Diverging Maternal and Cord Antibody Functions From SARS-CoV-2 Infection and Vaccination in Pregnancy.

Maternal immunity impacts the infant, but how is unclear. To understand the implications of the immune exposures of vaccination and infection in pregnancy for neonatal immunity, we evaluated antibody functions in paired peripheral maternal and cord blood. We compared those who in pregnancy received mRNA coronavirus disease 2019 (COVID-19) vaccine, were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the combination. We found that vaccination enriched a subset of neutralizing activities and Fc effector functions that was driven by IgG1 and was minimally impacted by antibody glycosylation in maternal blood. In paired cord blood, maternal vaccination also enhanced IgG1. However, Fc effector functions compared to neutralizing activities were preferentially transferred. Moreover, changes in IgG posttranslational glycosylation contributed more to cord than peripheral maternal blood antibody functional potency. These differences were enhanced with the combination of vaccination and infection as compared to either alone. Thus, Fc effector functions and antibody glycosylation highlight underexplored maternal opportunities to safeguard newborns.

USP29 activation mediated by FUBP1 promotes AURKB stability and oncogenic functions in gastric cancer.

BACKGROUND: Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear. METHODS: The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays. RESULTS: In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues. CONCLUSIONS: These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.

The emerging role of USP29 in cancer and other diseases.

Reversible protein ubiquitination is a key process for maintaining cellular homeostasis. Deubiquitinases, which can cleave ubiquitin from substrate proteins, have been reported to be deeply involved in disease progression ranging from oncology to neurological diseases. The human genome encodes approximately 100 deubiquitinases, most of which are poorly characterized. One of the well-characterized deubiquitases is ubiquitin-specific protease 29 (USP29), which is often upregulated in pathological tissues and plays important roles in the progression of different diseases. Moreover, several studies have shown that deletion of Usp29 in mice does not cause visible growth and developmental defects, indicating that USP29 may be an ideal therapeutic target. In this review, we provide a comprehensive summary of the important roles and regulatory mechanisms of USP29 in cancer and other diseases, which may help us better understand its biological functions and improve future studies to construct suitable USP29-targeted therapy systems.

The hidden hurdles of clinical clerkship: unraveling the types and distribution of professionalism dilemmas among South Korean medical students.

BACKGROUND: To improve the medical professionalism of medical students, it is essential to understand the dilemmas they face in various situations. This study explored the types and distribution of dilemmas Korean medical students encounter during their clinical clerkships. It then compared these with previous dilemma frameworks and identified the types and distribution of "complexity dilemmas," wherein two dilemma themes emerge in a single clinical situation. METHODS: The researchers organized and recorded a group discussion with 106 third-year medical students who had completed their clinical clerkships. These students participated in the discussion as part of an assignment, focusing on the dilemmas they encountered during their clerkships. For data analysis and visualization, the researchers employed the MAXQDA software program and utilized the template analysis method, a qualitative research methodology. RESULTS: A total of seven dilemma themes and sixteen sub-themes were identified. The identity-related dilemma concerning student-doctors had the highest frequency. The themes "mismatch" and "Nun-chi" emerged as new additions not found in previous dilemma frameworks. The complexity dilemmas appeared in the sequence of "identity-dignity," "identity-abuse," and "identity-consent". CONCLUSIONS: To navigate the unique dilemmas present within South Korea's clinical culture, several key issues need consideration: elevating the role of student-doctors, balancing the primary emphasis of educational hospitals on delivering medical services, and understanding interpersonal strategies, such as "Nun-chi".

A Case Report of Acute Bilateral Mydriasis Induced by Herbal Medication.

