Publications by authors named "Wenjing Zhang"

836 Publications

Identification of estrogen receptor down-regulators for endocrine resistant breast cancer.

J Steroid Biochem Mol Biol 2022 Aug 4;224:106162. Epub 2022 Aug 4.

Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address:

Resistance to endocrine therapies remains an impediment for the treatment of estrogen receptor (ER) positive breast cancer. ER down regulator Fulvestrant has showed great activity to overcome the endocrine resistance. However, Fulvestrant has poor bioavailability due to the hydrophobicity. Identification of novel ER down regulator is still important. Compounds 172 and 183 are two steroidal compounds with androgen scaffold but significantly down regulated ER in multiple breast cancer cell lines. RT-PCR results indicated that both compounds did not affect ER gene expression. Proteasome inhibitor MG132 could attenuate ER down regulation effect of the compounds, suggesting that the ER down regulation was via ubiquitin-proteasomal pathway. Furthermore, compounds 172 and 183 could downregulate ER in endocrine resistant breast cancer cell model long term estrogen deprivation (LTED) MCF-7 cells. Hydrophobicity of compounds 172 and 183 were determined and showed improved solubility compared to Fulvestrant. All these results suggested that compounds 172 and 183 could be potential lead compounds for drug development for the treatment of endocrine resistance breast cancer.
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http://dx.doi.org/10.1016/j.jsbmb.2022.106162DOI Listing
August 2022

Effects of Antipsychotic Medications and Illness Duration on Brain Features That Distinguish Schizophrenia Patients.

Schizophr Bull 2022 Aug 4. Epub 2022 Aug 4.

Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.

Background And Hypothesis: Previous studies have reported effects of antipsychotic treatment and illness duration on brain features. This study used a machine learning approach to examine whether these factors in aggregate impacted the utility of MRI features for differentiating individual schizophrenia patients from healthy controls.

Study Design: This case-control study used patients with never-treated first-episode schizophrenia (FES, n = 179) and long-term ill schizophrenia (LTSZ, n = 30), with follow-up of the FES group after treatment (n = 71), a group of patients who had received long-term antipsychotic treatment (n = 93) and age and sex-matched healthy controls (n = 373) for each patient group. A multiple kernel learning classifier combining both structural and functional brain features was used to discriminate individual patients from controls.

Study Results: MRI features differentiated untreated FES (0.73) and LTSZ (0.83) patients from healthy controls with moderate accuracy, but accuracy was significantly higher in antipsychotic-treated FES (0.94) and LTSZ (0.98) patients. Treatment was associated with significantly increased accuracy of case identification in both early course and long-term ill patients (both p < .001). Effects of illness duration, examined separately in treated and untreated patients, were less robust.

Conclusions: Our results demonstrate that initiation of antipsychotic treatment alters brain features in ways that further distinguish individual schizophrenia patients from healthy individuals, and have a modest effect of illness duration. Intrinsic illness-related brain alterations in untreated patients, regardless of illness duration, are not sufficiently robust for accurate identification of schizophrenia patients.
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http://dx.doi.org/10.1093/schbul/sbac094DOI Listing
August 2022

Sulfated Fucogalactan From Ameliorates β-Cell Failure by Attenuating Mitochondrial Dysfunction SIRT1-PGC1-α Signaling Pathway Activation.

Front Endocrinol (Lausanne) 2022 13;13:881256. Epub 2022 Jul 13.

Department of Endocrinology and Metabolism, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

As mitochondrial metabolism is a major determinant of β-cell insulin secretion, mitochondrial dysfunction underlies β-cell failure and type 2 diabetes mellitus progression. An algal polysaccharide of , sulfated fucogalactan (SFG) displays various pharmacological effects in a variety of conditions, including metabolic disease. We investigated the protective effects of SFG against hydrogen peroxide (HO)-induced β-cell failure in MIN6 cells and islets. SFG significantly promoted the HO-inhibited proliferation in the cells and ameliorated their senescence, and potentiated β-cell function by regulating β-cell identity and the insulin exocytosis-related genes and proteins in HO-induced β-cells. SFG also attenuated mitochondrial dysfunction, including alterations in ATP content, mitochondrial respiratory chain genes and proteins expression, and reactive oxygen species and superoxide dismutase levels. Furthermore, SFG resulted in SIRT1-PGC1-α pathway activation and upregulated the downstream Nrf2 and Tfam. Taken together, the results show that SFG attenuates HO-induced β-cell failure by improving mitochondrial function SIRT1-PGC1-α signaling pathway activation. Therefore, SFG is implicated as a potential agent for treating pancreatic β-cell failure.
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http://dx.doi.org/10.3389/fendo.2022.881256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326112PMC
August 2022

Curcumin regulates anti-inflammatory responses by AXL/JAK2/STAT3 signaling pathway in experimental autoimmune encephalomyelitis.

Neurosci Lett 2022 Jul 28;787:136821. Epub 2022 Jul 28.

Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, China. Electronic address:

Microglia-mediated neuroinflammation plays an important role in multiple sclerosis (MS). This study explored whether curcumin has a protective effect on experimental autoimmune encephalomyelitis (EAE), and the specific mechanism was investigated. We found that curcumin attenuates the severity of EAE mice. It inhibits the activation of microglia in the spinal cord of EAE mice and LPS-stimulated BV-2 cells. The findings clarify that curcumin may inhibit the inflammatory response mediated by microglia by inactivating the AXL/JAK2/STAT3 signaling pathway, which laid a theoretical foundation for the clinical management of MS.
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http://dx.doi.org/10.1016/j.neulet.2022.136821DOI Listing
July 2022

A Non-Cell-Autonomous Mode of DNA Damage Response in Soma of .

Int J Mol Sci 2022 Jul 7;23(14). Epub 2022 Jul 7.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Life has evolved a mechanism called DNA damage response (DDR) to sense, signal and remove/repair DNA damage, and its deficiency and dysfunction usually lead to genomic instability and development of cancer. The signaling mode of the DDR has been believed to be of cell-autonomy. However, the paradigm is being shifted with in-depth research into model organism . Here, we mainly investigate the effect of DDR activation on the radiosensitivity of vulva of , and first found that the vulval radiosensitivity is mainly regulated by somatic DDR, rather than the DDR of germline. Subsequently, the worm lines with pharynx-specific rescue of DDR were constructed, and it is shown that the 9-1-1-ATR and MRN-ATM cascades in pharynx restore approximately 90% and 70% of vulval radiosensitivity, respectively, through distantly regulating the NHEJ repair of vulval cells. The results suggest that the signaling cascade of DDR might also operate in a non-cell autonomous mode. To further explore the underlying regulatory mechanisms, the mutated gene is introduced into the DDR-rescued worms, and CPR-4, a cysteine protease cathepsin B, is confirmed to mediate the inter-tissue and inter-individual regulation of DDR as a signaling molecule downstream of 9-1-1-ATR. Our findings throw some light on the regulation of DNA repair in soma of , and might also provide new cues for cancer prevention and treatment.
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http://dx.doi.org/10.3390/ijms23147544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318560PMC
July 2022

Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer.

