Publications by authors named "Fei Li"

3,106 Publications

  • Page 1 of 1

Effect of artificial skin membrane on the expression of miR-155 and miR-506-3p in patients with second-degree burns.

J Clin Lab Anal 2022 Aug 10:e24564. Epub 2022 Aug 10.

Department of Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.

Objective: To investigate the effect of artificial skin on the expression of miR-155 and miR-506-3p in patients with second-degree burns.

Methods: The study subjects included 50 patients with second-degree burns treated from July 2019 to July 2021. The control group received routine nursing, while the research group received both routine and artificial skin intervention simultaneously. The changes in wound tissue fibrosis and prognosis were observed. The expression levels of miR-155 and miR-506-3p and their downstream regulatory factors were detected and correlated with the rehabilitation of patients after artificial skin treatment.

Results: After treating second-degree burns with artificial skin membranes, the patient's wound tissue fibrosis and inflammation level improved. At the same time, the expression levels of miR-155 and miR-506-3p in related tests were higher than those in patients with available treatment.

Conclusion: The effect of artificial skin membrane on the wound healing of second-degree burn patients may be realized by influencing the expression levels of miR-155 and miR-506-3p and their related signaling pathways.
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http://dx.doi.org/10.1002/jcla.24564DOI Listing
August 2022

Aspiration versus Stent Retriever Thrombectomy in Posterior Circulation Stroke: A Systematic Review and Meta-Analysis.

Eur Neurol 2022 Aug 10:1-13. Epub 2022 Aug 10.

Preventive Treatment Center, Huzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Huzhou, China.

Introduction: The management of posterior circulation stroke is primarily carried out by endovascular approaches including aspiration or stent retrevier thrombectomy. Existing reviews have attempted to comparatively evaluate their efficacy in terms of morbidity and mortality-related outcomes, however, with several limitations. Therefore, in this review, we attempt to address the gap in the existing literature by evaluating the comparative impact of stent retriever-based and aspiration-based thrombectomy interventions in posterior circulation stroke patients on the following parameters: overall procedure duration, recanalization time, rescue therapy usage, complication risk, and mortality risk.

Methods: A systematic search of the academic literature was performed according to PRISMA guidelines across five databases. We conducted a random-effect meta-analysis to evaluate comparative outcomes, including procedural duration, time to recanalization, risk of complications, use of rescue therapy, and risk of mortality in patients with posterior circulation stroke undergoing stent retriever- and aspiration-based thrombectomies. We also performed comparative subgroup analyses to evaluate differences in outcomes between contact and manual aspiration interventions.

Results: From 963 studies, we found nine eligible studies containing data on 840 patients. Meta-analysis revealed a large-to-medium size positive effect for stent retriever-based thrombectomy on overall procedure duration and recanalization compared to aspiration-based thrombectomy. Additional analysis revealed higher risk of complications and mortality in posterior circulation stroke patients undergoing stent retriever-based thrombectomy as compared to aspiration-based thrombectomy. We also observed that the use of rescue therapy was elevated in patients undergoing aspiration-based thrombectomy compared to stent retriever-based thrombectomy.

Conclusion: This study provides preliminary evidence for improved morbidity and mortality outcomes in posterior circulation stroke patients undergoing aspiration-based thrombectomies as compared to stent retriever-based thrombectomy. The study also provides evidence for improved endovascular outcomes for patients undergoing aspiration-based thrombectomies. The findings from this study can have implications in developing awareness among neurosurgeons for stratifying patients to manage posterior circulation stroke according to the risks associated with aspiration and stent retriever-based thrombectomies.
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http://dx.doi.org/10.1159/000525406DOI Listing
August 2022

Role of m6A writers, erasers and readers in cancer.

Exp Hematol Oncol 2022 Aug 9;11(1):45. Epub 2022 Aug 9.

Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

The N(6)-methyladenosine (m6A) modification is the most pervasive modification of human RNAs. In recent years, an increasing number of studies have suggested that m6A likely plays important roles in cancers. Many studies have demonstrated that m6A is involved in the biological functions of cancer cells, such as proliferation, invasion, metastasis, and drug resistance. In addition, m6A is closely related to the prognosis of cancer patients. In this review, we highlight recent advances in understanding the function of m6A in various cancers. We emphasize the importance of m6A to cancer progression and look forward to describe future research directions.
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http://dx.doi.org/10.1186/s40164-022-00298-7DOI Listing
August 2022

Discovery of 1-(Hetero)aryl-β-carboline Derivatives as IDO1/TDO Dual Inhibitors with Antidepressant Activity.

