PB-LKS: a python package for predicting phage-bacteria interaction through local K-mer strategy.

Bacteriophages can help the treatment of bacterial infections yet require in-silico models to deal with the great genetic diversity between phages and bacteria. Despite the tolerable prediction performance, the application scope of current approaches is limited to the prediction at the species level, which cannot accurately predict the relationship of phages across strain mutants. This has hindered the development of phage therapeutics based on the prediction of phage-bacteria relationships. In this paper, we present, PB-LKS, to predict the phage-bacteria interaction based on local K-mer strategy with higher performance and wider applicability. The utility of PB-LKS is rigorously validated through (i) large-scale historical screening, (ii) case study at the class level and (iii) in vitro simulation of bacterial antiphage resistance at the strain mutant level. The PB-LKS approach could outperform the current state-of-the-art methods and illustrate potential clinical utility in pre-optimized phage therapy design.

The spontaneously produced lysogenic prophage phi456 promotes bacterial resistance to adverse environments and enhances the colonization ability of avian pathogenic Escherichia coli strain DE456.

In the last decade, prophages that possess the ability of lysogenic transformation have become increasingly significant. Their transfer and subsequent activity in the host have a significant impact on the evolution of bacteria. Here, we investigate the role of prophage phi456 with high spontaneous induction in the bacterial genome of Avian pathogenic Escherichia coli (APEC) DE456. The phage particles, phi456, that were released from DE456 were isolated, purified, and sequenced. Additionally, phage particles were no longer observed either during normal growth or induced by nalidixic acid in DE456Δphi456. This indicated that the released phage particles from DE456 were only phi456. We demonstrated that phi456 contributed to biofilm formation through spontaneous induction of the accompanying increase in the eDNA content. The survival ability of DE456Δphi456 was decreased in avian macrophage HD11 under oxidative stress and acidic conditions. This is likely due to a decrease in the transcription levels of three crucial genes-rpoS, katE, and oxyR-which are needed to help the bacteria adapt to and survive in adverse environments. It has been observed through animal experiments that the presence of phi456 in the DE456 genome enhances colonization ability in vivo. Additionally, the number of type I fimbriae in DE456Δphi456 was observed to be reduced under transmission electron microscopy when compared to the wild-type strain. The qRT-PCR results indicated that the expression levels of the subunit of I fimbriae (fimA) and its apical adhesin (fimH) were significantly lower in DE456Δphi456. Therefore, it can be concluded that phi456 plays a crucial role in helping bacterial hosts survive in unfavorable conditions and enhancing the colonization ability in DE456.

Deletion of Nox from Listeria monocytogenes Strain EGDe Enhances Bacterial Virulence and Reduces the Production of Reactive Oxygen Species and Inflammatory Factors In Vivo.

The foodborne pathogens have a serious threat to human health, especially Listeria monocytogenes. NADPH oxidase (NOX) is involved in cellular respiration and the production of reactive oxygen species (ROS), acting as messengers to host cells during the infection. However, the role of nox in the process of L. monocytogenes infection is unclear. In this study, we examined the impact of nox in L. monocytogenes by gene deletion. The results of cell experiment showed that knocking out nox from L. monocytogenes strain EGDe resulted in a twofold increase invasion ability to Caco-2 cells compared with that of wild-type strain (WT), but did not affect adhesion ability. Animal infection assays also showed that bacterial loads in the liver and spleen of mice challenged with EGDe-Δnox were approximately two times higher compared with those challenged with the WT strain. On the one hand, quantitative real-time polymerase chain reaction revealed that deletion of nox leads to upregulation of genes related to the internalization of L. monocytogenes (inlA, inlB, and inlC). More importantly, the expression of listeriolysin-positive regulatory (prfA) gene increased by three times in vivo compared with that of WT. On the other hand, the deletion of nox resulted in a reduction of the upregulation of proinflammatory factors in EGDe-Δnox compared with the WT and complementary strains. Thus, our study revealed that nox affected the virulence of L. monocytogenes by upregulating the expression of virulence genes and regulating the production of ROS and inflammatory factors in vivo.

Relationship between secondary metabolites and insect loads in cabbage with different leaf shapes and positions.

