A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin.

Natural product-based antiviral candidates have received significant attention. However, there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance. Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi. They have proven to be effective against a broad range of viruses by directly killing virus particles, protecting infected cells, and targeting viral antigens on their surface, among other mechanisms. As natural products, they both possess the advantage of lower toxicity, enhanced therapeutic efficacy, and even antagonistic effects against drug-resistant viral strains. Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds, demonstrating their antiviral properties. However, to date, no review on the antiviral effects of baicalein and baicalin has been published. This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms. The aim is to provide a basis for the rational development and utilization of baicalein and baicalin, as well as to promote antiviral drug research. Please cite this article as: Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. J Integr Med. 2024; Epub ahead of print.

Explore an open-source value co-creation framework: A multiple case study.

Open-source communities(OSCs) are gaining significant attention in the current business environment of information technology(IT). More and more IT companies and individuals are exploring how to achieve innovation through open-source collaboration, and value co-creation(VCC) in the OSCs has become a trend. Therefore, it is particularly important to examine the mechanism of OSCs under the background of VCC theory. This study proposes a conceptual framework of open-source value co-creation (OSVCC), which is characterized by openness, sharing, collaboration, and freedom, for understanding the internal mechanisms and contextual conditions in the relationship between OSCs participants. This study constructed a pairwise combined four-category classification model combining the perspectives of the commercialization level (low and high) and the maturity stage (developmental and mature) of the OSCs. Based on the model, this study selects and analyzes four presentive cases of OSCs using a multiple case study approach. Then, this study proposes a framework for OSVCC to identify the crucial factors that promote the successful implementation of innovation and value creation. The OSVCC framework encompasses three primary participants, effective VCC processes, and key open-source principles. This study offers valuable managerial implications for enterprises that plan to participate in OSCs.

Synthesis and antifungal evaluation of novel triazole derivatives bearing a pyrazole-methoxyl moiety.

Life-threatening invasive fungal infections pose a serious threat to human health. A series of novel triazole derivatives bearing a pyrazole-methoxyl moiety were designed and synthesized in an effort to obtain antifungals with potent, broad-spectrum activity that are less susceptible to resistance. Most of these compounds exhibited moderate to excellent in vitro antifungal activities against Candida albicans SC5314 and 10,231, Cryptococcus neoformans 32,609, Candida glabrata 537 and Candida parapsilosis 22,019 with minimum inhibitory concentration (MIC) values of ≤0.125 µg/mL to 0.5 µg/mL. Use of recombinant Saccharomyces cerevisiae strains showed compounds 7 and 10 overcame the overexpression and resistant-related mutations in ERG11 of S. cerevisae and several pathogenic Candida spp. Despite being substrates of the C. albicans and Candida auris Cdr1 drug efflux pumps, compounds 7 and 10 showed moderate potency against five fluconazole (FCZ)-resistant fungi with MIC values from 2.0 µg/mL to 16.0 µg/mL. Growth kinetics confirmed compounds 7 and 10 had much stronger fungistatic activity than FCZ. For C. albicans, compounds 7 and 10 inhibited the yeast-to-hyphae transition, biofilm formation and destroyed mature biofilm more effectively than FCZ. Preliminary mechanism of action studies showed compounds 7 and 10 blocked the ergosterol biosynthesis pathway at Erg11, ultimately leading to cell membrane disruption. Further investigation of these novel triazole derivatives is also warranted by their predicted ADMET properties and low cytotoxicity.

A new integrated rough multi-criteria decision-making model for enterprise resource planning software selection.

Enterprise resource planning (ERP) is widely used to boost the total market power of businesses. The wrong selection is one of the key reasons why ERP installations fail. Due to the complexity of the business environment and the range of ERP systems, choosing an ERP system is a complex and time-consuming procedure. ERP alternatives may be assessed using several criteria, so the ERP selection process may be considered a multi-criteria decision-making (MCDM) problem. In this study, the rough best worst method (BWM) was used to determine criteria weights, while the newly developed rough integrated simple weighted sum product (WISP) was used to rank ERP alternatives. Results suggest that the SFT-4 coded software is regarded as the best option, followed by SFT-5, SFT-6, SFT-2, SFT-3, and SFT-1. Results of the newly developed rough WISP method are compared to those of existing rough techniques in the sensitivity analysis. The differences between them have been found to be negligible. The outcomes show how effectively developed rough BWM and WISP integrated method performs in terms of ERP selection with usability, accuracy, ease of use, and consistency. This study will help decision-makers in a context where ERP is implemented choose the best ERP software for different sectors.

