StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.

Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field. Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry. An algorithm named StrucGP is also developed to automate the interpretation process for large-scale analysis. By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes. Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures. The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.

Effectiveness of Acupuncture and Brief Telehealth Intervention for Individuals With Posttraumatic Stress Disorder.

PURPOSE: This open-trial pilot study evaluated the feasibility and effectiveness of acupuncture with brief therapy (ABT) for individuals with posttraumatic stress disorder (PTSD). METHOD: Participants included 27 individuals with PTSD diagnoses confirmed using the Clinician-Administered PTSD Scale for DSM-5. Before ABT, 22 participants completed eight acupuncture sessions and three telehealth sessions of a brief treatment program for PTSD (Brief Relaxation, Education, and Trauma Healing [BREATHE]). RESULTS: ABT significantly reduced PTSD symptoms, depression symptoms, anxiety, and improved trauma-related cognition. CONCLUSION: Acupuncture can play an important role in mental health recovery, and combining acupuncture with a brief, telehealth-based treatment (BREATHE) may assist recovery among individuals with PTSD. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

Role of lncRNAs in cis- and trans-regulatory responses to salt in Populus trichocarpa.

Long non-coding RNAs (lncRNAs) are emerging as versatile regulators in diverse biological processes. However, little is known about their cis- and trans-regulatory contributions in gene expression under salt stress. Using 27 RNA-seq data sets from Populus trichocarpa leaves, stems and roots, we identified 2988 high-confidence lncRNAs, including 1183 salt-induced differentially expressed lncRNAs. Among them, 301 lncRNAs have potential for positively affecting their neighboring genes, predominantly in a cis-regulatory manner rather than by co-transcription. Additionally, a co-expression network identified six striking salt-associated modules with a total of 5639 genes, including 426 lncRNAs, and in these lncRNA sequences, the DNA/RNA binding motifs are enriched. This suggests that lncRNAs might contribute to distant gene expression of the salt-associated modules in a trans-regulatory manner. Moreover, we found 30 lncRNAs that have potential to simultaneously cis- and trans-regulate salt-responsive homologous genes, and Ptlinc-NAC72, significantly induced under long-term salt stress, was selected for validating its regulation of the expression and functional roles of the homologs PtNAC72.A and PtNAC72.B (PtNAC72.A/B). The transient transformation of Ptlinc-NAC72 and a dual-luciferase assay of Ptlinc-NAC72 and PtNAC72.A/B promoters confirmed that Ptlinc-NAC72 can directly upregulate PtNAC72.A/B expression, and a presence/absence assay was further conducted to show that the regulation is probably mediated by Ptlinc-NAC72 recognizing the tandem elements (GAAAAA) in the PtNAC72.A/B 5' untranslated region (5'-UTR). Finally, the overexpression of Ptlinc-NAC72 produces a hypersensitive phenotype under salt stress. Altogether, our results shed light on the cis- and trans-regulation of gene expression by lncRNAs in Populus and provides an example of long-term salt-induced Ptlinc-NAC72 that could be used to mitigate growth costs by conferring plant resilience to salt stress.

A pilot study of wellness coaching for smoking cessation among individuals with mental illnesses.

BACKGROUND: Smoking continues to be a major health concern among persons with mental illnesses. AIMS: This pilot study compared smoking outcomes between wellness-coaching for smoking cessation and a control group. METHODS: Thirty-one individuals were enrolled in an educational group on smoking cessation and 23 completed an eight-session manualized education. Following this educational group, 11 of 23 participants were randomly assigned to wellness coaching for four months and 12 to a control condition. ANCOVAs were used to compare group differences in smoking outcomes. RESULTS: Fagerström Nicotine Dependence Index (FTND) score of the participants who received the wellness coaching intervention decreased significantly as compared to the control group, indicating a lower level of nicotine dependence. The outcomes of average number of cigarettes smoked daily and breath carbon monoxide level showed tendencies towards reductions for wellness coaching, although not statistically significant compared to the control condition. CONCLUSIONS: Suggestions are shared about the feasibility of wellness coaching as well as barriers and challenges learned in implementing such an intervention to assist individuals with mental illnesses in quitting or reducing smoking.

Healing Trauma While Staying at Home: Using Telehealth to Conduct a Brief Treatment Program for Posttraumatic Stress Disorder.