INTRODUCTION: Secondary metabolites in plants play a crucial role in defense mechanisms against insects, pests, and pathogens. These metabolites exhibit varying distributions within and among plant parts under different biotic and abiotic conditions. Understanding the intricate relationships between secondary metabolites and insect populations can be helpful for elucidating plant defense mechanisms and enhancing agricultural managing efficiencies. OBJECTIVE: To investigate the influence of the glucosinolate profile in the leaves of three cabbage (Brassica oleracea var. capitata L.) varieties on insect loads. METHODS: Glucosinolate profiles across different leaf positions (such as bottom, middle, and center) and leaf shapes (such as curly and non-curly leaf) of three cabbage varieties (Xiagan [XGA], Xiaguang [XGU], and Qiangxia [QIX]) were analyzed by using high-performance liquid chromatography-mass spectrometry (LC-MS). The insect loads were recorded by visually inspecting the upper and lower layers of each target leaf. RESULTS: Increasing concentrations of four glucosinolates, namely, glucoiberin, progoitrin, glucoraphanin, and glucobrassicin, were positively related to insect loads. While increasing concentrations of the other four glucosinolates, such as neoglucobrassicin, 4-methoxyglucobrassicin, sinigrin, and gluconapin, were negatively related to insect loads. Furthermore, both glucosinolate synthesis and insect loads were significantly higher in the curly-shaped and middle-position leaves than in the non-curly-shaped and bottom- and central-position leaves across the cabbage varieties. CONCLUSION: Differences in glucosinolate profiles across leaf positions and shapes strongly influenced the insect loads of the three Brassica varieties. This link may further extend our understanding of the real defense power of a particular variety against herbivore damage.

Uridine alleviates carbon tetrachloride-induced liver fibrosis by regulating the activity of liver-related cells.

At present, liver fibrosis is a major challenge of global health. When hepatocyte regeneration cannot compensate for hepatocyte death, it will develop into liver fibrosis in chronic liver disease. Initially, collagen produced by myofibroblasts plays a role in maintaining liver integrity, but excessive collagen accumulation can inhibit the residual liver function, leading to liver failure. At present, many scientists are actively looking for drugs to alleviate liver fibrosis. In the current study, we investigated the potential role of uridine in the treatment of liver fibrosis (uridine is a plant/animal-derived pyrimidine nucleoside, therefore uridine can also be ingested and absorbed by the body, accompanied by the process of food intake). For this, we systematically studied the effect of uridine on CCl4-induced liver fibrosis in vitro and in vivo through a series of technologies, such as Western blot, laser confocal scanning microscope, ELISA and immunohistochemistry. The experimental results showed that uridine can effectively reduce the accumulation of collagen in liver. Furthermore, uridine can improve the activity of liver cells and alleviate CCl4-induced liver injury. Furthermore, uridine can significantly alleviate the risk factors caused by hepatic stellate cell activation, uridine treatment significantly down-regulated the expression of α-SMA, collagen type-I and fibronectin. In conclusion, the current research shows that uridine can alleviate CCl4-induced liver fibrosis, suggesting that uridine can be used as a potential drug to alleviate liver fibrosis.

Long-term Spartina alterniflora invasion simplified soil seed bank and regenerated community in a coastal marsh wetland.

