The efficacy of modified binding technique for renorrhaphy during robotic partial nephrectomy: surgical and functional outcomes from single-center experience.

BACKGROUND: To compare the traditional single-layer and double-layer suture renorrhaphy with modified "Binding" suture renorrhaphy (whole rim of the wound was closed by the all-layer flow suture starting from the parenchyma cut edges to hilum, followed by the final defect closure) in robotic partial nephrectomy (RPN) for treating localized renal cell carcinoma in our large institutional experience. METHODS: We retrospectively reviewed clinical data of 406 consecutive patients who underwent RPN from May 2018 and December 2020 in our center. The demographic and oncologic outcome variables were compared between different renal reconstruction groups and the effect of these suture techniques on renal function outcomes was also evaluated. RESULTS: For the single-layer group, median operative time and warm ischemic time were significantly less than that of the double-layer and "Binding" groups (p < 0.001), while the significantly lower eGFR drop (p = 0.014) was also detected within postoperative 3 months from baseline, but this difference lost its statistical significance from 3th month to the last follow-up. The changes in postoperative creatinine values were clinically insignificant among the three groups. In a sub-analysis over 258 patients with moderate/high nephrometry score, those patients who underwent "Binding" suture had an undifferentiated warm ischemic time, estimated blood loss, and length of hospitalization stay with a decreased risk of Grade III complications (postoperative hemorrhage requiring intervention) and improved renal function recovery during the whole follow-up. CONCLUSION: Single-layer suture renorrhaphy may be associated with better renal functional preservation and could prove to be reliable in patients with low-complexity tumor (RENAL score ≤ 6). Patients with moderate/high-complexity tumor (RENAL score ≥ 7) might represent a subgroup of patients having a functional benefit after "Binding" suture renorrhaphy even in the long-term period.

[Expression and significance analysis of GDF3 in testicular cancer based on TCGA and GTEx databases].

OBJECTIVE: To investigate the expression and significance of GDF3 in testicular cancer through bioinformatics analysis. METHODS: Using the TCGA and GTEx databases, differential expression analysis and pan-cancer analysis were performed to identify the target gene GDF3, and the clinical relevance of GDF3 in testicular cancer was analyzed using the UALCAN database. Based on the R packages "org.Hs.eg.db" and "clusterProfiler," gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore the potential functions of GDF3 in testicular cancer. The correlation of GDF3 with immune chemokines and immune inhibitors in testicular cancer was investigated using the TISIDB database. RESULTS: The GDF3 was significantly upregulated in testicular cancer (P<0.001) and closely associated with clinical staging (P<0.05) and tumor subtypes (P<0.001). The immune-related analysis revealed that GDF3 was strongly correlated with immune chemokines CCL26 (rho=0.599, P<0.001), CCL7 (rho=0.525, P<0.001), immune inhibitor ADORA2A (rho=0.723, P<0.001), and PVRL2 (rho=0.585, P<0.001). CONCLUSION: The GDF3 is closely related to the occurrence, development, and immune microenvironment of testicular cancer.

Clinical efficacy of immunotherapy combined with chemotherapy in patients with advanced gastric cancer, its effect on nutritional status and Changes of peripheral blood T lymphocyte subsets.

OBJECTIVES: To evaluate the clinical efficacy of immunotherapy combined with chemotherapy in patients with advanced gastric cancer and its effect on nutritional status and changes of peripheral blood T lymphocyte subsets. METHODS: Sixty patients with locally advanced gastric cancer who were admitted by Affiliated Hospital of Hebei University from March 2020 to February 2021 were enrolled and randomly divided into two groups, with 30 cases in each group. The control group was treated with FOLFOX4 chemotherapy, while the experimental group was additively treated with cindilizumab on the basis of control group. The incidence of adverse reactions, clinical efficacy, improvement of nutritional and physical status, and changes in the levels of T lymphocyte subgroups in the two groups were compared and analyzed. RESULTS: The total effective rate was 70% in the experimental group, which was better than 43.3% of the control group (p=0.04). The improvement rate of performance status (ECOG) score and nutritional indicators in the experimental group was significantly better than that in the control group (p<0.05). Moreover, the indicators of CD3+, CD4+, CD4+/CD8+ in the experimental group were significantly higher than those in the control group after treatment, with statistically significant differences (CD3+, p=0.01; CD4 +, p= 0.02; CD4+/CD8+, p=0.01). CONCLUSION: Immunotherapy combined with chemotherapy has a significant effect on locally advanced gastric cancer patients, with significant improvement in physical strength and nutritional status, significant improvement in T lymphocyte function, and no obvious adverse reactions. It is worth promoting in clinical application.

