A nomogram based on the quantitative and qualitative features of CT imaging for the prediction of the invasiveness of ground glass nodules in lung adenocarcinoma.

PURPOSE: Based on the quantitative and qualitative features of CT imaging, a model for predicting the invasiveness of ground-glass nodules (GGNs) was constructed, which could provide a reference value for preoperative planning of GGN patients. MATERIALS AND METHODS: Altogether, 702 patients with GGNs (including 748 GGNs) were included in this study. The GGNs operated between September 2020 and July 2022 were classified into the training group (n = 555), and those operated between August 2022 and November 2022 were classified into the validation group (n = 193). Clinical data and the quantitative and qualitative features of CT imaging were harvested from these patients. In the training group, the quantitative and qualitative characteristics in CT imaging of GGNs were analyzed by using performing univariate and multivariate logistic regression analyses, followed by constructing a nomogram prediction model. The differentiation, calibration, and clinical practicability in both the training and validation groups were assessed by the nomogram models. RESULTS: In the training group, multivariate logistic regression analysis disclosed that the maximum diameter (OR = 4.707, 95%CI: 2.06-10.758), consolidation/tumor ratio (CTR) (OR = 1.027, 95%CI: 1.011-1.043), maximum CT value (OR = 1.025, 95%CI: 1.004-1.047), mean CT value (OR = 1.035, 95%CI: 1.008-1.063; P = 0.012), spiculation sign (OR = 2.055, 95%CI: 1.148-3.679), and vascular convergence sign (OR = 2.508, 95%CI: 1.345-4.676) were independent risk parameters for invasive adenocarcinoma. Based on these findings, we established a nomogram model for predicting the invasiveness of GGN, and the AUC was 0.910 (95%CI: 0.885-0.934) and 0.902 (95%CI: 0.859-0.944) in the training group and the validation group, respectively. The internal validation of the Bootstrap method showed an AUC value of 0.905, indicating a good differentiation of the model. Hosmer-Lemeshow goodness of fit test for the training and validation groups indicated that the model had a good fitting effect (P > 0.05). Furthermore, the calibration curve and decision analysis curve of the training and validation groups reflected that the model had a good calibration degree and clinical practicability. CONCLUSION: Combined with the quantitative and qualitative features of CT imaging, a nomogram prediction model can be created to forecast the invasiveness of GGNs. This model has good prediction efficacy for the invasiveness of GGNs and can provide help for the clinical management and decision-making of GGNs.

Development and validation of a risk prediction model for invasiveness of pure ground-glass nodules based on a systematic review and meta-analysis.

BACKGROUND: Assessing the aggressiveness of pure ground glass nodules early on significantly aids in making informed clinical decisions. OBJECTIVE: Developing a predictive model to assess the aggressiveness of pure ground glass nodules in lung adenocarcinoma is the study's goal. METHODS: A comprehensive search for studies on the relationship between computed tomography(CT) characteristics and the aggressiveness of pure ground glass nodules was conducted using databases such as PubMed, Embase, Web of Science, Cochrane Library, Scopus, Wanfang, CNKI, VIP, and CBM, up to December 20, 2023. Two independent researchers were responsible for screening literature, extracting data, and assessing the quality of the studies. Meta-analysis was performed using Stata 16.0, with the training data derived from this analysis. To identify publication bias, Funnel plots and Egger tests and Begg test were employed. This meta-analysis facilitated the creation of a risk prediction model for invasive adenocarcinoma in pure ground glass nodules. Data on clinical presentation and CT imaging features of patients treated surgically for these nodules at the Third Affiliated Hospital of Kunming Medical University, from September 2020 to September 2023, were compiled and scrutinized using specific inclusion and exclusion criteria. The model's effectiveness for predicting invasive adenocarcinoma risk in pure ground glass nodules was validated using ROC curves, calibration curves, and decision analysis curves. RESULTS: In this analysis, 17 studies were incorporated. Key variables included in the model were the largest diameter of the lesion, average CT value, presence of pleural traction, and spiculation. The derived formula from the meta-analysis was: 1.16×the largest lesion diameter + 0.01 × the average CT value + 0.66 × pleural traction + 0.44 × spiculation. This model underwent validation using an external set of 512 pure ground glass nodules, demonstrating good diagnostic performance with an ROC curve area of 0.880 (95% CI: 0.852-0.909). The calibration curve indicated accurate predictions, and the decision analysis curve suggested high clinical applicability of the model. CONCLUSION: We established a predictive model for determining the invasiveness of pure ground-glass nodules, incorporating four key radiological indicators. This model is both straightforward and effective for identifying patients with a high likelihood of invasive adenocarcinoma.

