Prediction of endotracheal tube size in pediatric patients: Development and validation of machine learning models.

Objective: We aimed to construct and validate machine learning models for endotracheal tube (ETT) size prediction in pediatric patients. Methods: Data of 990 pediatric patients underwent endotracheal intubation were retrospectively collected between November 2019 and October 2021, and separated into cuffed and uncuffed endotracheal tube subgroups. Six machine learning algorithms, including support vector regression (SVR), logistic regression (LR), random forest (RF), gradient boosting tree (GBR), decision tree (DTR) and extreme gradient boosting tree (XGBR), were selected to construct and validate models using ten-fold cross validation in training set. The optimal models were selected, and the performance were compared with traditional predictive formulas and clinicians. Furthermore, additional data of 71 pediatric patients were collected to perform external validation. Results: The optimal 7 uncuffed and 5 cuffed variables were screened out by feature selecting. The RF models had the best performance with minimizing prediction error for both uncuffed ETT size (MAE = 0.275 mm and RMSE = 0.349 mm) and cuffed ETT size (MAE = 0.243 mm and RMSE = 0.310 mm). The RF models were also superior in predicting power than formulas in both uncuffed and cuffed ETT size prediction. In addition, the RF models performed slightly better than senior clinicians, while they significantly outperformed junior clinicians. Based on SVR models, we proposed 3 novel linear formulas for uncuffed and cuffed ETT size respectively. Conclusion: We have developed machine learning models with excellent performance in predicting optimal ETT size in both cuffed and uncuffed endotracheal intubation in pediatric patients, which provides powerful decision support for clinicians to select proper ETT size. Novel formulas proposed based on machine learning models also have relatively better predictive performance. These models and formulas can serve as important clinical references for clinicians, especially for performers with rare experience or in remote areas.

Infrared Laser Pulses Excite Action Potentials in Primary Cortex Neurons In Vitro.

Infrared neural modulation (INM) has been well studied in the peripheral nervous system (PNS) for potential clinical applications. However, limited research has been conducted on the central nervous systems (CNS). In this study, we aimed at investigating the feasibility of using pulsed infrared (IR) laser with a wavelength of 1940 nm to excite network activity of cultivated rat cortex neurons.We cultured rat cortex neurons, forming neural networks with spontaneous neural activity, on glass multi-electrode arrays (MEAs). Laser at a power of 600 mW and a pulse rate of 10 Hz were used to stimulate the neural networks using the optics of an inverted microscope. Pulse durations were varied from 200 µs to 1 ms. The spike rate was calculated to evaluate the change of the neural network activity during the IR stimuli and the corresponding frequency components of neural response were calculated to examine whether recorded spikes were evoked by the IR pulse or not. A temperature model was adapted from a previous study to estimate the temperature rise during laser pulsing.We observed that the IR irradiation with a pulse duration of 800 µs and 1 ms could excite neuronal action potentials. The temperature rose 18.5 and 23.9 °C, for pulse durations of 800 µs and 1 ms, respectively. Thus, in addition to previously shown inhibition of IR irradiation with a wavelength of 1550 nm, we demonstrate an optical method that can modulate neural network activity in vitro. The preliminary results from this paper also suggested that MEA recording technology coupled with a laser and microscope systems can be exploited as a new approach for future studies to understand mechanisms and characterize laser parameters of INM for CNS neurons.

Appropriate technologies for upgrading wastewater treatment plants: methods review and case studies in China.

Upgrading existing wastewater treatment plants (WWTPs) is a more challenging task than constructing new plants. The aim is usually to overcome overloading and to reduce pollution concentrations in the effluent. There are various methods that can be used to upgrade WWTPs. This article reviews some of the methodologies, such as inserting new tanks as additional treatment steps and modifying the WWTP by introducing new technologies. A number of effective technologies are reviewed in terms of their basic concepts, operational conditions, and treatment performances. Examples of WWTPs in China that have been successfully upgraded using these technologies are also highlighted.

Experimental demonstration of high sensitivity refractive index sensing based on magnetic plasmons in a simple metallic deep nanogroove array.

