Publications by authors named "Jing Zhao"

4,823 Publications

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Self-Strained Platinum Clusters with Finite Size: High-Performance Catalysts with CO Tolerance for PEMFCs.

ACS Appl Mater Interfaces 2022 Jun 29. Epub 2022 Jun 29.

Beijing Key Laboratory of Electrochemical Process and Technology for Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

Strained platinum-based materials with high performance have been regarded as the most promising electrocatalysts for proton exchange membrane fuel cells (PEMFCs) recently. Herein, self-strained platinum clusters with finite size (about 1 nm) are prepared by a combining liquid- and solid-phase UV irradiation cycle strategy. It started with a fresh HPtCl solution irradiated by UV light and then mixed with a graphitized carbon, followed by the dried mixture being subjected to UV light to generate monodispersed Pt clusters on the carbon surface. The obtained platinum clusters feature narrower size distribution and higher loading on carbon, exhibiting significantly improved activity and durability, much higher than that of the-state-of-art commercial Pt/C for the oxygen reduction reaction. More importantly, the self-strained Pt clusters display a surprising CO tolerance, which can be attributed to the unique adaptive lattice compressive strain that triggers an electron enrichment phenomenon for the Pt clusters. Therefore, this stepwise UV irradiation method solves the long-standing problem of both wide size distribution and low loading of metal clusters fabricated by one-step photochemical reduction, providing a potential route for the synthesis of other metal clusters with strained structures.
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http://dx.doi.org/10.1021/acsami.2c04033DOI Listing
June 2022

Attenuated Viral Replication of Avian with a Novel 82-Nucleotide Deletion in the 5a Gene Indicates a Critical Role for 5a in Virus-Host Interactions.

Microbiol Spectr 2022 Jun 29:e0140522. Epub 2022 Jun 29.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.

We previously found that a deletion in γ-coronavirus (IBV) accessory gene 5a is critical for decreased viral pathogenicity in chickens. Here, we systematically analyzed IBV virus infection: invasion, genome replication, subgenomic mRNA (sgmRNA) synthesis, protein synthesis, and virion release. The ability of the mutant IBV strain rYN-Δ5a to invade susceptible cells was not significantly different from that of parental rYN. However, compared with rYN, the level of sgmRNA synthesis and genome replication after cell entry by rYN-Δ5a was significantly lower in the early stage, resulting in a significantly lower level of nucleoprotein (N) synthesis and a consequent significantly lower number of offspring viruses released into the supernatant. The detected 5a protein was diffusely distributed in the cytoplasm and perinuclear area. We identified 16 differentially expressed host proteins, 8 of which were found to be host nuclear and cytoplasmic transport-related proteins. Coimmunoprecipitation revealed an interaction between hemagglutinin (HA)-tagged TNPO1, TNPO3, XPO1, XPOT, RanBP1, and EIF2B4 proteins and Flag-tagged 5a protein, and laser confocal microscopy confirmed 5a protein colocalization with these proteins, indicating that 5a protein can cause changes in the host protein localization. These host proteins promote the nuclear localization of N proteins, so we believe that 5a protein can hijack host nucleoplasmic transport-related proteins to help N enter the nucleus. This may involve regulating the cell cycle to promote the optimal intracellular conditions for virus assembly or by participating in the regulation of nucleolar function as a strategy to optimize virus replication. Coronaviruses (CoVs) have a huge impact on humans and animals. It is important for the prevention and control of the viruses to assess the molecular mechanisms related to virulence attenuation. Here, we systematically analyzed a single cycle of virus infection by γ-CoV IBV lacking accessory protein 5a. We observed that a 5a deletion in the IBV genome affected virus replication and sgmRNA synthesis early in the virus life cycle, leading to decreases in protein synthesis, offspring virus assembly, and virion release in chicken embryonic kidney cells. IBV 5a protein was found to interact with multiple host nuclear and cytoplasmic transport- and translation-related proteins, which can also interact with IBV N and relocate it into the cell nucleus. These findings provide a comprehensive view regarding the importance of IBV accessory protein 5a and an important theoretical basis for studying the interaction between coronavirus and host cell proteins.
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http://dx.doi.org/10.1128/spectrum.01405-22DOI Listing
June 2022

Autoregressive count data modeling on mobility patterns to predict cases of COVID-19 infection.

Stoch Environ Res Risk Assess 2022 Jun 23:1-16. Epub 2022 Jun 23.

School of Software and IoT Engineering, Jiangxi University of Finance and Economics, Nanchang, 330013 China.

At the beginning of 2022 the global daily count of new cases of COVID-19 exceeded 3.2 million, a tripling of the historical peak value reported between the initial outbreak of the pandemic and the end of 2021. Aerosol transmission through interpersonal contact is the main cause of the disease's spread, although control measures have been put in place to reduce contact opportunities. Mobility pattern is a basic mechanism for understanding how people gather at a location and how long they stay there. Due to the inherent dependencies in disease transmission, models for associating mobility data with confirmed cases need to be individually designed for different regions and time periods. In this paper, we propose an autoregressive count data model under the framework of a generalized linear model to illustrate a process of model specification and selection. By evaluating a 14-day-ahead prediction from Sweden, the results showed that for a dense population region, using mobility data with a lag of 8 days is the most reliable way of predicting the number of confirmed cases in relative numbers at a high coverage rate. It is sufficient for both of the autoregressive terms, studied variable and conditional expectation, to take one day back. For sparsely populated regions, a lag of 10 days produced the lowest error in absolute value for the predictions, where weekly periodicity on the studied variable is recommended for use. Interventions were further included to identify the most relevant mobility categories. Statistical features were also presented to verify the model assumptions.
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http://dx.doi.org/10.1007/s00477-022-02255-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223272PMC
June 2022

Upregulation of lncRNA PINK1-AS Predicts the Distant Metastasis of Patients with Small Cell Lung Cancer.

Mol Biotechnol 2022 Jun 28. Epub 2022 Jun 28.