MyoFold: Joint myocardial tissue composition and wall motion quantification via a highly folded sequence.

PURPOSE: This study aims to develop and evaluate a novel cardiovascular MR sequence, MyoFold, designed for the simultaneous quantifications of myocardial tissue composition and wall motion. METHODS: MyoFold is designed as a 2D single breathing-holding sequence, integrating joint T1/T2 mapping and cine imaging. The sequence uses a 2-fold accelerated balanced SSFP (bSSFP) for data readout and incorporates electrocardiogram synchronization to align with the cardiac cycle. MyoFold initially acquires six single-shot inversion-recovery images, completed during the diastole of six successive heartbeats. T2 preparation (T2-prep) is applied to introduce T2 weightings for the last three images. Subsequently, over the following six heartbeats, segmented bSSFP is performed for the movie of the entire cardiac cycle, synchronized with an electrocardiogram. A neural network trained using numerical simulations of MyoFold is used for T1 and T2 calculations. MyoFold was validated through phantom and in vivo experiments, with comparisons made against MOLLI, SASHA, T2-prep bSSFP, and the conventional cine. RESULTS: In phantom studies, MyoFold exhibited a 10% overestimation in T1 measurements, whereas T2 measurements demonstrated high accuracy. In vivo experiments revealed that MyoFold T1 had comparable accuracy to SASHA and precision similar to MOLLI. MyoFold demonstrated good agreement with T2-prep bSSFP in myocardial T2 measurements. No significant differences were observed in the quantification of left-ventricle wall thickness and function between MyoFold and the conventional cine. CONCLUSION: MyoFold presents as a rapid, simple, and multitasking approach for quantitative cardiovascular MR examinations, offering simultaneous assessment of tissue composition and wall motion. The sequence's multitasking capabilities make it a promising tool for comprehensive cardiac evaluations in clinical settings.

Denitrification Characteristics of the Low-Temperature Tolerant Denitrification Strain Achromobacter spiritinus HS2 and Its Application.

The low-temperature environment significantly inhibits the growth and metabolism of denitrifying bacteria, leading to an excessive concentration of ammonia nitrogen and total nitrogen in sewage treatment plants during the cold season. In this study, an efficient denitrifying strain of heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria named HS2 was isolated and screened from industrial sewage of a chemical factory in Inner Mongolia at 8 °C. The strain was confirmed to be Achromobacter spiritinus, a colorless rod-shaped bacterium. When cultured with sodium succinate as the carbon source, a carbon-to-nitrogen ratio of 20-30, a shaking rate of 150-180 r/min, and an initial pH of 6-10, the strain HS2 exhibited excellent nitrogen removal at 8 °C. Through the results of whole-genome sequencing, gene amplification, and gas product detection, the strain HS2 was determined to possess key enzyme genes in both nitrification and denitrification pathways, suggesting a HN-AD pathway of NH4+-N → NH2OH → NO2-N → NO → N2O → N2. At 8 °C, the strain HS2 could completely remove ammonia nitrogen from industrial sewage with an initial concentration of 127.23 mg/L. Microbial species diversity analysis of the final sewage confirmed Achromobacter sp. as the dominant genus, which indicated that the low-temperature denitrifying strain HS2 plays an important role in nitrogen removal in actual low-temperature sewage.

From Synergy to Monotherapy: Discovery of Novel 2,4,6-Trisubstituted Triazine Hydrazone Derivatives with Potent Antifungal Potency In Vitro and In Vivo.

Invasive fungal infections pose a serious threat to public health and are associated with high mortality and incidence rates. The development of novel antifungal agents is urgently needed. Based on hit-to-lead optimization, a series of 2,4,6-trisubstituted triazine hydrazone compounds were designed, synthesized, and biological evaluation was performed, leading to the identification of compound 28 with excellent in vitro synergy (FICI range: 0.094-0.38) and improved monotherapy potency against fluconazole-resistant Candida albicans and Candida auris (MIC range: 1.0-16.0 µg/mL). Moreover, 28 exhibited broad-spectrum antifungal activity against multiple pathogenic strains. Furthermore, 28 could inhibit hyphal and biofilm formation, which may be related to its ability to disrupt the fungal cell wall. Additionally, 28 significantly reduced the CFU in a mouse model of disseminated infection with candidiasis at a dose of 10 mg/kg. Overall, the triazine-based hydrazone compound 28 with low cytotoxicity, hemolysis, and favorable ADME/T characteristics represents a promising lead to further investigation.