J Med Chem 2022 Aug 7. Epub 2022 Aug 7.

Key Laboratory of Cardiovascular & Cerebrovascular Medicine, Drug Target and Drug Discovery Center, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Depression is the leading cause of global burden of disease and disability. Abnormalities in the kynurenine pathway of tryptophan degradation have been closely linked to the pathogenesis of depression. An integrative bioinformatics analysis demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are potential targets for the development of antidepressants. A series of 1-(hetero)aryl-β-carboline derivatives were designed, synthesized, and evaluated as novel IDO1/TDO dual inhibitors. Among them, compound displayed potent inhibition of both IDO1 (IC = 3.53 μM) and TDO (IC = 1.15 μM) and had an acceptable safety profile and pharmacokinetic properties. Compound also rescued lipopolysaccharide-induced depressive-like behavior in mice. Further studies revealed that likely had unique antidepressant mechanisms involving suppressing microglial activation, lowering IDO1 expression, and reducing proinflammatory cytokine and kynurenine levels in the mouse brain. Overall, this work provides practical guidance for the development of IDO1/TDO dual inhibitors to treat inflammation-induced depression.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00677DOI Listing
August 2022

Identification of candidate genes and clarification of the maintenance of the green pericarp of weedy rice grains.

Front Plant Sci 2022 22;13:930062. Epub 2022 Jul 22.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

The weedy rice ( f. ) pericarp has diverse colors (e.g., purple, red, light-red, and white). However, research on pericarp colors has focused on red and purple, but not green. Unlike many other common weedy rice resources, LM8 has a green pericarp at maturity. In this study, the coloration of the LM8 pericarp was evaluated at the cellular and genetic levels. First, an examination of their ultrastructure indicated that LM8 chloroplasts were normal regarding plastid development and they contained many plastoglobules from the early immature stage to maturity. Analyses of transcriptome profiles and differentially expressed genes revealed that most chlorophyll (Chl) degradation-related genes in LM8 were expressed at lower levels than Chl / cycle-related genes in mature pericarps, suggesting that the green LM8 pericarp was associated with inhibited Chl degradation in intact chloroplasts. Second, the F generation derived from a cross between LM8 (green pericarp) and SLG (white pericarp) had a pericarp color segregation ratio of 9:3:4 (green:brown:white). The bulked segregant analysis of the F populations resulted in the identification of 12 known genes in the chromosome 3 and 4 hotspot regions as candidate genes related to Chl metabolism in the rice pericarp. The RNA-seq and sqRT-PCR assays indicated that the expression of the Chl / cycle-related structural gene (encoding divinyl reductase) was sharply up-regulated. Moreover, genes encoding magnesium-chelatase subunit D and the light-harvesting Chl /-binding protein were transcriptionally active in the fully ripened dry pericarp. Regarding the ethylene signal transduction pathway, the (encoding an ethylene-responsive protein kinase) and (encoding an ethylene-responsive factor) genes expression profiles were determined. The findings of this study highlight the regulatory roles of Chl biosynthesis- and degradation-related genes influencing Chl accumulation during the maturation of the LM8 pericarp.
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http://dx.doi.org/10.3389/fpls.2022.930062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354532PMC
July 2022

Corrigendum: Biomarking and induction of apoptosis in ovarian cancer using bifunctional polyethyleneimine-caged platinum nanoclusters.

Front Oncol 2022 20;12:983959. Epub 2022 Jul 20.

Department of Light Chemical Engineering, School of Textiles, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fonc.2022.898917.].
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http://dx.doi.org/10.3389/fonc.2022.983959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346211PMC
July 2022

Mowing enhances the positive effects of nitrogen addition on ecosystem carbon fluxes and water use efficiency in a semi-arid meadow steppe.

J Environ Manage 2022 Aug 3;320:115889. Epub 2022 Aug 3.

