Molecular insights into the interaction of CAG trinucleotide RNA repeats with nucleolin and its implication in polyglutamine diseases.

Polyglutamine (polyQ) diseases are a type of inherited neurodegenerative disorders caused by cytosine-adenine-guanine (CAG) trinucleotide expansion within the coding region of the disease-associated genes. We previously demonstrated that a pathogenic interaction between expanded CAG RNA and the nucleolin (NCL) protein triggers the nucleolar stress and neuronal cell death in polyQ diseases. However, mechanisms behind the molecular interaction remain unknown. Here, we report a 1.45 Å crystal structure of the r(CAG)5 oligo that comprises a full A'-form helical turn with widened grooves. Based on this structure, we simulated a model of r(CAG)5 RNA complexed with the RNA recognition motif 2 (RRM2) of NCL and identified NCL residues that are critical for its binding to CAG RNA. Combined with in vitro and in vivo site-directed mutagenesis studies, our model reveals that CAG RNA binds to NCL sites that are not important for other cellular functions like gene expression and rRNA synthesis regulation, indicating that toxic CAG RNA interferes with NCL functions by sequestering it. Accordingly, an NCL mutant that is aberrant in CAG RNA-binding could rescue RNA-induced cytotoxicity effectively. Taken together, our study provides new molecular insights into the pathogenic mechanism of polyQ diseases mediated by NCL-CAG RNA interaction.

CAG RNAs induce DNA damage and apoptosis by silencing NUDT16 expression in polyglutamine degeneration.

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the Nudix hydrolase 16 (NUDT16) gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing NUDT16 mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of NUDT16 and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNA-expressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent NUDT16 silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases.

Artificial dermis combined with negative pressure wound therapy and platelet-rich plasma to treat traumatic wounds: a retrospective study.

OBJECTIVE: The reconstruction of complex soft tissue defects with exposure of bones and tendons represents an increasing challenge in wound care, especially in large extremity wounds. The aim of this study was to detect the clinical efficacy of combined use of negative pressure wound therapy (NPWT), artificial dermis (ADM), platelet-rich plasma (PRP) and split-thickness skin grafting (STSG) in the reconstruction of large traumatic extremity skin defects. METHOD: In this study, eight cases were treated with combined therapies for repairing complex extremity wounds and the results were reviewed retrospectively. After surgical debridement, all wounds received ADM, PRP and delayed STSG, which were all aided with NPWT. RESULTS: The patients consisted of five males and three females, with a mean age of 44 years. A total of six lower extremity wounds were located at the foot/ankle, with exposed tendon in five, bone exposure in three and both in two. Of the group, two patients had exposed tendon on arm/hand wounds. The size of wounds and ADM averaged 126cm2 and 42.3cm2, respectively. ADM was used to cover the exposed bone or tendon, the granulation and muscular tissue were covered with vacuum sealing drainage (VSD) directly, for NPWT. The survival rate of ADM averaged 98.9%. The average time for survival of ADM was 12.8 days and the mean uptake of autologous skin graft was 93.5%. Only one patient received repeated skin grafts. All patients achieved successful healing and reported no complications. The mean length of hospital stay was 36.1 days. CONCLUSION: Our study revealed that ADM in conjunction with NPWT, PRP and STSG could be used for repairing large traumatic extremity wounds. Wound closure was achieved without flaps, the aesthetic and functional outcomes were acceptable, and only one patient developed a 35% loss of skin graft. DECLARATION OF INTEREST: This work was supported by grants from the Natural Science Foundation of Hubei Province (grant no. 2020CFB464) and Youth Foundation of Wuhan Municipal Health Commission (grant no. WX20Q15). The authors have no conflicts of interest to declare.

A new classification for emergency critically ill patients and analysis of their adverse events during intrahospital transport: A cluster analysis.