Dynamic contrast-enhanced MRI to predict response to vinorelbine-cisplatin alone or with rh-endostatin in patients with non-small cell lung cancer and bone metastases: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Metastatic bone disease is a frequent complication of advanced non-small-cell lung cancer and causes skeletal-related events which result in a poor prognosis. A standard method to assess the therapeutic response of bone metastases does not currently exist. We used dynamic contrast-enhanced MRI to obtain quantitative measures to assess the suitability of this technique to gauge therapeutic response to vinorelbine-cisplatin plus rh-endostatinfor previously untreated non-small cell lung cancer with bone metastases. METHODS: We did a phase 4, randomised, prospective, double-blind, placebo-controlled clinical trial in Shanghai Sixth People's Hospital, Shanghai, China. Inclusion criteria were non-small-cell lung cancer patients with bone metastases confirmed by pathology or cytology; available imaging data of pelvic metastatic lesions; aged 18 to 75 years old; expected survival at least 3 months; not receiving taxane, bevacizumab, thalidomide, rh-endostatin, or bisphosphonate; not having radiation therapy within 3 months of enrollment into study; normal results of routine blood tests, liver and kidney function, and electrocardiogram; absence of cardiovascular disease, autoimmune disease, vasculitis, severe infection, diabetes, and other concomitant disease; and signed informed consent. Exclusion criteria were receiving granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor during chemotherapy, intolerance to adverse reaction, and allergy to contrast agents. Patients were randomly assigned to treatment group and control group at a ratio of 2:1 by random code generation by an independent biostatistician in a double-blind fashion. Participants received either vinorelbine-cisplatin plus rh-endostatin or vinorelbine-cisplatin plus placebo. Vinorelbine (25 mg/m2) and cisplatin (75 mg/m2) were administered intravenously on the first day of a 21 day cycle. Patients received rh-endostatin (7·5 mg/m2) or placebo on days 1-14 of a cycle. The primary end points were objective response rate (complete remission+partial remission)/total × 100) and disease control rate (complete remission+partial remission+stable disease)/total × 100). Measurements including Ktrans, Kep, and Ve were evaluated by dynamic contrast-enhanced MRI before treatment and after completion of 2 treatment cycles. Blood concentrations of bone metabolites, tumour markers, and tumour vascular growth related factors were measured before and after treatment. Comparisons were made using paired t-test. Kaplan-Meier survival analysis was used to indicate the correlation between some measurements and progression-free survival or overall survival. The difference in Ktrans between patients who had partial remission or stable disease group and those who had disease progression was tested using the Chi-square test. All statistical analyses were performed with SPSS version 21.0. This trial was approved by the State Food and Drug Administration (No: S20050088) and China State Food and Drug Administration. The trial is registered with China Clinical Trials Registry, number chictr-ctr-09000569. Written informed consent and ethical approval was obtained. FINDINGS: We enrolled 33 patients (aged 52-70, 15 men and 18 women) of whom 28 were evaluable (20 in treatment group and 8 in control group). Five patients were excluded: 2 patients in treatment group and 1 patient in control group used granulocyte-macrophage colony stimulating factor, and 2 patients in the control group refused treatment. Objective response rate was higher (30% vs 0%; p<0·00001), mean overall survival was longer (21·44 [SD 17·28] vs 7·71 [4·68] months, p=0·008), and reduction in capillary permeability (measured by Ktrans) was greater (60·0% vs 4·4%; p=0·026) in the group given rh-endostatin than in the control group. Disease control rate was 80% in the treatment group and 75% in the control group (p=0·07). Overall survival was longer in patients with a greater than 50% reduction in Ktrans than in patients with a decrease of up to 50% (13·2 [1·8] vs 9·8 [0·2] months, p=0·026). INTERPRETATION: Addition of rh-endostatin to treatment with vinorelbine-cisplatin increased the treatment response in patients with non-small cell lung cancer and bone metastases. Quantitative analysis using dynamic contrast-enhanced MRI can be used to evaluate therapeutic response and to predict survival of bone metastases after anti-angiogenesis therapy. Limitations of this study include the small number of patients and the single-centre design. FUNDING: National Natural Science Foundation of China [grant number 81201628].