Department of Pulmonary and Critical Care Medicine, First Hospital of Qinhuangdao, No. 258 Wenhua Road, Haigang District, Qinhuangdao, 066000, Hebei, People's Republic of China.

PINK1-AS has been shown to participate in gastric cancer, while its role in other tumors is unclear. This study was carried out to explore the participation of PINK1-AS in small cell lung cancer (SCLC). In this study, the expression of PINK1-AS in SCLC and paired non-cancer tissues from 60 SCLC patients and in plasma samples from 60 SCLC patients and 60 healthy controls was analyzed with RT-qPCR. Chi-squared t test was applied to analyze the associations between plasma expression levels of PINK1-AS and the clinical factors of the patients. Patients were followed up for 5 years to explore the role of PINK1-AS in the prognosis of SCLC. ROC curve analysis was applied to explore the role of PINK1-AS in the prediction of distant metastasis. Transwell assays were performed to evaluate the role of silencing and overexpression of PINK1-AS in the invasion and migration of SCLC cells. We found that PINK1-AS was upregulated in SCLC tissues compared to that in non-cancer tissues. Plasma expression levels of PINK1-AS were increased in SCLC patients compared to that in the controls. High plasma expression levels of PINK1-AS were closely associated with worse survival. Plasma expression of PINK1-AS was only closely correlated with distant tumor metastasis, but not other factors. High plasma expression levels of PINK1-AS effectively separated patients with distant metastasis from non-metastatic patients. Moreover, PINK1-AS positively regulated the migration and invasion of SCLC cells. Therefore, the upregulation of PINK1-AS predicts the distant metastasis of patients with SCLC.
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http://dx.doi.org/10.1007/s12033-022-00512-1DOI Listing
June 2022

Effects of homoeologous exchange on gene expression and alternative splicing in a newly formed allotetraploid wheat.

Plant J 2022 Jun 28. Epub 2022 Jun 28.

Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, Changchun, 130024, China.

Homoeologous exchange (HE) is a major mechanism generating post-polyploidization genetic variation with important evolutionary consequences. However, the direct impacts of HE on gene expression and transcript diversity in allopolyploids without the intertwined evolutionary processes remains to be fully understood. Here, we analyzed high-throughput RNA-seq data of young leaves from plant groups of a synthetic allotetraploid wheat (AADD), which contained variable numbers of HEs. We aimed to investigate if and to which extent HE directly impacts gene expression and alternative splicing (AS). We found that HE impacts expression of genes located within HE regions primarily via cis-acting dosage effect, which led to significant changes in the total expression level of homoeologous gene pairs, especially for homoeologs whose original expression was biased. In parallel, HE also influences expression of a large number of genes residing in non-HE regions by trans-regulation leading to convergent expression of homoeologs. Intriguingly, when taking into account of the original relative homoeolog expression states, homoeolog pairs under trans-effect are more prone to manifesting convergent response to the HEs whereas those under cis-regulation trended to show further exacerbated subgenome-biased expression. Moreover, HE-induced quantitative, largely individual-specific, changes of alternative splicing (AS) events were detected. Similar to homoeologous expression, homoeo-AS events under trans effect were more responsive to HE. HE therefore exerts multifaceted immediate effects on gene expression and, to a less extent, on individualized transcript diversity in nascent allopolyploidy.
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http://dx.doi.org/10.1111/tpj.15886DOI Listing
June 2022

Prevalence of developmental dyslexia in primary school children: a protocol for systematic review and meta-analysis.

World J Pediatr 2022 Jun 27. Epub 2022 Jun 27.

Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, 55 Zhongshan Avenue West, Tianhe District, Guangzhou, 510631, China.

Background: Developmental dyslexia (DD) is a specific impairment during the acquisition of reading skills and may have a lifelong negative impact on individuals. Reliable estimates of the prevalence of DD serve as the basis for evidence-based health resource allocation and policy making. However, the prevalence of DD in primary school children varies largely across studies. Moreover, it is unclear whether there are differences in prevalence in different genders and writing systems. Hence, the present study aims to conduct a systematic review and meta-analysis to assess the global prevalence of DD and to explore related factors.

Methods: We will undertake a comprehensive literature search in 14 databases, including EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure and Cochrane, from their inception to June 2021. Cross-sectional and longitudinal studies that describe the prevalence of DD will be eligible. The quality of the included observational studies will be assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement. The risk of bias will be determined by sensitivity analysis to identify publication bias.

Results: One meta-analysis will be conducted to estimate the prevalence of DD in primary school children. Heterogeneity will be assessed in terms of the properties of subjects (e.g., gender, grade and writing system) and method of diagnosis in the included primary studies. Subgroup analyses will also be performed for population and secondary outcomes.

Conclusion: The results will synthesize the prevalence of DD and provide information for policy-makers and public health specialists.
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http://dx.doi.org/10.1007/s12519-022-00572-yDOI Listing
June 2022

Melatonin inhibits testosterone synthesis in Roosters Leydig cells by regulating lipolysis of lipid droplets.

Theriogenology 2022 Jun 19;189:118-126. Epub 2022 Jun 19.

