Robust deep learning from incomplete annotation for accurate lung nodule detection.

Deep learning plays a significant role in the detection of pulmonary nodules in low-dose computed tomography (LDCT) scans, contributing to the diagnosis and treatment of lung cancer. Nevertheless, its effectiveness often relies on the availability of extensive, meticulously annotated dataset. In this paper, we explore the utilization of an incompletely annotated dataset for pulmonary nodules detection and introduce the FULFIL (Forecasting Uncompleted Labels For Inexpensive Lung nodule detection) algorithm as an innovative approach. By instructing annotators to label only the nodules they are most confident about, without requiring complete coverage, we can substantially reduce annotation costs. Nevertheless, this approach results in an incompletely annotated dataset, which presents challenges when training deep learning models. Within the FULFIL algorithm, we employ Graph Convolution Network (GCN) to discover the relationships between annotated and unannotated nodules for self-adaptively completing the annotation. Meanwhile, a teacher-student framework is employed for self-adaptive learning using the completed annotation dataset. Furthermore, we have designed a Dual-Views loss to leverage different data perspectives, aiding the model in acquiring robust features and enhancing generalization. We carried out experiments using the LUng Nodule Analysis (LUNA) dataset, achieving a sensitivity of 0.574 at a False positives per scan (FPs/scan) of 0.125 with only 10% instance-level annotations for nodules. This performance outperformed comparative methods by 7.00%. Experimental comparisons were conducted to evaluate the performance of our model and human experts on test dataset. The results demonstrate that our model can achieve a comparable level of performance to that of human experts. The comprehensive experimental results demonstrate that FULFIL can effectively leverage an incomplete pulmonary nodule dataset to develop a robust deep learning model, making it a promising tool for assisting in lung nodule detection.

Predicting miRNA-disease association via graph attention learning and multiplex adaptive modality fusion.

miRNAs are a class of small non-coding RNA molecules that play important roles in gene regulation. They are crucial for maintaining normal cellular functions, and dysregulation or dysfunction of miRNAs which are linked to the onset and advancement of multiple human diseases. Research on miRNAs has unveiled novel avenues in the realm of the diagnosis, treatment, and prevention of human diseases. However, clinical trials pose challenges and drawbacks, such as complexity and time-consuming processes, which create obstacles for many researchers. Graph Attention Network (GAT) has shown excellent performance in handling graph-structured data for tasks such as link prediction. Some studies have successfully applied GAT to miRNA-disease association prediction. However, there are several drawbacks to existing methods. Firstly, most of the previous models rely solely on concatenation operations to merge features of miRNAs and diseases, which results in the deprivation of significant modality-specific information and even the inclusion of redundant information. Secondly, as the number of layers in GAT increases, there is a possibility of excessive smoothing in the feature extraction process, which significantly affects the prediction accuracy. To address these issues and effectively complete miRNA disease prediction tasks, we propose an innovative model called Multiplex Adaptive Modality Fusion Graph Attention Network (MAMFGAT). MAMFGAT utilizes GAT as the main structure for feature aggregation and incorporates a multi-modal adaptive fusion module to extract features from three interconnected networks: the miRNA-disease association network, the miRNA similarity network, and the disease similarity network. It employs adaptive learning and cross-modality contrastive learning to fuse more effective miRNA and disease feature embeddings as well as incorporates multi-modal residual feature fusion to tackle the problem of excessive feature smoothing in GATs. Finally, we employ a Multi-Layer Perceptron (MLP) model that takes the embeddings of miRNA and disease features as input to anticipate the presence of potential miRNA-disease associations. Extensive experimental results provide evidence of the superior performance of MAMFGAT in comparison to other state-of-the-art methods. To validate the significance of various modalities and assess the efficacy of the designed modules, we performed an ablation analysis. Furthermore, MAMFGAT shows outstanding performance in three cancer case studies, indicating that it is a reliable method for studying the association between miRNA and diseases. The implementation of MAMFGAT can be accessed at the following GitHub repository: https://github.com/zixiaojin66/MAMFGAT-master.

