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This study selected Trachinotus ovatus and Nibea albiflora as the focal subjects to investigate the impacts of probabilistic frequency of temperature increment through laboratory simulations that mimicked the seasonal water elevated temperature adjacent to two coastal nuclear power plants. This research was underpinned by the probabilistic analysis of temperature increase frequencies, aiming to evaluate the thermal tolerance of these species across different seasonal contexts. Results demonstrated that the T. ovatus did not exhibit mortality in the spring, autumn, and winter. Mortality in T. ovatus occurred only during the summer in temperature-duration probability experimental groups subjected to 8.5ºC above ambient temperature with exposure probabilities of 50%, 75%, and 100%. The average survival rates were (93.3±3.3) %, (93.3±5.1) %, and (86.7±2.9) % respectively. The N. albiflora experienced mortality in spring, summer, autumn, and winter, with the highest mortality rate in summer. Compared to N. albiflora, T. ovatus exhibited significantly higher thermal tolerance across all seasons. As the experimental temperature increased and the duration probability rose, the mortality rates of both fish species showed an upward trend. There was an interaction between elevated temperature and duration probability, with the duration of different elevated temperature amplitudes significantly impacting the fish's survival rates.

IntroductionThe relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC).MethodsData from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses.ResultsAmong 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction<0.001) and obese categories (pinteraction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers.ConclusionUnderweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.

BackgroundSomatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches.MethodsThrough analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status.ResultsOf 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients.ConclusionsWe introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC.ImpactThe proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

BACKGROUND: Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-derived RPE) are a promising source for cell-replacement therapy to treat retinal degenerative diseases, but research on RPE cryopreservation is limited. This study aimed to determine the best phase for RPE cryopreservation to preserve the post-thaw function and uncover the mechanism underlying RPE freezing tolerance. METHODS: hESC-derived RPE cells were cryopreserved at various time points after seeding. After thawing, the survival and attachment rates, RPE marker gene expression, apical-basal polarity, PEDF secretion, transepithelial resistance, and phagocytotic ability of post-thaw RPE cells were evaluated. RNA sequencing was performed on RPE cells at three-time points, differentially expressed genes were identified, and gene ontology, Kyoto encyclopedia of genes and genomes, and protein-protein interaction analyses were used to investigate the key pathways or molecules associated with RPE cell freezing tolerance. RESULTS: RPE frozen at passage 2 day 5 (P2D5) had the highest cell viability and attachment after thawing. They also retained properly localized expression of RPE marker genes and biological functions such as PEDF secretion, high transepithelial resistance, and phagocytic ability. The RNA-sequencing analysis revealed that RPE cells at P2D5 expressed high levels of cell cycle/DNA replication and ECM binding associated genes, as well as THBS1, which may serve as a possible hub gene involved in freezing tolerance. We also confirmed that the RPE cells at P2D5 were in the exponential stage with active DNA replication. CONCLUSIONS: We propose that freezing hESC-derived RPE cells during their exponential phase results in the best post-thawing outcome in terms of cell viability and preservation of RPE cell properties and functions. The high expression levels of the cell cycle and ECM binding associated genes, particularly THBS1, may contribute to better cell recovery at th

Mei Jiang1 *,* Qi Chen1 *,* Xiaoting Zhao,1 Yu Teng,1 Chenghong Yin,2 Wentao Yue1 1Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, People’s Republic of China; 2Departments of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wentao YueCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 251, Yaojiayuan Road, Chaoyang District, Beijing 100026, People’s Republic of ChinaEmail yuewt2000@yahoo.comChenghong YinDepartments of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 251, Yaojiayuan Road, Chaoyang District, Beijing 100026, People’s Republic of ChinaEmail modscn@126.comBackground: PFTK1, a novel cyclin-dependent kinase, plays pivotal roles in tumorigenesis. Cell motility and invasiveness could be enhanced by PFTK1 in various tumors. However, the function of PFTK1 in NSCLC metastasis remains unclear. In this study, the potential role of PFTK1 in NSCLC metastasis was determined.Materials and Methods: In this study, the potential function of PFTK1 in lung cancer patients was analyzed with the Kaplan–Meier plotter database. RNA interference-mediated knockdown of PFTK1 was established in two NSCLC cell lines (H1299 and 95C) to explore the role of PFTK1 in NSCLC. The efficacy of downregulation of PFTK1 was examined by Western blot and immunofluorescence. The role of PFTK1 in cell migration and invasion ability was detected by wound healing and transwell assays. The protein levels in lung cancer cells were determined by Western blot. Immunofluorescence analysis was used to evaluate the structure of filamentous actin.Results: Overexpression of PFTK1 was associated with the poor survival prognosis in NSCLC patients. PFTK1 knockdown cell

The original article [1] contains an error in the legend of Fig 5 whereby the descriptions for panels 5d and 5e are incorrect; as such, the corrected legend can be viewed below with its respective figure images.

