Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome.

Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome-derived commensals produce lantibiotics to impair pathogens' colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and targeted antimicrobial properties against known oral pathogens and multispecies biofilms. Strikingly, the immunomodulatory activities observed include upregulation of neutrophil-mediated phagocytosis, promotion of antiinflammatory M2 macrophage polarization, and stimulation of neutrophil chemotaxis-these activities have been attributed to the phosphorylation site identified on the N-terminal region of the peptides. Salivaricin 10 peptides were determined to be produced by S. salivarius strains found in healthy human subjects, and their dual bactericidal/antibiofilm and immunoregulatory activity may provide new means to effectively target infectious pathogens while maintaining important oral microbiota.

N-glycosylation of the SARS-CoV-2 spike protein at Asn331 and Asn343 is involved in spike-ACE2 binding, virus entry, and regulation of IL-6.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global public health crisis. The causative agent, the SARS-CoV-2 virus, enters host cells via molecular interactions between the viral spike protein and the host cell ACE2 surface protein. The SARS-CoV-2 spike protein is extensively decorated with up to 66 N-linked glycans. Glycosylation of viral proteins is known to function in immune evasion strategies but may also function in the molecular events of viral entry into host cells. Here, we show that N-glycosylation at Asn331 and Asn343 of SARS-CoV-2 spike protein is required for it to bind to ACE2 and for the entry of pseudovirus harboring the SARS-CoV-2 spike protein into cells. Interestingly, high-content glycan binding screening data have shown that N-glycosylation of Asn331 and Asn343 of the RBD is important for binding to the specific glycan molecule G4GN (Galß-1,4 GlcNAc), which is critical for spike-RBD-ACE2 binding. Furthermore, IL-6 was identified through antibody array analysis of conditioned media of the corresponding pseudovirus assay. Mutation of N-glycosylation of Asn331 and Asn343 sites of the spike receptor-binding domain (RBD) significantly reduced the transcriptional upregulation of pro-inflammatory signaling molecule IL-6. In addition, IL-6 levels correlated with spike protein levels in COVID-19 patients' serum. These findings establish the importance of RBD glycosylation in SARS-CoV-2 pathogenesis, which can be exploited for the development of novel therapeutics for COVID-19.

Identification and validation of circulating biomarkers for detection of liver cancer with antibody array.

The aim of this study was to find new protein biomarkers that could be used to detect hepatocellular carcinoma (HCC) in the serum. We identified 11 proteins in the tissue that could be used to classify samples from HCC and control subjects. The 11 identified tissue biomarkers were combined with 10 commonly used serum HCC biomarkers for further verification in a large number of serum samples from HCC patients and healthy controls. 17 of the 21 prospective serum biomarkers were determined to be differentially expressed through collinearity and significance analysis. Through the method of supervised learning, a random forest model was constructed to reduce the dimensionality of the number of differentially expressed proteins, and finally, 4 differentially expressed proteins were identified: AFP, GDF15, CEACAM-1, and MMP-9, and suggested to have potential application in clinical diagnosis of HCC.

Transcriptomic and Proteomic Landscape of Sugarcane Response to Biotic and Abiotic Stressors.

Sugarcane, a C4 plant, provides most of the world's sugar, and a substantial amount of renewable bioenergy, due to its unique sugar-accumulating and feedstock properties. Brazil, India, China, and Thailand are the four largest sugarcane producers worldwide, and the crop has the potential to be grown in arid and semi-arid regions if its stress tolerance can be improved. Modern sugarcane cultivars which exhibit a greater extent of polyploidy and agronomically important traits, such as high sugar concentration, biomass production, and stress tolerance, are regulated by complex mechanisms. Molecular techniques have revolutionized our understanding of the interactions between genes, proteins, and metabolites, and have aided in the identification of the key regulators of diverse traits. This review discusses various molecular techniques for dissecting the mechanisms underlying the sugarcane response to biotic and abiotic stresses. The comprehensive characterization of sugarcane's response to various stresses will provide targets and resources for sugarcane crop improvement.

Induction of a cytokine storm involves suppression of the Osteopontin-dependent TH1 response.