Studies suggest that a three-session brief treatment program (Brief Relaxation, Education, and Trauma Healing [BREATHE]) can help treat posttraumatic stress disorder (PTSD) and symptoms of trauma; however, the program has not been examined via telehealth. Thus, the current study evaluated the feasibility of BREATHE delivered via telehealth. The intervention included breathing retraining and psychoeducation about PTSD and trauma. Thirty participants from the community with confirmed PTSD diagnoses participated in this telehealth program. Treatment retention was high, and participants showed decreased PTSD symptoms, posttraumatic cognitions, depression, anxiety, overall psychiatric symptoms, and internalized stigma and increased resiliency at posttreatment and 3-month follow up. Results suggest that a telehealth brief treatment program for PTSD is feasible and effective for individuals with PTSD. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].

Increased Fibronectin Impairs the Function of Excitatory/Inhibitory Synapses in Hirschsprung Disease.

Although approximately 50% of cases have a known genetic defect, the precise pathogenesis of Hirschsprung disease (HSCR) is still unclear. We recently reported that expression of fibronectin (FN), which is involved in the migration, colonization, and differentiation of enteric neural crest cells (ENCCs), is increased in aganglionic colonic segments obtained from patients. We hypothesized that abnormally high levels of FN might play a role in the etiology of HSCR. Here, to test this hypothesis, we investigated aganglionic, transitional, and ganglionic colon segments from 63 children with HSCR and distal colon from thirty healthy Wistar rats at embryonic day 20, in addition to in vitro studies with PC12 Adh neural crest cells. We measured the protein and mRNA expression levels of FN, together with a panel of excitatory (VGLUT1, GluA1, GluN1, PSD-95, and NL-1) and inhibitory (GAD67, GABA AR-α1, NL-2, and SLC32) synaptic markers. Expression of all these synaptic markers was significantly decreased in aganglionic colon, compared to ganglionic colon, whereas expression of FN was significantly increased. In a neural crest cell line, PC12 Adh, knockdown of FN with small-interfering RNA increased the expression of synaptic markers. Co-culture of colons from embryonic day 20 rats with RGD recombinant protein, which contains the RGD motif of FN, reduced the expression of excitatory and inhibitory synaptic markers. These results are consistent with the idea that the etiology of HSCR involves aberrant overexpression of FN, which may impair synaptic function and enteric nervous system development, leading to motor dysfunction of intestinal muscles.

Aberrant Distributions of Collagen I, III, and IV in Hirschsprung Disease.

BACKGROUND: Hirschsprung disease (HSCR) is the most common congenital gut motility disorder, involving a severe anomaly of the enteric nervous system, and is characterized by functional intestinal obstruction due to lack of intrinsic innervation (aganglionosis) in the distal bowel. OBJECTIVE: The aim of this study was to examine the distribution patterns of collagens I (Col I), III (Col III), and IV (Col IV) in the enteric nervous system of HSCR patients, to determine whether or not collagen levels are altered in the aganglionic bowel. METHODS: We measured the expression levels of Col I, Col III, and Col IV in colonic muscle from 129 children with HSCR. The localizations of the 3 collagens and myenteric ganglia were assessed morphologically by immunofluorescence staining. western blots and real-time fluorescence quantitative polymerase chain reaction were performed to examine the relative levels of these collagens in aganglionic, transitional, and ganglionic colon segments. RESULTS: Immunoreactivities of Col I and Col III were high around and within myenteric ganglia in the ganglionic segment, moderate in the transitional segment, and weak in the aganglionic segment. Col IV immunoreactivity showed the opposite pattern, being lowest in the ganglionic segment and highest in the aganglionic segment. CONCLUSION: Col I and Col III are decreased and Col IV is increased in the distal colon of patients with HSCR.

Three-Dimensional Texture Feature Analysis of Pulmonary Nodules in CT Images: Lung Cancer Predictive Models Based on Support Vector Machine Classifier.