The original article [1] contains an error in the legend of Fig 5 whereby the descriptions for panels 5d and 5e are incorrect; as such, the corrected legend can be viewed below with its respective figure images.

Xiaoting Zhao, Mei Jiang, Ziyu WangDepartment of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University /Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou, Beijing, People’s Republic of ChinaBackground: Tropomyosin 4 (TPM4) is a member of the tropomyosin family of actin-binding proteins. Abnormal level of TPM4 is found in several cancers, and TPM4 is considered as a potential detecting marker for ovarian cancer, breast cancer, colon cancer, keratoacanthoma and esophageal squamous cell carcinoma. In this paper, the function of TPM4 in lung cancer cell lines was determined.Materials and methods: TPM4 knockout cells were constructed by CRISPR/CAS9 technique. TPM4 overexpression cells were also constructed based on TPM4 knockout cells. Cell growth ability was detected by MTS assay. The potency of cell motility was investigated using transwell assay and wound scratch assay. The protein levels in lung cancer cells were determined by western-blot. Immunofluorescence technique was used to image the structure of F-actin.Results: As a result, TPM4 downregulation and TPM4 upregulation cell models were obtained successfully. Cell motility was inhibited by the suppression of TPM4 while cell migration was enhanced in TPM4 upregulated cells. But TPM4 was not involved in cell proliferation and EMT progression. Microfilaments were depolymerized result from the suppression of TPM4 expression. And F-actin assembly was increased when TPM4 was upregulated.Conclusion: In summary, TPM4 was able to promote cell motility by altering the actin cytoskeleton directly.Keywords: TPM4, cell migration, F-actin, lung cancer

Fengyan Wang,1,* Zhenyu Liang,1,* Yuqiong Yang,1 Luqian Zhou,1 Lili Guan,1 Weiliang Wu,1 Mei Jiang,1 Weijuan Shi,1 Kuimiao Deng,1 Jianhua Chen,2 Rongchang Chen1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, People’s Republic of China; 2Respiratory Medicine Department, Guangzhou Panyu Central Hospital, Guangzhou 511400, People’s Republic of China *These authors contributed equally to this work Purpose: The purpose of this study was to investigate the reproducibility of fluid-phase measurements in PBS-treated sputum supernatant, processed using the two-step method, of healthy and stable COPD individuals.Methods: Nine healthy subjects and 23 stable COPD patients provided sputum twice within 6 days. A two-step sputum processing method was used to obtain PBS-treated supernatant and sputum cells. Soluble protein markers and IgG and IgM autoantibody profiles in PBS supernatant were analyzed using customized microarrays. Repeatability of measurements was assessed by paired-sample testing and an intraclass correlation coefficient, then graphically reported by Bland–Altman plot.Results: There was no significant difference between the repeated detection of 8/10 types of soluble protein markers, all 13 types of IgG autoantibodies, and 12/13 types of corresponding IgM autoantibodies in PBS supernatant. The repeatability of measurements in PBS supernatant was substantial to very good for interleukin 6 (IL6), IL8, IL13, IL10, IL33, vascular endothelial growth factor, soluble receptor for advanced glycation end-products, and tumor necrosis factor-α; for IgG autoantibodies against aggrecan, centromere protein B (CENP-B), collagen II, collagen IV, cytochrome C, elastin, heat shock protein 47 (HSP47), HSP70, and La/Sjögren syndrome type B antigen; for

The degradation of phagosomes, derived from the ingestion of photoreceptor outer segment (POS) disk membranes, is a major role of the retinal pigment epithelium (RPE). Here, POS phagosomes were observed to associate with myosin-7a, and then kinesin-1, as they moved from the apical region of the RPE. Live-cell imaging showed that the phagosomes moved bidirectionally along microtubules in RPE cells, with kinesin-1 light chain 1 (KLC1) remaining associated in both directions and during pauses. Lack of KLC1 did not inhibit phagosome speed, but run length was decreased, and phagosome localization and degradation were impaired. In old mice, lack of KLC1 resulted in RPE pathogenesis that was strikingly comparable to aspects of age-related macular degeneration (AMD), with an excessive accumulation of RPE and sub-RPE deposits, as well as oxidative and inflammatory stress responses. These results elucidate mechanisms of POS phagosome transport in relation to degradation, and demonstrate that defective microtubule motor transport in the RPE leads to phenotypes associated with AMD.