Cancers (Basel) 2022 Jul 19;14(14). Epub 2022 Jul 19.

Key Laboratory of Medicine and Health of Shandong Province, Department of Health Statistics, School of Public Health, Weifang Medical University, Weifang 261053, China.

Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind mutations were elucidated. Melanoma patients with mutations had a markedly extended ICI outcome than other patients. An association between mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in -mutated NSCLC patients (81.8% vs. 29.7%, = 0.002). Subsequent analyses revealed that -mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies.
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http://dx.doi.org/10.3390/cancers14143495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315784PMC
July 2022

Synthesis of 2D anatase TiO with highly reactive facets by fluorine-free topochemical conversion of 1T-TiS nanosheets.

J Mater Chem A Mater 2022 Jul 21;10(26):13884-13894. Epub 2022 Jun 21.

Department of Chemistry, University of Manchester Oxford Road Manchester UK M13 9PL

Two-dimensional (2D) anatase titanium dioxide (TiO) is expected to exhibit different properties as compared to anatase nanocrystallites, due to its highly reactive exposed facets. However, access to 2D anatase TiO is limited by the non-layered nature of the bulk crystal, which does not allow use of top-down chemical exfoliation. Large efforts have been dedicated to the growth of 2D anatase TiO with high reactive facets by bottom-up approaches, which relies on the use of harmful chemical reagents. Here, we demonstrate a novel fluorine-free strategy based on topochemical conversion of 2D 1T-TiS for the production of single crystalline 2D anatase TiO, exposing the {001} facet on the top and bottom and {100} at the sides of the nanosheet. The exposure of these faces, with no additional defects or doping, gives rise to a significant activity enhancement in the hydrogen evolution reaction, as compared to commercially available Degussa P25 TiO nanoparticles. Because of the strong potential of TiO in many energy-based applications, our topochemical approach offers a low cost, green and mass scalable route for production of highly crystalline anatase TiO with well controlled and highly reactive exposed facets.
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http://dx.doi.org/10.1039/d1ta06695aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255669PMC
July 2022

Characterization of the Bacteriophage BUCT603 and Therapeutic Potential Evaluation Against Drug-Resistant in a Mouse Model.

Front Microbiol 2022 5;13:906961. Epub 2022 Jul 5.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.

() is a common opportunistic pathogen that is resistant to many antibiotics. Bacteriophages are considered to be an effective alternative to antibiotics for the treatment of drug-resistant bacterial infections. In this study, we isolated and characterized a phage, BUCT603, infecting drug-resistant . Genome sequencing showed BUCT603 genome was composed of 44,912 bp (32.5% G + C content) with 64 predicted open reading frames (ORFs), whereas no virulence-related genes, antibiotic-resistant genes or tRNA were identified. Whole-genome alignments showed BUCT603 shared 1% homology with other phages in the National Center for Biotechnology Information (NCBI) database, and a phylogenetic analysis indicated BUCT603 can be classified as a new member of the family. Bacteriophage BUCT603 infected 10 of 15 and used the TonB protein as an adsorption receptor. BUCT603 also inhibited the growth of the host bacterium within 1 h and effectively increased the survival rate of infected mice in a mouse model. These findings suggest that bacteriophage BUCT603 has potential for development as a candidate treatment of infection.
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http://dx.doi.org/10.3389/fmicb.2022.906961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294509PMC
July 2022

The quality of life of older carers and the people they support: An international scoping review.

Health Soc Care Community 2022 Jul 21. Epub 2022 Jul 21.

Personal Social Services Research Unit (PSSRU), University of Kent, Canterbury, UK.

Older carers, aged 65 or over, may find it difficult to balance caring while maintaining their own health and quality of life (QoL). For older carers, especially, established approaches to separately identifying, assessing and addressing carers' and care-recipients' needs, may not fully consider the interwoven nature of caregiving relationships and the ways in which community-based social care services may impact the QoL of both parties. The purpose of this scoping review is to identify and synthesise what is already known about the QoL of older carers and care-recipients, considered together, which we refer to as 'dyadic QoL'; both in general, and with regard to the impact of community-based social care. We searched 16 electronic databases and grey literature in October and November 2020. A total 822 items were identified and reviewed based on the inclusion criteria: focusing on older carers and care-recipients from a dyadic perspective and their QoL or well-being, published since 2000 and in English. Fourteen papers were thematically analysed, and the findings were presented under two themes. First, the value of applying an overarching conceptual framework of 'interdependence theory' in understanding dyadic QoL, including two broad approaches: dyadic data analysis and the dynamics of caring relationships. Second, a number of papers highlighted the role of support from family, friends and neighbours and community-based social care services in promoting QoL outcomes of caring dyads. This review emphasised that considering the QoL of carers and care-recipients, together, would potentially improve the understanding of care needs, provision of care services and QoL outcomes. However, there is limited and fragmentary evidence about dyadic QoL or the impact of social care services on dyadic QoL outcomes. Future work is required to explore and evaluate the use of a dyadic approach in social care practice and research.
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http://dx.doi.org/10.1111/hsc.13916DOI Listing
July 2022

Entrustable Professional Activities for Chinese Standardized Residency Training in Pediatric Intensive Care Medicine.

Front Pediatr 2022 4;10:919481. Epub 2022 Jul 4.

Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.

Background: Entrustable professional activities (EPAs) were first introduced by Olle ten Cate in 2005. Since then, hundreds of applications in medical research have been reported worldwide. However, few studies discuss the use of EPAs for residency training in pediatric intensive care medicine. We conducted a pilot study of EPA for pediatric intensive care medicine to evaluate the use of EPAs in this subspecialty.

Materials And Methods: A cross-sectional study was implemented in pediatric intensive care medicine standardized residency training at the Qilu Hospital of Shandong University. An electronic survey assessing EPA performance using eight scales composed of 15 categories were distributed among residents and directors.