[Exosome and prevention of Alzheimer's disease: based on theory of kidney storing essence].

The theory of kidney storing essence storage, an important part of the basic theory of traditional Chinese medicine(TCM), comes from the Chapter 9 Discussion on Six-Plus-Six System and the Manifestations of the Viscera in the Plain Questions, which says that "the kidney manages closure and is the root of storage and the house of Jing(Essence)". According to this theory, essence is the fundamental substance of human life activities and it is closely related to the growth and development of the human body. Alzheimer's disease(AD) is one of the common neurodegenerative diseases, with the main pathological features of Aß deposition and Tau phosphorylation, which activate neurotoxic reactions and eventually lead to neuronal dysfunction and cell death, severely impairing the patient's cognitive and memory functions. Although research results have been achieved in the TCM treatment of AD, the complex pathogenesis of AD makes it difficult to develop the drugs capable of curing AD. The stem cell therapy is an important method to promote self-repair and regeneration, and bone marrow mesenchymal stem cells(BMSCs) as adult stem cells have the ability of multi-directional differentiation. By reviewing the relevant literature, this paper discusses the association between BMSCs and the TCM theory of kidney storing essence, and expounds the material basis of this theory from the perspective of molecular biology. Studies have shown that TCM with the effect of tonifying the kidney in the treatment of AD are associated with BMSCs. Exosomes produced by such cells are one of the main substances affecting AD. Exosomes containing nucleic acids, proteins, and lipids can participate in intercellular communication, regulate cell function, and affect AD by reducing Aß deposition, inhibiting Tau protein phosphorylation and neuroinflammation, and promoting neuronal regeneration. Therefore, discussing the prevention and treatment of exosomes and AD based on the theory of kidney storing essence will provide a new research idea for the TCM treatment of AD.

Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.

Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.

Boundary-Layer Disruption and Heat-Transfer Enhancement in Convection Turbulence by Oscillating Deformations of Boundary.

In this Letter, we propose a novel strategy for significantly enhancing the heat transfer in convection turbulence. By introducing a boundary deformation of the standing-wave type, flow modulation can be realized when the amplitude is comparable or larger than the boundary-layer thickness. For a fixed moderate frequency, the entire fluid layer follows the boundary motion at small wave numbers, while only the near-wall regions are affected by the boundary deformation at large wave numbers. The heat-flux enhancement happens for the latter. For a fixed wave number and gradually increasing frequency, the vortical flows inside the wave valleys exhibit nonlinear transition and alter the distribution of boundary heat flux, and the global heat flux increases significantly at large enough frequencies. The current findings suggest that oscillating deformations of boundary can efficiently break the boundary layers, which serves as the bottleneck of global heat transfer, and open a new venue for modulating the convection turbulence.

Multiple states and transport properties of double-diffusive convection turbulence.