A high-performance wide-angle refractive index sensor based on a simple one-dimensional (1D) metallic deep nanogroove array with a high aspect ratio is experimentally fabricated and demonstrated. The 1D deep groove array is featured by the excitation of magnetic plasmon (MP), referring to an effective coupling of incident electromagnetic waves with a strong magnetic response induced inside the deep grooves. Utilizing the MP resonances that are extremely sensitive to the surrounding dielectric medium, we successfully achieve a refractive index sensitivity (RIS) up to ∼1300 nm/RIU, which is higher than that of most experimentally designed plasmonic sensors in the infrared region. Importantly, benefiting from angle-independent MP resonances with strong confinement of the magnetic field inside the deep grooves and strong electric field localization at the groove openings, we demonstrate wide-angle sensing capability valid in a broadband infrared region with an excellent linear dependence on the change of refractive index. Such a MP-based sensor, together with its simple 1D flat nature and ease of fabrication, has great potential for the practical design of high sensitive, cost-effective and compact sensing devices.

Activation of the STING-IRF3 pathway promotes hepatocyte inflammation, apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common result of obesity and metabolic syndrome. Hepatocyte injury and metabolic disorders are hallmarks of NAFLD. Stimulator of interferon genes (STING) and its downstream factor interferon regulatory factor 3 (IRF3) trigger inflammatory reaction in response to the presence of cytosolic DNA. STING has recently been shown to play an important role in early alcoholic liver disease. However, little is known about the role of STING-IRF3 pathway in hepatocyte injury. Here, we aimed to examine the effect of STING-IRF3 pathway on hepatocyte metabolism, inflammation and apoptosis. METHODS: We examined the activation of the STING-IRF3 pathway, a high-fat diet (HFD)-induced obese mouse model, and determined the role of this pathway in a free fatty acid (FFA)-induced hepatocyte inflammatory response, injury, and dysfunction in L-O2 human liver cells. RESULTS: STING and IRF3 were upregulated in livers of HFD-fed mice and in FFA-induced L-O2 cells. Knocking down either STING or IRF3 led to a significant reduction in FFA-induced hepatic inflammation and apoptosis, as evidenced by modulation of the nuclear factor κB (NF-κB) signaling pathway, inflammatory cytokines, and apoptotic signaling. Additionally, STING/IRF3 knockdown enhanced glycogen storage and alleviated lipid accumulation, which were found to be associated with increased expression of hepatic enzymes in glycolysis and lipid catabolism, and attenuated expression of hepatic enzymes in gluconeogenesis and lipid synthesis. CONCLUSIONS: Our results suggest that the STING-IRF3 pathway promotes hepatocyte injury and dysfunction by inducing inflammation and apoptosis and by disturbing glucose and lipid metabolism. This pathway may be a novel therapeutic target for preventing NAFLD development and progression.

Sensitivity of various body indices and visceral adiposity index in predicting metabolic syndrome among Chinese patients with adult growth hormone deficiency.