Cytokine release syndromes represent a severe turn in certain disease states, which may be caused by several infections, including those with the virus SARS-CoV-2. This inefficient, even harmful, immune response has been associated with a broad release of chemokines. Although a cellular (type I) immune reaction is efficacious against viral infections, we noted a type I deficit in the cytokine patterns produced by cytokine storms of all reported etiologies. Agents including lipopolysaccharide (LPS, bacterial), anti-CD3 (antibody) and a version of the prominent SARS-CoV-2 viral surface molecule, Spike Glycoprotein, were individually sufficient to induce IL-6 and multiple chemokines in mice. They failed to upregulate the TH1 inducer cytokine Osteopontin, and the pathophysiologic triggers actually suppressed the PMA-induced Osteopontin secretion from monocytic cells. Osteopontin administration partially reversed the chemokine elevation, more effectively so in a mouse strain with TH1 bias. Corroboration was obtained from the inverse correlation in the levels of IL-6 and Osteopontin in plasma samples from acute COVID-19 patients. We hypothesize that the inhibition of Osteopontin by SARS-CoV-2 Spike Glycoprotein or LPS represents an immune evasion mechanism employed by the pathogens of origin. The ensuing dysfunctional inflammatory response promotes a vicious cycle of amplification, resulting in a cytokine storm.

Ketone body ß-hydroxybutyrate ameliorates colitis by promoting M2 macrophage polarization through the STAT6-dependent signaling pathway.

BACKGROUND: Ketone body ß-hydroxybutyrate (BHB) has received more and more attentions, because it possesses a lot of beneficial, life-preserving effects in the fields of clinical science and medicine. However, the role of BHB in intestinal inflammation has not yet been investigated. METHODS: Colonic mucosa of inflammatory bowel disease (IBD) patients and healthy controls were collected for evaluation of BHB level. Besides, the therapeutic effect of exogenous BHB in a murine model of acute dextran sulfate sodium (DSS)-induced colitis were assessed by body weight change, colon length, disease activity index, and histopathological sections. The regulatory effectors of BHB were analyzed by RT-qPCR, immunofluorescence, and microbe analysis in vivo. Moreover, the molecular mechanism of BHB was further verified in bone marrow-derived macrophages (BMDMs). RESULTS: In this study, significantly reduced BHB levels were found in the colonic mucosa from IBD patients and correlated with IBD activity index. In addition, we demonstrated that the administration of exogenous BHB alleviated the severity of acute experimental colitis, which was characterized by less weight loss, disease activity index, colon shortening, and histology scores, as well as decreased crypt loss and epithelium damage. Furthermore, BHB resulted in significantly increased colonic expression of M2 macrophage-associated genes, including IL-4Ra, IL-10, arginase 1 (Arg-1), and chitinase-like protein 3, following DSS exposure, suggesting an increased M2 macrophage skewing in vivo. Moreover, an in vitro experiment revealed that the addition of BHB directly promoted STAT6 phosphorylation and M2 macrophage-specific gene expression in IL-4-stimulated macrophages. Besides, we found that BHB obviously increased M2 macrophage-induced mucosal repair through promoting intestinal epithelial proliferation. However, the enhancement effect of BHB on M2 macrophage-induced mucosal repair and anti-inflammation was completely inhibited by the STAT6 inhibitor AS1517499. CONCLUSIONS: In summary, we show that BHB promotes M2 macrophage polarization through the STAT6-dependent signaling pathway, which contributes to the resolution of intestinal inflammation and the repair of damaged intestinal tissues. Our finding suggests that exogenous BHB supplement may be a useful therapeutic approach for IBD treatment.

Development and evaluation of time-resolved fluorescent immunochromatographic assay for quantitative detection of SARS-CoV-2 spike antigen.

BACKGROUND: The spread of COVID-19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15-minute time-resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS-CoV-2 spike protein receptor-binding domain (S1-RBD). OBJECTIVES: Our objective was to develop an efficient method of detecting SARS-CoV-2 within 15 min of sample collection. METHODS: We constructed and evaluated a portable, disposable lateral flow device, which detected the S1-RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1-RBD, which can be captured by an automated TRF instrument. RESULTS: The TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1-RBD antigen. CONCLUSION: The new S1-RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR-based methodology in nasopharyngeal swab samples, showing that the detected S1-RBD antigen levels correlate with SARS-CoV-2 virus load. Therefore, the new TRF lateral flow test for S1-RBD has potential application in point-of-care settings.

Xanthones from Calophyllum Polyanthum Wallich ex Choisy with CYP1 Enzymes Inhibitory Activity.