Institute of Grassland Science, Key Laboratory of Vegetation Ecology of the Ministry of Education, Jilin Songnen Grassland Ecosystem National Observation and Research Station, Northeast Normal University, Changchun, 130024, China. Electronic address:

Grasslands are now facing a continuously increasing supply of nitrogen (N) fertilizers, resulting in alterations in ecosystem functioning, including changes in carbon (C) and water cycling. Mowing, one of the most widely used grassland management techniques, has been shown to mitigate the negative impacts of increased N availability on species richness. However, knowledge of how N addition and mowing, alone and/or in combination, affect ecosystem-level C fluxes and water use efficiency (W) is still limited. We experimentally manipulated N fertilization (0 and 10 g N m yr) and mowing (once per year at the end of the growing season) following a randomized block design in a meadow steppe characterized by salinization and alkalinization in northeastern China. We found that, compared to the control plots, N addition, mowing, and their interaction increased net ecosystem CO exchange by 65.1%, 14.7%, and 133%, and W by 40.7%, 18.5%, and 96.1%, respectively. Nitrogen enrichment also decreased soil pH, which resulted in greater aboveground biomass (AGB). Moreover, N addition indirectly increased AGB by inducing changes in species richness. Our results indicate that mowing enhances the positive effects of N addition on ecosystem C fluxes and W. Therefore, appropriate grassland management practices are essential to improve ecosystem C sequestration, W, and mitigate future species diversity declines due to ecosystem eutrophication.
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http://dx.doi.org/10.1016/j.jenvman.2022.115889DOI Listing
August 2022

Efficacy of Low Molecular Weight Heparin in Preventing Perinatal Venous Thrombosis: A Meta-Analysis.

Comput Math Methods Med 2022 26;2022:1248577. Epub 2022 Jul 26.

Department of Pharmacy, Hainan Women and Children's Medical Center, Haikou 570216, China.

Background: There have been controversies about the preventive effect of low molecular weight heparin (LMWH) on venous thrombosis (VT) in the perinatal period. This study is aimed at exploring the effectiveness of LMWH in preventing perinatal VT through meta-analysis.

Methods: Databases such as CNKI, China Biology Medicine disc (CBMdisc), Wanfang, PubMed, MEDLINE, Embase, and Central were searched. Inclusion criteria were as follows: (1) subjects: women at high risk of perinatal VT; (2) experimental group and control group; (3) intervention measures: the experimental group was given LMWH, while the control group was given placebo or standard heparin or physical therapy; (4) outcomes: perinatal VT events or bleeding events; and (5) randomized controlled trials (RCTs). Jadad scale was used to evaluate the literature quality. The Mantel-Haenszel method was used to calculate the odds ratio (OR) and 95% confidence interval (CI). The chi-square test was used to analyze the heterogeneity of the included literature. Subgroup analysis was used to explore the source of heterogeneity. Publication bias was evaluated via funnel plot and Egger test.

Results: The incidence of perinatal VT in the LMWH group was lower than that in the control group (OR = 0.16, 95% CI (0.08, 0.32), < 0.00001). There was no heterogeneity among literatures ( = 0.77, = 0%) and no publication bias. The incidence of postpartum VT in the LMWH group was lower than that in the control group (OR = 0.14, 95% CI (0.07, 0.30), < 0.00001). There was no heterogeneity among literatures ( = 0.69, = 0%) and no publication bias. The incidence of perinatal bleeding in the LMWH group was higher than in the control group (OR = 1.72, 95% CI (1.06, 2.77), = 0.03). There was no heterogeneity among literatures ( = 0.25, = 26%) and no publication bias.

Conclusion: LMWH can reduce the incidence of perinatal VT in high-risk women but increase the risk of bleeding. The use of LMWH to prevent perinatal VT should be closely monitored.
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http://dx.doi.org/10.1155/2022/1248577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345706PMC
August 2022

Duration of Acute Kidney Injury and In-Hospital Mortality in Elder Patients with Severe COVID-19: A Retrospective Cohort Study.

Biomed Res Int 2022 26;2022:9929038. Epub 2022 Jul 26.

Department of Cardiology, Xijing Hospital, Changle West Road, Xi'an 710032, China.

Background: Patients with severe coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) in the intensive care unit (ICU) have extremely high rates of mortality. This study evaluated the prognostic impact of AKI duration on in-hospital mortality in elder patients.

Methods: We performed a retrospective study of 126 patients with confirmed COVID-19 with severe or critical disease who treated in the ICU from February 4, 2020, to April 16, 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes serum creatinine (Scr) criteria. AKI patients were divided into transient AKI and persistent AKI groups based on whether Scr level returned to baseline within 48 h post-AKI.

