Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

Isoliquiritin Ameliorates Ulcerative Colitis in Rats through Caspase 3/HMGB1/TLR4 Dependent Signaling Pathway.

BACKGROUND: Isoliquiritin belongs to flavanol glycosides and has a strong antiinflammatory activity. This study sought to investigate the anti-inflammatory effect of isoliquiritin and its underlying mechanism. METHODS: The inflammatory (trinitro-benzene-sulfonic acid-TNBS-induced ulcerative colitis (UC)) model was established to ascertain the effect of isoliquiritin on the caspase-3/HMGB1/TLR4 pathway in rats. We also explored its protective effect on intestinal inflammation and its underlying mechanism using the LPS-induced inflammation model of Caco-2 cells. Besides, Deseq2 was used to analyze UCassociated protein levels. RESULTS: Isoliquiritin treatment significantly attenuated shortened colon length (induced by TNBS), disease activity index (DAI) score, and body weight loss in rats. A decrease in the levels of inflammatory mediators (IL-1ß, I IL-4, L-6, IL-10, PGE2, and TNF-α), coupled with malondialdehyde (MDA) and superoxide dismutase (SOD), was observed in colon tissue and serum of rats after they have received isoliquiritin. Results of techniques (like western blotting, real-time PCR, immunohistochemistry, and immunofluorescence-IF) demonstrated the potential of isoliquiritin to decrease expressions of key genes in the TLR4 downstream pathways, viz., MyD88, IRAK1, TRAF6, NF-κB, p38, and JNK at mRNA and protein levels as well as inhibit HMGB1 expression, which is the upstream ligand of TLR4. Bioinformational analysis showed enteritis to be associated with a high expression of HMGB1, TLR4, and caspase-3. CONCLUSION: Isoliquiritin could reduce intestinal inflammation and mucosal damage of TNBS-induced colitis in rats with a certain anti-UC effect. Meanwhile, isoliquiritin treatment also inhibited the expression of HMGB1, TLR4, and MyD88 in LPS-induced Caco-2 cells. These results indicated that isoliquiritin could ameliorate UC through the caspase-3/HMGB1/TLR4-dependent signaling pathway.

High-performance thermomagnetic generator controlled by a magnetocaloric switch.

Low grade waste heat accounts for ~65% of total waste heat, but conventional waste heat recovery technology exhibits low conversion efficiency for low grade waste heat recovery. Hence, we designed a thermomagnetic generator for such applications. Unlike its usual role as the coil core or big magnetic yoke in previous works, here the magnetocaloric material acts as a switch that controls the magnetic circuit. This makes it not only have the advantage of flux reversal of the pretzel-like topology, but also present a simpler design, lower magnetic stray field, and higher performance by using less magnetocaloric material than preceding devices. The effects of key structural and system parameters were studied through a combination of experiments and finite element simulations. The optimized max power density PDmax produced by our device is significantly higher than those of other existing active thermomagnetic, thermo, and pyroelectric generators. Such high performance shows the effectiveness of our topology design of magnetic circuit with magnetocaloric switch.

METTL14 is decreased and regulates m6 A modification of α-synuclein in Parkinson's disease.

N6-methyladenosine (m6A), an emerging modification of messenger RNA, has been implicated in many biological processes. However, its role in Parkinson's disease (PD) remains largely unknown. Here, we investigated the role of m6A modification and its underlying mechanism in PD. First, 86 individuals with PD and 86 healthy controls were recruited from a pilot multicenter cohort. Levels of m6A and its modulators in peripheral blood mononuclear cells of patients with PD and controls were measured using an m6A RNA methylation quantification kit and quantitative real-time PCR. The underlying mechanism of m6A modification in PD was investigated in vitro through RNA immunoprecipitation assay, RNA stability assay, gene silencing or overexpression, western blot, and confocal immunoassay. The results show that mRNA levels of m6A, METTL3, METTL14, and YTHDF2 in patients with PD were significantly lower than in healthy controls, and METTL14 was the main factor involved in abnormal m6A modification. Area under the curve (AUC) analysis suggests METTL14 may provide excellent diagnostic capability for PD, especially when combined with plasma α-synuclein (α-syn). Spearman correlation analysis identified that METTL14 was moderately negatively correlated with plasma α-syn and the motor function of PD. Mechanistic experiments demonstrated that Mettl14 targets and regulates the expression of the α-syn gene using its methylation function. Overexpression of Mettl14 dramatically increased m6 A modification of α-syn mRNA and weakened its stability. Further results suggest that α-syn mRNA was modified by Mettl14 binding of an m6 A motif in the coding region of α-syn mRNA, while the reading protein Ythdf2 was involved in recognizing m6 A-modified α-syn mRNA. Taken together, our results reveal the potential of METTL14 as a novel diagnostic biomarker for PD and identify modification of pathogenic α-syn protein by METTL14 via an m6 A-YTHDF2-dependent mechanism.

SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway.

Nasopharyngeal carcinoma is one of the common malignant tumors that the pathogenesis has not yet been completely defined. SETD1A (histone lysine methyltransferase SET domain-containing 1A) is related to the occurrence of various cancers. However, the role of SETD1A in nasopharyngeal carcinoma remains unclear. The SETD1A overexpression vector, si-NC, si-SETD1A#1, and si-SETD1A#2 were transfected into nasopharyngeal carcinoma cells to overexpress or knockdown SETD1A expression. The assay of biofunction was used to explore the role of SETD1A in nasopharyngeal carcinoma cells. The assay of glucose uptake, lactate release, ATP level, western blot, cell proliferation, and cellular apoptosis analysis were performed to investigate the potential mechanism of SETD1A regulation in nasopharyngeal carcinoma. This study was the first to show that SETD1A was upregulated in nasopharyngeal carcinoma cells and the overexpression of SETD1A significantly promoted the cell proliferation and glycolysis and suppressed the cellular apoptosis. Moreover, SETD1A enhances aerobic glycolysis and cell biological function of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway. SETD1A induced PI3K/AKT activation and subsequently prevented cellular apoptosis. In conclusion, this study identified overexpressed SETD1A as a positive regulator of proliferation that induced nasopharyngeal carcinoma cells' aerobic glycolysis via PI3K/AKT signaling activation in vitro. This study laid a strong foundation for unveiling the precise anticancer mechanism of SETD1A. The SETD1A may become a novel biomarker for further inhibitor design to obstruct the PI3K/AKT-dependent nasopharyngeal carcinoma progression.

Relationship Between Mortality and Seizures After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

Background: The relationship between mortality and seizures after intracerebral hemorrhage (ICH) has not yet been understood until now. A meta-analysis was performed to assess the effect of post-ICH seizures on mortality among patients with ICH. Methods: PubMed and Embase were searched from the establishment of the databases to December 2021 to identify literature that evaluated the relationship between post-ICH seizures and mortality in ICH. Crude odds ratios and adjusted odds ratios with a 95% confidence interval (CI) were pooled using a random-effects model. Results: Thirteen studies involving 245,908 participants were eventually included for analysis. The pooled estimate suggested that post-ICH seizures were not associated with significantly increased mortality in patients with ICH (crude odds ratios 1.35, 95% CI: 0.91-2; adjusted adds ratios 1.22, 95% CI: 0.78-1.88). However, the relationship was not consistent in subgroup analysis or robust in a sensitivity analysis. Conclusions: This meta-analysis proved that post-ICH seizures were not associated with significantly increased mortality in patients with ICH. However, this result could be influenced by confounding factors, so more high-quality research is needed.

Preparation of Fraxetin Long Circulating Liposome and Its Anti-enteritis Effect.

This study sought to improve the oral bioavailability and enhance the anti-enteritis effect of fraxetin by incorporating it into long circulating liposomes (F-LC-Lipo). The optimal formulation of F-LC-Lipo was obtained via orthogonal design. The particle size, morphology, encapsulation efficiency, stability, and anti-enteritis effect of F-LC-Lipo were evaluated. The particle size of F-LC-Lipo was 166.65 ± 8.75 nm with entrapment efficiency (EE) of 92.18 ± 0.17%. The release rate in different dissolution media (pH 1.2 HCl, DDW, and pH 7.4 PBS) was significantly higher than that of fraxetin solution. Compared with the free fraxetin solution, F-LC-Lipo increased oral bioavailability of fraxetin by 4.43 times (443%). More importantly, F-LC-Lipo could improve the levels of interleukin-1 beta (IL-1ß), IL-6, malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), prostaglandin E2 (PEG2), and IL-10 in rats with enteritis. Overall, these results suggested that LC-Lipo may serve as a potential carrier for improving the solubility and oral bioavailability of fraxetin as well as improving its enteritis effect.

Relationship between annualized case volume and in-hospital motality in subarachnoid hemorrhage: A systematic review and meta-analysis.

