The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.

NADPH oxidase, as a major source of intracellular reactive oxygen species (ROS), assumes an important role in the immune response and oxidative stress response of the body. NADPH 9 oxidase 2 (NOX2) is the first and most representative member of the NADPH oxidase family, and its effects on the development of tumor cells are gaining more and more attention. Our previous study suggested that NCF4 polymorphism in p40phox, a key subunit of NOX2, affected the outcome of diffuse large B-cell lymphoma patients treated with rituximab. It hypothesized that NOX2-mediated ROS could enhance the cytotoxic effects of some anti-tumor drugs in favor of patients with tumors. Several reviews have summarized the role of NOX2 and its congeners-mediated ROS in anti-tumor therapy, but few studies focused on the relationship between the expression of NOX2 and anti-tumor drug resistance. In this article, we systematically introduced the NOX family, represented by NOX2, and a classification of the latest inhibitors and agonists of NOX2. It will help researchers to have a more rational and objective understanding of the dual role of NOX2 in tumor drug resistance and is expected to provide new ideas for oncology treatment and overcoming drug resistance in cancer.

A Cu-Based Metal-Organic Framework Cu-Cip with Cuproptosis for Cancer Therapy and Inhibition of Cancer Cell Migration.

Microflora within cancer cells plays a pivotal role in promoting metastasis of cancer. However, contemporary anticancer research often overlooks the potential benefits of combining anticancer and antibacterial agents. Consequently, a metal-organic framework Cu-Cip with cuproptosis and antibacterial properties was synthesized for cancer therapy. To enhance the anticancer effect of the material, Mn2+ was loaded into Cu-Cip, yielding Mn@Cu-Cip. The fabricated material was characterized using single-crystal X-ray diffraction, PXRD, and FT-IR. By interacting with overexpressed H2O2 to produce ROS and accumulating Cu ions in cancer cells, MOFs exhibited excellent anticancer performance. Moreover, the material displayed the function of damaging Staphylococcus aureus and Escherichia coli, revealing the admirable antibacterial properties of the material. In addition, the antibacterial ability could inhibit tumor cell migration. The Cu-based MOF revealed promising applications in the field of tumor treatment.

Differential fluorescent response to amino acids based on metal-organic framework Zn-PBC.

A novel metal-organic framework (MOF) Zn-PBC (H2PBC = pyridine-3,5-bis(phenyl-4-carboxylic acid)) was designed and synthesized via a solvothermal reaction with the H2PBC ligand, and produced a strong fluorescence. The material exhibited good stability and an ideal luminescent property in water. In addition, it was found that Zn-PBC displayed a different fluorescent response to different types of amino acids, and the mechanism was investigated. This research might give insight to the interaction between MOFs and amino acids, which would provide a strategy to fabricate MOF-based sensors for biomolecules in future.

Construction of Core-Shell MOF CSMnP with Enzyme-Like Activity for Chemotherapy and Chemodynamic Therapy.

Materials with enzyme-like activity have received a lot of attention in the field of tumor catalytic therapy. Here, biocompatible core-shell MOF CSMnP with two valence states of Mn ion, which could process chemodynamic therapy (CDT), was designed and synthesized. Besides, it could also promote a series of catalytic processes in the tumor microenvironment (TME). CSMnP catalyzed endogenous hydrogen peroxide (H2O2) to oxygen (O2) via catalase-like activity and then combined with the outer layer Mn(II)-PBC to convert O2 into superoxide radicals (•O2-), exhibiting oxidase-like activity. Besides, intracellular glutathione (GSH) could be effectively consumed through the glutathione oxidase-like activity of Mn3+. The occurrence of the cascade reactions effectively amplified the enzymatic production to enhance CDT. Furthermore, the therapeutic effect of CSMnP was improved through the loading of cationic drug DOX. The loading capacity was 11.10 wt %, which was 2.2 times that of Mn(III)-PBC (4.95 wt %), and the release of DOX showed a characteristic response. Therefore, the core-shell MOF with enzyme-like activity had a potential application for tumor combination therapy.

Sevoflurane suppresses the malignant progression of breast cancer via the hsa_circ_0000129/miR-578/EPSTI1 axis.