Tailoring a N-Doped Nanoporous Carbon Host for a Stable Lithium Metal Anode.

Li metal is a promising anode candidate due to its high theoretical capacity and low electrochemical potential. However, dendrite formation and the resulting dead Li cause continuous Li consumption, which hinders its practical application. In this study, we realized N-doped nanoporous carbon for a stable Li metal host composed only of lightweight elements C and N through the simple calcination of a nitrogen-containing metal-organic framework (MOF). During the calcination process, we effectively controlled the amount of lithophilic N and the electrical conductivity of the N-doped porous carbons to optimize their performance as Li metal hosts. As a result, the N-doped porous carbon exhibited excellent electrochemical performances, including 95.8% coulombic efficiency and 91% capacity retention after 150 cycles in a full cell with an LFP cathode. The N-doped nanoporous carbon developed in this study can realize a stable Li metal host without adding lithium ion metals and metal oxides, etc., which is expected to provide an efficient approach for reliable Li metal anodes in secondary battery applications.

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights.

Baicalein (BE), the major component of Scutellaria Baicalensis, exhibited potently antifungal activity against drug-resistant Candida albicans, and strong inhibition on biofilm formation. Therefore, a series of baicalein-core derivatives were designed and synthesized to find more potent compounds and investigate structure-activity relationship (SAR) and mode of action (MoA). Results demonstrate that A4 and B5 exert a more potent antifungal effect (MIC80 = 0.125 µg/mL) than BE (MIC80 = 4 µg/mL) when used in combination with fluconazole (FLC), while the MIC80 of FLC dropped from 128 µg/mL to 1 µg/mL. SAR analysis indicates that the presence of 5-OH is crucial for synergistic antifungal activities, while o-dihydroxyls and vic-trihydroxyls are an essential pharmacophore, whether they are located on the A ring or the B ring of flavonoids. The MoA demonstrated that these compounds exhibited potent antifungal effects by inhibiting hypha formation of C. albicans. However, sterol composition assay and enzymatic assay conducted in vitro indicated minimal impact of these compounds on sterol biosynthesis and Eno1. These findings were further confirmed by the results of the in-silico assay, which assessed the stability of the complexes. Moreover, the inhibition of hypha of this kind of compound could be attributed to their effect on the catalytic subunit of 1,3-ß-d-glucan synthase, 1,3-ß-d-glucan-UDP glucosyltransferase and glycosyl-phosphatidylinositol protein, rather than inhibiting ergosterol biosynthesis and Eno1 activity by Induced-Fit Docking and Molecular Dynamics Simulations. This study presents potential antifungal agents with synergistic effects that can effectively inhibit hypha formation. It also provides new insights into the MoA.

The Effect of Dihydromyricetin on the Pharmacokinetics of Fluconazole in Sprague-Dawley Rat Plasma, Based on High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Background: The synergistic effect of dihydromyricetin (DHM) and fluconazole (FLC) can improve the killing effect of FLC-resistant Candida albicans in vitro and in vivo. However, it is not clear whether DHM affects the pharmacokinetic characteristics of FLC. Methods: In this study, 12 Sprague-Dawley (SD) rats were randomly divided into two groups as follows: (1) an FLC group in which rats were administered FLC only (42 mg/kg orally); (2) an FLC with the combined administration of DHM group, in which rats received an equivalent FLC dose immediately following the administration of DHM (100 mg/kg). Blood samples were collected from the ocular choroid vein of rats and converted into plasma. The concentrations of FLC in the rat plasma were then determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the related pharmacokinetic parameters were analysed. The initial mobile phase included 0.1% acetonitrile and water with gradient elution. Multiple reaction monitoring modes of m/z 307.2→220.1 for FLC, and m/z 237.1→194.2 for carbamazepine, were utilised to conduct quantitative analysis. Results: The calibration curve of FLC in rat plasma demonstrated good linearity in the range of 0.1-30 µg/mL (r > 0.99), and the lower limit of quantification was 0.1 µg/mL. Moreover, the intra- and inter-day precision relative standard deviation of FLC was less than 9.09% and 6.51%, respectively. There were no significant differences in the pharmacokinetic parameters between the two groups. Conclusion: The results showed that DHM administration did not significantly alter FLC pharmacokinetics in SD rat plasma.

