Functional loss of ERBB receptor feedback inhibitor 1 (MIG6) promotes glioblastoma tumorigenesis by aberrant activation of epidermal growth factor receptor (EGFR).

Dysregulation of epidermal growth factor receptor (EGFR) is one of the most common mechanisms associated with the pathogenesis of various cancers. Mitogen-inducible gene 6 [MIG6; also known as ERBB receptor feedback inhibitor 1 (ERRFI1)], identified as a feedback inhibitor of EGFR, negatively regulates EGFR by directly inhibiting its kinase activity and facilitating its internalization, subsequently leading to degradation. Despite its proposed role as an EGFR-dependent tumor suppressor, the functional consequences and clinical relevance in cancer etiology remain incompletely understood. Here, we identify that the stoichiometric balance between MIG6 and EGFR is crucial in promoting EGFR-dependent oncogenic growth in various experimental model systems. In addition, a subset of ERRFI1 (the official gene symbol of MIG6) mutations exhibit impaired ability to suppress the enzymatic activation of EGFR at multiple levels. In summary, our data suggest that decreased or loss of MIG6 activity can lead to abnormal activation of EGFR, potentially contributing to cellular transformation. We propose that the mutation status of ERRFI1 and the expression levels of MIG6 can serve as additional biomarkers for guiding EGFR-targeted cancer therapies, including glioblastoma.

Socioeconomic status and cardiovascular mortality in over 170,000 cancer survivors.

AIMS: Cardiovascular health is acknowledged as a crucial concern among cancer survivors. Socioeconomic status (SES) is an essential but often neglected risk factor for cardiovascular disease (CVD). We conducted this study to identify the relationship between SES and CVD mortality in cancer survivors. METHODS AND RESULTS: Using the National Health Insurance Service-National Health Examinee database, we identified cancer survivors diagnosed and surviving beyond 5 years post-diagnosis. SES was assessed based on insurance premiums and classified into 5 groups. The primary outcome was overall CVD mortality. This study analyzed 170 555 individuals (mean age 60.7 ± 11.9 years, 57.8% female). A gradual increase in risk was observed across SES groups: adjusted hazard ratios (95% confidence intervals) for overall CVD mortality were 1.15 (1.04-1.26), 1.28 (1.15-1.44), 1.31 (1.18-1.46), and 2.13 (1.30-3.49) for the second, third, and fourth quartile, and medical aid group (the lowest SES group) compared to the highest SES group, respectively (p for trend < 0.001). The lowest SES group with hypertension exhibited a 3.4-fold higher risk of CVD mortality compared to the highest SES group without hypertension. Interaction analyses revealed that low SES synergistically interacts with hypertension, heightening the risk of CVD mortality (synergy index 1.62). CONCLUSION: This study demonstrates a significant correlation between low SES and increased CVD mortality among cancer survivors. Particularly, the lowest SES group, when combined with hypertension, significantly escalates CVD mortality. Our findings underscore the critical importance of recognizing SES as a significant risk factor for CVD mortality in this population of cancer survivors.

Our population-based cohort study, involving over 170 000 cancer survivors, demonstrates a significant association between socioeconomic status (SES) and cardiovascular disease (CVD) mortality.

Digital technology revolutionizing mandibular fracture treatment: a comparative analysis of patient-specific plates and conventional titanium plates.

OBJECTIVES: The treatment of fractures prioritizes the restoration of functionality through the realignment of fractured segments. Conventional methods, such as titanium plates, have been employed for this purpose; however, certain limitations have been observed, leading to the development of patient-specific plates. Furthermore, recent advancements in digital technology in dentistry enable the creation of virtual models and simulations of surgical procedures. The aim was to assess the clinical effectiveness of patient-specific plates utilizing digital technology in treating mandibular fractures compared to conventional titanium plates. MATERIALS AND METHODS: Twenty patients diagnosed with mandibular fractures were included and randomly assigned to either the study or control groups. The surgical procedure comprised reduction and internal fixation utilizing patient-specific plates generated through virtual surgery planning with digital models for the study group, while the control group underwent the same procedure with conventional titanium plates. Assessment criteria included the presence of malunion, infection, sensory disturbance, subjective occlusal disturbance and occlusal force in functional maximum intercuspation (MICP). Statistical analysis involved using the Chi-square test and one-way repeated measures analysis of variance. RESULTS: All parameters showed no statistically significant differences between the study and control groups, except for the enhancement in occlusal force in functional MICP, where a statistically significant difference was observed (p = 0.000). CONCLUSION: Using patient-specific plates using digital technology has demonstrated clinical effectiveness in treating mandibular fractures, offering advantages of time efficiency and benefits for less experienced surgeons. CLINICAL RELEVANCE: Patient-specific plates combined with digital technology can be clinically effective in mandibular fracture treatment.