The coastal wetland is easily invaded by alien species due to locating in the land and sea transitional area. As a potential driving regeneration force, the soil seed bank is vital to the community restoration and species diversity protection. To reveal the long-term Spartina alterniflora invasion impact on the soil seed banks and regenerated communities, we investigated the seed banks under the different vegetation types (S. alterniflora, Phragmites australis, Scirpus mariqueter, ruderal and unvegetated site) and soil depths (0-5 and 5-10 cm) in the coastal salt marsh wetland, Chongming island, eastern China. The results showed that the soil seed bank richness and species density under different vegetation types were higher than the aboveground vegetation, and those of 0-5 cm seed banks were higher than 5-10 cm, except for the unvegetated site. The species richness and S. alterniflora seed proportion in the seed banks under S. alterniflora communities (S.AS) were lower and larger respectively than those of other sites. The species composition between S.AS and the aboveground communities showed high similarity with aggregation phylogenetic structures in two soil depths. The seed bank variations at 0-5 and 5-10 cm depths were interpreted 3.03% and 2.25% by the aboveground communities, while 4.92% and 5.55% were interpreted by the soil microbial biomass. The SEM model explained 98.1% and 91.8% of the seed banks richness at the 0-5 cm depth and 5-10 cm depth, respectively, and explained 98.8% and 46.1% of the seed banks species density at the 0-5 cm depth and 5-10 cm depth, respectively. The aboveground vegetation biomass and abundance directly affected the 0-5 cm seed banks richness and species density, while its height and biomass only affected the 5-10 cm seed banks species density. The 0-10 cm soil depth microbial biomass indirectly affected the 0-5 cm seed banks richness and species density, while affected the 5-10 cm seed banks richness. Soil physical and chemical properties only indirectly affected the 0-5 cm seed banks species density. The results provided a reference for the ecological evaluation of the impacts of S. alterniflora invasion into the coastal salt marsh wetland of eastern China, and guidance for the protection and restoration of the native plant communities.

Anti-aging effect of ß-carotene through regulating the KAT7-P15 signaling axis, inflammation and oxidative stress process.

BACKGROUND: Research on aging is growing as the elderly make up a greater share of the population, focusing on reversing and inhibiting the aging process. The exhaustion and senescence of stem cells are the fundamental drivers behind aging. ß-Carotene has been depicted to have many biological functions, and we speculate that it may have an anti-aging effect. METHODS: Firstly, the anti-aging property of ß-carotene was investigated in vitro using mesenchymal stem cells (MSCs) induced by H2O2. The anti-aging effect was characterized using Western-bloting, confocal laser scanning microscopy, indirect immunofluorescence, and immunohistochemistry. The anti-aging property was also tested in vivo using aged mice. RESULTS: The in vitro experiment revealed that ß-carotene could relieve the aging of MSCs, as evidenced by a series of aging marker molecules such as p16 and p21. ß-Carotene appeared to inhibit aging by regulating the KAT7-P15 signaling axis. The in vivo experiment revealed that ß-carotene treatment has significantly down-regulated the aging level of tissues and organs. CONCLUSIONS: In this work, we explored the anti-aging effect of ß-carotene in vivo and in vitro. The experimental results indicate that ß-carotene may be an important potential anti-aging molecule, which can be used as a drug or in functional food to treat aging in the future.

Reconfigurable hybrid dielectric antenna with less graphene surface area.

A hybrid dielectric reconfigurable graphene antenna is designed by combining the Yagi antenna and absorption characteristics of graphene. Graphene is selectively covered in the Yagi antenna directors to obtain a change of the beam from unidirectional to bidirectional by changing the graphene potential. By reducing the area covered by graphene, we obtain a radiation efficiency of more than 95 percent. After adding a gold bowtie antenna at 1550 nm, the antenna shows a larger directivity and a smaller beam width, as well as a maximum directivity of 7.2 dBi. Furthermore, the surface area of graphene has been reduced three times, while the directivity improves from 4.7 to 5.6 dBi after comparing the effect of different surface distributions, which will be helpful to reduce the difficulty of graphene antenna manufacturing and improve the performance of the antenna beam.

Strontium gluconate potently promotes osteoblast development and restores bone formation in glucocorticoid-induced osteoporosis rats.

Glucocorticoid-induced osteoporosis (GIOP) has emerged as a challenge after long-term glucocorticoid administration during the clinical therapy of diverse diseases. Although some candidates for GIOP treatment have been explored, there is still a lack of reliable drugs for GIOP prevention. In this study, rat bone marrow stem cells (rBMSCs) were utilized to investigate the feasibility of applying strontium gluconate (GluSr), which displays mild activity, easy absorption and good biocompatibility, for GIOP prevention. Thirty-two SD rats were divided into 4 groups to explore the effects of GluSr on osteoporosis rescue in vivo. Our results suggested that GluSr markedly alleviated dexamethasone (DEX)-induced apoptosis of osteoblast precursor cells and rBMSCs and enhanced rBMSC osteogenesis differentiation in vitro. GluSr also effectively promoted osteoblast survival, inhibited osteoclast differentiation and restored bone formation in GIOP rat models. Microarray analysis of the femora from GIOP rats treated with GluSr revealed that the signalling pathways of the glucocorticoid receptor (GR), oestrogen receptor gene (ESR) and vitamin D receptor (VDR) were involved in bone restoration by GluSr. In summary, our study proved that GluSr enhanced osteoblast differentiation and suppressed osteoclast activity both in vitro and in vivo. GluSr might function as a novel strontium reagent for GIOP prevention.

Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis.

Tongue cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, cell morphological observation, scratch wound-healing assay, transwell migration assay, transmission electron microscope, flow cytometry and cellular reactive oxygen species were assessed in vitro. The results showed that quisinostat can significantly inhibit the viability, growth and migration of TSCC cells. And quisinostat could significantly induce TSCC cells apoptosis, pyroptosis, and ferroptosis. Quisinostat significantly inhibited tumor tissue growth in animal experiments. Up-regulation of the expression of Bax, cleaved-caspase3, caspase-1, p53, phospho-p53 and down-regulated of the expression of caspase-3, Bcl-2, GPX4 in cell lines and tumor tissues of nude mice were observed by Western blotting analysis. Up-regulation of the expression of caspase-1, Bax, cleaved-caspase3, p53 and down-regulated of the expression of ki67, caspase-3, Bcl-2, GPX4 in tumor tissues of nude mice were observed by immunohistochemistry. TUNEL analysis showed that quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Based on these findings, quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.

Development overview of Raman-activated cell sorting devoted to bacterial detection at single-cell level.

Understanding the metabolic interactions between bacteria in natural habitat at the single-cell level and the contribution of individual cell to their functions is essential for exploring the dark matter of uncultured bacteria. The combination of Raman-activated cell sorting (RACS) and single-cell Raman spectra (SCRS) with unique fingerprint characteristics makes it possible for research in the field of microbiology to enter the single cell era. This review presents an overview of current knowledge about the research progress of recognition and assessment of single bacterium cell based on RACS and further research perspectives. We first systematically summarize the label-free and non-destructive RACS strategies based on microfluidics, microdroplets, optical tweezers, and specially made substrates. The importance of RACS platforms in linking target cell genotype and phenotype is highlighted and the approaches mentioned in this paper for distinguishing single-cell phenotype include surface-enhanced Raman scattering (SERS), biomarkers, stable isotope probing (SIP), and machine learning. Finally, the prospects and challenges of RACS in exploring the world of unknown microorganisms are discussed. KEY POINTS: • Analysis of single bacteria is essential for further understanding of the microbiological world. • Raman-activated cell sorting (RACS) systems are significant protocol for characterizing phenotypes and genotypes of individual bacteria.

[Potential therapeutic effect of Saussureae Involucratae Herba on breast cancer and its mechanism based on network pharmacology].

As one of the most commonly diagnosed cancers in the world, female breast cancer is induced by the high level of estrogen. Saussureae Involucratae Herba(SIH), a gynecological medicinal, regulates estrogen-induced diseases. However, the therapeutic effect of SIH on breast cancer has not been reported. Therefore, this study aims to explore the potential efficacy of SIH on breast cancer based on in vitro experiment and network pharmacology. The inhibitory effect of SIH water extract on proliferation and migration of breast cancer MDA-MB-231 cells was examined. The result demonstrated SIH water extract significantly suppressed the proliferation of breast cancer cells(IC_(50)=6.47 mg·mL~(-1)) and also restricted the migration. A total of 39 components of SIH were retrieved from traditional Chinese medicine database(TCMD) and 160 targets of SIH were screened by target fishing with the PharmaDB database. The Online Mendelian Inheritance in Man(OMIM) was used to establish a 1 001-targets data set of breast cancer. Based on the overlaps(45) of targets between SIH and breast cancer, a protein-protein interaction(PPI) network was built to analyze the interactions among these targets with STRING platform and Cytoscape. Finally, through topology and GO and KEGG analysis, 8 targets, 101 pathways and 85 biological processes were found to involve the treatment of breast cancer by SIH. SIH may exert the anti-breast cancer effect by regulating cell cycle, inhibiting proliferation, migration and adhesion of cancer cells, and modulating estrogen receptor. This study clarified the mechanism of SIH in treating breast cancer, which lays a foundation for the further development of SIH.