When fluid stratification is induced by the vertical gradients of two scalars with different diffusivities, double-diffusive convection (DDC) may occur and play a crucial role in mixing. Such a process exists in many natural and engineering environments. Especially in the ocean, DDC is omnipresent since the seawater density is affected by temperature and salinity. The most intriguing phenomenon caused by DDC is the thermohaline staircase, i.e., a stack of alternating well-mixed convection layers and sharp interfaces with very large gradients in both temperature and salinity. Here we investigate DDC and thermohaline staircases in the salt finger regime, which happens when warm saltier water lies above cold fresher water and is commonly observed in the (sub)tropic regions. By conducting direct numerical simulations over a large range of parameters, we reveal that multiple equilibrium states exist in fingering DDC and staircases even for the same control parameters. Different states can be established from different initial scalar distributions or different evolution histories of the flow parameters. Hysteresis appears during the transition from a staircase to a single salt finger interface. For the same local density ratio, salt finger interfaces in the single-layer state generate very different fluxes compared to those within staircases. However, the salinity flux for all salt finger interfaces follows the same dependence on the salinity Rayleigh number of the layer and can be described by an effective power law scaling. Our findings have direct applications to oceanic thermohaline staircases.

Evaluation of surgical outcomes and prognostic factors of second primary lung cancer based on a systematic review and meta-analysis.

BACKGROUND: Although surgery has been widely applied for SPLC therapy, there is still no uniform treatment approach. Whether SPLC and primary lung cancer have similar prognostic characteristics remains controversial. Herein, based on a systematic review and meta-analysis, we aimed to enucleate the influences of diverse surgical strategies and underlying prognostic factors on the prognosis of patients with both the first primary lung cancer and SPLC underwent surgical resection. METHODS: A comprehensive and systematic literature search was implemented in three databases (MEDLINE, EMBASE, and Cochrane), and eligible studies were screened following inclusion and exclusion criteria. Meanwhile, we extracted the hazard ratios (HR) together with 95% confidence intervals (CI) for each prognostic factor, either directly or indirectly, from the enrolled literature. RESULTS: Eleven studies (published between 2000 and 2022) were included in this study, including 1,131 SPLC patients. The overall survival (OS) exhibited no difference between patients with lobectomy and sublobar resection after SPLC (HR: 0.87, 95%CI: 0.62-1.21, P = 0.41). The patients after completion pneumonectomy had a poor prognosis (HR: 1.85, 95% CI: 1.34-2.55, P < 0.01). Poor prognostic factors after SPLC surgery included synchronous SPLC (HR: 3.38, 95%CI: 1.53-7.46, P < 0.01), tumor diameter > 2 cm (HR: 2.44, 95%CI: 1.73-3.44, P < 0.01), solid predominant in CT morphology (HR: 3.08, 95% CI: 1.14-8.33, P = 0.03), lymph node metastasis (HR: 2.79, 95%CI: 1.40-5.56), and smoking (HR: 2.37, 95%CI: 1.08-26.82, P < 0.01). Tumor disease-free interval (DFI), tumor histological type, and gender had no impact on the prognosis of patients received SPLC surgery. CONCLUSIONS: Patients with SPLC, especially those with poor cardiopulmonary function reserve, should be prioritized for sublobar resection for treatment. These patients should also try to avoid completion pneumonectomy. Patients with synchronous SPLC, tumor diameter > 2 cm, solid predominant in CT morphology, lymph node metastasis, and smoking had a poor prognosis. Meanwhile, SPLC has similar prognostic characteristics with single primary lung cancer. However, the study has some limitations and more evidence is warranted to verify the findings.

A Review of Research on the Association between Neuron-Astrocyte Signaling Processes and Depressive Symptoms.

Depression is a mental illness that has a serious negative impact on physical and mental health. The pathophysiology of depression is still unknown, and therapeutic medications have drawbacks, such as poor effectiveness, strong dependence, adverse drug withdrawal symptoms, and harmful side effects. Therefore, the primary purpose of contemporary research is to understand the exact pathophysiology of depression. The connection between astrocytes, neurons, and their interactions with depression has recently become the focus of great research interest. This review summarizes the pathological changes of neurons and astrocytes, and their interactions in depression, including the alterations of mid-spiny neurons and pyramidal neurons, the alterations of astrocyte-related biomarkers, and the alterations of gliotransmitters between astrocytes and neurons. In addition to providing the subjects of this research and suggestions for the pathogenesis and treatment techniques of depression, the intention of this article is to more clearly identify links between neuronal-astrocyte signaling processes and depressive symptoms.

