Euchronin A-F isolated from the Arnebia euchroma (Royle) Johnst. and their anti-proliferative activities in vitro.

Six new naphthoquinones, euchronin A-F (1-6) and nine known naphthoquinones (7-15), were isolated from the roots of Arnebia euchroma (Royle) Johnst. The structures of the new compounds were confirmed by extensive spectroscopic analyses, including UV, IR, HR-ESI-MS, 1D and 2D NMR. In the present study, we estimated the anti-proliferative activities of these compounds with HaCaT cells. The results indicated that compounds 2 and 4 showed strong anti-proliferative activities at 25 µM, with relative viability at 38.83% and 68.44%, respectively.

Cytoplasmic Escape of Mitochondrial DNA Mediated by Mfn2 Downregulation Promotes Microglial Activation via cGas-Sting Axis in Spinal Cord Injury.

Neuroinflammation is associated with poor outcomes in patients with spinal cord injury (SCI). Recent studies have demonstrated that stimulator of interferon genes (Sting) plays a key role in inflammatory diseases. However, the role of Sting in SCI remains unclear. In the present study, it is found that increased Sting expression is mainly derived from activated microglia after SCI. Interestingly, knockout of Sting in microglia can improve the recovery of neurological function after SCI. Microglial Sting knockout restrains the polarization of microglia toward the M1 phenotype and alleviates neuronal death. Furthermore, it is found that the downregulation of mitofusin 2 (Mfn2) expression in microglial cells leads to an imbalance in mitochondrial fusion and division, inducing the release of mitochondrial DNA (mtDNA), which mediates the activation of the cGas-Sting signaling pathway and aggravates inflammatory response damage after SCI. A biomimetic microglial nanoparticle strategy to deliver MASM7 (named MSNs-MASM7@MI) is established. In vitro, MSNs-MASM7@MI showed no biological toxicity and effectively delivered MASM7. In vivo, MSNs-MASM7@MI improves nerve function after SCI. The study provides evidence that cGas-Sting signaling senses Mfn2-dependent mtDNA release and that its activation may play a key role in SCI. These findings provide new perspectives and potential therapeutic targets for SCI treatment.

Chinese Herbal Medicine for the Treatment of Adult Viral Myocarditis: An Overview of Systematic Reviews and Meta-analyses of Randomized Controlled Trials.

PURPOSE: Viral myocarditis (VMC) is a life-threatening disease that can affect all ages and genders, with middle-aged adults being particularly susceptible. Numerous systematic reviews have been conducted to investigate the efficacy and safety of Chinese herbal medicine (CHM) in treating adult viral myocarditis (AVM). The objective of this study was to conduct a comprehensive overview of systematic reviews and meta-analyses of randomized controlled trials (RCTs) regarding the efficacy and safety of CHM for AVM. METHODS: A comprehensive systematic search was conducted across 8 electronic databases from their inception to June 23, 2022, augmented by manual searches of the gray literature. Systematic reviews were independently selected and data extracted in accordance with predetermined criteria by 2 reviewers. Included systematic reviews were assessed for methodologic and reporting quality using Assessing the Methodological Quality of Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of evidence relating to outcome measures was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Recalculation of effect sizes and subsequent determination of 95% CIs were conducted with either a fixed-effects or random-effects model. FINDINGS: The current overview of systematic reviews included a total of 6 systematic reviews, which reported on 67 RCTs with a participant pool of 5611 individuals. The findings of our study indicate that the combination of CHM and Western medications had positive effects on the effective rate, cure rate, ECG recovery, atrial premature contraction/premature ventricular contraction, left ventricular ejection fraction, myocardial enzymes, and improvement of clinical symptoms for AVM. The adverse drug reactions in the combination therapy group were generally less than or lighter than that in the Western medication group (relative risk = 0.79; 95% CI, 0.44-1.40; P > 0.05, I2 = 0). IMPLICATIONS: Our research results provide evidence that combining CHM with Western medicine could offer potential benefits for patients with AVM. However, the number of studies included in our review is limited and the methodologic quality of these studies is modest. Therefore, there are potential uncertainties regarding the conclusion that CHM with Western medication may benefit patients with AVM. We call for more large-scale, high-quality studies with standardized designs to further verify and support our findings. This would promote a better understanding of the efficacy and safety profile of CHM and provide reliable reference evidence for clinical practice and policy making. Moreover, future research should explore optimal drug combinations, examine therapeutic doses and durations of CHM combination therapy, and evaluate its long-term efficacy and safety.

