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.

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.].

A case report of dangerous pelvic infundibulum ligament in the second trimester of pregnancy with massive hemorrhage.

RATIONALE: Abdominal pregnancy is a rare ectopic pregnancy and its diagnosis and treatment are more challenging than those of other ectopic pregnancies. Because of a variable pregnancy site, abdominal pregnancy is associated with an increased risk of fatal abdominal hemorrhage, and consequently, an increased risk of maternal death compared with intrauterine pregnancy. DIAGNOSES: Pelvic infundibulum ligament pregnancy complicated with massive hemorrhage. PATIENT CONCERNS: 42-year-old pregnant woman who did not undergo an obstetric examination during the first trimester presented with sudden abdominal pain during the second trimester. Abdominal pregnancy was confirmed after emergency treatment, causing difficulty in the comprehensive preoperative evaluation.Interventions: In order to save the patient life, we actively carried out surgical treatment. OUTCOMES: The patient recovered well after the operation and was discharged on the 11th postoperative day. Blood ß-human chorionic gonadotropin (ß-hCG) levels and routine blood test results were normal 1 month after the surgery, and the patient had recovered. LESSONS: Several challenges are encountered in the diagnosis of abdominal pregnancy with regard to insufficient economic, cultural, and medical resources. In case of ectopic pregnancies, surgery should be the first choice of treatment, and preparations of blood transfusion are essential to combat the risk of rapid hemorrhagic shock caused by placenta implantation in the infundibulum ligament of the pelvis. The operation must be performed by experienced obstetricians and gynecologists.

Ammonium Sulfite Slurry from Ammonia-Based Desulfurization Activates Water-Soluble Humic Substances from Lignite: Performance, Application, and Mechanism.

Both ammonium sulfite slurry (ASS) from ammonia-based desulfurization and lignite are waste materials with low value. In this work, an innovative method was developed by applying ASS in lignite activation to produce water-soluble humic substances (WHSs) with a high bioactivity and economic value. The optimal activation method was to mix lignite and ASS at a 4:1-liquid-solid ratio by vortex blender and then oscillate it for 30 min at 25 °C. Compared with that of the unactivated lignite (UAL), the yield of WHSs from activated lignite (AL) increased by 42.72%. WHSs from AL consisted of a large number of aliphatic carbons with low molecular weight and functional groups such as amides, amines, sulfonic acid groups, C-O, and so forth. Moreover, WHSs from AL at lower concentrations (2 mg/L) has a more obvious root-elongation-promoting effect than WHSs from UAL (10 mg/L). Activation experiment with the lignite-related model compounds revealed that ASS caused the breakage of Caliph-O, Caliph-Caliph, and Carom-Caliph linkages between aromatic rings. These findings provide a theoretical basis for the development of green and sustainable technologies for the beneficial reuse of ASS and lignite in agriculture.

Engineered Extracellular Vesicle-Delivered CRISPR/CasRx as a Novel RNA Editing Tool.

Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide-optimized and EVs-delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)-triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short-acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases.

Social media use and academic, social, and career development among college students with disabilities.

OBJECTIVE: This study explores the use of social media and its impact on the college life of students with disabilities. PARTICIPANTS: 341 college students who identified as having disabilities were recruited from two universities in the Northeastern United. METHODS: Multivariate multiple regression models examined the relationship between social media use and academic achievement, social connectedness, and work preparedness. RESULTS: The findings indicate that students' GPA was not associated with any social media use variables, but the time spent on using social media was negatively associated with the work hope and social connectedness. Social media learning was positively associated with work preparedness and social connectedness. CONCLUSIONS: The study findings suggest that social media used for learning purposes can have a positive impact on career and social development among college students with disabilities. However, the time spent for non-learning purposes did not show positive benefits.

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.

Study on Vertical Joint Performance of Single-Faced Superposed Shear Wall Based on Finite Element Analysis and Calculation.

In this paper, a new type of single-faced superposed shear wall system is proposed based on the single-faced superposed shear wall structure. The nonlinear finite element analysis of a new splicing form of single-faced superposed shear wall components is carried out by using the method of combining experimental research and ABAQUS finite element software analysis. The impact of noncolumn on the connection performance of vertical seam is studied. The analysis shows no significant difference in the effect of eliminating concealed column on the hysteretic performance and bearing capacity of the single-faced superposed shear wall with the joint. The single-faced composite shear wall with two different splicing forms presents bending-shear failure. The single-faced composite shear wall model without concealed column design can also maintain good overall performance and seismic behavior.

The experiences and impact on wellness among international students in the United States during the COVID-19 pandemic.