AIM: Adult growth hormone deficiency (AGHD) refers to decreased secretion of growth hormones in the adults, which is associated with increased clustering of conventional cardiovascular risk factors such as central obesity, insulin resistance and dyslipidemia. Metabolic syndrome (MetS), a recognized risk factor of cardiovascluar diseases, shares some clinical features. Given that the prevalence of MetS is on the rise in patients with AGHD, and that cardiovascular disease (CVD) is an important cause of morbidity and mortality in that population, the alternative, simple, non-invasive methods of assessing MetS among this population are needed. This study aims to determine the sensitivity of five anthropometric indices [Body mass index (BMI), Waist circumference (WC), Waist-to-hip ratio (WHR), Waist-to-height ratio (WHtR) and Visceral adiposity index (VAI)] in predicting metabolic syndrome in Chinese population-based patients with adult growth hormone deficiency. MATERIALS AND METHODS: A total of 96 Chinese patients with adult growth hormone deficiency were included in this study. They were compared with equal number of apparently healthy persons with similar characteristics (matched with age and gender) to the previous group. Anthropometric measurements including weight, height, serum lipids indices, blood pressure (BP), fasting plasma glucose (FPG), WC were measured. BMI, WHR, WHtR, and VAI were calculated. RESULTS AND DISCUSSION: AGHD patients with MetS had higher WC (91.00 ± 8.28 vs 78.01 ± 7.12), BMI (24.95 ± 2.91 VS 23.30 ± 2.80), WHR (0.92 ± 0.06 VS 0.87 ± 0.07), WHtR (0.53 ± 0.06 VS 0.47 ± 0.05), VAI [(5.59 (4.02, 7.55) VS 1.69 (0.87, 3.05)] levels in comparison to those without MetS. Meantime WC, BMI, WHR, WHtR, VAI was positively correlated to MetS components. ROC curve for participants with AGHD showed that VAI had the highest SS of 92% (BMI 0.812; WHR 0.706; WHtR 0.902; VAI 0.920, respectively) for prediction of MetS in AGHD. The optimal cutoff values for different adiposity markers in predicting MetS were as follows: WC (79.65), BMI (23.46); WHR (0.89); WHtR (0.54); VAI (2.29). CONCLUSION: In conclusion, our study showed all adiposity measures of interest present themselves as easy and practical tools for use in population studies and clinical practice for evaluating MetS in AGDH and VAI was identified as the best in Chinese AGHD patients among them.

Development of time resolved fluorescence microparticle-conjugated anti-human procalcitonin antibody for homogeneous immunoassay / 军事医学

Objective To develop europium (Ⅲ) [Eu (Ⅲ)] chelated microparticles for homogeneous immunoassay.Methods Anti-human PCT antibodies were labeled with Eu (Ⅲ) chelated nanoscale microparticles as the detection antibody,and another anti-human PCT antibody was labeled with biotin as the solid-phase antibody.Magnetic microspheres labeled with streptavidin were used to separate the complexes of Eu-IgM-PCT-IgM-Biotin.Results In the homogeneous immunoassay,the standard curve fit was not linear.The quadratic curve was Y =19170.12 + 75493.74X-26.00X2(r =0.9986).According to the standard curve,the limit of detection for PCT was 0.04 ng/ml.Conclusion The homogeneous immunoassay which uses Eu (Ⅲ) chelated microparticles is highly sensitive for detection of PCT recombinant antigens and may serve as a promising method to measure serum PCT levels in the future.

Lipid Accumulation Product: a Simple and Accurate Index for Predicting Metabolic Syndrome in Patients with Adult Growth Hormone Deficiency.

PURPOSE: It has been demonstrated that metabolic risk factors were increased in adult growth hormone deficiency (AGHD) patients. Lipid accumulation product (LAP) is a novel biomarker of central lipid accumulation related to risk of metabolic syndrome (MS), diabetes and cardiovascular disease. The aim of this study was to investigate the ability of LAP to identify MS in AGHD Patients. MATERIALS AND METHODS: In this cross-sectional study, 75 AGHD patients and 75 controls matched with age and gender were enrolled. The general anthropometries and blood biochemical indexes were measured. Body mass index(BMI), waist-hip ratio (WHR), LAP, HOMA-IR were calculated. Receiver operating characteristic (ROC) analysis was used to find out the cut-off points of LAP to predict MS. RESULTS: Compared with control group, waist circumference (WC), WHR, Systolic blood pressure (SBP), Diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG) and LAP were increased in AGHD group, while high density lipoprotein cholesterol (HDL-c) level was lower in AGHD group (P<0.05). The prevalence of MS was 41.3% in AGHD patients. AGHD patients with MS had significantly higher LAP levels compared to those without MS. LAP was highly correlated with components of MS. ROC analysis showed that LAP was a significant discriminator for MS in AGHD patients, and the optimal cutoff point of LAP to predict MS was 44.96 (96.8% sensitivity, 86.4% specificity). CONCLUSIONS: LAP was associated with MS and had a strong and reliable diagnostic accuracy for MS in AGHD patients.