Cellular differentiation into hyphae and spores in halophilic archaea.

Several groups of bacteria have complex life cycles involving cellular differentiation and multicellular structures. For example, actinobacteria of the genus Streptomyces form multicellular vegetative hyphae, aerial hyphae, and spores. However, similar life cycles have not yet been described for archaea. Here, we show that several haloarchaea of the family Halobacteriaceae display a life cycle resembling that of Streptomyces bacteria. Strain YIM 93972 (isolated from a salt marsh) undergoes cellular differentiation into mycelia and spores. Other closely related strains are also able to form mycelia, and comparative genomic analyses point to gene signatures (apparent gain or loss of certain genes) that are shared by members of this clade within the Halobacteriaceae. Genomic, transcriptomic and proteomic analyses of non-differentiating mutants suggest that a Cdc48-family ATPase might be involved in cellular differentiation in strain YIM 93972. Additionally, a gene encoding a putative oligopeptide transporter from YIM 93972 can restore the ability to form hyphae in a Streptomyces coelicolor mutant that carries a deletion in a homologous gene cluster (bldKA-bldKE), suggesting functional equivalence. We propose strain YIM 93972 as representative of a new species in a new genus within the family Halobacteriaceae, for which the name Actinoarchaeum halophilum gen. nov., sp. nov. is herewith proposed. Our demonstration of a complex life cycle in a group of haloarchaea adds a new dimension to our understanding of the biological diversity and environmental adaptation of archaea.

First-Principles Study of n*AlN/n*ScN Superlattices with High Dielectric Capacity for Energy Storage.

As a paradigm of exploiting electronic-structure engineering on semiconductor superlattices to develop advanced dielectric film materials with high electrical energy storage, the n*AlN/n*ScN superlattices are systematically investigated by first-principles calculations of structural stability, band structure and dielectric polarizability. Electrical energy storage density is evaluated by dielectric permittivity under a high electric field approaching the uppermost critical value determined by a superlattice band gap, which hinges on the constituent layer thickness and crystallographic orientation of superlattices. It is demonstrated that the constituent layer thickness as indicated by larger n and superlattice orientations as in (111) crystallographic plane can be effectively exploited to modify dielectric permittivity and band gap, respectively, and thus promote energy density of electric capacitors. Simultaneously increasing the thicknesses of individual constituent layers maintains adequate band gaps while slightly reducing dielectric polarizability from electronic localization of valence band-edge in ScN constituent layers. The AlN/ScN superlattices oriented in the wurtzite (111) plane acquire higher dielectric energy density due to the significant improvement in electronic band gaps. The present study renders a framework for modifying the band gap and dielectric properties to acquire high energy storage in semiconductor superlattices.

Schisandraceae triterpenoids: A review of phytochemistry, bioactivities and synthesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Schisandraceae family have a rich and medicinal history dating back to ancient times. Many of them are used as folk medicine in the treatment of chronic coughs, asthma, nocturnal emission, spontaneous sweating, night sweats, palpitation, insomnia and thirst. AIM OF THE REVIEW: The current review is carried out on triterpenoids from the Schisandraceae family, aiming to comprehensively summarize their phytochemistry, pharmacology and synthesis and provide new insights to the chemical and pharmacological study and rational utilization on medicinal plants of the Schisandarceae family. MATERIALS AND METHODS: The information was searched from the scientific literature published from June 2014 to November 2021 on the online databases (including PubMed, CNKI, Elsevier, SciFinder and Web of Science) and other bibliography (e.g. the Chinese Pharmacopoeia, 2020 edition, Chinese herbal books). The scientific literature related to phytochemistry, pharmacology, biological activites and synthesis of triterpenoids from the Schisandraceae family was gathered. RESULTS: From June 2014 to November 2021, there were approximately 211 novel triterpenoids isolated and identified from 18 species of the Schisandraceae family. These compounds exhibit tremendous diversity in their structures, and some of them possess promising pharmacological activities, including anti-viral, anti-tumor, anti-inflammatory, hepatoprotective, immunosuppressive activities and neuroprotective effects. In the attempt to synthesize active compounds, the total synthesis of 13 schinortriterpenoids belonging to five structural types was successfully completed. CONCLUSIONS: Studies of triterpenoids from the Schisandraceae family are well documented in this review (from June 2014 to November 2021), and it is also well acknowledged that they are valuable resources with medicinal efficacy. However, relevant pharmacological studies are limited to in vitro tests, and data from in vivo studies and toxicology are lacking or unavailable. Fortunately, there is growing interest in the synthesis of active compounds, which should serve as an approach for accessing active compounds to develop in vivo or toxicity studies, with a view of clarifying their in vitro and vivo mechanisms for more effective and safe natural drugs.

Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway.

OBJECTIVE: To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved. METHODS: MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-ß (TGF-ß1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively. RESULTS: PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-ß1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05). CONCLUSIONS: PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

Contemporary treatment of Western and Chinese medicine for cardiac syndrome X.

Clinical reports on cardiac syndrome X (CSX) have been increasing in recent years. In general, CSX does not increase the cardiovascular mortality, but it can affect the patient's quality of life (QOL) and increase the incidence rates of cardiovascular and cerebrovascular events. Although a variety of drugs and therapies have been utilized in the clinical treatment, the management of CSX still represents a major challenge due to its unclear pathogenesis. It is necessary to explore more effective treatment programs. Many attempts have been made on trials of the Chinese medicine (CM) treatment for CSX and proved that CM has a certain advantage in efficacy to improve clinical symptoms and QOL. CM may provide a new approach for the effective treatment of CSX.

[Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure].

OBJECTIVE: To explore the effects of Shenmai Injection (SMI), a compound traditional Chinese herbal medicine, on pharmacokinetics and serum concentration of digoxin when applied together with digoxin. METHODS: Twenty dogs with heart failure were randomly divided into 4 groups: control group and low-, medium- and high-dose SMI groups, with 5 dogs in each group. After intravenous injection of digoxin injection at a dose of 7.41 µg/kg, dogs in the control group were administered intravenously with normal saline 20 mL daily for 5 d, and the other groups were intravenously administered with SMI at the doses of 0.517, 1.034 and 1.551 mL/kg respectively. After the administration, the blood was collected at designed time points. Serum concentration of digoxin was determined by high-performance liquid chromatography with electrospray tandem mass spectrometry (HPLC/MS/MS). RESULTS: The low-, medium- and high-dose SMI showed different effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI revealed a tendency to decrease the elimination half-life (T(1/2ß)) of digoxin. The low-dose SMI showed a tendency to decrease the digoxin concentration. Serum clearance (CL) in the low-dose SMI group was higher than that in the control, and also significantly higher than those in the medium- and high-dose SMI groups (P<0.05). The area under concentration-time curve (AUC(0→∞)) in the low-dose SMI group was lower than that in the control group (P=0.05); the AUC(0→72 h) and AUC(0→∞) in the low-dose SMI group were significantly lower than those in the medium- and high-dose SMI groups. Low-dose SMI accelerated the clearance of digoxin in blood. CONCLUSION: Low-, medium- and high-dose SMI shows different effects on pharmacokinetics of digoxin and reveals a tendency to shorten T(1/2ß) of digoxin. Low-dose SMI can accelerate the clearance of digoxin in blood.

Stereological assessment of extracellular polymeric substances, exo-enzymes, and specific bacterial strains in bioaggregates using fluorescence experiments.

This review addresses the introduction of fluorescent molecular tags into exo-enzymes and extra polymeric substances of bioaggregates and the use of confocal laser scanning microscopy (CLSM) to map their role, purpose and quantitative description of the biological processes they undertake. Multiple color staining coupled with CLSM and fluorescent in situ hybridisation (FISH) and flow cytometry have identified the individual polymeric substances, whether they are proteins, lipids, polysaccharides, nucleic acids or antibodies, as well as the microorganisms in the bioaggregate. Procedures are presented for simultaneous multicolor staining with seven different fluorochromes - SYTOX Blue for nucleic acids; Nile red for lipids; Calcofluor white [CW] for beta-polysaccharides; concanavalin A [Con A] for alpha-poly-saccharides; fluorescein-isothiocyanate [FITC] for proteins; SYTO 63 for live microbial cells and Calcium Green for monitoring calcium levels in the microbial cells. For the distribution of certain microbial strains, metabolic enzymes and extrapolymeric substances to be quantitatively described the generated colored images are converted into digital forms under specific predefined criteria. Procedures and computer software programs (Amira; MATLAB) are presented in order to quantitatively establish grid patterns from the CLSM images. The image is digitized using a threshholding algorithm followed by a reconstruction of the image as a volumetric grid for finite element simulation. The original color image is first converted to a grey followed by resizing, detection and modification of bilevel images and finally a total reversal of the image colors. The grid file is then used by specific computer software (Gambit, Fluent) for further numerical studies incorporating chemical reactions, transport processes and computational fluid dynamics including intra-bioaggregate fluid flow, and heat and mass transfer within the bioaggregate matrix.