Results: A total of 217 director-assessment and 44 residents' self-assessment questionnaires were collected, both demonstrating a rising trend in scores across postgraduate years. There were significant differences in PGY1-vs.-PGY2 and PGY1-vs.-PGY3 director-assessment scores, while there were no differences in PGY2-vs.-PGY3 scores. PGY had a significant effect on the score of each EPA, while position significantly affected the scores of all EPAs except for EPA1 (Admit a patient) and EPA2 (Select and interpret auxiliary examinations). Gender only significantly affected the scores of EPA6 (Report a case), EPA12 (Perform health education), and EPA13 (Inform bad news).

Conclusion: This study indicates that EPA assessments have a certain discriminating capability among different PGYs in Chinese standardized residency training in pediatric intensive care medicine. Postgraduate year, gender, and resident position affected EPA scores to a certain extent. Given the inconsistency between resident-assessed and director-assessed scores, an improved feedback program is needed in the future.
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http://dx.doi.org/10.3389/fped.2022.919481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289143PMC
July 2022

Applying a dyadic outcomes approach to supporting older carers and care-recipients: A qualitative study of social care professionals in England.

Health Soc Care Community 2022 Jul 20. Epub 2022 Jul 20.

School of Social Policy, Sociology and Social Research (SSPSSR), University of Kent, Canterbury, UK.

There are an estimated 2 million older carers, aged 65 or over, in the UK. Older carers are more likely to care for a co-resident spouse/partner, provide high-intensity support and have their own health problems. The literature suggests that a 'dyadic outcomes approach' to social care (i.e. services and support that seek to understand and improve the quality of life of the older carer and the person they support, individually and together) may be especially beneficial for older carers. Such an approach may be applied in needs assessment and review, service evaluation, planning and delivery, or commissioning. However, there is a paucity of evidence of its effectiveness and feasibility in practice. In this qualitative study, we explored views of social care professionals in England on supporting older carers, as well as the feasibility, potential benefits and challenges of applying a dyadic outcomes approach into policy and practice. Overall, 25 professionals were interviewed between January and July 2021, including social workers, team leads, managers, commissioners and other representatives from local authorities, care providers and carer organisations. Findings indicate that there is limited focus on the specific needs of older carers in practice. Participants recognised the potential benefits of a dyadic approach, including the development of a holistic view that enables an effective response to supporting quality of life, for both carer and care-recipient, and building trust when working to support the caring dyad. Barriers to applying a dyadic approach included data protection and sharing, both within and between organisations; required workforce skills, experience and knowledge; and insufficient and competition-oriented adult social care funding that discourages collaborations between agencies. Despite the potential of the approach to improve the effectiveness of support for older caring dyads, these challenges need to be recognised and addressed if it is to be implemented.
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http://dx.doi.org/10.1111/hsc.13914DOI Listing
July 2022

Effects of commercial beverages on the neurobehavioral motility of .

PeerJ 2022 14;10:e13563. Epub 2022 Jul 14.

Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China.

To study the effects of different types of commercially available drinks/beverages on neurobehavior using the model organism , and critically review their potential health hazards. Eighteen kinds of beverages from the supermarket were randomly selected and grouped into seven categories namely functional beverage, tea beverage, plant protein beverage, fruit juice beverage, dairy beverage, carbonated beverage and coffee beverage. The pH value, specific gravity and osmotic pressure were also examined. The L4 stage N2 worms were exposed to different concentration of tested beverages (0, 62.5, 125, 250 and 500 µL/mL) for 24 h to measure the survival rate and locomotory behavior such as head thrashing, body bending as well as pharyngeal pumping. All the 18 beverages tested did not induce any visible lethal effects in the nematodes. However, exposure to different types of tested beverages exhibited different effects on the behavioral ability of : (1) sports functional beverage and herbal tea drink accelerated the head thrashing and body bending of nematodes when compared to the control group ( < 0.05). (2) The vibration frequency of the pharyngeal pump of nematodes was significantly accelerated after treated with three plant protein beverages (almond milk, coconut milk and milk tea) and dairy products A and B ( < 0.05), and decelerated after treatment with other tested beverages. (3) Carbonated beverage significantly inhibits the head thrashing, body bending and pharyngeal pumping vibration ( < 0.05). Our results indicate that 18 kinds of popular beverages in the market have different influence on the neurobehavior in , which may be related to their different components or properties. Further research would be required to conduct a systematic analysis of the effect of beverages by appropriate kinds, taking into consideration other endpoints such as reproduction, lifespan and molecular stress response, , and to elucidate the mechanism for its potential health hazards.
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http://dx.doi.org/10.7717/peerj.13563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288823PMC
July 2022

Reading-related Brain Function Restored to Normal After Articulation Training in Patients with Cleft Lip and Palate: An fMRI Study.

Neurosci Bull 2022 Jul 18. Epub 2022 Jul 18.

School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China.

Cleft lip and/or palate (CLP) are the most common craniofacial malformations in humans. Speech problems often persist even after cleft repair, such that follow-up articulation training is usually required. However, the neural mechanism behind effective articulation training remains largely unknown. We used fMRI to investigate the differences in brain activation, functional connectivity, and effective connectivity across CLP patients with and without articulation training and matched normal participants. We found that training promoted task-related brain activation among the articulation-related brain networks, as well as the global attributes and nodal efficiency in the functional-connectivity-based graph of the network. Our results reveal the neural correlates of effective articulation training in CLP patients, and this could contribute to the future improvement of the post-repair articulation training program.
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http://dx.doi.org/10.1007/s12264-022-00918-6DOI Listing
July 2022

The predictive value of tumor volume reduction ratio on three-dimensional endorectal ultrasound for tumor response to chemoradiotherapy for locally advanced rectal cancer.

Ann Transl Med 2022 Jun;10(12):666

Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Preoperative chemoradiotherapy remains part of the standard treatment for patients with locally advanced rectal cancer. Subsequent treatment individualization requires accurate prediction of tumor response to chemoradiotherapy. Three-dimensional endorectal ultrasound (3D-ERUS) can automatically capture and store the images of the rectal wall and rectal cancer with high resolution. In this study, we aimed to assess the correlation and predictive value between tumor volume changes measured on 3D-ERUS and the histopathological tumor response after chemoradiotherapy for patients with locally advanced rectal cancer.

Methods: A total of 54 patients with locally advanced rectal cancer who underwent chemoradiotherapy and had complete 3D-ERUS data pre-and post-chemoradiotherapy were enrolled in the study. The tumor volume pre-and post-chemoradiotherapy was measured manually on 3D-ERUS, and the tumor volume reduction ratio was calculated. The histopathological tumor regression grade (TRG) was used to assess tumor response. The differences in volumetry parameters were compared between groups with varying tumor response. The diagnostic efficacy of the tumor volume reduction ratio was evaluated by the receiver operating characteristic (ROC) curve.