Contribution of 3CD Region to the Virulence of Enterovirus 71.

Enterovirus 71 is a neuroinvasive virus that is associated with severe neurological complications. We had earlier suggested that the replication capacity of a severe strain was higher than that of a mild strain. The recombinant 3CRV and 3CDRV virus strains were successfully rescued in our previous study. In the present study, we found no difference in virulence between 3CRV and severe strains. However, the capacity of replication and to cause cell injury of 3CDRV strain decreased in vitro, especially at 39.5 °C. Replacement of 3CD region in the severe strain led to milder symptoms, less body weight loss, and lower viral load in ICR mice. Histopathological findings indicated less severe injury in mice infected with 3CDRV strain. This study suggests that the 3CD region contributes to the attenuation of the severe strain, including its replication capacity and temperature sensitivity.

Thrombocytopenia as a predictor of severe acute kidney injury in patients with heat stroke.

BACKGROUND: Abnormalities of blood system often occur several days before acute kidney injury (AKI) in patients with heat stroke (HS). We aimed to investigate the prevalence and prognostic value of the early hematological markers in patients with AKI induced by HS. METHODS: In a retrospective cohort study, we analyzed the case records of 176 patients with HS and evaluated the hematological markers for early prediction and risk classification in the patients with AKI. RESULTS: Of 176, 103 (58%) HS cases developed AKI, and men comprised more than half (75%) of the sample population. The nadir platelet count significantly correlated with the levels of peak serum creatinine (r = -0.608, p < 0.01) and blood urea nitrogen (r = -0.546, p < 0.01), and the length of hospital stay (r = -0.393, p < 0.01). The areas under the receiver operating characteristic curves (AU-ROC) indicated the prognostic accuracy of hematological markers, AU-ROC was significantly higher with the nadir platelet count than that with the admission platelet count (AU-ROC of the nadir platelet: 0.73; 95% CI: 0.67-0.82; vs. AU-ROC of the admission platelet: 0.67; 95% CI: 0.59-0.75; p < 0.01). Multiple logistic regression results indicated that the nadir platelet count (adjusted ORs: 37.92; 95% CI: 2.18-87.21; p < 0.01) was independent predictor of AKI in HS. CONCLUSION: The high mortality observed in HS complicated with AKI, and among the various hematological parameters assessed, thrombocytopenia is associated with AKI induced by HS independently.

Short-term ethanol exposure causes imbalanced neurotrophic factor allocation in the basal forebrain cholinergic system: a novel insight into understanding the initial processes of alcohol addiction.

