Construction of m7G RNA modification-related prognostic model and prediction of immune therapy response in hepatocellular carcinoma.

Background: RNA plays an important role in tumorigenesis. Changes in RNA may cause changes in the biological function. The N7-methylguanosine (m7G) methylation modification performs an integral function in tumor progression as the most widely existed RNA modification. Hepatocellular carcinoma (HCC) is among the greatest threats to human health worldwide. Low detection rates remain the main cause of advanced disease progression. Therefore, finding significant biomarkers for prognosis prediction and immune therapy response in HCC is valuable and urgently needed. Methods: RNA expression and clinical data were acquired from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Different subtypes screening was finished by consensus cluster. Different expression was performed by R software. The results were validated by western blot (WB) methods. Genes with HCC prognostic potential were identified utilizing least absolute shrinkage and selection operator (LASSO) analyses. A prognosis model was established with the help of the risk score that we calculated. Related genes screening and protein-protein interactions (PPI) network construction were performed using the GeneMANIA database. Functional annotation was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) databases. In addition, gene set enrichment analysis (GSEA) of key genes and immune infiltration status were both done by R software. Finally, the immune infiltration was performed by cibersort method and single sample GSEA (ssGSEA) method. The response of immune therapy was validated by Tumor Immune Dysfunction and Exclusion database (TIDE) and the immune therapy cohort in GEO database. Results: We found that two different subtypes related with m7G RNA modification and four genes associated with m7G RNA modification were differentially expressed in the TCGA-Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Additionally, to examine the value of these four genes in the HCC patients' prognoses according to the LASSO, we selected three genes, including WDR4, AGO2, and NCBP2, as prognostic related genes. Premised on the expression of these three genes, a risk score model and nomogram were constructed to provide a prediction of the HCC patients' prognoses. We performed functional annotation and created a PPI network based on the three genes (WDR4, NCBP2, and AGO2). Using R software, we performed the GSEA and immune regulation analyses. Finally, we predicted the relationship between the gene expression and the response of immune therapy. Conclusions: Our study suggests that high expression of m7G RNA modification subtype is related with poor prognosis and immune response. WDR4, AGO2, and NCBP2 are key regulators of m7G RNA modification which can be clinically promising biomarkers that can be used to treat HCC. In addition, our risk score model was shown to have a strong link to OS in patients with HCC.

Inhibition of KIAA1429/HK1 axis enhances the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect.

N6-methyladenosine (m6A) serves as the most abundant posttranscription modification. However, the role of m6A in tumorigenesis and chemotherapeutic drugs sensitivity remains largely unclear. Present research focuses on the potential function of the m6A writer KIAA1429 in tumor development and sorafenib sensitivity in liver cancer. We found that the level of KIAA1429 was significantly elevated in liver cancer tissues and cells and was closely associated with poorer prognosis. Functionally, KIAA1429 promoted the proliferation and Warburg effect of liver cancer cells in vitro and in vivo. RNA-seq and MeRIP-seq analysis revealed the glycolysis was one of the most affected pathways by KIAA1429, and m6A-modified HK1 was the most likely targeted gene to regulate the Warburg effect. KIAA1429 depletion decreased Warburg effect and increased sorafenib sensitivity in liver cancer. Mechanistically, KIAA1429 could affect the m6A level of HK1 mRNA through directly binding with it. Moreover, KIAA1429 cooperated with the m6A reader HuR to enhance HK1 mRNA stability, thereby upregulating its expression. These findings demonstrated that KIAA1429/HK1 axis decreases the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect, which may provide a novel therapeutic target for liver cancer treatment.

The Importance of Knowledge on Dementia Risk Factors in the General Public: A Cross-Sectional Study.