Three new xanthone compounds, 1,3,5-trihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-4-(3-methylbut-2-enyl)xanthone (1), toxyloxanthone E (2), dehydrocycloguanandin B (3) along with 15 known xanthones (4-18) were isolated from the aerial parts of Calophyllum polyanthum Wall. ex Choisy. Their structures were fully characterised using spectroscopic data, as well as comparison with the previous literature data. All isolated compounds had inhibitory effects against CYP1A1, CYP1A2 and CYP1B1 enzymes at working concentration of 10 µM, 1 µM and 10 µM, respectively. Among them, compounds 10, 11, and 12 exhibited better CYP1A2 enzyme inhibitory effects than that of the positive control α-naphthoflavone, with 51.05 %, 56.82 % and 44.93 % inhibition, respectively.

Positive signs on physical examination are not always indications for endotracheal tube intubation in patients with facial burn.

BACKGROUND: After clinical evaluation in the emergency department (ED), facial burn patients are usually intubated to protect their airways. However, the possibility of unnecessary intubation or delayed intubation after admission exists. Objective criteria for the evaluation of inhalation injury and the need for airway protection in facial burn patients are needed. METHODS: Facial burn patients between January 2013 and May 2016 were reviewed. Patients who were and were not intubated in the ED were compared. All the intubated patients received routine bronchoscopy and laboratory tests to evaluate whether they had inhalation injuries. The patients with and without confirmed inhalation injuries were compared. Multivariate logistic regression analysis was used to identify the independent risk factors for inhalation injuries in the facial burn patients. The reasons for intubation in the patients without inhalation injuries were also investigated. RESULTS: During the study period, 121 patients were intubated in the ED among a total of 335 facial burn patients. Only 73 (60.3%) patients were later confirmed to have inhalation injuries on bronchoscopy. The comparison between the patients with and without inhalation injuries showed that shortness of breath (odds ratio = 3.376, p = 0.027) and high total body surface area (TBSA) (odds ratio = 1.038, p = 0.001) were independent risk factors for inhalation injury. Other physical signs (e.g., hoarseness, burned nostril hair, etc.), laboratory examinations and chest X-ray findings were not predictive of inhalation injury in facial burn patients. All the patients with a TBSA over 60% were intubated in the ED even if they did not have inhalation injuries. CONCLUSIONS: In the management of facial burn patients, positive signs on conventional physical examinations may not always be predictive of inhalation injury and the need for endotracheal tube intubation in the ED. More attention should be given to facial burn patients with shortness of breath and a high TBSA. Airway protection is needed in facial burn patients without inhalation injuries because of their associated injuries and treatments.

Genome-wide identification and evolutionary analysis of RLKs involved in the response to aluminium stress in peanut.

BACKGROUND: As an important cash crop, the yield of peanut is influenced by soil acidification and pathogen infection. Receptor-like protein kinases play important roles in plant growth, development and stress responses. However, little is known about the number, location, structure, molecular phylogeny, and expression of RLKs in peanut, and no comprehensive analysis of RLKs in the Al stress response in peanuts have been reported. RESULTS: A total of 1311 AhRLKs were identified from the peanut genome. The AhLRR-RLKs and AhLecRLKs were further divided into 24 and 35 subfamilies, respectively. The AhRLKs were randomly distributed across all 20 chromosomes in the peanut. Among these AhRLKs, 9.53% and 61.78% originated from tandem duplications and segmental duplications, respectively. The ka/ks ratios of 96.97% (96/99) of tandem duplication gene pairs and 98.78% (646/654) of segmental duplication gene pairs were less than 1. Among the tested tandem duplication clusters, there were 28 gene conversion events. Moreover, all total of 90 Al-responsive AhRLKs were identified by mining transcriptome data, and they were divided into 7 groups. Most of the Al-responsive AhRLKs that clustered together had similar motifs and evolutionarily conserved structures. The gene expression patterns of these genes in different tissues were further analysed, and tissue-specifically expressed genes, including 14 root-specific Al-responsive AhRLKs were found. In addition, all 90 Al-responsive AhRLKs which were distributed unevenly in the subfamilies of AhRLKs, showed different expression patterns between the two peanut varieties (Al-sensitive and Al-tolerant) under Al stress. CONCLUSIONS: In this study, we analysed the RLK gene family in the peanut genome. Segmental duplication events were the main driving force for AhRLK evolution, and most AhRLKs subject to purifying selection. A total of 90 genes were identified as Al-responsive AhRLKs, and the classification, conserved motifs, structures, tissue expression patterns and predicted functions of Al-responsive AhRLKs were further analysed and discussed, revealing their putative roles. This study provides a better understanding of the structures and functions of AhRLKs and Al-responsive AhRLKs.

Characterization and prognostic significance of alternative splicing events in lower-grade diffuse gliomas.