Biodegradation of 4-aminobenzenesulfonate by a novel Pannonibacter sp. W1 isolated from activated sludge.

4-Aminobenzenesulfonate (4-ABS) is a representative intermediate of some sulfonated azo dyes. A novel Pannonibacter sp. strain W1 capable of degrading 4-ABS as sole carbon as well as energy, nitrogen and sulfur source was isolated and identified from the activated sludge of a municipal wastewater treatment plant. Strain W1 was able to completely degrade 4-ABS with initial concentrations of 200-2500 mg L(-1) within 40 h. Haldane inhibition model was used to fit the special degradation rate at different initial concentrations, and the parameters micro(max), K(s) and K(i) were determined to be 227.977 mg (gh)(-1), 84.306 mg L(-1) and 1270.675 mg L(-1), respectively. Elements N and S of 4-ABS were released in respective forms of ammonia and sulfate while degrading 4-ABS by strain W1, accounting for 77.6% and 92.2% of theoretical values, respectively. Relatively low recoveries of dissolved N and S were probably owing to the fact that part of the released ammonia and sulfate were utilized by strain W1 for cell growth. It was found that the reduction of total organic carbon (TOC) was proportional to the degradation of 4-ABS and 84.4% TOC removal rate, corresponding to a 4-ABS degradation rate of 94.7%, was achieved at the end of the test. Additionally, HPLC and UV analyses indicated that there were no other aromatic intermediates detectable, suggesting the achievement of a complete mineralization of 4-ABS with strain W1.

Stability of partial nitrification and microbial population dynamics in a bioaugmented membrane bioreactor.

Bioaugmentation of bioreactors focuses on the removal of numerous organics, with little attention typically paid to the maintenance of high and stable nitrite accumulation in partial nitrification. In this study, a bioaugmented membrane bioreactor (MBR) inoculated with enriched ammonia-oxidizing bacteria (AOB) was developed, and the effects of dissolved oxygen (DO) and temperature on stability of partial nitrification and microbial community structure, in particular on nitrifying community were evaluated. The results showed that DO and temperature played the most important roles in the stability of partial nitrification in the bioaugmented MBR. The optimal operation conditions were found at 2-3 mgDO/L and 30 degrees C, achieving 95% ammonia oxidization efficiency and 0.95 of nitrite ratio (NO2-/NOx-). High-DO (5-6 mg/L) and low-temperature (20 degrees C) had negative impacts on nitrite accumulation, leading to its drop to 0.6. However, the nitrite ratio achieved in the bioaugmented MBR was higher than that in most previous literatures. Denaturing gradient gel electrophoresis (DGGE) and fluorescence in situ hybridization (FISH) were used to provide an insight into the microbial community. It showed that Nitrosomonas-like species as the only detected AOB remained predominant in the bioaugmented MBR all the time, which coexisted with numerous heterotrophic bacteria. The heterotrophic bacteria responsible for mineralizing soluble microbial products (SMP) produced by nitrifiers belonged to Cytophaga-Flavobacterium-Bacteroides (CFB) group, alpha-, beta-, and gamma- Proteobacteria. The fraction of AOB ranging from 77% to 54% was much higher than that of NOB (0.4-0.9%), which might be the primary cause for the high and stable nitrite accumulation in the bioaugmented MBR.

A novel application of TPAD-MBR system to the pilot treatment of chemical synthesis-based pharmaceutical wastewater.

A pilot-scale test was conducted with a two-phase anaerobic digestion (TPAD) system and a subsequential membrane bioreactor (MBR) treating chemical synthesis-based pharmaceutical wastewater. The TPAD system comprised a continuous stirred tank reactor (CSTR) and an upflow anaerobic sludge blanket-anaerobic filter (UASBAF), working as the acidogenic and methanogenic phases, respectively. The wastewater was high in COD, varying daily between 5789 and 58,792 mg L(-1), with a wide range of pH from 4.3 to 7.2. The wastewater was pumped at a fixed flow rate of 1m(3)h(-1) through the CSTR, the UASBAF and the MBR in series, resulting in respective HRTs of 12, 55 and 5h. Almost all the COD was removed by the TPAD-MBR system, leaving a COD of around 40 mg L(-1) in the MBR effluent. The pH of the MBR effluent was found in a narrow range of 6.8-7.6, indicating that the MBR effluent can be directly discharged into natural waters. A model, built on the back propagation neural network (BPNN) theory and linear regression techniques, was developed for the simulation of TPAD-MBR system performance in the biodegradation of chemical synthesis-based pharmaceutical wastewater. The model well fitted the laboratory data, and was able to simulate the removal of COD.

