Abstract The incidence of colorectal cancer (CRC) is increasing, with 1,931,590 new colorectal cancer patients worldwide in 2020. Fusobacterium nucleatum (Fn) has been widely reported as a harmful microorganism that promotes the development of CRC. Fn was found to enhance proliferation and metastasis of CRC cells by regulating cellular glucose metabolism and amino acid metabolism in trials. In a previous study, phenyl lactic acid (PLA), a natural metabolite of various probiotic bacteria, was found to have the ability to inhibit Fn as an organic acid. Therefore, further in-depth analysis of the mechanism of action of PLA in weakening Fn invasion into tumor cells provides a new therapeutic avenue for exacerbating CRC problems caused by intestinal pathogenic bacteria.

Resumen Objetivo: se utilizaron métodos bioinformáticos y técnicas de acoplamiento molecular para predecir los componentes efectivos, los objetivos y las vías biológicas relacionadas de la cápsula Xiexin en la intervención de la dislipidemia y explorar su mecanismo. Métodos: los componentes activos y los objetivos de la cápsula Xiexin fueron seleccionados por la base de datos TCMSP. Se utilizaron las plataformas Genecards, OMIM, PharmGkb, TTD (Therapeutic Target Database) y Drugbank para buscar las dianas de la enfermedad en la dislipidemia. El diagrama reticular “componente-diana” fue construido por el software Cytoscape 3.7.0, y la interacción proteína-proteína (PPI) fue analizada por la plataforma STRING. Los análisis de enriquecimiento de Gene Ontology (GO) y Kyoto Encyclopedia of Genes and Genomics (KEGG) se realizaron mediante paquetes de datos en lenguaje R para predecir el mecanismo de acción. El software AutoDockVina y PyMol se utilizó para unir los componentes activos clave de la cápsula Xiexin y las proteínas clave de la PPI. Resultados: se seleccionaron 65 componentes activos y 114 dianas. Veintitrés compuestos activos clave fueron seleccionados a partir de la tabla “componentes farmacéuticos-dianas”. Las redes PPI incluyen principalmente proteínas básicas como PTGS2, PTGS1 y HSP90AA1. Los resultados del análisis de enriquecimiento de GO y KEGG en los objetivos comunes se refieren principalmente a la vía de señalización mediada por esteroides, la respuesta hormonal esteroidea, el transporte y metabolismo lipídicos, la regulación del almacenamiento de colesterol, la vía de la ciclooxigenasa y otras vías biológicas, así como la vía de señalización de PPAR, la vía de señalización de IL-17, la vía de señalización de PI3K-Akt, la vía de señalización de FcnnnnnnnnRI y otras vías relacionadas. La prueba de acoplamiento molecular mostró que la quercetina se une mejor a la proteína diana central HSP90AA1, que es la proteína diana con la mejor actividad de unión de los componentes químicos clave de la cápsula Xiexin. Conclusión: los principales componentes químicos de la cápsula Xiexin pueden participar en la regulación de la PPAR y otras vías de señalización mediante la regulación de genes clave como ESR1, MAPK14 (mitogen-activated protein kinase 14), HSP90AA1, por lo que pueden desempeñar un papel farmacológico en la intervención de la dislipidemia.

Abstract Objective: bioinformatic methods and molecular docking technology were used to predict the active components, targets, and related biological pathways of the Xiexin capsule in the intervention for dyslipidemia, exploring its mechanism. Methods: the active components and targets of the Xiexin capsule were screened by the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform )database. Genecards (The Human Gene Database), OMIM (Online Mendelian Inheritance in Man), PharmGkb (Pharmacogenomics Knowledge Base database), TTD (Therapeutic Target Database), and Drugbank platforms were used to search the disease targets of dyslipidemia. The Cytoscape 3.8.0 software was used to construct the 'component-target' network diagram, and the STRING (functional protein association networks) platform was used to analyze protein-protein interaction (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed by R language data packets to predict the mechanism of action. The AutoDockVina and PyMol software were used to dock the key active components in the Xiexin capsule and the core proteins in PPI. Results: a total of 66 effective components were screened, involving 114 targets; 87 key active compounds were screened from the 'drug-component-target' diagram. The PPI network mainly involved core proteins such as PTGS2 (prostaglandin-endoperoxide synthase 2), PTGS1 (prostaglandin-endoperoxide synthase 1), and HSP90AA1 (heat shock protein 90 alpha family class A member 1). GO and KEGG enrichment analysis results of common targets mainly involved hormone-mediated signaling pathway, steroid hormone response, lipid transport and metabolism, regulation of cholesterol storage, cyclooxygenase pathway, and other biological pathways, as well asMM PPAR (peroxisome proliferators-activated receptor) signaling pathway, IL-17 (interleukin 17) signaling pathway, PI3K-Akt (protein kinase b) signaling pathway, FcεRI signaling pathway, and other related pathways. Molecular docking verification showed that quercetin had the best binding with the core target protein HSP90AA1, and HSP90AA1 was the target protein with the best binding activity for the key chemical components in Xiexin capsules. Conclusion: the main chemical components in the Xiexin capsules may participate in the regulation of PPAR and other signaling pathways by regulating key genes such as ESR1 (estrogen receptor 1), MAPK14 (mitogen-activated protein kinase 14), and HSP90AA1, to exert the pharmacological effect of the intervention on dyslipidemia.