To extract texture features of pulmonary nodules from three-dimensional views and to assess if predictive models of lung CT images from a three-dimensional texture feature could improve assessments conducted by radiologists. Clinical and CT imaging data for three dimensions (axial, coronal, and sagittal) in pulmonary nodules in 285 patients were collected from multiple centers and the Cancer Imaging Archive after ethics committee approval. Three-dimensional texture feature values (contourlets), and clinical and computed tomography (CT) imaging data were built into support vector machine (SVM) models to predict lung cancer, using four evaluation methods (disjunctive, conjunctive, voting, and synthetic); sensitivity, specificity, the Youden index, discriminant power (DP), and F value were calculated to assess model effectiveness. Additionally, diagnostic accuracy (three-dimensional model, axial model, and radiologist assessment) was assessed using the area under the curves for receiver operating characteristic (ROC) curves. Cross-sectional data from 285 patients (median age, 62 [range, 45-83] years; 115 males [40.4%]) were evaluated. Integrating three-dimensional assessments, the voting method had relatively high effectiveness based on both sensitivity (0.98) and specificity (0.79), which could improve radiologist diagnosis (maximum sensitivity, 0.75; maximum specificity, 0.51) for 23% and 28% respectively. Furthermore, the three-dimensional texture feature model of the voting method has the best diagnosis of precision rate (95.4%). Of all three-dimensional texture feature methods, the result of the voting method was the best, maintaining both high sensitivity and specificity scores. Additionally, the three-dimensional texture feature models were superior to two-dimensional models and radiologist-based assessments.

Intact Glycopeptide Analysis of Influenza A/H1N1/09 Neuraminidase Revealing the Effects of Host and Glycosite Location on Site-Specific Glycan Structures.

Influenza H1N1 virus has posed a serious threat to human health. The glycosylation of neuraminidase (NA) could affect the infectivity and virulence of the influenza virus, but detailed site-specific glycosylation information of NA is still missing. In this study, intact glycopeptide analysis is performed on an influenza NA (A/H1N1/California/2009) that is expressed in human 293T and insect Hi-5 cells. The data indicate that three of four potential N-linked glycosylation sites are glycosylated, including one partial glycosylation site from both cell lines. The NA expressed in human cells has more complex glycans than that of insect cells, suggesting the importance of selecting an appropriate expression system for the production of functional glycoproteins. Different types of glycans are identified from different glycosites of NA expressed in human cells, which implies the site-dependence of glycosylation on NA. This study provides valuable information for the research of influenza virus as well as the functions of viral protein glycosylation.

Taurine improves low-level inorganic arsenic-induced insulin resistance by activating PPARγ-mTORC2 signalling and inhibiting hepatic autophagy.

Inorganic arsenic (iAs) is reportedly associated with the increased incidence of type 2 diabetes in the population. Here, we found that iAs exposure significantly decreased the expression of glycolytic genes and glycogen content and increased gluconeogenesis gene levels in C57/BL6J mice. The expression of peroxisome proliferator-activated receptor γ (PPARγ), and mechanistic target of rapamycin complex 2 (mTORC2) were decreased in the livers of iAs-treated mice. Furthermore, in iAs-treated HepG2 cells, we found that PPARγ agonist rosiglitazone (RGS) increased the expression of mTORC2, inhibited autophagy, and improved glucose metabolism. mTORC2 agonist palmitic acid inhibited autophagy and improved glucose metabolism as well as the autophagosome formation inhibitor 3-methyladenine. Taurine, a natural compound, reversed impaired glucose metabolism and decreased expression of PPARγ and mTORC2 induced by iAs in mice liver and HepG2 cells. These data indicated that taurine administration could ameliorate iAs-induced insulin resistance through activating PPARγ-mTORC2 signalling and subsequently inhibiting hepatic autophagy.

Contourlet-based hippocampal magnetic resonance imaging texture features for multivariant classification and prediction of Alzheimer's disease.