ABSTRACT: The purpose of this study was to determine the influence of knowledge and beliefs on beneficial behaviors and dementia risk scores. A online survey was conducted among Chinese community residents over 18 years old. Multivariate logistic regression was used to identify the impact of knowledge and beliefs on dementia risk scores and beneficial behaviors. The respondents were 760 adults (mean age = 47.6 years, 60.8% female). Knowledge and beliefs were associated with cognitive activities (knowledge, odds ratio [OR] = 1.04; beliefs, OR = 1.17) and dementia risk scores (knowledge, OR = 0.95; beliefs, OR = 0.82). Additionally, lower perceived susceptibility (OR = 1.68; 95% CI, 1.04 to 2.72) and higher perceived benefits (OR = 0.68; 95% CI, 0.57 to 0.80) were associated with lower dementia risk scores. Knowledge and beliefs can promote beneficial behaviors and reduce dementia risk. In particular, perceptions of dementia susceptibility and benefits should be enhanced, which will greatly reduce dementia risk in the general public.

Unilateral severe gynecomastia in a 14 year-old adolescent with neurofibromatosis type 1 undergoing endoscopic mastectomy: a case report.

Gynecomastia can be caused by neurofibromas but has rarely been reported. The present case report describes the clinical appearance, diagnosis, and therapy of a rare combination of a 14 year-old adolescent male unilateral severe gynecomastia with NF-1 neurofibromatosis. In this particular case, we successfully performed minimally invasive surgery using endoscopic mastectomy, which not only resulted in a satisfactory appearance but also confirmed the presence of neurofibroma type 1 by detecting typical immunohistochemical indicators associated with the disease. Additionally, we analyzed the gene responsible for the disease, c.1431del: p. F477Lfs*21, based on the patient's family history.

A robust aluminum-octacarboxylate framework with scu topology for selective capture of sulfur dioxide.

The high structural diversity and porosity of metal-organic frameworks (MOFs) promote their applications in selective gas adsorption. The development of robust MOFs that are stable against corrosive SO2 remains a daunting challenge. Here, we report a highly robust aluminum-based MOF (HIAM-330) built on a 4-connected Al3(OH)2(COO)4 cluster and 8-connected octacarboxylate ligand with a (4,8)-connected scu topology. It exhibits a fully reversible SO2 uptake of 12.1 mmol g-1 at 298 K and 1 bar. It is capable of selective capture of SO2 over other gases (CO2, CH4, and N2) with high adsorption selectivities of 60, 330, and 3537 for equimolar mixtures of SO2/CO2, SO2/CH4, and SO2/N2, respectively, at 298 K and 1 bar. Breakthrough measurements verified the capability of HIAM-330 for selective capture of SO2 (2500 ppm) over CO2 or N2. High-resolution synchrotron X-ray powder diffraction of SO2 loaded HIAM-330 revealed the binding domains of adsorbed SO2 molecules and host-guest interactions.

Ferroelectric Order Evolution in Freestanding PbTiO3 Films Monitored by Optical Second Harmonic Generation.

The demand for low-dimensional ferroelectric devices is steadily increasing, however, the thick substrates in epitaxial films impede further size miniaturization. Freestanding films offer a potential solution by eliminating substrate constraints. Nevertheless, it remains an ongoing challenge to improve the stability in thin and fragile freestanding films under strain and temperature. In this work, the structure and ferroelectric order of freestanding PbTiO3 (PTO) films are investigated under continuous variation of the strain and temperature using nondestructive optical second harmonic generation (SHG) technique. The findings reveal that there are both out-of-plane and in-plane domains with polarization along out-of-plane and in-plane directions in the orthorhombic-like freestanding PTO films, respectively. In contrast, only out-of-plane domains are observed in the tetragonal epitaxial PTO films. Remarkably, the ferroelectricity of freestanding PTO films is strengthened under small uniaxial tensile strain from 0% up to 1.66% and well-maintained under larger biaxial tensile strain up to 2.76% along the [100] direction and up to 4.46% along the [010] direction. Moreover, a high Curie temperature of 630 K is identified in 50 nm thick freestanding PTO films by wide-temperature-range SHG. These findings provide valuable understanding for the development of the next-generation electronic nanodevices with flexibility and thermostability.

