Drug repurposing for COVID-19: could vitamin C combined with glycyrrhizic acid be at play by the findings of Li et al.'s database-based network pharmacology analysis?

The outbreak and pandemic of SARS-CoV-2 in 2019 has caused a severe public health burden and will challenge global health for the future. The discovery and mechanistic investigation of drugs against Coronavirus disease 2019 (COVID-19) is in deadly demand. The paper published by Li and colleagues proposed the hypothesis that vitamin C combined with glycyrrhizic acid in treating COVID-19 and its mechanistic investigation was performed by a database-based network pharmacology. In this letter, we present critical comments on the limitations and insufficiencies involved, from both the perspective of network pharmacology and current evidence on COVID-19.

Interferometric speckle visibility spectroscopy (iSVS) for measuring decorrelation time and dynamics of moving samples with enhanced signal-to-noise ratio and relaxed reference requirements.

Diffusing wave spectroscopy (DWS) is a group of techniques used to measure the dynamics of a scattering medium in a non-invasive manner. DWS methods rely on detecting the speckle light field from the moving scattering medium and measuring the speckle decorrelation time to quantify the scattering medium's dynamics. For DWS, the signal-to-noise (SNR) is determined by the ratio between measured decorrelation time to the standard error of the measurement. This SNR is often low in certain applications because of high noise variances and low signal intensity, especially in biological applications with restricted exposure and emission levels. To address this photon-limited signal-to-noise ratio problem, we investigated, theoretically and experimentally, the SNR of an interferometric speckle visibility spectroscopy (iSVS) compared to more traditional DWS methods. We found that iSVS can provide excellent SNR performance through its ability to overcome camera noise. We also proved an iSVS system has more relaxed constraints on the reference beam properties. For an iSVS system to function properly, we only require the reference beam to exhibit local temporal stability, while incident angle, reference phase and intensity uniformity do not need to be constrained. This flexibility can potentially enable more unconventional iSVS implementation schemes.

[Identification of quality markers of Qixuehe Capsules based on analytic hierarchy process and entropy weight methods].

Qixuehe Capsules is a compound Chinese patent medicine developed for treating the disorder of Qi and blood(a common etiology of gynecological disease), which has remarkable effects on smoothing liver and regulating Qi, activating blood circulation, and relieving pain. However, due to its complex prescriptions(15 herbs) and multiple effects, the quality control of Qixuehe Capsules has always been a bottleneck problem limiting its sustainable development. Therefore, this study adopted the traditional Chinese medicine Q-markers quantitative identification system established previously by our research group based on the combination of analytic hierarchy process and entropy weight methods. With the different effects of Qixuehe Capsules as the entry point, the comprehensive scores of chemical ingre-dients in Qixuehe Capsules under the items of effectiveness(smoothing liver and regulating qi, activating blood circulation, and relieving pain), testability and specificity were calculated and integrated, respectively. Subsequently, through the analysis of compatibility relationship of Qixuehe Capsules, 15 active ingredients with high comprehensive scores were found to be the top Q-mar-kers of Qixuehe Capsules, including ferulic acid, quercetin, caffeic acid, kaempferol, rutin, Z-ligustilide, senkyunolide Ⅰ, vanillic acid, protocatechuic acid, chlorogenic acid, rosmarinic acid, senkyunolide A, gallic acid, tetrahydropalmatine and eugenol. Collectively, this study not only provided scientific evidence for further research on the improvement and standardization of quality standards of Qixuehe Capsules but also provided methodological references for the quantitative identification of Q-markers of multi-effect traditional Chinese medicine formulae.

Novel Janus Membrane for Membrane Distillation with Simultaneous Fouling and Wetting Resistance.

