SEC61G assists EGFR-amplified glioblastoma to evade immune elimination.

Amplification of chromosome 7p11 (7p11) is the most common alteration in primary glioblastoma (GBM), resulting in gains of epidermal growth factor receptor (EGFR) copy number in 50 to 60% of GBM tumors. However, treatment strategies targeting EGFR have thus far failed in clinical trials, and the underlying mechanism remains largely unclear. We here demonstrate that EGFR amplification at the 7p11 locus frequently encompasses its neighboring genes and identifies SEC61G as a critical regulator facilitating GBM immune evasion and tumor growth. We found that SEC61G is always coamplified with EGFR and is highly expressed in GBM. As an essential subunit of the SEC61 translocon complex, SEC61G promotes translocation of newly translated immune checkpoint ligands (ICLs, including PD-L1, PVR, and PD-L2) into the endoplasmic reticulum and promotes their glycosylation, stabilization, and membrane presentation. Depletion of SEC61G promotes the infiltration and cytolytic activity of CD8+ T cells and thus inhibits GBM occurrence. Further, SEC61G inhibition augments the therapeutic efficiency of EGFR tyrosine kinase inhibitors in mice. Our study demonstrates a critical role of SEC61G in GBM immune evasion, which provides a compelling rationale for combination therapy of EGFR-amplified GBMs.

Chemical Cross-linked Electrode-Electrolyte Interface Boosting the Structural Integrity of High Nickel Cathode Materials.

High nickel cathode material LiNixCoyMn1-x-yO2 (NCM) (x ≥ 0.6) has represented the most critical material in virtue of outstanding specific capacity and low self-discharge. However, the high surface alkalinity and detrimental interfacial stability lead to the parasitic reaction and a series of phase deterioration. Herein, in situ cross-linking binder molecular chains with a 3D network structure to construct a stable and robust electrode-electrolyte interface, which can maintain the structural integrity and restrain side reactions is designed. Simultaneously, the cross-linked polymer can form stable hydrogen bonds with the pristine binder, greatly enhancing the bonding property. More importantly, the functional groups contained in the cross-linked co-polymers can chemically anchor transition metals, effectively preventing the dissolution of transition metals. Theoretical calculations confirm the feasibility and advancement of the anchoring mechanism, driving excellent structural stability and inhibition of the NiO impurity phase. This work provides a practical strategy to realize the high stability of cathode materials.

Co(II) Metal-Organic Complex: Fluorescence Performances and Loaded With Drug Vitamin B2 Hydrogels Against Recurrent Oral Ulcers.

A new coordination polymer (CP) based on Co(II), namely, {[Co3(L)2(4,4'-bipy)(DMA)2]·H2O}n (1) has been synthesized after reacting Co(NO3)2·6H2O with H3L ligand in the existence of N-donor ligand 4,4'-bipyridine (4,4'-bipy), via utilizing a flexible tricarboxylic acid ligand 5-((formic acid-3-sulfur)methyl)isophthalic acid (H3L) with -S-CH2- joint. Additionally, the excellent blue fluorescence properties of CP 1 were confirmed through fluorescence spectroscopy compared to the original ligand. Using natural polysaccharide hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials, HA/CMCS hydrogel was prepared by chemical synthesis method. Taking vitamin B2 as the drug model, we designed and synthesized gels loaded with vitamin B2 metal framework and evaluated their efficacy in the treatment of recurrent oral ulcer.

Clinical features of histiocytic necrotizing lymphadenitis in children.