Dietary Grape Seed Proanthocyanidin Alleviates the Liver Injury Induced by Long-Term High-Fat Diets in Sprague Dawley Rats.

In mammals, the liver is the most important organ that plays a vital function in lipid metabolism. Grape seed proanthocyanidin (GSPE) is a kind of natural polyphenolic compound primarily obtained from grape skin and seeds. Recent research found it had high bioavailability in defending against obesity, hyperlipidemia, inflammatory, oxidative stress, and targeting liver tissue. However, the mechanism of GSPE in regulating obesity induced by dietary high-fat (HF) was not fully understood, particularly the influences on liver functions. Therefore, this study aimed to investigate the effects of GSPE supplementation on the liver function and lipid metabolic parameters in rats fed HF diets long-term. A total of 40 healthy female Sprague Dawley rats were selected. After 8 weeks of obesity model feeding, the rats were randomly divided into four treatments: NC, standard diet; NC + GSPE, standard diet + 500 mg/kg body weight GSPE; HF, high-fat diet; HG + GSPE, high fat diet + 500 mg/kg body weight GSPE. Results indicated that long-term HF feeding caused severe liver problems including megalohepatia, steatosis, inflammation, and hepatocyte apoptosis. The supplementation of GSPE alleviated these symptoms. The results of the current experiment confirmed that GSPE addition up-regulated the expression of the Wnt3a/ß-catenin signaling pathway, thereby restraining the liver cell endoplasmic reticulum stress and hepatocyte apoptosis. Furthermore, the microRNA-103 may play a role in this signal-regulated pathway. In summary, GSPE had a protective effect on the liver and the current experiment provided a reference for the application of GSPE in animal nutrition as a kind of natural feed additive.

Enhancing adoptive T cell therapy for solid tumor with cell-surface anchored immune checkpoint inhibitor nanogels.

The efficacy of Adoptive Cell Therapy (ACT) for solid tumor is still mediocre. This is mainly because tumor cells can hijack ACT T cells' immune checkpoint pathways to exert immunosuppression in the tumor microenvironment. Immune Checkpoint Inhibitors such as anti-PD-1 (aPD1) can counter the immunosuppression, but the synergizing effects of aPD1 to ACT was still not satisfactory. Here we demonstrate an approach to safely anchor aPD1-formed nanogels onto T cell surface via bio-orthogonal click chemistry before adoptive transfer. The spatial-temporal co-existence of aPD1 with ACT T cells and the responsive drug release significantly improved the treatment outcome of ACT in murine solid tumor model. The average tumor weight of the group treated by cell-surface anchored aPD1 was only 18 % of the group treated by equivalent dose of free aPD1 and T cells. The technology can be broadly applicable in ACTs employing natural or Chimeric Antigen Receptor (CAR) T cells.

Curcumin alleviated lipopolysaccharide-induced lung injury via regulating the Nrf2-ARE and NF-κB signaling pathways in ducks.

BACKGROUND: Under the intensive modern poultry farming system, the lung of duck is one of the main target organs for various bacterial and viral infections. Curcumin is a kind of natural polyphenol compound for which various beneficial biological functions exist, including being an anti-inflammatory, antioxidant, and antiviral. The aim of this work was to investigate the mechanism of curcumin-alleviated lipopolysaccharide (LPS)-induced lung damage by the nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant reaction element (ARE) and nuclear factor kappa B (NF-κB) signaling pathway in ducks. RESULTS: In total, 450 one-day-old male specific pathogen-free ducks were randomly assigned into three dietary treatments: CON, basal diet; LPS, basal diet + LPS treatment; LPS + CUR, basal diet + LPS + 500 mg kg-1 of curcumin. At the end of the experiment (21 days), ducks in LPS treatment were challenged with 5 mg LPS per kilogram of body weight and the other two treatments were injected with the same dose of phosphate-buffered saline solution. The results showed that LPS caused acute inflammation, oxidation stress, and lung injury. Dietary addition of curcumin significantly relieved the oxidation stress and inflammation parameters. Moreover, the results showed that remission may be through the signaling pathways of both Nrf2-ARE and NF-κB. CONCLUSION: In conclusion, dietary supplementation of 500 mg kg-1 of curcumin exhibited a lung-protective effect in ducks. This experiment broadens the mode of metabolism actions of curcumin in the target organs and provides an insight for the application of curcumin in waterfowl feed. © 2022 Society of Chemical Industry.