BACKGROUND: Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before transporting them from the emergency department and focusing on managing high-risk patients are critical. At present, no unified classification method exists; all the current approaches are subjective. AIMS: To ensure transportation safety, we conducted a cluster analysis of critically ill patients transferred from the emergency department to the intensive care unit. STUDY DESIGN: Single-centre cohort study. This study was conducted at a comprehensive first-class teaching hospital in Beijing. Convenience sampling and continuous enrolment were employed. We collected data from 1 January 2019, to 31 December 2021. All patients were transferred from the emergency department to the intensive care unit, and cluster analysis was conducted using five variables. RESULTS: A total of 584 patients were grouped into three clusters. Cluster 1 (high systolic blood pressure group) included 208 (35.6%) patients. Cluster 2 (high heart rate and low blood oxygen group) included 55 (9.4%) patients. Cluster 3 (normal group) included the remaining 321 (55%) patients. The oxygen saturation levels of all the patients were lower after transport, and the proportion of adverse events (61.8%) was the highest in Cluster 2 (p < .05). CONCLUSIONS: This study utilized data on five important vital signs from a cluster analysis to explore possible patient classifications and provide a reference for ensuring transportation safety. RELEVANCE TO CLINICAL PRACTICE: Before transferring patients, we should classify them and implement targeted care. Changes in blood oxygen levels in all patients should be considered, with a focus on the occurrence of adverse events during transportation among patients with high heart rates and low blood oxygen levels.

Biodentine as a pulpotomy medicament for primary molars: a retrospective chart review.

This retrospective chart review study investigates the long-term clinical outcome of Biodentine® (Tricalcium silicate) as a medicament for pulpotomy in primary molars. Data in this retrospective study was collected from the dental records of all patients that had at least one primary molar receive pulpotomy treatment (CDT code: D3221) between 01 July 2012 and 01 July 2015. This data includes child's age, medical history, dental history, dental radiographs, pulpotomy procedure details and follow-up clinical notes. Kaplan-Meier Estimate was used to measure the fraction of successful pulpotomy procedures for up to 24 months. A total of 1758 pulpotomy procedures were performed on 1032 patients in our institute in the three-year period and 21.4% of them (N = 376) had follow-up dental records that qualified for the study. Eleven teeth out of 376 teeth were excluded from the statistical analysis due to loss of/broken stainless steel crowns (3.1%). Seventeen pulpotomy failures were identified out of the remaining 365 procedures. The survival probablity of using Biodentine® as a pulpotomy medicament is 96.3% for 18-month follow-up and 95.4% for 24-month follow-up. Biodentine®, a tricalcium silicate formulation, used as a pulpotomy medicament demonstrates a high clinical success rate (95.4%) over a 24-month peroid in primary molars.

High glucose-induced endothelial STING activation inhibits diabetic wound healing through impairment of angiogenesis.

Chronic hyperglycemia-induced impairment of angiogenesis is important in diabetic foot ulcer (DFU). Additionally, the stimulator of interferon gene (STING), which is a key protein in innate immunity, mediates palmitic acid-induced lipotoxicity in metabolic diseases through oxidative stress-induced STING activation. However, the role of STING in DFU is unknown. In this study, we established a DFU mouse model with streptozotocin (STZ) injection and found that the expression of STING was significantly increased in the vascular endothelial cells of wound tissues from diabetic patients and in the STZ-induced diabetic mouse model. We further established high glucose (HG)-induced endothelial dysfunction with rat vascular endothelial cells and found that the expression of STING was also increased by high-glucose treatment. Moreover, the STING inhibitor, C176, promoted diabetic wound healing, whereas the STING activator, DMXAA, inhibited diabetic wound healing. Consistently, STING inhibition reversed the HG-induced reduction of CD31 and vascular endothelial growth factor (VEGF), inhibited apoptosis, and promoted migration of endothelial cells. Notably, DMXAA treatment alone was sufficient to induce endothelial cell dysfunction as a high-glucose treatment. Mechanistically, STING mediated HG-induced vascular endothelial cell dysfunction by activating the interferon regulatory factor 3/nuclear factor kappa B pathway. In conclusion, our study reveals an endothelial STING activation-mediated molecular mechanism in the pathogenesis of DFU and identifies STING as a novel potential therapeutic target for DFU.

The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.

Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.

Hyperglycemia-induced STING signaling activation leads to aortic endothelial injury in diabetes.