Alcohol ingestion affects both motor and cognitive functions. One brain system that is influenced by ethanol is the basal forebrain (BF) cholinergic projection system, which projects to diverse neocortical and limbic areas. The BF is associated with memory and cognitive function. Our primary interest is the examination of how regions that receive BF cholinergic projections are influenced by short-term ethanol exposure through alterations in the mRNA levels of neurotrophic factors [nerve growth factor/TrkA, brain-derived neurotrophic factor/TrkB, and glial-derived neurotrophic factor (GDNF)/GDNF family receptor α1]. Male BALB/C mice were fed a liquid diet containing 5 % (v/v) ethanol. Pair-fed control mice were maintained on an identical liquid diet, except that the ethanol was isocalorically substituted with sucrose. Mice exhibiting signs of ethanol intoxication (stages 1-2) were used for real-time reverse transcription-polymerase chain reaction analyses. Among the BF cholinergic projection regions, decreased levels of GDNF mRNA and increased levels of TrkB mRNA were observed in the basal nucleus, and increased levels of TrkB mRNA were observed in the cerebral cortex. There were no significant alterations in the levels of expression of relevant neurotrophic factors in the septal nucleus and hippocampus. Given that neurotrophic factors function in retrograde/anterograde or autocrine/paracrine mechanisms and that BF cholinergic projection regions are neuroanatomically connected, these findings suggested that an imbalanced allocation of neurotrophic factor ligands and receptors is an initial phenomenon in alcohol addiction. The exact mechanisms underlying this phenomenon in the BF cholinergic system are unknown. However, our results provide a novel notion for the understanding of the initial processes in alcohol addiction.

Effects of HIV-1 tat on secretion of TNF-α and IL-1ß by U87 cells in AIDS patients with or without AIDS dementia complex.

OBJECTIVE: To explore the role of HIV-1 tat gene variations in AIDS dementia complex (ADC) pathogenesis. METHODS: HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1ß concentrations in the supernatant of U87 cells were determined with ELISA. RESULTS: HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area (38-47aa). All Tat proteins could induce U87 cells to produce TNF-α and IL-1ß, but the level of IL-1ß production was different among Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen. The level of Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen were obviously higher than that from the non-ADC patient's basal ganglia. CONCLUSION: Tat protein core functional area (38-47aa) may serve as the key area of enhancing the secretion of IL-1ß. This may be related with the neurotoxicity of HIV-1 Tat.

Ecosystem service tradeoff and synergistic relationship in the Yellow River Delta High-Efficiency Eco-Economic Zone.

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.

Modulatory Effects of XIAOPI Formula on CXCL1 and Selected Outcomes in Triple-Negative Breast Cancer: A Randomized Controlled Clinical Trial.

Background: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients' emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown. Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores. Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials. Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.

Comprehensive pan-cancer analysis reveals prognostic implications of TMEM92 in the tumor immune microenvironment.

BACKGROUND: Transmembrane protein 92 (TMEM92) has been implicated in the facilitation of tumor progression. Nevertheless, comprehensive analyses concerning the prognostic significance of TMEM92, as well as its role in immunological responses across diverse cancer types, remain to be elucidated. METHODS: In this study, data was sourced from a range of publicly accessible online platforms and databases, including TCGA, GTEx, UCSC Xena, CCLE, cBioPortal, HPA, TIMER2.0, GEPIA, CancerSEA, GDSC, exoRBase, and ImmuCellAI. We systematically analyzed the expression patterns of TMEM92 at both mRNA and protein levels across diverse human organs, tissues, extracellular vesicles (EVs), and cell lines associated with multiple cancer types. Subsequently, analyses were conducted to determine the relationship between TMEM92 and various parameters such as prognosis, DNA methylation, copy number variation (CNV), the tumor microenvironment (TME), immune cell infiltration, genes with immunological relevance, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and half-maximal inhibitory concentration (IC50) values. RESULTS: In the present study, we observed a pronounced overexpression of TMEM92 across a majority of cancer types, which was concomitantly associated with a less favorable prognosis. A notable association emerged between TMEM92 expression and both DNA methylation and CNV. Furthermore, a pronounced relationship was discerned between TMEM92 expression, the TME, and the degree of immune cell infiltration. Intriguingly, while TMEM92 expression displayed a positive correlation with macrophage presence, it inversely correlated with the infiltration level of CD8 + T cells. Concurrently, significant associations were identified between TMEM92 and the major histocompatibility complex, TMB, MSI, and MMR. Results derived from Gene Set Enrichment Analysis and Gene Set Variation Analysis further substantiated the nexus of TMEM92 with both immune and metabolic pathways within the oncogenic context. CONCLUSIONS: These findings expanded the understanding of the roles of TMEM92 in tumorigenesis and progression and suggest that TMEM92 may have an immunoregulatory role in several malignancies.