Due to its nonspecific clinical characteristics, histiocytic necrotizing lymphadenitis (HNL) is often misdiagnosed as a suppurative cervical lymphadenitis and lymphoma. Thus, this study aimed to investigate the clinical characteristics of HNL in pediatric patients. We retrospectively identified 61 patients with histopathologically confirmed HNL. Clinical and laboratory data, including age, sex, clinical manifestations, laboratory investigations, histological discoveries, treatment, and outcomes, were collected from the medical records to determine associations with extracervical lymph node (LN) involvement. The mean age of patients was 9.7 ± 2.8 years (range, 1.5-14.0 years), and the male-to-female ratio was 2.2:1. The most common systemic symptom was fever in all patients. The median pre-admission and total durations of fever were 13.0 (interquartile range [IQR]: 9.0-22.5 days) and 22.0 days (IQR: 17.0-33.0 days), respectively. Patients with temporary fever (< 2 weeks) had a higher peak temperature and were more likely to undergo LN biopsy after admission than those with a prolonged fever (≥ 2 weeks). Multivariate analysis revealed that peak temperature ≥ 40 °C was significantly associated with a longer fever duration (P = 0.023). Laboratory values showed leukopenia (68.9%), which presented more frequently in solitary cervical LNs than in extracervical LNs (82.4% vs. 52.9%, p = 0.027) in patients with prolonged fever. CONCLUSIONS: HNL is often misdiagnosed in older children with persistent fever and lymphadenopathy, leading to unnecessary diagnostic tests and evaluations, inappropriate antibiotic administration, and mismanagement. A multidisciplinary team, including primary care providers, rheumatologists, and pathologists, can improve patient outcomes by increasing their awareness of this rare condition. WHAT IS KNOWN: • Histiocytic necrotizing lymphadenitis (HNL) is characterized by fever, leukopenia, and neck lymphadenopathy with unknown etiology. • The lack of neutrophils or eosinophils in the histology, immunohistochemistry results help distinguish HNL from infectious causes. Although HNL is a self-limiting disease, antibiotics and steroid treatments were used inappropriately. WHAT IS NEW: • A fever peak ≥ 40 °C was associated with a longer fever duration in HNL patients. Leukopenia presented more frequently in solitary cervical lymph node (LNs) than in extracervical LNs inpatients with prolonged fever. • Steroids are not recommended as a routine treatment, however, in some severe or relapsing cases with persistent symptoms, prednisolone (5 mg twice a day for 2 days) or other steroids (an equivalent dose of prednisolone) responded favorably.

COVID-19 vaccination uptake in children with epilepsy and vaccine hesitancy among their parents: a survey.

This study explored the coronavirus disease 2019 (COVID-19) vaccination coverage among children with epilepsy (CwE), factors affecting vaccination coverage, and the effect of COVID-19 vaccines on epilepsy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A questionnaire was administered to CwE and their parents at the Pediatric Neurology Clinic of the Second Affiliated Hospital of Xi'an Jiaotong University between December 12, 2022, and February 28, 2023. Data were analyzed using the t-tests, chi-square tests, and logistic regression. The analysis included 250 CwE who responded to the survey; of these, 152 (60.8%) had been vaccinated against COVID-19. COVID-19 vaccine hesitancy in parents whose CwE were not vaccinated was mostly due to concerns of vaccine-related exacerbation of seizures and of vaccine-related adverse reactions (44.30% and 41.90% of the respondents, respectively). Univariate analysis showed that vaccination and number of doses of vaccine did not affect seizure incidence within 1 month of SARS-CoV-2 infection. Logistic regression analysis showed that CwE below primary school age, and those taking two or more antiseizure medication (ASMs) were less likely to be vaccinated (p = 0.007).   Conclusion: The primary reasons for vaccine hesitancy among parents of unvaccinated CwE were concerns regarding seizure exacerbation and adverse reactions following COVID-19 vaccination. CwE who were below primary school age and those who took two or more ASMs were less likely to be vaccinated. Addressing parents' concerns is necessary to build their confidence in COVID-19 vaccines and ensure that CwE are vaccinated. What is Known: • People with epilepsy have a higher risk of severe and fatal COVID-19 than those without epilepsy but, despite this, COVID-19 vaccination coverage is considerably lower in people with epilepsy than in people without epilepsy. What is New: • In unvaccinated children with epilepsy, the foremost reasons for COVID-19 vaccine hesitancy among parents were concerns about seizure exacerbation and vaccine-related adverse reactions. • Vaccination and number of doses of vaccine did not exacerbate seizures in children with epilepsy, those below primary school level and those taking two or more antiseizure medications were less likely to be vaccinated.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

UBE2C as an Immune-Related Biomarker for Breast Cancer: A Study Based on Multiple Databases.

