responses and negligible body weight loss. These results suggested that T7-LPC/siRNA NPs could be an effective and safe systemic siRNA delivery system for RNAi-based breast cancer therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In our previous study, a H-shape gemini-like cationic lipid (ssGLCL, formerly named as CLD), composed of two hydrophilic lysine heads and two hydrophobic oleyl alcohol tails with a bridge of the redox-active disulfide-bond, had been synthesized and used as a nanocarrier for delivering small interfering RNAs (siRNAs) into cells. In order to further elucidate the role of disulfide (-S-S-) bridge on the activity of ssGLCL based siRNA delivery, a comparable ccGLCL bridged with a non-reducible carbon-carbon bond was synthesized and used as control in this study. Both two H-shape GLCL molecules could individually self-assemble into cationic nanoparticles in water phase and complex with negatively-charged siRNA into nanoplexes with particle size of ~200nm and zeta potential of ~ +30mV, and exhibit effective siRNA delivery both in vitro and in vivo. Investigation of internalization pathway displayed that both ssGLCL/siRNA and ccGLCL/siRNA nanoplexes were predominantly internalized into MCF-7 cells by the clathrin-mediated endocytosis pattern. Although a lower cellular uptake of siRNA was found in the human breast cancer MCF-7 cells, the ssGLCL/siRNA nanoplexes could exhibit similar or even stronger down-regulation effects on the targeted EGFR mRNA and protein in MCF-7 cells when compared to the ccGLCL/siRNA nanoplexes. Furthermore, mechanistic study showed that the enhanced down-regulation effects of ssGLCL/siRNA nanoplexes on targeted mRNA and protein were probably attributed to the increased release of siRNA from lysosomes to cytoplasm following the cleavage of redox-active disulfide-bridge in ssGLCL. Therefore, we believed that the redox-active H-shape ssGLCL could be a potential nanocarrier towards improving siRNA delivery., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A somatostatin analog, vapreotide (VAP), can be used as a ligand for targeting drug delivery based on its high affinity to somatostatin receptors (SSTRs), which is overexpressed in many tumor cells. RNA interference plays an important role on downregulation of vascular endothelial growth factor (VEGF), which is important for tumor growth, progression and metastasis. To improve tumor therapy efficacy, the vapreotide-modified core-shell type nanoparticles co-encapsulating VEGF targeted siRNA (siVEGF) and paclitaxel (PTX), termed as VAP-PLPC/siRNA NPs, were developed in this study. When targeted via somatostatin receptors to tumor cells, the VAP-PLPC/siRNA NPs could simultaneously delivery siVEGF and PTX into cells and achieve a synergistic inhibition of tumor growth. Interestingly, in vitro cell uptake and gene silencing experiments demonstrated that the targeted VAP-PLPC/siRNA NPs exhibited significant higher intracellular siRNA accumulation and VEGF downregulation in human breast cancer MCF-7 cells, compared to those of the non-targeted PEG-PLPC/siRNA NPs. More importantly, in vivo results further demonstrated that the targeted VAP-PLPC/siRNA NPs had significant stronger drug distribution in tumor tissues and tumor growth inhibition efficacy via receptor-mediated targeting delivery, accompany with an obvious inhibition of neovascularization induced by siVEGF silencing. These results suggested that the co-delivery of siRNA and paclitaxel via vapreotide-modified core-shell nanoparticles would be a promising approach for tumor targeted therapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Our previous study had reported that cholesterol-grafted poly(amidoamine) (rPAA-Chol polymer) was able to self-assemble into cationic nanoparticles and act as a potential carrier for siRNA transfection. In this study, the core-shell type lipid/rPAA-Chol hybrid nanoparticles (PEG-LP/siRNA NPs and T7-LP/siRNA NPs) were developed for improving in vivo siRNA delivery by modifying the surface of rPAA-Chol/siRNA nanoplex core with a lipid shell, followed by post-insertion of polyethylene glycol phospholipid (DSPE-PEG) and/or peptide (HAIYPRH, named as T7) modified DSPE-PEG-T7. The integrative hybrid nanostructures of LP/siRNA NPs were evidenced by dynamic light scattering (DLS), confocal laser scanning microscope (CLSM), cryo-transmission electron microscope (Cryo-TEM) and surface plasmon resonance (SPR) assay. It was demonstrated that the T7 peptide modified LP/siRNA NPs (T7-LP/siRNA NPs) exhibited uniform and spherical structures with particle size of 99.39 ± 0.65 nm and surface potential of 42.53 ± 1.03 mV, and showed high cellular uptake efficiency and rapid endosomal/lysosomal escape ability in MCF-7 cells. Importantly, in vitro gene silencing experiment demonstrated that both of pegylated and targeted LP/siEGFR NPs exhibited significantly stronger downregulation of EGFR protein expression level in MCF-7 cells, compared to that of the physical mixture of siRNA lipoplexes and rPAA-Chol/siRNA nanoplexes. In vivo tumor therapy on nude mice bearing MCF-7 tumors further confirmed that the targeted T7-LP/siEGFR NPs exhibited the greatest inhibition on tumor growth via transferrin receptor-mediated targeting delivery, without any activation of immune responses and significant body weight loss following systemic administration. These findings indicated that the core-shell type T7-LP/siRNA nanoparticles would be promising siRNA delivery systems for in vivo tumor-targeted therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The distributions and effects of 31 selected endocrine disrupting chemicals (EDCs) in two drinking water factories were analyzed in this study. The distributions of EDCs were analyzed by solid phase extraction (SPE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS). The concentrations of these EDCs were from lower than the LOD (limit of detection) to 23.13 ng L (- 1) in the samples; most of them were lower than 1 ng L (- 1). The highest concentration (23.13 ± 1.45 ng L (- 1)) was detected in the raw water. Twenty-six chemicals were found in the raw water and only five in the finished water of drinking water factory A, while 25 chemicals were detected in the raw water and two in the finished water of drinking water factory B. The results indicate that most of the EDCs can be removed by the water treatment process. In the advanced treatment process, the ozonation processes have the highest removal efficiency. Separate analyses in May and September show similar results. Apart from the chemical analysis, yeast strain transformed when the estrogen receptor α (ERα) gene was employed to test the estrogenic effects of the water samples. Due to the low concentrations of these EDCs, no significant estrogenic effects were found from the samples.