Therapeutic and prognostic effect of disulfidptosis-related genes in lung adenocarcinoma.

Disulfidptosis, a new form of cell death, may be induced by disulfide stress associated with cystine disulfide buildup, which can promote cell toxicity, leading to cell death. Nevertheless, the role of direct prognosis and the mechanism underlying the regulation of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD) are still unknown. This study aimed to investigate the role of DRGs in LUAD prognosis and diagnosis through multiomics analysis. First, copy number variations (CNVs) and mutations in the 10 genes were assessed. Considering that five differentially expressed genes (DEGs) were associated with disulfidptosis, a novel DRG score that can be utilized to anticipate LUAD prognosis was developed. Next, the generated receiver operating characteristic (ROC) and survival curves demonstrated that the model had an excellent predictive quality in LUAD in both the training and validation cohorts. Meanwhile, substantial functional disparities between the high DRG group and the low DRG group were observed, and the second gap mitosis (G2M) checkpoint, E2 promoter-binding factor (E2F) targets, and myelocytomatosis (MYC) target activities were consistently higher in the high DRG group than in the low DRG group. Additionally, the T-cell dysfunction score and tumor inflammation signature (Merck18) were negatively correlated with DRGs, whereas myeloid-derived suppressor cells (MDSCs) were positively correlated with DRGs. Moreover, DRGs were negatively linked to most of the immunological checkpoints. Meanwhile, samples of low DRGs benefited more from immune checkpoint blockade (ICB). The correlation analysis between DRGs and clinical characteristics revealed increasing malignancy with increasing DRG scores. Drug sensitization experiment results indicated that sensitivity to cisplatin, vincristine, docetaxel, and gemcitabine was higher in the high DRG group than in the low DRG group. The function of model genes in LUAD was also verified using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, 5-ethynyl-2'-deoxyuridine (EDU), and clonogenic formation.

Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells.

The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with tumor-infiltrating M0 cells, we developed a risk model to provide therapeutic and prognostic guidance in clear cell renal cell carcinoma (ccRCC). First, the infiltration abundance of each immune cell type and its correlation with patient prognosis were analyzed. After assessing the potential link between the depth of immune cell infiltration and prognosis, we screened the infiltrating M0 cells to establish a risk model centered on three key genes (TMEN174, LRRC19, and SAA1). The correlation analysis indicated a positive correlation between the risk score and various stages of the tumor immune cycle, including B-cell recruitment. Furthermore, the risk score was positively correlated with CD8 expression and several popular immune checkpoints (ICs) (TIGIT, CTLA4, CD274, LAG3, and PDCD1). Additionally, the high-risk group (HRG) had higher scores for tumor immune dysfunction and exclusion (TIDE) and exclusion than the low-risk group (LRG). Importantly, the risk score was negatively correlated with the immunotherapy-related pathway enrichment scores, and the LRG showed a greater therapeutic benefit than the HRG. Differences in sensitivity to targeted drugs between the HRG and LRG were analyzed. For commonly used targeted drugs in RCC, including axitinib, pazopanib, temsirolimus, and sunitinib, LRG had lower IC50 values, indicating increased sensitivity. Finally, immunohistochemistry results of 66 paraffin-embedded specimens indicated that SAA1 was strongly expressed in the tumor samples and was associated with tumor metastasis, stage, and grade. SAA1 was found to have a significant pro-tumorigenic effect by experimental validation. In summary, these data confirmed that tumor-infiltrating M0 cells play a key role in the prognosis and treatment of patients with ccRCC. This discovery offers new insights and directions for the prognostic prediction and treatment of ccRCC.

Prognostic and therapeutic model based on disulfidptosis-related genes for patients with clear cell renal cell carcinoma.