The study is aimed to assess whether the addition of contourlet-based hippocampal magnetic resonance imaging (MRI) texture features to multivariant models improves the classification of Alzheimer's disease (AD) and the prediction of mild cognitive impairment (MCI) conversion, and to evaluate whether Gaussian process (GP) and partial least squares (PLS) are feasible in developing multivariant models in this context. Clinical and MRI data of 58 patients with probable AD, 147 with MCI, and 94 normal controls (NCs) were collected. Baseline contourlet-based hippocampal MRI texture features, medical histories, symptoms, neuropsychological tests, volume-based morphometric (VBM) parameters based on MRI, and regional CMgl measurement based on fluorine-18 fluorodeoxyglucose-positron emission tomography were included to develop GP and PLS models to classify different groups of subjects. GPR1 model, which incorporated MRI texture features and was based on GPG, performed better in classifying different groups of subjects than GPR2 model, which used the same algorithm and had the same data as GPR1 except that MRI texture features were excluded. PLS model, which included the same variables as GPR1 but was based on the PLS algorithm, performed best among the three models. GPR1 accurately predicted 82.2% (51/62) of MCI convertors confirmed during the 2-year follow-up period, while this figure was 53 (85.5%) for PLS model. GPR1 and PLS models accurately predicted 58 (79.5%) vs. 61 (83.6%) of 73 patients with stable MCI, respectively. For seven patients with MCI who converted to NCs, PLS model accurately predicted all cases (100%), while GPR1 predicted six (85.7%) cases. The addition of contourlet-based MRI texture features to multivariant models can effectively improve the classification of AD and the prediction of MCI conversion to AD. Both GPR and LPS models performed well in the classification and predictive process, with the latter having significantly higher classification and predictive accuracies. Advances in knowledge: We combined contourlet-based hippocampal MRI texture features, medical histories, symptoms, neuropsychological tests, volume-based morphometric (VBM) parameters, and regional CMgl measurement to develop models using GP and PLS algorithms to classify AD patients.

Near-infrared-emitting NaYF4:Yb,Tm/Mn upconverting nanoparticle/gold nanorod electrochemiluminescence resonance energy transfer system for sensitive prostate-specific antigen detection.

An electrochemiluminescence resonance energy transfer (ECL-RET) system that detects prostate-specific antigen (PSA) was created. Near-infrared (NIR)-emitting NaYF4:Yb,Tm/Mn upconverting nanoparticles (UCNPs) are used as donors, and gold nanorods (GNRs) are used as acceptors. The ECL was enhanced nearly threefold by Mn2+ doping, with an emission peak appearing at an NIR wavelength of 808 nm. Anti-PSA 1 (Ab1) was bound to the surfaces of UCNPs after being modified with poly(acrylic acid) (PAA). As for acceptors, cetyltrimethylammonium bromide (CTAB)-capped GNRs were treated with 11-mercaptoundecanoic acid (MUDA) and then conjugated with Anti-PSA 2 (Ab2). When PSA was added, donors and acceptors were brought in close proximity through specific interactions of antibodies and antigens, resulting in high quenching efficiency levels. Under optimal conditions, the linear range of detection was 3.75-938 pg/mL for PSA (R = 0.999), with a detection limit as low as 3.16 pg/mL. This method can be applied to detect PSA in human serums with satisfactory results. Graphical abstract An electrochemiluminescence resonance energy transfer system was developed for determination of prostate-specific antigen using near-infrared-emitting NaYF4:Yb,Tm/Mn upconverting nanoparticles as donors and gold nanorods as acceptors.

A Retrospective Study on Efficacy of Pulsed Dye Laser and Intense Pulsed Light for the Treatment of Facial Telangiectasia.

Both pulsed dye laser (PDL) and intense pulsed light (IPL) systems have been demonstrated to be effective for treatment of facial telangiectasia, however there have been very few comparative studies between both treatments involving purely Asian patient populations. In this study, we performed a retrospective analysis to compare the efficacy of PDL and IPL systems for the treatment of facial telangiectasia. A total of 416 patients with facial telangiectasia who were treated by PDL or IPLs in our department from August 2012 to March 2015 were included in this study. The subjects received one of the following five treatments: PDL 595 nm (9-12 J/cm2), MaxG (500-670 nm & 870-1200 nm, 30-46 J/cm2), IPL (560-1200 nm, 18-24 J/cm2), M22 560 (560-1200 nm, 15-18 J/cm2), and M22 590 (590-1200 nm, 15-20 J/cm2). Each treatment had two sessions with 6-week intervals. The improvement percentage score in facial telangiectasia after the final treatment was evaluated by two non-treating physicians. We found almost all patients (less than 95.00%) had marked improvements or nearly complete clearance of the lesions after PDL 595 nm or MaxG treatment, as compared to 41.38%-56.58% patients in the other three groups that showed similar degrees of improvements. Both PDL 595 nm (9-12 J/cm2) and MaxG (500-670 nm & 870-1200 nm, 30-46 J/cm2) treatments resulted in significantly superior vessel clearance than the IPL systems with other wavelength bands (560-1200 nm or 590-1200 nm) and relatively lower fluence (15-24 J/cm2). Our results also suggested fluence levels account for the significant differences in the effectiveness delivered by different IPL systems. We concluded that PDL 595 nm and MaxG showed comparable clinical efficacy and both treatments resulted in most beneficial outcomes.