Outdoor, indoor, and personal black carbon exposure from cookstoves burning solid fuels.

Black carbon (BC) emissions from solid fuel combustion are associated with increased morbidity and mortality and are important drivers of climate change. We studied BC measurements, approximated by particulate matter (PM2.5 ) absorbance, in rural Yunnan province, China, whose residents use a variety of solid fuels for cooking and heating including bituminous and anthracite coal, and wood. Measurements were taken over two consecutive 24-h periods from 163 households in 30 villages. PM2.5 absorbance (PMabs ) was measured using an EEL 043 Smoke Stain Reflectometer. PMabs measurements were higher in wood burning households (16.3 × 10(-5) /m) than bituminous and anthracite coal households (12 and 5.1 × 10(-5) /m, respectively). Among bituminous coal users, measurements varied by a factor of two depending on the coal source. Portable stoves (which are lit outdoors and brought indoors for use) were associated with reduced PMabs levels, but no other impact of stove design was observed. Outdoor measurements were positively correlated with and approximately half the level of indoor measurements (r = 0.49, P < 0.01). Measurements of BC (as approximated by PMabs ) in this population are modulated by fuel type and source. This provides valuable insight into potential morbidity, mortality, and climate change contributions of domestic usage of solid fuels.

Construction of conditionally replicating adenovirus expressing staphylococcal enterotoxin A gene: potential usefulness for anti-tumor therapies.

OBJECTIVE: The aim of this study was to construct a conditionally replicating adenovirus pPE3-SEA expressing staphylococcal enterotoxin A (SEA) gene. MATERIALS AND METHODS: A full-length SEA gene fragment was cloned into pENTR12 plasmid to obtain a recombinant viral plasmid pENTR12-SEA. The pENTR12-SEA plasmid was co-transfected into HEK293 cells along with pPE3-ccdB, which encoded for the virus backbone, to generate recombinant adenovirus pPE3-SEA vector. Amplified pPE3-SEA vectors were purified, and viral titer was determined using the 50% tissue culture infective dose method. RESULTS: The PCR, restriction enzyme digestion, and sequence analyses proved successful construction of replicating oncolytic adenovirus pENTR12-SEA and recombinant SEA expressing oncolytic adenovirus pPE3-SEA. The viral titer was 2.5 × 1010 pfu/ml. CONCLUSIONS: We successfully constructed conditionally replicating adenovirus pPE3-SEA which can be utilized for experimental studies of tumor-targeted therapies.

Optical stimulation of primary motor cortex with 980nm infrared neural stimulation.

To explore the penetration depth with short-wavelength infrared light, 980 nm pulse infrared light was used to stimulate the primary motor cortex of rat. The heating model was created to simulate the temperature distribution for 1875 nm and 980 nm infrared neural stimulation. Post-stimulus time histogram was used to observe the neural response induced by Infrared neural stimulation on primary motor cortex. The model predicted the penetration depth of 980 nm was deep into 1.2 mm. Cortical neural located between 500 µm to 1000 µm were successfully activated by 980 nm INS. The preliminary results suggested that, 980 nm pulse INS could serve as a candidate for deep tissue stimulation.

Regulation of IGF-1 but not TGF-ß1 by NGF in the smooth muscle of the inflamed urinary bladder.

Intraperitoneal injection of cyclophosphamide (CYP) causes hemorrhagic cystitis with excess growth of muscular layer leading to bladder hypertrophy; this could be attributable to changes in the expression profiles of growth factors in the inflamed urinary bladder. The growth factors characterized in the current study include nerve growth factor (NGF), insulin-like growth factor (IGF)-1, and transforming growth factor (TGF)-ß1. We found that following CYP injection for 8 h and 48 h, the mRNA levels of all three factors were increased in the inflamed bladder when compared to control. The level of NGF mRNA was mainly increased in the urothelium layer while the levels of IGF-1 mRNA and TGF-ß1 mRNA were increased in the smooth muscle layer. The level of NGF high affinity receptor TrkA mRNA was also increased in both the urothelium and the smooth muscle layers during bladder inflammation. When we blocked NGF action with NGF neutralizing antibody in vivo, we found that the up-regulation of IGF-1 in the inflamed bladder was reversed while the up-regulation of TGF-ß1 was not affected by NGF neutralization. The effect of NGF on regulating IGF-1 expression was further confirmed in bladder smooth muscle culture showing that exogenous NGF increased the mRNA level of IGF-1 after 30 min to 1 h stimulation. These results suggested that bladder inflammation induced region-specific changes in the expression profiles of NGF, IGF-1 and TGF-ß1. The up-regulation of NGF in the urothelium may have a role in affecting bladder smooth muscle cell physiology by regulating IGF-1 expression.