Disulfidptosis, a newly discovered mode of cell death caused by excessive accumulation of intracellular disulfide compounds, is closely associated with tumor development. This study focused on the relationship between disulfidptosis and clear cell renal cell carcinoma (ccRCC). Firstly, the characterizations of disulfidptosis-related genes (DRGs) in ccRCC were showed, which included number variation (CNV), single nucleotide variation (SNV), DNA methylation, mRNA expression and gene mutation. Then, the ccRCC samples were classified into three clusters through unsupervised clustering based on DRGs. Survival and pathway enrichment differences were evaluated among the three clusters. Subsequently, the differentially expressed genes (DEGs) among the three clusters were screened by univariate Cox, LASSO, and multivariate Cox analysis, and five key DEGs were obtained. Based on the five key DEGs, the ccRCC samples were reclassified into two geneclusters and the survival differences and immune cell infiltration between two geneclusters was investigated. In next step, ccRCC samples were divided into two groups according to PCA scores of five key DEGs, namely high PCA score group (HPSG) and low PCA score group (LPSG). On this basis, differences in survival prognosis, immune cell infiltration and correlation with immune checkpoint, as well as differences in sensitivity to targeted drugs were compared between HPSG and LPSG. The expression levels of four immune checkpoints were higher in HPSG than in LPSG, whereas the LPSG was more sensitive to targeted drug therapy than the HPSG. Finally, validation experiments on HDAC4 indicated that HDAC4 could increase the proliferation and colony formation ability of ccRCC cells.

Nexus of food waste and climate change framework: Unravelling the links between impacts, projections, and emissions.

This communication explores the intricate relationship between food waste and climate change, considering aspects such as impacts, projections, and emissions. It focuses on the pressing issue of waste generation and its potential consequences if current trends persist, and emphasises the importance of efficient solid waste management in improving environmental quality and fostering economic development. It also highlights the challenges faced by developing countries in waste collection and disposal, drawing comparisons with the waste utilisation methods used by developed nations. The review delves into the link between food waste and climate change, noting the paradoxical situation of food wastage against the backdrop of global hunger and malnutrition. It underscores the scientific evidence connecting food waste to climate change and its implications for food security and climate systems. Additionally, it examines the environmental burden imposed by food waste, including its contribution to greenhouse gas emissions and the depletion of resources such as energy, water, and land. Besides environmental concerns, this communication also highlights the ethical and socioeconomic dimensions of food waste, discussing its influence on Sustainable Development Goals, poverty, and social inequality. The communication concludes by advocating for collective action and the development of successful mitigation strategies, technological solutions, and policy interventions to address food waste and its climate impacts. It emphasises the need for collaboration, awareness, and informed decision-making to ensure a more sustainable and equitable future.

Fully Integrated Patch Based on Lamellar Porous Film Assisted GaN Optopairs for Wireless Intelligent Respiratory Monitoring.

Respiratory pattern is one of the most crucial indicators for accessing human health, but there has been limited success in implementing fast-responsive, affordable, and miniaturized platforms with the capability for smart recognition. Herein, a fully integrated and flexible patch for wireless intelligent respiratory monitoring based on a lamellar porous film functionalized GaN optoelectronic chip with a desirable response to relative humidity (RH) variation is reported. The submillimeter-sized GaN device exhibits a high sensitivity of 13.2 nA/%RH at 2-70%RH and 61.5 nA/%RH at 70-90%RH, and a fast response/recovery time of 12.5 s/6 s. With the integration of a wireless data transmission module and the assistance of machine learning based on 1-D convolutional neural networks, seven breathing patterns are identified with an overall classification accuracy of >96%. This integrated and flexible on-mask sensing platform successfully demonstrates real-time and intelligent respiratory monitoring capability, showing great promise for practical healthcare applications.

[Preliminary observation on the clinical application of rehabilitation support for lumbar disc herniation based on 3D printing technology].

OBJECTIVE: To analyze the important effect of 3D printing personalized lumbar support on lumbar pain and lumbar function in patients with lumbar disc herniation. METHODS: From October 2018 to May 2021, 60 patients initially diagnosed with lumbar disc herniation were selected and divided into an observation group and a control group, with 30 patients in each group. Among them, there were 18 males and 12 females in the observation group;the age ranged from 24 to 56 years old, with an average of (45.23±6.07) years old. The course of disease ranged from 1 to 24 months, with an average of(6.25±0.82) months, and rehabilitation treatment was carried out by wearing 3D printed personalized lumbar support. There were 19 males and 11 females in the control group;the age ranged from 25 to 57 years old, with an average of (42.78±7.58) years old. The course of disease ranged from 1 to 24 months, with an average of (6.72±1.36) months, and rehabilitation treatment is carried out by wearing traditional lumbar protective equipment. The Japanese Orthopaedic Association (JOA) scores, lumbar Oswestry dysfunction index (ODI) and visual analogue scale (VAS) were evaluated and compared between the two groups before and 1 course after treatment (3 weeks). RESULTS: There was no statistically significant difference in JOA, ODI, and VAS between two groups before treatment (P>0.05). After one course of treatment (3 weeks), JOA scores of both groups was increased compared to before treatment (P<0.05), while ODI and VAS decreased compared to before treatment (P<0.05). After treatment, JOA score of observation group was higher than that of control group (P<0.05), while ODI and VAS scores were lower than those of control group. No adverse events occurred in both groups. CONCLUSION: The application of 3D printing personalized lumbar support can effectively alleviate the pain of patients with lumbar disc herniation and improve their lumbar function of patients.