The degradation of phagosomes, derived from the ingestion of photoreceptor outer segment (POS) disk membranes, is a major role of the retinal pigment epithelium (RPE). Here, POS phagosomes were observed to associate with myosin-7a, and then kinesin-1, as they moved from the apical region of the RPE. Live-cell imaging showed that the phagosomes moved bidirectionally along microtubules in RPE cells, with kinesin-1 light chain 1 (KLC1) remaining associated in both directions and during pauses. Lack of KLC1 did not inhibit phagosome speed, but run length was decreased, and phagosome localization and degradation were impaired. In old mice, lack of KLC1 resulted in RPE pathogenesis that was strikingly comparable to aspects of age-related macular degeneration (AMD), with an excessive accumulation of RPE and sub-RPE deposits, as well as oxidative and inflammatory stress responses. These results elucidate mechanisms of POS phagosome transport in relation to degradation, and demonstrate that defective microtubule motor transport in the RPE leads to phenotypes associated with AMD.

The present prospective, randomized, double-blind study aimed to determine the impact of transversus abdominis plane (TAP) block on propofol and remifentanil consumption, when administered by closed-loop titration guided by processed electroencephalography, i.e., bispectral index (BIS) values. Following institutional review board approval, 60 patients were scheduled for laparoscopic colectomy under general anesthesia. Patients were randomly assigned to receive bilateral TAP block with 20 ml 0.375% ropivacaine (TAP group) or 20 ml 0.9% saline [control (CON) group]. General anesthesia was maintained with propofol and remifentanil administration using closed-loop titration guided by BIS values. The primary outcome was perioperative propofol and remifentanil consumption. The secondary outcomes were hypertensive or hypotensive events requiring treatment, recovery time in PACU and time to first rescue analgesia following surgery. A total of 58 patients participated in the present study. At similar depths of anesthesia, as measured by BIS during the maintenance phase (45-55), patients who received TAP blocks required less propofol (4.2±1.3 vs. 5.5±1.6 mg/kg/h; P<0.001) and remifentanil (0.16±0.05 vs. 0.21±0.05 µg/kg/min; P<0.001). Time to extubation was significantly shorter in the TAP group (9.8±3.2 min) than in the CON group (14.2±4.9 min) (P<0.05). The requirement to treat hemodynamic change was also significantly lower (P<0.05). Pain score at 2 h after surgery was also significantly reduced in the TAP group compared with the CON group (P<0.05), whereas the time to first rescue analgesia was delayed in patients who received TAP block (P<0.05). Postoperative nausea and vomiting occurred at comparable rates in each group (P>0.05). In conclusion, TAP block combined with general anesthesia reduced propofol and remifentanil consumption, shortened time to tracheal extubation and promoted hemodynamic stability in laparoscopic colectomy.

Trypanosoma evansi, known as an animal trypanosome, is widely distributed in many countries of Africa, Asia and South America; it causes significant economic loss in these countries. A few cases have also occurred in some countries of Europe due to the importation of infected animals from endemic regions. Rare human T. evansi infections were attended by the health departments and international health organizations in these endemic countries. Trypanosoma lewisi, a cosmopolitan parasite of rats, sometimes found in humans, is currently considered as a zoonotic pathogen and has gained special attention from scientists and international health organizations such as the World Health Organization. The current study considered the serological screening of human infection by T. evansi and T. lewisi in a Chinese human population. None of the 622 samples was found positive for T. evansi infection using the card agglutination test for the trypanosome antigen Rotat 1.2, while, 2.41% of the examined serum samples exhibited some seropositivity to T. lewisi using enzyme-linked immunosorbent assay. No significant difference was found between the samples from areas in the South (Zhaoqing, Guangdong) and Central (Zhengzhou, Henan) China.