BACKGROUND: Sevoflurane (Sev) is a commonly used volatile anesthetic that might suppress the process of breast cancer. Also, circular RNAs (circRNAs) have been reported to partake in the pathogenesis of breast cancer. Accordingly, this research was designed to investigate the mechanism of hsa_circ_0005962 on Sev-mediated breast cancer development. METHODS: Sev was applied to treat breast cancer cells. Cell proliferation ability, migration, invasion, and apoptosis were detected using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and flow cytometry assay. Proliferating cell nuclear antigen (PCNA), Matrix metallopeptidase 9 (MMP9), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and Epithelial stromal interaction 1 (EPSTI1) were assessed using western blot assay. circ_0000129, microRNA-578 (miR-578), and EPSTI1 levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Using bioinformatics software (Circinteractome and Targetscan), the binding between miR-578 and circ_0000129 or EPSTI1 were predicted, and proved using dual-luciferase reporter and RNA pull-down assay. The biological roles of circ_0000129 and Sevoflurane on tumor growth were analyzed using a xenograft tumor model in vivo. RESULTS: Sevoflurane blocked tumor cell proliferation, migration, invasion, and promoted apoptosis. Circ_0000129 and EPSTI1 expression were increased, and miR-578 was decreased in breast cancer cells. Also, they presented an opposite trend in Sev-treated tumor cells. Circ_0000129 upregulation might abolish Sev-mediated tumor progression in vitro. Mechanically, circ_0000129 can affect EPSTI1 expression by sponging miR-578. Sev might inhibit tumor growth by regulating circ_0000129 in vivo. CONCLUSION: Circ_0000129 relieved Sev-triggered suppression impacts on breast cancer development partly via the miR-578/EPSTI1 axis, which provides a new mechanism for studying mediated therapy of breast cancer treatment.

Electrical Resistance Performance of Cable Accessory Interface Considering Thermal Effects.

Power cables are widely used in various fields of power transmission, and cable accessories are the weakest link in power cable systems due to their complex structure and multi-layer insulation coordination issues. This paper investigates the changes in electrical properties of the silicone rubber/cross-linked polyethylene (SiR/XLPE) interface at high temperatures. The physicochemical properties of XLPE material under thermal effects with different times are characterized through FTIR, DSC, and SEM tests. Finally, the mechanism of the effects of the interface state on the electrical properties of the SiR/XLPE interface is analyzed. It is found that with the increase in temperature, the changes in electrical performance of the interface do not show a monotonic downward trend, while interestingly, they can be divided into three stages. Under the thermal effects for 40 d, the internal recrystallization of XLPE in the early stage improves the electrical properties of the interface. In the later stage of thermal effects, the amorphous region inside the material is severely damaged and the molecular chains are severely broken, resulting in a decrease in the electrical properties of the interface. The results above provide a theoretical basis for the interface design of cable accessories at high temperatures.

Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review.

BACKGROUND: Carbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1. CASE PRESENTATION: We present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis. CONCLUSION: A comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.

Genome-wide association study for biomass accumulation traits in soybean.

Soybean is one of the most versatile crops for oil production, human diets, and feedstocks. The vegetative biomass of soybean is an important determinant of seed yield and is crucial for the forage usages. However, the genetic control of soybean biomass is not well explained. In this work, we used a soybean germplasm population, including 231 improved cultivars, 207 landraces, and 121 wild soybeans, to investigate the genetic basis of biomass accumulation of soybean plants at the V6 stage. We found that biomass-related traits, including NDW (nodule dry weight), RDW (root dry weight), SDW (shoot dry weight), and TDW (total dry weight), were domesticated during soybean evolution. In total, 10 loci, encompassing 47 putative candidate genes, were detected for all biomass-related traits by a genome-wide association study. Among these loci, seven domestication sweeps and six improvement sweeps were identified. Glyma.05G047900, a purple acid phosphatase, was a strong candidate gene to improve biomass for future soybean breeding. This study provided new insights into the genetic basis of biomass accumulation during soybean evolution. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-023-01380-6.

Effects of EEG burst suppression on cerebral oxygen metabolism and postoperative cognitive function in elderly surgical patients: A randomized clinical trial.