Enhanced degradation of VOCs from biomass gasification catalyzed by Ni/HZSM-5 series catalyst.

Volatile organic compounds (VOCs) evolved from biomass gasification plays a positive role in the formation of PM2.5 and odor pollution. In order to improve the removal rate of various VOCs produced by biomass gasification, a nickel-based supported HZSM-5 cataly st (Ni/HZSM-5 and Ni-Ca-Co/HZSM-5) was prepared by different auxiliary methods, Ni loadings, and pyrolysis temperatures. The catalytic cracking performance of Ni/HZSM-5 catalysts for different VOCs model compounds such as toluene, phenol, furan, acetic acid and cyclohexane were studied in a fixed-bed reactor. The catalysts were further characterized and analyzed by XRD, SEM, XPS and BET. The results showed that the Ni/HZSM--C-Co5 catalyst prepared by ultrasonic-assisted excess impregnation method with Ni loading of 8 wt%, Ca loading of 4 wt%, Co loading of 0.1 wt% had strong catalytic activity for VOCs degradation. With the increase of the cracking temperature, the conversion rate and gas yield of from model compound cracking improved significantly. At 800 °C, the conversion of each model compound was more than 90%, accompanied by the generation of cracking gases such as H2 and CH4. The selectivity of H2 and CH4 from toluene cracking reached 93%, and cyclohexane reached 98%. The models with higher oxygen content and lower bond energy were more likely to undergo reforming reaction to form small molecular gas. Model compounds with large molecular weight and high carbon content provided more carbon sources. Under the conversion degree towards the gas direction was high. This study provides a new idea on the removal of VOCs for the efficient utilization of biomass resources.

A c-di-GMP Signaling Cascade Controls Motility, Biofilm Formation, and Virulence in Burkholderia thailandensis.

As a key bacterial second messenger, cyclic di-GMP (c-di-GMP) regulates various physiological processes, such as motility, biofilm formation, and virulence. Cellular c-di-GMP levels are regulated by the opposing activities of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs). Beyond that, the enzymatic activities of c-di-GMP metabolizing proteins are controlled by a variety of extracellular signals and intracellular physiological conditions. Here, we report that pdcA (BTH_II2363), pdcB (BTH_II2364), and pdcC (BTH_II2365) are cotranscribed in the same operon and are involved in a regulatory cascade controlling the cellular level of c-di-GMP in Burkholderia thailandensis. The GGDEF domain-containing protein PdcA was found to be a DGC that modulates biofilm formation, motility, and virulence in B. thailandensis. Moreover, the DGC activity of PdcA was inhibited by phosphorylated PdcC, a single-domain response regulator composed of only the phosphoryl-accepting REC domain. The phosphatase PdcB affects the function of PdcA by dephosphorylating PdcC. The observation that homologous operons of pdcABC are widespread among betaproteobacteria and gammaproteobacteria suggests a general mechanism by which the intracellular concentration of c-di-GMP is modulated to coordinate bacterial behavior and virulence. IMPORTANCE The transition from planktonic cells to biofilm cells is a successful strategy adopted by bacteria to survive in diverse environments, while the second messenger c-di-GMP plays an important role in this process. Cellular c-di-GMP levels are mainly controlled by modulating the activity of c-di-GMP-metabolizing proteins via the sensory domains adjacent to their enzymatic domains. However, in most cases how c-di-GMP-metabolizing enzymes are modulated by their sensory domains remains unclear. Here, we reveal a new c-di-GMP signaling cascade that regulates motility, biofilm formation, and virulence in B. thailandensis. While pdcA, pdcB, and pdcC constitute an operon, the phosphorylated PdcC binds the PAS sensory domain of PdcA to inhibit its DGC activity, with PdcB dephosphorylating PdcC to derepress the activity of PdcA. We also show this c-di-GMP regulatory model is widespread in the phylum Proteobacteria. Our study expands the current knowledge of how bacteria regulate intracellular c-di-GMP levels.