Objective To screen the target gene UBE2C and explore its prognostic value and immune correlation in breast cancer (BRCA) using multiple databases. Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database (GEO) and analyzed to obtain differentially expressed genes (DEGs). Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs. Then the key gene UBE2C was determined using R language, STRING, and Cytoscape, and the differential expression of UBE2C was verified using the external datasets, The Cancer Genome Atlas (TCGA) , and quantitative real-time PCR (qRT-PCR). The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis (GSEA).Results The expression of UBE2C was differentially upregulated in BRCA, as verified by TCGA and qRT-PCR. Prognostic analysis revealed that UBE2C served as an independent prognostic factor. High expression of UBE2C was associated with decreased immune infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, and myeloid dendritic cells in BRCA tissue. The expression of UBE2C in BRCA showed a significant correlation with PDCD1, CD274, and CTLA4 expressions. There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability. GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues can predict the survivals and prognosis of BRCA patients. Also, it is closely related to the BRCA immune microenvironment and can predict the effecacy of immunotherapy in BRCA patients. Therefore, UBE2C may be an potential immune-related prognostic biomarker for BRCA.

In Situ Fluorescence Imaging Reveals Contribution of Cerebral Hydroxyl Radicals in Hyperhomocysteinemia-Induced Alzheimer-like Dementia.

Elevated plasma level of homocysteine, also termed as hyperhomocysteinemia, is acknowledged as a significant and independent risk factor of Alzheimer's disease. However, the mechanistic insight has not been thoroughly elucidated yet. In this work, 3,5-dihydroxybenzyloxy was explored as the unique reaction trigger and integrated into the naphthalimide fluorophore via a carbamate linker to afford a new probe for •OH imaging. •OH treatment induced aromatic hydroxylation and subsequent elimination reaction to release the caged fluorophore, accompanied with a highly specific and sensitive turn-on fluorescence response. Cell imaging results revealed that excess homocysteine triggered overwhelming •OH production, which was mediated by N-methyl-d-aspartate receptor and NADPH oxidase, and the resultant •OH stress further initiated neuronal ferroptosis, also confirmed by western blot analyses. Additionally, hyperhomocysteinemic mouse models were established, and Alzheimer-like dementia of the mice was observed from behavioral tests. Most importantly, with this probe, cerebral •OH fluctuation was in situ visualized in live mice, which positively correlated with the severity of Alzheimer-like dementia induced by hyperhomocysteinemia. These results reveal that cerebral •OH stress may be the critical nexus linking hyperhomocysteinemia and Alzheimer's disease. This work provides a robust fluorescence probe for in situ visualizing the cerebral •OH fluctuations and illuminating critical insights into •OH contributions in brain disorders.

Therapeutic actions of tea phenolic compounds against oxidative stress and inflammation as central mediators in the development and progression of health problems: A review focusing on microRNA regulation.

Many health problems including chronic diseases are closely associated with oxidative stress and inflammation. Tea has abundant phenolic compounds with various health benefits including antioxidant and anti-inflammatory properties. This review focuses on the present understanding of the impact of tea phenolic compounds on the expression of miRNAs, and elucidates the biochemical and molecular mechanisms underlying the transcriptional and post-transcriptional protective actions of tea phenolic compounds against oxidative stress- and/or inflammation-mediated diseases. Clinical studies showed that drinking tea or taking catechin supplement on a daily basis promoted the endogenous antioxidant defense system of the body while inhibiting inflammatory factors. The regulation of chronic diseases based on epigenetic mechanisms, and the epigenetic-based therapies involving different tea phenolic compounds, have been insufficiently studied. The molecular mechanisms and application strategies of miR-27 and miR-34 involved in oxidative stress response and miR-126 and miR-146 involved in inflammation process were preliminarily investigated. Some emerging evidence suggests that tea phenolic compounds may promote epigenetic changes, involving non-coding RNA regulation, DNA methylation, histone modification, ubiquitin and SUMO modifications. However, epigenetic mechanisms and epigenetic-based disease therapies involving phenolic compounds from different teas, and the potential cross-talks among the epigenetic events, remain understudied.