Objective Assessing experiences and impact on wellness among international students during the COVID-19 pandemic. Participants: 405 undergraduate and graduate international students from 65 countries studying at a large public university. Methods: An online, voluntary and anonymous survey consisting of 50 quantitative and qualitative questions was conducted through Qualtrics. Descriptive and frequency analyses were used. Results: 27% of the students had concerns about the changes in student visa status that could seriously disrupt their studies in the U.S. 66.2% of them reported a moderate level, 18.8% reported a high level of stress related to the pandemic. Students identified the highest confidence in getting tested for infection but the lowest confidence in getting treatment if infected. They preferred telehealth for mental health services. Conclusions: Universities can best help international students by assisting with student visa and international travel issues, access to treatment for COVID-19 infection and developing telehealth for mental health services.

A one-year follow-up study of changes in social media addiction and career networking among college students with disabilities.

OBJECTIVE: This one-year follow-up study examined the changes of impact of using social media among college students with disabilities from the initial survey. PARTICIPANTS: 193 students completed the follow-up survey of the 341 who agreed to participate. METHODS: Paired t-test compared the changes in social media usage between the two surveys. Multiple linear regressions examined the relationship of social media use variables and social media addiction, career networking, disability subtypes between the two surveys. RESULTS: The daily average time spent on social media remained similar over one year. However, the level of social media addiction increased, especially among male students. One positive change was that students spent more time using social media for career networking purposes. CONCLUSION: Public awareness and education of social media addiction should be raised. Additionally, students could benefit from being guided and encouraged to use social media for positive activities such as career networking.

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.

An AAV vaccine targeting the RBD of the SARS-CoV-2 S protein induces effective neutralizing antibody titers in mice and canines.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in catastrophic damage worldwide. Accordingly, the development of powerful, safe, easily accessible vaccines with long-term effectiveness is understood as an urgently needed countermeasure against this ongoing pandemic. Guided by this strong promise of using AAVs, we here designed, optimized, and developed an AAV-based vaccines (including AAV-RBD(max), AAV-RBD(wt), AAV-2xRBD, and AAV-3xRBD) that elicit strong immune responses against the RBD domain of the SARS-CoV-2 S protein. These immunogenic responses have proven long-lived, with near peak levels for at least six months in mice. Notably, the sera immunized with AAV-3xRBD vaccine contains powerful neutralizing antibodies against the SARS-CoV-2 pseudovirus. Further evidence proven that potent specific antibodies could also be elicited in canines after vaccination with AAV-3xRBD vaccine.

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.

Endogenous promoter-driven sgRNA for monitoring the expression of low-abundance transcripts and lncRNAs.

Detection of endogenous signals and precise control of genetic circuits in the natural context are essential to understand biological processes. However, the tools to process endogenous information are limited. Here we developed a generalizable endogenous transcription-gated switch that releases single-guide RNAs in the presence of an endogenous promoter. When the endogenous transcription-gated switch is coupled with the highly sensitive CRISPR-activator-associated reporter we developed, we can reliably detect the activity of endogenous genes, including genes with very low expression (<0.001 relative to Gapdh; quantitative-PCR analysis). Notably, we could also monitor the transcriptional activity of typically long non-coding RNAs expressed at low levels in living cells using this approach. Together, our method provides a powerful platform to sense the activity of endogenous genetic elements underlying cellular functions.

Nutrient Intake Differences Among Ethnic Groups and Risks of Depression.

The cultural background of participants has not been considered in studies of dietary intake and depression, even though food choices are affected by culture. This study aims to examine the dietary patterns of people from diverse backgrounds and the correlation of diet and risk of depression. Relationships between depression and nutrient intake were analyzed with 4747 adult respondents from NHANES data. Multiple regressions were used with depression as dependent variable. Nutrient intake pattern differed among ethnic groups. After considering demographic factors, total fat and protein intake ratio to energy were associated with depressive symptoms among Hispanic respondents. Among White, dietary fiber and sugar were associated with depressive symptoms, and among Black, energy was associated with depressive symptoms. Total sugar and dietary fiber were associated with depressive symptoms among Asian. The relationship between depressive symptoms and nutrient intake varied based on the cultural background of participants.

Self-Assembly of Hydrophobic and Self-Healing Bionanocomposite-Coated Controlled-Release Fertilizers.