Alternative splicing (AS) is assumed to play important roles in the progression and prognosis of cancer. Currently, the comprehensive analysis and clinical relevance of AS in lower-grade diffuse gliomas have not been systematically addressed. Here, we gathered alternative splicing data of lower-grade diffuse gliomas from SpliceSeq. Based on the Percent Spliced In (PSI) values of 515 lower-grade diffuse glioma patients from the Cancer Genome Atlas (TCGA), we performed subtype-differential AS analysis and consensus clustering to determine robust clusters of patients. A total of 48 050 AS events in 10 787 genes in lower-grade diffuse gliomas were profiled. Subtype-differential splicing analysis and functional annotation revealed that spliced genes were significantly enriched in numerous cancer-related biological phenotypes and signalling pathways. Consensus clustering using AS events identified three robust clusters of patients with distinguished pathological and prognostic features. Moreover, each cluster was also associated with distinct genomic alterations. Finally, we developed and validated an AS-related signature with Cox proportional hazards model. The signature, significantly associated with clinical and molecular features, could serve as an independent prognostic factor for lower-grade diffuse gliomas. Thus, our results indicated that AS events could discriminate molecular subtypes and have prognostic impact in lower-grade diffuse gliomas.

Identification of eight-protein biosignature for diagnosis of tuberculosis.

BACKGROUND: Biomarker-based tests for diagnosing TB currently rely on detecting Mycobacterium tuberculosis (Mtb) antigen-specific cellular responses. While this approach can detect Mtb infection, it is not efficient in diagnosing TB, especially for patients who lack aetiological evidence of the disease. METHODS: We prospectively enrolled three cohorts for our study for a total of 630 subjects, including 160 individuals to screen protein biomarkers of TB, 368 individuals to establish and test the predictive model and 102 individuals for biomarker validation. Whole blood cultures were stimulated with pooled Mtb-peptides or mitogen, and 640 proteins within the culture supernatant were analysed simultaneously using an antibody-based array. Sixteen candidate biomarkers of TB identified during screening were then developed into a custom multiplexed antibody array for biomarker validation. RESULTS: A two-round screening strategy identified eight-protein biomarkers of TB: I-TAC, I-309, MIG, Granulysin, FAP, MEP1B, Furin and LYVE-1. The sensitivity and specificity of the eight-protein biosignature in diagnosing TB were determined for the training (n=276), test (n=92) and prediction (n=102) cohorts. The training cohort had a 100% specificity (95% CI 98% to 100%) and 100% sensitivity (95% CI 96% to 100%) using a random forest algorithm approach by cross-validation. In the test cohort, the specificity and sensitivity were 83% (95% CI 71% to 91%) and 76% (95% CI 56% to 90%), respectively. In the prediction cohort, the specificity was 84% (95% CI 74% to 92%) and the sensitivity was 75% (95% CI 57% to 89%). CONCLUSIONS: An eight-protein biosignature to diagnose TB in a high-burden TB clinical setting was identified.

The relationship between gastric cancer and Helicobacter pylori cytotoxin-related gene A genotypes.

Gastric cancer has been known as the third leading cause of cancer-related death in the world. It is when cancer cells form on the lining of the stomach. Early symptoms include heartburn, upper abdominal pain, nausea, and loss of appetite. Helicobacter pylori is the most common microscopic creature that has infected humans worldwide. More than half of the world's population is infected with the bacterium. It is the main cause of diseases such as stomach ulcers and stomach and intestinal disorders. H. pylori infection is related to gastric adenocarcinoma and cagA genotype is believed to be related to cancer development. cytotoxin-associated gene A (CagA) is a 120-145kDa protein encoded on the 40kb cag pathogenicity island (PAI). This study investigates the association between cagA H. pylori genotypes and gastric cancer. For this purpose, 65 stomach biopsies of the gastric cancer patients and 100 saliva samples were collected from healthy and H. pylori-infected individuals. Then genomic DNA was purified and Polymerase Chain Reaction (PCR) was performed for the studied gene using specific primers. The presence of H. pylori was investigated by PCR and a pair of specific primers for a protected region in the bacterium glmM gene. Then cagA+ and cagA- genotypes frequencies were determined in H. pylori-infected cases. Statistical analysis showed that there were significant differences between healthy and diseased ones for genotypes cagA+ and cagA-. Then the cagA+ can be a risk factor genotype for gastric cancer.

Discovering endometriosis biomarkers with multiplex cytokine arrays.