Fetal echocardiography changes of the right ventricle of well-controlled gestational diabetes mellitus.

BACKGROUND: There is few evidence of right ventricular (RV) function in fetuses with gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the RV function of fetuses using routine and two-dimensional speckle-tracking echocardiography (2D STE) to determine the effects of well-controlled GDM in the third trimester. METHODS: We used a Philips Epiq7C ultrasound instrument to obtain RV data sets from 63 subjects from July 2019 to February 2022. We compared the free wall thickness (FWT), fractional area change (FAC), Tei index (TEI), tricuspid annular plane systolic excursion (TAPSE) and free wall longitudinal strain(FWLS)of the RV in mothers with well-controlled GDM and normal gestational age-matched fetuses. RESULTS: 63 third trimester fetuses (32 GDM; 31 healthy controls) met the enrolment criteria. Significant differences in fetal RV were detected between the GDM and control groups for the FAC (36.35 ± 6.19 vs. 41.59 ± 9.11; P = 0.008) and the FWLS (-18.28 ± 4.23 vs. -20.98 ± 5.49; P = 0.021). There was a significant difference among the segmental strains of the base, middle and apex of the RV free wall in the healthy controls (P = 0.003), but in the GDM group, there was no statistical difference (p = 0.076). RV FWLS had a strong correlation with FAC (r = 0.467; P = 0.0002). CONCLUSIONS: In well-controlled GDM, there was measurable fetal RV hypertrophy and significant systolic function decline, indicating the presence of ventricular remodeling and dysfunction. 2D-STE can evaluate the RV free wall contraction in a more comprehensive way.

The SMC5/6 complex subunit MMS21 regulates stem cell proliferation in rice.

KEY MESSAGE: SMC5/6 complex subunit OsMMS21 is involved in cell cycle and hormone signaling and required for stem cell proliferation during shoot and root development in rice. The structural maintenance of chromosome (SMC)5/6 complex is required for nucleolar integrity and DNA metabolism. Moreover, METHYL METHANESULFONATE SENSITIVITY GENE 21 (MMS21), a SUMO E3 ligase that is part of the SMC5/6 complex, is essential for the root stem cell niche and cell cycle transition in Arabidopsis. However, its specific role in rice remains unclear. Here, OsSMC5 and OsSMC6 single heterozygous mutants were generated using CRISPR/Cas9 technology to elucidate the function of SMC5/6 subunits, including OsSMC5, OsSMC6, and OsMMS21, in cell proliferation in rice. ossmc5/ + and ossmc6/ + heterozygous single mutants did not yield homozygous mutants in their progeny, indicating that OsSMC5 and OsSMC6 both play necessary roles during embryo formation. Loss of OsMMS21 caused severe defects in both the shoot and roots in rice. Transcriptome analysis showed a significant decrease in the expression of genes involved in auxin signaling in the roots of osmms21 mutants. Moreover, the expression levels of the cycB2-1 and MCM genes, which are involved the cell cycle, were significantly lower in the shoots of the mutants, indicating that OsMMS21 was involved in both hormone signaling pathways and the cell cycle. Overall, these findings indicate that the SUMO E3 ligase OsMMS21 is required for both shoot and root stem cell niches, improving the understanding of the function of the SMC5/6 complex in rice.

Impact of additional theoretical training program in the diagnosis of the fetal head position during labor: a prospective observational study.