Ma Huang (Ephedra), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug Administration in 2004, it is still used for weight loss and energy boosting in some countries. A previous healthy 42-year-old woman experienced sudden blurred vision in both eyes. Her pupils were dilated to 6 mm each, showing diminished light reflex responses, and were not responsive to both 0.1% and 1% pilocarpine. The day before the onset of her symptoms she had taken a herbal supplement. The woman's herbal medicine was believed to contain ephedrine, a component found in Ma Huang. The sympathomimetic effects of this substance could potentially induce mydriasis. After discontinuing the medication, her symptoms improved over 4 days, leading to a suspicion of drug-induced bilateral mydriasis. Herbal products prescribed for weight loss, which may contain potential elements such as Ma Huang, could lead to unforeseen side effects like bilateral mydriasis, and should be appropriately highlighted.

Melatonin regulates cancer migration and stemness and enhances the anti-tumour effect of cisplatin.

Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133+ cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133+ cells compared to CD133- cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.

Clinical perspectives and outcomes of the giant breast phyllodes tumor and sarcoma: a real-world retrospective study.

BACKGROUND: Giant breast malignant phyllodes tumor or sarcoma (GBPS) are rare entities with diameter larger than 10 cm and variously histological pleomorphisms. This disease poses a significant threat to the quality of life of individuals, and its prognosis remains unclear. This study aimed to explore the differential diagnosis, treatment, and prognosis of GBPS in a real-world retrospective cohort. METHODS: We collected GBPS (diameter > 10 cm, n = 10) and BPS (diameter ≤ 10 cm, n = 126) from patients diagnosed with sarcoma or malignant phyllodes tumor between 2008 and 2022. We analyzed clinical characteristics, histological status, treatment, and local recurrence using the Fisher's exact test between GBPS (diameter > 10 cm) and BPS (diameter ≤ 10 cm) cohort. We described overall survival (OS) and disease-free survival (DFS) using Kaplan-Meier curves and identified risk factors for local recurrence using logistic regression. The tumor size, age at diagnosis, and differential immunohistochemistry markers of breast sarcoma or phyllodes tumor to determine the prognosis of GBPS. RESULTS: In our retrospective analysis of breast malignancies, we identified 10 cases of GBPS and 126 cases of BPS, corresponding to a GBPS prevalence of 0.17% (10/6000). The median age was 38.5 years (inter-quartile range, IQR: 28.25-48.5 years). During the follow-up of period (median: 80.5 months, IQR: 36.75-122 months), the local recurrence (LR) rate was 40% and 20.6%, respectively. Clinical characteristics of young age (HR:2.799, 95%CI -00.09276-0.017, p < 0.05) and cytological characteristics of marked stromal atypia (HR:0.88, 95% CI 0.39-1.40, p < 0.05) were risk factors for the poor prognosis of GBPS by COX regression model analysis. The Kaplan-Meier curves of GBPS 5-year disease-free survival (DFS) and overall survival (OS) were 31.5 months and 40 months, respectively, and were not associated with adjuvant radiation or chemotherapy. CONCLUSION: We recommend mastectomy with a clear surgical margin as the preferred treatment for GBPS. Age and stromal atypia are significantly associated with recurrence. Adjuvant radiation therapy is advised; however, there was no improvement in overall survival. There is no consensus on the effectiveness of adjuvant chemotherapy and genetic methods, highlighting the need for further research into this aggressive tumor. We recommend a multidisciplinary approach involving a dedicated team for the management of GBPS.

Relationship matters: a qualitative study of medical students' experiences in a learner-driven research program in South Korea.

BACKGROUND: Although research experience is important for medical students, it is difficult to develop research skills only through a formal curriculum. To develop research programs that address the authentic needs of students and align with the entirety of the medical school curriculum, a learner-centered approach may be more effective than an instructor-centered approach. This study investigates medical student perspectives on factors that help them develop research competency. METHODS: Hanyang University College of Medicine in South Korea operates the Medical Scientist Training Program (MSTP) as a supplement to its formal curriculum. Semi-structured interviews were held with 18 students (20 cases) in the program, and qualitative content analysis was performed using the software tool MAXQDA20. RESULTS: The findings are discussed in relation to three domains: learner engagement, instructional design, and program development. The students were more engaged when they perceived the program as a new experience, had prior research experience, wanted to make a good impression, and felt a sense of contribution. In terms of instructional design, they positively participated in research when their supervisors respected them, set clear tasks, provided constructive feedback, and invited them into the research community. In particular, the students highly valued relationships with their professors, and these relationships served not only as a main motivating factor in their research participation but also affected their college lives and careers. CONCLUSIONS: The longitudinal relationship between students and professors has newly emerged in the Korean context as a factor that strengthens student engagement in research and the complementary relationship between formal curriculum and MSTP was highlighted to encourage student engagement in research.