Key Lab of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Jilin, Changchun, 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China. Electronic address:

Leydig cells are important component of testis cells, which can synthesize testosterone with free cholesterol derived from lipid droplets (LDs). It is well known that melatonin could regulate synthesis of testosterone. However, it is still unclear whether melatonin participates in the synthesis of testosterone by regulating the lipolysis of LDs in Leydig cells. The purpose of this study was to elucidate the effect of melatonin on synthesis of testosterone in roosters Leydig cells by regulating lipolysis of LDs. The results showed that melatonin decreased synthesis of testosterone and intracellular free cholesterol in roosters Leydig cells. Exogenous addition of 22-OH-Cholesterol counteracted the inhibitory effect of melatonin on synthesis of testosterone. Furthermore, melatonin increased the LDs content and expression of perilipin 1 (PLIN1), and decreased expression of hormone-sensitive lipase (HSL) and triacylglycerol hydrolase (ATGL) in roosters Leydig cells. In addition, silencing PLIN1 reversed the inhibitory effect of melatonin on synthesis of testosterone in roosters Leydig cells by increasing free cholesterol content and expression of HSL and ATGL, and decreasing the lipid droplet content. Activation of cAMP/PKA pathway by using the pathway activators Forskolin and 8-Bromo-cAMP attenuated the inhibitory effect of melatonin on synthesis of testosterone accompanied by increasing level of free cholesterol content and expression of HSL and ATGL, and decreasing level of lipid droplet content and expression of PLIN1 in roosters Leydig cells. These results suggested that melatonin could inhibit the synthesis of testosterone in roosters Leydig cells by reducing the content of intracellular free cholesterol in which expression of PLIN1 and cAMP/PKA pathway were inhibited to reduce the lipolysis of LDs.
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http://dx.doi.org/10.1016/j.theriogenology.2022.06.016DOI Listing
June 2022

The Expression and Bioinformatics Analysis of Circular RNAs in Endometritis Mouse Uterus Tissues.

Molecules 2022 Jun 8;27(12). Epub 2022 Jun 8.

Joint Laboratory of the Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.

Previous studies have shown that circular RNAs are directly or indirectly involved in the occurrence of various diseases by regulating gene expression. However, the acting mechanism of circular RNAs in endometritis remains unclear. In this study, we successfully established an endometritis model in mouse using ; endometrial integrity was destroyed, inflammatory cells infiltrated and the expression of IL-6, IL-1β, TNF-α was significantly up-regulated. We analyzed and screened the circular RNA expression profiles between healthy and endometritis-stricken mice by the Illumina HiSeq platform, and used qRT-PCR method to verify the different expressions of circular RNAs. Gene ontology (GO) analysis showed that circular RNAs were mainly involved in biological processes such as the positive regulation of transcription from RNA polymerase POL II promoter and the negative regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of circular RNAs target genes may be involved in the TGF-β signaling pathway. We verified the expression of TGF-β and its related factors; the mRNA of TGF-β1 and smad7 were significantly up-regulated in endometritis mouse ( < 0.01) and the protein expression level of p-smad3 was significantly decreased ( < 0.01). Finally, we constructed a circular RNAs-miRNA network to elucidate the potential regulatory relationship between two small molecules. This research may provide new ideas for circular RNAs in the treatment of endometritis.
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http://dx.doi.org/10.3390/molecules27123682DOI Listing
June 2022

Design and Characterization of a Novel Hapten and Preparation of Monoclonal Antibody for Detecting Atrazine.

Foods 2022 Jun 13;11(12). Epub 2022 Jun 13.

Department of Entomology & Nematology and the UC Davis Comprehensive Cancer Center, University of California, Davis, CA 95616, USA.

This study provides the first design and synthetic protocol for preparing highly sensitive and specific atrazine (ATR) monoclonal antibodies (mAbs). In this work, a previously unreported hapten, 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine, was designed and synthesized, which maximally exposed the characteristic amino group ATR to an animal immune system to induce the expected antibody. The molecular weight of the ATR hapten was 259.69 Da, and its purity was 97.8%. The properties of the anti-ATR mAb were systematically characterized. One 9F5 mAb, which can detect ATR, was obtained with an IC value (the concentration of analyte that produced 50% inhibition of ATR) of 1.678 µg/L for ATR. The molecular weight for the purified 9F5 mAb was approximately 52 kDa for the heavy chain and 15 kDa for the light chain. The anti-ATR mAb prepared in this study was the IgG type. The working range of the standard curve (IC (the concentration of analyte that produced 20% inhibition of ATR)IC (the concentration of analyte that produced 80% inhibition of ATR)) was 0.384 to 11.565 µg/L. The prepared anti-ATR mAb had high specificity, sensitivity, and affinity with low cross-reactivity. The prepared anti-ATR mAb could provide the core raw material for establishing an ATR immunoassay.
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http://dx.doi.org/10.3390/foods11121726DOI Listing
June 2022

Model-Guided Metabolic Rewiring for Gamma-Aminobutyric Acid and Butyrolactam Biosynthesis in &nbsp; ATCC13032.

Biology (Basel) 2022 May 31;11(6). Epub 2022 May 31.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Gamma-aminobutyric acid (GABA) can be used as a bioactive component in the pharmaceutical industry and a precursor for the synthesis of butyrolactam, which functions as a monomer for the synthesis of polyamide 4 (nylon 4) with improved thermal stability and high biodegradability. The bio-based fermentation production of chemicals using microbes as a cell factory provides an alternative to replace petrochemical-based processes. Here, we performed model-guided metabolic engineering of for GABA and butyrolactam fermentation. A GABA biosynthetic pathway was constructed using a bi-cistronic expression cassette containing mutant glutamate decarboxylase. An in silico simulation showed that the increase in the flux from acetyl-CoA to α-ketoglutarate and the decrease in the flux from α-ketoglutarate to succinate drove more flux toward GABA biosynthesis. The TCA cycle was reconstructed by increasing the expression of and genes and deleting the gene. Blocking GABA catabolism and rewiring the transport system of GABA further improved GABA production. An acetyl-CoA-dependent pathway for in vivo butyrolactam biosynthesis was constructed by overexpressing -encoding ß-alanine CoA transferase. In fed-batch fermentation, the engineered strains produced 23.07 g/L of GABA with a yield of 0.52 mol/mol from glucose and 4.58 g/L of butyrolactam. The metabolic engineering strategies can be used for genetic modification of industrial strains to produce target chemicals from α-ketoglutarate as a precursor, and the engineered strains will be useful to synthesize the bio-based monomer of polyamide 4 from renewable resources.
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http://dx.doi.org/10.3390/biology11060846DOI Listing
May 2022

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI.

Cancers (Basel) 2022 Jun 13;14(12). Epub 2022 Jun 13.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.

Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm and 1000 mm. Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume ( = 14; < 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm than for 1000 mm. These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm tumors had 1.5% iron content ( = 14; σ = 1.1), while the 1000 mm tumors contained only 0.4% iron ( = 14; σ = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R = 0.83) ( = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa.
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http://dx.doi.org/10.3390/cancers14122909DOI Listing
June 2022

Tailoring Materials for Epilepsy Imaging: From Biomarkers to Imaging Probes.

Adv Mater 2022 Jun 23:e2203667. Epub 2022 Jun 23.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Zhangheng Road 826, Shanghai, 201203, China.

Excising epileptic foci (EF) is the most efficient approach for treating drug-resistant epilepsy (DRE). However, owing to the vast heterogeneity of epilepsies, EF in one-third of patients cannot be accurately located, even after exhausting all current diagnostic strategies. Therefore, identifying biomarkers that truly represent the status of epilepsy and fabricating probes with high targeting specificity are prerequisites for identifying the "concealed" EF. However, no systematic summary of this topic has been published. In this paper, we first summarize the potential biomarkers of EF and classify them into three categories: functional, molecular, and structural aberrances during epileptogenesis, a procedure of non-epileptic brain biasing toward epileptic tissue. The materials used to fabricate these imaging probes and their performance in defining the EF in preclinical and clinical studies are highlighted. Finally, the perspectives for developing the next generation of probes and their challenges in clinical translation are discussed. In general, this review will be helpful in guiding the development of imaging probes defining EF with improved accuracy and holds promise for increasing the number of DRE patients who are eligible for surgical intervention. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202203667DOI Listing
June 2022

Circulating folate concentrations and the risk of mild cognitive impairment: a prospective study on the older Chinese population without folic acid fortification.

Eur J Neurol 2022 Jun 23. Epub 2022 Jun 23.

Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.

Background: The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid was not implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI.

Methods: We performed a longitudinal analysis of 3974 participants aged ≥ 60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate-MCI association were explored via a path analysis approach.

Results: Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (P for trend < 0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (P < 0.05).

Conclusions: Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.
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http://dx.doi.org/10.1111/ene.15474DOI Listing
June 2022

Prevalence and predictors of psychological distress among patients with thyroid cancer during transitional period in China: a cross-sectional study.

Support Care Cancer 2022 Jun 21. Epub 2022 Jun 21.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Objective: This study aimed to explore the psychological distress and its predictors among Chinese patients with thyroid cancer during their transitional period from hospital to home.

Methods: A cross-sectional study was conducted in a cancer hospital in Tianjin, China. A total of three hundred patients with thyroid cancer completed the Chinese version of the National Comprehensive Cancer Network Distress Thermometer (DT), Cancer Fatigue Scale, and the Brief Illness Perception Questionnaire. Logistic regression was used to obtain the model of predictors of psychological distress among patients with thyroid cancer during the transitional period.

Results: The DT score of 300 patients with thyroid cancer ranged from 0 to 10, and the median DT score was 2 [1-4]. The prevalence of clinically relevant psychological distress (DT score ≥ 4) in Chinese patients with thyroid cancer during their transitional period was 29.33% (88/300). The results of logistic regression analysis showed that gender (OR = 2.505, P = 0.036), fatigue (OR = 1.086, P = 0.005), and illness perception (OR = 1.137, P < 0.001) were significantly related to psychological distress in patients with thyroid cancer.

Conclusions: The psychological distress of patients with thyroid cancer during the transitional period is medium level. Patients with thyroid cancer who are female, easily fatigued, and have worse illness perceptions are more likely to experience psychological distress. Therefore, clinical attention should be paid to female patients and potential interventions aimed at improving fatigue and illness perception. It may reduce the prevalence of psychological distress during the transitional period.
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http://dx.doi.org/10.1007/s00520-022-07225-wDOI Listing
June 2022

Neoadjuvant immunotherapy followed by surgery with curative intent in 35 patients with advanced NSCLC: the retrospective experiences of a multidisciplinary team.

Ann Transl Med 2022 May;10(10):609

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Background: In recent years, neoadjuvant immunotherapy combined with chemotherapy has been used to treat locally advanced non-small cell lung cancer (NSCLC); however, no data are available to guide the selection of patients suitable for radical resection. In this paper, we report a clinical mode based on a multidisciplinary team (MDT).

Methods: We retrospectively analyzed the clinical data of patients with advanced NSCLC who were treated in our center between 26 December, 2019 and 1 October, 2021. These cases received an MDT assessment first. Eligible patients then received chemotherapy combined with personalized neoadjuvant immunotherapy. Adverse events were recorded. Chest computed tomography (CT) was performed every other cycle for tumor assessment. Radical resection was subsequently performed for potentially resectable tumors. Intraoperative conditions and surgical complications were recorded. The resected specimens were evaluated to determine the response to neoadjuvant therapy.

Results: The MDT team selected a total of 35 patients (squamous cell carcinoma: n=26, adenocarcinoma: n=8, adenosquamous carcinoma: n=1) for radical resection following neoadjuvant immunotherapy combined with chemotherapy. According to the Response Evaluation Criteria in Solid Tumors (RECIST) findings, 1 patient had complete remission, 27 had partial remission, 6 had progressive disease, and 1 had stable disease. All participants underwent radical resection, including video-assisted thoracoscopic surgery [VATS; 32 (91.4%)], sleeve resection [7 (20.0%)], and multilobar resection [7 (20.0%)]. A total of 17 patients (48.6%) achieved complete pathological remission, and 10 (28.6%) achieved major pathological remission. After surgery, the pathological grade was reduced in 33 patients (94.2%); the RECIST findings were unrelated to postoperative pathological remission (P=0.15).

Conclusions: The MDT mode helps to select suitable patients for radical resection and results in satisfactory pathological remission.
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http://dx.doi.org/10.21037/atm-22-2271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201164PMC
May 2022

Metformin in the Treatment of Amisulpride-Induced Hyperprolactinemia: A Clinical Trial.