A novel Janus membrane integrating an omniphobic substrate and an in-air hydrophilic, underwater superoleophobic skin layer was developed to enable membrane distillation (MD) to desalinate hypersaline brine with both hydrophobic foulants and amphiphilic wetting agents. Engineered to overcome the limitations of existing MD membranes, the Janus membrane has been shown to exhibit novel wetting properties unobserved in any existing membrane, including hydrophobic membranes, omniphobic membranes, and hydrophobic membranes with a hydrophilic surface coating. Being simultaneously resistant to both membrane fouling and wetting, a Janus membrane can sustain stable MD performance even with challenging feed waters and can thus potentially transform MD to be a viable technology for desalinating hypersaline wastewater with complex compositions using low-grade-thermal energy.

Synthesis of BiOClx Br1-x Nanoplate Solid Solutions as a Robust Photocatalyst with Tunable Band Structure.

The use of bismuth oxyhalides as photocatalysts has received extensive interest because of their high photocatalytic activity and stability. However, available methods for the synthesis of bismuth oxyhalides with tailored morphologies, well-defined facets, and tunable band gaps are still lacking. In this work, two-dimensional BiOClx Br1-x solid solution with exposed {001} facets and tunable band gaps were synthesized by using solvothermal methods. The BiOClx Br1-x solid solution nanoplates crystallized in a homogeneous crystal structure but possessed continuously tuned band gaps from 3.39 to 2.78 eV by decreasing the ratio of Cl/Br. Among the synthesized nanoplates, the BiOCl0.5 Br0.5 sample exhibited the highest photocatalytic activity for degrading Rhodamine B (RhB), a typical organic pollutant, under visible light. The highest photoactivity of the BiOCl0.5 Br0.5 sample was attributed to a synergetic effect of higher surface area, facets exposed, and optimized band structure. The results are of profound significance for the design of novel photocatalyst materials.

Light-driven microbial dissimilatory electron transfer to hematite.

The ability of dissimilatory metal-reducing microorganisms (DMRM) to conduct extracellular electron transfer with conductive cellular components grants them great potential for bioenergy and environmental applications. Crystalline Fe(III) oxide, a type of widespread electron acceptor for DMRM in nature, can be excited by light for photocatalysis and microbial culture-mediated photocurrent production. However, the feasibility of direct electron transfer from living cells to light-excited Fe(III) oxides has not been well documented and the cellular physiology in this process has not been clarified. To resolve these problems, an electrochemical system composed of Geobacter sulfurreducens and hematite (α-Fe2O3) was constructed, and direct electron transfer from G. sulfurreducens cells to the light-excited α-Fe2O3 in the absence of soluble electron shuttles was observed. Further studies evidenced the efficient excitation of α-Fe2O3 and the dependence of photocurrent production on the biocatalytic activity. Light-induced electron transfer on the cell-α-Fe2O3 interface correlated linearly with the rates of microbial respiration and substrate consumption. In addition, the G. sulfurreducens cells were found to survive on light-excited α-Fe2O3. These results prove a direct mechanism behind the DMRM respiration driven by photo-induced charge separation in semiconductive acceptors and also imply new opportunities to design photo-bioelectronic devices with living cells as a catalyst.

Monodisperse M(x)Fe(3-x)O4 (M = Fe, Cu, Co, Mn) nanoparticles and their electrocatalysis for oxygen reduction reaction.

Sub-10 nm nanoparticles (NPs) of M(II)-substituted magnetite MxFe3-xO4 (MxFe1-xO•Fe2O3) (M = Mn, Fe, Co, Cu) were synthesized and studied as electrocatalysts for oxygen reduction reaction (ORR) in 0.1 M KOH solution. Loaded on commercial carbon support, these MxFe3-xO4 NPs showed the M(II)-dependent ORR catalytic activities with MnxFe3-xO4 being the most active followed by CoxFe3-xO4, CuxFe3-xO4, and Fe3O4. The ORR activity of the MnxFe3-xO4 was further tuned by controlling x and MnFe2O4 NPs were found to be as efficient as the commercial Pt in catalyzing ORR. The MnFe2O4 NPs represent a new class of highly efficient non-Pt catalyst for ORR in alkaline media.

