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Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , China/epidemiology , Retrospective Studies , Hospitalization/statistics & numerical data , Bayes Theorem , Health Policy , PandemicsABSTRACT
PURPOSE OF REVIEW: Traditional Chinese Medicine has a unique system to diagnose and treat bone diseases with symptoms similar to those of osteoporosis. Sambucus williamsii Hance (SWH), a folk medicine in northern part of China for fractures healing and pain alleviation, has been demonstrated to exert bone anabolic effects in ovariectomized (OVX) rat and mice models in our previous studies. Lignans were identified to be the main bioactive fractions of SWH. However, pharmacokinetics study showed that the levels of lignan were too low to be detected in rat serum even upon taking 15 times of the effective dose of lignan-rich fraction from SWH. We hypothesize that lignans from SWH might exert its bone protective effect via the gut microbiome. RECENT FINDINGS: Our study revealed that the lignan-rich fraction of SWH did not influence the diversity of gut microbiota in OVX rats, but significantly increased the abundance of a few phyla, in particular, the restoration of the abundance of several genera that was directly correlated with bone mineral density (BMD). In addition, a subsequent metabolomic study indicated that serotonin, a neurotransmitter synthesized in the intestine and influenced by gut microbiota, may be involved in mediating the bone protective action of the lignans. Gut-derived serotonin is thought to inhibit bone growth. Based on this finding, several inhibitors that suppressed the synthesis of serotonin were identified from the lignans of SWH. Our studies suggested that microbiome is an indispensable factor for lignans derived from S. willimasii to exert bone beneficial effects.
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Tea pigment, as a natural pigment component in tea, has attracted much attention because of its unique health benefits. In recent years, with the deepening of scientific research, the research on biological activity, extraction technology and application of tea pigment has made remarkable progress. Through systematic bibliometrics analysis, this paper comprehensively combs and evaluates the research status of tea pigment. The propose is to provide valuable reference for future research and application. In this paper, the chemical structure of tea pigment is firstly summarized, and then its diverse biological activities, such as antioxidant, anti-inflammatory and anti-tumor, are deeply discussed, especially its potential application in the treatment of cardiovascular diseases and diabetes. In addition, the application prospect of tea pigment in food coloring, textile dyeing and other industrial fields is also discussed in detail. Through the collection and arrangement of a large number of research literatures, this paper analyzes the development trend, research methods and main achievements of tea pigment research, and pays special attention to the dosage and effect of tea pigment in practical application. These analyses not only contribute to a more comprehensive understanding of the characteristics and functions of tea pigments, but also provide scientific basis for the further development and application of tea pigments.
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Four previously unreported phenylpropanoid glycosides (1-4), together with four known analogues (5-8), were isolated from the leaves of Illicium dunnianum. The structures of these new compounds were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR, IR, UV) and chemical methods. In addition, the neuroprotective activities of all the isolates were evaluated by measuring their cell viability in H2O2-induced OLN-93 cell injury model.
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ortho-Quinone methides (o-QMs) are a class of highly reactive intermediates that serve as important nonisolable building blocks (NBBs) in organic synthesis and small-molecule library construction. Because of their instability and nonisolability, most reported o-QMs are generated through in situ chemical synthesis, and only a few natural o-QMs have been reported due to the lack of directed discovery strategies. Herein, a new natural o-QM precursor (trichophenol A, 2) was identified from the fungal strain of Trichoderma sp. AT0167 through genome mining, which was generated by trilA (nonreducing polyketide synthase) and trilB (2-oxoglutarate dependent dioxygenase). Combinatorial biosynthesis via two other known NRPKS genes with trilA and trilB was performed, leading to the generation of five new trichophenol o-QM oligomers (trichophenols D-H, 5-9). The strategy combining genome mining with combinatorial biosynthesis not only targetedly uncovered a new natural o-QM precursor but also produced various new molecules through oligomerization of the new o-QM and its designated o-QM acceptors without chemical synthesis and isolation of intermediates, which was named NBB genome mining-combinatorial biosynthesis strategy for o-QM molecule library construction. This study provides a new strategy for the targeted discovery of natural o-QMs and small-molecule library construction with natural o-QMs.
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Facile synthesis of high-efficiency and stable bifunctional electrocatalyst is essential for producing clean hydrogen in energy storage systems. Herein, low Rh-doped flower-like Ni3S2/Co3S4 heterostructures were facilely prepared on porous nickel foam (labeled Rh-Ni3S2/Co3S4/NF) by a hydrothermal method. The correlation of the precursors types with the morphological structures and catalytic properties were rigorously investigated for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in the control groups. The low Rh doping within the catalyst played important role in boosting the catalytic characteristics. The resulting catalyst showed the smaller overpotentials of 197 and 78 mV to drive a current density of 10 mA cm-2 for the OER and HER in alkaline electrolyte, respectively. And the potential only required 1.71 V to drive a current density of 100 mA cm-2 in a water splitting device. It reflects excellent overall water splitting of the home-made Rh-Ni3S2/Co3S4/NF. This strategy shed some constructive light for preparing transition metal sulfide-based electrocatalysts in water splitting devices.