Front Mol Neurosci 2022 26;15:892477. Epub 2022 May 26.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To evaluate the efficacy and safety of metformin in the treatment of amisulpride-induced hyperprolactinemia.

Methods: A total of 86 schizophrenic patients who developed hyperprolactinemia after taking amisulpride were screened and randomly assigned to the metformin group (42 patients) and placebo group (44 patients) and followed up for eight weeks. The patients' serum prolactin levels, blood glucose and lipids were measured at the baseline and the end of the intervention. The treatment emergent symptom scale (TESS) was also assessed.

Results: After eight weeks of intervention, serum prolactin levels in the metformin group decreased from (1737.360 ± 626.918) mIU/L at baseline to (1618.625 ± 640.865) mIU/L, whereas serum prolactin levels in the placebo group increased from (2676.470 ± 1269.234) mIU/L at baseline to (2860.933 ± 1317.376) mIU/L. There was a significant difference in prolactin changes (F = 9.982, = 0.002) between the two groups. There was no significant difference in the incidence of adverse drug reactions ( > 0.05) between the two groups.

Conclusion: Metformin is able to improve amisulpride-induced hyperprolactinemia with its safety.
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http://dx.doi.org/10.3389/fnmol.2022.892477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205636PMC
May 2022

The Efficacy and Safety of Remimazolam Tosilate Versus Dexmedetomidine in Outpatients Undergoing Flexible Bronchoscopy: A Prospective, Randomized, Blind, Non-Inferiority Trial.

Front Pharmacol 2022 2;13:902065. Epub 2022 Jun 2.

Department of Anaesthesiology, Liaocheng People's Hospital, Liaocheng, China.

This study aimed to compare the efficacy and safety of remimazolam tosilate-remifentanil (RT-RF) vs dexmedetomidine-remifentanil (Dex-RF) for outpatients undergoing fiberoptic bronchoscopy (FB). We conducted a double-blind, randomized, prospective study involving a total of 146 outpatients undergoing FB divided into two groups. The RT-RF (RR) group ( = 73) received an initial dose of 12 mg/kg/h of RT for 10 min followed by a maintenance dose of 1-2 mg/kg/h, while the Dex-RF (DR) group ( = 73) received an initial dose of 0.5 μg/kg of Dex for 10 min followed by a maintenance dose of 0.2-0.7 μg/kg/h. All outpatients also received 0.05-0.2 μg/kg/min RF to maintain the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale <3. The primary outcome was rate of successful FB completed. Secondary outcomes were time metrics, hemodynamics, intubating conditions, oxygen saturation, coughing severity, number of remedies, total dose of fentanyl, RF, RT, and Dex, incidence of dreaming, patient and bronchoscopist satisfaction, willingness to repeat bronchoscopy, and adverse events. The FB successful completion rate was 94.52% (95% CI: 89.20-99.90) in the RR group and 91.78% (95% CI: 85.30-98.20) in the DR group. Compared with patients in the DR group, the onset time, time to fully alert, and hospital discharge were all significantly shorter in the RR group ( < 0.01), and hemodynamics were more stable in the RR group. Intubating conditions, clinically acceptable intubating conditions, lowest oxygen saturation, coughing severity, consumption of fentanyl and RF, number of remedies, and patient and bronchoscopist satisfaction were similar between the groups ( > 0.05), as were demographic characteristics, incidence of dreaming, willingness to repeat bronchoscopy, and adverse events ( > 0.05). RT-RF has non-inferior efficacy, better time metrics and hemodynamic stability for outpatients undergoing FB than Dex-RF. : [http://www.chictr.org.cn/showproj.aspx?proj=66673], identifier [ChiCTR2000041524].
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http://dx.doi.org/10.3389/fphar.2022.902065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201326PMC
June 2022

Efficient Detection of the Alternative Spliced Human Proteome Using Translatome Sequencing.

Front Mol Biosci 2022 2;9:895746. Epub 2022 Jun 2.

Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.

Alternative splicing (AS) isoforms create numerous proteoforms, expanding the complexity of the genome. Highly similar sequences, incomplete reference databases and the insufficient sequence coverage of mass spectrometry limit the identification of AS proteoforms. Here, we demonstrated full-length translating mRNAs (ribosome nascent-chain complex-bound mRNAs, RNC-mRNAs) sequencing (RNC-seq) strategy to sequence the entire translating mRNA using next-generation sequencing, including short-read and long-read technologies, to construct a protein database containing all translating AS isoforms. Taking the advantage of read length, short-read RNC-seq identified up to 15,289 genes and 15,906 AS isoforms in a single human cell line, much more than the Ribo-seq. The single-molecule long-read RNC-seq supplemented 4,429 annotated AS isoforms that were not identified by short-read datasets, and 4,525 novel AS isoforms that were not included in the public databases. Using such RNC-seq-guided database, we identified 6,766 annotated protein isoforms and 50 novel protein isoforms in mass spectrometry datasets. These results demonstrated the potential of full-length RNC-seq in investigating the proteome of AS isoforms.
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http://dx.doi.org/10.3389/fmolb.2022.895746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201276PMC
June 2022

The Efficacy and Safety of Sintilimab Combined With Nab-Paclitaxel as a Second-Line Treatment for Advanced or Metastatic Gastric Cancer and Gastroesophageal Junction Cancer.

Front Oncol 2022 1;12:924149. Epub 2022 Jun 1.

Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou, University and Henan Cancer Hospital, Zhengzhou, China.

Background: Unresectable advanced or recurrent gastric cancer patients have a poor prognosis. PD-1 monotherapy regimen and PD-1 combined chemotherapy regimen have become the standard third- and first-line treatment for advanced gastric cancer, respectively. However, the status of immune checkpoint inhibitors in the second-line treatment for advanced gastric cancer has not been established. The combination of chemotherapy and anti-PD-1 antibody has been demonstrated to have a synergistic effect. In this study, we aimed to evaluate the efficacy and safety of sintilimab combined with nab-paclitaxel in the second-line treatment for advanced gastric cancer (GC)/gastroesophageal junction (GEJ) cancer patients.