BACKGROUND: The accuracy of transvaginal digital examination in determining foetal head position is not high enough. This study aimed to evaluate whether an additional training on our new theory could improve the diagnostic accuracy of the foetal head position. METHODS: This was a prospective study conducted at a 3a grade hospital. The study included 2 residents in their first year of training in obstetrics without prior experience in transvaginal digital examination. In the observational study, 600 pregnant women without contraindications to vaginal delivery were included. Two residents were simultaneously trained in the theory of traditional vaginal examination, but resident B received an additional theoretical training program. The pregnant women were randomly assigned to have the foetal head position examined by resident A and resident B. The foetal head position was then confirmed by ultrasound, which was performed by the main investigator. After 300 examinations were independently performed by each resident, the accuracy of foetal head position and perinatal outcomes were compared between the two groups. RESULTS: During the 3-month period, 300 post training transvaginal digital examinations were performed by each resident in our hospital. The two groups were found to be homogeneous for age at delivery, BMI before delivery, parity, gestational weeks at delivery, the rate of epidural analgesia, foetal head position, presence of caput succedaneum, presence of moulding and foetal head station(p > 0.05). The diagnostic accuracy of head position by digital examination was higher for resident B, who was subjected to an additional theoretical training program, than for resident A (75.00% vs. 60.67%, p < 0.001). There were no significant differences in maternal and neonatal outcomes between the two groups (p > 0.05). CONCLUSION: An additional theoretical training program for residents increased the accuracy of vaginal assessment of foetal head position. TRIAL REGISTRATION: Registered at Chinese Clinical Trial Registry Platform (ChiCTR2200064783), October 17, 2022. https://www.chictr.org.cn/edit.aspx?pid=182857&htm=4.

Long non-coding RNA MRPL23-AS1 suppresses anoikis in salivary adenoid cystic carcinoma in vitro.

Distant lung metastasis is the main factor that affects the survival rate of patients with salivary adenoid cystic carcinoma (SACC). Anoikis resistance is a feature of tumor cells that easily metastasize. The long non-coding RNA (lncRNA) MRPL23 antisense RNA 1 (MPRL23-AS1) is related to lung metastasis in SACC, but its role in anoikis resistance is unknown. After altering MPRL23-AS1 expression in SACC cells, anoikis resistance was detected by calcein AM/PI staining and annexin V/PI flow cytometry. The apoptosis marker activated caspase-3 and the bcl-2/bax ratio were detected by Western blotting. The relationship between MPRL23-AS1 and the promoter of the potential downstream target gene p19INK4D was identified by chromatin immunoprecipitation (ChIP)-PCR assay. p19INK4D expression in patient tissues was determined using qRT-PCR and immunohistochemistry. The functional experiments showed that MPRL23-AS1 could promote anoikis resistance in vitro. MRPL23-AS1 recruited the EZH2 to the promoter region of p19INK4D, inhibited p19INK4D expression, and promoted tumor cell anoikis resistance. p19INK4D overexpression did not affect anoikis in attached cells; however, it attenuated the anoikis resistance effect of MPRL23-AS1 in suspension cells. p19INK4D expression was significantly lower in SACC tissues than in normal tissues. The novel MRPL23-AS1/p19INK4D axis may be a potential SACC biomarker or therapeutic target.

​Occult extracranial malignancy after complete remission of pineal mixed germ cell tumors: a rare case report and literature review.

BACKGROUND: ​Extracranial metastasis can occur in intracranial germ cell tumors (GCTs), but it is very rare. Recurrence or metastasis of non-germinomatous germ cell tumors (NGGCTs) is often accompanied by elevated tumor markers. ​Occult extracranial metastases or recurrences with negative markers are often difficult to detect in time, resulting in a very poor prognosis. CASE PRESENTATION: A 12-year-old boy was admitted to our institution with dizziness, headache, vomiting, and sleepiness. Magnetic resonance imaging (MRI) showed a pineal mass, accompanied by a significant increase in serum alpha-fetoprotein (AFP). The patient subsequently underwent total removal of the tumor. Pathology revealed that the tumor was a mixed GCT, consisting of mature teratoma, germinoma, and yolk sac tumor. Intracranial GCT achieved complete remission after intensive adjuvant chemotherapy and radiotherapy. Regular follow-up MRI revealed no recurrence of the intracranial tumor and continued monitoring of tumor markers revealed no abnormalities. ​Eight months later, the patient was readmitted due to progressive abdominal pain. Imaging and physical examination revealed abdominal occupation and lymphatic mass in the neck. He received salvage chemotherapy, anti-PD-1 immunotherapy, and palliative chemotherapy, but still developed multiple organ dysfunction syndromes (MODS) due to tumor progression and eventually died after one month. CONCLUSIONS: ​This profound case suggests that intracranial NGGCTs may develop occult extracranial malignancy, which can be very severe at the time of clinical symptoms and has an extremely poor prognosis. Therefore, in addition to tumor marker monitoring, regular follow-up with extracranial imaging may be warranted to detect extracranial tumors as early as possible, although perhaps not as frequently as with neuroimaging.