The present prospective, randomized, double-blind study aimed to determine the impact of transversus abdominis plane (TAP) block on propofol and remifentanil consumption, when administered by closed-loop titration guided by processed electroencephalography, i.e., bispectral index (BIS) values. Following institutional review board approval, 60 patients were scheduled for laparoscopic colectomy under general anesthesia. Patients were randomly assigned to receive bilateral TAP block with 20 ml 0.375% ropivacaine (TAP group) or 20 ml 0.9% saline [control (CON) group]. General anesthesia was maintained with propofol and remifentanil administration using closed-loop titration guided by BIS values. The primary outcome was perioperative propofol and remifentanil consumption. The secondary outcomes were hypertensive or hypotensive events requiring treatment, recovery time in PACU and time to first rescue analgesia following surgery. A total of 58 patients participated in the present study. At similar depths of anesthesia, as measured by BIS during the maintenance phase (45-55), patients who received TAP blocks required less propofol (4.2±1.3 vs. 5.5±1.6 mg/kg/h; P<0.001) and remifentanil (0.16±0.05 vs. 0.21±0.05 µg/kg/min; P<0.001). Time to extubation was significantly shorter in the TAP group (9.8±3.2 min) than in the CON group (14.2±4.9 min) (P<0.05). The requirement to treat hemodynamic change was also significantly lower (P<0.05). Pain score at 2 h after surgery was also significantly reduced in the TAP group compared with the CON group (P<0.05), whereas the time to first rescue analgesia was delayed in patients who received TAP block (P<0.05). Postoperative nausea and vomiting occurred at comparable rates in each group (P>0.05). In conclusion, TAP block combined with general anesthesia reduced propofol and remifentanil consumption, shortened time to tracheal extubation and promoted hemodynamic stability in laparoscopic colectomy.

Trypanosoma evansi, known as an animal trypanosome, is widely distributed in many countries of Africa, Asia and South America; it causes significant economic loss in these countries. A few cases have also occurred in some countries of Europe due to the importation of infected animals from endemic regions. Rare human T. evansi infections were attended by the health departments and international health organizations in these endemic countries. Trypanosoma lewisi, a cosmopolitan parasite of rats, sometimes found in humans, is currently considered as a zoonotic pathogen and has gained special attention from scientists and international health organizations such as the World Health Organization. The current study considered the serological screening of human infection by T. evansi and T. lewisi in a Chinese human population. None of the 622 samples was found positive for T. evansi infection using the card agglutination test for the trypanosome antigen Rotat 1.2, while, 2.41% of the examined serum samples exhibited some seropositivity to T. lewisi using enzyme-linked immunosorbent assay. No significant difference was found between the samples from areas in the South (Zhaoqing, Guangdong) and Central (Zhengzhou, Henan) China.

Zhu-Quan Su,1,* Wei-Jie Guan,1,* Shi-Yue Li,1,* Ming Ding,2 Yu Chen,1 Mei Jiang,1 Xiao-Bo Chen,1 Chang-Hao Zhong,1 Chun-Li Tang,1 Nan-Shan Zhong1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Zhongda Hospital of Southeast University, Medical School of Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Spirometry confers limited value for identifying small-airway disorders (SADs) in early-stage COPD, which can be detected with impulse oscillometry (IOS) and endobronchial optical coherence tomography (EB-OCT). Whether IOS is useful for reflecting small-airway morphological abnormalities in COPD remains unclear. Objectives: To compare the diagnostic value of spirometry and IOS for identifying SADs in heavy-smokers and COPD based on the objective assessment with EB-OCT. Methods: We recruited 59 COPD patients (stage I, n=17; stage II, n=18; stage III–IV, n=24), 26 heavy-smokers and 21 never-smokers. Assessments of clinical characteristics, spirometry, IOS and EB-OCT were performed. Receiver operation characteristic curve was employed to demonstrate the diagnostic value of IOS and spirometric parameters. Results: More advanced staging of COPD was associated with greater abnormality of IOS and spirometric parameters. Resonant frequency (Fres) and peripheral airway resistance (R5–R20) conferred greater diagnostic values than forced expiratory volume in one second (FEV1%) and maximal (mid-)expiratory flow (MMEF%) predicted in discriminating SADs in never-smokers from heavy-smokers (area under curve [AUC]: 0.771 and 0.753 vs 0.570 and 0.558, respectively), and heavy-smokers from patients with stage I COPD (AUC: 0.726 an