Improving nutrients ratio in class A biosolids through vivianite recovery: Insights from a wastewater resource recovery facility.

Class A biosolids from water resource recovery facilities (WRRFs) are increasingly used as sustainable alternatives to synthetic fertilizers. However, the high phosphorus to nitrogen ratio in biosolids leads to a potential accumulation of phosphorus after repeated land applications. Extracting vivianite, an FeP mineral, prior to the final dewatering step in the biosolids treatment can reduce the P content in the resulting class A biosolids and achieve a P:N ratio closer to the 1:2 of synthetic fertilizers. Using ICP-MS, IC, UV-Vis colorimetric methods, Mössbauer spectroscopy, and SEM-EDX, a full-scale characterization of vivianite at the Blue Plains Advanced Wastewater Treatment Plant (AWTTP) was surveyed throughout the biosolids treatment train. Results showed that the vivianite-bound phosphorus in primary sludge thickening, before pre-dewatering, after thermal hydrolysis, and after anaerobic digestion corresponded to 8 %, 52 %, 40 %, and 49 % of the total phosphorus in the treatment influent. Similarly, the vivianite-bound iron concentration also corresponded to 8 %, 52 %, 40 %, and 49 % of the total iron present (from FeCl3 dosing), because the molar ratio between total iron and total incoming phosphorus was 1.5:1, which is the same stoichiometry of vivianite. Based on current P:N levels in the Class A biosolids at Blue Plains, a vivianite recovery target of 40 % to ideally 70 % is required in locations with high vivianite content to reach a P:N ratio in the resulting class A biosolid that matches synthetic fertilizers of 1:1.3 to 1:2, respectively. A financial analysis on recycling iron from the recovered vivianite had estimated that 14-25 % of Blue Plain's annual FeCl3 demand can potentially be met. Additionally, model simulations with Visual Minteq were used to evaluate the pre-treatment options that maximize vivianite recovery at different solids treatment train locations.

mTORC1-CTLH E3 ligase regulates the degradation of HMG-CoA synthase 1 through the Pro/N-degron pathway.

Mammalian target of rapamycin (mTOR) senses changes in nutrient status and stimulates the autophagic process to recycle amino acids. However, the impact of nutrient stress on protein degradation beyond autophagic turnover is incompletely understood. We report that several metabolic enzymes are proteasomal targets regulated by mTOR activity based on comparative proteome degradation analysis. In particular, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) synthase 1 (HMGCS1), the initial enzyme in the mevalonate pathway, exhibits the most significant half-life adaptation. Degradation of HMGCS1 is regulated by the C-terminal to LisH (CTLH) E3 ligase through the Pro/N-degron motif. HMGCS1 is ubiquitylated on two C-terminal lysines during mTORC1 inhibition, and efficient degradation of HMGCS1 in cells requires a muskelin adaptor. Importantly, modulating HMGCS1 abundance has a dose-dependent impact on cell proliferation, which is restored by adding a mevalonate intermediate. Overall, our unbiased degradomics study provides new insights into mTORC1 function in cellular metabolism: mTORC1 regulates the stability of limiting metabolic enzymes through the ubiquitin system.

Developing MiR-133a Zipper Nanoparticles for Targeted Enhancement of Thermogenic Adipocyte Generation.