Dynein light chain LC8 alleviates nonalcoholic steatohepatitis by inhibiting NF-κB signaling and reducing oxidative stress.

Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation and chronic inflammation in the liver. Dynein light chain of 8 kDa (LC8) was identified previously as an inhibitor of nuclear factor kappa B (NF-κB), a key regulator of inflammation, however, its role in NASH remains unknown. In this study, we investigated whether LC8 can alleviate NASH using a mouse model of methionine and choline-deficient (MCD) diet-induced NASH and examined the underlying mechanism. LC8 transgenic (Tg) mice showed lower hepatic steatosis and less progression of NASH, including hepatic inflammation and fibrosis, compared to wild-type (WT) mice after consuming an MCD diet. The hepatic expression of lipogenic genes was lower, while that of lipolytic genes was greater in LC8 Tg mice than WT mice, which might be associated with resistance of LC8 Tg mice to hepatic steatosis. Consumption of an MCD diet caused oxidative stress, IκBα phosphorylation, and subsequent p65 liberation from IκBα and nuclear translocation, resulting in induction of proinflammatory cytokines and chemokines. However, these effects of MCD diet were reduced by LC8 overexpression. Collectively, these results suggest that LC8 alleviates MCD diet-induced NASH by inhibiting NF-κB through binding to IκBα to interfere with IκBα phosphorylation and by reducing oxidative stress via scavenging reactive oxygen species. Thus, boosting intracellular LC8 could be a potential therapeutic strategy for patients with NASH.

c-MYC-USP49-BAG2 axis promotes proliferation and chemoresistance of colorectal cancer cells in vitro.

Deubiquitinases (DUBs) play critical roles in tumorigenesis and are emerging as potential therapeutic targets. However, it remains less clear which DUBs may play important roles and represent a realistic vulnerability for a particular type of tumor. Here we revealed that Ubiquitin Specific Peptidase 49 (USP49) is transcriptionally activated by c-MYC in colorectal cancer (CRC), and CRC patients with elevated USP49 levels exhibited significantly shorter survival. Knockdown of USP49 markedly inhibited CRC cell proliferation, colony formation, and chemotherapy resistance in vitro. Investigation of mechanisms unravels that USP49 deubiquitinates and stabilizes Bcl-2-Associated Athanogene 2 (BAG2), a well-known protein that antagonizes apoptosis and enables adaptive response of CRC cells. This study identified a novel mechanism by which USP49 promotes CRC cell survival by stabilizing BAG2 through the c-MYC-USP49-BAG2 axis, indicating that USP49 may become a potential therapeutic target for CRC.

The emerging role of deubiquitylating enzymes as therapeutic targets in cancer metabolism.

Cancer cells must rewire cellular metabolism to satisfy the unbridled proliferation, and metabolic reprogramming provides not only the advantage for cancer cell proliferation but also new targets for cancer treatment. However, the plasticity of the metabolic pathways makes them very difficult to target. Deubiquitylating enzymes (DUBs) are proteases that cleave ubiquitin from the substrate proteins and process ubiquitin precursors. While the molecular mechanisms are not fully understood, many DUBs have been shown to be involved in tumorigenesis and progression via controlling the dysregulated cancer metabolism, and consequently recognized as potential drug targets for cancer treatment. In this article, we summarized the significant progress in understanding the key roles of DUBs in cancer cell metabolic rewiring and the opportunities for the application of DUBs inhibitors in cancer treatment, intending to provide potential implications for both research purpose and clinical applications.