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The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.
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Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.
Subject(s)
Abies , Endangered Species , Endophytes , Polyketides , Endophytes/chemistry , Polyketides/pharmacology , Polyketides/isolation & purification , Polyketides/chemistry , Molecular Structure , China , Abies/chemistry , Phomopsis/chemistry , Microbial Sensitivity Tests , Penicillium/chemistry , Bacteria/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/isolation & purification , 4-Butyrolactone/pharmacology , 4-Butyrolactone/chemistryABSTRACT
BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.
Subject(s)
Cognitive Dysfunction , Dementia, Vascular , Disease Models, Animal , Neuroprotective Agents , Oxidative Stress , White Matter , Animals , Dementia, Vascular/drug therapy , Cognitive Dysfunction/drug therapy , Neuroprotective Agents/pharmacology , Male , White Matter/drug effects , Oxidative Stress/drug effects , Mice , Gardenia/chemistry , Mice, Inbred C57BL , Carotenoids/pharmacology , Carotenoids/therapeutic use , Cerebrovascular Circulation/drug effects , Lipid Metabolism/drug effects , Plant Extracts/pharmacologyABSTRACT
Zhu-Ling decoction (ZLD), a classical traditional Chinese medicine (TCM) formula, is used for the treatment of chronic kidney diseases. However, the structure and activity of absorbed oligosaccharides (OSs) in ZLD are not clear. In this study, a novel strategy with in vivo characterization, extraction, isolation, activity evaluation was established and applied to identify absorbed anti-inflammatory OSs in ZLD. The results revealed that 30 OSs (22 reducing and 8 non-reducing OSs) and 11 OSs (7 reducing and 4 non-reducing OS) were characterized from ZLD in vitro and in vivo by using UPLC/Q-TOF-MS with PMP derivatization, respectively. Among them, a series of -1 â 3-ß-D-Glcp-OSs were isolated and identified by HPLC-HILIC-UVD-ELSD, SPHPLC-HILIC-RID, monosaccharide composition, MS and 1D/2D-NMR spectroscopy, including laminaritriose, laminaritetraose, laminaripentaose, laminarihexaose, laminariheptaose, laminarioctaose and laminarinonaose. Moreover, the 4 non-reducing absorbed OSs were identified by comparison with reference standards, including sucrose, trehalose, raffinose and stachyose. Among them, laminaritriose, laminaritetraose and laminaripentaose significantly inhibited TNF-α and IL-6 levels in LPS-induced HK-2 cell and exerted significant anti-inflammatory effects via the NF-κB and Akt/mTOR signaling pathways. Together, our work provides a novel strategy for discovery of absorbed anti-inflammatory OSs and broadens new horizons for the discovery of in vivo pharmacodynamic substances in TCM formulas.
Subject(s)
Anti-Inflammatory Agents , Drugs, Chinese Herbal , Oligosaccharides , Animals , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Oligosaccharides/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Mice , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/isolation & purification , Male , Lipopolysaccharides , NF-kappa B/metabolismABSTRACT
The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and-according to a structural model-active site architecture are highly similar to those of the fusicocca-2,10(14)-diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6-5-5-5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations. The reaction cascade proceeds in its initial steps through similar intermediates as for the PaFS cascade, but then diverges through an unusual vicinal deprotonation-reprotonation process that triggers a skeletal rearrangement at the entrance to the steps leading to the unique asperfumene skeleton. The structural model revealed only one major difference between the active sites: The PaFS residueâ F65 is substituted by I65 in AfAS. Intriguingly, site-directed mutagenesis experiments with both diterpene synthases revealed that position 65 serves as a bidirectional functional switch for the biosynthesis of tetracyclic asperfumene versus structurally less complex diterpenes.
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Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles' pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles' pore closure and that clathrin around Ω-profiles' base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles' base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin's well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents' function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin's pivotal role in pore constriction/closure.
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BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.