Patients And Methods: We retrospectively analyzed patients with advanced GC/GEJ cancer that progressed after first-line systemic therapies with sintilimab combined with nab-paclitaxel from April 1, 2019 to December 31, 2021. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety.

Results: Thirty-nine patients were enrolled and eligible for response assessment. Complete response (CR) was not observed, 15 patients achieved partial response (PR), 16 patients had stable disease (SD) and 9 patients had progressive disease (PD). The ORR and DCR were 15 (38.5%) and 31 (79.5%), respectively. Median PFS was 5.4 months (95%CI: 3.072-7.728). PFSs between different subgroups were analyzed. The results showed that gender, age, Human epidermal growth factor receptors 2 (HER2) status, PD-L1 expression, primary tumor site and chemotherapy cycles had no significant effect on PFS. Most of the adverse events (AEs) were of grade 1-2 and manageable. The common treatment-related adverse events of grade 3 or 4 included anemia (12.8%), neutropenia (12.8%), leukopenia (10.3%), hand-foot syndrome (7.7%), thrombocytopenia (7.7%). The potential immune-related adverse events (irAEs) were grade 1 pneumonia (1 pts [2.6%]) and grade 4 hepatitis (1 pts [2.6%]). There were no treatment-related deaths.

Conclusion: These results indicate that sintilimab combined with nab-paclitaxel exhibits good anti-tumor activity and an acceptable safety profile as a second-line treatment for advanced or metastatic gastric cancer. These results warrant further investigation and evaluation to identify patients who can benefit more from the combined treatment strategy.
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http://dx.doi.org/10.3389/fonc.2022.924149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198424PMC
June 2022

KIF23 is a potential biomarker of diffuse large B cell lymphoma: Analysis based on bioinformatics and immunohistochemistry.

Medicine (Baltimore) 2022 Jun 17;101(24):e29312. Epub 2022 Jun 17.

Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract: Diffuse Large B Cell Lymphoma (DLBCL), the most common form of blood cancer. The genetic and clinical heterogeneity of DLBCL poses a major barrier to diagnosis and treatment. Hence, we aim to identify potential biomarkers for DLBCL.Differentially expressed genes were screened between DLBCL and the corresponding normal tissues. Kyoto Encyclopedia of Genes and Genomes and Gene oncology analyses were performed to obtain an insight into these differentially expressed genes. PPI network was constructed to identify hub genes. survival analysis was applied to evaluate the prognostic value of those hub genes. DNA methylation analysis was implemented to explore the epigenetic dysregulation of genes in DLBCL.In this study, Kinesin family member 23 (KIF23) showed higher expression in DLBCL and was identified as a risk factor in DLBCL. The immunohistochemistry experiment further confirmed this finding. Subsequently, the univariate and multivariate analysis indicated that KIF23 might be an independent adverse factor in DLBCL. Upregulation of KIF23 might be a risk factor for the overall survival of patients who received an R-CHOP regimen, in late-stage, whatever with or without extranodal sites. Higher expression of KIF23 also significantly reduced 3, 5, 10-year overall survival. Furthermore, functional enrichment analyses (Kyoto Encyclopedia of Genes and Genomes, Gene oncology, and Gene Set Enrichment Analysis) showed that KIF23 was mainly involved in cell cycle, nuclear division, PI3K/AKT/mTOR, TGF-beta, and Wnt/beta-catenin pathway in DLBCL. Finally, results of DNA methylation analysis indicated that hypomethylation in KIF23's promoter region might be the result of its higher expression in DLBCL.The findings of this study suggested that KIF23 is a potential biomarker for the diagnosis and prognosis of DLBCL. However, further studies were needed to validate these findings.
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http://dx.doi.org/10.1097/MD.0000000000029312DOI Listing
June 2022

Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms.

Front Pharmacol 2022 31;13:881231. Epub 2022 May 31.

Laboratory of Clinical Pharmacokinetics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Cholestasis is a clinical syndrome triggered by the accumulation and aggregation of bile acids by subsequent inflammatory responses. The present study investigated the protective effect of glycyrrhetinic acid (GA) on the cholestatic liver injury induced by lithocholic acid (LCA) from both anti-inflammatory and choleretic mechanistic standpoints. Male C57BL/6 mice were treated with LCA twice daily for 4 days to induce intrahepatic cholestasis. GA (50 mg/kg) and pregnenolone 16α-carbonitrile (PCN, 45 mg/kg) were intraperitoneally injected 3 days before and throughout the administration of LCA, respectively. Plasma biochemical indexes were determined by assay kits, and hepatic bile acids were quantified by LC-MS/MS. Hematoxylin and eosin staining of liver sections was performed for pathological examination. Protein expression of the TLRs/NF-κB pathway and the mRNA levels of inflammatory cytokines and chemokines were examined by Western blotting and PCR, respectively. Finally, the hepatic expression of pregnane X receptor (PXR) and farnesoid X receptor (FXR) and their target genes encoding metabolic enzymes and transporters was evaluated. GA significantly reversed liver necrosis and decreased plasma ALT and ALP activity. Plasma total bile acids, total bilirubin, and hepatic bile acids were also remarkably preserved. More importantly, the recruitment of inflammatory cells to hepatic sinusoids was alleviated. Additionally, the protein expression of TLR2, TLR4, and p-NF-κBp65 and the mRNA expression of CCL2, CXCL2, IL-1β, IL-6, and TNF-α were significantly decreased. Moreover, GA significantly increased the expression of hepatic FXR and its target genes, including BSEP, MRP3, and MRP4. In conclusion, GA protects against LCA-induced cholestatic liver injury by inhibiting the TLR2/NF-κB pathway and upregulating hepatic FXR expression.
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http://dx.doi.org/10.3389/fphar.2022.881231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194553PMC
May 2022

Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial-mesenchymal transition and endothelial injury by suppressing MAPK activation.

