Revealing quality chemicals of Tetrastigma hemsleyanum roots in different geographical origins using untargeted metabolomics and random-forest based spectrum-effect analysis.

Tetrastigma hemsleyanum root is a popular functional food in China, and the price varies based on the origin of the product. The link between the origin, metabolic profile, and bioactivity of T. hemsleyanum must be investigated. This study compares the metabolic profiles of 254 samples collected from eight different areas with 49 potential key chemical markers using plant metabolomics. The metabolic pathways of the five critical flavonoid metabolites were annotated and enriched using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Moreover, a random forest model aiding the spectrum-effect relationship analysis was developed for the first time indicating catechin and darendoside B as potential quality markers of antioxidant activity. The findings of this study provide a comprehensive understanding of the chemical composition and bioactive compounds of T. hemsleyanum as well as valuable information on the evaluation of the quality of various samples and products in the market.

Photoinduced Cobalt Catalyzed Radical Heck-Type Reaction of Alkyl Electrophiles.

We report here a general alkylation reaction of terminal alkenes with nucleophilic cobaloxime complex catalysis under visible light irradiation. A broad range of vinyl arenes and heteroarenes, as well as a diverse set of alkyl(pseudo)halides or strained rings as alkyl electrophiles, can efficiently undergo the transformation up to the gram scale. Mechanistic study reveals the radical nature of the reaction and corroborates our design involving alkylcobaloxime as the key intermediate.

Way to efficient microbial paclitaxel mass production.

The microbial synthesis of paclitaxel is attractive for its short-cycle, cost-effectiveness, and sustainability. However, low paclitaxel productivity, depleted capacity during subculture and storage, and unclear biosynthesis mechanisms restrain industrial microbial synthesis. Along with the isolation of various paclitaxel-producing microorganisms and the development of versatile molecular tools, tremendous promises for microbial paclitaxel synthesis have become increasingly prominent. In this review, we summarize the progress of microbial synthesis of paclitaxel in recent years, focusing on paclitaxel-producing endophytes and representative engineering microorganism hosts that were used as chassis for paclitaxel precursor synthesis. Numerous wide-type microbes can manufacture paclitaxel, and fermentation process optimization and strain improvement can greatly enhance the productivity. Engineered microbes can efficiently synthesize precursors of paclitaxel by introducing exogenous synthetic pathway. Mining paclitaxel synthetic pathways and genetic manipulation of endophytes will accelerate the construction of microbial cell factories, indefinitely contributing to paclitaxel mass production by microbes. This review emphasizes the potential and provides solutions for efficient microbial paclitaxel mass production.

Regioselective [2 + 1] photocycloaddition of 2-pyridones with diazo compounds.

Herein, we report a novel regioselective [2 + 1] cyclization reaction of 2-pyridones with carbenes generated in situ via visible light irradiation, without the requirement for catalysts or additives. The diverse functional groups of 2-pyridones and diazo compounds exhibit good tolerance, enabling the rapid synthesis of highly valuable cyclopropanated dihydro-2-pyridone scaffolds with exceptional regio- and stereoselectivity. Furthermore, DFT calculations provide a comprehensive explanation for the regio- and stereoselectivity observed in the reaction.

Five undescribed abietane-type diterpenes of Callicarpa macrophylla.

A phytochemical investigation of the medicinal plant Callicarpa macrophylla resulted in the characterization of two rare rearrangement abietane-type diterpenoids, macrophypene F-G (1-2), and three abietane diterpenoids, named macrophypene H-J (3-5). Additionally, five known diterpenoids (6-10) were identified. The structures of the newly discovered compounds were fully established through extensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations of the isolated compounds were determined using CD comparison, chemical methods, and X-ray crystal diffraction experiments. Subsequently, all isolated diterpenoids were evaluated for their inhibitory effects on extracellular PCSK9 protein levels by PCSK9 AlphaLISA screening. Jiadfenoic acid B (6, 56.80% inhibition at 20 µM) and holophyllin F (10, 43.18% inhibition at 20 µM) significantly decreased PCSK9 protein levels in medium of HepG2 cells.

Five undescribed guanidine alkaloids from Plumbago zeylanica.