Hematuria after inguinal hernia repair in a child: a case report.

Inguinal hernia repair is one of the most common surgical procedures in the pediatric population. While a rare complication, bladder injury can impose a significant burden on patients. This study outlined a case of bladder injury following selective inguinal hernia repair and summarized methods to prevent this complication, aiming to emphasize the importance of not underestimating interventions labeled as "routine surgery" in order to avoid avoidable harm to patients.

Microenvironment regulation breaks the Faradaic efficiency-current density trade-off for electrocatalytic deuteration using D2O.

The high Faradaic efficiency (FE) of the electrocatalytic deuteration of organics with D2O at a large current density is significant for deuterated electrosynthesis. However, the FE and current density are the two ends of a seesaw because of the severe D2 evolution side reaction at nearly industrial current densities. Herein, we report a combined scenario of a nanotip-enhanced electric field and surfactant-modified interface microenvironment to enable the electrocatalytic deuteration of arylacetonitrile in D2O with an 80% FE at -100 mA cm-2. The increased concentration with low activation energy of arylacetonitrile due to the large electric field along the tips and the accelerated arylacetonitrile transfer and suppressed D2 evolution by the surfactant-created deuterophobic microenvironment contribute to breaking the trade-off between a high FE and large current density. Furthermore, the application of our strategy in other deuteration reactions with improved Faradaic efficiencies at -100 mA cm-2 rationalizes the design concept.

Endoplasmic reticulum stress response modulator OsbZIP39 regulates cadmium accumulation via activating the expression of defensin-like gene OsCAL2 in rice.

Accumulation of cadmium (Cd) in rice is not only harmful to the growth of plants but also poses a threat to human health. Exposure to Cd triggers unfolded protein response (UPR) within cells, a process that is still not completely understood. The study demonstrated that the lack of OsbZIP39, an essential endoplasmic reticulum (ER)-resident regulator of the UPR, resulted in decreased Cd intake and reduced Cd levels in the roots, stems, and grains of rice. Upon exposure to Cd stress, GFP-OsbZIP39 translocated from ER to nucleus, initiating UPR. Further investigation revealed that Cd treatment caused changes in sphingolipid levels in the membrane, influencing the localization and activation of OsbZIP39. Yeast one-hybrid and dual-LUC assays were conducted to validate the interaction between activated OsbZIP39 and the promoter of the defensin-like gene OsCAL2, resulting in an increase in its expression. Different variations were identified in the coding region of OsbZIP39, which may explain the varying levels of Cd accumulation observed in the indica and japonica subspecies. Under Cd treatment, OsbZIP39ind exhibited a more significant enhancement in the transcription of OsCAL2 compared to OsbZIP39jap. Our data suggest that OsbZIP39 positively regulates Cd uptake in rice, offering an encouraging objective for the cultivation of low-Cd rice.

Nanosheets of a Layered Metal-Organic Framework for Separation of CO2/CH4 using Mixed Matrix Membranes.

Mixed matrix membranes represent an important technology for gas separations. Nanosheets of metal-organic framework (MOF) materials of high aspect ratio and size-selective gas transport properties have the potential to promote the efficient mixing of components to form membranes for gas separation. Herein, we report a bottom-up synthesis of extended sheets of kagomé (kgm) topology, kgmt-Bu, via the linkage of [Cu2(O2CR)4] paddlewheels with 5-tert-butylisophthalic acid. The growth of the layered structure can be controlled by the choice of solvent and modulator. Nanosheets of kgmt-Bu of average thickness of 20 nm and aspect ratio of 40 to 50 can be obtained, and the sieving effect of the channels in kgmt-Bu boost the efficient separation of CO2 over CH4. A mixed matrix membrane comprising kgmt-Bu nanosheets with Matrimid shows a 32% enhancement in CO2/CH4 selectivity compared with the membrane incorporating the MOF in the particulate form.