Recurrent granular cell tumor of the thyroid: a case report and literature review.

BACKGROUND: Granular cell tumor (GCT) of the thyroid is a rare benign tumor of Schwann cell origin with a favorable prognosis and only 10 cases have been reported so far in scientific literature. The present case study describes the first case of recurrent thyroid GCT. CASE PRESENTATION: Our case describes a 20-year-old woman who had undergone lobectomy for GCT of the thyroid 4 years ago. Hematoxylin-eosin (HE) staining revealed that the lesion was composed of epithelioid cells with an abundance of eosinophilic granular cytoplasm. Immunohistochemical analysis showed that tumor cells tested positive for S-100 protein and negative for desmin. Both histological and immunohistochemical analyses supported the diagnosis of recurrent GCT of the thyroid. CONCLUSIONS: Our case suggested that a tumor-free margin excision and post-operative follow-up are necessary for the treatment of GCT of the thyroid.

Comparative genomic analysis of 127 Escherichia coli strains isolated from domestic animals with diarrhea in China.

BACKGROUND: Escherichia coli is an important pathogen that causes diarrhea in both humans and animals. To determine the relationships between putative virulence factors and pathotypes or host taxa, many molecular studies on diarrhea-associated E. coli have been reported. However, little is known regarding genome-wide variation of E. coli from animal hosts. In this study, we performed whole genome sequencing of 127 E. coli isolates from sheep and swine with diarrhea in China. We compared isolates to explore the phylogenomic relatedness based on host origin. We explored the relationships of putative virulence factors across host taxa and pathotypes. Antimicrobial resistance was also tested. RESULTS: The E. coli genomes in this study were diverse with clear differences in the SNP, MLST, and O serotypes. Seven putative virulence factors (VFs) were prevalent (> 95%) across the isolates, including Hcp, csgC, dsdA, feoB, fepA, guaA, and malX. Sixteen putative VFs showed significantly different distributions (P < 0.05) in strains from sheep and swine and were primarily adhesion- and toxin-related genes. Some putative VFs were co-occurrent in some specific pathotypes and O serotypes. The distribution of 4525 accessory genes of the 127 strains significantly differed (P < 0.05) between isolates obtained from the two animal species. The 127 animal isolates sequenced in this study were each classified into one of five pathotypes: EAEC, ETEC, STEC, DAEC, and EPEC, with 66.9% of isolates belonging to EAEC. Analysis of stx subtypes and a minimum spanning tree based on MLST revealed that STEC isolates from sheep and EAEC isolates from sheep and swine have low potential to infect humans. Antibiotic resistance analysis showed that the E. coli isolates were highly resistant to ampicillin and doxycycline. Isolates from southeast China were more resistant to antibiotics than isolates from northwest China. Additionally, the plasmid-mediated colist in resistance gene mcr-1 was detected in 15 isolates, including 4 from sheep in Qinghai and 11 from swine in Jiangsu. CONCLUSIONS: Our study provides insight into the genomes of E. coli isolated from animal sources. Distinguishable differences between swine and sheep isolates at the genomic level provides a baseline for future investigations of animal E. coli pathogens.

Isolation and characterization of a broad-spectrum phage of multiple drug resistant Salmonella and its therapeutic utility in mice.