BACKGROUND: Chronic pelvic pain is often overlooked during primary examinations because of the numerous causes of such "vague" symptoms. However, this pain can often mask endometriosis, a smoldering disease that is not easily identified as a cause of the problem. As such, endometriosis has been shown to be a potentially long-term and often undiagnosed disease due to its vague symptoms and lack of any non-invasive testing technique. Only after more severe symptoms arise (severe pelvic pain, excessive vaginal bleeding, or infertility) is the disease finally uncovered by the attending physician. Due to the nature and complexity of endometriosis, high throughput approaches for investigating changes in protein levels may be useful for elucidating novel biomarkers of the disease and to provide clues to help understand its development and progression. METHODS: A large multiplex cytokine array which detects the expression levels of 260 proteins including cytokines, chemokines, growth factors, adhesion molecules, angiogenesis factors and other was used to probe biomarkers in plasma samples from endometriosis patients with the intent of detecting and/or understanding the cause of this disease. The protein levels were then analyzed using K-nearest neighbor and split-point score analysis. RESULTS: This technique identified a 14-marker cytokine profile with the area under the curve of 0.874 under a confidence interval of 0.81-0.94. Our training set further validated the panel for significance, specificity, and sensitivity to the disease samples. CONCLUSIONS: These findings show the utility and reliability of multiplex arrays in deciphering new biomarker panels for disease detection and may offer clues for understanding this mysterious disease.

Concomitant external and internal hemorrhage: Challenges to managing patients with open pelvic fracture.

INTRODUCTION: Managing patients with open pelvic fractures continues to be challenging and requires a multidisciplinary approach. In this study, we examined the characteristics of patients with open pelvic fractures and strategies for managing such patients. MATERIALS AND METHODS: The records of patients with open pelvic fractures from January 2010 to August 2016 were retrospectively reviewed. Emergency surgery was performed to control hemorrhaging in patients with an active external hemorrhage. Transcatheter arterial embolization (TAE) was used for definitive hemostasis. The relation between cause of death and timing of death was examined. We also compared the characteristics of surviving and non-surviving patients. Furthermore, patients who received both surgery and post-operative TAE were analyzed in detail. RESULTS: In total, 42 patients with open pelvic fractures were enrolled in the study. The overall mortality rate among patients with open pelvic fractures was 26.2%. Patients whose deaths were related to hemorrhaging and associated injuries died significantly earlier than patients whose deaths were related to sepsis and multiple organ failure (1.3days vs. 12.3days, p<0.001). Sixteen patients (38.1%) received TAE for hemostasis, and their systolic blood pressure (SBP) improved significantly following TAE (from 88.4mmHg to 111.6mmHg, p<0.05). In the patients who received both surgery and post-operative TAE (n=8), the SBP increased significantly after surgery (from 58.8mmHg to 81.1mmHg, p<0.05). Similarly, the patients' SBP after TAE was significantly higher than their post-operative SBP (110.5mmHg vs. 81.1mmHg, p<0.05). CONCLUSION: Active external hemorrhaging was initially controlled when managing patients with open pelvic fractures; however, most patients also required TAE for definitive hemorrhage control. Early TAE should be considered due to the high probability of concomitant internal and external hemorrhage. Close observation and further infection control are important following the hemostatic procedure.

New Insights into the Tumor Microenvironment Utilizing Protein Array Technology.

The tumor microenvironment (TME) is a considerably heterogeneous niche, which is created by tumor cells, the surrounding tumor stroma, blood vessels, infiltrating immune cells, and a variety of associated stromal cells. Intercellular communication within this niche is driven by soluble proteins synthesized by local tumor and stromal cells and include chemokines, growth factors, interferons, interleukins, and angiogenic factors. The interaction of tumor cells with their microenvironment is essential for tumorigenesis, tumor progression, growth, and metastasis, and resistance to drug therapy. Protein arrays enable the parallel detection of hundreds of proteins in a small amount of biological sample. Recent data have demonstrated that the application of protein arrays may yield valuable information regarding the structure and functional mechanisms of the TME. In this review, we will discuss protein array technologies and their applications in TME analysis to discern pathways involved in promoting the tumorigenic phenotype.

Use of Masquelet's technique for treating the first metatarsophalangeal joint in cases of gout combined with a massive bone defect.