The impact of gender differences on the clinical characteristics of critically ill patients with venous thromboembolism: A retrospective, observational study.

The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the characteristics of severe patients with deep venous VTE and provide clinical reference data for the prevention and treatment of VTE in critically ill patients. This study carried out a retrospective study on the medical records of patients who were treated in the intensive care unit of Affiliated Hospital of Jining Medical College from 2020 to 2022. The general data, general conditions, drug use, past history, VTE prevention measures, post-VTE conditions, and Padua risk score of 297 patients with VTE during the period of hospitalization in intensive care unit (ICU) were classified and statistically analyzed. A total of 297 including 171 male and 126 male patient medical records were included in the analysis, we compared multiple clinical indicators between male and female patients. Compared to women, male patients have a higher acute physiology and chronic health evaluation II score(APACHE-II score) (P = .027), a higher state of consciousness (P = .003), a higher rate of smoking and drinking history (P < .001), a lower rate of heart failure (P = .003) and chronic depression (P = .013), and a higher rate of recommended operations for male patients after VTE (P = .031). The prothrombin time (PT) (P = .041) and activated partial thromboplastin time (APTT) (P = .040) of male patients were significantly higher than those of female patients, while triglyceride (P = .009) and total cholesterol (TC) (P = .001) were significantly lower than those of female patients. The difference in D-dimer (P = .739) was not significant. This study shows that male and female patients with VTE in the ICU have significant differences in general characteristics, general clinical conditions, history of past illness, thrombosis character, and examination items, this may be the reason for the different rates of VTE between male and female patients in the ICU.

[Landscape Pattern Vulnerability and Its Driving Forces in Different Geomorphological Divisions in the Middle Yellow River].

The ecological environment of the middle Yellow River is highly vulnerable. Conducting a scientific assessment of landscape pattern vulnerability holds great significance, as it serves as the basis for the rational construction of the ecological environment in this area. Based on five periods of land use data from the middle Yellow River from 1990 to 2018, the landscape pattern vulnerability index was employed to analyze the spatio-temporal evolution of the landscape pattern vulnerability. Furthermore, the influencing factors for landscape pattern vulnerability in different natural geomorphological divisions were explored using an optimal parameters-based geographical detector model. The results showed that:① From 1990 to 2018, cultivated land (which accounted for 36.96 % to 39.97 % of the area) remained the predominant landscape in the middle Yellow River. Among all landscape types, cultivated land and construction land exhibited the most significant changes. The area of cultivated land decreased by 10 185.00 km2, whereas the area of construction land increased by 7 678.46 km2. ② From 1990 to 2018, the landscape pattern was dominated by low and medium vulnerability and accounted for 70 %-80 % of the total area. The high and higher vulnerability areas were concentrated in the loess hilly and gully region, whereas the lower vulnerability area was concentrated in the valley plain and the earth-rock mountain regions. During this period, landscape pattern vulnerability underwent an incipient decrease, followed by a subsequent increase. From 1990 to 2000 and from 2000 to 2005, the changes in the level of landscape pattern vulnerability were dominated by a "reduction in the degree of vulnerability". However, from 2005 to 2010 and from 2010 to 2018, it was mainly an "increase in the degree of vulnerability". ③ Annual precipitation and NDVI were the main factors influencing the vulnerability of landscape patterns, whereas the influencing factors varied across different natural geomorphological divisions:the loess hilly and gully region and the earth-rock mountain region were dominated by natural factors, with annual precipitation and DEM being the dominant factors, respectively; the loess plateau tableland-gully region, valley plain region, and sandy land and desert region were dominated by human factors, with population density, degree of land use, and distance from roads being the dominant factors, respectively. The interaction results of any two influencing factors were manifested as two-factor enhancement or nonlinear enhancement. Risk detection revealed that high vulnerability areas of landscape patterns in different natural geomorphological divisions were distributed over distinct ranges of their corresponding dominant factors. Therefore, in the practices of ecological management in the middle Yellow River, appropriate management strategies should be implemented based on the vulnerability characteristics of different natural landforms, to further improve the ecological management level of the watershed.