Comparison of Neoadjuvant Chemotherapy Efficiency in Advanced Ovarian Cancer Patients Treated With Paclitaxel Plus Carboplatin and Intraperitoneal Bevacizumab vs. Paclitaxel With Carboplatin.

Objective: This study evaluated the role of neoadjuvant chemotherapy (NACT) with bevacizumab intraperitoneal perfusion in advanced ovarian cancer (AOC). Methods: In this study, 80 patients with advanced epithelial ovarian cancer (stage IIIc or IV) who received NACT at the Central Hospital of Zhuzhou between February 2019 and October 2020 were enrolled. Patients were randomized to receive paclitaxel plus carboplatin (TC) or TC plus intraperitoneal perfusion of bevacizumab (TCB). The effect of chemotherapy was assessed following two cycles of chemotherapy. Cancer antigen 125 (CA125), tumor size, ascites volume, bleeding volume, duration of operation, surgical satisfaction rate, complication rate, and residual tumor were assessed to monitor response to chemotherapy. Results: Treatment with TCB regimen significantly reduced serum levels of CA125 and ascites volume (p < 0.001). Meanwhile, the TCB group had significantly lower intraoperative blood loss and shorter operation time (p < 0.001). Most importantly, patients treated with TCB regimen had a higher surgical satisfaction rate (p < 0.01). Moreover, the incidence of postoperative wound infection, hypoproteinemia, abdominal distension, and fever was lower in the TCB group compared with the TC group. Assessment of adverse reactions during chemotherapy showed no severe complications between the two groups. Conclusions: The results demonstrated that the TCB regimen is superior to the TC regimen alone in the treatment of AOC. These findings could help improve the surgical satisfaction rate, provide more effective treatment strategies to prolong progression-free survival and reduce postoperative complications, and promote surgical recovery in AOC.

Knockdown of lncRNA GHET1 suppresses cell proliferation, invasion and LATS1/YAP pathway in non small cell lung cancer.

BACKGROUND: The aim in this study was to explore the role of long non-coding RNA GHET1 in development of non small cell lung cancer (NSCLC). METHODS: LncRNA GHET1 expression levels were analyzed by qRT-PCR in tumor tissues and adjacent normal tissues in NSCLC. Measuring the cell proliferation and invasion abilities by CCK8, cell colony formation and transwell invasion assays. Relative protein expression was analyzed by western blot assays. RESULTS: Expression of lncRNA GHET1 was notably higher in NSCLC tissues compared with adjacent normal tissues by using qRT-PCR analyses. Higher lncRNA GHET1 expression associated with lymph node metastasis, TNM stage and showed poor outcome in NSCLC patients. Knockdown of lncRNA GHET1 suppressed cell proliferation and invasion capacity and Epithelial-Mesenchymal Transition (EMT) phenomenon of NSCLC cells. Moreover, we demonstrated that knockdown of lncRNA GHET1 suppresses LATS1/YAP pathway signaling pathway by downregulating YAP1 expression in NSCLC cells. CONCLUSIONS: GHET1 predicted a poor outcome and acted as a tumor-promoting gene in NSCLC. Thus, inhibition of GHET1 may be a potential target of NSCLC treatment.

Selenium Deficiency Affects the mRNA Expression of Inflammatory Factors and Selenoprotein Genes in the Kidneys of Broiler Chicks.