BACKGROUND: To examine the safety and efficacy of Masquelet's technique as a surgical method for treating the first metatarsophalangeal joint in cases of gout accompanied by a massive bone defect. METHODS: From January 2010 to January 2016, eleven patients (7 males and 4 females; mean age 33.1 years; range, 23-43 years) received surgical treatment for a first metatarsophalangeal joint tophus which caused a serious bone defect. The first metatarsophalangeal bone defects ranged from 3-6cm, or nearly 50% of the length of normal bone. During the first stage of Masquelet's technique, we removed the tophus and infused that area with bone cement that contained antibiotics. Two months later, we performed the second stage, in which the prosthesis was replaced with iliac cancellous bone, and the operated area was stabilized via locking plate fixation. RESULTS: All of the surgeries were successful, and the 11 patients were followed up for an average of 10.9 months. Postoperative evaluations showed that 10 of the 11 patients healed between 9 and 14 days after the initial surgery. Bone fusion occurred between 2.3 and 3.6 months after the operation, and the average healing time was 3.0 months. One foot wound became infected, but healed after vacuum aspiration. When the American Association of Foot and Ankle Surgery Maryland Foot scoring system was used to evaluate the foot function of the 11 patients prior to surgery, all 11 patients were graded as "failures." Following surgery, 2 patients were graded excellent, 5 were good, 3 were fair, and only 1 patient failed. The total combined excellent and good rate was 63.6%. The total mean Maryland scores pre- and post-surgery were 27.8 points and 74.1 points, respectively; thus the average patient score increased by 46.3 points. CONCLUSIONS: Joints with advanced tophus nodules develop segmental bone defects. Masquelet's technique is an effective method for treating such nodules and their associated bone defects.

Cytokines in cancer drug resistance: Cues to new therapeutic strategies.

The development of oncoprotein-targeted anticancer drugs is an invaluable weapon in the war against cancer. However, cancers do not give up without a fight. They may develop multiple mechanisms of drug resistance, including apoptosis inhibition, drug expulsion, and increased proliferation that reduce the effectiveness of the drug. The collective work of researchers has highlighted the role of cytokines in the mechanisms of cancer drug resistance, as well as in cancer cell progression. Furthermore, recent studies have described how specific cytokines secreted by cancer stromal cells confer resistance to chemotherapeutic treatments. In order to gain a better understanding of mechanism of cancer drug resistance and a prediction of treatment outcome, it is imperative that correlations are established between global cytokine profiles and cancer drug resistance. Here we discuss the recent discoveries in this field of research and discuss their implications for the future development of effective anti-cancer medicines.

[Spectroscopy Identification of Untreated and Heated Corundum].

Nowadays, a great quantity of heat treating corundums are emerging in our market. It is hard to distinguish them scientifically just by conventional methods. In order to accurately determine whether the corundums have been heated or not, we need to analyse their spectral characteristics. This paper describes the spectroscopy identification of untreated and heated corundum. The experiment is conducted as follows: First, We observed the inclusions of corundum samples, then measured and recorded their infrared spectra, UV-Vis spectra by Fourier Transform Infrared Spectrometer and Ultraviolet-visible Spectrophotometer respectively. Next we chose a part of samples to heat, after the heat treatment, we recorded their spectra and made a comparison with that of untreated corundums. The results showed that we can detect the absorption peaks at 1 980 and 2 110 cm(-1) which represent diaspore in untreated ruby. However, after heat treatment, the absorption peaks disappear which means the structure of AlO(OH) has been destroyed. The sapphires which grown in alkali basalt under reductive condition appear the absorption peak at 3 310 cm(-1). However, this peak vanishes after 18 h heat treatment when the temperature is 1 600 ℃. For UV-Vis spectra of ruby, after heat treatment, the slight shift occurs in strong, wide absorption band at around 555 nm, and this band becomes more pointed. In addition, absorption intensity difference between wave crest and wave hollow increases. The absorption bands at 375, 387, 454 nm of heated sapphires are more pointed than that of the untreated sapphires, and absorption intensity difference rises. These changes in spectral characteristics can help us to distinguish untreated corundum from heat treating corundum.

Application of multiplex immunoassay technology to investigations of ocular disease.

Eye-derived fluids, including tears, aqueous humour and vitreous humour often contain molecular signatures of ocular disease states. These signatures can be composed of cytokines, chemokines, growth factors, proteases and soluble receptors. However, the small quantities (<10 µl) of these fluids severely limit the detection of these proteins by traditional enzyme-linked immunosorbent assay or Western blot. To maximise the amount of information generated from the analysis of these specimens, many researchers have employed multiplex immunoassay technologies for profiling the expression or modification of multiple proteins from minute sample volumes.