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N6-methyladenosine (m6A) is one of the major epigenetic modifications in eukaryotes. Although increasing functions of m6A have been identified in insects, its role in Plutella xylostella L. for host plant adaptation remains unclear. In the current study, we show that the m6A content of P. xylostella was relatively low in different developmental stages and tissues, with no significant differences. Two RNA methyltransferase genes, PxMETTL3 (methyltransferase-like 3) and PxMETTL14 (methyltransferase-like 14), were identified and characterized. PxMETTL3 could be transcribed into two transcripts, and PxMETTL14 had only one transcript; both of these genes were highly expressed in egg and adult stages and reproductive tissues. The CRISPR/Cas9-mediated knockout of PxMETTL3 (ΔPxMETTL3-2) or PxMETTL14 (ΔPxMETTL14-14) confirmed their function in m6A installation into RNA. Furthermore, upon transfer from an artificial diet to the host plant, the mutant strains were affected in terms of larval and pupal weight or adult emergence rate, while the wildtype (WT) strain did not exhibit any difference. In addition, the fecundity and egg hatching rate of the WT strain decreased significantly, whereas only the ΔPxMETTL14-14 mutant strain displayed significantly decreased fecundity. There seemed to be a tradeoff between the stress adaptation and reproduction in P. xylostella mediated by m6A modification. During host transfer, the expression of PxMETTL14 was consistent with the change in m6A content, which implied that PxMETTL14 could respond to host plant defense effectively, and may regulate m6A content. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially expressed transcripts with changes in m6A levels revealed that the potential functions of m6A-related genes may be involved in steroid biosynthesis for larval performance and metabolic pathways for adult reproduction. Overall, our work reveals an epigenetic regulation mechanism for the rapid adaptation of P. xylostella to variations in the host environment.

Introduction The “Shih–Hsu Test of Attention” (SHTA) is an iPad-based attention assessment tool developed in recent years by occupational therapists and has acceptable criterion-related validity and high test–retest reliability in preliminary application. This research project explores the criterion-related validity and test–retest reliability of SHTA between people with and without schizophrenia. Method The participants were 76 adults with schizophrenia aged 20–64 years, and 66 adults without diagnosed mental illness aged 20–64 years were recruited in this study on a voluntary basis. Each participant was assessed twice. The participants completed both the SHTA and Chu’s Attention Test (CAT) in the first test and the SHTA after 3 weeks. Findings Analytical results indicate that the SHTA has satisfactory test–retest reliability (ICC = 0.67) and criterion-related validity (γ = 0.29, p < 0.05*) for adults with schizophrenia and has high test–retest reliability (ICC = 0.90) and criterion-related validity (γ = 0.25, p < 0.05*) for adults without diagnosed mental illness. The MDC% value for the subjects without diagnosed mental illness was 12.1%, indicating acceptable random measurement error. Conclusion Our preliminary findings show that the iPad-based attention assessment tool, SHTA, has satisfactory criterion-related validity and test–retest reliability, supporting the future application of SHTA as an attention assessment tool.

Cisplatin is a prevalent chemotherapeutic agent used for non-small cell lung cancer (NSCLC) that is difficult to treat by targeted therapy, but the emergence of resistance severely limits its efficacy. Thus, an effective strategy to combat cisplatin resistance is required. This study demonstrated that, at clinically achievable concentrations, the combination of selenium yeast (Se-Y) and fish oil (FO) could synergistically induce the apoptosis of cancer stem cell (CSC)-like A549 NSCLC sphere cells, accompanied by a reversal of their resistance to cisplatin. Compared to parental A549 cells, sphere cells have higher cisplatin resistance and possess elevated CSC markers (CD133 and ABCG2), epithelial–mesenchymal transition markers (anexelekto (AXL), vimentin, and N-cadherin), and cytoprotective endoplasmic reticulum (ER) stress marker (glucose-regulated protein 78) and increased oncogenic drivers, such as yes-associated protein, transcriptional coactivator with PDZ-binding motif, β-catenin, and cyclooxygenase-2. In contrast, the proapoptotic ER stress marker CCAAT/enhancer-binding protein homologous protein and AMP-activated protein kinase (AMPK) activity were reduced in sphere cells. The Se-Y and FO combination synergistically counteracted the above molecular features of A549 sphere cells and diminished their elevated CSC-like side population. AMPK inhibition by compound C restored the side population proportion diminished by this nutrient combination. The results suggest that the Se-Y and FO combination can potentially improve the outcome of cisplatin-treated NSCLC with phenotypes such as A549 cells.