Application of electrophysiologic techniques in poor outcome prediction among patients with severe focal and diffuse ischemic brain injury.

OBJECTIVE: To explore various electrophysiologic examinations as predictors for poor outcome in patients with severe ischemic brain injury, by comparing the prognostic ability of EEG, short-latency somatosensory evoked potentials (SLSEP), and brain stem auditory evoked potentials (BAEP). METHODS: EEG, SLSEP, and BAEP were recorded in 161 patients with severe ischemic brain injuries (Glasgow Coma Scale ≤ 8), 77 with anoxic-ischemic encephalopathy after cardiopulmonary resuscitation, while 84 experienced massive hemispheric infarction at between 1 and 7 days after the onset. Outcomes were reviewed after 6 months using the Glasgow Outcome Scale. RESULTS: Six months after the onset, poor outcomes (Glasgow Outcome Scale, 1-2) were identified in 66 and 54 patients among the anoxic-ischemic encephalopathy and the massive hemispheric infarction group, respectively. By using the prognostic authenticity analysis of predictors, unfavorable EEG patterns, lack of EEG reactivity, pathologic N20 of SLSEP, and pathologic wave V of BAEP showed the high sensitivity (92.4%-97.0%, 95% confidence interval [CI]: 82.5%-99.5%), while bilateral absence of SLSEP N20 showed the highest specificity (100%, 95% CI: 67.9%-100%) and positive predictive value (100%, 95% CI: 90.4%-100%) in the anoxic-ischemic encephalopathy group. In the massive hemispheric infarction group, unfavorable EEG patterns showed the highest sensitivity (96.3%, 95% CI: 86.2%-99.4%) while bilateral absence of SLSEP N20 and BAEP wave V showed the highest specificity (100%, 95% CI: 85.9%-100%) and positive predictive value (100%, 95% CI: 80.8%-100%). CONCLUSIONS: The predictive power of electrophysiologic examinations is different according to the etiology of ischemic brain injury. Short-latency somatosensory evoked potentials (N20) can be considered the most powerful method to predict poor outcome in anoxic-ischemic encephalopathy. Combination of EEG (unfavorable EEG patterns) and SLSEP (N20)/BAEP (wave V) is best suited in massive hemispheric infarction to predict poor outcome.

Trace metals as biomarkers for eumelanin pigment in the fossil record.

Well-preserved fossils of pivotal early bird and nonavian theropod species have provided unequivocal evidence for feathers and/or downlike integuments. Recent studies have reconstructed color on the basis of melanosome structure; however, the chemistry of these proposed melanosomes has remained unknown. We applied synchrotron x-ray techniques to several fossil and extant organisms, including Confuciusornis sanctus, in order to map and characterize possible chemical residues of melanin pigments. Results show that trace metals, such as copper, are present in fossils as organometallic compounds most likely derived from original eumelanin. The distribution of these compounds provides a long-lived biomarker of melanin presence and density within a range of fossilized organisms. Metal zoning patterns may be preserved long after melanosome structures have been destroyed.

Effects of cyclic AMP on development and secondary metabolites of Monascus ruber M-7.