SUMMARY: Variations in subclavian artery branches are relatively common and may impact surgical procedures and effects. During educational dissection of a male cadaver, we encountered an extremely rare variation of the right subclavian artery branches. The internal thoracic artery, the thyrocervical trunk, and the costocervical trunk arose from the third part of the right subclavian artery. In addition, the phrenic nerve displaced remarkably laterally by the thyrocervical trunk, and the course of the costocervical trunk was between the upper trunk and the middle trunk of the brachial plexus. These variations may pose a potential risk for nerve compression and increase the risk of arterial and nerve puncture. This case report would bring attention to the possibility of other similar cases, and early detection of these variations through diagnostic interventions is helpful to reduce postoperative complications.

RESUMEN: Las variaciones en las ramas de la arteria subclavia son relativamente comunes y pueden afectar los procedimientos y efectos quirúrgicos. Durante la disección educativa de un cadáver masculino, encontramos una variación extremadamente rara de las ramas de la arteria subclavia derecha. La arteria torácica interna, el tronco tirocervical y el tronco costocervical nacían de la tercera parte de la arteria subclavia derecha. Además, el nervio frénico se desplazaba lateralmente por el tronco tirocervical, y el trayecto del tronco costocervical se encontraba entre el tronco superior y el tronco medio del plexo braquial. Estas variaciones pueden suponer un riesgo potencial de compresión nerviosa y aumentar el riesgo de punción arterial y nerviosa. Este reporte de caso llamaría la atención sobre la posibilidad de otros casos similares, y la detección temprana de estas variaciones a través de diagnósticos es útil para reducir las complicaciones postoperatorias.

Abstract Osteoarthritis (OA) is a degenerative joint disease associated with inflammation. Polygonatum sibiricum polysaccharide (PSP) is a major group of active components isolated from Polygonatum sibiricum with broad activities including anti-inflammatory effect. However, the role of PSP in OA is unclear. In the present study, we aimed to investigate the effects of PSP on IL-1β-induced inflammatory response in primary human OA chondrocytes. The results showed that PSP improved cell viability of chondrocytes in response to IL-1β induction. The increased levels of several inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IL-1β-induced chondrocytes were attenuated by PSP in a dose-dependent manner. The IL-1β-induced production of pro-inflammatory cytokines, TNF-α and IL-6, were mitigated by PSP in chondrocytes. Besides, PSP also suppressed the production of matrix metalloproteinases (MMPs), including MMP-1, MMP-3 and MMP-13 in IL-1β-stimulated chondrocytes. Furthermore, the IL-1β-induced activation of NF-κB signaling pathway in chondrocytes was also prevented by PSP. These findings suggested that PSP alleviated IL-1β-induced inflammatory response in chondrocytes via inhibiting NF-κB signaling pathway.

Abstract As an alternative type of tea product, tartary buckwheat tea (TBT) has become popular in the current market because of its rich taste, natural healthiness and convenience of use. Because sensory evaluation is easily affected by the individual differences and external factors that affect human assessors, the present study used intelligent sensory systems (electronic nose, electronic tongue and electronic eye) to analyze different types of TBT to establish a scientific basis for its quality characteristics. Results showed that obvious differences in color, aroma and taste were found among the different types of teas. The taste differences in the TBT were mainly acquired by the CTS sensor (saltiness) and ANS sensor (sweetness), with the greatest number of volatile substance was detected in the whole plant tea. Overall, intelligent sensory technology could accurately evaluate TBT thus providing the capability to meet the needs of different types of consumers and of different occasions.

