The tumor immune microenvironment remodeling and response to HER2-targeted therapy in HER2-positive advanced gastric cancer.

Combination therapy with anti-HER2 agents and immunotherapy has demonstrated significant clinical benefits in gastric cancer (GC), but the underlying mechanism remains unclear. In this study, we used multiplex immunohistochemistry to assess the changes of the tumor microenvironment in 47 advanced GC patients receiving anti-HER2 therapy. Additionally, we performed single-cell transcriptional sequencing to investigate potential cell-to-cell communication and molecular mechanisms in four HER2-positive GC baseline samples. We observed that post-treated the infiltration of NK cells, CD8+ T cells, and B lymphocytes were significantly higher in patients who benefited from anti-HER2 treatment than baseline. Further spatial distribution analysis demonstrated that the interaction scores between NK cells and CD8+ T cells, B lymphocytes and M2 macrophages, B lymphocytes and Tregs were also significantly higher in benefited patients. Cell-cell communication analysis from scRNA sequencing showed that NK cells utilized CCL3/CCL4-CCR5 to recruit CD8+ T cell infiltration. B lymphocytes employed CD74-APP/COPA/MIF to interact with M2 macrophages, and utilized TNF-FAS/ICOS/TNFRSR1B to interact with Tregs. These cell-cell interactions contribute to inhibit the immune resistance of M2 macrophages and Tregs. Our research provides potential guidance for the use of anti-HER2 therapy in combination with immune therapy.

The impact of the COVID-19 pandemic on SLE.

Little is known about the association between coronavirus disease 2019 (COVID-19) and autoimmune diseases, especially in the case of systemic lupus erythematosus (SLE). SLE patients met with many questions during the pandemic in COVID-19, such as how to minimize risk of infection, the complex pathological features and cytokine profiles, diagnosis and treatment, rational choice of drugs and vaccine, good nursing, psychological supervision, and so on. In this study, we review and discuss the multifaceted effects of the COVID-19 pandemic on patients living with SLE using the available literature. Cross-talk in implicated inflammatory pathways/mechanisms exists between SLE and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and SARS-CoV-2 displays similar clinical characteristics and immuno-inflammatory responses to SLE. Current epidemiological data inadequately assess the risk and severity of COVID-19 infection in patients with SLE. More evidence has shown that hydroxychloroquine and chloroquine cannot prevent COVID-19. During the pandemic, patients with SLE had a higher rate of hospitalization. Vaccination helps to reduce the risk of infection. Several therapies for patients with SLE infected with COVID-19 are discussed. The cases in the study can provide meaningful information for clinical diagnosis and management. Our main aim is to help preventing infection and highlight treatment options for patients with SLE infected with COVID-19.

Neutrophil extracellular traps induced by the hypoxic microenvironment in gastric cancer augment tumour growth.

BACKGROUND: Inflammation-related predisposition to cancer plays an essential role in cancer progression and is associated with poor prognosis. A hypoxic microenvironment and neutrophil infiltration are commonly present in solid tumours, including gastric cancer (GC). Neutrophil extracellular traps (NETs) have also been demonstrated in the tumour immune microenvironment (TIME), but how NETs affect GC progression remains unknown. Here, we investigated the role of NET formation in the TIME and further explored the underlying mechanism of NETs in GC tumour growth. METHODS: Hypoxia-induced factor-1α (HIF-1α), citrulline histone 3 (citH3) and CD66b expression in tumour and adjacent nontumor tissue samples was evaluated by western blotting, immunofluorescence and immunohistochemical staining. The expression of neutrophil-attracting chemokines in GC cells and their hypoxic-CM was measured by qRT‒PCR and ELISA. Neutrophil migration under hypoxic conditions was evaluated by a Transwell assay. Pathway activation in neutrophils in a hypoxic microenvironment were analysed by western blotting. NET formation was measured in vitro by immunofluorescence staining. The protumour effect of NETs on GC cells was identified by Transwell, wound healing and cell proliferation assays. In vivo, an lipopolysaccharide (LPS)-induced NET model and subcutaneous tumour model were established in BALB/c nude mice to explore the mechanism of NETs in tumour growth. RESULTS: GC generates a hypoxic microenvironment that recruits neutrophils and induces NET formation. High mobility group box 1 (HMGB1) was translocated to the cytoplasm from the nucleus of GC cells in the hypoxic microenvironment and mediated the formation of NETs via the toll-like receptor 4 (TLR4)/p38 MAPK signalling pathway in neutrophils. HMGB1/TLR4/p38 MAPK pathway inhibition abrogated hypoxia-induced neutrophil activation and NET formation. NETs directly induced GC cell invasion and migration but not proliferation and accelerated the augmentation of GC growth by increasing angiogenesis. This rapid tumour growth was abolished by treatment with the NET inhibitor deoxyribonuclease I (DNase I) or a p38 MAPK signalling pathway inhibitor. CONCLUSIONS: Hypoxia triggers an inflammatory response and NET formation in the GC TIME to augment tumour growth. Targeting NETs with DNase I or HMGB1/TLR4/p38 MAPK pathway inhibitors is a potential therapeutic strategy to inhibit GC progression. Video Abstract.