A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma.

PURPOSE: Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear. METHODS: To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model. RESULTS: Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1. CONCLUSION: The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.

Oribron: An Origami-Inspired Deformable Rigid Bronchoscope for Radial Support.

The structure of a traditional rigid bronchoscope includes proximal, distal, and body, representing an important means to treat hypoxic diseases. However, the body structure is too simple, resulting in the utilization rate of oxygen being usually low. In this work, we reported a deformable rigid bronchoscope (named Oribron) by adding a Waterbomb origami structure to the body. The Waterbomb's backbone is made of films, and the pneumatic actuators are placed inside it to achieve rapid deformation at low pressure. Experiments showed that Waterbomb has a unique deformation mechanism, which can transform from a small-diameter configuration (#1) to a large-diameter configuration (#2), showing excellent radial support capability. When Oribron entered or left the trachea, the Waterbomb remained in #1. When Oribron is working, the Waterbomb transforms from #1 to #2. Since #2 reduces the gap between the bronchoscope and the tracheal wall, it effectively slows down the rate of oxygen loss, thus promoting the absorption of oxygen by the patient. Therefore, we believe that this work will provide a new strategy for the integrated development of origami and medical devices.

Spermidine Retarded the Senescence of Multipotent Mesenchymal Stromal Cells In Vitro and In Vivo through SIRT3-Mediated Antioxidation.

Multipotent mesenchymal stromal cells (MSCs) expand in vitro and undergo replicative senescence, thereby restricting their clinical utilization. Thus, an effective strategy is required to impede MSC senescence. Since spermidine (SPD) supplementation can prolong the lifespan of yeast by inhibiting oxidative stress, spermidine is a potential option for delaying MSC senescence. In this study, to test our hypothesis, we first isolated primary human umbilical cord mesenchymal stem cells (hUCMSCs). Subsequently, the appropriate SPD dose was administered during continuous cell cultivation. Next, we evaluated the antisenescence effects by SA-ß-gal staining, Ki67 expression, reactive oxygen species (ROS) levels, adipogenic or osteogenic ability, senescence-associated markers, and DNA damage markers. The results revealed that early SPD intervention significantly delays the replicative senescence of hUCMSCs and constrains premature H2O2-induced senescence. Additionally, by silencing SIRT3, the SPD-mediated antisenescence effects disappear, further demonstrating that SIRT3 is necessary for SPD to exert its antisenescence effects on hUCMSCs. Besides, the findings of this study also suggest that SPD in vivo protects MSCs against oxidative stress and delays cell senescence. Thus, MSCs maintain the ability to proliferate and differentiate efficiently in vitro and in vivo, which reflects the potential clinical utilization of MSCs in the future.

A dual-functional catalyst: wood-templated BiVO4-CdS for wood dye wastewater.

A large quantity of wastewater is released from wood processing, posing a serious pollution problem to the natural environment. Photocatalysis has become a reliable method for effluent purification. In this paper, balsa-templated BiVO4-CdS (BBC) was synthesized by impregnation calcination and chemical deposition using wood residue as a template. Rhodamine B (RhB) is used as a wood colorant and is present in wood processing wastewater. The performance of BBC in photocatalytic degradation with simultaneous hydrogen production was identified using RhB as simulated wood dye wastewater and a sacrificial electron donor. Compared to the BiVO4-CdS without a template, the BBC exhibited higher photocatalytic degradation performance (98.32%), which was attributed to the laminar porous structure of the wood being replicated. Because of the existence of a porous structure, BBC has better adsorption properties, which accelerated photodegradation and the production process of H2. Furthermore, surface modification with CdS nanoparticles formed Z-scheme heterojunctions, which greatly inhibited the photogenerated electron-hole compounds. When RhB provided electrons to BiVO4 and CdS, it was also removed by the oxidation of h+ and ·OH, which were simultaneously generated by balsa-templated BiVO4-CdS. BBC produced hydrogen at a higher rate (61.2 µmol g-1 h-1), realizing dual-functional photocatalysis. Therefore, the results support further development of dual-functional catalysts by the use of wood residues.