Complete genome sequencing and analysis of six enterovirus 71 strains with different clinical phenotypes.

BACKGROUND: Hand, foot and mouth diseases (HFMD) caused by enterovirus 71(EV71) presents a broad spectrum of clinical manifestations ranging from mild febrile disease to fatal neurolocal disease. However, the mechanism of virulence is unknown. METHODS: We isolated 6 strains of EV71 from HFMD patients with or without neurological symptoms, and sequenced the whole genomes of the viruses to reveal the virulence factors of EV71. RESULTS: Phylogenetic tree based on VP1 region showed that all six strains clustered into C4a of C4 sub-genotype. In the complete polypeptide, 298 positions were found to be variable in all strains, and three of these positions (Val(P814)/Ile(P814) in VP1, Val(P1148)/Ile(P1148) in 3A and Ala(P1728)/Cys)/Val(P1728) in 3C) were conserved among the strains with neurovirulence, but variable in strains without neurovirulence. In the 5'-UTR region, it showed that the first 10 nucleotides were mostly conserved, however from the 11th nucleotide, nucleotide insertions and deletions were quite common. The secondary structure prediction of 5'-UTR sequences showed that two of three strains without neurovirulence (SDLY11 and SDLY48) were almost the same, and all strains with neurovirulence (SDLY96, SDLY107 and SDLY153) were different from each other. SDLY107 (a fatal strain) was found different from other strains on four positions (C(P241)/T(P241), A(P571)/T(P571), C(P579)/T(P579) in 5'-UTR and T(P7335)/C(P7335) in 3'-UTR). CONCLUSIONS: The three positions (Val(P814)/Ile(P814) in VP1, Val(P1148)/Ile(P1148) in 3A and Ala(P1728)/Cys(P1728)/Val(P1728) in 3C), were different between two phenotypes. These suggested that the three positions might be potential virulent positions. And the three varied positions were also found to be conserved in strains with neurovirulence, and variable in strains without neurovirulence. These might reveal that the conservation of two of the three positions or the three together were specific for the strains with neurovirulence. Varation of secondary structure of 5'-UTR, might be correlated to the changes of viral virulence. SDLY107 (a fatal strain) was found different from other strains on four positions, these positions might be related with death.

[Analysis of evolution features of whole genome of influenza virus H3N2 in Qingdao between year 2007 and 2011].

OBJECTIVE: To investigate the evolution features of whole-genome of influenza virus H3N2 prevalent in Qingdao from year 2007 to 2011. METHODS: The RNA of 58 strains of influenza virus H3N2 prevalent in Qingdao between 2007 and 2011 was extracted and all segments amplified by RT-PCR. The sequence was then detected and assembled by software Sequencer. A total of 589 strains of influenza virus H3N2 with more than 300 amino acid recorded by GenBank were selected. The phylogeny and molecular features of all gene segments were analyzed by software Mega 5.0, referred by the heavy chain of hemagglutinin (HA1). RESULTS: Hemagglutinin (HA) genes of influenza virus H3N2 prevalent in Qingdao between year 2007 and 2011 formed a single trunk of phylogenetic tree. Every prevalent strain originated in last season. The analysis of the evolution of whole genome found that reassortment virus strains were prevalent between year 2009 and 2010, but between 2010 and 2011 there were two series of prevalent strains, which showed complicated reassortment. Compared with the vaccine strains, the variant amino acids of protein of virus HA1 between year 2007 and 2011 were 8, 6, 6, 8 and 11, involving 13 antigenic sites. The sequence analysis of M2 protein showed that the isolated influenza virus H3N2 mutated in amino acid site 31, from serine to asparagine (S31N). HA1 gene of influenza virus H3N2 isolated in Qingdao between 2007 and 2011 shared the similar phylogenetic tree with the globally prevalent strain. The comparison of the sequence and the analysis of the antigenicity found co-infection between H3N2 and A/H1N1 in the strain A/Qingdao/F521/2011. CONCLUSION: The evolution features of all segments of influenza virus H3N2 prevalent in Qingdao between year 2007 and 2011 were complicated.