Featured immune characteristics of COVID-19 and systemic lupus erythematosus revealed by multidimensional integrated analyses.

BACKGROUND: Coronavirus disease 2019 (COVID-19) shares similar immune characteristics with autoimmune diseases like systemic lupus erythematosus (SLE). However, such associations have not yet been investigated at the single-cell level. METHODS: We integrated and analyzed RNA sequencing results from different patients and normal controls from the GEO database and identified subsets of immune cells that might involve in the pathogenesis of SLE and COVID- 19. We also disentangled the characteristic alterations in cell and molecular subset proportions as well as gene expression patterns in SLE patients compared with COVID-19 patients. RESULTS: Key immune characteristic genes (such as CXCL10 and RACK1) and multiple immune-related pathways (such as the coronavirus disease-COVID-19, T-cell receptor signaling, and MIF-related signaling pathways) were identified. We also highlighted the differences in peripheral blood mononuclear cells (PBMCs) between SLE and COVID-19 patients. Moreover, we provided an opportunity to comprehensively probe underlying B-cell‒cell communication with multiple ligand-receptor pairs (MIF-CD74+CXCR4, MIF-CD74+CD44) and the differentiation trajectory of B-cell clusters that is deemed to promote cell state transitions in COVID-19 and SLE. CONCLUSIONS: Our results demonstrate the immune response differences and immune characteristic similarities, such as the cytokine storm, between COVID-19 and SLE, which might pivotally function in the pathogenesis of the two diseases and provide potential intervention targets for both diseases.

Improved BDS-2/3 Satellite Ultra-Fast Clock Bias Prediction Based with the SSA-ELM Model.

Ultra-fast satellite clock bias (SCB) products play an important role in real-time precise point positioning. Considering the low accuracy of ultra-fast SCB, which is unable to meet the requirements of precise point position, in this paper, we propose a sparrow search algorithm to optimize the extreme learning machine (SSA-ELM) algorithm in order to improve the performance of SCB prediction in the Beidou satellite navigation system (BDS). By using the sparrow search algorithm's strong global search and fast convergence ability, we further improve the prediction accuracy of SCB of the extreme learning machine. This study uses ultra-fast SCB data from the international GNSS monitoring assessment system (iGMAS) to perform experiments. First, the second difference method is used to evaluate the accuracy and stability of the used data, demonstrating that the accuracy between observed data (ISUO) and predicted data (ISUP) of the ultra-fast clock (ISU) products is optimal. Moreover, the accuracy and stability of the new rubidium (Rb-II) clock and hydrogen (PHM) clock onboard BDS-3 are superior to those of BDS-2, and the choice of different reference clocks affects the accuracy of SCB. Then, SSA-ELM, quadratic polynomial (QP), and a grey model (GM) are used for SCB prediction, and the results are compared with ISUP data. The results show that when predicting 3 and 6 h based on 12 h of SCB data, the SSA-ELM model improves the prediction model by ~60.42%, 5.46%, and 57.59% and 72.27%, 44.65%, and 62.96% as compared with the ISUP, QP, and GM models, respectively. When predicting 6 h based on 12 h of SCB data, the SSA-ELM model improves the prediction model by ~53.16% and 52.09% and by 40.66% and 46.38% compared to the QP and GM models, respectively. Finally, multiday data are used for 6 h SCB prediction. The results show that the SSA-ELM model improves the prediction model by more than 25% compared to the ISUP, QP, and GM models. In addition, the prediction accuracy of the BDS-3 satellite is better than that of the BDS-2 satellite.