Neonatal sepsis is an inflammatory system syndrome and a main cause of neonatal mortality. However, there is a lack of ideal biomarkers for early neonatal sepsis diagnosis. The aim of this study was to evaluate the clinical significance of miR-141 in sepsis in neonates, and explore the regulatory effects of miR-141 on inflammation in monocytes. This study used qRT-PCR to calculate the expression of miR-141 in the serum of septic neonates. The diagnostic values of procalcitonin (PCT) and serum miR-141 were evaluated by receiver operating characteristic (ROC) curves. The relationship between miR-141 and TLR4 was determined using luciferase reporter assay. An inflammation model was established using monocytes with lipopolysaccharide (LPS) treatment. ELISA assay was used to analyze the levels of pro-inflammatory cytokines. The expression of miR-141 in neonatal sepsis was significantly lower than healthy controls. ROC curves showed that miR-141 had diagnostic accuracy. LPS stimulation in monocytes led to a decrease in the expression of miR-141. A luciferase reporter assay proved that miR-141 targeted TLR4, and a negative correlation of miR-141 with TLR4 was found in septic neonates. ELISA results demonstrated that the overexpression of miR-141 inhibited LPS-induced inflammation in monocytes. In conclusion, serum decreased miR-141 expression served as a candidate diagnostic biomarker of neonatal sepsis. TLR4 is a target gene of miR-141, which may mediate the inhibitory effects of miR-141 overexpression on LPS-induced inflammation in monocytes. Therefore, miR-141 is expected to be a potential diagnostic biomarker and a therapeutic target in neonatal sepsis.

Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

High specific surface area activated carbon prepared by Perilla frutescens (PFHSAAC) was modified on the surface of the glassy carbon electrode (GCE) by drop-coating method to construct a PFHSAAC/GCE. The electrochemical properties of the modified electrode were investigated in detail by some electrochemical methods such as cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Experiment results show that the modified electrode has excellent redox activity and distinction capability toward the two isomers of catechol (CC) and hydroquinone (HQ). The separation of oxidation peak potential for HQ and CC of DPV is 112.8 mV. Under the optimal conditions, the oxidation peak currents of HQ and CC show good linear relationships with their concentrations in the ranges of 1.0 × 10-6-2.0 × 10-4 and 1.0 × 10-6-1.5 × 10-4 mol L-1, respectively. The limits of detection for HQ and CC are 3.57 × 10-7 and 4.23 × 10-7 mol L-1, respectively. The PFHSAAC/GCE exhibits good stability, repeatability and sensitivity. The developed method was used to determine HQ and CC in water samples with best results.

Abstract Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.

ABSTRACT Phytoene synthase (PSY) is the rate-limiting enzyme for carotenoid biosynthesis. To date, several studies focused on PSY genes in the context of abiotic stress responses. In this study, two phytoene synthase encoding genes, IbPSY1 and IbPSY2, were identified from a published transcriptome and bioinformatic analysis showed that they shared conserved domains with phytoene synthases from other plants. The IbPSY1 gene was cloned and carefully characterized. Digital gene expression profiling (DGE) showed that the highest transcription level of IbPSY1 was in young leaves, and the lowest level was in stems. In vivo expression levels of IbPSY1 under abiotic stress were observed to be highest in stems at day 11. Over-expression of IbPSY1 in Escherichia coli and yeast cells endowed the cells with better growth under salt and drought stress than the control cells. This study demonstrated that IbPSY1 not only played an important role in vivo, but also in E. coli and yeast to improve tolerance to salinity and drought stress. Thus, IbPSY1 may be aid in the development of transgenic plants with enhanced stress tolerance.

Abstract Background: The biomechanical properties of maize stalks largely determine their lodging resistance, which affects crop yield per unit area. However, the quantitative and qualitative relationship between micro-phenotypes and the biomechanics of maize stalks is still under examined. In particular, the roles of the number, geometry, and distribution of vascular bundles of stalks in maize lodging resistance remain unclear. Research on these biomechanical properties will benefit from high-resolution micro-phenotypic image acquisition capabilities, which have been improved by modern X-ray imaging devices such as micro-CT and the development of micro-phenotyping analysis software. Hence, high-throughput image analysis and accurate quantification of anatomical phenotypes of stalks are necessary. Results: We have updated VesselParser version 1.0 to version 2.0 and have improved its performance, accuracy, and computation strategies. Anatomical characteristics of the second and third stalk internodes of the cultivars ‘Jingke968’ and ‘Jingdan38’ were analyzed using VesselParser 2.0. The relationships between lodging resistance and anatomical phenotypes of stalks between the two different maize varieties were investigated. The total area of vascular bundles in the peripheral layer, auxiliary axis diameter, and total area of vascular bundles were revealed to have the highest correlation with mechanical properties, and anatomical phenotypes of maize stalk were better predictors of mechanical properties than macro features observed optically from direct measurement, such as diameter and perimeter. Conclusions: This study demonstrates the utility of VesselParser 2.0 in assessing stalk mechanical properties. The combination of anatomical phenotypes and mechanical behavior research provides unique insights into the problem of stalk lodging, showing that micro phenotypes of vascular bundles are good predictors of maize stalk mechanical properties that may be important indices for the evaluation and identification of the biomechanical properties to improve lodging resistance of future maize varieties.