ABSTRACT: Studies on the relationship between hospital annualized case volume and in-hospital mortality in patients with subarachnoid hemorrhage (SAH) have shown conflicting results. Therefore, we performed a meta-analysis to further examine this relationship.The authors searched the PubMed and Embase databases from inception through July 2020 to identify studies that assessed the relationship between hospital annualized SAH case volume and in-hospital SAH mortality. Studies that reported in-hospital mortality in SAH patients and an adjusted odds ratio (OR) comparing mortality between low-volume and high-volume hospitals or provided core data to calculate an adjusted OR were eligible for inclusion. No language or human subject restrictions were imposed.Five retrospective cohort studies with 46,186 patients were included for analysis. The pooled estimate revealed an inverse relationship between annualized case volume and in-hospital mortality (OR, 0.53; 95% confidence interval, 0.42-0.68, P < .0001). This relationship was consistent in almost all subgroup analyses and was robust in sensitivity analyses.This meta-analysis confirms an inverse relationship between hospital annualized SAH case volume and in-hospital SAH mortality. Higher annualized case volume was associated with lower in-hospital mortality.

De novo design of an intercellular signaling toolbox for multi-channel cell-cell communication and biological computation.

Intercellular signaling is indispensable for single cells to form complex biological structures, such as biofilms, tissues and organs. The genetic tools available for engineering intercellular signaling, however, are quite limited. Here we exploit the chemical diversity of biological small molecules to de novo design a genetic toolbox for high-performance, multi-channel cell-cell communications and biological computations. By biosynthetic pathway design for signal molecules, rational engineering of sensing promoters and directed evolution of sensing transcription factors, we obtain six cell-cell signaling channels in bacteria with orthogonality far exceeding the conventional quorum sensing systems and successfully transfer some of them into yeast and human cells. For demonstration, they are applied in cell consortia to generate bacterial colony-patterns using up to four signaling channels simultaneously and to implement distributed bio-computation containing seven different strains as basic units. This intercellular signaling toolbox paves the way for engineering complex multicellularity including artificial ecosystems and smart tissues.

A genetically engineered Escherichia coli that senses and degrades tetracycline antibiotic residue.

Due to the abuse of antibiotics, antibiotic residues can be detected in both natural environment and various industrial products, posing threat to the environment and human health. Here we describe the design and implementation of an engineered Escherichia coli capable of degrading tetracycline (Tc)-one of the commonly used antibiotics once on humans and now on poultry, cattle and fisheries. A Tc-degrading enzyme, TetX, from the obligate anaerobe Bacteroides fragilis was cloned and recombinantly expressed in E. coli and fully characterized, including its K m and k cat value. We quantitatively evaluated its activity both in vitro and in vivo by UV-Vis spectrometer and LC-MS. Moreover, we used a tetracycline inducible amplification circuit including T7 RNA polymerase and its specific promoter PT7 to enhance the expression level of TetX, and studied the dose-response of TetX under different inducer concentrations. Since the deployment of genetically modified organisms (GMOs) outside laboratory brings about safety concerns, it is necessary to explore the possibility of integrating a kill-switch. Toxin-Antitoxin (TA) systems were used to construct a mutually dependent host-plasmid platform and biocontainment systems in various academic and industrious situations. We selected nine TA systems from various bacteria strains and measured the toxicity of toxins (T) and the detoxifying activity of cognate antitoxins (A) to validate their potential to be used to build a kill-switch. These results prove the possibility of using engineered microorganisms to tackle antibiotic residues in environment efficiently and safely.

Motivational interviewing for improving recovery after stroke.

BACKGROUND: Psychological problems are common complications following stroke that can cause stroke survivors to lack the motivation to take part in activities of daily living. Motivational interviewing provides a specific way for enhancing intrinsic motivation, which may help to improve activities of daily living for stroke survivors. OBJECTIVES: To investigate the effect of motivational interviewing for improving activities of daily living after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group's Trials Register (November 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1), MEDLINE (1948 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), PsycINFO (1806 to March 2015), PsycBITE (March 2015) and four Chinese databases. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers and conference proceedings, checked reference lists, and contacted authors of relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing motivational interviewing with no intervention, sham motivational interviewing or other psychological therapy for people with stroke were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted eligible data and assessed risk of bias. Outcome measures included activities of daily living, mood and death. MAIN RESULTS: One study involving a total of 411 participants, which compared motivational interviewing with usual care, met our inclusion criteria. The results of this review did not show significant differences between groups receiving motivational interviewing or usual stroke care for participants who were not dependent on others for activities of daily living, nor on the death rate after three-month and 12-month follow-up, but participants receiving motivational interviewing were more likely to have a normal mood than those who received usual care at three-months and 12-months follow-up. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of motivational interviewing for improving activities of daily living after stroke. Further well designed RCTs are needed.