AIM: To study effects of cyclic adenosine monophosphate (cAMP) on development and secondary metabolites of Monascus ruber M-7. METHODS AND RESULTS: Plate culture, liquid-state fermentation (LSF) and solid-state fermentation (SSF) were used to evaluate effects of cAMP on colonial growth, spore formation and polyketide production of Strain M-7. The results revealed that the variation trends of colonial sizes, numbers of sexual spores and red pigment contents of M-7 were in a dose-dependent manner. And generally they increased and decreased with cAMP concentrations in the ranges of low cAMP concentrations and high cAMP concentrations, respectively. But the variation trends of numbers of asexual spores and citrinin production in both LSF and SSF were opposite to those of colonial sizes, sexual sporulation and red pigment. CONCLUSIONS: The regulation of cAMP on development and secondary metabolites in Strain M-7 was in a dose-dependent pattern. And red pigment might convert to citrinin under changing cAMP concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The effects of cAMP on Strain M-7 in SSF give a new clue to enhance beneficial polyketides and reduce citrinin produced by M. ruber.

Anatomic site variability in rat skeletal uptake and desorption of fluorescently labeled bisphosphonate.

OBJECTIVES: Bisphosphonates commonly used to treat osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system. MATERIALS AND METHODS: Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial, and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate. RESULTS: Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was the highest in oral, relative to axial and appendicular bones (P < 0.05). CONCLUSIONS: This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial, and appendicular bones of immune deficient rats.

Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in Chinese renal transplant recipients.

The aims of this study were to investigate the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Chinese renal transplant recipients, so as to help rational administration in clinical practice. We calculated pharmacokinetic parameters of tacrolimus from blood concentrations in steady state at day 28. Polymerase chain reaction restriction fragment length polymorphisms were used for CYP3A5 and MDR1 analysis. The results showed that the dose-adjusted area under the concentration time curve (AUC(0-12)) and renal clearance showed a significant difference between CYP3A5*1 carriers and the CYP3A5*3/*3 genotype (P < .01). In the following study, a distinction was made between carriers of CYP3A5*1/ vs CYP3A5*3/*3 seeking to investigate the influence of the MDR13435T>C polymorphism on tacrolimus pharmacokinetics. MDR1 3435T>C polymorphism did not affect any tacrolimus pharmacokinetic parameter in either group. Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC(0-12) of tacrolimus. In contrast, MDR1 3435T>C polymorphism was not an important factor in tacrolimus pharmacokinetics. Pharmacogenetic methods may be used prospectively to aid dose selection and individualize immunosuppressive therapy.

First Report of Tobacco curly shoot virus Infecting Pepper in China.

In recent years, whitefly-transmitted begomovirues (family Geminiviridae) have caused severe leaf curl disease on tobacco and tomato in southern China, but have not been found on pepper. In August 2009, pepper plants (Capsicum frutescens) grown in the field in Panzhihua City of Sichuan Province (southwestern China), from where the occurrence of begomoviruses has not been reported previously, showed stunting, leaf yellowing, and mild curling symptoms. To identify possible begomoviruses, total DNA was extracted from three infected pepper plants (SC117, SC118, and SC119) with typical symptoms. Using degenerate primer pair PA/PB specific for members of the genus Begomovirus (2), a 500-bp DNA fragment covering parts of the intergenic region and V2 gene of the genome of begomoviruses was amplified from all samples. No amplification was observed from healthy plant extracts. The PCR product from SC118 was cloned and two clones were chosen to be sequenced. Alignment of the partial DNA sequences revealed that the cloned products from isolate SC118 were nearly identical (98.5%) and most closely related to Tobacco curly shoot virus isolate Y35 (TbCSV-[China:Yunnan 35:2001]; Accession No. AJ420318) (96.9 and 97.3% identity, respectively). Therefore, the entire genome of isolate SC118 was sequenced. Overlap primers TbCSV-F(5'-CCGCCGTCTCAACTTCGACAG-3') and TbCSV-R(5'-ATCTGCTGGTCGCTTCGACAT-3') were designed to amplify the full-length genome of SC118. The complete genome sequence of SC118 was determined to be 2,746 nucleotides (Accession No. GU001879) long, with two open reading frames (ORFs) in the virion-sense strand and four ORFs in the complementary-sense strand, typical of the Old World begomoviruses. A comparison with other reported sequences of begomoviruses shows that the genome of SC118 shares the highest nucleotide sequence identity (99.7%) with TbCSV-[China:Yunnan 35:2001]. When PCR was used to detect TbCSV from the other two isolates (SC117 and SC119) with TbCSV specific primer pair Y35F1 and Y35+10R (4), which amplified the fragment covering the whole C2 and C3 genes and the partial C1 and V1 genes of the genome of TbCSV, an amplicon of approximately 1.0 kb was obtained from all samples. To determine whether a satellite molecule was associated with the three virus isolates, a universal betasatellite abutting primer pair (beta01 and beta02) was used (1). No amplification product was detected. In previous studies, it was demonstrated that only 11 isolates were associated with betasatellites among 39 TbCSV-infected, field-collected samples (3), and betasatellites could be associated with noncognate begomoviruses (4). Therefore, the three isolates examined in this study are too few to come to a conclusion that betasatellites are not associated with TbCSV infection of pepper plants. A detailed search for the presence of betasatellites needs to be conducted to draw a definitive conclusion. The above results confirmed that samples SC117, SC118, and SC119 were infected by TbCSV. To our knowledge, this is the first report of TbCSV on pepper in China. References: (1) R. W. Briddon et al. Mol. Biotechnol. 20:317, 2002. (2) D. Deng et al. Ann. Appl. Biol. 125:327, 1994. (3) Z. Li et al. Phytopathology 95:902, 2005. (4) L. Qing et al. Phytopathology 99:716, 2009.