Five undescribed guanidine alkaloids, plumbagines HK (1-4) and plumbagoside E (5), as well as five known analogues (6-10) were isolated from the roots of Plumbago zeylanica. Their structures were established by extensive spectroscopic analyses and chemical methods. In addition, 1-10 were accessed their anti-inflammatory activities by measuring nitric oxide (NO) concentrations in LPS-induced RAW 264.7 cells. However, all compounds especially 1 and 3-5 could not inhibit the secretion of NO but significant increase the secretion of NO. The result reminded us that 1-10 may become potential novel immune potentiators.

A new efficient multi-stage strategy based on the complementarity of ultrafiltration and high resolution biochromatogram for the screening of skin-whitening candidates from the fibrous root of Bletilla striata.

Ultrafiltration-high performance liquid chromatography (UF-HPLC) and high resolution biochromatogram (HR-biochromatogram), have been proven to be effective methods for the rapid discovery of enzyme inhibitors in natural medicines. In attempt to conquer false-positive and false- negative screening results, a new multi-stage strategy based on the complementarity of UF-HPLC and HR-biochromatogram has been proposed for the fast screening of tyrosinase inhibitory components using the fibrous root of Bletilla striata as a case study. For the first two stages, UF- HPLC and HR-biochromatogram, were applied individually for the screening of high-affinity tyrosinase ligands and tyrosinase inhibitors. After that, the inconsistent results, which yielded two potential active fractions, indicated a third stage screening. Thus, a "strengthen" biochromatogram was established to microfractionate the concentrated extract and further evaluate the tyrosinase inhibitors. The complementarity nature of two different screening methods was firstly explored to distinguish tyrosinase inhibitors from the fibrous root of Bletilla striata. As a result, four compounds were screened, isolated and characterized as new potent tyrosinase inhibitors. The screening results were verified by tyrosinase inhibition assays, melanin inhibitory in zebrafish and molecular docking. All compounds possessed much higher tyrosinase inhibition than α-arbutin, especially, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol demonstrated stronger tyrosinase inhibition than kojic acid. This study presented a new screening strategy which had a great potential in rapidly and efficiently exploring tyrosinase inhibitors in complex mixtures. Moreover, it is the first time to reveal the skin-whitening nature of the fibrous root of B. striata, which indicating the promising prospect in the full utilization of B. striata plant.

A comprehensive strategy for prediction and quality evaluation of standardized planting herbs based on plant metabolomics coupled with extreme learning machine: Astragali Radix as an example.

INTRODUCTION: Standardizing the planting process is an effective way to control the quality stability of herbal resources, which are susceptible to external environmental factors (e.g., moisture, soil, etc.). However, how to scientifically and comprehensively assess the effects of standardized planting on plant quality and quickly test unknown samples has not been addressed. OBJECTIVE: The aim of this study was to determine and compare the metabolite levels of herbs before and after standardized planting, to quickly distinguish their sources, and to evaluate their quality, using the typical herb Astragali Radix (AR) as an example. METHODS: In this study, an efficient strategy using liquid chromatography-mass spectrometry (LC-MS) based on plant metabolomics combined with extreme learning machine (ELM) has been developed to efficiently distinguish and predict AR after standardized planting. Moreover, a comprehensive multi-index scoring method has been developed for the comprehensive evaluation of the quality of AR. RESULTS: The results confirmed that AR after standardized planting was significantly differentiated, with a relatively stable content of 43 differential metabolites, mainly including flavonoids. An ELM model was established based on LC-MS data, and the accuracy in predicting unknown samples could reach more than 90%. As expected, higher total scores were obtained for AR after standardized planting, indicating much better quality. CONCLUSION: A dual system for evaluating the impact of standardized planting on the quality of plant resources has been established, which will significantly contribute to innovation in the quality evaluation of medicinal herbs and support the selection of optimal planting conditions.

Steam explosion pretreatment to enhance extraction of active ingredients: current progress and future prospects.