Circular RNA circLOC101928570 suppresses systemic lupus erythematosus progression by targeting the miR-150-5p/c-myb axis.

BACKGROUND: Accumulating evidence supports the implication of circular RNAs (circRNAs) in systemic lupus erythematosus (SLE). However, little is known about the detailed mechanisms and roles of circRNAs in the pathogenesis of SLE. METHODS: Quantitative real-time PCR was used to determine the levels of circLOC101928570 and miR-150-5p in peripheral blood mononuclear cells of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization, RNA immunoprecipitation, luciferase reporter assays, Western blot, flow cytometry analysis and enzyme-linked immunosorbent assay were used to investigate the molecular mechanisms underlying the function of circLOC101928570. RESULTS: The results showed that the level of circLOC101928570 was significantly downregulated in SLE and correlated with the systemic lupus erythematosus disease activity index. Functionally, circLOC101928570 acted as a miR-150-5p sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promoted the transcriptional level of IL2RA by directly regulating the miR-150-5p/c-myb axis. CONCLUSION: Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The downregulation of circLOC101928570 suppressed SLE progression through the miR-150-5p/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serves as a potential biomarker for the diagnosis and therapy of SLE.

SIRT1 enhances oxaliplatin resistance in colorectal cancer through microRNA-20b-3p/DEPDC1 axis.

Oxaliplatin (L-OHP) is a standard treatment drug for colorectal cancer (CRC), but acquired drug resistance limits the outcome of patients. We investigated the involvement of sirtuin 1 (SIRT1) in L-OHP resistance in the setting of CRC via microRNA-20b-3p/DEP domain containing 1 (miR-20b-3p/DEPDC1) axis. CRC tissues that were resistant or sensitive to L-OHP were harvested, in which SIRT1, miR-20b-3p, and DEPDC1 levels were tested. L-OHP-resistant-resistant CRC cells were transfected, subsequently, cellular proliferation, invasion, migration, and apoptosis were tested, and tumor resistance to L-OHP was observed. The binding of SIRT1 to miR-20b-3p promoter and the targeting relationship between miR-20b-3p and DEPDC1 were verified. An aberrant elevation in SIRT1 expression was seen in L-OHP-resistant CRC tissues and cells. Knockdown of SIRT1 sensitized CRC cells and xenografted CRC tumors to L-OHP. SIRT1 bound with miR-20b-3p promoter to regulate DEPDC1. Reducing miR-20b-3p or raising DEPDC1 levels weakened the effect of SIRT1 knockdown on L-OHP-resistant-CRC cells. SIRT1 enhances L-OHP resistance in CRC by mediating miR-20b-3p/DEPDC1 axis.