Pancreatic islet transplantation: current advances and challenges.

Diabetes is a prevalent chronic disease that traditionally requires severe reliance on medication for treatment. Oral medication and exogenous insulin can only temporarily maintain blood glucose levels and do not cure the disease. Most patients need life-long injections of exogenous insulin. In recent years, advances in islet transplantation have significantly advanced the treatment of diabetes, allowing patients to discontinue exogenous insulin and avoid complications.Long-term follow-up results from recent reports on islet transplantation suggest that they provide significant therapeutic benefit although patients still require immunotherapy, suggesting the importance of future transplantation strategies. Although organ shortage remains the primary obstacle for the development of islet transplantation, new sources of islet cells, such as stem cells and porcine islet cells, have been proposed, and are gradually being incorporated into clinical research. Further research on new transplantation sites, such as the subcutaneous space and mesenteric fat, may eventually replace the traditional portal vein intra-islet cell infusion. Additionally, the immunological rejection reaction in islet transplantation will be resolved through the combined application of immunosuppressant agents, islet encapsulation technology, and the most promising mesenchymal stem cells/regulatory T cell and islet cell combined transplantation cell therapy. This review summarizes the progress achieved in islet transplantation, and discusses the research progress and potential solutions to the challenges faced.

Compact and cost-effective laser-powered speckle contrast optical spectroscopy fiber-free device for measuring cerebral blood flow.

Significance: In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF noninvasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. Aim: Our study aims to introduce a compact speckle contrast optical spectroscopy device for noninvasive CBF measurements at long source-to-detector distances, offering cost-effectiveness, and scalability while tracking blood flow (BF) with remarkable sensitivity and temporal resolution. Approach: The wearable sensor module consists solely of a laser diode and a board camera. It can be easily placed on a subject's head to measure BF at a sampling rate of 80 Hz. Results: Compared to the single-fiber-based version, the proposed device achieved a signal gain of about 70 times, showed superior stability, reproducibility, and signal-to-noise ratio for measuring BF at long source-to-detector distances. The device can be distributed in multiple configurations around the head. Conclusions: Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing noninvasive cerebral monitoring technologies.

A compact and cost-effective laser-powered speckle visibility spectroscopy (SVS) device for measuring cerebral blood flow.

In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF non-invasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. This study aims to introduce a compact speckle visibility spectroscopy (SVS) device designed for non-invasive CBF measurements, offering cost-effectiveness and scalability while tracking CBF with remarkable sensitivity and temporal resolution. The wearable hardware has a modular design approach consisting solely of a laser diode as the source and a meticulously selected board camera as the detector. They both can be easily placed on a subject's head to measure CBF with no additional optical elements. The SVS device can achieve a sampling rate of 80 Hz with minimal susceptibility to external disturbances. The device also achieves better SNR compared with traditional fiber-based SVS devices, capturing about 70 times more signal and showing superior stability and reproducibility. It is designed to be paired and distributed in multiple configurations around the head, and measure signals that exceed the quality of prior optical CBF measurement techniques. Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing non-invasive cerebral monitoring technologies.

Photoautotrophic cathodic oxygen reduction catalyzed by a green alga, Chlamydomonas reinhardtii.

Biofuel cells (BFCs) use enzymes and microbial cells to produce energy from bioavailable substrates and treat various wastewaters, and cathodic oxygen reduction is a key factor governing the efficiency of BFCs. In this study, we demonstrated that a green alga, Chlamydomonas reinhardtii, could directly mediate oxygen reduction. Cyclic voltammogram analysis revealed that the C. reinhardtii biofilm formed on a solid electrode was responsible for oxygen reduction without dosing of electron mediator. Furthermore, 4-electron oxygen reduction pathway was found in this self-sustained, light-responded BFC. The results of this study could expand our understanding and viewpoints of biocathode catalysis, which is essential for novel catalyst design and development for BFCs.

Assessing depth sensitivity in laser interferometry speckle visibility spectroscopy (iSVS) through source-to-detector distance variation and cerebral blood flow monitoring in humans and rabbits.