Hyperglycaemia-induced endothelial dysfunction is a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy. STING, which is a newly discovered regulator of innate immunity, has also been reported to play an important role in various metabolic diseases. However, the role of STING in diabetes-induced endothelial cell dysfunction is unknown. In this study, we established a diabetic macroangiopathy mouse model by streptozotocin (STZ) injection combined with high-fat diet (HFD) feeding and a glucotoxicity cell model in high glucose (HG)-treated rat aortic endothelial cells (RAECs). We found that STING expression was specifically increased in the endothelial cells of diabetic arteries, as well as in HG-treated RAECs. Moreover, genetic deletion of STING significantly ameliorated diabetes-induced endothelial cell dysfunction and apoptosis in vivo. Likewise, STING inhibition by C-176 reversed HG-induced migration dysfunction and apoptosis in RAECs, whereas STING activation by DMXAA resulted in migration dysfunction and apoptosis. Mechanistically, hyperglycaemia-induced oxidative stress promoted endothelial mitochondrial dysfunction and mtDNA release, which subsequently activated the cGAS-STING system and the cGAS-STING-dependent IRF3/NF-kB pathway, ultimately resulting in inflammation and apoptosis. In conclusion, our study identified a novel role of STING in diabetes-induced aortic endothelial cell injury and suggested that STING inhibition was a potential new therapeutic strategy for the treatment of diabetic macroangiopathy. Video Abstract.

LGTRL-DE: Local and Global Temporal Representation Learning with Demographic Embedding for in-hospital mortality prediction.

Predicting the patient's in-hospital mortality from the historical Electronic Medical Records (EMRs) can assist physicians to make clinical decisions and assign medical resources. In recent years, researchers proposed many deep learning methods to predict in-hospital mortality by learning patient representations. However, most of these methods fail to comprehensively learn the temporal representations and do not sufficiently mine the contextual knowledge of demographic information. We propose a novel end-to-end approach based on Local and Global Temporal Representation Learning with Demographic Embedding (LGTRL-DE) to address the current issues for in-hospital mortality prediction. LGTRL-DE is enabled by (1) a local temporal representation learning module that captures the temporal information and analyzes the health status from a local perspective through a recurrent neural network with the demographic initialization and the local attention mechanism; (2) a Transformer-based global temporal representation learning module that extracts the interaction dependencies among clinical events; (3) a multi-view representation fusion module that fuses temporal and static information and generates the final patient's health representations. We evaluate our proposed LGTRL-DE on two public real-world clinical datasets (MIMIC-III and e-ICU). Experimental results show that LGTRL-DE achieves area under receiver operating characteristic curve of 0.8685 and 0.8733 on the MIMIC-III and e-ICU datasets, respectively, outperforming several state-of-the-art approaches.

SPBERE: Boosting span-based pipeline biomedical entity and relation extraction via entity information.

Triplet extraction is one of the fundamental tasks in biomedical text mining. Compared with traditional pipeline approaches, joint methods can alleviate the error propagation problem from entity recognition to relation classification. However, existing methods face challenges in detecting overlapping entities and overlapping relations, which are ubiquitous in biomedical texts. In this work, we propose a novel pipeline method of end-to-end biomedical triplet extraction. In particular, a span-based detection strategy is used to detect the overlapping triplets by enumerating possible candidate spans and entity pairs. The strategy is further used to capture different contextualized representations via an entity model and a relation model, respectively. Furthermore, to enhance interrelation between spans, entity information from the output of the entity model is used to construct the input for the relation model without utilizing any external knowledge. Our approach is evaluated on the drug-drug interaction (DDI) and chemical-protein interaction (CHEMPROT) datasets, exhibiting improvement of the absolute F1-score in relation extraction by 3.5%-3.7% compared prior work. The experimental results highlight the importance of overlapping triplet detection using the span-based approach, acquisition of various contextualized representations via different in-domain pre-trained language models, and early fusion of entity information in the relation model.

Establishment of a simplified score for predicting risk during intrahospital transport of critical patients: A prospective cohort study.

AIMS AND OBJECTIVES: To establish a simple score that enables nurses to quickly, conveniently and accurately identify patients whose condition may change during intrahospital transport. BACKGROUND: Critically ill patients may experience various complications during intrahospital transport; therefore, it is important to predict their risk before they leave the emergency department. The existing scoring systems were not developed for this population. DESIGN: A prospective cohort study. METHODS: This study used convenience sampling and continuous enrolment from 1 January, 2019, to 30 June, 2021, and 584 critically ill patients were included. The collected data included vital signs and any condition change during transfer. The STROBE checklist was used. RESULTS: The median age of the modelling group was 74 (62, 83) years; 93 (19.7%) patients were included in the changed group, and 379 (80.3%) were included in the stable group. The five independent model variables (respiration, pulse, oxygen saturation, systolic pressure and consciousness) were statistically significant (p < .05). The above model was simplified based on beta coefficient values, and each variable was assigned 1 point, for a total score of 0-5 points. The AUC of the simplified score in the modelling group was 0.724 (95% CI: 0.682-0.764); the AUC of the simplified score in the validation group (112 patients) was 0.657 (95% CI: 0.566-0.741). CONCLUSIONS: This study preliminarily established a simplified scoring system for the prediction of risk during intrahospital transport from the emergency department to the intensive care unit. It provides emergency nursing staff with a simple assessment tool to quickly, conveniently and accurately identify a patient's transport risk. RELEVANCE TO CLINICAL PRACTICE: This study suggested the importance of strengthening the evaluation of the status of critical patients before intrahospital transport, and a simple score was formed to guide emergency department nurses in evaluating patients.