Bacterial butyrate mediates the anti-atherosclerotic effect of silybin.

Silybin (SIL) is a versatile bioactive compound used for improving liver damage and lipid disorders and is also thought to be beneficial for atherosclerosis (AS). The goal of this study was to investigate the efficacy of SIL in the treatment of AS in ApoE-/-mice fed a high-fat diet and explore the mechanism underlying treatment outcomes. We found that SIL significantly alleviated AS-related parameters, including the extent of aortic plaque formation, hyperlipidemia, and adhesion molecule secretion in the vascular endothelium. 16 S rRNA gene sequencing analysis, together with the application of antibiotics, showed that intestinal butyrate-producing bacteria mediated the ameliorative effect of SIL on AS. Further analysis revealed that SIL facilitated butyrate production by increasing the level of butyryl-CoA: acetate CoA-transferase (BUT). The increased expression of monocarboxylic acid transporter-1 (MCT1) induced by butyrate and MCT4 induced by SIL in the apical and basolateral membranes of colonocytes, respectively, resulted in enhanced absorption of intestinal butyrate into the circulation, leading to the alleviation of arterial endothelium dysfunction. Moreover, the SIL-mediated increase in intestinal butyrate levels restored gut integrity by upregulating the expression of tight junction proteins and promoting gut immunity, thus inhibiting the AS-induced inflammatory response. This is the first study to show that SIL can alleviate AS by modulating the production of bacterial butyrate and its subsequent absorption.

Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer.

Anti-angiogenesis targeting VEGFR-2 has been considered as an important strategy for cancer therapy. Ellagic acid is a naturally existing polyphenol widely found in fruits and vegetables. It was reported that ellagic acid interfered with some angiogenesis-dependent pathologies. Yet the mechanisms involved were not fully understood. Thus, we analyzed its anti-angiogenesis effects and mechanisms on human breast cancer utilizing in-vitro and in-vivo methodologies. The in-silico analysis was also carried out to further analyze the structure-based interaction between ellagic acid and VEGFR-2. We found that ellagic acid significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways including MAPK and PI3K/Akt in endothelial cells. Ellagic acid also obviously inhibited neo-vessel formation in chick chorioallantoic membrane and sprouts formation of chicken aorta. Breast cancer xenografts study also revealed that ellagic acid significantly inhibited MDA-MB-231 cancer growth and P-VEGFR2 expression. Molecular docking simulation indicated that ellagic acid could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR-2 kinase unit. Taken together, ellagic acid could exert anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer.

LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis.

LDH-A, as the critical enzyme accounting for the transformation from pyruvate into lactate, has been demonstrated to be highly expressed in various cancer cells and its silencing has also been approved relating to increased apoptosis in lymphoma cells. In this study, we intend to investigate the correlation between LDH-A and other clinicopathological factors of breast cancer and whether LDH-A silencing could suppress breast cancer growth, and if so the potential mechanisms. 46 breast cancer specimens were collected to study the relation between LDH-A expression and clinicopathological characteristics including menopause, tumor size, node involvement, differentiation, and pathological subtypes classified by ER, PR, and Her-2. shRNAs were designed and applied to silence LDH-A expression in breast cancer cell lines MCF-7 and MDA-MB-231. The effects of LDH-A reduction on cancer cells were studied by a series of in vitro and in vivo experiments, including cell growth assay, apoptosis evaluation, oxidative stress detection, transmission electron microscopy observation, and tumor formation assay on nude mice. LDH-A expression was found to correlate significantly with tumor size and to be independent for other clinicopathological factors. LDH-A reduction resulted in an inhibited cancer cell proliferation, elevated intracellular oxidative stress, and induction of mitochondrial pathway apoptosis. Meanwhile, the tumorigenic ability of LDH-A deficient cancer cells was significantly limited in both breast cancer xenografts. The Ki67 positive cancer cells were significantly reduced in LDH-A deficiency tumor samples, while the apoptosis ratio was enhanced. Our results suggested that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer.