An anisotropic immerse precipitation process for the preparation of polymer membranes.

We study the immerse precipitation process in a ternary polymer/solvent/non-solvent system by numerically solving the two-dimensional Cahn-Hilliard phase field equation. In particular, we introduce anisotropic mobility, namely the mobility of a polymer varies over different spatial directions, and focus on the porosity morphology of the obtained polymer membrane. Simulations reveal that as the anisotropy increases in the polymer mobility, the polymer pattern changes from nearly isotropic and random voids to strips parallel to the direction with smaller mobility. The influence of anisotropy quickly saturates. The anisotropic mobility model is also applied to a ternary system mimicking the preparation of a hollow fiber membrane, and shows strong effects on the membrane porosity pattern.

Coevolutionary dynamics of host-pathogen interaction with density-dependent mortality.

This study explores the coevolutionary dynamics of host-pathogen interaction based on a susceptible-infected population model with density-dependent mortality. We assume that both the host's resistance and the pathogen's virulence will adaptively evolve, but there are inevitable costs in terms of host birth rate and disease-related mortality rate. Particularly, it is assumed that both the host resistance and pathogen virulence can affect the transmission rate. By using the approach of adaptive dynamics and numerical simulation, we find that the finally coevolutionary outcome depends on the strength of host-pathogen asymmetric interaction, the curvature of trade-off functions, and the intensity of density-dependent natural mortality. To be specific, firstly, we find that if the strengths of host-pathogen asymmetric interaction and disease-related mortality are relatively weak, or the density-dependent natural mortality is relatively strong, then the host resistance and pathogen virulence will evolve to a continuously stable strategy. However, if the strength of host-pathogen asymmetric interaction and disease-related mortality becomes stronger, then the host resistance and pathogen virulence will evolve periodically. Secondly, we find that if the intensities of both the birth rate trade-off function and the density-dependent natural mortality are relatively weak, but the strength of host-pathogen asymmetric interaction becomes relatively strong, then the evolution of host resistance will have a relatively strongly accelerating benefit, the evolutionary branching of host resistance will first arise. However, if the strength of host-pathogen asymmetric interaction is relatively weak, but the intensity of the trade-off function of disease-related mortality becomes relatively strong, then the evolution of pathogen virulence will have a relatively strongly decelerating cost, and the evolutionary branching of pathogen virulence will first arise. Thirdly, after the evolutionary branching of host resistance and pathogen virulence, we further study the coevolutionary dynamics of two-hosts-one-pathogen interaction and one-host-two-pathogens interaction. We find that if the evolutionary branching of host resistance arises firstly, then the finally evolutionary outcome contains a dimorphic host and a monomorphic pathogen population. If the evolutionary branching of pathogen virulence arises firstly, then the finally evolutionary outcome may contain a monomorphic host and a dimorphic pathogen population.

A qualitative study on the working experiences of clinical pharmacists in fighting against COVID-19.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) has overwhelmed healthcare systems across the world. Along with the medical team, clinical pharmacists played a significant role during the public health emergency of COVID-19. This study aimed to explore the working experience of clinical pharmacists and provide reference for first-line clinical pharmacists to prepare for fighting against COVID-19. METHODS: A qualitative study based on descriptive phenomenology was employed with face-to-face and audio-recorded interviews to study the working experience of 13 clinical pharmacists (including two clinical nutritional pharmacists). All interviews were transcribed verbatim, and the interview data were analyzed thematically using NVivo software. RESULTS: Four themes emerged from interview data, including roles of clinical pharmacists, working experiences of clinical pharmacists, psychological feelings of clinical pharmacists, and career expectations of clinical pharmacists. CONCLUSIONS: The results contributed to a deeper understanding of the clinical pharmacists' work experiences in COVID-19 and offered guidance to better prepare clinical pharmacists in participating in a public health crisis.

Roles of Gag-RNA interactions in HIV-1 virus assembly deciphered by single-molecule localization microscopy.