The aim of this study was to investigate the influence of Se deficiency on the transcription of inflammatory factors and selenoprotein genes in the kidneys of broiler chicks. One hundred fifty 1-day-old broiler chicks were randomly assigned to two groups fed with either a low-Se diet (L group, 0.033 mg/kg Se) or an adequate Se diet (C group, 0.2 mg/kg Se). The levels of uric acid (UA) and creatinine (Cr) in the serum and the mRNA levels of 6 inflammatory factors and 25 selenoprotein genes in the kidneys were measured as the clinical signs of Se deficiency occurred at 20 days old. The results indicated that the contents of UA and Cr in the serum increased in L group (p < 0.05), and the mRNA levels of the inflammatory factors (NF-κB, iNOS, COX-2, and TNF-α) increased in L group (p < 0.05). Meanwhile, the mRNA levels of PTGEs and HO-1 were not changed. In addition, 25 selenoprotein transcripts displayed ubiquitous expression in the kidneys of the chicks. The mRNA levels of 14 selenoprotein genes (Dio1, Dio2, GPx3, Sepp1, SelH, SelI, SelK, Sepn1, SelO, SelW, Sep15, SelT, SelU, and SelS) decreased, and 9 selenoprotein genes (GPx1, GPx2, GPx4, SelPb, Txnrd1, Txnrd2, Txnrd3, SPS2, and SelM) increased in L group (p < 0.05), but the Dio3 and Sepx1 mRNA levels did not change. The results indicated that Se deficiency resulted in kidney dysfunction, activation of the NF-κB pathway, and a change in selenoprotein gene expression. The changes of inflammatory factor and selenoprotein gene expression levels were directly related to the abnormal renal functions induced by Se deficiency.

A negative feedback loop between miR-200b and the nuclear factor-κB pathway via IKBKB/IKK-ß in breast cancer cells.

MicroRNAs (miRNAs) act as important post-transcriptional regulators of gene expression in diverse signalling pathways. However, the relationship between miR-200b and the nuclear factor-κB (NF-κB) signalling pathway remains poorly understood in breast cancer cells. In the current study, we show that IKBKB is a direct target of miR-200b, and that miR-200b downregulates IKBKB expression via directly binding to its 3'-UTR. miR-200b inhibits IκBα phosphorylation, nuclear p50/p65 expression, NF-κB-binding activity, and the translocation of p65 to the nucleus. In addition, miR-200b also suppresses tumour necrosis factor (TNF)-α-induced NF-κB activation and the expression of NF-κB target genes. Importantly, IKBKB overexpression attenuates the inhibitory roles of miR-200b in NF-κB expression, NF-κB-binding activity, and the nuclear translocation of p65. We also show that NF-κB p65 knockdown reduces the binding of NF-κB to the miR-200b promoter and miR-200b promoter activity. Furthermore, p65 knockdown or inhibition of IκBα phosphorylation suppresses miR-200b expression. Finally, functional studies show that IKBKB overexpression can restore the cell growth and migration that are suppressed by miR-200b. In conclusion, our results demonstrate that miR-200b, a transcriptional target of NF-κB, suppresses breast cancer cell growth and migration, and NF-κB activation, through downregulation of IKBKB, indicating that miR-200b has potential as a therapeutic target in breast cancer patients.

Transgenic tobacco overexpressing Brassica juncea HMG-CoA synthase 1 shows increased plant growth, pod size and seed yield.