Existing delivery methods for RNAi therapeutics encounter challenges, including stability, specificity, and off-target effects, which restrict their clinical effectiveness. In this study, a novel miR-133a zipper nanoparticle (NP) system that integrates miRNA zipper technology with rolling circle transcription (RCT) to achieve targeted delivery and specific regulation of miR-133a in adipocytes, is presented. This innovative approach can greatly enhance the delivery and release of miR-133a zippers, increasing the expression of thermogenic genes and mitochondrial biogenesis. he miR-133a zipper NP is utilized for the delivery of miRNA zipper-blocking miR-133a, an endogenous inhibitor of Prdm16 expression, to enhance the thermogenic activity of adipocytes by modulating their transcriptional program. Inhibition of miR-133a through the miR-133a zipper NP leads to more significant upregulation of thermogenic gene expression (Prdm16 and Ucp1) than with the free miR-133a zipper strand. Furthermore, miR-133a zipper NPs increase the number of mitochondria and induce heat production, reducing the size of 3D adipose spheroids. In short, this study emphasizes the role of RNA NPs in improving RNAi stability and specificity and paves the way for broader applications in gene therapy. Moreover, this research represents a significant advancement in RNAi-based treatments, pointing toward a promising direction for future therapeutic strategies.

Advancements in computer-assisted orthognathic surgery: A comprehensive review and clinical application in South Korea.

OBJECTIVES: Orthognathic surgery (OS) has evolved with technological advancements, notably through the implementation of computer-assisted orthognathic surgery (CAOS). This article aims to elucidate various types of CAOS and their efficiency and accuracy, supplemented by a thorough literature review focusing on their clinical applications in South Korea. STUDY SELECTION, DATA, AND SOURCES: A comprehensive search strategy was employed, including systematic reviews, meta-analyses, randomized controlled trials, and observational studies published until December 2023 in the PubMed, MEDLINE, and Google Scholar databases. The literature search was limited to articles written in English. RESULTS: Static CAOS demonstrated high precision, reduced operative time, and high accuracy, suggesting its potential reliability in orthognathic procedures. Dynamic CAOS presented a promising avenue for exploration, showing an accuracy comparable to that of traditional methods. The critical considerations for CAOS include accuracy, time efficiency, and cost-effectiveness. Recent studies have indicated advancements in the time efficiency of static CAOS. Static CAOS requires less equipment and is more cost-effective than dynamic CAOS. CONCLUSIONS: CAOS offers clear advantages over conventional OS in terms of surgical convenience and accuracy in implementing the surgical plan. To achieve recognition as the gold standard method for maxillofacial deformity treatment, CAOS must overcome its limitations and undergo continuous verification via well-designed studies. CLINICAL SIGNIFICANCE: The introduction of CAOS, mainly static CAOS with high precision and reduced surgical time, signifies a notable advancement in OS. However, rigorous studies are warranted to validate CAOS as the gold standard for treating maxillofacial deformities.

Antecedents and outcomes of cyberbullying among Chinese university students: verification of a behavioral pathway model.

Introduction: Cyberbullying is a commonly-seen and hotly-debated social topic around the globe. This negative behavior is the source of many disastrous events, and so leading government bodies, organizations, schools and social communities attach great importance to addressing this topic. However, there is still much work to do in order to be clear about the causes of cyberbullying. Methods: The previous research cases were mostly viewed from the victims' perspectives; however, there is no comprehensive understanding of the perpetrators' viewpoints. Therefore, based on Social Cognitive Theory (SCT) and analysis of discussion in the literature, the following six variables were chosen as the focus of this study: overconfidence, excessive moral sense, cyberbullying, perceived value, happiness, and continued cyberbullying intention. This study established a research model of continued cyberbullying intention, which was verified by Structural Equation Modeling. In order to achieve the aims of the study, Chinese university students with an average age of 20.29 (SD = 1.43) were recruited as participants, from whom 1,048 valid questionnaires were collected. Results: The research results are as follows: 1. Overconfidence and excessive moral sense positively predicted cyberbullying behaviors; 2. Overconfidence positively predicted excessive moral sense; 3. Cyberbullying positively predicted perceived value and sense of happiness; and 4. Perceived value and sense of happiness positively predicted continued cyberbullying intentions. Conclusion: Students' biased self-perception significantly predicts their cyberbullying behaviors and continued cyberbullying intention. What is more, it is interesting to learn that perpetrators will continue to exhibit cyberbullying behaviors when they believe that what they do (cyberbullying) is valuable or allows them to experience positive feelings; this requires our attention.

A Comparative Analysis of Artificial Intelligence and Manual Methods for Three-Dimensional Anatomical Landmark Identification in Dentofacial Treatment Planning.

