Discovery of a Potent Antiosteoporotic Drug Molecular Scaffold Derived from Angelica sinensis and Its Bioinspired Total Synthesis.

Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.

A novel fluorescent sensor with an overtone peak reference for highly sensitive detection of mercury (II) ions and hydrogen sulfide: Mechanisms and applications in environmental monitoring and bioanalysis.

The present study introduces a novel fluorescent sensor with an overtone peak reference designed for the detection of mercury (Ⅱ) ions (Hg2+) and hydrogen sulfide (H2S). The study proposes two novel response mechanisms that hinges on the synergistic effect of cation exchange dissociation (CED) and photo-induced electron transfer (PET). This sensor exhibits a remarkable detection limit of 2.9 nM for Hg2+. Additionally, the sensor reacts with H2S to generate nickel sulfide (NiS) semiconductor nanoparticles, which amplify the fluorescence signal and enable a detection limit of 3.1 nM for H2S. The detection limit for H2S is further improved to 29.1 pM through the surface functionalization of the nanomaterial with pyridine groups (increasing reactivity) and chelation of gold nanoparticles (AuNPs), which enhances the sensor's specificity. This improvement is primarily due to the surface plasmon resonance (SPR) of AuNPs and their affinity for H2S. The single-emission strategy can yield skewed results due to environmental changes, whereas the overtone peak reference strategy enhances result accuracy and reliability by detecting environmental interference through reference emission peaks. In another observation, the low-toxicity dihydropyrene-bipyridine nanorods (TPP-BPY) has been successfully utilized for both endogenous and exogenous H2S detection in vivo using a mouse model. The successful development of TPP-BPY is expected to provide an effective tool for studying the role of H2S in biomedical systems.

Efficacy of Yiqi Wenyang Huoxue method in treating adult bronchial asthma: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Bronchial asthma (BA) is a chronic inflammatory disease of the airway, which has the characteristics of recurrent attacks and difficult to cure. Glucocorticoid and bronchodilator are the primary treatment drugs for asthma. Although the treatment has made some progress, the control status is still not ideal. According to clinical reports, the Yi-qi Wen-yang Huo-xue method (YQWYHXM) of Traditional Chinese Medicine (TCM) is safe and effective in the treatment of BA, but there is not enough evidence to prove it. Based on it, we conducted this systematic evaluation. METHODS: Eight databases and Clinical trial registries (Embase, Cochrane, PubMed, CNKI, CBM, Wanfang, VIP, China Clinical Trial Registry and Clinical Trails) were searched from the establishment of those until January 22, 2021 with the following terms for retrieval: BS, TCM, Chinese medicinal herb, Chinese herbal medicine and randomized controlled trial. Data analysis was performed by 2 researchers using RevMan 5.3 and SATA 16.0 separately from the Cochrane Collaboration. RESULTS: This study will be able to provide definitive evidence to clarify all the suspicions we seek, confirming the effectiveness of YQWYHXM in the treatment of adults with BA. CONCLUSION: This study will prove that YQWYHXM is a safe and effective TCM adjuvant therapy for BA. REGISTRATION: Efficacy of Yiqi Wenyang Huoxue method in Treating Adult Bronchial Asthma. ASTHMA: A protocol for Systematic Review and Meta-Analysis of Randomized Controlled Trials. PROSPERO 2021 CRD42021256791. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256791.

The isolation, structure and fragmentation characteristics of natural truxillic and truxinic acid derivatives in Abrus mollis leaves.

Five undescribed compounds were separated from Abrus mollis leaves, including two truxillate forms (abrusamide D, H) and three truxinate forms (abrusamide E, F, G). The absolute configuration of abrusamide D was determined by X-ray crystallography. Abrusamide A was reassessed and corrected to be ß-truxinate configuration rather than α-form. LC-MS/MS and CD spectroscopy were applied to determine and analyze ten compounds, including four truxillate forms (abrusamide B ~ D and H), four truxinate forms (abrusamide E ~ G and A), and two precursors [(E)-N-(4-hydroxycinnamoyl) tyrosine, (Z)-N-(4-hydroxycinnamoyl) tyrosine]. It showed that the fragmentation pattern of truxillate was symmetric, while that of truxinate was asymmetric and irregular. The CD Cotton effect was related to cyclobutane configuration. These findings provided strong evidence for the cyclobutane dimers to discriminate their configuration. In addition, the bioactivity assay showed that the compounds had low toxicity and anti-inflammatory effect.

[Cultivation of Spirulina platensis in Digested Piggery Wastewater Pretreated by SBR with Operating Conditions Optimization].

Digested piggery wastewater(DPW) contains high concentrations of nitrogen and phosphorus which could be used as a cost-effective culture medium for Spirulina platensis. However, Spirulina platensis would be limited by many factors in the complex composition of DPW, especially the high concentration of ammonium. In this paper, a traditional sequencing batch reactor(SBR) was used to remove these inhibitors in DPW. The retention of nitrate and nitrite in the effluent, which was used as nitrogen source for cultivating Spirulina platensis, was studied at different ratios of chemical oxygen demand(COD) to total nitrogen(TN) in the influent. By comparing the growth of Spirulina platensis in the related effluents, the operation condition of SBR was optimized. The lab-scale cultivation results showed that Spirulina platensis possessed a high biomass yield of 0.084 g·(L·d)-1 in the effluent when the COD/TN ratio of SBR influent was 3.0. In particular, the concentrations of ammonium, nitrate and nitrite in the effluent were 51.2 mg·L-1, 91.6 mg·L-1and 213.1 mg·L-1, respectively. Furthermore, the aforementioned effluent was also used to culture Spirulina platensis in a 120 L outdoor raceway pond, and the growth rate of Spirulina platensis reached(0.075±0.003)g·(L·d)-1 after 10-day culture. The protein content of Spirulina platensis was approximately 60% and the removal efficiency of ammonium was 99%. This study provides an alternative method for the utilization of DPW.

Role of nanoparticles in controlling arsenic mobilization from sediments near a realgar tailing.

Microcosm experiments were conducted to investigate the mechanism of microbial-mediated As mobilization from high arsenic tailing sediments amended with nanoparticles (NPs). The addition of SiO2 NPs could substantially stimulate arsenic mobilization in the sodium acetate amendment sediments. However, the addition of Fe2O3 and Fe3O4 NPs restrained arsenic release because these NPs resulted in Fe-As coprecipiate. Moreover, NP additions in sediments amended with sodium acetate as the electron donor clearly promoted microbial dissimilatory iron reduction. Nearly 4 times the Fe(II) (11.67-12.87 mg·L(-1)) from sediments amended with NPs and sodium acetate was released compared to sediments amended with only sodium acetate (3.49 mg·L(-1)). Based on molecular fingerprinting and sequencing analyses, the NP additions could potentially change the sediment bacterial community composition and increase the abundance of Fe(III) and As(V) reduction bacteria. Several potential NP-stimulated bacteria were related to Geobacter, Anaeromyxobacter, Clostridium, and Alicyclobacillus. The findings offer a relatively comprehensive assessment of NP (e.g., Fe2O3, Fe3O4, and SiO2) effects on sediment bacterial communities and As mobilization.