Chelerythrine (CH) and ethoxychelerythrine (ECH) are chemical reference substances for quality control of Chinese herbal medicines, and ECH is the dihydrogen derivative of CH. In this study, their ...fluorescence and absorption spectra, as well as their structural changes in different protic solvents were compared. It was observed that their emission fluorescence spectra in methanol were almost the same (both emitted at 400 nm), which may be attributed to the nucleophilic and exchange reactions of CH and ECH with methanol molecules with the common product of 6-methoxy-5,6-dihydrochelerythrine (MCH). When diluted with water, MCH was converted into CH, which mainly existed in the form of positively charged CH+ under acidic and near-neutral conditions with the fluorescence emission at 550 nm. With the increase of pH value of the aqueous solution, CH+ converted to 6-hydroxy-5,6-dihydrochelerythrine (CHOH) with the fluorescence emission at 410 nm. The fluorescence quantum yields of MCH and CHOH were 0.13 and 0.15, respectively, and both the fluorescence intensities were much stronger than that of CH+. It is concluded that CH and ECH can substitute each other in the same protic solvent, which was further verified by high-performance liquid chromatography. This study will help in the investigation of structural changes of benzophenanthridine alkaloids and will provide the possibility for the mutual substitution of standard substances in relevant drug testing.
In this work, the origins for the spectral difference between two isoflavones, formononetin (F) and ononin (FG), are revealed via a comparison study of the fluorescence molecular structure. The ...fluorescence enhancement of FG in hot alkaline conditions is reported for the first time. For F, there is almost no fluorescence under acidic conditions, but when the pH is >4.8, its fluorescence begins to increase due to the deprotonation of 7-OH. Under a pH between 9.3 and 12.0, the anionic form of F produces a strong and stable fluorescence. The fluorescence quantum yield (Yf) of F is measured to be 0.042. FG shows only weak fluorescence in aqueous solutions under a wide range of pH until it is placed in hot alkaline solutions, which is attributed to the cleavage reaction of the γ-pyrone ring in FG. The Yf of FG is determined to be 0.020. Based on the fluorescence sensitization methods of F and FG, the quantitative analysis and detection of two substances can be realized. The limit of the detections for F and FG are 2.60 ng·mL
and 9.30 ng·mL
, respectively. The linear detection ranges of F and FG are 11.7~1860 ng·mL
and 14.6~2920 ng·mL
, respectively. Although the structural relationship between F and FG is glycoside and aglycone, under hot alkaline conditions, the final products after the cleavage and hydrolysis reactions are essentially different. The different fluorescence characteristics between F and FG pave a way for further identification and a quantitative analysis of the corresponding components in Chinese herbal medicine.
The endolysin EFm1 from the E. faecalis 002 (002) phage IME-EF1 efficiently lyses E. faecalis, a gram-positive bacterium that severely threatens human health. Here, the structure and lytic activity ...of EFm1 toward E. faecalis were further investigated. Lytic activity shows that EFm1 specifically lyses 002 and 22 other clinically isolated E. faecalis, but not E. faecalis 945. Therefore, EFm1 may be an alternative biomaterial to prevent and treat diseases caused by E. faecalis. A structural analysis showed that EFm1D166Q is a tetramer consisting of one full-length unit with additional C-terminal domains (CTDs), while EFm1166–237 aa is an octamer in an asymmetric unit. Several crucial domains and novel residues affecting the lytic activity of EFm1 were identified, including calcium-binding sites (D20, D22 and D31), a putative classic amidohydrolase catalytic triad (C29, H90 and D108), a tetramerization site (M168 and M227), putative ion channel sites (IGGK, 186–198 aa), and other residues (R208 and Y209). Furthermore, EFm1 exhibited no significant activity when expressed alone in vivo, and IME-EF1 lytic activity decreased when efm1 was knocked down. These findings provide valuable insights into the molecule mechanism of a potential functional biomaterial for the treatment of the disease caused by the opportunistic pathogen E. faecalis.