BackgroundDysfunction of the retinal pigment epithelium (RPE) is implicated in numerous forms of retinal degeneration. The readily accessible environment of the eye makes it particularly suitable for the transplantation of RPE cells, which can now be derived from autologous induced pluripotent stem cells (iPSCs), to treat retinal degeneration. For RPE transplantation to become feasible in the clinic, patient-specific somatic cells should be reprogrammed to iPSCs without the introduction of reprogramming genes into the genome of the host cell, and then subsequently differentiated into RPE cells that are well characterized for safety and functionality prior to transplantation.MethodsWe have reprogrammed human dermal fibroblasts to iPSCs using nonintegrating RNA, and differentiated the iPSCs toward an RPE fate (iPSC-RPE), under Good Manufacturing Practice (GMP)-compatible conditions.ResultsUsing highly sensitive assays for cell polarity, structure, organelle trafficking, and function, we found that iPSC-RPE cells in culture exhibited key characteristics of native RPE. Importantly, we demonstrate for the first time with any stem cell-derived RPE cell that live cells are able to support dynamic organelle transport. This highly sensitive test is critical for RPE cells intended for transplantation, since defects in intracellular motility have been shown to promote RPE pathogenesis akin to that found in macular degeneration. To test their capabilities for in-vivo transplantation, we injected the iPSC-RPE cells into the subretinal space of a mouse model of retinal degeneration, and demonstrated that the transplanted cells are capable of rescuing lost RPE function.ConclusionsThis report documents the successful generation, under GMP-compatible conditions, of human iPSC-RPE cells that possess specific characteristics of healthy RPE. The report adds to a growing literature on the utility of human iPSC-RPE cells for cell culture investigations on pathogenicity and for therapeuti

BackgroundDysfunction of the retinal pigment epithelium (RPE) is implicated in numerous forms of retinal degeneration. The readily accessible environment of the eye makes it particularly suitable for the transplantation of RPE cells, which can now be derived from autologous induced pluripotent stem cells (iPSCs), to treat retinal degeneration. For RPE transplantation to become feasible in the clinic, patient-specific somatic cells should be reprogrammed to iPSCs without the introduction of reprogramming genes into the genome of the host cell, and then subsequently differentiated into RPE cells that are well characterized for safety and functionality prior to transplantation.MethodsWe have reprogrammed human dermal fibroblasts to iPSCs using nonintegrating RNA, and differentiated the iPSCs toward an RPE fate (iPSC-RPE), under Good Manufacturing Practice (GMP)-compatible conditions.ResultsUsing highly sensitive assays for cell polarity, structure, organelle trafficking, and function, we found that iPSC-RPE cells in culture exhibited key characteristics of native RPE. Importantly, we demonstrate for the first time with any stem cell-derived RPE cell that live cells are able to support dynamic organelle transport. This highly sensitive test is critical for RPE cells intended for transplantation, since defects in intracellular motility have been shown to promote RPE pathogenesis akin to that found in macular degeneration. To test their capabilities for in-vivo transplantation, we injected the iPSC-RPE cells into the subretinal space of a mouse model of retinal degeneration, and demonstrated that the transplanted cells are capable of rescuing lost RPE function.ConclusionsThis report documents the successful generation, under GMP-compatible conditions, of human iPSC-RPE cells that possess specific characteristics of healthy RPE. The report adds to a growing literature on the utility of human iPSC-RPE cells for cell culture investigations on pathogenicity and for therapeuti

The airway epithelia initiate and modulate the inflammatory responses to various pathogens. The cystic fibrosis transmembrane conductance regulator-mediated Cl(-) secretion system plays a key role in mucociliary clearance of inhaled pathogens. We have explored the effects of Toxoplasma gondii, an opportunistic intracellular protozoan parasite, on Cl(-) secretion of the mouse tracheal epithelia. In this study, ATP-induced Cl(-) secretion indicated the presence of a biphasic short-circuit current (Isc) response, which was mediated by a Ca(2+)-activated Cl(-) channel (CaCC) and the cystic fibrosis transmembrane conductance regulator. However, the ATP-evoked Cl(-) secretion in T. gondii-infected mouse tracheal epithelia and the elevation of [Ca(2+)]i in T. gondii-infected human airway epithelial cells were suppressed. Quantitative reverse transcription-PCR revealed that the mRNA expression level of the P2Y2 receptor (P2Y2-R) increased significantly in T. gondii-infected mouse tracheal cells. This revealed the influence that pathological changes in P2Y2-R had on the downstream signal, suggesting that P2Y2-R was involved in the mechanism underlying T. gondii infection in airways. These results link T. gondii infection as well as other pathogen infections to Cl(-) secretion, via P2Y2-R, which may provide new insights for the treatment of pneumonia caused by pathogens including T. gondii.