BACKGROUND: This randomized clinical trial determined the effects of electroencephalographic burst suppression on cerebral oxygen metabolism and postoperative cognitive function in elderly surgical patients. METHODS: The patients were placed into burst suppression (BS) and non-burst suppression (NBS) groups. All patients were under bispectral index monitoring of an etomidate target-controlled infusion for anesthesia induction and intraoperative combination sevoflurane and remifentanil for anesthesia maintenance. The cerebral oxygen extraction ratio (CERO2), jugular bulb venous saturation (SjvO2), and difference in arteriovenous oxygen (Da-jvO2) were measured at T0, T1, and T2. One day before surgery, and 1, 3, and 7 days after surgery, postoperative cognitive dysfunction was assessed using the mini-mental state examination (MMSE). RESULTS: Compared with T0, the Da-jvO2 and CERO2 values were decreased, and SjvO2 was increased in the 2 groups at T1 and T2 (P < .05). There was no statistical difference in the SjvO2, Da-jvO2, and CERO2 values between T1 and T2. Compared with the NBS group, the SjvO2 value increased, and the Da-jvO2 and CERO2 values decreased at T1 and T2 in the BS group (P < .05). The MMSE scores on the 1st and 3rd days postoperatively were significantly lower in the 2 groups compared to the preoperative MMSE scores (P < .05). The MMSE scores of the NBS group were higher than the BS group on the 1st and 3rd days postoperatively (P < .05). CONCLUSION: In elderly patients undergoing surgery, intraoperative BS significantly reduced cerebral oxygen metabolism, which temporarily affected postoperative neurocognitive function.

Identification of 1q21.1 microduplication in a family: A case report.

BACKGROUND: Copy number variation (CNV) has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research. 1q21.1 microduplication syndrome is a rare CNV disease that can manifest as multiple congenital developmental disorders, autism spectrum disorders, congenital malformations, and congenital heart defects with genetic heterogeneity. CASE SUMMARY: We reported a pediatric patient with 1q21.1 microduplication syndrome, and carried out a literature review to determine the correlation between 1q21.1 microduplication and its phenotypes. We summarized the patient's medical history and clinical symptoms, and extracted genomic DNA from the patient, her parents, elder brother, and sister. The patient was an 8-mo-old girl who was hospitalized for recurrent convulsions over a 2-mo period. Whole exon sequencing and whole genome low-depth sequencing (CNV-seq) were then performed. Whole exon sequencing detected a 1.58-Mb duplication in the CHR1:145883867-147465312 region, which was located in the 1q21.1 region. Family analysis showed that the pathogenetic duplication fragment, which was also detected in her elder brother's DNA originated from the mother. CONCLUSION: Whole exon sequencing combined with quantitative polymerase chain reaction can provide an accurate molecular diagnosis in children with 1q21.1 microduplication syndrome, which is of great significance for genetic counseling and early intervention.

Hexafluoro-2-propanol represses colorectal cancer proliferation by regulating transaminases.

Hexafluoro-2-propanol (HFIP) is a metabolite of sevoflurane used as part of the general anaesthesia technique. This study aims to investigate the effect of HFIP in colorectal cancer (CRC) and the regulation of associated genes. The differential expressed genes (DEGs) with HFIP treatment were analysed based on GEO dataset GSE56256. Due to the restricted number of studies performing RNA-Seq in CRC with HFIP treatment, we selected a CRC patient cohort (GSE23878) to obtain DEGs that were compared with DEGs from GSE56256. The DEGs with opposite expression patterns in these two GEO datasets indicate that the genes mediate the function of HFIP, thereby repress the progression of CRC. The DEGs from these two GEO datasets were analysed independently. We obtained 10 up-regulated genes in GSE23878 (CRC patient cohort) were also down-regulated in GSE56256 (HFIP cohort), therefore, these 10 genes may function as tumor suppressors in CRC and may be involved in the function of HFIP. STRING analysis demonstrated an interaction in GPT2, PSAT1 and SLC7A11. The high expression of GPT2, PSAT1 and SLC7A11 were confirmed in TCGA-COAD datasets and in CRC cells. HFIP treatment repressed GPT2, PSAT1 and SLC7A11, which resulted in an inhibited proliferation and colony formation ability of DLD-1 and HCT-116 cells. Silencing GPT2, PSAT1 and SLC7A11 showed similar effect compared to HFIP treatment. Overexpression of GPT2, PSAT1 and SLC7A11 abrogated the effect of HFIP. In conclusion, the sevoflurane metabolite HFIP plays a cancer suppression role depending on cell proliferation in colorectal cancer through the down-regulation of GPT2, PSAT1 and SLC7A11 expression.