With the growing demand for orthognathic surgery and other facial treatments, the accurate identification of anatomical landmarks has become crucial. Recent advancements have shifted towards using three-dimensional radiologic analysis instead of traditional two-dimensional methods, as it allows for more precise treatment planning, primarily relying on direct identification by clinicians. However, manual tracing can be time-consuming, mainly when dealing with a large number of patients. This study compared the accuracy and reliability of identifying anatomical landmarks using artificial intelligence (AI) and manual identification. Thirty patients over 19 years old who underwent pre-orthodontic and orthognathic surgery treatment and had pre-orthodontic three-dimensional radiologic scans were selected. Thirteen anatomical indicators were identified using both AI and manual methods. The landmarks were identified by AI and four experienced clinicians, and multiple ANOVA was performed to analyze the results. The study results revealed minimal significant differences between AI and manual tracing, with a maximum deviation of less than 2.83 mm. This indicates that utilizing AI to identify anatomical landmarks can be a reliable method in planning orthognathic surgery. Our findings suggest that using AI for anatomical landmark identification can enhance treatment accuracy and reliability, ultimately benefiting clinicians and patients.

What do they Need?-The academic counseling needs of students majoring in art and design in a higher vocational college in China.

Students in higher vocational education are always encountering various challenges. The way they attempt to conquer these challenges influences their success in achieving their academic goals. With the development of the times, the needs of students in China's vocational colleges to cope with challenges are also changing. In order to understand the changing needs of these students to cope with the challenges, based on Trautwein and Bosse's academic counseling demand model and Knowles's demand theory, this study adopted semi-structured interviews, key event collection methods, and purposive sampling to select 12 students of different grades majoring in art and design in a higher vocational college in Guangzhou, China. With reference to related studies on the key academic needs of students, interview outlines were designed, interviews were conducted, and coding and analysis were performed. Students' experiences were categorized according to learning-related, individual, organization, and social constructs. The study results showed that the academic counseling needs of China's higher vocational art and design students mainly focused on the learning-related construct, such as understanding the courses and course systems they were majoring in, setting and realizing academic goals, coping with setbacks, pressure and other students' comprehensive evaluation. This was followed by dealing with personal and financial issues, building social circles and peer relationships, and so on. Therefore, for students to overcome challenges and achieve academic goals, it is helpful to strengthen the collaboration between professional teachers and counselors, the influence of peers, the focus on academic consulting work related to learning, and to explore and carry out guidance on students' individual needs in higher vocational colleges.

A study on Taiwan's vocational senior high school teachers' teaching identity and teaching transformation when facing a new competency-based curriculum.

Introduction: The competency of education is advocated in the 2023 United Nations Sustainable Development Goals. UNESCO encourages countries to provide inclusive, equitable, competency education and lifelong learning opportunities for all. Starting from 2019, 12-Year-Basic-Education, a new curriculum, was fully implemented in Taiwan to conform to the competency education strategy. For the teachers on site, teachers' understanding of the new curriculum and teaching practice has a direct impact on the competency of the implementation of this new policy. The main purpose of this study was to explore the relationship between vocational senior high school teachers' competency-oriented teaching, teaching identity and teaching transformation regarding this new curriculum. Methods: In order to effectively expand teachers' understanding of competency-oriented teaching identity, this study put forward 6 hypothetical approaches based on the implicit theory of teaching transformation. The 747 valid questionnaires accounted for 97.1% of the total recovered questionnaires. The reliability and validity analyses, as well as overall model fitting analysis and research model validation were performed on these valid questionnaires. Results: The results of the study showed: (1) With the background of Competency-oriented teaching, teachers' teaching attitude and teaching willingness has a positive impact on teaching identity; (2) teachers' teaching identity has a positive impact on teaching preparation, teaching practice, further study, three types of teaching transformation. In summary, three conclusions from this study were concluded on the aspects of teaching preparation, teaching practice and further study on practical competency-oriented teaching, teaching identity and teaching transformation in the educational field. Conclusion: Three conclusions were derived for the relationships among these six constructs: (1) Teachers with a "good attitude" and "strong willingness" to teach, a "high sense of identification" acceptance and full implement of "teaching preparation" are considered as teachers with a "foresight and a visionary predictive style"; (2) Teachers with a high sense of self-awareness who can fully practice "teaching practice" are teachers with a "pragmatic teaching by example style"; (3) Teachers with a "good attitude," a "strong willingness" to teach, a "high sense of identification" acceptance and who are able to fully practice "advanced research" are considered as teachers with an "empowerment-enhancing coaching style".