The active ingredients extracted from plant materials play an important role in human life and health, and the extraction is a critical step in the preparation of them. It is necessary to develop a sustainable and green extraction. Steam explosion pretreatment enhanced extraction is a higher efficiency, lower equipment investment, less hazardous chemicals and environment-friendly technique, which has been widely used to extract active ingredients from various plant materials. In this paper, current progress and future prospects of steam explosion pretreatment enhanced extraction are overviewed. The equipment, operating steps, strengthening mechanism, critical process factors are comprehensively introduced. Furthermore, recent applications and comparisons with other techniques are discussed in depth. Finally, the future development trends are prospected. The current results show that steam explosion pretreatment enhanced extraction has the advantage of high efficiency. Moreover, steam explosion is simple in equipment, and easy to operate. In conclusion, steam explosion pretreatment can be effectively used to enhance the extraction of active ingredients from plant materials.

Five glycosylated phenolic derivatives from the bark of Ilex rotunda Thunb. and their anti-inflammatory activities.

Five new glycosylated phenolic derivatives, rotundosides A-E (1-5), and three known glycosides (6-8) were isolated from the 95% alcohol extract of the bark of Ilex rotunda. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature data. All new compounds possessed a [5-O-(E)-caffeoyl]-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranosyl group. The anti-inflammatory properties of all isolated compounds were evaluated using a modified nitric oxide (NO) production in lipopolysaccharide (LPS)-induced leukemia cells in mouse macrophage (RAW264.7) method. Compound 8, dracunculifoside H, showed significant anti-inflammatory activity in vitro.

Recent discovery of tyrosinase inhibitors in traditional Chinese medicines and screening methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Tyrosinase, the key rate-limiting enzyme for melanogenesis, is one of the main targets for skin senescence and some pigmented skin diseases, such as albinism and melanoma. Tyrosinase inhibitors are capable of reducing melanin generation and deposition in the skin through blocking the reaction chain of formation. Thus, it has been used for anti-melanoma and showed the potential to be developed into novel skin whitening and spot removing products. With the trend of back-to-nature, natural tyrosinase inhibitors are receiving more and more attention. Traditional Chinese medicines (TCMs) as the promising source of novel chemotypes and pharmacophores, are huge treasures for the discovery of natural tyrosinase inhibitors characterized with green, safe, and highly efficient. AIM OF THIS REVIEW: This review aims to provide a systematic overview of natural tyrosinase inhibitors and a detailed summary of the types of TCMs from which they originate. In addition, this paper also highlights the screening methods developed for exploring tyrosinase inhibitors in recent years, compares the advantages and disadvantages of various methods under the guidance of different screening principles, and predicts their applications in the future. MATERIALS AND METHODS: Relevant literature have been obtained using the keywords "tyrosinase inhibitors", "traditional Chinese medicines", "whitening", and "screening" in scientific databases, such as "PubMed", "SciFinder", "Web of Science", "Elsevier", "China Knowledge Resource Integrated databases". Information was also collected from Chinese pharmacopoeia, Chinese herbal classics books, "Google Scholar", "Baidu Scholar", and other literature sources, etc. RESULTS: An overview about the tyrosinase inhibitors derived from TCMs since 2002 has been compiled via the above-mentioned sources. Up to now, 186 components, mainly belonging to flavonoids, lignans, terpenoids, Diels-Alder adducts, simple phenylpropanoids and stilbenes, from 61 kinds of TCMs have been reported to possess tyrosinase inhibitory activity, among which flavonoids are mainly focused on. Furthermore, on the basis of bioactive detection strategies, the screening methods for tyrosinase inhibitors have been classified into bioaffinity-based, intrinsic enzymatic-based, and computer-aided drug design (CADD). Precisely because screening approaches are essential for rapid identification of tyrosinase inhibitors from TCMs, the principles, advantages and disadvantages, and specific applications of each method are presented along with a comparison of applicability. CONCLUSIONS: The summary of TCMs-derived inhibitors gives a clue on the discovery of candidates with the property to whiten the skin. Meanwhile, the outlook of developed screening methods provides technical references for the efficient exploration of safer and more effective tyrosinase inhibitors from TCMs.

Discovery of potential hypoglycemic metabolites in Cassiae Semen by coupling UHPLC-QTOF-MS/MS combined plant metabolomics and spectrum-effect relationship analyses.