Results: The mean age of all patients was 55.19±12.46 years. The relative proportions of TRG 0-3 were 29.6% (16/54), 16.6% (9/54), 50% (27/54), and 3.8% (2/54), respectively. The median tumor volumes post-chemoradiotherapy in good responders (TRG 0-1, median tumor volume =3.26 cm) and the complete response group (TRG 0, median tumor volume =2.61 cm) were smaller than those in poor responders (TRG 2-3, median tumor volume =5.43 cm) and the partial response group (TRG 1-3, median tumor volume =4.00 cm), while tumor volume reduction ratios were higher than those of poor responders (79.32% 59.67%) and the partial response group (82.22% 61.64%), with significant differences (all P values <0.05). The ROC curves showed that the cut-off values of the tumor volume reduction ratio to predict good responders and complete response were 67.77% and 72.02%, respectively. The corresponding areas under the curve in the prediction of good responders and complete response were 0.830 and 0.829, respectively.

Conclusions: The tumor volume reduction ratio measured on 3D-ERUS might be a helpful indicator for tumor response in patients with locally advanced rectal cancer.
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http://dx.doi.org/10.21037/atm-22-2418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279805PMC
June 2022

Electrospun aluminum silicate nanofibers as novel support material for immobilization of alcohol dehydrogenase.

Nanotechnology 2022 Aug 5;33(43). Epub 2022 Aug 5.

Department of Energy Conversion and Storage, Technical University of Denmark, Anker Engelunds Vej 301, DK 2800 Kongens Lyngby, Denmark.

Ceramic materials with high surface area, large and open porosity are considered excellent supports for enzyme immobilization owing to their stability and reusability. The present study reports the electrospinning of aluminum silicate nanofiber supports from sol-gel precursors, the impact of different fabrication parameters on the microstructure of the nanofibers and their performance in enzyme immobilization. A change in nanofiber diameter and pore size of the aluminum silicate nanofibers was observed upon varying specific processing parameters, such as the sol-composition (precursor and polymer concentration), the electrospinning parameters and the subsequent heat treatment (calcination temperature). The enzyme, alcohol dehydrogenase (ADH), was immobilized on the aluminum silicate nanofibers by physical adsorption and covalent bonding. Activity retention of 17% and 42% was obtained after 12 d of storage and repeated reaction cycles for physically adsorbed and covalently bonded ADH, respectively. Overall, the immobilization of ADH on aluminum silicate nanofibers resulted in high enzyme loading and activity retention. However, as compared to covalent immobilization, a marked decrease in the enzyme activity during storage for physically adsorbed enzymes was observed, which was ascribed to leakage of the enzymes from the nanofibers. Such fibers can improve enzyme stability and promote a higher residual activity of the immobilized enzyme as compared to the free enzyme. The results shown in this study thus suggest that aluminum silicate nanofibers, with their high surface area, are promising support materials for the immobilization of enzymes.
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http://dx.doi.org/10.1088/1361-6528/ac810aDOI Listing
August 2022

Removal of phosphorus using biochar derived from Fenton sludge: Mechanism and performance insights.

Water Environ Res 2022 Jul;94(7):e10763

School of Environmental Science and Engineering, Hebei University of Science and Technology, Shijiazhuang, China.

A phosphorus removal biochar adsorbent was prepared from Fenton sludge. The adsorption process was optimized, and its phosphorus adsorption mechanism was discussed. It was found that the phosphorus adsorption performance of biochar prepared from single Fenton sludge (FBC-400) was better than that of co-pyrolysis of Fenton sludge and bamboo powder. The optimum condition was that Fenton sludge pyrolyzed at 400°C (FBC-400). FBC-400 had a larger specific surface area than that prepared by co-pyrolysis with bamboo powder. And the high content of iron element could provide a higher surface charge of the biochar, thereby increasing the electrostatic adsorption of phosphorus onto FBC-400. The phosphorus adsorption was highly pH dependent by FBC-400, which can enhance electrostatic adsorption and increase adsorption capacity in acidic conditions. The effect of coexisting anion on adsorption performance was mainly affected by CO , reducing the adsorption capacity by at least 49%, whereas other anions had no obvious interference. The adsorption process of FBC-400 accorded with the pseudo-second-order kinetic model and the Langmuir model, which indicated that the adsorption process was monolayer adsorption and mainly chemical adsorption, and the maximum saturated phosphorus adsorption capacity was 8.77 mg g . The mechanisms for phosphorus adsorption were electrostatic adsorption and inner-sphere complexing. 1 M NaOH was used for desorption, and the adsorption capacity remained at 81% in the fifth cycle. PRACTITIONER POINTS: The Fenton sludge biochar usage as an adsorbent could be a win-win strategy to convert waste biomass to valuable - product. The adsorption process accorded with the Langmuir model, the maximum phosphorus adsorption capacity was 8.77 mg/g at 25°C. The adsorption mechanisms were electrostatic adsorption and inner-sphere complexing. 1M NaOH was used for desorption, and the adsorption capacity remained at 81% in the fifth cycle.
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http://dx.doi.org/10.1002/wer.10763DOI Listing
July 2022

Prediction scores of postoperative liver metastasis and long-term survival of pancreatic head cancer based on the distance between the mesenteric vessels and tumor, preoperative serum carbohydrate antigen 19-9 level, and lymph node metastasis rate.

Cancer Med 2022 Jul 13. Epub 2022 Jul 13.

Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.

Background: The shortest distance between the superior mesenteric artery (SMA) or superior mesenteric vein (SMV) and the tumor margin was combined with preoperative serum carbohydrate antigen (CA) 19-9 and lymph node ratio (LNR) to evaluate joint effects on long-term survival and liver metastasis in patients with pancreatic head cancer after radical surgery.

Methods: This retrospective study included 149 patients who underwent pancreaticoduodenectomy for pancreatic head cancer at Harbin Medical University Tumor Hospital from May 2011 to March 2021. The preoperative serum CA 19-9 level and LNR were combined with the SMA or SMV distance. The joint association between long-term survival and postoperative liver metastasis was evaluated.