Simultaneous sludge minimization and membrane fouling mitigation in membrane bioreactors by using a microaerobic - Settling pretreatment module.

Membrane fouling is the major obstacle for membrane bioreactors operated at a long sludge retention time to reduce sludge production. In this study, a sludge process reduction (SPR) module, consisting of a microaerobic tank and a settler, was inserted before an anoxic/oxic MBR (AO-MBR) to achieve dual objectives of fouling alleviation and sludge reduction. Three SPR-MBRs were operated to investigate influences of sludge recirculation ratios from the SPR settler to the microaerobic tank on process performance. Compared to AO-MBR, the SPR-MBRs reduced sludge production by 43.1-56.4% by maintaining sludge retention times above 175 d, and decreased foulant layer resistance and pore clogging resistance. Inserting SPR reduced the accumulation of dissolved organic matters and extracellular polymeric substances, enlarged sludge flocs, and decreased sludge viscoelasticity. However, increasing RSPR stimulated outward diffusion of extracellular polymeric substances and increased sludge viscosity. SPR-MBRs achieved effective sludge reduction by enriching hydrolytic (Trichococcus and Aeromonas) and fermentative genera (Lactococcus, Paludibacter, Macellibacteroides, and Acinetobacter) in the SPR, and alleviated membrane fouling by prohibiting the growth of extracellular polymeric substance-secreting bacteria and enriching filamentous bacteria to enlarge particle size. The results revealed that the SPR-MBR maximized sludge reduction with a very long sludge retention time, and alleviated membrane fouling synchronously.

Intelligent Electrocardiogram Analysis in Medicine: Data, Methods, and Applications.

Electrocardiogram (ECG) is a low-cost, simple, fast, and non-invasive test. It can reflect the heart's electrical activity and provide valuable diagnostic clues about the health of the entire body. Therefore, ECG has been widely used in various biomedical applications such as arrhythmia detection, disease-specific detection, mortality prediction, and biometric recognition. In recent years, ECG-related studies have been carried out using a variety of publicly available datasets, with many differences in the datasets used, data preprocessing methods, targeted challenges, and modeling and analysis techniques. Here we systematically summarize and analyze the ECG-based automatic analysis methods and applications. Specifically, we first reviewed 22 commonly used ECG public datasets and provided an overview of data preprocessing processes. Then we described some of the most widely used applications of ECG signals and analyzed the advanced methods involved in these applications. Finally, we elucidated some of the challenges in ECG analysis and provided suggestions for further research.

EDTA-Na2 as a recoverable draw solute for water extraction in forward osmosis.

Regeneration and reuse of draw solute (DS) is a key challenge in the application of forward osmosis (FO) technologies. Herein, EDTA-Na2 was studied as a recoverable DS for water extraction by taking advantages of its pH-responsive property. The FO system using EDTA DS achieved a higher water flux of 2.22 ± 0.06 L m-2 h-1 and a significantly lower reverse salt flux (RSF) of 0.06 ± 0.01 g m-2 h-1, compared to that with NaCl DS having either the same DS concentration or the same Na+ concentration. The suitable pH range for the application of EDTA DS was between 4.0 and 10.5. A simple recovery method via combined pH adjustment and microfiltration was employed to recover EDTA DS and could achieve the recovery efficiency (at pH 2) of 96.26 ± 0.48%, 97.13 ± 1.03% and 98.56 ± 1.40% by using H2SO4, H3PO4 and HCl, respectively. The lowest acid cost for DS recovery was estimated from 0.0012 ± 0.0001 to 0.0162 ± 0.0003 $ g-1 by using H2SO4. The recovered EDTA DS could be reused in the subsequent FO operation and the overall recovery efficiency was 94.4% for four reuse cycles. These results have demonstrated the feasible of EDTA-Na2 DS and a potentially cost-effective recovery approach, and encouraged further exploration of using EDTA-based compounds as a draw solute for FO applications.