BACKGROUND: Prior to the COVID-19 global health emergency, reducing direct contacts between therapists and patients is an important issue, and could be achieved by using robots to perform certain caring activities. OBJECTIVE: This study compares therapeutic factors of singing group activities directed by social robots and by occupational therapists at elderly care centers during this COVID-19 outbreak. METHODS: This project has a quasi-experimental research design, based on a pilot study of 14 subjects aged above 65 years. They received eight sessions of singing group therapy given by a social robot or an occupational therapist. Completed copies of a therapeutic-factor questionnaire were then collected. RESULTS: At the 4th week, the scores for 8 therapeutic factors were higher in sessions with the occupational therapist than the robot-directed sessions, reaching a statistically significant level; at the 8th week, the scores for 3 therapeutic factors, including imparting of information, were higher in sessions with the occupational therapist than in sessions with the robot. The top scoring therapeutic factor in the robot sessions was group cohesiveness. CONCLUSIONS: Social robots may be good companion tools for elderly care during this COVID-19 outbreak, but group therapy sessions supervised by real-person therapists still have higher therapeutic factor scores than those conducted by robots. The number of subjects needs to be increased to enhance the validity of future study results.

Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial–mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.

The effect of tea consumption on breast cancer survival remained to be explored. Meanwhile, green tea favorably facilitates lipid metabolisms in breast cancer survivors. This study aimed to examine the effect of tea consumption and the interactions with lipids on breast cancer survival. A total of 1551 breast cancer patients were recruited between April 2008 and March 2012 and followed up until 31 December 2017 in Guangzhou. The endpoint was progression-free survival (PFS). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox proportional to estimate the associations. PFS was better among women who regularly drank all teas (mainly green tea) except oolong after cancer diagnosis compared with non-tea drinkers (HR 0.52; 95% CI 0.29 ~ 0.91). This association was more evident among women with normal (HR 0.38; 95% CI 0.18 ~ 0.82) than higher (HR 1.22; 95% CI 0.13 ~ 11.82) total cholesterol, though the interaction was not significant. Moreover, the more they drank (≥ 7 times/week), the better prognosis was (HR 0.30; 95% CI 0.11 ~ 0.84). In contrast, oolong tea was observed to have a potential impaired effect on PFS. Our findings suggested that regularly drinking all teas (mainly green tea) except oolong after diagnosis was beneficial to breast cancer survival, particularly for women with normal lipids, while oolong tea may have an impaired effect.

Objetivo general: Exponer la relación entre el Síndrome de Intestino Irritable y los factores psicosociales en estudiantes de Medicina. Objetivos específicos: Establecer a través de los criterios Roma IV la proporción de estudiantes de Medicina con Síndrome de Intestino Irritable. Evaluar la de ansiedad y depresión mediante la escala de “Hospital Anxiety and Depression Scale” (HADS). Identificar la edad, sexo y curso de la muestra. Materiales y métodos: estudio observacional, transversal con componente analítico llevado a cabo mediante encuestas, previo consentimiento informado a estudiantes de Medicina del primer al quinto curso de la facultad de Medicina de la Universidad Nacional de Itapúa. Resultados: Población estudiada (n=160), la proporción de estudiantes con Sindrome de Intestino Irritable (SII) de acuerdo a los criterios Roma IV fue del 23,75% (n=38) y de estos, el 79% fueron mujeres y 21% hombres. La edad media fue de 22,8 +/- 1,92. En relación al subtipo de SII, el más frecuente fue con estreñimiento, correspondiente al 42%. Con respecto a los estudiantes con SII, la prevalencia de ansiedad fue de 71% (n=27) y depresión del 50% (n=19). Conclusión: Se observó una asociación significativa del síndrome de intestino irritable, con trastornos de ansiedad y depresión. Es importante no ignorar su diagnóstico, debido a las posibles repercusiones negativas en el estudiante de Medicina con el fin de mejorar la calidad de vida de los mismos.