The airway epithelia initiate and modulate the inflammatory responses to various pathogens. The cystic fibrosis transmembrane conductance regulator-mediated Cl(-) secretion system plays a key role in mucociliary clearance of inhaled pathogens. We have explored the effects of Toxoplasma gondii, an opportunistic intracellular protozoan parasite, on Cl(-) secretion of the mouse tracheal epithelia. In this study, ATP-induced Cl(-) secretion indicated the presence of a biphasic short-circuit current (Isc) response, which was mediated by a Ca(2+)-activated Cl(-) channel (CaCC) and the cystic fibrosis transmembrane conductance regulator. However, the ATP-evoked Cl(-) secretion in T. gondii-infected mouse tracheal epithelia and the elevation of [Ca(2+)]i in T. gondii-infected human airway epithelial cells were suppressed. Quantitative reverse transcription-PCR revealed that the mRNA expression level of the P2Y2 receptor (P2Y2-R) increased significantly in T. gondii-infected mouse tracheal cells. This revealed the influence that pathological changes in P2Y2-R had on the downstream signal, suggesting that P2Y2-R was involved in the mechanism underlying T. gondii infection in airways. These results link T. gondii infection as well as other pathogen infections to Cl(-) secretion, via P2Y2-R, which may provide new insights for the treatment of pneumonia caused by pathogens including T. gondii.

Haiying Lu,1,* Mei Jiang,2,* Lei Lu,3 Guo Zheng,1 Qiang Dong3 1Department of Neurology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, 2Department of Neurology, Shanghai Pudong New Area Gongli Hospital, Shanghai, 3Department of Neurology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Aim: The purpose of the study was to observe the ultrastructural changes of neuronal mitochondria in perihematomal brain tissue and assess the therapeutic potential of Huperzine A (HA, a mitochondrial protector) following intracerebral hemorrhage (ICH). Methods: Brain hemorrhage was induced in adult Sprague Dawley rats by injecting autologous blood into the striatum and then removing the brains 3, 6, 12, 24, or 48 hours later to analyze mitochondrial ultrastructure in a blinded manner. Parallel groups of ICH rats were treated with HA or saline immediately after ICH. Perihematomal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase-3 activation and cytochrome C translocation were tracked by immunoblots, and neurobehavioral test results were compared between the groups. Results: Mitochondria in perihematomal neurons demonstrated dramatic changes including mitochondrial swelling, intracristal dilation, and decreased matrix density. HA treatment decreased mitochondrial injury and apoptosis, inhibited caspase-3 activation and cytochrome C translocation, and improved behavioral recovery. Conclusion: These data show that ICH induces dramatic mitochondrial damage, and HA exhibits protective effects possibly through ameliorating mitochondrial injury and apoptosis. Collectively, these findings suggest a new direction for novel therapeutics. Keywords: apoptosis, intracerebral hemorrhage, mitochondria, huperzine A, neuroprotection

We investigate the problem of the maximum number of distinct primitively rooted squares in a string. In comparison to considering general strings, the number of distinct symbols in the string is introduced as an additional parameter of the problem. Let S(d,n) = max {s(x) | x is a (d,n)-string}, where s(x) denotes the number of distinct primitively rooted squares in a string x and a (d,n)-string denotes a string of length n with exactly d distinct symbols. Inspired by the d-step approach which was instrumental in Santos' tackling of the Hirsch conjecture, we introduce a (d,n-d) table with entries S(d,n) where d is the index for the rows and n-d is the index for the columns. We examine the properties of the S(d,n) function in the context of (d,n-d) table and conjecture that the value of S(d,n) is no more than n-d. We present several equivalent properties with the conjecture. We discuss the significance of the main diagonal of the (d,n-d) table, i.e. the square-maximal (d, 2d)-strings for their relevance to the conjectured bound for all strings. We explore their structural properties under both assumptions, complying or not complying with the conjecture, with the intention to derive a contradiction. The result yields novel properties and statements equivalent with the conjecture with computational application to the determination of the values S(d,n). To further populate the (d,n-d) table, we design and implement an efficient computational framework for computing S(d,n). Instead of generating all possible (d,n)-strings as the brute-force approach needs to do, the computational effort is significantly reduced by narrowing down the search space for square-maximal strings. With an easily accessible lower bound obtained either from the previously computed values inductively or by an effective heuristic search, only a relatively small set of candidate strings that might possibly exceed the lower bound is generated. To this end, the notions of s-cover and th, Doctor of Philosophy (PhD)