Hypoxia associated lncRNA HYPAL promotes proliferation of gastric cancer as ceRNA by sponging miR-431-5p to upregulate CDK14.

Gastric cancer (GC) is a common malignant solid tumor that is characterized by high hypoxia. The transcription of genes associated with hypoxia affects tumor occurrence and development. Long non-coding RNAs (lncRNAs) have been reported to play important roles in cancer development. In this study, we screened for differentially expressed ncRNAs (non-coding RNA) and mRNAs between hypoxia-inducible factor-1 (HIF-1α) knockdown GC cells and scrambled GC cells. Microarray data revealed that HIF-1α regulated the expression of LINC01355 (Hypoxia Yield Proliferation Associated LncRNA, HYPAL). HYPAL was found to be significantly upregulated in GC cells and tissues and was correlated with poor GC prognosis. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that HIF-1α promoted HYPAL expression by binding the promoter region. A regulatory network for the competing endogenous RNA (ceRNA) was constructed using bioinformatics tools. Mechanistic studies revealed that HYPAL acted as a ceRNA of miR-431-5p to regulate CDK14 expression. Carcinogenic effects of HYPAL were evaluated in vitro and in vivo. The HIF-1α/HYPAL/miR-431-5p/CDK14 (Cyclin-dependent kinase 14) axis activated the Wnt/ß-catenin signaling pathway and induced GC cell proliferation while inhibiting apoptosis. In conclusion, HYPAL is a potential molecular target for GC therapy.

Saliency-Based Rotor Spatial Position Displacement Self-Sensing for Self-Bearing Machines.

Self-bearing machines do not contain physical bearings but magnetic bearings. Both rotor rotary and spatial positions displacement are required in these types of machines to control the rotor position while it is levitating. Self-bearing machines often use external sensors for x (horizontal) and y (vertical) spatial position measurement, which will result in additional cost, volume, complexity, and number of parts susceptible to failure. To overcome these issues, this paper proposes a xy-position estimation self-sensing technique based on both main- and cross-inductance variation. The proposed method estimates x and y position based on inductive saliency between two sets of three-phase coils. The proposed idea is applied on a combined winding self-bearing machine which does not require additional suspension force winding. No additional search coil placement for xy-position estimation is required. Therefore, the proposed algorithm can result in a compact size self-bearing machine that does not require external sensors for xy-position measurement and suspension force winding.

Soybean Seedling Root Segmentation Using Improved U-Net Network.

Soybean seedling root morphology is important to genetic breeding. Root segmentation is a key technique for identifying root morphological characteristics. This paper proposed a semantic segmentation model of soybean seedling root images based on an improved U-Net network to address the problems of the over-segmentation phenomenon, unsmooth root edges and root disconnection, which are easily caused by background interference such as water stains and noise, as well as inconspicuous contrast in soybean seedling images. Soybean seedling root images in the hydroponic environment were collected for annotation and augmentation. A double attention mechanism was introduced in the downsampling process, and an Attention Gate mechanism was added in the skip connection part to enhance the weight of the root region and suppress the interference of background and noise. Then, the model prediction process was visually interpreted using feature maps and class activation mapping maps. The remaining background noise was removed by connected component analysis. The experimental results showed that the Accuracy, Precision, Recall, F1-Score and Intersection over Union of the model were 0.9962, 0.9883, 0.9794, 0.9837 and 0.9683, respectively. The processing time of an individual image was 0.153 s. A segmentation experiment on soybean root images was performed in the soil-culturing environment. The results showed that this proposed model could extract more complete detail information and had strong generalization ability. It can achieve accurate root segmentation in soybean seedlings and provide a theoretical basis and technical support for the quantitative evaluation of the root morphological characteristics in soybean seedlings.

Flunarizine inhibits osteoclastogenesis by regulating calcium signaling and promotes osteogenesis.