RESUMEN Introducción: El estudio de las percepciones de los estudiantes de Medicina sobre la salud mental es un tema de investigación significativo, puesto que su conocimiento puede ayudar a comprender las principales barreras a vencer para acceder a servicios de salud mental. Objetivos: Describir la percepción de los estudiantes de Medicina (campus de Sajonia y de San Lorenzo) de la Facultad de Ciencias Médicas de la Universidad Nacional de Asunción sobre los problemas de salud mental y sobre las barreras para acceder a los servicios de atención a la salud mental ofrecidos por la institución. Materiales y métodos: Estudio observacional descriptivo, de corte transversal y temporalmente prospectivo, con muestreo no probabilístico. A través de una encuesta en línea, se examinaron una serie de variables con el fin de describir las percepciones, tales como estigma, actitudes de la Facultad hacia la salud mental y barreras para acceder a los servicios de salud mental. Resultados: 243 estudiantes fueron encuestados. El 24,7 % mencionó haber sido tratado por un problema de salud mental. El 83,13% refirió conocer a algún estudiante con problemas de salud mental en la Facultad. 81,07% indicó que el estigma/vergüenza es la barrera más importante en el acceso a los servicios de salud mental ofrecidos por la institución. El 89,71% sostuvo que la Facultad tiene la responsabilidad de brindar mejor atención a los estudiantes con problemas de salud mental, mientras que el 37,04% estuvo de acuerdo con que la Facultad es amigable con estudiantes con problemas de salud mental. Conclusión: estos hallazgos servirán de base para futuras investigaciones sobre problemas prevalentes de salud mental en los estudiantes de Medicina, incluyendo las maneras de abordarlos y tratarlos, y sobre qué debe hacer la Facultad para mejorar el cuidado de la salud mental de sus estudiantes. ABSTRACT Introduction: The study of the medical students’ perceptions on mental health is a significant research topic, since its knowledge can help to understand the main barriers to overcome to access mental healthcare services. Objectives: To describe the perceptions of medical students (Sajonia and San Lorenzo campuses) of the Faculty of Medical Sciences of the National University of Asunción about mental health problems and about the barriers to accessing mental healthcare services offered by the institution. Materials and methods: Descriptive, cross-sectional and temporally prospective observational study, with non-probabilistic sampling. Through an online survey, a series of variables were examined to describe perceptions, such as stigma, Faculty attitudes towards mental health, and barriers to accessing mental healthcare services. Results: 243 students were surveyed. 24.7% mentioned having been treated for a mental health problem. 83.13% reported knowing a student with mental health problems at the Faculty. 81.07% indicated that stigma/shame is the most important barrier in accessing mental healthcare services offered by the institution. 89.71% said that the Faculty has the responsibility to provide better care to students with mental health problems, while 37.04% agreed that the Faculty is friendly with students with mental health problems. Conclusion: These findings will serve as the basis for future research on prevalent mental health problems in medical students, including ways to approach and treat them, and on what the Faculty should do to improve mental healthcare for its students.

Hepatic lipase (encoded by LIPC) is a glycoprotein in the triacylglycerol lipase family and mainly synthesized in and secreted from the liver. Previous studies demonstrated that hepatic lipase is crucial for reverse cholesterol transport and modulating metabolism and the plasma levels of several lipoproteins. This study was conducted to investigate the suppression effect of high-density lipoprotein cholesterol (HDL-C) levels in a genome-wide association study and explore the possible mechanisms linking triglyceride (TG) to LIPC variants and HDL-C. Genome-wide association data for TG and HDL-C were available for 4657 Taiwan-biobank participants. The prevalence of haplotypes in the LIPC promoter region and their effects were calculated. The cloned constructs of the haplotypes were expressed transiently in HepG2 cells and evaluated in a luciferase reporter assay. Genome-wide association analysis revealed that HDL-C was significantly associated with variations in LIPC after adjusting for TG. Three haplotypes (H1: TCG, H2: CTA and H3: CCA) in LIPC were identified. H2: CTA was significantly associated with HDL-C levels and H1: TCG suppressed HDL-C levels when a third factor, TG, was included in mediation analysis. The luciferase reporter assay further showed that the H2: CTA haplotype significantly inhibited luciferase activity compared with the H1: TCG haplotype. In conclusion, we identified a suppressive role for TG in the genome-wide association between LIPC and HDL-C. A functional haplotype of hepatic lipase may reduce HDL-C levels and is suppressed by TG.