Seeds are very important not only in the life cycle of the plant but they represent food sources for man and animals. We report herein a mutant of 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGS), the second enzyme in the mevalonate (MVA) pathway that can improve seed yield when overexpressed in a phylogenetically distant species. In Brassica juncea, the characterisation of four isogenes encoding HMGS has been previously reported. Enzyme kinetics on recombinant wild-type (wt) and mutant BjHMGS1 had revealed that S359A displayed a 10-fold higher enzyme activity. The overexpression of wt and mutant (S359A) BjHMGS1 in Arabidopsis had up-regulated several genes in sterol biosynthesis, increasing sterol content. To quickly assess the effects of BjHMGS1 overexpression in a phylogenetically more distant species beyond the Brassicaceae, wt and mutant (S359A) BjHMGS1 were expressed in tobacco (Nicotiana tabacum L. cv. Xanthi) of the family Solanaceae. New observations on tobacco OEs not previously reported for Arabidopsis OEs included: (i) phenotypic changes in enhanced plant growth, pod size and seed yield (more significant in OE-S359A than OE-wtBjHMGS1) in comparison to vector-transformed tobacco, (ii) higher NtSQS expression and sterol content in OE-S359A than OE-wtBjHMGS1 corresponding to greater increase in growth and seed yield, and (iii) induction of NtIPPI2 and NtGGPPS2 and downregulation of NtIPPI1, NtGGPPS1, NtGGPPS3 and NtGGPPS4. Resembling Arabidopsis HMGS-OEs, tobacco HMGS-OEs displayed an enhanced expression of NtHMGR1, NtSMT1-2, NtSMT2-1, NtSMT2-2 and NtCYP85A1. Overall, increased growth, pod size and seed yield in tobacco HMGS-OEs were attributed to the up-regulation of native NtHMGR1, NtIPPI2, NtSQS, NtSMT1-2, NtSMT2-1, NtSMT2-2 and NtCYP85A1. Hence, S359A has potential in agriculture not only in improving phytosterol content but also seed yield, which may be desirable in food crops. This work further demonstrates HMGS function in plant reproduction that is reminiscent to reduced fertility of hmgs RNAi lines in let-7 mutants of Caenorhabditis elegans.

Subcellular localization of rice acyl-CoA-binding proteins (ACBPs) indicates that OsACBP6::GFP is targeted to the peroxisomes.

Acyl-CoA-binding proteins (ACBPs) show conservation at the acyl-CoA-binding (ACB) domain which facilitates binding to acyl-CoA esters. In Arabidopsis thaliana, six ACBPs participate in development and stress responses. Rice (Oryza sativa) also contains six genes encoding ACBPs. We investigated differences in subcellular localization between monocot rice and eudicot A. thaliana ACBPs. The subcellular localization of the six OsACBPs was achieved via transient expression of green fluorescence protein (GFP) fusions in tobacco (Nicotiana tabacum) epidermal cells, and stable transformation of A. thaliana. As plant ACBPs had not been reported in the peroxisomes, OsACBP6::GFP localization was confirmed by transient expression in rice sheath cells. The function of OsACBP6 was investigated by overexpressing 35S::OsACBP6 in the peroxisomal abc transporter1 (pxa1) mutant defective in peroxisomal fatty acid ß-oxidation. As predicted, OsACBP1::GFP and OsACBP2::GFP were localized to the cytosol, and OsACBP4::GFP and OsACBP5::GFP to the endoplasmic reticulum (ER). However, OsACBP3::GFP displayed subcellular multi-localization while OsACBP6::GFP was localized to the peroxisomes. 35S::OsACBP6-OE/pxa1 lines showed recovery in indole-3-butyric acid (IBA) peroxisomal ß-oxidation, wound-induced VEGETATIVE STORAGE PROTEIN1 (VSP1) expression and jasmonic acid (JA) accumulation. These findings indicate a role for OsACBP6 in peroxisomal ß-oxidation, and suggest that rice ACBPs are involved in lipid degradation in addition to lipid biosynthesis.

Assessment of the association between XRCC1 Arg399Gln polymorphism and lung cancer in Chinese.

X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base excision repair and plays an important role in the maintenance of genomic integrity. Polymorphisms in XRCC1 may alter the function and repair capacity of XRCC1 protein which further results in the genetic instability and lung carcinogenesis. Previous studies investigating the relationship between XRCC1 Arg399Gln polymorphism and lung cancer risk in Chinese yielded contradictory results. A meta-analysis was performed to clarify the effect of XRCC1 Arg399Gln polymorphism on lung cancer. The association was assessed by calculating the pooled odds ratio (OR) with 95% confidence intervals (95%CI). Nineteen studies with a total of 12,835 participants were included into this meta-analysis. Overall, there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models (Gln vs. Arg: OR = 1.13, 95%CI 1.01-1.25, P = 0.029; GlnGln vs. ArArg: OR = 1.41, 95%CI 1.07-1.84, P = 0.013; GlnGln vs. ArArg/ArgGln: OR = 1.37, 95%CI 1.07-1.76, P = 0.013). Meta-analysis of 18 studies with high quality also found that there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models. There was no obvious risk of bias in the meta-analysis. Data from the current meta-analysis support the obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer in Chinese.