Results: In total, 107 patients were included in the final analysis. The mean age was 70 (64-78) years, and 69 (64.5%) patients were men. AKI occurred in 48 (44.9%) during their ICU stay. Of these, 11 (22.9%) had transient AKI, and 37 (77.9%) had persistent AKI. In-hospital mortality was 18.6% ( = 11) for patients without AKI, 72.7% ( = 8) for patients with transient AKI, and 86.5% ( = 32) for patients with persistent AKI ( < 0.001). Kaplan-Meier curve analysis revealed that patients with both transient AKI and persistent AKI had significantly higher death rates than those without AKI (log-rank < 0.001). Multivariate Cox regression analysis revealed that transient and persistent AKI were an important risk factor for in-hospital mortality in older patients with severe COVID-19 even after adjustment for variables (  [] = 2.582; 95% CI: 1.025-6.505; = 0.044; and = 6.974; 95% CI: 3.334-14.588; < 0.001).

Conclusions: AKI duration can be an important predictive parameter in elder patients suffering from COVID-19 and are admitted to ICU. Among these patients, those exhibiting persistent AKI have a lower in-hospital survival rate than those with transient AKI, emphasizing the importance of identifying an appropriate treatment window for early intervention.
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http://dx.doi.org/10.1155/2022/9929038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345708PMC
August 2022

Loss of YB-1 alleviates liver fibrosis by suppressing epithelial-mesenchymal transition in hepatic progenitor cells.

Biochim Biophys Acta Mol Basis Dis 2022 Aug 1:166510. Epub 2022 Aug 1.

Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address:

Previously, we reported that the nuclear translocation of Y-box binding protein 1 (YB-1) is induced by transforming growth factor-β (TGF-β) and promotes hepatic progenitor cells (HPCs) expansion. Here, we explored the mechanisms underlying YB-1 translocation and the impact of YB-1 on the epithelial-mesenchymal transition (EMT) in HPCs. YB-1cre (YB-1cre) mice and YB-1cre mice were fed with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or a choline-deficient, ethionine-supplemented (CDE) diet. Liver injury and fibrosis were assessed by performing hematoxylin and eosin (HE) and Masson staining. The expression of collagen and EMT-related markers (E-cadherin, N-cadherin, and Snail) was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence analyses. Protein kinase B (AKT) expression in HPCs was silenced via RNA interference. Nuclear YB-1 expression in HPCs was detected via western blotting and immunofluorescence analyses. HPC proliferation was detected by immunofluorescence. Our results indicate that YB-1 transcriptionally regulated the biological behavior of HPCs. HPC-specific YB-1 knockout alleviated liver fibrosis in mice fed with DDC and CDE diets. YB-1 nuclear translocation promoted matrix metallopeptidase 9 transcription. YB-1 depletion in HPCs significantly dampened the EMT and inhibited AKT phosphorylation in vitro and in vivo. AKT knockdown compromised TGF-β-induced YB-1 nuclear translocation, thereby inhibiting the EMT and HPC proliferation. EMT and AKT were highly activated in HPCs in cirrhotic livers. Collectively, our findings indicate that the loss of YB-1 suppressed EMT in HPCs and alleviated liver fibrosis in mice, and that AKT was essential for TGF-β-induced YB-1 nuclear translocation and HPC proliferation.
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http://dx.doi.org/10.1016/j.bbadis.2022.166510DOI Listing
August 2022

MC4R Deficiency Causes Dysregulation of Postsynaptic Excitatory Synaptic Transmission as a Crucial Culprit for Obesity.

Diabetes 2022 Aug 4. Epub 2022 Aug 4.

State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Melanocortin-4 receptor (MC4R) in paraventricular nucleus in hypothalamus (PVH) shows bidirectional characterization in modulating food intake and energy homeostasis. Here, we demonstrated that MC4R knock down (MC4R KD) in PVH could attenuate AMPA receptor (AMPAR) mediated postsynaptic responses by altering AMPAR GluA1 subunit phosphorylation via protein kinase A (PKA) dependent signaling cascade and simultaneously lead to rapid body weight gain. Further, PKA knock down (PKA KD) in PVH engendered similar electrophysiological and behavioral phenotypes as MC4R KD mice. Importantly, we observed that the reduction of AMPAR GluA1 expression not only led to attenuated synaptic responses but also caused body weight gain, suggesting that the aberration of synaptic responses may be one of the crucial pathogeny for obesity. Our study provided the synaptic and molecular explanations of how body weight is regulated by MC4R in PVH.
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http://dx.doi.org/10.2337/db22-0162DOI Listing
August 2022

Highly efficient and selective extraction of gold by reduced graphene oxide.