Cassiae Semen (CS) is consumed as fried tea or medicinal food in Asian areas. Its two commercial forms, namely raw and fried CS, exert different clinical applications, in which fried CS is commonly applied as a functional tea for losing weight. To prevent confusion in the use of the two forms of CS, a comprehensive strategy by combining plant metabolomics and spectrum-effect relationship analyses was developed for the fast and efficient discrimination of raw and fried CS, and further for the discovery of the potential hypoglycemic metabolites of CS to control its quality. First, the plant metabolic profiling of raw and processed samples was performed by UHPLC-QTOF-MS/MS. A total of 1111 differential metabolites were found to well distinguish the raw and fried CS after analyzing by MPP software. Subsequently, α-glucosidase inhibition of raw and fried CS was investigated. As a result, fried CS demonstrated much stronger α-glucosidase inhibition activity than the raw sample. By analyzing the spectrum-effect relationship with GRA, BCA, and PLSR, 14 potential hypoglycemic-related compounds were discovered. As anticipated, they were also found as the differential metabolites of the raw and fried samples with a potential hypoglycemic effect, which might be beneficial for the quality control of CS tea. Additionally, molecular docking analysis was conducted to reveal the underlying inhibition mechanisms of the four most critical constituents, including physcion, chrysoobtusin, aurantio-obtusin, and obtusifolin. This study provides a powerful tool for the discrimination of processed samples and fast screening of the active constituents in complex natural products on a high-throughput basis.

Dynamic high pressure microfluidization-assisted extraction of plant active ingredients: a novel approach.

The extraction method has a great influence on the yield, quality, chemical structure, and biological activities of active ingredients. Safe and efficient extraction of active ingredients is one of the important problems facing the food and pharmaceutical industry. As a pretreatment approach for the extraction of active ingredients, dynamic high pressure microfluidization (DHPM) is a promising strategy that can not only effectively increase the yield of active ingredients but also strengthen the bioactivities of active ingredients, and take the advantages of mild operating temperature and environmental friendliness. In this review, the research progress of DHPM-assisted extraction of active ingredients from plant materials in recent ten years is overviewed. The DHPM equipment, strengthening mechanism, operating procedure, critical factors and application of DHPM-assisted extraction are introduced in detail, together with the advantages and disadvantages. Furthermore, its future development trend is discussed at the end. DHPM-assisted extraction is considered as the ideal technique of better homogenization effects, less solvent consumption, more reliable operation, and so on, making it a promising method to acquire active ingredients efficiently. Therefore, this technique is worthy of further theoretical research and experimental operation.

Inhibitory effect of miR­182­5p on retinal neovascularization by targeting angiogenin and BDNF.

Retinal neovascularization (RNV) is a type of serious vision­threating disease, commonly induced by hypoxia of ischemic retinopathy, which happens in various ocular diseases including diabetic retinopathy and retinopathy of prematurity. In clinical work, anti­VEGF therapy is the preferred strategy for treating RNV. However, not all cases are sensitive to anti­VEGF injection. It is urgent and necessary to develop novel targets for inhibiting neovascularization in ocular diseases. Angiogenin (ANG) and brain­derived neurotrophic factor (BDNF) are implicated in angiogenesis, although their regulation and effects in RNV remain to be elucidated. microRNA (miRNA) is a type of small non­coding RNA, which can modulate targets by degrading transcripts or inhibiting protein translation. In the present study, miRNA­mediated modulation of ANG and BDNF was explored in an oxygen­induced retinopathy mouse model and human retinal microvascular endothelial cells (HRECs) under hypoxia. The results showed that downregulation of miR­182­5p and upregulation of ANG and BDNF were found in vivo and in vitro. Overexpression of miR­182­5p suppressed the expression of ANG and BDNF significantly in HRECs under hypoxia. In addition, knockdown of ANG and BDNF by miR­182­5p transfection significantly improved hypoxia­induced HRECs dysfunctions, including enhancing cell viability, reducing cell migration and improved tube integrity. In conclusion, miRNA­dependent regulation on ANG and BDNF indicates a critical role in hypoxia­induced retinal microvascular response. miR­182­5p­based therapy can influence the expression of ANG and BDNF, which demonstrates the potential for treating RNV diseases.

Annexin A2 promotes development of retinal neovascularization through PI3K/ AKT signaling pathway.