Results: Based on the receiver operating characteristic curve of postoperative liver metastasis or long-term survival, the optimal cut-off values of SMV distance were 3.1 and 0.7 mm, respectively, whereas the optimal cut-off value of SMA distance was 10.25 mm. The univariate model identified the liver metastasis score (p < 0.001) as a negative factor for postoperative liver metastasis of pancreatic head carcinoma. The SMV distance (p = 0.003), SMA distance (p < 0.001), LNR score (p < 0.001), and survival score (p < 0.001) were negatively correlated with long-term survival after pancreatic head cancer. The multivariate model highlighted SMA distance (p < 0.001), survival score (p = 0.001), and LNR score (p < 0.001) as independent risk factors for long-term survival in pancreatic head cancer.

Conclusion: Liver metastasis score may be an independent predictor of postoperative liver metastasis in patients with pancreatic head cancer. Survival and LNR scores may be independent predictors of long-term postoperative survival in patients with pancreatic head cancer. However, the LNR score appears to improve long-term survival.
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http://dx.doi.org/10.1002/cam4.4957DOI Listing
July 2022

Post-flowering Soil Waterlogging Curtails Grain Yield Formation by Restricting Assimilates Supplies to Developing Grains.

Front Plant Sci 2022 17;13:944308. Epub 2022 Jun 17.

Key Laboratory of Wheat Biology and Genetic Improvement on Southern Yellow and Huai River Valley, Ministry of Agriculture and Rural Affairs, College of Agronomy, Anhui Agricultural University, Hefei, China.

Soil waterlogging is among the major factors limiting the grain yield of winter wheat crops in many parts of the world, including the middle and lower reaches of the Yangtze River China. In a field study, we investigated the relationship between leaf physiology and grain development under a varying duration of post-flowering waterlogging. A winter wheat cultivar Ningmai 13 was exposed to soil waterlogging for 0 (W0), 3 (W3), 6 (W6), and 9 d (W9) at anthesis. Increasing waterlogging duration significantly reduced flag leaf SPAD (soil plant analysis development) values and net photosynthetic rate (Pn). There was a linear reduction in flag leaf Pn and SPAD as plant growth progressed under all treatments; however, the speed of damage was greater in the waterlogged leaves. For example, compared with their respective control (W0), flag leaves of W9 treatment have experienced 46% more reduction in Pn at 21 d after anthesis (DAA) than at 7 DAA. Increasing waterlogging duration also induced oxidative damage in flag leaves, measured as malondialdehyde (MDA) contents. The capacity to overcome this oxidative damage was limited by the poor performance of antioxidant enzymes in wheat leaves. Inhibited leaf Pn and capacity to sustain assimilate synthesis under waterlogged environments reduced grain development. Compared with W0, W6 and W9 plants experienced a 20 and 22% reduction in thousand grain weight (TGW) in response to W6 and W9, respectively at 7 DAA and 11 and 19%, respectively at 28 DAA. Sustained waterlogging also significantly reduced grain number per spike and final grain yield. Averaged across two years of study, W9 plants produced 28% lesser final grain yield than W0 plants. Our study suggested that wheat crops are highly sensitive to soil waterlogging during reproductive and grain filling phases due to their poor capacity to recover from oxidative injury to photosynthesis. Management strategies such as planting time, fertilization and genotype selection should be considered for the areas experiencing frequent waterlogging problems.
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http://dx.doi.org/10.3389/fpls.2022.944308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262124PMC
June 2022

The relationship between particulate matter and lung function of children: A systematic review and meta-analysis.

Environ Pollut 2022 Jul 7;309:119735. Epub 2022 Jul 7.

School of Public Health, Nanjing Medical University, Nanjing, 211100, China; China CDC Key Laboratory of Environment and Population, Health Chinese Center for Disease, China. Electronic address:

There have been many studies on the relationship between fine particulate matter (PM) and lung function. However, the impact of short-term or long-term PM exposures on lung function in children is still inconsistent globally, and the reasons for the inconsistency of the research results are not clear. Therefore, we searched the PubMed, Embase and Web of Science databases up to May 2022, and a total of 653 studies about PM exposures on children's lung function were identified. Random effects meta-analysis was used to estimate the combined effects of the 25 articles included. PM concentrations in short-term exposure studies mainly come from individual and site monitoring. And for every 10 μg/m increase, forced vital capacity (FVC), forced expiratory volume in the first second (FEV) and peak expiratory flow (PEF) decreased by 21.39 ml (95% CI: 13.87, 28.92), 25.66 ml (95% CI: 14.85, 36.47) and 1.76 L/min (95% CI: 1.04, 2.49), respectively. The effect of PM on lung function has a lag effect. For every 10 μg/m increase in the 1-day moving average PM concentration, FEV, FVC and PEF decreased by 14.81 ml, 15.40 ml and 1.18 L/min, respectively. PM concentrations in long-term exposure studies mainly obtained via ground monitoring stations. And for every 10 μg/m increase, FEV, FVC and PEF decreased by 61.00 ml (95% CI: 25.80, 96.21), 54.47 ml (95% CI: 7.29, 101.64) and 10.02 L/min (95% CI: 7.07, 12.98), respectively. The sex, body mass index (BMI), relative humidity (RH), temperature (Temp) and the average PM exposure level modify the relationship between short-term PM exposure and lung function. Our study provides further scientific evidence for the deleterious effects of PM exposures on children's lung function, suggesting that exposure to PM is detrimental to children's respiratory health. Appropriate protective measures should be taken to reduce the adverse impact of air pollution on children's health.
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http://dx.doi.org/10.1016/j.envpol.2022.119735DOI Listing
July 2022

Night warming at the vegetative stage improves pre-anthesis photosynthesis and plant productivity involved in grain yield of winter wheat.

Plant Physiol Biochem 2022 Sep 16;186:19-30. Epub 2022 Jun 16.

College of Agronomy, Anhui Agricultural University/Key Laboratory of Wheat Biology and Genetic Improvement in South Yellow & Huai River Valley, Ministry of Agriculture, Hefei, China. Electronic address:

We conducted pot experiments during the 2018-2020 growing seasons to study the effects of night warming at different growth stages of wheat on the photosynthetic performance; accumulation, transportation, and distribution of dry matter; and grain yield of winter wheat. Night warming at all the different growth stages resulted in an elevation of wheat yield by increasing the 1000-grain weight and the number of grains per ear. Night warming during the period from jointing to booting stage resulted in the greatest increase in wheat yield. It also increased the amount of overall dry matter and transferrable amount of dry matter in plants and increased the distribution of dry matter to grains to increase grain weight. Night warming treatments at three different growth stages enhanced pre-anthesis photosynthetic capacity by increasing flag leaf net photosynthetic rate, chlorophyll content, and photochemical efficiency of winter wheat at the early stage of grain filling, especially in the night warming treatment from jointing to booting stage. Night warming not only increased the stomatal density and stomatal index of wheat leaves but also increased stomatal conductance and transpiration rate in the early stage of grain filling, thus being conducive to the smooth progress of photosynthesis. In conclusion, night warming treatment at different growth stages increased the photosynthesis of flag leaves at the early stage of grain filling, and promoted the accumulation of dry matter in plants after anthesis, which was conducive to the grain yield of winter wheat.
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http://dx.doi.org/10.1016/j.plaphy.2022.06.015DOI Listing
September 2022

Host defense peptide mimicking cyclic peptoid polymers exerting strong activity against drug-resistant bacteria.