Correlation between the accumulation of skin glycosylation end products and the development of type 2 diabetic peripheral neuropathy.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured by AGE Reader. Here, we assessed the correlation between AGEs values and the development of type 2 diabetic peripheral neuropathy (DPN). METHODS: The basic clinical information of 560 patients with T2DM was collected through an electronic system. AGEs and diabetic complication risk score was measured by AGE Reader, a non-invasive optical signal detector. All of the participants were classified into 4 groups based on Dyck criteria: grade 0 (non-DPN group), grade 1 (early stage group), grade 2 (middle stage group) and grade 3 (advanced group). Pearson correlation analysis and Spearman correlation analysis were used to evaluate the correlation between AGEs and other indexes. The sensitivity and specificity of glycosylated products were evaluated by ROC curve. RESULTS: With the increase of DPN severity, the accumulative AGEs showed an increasing trend. Significant differences (P = 0.000) of AGEs were found among grades 0, 1, 2, and 3 of DPN, and significant differences (P = 0.000) of AGEs were found between grades 1 and 3. There were significant differences in DPN risk score between grades 0, 1, 2, and 3, between grades 1, 2, and 3, and between grades 2 and 3 (P < 0.01 or P < 0.05). AGEs were positively correlated with age, blood uric acid, disease course, systolic blood pressure, the risk scores of the four major complications of diabetes, renal function indicators (serum creatinine, Cystatin C, homocysteine, the ratio of urinary albumin and creatinine, urinary microalbumin, α-microglobulin, urinary transferrin, urinary immunoglobulin), inflammatory indicators (white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, C-reactive protein), and TCSS score. However, it was negatively correlated with BMI,fasting insulin, insulin 1-3 h postprandial, lymphocyte count, HOMA insulin resistance index and estimated glomerular filtration rate. The area under the AGEs cumulant and neuropathy risk score curve was 0.769 and 0.743, respectively. The confidence intervals were (71.2-82.6%) and (68.8-79.9%), respectively. The maximum Youden's index of AGEs cumulant was 0.440, and the corresponding AGEs cumulant value was 77.65. The corresponding sensitivity and specificity were 0.731 and 0.709, respectively. Furthermore, the maximum Youden's index of neuropathy risk score was 0.385, and the corresponding neuropathy risk score was 66.25. The corresponding sensitivity and the specificity were 0.676 and 0.709, respectively. CONCLUSION: The cumulative amount of skin AGEs can be used as the diagnostic index and the prediction and evaluation index of DPN severity. Moreover, the diabetic peripheral neuropathy risk score can predict the risk of DPN in patients with T2DM.

Airborne transmission of COVID-19 virus in enclosed spaces: An overview of research methods.

Since the outbreak of COVID-19 in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has spread worldwide. This study summarized the transmission mechanisms of COVID-19 and their main influencing factors, such as airflow patterns, air temperature, relative humidity, and social distancing. The transmission characteristics in existing cases are providing more and more evidence that SARS CoV-2 can be transmitted through the air. This investigation reviewed probabilistic and deterministic research methods, such as the Wells-Riley equation, the dose-response model, the Monte-Carlo model, computational fluid dynamics (CFD) with the Eulerian method, CFD with the Lagrangian method, and the experimental approach, that have been used for studying the airborne transmission mechanism. The Wells-Riley equation and dose-response model are typically used for the assessment of the average infection risk. Only in combination with the Eulerian method or the Lagrangian method can these two methods obtain the spatial distribution of airborne particles' concentration and infection risk. In contrast with the Eulerian and Lagrangian methods, the Monte-Carlo model is suitable for studying the infection risk when the behavior of individuals is highly random. Although researchers tend to use numerical methods to study the airborne transmission mechanism of COVID-19, an experimental approach could often provide stronger evidence to prove the possibility of airborne transmission than a simple numerical model. All in all, the reviewed methods are helpful in the study of the airborne transmission mechanism of COVID-19 and epidemic prevention and control.

Evaluation of airborne particle exposure for riding elevators.

Social distancing is a key factor for health during the COVID-19 pandemic. In many indoor spaces, such as elevators, it is difficult to maintain social distancing. This investigation used computational-fluid-dynamics (CFD) to study airborne particle exposure in riding an elevator in a typical building with 35 floors. The elevator traveled from the ground floor to the 35th floor with two stops on floor 10 and floor 20, comprising 114 s. The CFD simulated the dispersion of the aerosolized particles exhaled by an index person while breathing in both lobby and elevator areas. The study calculated the accumulated dose of susceptible riders riding in elevators with the index person under different conditions including different ventilation rates, air supply methods, and elevator cab geometries. This investigation also studied a case with a single cough from the index person as the person entered the elevator. The results show that, due to the short duration of the average elevator ride, the number of particles inhaled by a susceptible rider was low. For the reference case with a 72 ACH (air changes per hour) ventilation rate, the highest accumulated particle dose by a susceptible passenger close to the index person was only 1.59. The cough would cause other riders to inhale approximately 8 orders of magnitude higher particle mass than from continuous breathing by the index person for the whole duration of the ride.

Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystemic, chronic inflammatory disease characterized by destructive systemic organ involvement, which could cause the decreased functional capacity, increased morbidity and mortality. Previous studies show that SLE is characterized by autoimmune, inflammatory processes, and tissue destruction. Some seriously-ill patients could develop into lupus nephritis. However, the cause and underlying molecular events of SLE needs to be further resolved. METHODS: The expression profiles of GSE144390, GSE4588, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between SLE and healthy samples. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by metascape etc. online analyses. The protein-protein interaction (PPI) networks of the DEGs were constructed by GENEMANIA software. We performed Gene Set Enrichment Analysis (GSEA) to further understand the functions of the hub gene, Weighted gene co-expression network analysis (WGCNA) would be utilized to build a gene co-expression network, and the most significant module and hub genes was identified. CIBERSORT tools have facilitated the analysis of immune cell infiltration patterns of diseases. The receiver operating characteristic (ROC) analyses were conducted to explore the value of DEGs for SLE diagnosis. RESULTS: In total, 6 DEGs (IFI27, IFI44, IFI44L, IFI6, EPSTI1 and OAS1) were screened, Biological functions analysis identified key related pathways, gene modules and co-expression networks in SLE. IFI27 may be closely correlated with the occurrence of SLE. We found that an increased infiltration of moncytes, while NK cells resting infiltrated less may be related to the occurrence of SLE. CONCLUSION: IFI27 may be closely related pathogenesis of SLE, and represents a new candidate molecular marker of the occurrence and progression of SLE. Moreover immune cell infiltration plays important role in the progession of SLE.

Skin autofluorescence and the complexity of complications in patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured as skin autofluorescence (SAF). Here, we assessed the correlation between SAF values and the complexity and severity of type 2 diabetes mellitus (T2DM) complications. METHODS: The basic clinical information of 825 patients with T2DM was collected through an electronic system, and SAF was measured by adapting a DM-Scan, a non-invasive optical signal detector. Diabetic complications were diagnosed based on clinical criteria by experienced doctors. Linear regression analysis was used to evaluate the independent determinants of SAF, and multiple logistic regression analysis was performed to assess independent determinants that influence the severity of the complications. RESULTS: SAF was significantly associated with the complexity of T2DM complications. Similarly, independent relationships between SAF and age (ß = 0.389, P <  0.001), sex (ß = - 2.221, P = 0.004), 2-h C-peptide (ß = - 0.182, P = 0.017), aminotransferase (ALT, ß = - 0.158, P = 0.041), blood creatinine (BCr, ß = 0.206, P = 0.009), and fatty liver (ß = 0.161, P = 0.026) were observed. With the increasing number of complications, the SAF values increased significantly after adjusting for related risk factors. The SAF values correlated with diabetic retinopathy, diabetic kidney diseases, cardiovascular disease, and diabetic peripheral neuropathy when compared with patients without any T2DM-associated complications. Moreover, the AGE-based diabetic complication risk score for each complication demonstrated a relationship with the presence or absence of certain complications. CONCLUSION: SAF is an independent marker for diabetic retinopathy, diabetic kidney diseases, cardiovascular disease, and diabetic peripheral neuropathy, and it is also a predictor of the complexity of T2DM complications. Moreover, the diabetic complication risk score is capable of predicting the risk of diabetic complications in patients with T2DM.

Inverse design of the thermal environment in an airplane cockpit using the adjoint method with the momentum method.

Currently, the thermal environment in airplane cockpits is unsatisfactory and pilots often complain about a strong draft sensation in the cockpit. It is caused by the unreasonable air supply diffusers design. One of the best approaches to design a better cockpit environment is the adjoint method. The method can simultaneously and efficiently identify the number, size, location, and shape of air supply inlets, and the air supply parameters. However, the real air diffuser needed to design often have grilles, especially in the airplane cockpit, and the current method can only design the inlet as an opening. This study combined the adjoint method with the momentum method to directly identify the optimal air supply diffusers with grilles to create optimal thermal environment in an airplane cockpit (1) under ideal conditions and (2) with realistic constraints. Under the ideal conditions, the resulting design provides an optimal thermal environment for the cockpit, but it might not be feasible in practice. The design with realistic constraints provides acceptable thermal comfort in the cockpit, but it is not optimal. Thus, there is an engineering trade-off between design feasibility and optimization. All in all, the adjoint method with the momentum method can be effectively used to identify real air supply diffusers.