Nat Commun 2022 Aug 2;13(1):4472. Epub 2022 Aug 2.

Faculty of Materials Science and Engineering / Institute of Technology for Carbon Neutrality, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.

Materials capable of extracting gold from complex sources, especially electronic waste (e-waste), are needed for gold resource sustainability and effective e-waste recycling. However, it remains challenging to achieve high extraction capacity and precise selectivity if only a trace amount of gold is present along with other metallic elements . Here we report an approach based on reduced graphene oxide (rGO) which provides an ultrahigh capacity and selective extraction of gold ions present in ppm concentrations (>1000 mg of gold per gram of rGO at 1 ppm). The excellent gold extraction performance is accounted to the graphene areas and oxidized regions of rGO. The graphene areas spontaneously reduce gold ions to metallic gold, and the oxidized regions allow good dispersibility of the rGO material so that efficient adsorption and reduction of gold ions at the graphene areas can be realized. By controlling the protonation of the oxidized regions of rGO, gold can be extracted exclusively, without contamination by the other 14 co-existing elements typically present in e-waste. These findings are further exploited to demonstrate recycling gold from real-world e-waste with good scalability and economic viability, as exemplified by using rGO membranes in a continuous flow-through process.
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http://dx.doi.org/10.1038/s41467-022-32204-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345893PMC
August 2022

Disconnected in a pandemic: COVID-19 outcomes and the digital divide in the United States.

Authors:
Fei Li

Health Place 2022 Jul 15;77:102867. Epub 2022 Jul 15.

Urban Studies Institute, Georgia State University, 55 Park Pl NE, 8(th) Floor, Atlanta, GA, 30303, USA. Electronic address:

The COVID-19 pandemic has exacerbated inequalities related to the digital divide. With wide adoption of remote working and learning, telehealth, and virtual events and social activities, the technology have-nots and know-nots experienced substantial marginalization and elevated risks of COVID-19 exposure in daily lives. This study discusses the pathways through which digital exclusion could aggravate the impacts of the pandemic and explored the linkage between digital access and COVID-19 outcomes in U.S. counties. It finds that counties with higher percentages of digitally excluded populations have seen higher COVID-19 case and death rates throughout the pandemic and lower vaccination rates by January 2022.
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http://dx.doi.org/10.1016/j.healthplace.2022.102867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283607PMC
July 2022

Roll to roll in situ preparation of recyclable, washable, antibacterial Ag loaded nonwoven fabric.

Sci Rep 2022 Aug 1;12(1):13206. Epub 2022 Aug 1.

Engineering Research Center for Nanomaterials, Henan University, Kaifeng, 475004, China.

Functional fabrics with antibacterial performance are more welcome nowadays. However, the fabrication of functional fabrics with durable, steady performance via a cost-effective way remains a challenge. Polypropylene (denoted as PP) nonwoven fabric was modified by polyvinyl alcohol (denoted as PVA), followed by the in-situ deposition of silver nanoparticles (denoted as Ag NPs) to afford PVA-modified and Ag NPs-loaded PP (denoted as Ag/PVA/PP) fabric. The encapsulation of PP fiber by PVA coating contributes to greatly enhancing the adhesion of the loaded Ag NPs to the PP fiber, and the Ag/PVA/PP nonwoven fabrics exhibit significantly improved mechanical properties as well as excellent antibacterial activity against Escherichia coli (coded as E. coli). Typically, the Ag/PVA/PP nonwoven fabric obtained at a silver ammonia concentration of 30 mM has the best mechanical properties and the antibacterial rate reaches 99.99% against E. coli. The fabric retains excellent antibacterial activity even after washing for 40 cycles, showing prospects in reuse. Moreover, the Ag/PVA/PP nonwoven fabric could find promising application in industry, thanks to its desired air-permeability and moisture-permeability. In addition, we developed a roll-to-roll production process and conducted preliminary exploration to verify the feasibility of this method.
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http://dx.doi.org/10.1038/s41598-022-17484-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342839PMC
August 2022

All-Solid-State Photo-Assisted Li-CO Battery Working at an Ultra-Wide Operation Temperature.