Many bone diseases such as osteoporosis and periodontitis are caused by hyperactivation of osteoclasts. Calcium (Ca2+ ) signals are crucial for osteoclast differentiation and function. Thus, the blockade of Ca2+ signaling may be a strategy for regulating osteoclast activity and has clinical implications. Flunarizine (FN) is a Ca2+ channel antagonist that has been used for reducing migraines. However, the role of FN in osteoclast differentiation and function remains unknown. Here, we investigated whether FN regulates osteoclastogenesis and elucidated the molecular mechanism. FN inhibited osteoclast differentiation along with decreased expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and attenuated osteoclast maturation and bone resorption. FN inhibition of osteoclast differentiation was restored by ectopic expression of constitutively active NFATc1. FN reduced calcium oscillations and its inhibition of osteoclast differentiation and resorption function was reversed by ionomycin, an ionophore that binds Ca2+ . FN also inhibited Ca2+ /calmodulin-dependent protein kinase IV (CaMKIV) and calcineurin leading to a decrease in the cAMP-responsive element-binding protein-dependent cFos and peroxisome proliferator-activated receptor-γ coactivator 1ß expression, and NFATc1 nuclear translocation. These results indicate that FN inhibits osteoclastogenesis via regulating CaMKIV and calcineurin as a Ca2+ channel blocker. In addition, FN-induced apoptosis in osteoclasts and promoted osteogenesis. Furthermore, FN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting that it has therapeutic potential for treating inflammatory bone diseases and postmenopausal osteoporosis.

Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis.

Cinchonine (CN) has been known to exert antimalarial, antiplatelet, and antiobesity effects. It was also recently reported to inhibit transforming growth factor ß-activated kinase 1 (TAK1) and protein kinase B (AKT) through binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). However, its role in bone metabolism remains largely unknown. Here, we showed that CN inhibits osteoclast differentiation with decreased expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. Immunoblot and quantitative real-time polymerase chain reaction analysis as well as the reporter assay revealed that CN inhibits nuclear factor-κB and activator protein-1 by regulating TAK1. CN also attenuated the activation of AKT, cyclic AMP response element-binding protein, and peroxisome proliferator-activated receptor-γ coactivator 1ß (PGC1ß), an essential regulator of mitochondrial biogenesis. Collectively, these results suggested that CN may inhibit TRAF6-mediated TAK1 and AKT activation, which leads to downregulation of NFATc1 and PGC1ß resulting in the suppression of osteoclast differentiation. Interestingly, CN not only inhibited the maturation and resorption function of differentiated osteoclasts but also promoted osteoblast differentiation. Furthermore, CN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting its therapeutic potential for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Association between fasting blood glucose levels at admission and overall survival of patients with pancreatic cancer.

BACKGROUND: The associations between fasting blood glucose and staging and overall survival of patients with pancreatic cancer are still controversial. This study aimed to investigate the association between fasting blood glucose levels and overall survival (OS) of patients with pancreatic cancer and to evaluate the impact of differentiation and staging of pancreatic cancer. METHODS: This was a retrospective study of patients with pathologically confirmed pancreatic cancer admitted to Shengjing Hospital of China Medical University between 01/2012 and 12/2016. The outcome was the OS. The factors associated with OS were examined using univariable and multivariable Cox and logistic regression analyses. RESULTS: A total of 253 patients were included. Preoperative blood glucose levels were not significantly associated with the OS of patients with pancreatic cancer (HR = 1.04, 95%CI: 0.78-1.40, P = 0.781). Only CA199 > 1000 was independently associated with OS (HR = 1.86, 95%CI: 1.15-3.02, P = 0.012). The median survival in the normal glucose group was 20.5 months (95% confidence interval (CI): 14.2-26.9). The median survival in the high glucose group was 14.2 months (95% CI: 9.7-18.6). There was no statistically significant difference between the two groups (P = 0.573). Multivariable logistic regression analyses were performed to determine if blood glucose levels influenced the 1- and 2-year OS. No significant association was observed for 1-year (OR = 1.27, 95%CI: 0.71-2.29, P = 0.418) or 2-year (HR = 1.37, 95%CI: 0.76-2.46, P = 0.296) OS. CONCLUSIONS: Fasting blood glucose levels are not associated with the OS of patients with pancreatic adenocarcinoma.