Bioengineered 2022 05;13(5):13882-13892

Department of Ophthalmology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China.

Diabetic retinopathy (DR) is a common complication of diabetes, and the leading cause of blindness in adults. Sprouty-related proteins with EVH1 domain (SPRED2) play an important role in diabetes and are closely related to the lens and eye morphogenesis. This study attempted to investigate the role and related mechanism of SPRED2 in DR. DR rat model was established by administration streptozocin. Human retinal endothelial cells (HRECs) were treated with high glucose (HG) to mimic DR. The results showed that SPRED2 expression was decreased in the retinal tissues of DR rats and HG-treated HRECs. MTT assay and flow cytometry data showed that SPRED2 overexpression reduced cell viability of HG-treated HRECs. SPRED2 overexpression enhanced Caspase-3 activity and promoted apoptosis of HG-treated HRECs. Furthermore, the expressions of endothelial cell markers CD31 and E-cad were down-regulated, whereas the expressions of mesenchymal cell markers FSP1, SM22, and α-SMA were up-regulated in the HG-treated HRECs. SPRED2 overexpression reversed HG-induced endothelial-mesenchymal transition in HRECs. The expressions of tight junction components claudin 3, occludin, and ZO-1 were increased in HG-treated HRECs following SPRED2 up-regulation. In addition, SPRED2 overexpression downregulated the expression of p-ERK1/2, p-p38, and p-JNK in the HG-treated HRECs. In conclusion, this study demonstrated that SPRED2 overexpression repressed endothelial-mesenchymal transition and endothelial injury in HG-treated HRECs by suppressing MAPK signaling pathway. These findings suggested that SPRED2 may be a novel potential therapeutic target implicated in DR progression.
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http://dx.doi.org/10.1080/21655979.2022.2086351DOI Listing
May 2022

Discovery of 1Pyrazole Biaryl Sulfonamides as Novel G2019S-LRRK2 Kinase Inhibitors.

ACS Med Chem Lett 2022 Jun 23;13(6):981-988. Epub 2022 May 23.

Department of Pathology, Stanford University, 300 Pasteur Drive, Stanford, California 94305, United States.

G2019S (GS) is the most prevalent mutation in the leucine rich repeat protein kinase 2 gene (), a genetic predisposition that is common for Parkinson's disease, as well as for some forms of cancer, and is a shared risk allele for Crohn's disease. GS-LRRK2 has a hyperactive kinase, and although numerous drug discovery programs have targeted LRRK2 kinase, few have reached clinical development. We report the discovery and preliminary development of an entirely novel structural class of potent and selective GS-LRRK2 kinase inhibitors: biaryl-1-pyrazoles.
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http://dx.doi.org/10.1021/acsmedchemlett.2c00116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190033PMC
June 2022

Morin Inhibits Dox-Induced Vascular Inflammation By Regulating PTEN/AKT/NF-κB Pathway.

Inflammation 2022 Jun 15. Epub 2022 Jun 15.

Department of Hematology, The Second Hospital of Hebei Medical University, 215 Heping W Rd, Shijiazhuang, 050004, China.

The side effects of doxorubicin (Dox) may influence the long-term survival of patients with malignancies. Therefore, it is necessary to clarify the mechanisms generating these side effects induced by Dox and identify effective therapeutic strategies. Here, we found that interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels were significantly increased in vascular tissues of Dox-treated mice and Dox-treated vascular smooth muscle cells (VSMCs). Furthermore, we revealed that Dox downregulated the phosphatase and tension homology deleted on chromosome 10 (PTEN) level while upregulated p-AKT and p65 level in VSMCs in vitro. Overexpression of PTEN in VSMCs partly reversed Dox-induced inflammation. Importantly, we demonstrated that Morin could inhibit Dox-induced inflammation by facilitating an increase of PTEN, thus inhibiting the activation of protein kinase B (AKT)/nuclear factor kappa B (NF-κB)/pathway. Additionally, we showed that Morin could reduce the miR-188-5p level, which was increased in Dox-treated VSMCs. Inhibition of miR-188-5p suppressed Dox-induced vascular inflammation in vitro. In conclusion, Morin reduced the Dox-induced vascular inflammatory by moderating the miR-188-5p/PTEN/AKT/NF-κB pathway, indicating that Morin might be a therapeutic agent for overcoming the Dox-induced vascular inflammation.
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http://dx.doi.org/10.1007/s10753-022-01701-5DOI Listing
June 2022

High-Performance Osmotic Power Generators Based on the 1D/2D Hybrid Nanochannel System.

ACS Appl Mater Interfaces 2022 Jun 15;14(25):29197-29212. Epub 2022 Jun 15.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou730000, PR China.

Extracting clean energy by converting the salinity gradient between river and sea into energy is an effective way to reduce the global pollution and carbon emissions. Reverse electrodialysis (RED) is of great importance to realize the energy conversion assisting the ion-selective membrane. However, its higher ion resistance and lower conversion efficiency results in the undesirable power conversion performance. Here, we demonstrate a 1D/2D hybrid nanochannel system to achieve high osmotic energy conversion and output power. This heterogeneous structure is composed of two structures, in which the subnanometer nanochannels in graphene oxide membrane (GOM) can serve as a selective layer and reduce the ion diffusion energy barrier, while the nanochannel in the polymer can introduce asymmetry to enhance ionic rectification and conversion efficiency. This heterogeneous membrane exhibits excellent cation selectivity and enhanced ionic current rectification (ICR) performance. The application of the GOM/PET hybrid nanochannel system in osmotic energy harvesting is evaluated, and the output power can reach up to 118.2 pW with the energy conversion efficiency of 40.3%. Theoretical calculation indicates that the 1D/2D hybrid system can effectively take the advantage of excellent cation selectivity of 2D lamellar nanochannels to improve its RED performance significantly.
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http://dx.doi.org/10.1021/acsami.2c05247DOI Listing
June 2022

A unified framework for weighted parametric group sequential design.