Salmonella are causes of livestock, poultry, and other animal diseases but they also have the potential to infect people. Currently, antibiotics are the first choice for treatment of Salmonella infections. Thus, the utility of phage has become the research focus for scientists for several reasons. There are efficient, non-toxic, ubiquitous, easy to prepare and can result in the lysis of host bacteria. In this study, a broad spectrum bacteriophage of Salmonella was isolated from the fecal samples of a poultryfarm and we studied the morphological aspects, thermal stability, pH stability, optimal multiplicity of infection (MOI), and one-step growth curve of this phage. This phage was named Salmonella phage SaFB14 and lysed 54.12%(105/194)Salmonella spp. SaFB14 belongs to the Siphoviridae and has a polyhedron head with a diameter approximating 60 × 60 nm and a tail approximating 140 nm. The optimum growth temperature was 37 °C and maintained high activity over a widepH range(pH3-10) with an optimum of pH 7.0. The optimal MOI was 0.1. A one-step growth curve showed that its latency time was 10 min, burst time was 70 min, and burst was 23 particles. In order to study the therapeutic effect of phage SaFB14 in infected mice, mice were challenged with 2 × 109 CFU/mouse Salmonella (cs20130523-001-1). Each mouse was injected to 2 × 1010 PFU SaFB14 1 h later. SaFB14 protected 40% of mice from infection. Then, the same dose of phage was given to mice for 3 days continuously. After 3 days treatment, the survival rate increased to 60%.In conclusion, phage SaFB14 showed wide host range and good activity in vivo, it is promising against diseases caused by Salmonella.

Oxaliplatin induces immunogenic cells death and enhances therapeutic efficacy of checkpoint inhibitor in a model of murine lung carcinoma.

Background: Platinum compounds are commonly used for lung cancer treatment. However, the severe side effects and relatively poor prognosis limit their therapeutic effect. Therefore, developing novel platinum derivative and treatment strategy are critical for current lung cancer therapy. Methods: Flow cytometry, HMGB1 and ATP release, and immunoblotting were performed to evaluate the Oxaliplatin-induced immunogenic cell death (ICD) in two lung carcinoma cells. Vaccination approach and subcutaneous tumor models were created to analyze the tumor regression effect of Oxaliplatin. PD-L1 mRNA and protein levels were detected in LLC (Lewis lung carcinoma). Enhanced therapeutic efficacy of LLC was assessed by co-administration Oxaliplatin and aPD-L1 in murine lung tumor model. Results: Oxaliplatin induced robust ICD in LLC cells, activated dendritic cells (DCs, CD80+CD86+) and enhanced cytotoxic T cells (CD8+) in LLC tumor tissues, which resulted in tumor regression. Co-administration of Oxaliplatin and checkpoint inhibitor, aPD-L1, could enhance the therapeutic efficacy of LLC in murine lung carcinoma. Conclusion: This study reveals Oxaliplatin can induce robust ICD in tumor tissues and suppress tumor growth by activating DCs and enhancing T-cell infiltration. Notably, the Oxaliplatin-induced ICD provides an immunogenic microenvironment, which enhances the checkpoint inhibitor therapeutic efficacy of LLC.

Safety and complications of medical thoracoscopy in the management of pleural diseases.

BACKGROUND: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications of diagnostic thoracoscopy and talc poudrage pleurodesis. We conduct this study to evaluate the safety of medical thoracoscopy in the management of pleural diseases and to compare complications in different therapeutic thoracoscopic procedures. METHODS: A retrospective study was performed in 1926 patients, 662 of whom underwent medical thoracoscopy for diagnosis and 1264 of whom for therapeutic interventions of pleural diseases. Data on complications were obtained from the patients, notes on computer system, laboratory and radiographic findings. Chi-square test was performed to compare categorical variables and Fisher's exact test was used for small samples. RESULTS: The mean age was 51 ± 8.4 (range 21-86) years and 1117 (58%) were males. Diagnostic procedure was taken in 662 (34.4%) patients, whereas therapeutic procedure was taken in 1264 (65.6%) patients. Malignant histology was reported in 860 (44.6%) and 986 (51.2%) revealed benign pleural diseases. Eighty patients (4.2%) were not definitely diagnosed and they were considered as unidentified pleural effusion. One patient died during the creation of artificial pneumothorax, and the causes of death were supposed as air embolism or an inhibition of phrenic motoneurons and circulatory system. Complication of lung laceration was found in six patients (0.3%) and reexpansion pulmonary edema was observed in two patients (0.1%). Higher incidence of prolonged air leak was observed in bulla electrocoagulation group, in comparison with pleurodesis group. Moreover, pain and fever were the most frequently complications in pleurodesis group and cutaneous infection in entry site was the most frequently reported complication in pleural decortication of empyema group. CONCLUSIONS: Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases. Mastering medical thoracoscopy well, improving patient management after the procedure and attempts to reduce the occurrence of post-procedural complications are the targets that physicians are supposed to achieve in the future.