Architecture Design and Catalytic Activity: Non-Noble Bimetallic CoFe/fe3 O4 Core-Shell Structures for CO2 Hydrogenation.

Non-noble metal catalysts now play a key role in promoting efficiently and economically catalytic reduction of CO2 into clean energy, which is an important strategy to ameliorate global warming and resource shortage issues. Here, a non-noble bimetallic catalyst of CoFe/Fe3 O4 nanoparticles is successfully designed with a core-shell structure that is well dispersed on the defect-rich carbon substrate for the hydrogenation of CO2 under mild conditions. The catalysts exhibit a high CO2 conversion activity with the rate of 30% and CO selectivity of 99%, and extremely robust stability without performance decay over 90 h in the reverse water gas shift reaction process. Notably, it is found that the reversible exsolution/dissolution of cobalt in the Fe3 O4 shell will lead to a dynamic and reversible deactivation/regeneration of the catalysts, accompanying by shell thickness breathing during the repeated cycles, via atomic structure study of the catalysts at different reaction stages. Combined with density functional theory calculations, the catalytic activity reversible regeneration mechanism is proposed. This work reveals the structure-property relationship for rational structure design of the advanced non-noble metallic catalyst materials with much improved performance.

Correction: Preparation of nanoscale cationic metal-organic framework Nano Mn(III)-TP for theranostics based on valence changes.

Correction for 'Preparation of nanoscale cationic metal-organic framework Nano Mn(III)-TP for theranostics based on valence changes' by Shijiang Yu et al., J. Mater. Chem. B, 2022, 10, 8988-8995, https://doi.org/10.1039/D2TB01619B.

Metal Hydrogen-Bonded Organic Framework as a pH Sensor for the Detection of Strong Acids.

pH detection is related to human beings' life closely. Herein, a porous metal hydrogen-bonded organic framework (MHOF) Co-CDI-CO32- was designed and synthesized, which could be utilized to detect the pH values of strong acids. The sensitivity of pH detection was in the range of pH 2.0-2.4 with an accuracy of 0.1, which mainly depended on the different degree of crystal surface damage. The MHOF Co-CDI-CO32- had potential applications with the advantages of low cost, easy storage, and great sensitivity for pH detection as a pH sensor.

Preparation of nanoscale cationic metal-organic framework Nano Mn(III)-TP for theranostics based on valence changes.

A single treatment strategy to produce a significant effect on cancer treatment is difficult due to the complex variability of the tumor environment. Herein, considering over-expressed glutathione (GSH) in the tumor environment can reduce Mn3+ to Mn2+, and Mn2+ exhibits an excellent T1-weighted magnetic resonance imaging performance and a good Fenton-like effect. A Mn-based nano-cation metal-organic framework (MOF) with a size of about 200 nm was synthesized and labeled as Nano Mn(III)-TP. It showed an outstanding T1-weighted MRI performance and Fenton-like effect due to valence changes of the Mn ions. Meanwhile, MTXNa@Nano Mn(III)-TP was obtained by loading with the anionic anticancer drug methotrexate disodium (MTXNa), and it could release MTXNa specifically in GSH solution with different pH values and temperatures, resulting in an improvement in the tumor suppressive effect of the Nano Mn(III)-TP. Based on the nanoplatform, the effective combination of magnetic resonance imaging (MRI), CDT and chemotherapy could be used as a potential therapeutic agent for multimodal therapy, which is also expected to be applied to clinical tumor treatment.

Using Logistic Multivariate Analysis to Explore the Effects of Nursing and Psychological Factors on Motor and Cognitive Rehabilitation in Patients with Stroke: Based on a Retrospective Case-Control Study.