Impact of hypertriglyceridaemia on cardiovascular mortality according to low-density lipoprotein cholesterol in a 15.6-million population.

AIMS: The aim of this study was to assess the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality concerning low-density lipoprotein cholesterol (LDL-C) and age in the general population. METHODS AND RESULTS: From the Korean National Health Insurance Service database, 15 672 028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios for CVD mortality were calculated using Cox models after adjusting for various confounders. During a mean of 8.8 years of follow-up, 105 174 individuals died of CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold [ischaemic heart disease (IHD)], 1.24-fold [acute myocardial infarction (AMI)], and 1.10-fold (ischaemic stroke) higher CVD mortality. Haemorrhagic stroke and heart failure were not associated with TG levels. The impact of hypertriglyceridaemia (HTG) on CVD weakened but remained present in persons with LDL-C < 100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischaemic stroke) higher CVD mortality. The younger population (18-44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population. CONCLUSION: Hypertriglyceridaemia independently raises CVD mortality with lingering risks in young and older individuals with low LDL-C levels, suggesting the importance of management of HTG even with controlled LDL-C.

This prospective study evaluated the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality in the general population, particularly in individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. The TG levels log-linearly increased the mortality from CVD, especially ischaemic heart disease and ischaemic stroke, down to at least 50 mg/dL (0.56 mmol/L), as residual CVD risks associated with high TG were apparent in individuals, even with LDL-C < 100 mg/dL (2.59 mmol/L). Maintaining TG levels below 100 mg/dL may be beneficial even in seemingly low-risk groups, such as young people with normal or optimal LDL-C levels.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.

Current Status of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Maxillofacial Surgery: Should It Be Continued?

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has shown potential in maxillofacial surgery owing to its osteoinductive properties. However, concerns about its safety and high cost have limited its widespread use. This review presents the status of rhBMP-2 use in maxillofacial surgery, focusing on its clinical application, efficacy, safety, and limitations. Studies have demonstrated rhBMP-2's potential to reduce donor site morbidity and increase bone height in sinus and ridge augmentation; however, it may not outperform autogenous bone grafts. In medication-related osteonecrosis of the jaw treatment, rhBMP-2 has been applied adjunctively with promising results, although its long-term safety requires further investigation. However, in maxillofacial trauma, its application is limited to the restoration of large defects. Safety concerns include postoperative edema and the theoretical risk of carcinogenesis. Although postoperative edema is manageable, the link between rhBMP-2 and cancer remains unclear. The limitations include the lack of an ideal carrier, the high cost of rhBMP-2, and the absence of an optimal dosing regimen. In conclusion, rhBMP-2 is a promising graft material for maxillofacial surgery. However, it has not yet become the gold standard owing to safety and cost concerns. Further research is required to establish long-term safety, optimize dosing, and develop better carriers.

Clinical Stability of Bespoke Snowman Plates for Fixation following Sagittal Split Ramus Osteotomy of the Mandible.

Maxillofacial skeletal surgery often involves the use of patient-specific implants. However, errors in obtaining patient data and designing and manufacturing patient-specific plates and guides can occur even with accurate virtual surgery. To address these errors, bespoke Snowman plates were designed to allow movement of the mandible. This study aimed to compare the stability of bespoke four-hole miniplates with that of a bespoke Snowman plate for bilateral sagittal split ramus osteotomy (SSRO), and to present a method to investigate joint cavity changes, as well as superimpose virtual and actual surgical images of the mandible. This retrospective study included 22 patients who met the inclusion criteria and underwent orthognathic surgery at a university hospital between 2015 and 2018. Two groups were formed on the basis of the plates used: a control group with four-hole bespoke plates and a study group with bespoke Snowman plates. Stability was assessed by measuring the condyle-fossa space and superimposing three-dimensional virtual surgery images on postoperative cone-beam computed tomography (CBCT) scans. No significant differences were observed in the condyle-fossa space preoperatively and 1 year postoperatively between the control and study groups. Superimposing virtual surgery and CBCT scans revealed minimal differences in the landmark points, with no variation between groups or timepoints. The use of bespoke Snowman plates for stabilizing the mandible following SSRO exhibited clinical stability and reliability similar to those with bespoke four-hole plates. Additionally, a novel method was introduced to evaluate skeletal stability by separately analyzing the condyle-fossa gap changes and assessing the mandibular position.