Subject(s)
Administration, Intranasal , Chitosan , Foot-and-Mouth Disease Virus , Foot-and-Mouth Disease , Nanospheres , Polylactic Acid-Polyglycolic Acid Copolymer , Viral Vaccines , Animals , Chitosan/chemistry , Chitosan/administration & dosage , Foot-and-Mouth Disease Virus/immunology , Foot-and-Mouth Disease Virus/genetics , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Foot-and-Mouth Disease/prevention & control , Foot-and-Mouth Disease/immunology , Mice , Nanospheres/chemistry , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Mice, Inbred BALB C , Antibodies, Viral/blood , Antibodies, Viral/immunology , Female , Nucleic Acids/administration & dosage , Immunity, Mucosal , Drug Delivery SystemsABSTRACT
Maintaining optimal ecological security in the Yangtze River-connected and isolated lake basins is of great significance to national projects involving Yangtze River protection. Ecosystem stability and associated factors are important components of ecological security in these basins. However, few studies have focused on ecosystem stability and its driving factors over long periods in the Yangtze River Basin. In this study, a remote sensing index was used to analyze the spatiotemporal variation in the ecosystem stability of the Dongting Lake Basin (DTL), Poyang Lake Basin (PYL), and the isolated Chaohu Lake Basin (CHL) and Taihu Lake Basin (THL) in the Yangtze River over the period 2000-2022 to determine the potential affecting factors. The results showed fluctuations in the ecosystem stability of the DTL and PYL, while a V-shape was observed for the CHL and THL during the same period; the closer to the lake, the weaker the stability of the ecosystem, especially in the DTL and PYL. Moreover, the ecosystem stability was greater in the DTL and PYL than in the CHL and THL. The spillover effect of anthropogenic activities on the ecosystem stability of the four basins and the direct effect of temperature have the greatest effect on the ecosystem stability. Specifically, the ecosystem stability index for the area around the DTL and PYL decreased with increasing human interference, whereas the opposite was observed in the CHL and THL. The effect of temperature was negative for the ecosystem stability of DTL and PYL and significantly positive for CHL and THL, at a level of 0.01 %. The findings of this study provide significant information for targeted ecological restoration of the Yangtze River Basin.
Subject(s)
Ecosystem , Lakes , Rivers , Rivers/chemistry , Environmental Monitoring , Climate , ChinaABSTRACT
Objective: This retrospective study aimed to investigate the clinical features of optic neuritis associated with COVID-19 (COVID-19 ON), comparing them with neuromyelitis optica-associated optic neuritis (NMO-ON), myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON), and antibody-negative optic neuritis (antibody-negative ON). Methods: Data from 117 patients (145 eyes) with optic neuritis at the Shantou International Eye Center (March 2020-June 2023) were categorized into four groups based on etiology: Group 1 (neuromyelitis optica-related optic neuritis, NMO-ON), Group 2 (myelin oligodendrocyte glycoprotein optic neuritis, MOG-ON), Group 3 (antibody-negative optic neuritis, antibody-negative ON), and Group 4 (optic neuritis associated with COVID-19, COVID-19 ON). Characteristics of T2 and enhancement in orbital magnetic resonance imaging (MRI) were assessed. Best-corrected visual acuity (BCVA) was compared before treatment, at a short-term follow-up (14 days), and at the last follow-up after treatment. Results: The COVID-19-associated optic neuritis (COVID-19 ON) group exhibited 100% bilateral involvement, significantly surpassing other groups (P < 0.001). Optic disk edema was observed in 100% of COVID-19 ON cases, markedly differing from neuromyelitis optica-related optic neuritis (NMO-ON) (P = 0.023). Orbital magnetic resonance imaging (MRI) revealed distinctive long-segment lesions without intracranial involvement in T1-enhanced sequences for the COVID-19 ON group compared to the other three groups (P < 0.001). Discrepancies in optic nerve sheath involvement were noted between the COVID-19 ON group and both NMO-ON and antibody-negative optic neuritis (antibody-negative ON) groups (P = 0.028). Before treatment, no significant difference in best-corrected visual acuity (BCVA) existed between the COVID-19 ON group and other groups. At the 14-day follow-up, BCVA in the COVID-19 ON group outperformed the NMO-ON (P < 0.001) and antibody-negative ON (P = 0.028) groups, with no significant difference observed compared to the myelin oligodendrocyte glycoprotein optic neuritis (MOG-ON) group. At the last follow-up after treatment, BCVA in the COVID-19 ON group significantly differed from the NMO-ON group (P < 0.001). Conclusion: Optic neuritis associated with COVID-19 (COVID-19 ON) predominantly presents with bilateral onset and optic disk edema. Orbital magnetic resonance imaging (MRI) demonstrates that COVID-19 ON presents as long-segment enhancement without the involvement of the intracranial segment of the optic nerve in T1-enhanced images. Glucocorticoid therapy showed positive outcomes.
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Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.
Subject(s)
Antifungal Agents , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Aspergillus oryzae/enzymology , Aspergillus oryzae/metabolism , Multigene Family , Triterpenes/chemistry , Triterpenes/metabolism , Cytochrome P-450 Enzyme System/metabolismABSTRACT
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.