A two-stage spatial allocation model for elderly healthcare facilities in large-scale affordable housing communities: a case study in Nanjing City.

BACKGROUND: As the proportion of elderly residents living in large-scale affordable housing communities (LAHCs) increases in China, serious problems have become apparent related to the spatial allocation of elderly healthcare facilities (EHFs), e.g., insufficient provision and inaccessibility. To address these issues, this study developed a location allocation model for EHFs to ensure equitable and efficient access to healthcare services for the elderly in LAHCs. METHODS: Based on discrete location theory, this paper develops a two-stage optimization model for the spatial allocation of EHFs in LAHCs. In the first stage, the candidate locations of EHFs are specified using geographic information system (GIS) techniques. In the second stage, the optimal location and size of each EHF are determined based on the greedy algorithm (GA). Finally, the proposed two-stage optimization model is tested using the Daishan LAHC in Nanjing, Eastern China. RESULTS: The demand of the elderly for accessibility to EHFs is in line with Nanjing's planning standards. Deep insights into spatial data are revealed by GIS techniques that enable candidate locations of EHFs to be obtained. In addition, the model helps EHF planners achieve equity and efficiency simultaneously. Two optimal locations for EHFs in the Daishan LAHC are identified, which in turn verifies the validity of the model. CONCLUSIONS: As a strategy for allocating EHFs, this two-stage model improves the equity and efficiency of access to healthcare services for the elderly by optimizing the potential sites for EHFs. It can also be used to assist policymakers in providing adequate healthcare services for the low-income elderly. Furthermore, the model can be extended to the allocation of other public-service facilities in different countries or regions.

Imatinib induces autophagy via upregulating XIAP in GIST882 cells.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms originating from the gastrointestinal tract with gain of function mutations in receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA). The main effective treatment for GISTs is tyrosine kinase inhibitors, such as imatinib mesylate. However, GISTs respond to imatinib treatment eventually develop acquired resistance, which is a main obstacle for GISTs therapy. Therefore, it's urgent to have a better understanding of the mechanisms underlying the imatinib resistance in GISTs to develop novel therapeutic strategies. X-linked inhibitor of apoptosis (XIAP) is the most potent apoptosis inhibitor among the inhibitor of apoptosis protein (IAP) family members. Increased cellular expression of XIAP often leads to drug resistance in cancers. Here we report that XIAP is induced upon imatinb treatment in GIST882 cells, leading to imatinib-induced autophagy. Imatinib-induced autophagy was impaired in XIAP-knockout cells generated by CRISPR/Cas9 system demonstrated by the decreasing of LC3 lipidation. XIAP knockout sensitizes GIST882 cells to imatinib-induced apoptotic cell death, suggesting that XIAP protects GIST882 cells from imatinib-induced cell death by inducing autophagy. Thus, the resistance of the GIST882 cells to imatinib appears to be, in part, due to the increasing of XIAP and subsequent induction of autophagy.

Engineered antibody CH2 domains binding to nucleolin: Isolation, characterization and improvement of aggregation.

Smaller recombinant antibody fragments are now emerging as alternatives of conventional antibodies. Especially, immunoglobulin (Ig) constant CH2 domain and engineered CH2 with improved stability are promising as scaffolds for selection of specific binders to various antigens. We constructed a yeast display library based on an engineered human IgG1 CH2 scaffold with diversified loop regions. A group of CH2 binders were isolated from this yeast display library by panning against nucleolin, which is a tumor-associated antigen involved in cell proliferation, tumor cell growth and angiogenesis. Out of 20 mutants, we selected 3 clones exhibiting relatively high affinities to nucleolin on yeasts. However, recombinant CH2 mutants aggregated when they were expressed. To find the mechanism of the aggregation, we employed computational prediction approaches through structural homology models of CH2 binders. The analysis of potential aggregation prone regions (APRs) and solvent accessible surface areas (ASAs) indicated two hydrophobic residues, Val264 and Leu309, in the ß-sheet, in which replacement of both charged residues led to significant decrease of the protein aggregation. The newly identified CH2 binders could be improved to use as candidate therapeutics or research reagents in the future.