Elsholtzia ciliata (Thunb.) Hyland: A Review of Phytochemistry and Pharmacology.

In this paper, the confusion of the sources of medicinal materials was briefly expounded, and the differences among the varieties were pointed out. At the same time, the chemical components and pharmacological properties of Elsholtzia ciliata (Thunb.) Hyland (E. ciliata) were reviewed. The structures of 352 compounds that have been identified are listed. These mainly include flavonoids, terpenoids, phenylpropanoids, alkaloids, and other chemical components. They have antioxidant, anti-inflammatory, antimicrobial, insecticidal, antiviral, hypolipidemic, hypoglycemic, analgesic, antiarrhythmic, antitumor, antiacetylcholinesterase, and immunoregulator activities. At present, there are many researches using essential oil and alcohol extract, and the researches on antioxidant, anti-inflammatory, anti-microbial, and other pharmacological activities are relatively mature. This paper aims to summarize the existing research, update the research progress regarding the phytochemicals and pharmacology of E. ciliate, and to provide convenience for subsequent research.

The Genus Broussonetia: An Updated Review of Phytochemistry, Pharmacology and Applications.

The Broussonetia genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes Broussonetia papyrifera (L.) L'Hér. ex Vent. (BP), Broussonetia kazinoki Siebold (BK), and Broussonetia luzonica (Blanco) Bureau (BL). Hitherto, researchers have found 338 compounds isolated from BP, BK, and BL, which included flavonoids, polyphenols, phenylpropanoids, alkaloids, terpenoids, steroids, and others. Moreover, its active compounds and extracts have exhibited a variety of pharmacological effects such as antitumor, antioxidant, anti-inflammatory, antidiabetic, anti-obesity, antibacterial, and antiviral properties, and its use against skin wrinkles. In this review, the phytochemistry and pharmacology of Broussonetia are updated systematically, after its applications are first summarized. In addition, this review also discusses the limitations of investigations and the potential direction of Broussonetia. This review can help to further understand the phytochemistry, pharmacology, and other applications of Broussonetia, which paves the way for future research.

[Neuroprotective effect of cinnamaldehyde in MPTP-induced mouse model of subacute Parkinson's disease].

This paper aims to explore the neuroprotective effect of cinnamaldehyde(CA) in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson's disease(PD) and the mechanism. To be specific, male C57 BL/6 mice(n=72, SPF) were randomized into control group, model group, positive control(madopar 0.1 mg·g~(-1)) group, and low-dose, me-dium-dose, and high-dose CA groups(0.15, 0.30, 0.60 mg·g~(-1)). MPTP(intraperitoneal injection, 0.03 mg·g~(-1), once a day for 5 days) was used to induce subacute PD in mice except for the control group. The administration began from the day of modeling and lasted 19 days. On the 0 th, 12 th, and 19 th day, the open field test, pole test, and rotarod test were carried out. After the tests, the mice were killed and brains were separated. In addition, the organ index was measured. The number of cells in substantia nigra(SN) in the midbrain of MPTP-induced PD model mice was detected based on hematoxylin and eosin(HE) staining. The levels of tyrosine hydroxylase(TH)-and α-synuclein(α-Syn)-positive cells in SN were determined by immunohistochemical staining, and the protein levels of TH and α-Syn in SN by Western blot. The results showed that the MPTP-stimulated mice had abnormal behaviors such as erect hair, arched back, rigidity of the tail, slow movement, and tremor, decreased number of crossings and rearing, increased frequency of urination and defecation, longer time of pole climbing, and shorter time of staying on the rotating rod. In addition, the mice showed obvious damage of neurons in the SN and reduced neuron cells in irregular arrangement with some shrinking. In addition, the average optical density of TH in SN decreased and that of α-Syn increased. All these suggested the successful modeling. CA displayed obvious therapeutic effect on the PD mice, as manifested by the increased number of crossings and rearing, decreased frequency of urination and defecation, shorter time of climbing pole, longer time of staying on the rotating rod, and more neuron cells in the SN with a few pykno-tic cells. Moreover, CA significantly alleviated the decrease of TH and the overexpression of α-Syn in SN. As a result, the MPTP-induced injury of dopaminergic neurons was alleviated. The performance of 0.3 mg·g~(-1) CA was the best. This study is expected to lay a scientific basis for the development of CA products.