PURPOSE: Retinal Neovascularization (RNV) is a pathological characteristic of ocular diseases. Annexin A2 (ANXA2) plays important roles in RNV while the mechanism remains unclear. The study aimed to explore relationship between ANXA2 and PI3K/AKT signaling pathway in RNV. METHODS: We used human retinal vascular endothelial cells (HRECs) and oxygen-induced retinopathy (OIR) mice model to show ANXA2 can promote the development of RNV through PI3K/AKT signaling pathway. We divided HRECs into six groups by infecting lentivirus containing appropriate plasmid and adding corresponding solution. Assays showing ability of HRECs were performed in vitro. Mice were randomly divided into three groups and treated accordingly. RESULTS: Expression of ANXA2 and activity of PI3K/AKT signaling pathway in HRECs were detected. RNV and expression of ANXA2 in mice retinas were detected. Results showed that ANXA2 expression is positively related with RNV-forming ability of HRECs in vitro and development of RNV in vivo while low activity of PI3K/AKT signaling pathway could attenuate the role of ANXA2. CONCLUSIONS: We can make ANXA2 and PI3K/ AKT signaling pathway as a promising target for the regulation of pathological neovascularization of the retina, which also provides a novel idea for effective prevention and treatment of diseases related to RNV in future.

Infrared assisted extraction of bioactive compounds from plant materials: Current research and future prospect.

The extraction of bioactive compounds from plant materials has attracted much attention due to their potential therapeutic effects. This article reviews the basic principles, characteristics, and recent applications of infrared assisted extraction (IAE) of bioactive compounds from plant materials. The advantages and disadvantages of IAE are considered, and operation mode and technological improvements, processes, solvents used and other future developments are identified. The review indicated that IAE was a simple, rapid, and cost-effective technique with the capacity for industrial scale application. Future research should focus on energy consumption reduction, green chemistry extraction processes, simplified operation steps, intelligent extraction process, and the establishment of kinetic and thermodynamic models. This article provides a comprehensive understanding of the principles and applications of IAE for the preparation of bioactive compounds, which will be of benefit to researchers and users of the technology.

The accumulation of exosome-associated microRNA-1246 and microRNA-150-3p in human red blood cell suspensions.

BACKGROUND: Transfusion-related immunomodulation (TRIM) can be caused by exosomes, in which case, microRNAs (miRNAs) are one critical factor impacting exosome behavior. This study aims to investigate and analyze the expression profiles of exosomal miRNA in red blood cell (RBC) suspensions during storage and to identify potential TRIM-related miRNAs as well as their potential functions. METHODS: A total of 25 packs of RBC suspensions were randomly collected. Exosome were extracted by ultracentrifugation and then identified and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blot (WB). Exosomal miRNA profiles were acquired using gene chips in five packs on week 1 and week 5. The expression data were compared from the two time points identifying accumulated miRNAs with statistical significance and their predicted targeting genes were analyzed. Based on the gene chip results, quantitative reverse transcription-polymerase chain reactions (qRT-PCR) were performed to verify miRNA accumulation in the rest 20 packs sampling on week 1, 3 and 5. RESULTS: Gene chip analysis revealed that most exosomal miRNAs were enriched as the storage period progressed. Compared to samples from week 1, week 5 samples exhibited a total of 539 differential miRNA expressions, among which, 159 were statistically significant (P < 0.05) and 148 (93.08%) were accumulated. In the bioinformatics functional analysis, significant immunoregulatory annotations related to the thyroid hormone, mitogen-activated protein kinase (MAPK), focal adhesion and RAS signaling pathways were identified. The top 17 differential expression miRNAs were validated by qRT-PCR. The results confirmed that all the 17 miRNAs were accumulated with increasing storage time. In particular, miRNA-1246 and miRNA-150-3p were the most enriched strands by more than 150-folds in the 5-week storage period. CONCLUSIONS: As storage progressed, numerous exosomal miRNAs accumulated in the RBC suspensions, which are informatically connected to multiple immuno-signaling pathways. MiRNA-1246 and miRNA-150-3p may be essential mediators impacting the immunoregulation functions of exosomes in RBC suspensions, considering their significant accumulating scales. Further research should therefore focus on the relationship between these miRNAs and TRIM.

Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation.

BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION: This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial.

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

A network pharmacology-based study on Alzheimer disease prevention and treatment of Qiong Yu Gao.

BACKGROUND AND OBJECTIVE: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. METHODS: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. RESULTS: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. CONCLUSION: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.