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Toona ciliata is a deciduous or semi-deciduous tree species and belongs to the Toona genus of the Meliaceae family. Owing to low natural regeneration and over-exploitation, the species is listed as an endangered species at level II in China and its conservation has received increasing concern. Here, we sampled 447 individuals from 29 populations across the range-wide distribution of the T. ciliata complex in China and assessed their genetic variation using two chloroplast DNA markers. The results showed that the overall haplotype diversity and nucleotide diversity per site were high at h = 0.9767 and π = 0.0303 for the psbA-trnH fragment and h= 0.8999 and π = 0.0189 for the trnL-trnL fragment. Phylogenetic analysis supported the division of the natural distribution of T. ciliata complex into western and eastern regions. The genetic diversity was higher in the western region than in the eastern region, showing significant phylogeographic structure. Genetic differentiation among populations was moderate (Φst=42.87%), and the effects of isolation by distance (IBD) were significant. A neutrality test and mismatch distribution analysis indicated that the distribution of the T. ciliata complex generally did not expand, although a few local populations could likely expand after bottleneck effects. The overall results were complementary to and consolidated previous studies using mitochondrial and nuclear DNA markers. We finally discussed strategies for the genetic conservation of the T. ciliata complex.
Subject(s)
Meliaceae , Humans , Meliaceae/genetics , Toona/genetics , DNA, Chloroplast/genetics , Genetic Variation/genetics , Phylogeny , Genetic MarkersABSTRACT
Forest genetic conservation is typically species-specific and does not integrate interspecific interaction and community structure. It mainly focuses on the theories of population and quantitative genetics. This approach depicts the intraspecific patterns of population genetic structure derived from genetic markers and the genetic differentiation of adaptive quantitative traits in provenance trials. However, it neglects possible interspecific interaction in natural forests and overlooks natural hybridization or subspeciation. We propose that the genetic diversity of a given species in a forest community is shaped by both intraspecific population and interspecific community evolutionary processes, and expand the traditional forest genetic conservation concept under the community ecology framework. We show that a community-specific phylogeny derived from molecular markers would allow us to explore the genetic mechanisms of a tree species interacting with other resident species. It would also facilitate the exploration of a species' ecological role in forest community assembly and the taxonomic relationship of the species with other species specific to its resident forest community. Phylogenetic ß-diversity would assess the similarities and differences of a tree species across communities regarding ecological function, the strength of selection pressure, and the nature and extent of its interaction with other species. Our forest genetic conservation proposal that integrates intraspecific population and interspecific community genetic variations is suitable for conserving a taxonomic species complex and maintaining its evolutionary potential in natural forests. This provides complementary information to conventional population and quantitative genetics-based conservation strategies.
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Background: Sharp esophageal foreign body (SEFB) impaction can cause varying degrees of damage to the esophagus. There are few studies analyzing the postoperative fasting time in SEFB patients. Methods: We retrospectively collected 835 SEFB patients. According to the fasting time after the endoscopic removal (ER) of SEFBs, the patients were divided into two groups: short fasting time (SFT, fasted ≤24 h) and long fasting time (LFT, fasted >24 h). Results: There were 216 and 619 patients in the SFT and LFT group, respectively. The average age of the SFT group (52.97 years) was younger than that of the LFT group (55.96 years) (p = 0.025). The LFT group had lower proportion of duration of impaction (DOI) within 12 hours (14.2% vs 22.2%, p = 0.006) and erosion rates (89.0% vs 94.0%, p = 0.034) as well as higher proportion of esophageal perforation (19.5 vs 6.5%, p = 0.010) and patients who got intravenous anesthesia (63.78% vs 31.9%, p = 0.000) than the SFT group. The longest diameter of the foreign body (Lmax) in the LFT group (2.60 ± 1.01 cm) was greater than that in the SFT group (2.41 ± 0.83 cm; p = 0.01). Multivariate regression analysis found that age (OR = 1.726[1.208-2.465], p = 0.003), DOI (OR = 1.793[1.175-2.737], p = 0.007), Lmax (OR = 1.477[1.033-2.111], p = 0.032), perforation (OR = 3.698[2.038-6.710]; p < 0.01) and intravenous anesthesia (OR = 3.734[2.642-5.278]; p < 0.01) were the independent factors that prolonged fasting time in patients with SEFBs, while esophageal mucosal erosion (OR = 0.433[0.229-0.820]; p = 0.01) was the influencing factor leading to shortened fasting time. Conclusion: For the first time, we analyzed factors influencing the fasting time after ER in SEFB patients. Age, DOI, Lmax, perforation and intravenous anesthesia were risk factors for a prolonged postoperative fasting time.