During HIV-1 assembly, the retroviral structural protein Gag forms an immature capsid, containing thousands of Gag molecules, at the plasma membrane (PM). Interactions between Gag nucleocapsid (NC) and viral RNA (vRNA) are thought to drive assembly, but the exact roles of these interactions have remained poorly understood. Since previous studies have shown that Gag dimer- or trimer-forming mutants (GagZiL) lacking an NC domain can form immature capsids independent of RNA binding, it is often hypothesized that vRNA drives Gag assembly by inducing Gag to form low-ordered multimers, but is dispensable for subsequent assembly. In this study, we examined the role of vRNA in HIV-1 assembly by characterizing the distribution and mobility of Gag and Gag NC mutants at the PM using photoactivated localization microscopy (PALM) and single-particle tracking PALM (spt-PALM). We showed that both Gag and GagZiL assembly involve a similar basic assembly unit, as expected. Unexpectedly, the two proteins underwent different subsequent assembly pathways, with Gag cluster density increasing asymptotically, while GagZiL cluster density increased linearly. Additionally, the directed movement of Gag, but not GagZiL, was maintained at a constant speed, suggesting that the two proteins experience different external driving forces. Assembly was abolished when Gag was rendered monomeric by NC deletion. Collectively, these results suggest that, beyond inducing Gag to form low-ordered multimer basic assembly units, vRNA is essential in scaffolding and maintaining the stability of the subsequent assembly process. This finding should advance the current understanding of HIV-1 and, potentially, other retroviruses.

Human replication protein A induces dynamic changes in single-stranded DNA and RNA structures.

Replication protein A (RPA) is the major eukaryotic ssDNA-binding protein and has essential roles in genome maintenance. RPA binds to ssDNA through multiple modes, and recent studies have suggested that the RPA-ssDNA interaction is dynamic. However, how RPA alternates between different binding modes and modifies ssDNA structures in this dynamic interaction remains unknown. Here, we used single-molecule FRET to systematically investigate the interaction between human RPA and ssDNA. We show that RPA can adopt different types of binding complexes with ssDNAs of different lengths, leading to the straightening or bending of the ssDNAs, depending on both the length and structure of the ssDNA substrate and the RPA concentration. Importantly, we noted that some of the complexes are highly dynamic, whereas others appear relatively static. On the basis of the above observations, we propose a model explaining how RPA dynamically engages with ssDNA. Of note, fluorescence anisotropy indicated that RPA can also associate with RNA but with a lower binding affinity than with ssDNA. At the single-molecule level, we observed that RPA is undergoing rapid and repetitive associations with and dissociation from the RNA. This study may provide new insights into the rich dynamics of RPA binding to ssDNA and RNA.

Administration of a mixture of triterpenoids from yeyachun and phenolic acids from danshen ameliorates carbon tetrachloride-induced liver fibrosis in mice by the regulation of intestinal flora.

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.

Combination of high-resolution accurate mass spectrometry and network pharmacology provides a new method for the chemical constituents' study and target prediction in vivo of Garcinia multiflora.

Garcinia multiflora is a kind of evergreen tree which is widely distributed in the south of China. However, few researches focused on the constituents in different parts of G. multiflora as well as their potential targets and pathways in vivo. To clarify the chemical constituents of G. multiflora rapidly and predict the potential targets as well as pathways in vivo that this plant may have effects on, a feasible and accurate strategy was developed to identify the chemical constituents in fruits, leaves, and branches of G. multiflora by ultra-high performance liquid chromatography with Q-Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry. Network pharmacology was then employed and a "compounds-targets-diseases" network was established. Sixty-one compounds including polycyclic polyprenylated acylphloroglucinols, xanthones, and flavonoids were finally identified in different parts of G. multiflora, and the contents of seven constituents were quantified, respectively. On the basis of the network pharmacology analysis results, compounds in this plant were speculated to have potential pharmacodynamic effect on cancer, inflammatory, respiratory diseases, cardiovascular diseases, and metabolic diseases. This research will provide a new method for the advanced study on the pharmacodynamic materials basis of G. multiflora, and offer valuable evidences for medicinal purpose of this plant.