Pre-medical students' perceptions of educational environment and their subjective happiness: a comparative study before and after the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic necessarily changed pre-medical students' educational environment into an online format-and students' subjective happiness (SH) is highly impacted by their educational environment. This study investigates changes in pre-medical students' perceptions of their educational environment and their SH before and after the pandemic, as well as explores the predictors related to their SH. METHODS: The Korean version of the Dundee Ready Educational Environment Measure (DREEM) questionnaire and single-item measures of SH and professional identity (PI) were used. The t-test was employed to analyze the differences of the SH, PI, and DREEM subscales scores before and after the onset of COVID-19. Cohen's d was used as effect size and correlations between SH and different subscales of DREEM were analyzed using Pearson's correlation. The multiple regression analysis was performed to reveal associations between predictors and SH. RESULTS: A total of 399 pre-medical students completed the survey both before and after the COVID-19 pandemic. The DREEM scores and all subscales scores significantly increased but each presents a different effect size. Students' Perceptions of Learning (SPL: Cohen's d = 0.97), Students' Perceptions of Teaching (SPT: Cohen's d = 1.13), and Students' Perceptions of Atmosphere (SPA: Cohen's d = 0.89) have large effect sizes. Students' Academic Self-Perceptions (SASP: Cohen's d = 0.66) have a medium effect size and Students' Social Self-Perceptions (SSSP: Cohen's d = 0.40) have a small effect size. In contrast, no significant change was noted in the SH and PI. Both PI and SSSP impacted SH before COVID-19, but after the pandemic, SH was impacted by SPL, SPA, and SSSP. CONCLUSIONS: Students' overall perception of their educational environment was more positive after the onset of COVID-19, but their social self-perceptions improved the least. Additionally, SSSP is the only predictor of SH both before and after the pandemic. The findings of this study suggest that educational institutions must pay attention to students' social relationships when trying to improve their educational environment. Furthermore, so as to increase students' SH, development of both educational environment and PI is essential.

miR-130a-3p inhibition protects against renal fibrosis in vitro via the TGF-ß1/Smad pathway by targeting SnoN.

BACKGROUND: Renal fibrosis, a common pathological outcome of chronic kidney disease (CKD), is characterized by extracellular matrix (ECM) accumulation, damage to the tubular epithelium, and the proliferation and activation of fibroblasts. SnoN, a TGF-ß1/Smad transcriptional co-suppressor, is downregulated in obstructive nephropathy. However, the relationship between miR-130a-3p and SnoN expression in the regulation of renal fibrosis is still unknown. METHODS: We used human renal proximal tubular epithelial cells (HRPTEpiCs, HK-2 and primary HRPTEpiCs) treated with TGF-ß1 to establish an in vitro renal fibrosis model. The expression of miR-130a-3p, SnoN and other proteins related to epithelial mesenchymal transition (EMT) and TGF-ß1/Smad signalling was investigated by western blotting or qRT-PCR. A luciferase reporter assay was conducted to confirm the interaction of SnoN mRNA and miR-130a-3p. The translocation of p-Smad 2/3 and Smad 7 was determined using immunofluorescence staining. RESULTS: After TGF-ß1 treatment, miR-130a-3p was highly expressed in renal tubular epithelial cells, while SnoN was poorly expressed. The cell morphology changed to fibroblast-like, indicating evidence of EMT. The levels of EMT and fibrosis-related proteins were decreased through miR-130a-3p inhibition. Additionally, miR-130a-3p acted upon the 3'-UTR of SnoN directly to suppress SnoN expression. Furthermore, miR-130a-3p/SnoN promoted the activation of TGF-ß1/Smad signalling, as revealed by p-Smad 2/3 and Smad 7 expression levels and distribution patterns. CONCLUSION: Our study verified that miR-130a-3p facilitates the TGF-ß1/Smad pathway in renal tubular epithelial cells and may participate in renal fibrosis by targeting SnoN, which could be a possible strategy for renal fibrosis treatment.