Inverse design of an indoor environment using a filter-based topology method with experimental verification.

In order to create a healthy, comfortable, productive, and energy-efficient indoor environment, the computational fluid dynamics (CFD)-based adjoint method with an area-constrained topology method can be used to inversely design the optimal number, size, location, and shape of air supply inlets and air supply parameters. However, this method is not very mature, and the distribution of retained inlets is always scattered. To solve that problem, this investigation introduced a filter method that smooths the intermediate results during the inverse design process. Using a three-dimensional, non-isothermal, asymmetrical office with pre-set air supply inlets as an example, this study verified the performance of the proposed filter-based topology method. The verified method was then used to solve a multi-objective design problem and design an optimal indoor environment for a room. The results indicate that the proposed method was able to find the optimal number, location, and shape of air supply inlets and the optimal air supply temperature, velocity, and angle that led to a thermally comfortable, healthy, productive, and energy-efficient indoor environment. Finally, this investigation installed the optimal inlets in an environmental chamber to mimic the room. The measured air temperature, velocity, and mean age of air in several typical locations in the environmental chamber matched the CFD simulation results very closely.

Aliifodinibius salipaludis sp. nov., Isolated from Saline-Alkaline Soil.

A Gram-staining-negative, oblong or rod-shaped, non-flagellated and facultatively anaerobic bacterium, designated WN023T, was isolated from natural saline-alkali wetland soil of Binhai new district, Tianjin, China. The colonies of strain WN023T on marine agar 2216 (MA) have a brown, circular, wet pigmentation, and its cells are approximately 1-1.5 µm × 2.0-2.5 µm in size. Growth occurred at 15-45 °C, but optimally at 33-37 °C, in the presence of 5.0-25.0% (w/v) NaCl, but optimally at 10.0-15.0% (w/v) NaCl, and at a pH 6.5-11.0, but optimally at 7.5-8.0. Phylogenetic analysis of the 16S rRNA gene indicates that strain WN023T is a member of the genus Aliifodinibius within the family Balneolaceae, and the 16S rRNA gene sequence similarity of strain WN023T with its close relative Aliifodinibius halophilus KCTC 42497T, Aliifodinibius salicampi KACC 19060T, Aliifodinibius roseus KCTC 23442T, Aliifodinibius sediminis ACCC 10714T, and Fodinibius salinus ACCC 10716T was 97.3%, 94.5%, 93.9%, 93.71%, and 92.7%, respectively. Strain WN023T contained menaquinone-7 (MK-7) as the predominant menaquinone, and iso C15:0, Sum in feature 3 (C16:1ω6c and/or C16:1ω7c), and iso C17:1ω9c as the major fatty acids. The major polar lipids were glycolipid (GL), aminolipid (AL), phospholipid (PL), phosphatidylcholine (PC), phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), and lipid (L). The size of the draft genome as presented here was 3,583,276 bp in size, and the G+C content is 42.2 mol%. These combined physiological, biochemical, phylogenetic, and genotypic data supported placement of strain WN023T in the genus Aliifodinibius and indicated that it was distinct from all other members in the genus Aliifodinibius. This was also confirmed by the low DNA-DNA hybridization values (38.4%) between strain WN023T and the most closely related recognized Aliifodinibius species-A. halophilus KCTC 42497T. Therefore, we propose a novel species in the genus Aliifodinibius to accommodate the novel isolate: Aliifodinibius salipaludis sp. nov. (type strain WN023T = KCTC 52855T = ACCC 19978T).

Distinguish different Chinese medicine types of metabolic syndrome by combining body mass index and uric acid.