Hepatic lipase (encoded by LIPC) is a glycoprotein in the triacylglycerol lipase family and mainly synthesized in and secreted from the liver. Previous studies demonstrated that hepatic lipase is crucial for reverse cholesterol transport and modulating metabolism and the plasma levels of several lipoproteins. This study was conducted to investigate the suppression effect of high-density lipoprotein cholesterol (HDL-C) levels in a genome-wide association study and explore the possible mechanisms linking triglyceride (TG) to LIPC variants and HDL-C. Genome-wide association data for TG and HDL-C were available for 4657 Taiwan-biobank participants. The prevalence of haplotypes in the LIPC promoter region and their effects were calculated. The cloned constructs of the haplotypes were expressed transiently in HepG2 cells and evaluated in a luciferase reporter assay. Genome-wide association analysis revealed that HDL-C was significantly associated with variations in LIPC after adjusting for TG. Three haplotypes (H1: TCG, H2: CTA and H3: CCA) in LIPC were identified. H2: CTA was significantly associated with HDL-C levels and H1: TCG suppressed HDL-C levels when a third factor, TG, was included in mediation analysis. The luciferase reporter assay further showed that the H2: CTA haplotype significantly inhibited luciferase activity compared with the H1: TCG haplotype. In conclusion, we identified a suppressive role for TG in the genome-wide association between LIPC and HDL-C. A functional haplotype of hepatic lipase may reduce HDL-C levels and is suppressed by TG.

Background: The noggin protein encoded by the NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint development. The symptoms include abnormal skeletal development and conductive deafness.Methods: In a retrospective study, clinical data of the proband and her family members, including 8 people and 50 healthy normal controls, were collected. Second-generation sequencing was performed on peripheral blood samples from them.Results: The sequencing analysis indicated that in the proband, the NOG gene had a c.532T>C, p.C178R (cytosine deletion, NM_005450.6:c.532T>C), leading to an amino acid change. The proband's father, grandmother, second sister, and third sister also had this mutation, whereas family members with normal phenotypes did not have the mutation.Conclusion: Analysis of this family showed that the novel presentation of the c.532T>C, p.C178R mutation in the NOG gene resulted in syndrome-type autosomal dominant inheritance reflected in a mild clinical phenotype, which is of great importance for further studies of the clinical phenotype and pathogenesis of stapes sclerosis.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a global pandemic. The hyperglycemia in patients with diabetes mellitus (DM) substantially compromises their innate immune system. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) receptors to enter the affected cell. Uncontrolled hyperglycemia-induced glycosylation of ACE2 and the S protein of SARS-CoV-2 could facilitate the binding of S protein to ACE2, enabling viral entry. Downregulation of ACE2 activity secondary to SARS-CoV-2 infection, with consequent accumulation of angiotensin II and metabolites, eventually leads to poor outcomes. The altered binding of ACE2 with SARS-CoV-2 and the compromised innate immunity of patients with DM increase their susceptibility to COVID-19; COVID-19 induces pancreatic β-cell injury and poor glycemic control, which further compromises the immune response and aggravates hyperglycemia and COVID-19 progression, forming a vicious cycle. Sequential cleavage of viral S protein by furin and transmembrane serine protease 2 (TMPRSS2) triggers viral entry to release the viral genome into the target cell. Hence, TMPRSS2 and furin are possible drug targets. As type 1 DM exhibits a Th1-driven autoimmune process, the relatively lower mortality of COVID-19 in type 1 DM compared to type 2 DM might be attributed to an imbalance between Th1 and Th2 immunity. The anti-inflammatory effects of dipeptidyl peptidase-4 inhibitor may benefit patients with DM and COVID-19. The potential protective effects of sodium–glucose cotransporter-2 inhibitor (SGLT2i), including reduction in lactate level, prevention of lowering of cytosolic pH and reduction in pro-inflammatory cytokine levels may justify the provision of SGLT2i to patients with DM and mild or asymptomatic COVID-19. For patients with DM and COVID-19 who require hospitalization, insulin-based treatment is recommended with cessation of metformin and SGLT2i. Further evidence from randomized or case–control clinical trials is necessary to elucidate the effectiveness and pitfalls of different types of medication for DM.