The influence of the national drug price negotiation policy reform on the medical expenses of patients in Xuzhou City: an interrupted time series analysis.

Background: To reduce the burden of patients' medical care, the Xuzhou Municipal Government has initiated an exploratory study on the supply model and categorized management of nationally negotiated drugs. This study aims to understand the extent to which Xuzhou's 2021 reform of the National Drug Price Negotiation (NDPN) policy has had a positive impact on the healthcare costs of individuals with different types of health insurance. Methods: The Interrupted Time Series Analysis method was adopted, and the changes in average medical expenses per patient, average medical insurance payment cost per patient and actual reimbursement ratio were investigated by using the data of single-drug payments in Xuzhou from October 2020 to October 2022. Results: Following the implementation of the policy, there was a significant decrease in the average medical expenses per patient of national drug negotiation in Xuzhou, with a reduction of 62.42 yuan per month (p < 0.001). Additionally, the average medical insurance payment cost per patient decreased by 44.13 yuan per month (p = 0.01). Furthermore, the average medical expenses per patient of urban and rural medical insurance participants decreased by 63.45 yuan (p < 0.001), and the average monthly medical insurance payment cost per patient decreased by 57.56 yuan (p < 0.04). However, the mean total medical expenditures for individuals enrolled in employee medical insurance decreased by 63.41 yuan per month (p < 0.001), whereas the monthly decrease was 22.11 yuan per month (p = 0.21). On the other hand, there was no discernible change in the actual reimbursement ratio. Conclusion: After the adoption of the NDPN policy, a noticeable decline has been observed in the average medical expenses per patient and the mean cost of the average medical insurance payment per patient, although to a limited extent. Notably, the reduction in employee medical insurance surpasses that of urban and rural medical insurance.

Metal-ligand cross-link strategy engineered iron-doped dopamine-based superstructure as peroxidase-like nanozymes for detection of glucose.

Nanozymes are nanomaterials with mimetic enzyme properties and the related research has attracted much attention. It is of great value to develop methods to construct nanozymes and to study their application in bioanalysis. Herein, the metal-ligand cross-linking strategy was developed to fabricate superstructure nanozymes. This strategy takes advantage of being easy to operate, adjustable, cheap, and universal. The fabricated superstructure nanozymes possess efficient peroxidase-like catalytic activity. The enzyme reaction kinetic tests demonstrated that for TMB and H2O2, the Km is 0.229 and 1.308 mM, respectively. Furthermore, these superstructure nanozymes are applied to highly efficient and sensitive detection of glucose. The linear range for detecting glucose is 20-2000 µM, and the limit of detection is 17.5 µM. Furthermore, mechanistic research illustrated that this integrated system oxidizes glucose to produce hydrogen peroxide and further catalyzes the production of ·OH and O2·-, which results in a chromogenic reaction of oxidized TMB for the detection of glucose. This work could not only contribute to the development of efficient nanozymes but also inspire research in the highly sensitive detection of other biomarkers.

Characteristic cembrane-type diterpenoids with nitric oxide inhibitory activity from the gum resin of Boswellia carterii Birdw.

Five new characteristic cembrane-type diterpenoids (olibacartiols A-E, 1-5) were acquired from the gum resin of Boswellia carterii. The structures of these diterpenoids were characterized by detailed spectroscopic analysis, and compounds 1-3 were unambiguously confirmed by single-crystal X-ray diffraction experiments. The anti-inflammatory activities of the isolated compounds were evaluated using LPS-induced BV2 cell model and compounds 2-5 showed moderate NO inhibitory effects with IC50 values of 8.84 ± 1.02, 9.82 ± 1.95, 9.75 ± 2.24, and 7.39 ± 1.24 µM, respectively.