The influence of isoleucine and arginine on biological activity and peptide-membrane interactions of antimicrobial peptides from the bactericidal domain of AvBD4.

In this study, the influence of isoleucine and arginine on the biological activity and peptide-membrane interactions of linear avian ß-defensin-4 (RL38) analogs was investigated. Results of biological activities showed that the antimicrobial activities of AvBD-4 analogs were closely related to hydrophobicity and amphipathicity. The peptide GLI19 with high hydrophobicity value and amphipathicity displayed broad spectrum antimicrobial activity against both gram-negative and gram-positive, whereas GLR19 with increasing multiple charges only exhibited activity against gram-negative. The interaction between peptides and the liposome membrane demonstrated that the peptides preferentially bound to negatively charged phospholipids over zwitterionic phospholipids, which supported the antimicrobial activity data. The outer membranes assay further demonstrated that GLI19 had a greater capacity than the other tested peptides to penetrate the cell membrane at a low concentration. Collectively, the peptides derived from the bactericidal domain of linear ß- defensins by truncation and hydrophobic amino acid substitution may be effective high-potential antibacterial agents.

Biochemical property and membrane-peptide interactions of de novo antimicrobial peptides designed by helix-forming units.

Typical peptides composed of Phe, Ile, and Arg residues have not been reported, and the effect of the helix-forming unit (HFU) composed of the tripeptide core on biological activity remains unclear. In this study, multimers of the 3-residue HFU were designed to investigate the structure-function relationships. The in vitro biological activities of the peptides were determined. We used synthetic lipid vesicles and intact bacteria to assess the interactions of the peptides with cell membranes. The well-studied peptide melittin was chosen as a control peptide. The results showed that the antimicrobial and hemolytic activities of the peptides increased with the number of HFUs. HFU3 had optimal cell selectivity as determined by the therapeutic index. HFU3 and HFU4 exhibited strong resistance to salts, pH, and heat. CD spectra revealed that the peptides except HFU2 displayed α-helix-rich secondary structures in the presence of SDS or trifluoroethanol (TFE). The peptides interacted weakly with zwitterionic phospholipids (mimicking mammalian membranes) but strongly with negatively charged phospholipids (mimicking bacterial membranes), which corresponds well with the data for the biological activities. There was a correlation between the cell selectivity of the peptides and their high binding affinity with negatively charged phospholipids. Cell membrane permeability experiments suggest that the peptides targeted the cell membrane, and HFU3 showed higher permeabilization of the inner membrane but lower permeabilization of the outer membrane than melittin. These findings provide the new insights to design antimicrobial peptides with antimicrobial potency by trimers.

Influence of truncation of avian ß-defensin-4 on biological activity and peptide-membrane interaction.

Defensins are important components in host defense systems. The therapeutic use of ß-defensins is limited by their innate toxicity and high cost due to the size and complex disulfide pairing. In this study, we used linear avian ß- defensin-4 (RL38) without disulfide bonds as model peptide to derive two peptides by the truncation. GL23 is the C-terminal truncated sequence of RL38, and GLI23 is the derivative of GL23 by the replacement of cysteines with isoleucines. Results showed that these peptides exhibited strong antibacterial activity against gram-negative and gram-positive bacteria. An exception was that GL23 showed weak antimicrobial activity against gallinaceous pathogenic bacteria Salmonella Pullorum C79-13. Two truncated peptides GL23 and GLI23 displayed no or weak hemolysis, which was in accordance with little blue shifts of the peptides in the presence of synthetic eukaryotic membranes. CD spectroscopy demonstrated that these peptides appeared to be unfolded in aqueous solution but acquire structure in the presence of membrane- mimicking phospholipids. GLI23 kept the antibacterial activity at high concentrations of NaCl or low concentration of divalent cations (Mg2+ and Ca2+). The peptides preferentially bound to negatively charged phospholipids over zwitterionic phospholipids, which led to greater cell selectivity. The outer and inner membranes assay displayed that GLI23 killed bacteria by targeting the cell membrane. These results suggest the peptides derived by truncation of linear ß-defensins may be a promising candidate for future antibacterial agent.