The recombinant Newcastle disease virus Anhinga strain expressing human TRAIL exhibit antitumor effects on a glioma nude mice model.

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. However, the potential oncolytic ability of the recombinant newcastle disease virus (NDV) Anhinga strain carried with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has not been fully explored at present. In the present study, the recombinant NDV/Anh-TRAIL that secretes soluble TRAIL was constructed and the experiment results suggested NDV/Anh-TRAIL as a promising candidate for glioma therapy. Growth kinetic and TRAIL secreted quantity of recombinant NDV/Anh-TRAIL virus were measured. Cytotoxic and cell apoptosis were analyzed for its anti-glioma therapy in vitro. Nude mice were used for the in vivo evaluation. Both tumor volume and mice behavior after injection were observed. The recombinant virus replicated with the same kinetics as the parental virus and the highest expression of TRAIL (77.8 ng/L) was found at 48 hours. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole and flow cytometry data revealed that the recombinant NDV/Anh-TRAIL (56.1 ± 8.2%) virus could induce a more severe apoptosis rate, when compared with the NDV wild type (37.2 ± 7.0%) and mock (7.0 ± 1.8%) groups (P < .01), in U251 cells. Furthermore, in the present animal study, the average tumor volume was smaller in the NDV/Anh-TRAIL group (97.21 mm3 ), when compared with the NDV wild type (205.03 mm3 , P < .05) and PBS (310.30 mm3 , P < .01) groups.

Bacterial and Microfauna Mechanisms for Sludge Reduction in Carrier-Enhanced Anaerobic Side-Stream Reactors Revealed by Metagenomic Sequencing Analysis.

Packing carriers into the anaerobic side-stream reactor (ASSR) can enhance sludge reduction and save footprint by investigating ASSR-coupled membrane bioreactors (AP-MBRs) under different hydraulic residence times of the ASSR (HRTSR). Three AP-MBRs and an anoxic-aerobic MBR (AO-MBR) showed efficient chemical oxygen demand (>94.2%) and ammonium nitrogen removal (>99.3%). AP-MBRs have higher (p < 0.05) total nitrogen (61.4-67.7%) and total phosphorus (57.5-63.8%) removal than AO-MBRs (47.8 and 47.7%). AP-MBRs achieved sludge reduction efficiencies of 11.8, 31.8, and 36.2% at HRTSR values of 2.5, 5.0, and 6.7 h. Packing carriers greatly improved sludge reduction under low HRTSR and is promising for accelerating sludge reduction in compact space. Metagenomic sequencing analysis showed that genes responsible for metabolism were enriched in AO-MBRs, while genes related to cellular motility and cell signaling were more abundant in the AP-MBRs. A longevity-regulating pathway showed that long lifespan provided more opportunities for worms to prey bacteria. Microscopic examination revealed that some specific protozoa (Arcella, Clathrulina, Aspidisca, Litonotus, Chiloclonella, and Vorticella) and metazoa (Rotaria and Aeolosoma hemprichi) were enriched in ASSRs. Aeolosoma hemprichi was only detected in ASSRs, and unique Cylops appeared on carriers. These results contribute to growing understanding of micrometabolic mechanisms including functional genes and microfauna-driving sludge reduction.

Identifying the essential nodes in network pharmacology based on multilayer network combined with random walk algorithm.

Compared with the general complex network, the multilayer network is more suitable for the description of reality. It can be used as a tool of network pharmacology to analyze the mechanism of drug action from an overall perspective. Combined with random walk algorithm, it measures the importance of nodes from the entire network rather than a single layer. Here a four-layer network was constructed based on the data about the action process of prescriptions, consisting of ingredients, target proteins, metabolic pathways and diseases. The random walk algorithm was used to calculate the betweenness centrality of the protein layer nodes to get the rank of their importance. According to above method, we screened out the top 10% proteins that play a key role in treatment. Prescriptions Xiaochaihu Decoction was taken as example to prove our method. The selected proteins were measured with the ones that have been validated to be associated with the treated diseases. The results showed that its accuracy was no less than the topology-based method of single-layer network. The applicability of our method was proved by another prescription Yupingfeng Decoction. Our study demonstrated that multilayer network combined with random walk algorithm was an effective method for pre-screening vital target proteins related to prescriptions.