Recently, speckle visibility spectroscopy (SVS) was non-invasively applied on the head to monitor cerebral blood flow. The technique, using a multi-pixel detecting device (e.g., camera), allows the detection of a larger number of speckles, increasing the proportion of light that is detected. Due to this increase, it is possible to collect light that has propagated deeper through the brain. As a direct consequence, cerebral blood flow can be monitored. However, isolating the cerebral blood flow from the other layers, such as the scalp or skull components, remains challenging. In this paper, we report our investigations on the depth-sensitivity of laser interferometry speckle visibility spectroscopy (iSVS). Specifically, we varied the depth of penetration of the laser light into the head by tuning the source-to-detector distance, and identified the transition point at which cerebral blood flow in humans and rabbits starts to be detected.

Analysis of phellinus igniarius effects on gastric cancer cells by atomic force microscopy.

Gastric cancer is one of the common malignant tumors in the world, which originates from the gene mutation of human cells. In this work, an atomic force microscope was used to quantitatively detect the changes of multiple physical parameters such as the cell morphology, surface roughness, elasticity modulus and adhesion force before and after Phellinus linteus stimulation. The experimental results show that Phellinus linteus can change the shape of gastric cancer cells (SGC-7901) from flat to spherical, and increase their height and surface roughness values. The adhesion force of cells is reduced and the elasticity modulus is increased. But there are no significant differences in the morphology and mechanical properties of gastric epithelial cells (GES-1). The results indicate that Phellinus linteus has a high anticancer effect on the gastric cancer cells, but has less toxic side effects on the gastric epithelial cells. This work proves that Phellinus linteus can be used as a preferred anticancer drug for the treatment of gastric cancer cells.

Comparing biotransformation of extracellular polymeric substances (EPS) under aerobic and anoxic conditions: Reactivities, components, and bacterial responses.

This study aimed to better understand the transformation behaviors of extracellular polymeric substances (EPS) and their roles in regulating bacterial community in biological wastewater treatment processes. Herein, well-controlled bioassays under aerobic and anoxic conditions were performed to investigate degradation dynamics, composition variations, and bacterial response during EPS transformation. Reactivity continuum modeling showed that organic pools of EPS had continuous reactivity distributions, and most labile organic fraction with a degrading rate >0.1 h-1 was substantially higher under aerobic (20.47%) than anoxic (2.02%) condition. Rapid degradation of protein-like substances in the initial degradation stage was accompanied by the humification process, as revealed by UV absorption spectroscopy, fluorescence spectroscopy, and size exclusion chromatography with continuous organic carbon detection analysis. The 16S rRNA gene sequencing results showed that the selection effect of EPS in controlling abundant populations during their transformation, e.g., Acinetobacter was enriched, and Candidatus Competibacter was washed out relative to the source community. Furthermore, taxonomic normalized stochasticity ratio-based null model and bacterial ecological network analysis indicated higher relative importance of deterministic process in shaping the EPS-degrading communities under aerobic than anoxic condition, likely explaining the faster EPS biotransformation under aerobic condition. Intriguingly, the keystone populations driving EPS metabolism showed the environmental filtering characteristics (e.g., capable of degrading refractory and aromatic compounds or adapting to harsh environments) and cooperative interactions with the co-occurring species under both conditions. This work is expected to reveal the fates and roles of EPS in wastewater treatment plants extensively.

Stabilization of Antitumor Agent Busulfan through Encapsulation within a Water-Soluble Pillar[5]arene.

The complexation of the antitumor agent busulfan by negatively charged carboxylatopillar[5]arene in water is reported. The encapsulation within carboxylatopillar[5]arene reduces the hydrolytic degradation of busulfan from 90.7% to 25.2% after 24 days and accordingly enhances its stability by providing a hydrophobic shelter for busulfan in water. Moreover, the complexation results in 12 times improvement of water solubility for busulfan. Our result provides a supramolecular approach for stabilizing the anticancer agent busulfan.