Biomater Sci 2022 Aug 9;10(16):4515-4524. Epub 2022 Aug 9.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.

Extensive use of antibiotics accelerates the emergence of drug-resistant bacteria and related infections. Host defense peptides (HDPs) have been studied as promising and potential therapeutic candidates. However, their clinical applications of HDPs are limited due to their high cost of synthesis and low stability upon proteolysis. Therefore, HDP mimics have become a new approach to address the challenge of bacterial resistance. In this work, we design the amphiphilic peptoid polymers by mimicking the positively charged and hydrophobic structures of HDPs and synthesize a series of cyclic peptoid polymers efficiently the polymerization on α-amino acid -substituted glycine -carboxyanhydrides (α-NNCAs) using 1,8-diazabicycloundec-7-ene (DBU) as the initiator. The optimal cyclic peptoid polymer, poly(NaegNpfbg), displays strong antibacterial activities against drug-resistant bacteria, but low hemolysis and cytotoxicity. In addition, the mode-of-action study indicates that the antibacterial mechanism is associated with bacterial membrane interaction. Our study implies that HDP mimicking cyclic peptoid polymers have potential application in treating drug-resistant bacterial infections.
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http://dx.doi.org/10.1039/d2bm00587eDOI Listing
August 2022

TyG index is positively associated with risk of CHD and coronary atherosclerosis severity among NAFLD patients.

Cardiovasc Diabetol 2022 Jul 1;21(1):123. Epub 2022 Jul 1.

Department of Cardiology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001, Shanxi, China.

Background: Insulin resistance (IR), endothelial dysfunction, inflammation, glucose and lipid metabolism disorders, and thrombosis are believed involved in coronary heart disease (CHD) and non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index, a new IR indicator, is correlated with NAFLD occurrence and severity, but its relationship with CHD risk remains unclear. This study investigated the correlation between TyG index and CHD risk among NAFLD patients.

Methods: This cross-sectional study included 424 patients with NAFLD and chest pain in the Department of Cardiology, The Second Hospital of Shanxi Medical University, from January 2021 to December 2021. The TyG index was calculated and coronary angiography performed. All individuals were divided into NAFLD + CHD and NAFLD groups and then by TyG index level. The t-test, Mann-Whitney U-test, or one-way analysis of variance compared differences in continuous variables, while the chi-square test or Fisher's exact test compared differences in categorical variables. Logistic regression analysis determined the independent protective or hazardous factors of NAFLD with CHD. The receiver operating characteristic curve evaluated the ability of different TyG index rule-in thresholds to predict CHD. The relationship between Gensini score and TyG index was evaluated using linear correlation and multiple linear regression.

Results: CHD was detected in 255 of 424 patients. Compared to NAFLD group, multivariate logistic regression showed that TyG index was a risk factor for CHD among NAFLD patients after adjustment for age, sex, hypertension, and diabetes mellitus with the highest odds ratio (OR, 2.519; 95% CI, 1.559-4.069; P < 0.001). TG, low-density lipoprotein cholesterol, FBG and TYG-body mass index were also risk factors for CHD among NAFLD patients. High-density lipoprotein cholesterol level was a protective factor for CHD events in patients with NAFLD. In an in-depth analysis, multivariate logistic regression analysis showed that each 1-unit increase in TyG index was associated with a 2.06-fold increased risk of CHD (OR, 2.06; 95% CI, 1.16-3.65; P = 0.013). The multifactor linear regression analysis showed each 0.1-unit increase in TyG in the NAFLD-CHD group was associated with a 2.44 increase in Gensini score (β = 2.44; 95% CI, 0.97-3.91; P = 0.002).

Conclusions: The TyG index was positively correlated with CHD risk in NAFLD patients and reflected coronary atherosclerosis severity.
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http://dx.doi.org/10.1186/s12933-022-01548-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250269PMC
July 2022

HCV Core protein represses DKK3 expression via epigenetic silencing and activates the Wnt/β-catenin signaling pathway during the progression of HCC.

Clin Transl Oncol 2022 Jun 29. Epub 2022 Jun 29.

Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, China.

The Wnt/β-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). A number of studies have focused on the aberrant hypermethylation of the DKK family proteins and its role in regulating the activation of specific signaling pathways. However, the exact way by which DKK regulates the signaling pathway caused by Core protein of HCV has not been reported. In the present study, we evaluated the expression level of DKK and its aberrant promoter methylation to investigate the involvement of epigenetic regulation in hepatoma cell lines. The transcription and protein expression of DKK1 was significantly increased, whereas the transcription and protein expression levels of DKK2, DKK3, and DKK4 were significantly decreased following overexpression of Core protein. Pyrosequencing indicated that hypermethylation of DKK3 was increased. This was associated with increased expression of Dnmt1. The investigation of the molecular mechanism indicated that HCV Core protein interacted with Dnmt1, which combined with the promoter of DKK3, leading to methylation of DKK3. Functional studies indicated that Core protein promoted the growth, migration and invasion of cancer cells. However, upregulation of the expression of DKK3 and/or the knockdown of the expression of Dnmt1 inhibited the growth, migration and invasion of cancer cells. Taken together, the data indicated that epigenetic silencing of DKK3 caused by Dnmt1 activated the Wnt/β-catenin pathway in HCV Core-mediated HCC. Therefore, DKK3 may be a potential diagnostic and therapeutic target for HCC.
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http://dx.doi.org/10.1007/s12094-022-02859-yDOI Listing
June 2022

Construction and Biological Evaluation of Multiple Modification Hollow Mesoporous Silicone Doxorubicin Nanodrug Delivery System.

AAPS PharmSciTech 2022 Jun 27;23(6):180. Epub 2022 Jun 27.

College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China.