Impact of primary prophylaxis by pegfilgrastim in diffuse large B-cell lymphoma treated with R-CHOP.

Febrile neutropenia (FN) and chemotherapy-induced neutropenia (CIN) are common conditions that lead to dose reduction or delayed chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). Primary prophylaxis (PP) with long-acting granulocyte colony-stimulating factor (G-CSF) was introduced in South Korea in 2014. We aimed to investigate the effects of PP on FN-related hospitalization and death in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Korean individuals (n = 11,491) with incident DLBCL and receiving R-CHOP during 2010-2016 were followed for FN-related hospitalization and mortality. The PP exposure group (patients during 2014-2015, n = 3599), patients during 2010-2016 (n = 11,491), and patients receiving PP during 2014-2016 (n = 4421) were compared with the non-exposure group (patients during July 2011-June 2013, n = 3017), patients in 2013 (n = 1596), and patients not receiving PP during 2014-2016 (n = 1289), respectively. Multivariable-adjusted hazard ratios (HRs) were calculated using the Cox model. The PP exposure group had 16% lower FN-related hospitalizations than the non-exposure group (HR = 0.84, P < 0.001). PP exposure had no beneficial effect on 1-year (HR = 0.98, P = 0.782) and 5-year mortality (HR = 0.97, P = 0.474). Patients in 2014 (HR = 0.85, P < 0.001), 2015 (HR = 0.88, P = 0.003), and 2016 (HR = 0.80, P < 0.001) had a decreased risk of FN-related hospitalizations compared with those in 2013. Among patients receiving their first R-CHOP cycle during 2014-2016, the HR for FN-related hospitalization was 0.90 (P = 0.014) in PP users compared with non-users. PP with a long-acting G-CSF lowered the FN-related hospitalization risk but did not benefit survival in patients with DLBCL receiving R-CHOP.

Peptide-Assembled Single-Chain Atomic Crystal Enhances Pluripotent Stem Cell Differentiation to Neurons.

Nanomaterials hybridized with biological components have widespread applications. among many candidates, peptides are attractive in that their peptide sequences can self-assemble with the surface of target materials with high specificity without perturbing the intrinsic properties of nanomaterials. Here, a 1D hybrid nanomaterial was developed through self-assembly of a designed peptide. A hexagonal coiled-coil motif geometrically matched to the diameter of the inorganic nanomaterial was fabricated, whose hydrophobic surface was wrapped along the axis of the hydrophobic core of the coiled coil. Our morphological and spectroscopic analyses revealed rod-shaped, homogeneous peptide-inorganic nanomaterial complexes. Culturing embryonic stem cells on surfaces coated with this peptide-assembled single-chain atomic crystal increased the growth and adhesion of the embryonic stem cells. The hybridized nanomaterial also served as an ECM for brain organoids, accelerating the maturation of neurons. New methods to fabricate hybrid materials through peptide assembly can be applied.

Mechanisms of Epichloë bromicola to Promote Plant Growth and Its Potential Application for Coix lacryma-jobi L. Cultivation.

Endophytic fungi play important roles in regulating plant growth and development and usually used as a promising strategy to enhance the biosynthesis of host valuable secondary metabolite, but the underlying growth-promoting mechanisms are only partly understood. In this study, the wild-type Arabidopsis thaliana seedlings co-cultured with fungal endophyte Epichloë bromicola showed auxin (IAA)-stimulated phenotypes, and the growth-promoting effects caused by E. bromicola were further verified by the experiments of spatially separated co-culture and fungal extract treatment. IAA was detected and identified in the extract of E. bromicola culture by LC-HRMS/MS, whereas 2,3-butanediol was confirmed to be the predominant volatile active compound in the diethyl ether and ethyl acetate extracts by GC-MS. Further study observed that IAA-related genes including synthesis key enzyme genes (CYP79B2, CYP79B3, NIT1, TAA1 and YUCCA1) and controlling polar transport genes (AUX1, BIG, EIR1, AXR3 and ARF1), were highly expressed at different periods after E. bromicola inoculation. More importantly, the introduction of fungal endophyte E. bromicola could effectively promote the growth and accumulation of coixol in Coix under soil conditions. Our study showed that endophytic fungus E. bromicola might be considered as a potential inoculant for improving medicinal plant growth.