J Drugs Dermatol. 2017;16(11):1112-1116.

Correlates of Current Smoking Among Adults Served by the Public Mental Health System.

OBJECTIVE: As part of a study of health status among 457 adults with diagnostically heterogeneous serious mental illnesses served by the public mental health system in four U.S. states, we assessed predictors of current cigarette smoking. METHODS: We examined bivariate relationships between smoking status and risks for drug and alcohol use disorders, residential setting, parental status, and employment. Finally, we used multivariable logistic regression to predict current smoking, controlling for significant confounds. RESULTS: Of the total sample, 44% of participants reported that they currently smoked and most (62%) were moderately to severely nicotine-dependent. Those at high risk for drug use disorders were more than three times as likely and those at high risk for alcohol use disorders were more than twice as likely to smoke, compared to their counterparts with little or no drug or alcohol use disorder risk. Controlling for all other model variables including drug and alcohol disorder risk, current smokers were less likely to be parents and more likely to reside in supervised settings than nonsmokers. Younger people and those without a college degree were more likely to smoke, controlling for all other model variables. CONCLUSIONS: Given the high degree of comorbidity of smoking, alcohol disorders, and drug use disorders, the authors highlight the need for integrated interventions that address these issues simultaneously.

Enhancement of tolerance of Ganoderma lucidum to cadmium by nitric oxide.

Nitric oxide (NO) is considered as a signaling molecule involved in regulation of diverse physiological processes and stress responses in animals and plants. However, whether NO regulates fungal, particularly edible fungi, response to heavy metal stresses, is unknown. This study investigated the effect of nitric oxide on biological responses of mycelia of Ganoderma lucidum to cadmium (Cd) toxicity. Exposure of Ganoderma lucidum to Cd (400 µM) triggered production of H2O2 and O2(-) in the mycelia and further induced lipid peroxidation as well as sharply decrease of fresh biomass. However, such an effect can be reversed by exogenous supply of NO. Mycelia treated with 100 µM SNP accumulated less H2O2, O2(-), thiobarbituric acid reactive substances (TBARS), and fresh biomass of this treatment was improved. Treatment with SNP significantly increased activities of antioxidant enzyme (peroxidase and catalase) to resist Cd stress. Meanwhile, NO-mediated alleviation of Cd toxicity was closely related to the accumulated proline as well as reduced Cd accumulation. These results suggested that NO plays a crucial role in preventing the mycelia of Ganoderma lucidum from Cd toxicity.

Fates of nickel and fluoranthene during the bioremediation by Pleurotus eryngii in three different soils.

This study focused on the bioremediation role of Pleurotus eryngii in different characteristics soils contaminated with nickel (Ni) and fluoranthene. The results of bioremediation experiments showed that fluoranthene had a positive effect on the growth of P. eryngii, whereas Ni exerted a negative influence. The concentration of fluoranthene significantly decreased in inoculated soil accounting for 86.39-91.95% of initial concentration in soils and 71.46-81.76% in non-inoculated soils, which showed that the dissipation of fluoranthene was enhanced by mushroom inoculating. The highest removal rates of fluoranthene in sandy loam, loamy clay, and sandy soils reached to 87.81, 86.39, and 91.95%, respectively, which demonstrated that P. eryngii was more suitable for the bioremediation of sandy soil contaminated with fluoranthene. In addition, the presence of Ni tended to decrease the dissipation of fluoranthene in inoculated soil. Higher ligninolytic enzymes activities were detected in inoculated soils, resulting in the enhanced dissipation of fluoranthene in inoculated soils. Furthermore, P. eryngii had the ability to uptake Ni (4.88-39.53 mg kg-1 ) in co-contamination soil. In conclusion, the inoculating of P. eryngii was effective in remediating of Ni-fluoranthene co-contaminated soils.

Combined remediation of Cd-phenanthrene co-contaminated soil by Pleurotus cornucopiae and Bacillus thuringiensis FQ1 and the antioxidant responses in Pleurotus cornucopiae.