The combination of functionalized nanoparticles and chemotherapy drugs can effectively target tumor tissue, which can improve efficacy and reduce toxicity. In this article, [email protected] nanoparticles (phosphopeptide-modified polydopamine encapsulates doxorubicin-loaded hollow mesoporous organosilica nanoparticles) were constructed that based on multiple modification hollow mesoporous organosilica nanoparticles (HMONs). The [email protected] nanoparticles retain the biological functions of phosphorylated peptide while exhibiting biological safety that are suitable for effective drug delivery and stimulus responsive release. The degradation behaviors showed that [email protected] has dual-responsive to drug release characteristics of pH and glutathione (GSH). In addition, the prepared [email protected] nanoparticles have good biological safety, and their anti-tumor efficacy was significantly better than doxorubicin (DOX). This provided new research ideas for the construction of targeted nanodrug delivery systems based on mesoporous silicon. Scheme 1 The preparation of [email protected] and the process of drug release under multiple responses. (A) Schematic diagram of the synthesis process of [email protected] (B) The process in which nanoparticles enter the cell and decompose and release DOX in response to pH and GSH.
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http://dx.doi.org/10.1208/s12249-022-02226-8DOI Listing
June 2022

Expression and Regulatory Network Analysis of BICC1 for Aged Sca-1-Positive Bone Narrow Mesenchymal Stem Cells.

Dis Markers 2022 15;2022:4759172. Epub 2022 Jun 15.

Department of Stomatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055 Guangdong, China.

Background: The impaired osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a major cause of bone remodeling imbalance and osteoporosis. The bicaudal C homologue 1 (BICC1) gene is a genetic regulator of bone mineral density (BMD) and promotes osteoblast differentiation. The purpose of this study is to explore the probable function of BICC1 in osteoporosis and osteogenic differentiation of aged BMSCs.

Methods: We examined the GSE116925 microarray dataset obtained from the Gene Expression Omnibus (GEO) database. The GEO2R algorithm identified differentially expressed genes (DEGs) in Sca-1+ BMSCs from young (3 months old) and old (18 months old) mice. Then, to identify the most crucial genes, we used pathway enrichment analysis and a protein-protein interaction (PPI) network. Furthermore, starBase v2.0 was used to generate the regulatory networks between BICC1 and related competing endogenous RNAs (ceRNAs). NetworkAnalyst was used to construct TF-gene networks and TF-miRNA-gene networks of BICC1 and ceRNA. Furthermore, we investigated the expression in aged Sca-1-positive BMSCs.

Result: We detected 923 DEGs and discovered that epidermal growth factor receptor (EGFR) was the top hub gene with a high degree of linkage. According to the findings of the PPI module analysis, EGFR was mostly engaged in cytokine signaling in immune system and inflammation-related signaling pathways. 282 ceRNAs were found to interact with the BICC1 gene. EGFR was not only identified as a hub gene but also as a BICC1-related ceRNA. Then, we predicted 11 common TF-genes and 7 miRNAs between BICC1 and EGFR. Finally, we found that BICC1 mRNA and EGFR mRNA were significantly overexpressed in aged Sca-1-positive BMSCs.

Conclusion: As a genetic gene that affects bone mineral density, BICC1 may be a new target for clinical treatment of senile osteoporosis by influencing osteogenic differentiation of BMSCs through EGFR-related signaling. However, the application of the results requires support from more experimental data.
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http://dx.doi.org/10.1155/2022/4759172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217532PMC
June 2022

Mongolia Gerbils Are Broadly Susceptible to Hepatitis E Virus.

Viruses 2022 05 24;14(6). Epub 2022 May 24.

Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.

Although cell culture systems for hepatitis E virus (HEV) have been established by using cell lines such as PLC/PRF/5 and A549, small-animal models for this virus are limited. Since Mongolia gerbils are susceptible to genotype 1, 3 and 4 HEV (HEV-1, HEV-3 and HEV4), we intraperitoneally inoculated Mongolia gerbils with HEV-5, HEV-7, HEV-8, rabbit HEV or rat HEV in addition to the above three genotypes to investigate the infectivity and to assess whether Mongolia gerbil is an appropriate animal model for HEV infection. The results indicated that (i) HEV-5 and rat HEV were effectively replicated in the Mongolia gerbils in the same manner as HEV-4: large amounts of the viral RNA were detected in the feces and livers, and high titers of the serum anti-HEV IgG antibodies were induced in all animals. The feces were shown to contain HEV that is infectious to naïve gerbils. Furthermore, HEV-4, HEV-5 and rat HEV were successfully transmitted to the gerbils by oral inoculation. (ii) Although the viral RNA and serum anti-HEV IgG antibodies were detected in all animals inoculated with HEV-1 and HEV-8, both titers were low. The viral RNA was detected in the feces collected from two of three HEV-3-inoculated, and one of three HEV-7-inoculated gerbils, but the titers were low. The serum antibody titers were also low. The viruses excreted into the feces of HEV-1-, HEV-3-, HEV-7- and HEV-8-inoculated gerbils failed to infect naïve Mongolia gerbils. (iii) No infection sign was observed in the rabbit HEV-inoculated gerbils. These results demonstrated that Mongolia gerbils are broadly susceptible to HEV, and their degree of sensitivity was dependent on the genotype. Mongolia gerbils were observed to be susceptible to not only HEVs belonging to HEV-A but also to rat HEV belonging to HEV-C1, and thus Mongolia gerbil could be useful as a small-animal model for cross-protection experiments between HEV-A and HEV-C1. Mongolia gerbils may also be useful for the evaluation of the efficacy of vaccines against HEV.
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http://dx.doi.org/10.3390/v14061125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229706PMC
May 2022

Favorable immune checkpoint inhibitor outcome of patients with melanoma and NSCLC harboring FAT1 mutations.

NPJ Precis Oncol 2022 Jun 23;6(1):46. Epub 2022 Jun 23.

Department of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, 261053, Weifang, Shandong, China.

Immune checkpoint inhibitors (ICIs) are most commonly used for melanoma and non-small cell lung cancer (NSCLC) patients. FAT atypical cadherin 1 (FAT1), which frequently mutates in melanoma and NSCLC. In this study, we aim to investigate the association of FAT1 mutations with ICI response and outcome. We collected somatic mutation profiles and clinical information from ICI-treated 631 melanoma and 109 NSCLC samples, respectively. For validation, a pan-cancer cohort with 1661 patients in an immunotherapy setting was also used. Melanoma and NSCLC samples from the Cancer Genome Atlas were used to evaluate the potential immunologic mechanisms of FAT1 mutations. In melanoma, patients with FAT1 mutations had a significantly improved survival outcome than those wild-type patients (HR: 0.67, 95% CI: 0.46-0.97, P = 0.033). An elevated ICI response rate also appeared in FAT1-mutated patients (43.2% vs. 29.2%, P = 0.032). Associations of FAT1 mutations with improved prognosis and ICI response were confirmed in NSCLC patients. In the pan-cancer cohort, the association between FAT1 mutations and favorable ICI outcome was further validated (HR: 0.74, 95% CI: 0.58-0.96, P = 0.022). Genomic and immunologic analysis showed that a high mutational burden, increased infiltration of immune-response cells, decreased infiltration of immune-suppressive cells, interferon and cell cycle-related pathways were enriched in patients with FAT1 mutations. Our study revealed that FAT1 mutations were associated with better immunogenicity and ICI efficacy, which may be considered as a biomarker for selecting patients to receive immunotherapy.
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http://dx.doi.org/10.1038/s41698-022-00292-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226130PMC
June 2022

Uncovering the genetic links of SARS-CoV-2 infections on heart failure co-morbidity by a systems biology approach.