Abstract Background: Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. Objectives: To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. Methods: Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. Results: On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (P<0.05). However, no improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (P<0.05). The adverse event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT group (P<0.05) Study limitations: The unblindness of the study and temporary animal models of acne induced may hamper the assessment and monitoring of the results, and future studies are still needed to clarify it further. Conclusion: The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.

Objective: To study the effect of Lactobacillus sp. A-2 metabolites on viability of CAL-27 cells and apoptosis in CAL-27 cells. Methods: Lactobacillus sp. A-2 metabolites 1 and 2 (LM1 and LM2) were obtained by culturing Lactobacillus sp. A-2 in reconstituted whey medium and whey-inulin medium; the cultured CAL-27 cells were treated with different concentrations of LM1 and LM2 (0, 3, 6, 12, 24, 48 mg/mL) and assayed by methyl thiazolyltetrazolium (MTT) method; morphological changes of apoptotic cell were observed under fluorescence microscopy by acridine orange (Ao) fluorescent staining; flow cytometry method (FCM) and agarose gel electrophoresis were used to detect the apoptosis of CAL-27 cells treated LM1 and LM2. Results: The different concentrations of LM1 and LM2 could restrain the growth of CAL-27 cells, and in a dose-dependent manner; the apoptosis of CAL-27 cells was obviously induced and was time-dependent. Conclusions: Viability of CAL-27 cells was inhibited by Lactobacillus sp. A-2 metabolites; Lactobacillus sp. A-2 metabolites could induce CAL-27 cells apoptosis; study on the bioactive compounds in the Lactobacillus sp. A-2 metabolites and their molecular mechanism is in progress.

OBJECTIVES: The aim of the study was to determine rates of mask-wearing, of respiratory infection and the factors associated with mask-wearing and of respiratory infection in healthcare workers (HCWs) in Beijing during the winter of 2007/2008. METHODS: We conducted a survey of 400 HCWs working in eight hospitals in Beijing by face to face interview using a standardized questionnaire. RESULTS: We found that 280/400 (70.0%) of HCWs were compliant with mask-wearing while in contact with patients. Respiratory infection occurred in 238/400 (59.5%) subjects from November, 2007 through February, 2008. Respiratory infection was higher among females (odds ratio [OR], 2.00 [95% confidence interval {CI}, 1.16-3.49]) and staff working in larger hospitals (OR, 1.72 [95% CI, 1.092.72]), but was lower among subjects with seasonal influenza vaccination (OR, 0.46 [95% CI, 0.280.76]), wearing medical masks (reference: cotton-yarn; OR, 0.60 [95% CI, 0.39-0.91]) or with good mask-wearing adherence (OR, 0.60 [95% CI, 0.37-0.98]). The risk of respiratory infection of HCWs working in low risk areas was similar to that of HCWs in high risk area. CONCLUSION: Our data suggest that female HCWs and staffs working in larger hospitals are the focus of prevention and control of respiratory infection in Beijing hospitals. Mask-wearing and seasonal influenza vaccination are protective for respiratory infection in HCWs; the protective efficacy of medical masks is better than that of cotton yarn ones; respiratory infection of HCWs working in low risk areas should also be given attention.

In this paper, we consider the pest management model with spraying microbial pesticide and releasing the infected pests, and the infected pests have the function similar to the microbial pesticide and can infect the healthy pests, further weaken or disable their prey function till death. By using the Floquet theory for impulsive differential equations, we show that there exists a globally asymptotically stable pest eradication periodic solution when the impulsive period τ < τmax, we further prove that the system is uniformly permanent if the impulsive period τ > τmax. Finally, by means of numerical simulation, we showthatwith the increaseof impulsive period, the system displays complicated behaviors.