Endogenous nerve growth factor regulates collagen expression and bladder hypertrophy through Akt and MAPK pathways during cystitis.

Type I collagen forms the main constituent of the extracellular matrix in visceral organs. We reported here that cyclophosphamide (CYP)-induced cystitis significantly increased the production of type I collagen in the inflamed bladder leading to increases in the bladder weight and the thickness of the bladder wall. The endogenous nerve growth factor (NGF) in the urinary bladder regulated type I collagen expression because the neutralizing NGF antibody attenuated cystitis-induced type I collagen up-regulation in the inflamed bladder. Neutralizing NGF antibody also subsequently reversed cystitis-induced increases in bladder weight. Further studies on the intermediate signaling pathways mediating NGF-induced type I collagen expression in the inflamed bladder during cystitis revealed that Akt, JNK, and ERK1/2 activities were increased in the inflamed bladder, whereas p38 MAPK remained unchanged. Suppression of endogenous NGF level with neutralizing NGF antibody significantly blocked the increased activity of Akt, JNK, and ERK1/2 in the inflamed bladder during cystitis. These results indicate that endogenous NGF plays an important role in the activation of Akt and MAPK in the urinary bladder and in bladder hypertrophy during cystitis.

Ala42S100A8 ameliorates psychological-stress impaired cutaneous wound healing.

Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological-stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site. It has been suggested that wound hypoxia may contribute to the mechanisms of impaired cutaneous wound healing in the mouse SKH-1 model. Optimal healing of a cutaneous wound is a stepwise repair program. In its early phase, an inflammatory oxidative burst generated by neutrophils is observed. About 40% of neutrophils cytosolic protein weight is comprised of two calcium binding proteins S100A8 and S100A9. Our previous work has shown that S100A8 act as an oxidation-sensitive repellent of human neutrophils in-vitro. Ala(42)S100A8, a site-directed mutant protein is resistant to oxidative inhibition and inhibits neutrophil recruitment in-vivo. Accordingly, we tested the hypothesis that S100A8 may ameliorate wound healing in this model. We examined the effect of wild-type and ala(42)S100A8 for their ability to ameliorate wound closure rates. The data indicated that a single local application of ala(42)S100A8 ameliorated the decreased rate of wound closure resulting from stress. This occurred without significantly affecting wound bacterial clearance. Wild-type S100A8 only had a partial beneficial effect on the rate of wound closure. Those findings support further translational studies of S100 based intervention to ameliorate impaired wound healing.