Novel oxoisoaporphine-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation.

A series of novel oxoisoaporphine-based inhibitors (10-aminoalkylamino-1-azabenzanthrone Ar-NH(CH(2))(n)NR(1)R(2)) of acetylcholinesterase (AChE) has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE) and AChE-induced ß-amyloid (Aß) aggregation. The synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in the submicromolar range in most cases. Non-competitive binding mode was found for these derivatives by the graphical analysis of steady-state inhibition data. Moreover, all compounds exhibit significant inhibitory activity on AChE-induced Aß aggregation with inhibitory potency from 54.5% to 93.5%. Finally, six out of twelve synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically.

6-[(2-Hy-droxy-eth-yl)amino]-7H-dibenzo[de,h]quinolin-7-one.

The title compound, C(18)H(14)N(2)O(2), is a new oxoisoaporphine derivative synthesized by alkyl-ation of 6-chloro-1-aza-benzanthrone. The oxoisoaporphine fragment deviates significantly from planarity with a dihedral angle of 5.1 (1)° between the heterocycle and the remote benzene ring. The amino and oxo groups are involved in an intra-molecular N-H⋯O hydrogen bond, while the hy-droxy groups form inter-molecular O-H⋯N hydrogen bonds, which link pairs of mol-ecules into inversion dimers. In the dimer, two approximately parallel oxoisoaporphine fragments exhibit π-π inter-actions between the aromatic rings, the shortest centroid-centroid distance being 3.649 (3) Å.

[Size Distribution and Source Appointment of Road Particles During Winter in Tianjin].

The significant role of traffic emissions mixed from various sources in urban air pollution has been widely recognized. However, the corresponding contributions to the roadside particle distribution are poorly understood due to the mixed impacts of various sources. Particle number concentrations of different sizes at the roadside in Nankai District of Tianjin were continuously monitored using a portable aerosol particle spectrometer during the morning rush hour (07:30-09:20) from Nov. 9, 2018 to Jan. 6, 2019. Characteristic and influencing factors of particle size distributions were discussed combined with temperature and relative humidity data, while potential sources of particles at the roadside were identified based on size distribution analysis. The results showed that the average total particle number concentrations were 502 cm-3, and the concentrations of the accumulation mode and coarse mode were 500 cm-3 and 2 cm-3, respectively. The distribution of number concentrations at the roadside was unimodal and primarily concentrated at 0.25-0.50 µm, with peak sizes at 0.28-0.30 µm. The same distribution trend of particle number concentration and difference in the concentration in the same segment size were observed at different periods. Vehicle activity level was the main influencing factor of road particulate matter concentration on different weekdays; the probability of the high value of road particulate matter concentration was reduced by a reasonable combination of the vehicle tail numbers. Temperature and relative humidity were both found to be positively correlated with the number concentration of particles. With the increase in temperature and relative humidity, the total and peak particle number concentration showed an overall upward trend. In addition, the peak particle size increased from 0.28-0.30 µm to 0.35-0.40 µm when relative humidity was higher than 80%. Three sources, including road dust, brake and tire wear, and the aging particles from vehicle exhaust, were identified using positive matrix factorization in this study. Road dust contributed 8.6% of the total number concentration, which mainly consisted of particles with sizes above 5.00 µm. Brake and tire wear contributed 2.8% of the total number concentration of particles with a size range of 0.80-4.00 µm. The aging particles from vehicle exhaust contributed the most (88.5%), with a peak at 0.25-0.65 µm. The sources of roadside particles were mainly related to vehicle activity, whereas temperature and relative humidity also affected the particle number size distribution.

Chiral metal-organic frameworks for high-resolution gas chromatographic separations.

Chiral metal-organic framework coated open tubular columns are used in the high-resolution gas chromatographic separation of chiral compounds. The columns have excellent selectivity and also possess good recognition ability toward a wide range of organic compounds such as alkanes, alcohols, and isomers.