OBJECTIVE: To provide clinical support for traditional Chinese medicine classification of metabolic syndrome patients. METHODS: The retrospective study was conducted at Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, and Sichuan Provincial Hospital of Chinese Medicine, Chengdu, China, and comprised data of metabolic syndrome patients having visited the two hospitals between January and December 2017. The patients were divided into 2 groups based on the different types of Chinese medicine. Group1 had Qi-Yin deficiency and group 2 had phlegm-blood stasis. Various laboratory tests related to metabolic syndrome were conducted, analysed and compared in both the groups. RESULTS: Of the 263 patients, 173(66%) were in group 1 and 90(34%) were in group 2. Body mass index and blood uric acid level had statistical significance between the groups (p<05) .The sensitivity was over 90% and the accuracy was 60%. CONCLUSIONS: Body mass index and blood uric acid level were found to be the two independent factors to distinguish between different types of metabolic syndrome.

Inverse design of indoor environment using an adjoint RNG k-ε turbulence model.

The adjoint method can determine design variables of an indoor environment according to the optimal design objective, such as minimal predicted mean vote (PMV) for thermal comfort. The method calculates the gradient of the objective function over the design variables so that the objective function can be minimized along the fastest direction using an optimization algorithm. Since the objective function is controlled by the Reynolds-averaged Navier-Stokes (RANS) equations with the RNG k-ε model during the optimization process, all the corresponding adjoint equations should be solved, rather than the "frozen turbulence" assumption used in previous studies. This investigation developed adjoint equations for the RNG k-ε turbulence model and applied it to a two-dimensional ventilated cavity and a three-dimensional, two-person office. Design processes with the adjoint RNG k-ε turbulence model led to a near-zero design function for the two cases, while those with the "frozen turbulence" assumption did not. This investigation has successfully used the new method to design a two-person office with optimal thermal comfort level around the two occupants.

Impact of Colon-Specific DNA Methylation-Regulated Gene Modules on Colorectal Cancer Patient Survival.

BACKGROUND Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females and the third in males worldwide. Although existing evidence explained some critical functions of the single genetic abnormality in the pathogenesis of CRC, the function of interactors involved in the colon-specific regulatory network, especially DNA methylation regulated network is still poorly understood. MATERIAL AND METHODS In this work, matched gene expression and DNA methylation samples of CRC patients were retrieved. Differential gene expression and methylation analyses were performed. In addition, gene expression and DNA methylation were integrated into a colon-specific regulatory gene network, detecting the epigenetically regulated gene modules which drive CRC through an underlying epigenetic mechanism. Finally, the colon-specific DNA methylation-regulated gene modules were validated using an independent set of CRC patients. RESULTS Differential gene expression analysis demonstrated the upregulation of the cell cycle and DNA replication and downregulation of cGMP-PKG signaling pathway and calcium signaling pathway in CRC. Differentially methylated regions (DMRs) showed the different levels of methylation in promoters, CpG islands, and genes in CRC. In addition, gene expression and DNA methylation were integrated into a colon-specific regulatory gene network, detecting 8 epigenetically regulated gene modules which drive CRC through an underlying epigenetic mechanism. Interestingly, 2 of the colon-specific DNA methylation-regulated gene modules showed a significant predictive ability for the survival of an independent set of CRC patients. CONCLUSIONS The results of this study could open a new era and aid the development of novel therapeutic targets for the treatment of CRC patient.

An innovative personalized displacement ventilation system for airliner cabins.

In airliner cabins, mixing ventilation systems with gaspers are not efficient in controlling contaminant transport. To improve the cabin environment, this investigation proposed an innovative ventilation system that would reduce contaminant transport and maintain thermal comfort. We manufactured and installed the proposed ventilation system in an occupied seven-row, single-aisle aircraft cabin mockup. Air velocity, air temperature, and contaminant distribution in the cabin mockup were obtained by experimental measurements. The investigation used the experimental data to validate the results of CFD simulation. The validated CFD program was then used to study the impact of the locations and number of exhausts on contaminant removal and thermal comfort in a one-row section of a fully occupied Boeing-737 cabin. Although the diffusers in the proposed system were close to the passengers' legs, the air velocity magnitude was acceptable in the lower part of the cabin and the leg area. The proposed system provided an acceptable thermal environment in the cabin, although passengers could feel cold when placing their legs directly in front of the diffusers. The four-exhaust configuration of the new ventilation system was the best, and it decreased the average exposure in the cabin by 57% and 53%, respectively, when compared with the mixing and displacement ventilation systems.