Characteristics of rapidly formed hydrogen-producing granules and biofilms.

The physicochemical and microbiological characteristics of rapidly formed hydrogen-producing granules and biofilms were evaluated in the present study. Microbial species composition was examined using the 16S rDNA-based separation and sequencing techniques, and spatial distribution and internal structure of microbial components were evaluated by examining the confocal laser scanning microscope (CLSM) images. Phylogenetic analysis indicated that a pure culture of Clostridium pasteurianum-like bacterium (98% similarity) was found in microbial community of granules and biofilms. It is postulated that containing such a species favored the rapid immobilization of hydrogen-producing culture. Manure granules and biofilms secreted 24-35 mg extracellulous proteins and 142-175 mg extracellulous polysaccharides in each gram of culture (in VSS). Such a high productivity of extracellulous polymers (ECP), a bio-glue to facilitate cell-to-cell and/or cell-to-substratum interaction, may work as the driving forces for the immobilization of C. pasteurianum. As abundant proteins were noted in the granule cores, it can be derived that rapid formation of the hydrogen-producing granules could be due to the establishment of precursor protein-rich microbial nuclei.

Summary of 32 patients with cardiac syndrome X treated by TCM therapy of regulating qi relieving chest stuffiness and promoting blood circulation.

OBJECTIVE: To evaluate the clinical effect of Liqi Kuanxiong Huoxue method LKH, traditional Chinese medicine, TCM therapeutic method for regulating qi, relieving chest stuffiness and promoting blood circulation) in treating patients with cardiac syndrome X (CSX). METHODS: The prospective, non-randomized controlled study was conducted on 51 selected patients with CSX, who were non-randomly assigned to 2 groups, the treated group treated with LKH in addition to the conventional treatment (32 patients), and the control group treated with conventional treatment (19 patients) like nitrate, diltiazem hydrochloride, etc. The treatment course was 14 days. The changes of such symptoms as angina pectoris, TCM syndrome and indexes of treadmill exercise test before and after treatment were observed. RESULTS: After treatment, such symptoms as chest pain and stuffy feeling and palpitation in the treated group were improved more than those in the control group (P<0.05); the total effective rate on angina pectoris and TCM syndrome in the treated group was better than that in the control group (P<0.05). The treadmill exercise test showed that the maximal metabolic equivalent (Max MET), the time of angina onset and ST segment depression by 0.1 mV were obviously improved after treatment in both groups, but the improvement in the treated group was better than that in the control group respectively (P<0.05). CONCLUSION: The LKH method could reduce the frequency of angina attacks and improve the clinical condition of patients with CSX.

Rapid formation of hydrogen-producing granules in an anaerobic continuous stirred tank reactor induced by acid incubation.

A novel approach to rapidly initiate granulation of hydrogen-producing sludge was developed in an anaerobic continuous stirred tank reactor at 37 degrees C. To induce microbial granulation, the acclimated culture was subject to an acid incubation for 24 h by shifting the culture pH from 5.5 to 2.0. The culture was resumed to pH 5.5 after the incubation and the reactor was operated at hydraulic retention times (HRTs) of 12, 6, 2, 1, and 0.5 h in sequence. Microbial aggregation took place immediately with the initiation of acid incubation and granules were developed at 114 h. No granule was observed in the absence of acid incubation in the control test. Changing the culture pH resulted in improvement in surface physicochemical properties of the culture favoring microbial granulation. The zeta potential increased from -11.6 to -3.5 mV, hydrophobicity in terms of contact angle improved from 31 degrees to 43 degrees and extracellular proteins/polysaccharides ratio increased from 0.2 to 0.5-0.8. Formation of granular sludge facilitated biomass retention of up to 32.2 g-VSS/L and enhanced hydrogen production. The hydrogen production rate and hydrogen yield increased with the reduction in HRT at an influent glucose concentration of 10 g/L once steady granular sludge layer was formed, achieving the respective peaks of 3.20 L/L x h and 1.81 mol-H(2)/mol-glucose at 0.5 h HRT. The experimental results suggested that acid incubation was able to initiate the rapid formation of hydrogen-producing granules by regulating the surface characteristics of microbial aggregates in a well-mixed reactor, which enhanced the hydrogen production.