Objective: Based on a retrospective case-control study, logistic multivariate analysis was employed to explore the effects of nursing and psychological factors on the rehabilitation of motor and cognitive function in patients with stroke. Methods: A total of 200 stroke patients treated from February 2019 to April 2020 were enrolled in our hospital. According to the results of exercise and cognitive rehabilitation, the patients with good rehabilitation were divided into the control group (n = 140) and the research group (n = 60). The effects of nursing and psychological factors on the rehabilitation of motor and cognitive function in patients with stroke were analyzed. Results: First of all, we compared the general data. There were significant differences in terms of age, years of education, occupational status, payment methods of medical expenses, family income and the course of the disease, and the difference was statistically significant (P < 0.05). There was no significant difference in general data (P > 0.05). Secondly, we compared the nursing effective rates. The nursing effective rates of the study group were 10 cases, 15 cases, 12 cases, and 23 cases, and the nursing effective rate was 61.67%. In the control group, 78 cases were markedly effective, 33 cases were effective, 25 cases were general and 14 cases were ineffective, and the nursing effective rate was 90.00%. The effective rate of nursing in the study group was higher than that in the control group, and the difference was statistically significant (P < 0.05). There was no significant difference in anxiety and depression scores before nursing (P > 0.05), but they decreased after nursing. In addition, the scores of anxiety and depression in the study group were higher than those in the control group, and the difference was statistically significant (P < 0.05). There was no significant difference in motor function and cognitive function between prenursing and prenursing (P > 0.05); after nursing, the motor function increased and the score of cognitive function decreased. Furthermore, the motor function of the study group was lower compared to the control group, and the score of cognitive function of the study group was higher compared to the control group, and the difference was statistically significant (P < 0.05). The results of the Person correlation analysis showed that there was a significant correlation between nursing anxiety depression and the rehabilitation effect of motor cognitive function in stroke patients. The results of logistic regression analysis showed that age, family income, nursing efficiency, anxiety, and depression were the factors affecting the rehabilitation of motor and cognitive function in stroke patients. Conclusion: Age and family income may be the risk factors affecting the psychological mood of patients. Medical staff should pay attention to the negative emotion of patients and strengthen the nursing intervention of patients.

Synthesis of novel 4,7-disubstituted quinoline derivatives as autophagy inducing agents via targeting stabilization of ATG5.

A series of new 4,7-disubstituted quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 10c, 10g, 10i, 10j and 10k displayed potent antiproliferative activity with IC50 value of lower than 5.0 µM against human tumor cell lines, and N-(3-nitrophenyl)-7-((3,4,5-trimethoxybenzyl)oxy)quinoline - 4-amine 10k was found to be the most potent antiproliferative agent against HCT-116, HepG2, BCG-823, A549 and A2780 cell lines with IC50 values of 0.35, 1.98, 0.60, 0.39 and 0.67 µM, respectively. The antitumor efficacy of the representative compound 10k in mice was also evaluated, and the results showed that compound 10k effectively inhibited tumor growth and decreased tumor weight in animal models. Further investigation on mechanism of action indicated that compound 10k could inhibit colorectal cancer growth through inducing autophagy via excessively targeting stabilization of ATG5. Therefore, these quinoline derivatives are a new class of molecules that have the potential to be developed as new antitumor drugs.

Novel compound heterozygous GPR56 gene mutation in a twin with lissencephaly: A case report.

BACKGROUND: Lissencephaly (LIS) is a malformation of cortical development with broad gyri, shallow sulci and thickened cortex characterized by developmental delays and seizures. Currently, 20 genes have been implicated in LIS. However, GRP56-related LIS has never been reported. GRP56 is considered one of the causative genes for bilateral frontoparietal polymicrogyria. Here, we report a twin infant with LIS and review the relevant literature. The twins both carried the novel compound heterozygous GPR56 mutations. CASE SUMMARY: A 5-mo-old female infant was hospitalized due to repeated convulsions for 1 d. The patient had a flat head deformity that manifested as developmental delays and a sudden onset of generalized tonic-clonic seizures at 5 mo without any causes. The electroencephalography was normal. Brain magnetic resonance imaging revealed a simple brain structure with widened and thickened gyri and shallow sulci. The white matter of the brain was significantly reduced. Patchy long T1 and T2 signals could be seen around the ventricles, which were expanded, and the extracerebral space was widened. Genetic testing confirmed that the patient carried the GPR56 gene compound heterozygous mutations c.228delC (p.F76fs) and c.1820_1821delAT (p.H607fs). The unaffected father carried a heterozygous c.1820_1821delAT mutation, and the unaffected mother carried a heterozygous c.228delC mutation. The twin sister carried the same mutations as the proband. The patient was diagnosed with LIS. CONCLUSION: This is the first case report of LIS that is likely caused by mutations of the GPR56 gene.