Background Galectin‐3 plays a crucial role in the regulation of inflammation. The aim of this study was to elucidate the association between LGALS3 genotypes, galectin‐3 levels, and inflammatory marker levels in patients with coronary artery disease (CAD). Results A total of 474 patients with CAD were enrolled. Significant correlations were discerned between galectin‐3 levels and leukocyte counts, C‐reactive protein, soluble intercellular adhesion molecule‐1, and matrix metalloproteinase 9 levels (all p, Galectin‐3 levels significantly correlated with leukocyte counts, C‐reactive protein, soluble intercellular adhesion molecule‐1, and matrix metalloproteinase 9 levels while LGALS3 SNPs rs2274273 and rs4644 genotypes independently associated with and contributed to 20.8% of galectin‐3 levels in patients with coronary artery disease. The absence of a significant association between LGALS3 gene variants and the inflammation markers levels suggested that it should be cautious when galectin‐3 was used as a therapeutic target for chronic inflammatory disorders, such as coronary artery disease.

Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated &beta, catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.

Purpose This study differentiates patient and care delays of breast cancer and explores the related factors as well as the associations with the prognosis in Guangzhou, a southern city of China. Methods A cohort of female incident breast cancer patients (n=1,551) was recruited from October 2008 to March 2012 and followed up until January 1, 2016 (n=1,374) in the affiliated hospitals of Sun Yat-sen University. The factors associated with patient and care delays were analyzed with multivariable logistic models. Cox proportional hazards regression models were constructed to estimate the impacts of the delays on the prognosis. Results There were 40.4% patient delay (≥3 months) and 15.5% care delay (≥1 month). The patient delay, but not the care delay, was significantly related to the clinical stage and consequently worsened the prognosis of breast cancer (hazard ratio, 1.45; 95% confidence interval, 1.09 to 1.91 for progression-free survival). The factors related to an increased patient delay included premenopausal status, history of benign breast disease, and less physical examination. Conclusion Patient delay was the main type of delay in Guangzhou and resulted in higher clinical stage and poor prognosis of breast cancer. Screening for breast cancer among premenopausal women may be an effective way to reduce this delay.

Stem cell surface markers may facilitate a better understanding of stem cell biology through molecular function studies or serve as tools to monitor the differentiation status and behavior of stem cells in culture or tissue. Thus, it is important to identify additional novel stem cell markers. We used glycoproteomics to discover surface glycoproteins on human embryonic stem cells (hESCs) that may be useful stem cell markers. We found that a surface glycoprotein, leucine-rich repeat neuronal protein 1 (LRRN1), is expressed abundantly on the surface of hESCs before differentiation into embryoid bodies (EBs). Silencing of LRRN1 with short hairpin RNA (shLRRN1) in hESCs resulted in decreased capacity of self-renewal, and skewed differentiation toward endoderm/mesoderm lineages in vitro and in vivo. Meanwhile, the protein expression levels of the pluripotency factors OCT4, NANOG, and SOX2 were reduced. Interestingly, the mRNA levels of these pluripotency factors were not affected in LRRN1 silenced cells, but protein half-lives were substantially shortened. Furthermore, we found LRRN1 silencing led to nuclear export and proteasomal degradation of all three pluripotency factors. In addition, the effects on nuclear export were mediated by AKT phosphorylation. These results suggest that LRRN1 plays an important role in maintaining the protein stability of pluripotency factors through AKT phosphorylation, thus maintaining hESC self-renewal capacity and pluripotency. Overall, we found that LRRN1 contributes to pluripotency of hESC by preventing translocation of OCT4, NANOG, and SOX2 from nucleus to cytoplasm, thereby lessening their post-translational modification and degradation.