Simultaneous methanogenesis and denitrification coupled with nitrifying biofilm for high-strength wastewater treatment: Performance and microbial mechanisms.

A combined system consisting of an upflow blanket filter (UBF) and a moving-bed biofilm reactor (MBBR) was developed for the simultaneous removal of organic matters and ammonia from high-strength wastewater. With a constant COD of approximately 2000 mg/L and ammonium nitrogen in a series of concentrations (e.g., 50, 200 and 400 mg/L in stages I to III) of the influent wastewater, the removal efficiencies of COD, ammonium nitrogen and total nitrogen reached 96.10%-98.19%, 100%, and 79.12%-82.15%, respectively. With the increase of influent ammonia nitrogen concentration, the specific methanogenic activity of the UBF granules decreased significantly, while the specific denitrification rates of the UBF granules and specific nitrification rates of the MBBR biofilms increased significantly. Microbial community analysis showed that Methanobacterium and Methanosaeta were the dominant methanogens in the UBF granules, while Candidatus Competibacter, Thauera and Acinetobacter were identified as dominant denitrifiers. In addition, nitrifiers were enriched in MBBR biofilms at 11.33% and 13.87% of the average abundance of Nitrosomonas and Nitrospira, respectively, at stage III (influent ammonium at 400 mg/L, COD/NH4+-N =  5). The ecological network analysis, including full-networks and sub-networks, indicated that the interactions between methanogens and denitrifiers in the UBF granules were strong when the influent ammonium concentration reached 400 mg/L. No intensive interactions were observed among the functional bacteria in the MBBR biofilms over the entire operation. Overall, this study provides a new strategy for the application and construction of efficient biological processes to achieve simultaneous removal of organic matter and nitrogen for high-strength wastewater treatment.

Multi-Layered Branched Surface Fluorination on PVDF Membrane for Anti-Scaling Membrane Distillation.

Membrane distillation (MD) has emerged as a promising technology for hypersaline wastewater treatment. However, membrane scaling is still a critical issue for common hydrophobic MD membranes. Herein, we report a multi-layered surface modification strategy on the commercial polyvinylidene fluoride (PVDF) membrane via plasma treatment and surface fluorination cycles. The repeated plasma treatment process generates more reaction sites for the fluorination reaction, leading to higher fluorination density and more branched structures. MD tests with CaSO4 as the scaling agent show that the modification strategy mentioned above improves the membrane scaling resistance. Notably, the PVDF membrane treated with three cycles of plasma and fluorination treatments exhibits the best anti-scaling performance while maintaining almost the same membrane flux as the unmodified PVDF membrane. This study suggests that a highly branched surface molecular structure with low surface energy benefits the MD process in both membrane flux and scaling resistance. Besides, our research demonstrates a universal and facile approach for membrane treatment to improve membrane scaling resistance.

Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review.

Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.

Bioactive prenylated phenolic compounds from the aerial parts of Glycyrrhiza uralensis.

In this work, a bioassay-guided fractionation strategy was used to isolate 26 phenolic compounds from the ethyl acetate partition of an ethanol extract of the aerial parts of Glycyrrhiza uralensis Fisch. ex DC. Among them, 8 prenylated phenolic compounds (glycyuralins Q-X) were described for the first time. The two enantiomers of glycyuralin Q were purified and their absolute configurations were established by ECD spectral calculations. (1″R, 2″S)-glycyuralin Q and (1″S, 2″R)-glycyuralin Q showed significant inhibitory activities against SARS-CoV-2 virus proteases 3CLpro with IC50 values of 1.5 ± 1.0 and 4.0 ± 0.3 µM, and PLpro with IC50 values of 2.4 ± 0.2 and 1.9 ± 0.1 µM, respectively. Four compounds showed potent cytotoxic activities against A549, Huh-7, and HepG2 human cancer cells with IC50 values ranging from 0.5 to 2.5 µM.