Toxoplasma gondii infects humans and warm blooded animals causing devastating disease worldwide. It has long been a mystery as to why the peritoneal macrophages of rats are naturally resistant to T. gondii infection while those of mice are not. Here, we report that high expression levels and activity of inducible nitric oxide synthase (iNOS) and low levels of arginase-1 (Arg 1) activity in the peritoneal macrophages of rats are responsible for their resistance against T. gondii infection, due to high nitric oxide and low polyamines within these cells. The opposite situation was observed in the peritoneal macrophages of mice. This discovery of the opposing functions of iNOS and Arg 1 in rodent peritoneal macrophages may lead to a better understanding of the resistance mechanisms of mammals, particularly humans and livestock, against T. gondii and other intracellular pathogens.

Toxoplasma gondii infects humans and warm blooded animals causing devastating disease worldwide. It has long been a mystery as to why the peritoneal macrophages of rats are naturally resistant to T. gondii infection while those of mice are not. Here, we report that high expression levels and activity of inducible nitric oxide synthase (iNOS) and low levels of arginase-1 (Arg 1) activity in the peritoneal macrophages of rats are responsible for their resistance against T. gondii infection, due to high nitric oxide and low polyamines within these cells. The opposite situation was observed in the peritoneal macrophages of mice. This discovery of the opposing functions of iNOS and Arg 1 in rodent peritoneal macrophages may lead to a better understanding of the resistance mechanisms of mammals, particularly humans and livestock, against T. gondii and other intracellular pathogens.

Black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) are two atmospheric pollutants produced by motor vehicles using carbonaceous fuels. As a part of the Mexico City Project, measurements of BC, PPAHs and many other gas- and particle-phase emissions were measured in Mexico City using a mobile laboratory during the Mexico City Metropolitan Area field campaign in April 2003 (MCMA-2003). The main goal of this research is to estimate emissions of BC and particulate PAHs (PPAHs) for Mexico City's vehicle fleet. The emissions of gas-phase pollutants such as carbon monoxide (CO), total nitrogen oxides (NOy) and volatile organic compounds (VOC) are also estimated. The mobile lab has previously been used to chase vehicles and measure their emissions, but analysis has traditionally focused on determining emission factors of individual vehicles associated with specific chasing events. The laboratory continuously samples ambient air from an inlet at the front of the van, and it is always "seeing" exhaust plumes from the vehicles around it while driving through traffic. We have developed an algorithm that automatically identifies the exhaust plume measurement points, which are then used as the basis for calculation of emission factors. In the nearly 90 hours of on-road sampling during the field campaign, we have identified ~30,000 exhaust measurement points. The large sample size enables us to estimate fleet-average emission factors and thus the emission inventory. Motor vehicles are estimated to emit annually 1,960 tons of BC, 56.2 tons of PPAHs, 1,320,000 tons of CO, 125,000 tons of NOy and 2440 tons of VOCs. The spatial and temporal patterns of BC and PPAHs in different locations with in MCMA are also studied.

The paper describes the geographical distribution of loess and the associated characteristics and explains the meaning of representation of loess landforms on large-scale maps. The various types of loess landform are systematically classified and tabulated. The classification of types required for the preparation of topographical maps is achieved through field experiments. Loess landforms, such as valley, plateau, ridge, knoll and platform, their characteristics and contour profiles are examined. The principles of cartographic representation and synthesis are discussed. Configurations from similar type regions are presented as examples. (Author), Trans. of Ts'e Hui Hsueh Pao (Mainland China) v9 n1 p44-62 1966.