An autophagy-related long non-coding RNA signature in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is the most common oral cancer with a poor prognosis. At present, there is not any systematic study on autophagy-related long non-coding RNA (lncRNA) to predict the survival of patients with TSCC. MATERIAL AND METHODS: In this research, the cohort of TSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis showed that ten lncRNAs related to autophagy AC010326.3, AL160006.1, AL122010.1, AC139530.1, AC092747.4, AL139287.1, MIR503HG, AC009318.2, LINC01711, and LINC02560 are significantly correlated with prognosis. Based on these lncRNAs, a prognostic signature was established. This signature has an AUC value of 0.782, which accurately distinguishes patients of TSCC into high-risk and low-risk groups in different clinical hierarchical information (such as gender, age, etc.). RESULTS: The clinical nomogram with autophagy-related lncRNA prognostic characteristics has a concordance index of 0.81, and accurately predicts the survival time at 1-year and 3-year of TSCC patients. Related functional enrichment results indicate that the pathways of the high-risk group are enriched on cancer and autophagy. CONCLUSIONS: The autophagy-related lncRNA prognostic signature established in this study could accurately predict the prognosis of TSCC patients and may be a molecular biomarker and therapeutic target.

A comparative study of two-step anodization with one-step anodization at constant voltage.

Two-step anodization has been widely used because it can produce highly self-organized anodic TiO2nanotubes, but the differences in morphology and current-time curve of one-step anodization and two-step anodization are rarely reported. Here, one-step anodization and two-step anodization were conducted at different voltages. By comparing the FESEM image of anodic TiO2nanotubes fabricated by one-step anodization and two-step anodization, it was found that the variation of morphology characteristics is same with voltage. The distinction of morphology and current-time curve between one-step anodization and two-step anodization at the same voltage were analyzed: the nanotube average growth rate and porosity of two-step anodization are greater than that of one-step anodization. In the current-time curve, the duration of stage I and stage II in two-step anodization are significantly shorter than one-step anodization. The traditional field-assisted dissolution theory cannot explain the three stages of the current-time curves and their physics meaning under different voltages in the same fluoride electrolyte. Here, the distinction between one-step anodization and two-step anodization was clarified successfully by the theories of ionic current and electronic current and oxygen bubble mould.

SWI2/SNF2 chromatin remodeling ATPases SPLAYED and BRAHMA control embryo development in rice.

KEY MESSAGE: Chromatin remodeling ATPases OsSYD and OsBRM are involved in shoot establishment, and both affect OSH gene transcription. OsSYD protein interacts with RFL, but OsBRM does not. In plants, SPLAYED (SYD) and BRAHMA (BRM) encode chromatin remodeling ATPases that use the energy derived from ATP hydrolysis to restructure nucleosomes and render certain genomic regions available to transcription factors. However, the function of SYD and BRM on rice growth and development is unknown. Here, we constructed ossyd and osbrm mutants using CRISPR/Cas9 technology and analyzed the effects of mutations on rice embryo development. We discovered that the ossyd and osbrm mutants exhibited severe defects during embryonic development, whereas endosperm development was normal. These results indicated that the development of the embryo and endosperm is independent of each other. Consequently, the ossyd- and osbrm-null mutants did not germinate due to the abnormal embryos. Furthermore, we observed the embryos of ossyd- and osbrm-null mutants, and they indeed had distinct differentiation defects in shoot establishment, acquired during embryogenesis. To verify the function of OsSYD and OsBRM in embryogenesis, we measured the transcript levels of marker genes at different stages. Compared with wild type, the expression levels of multiple OSH genes were significantly reduced in the mutants, which was consistent with the defective shoot establishment phenotypes. The interaction between SYD and RICE FLORICAULA/LFY (RFL) was revealed using a yeast two-hybrid screening system, suggesting that the interaction between the LFY homolog and chromatin remodeling ATPases is ubiquitous in plants. Collectively, our findings provide the basis for elucidating the function of OsSYD and OsBRM during embryo development in rice.