Remediation of soil co-contaminated with heavy metals and PAHs by mushroom and bacteria is a novel technique. In this study, the combined remediation effect of mushroom (Pleurotus cornucopiae) and bacteria (FQ1, Bacillus thuringiensis) on Cd and phenanthrene co-contaminated soil was investigated. The effect of bacteria (B. thuringiensis) on mushroom growth, Cd accumulation, phenanthrene degradation by P. cornucopiae and antioxidative responses of P. cornucopiae were studied. P. cornucopiae could adapt easily and grow well in Cd-phenanthrene co-contaminated soil. It was found that inoculation of FQ1 enhanced mushroom growth (biomass) and Cd accumulation with the increment of 26.68-43.58% and 14.29-97.67% respectively. Up to 100% and 95.07% of phenanthrene were removed in the bacteria-mushroom (B+M) treatment respectively spiked with 200mg/kg and 500mg/kg phenanthrene. In addition, bacterial inoculation alleviated oxidative stress caused by co-contamination with relative decreases in lipid peroxidation and enzyme activity, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). This study demonstrated that the integrated remediation strategy of bacteria and mushroom is an effective and promising method for Cd-phenanthrene co-contaminated soil bioremediation.

Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management.

OBJECTIVES: Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates. AIMS: (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations. METHODS: Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations. RESULTS: All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations. DISCUSSION: Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients' health, expenditure and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT01144338 and NCT00790205.

Dezocine as preemptive analgesia alleviates ultrapulse CO2 fractional laser treatment induced pain in patients with acne scars.

BACKGROUND: Ultrapluse CO2 fractional laser technology has emerged as an effective treatment for scar management. However, one drawback of this modality is the pain caused during the procedure. This study aims to explore the efficacy and safety of dezocine (DZC) as preemptive analgesia for reduction of pain induced by ultrapulse CO2 fractional laser treatment for acne scars. METHODS: The study cohort included 78 outpatients with acne scars between February and April 2023. Patients were randomly assigned into three groups with intravenous injection (iv) of DZC prior to laser treatment: (1) control, iv of saline; (2) DZC group 1 (DZC_1), iv of DZC at 0.15 mg/kg; and (3) DZC_2, iv of DZC at 0.20 mg/kg. After 30 min, one session of ultrapulse CO2 fractional laser treatment on acne scars was performed. Hemodynamics, visual analogue scale (VAS), and anxiety visual analog test (AVAT) were monitored prior to, during, and after the procedure. RESULTS: Operative success rates for patients in the control, DZC_1, and DZC_2 groups were 34.6%, 84.6%, and 100%, respectively. DZC administered with either dosage significantly reduced the VAS and AVAT scores of patients in treatment groups as compared with the subjects in the control group during the course of ultrapulse CO2 fractional laser treatment. Patients in DZC_1 and DZC_2 groups did not show any significant difference in hemodynamic parameters, VAS, and AVAT scores. Temporary adverse effects such as nausea and dizziness were observed in some subjects after treatment; the symptoms were quickly dissolved after a rest in supine position. CONCLUSIONS: DZC as preemptive analgesia could effectively reduce pain and anxiety induced by ultrapulse CO2 fractional laser treatment in patients. This study provided an option of preemptive anesthesia to minimize the pain and discomforts associated with laser treatments in clinical practices.

TRAF4-Mediated LAMTOR1 Ubiquitination Promotes mTORC1 Activation and Inhibits the Inflammation-Induced Colorectal Cancer Progression.

Mechanistic target of rapamycin complex 1 (mTORC1) is a conserved serine/threonine kinase that integrates various environmental signals to regulate cell growth and metabolism. mTORC1 activation requires tethering to lysosomes by the Ragulator-Rag complex. However, the dynamic regulation of the interaction between Ragulator and Rag guanosine triphosphatase (GTPase) remains unclear. In this study, that LAMTOR1, an essential component of Ragulator, is dynamically ubiquitinated depending on amino acid abundance is reported. It is found that the E3 ligase TRAF4 directly interacts with LAMTOR1 and catalyzes the K63-linked polyubiquitination of LAMTOR1 at K151. Ubiquitination of LAMTOR1 by TRAF4 promoted its binding to Rag GTPases and enhanced mTORC1 activation, K151R knock-in or TRAF4 knock-out blocks amino acid-induced mTORC1 activation and accelerates the development of inflammation-induced colon cancer. This study revealed that TRAF4-mediated LAMTOR1 ubiquitination is a regulatory mechanism for mTORC1 activation and provides a therapeutic target for diseases involving mTORC1 dysregulation.