Biom J 2022 Jun 15. Epub 2022 Jun 15.

Merck & Co., Inc., Rahway, NJ, USA.

Group sequential design (GSD) is widely used in clinical trials in which correlated tests of multiple hypotheses are used. Multiple primary objectives resulting in tests with known correlations include evaluating (1) multiple experimental treatment arms, (2) multiple populations, (3) the combination of multiple arms and multiple populations, or (4) any asymptotically multivariate normal tests. In this paper, we focus on the first three of these and extend the framework of the weighted parametric multiple test procedure from fixed designs with a single analysis per objective to a GSD setting where different objectives may be assessed at the same or different times, each in a group sequential fashion. Pragmatic methods for design and analysis of weighted parametric group sequential design under closed testing procedures are proposed to maintain the strong control of the family-wise Type I error rate when correlations between tests are incorporated. This results in the ability to relax testing bounds compared to designs not fully adjusting for known correlations, increasing power, or allowing decreased sample size. We illustrate the proposed methods using clinical trial examples and conduct a simulation study to evaluate the operating characteristics.
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http://dx.doi.org/10.1002/bimj.202100085DOI Listing
June 2022

Spatiotemporal tracking of the transport of RNA nano-drugs: from transmembrane to intracellular delivery.

Nanoscale 2022 Jun 14. Epub 2022 Jun 14.

School of Chemistry and Life Science, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, China.

The popularity of RNA nanoparticles (RNPs) has risen rapidly during the past decade due to the development of RNA nanotechnology. Understanding the fast dynamic process of cell entry and intracellular delivery of RNPs is essential for the design of intelligent therapeutic RNA nano-drugs and mRNA vaccines.How the interaction between the membrane and target ligand of RNPs influences the cell entry, and how the dynamic mechanism of RNPs takes place in different organelles remain ill-defined. Herein, the cell entry of Antimir21-RNP-Apt is monitored using a force tracing technique with a high spatiotemporal resolution at the single particle level, the specific interaction of Apt and EGFR promotes the cell entry efficiency and achieves long-lasting curative effects. Furthermore, the intracellular delivery pathway through different organelles is discovered using fluorescence tracking, and the low motility in early endosomes and the high motility in late endosomes are analyzed. This report provides key strategies for engineering RNA nanomedicines and facilitating clinical translation.
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http://dx.doi.org/10.1039/d2nr00988aDOI Listing
June 2022

Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta-analysis.

J Obstet Gynaecol Res 2022 Jun 13. Epub 2022 Jun 13.

Department of Gynaecology, Hebei General Hospital, Shijiazhuang, China.

Aim: This meta-analysis was conducted to evaluate the impact of BRCA mutations on survival outcomes of ovarian cancer patients and assess whether the BRCA status was an independent predictor of complete cytoreduction.

Methods: We searched the PubMed, Cochrane, EMBASE, Scopus, Web of Science, and Google Scholar databases for studies that evaluated the associations among BRCA mutations, ovarian cancer survival and surgical cytoreduction before August 2021 based on specific inclusion and exclusion criteria.

Results: We identified 61 articles that compared the clinical features, survival outcomes, and optimal surgical cytoreduction rates between BRCA-positive patients and BRCA-negative patients. The results showed that BRCA mutation carriers were diagnosed with ovarian cancer at a younger age than the age at which nonmutation carriers were diagnosed. In addition, BRCA mutation carriers were more likely to be in the International Federation of Gynecology and Obstetrics (FIGO) stage III-IV, and the pathological grade was commonly grade 3. The pathological type of BRCA mutation carriers was more likely to be high-grade serous carcinoma. Patients with BRCA mutations had higher response rates to platinum-based chemotherapy than the noncarriers. However, patients in both groups had equivalent rates of surgical cytoreduction, and BRCA-positive patients had longer overall survival (OS) time (HR = 0.65; 95% confidence interval [CI]: 0.59, 0.73; p < 0.001) and longer progression-free survival (PFS) (HR = 0.72; 95% CI: 0.63, 0.82; p < 0.001).

Conclusion: BRCA mutations appear to be associated with improved OS and PFS in patients with ovarian cancer. However, we did not find any difference in the surgical resection rate between participants in the two groups.
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http://dx.doi.org/10.1111/jog.15326DOI Listing
June 2022

Probing the serum albumin binding site of fenamates and photochemical protein labeling with a fluorescent dye.

Org Biomol Chem 2022 Jun 29;20(25):5076-5085. Epub 2022 Jun 29.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China.

Human serum albumin (HSA) can bind with numerous drugs, leading to a significant influence on drug pharmacokinetics as well as undesirable drug-drug interactions due to competitive binding. Probing the HSA drug binding site thus offers great opportunities to reveal drug-HSA binding profiles. In the present study, a fluorescent probe ()-4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-propylpyridin-1-ium (TTPy) has been prepared, which exhibits enhancement of deep-red to near-infrared (NIR) fluorescence upon HSA binding. The competitive binding assay indicated that TTPy can target the HSA binding site of fenamates, a group of non-steroidal anti-inflammatory drugs (NSAIDs), with moderate binding affinity (1.95 × 10 M at 303 K). More interestingly, TTPy enables fluorescent labeling of HSA upon visible light irradiation. This study provides promising ways for HSA drug binding site identification and photochemical protein labeling.
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http://dx.doi.org/10.1039/d2ob00717gDOI Listing
June 2022

Melanotic Xp11/TFE3 translocation perivascular epithelioid cell tumor of the kidney in an 11-year-old female.

Pediatr Blood Cancer 2022 Jun 13:e29843. Epub 2022 Jun 13.

Department of Pathology, Children's Hospital of Fudan University, Shanghai, China.

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http://dx.doi.org/10.1002/pbc.29843DOI Listing
June 2022
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