Constructing Ni4/Fe@Fe3O4-g-C3N4 nanocomposites for highly efficient degradation of carbon tetrachloride from aqueous solution.

Catalytic hydrodechlorination is one of the most potential remediation methods for chlorinated organic pollutants. In this study, Ni4/Fe@Fe3O4-g-C3N4 (NFFOCN) nanocomposites were synthesized for carbon tetrachloride (CT) removal and characterized by SEM, XPS and FTIR. The characterization results demonstrated that the special functional groups of g-C3N4, especially NH groups, effectively alleviated the aggregation of nanoparticles. In addition, the C and N groups of g-C3N4 enhanced the catalytic dechlorination of CT by providing binding sites. The experimental results showed that NFFOCN could effectively remove CT over a wide initial pH range of 3-9, and the CT removal efficiency reached 94.7% after 35 min with only 0.15 g/L of NFFOCN at pH 5.5. The Cl-, SO42-, and HCO3- promoted the removal of CT, while HA and NO3- had the opposite effect. Furthermore, good sequential CT removal by NFFOCN nanocomposites was observed, and the CT removal efficiency reached 77.3% after four cycles. Based on the identification of products, a possible degradation pathway of CT was proposed. Moreover, the main mechanisms regarding CT removal included the direct reduction of nZVI (about 40.51%), adsorption (around 34.79%), and hydrodechlorination of CT by Ni0 using H2 (about 19.40%).

A comparison study of Fenton-like and Fenton reactions in dichloromethane removal.

Dichloromethane (DCM), as a low-chlorinated organic compound, is hardly to be degraded through the reductive dechlorination pathway. In this study, the removal of DCM in Fenton-like system, using activated carbon fibres-supported zero-valence Fe/Ni nanoparticles (ACF-Fe/Ni) as catalysts, was investigated and compared with that of a traditional Fenton system (Fe2+/H2O2). The influence of vital parameters, including initial solution pH, DCM concentration, catalyst and H2O2 dosages, temperature and cosolute on the removal of DCM, was systematically studied. The results showed that 94.2% of DCM with an initial concentration of 5 mg/L could be removed in the Fenton-like reaction under the optimum condition: initial pH of 2.0, 0.4 g/L of ACF-Fe/Ni, 10 mM of H2O2 and a temperature of 30°C. In comparison, the removal of DCM in the Fenton-like system was faster than that of the Fenton system and the corresponding activation energies were 39.69 and 33.82 kJ/mol, respectively. The coexistence of solute was adverse to the removal of DCM in both Fenton-like and Fenton systems. Moreover, the active species for DCM removal in the Fenton-like system was confirmed as hydroxyl radical (·OH) via the quenching experiment and electron paramagnetic resonance measurement. The incomplete mineralisation (41.7%) of DCM after reaction indicated that the Fenton-like technology had the potential to realise DCM's non-toxic and harmless conversion and organic intermediates formed needed to take longer time to be decomposed.

Drag forces on nanoparticles in the free-molecule regime: Effect of the particle temperature.

In the present paper, we theoretically study the drag force on nanoparticles in the free-molecule regime. It has been widely assumed that the particle temperature is equal to the gas media temperature in the open literature. However, this assumption can be invalid in some real applications. Based on the kinetic theory, we obtain the generalized formulas for the drag force on nanoparticles in the free-molecule regime. It is found that there exists a significant error induced by the assumption of equal temperature between the particle and the surrounding gas. Therefore, it is necessary to consider the effect of the particle temperature in the analysis of the particle transport properties.

Syngas to light olefins conversion with high olefin/paraffin ratio using ZnCrOx/AlPO-18 bifunctional catalysts.