Design, synthesis and in vitro biological studies of novel triazoles with potent and broad-spectrum antifungal activity.

A series of novel triazole derivatives containing aryl-propanamide side chains was designed and synthesised. In vitro antifungal activity studies demonstrated that most of the compounds inhibited the growth of six human pathogenic fungi. In particular, parts of phenyl-propionamide-containing compounds had excellent, broad-spectrum antifungal activity against Candida albicans SC5314, Cryptococcus neoformans 22-21, Candida glabrata 537 and Candida parapsilosis 22-20 with MIC values in the range of ≤0.125 µg/mL-4.0 µg/mL. In addition, compounds A1, A2, A6, A12 and A15 showed inhibitory activities against fluconazole-resistant Candida albicans and Candida auris. Preliminary structure-activity relationships (SARs) are also summarised. Moreover, GC-MS analysis demonstrated that A1, A3, and A9 interfered with the C. albicans ergosterol biosynthesis pathway by inhibiting Cyp51. Molecular docking studies elucidated the binding modes of A3 and A9 with Cyp51. These compounds with low haemolytic activity and favourable ADME/T properties are promising for the development of novel antifungal agents.

Novel antifungal triazoles with alkynyl-methoxyl side chains: Design, synthesis, and biological activity evaluation.

Previous work led to the rational design, synthesis and testing of novel antifungal triazole analogues bearing alkynyl-methoxyl side chains. Tests of in vitro antifungal activity showed Candida albicans SC5314 and Candida glabrata 537 gave MIC values of ≤0.125 µg/mL for most of the compounds. Among these, compounds 16, 18, and 29 displayed broad-spectrum antifungal activity against seven human pathogenic fungal species, two fluconazole-resistant C. albicans isolates and two multi-drug resistant Candida auris isolates. Moreover, 0.5 µg/mL of 16, 18, and 29 was more effective than 2 µg/mL of fluconazole at inhibiting fungal growth of the strains tested. The most active compound (16) completely inhibited the growth of C. albicans SC5314 at 16 µg/mL for 24 h, affected biofilm formation and destroyed the mature biofilm at 64 µg/mL. Several Saccharomyces cerevisiae strains, overexpressing recombinant Cyp51s or drug efflux pumps, indicated 16, 18, and 29 targeted Cyp51 without being significantly affected by a common active site mutation, but were susceptible to target overexpression and efflux by both MFS and ABC transporters. GC-MS analysis demonstrated that 16, 18, and 29 interfered with the C. albicans ergosterol biosynthesis pathway by inhibition at Cyp51. Molecular docking studies elucidated the binding modes of 18 with Cyp51. The compounds showed low cytotoxicity, low hemolytic activity and favorable ADMT properties. Importantly, compound 16 showed potent in vivo antifungal efficacy in the G. mellonella infection model. Taken together, this study presents more effective, broad-spectrum, low toxicity triazole analogues that can contribute to the development of novel antifungal agents and help overcome antifungal resistance.

Natural Products as Antifungal Agents against Invasive Fungi.

BACKGROUND: Invasive fungal infections (IFIs) are primarily caused by Candida spp., Cryptococcus neoformans, Aspergillus spp., Mucor spp., Sporothrix spp., and Pneumocystis spp., which attack human organs with a strong pathogenicity and exhibit drug resistance against commonly used chemical drugs. Therefore, the search for alternative drugs with high efficacy, low resistance rates, few side effects, and synergistic antifungal effects remains a major challenge. The characteristics of natural products with structural and bioactive diversity, lower drug resistance, and rich resources make them a major focus of the development of antifungal drugs. OBJECTIVES: This review attempts to summarize the origin, structure, and antifungal activity of natural products and their derivatives with MIC ≤ 20 µg/mL or 100 µM, focusing on their MoA and SAR. METHODS: All pertinent literature databases were searched. The search keywords were antifungal or antifungals, terpenoids, steroidal saponins, alkaloid, phenols, lignans, flavonoids, quinones, macrolide, peptide, tetramic acid glycoside, polyene, polyketide, bithiazole, natural product, and derivatives. All the related literature (covering the past 20 years, 2001-2022) was evaluated. RESULTS: In total, 340 natural products and 34 synthesized derivatives with antifungal activity from 301 studies were included in this review. These compounds were derived from terrestrial plants, ocean life, and microorganisms and exhibited in vitro and in vivo potent antifungal activity alone or in combination. The MoA and SARs of reported compounds were summarized whenever applicable. CONCLUSION: In this review, we attempted to review the available literature on natural antifungal products and their derivatives. Most of the studied compounds showed potent activity against Candida species, Aspergillus species, or Cryptococcus species. Some of the studied compounds also demonstrated the ability to impair the cell membrane and cell wall, inhibit hypha and biofilms, and cause mitochondrial dysfunction. Although the MoAs of these compounds are not well understood yet, they can be used as lead components for the development of new, effective, and safe antifungal agents through their novel mechanisms.