A CRISPR/molecular beacon hybrid system for live-cell genomic imaging.

The clustered regularly interspersed short palindromic repeat (CRISPR) gene-editing system has been repurposed for live-cell genomic imaging, but existing approaches rely on fluorescent protein reporters, making sensitive and continuous imaging difficult. Here, we present a fluorophore-based live-cell genomic imaging system that consists of a nuclease-deactivated mutant of the Cas9 protein (dCas9), a molecular beacon (MB), and an engineered single-guide RNA (sgRNA) harboring a unique MB target sequence (sgRNA-MTS), termed CRISPR/MB. Specifically, dCas9 and sgRNA-MTS are first co-expressed to target a specific locus in cells, followed by delivery of MBs that can then hybridize to MTS to illuminate the target locus. We demonstrated the feasibility of this approach for quantifying genomic loci, for monitoring chromatin dynamics, and for dual-color imaging when using two orthogonal MB/MTS pairs. With flexibility in selecting different combinations of fluorophore/quencher pairs and MB/MTS sequences, our CRISPR/MB hybrid system could be a promising platform for investigating chromatin activities.

From convection rolls to finger convection in double-diffusive turbulence.

Double-diffusive convection (DDC), which is the buoyancy-driven flow with fluid density depending on two scalar components, is ubiquitous in many natural and engineering environments. Of great interests are scalars' transfer rate and flow structures. Here we systematically investigate DDC flow between two horizontal plates, driven by an unstable salinity gradient and stabilized by a temperature gradient. Counterintuitively, when increasing the stabilizing temperature gradient, the salinity flux first increases, even though the velocity monotonically decreases, before it finally breaks down to the purely diffusive value. The enhanced salinity transport is traced back to a transition in the overall flow pattern, namely from large-scale convection rolls to well-organized vertically oriented salt fingers. We also show and explain that the unifying theory of thermal convection originally developed by Grossmann and Lohse for Rayleigh-Bénard convection can be directly applied to DDC flow for a wide range of control parameters (Lewis number and density ratio), including those which cover the common values relevant for ocean flows.

A new similarity method for assessment of pharmacokinetic interaction between flucloxacillin and midazolam.

The purpose of this study was to develop a new similarity method to assess the drug-drug interaction between midazolam and flucloxacillin. Total quantum statistical moment (TQSM) of pharmacokinetic profiles were expressed by parameters AUCT, MRTT, VRTT et al. Statistical moment similarity (SMS) expressions were deduced to evaluate the similarity of the converted pharmacokinetic profiles. A trial of the pharmacokinetic interaction between midazolam and flucloxacillin by the SMS method was conducted. For midazolam, total quantum SMS (SMST) was 0.9582; total deviation was 0.0525; total variable probability was 4.18 %; total confidence of probability ß was 97.17 % under significance level 0.05; AUC0-∞ were 334.3±334.1 ng•h•mL-1 (after administration of midazolam alone) and 206.9±172.2 ng•h•mL-1 (after co-administration of midazolam and flucloxacillin), respectively. While, for 1'-hydroxy midazolam, SMST was 0.6920; total deviation was 0.3960; total variable probability was 30.80 %; total confidence of probability ß was 94.10 % under significance level 0.05; AUC0-∞ were 1364±810.7 ng•h•mL-1 (after administration of midazolam alone) and 1637±632.6 ng•h•mL-1 (after co-administration of midazolam and flucloxacillin), respectively. These results revealed that flucloxacillin might have weak pharmacokinetic interactions on midazolam metabolized into 1'-hydroxy midazolam, indicating that there was weak induction to CYP3A by flucloxacillin and that there was at least 30.80 % of metabolic behaviour in change with bioavailability decreased by 38.11 % that took effect to flucloxacillin metabolism for liver injury in CPY3A4 poor metabolic polymorphisms. SMS can be an optional method applied to characterize and analyze pharmacokinetic profiles.