Altered GC- and AT-biased genotypes of Ophiocordyceps sinensis in the stromal fertile portions and ascospores of natural Cordyceps sinensis.

OBJECTIVE: To examine multiple genotypes of Ophiocordyceps sinensis in a semi-quantitative manner in the stromal fertile portion (SFP) densely covered with numerous ascocarps and ascospores of natural Cordyceps sinensis and to outline the dynamic alterations of the coexisting O. sinensis genotypes in different developmental phases. METHODS: Mature Cordyceps sinensis specimens were harvested and continuously cultivated in our laboratory (altitude 2,254 m). The SFPs (with ascocarps) and fully and semi-ejected ascospores were collected for histological and molecular examinations. Biochip-based single nucleotide polymorphism (SNP) MALDI-TOF mass spectrometry (MS) was used to genotype multiple O. sinensis mutants in the SFPs and ascospores. RESULTS: Microscopic analysis revealed distinct morphologies of the SFPs (with ascocarps) before and after ascospore ejection and SFP of developmental failure, which, along with the fully and semi-ejected ascospores, were subjected to SNP MS genotyping analysis. Mass spectra showed the coexistence of GC- and AT-biased genotypes of O. sinensis that were genetically and phylogenetically distinct in the SFPs before and after ejection and of developmental failure and in fully and semi-ejected ascospores. The intensity ratios of MS peaks were dynamically altered in the SFPs and the fully and semi-ejected ascospores. Mass spectra also showed transversion mutation alleles of unknown upstream and downstream sequences with altered intensities in the SFPs and ascospores. Genotype #5 of AT-biased Cluster-A maintained a high intensity in all SFPs and ascospores. An MS peak with a high intensity containing AT-biased Genotypes #6 and #15 in pre-ejection SFPs was significantly attenuated after ascospore ejection. The abundance of Genotypes #5‒6 and #16 of AT-biased Cluster-A was differentially altered in the fully and semi-ejected ascospores that were collected from the same Cordyceps sinensis specimens. CONCLUSION: Multiple O. sinensis genotypes coexisted in different combinations with altered abundances in the SFPs prior to and after ejection, the SFP of developmental failure, and the two types of ascospores of Cordyceps sinensis, demonstrating their genomic independence. Metagenomic fungal members present in different combinations and with dynamic alterations play symbiotic roles in different compartments of natural Cordyceps sinensis.

Effect of music on colonoscopy performance: A propensity score-matched analysis.

BACKGROUND: Music has been used to reduce stress and improve task performance during medical therapy. AIM: To assess the effects of music on colonoscopy performance outcomes. METHODS: We retrospectively reviewed patients who underwent colonoscopy performed by four endoscopists with popular music. Colonoscopy performance outcomes, such as insertion time, adenoma detection rate (ADR), and polyp detection rate (PDR), were compared between the music and non-music groups. To reduce selection bias, propensity score matching was used. RESULTS: After one-to-one propensity score matching, 169 colonoscopies were selected from each group. No significant differences in insertion time (4.97 vs 5.17 min, P = 0.795) and ADR (39.1% vs 46.2%, P = 0.226) were found between the two groups. Subgroup analysis showed that the insertion time (3.6 vs 3.8 min, P = 0.852) and ADR (51.1% vs 44.7%, P = 0.488) did not significantly differ between the two groups in experts. However, in trainees, PDR (46.9% vs 66.7%, P = 0.016) and ADR (25.9% vs 47.6%, P = 0.006) were significantly lower in the music than in the non-music group. CONCLUSION: The current study found that listening to music during colonoscopy did not affect procedure performance. Moreover, it suggested that music may distract trainees from appropriately detecting adenomas and polyps.