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives.

Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.

Morphology-Tailored Hydroxyapatite Nanocarrier for Rhizosphere-Targeted Phosphorus Delivery.

High hydrophilicity and soil fixation collectively hamper the delivery of phosphorus (P) released from conventional chemical phosphorus fertilizers (CPFs) to plant rhizosphere for efficient uptake. Here, a phosphorus nutrient nanocarrier (PNC) based on morphology-tailored nanohydroxyapatite (HAP) is constructed. By virtue of kinetic control of building blocks with designed calcium phosphate intermediates, rod-like and hexagonal prism-like PNCs are synthesized, both having satisfactory hydrophobicity (water contact angle of 105.4- 132.9°) and zeta potential (-17.43 to -58.4 mV at pH range from 3 to 13). Greenhouse experiments demonstrate that the P contents increase by up to 183% in maize rhizosphere and up to 16% in maize biomass when compared to the CPF. Due to the water potential gradient driven by photosynthesis and transpiration, both PNCs are stably transported to maize rhizosphere, and they are capable to counteract soil fixation prior to uptake by plant roots. Within the synergies of the HAP morphological characteristics and triggered phosphate starvation response, root anatomy confirms that two pathways are elucidated to enhance plant P replenishment from the PNCs. Together with structure tunability and facile synthesis, our results offer a new nanodelivery prototype to accommodate plant physiological traits by tailoring the morphology of HAP.

Enhancing the Stability and Initial Coulombic Efficiency of Silicon Anodes through Coating with Glassy ZIF-4.

The high capacity of electrodes allows for a lower mass of electrodes, which is essential for increasing the energy density of the batteries. According to this, silicon is a promising anode candidate for Li-ion batteries due to its high theoretical capacity. However, its practical application is hampered by the significant volume expansion of silicon during battery operation, resulting in pulverization and contact loss. In this study, we developed a stable Li-ion anode that not only solves the problem of the short lifetime of silicon but also preserves the initial efficiency by using silicon nanoparticles covered with glassy ZIF-4 (SZ-4). SZ-4 suppresses silicon pulverization, contact loss, etc. because the glassy ZIF-4 wrapped around the silicon nanoparticles prevents additional SEI formation outside the silicon surface due to the electrically insulating characteristics of glassy ZIF-4. The SZ-4 realized by a simple heat treatment method showed 74% capacity retention after 100 cycles and a high initial efficiency of 78.7%.

Discovery of Novel Thiosemicarbazides Containing 1,3,5-Triazines Derivatives as Potential Synergists against Fluconazole-Resistant Candida albicans.

The clinical prevalence of antifungal drug resistance has been increasing over recent years, resulting in the failure of treatments. In an attempt to overcome this critical problem, we sought novel synergistic enhancers to restore the effectiveness of fluconazole against resistant Candida albicans. Based on the structural optimization of hit compound 8 from our in-house library, a series of novel 1,3,5-triazines derivatives was designed, synthesized, and biologically evaluated for synergistic activity in combination with fluconazole. Among them, compounds 10a-o, which contain thiosemicarbazides side chains, exhibited excellent in vitro synergistic antifungal potency (MIC80 = 0.125-2.0 µg/mL, FICI range from 0.127 to 0.25). Interestingly, compound 10l exhibited moderate C. albicans activity as monotherapy with an MIC80 value of 4.0 µg/mL, and also on several Cryptococcus strains (MIC80 ranging from ≤ 0.125-0.5 µg/mL) and C. glabrata (MIC80 ≤ 0.125 µg/mL). These effects were fungal-selective, with much lower levels of cytotoxicity towards human umbilical vein endothelial cells. Here, we report a series of thiosemicarbazides containing 1,3,5-triazines derivatives as potent synergists with fluconazole, and have preliminarily validated compound 10l as a promising antifungal lead for further investigation.

Design, synthesis, and in vitro evaluation of novel antifungal triazoles containing substituted 1,2,3-triazole-methoxyl side chains.