Mycophenolate mofetil for relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system and a leading cause of disability in young and middle-aged adults. Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been used for the prevention of allograft rejection after renal, cardiac, or liver transplant and in patients with autoimmune diseases such as active relapsing-remitting (RRMS) and progressive MS. OBJECTIVES: To assess the efficacy and safety of MMF for preventing disease activity in patients with RRMS. SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (January 14, 2013). We searched three Chinese databases (January 2013) and checked reference lists of identified trials. We contacted authors and pharmaceutical companies to ask for additional information. We applied no language restrictions. SELECTION CRITERIA: We included randomized controlled trials with a follow-up of at least 12 months that compared MMF as monotherapy or in combination with other treatments versus placebo, another drug, or the same cointervention as the treated group. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials for inclusion, assessed trial quality, and extracted data. MAIN RESULTS: One included study involving 26 participants with new-onset RRMS investigated the efficacy and safety of MMF (13 participants) versus placebo in interferon ß-1a-treated participants. It was assessed to be at high risk of bias, and had a small numbers of participants receiving treatment with short-term duration. There was inadequate information provided by the study to determine the effect of MMF in reducing relapses, preventing disability progression, or developing new T2- or new gadolinium (Gd)-enhanced lesions on magnetic resonance imaging (MRI) after a 12-month follow-up period. No data were available at 24 months. No serious adverse effects were reported. All participants in the MMF-treated group suffered from gastrointestinal upset, but none of them discontinued therapy as a result. AUTHORS' CONCLUSIONS: The evidence we found from one small study was insufficient to determine the effects of MMF as an add-on therapy for interferon ß-1a in new-onset RRMS participants.

[Spatiotemporal characteristics of zooplankton community structure and diversity in the strong temperature increment seawaters near Guohua power plant in Xiangshan Bay].

To explore the spatiotemporal characteristics of the zooplankton community structure and diversity in the strong temperature increment seawaters near a power plant, zooplankton samples were seasonally collected in duplicate by the type II net with mesh size of 160 microm at 10 stations near Guohua power plant in Xiangshan Bay in 2011. The results showed that a total of 62 species (including larvae) were identified in the samples, and the average abundance was 9 531.1 ind x m(-3). In the seawaters, zooplankton communities were mainly composed of copepods and pelagic larvae, and pelagic larvae were the dominant with an average percentage of abundance reached up to 66.6%. Analysis of similarities demonstrated that significant differences existed in zooplankton community structures among different months (P < 0.01). In these zooplankton communities, there were 18 dominant species controlling these community structures, among which the most important discriminating species were Centropages tenuiremis, Oithona similis, Oithona fallax, Acartia clausi, Clausocalanus furcatus, Paracalanus aculeatus and Paracalanus parvwus. GLM analysis indicated that diversity indices were also significantly different among different months (P < 0.01). According to the calculation results, the inflection point, where the diversity index began to decrease with increasing water temperature, fell within 20.31-22.31 degrees C. In sections, the average water temperature in the 0.2 km section (D02), away from the outfall, was 2.16: higher than that in the 2 km section. Driven by temperature, the main dominant species such as C. tenuiremis and O. similis tended to move into the 0.2 km section, while A. clause and especially large zooplankton tended to stay away from the outfall, and then gathered in the 1.2 km section. As a result, the number of species (33 species) and abundance (5 522.8 ind x m(-3)) were minimum in the section D02, while the number of species (53 species) and abundance (16 491.0 ind x m(-3)) reached the highest in the 1.2 km section. Meanwhile, diversity indices in the 0.2 km section were also obviously lower than those in other sections. Linear regression analysis showed that the diversity indices significantly decreased with increasing water temperature (P < 0.01). The zooplankton richness decreased by 12.3% when the water temperature increased by 1 degrees C.

A study of field independence versus field dependence of school teachers and university students in mathematics.

The Group Embedded Figures Test was administered to 72 secondary school teachers and 54 university students in mathematics to measure their cognitive styles of field independence-dependence. A mean difference was found between the teachers and students as teachers scored more field-independent than the students. There was also a group-by-sex interaction, which indicated that the female teachers scored more field-independent than the male teachers, whereas the male students scored as more field-independent than the female students. Implications of the findings are reflected in the discussion.

Thinking styles of school teachers and university students in mathematics.

This research studied the thinking styles of 18 school teachers and 15 college students in the field of mathematics, using the Inquiry Mode Questionnaire by Harrison and Bramson. The multivariate analysis of variance showed that the 21 female teachers and college students scored as more Idealistic than their 12 male peers. There also was a significant group-by-sex interaction, which indicated that the female college students preferred the Analyst thinking style more frequently than their male peers, whereas the male teachers preferred the Analyst style more frequently than the female teachers. On the whole, the most preferred thinking style was the Analyst style, and the least preferred one was the Synthesist style. The implications of findings are discussed.