Direct synthesis of light olefins from syngas (STO) using a bifunctional catalyst composed of oxide and zeolite has attracted extensive attention in both academia and industry. It is highly desirable to develop robust catalysts that could enhance the CO conversion while simultaneously maintain high selectivity to C2-C4 olefins. Herein, we report a bifunctional catalyst consisting of ZnCr binary oxide (ZnCrOx) and low-Si AlPO-18 zeolite, showing both satisfying selectivity to C2-C4 olefins of 45.0% (86.7%, CO2 free) and high olefin/paraffin ratio of 29.9 at the CO conversion of 25.2% under mild reaction conditions (4.0 MPa, 390 °C). By optimizing the reaction conditions, the CO conversion could be markedly increased to 49.3% with a slight drop in selectivity. CD3CN/CO-FTIR characterizations and theoretical calculations demonstrate that low-Si AlPO-18 zeolite has lower acid strength, and is therefore less reactive toward the hydride transfer in the STO reaction, leading to a higher olefin/paraffin ratio.

The Long-Term Efficacy and Safety of Carotid Artery Stenting among the Elderly: A Single-Center Study in China.

Compared to carotid endarterectomy, carotid artery stenting (CAS) is reportedly associated with higher perioperative risks in elderly patients. To verify the long-term safety and efficacy of CAS with embolic protection in elderly patients, we retrospectively reviewed the medical records of patients with carotid stenosis treated between January 2003 and March 2010 at the Department of Neurology of a large university hospital in China. We included patients with symptomatic, moderate, or severe carotid stenosis of atherosclerotic etiology (other etiologies were excluded), with a disability score ≤ 3 on the modified Rankin Scale, and who received CAS instead of carotid endarterectomy. The clinical endpoints studied were stroke recurrence and all-cause death. The 84 patients included in this study (median follow-up, 8.08 years) were stratified according to age at surgery (<70 vs. ≥70 years), and no significant between-group difference was found regarding baseline characteristics. Of the 14 patients (16.67%) who experienced a defined clinical endpoint, 4 (7.14%) were aged <70 years and 10 (35.71%) were aged ≥70 years (P = 0.002). Overall mortality was 14.29% (12/84), with 3 (5.36%) and 9 (32.14%) deaths among patients aged <70 and ≥ 70 years, respectively (P = 0.002). Heart disease and cancer accounted for most deaths. The two groups did not differ regarding stroke recurrence, disability score, or rate of in-stent restenosis (blockage ≥ 50%), but patients aged ≥70 years had a higher risk of mortality (odds ratio, 8.3684; 95% confidence interval, 2.048-34.202; P = 0.003), and age was an independent risk factor for death (odds ratio, 20.054; 95% confidence interval, 3.094-129.987, P = 0.002). Among elderly patients in Southwest China, CAS can effectively prevent stroke recurrence without increasing the risk of stroke-related death, but the risk of all-cause death is higher, with age as an independent risk factor. Careful patient selection is of key importance in the treatment of symptomatic carotid artery stenosis.

Cross-cultural leadership: leading around the world.

Situational models of leadership have been discussed since the mid-1960s. In this paper, we review the evidence concerning one such contextual variable, societal culture. The traditional cross-cultural literature shows how culture affects the kind of leadership characteristics, attributes, and behaviors desired and believed to be important in a society. The research also shows that culture moderates the outcomes resulting from different styles of leadership. The newly emerging global leadership literature focuses on leadership when followers are culturally diverse. We review the current state of these literatures and provide research suggestions.

[Progress in the physiological and pathophysiological functions of sodium calcium exchangers].

Sodium calcium exchanger (NCX), which is widely expressed in the plasma membrane, mitochondrial membrane and secretory vesicles in diverse kinds of cells, belongs to a type of cation translocators. NCX works in two modes, the forward mode and reverse mode, to regulate the intracellular Ca(2+) concentration bi-directionally. In the forward mode, NCX carries Ca(2+) out of the cell against its electrochemical gradients coupled to the influx of Na(+) down its electrochemical gradients; alternatively, Ca(2+) enters through the reverse mode of NCX, and Na(+) is carried out of the cell. Exactly through the two-way modes, NCX can regulate intracellular Ca(2+) concentration fleetly and accurately, and plays a critical role in a series of physiological processes including intracellular signal transduction, growth and development of cells, excitation and its coupled functions of excitable cells. NCX are acknowledged to be involved in myofiber contraction, neurotransmission, migration and differentiation of neurogliocyte, activation of immune cells, secretion of cytokines and hormones etc. Moreover, abnormal activation of the reverse mode of NCX plays a vital role in many pathological processes including cell apoptosis, ischemia-reperfusion injury, insulin secretion, tumor etc. Here we reviewed the research status about the NCX's participation in some physiological and pathophysiological processes, so as to provide comprehensive understanding about its functions.