In order to develop new triazole derivatives, we optimized the lead compound a6 by structural modifications to obtain a series of (2R,3R)-3-((1-substituted-1H-1,2,3-triazol-4-yl) methoxy)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol, compounds 5-36. Most of the target compounds exhibited excellent in vitro antifungal activity against Candida albicans 10231 and Candida glabrata 537 with MIC ≤ 0.125 µg/mL. Of particular note, compounds 6, 22, 28, 30 and 36 were highly active against Candida neoformans 32609 with MIC ≤ 0.125 µg/mL and showed broad-spectrum antifungal activity including against fluconazole-resistant Candida auris 891. In addition, compounds 6 and 22 demonstrated inhibitory effects on filamentation in the azole-resistant C. albicans isolate. Moreover, compounds 6 and 22 were minimally toxic to HUVECs and possessed weak inhibitory effects on the human CYP3A4 and CYP2D6. SARs and docking study further indicated that ortho-substituted groups in the terminal phenyl ring can promote the compounds to improve their antifungal activity.

Synthesis of baicalein derivatives and evaluation of their antiviral activity against arboviruses.

Natural plant-derived baicalein which is extracted from Chinese herb Scutellaria baicalensis Georgi belongs to the flavonoid compounds and possesses multiple pharmacological activities. In this study, we designed and synthesized new series of derivatives of baicalein (BE) through catalytic coupling reactions, and screened for their antiviral activity against arboviruses including Chikungunya virus (CHIKV), West Nile virus (WNV) or Zika virus (ZIKV). Our results revealed for the first time that BE and its derivatives had potent anti-CHIKV, anti-WNV and anti-ZIKV effects. And modification of 8 or 4' position could lead to obtain potent antiviral compounds against CHIKV, WNV and ZIKV with lower cytotoxicity. Among the baicalein derivatives, C3 and F3 showed the most potent antiviral activities against CHIKV, WNV and ZIKV, which were 5-10 times more potent than baicalein. Our findings will provide research basis for the development of baicalein derivatives as effective antiviral agents.

[Composition and histopathological features of prostatic calculi in patients with benign prostatic hyperplasia].

OBJECTIVE: To analyze the composition of prostatic calculus in patients with BPH and explore its pathogenic factors and histopathological characteristics. METHODS: Strictly following the inclusion and exclusion criteria, we included in this retrospective study 580 cases of bipolar transurethral plasma kinetic prostatectomy (TUPKP) performed in our hospital from May 2015 to May 2019, analyzed the histopathological and calculus-composition features of the patients with BPH complicated by prostatic calculi (the BPH+PC group) and the histopathological data of those with BPH only (the BPH group). We compared the related factors between the two groups of patients and performed uni- and multivariate logistic regression analyses of the data on those in the BPH+PC group. RESULTS: The incidence rate of chronic inflammation was significantly higher in the BPH+PC than in the BPH group (83.1% vs 61.1%, P < 0.05), 90% of the cases moderate to severe and 81% with inflammatory cells mainly distributed in the prostate gland in the BPH+PC group, and 74% with inflammatory cells chiefly distributed in the prostate gland and stroma in the BPH group, with statistically significant difference between the two groups (P < 0.05). Prostatic calculi were found in 302 (52.1%) of the patients, including 71 cases of simple calculi (23.5%) and 231 cases of mixed calculi (76.5%). As for the chemical composition, calcium oxalate was detected in 212 cases (70.2%), carbonate apatite in 206 (68.2%), magnesium ammonium phosphate in 158 (52.3%), and uric acid calculi in 19 (6.3%). The calculus composition was not correlated with the age of the patients. There were statistically significant differences between the two groups of patients in age, prostate volume and IPSS (P < 0.05), but not in the PSA level, postvoid residual urine volume (PRV) or maximum urinary flow rate (Qmax) (P > 0.05). Logistic regression analyses showed that prostatic calculus was significantly correlated with chronic inflammation of the prostate, the patient's age and IPSS (P < 0.05) but not with the PSA level, PRV or Qmax (P > 0.05). CONCLUSIONS: Prostatic calculus has a high incidence in BPH patients and varies widely in composition, chiefly consisting of calcium oxalate and carbonate apatite. The major factors contributing to prostatic calculi include chronic inflammation of the prostate (primarily the severe type), age and BPH. Prostate calculi may aggravate lower urinary tract symptoms, especially urinary storage symptoms, in patients with BPH, but not significantly affect the PSA level.？.