Flood disasters are one of the most destructive hazards faced across the globe, and thus flood hazard analysis is an essential factor for flood management. Due to the randomness and fuzziness of ...flood hazard, a series of possibilities is required for a certain flood level rather than just one exact probability. As a method for fuzzy hazard analysis derived from the information diffusion theory, the Interior-Outer-Set Model (IOSM) has the potential to reflect the randomness and fuzziness of flood hazard, however, the controlling intervals might have no sample points particularly when there are extraordinarily large flood peak flows or the flood samples concentrate. Based on this, the current study proposes a new framework for flood hazard analysis. First, flood samples are extracted from daily observed peak flow data. Second, the traditional IOSM is improved using design peak flows from flood frequency analysis (FFA) as the controlling points. From this, probability and floods hazard values are estimated via the FFA based IOSM (FFA-IOSM).The proposed framework is applied using data from the Dongjiang River, South China. Results demonstrate that the estimated flood probability was able to more effectively reflect the randomness and fuzziness of flood hazard compared to the traditional IOSM. This study provides a basis for reasonable flood engineering practices and supports the government with effective guidance on flood risk management, particularly under the increasing frequencies of the extreme precipitation events.
The utilisation of activated porous carbon (APC) for the removal of volatile methyl siloxane (VMS) has attracted significant research attention. However, the development of materials with high ...adsorption capacity remains a challenge. In this study, we successfully developed a high-specific-surface-area (2551 m2 g−1) APC material with a large porous texture (1.30 cm3 g−1) using coconut shell waste and NaOH as the activating agent. The performance of the APC material in the removal of hexamethyldisiloxane (L2) was evaluated using a fixed-bed dynamic adsorption setup. Notably, at 0 °C, the APC demonstrated a remarkable L2 removal ability, achieving a breakthrough adsorption capacity of 898.6 mg g−1. By increasing the inlet concentration of L2 and decreasing the temperature appropriately, the L2 adsorption capacity could be further improved. One advantage of APCs is their simple recycling process, which allows for sustained adsorption performance even after five consecutive cycles of adsorption and desorption. Therefore, the prepared APC material holds great promise as an efficient adsorbent for the removal of VMS.
Change in the composition of intestinal microbiota is associated with metabolic disorders such as gestational diabetes mellitus (GDM).
To understand how the microbiota impacts the development of ...gestational diabetes mellitus, we profiled the intestinal microbiome of 54 pregnant women, including 27 GDM subjects, by employing 16S rRNA gene sequencing. Additionally, we conducted targeted metabolomics assays to validate the identified pathways with overrepresented metabolites.
We evaluated the patterns of changing abundances of operational taxonomic units (OTU) between GDM and the healthy counterparts over three timepoints. Based on the significant OTUs, we inferred 132 significantly altered metabolic pathways in GDM. And identified two overrepresented metabolites of pregnancy hormone, butyrate and mevalonate, as potential intermediary metabolites of intestinal microbiota in GDM. Finally, we validated the impacts of the intestinal microbiota on GDM by demonstrating consistent changes of the serum levels of progesterone, estradiol, butyrate, and mevalonate in an independent cohort.
Our findings confirm that alterations in the microbiota play a role in the development of GDM by impacting the metabolism of pregnancy hormones. This provides a novel perspective on the pathogenesis of GDM and introduces potential biomarkers that can be used for early diagnosis and prevention of the disease.
In the background of global climate change and rapid urbanization, extreme climate events are frequent, and highly urbanized areas flooding problems are becoming increasingly prominent. It becomes ...important to develop qualitative scenario storylines to assess future flooding risk in a changing environment over the highly urbanized areas. In this study, the future (2030–2050) flood risk in the Pearl River Delta (PRD) region of China was assessed based on the MaxEnt model. We have developed four future scenarios under different emission conditions based on the representative concentration pathways (RCPs) and the shared socio-economic pathways (SSPs). The MaxEnt model was trained by using flood hazard sample point data and flood risk indicators, meanwhile, food risk prediction with high accuracy was obtained. We analyzed the influencing factors of flood risk and predicted the flood risk of the PRD under four future scenarios. According to the results, there is a significant increase in the size and proportion of high flood risk areas in most scenarios. Flood risk under scenario SSP5-RCP8.5 are expected to be the most serious in the future. Population density (POPD) and Gross domestic product density (GDPD) have the highest explanatory power for flood risk. This study predict the changes of flood risk under the combined influence of climate change and human activities, and hoped to provide a reference for future planning and disaster mitigation construction in PRD cities.