Identification of diagnostic subnetwork markers for cancer in human protein-protein interaction network.

BACKGROUND: Finding reliable gene markers for accurate disease classification is very challenging due to a number of reasons, including the small sample size of typical clinical data, high noise in gene expression measurements, and the heterogeneity across patients. In fact, gene markers identified in independent studies often do not coincide with each other, suggesting that many of the predicted markers may have no biological significance and may be simply artifacts of the analyzed dataset. To find more reliable and reproducible diagnostic markers, several studies proposed to analyze the gene expression data at the level of groups of functionally related genes, such as pathways. Studies have shown that pathway markers tend to be more robust and yield more accurate classification results. One practical problem of the pathway-based approach is the limited coverage of genes by currently known pathways. As a result, potentially important genes that play critical roles in cancer development may be excluded. To overcome this problem, we propose a novel method for identifying reliable subnetwork markers in a human protein-protein interaction (PPI) network. RESULTS: In this method, we overlay the gene expression data with the PPI network and look for the most discriminative linear paths that consist of discriminative genes that are highly correlated to each other. The overlapping linear paths are then optimally combined into subnetworks that can potentially serve as effective diagnostic markers. We tested our method on two independent large-scale breast cancer datasets and compared the effectiveness and reproducibility of the identified subnetwork markers with gene-based and pathway-based markers. We also compared the proposed method with an existing subnetwork-based method. CONCLUSIONS: The proposed method can efficiently find reliable subnetwork markers that outperform the gene-based and pathway-based markers in terms of discriminative power, reproducibility and classification performance. Subnetwork markers found by our method are highly enriched in common GO terms, and they can more accurately classify breast cancer metastasis compared to markers found by a previous method.

Loss of IrpT function in Lactococcus lactis subsp. lactis N8 results in increased nisin resistance.

The antibiotic nisin, produced by Lactococcus lactis subsp. lactis N8, offers an extensive commercial prospect as natural food preservatives. The nisin immunity of the L. lactis strains is regulated by a variety of mechanisms. In this study, we isolated a L. lactis L31 strain with increased nisin resistance from a mini-Mu transposon mutant pool of strain N8. The single Mu insertion in strain L31 was in the irpT gene with unknown function. By comparing the proteomic profiles of L. lactis L31 and its parental strain, we found that changes occurred in the synthesis of a protein involved in cell wall biosynthesis (RmlD). Strain L31 had 13.7% higher content of rhamnose in the cell wall than the N8 strain. Overexpression of RmlD involved in the synthesis of dTDP-L: -rhamnose in the nisin-sensitive MG1363 strain increased nisin resistance of the strain. The results indicate that these cellular proteins effected nisin resistance in L. lactis N8.

Accurate and reliable cancer classification based on probabilistic inference of pathway activity.

With the advent of high-throughput technologies for measuring genome-wide expression profiles, a large number of methods have been proposed for discovering diagnostic markers that can accurately discriminate between different classes of a disease. However, factors such as the small sample size of typical clinical data, the inherent noise in high-throughput measurements, and the heterogeneity across different samples, often make it difficult to find reliable gene markers. To overcome this problem, several studies have proposed the use of pathway-based markers, instead of individual gene markers, for building the classifier. Given a set of known pathways, these methods estimate the activity level of each pathway by summarizing the expression values of its member genes, and use the pathway activities for classification. It has been shown that pathway-based classifiers typically yield more reliable results compared to traditional gene-based classifiers. In this paper, we propose a new classification method based on probabilistic inference of pathway activities. For a given sample, we compute the log-likelihood ratio between different disease phenotypes based on the expression level of each gene. The activity of a given pathway is then inferred by combining the log-likelihood ratios of the constituent genes. We apply the proposed method to the classification of breast cancer metastasis, and show that it achieves higher accuracy and identifies more reproducible pathway markers compared to several existing pathway activity inference methods.