Self-healing materials have received increased attention because of their automatic detecting and repairing damage function. In this paper, a novel self-assembly and self-healing bionanocomposite was developed as a coating material for controlled release fertilizers. This nanotechnology-enabled coating is environmentally friendly and highly efficient and possesses a tunable nutrient-releasing characteristic. In the synthesis process, bio-based polyurethane coated urea (BPCU) was prepared by the reaction of bio-polyols with isocyanate. The BPCU was then modified by the layer-by-layer technology to prepare self-assembling modified BPCU (SBPCU). Last, hollow nano-silica (HNS) particles loaded with the sodium alginate (SA) were used to modify SBPCU to fabricate of self-assembling and self-healing BPCU (SSBPCU). The results show that the self-assembled materials were synthesized through electrostatic adsorption. The self-healing was observed through scanning electron microscopy and 3D-X-ray computed tomography, revealing the mechanism was that the repair agent released from HNS reacted with the curing agent to block the pore channels and cracks of the coating. As a result, the SSBPCU exhibited the highest hydrophobicity and surface roughness and thus the slowest release rate. For the first time, this work has designed a novel strategy to solve the bottleneck problem that restricts the development of a controlled-release fertilizer.

Effect of Neuroligin1 and Neurexin1 on the Colonic Motility in a Mouse Model of Neuronal Intestinal Dysplasia.

AIM: To investigate the expressions of neuroligin1 (NL1) and neurexin1 (NX1) in a mouse model of neuronal intestinal dysplasia (Tlx2-/- mice) and to explore their effects on colonic motility. METHODS: Immunohistochemistry staining was employed to explore the histological appearances of NL1, NX1, the presynaptic marker of glutamatergic synapses VGLUT1, and the subunit of NMDA receptors of NR1 in the colon of mice with or without Tlx2 mutation. Western blotting and qRT-PCR were performed to detect their relative expressions in the colon. Colonic motility was measured by a glass bead technique. Then, the Tlx2-/- mice were intervened by Huperzine A. Variations on expressions of NL1, NX1, VGLUT1, and NR1 and variations on colonic motility were measured. Additionally, serum concentrations of Glu were measured by ELISA. RESULTS: Immunohistochemistry staining reveals that NL1, NX1, VGLUT1, and NR1 were mainly concentrated in the myenteric plexus of ENS. Compared to those in WT and Tlx2+/- mice, expressions of NL1 and NX1 in colon of Tlx2-/- mice were upregulated with increased VGLUT1 and NR1 abundances and impaired colonic motility (P < 0.05). After intervention, the upregulated expressions of NL1 and NX1 were decreased with a correlated reduce of VGLUT1 and NR1 and a recovery of the impaired colonic motility (P < 0.05). After intervention, the upregulated expressions of NL1 and NX1 were decreased with a correlated reduce of VGLUT1 and NR1 and a recovery of the impaired colonic motility (P < 0.05). After intervention, the upregulated expressions of NL1 and NX1 were decreased with a correlated reduce of VGLUT1 and NR1 and a recovery of the impaired colonic motility (. CONCLUSION: NL1 and NX1 are closely related to the colonic motility through their effects of targeting the formation of glutamatergic synapses and may be involved in the pathogenesis of NID. The variations of serum Glu seem to be a potential and less painful auxiliary measure for colonic motility and NID.

Paid work, household work, or leisure? Time allocation pathways among women following a cancer diagnosis.

BACKGROUND: There is extensive evidence on the relationship between receiving a cancer diagnosis and labour market outcomes. However, there is limited evidence on the relationship between a cancer diagnosis and non-labour market outcomes such as household work, passive leisure and physical leisure. Furthermore, most current research focuses on time allocation at a given time point, ignoring both the life course perspective and long term effects. METHODS: Using data from the Australian Longitudinal Study on Women's Health (ALSWH), we observe time allocation for 91 women diagnosed with breast cancer and 486 women diagnosed with skin cancer, and 2711 women living without cancer. Our analysis is unique in combining sequence analysis and multivariate multinomial logit modelling. Using sequence analysis, we first analyse life-courses post a cancer diagnosis for paid work, household work, passive leisure and physical leisure from 2004 to 2016. Using multivariate multinomial logit modelling, we test whether a cancer diagnosis influences such life-courses. We consider the robustness of results to cancer severity and change in time allocation before and after a cancer diagnosis. RESULTS: We identify three clusters for paid work and two clusters for household work, passive leisure and physical leisure. Neither a breast cancer nor skin cancer diagnosis has a significant effect on the pathways of time allocation. Such results are robust to severity of diagnosis with 'cured' and 'non-cured' breast cancer, and skin cancer treated with and without 'chemotherapy or radiotherapy'. Women post a breast cancer diagnosis are less likely to maintain their pre-cancer's time use on paid work, household work and passive leisure; however, such effects are not significant. CONCLUSION: Being diagnosed with breast cancer or skin cancer has no significant long-term effect on the pathways of time allocation. Future work should explore the relationship between time allocation and wellbeing and the preference for time allocation.

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.