Volatile methyl siloxanes (VMSs) as a trace impurity in biogas decreases its energy utilization, and thus need to be removed. In this paper, a one-step hydrothermal reduction was performed to produce ...three-dimensional reduced graphene oxide aerogels (rGOAs) using industrial-grade graphene oxide (IGGO) as raw material and vitamin C (VC) as a reductant to facilitate the fabrication of rGOAs. The synthesis of rGOAs was a simple, green, and energy-efficient process. The developed rGOAs were characterized using the Brunauer–Emmett–Teller method, Raman spectrometry, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction measurements and contact angle. The results obtained showed that rGOA-1 with a VC/IGGO ratio of 1/1 (m/m) exhibited a hierarchical porous structure and super-hydrophobicity, yielding a high specific surface area (137.9 m2 g−1) and superior water contact angle (143.8°). The breakthrough adsorption capacity of rGOA-1 for hexamethyldisiloxane (L2, a VMS model) was 11 times higher than that of IGGO. Low inlet concentration and bed temperature were considered beneficial for the L2 adsorption. Interestingly, rGOA-1 was less sensitive to water, and it was readily regenerated for reuse by annealing at 80 °C. The rGOAs have been demonstrated to have great potential for the removal of siloxanes from biogas.
Reprogramming the immunosuppressive tumor microenvironment by modulating macrophages holds great promise in tumor immunotherapy. As a class of professional phagocytes and antigen‐presenting cells in ...the innate immune system, macrophages can not only directly engulf and clear tumor cells, but also play roles in presenting tumor‐specific antigen to initiate adaptive immunity. However, the tumor‐associated macrophages (TAMs) usually display tumor‐supportive M2 phenotype rather than anti‐tumor M1 phenotype. They can support tumor cells to escape immunological surveillance, aggravate tumor progression, and impede tumor‐specific T cell immunity. Although many TAMs‐modulating agents have shown great success in therapy of multiple tumors, they face enormous challenges including poor tumor accumulation and off‐target side effects. An alternative solution is the use of advanced nanostructures, which not only can deliver TAMs‐modulating agents to augment therapeutic efficacy, but also can directly serve as modulators of TAMs. Another important strategy is the exploitation of macrophages and macrophage‐derived components as tumor‐targeting delivery vehicles. Herein, we summarize the recent advances in targeting and engineering macrophages for tumor immunotherapy, including (1) direct and indirect effects of macrophages on the augmentation of immunotherapy and (2) strategies for engineering macrophage‐based drug carriers. The existing perspectives and challenges of macrophage‐based tumor immunotherapies are also highlighted.
Modulating macrophages for tumor immunotherapy holds great promise to improve anti‐tumor efficacy. Inhibition of macrophage recruitment, depleting tumor‐associated macrophages (TAMs), repolarizing TAMs, and regulating macrophage‐mediated phagocytosis of tumor cells are the four major strategies for manipulating macrophage‐mediated tumor immunotherapy.
Mycobacterium tuberculosis
(
Mtb
), the causative agent of tuberculosis (TB), is a tenacious pathogen that has latently infected one third of the world’s population. However, conventional TB ...treatment regimens are no longer sufficient to tackle the growing threat of drug resistance, stimulating the development of innovative anti-tuberculosis agents, with special emphasis on new protein targets. The
Mtb
genome encodes ~4000 predicted proteins, among which many enzymes participate in various cellular metabolisms. For example, more than 200 proteins are involved in fatty acid biosynthesis, which assists in the construction of the cell envelope, and is closely related to the pathogenesis and resistance of mycobacteria. Here we review several essential enzymes responsible for fatty acid and nucleotide biosynthesis, cellular metabolism of lipids or amino acids, energy utilization, and metal uptake. These include InhA, MmpL3, MmaA4, PcaA, CmaA1, CmaA2, isocitrate lyases (ICLs), pantothenate synthase (PS), Lysine-ε amino transferase (LAT), LeuD, IdeR, KatG, Rv1098c, and PyrG. In addition, we summarize the role of the transcriptional regulator PhoP which may regulate the expression of more than 110 genes, and the essential biosynthesis enzyme glutamine synthetase (GlnA1). All these enzymes are either validated drug targets or promising target candidates, with drugs targeting ICLs and LAT expected to solve the problem of persistent TB infection. To better understand how anti-tuberculosis drugs act on these proteins, their structures and the structure-based drug/inhibitor designs are discussed. Overall, this investigation should provide guidance and support for current and future pharmaceutical development efforts against mycobacterial pathogenesis.
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