New alkaloids from Stemona tuberosa and structural revision of tuberostemonols P and R.

Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C17N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC50 values of 37.1 and 23.2 µM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1H and 13C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a.

High adsorption of ammonia in a titanium-based metal-organic framework.

We report the high adsorption of NH3 in a titanium-based metal-organic framework, MFM-300(Ti), comprising extended [TiO6]∞ chains linked by biphenyl-3,3',5,5'-tetracarboxylate ligands. At 273 K and 1 bar, MFM-300(Ti) shows an exceptional NH3 uptake of 23.4 mmol g-1 with a record-high packing density of 0.84 g cm-3. Dynamic breakthrough experiments confirm the excellent uptake and separation of NH3 at low concentration (1000 ppm). The combination of in situ neutron powder diffraction and spectroscopic studies reveal strong, yet reversible binding interactions of NH3 to the framework oxygen sites.

Berberine increases the killing effect of pirarubicin on HCC cells by inhibiting ATG4B-autophagy pathway.

Pirarubicin (THP) is a new generation of cell cycle non-specific anthracycline-based anticancer drug. In the clinic, THP and THP combination therapies have been shown to be effective in hepatocellular carcinoma (HCC) patients with transcatheter arterial chemoembolization (TACE) without serious side effects. However, drug resistance limits its therapeutic efficacy. Berberine (BBR), an isoquinoline alkaloid, has been shown to possess antitumour properties against various malignancies. However, the synergistic effect of BBR and THP in the treatment of HCC is unknown. In the present study, we demonstrated for the first time that BBR sensitized HCC cells to THP, including enhancing THP-induced growth inhibition and apoptosis of HCC cells. Moreover, we found that BBR sensitized THP by reducing the expression of autophagy-related 4B (ATG4B). Mechanistically, the inhibition of HIF1α-mediated ATG4B transcription by BBR ultimately led to attenuation of THP-induced cytoprotective autophagy, accompanied by enhanced growth inhibition and apoptosis in THP-treated HCC cells. Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.

Virtual reality-based dementia educational programmes for formal and informal caregivers of people with dementia: A scoping review.

AIM: To map evidence of the existing virtual reality-based dementia educational programmes and the effects of these educational programmes on dementia formal and informal caregivers. DESIGN: A scoping review. METHODS: A comprehensive search of nine databases was conducted to find studies from the inception of the databases to October 2023. Two authors independently screened the titles and abstracts related to the eligibility criteria. Full texts of potentially relevant studies were read by one author and checked by a second. Data extraction and synthesis using NVivo 12 were undertaken by one author and checked by two other authors. RESULTS: Nineteen studies published between 2002 and 2022. The four randomised controlled studies and five qualitative studies were of moderate to good methodological quality. The 10 quasi-experimental studies were of weak to moderate quality. Fifteen virtual reality-based educational programmes had a positive influence on formal and informal caregivers, including improving caregivers' perceptions changing attitudes towards people with dementia, while the nursing competence of formal caregivers did not improve in short term. Educational programmes that covered dementia-related information and care strategies better improved the knowledge level of dementia formal and informal caregivers. CONCLUSIONS: The qualitative and quantitative studies of moderate to good quality included in this study support the idea that virtual reality-based dementia educational programmes may be a safe and effective way and have potential benefits for improving knowledge, perceptions, attitudes and nursing competence. IMPACT: This scoping review will provide an emerging teaching model for formal and informal caregivers of people with dementia and help them better understand the types and the influence of virtual reality-based dementia educational programmes. REPORTING METHOD: PRISMA-ScR. NO PATIENT OR PUBLIC CONTRIBUTION: Not required as this review in accordance with the aim to map existing literature from the dementia formal and informal caregivers' perspective.