First Report of Leaf Spot Caused by Alternaria alternata on Sonchus asper in China.

Sonchus asper (Spiny sowthistle), belonging to the Asteraceae, is a problematic weed in grain crops, orchards as well as turf (Cho et al., 2019). In April 2016, about 90% of the S. asper plants infesting a pear orchard had symptomatic with black spots densely distributed on the leaves and stems in Da Yang Town, Luyang District, Hefei, Anhui (N31°55'43″, E117°11'40″). The foliar lesions were mostly circular (3.0 mm to 1.5 cm in diameter) or irregular in shape; lesions on the stem were elliptical to irregular in shape running along the vascular bundle and about 3 to 6mm long × 2 to 3mm wide. Severely affected plants had their leaves become completely blighted and eventually the plants died. Fifteen tissue pieces from five symptomatic leaves and stems were surface sterilized with 0.5% NaClO for two min, rinsed three times with sterile water, and then plated on 1/4-strength potato dextrose agar (PDA) medium. Fourteen fungal isolated were obtained from the tissues, the isolation frequency from the plant tissue pieces was almost 93%. Fungal colonies were circular, initially white, and eventually turned to dark olive or black along with profuse sporulation. The conidia were tawny to brownish green, obclavate to obpyriform, with a cylindrical or coniform short beak, ranging from 16.8 to 39.8 µm long × 6.3 to 14.7 µm wide with two to five transverse and zero to two longitudinal septa (n = 50) and were borne on branched conidiophores. These morphological characteristics were similar to those described for Alternaria alternata (Simmons, 2007). For one representative isolate, the internal transcribed spacer (ITS) region of rDNA, partial coding sequence of the actin (ACT) gene, partial Alt a 1 major allergen (ALT) gene and partial Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene were amplified and sequenced with primers ITS1/ITS4 (White et al., 1990), ACT512F/ACT783R (Carbone and Kohn, 1999), Alt-4for/Alt-4rev and gpd1/gpd2 (Lawrence et al., 2013) respectively. Sequences were submitted to GenBank (ITS: MH886523; ACT: MH892480; ALT: MN655781; GAPDH: MN655782). Based on a BLAST analysis, ITS, ACT gene and GAPDH gene had 100%-99.8% identity with the existing sequences of the ex-type CBS 916.96 of A. alternata (Fries) Keissler (ITS: AF347031; ACT: JQ671702; GAPDH: AY278808, respectively) and ALT gene showed 100% identity with the A. alternata isolate SCWC10 (MG199093). Thus the pathogen was identified as A. alternata based on its morphological and molecular characteristics. Pathogenicity tests were conducted on six to seven-leaf stage potted S. asper plants (one plant per pot). Five mm diameter fungal disks, which were excised from the edge of a three-day old A. alternata colony, were placed on healthy leaves of five plants. Same size sterile PDA disks were used as controls. In addition, a conidial suspension (107 conidia/ml) was also inoculated on healthy leaves of five plants, sterile distilled water was used as control. Both inoculation experiments were conducted in the greenhouse at 25 ± 2°C, 90 % relative humidity, 12 h light/dark photoperiod and repeated at least three times. Lesions were observed on all the leaves within 12 h after fungal disk inoculation. All pathogen inoculated plants developed lesions, similar to those observed on the symptomatic leaves in the field 12 days after conidial inoculation. No symptoms were observed on both control treatments. A. alternata was re-isolated from the inoculated leaves and confirmed by both morphological and molecular techniques, confirming Koch's postulates. To our knowledge, this is the first report of A. alternata causing leaf spot on S. asper in China. The pathogen could cause severe disease in S. asper, and has the potential to be further studied as a fungal weed biocontrol.