Dictamnine inhibits pancreatic cancer cell growth and epithelial-mesenchymal transition by blocking the PI3K/AKT signaling pathway.

Many different treatments are available for pancreatic cancer (PC), including surgical resection, chemotherapy, radiotherapy, and immunotherapy, but these treatments are often ineffective at curing PC. Hence, identifying new and effective agents or strategies to improve therapeutic effects is critical. This study focused on the efficacy of dictamnine (DTM), a furan quinoline alkaloid extracted from Dictamnus dasycarpus Turcz., in treating PC. Our in vitro results showed that DTM can mitigate cell proliferation and induce cell cycle arrest and apoptosis in two different human PC cell lines. Moreover, epithelial-mesenchymal transition (EMT) was prevented during DTM treatment, reflected by reduced cell migration and invasion abilities. In vivo studies demonstrated that DTM treatment led to a remarkable inhibition of tumor growth in a xenograft nude mouse model. Mechanistic investigation showed that DTM might act by restraining constitutive and induced PI3K/AKT activity. In summary, our results demonstrated that DTM slows PC progression by inhibiting the activity of the PI3K/AKT signaling pathway and its downstream effectors and that DTM is effective as a pathway-specific cancer therapy. These findings could provide a greater understanding of the function of anticancer drugs and new options for PC treatment.

An aqueous extract from Artemisia capillaris inhibits acute gastric injury through mucosal stabilization.

BACKGROUND: Artemisia capillaris is among the most abundantly used traditional medicines, utilized in East Asia to treat diverse illnesses, including gastrointestinal tract diseases. We previously reported that an aqueous extract of A. capillaris (AEAC) inhibited gastric inflammation induced by HCl/ethanol via reactive oxygen species scavenging and NF-κB downregulation. To date, the pharmacological potential of AEAC for promoting mucosal integrity has not been studied. RESULTS: Here, we report that a single treatment with AEAC increased mucus production, and repeated administration of AEAC abolished HCl/ethanol-induced mucosal injury in vivo. Single- and multiple-dose AEAC treatments measurably increased the expression of mucosal stabilizing factors in vivo, including mucin (MUC) 5 AC, MUC6, and trefoil factor (TFF) 1 and TFF2 (but not TFF3). AEAC also induced mucosal stabilizing factors in both SNU-601 cells and RGM cells through phosphorylation of extracellular signal-regulated kinases. CONCLUSION: Taken together, our results suggest that AEAC protects against HCl/ethanol-induced gastritis by upregulating MUCs and TFFs and stabilizing the mucosal epithelium. © 2021 Society of Chemical Industry.

Bipolar Electrochemical Anodization Route for the Fabrication of Porous Anodic Alumina with Nanopore Gradients.

Porous anodic alumina (PAA) films with homogeneous nanopores are achieved by traditional anodization. Here, we present a unique anodization technique based on bipolar electrochemistry to fabricate PAA films with nanopore gradients. In an oxalic acid solution dissolved in ethylene glycol, a stable bipolar anodization process is realized. The PAA film prepared at 280 V exhibits a continuous change in interpore distance from ∼171 to ∼83 nm over a range of only 5 mm on the aluminum sheet. Higher driving voltages lead to larger interpore distances and steeper nanopore gradients. Further, no direct electrical connection is required for this bipolar anodization.