ESC Heart Fail 2022 Jun 21. Epub 2022 Jun 21.

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Aims: The co-morbidities contribute to the inferior prognosis of COVID-19 patients. Recent reports suggested that the higher co-morbidity rate between COVID-19 and heart failure (HF) leads to increased mortality. However, the common pathogenic mechanism between them remained elusive. Here, we aimed to reveal underlying molecule mechanisms and genetic correlation between COVID-19 and HF, providing a new perspective on current clinical management for patients with co-morbidity.

Methods: The gene expression profiles of HF (GSE26887) and COVID-19 (GSE147507) were retrieved from the GEO database. After identifying the common differentially expressed genes (|log2FC| > 1 and adjusted P < 0.05), integrated analyses were performed, namely, enrichment analyses, protein-protein interaction network, module construction, critical gene identification, and functional co-expression analysis. The performance of critical genes was validation combining hierarchical clustering, correlation, and principal component analysis in external datasets (GSE164805 and GSE9128). Potential transcription factors and miRNAs were obtained from the JASPER and RegNetwork repository used to construct co-regulatory networks. The candidate drug compounds in potential genetic link targets were further identified using the DSigDB database.

Results: The alteration of 12 genes was identified as a shared transcriptional signature, with the role of immune inflammatory pathway, especially Toll-like receptor, NF-kappa B, chemokine, and interleukin-related pathways that primarily emphasized in response to SARS-CoV-2 complicated with HF. Top 10 critical genes (TLR4, TLR2, CXCL8, IL10, STAT3, IL1B, TLR1, TP53, CCL20, and CXCL10) were identified from protein-protein interaction with topological algorithms. The unhealthy microbiota status and gut-heart axis in co-morbidity were identified as potential disease roads in bridging pathogenic mechanism, and lipopolysaccharide acts as a potential marker for monitoring HF during COVID-19. For transcriptional and post-transcriptional levels, regulation networks tightly coupling with both disorders were constructed, and significant regulator signatures with high interaction degree, especially FOXC1, STAT3, NF-κB1, miR-181, and miR-520, were detected to regulate common differentially expressed genes. According to genetic links targets, glutathione-based antioxidant strategy combined with muramyl dipeptide-based microbe-derived immunostimulatory therapies was identified as promising anti-COVID-19 and anti-HF therapeutics.

Conclusions: This study identified shared transcriptomic and corresponding regulatory signatures as emerging therapeutic targets and detected a set of pharmacologic agents targeting genetic links. Our findings provided new insights for underlying pathogenic mechanisms between COVID-19 and HF.
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http://dx.doi.org/10.1002/ehf2.14003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349450PMC
June 2022

Lenvatinib Combined With a PD-1 Inhibitor as Effective Therapy for Advanced Intrahepatic Cholangiocarcinoma.

Front Pharmacol 2022 1;13:894407. Epub 2022 Jun 1.

Department of Ultrasound, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Lenvatinib combined with a PD-1 inhibitor has obtained a satisfactory antitumor effect in several solid tumors. However, the efficacy and tumor response of lenvatinib with a PD-1 inhibitor in advanced intrahepatic cholangiocarcinoma still need further exploration. This is a single-arm study for the assessment of the efficacy and tolerability of lenvatinib with a PD-1 inhibitor in intrahepatic cholangiocarcinoma patients who had chemotherapy failure. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). A total of 40 patients with advanced intrahepatic cholangiocarcinoma were enrolled after the chemorefractory effect. The median progression-free survival was 5.83 ± 0.76 months. The 3-month and 6-month progression-free survival rates were 80.0% and 32.5%, respectively. The median overall survival was 14.30 ± 1.30 months. The 12-month and 18-month overall survival rates were 61.4% and 34.7%. The 3-month RECIST 1.1 evaluation was that seven patients (17.5%) showed partial response, 23 patients (57.5%) had stable disease, and 10 patients (25.0%) had progressive disease. The objective response rate was 17.5%, and the disease control rate was 75.0%. All the recorded any-grade adverse events inducing treatment termination were controllable, and there were no AE-related deaths. Our study showed that a combination of lenvatinib with the PD-1 inhibitor could be an effective treatment for advanced intrahepatic cholangiocarcinoma after the chemorefractory effect.
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http://dx.doi.org/10.3389/fphar.2022.894407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198573PMC
June 2022

Water-Induced Surface Reconstruction of CoO on the (111) Plane for High-Efficiency Li-O Batteries in a Hybrid Electrolyte.

ACS Appl Mater Interfaces 2022 Jun 15;14(25):28965-28976. Epub 2022 Jun 15.

Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing 100049, PR China.

The crystal plane effect of cobalt oxide has attracted much attention in Li-O batteries (LOBs) and other electrocatalytic fields. However, boosting the catalytic activity of a specific plane still faces significant challenges. Herein, a strategy of adding water into the electrolyte is developed to construct a LiOH-based Li-O battery system using the (111) plane-exposed CoO as a cathode catalyst. The electrochemical performance shows that on the (111) plane, in the presence of water, the overpotential is largely reduced from 1.5 to 1.0 V and the cycling performance is enhanced. It is confirmed that during the discharge process, water reacts to form LiOH and induce the phase transformation of CoO to amorphous CoO(OH). At the recharge stage, LiOH is first decomposed and then CoO(OH) is reduced to CoO. Compared with pristine (111), the newly formed CoO surface exhibits more active sites, which accelerates the following oxygen reduction and oxygen evolution processes. This work not only reveals the reaction mechanism of water-induced reaction on the (111) plane of CoO but also provides a new perspective for further design of hybrid Li-O batteries with a low polarization and a longer cycle life.
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http://dx.doi.org/10.1021/acsami.2c06990DOI Listing
June 2022
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