The effects of Leu or Val residues on cell selectivity of α-helical peptides.

In this study, the peptides were designed to compare the effect of multiple Leu or Val residues as the hydrophobic side of an α-helical model on their structure, function, and interaction with model membranes. The Leu-rich peptides displayed 4- to 16-fold stronger antimicrobial activity than Val-rich peptides, while Val-containing peptides showed no haemolysis and weak cytotoxicity. The peptides LR and VR showed an α-helical-rich structure under a membranemimicking environment. Different cell selectivity for Leu- or Val-containing peptides correlated with the targeted cell membranes. The Leu-rich peptide LR(W) and Val-rich peptide VR(W) interacted preferentially with negatively charged phospholipids over zwitterionic phospholipids. VR(W) displayed no interaction with zwitterionic phospholipids, which was consistent with its lack of haemolytic activity. The ability of LR to depolarize bacterial cells was much greater than that of VR. Val- and Leu-rich peptides appeared to kill bacteria in a membrane-targeted fashion, with different modes of action. Leu-rich peptides appeared to be active via a membrane-disrupting mode, while Val-rich peptides were active via the formation of small channels.

Effects of BmKNJX11, a bioactive polypeptide purified from Buthus martensi Karsch, on sodium channels in rat dorsal root ganglion neurons.

A long-chain polypeptide BmKNJX11 was purified from the venom of Asian scorpion Buthus martensi Karsch (BmK) by a combination of gel filtration, ion-exchange chromatography, and reverse-phase high-performance liquid chromatography. The molecular mass was found to be 7036.85 Da by electrospray ionization mass spectrometry. The first 15 N-terminal amino acid sequence of BmKNJX11 was determined to be GRDAY IADSE NCTYT by Edman degradation. With whole cell recording, BmKNJX11 inhibited tetrodotoxin-sensitive voltage-gated sodium channels (TTX-S VGSC) in freshly isolated rat dorsal root ganglion (DRG) neurons in a concentration- and voltage-dependent manner. At a concentration of 40 mug/ml BmKNJX11 lowered the activation threshold and produced negative shifting of TTX-S sodium current (I(Na)) activation curve. In addition, BmKNJX11 induced shifting of the steady-state inactivation curve to the left, delayed the recovery of TTX-S I(Na) from inactivation, and also reduced the fraction of available sodium channels. These results suggested that BmKNJX11 might exert effects on VGSC by binding to a specific site. Considering that TTX-S VGSC expressed in DRG neurons play a critical role in nociceptive transmission, the interaction of BmKNJX11 with TTX-S VGSC might lead to a change in excitability of nociceptive afferent fibers, which may be involved in the observed peripheral pain expression.

[Laparoscopic cholecystectomy with remote zeus surgical robotic system: report of 16 cases].

OBJECTIVE: To explore the methodology and operative essentials of laparoscopic cholecystectomy with remote Zeus surgical robotic system. METHODS: Based on strict training and successful experiment in animal model of swine, laparoscopic cholecystectomy using Zeus robotic system was performed on 16 patients with biliary diseases, including choledocholithiasis, cholelithiasis, polyposis of gallbladder, and chronic cholecystitis, 10 males and 16 females, aged 33 (14 approximately 27), 26 April to 31 August 2004. The general data, preoperative preparation time, operation time, amount of bleeding, complications, and hospitalization time were analyzed. RESULTS: All operations were performed without event. Along with the accumulation of experience the preoperative preparation time was shortened from 90 min to 30 min with an average of 41.7 min, and the operation time from 120 min to 30 min with an average of 64.4 min. The average amount of bleeding was 27.7 ml, and the average postoperative hospitalization time was 2.4 d. A telephone follow-up 30 days after operation showed no abnormality. CONCLUSION: Laparoscopic cholecystectomy with Zeus surgical robotic system is feasible and reliable with the advantages of clearer images in the field of operation, more precise handling, and remote surgery or education.