ACS Nano 2022 Aug 1. Epub 2022 Aug 1.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012, China.

At present, photoassisted Li-air batteries are considered to be an effective approach to overcome the sluggish reaction kinetics of the Li-air batteries. And, the organic liquid electrolyte is generally adopted by the current conventional photoassisted Li-air batteries. However, the superior catalytic activity of photoassisted cathode would in turn fasten the degradation of the organic liquid electrolyte, leading to limited battery cycling life. Herein, we tame the above limitation of the traditional liquid electrolyte system for Li-CO batteries by constructing a photoassisted all-solid-state Li-CO battery with an integrated bilayer [email protected]/LiAlGe(PO) (LAGP)/LAGP (ATLL) framework, which can essentially improve battery stability. Taking advantage of photoelectric and photothermal effects, the [email protected]/LAGP layer enables the acceleration of the slow kinetics of the carbon dioxide reduction reaction and evolution reaction processes. The LAGP layer could resolve the problem of liquid electrolyte decomposition under illumination. The integrated double-layer LAGP framework endows the direct transportation of heat and Li in the entire system. The photoassisted all-solid-state Li-CO battery achieves an ultralow polarization of 0.25 V with illumination, as well as a high round-trip efficiency of 92.4%. Even at an extremely low temperature of -73 °C, the battery can still deliver a small polarization of 0.6 V by converting solar energy into heat to achieve self-heating. This study is not limited to the Li-air batteries but can also be applied to other battery systems, constituting a significant step toward the practical application of all-solid-state photoassisted Li-air batteries.
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http://dx.doi.org/10.1021/acsnano.2c03534DOI Listing
August 2022

Transient upregulation of EGR1 signaling enhances kidney repair by activating SOX9 renal tubular cells.

Theranostics 2022 11;12(12):5434-5450. Epub 2022 Jul 11.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.

Acute kidney injury (AKI) is associated with damage to the nephrons and tubular epithelial cells (TECs), which can lead to chronic kidney disease and end-stage renal disease. Identifying new biomarkers before kidney dysfunction will offer crucial insight into preventive and therapeutic options for the treatment of AKI. Early growth response 1 (EGR1) has been found to be a pioneer transcription factor that can sequentially turn on/off key downstream genes to regulate whole-body regeneration processes in the leopard worm. Whether EGR1 modulates renal regeneration processes in AKI remains to be elucidated. AKI models of ischemia-reperfusion injury (IRI) and folic acid (FA) were developed to investigate the roles of EGR1 in kidney injury and regeneration. To further determine the function of EGR1, mice were applied. Furthermore, RNA sequencing of renal TECs, Chromatin Immunoprecipitation (ChIP) assay, and Dual-luciferase reporter assay were carried out to investigate whether EGR1 affects the expression of SOX9. EGR1 is highly expressed in the kidney after AKI both in humans and mice through analysis of the Gene Expression Omnibus (GEO) database. Furthermore, we verified that EGR1 rapidly up-regulates in the very early stage of IRI and nephrotoxic models of AKI, and validation studies confirmed the essential roles of EGR1 in renal tubular cell regeneration. Further experiments affirmed that genetic inhibition of aggravates the severity of AKI in mouse models. Furthermore, our results revealed that EGR1 could increase SOX9 expression in renal TECs by directly binding to the promoter of the gene, thus promoting SOX9 cell proliferation by activating the Wnt/β-catenin pathway. Together, our results demonstrated that rapid and transient induction of EGR1 plays a renoprotective role in AKI, which highlights the prospects of using EGR1 as a potential therapeutic target for the treatment of AKI.
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http://dx.doi.org/10.7150/thno.73426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330523PMC
August 2022

Complex dynamics in a Hopfield neural network under electromagnetic induction and electromagnetic radiation.

Chaos 2022 Jul;32(7):073107

College of Information Science and Engineering, Hunan Normal University, Changsha 410081, People's Republic of China.

Due to the potential difference between two neurons and that between the inner and outer membranes of an individual neuron, the neural network is always exposed to complex electromagnetic environments. In this paper, we utilize a hyperbolic-type memristor and a quadratic nonlinear memristor to emulate the effects of electromagnetic induction and electromagnetic radiation on a simple Hopfield neural network (HNN), respectively. The investigations show that the system possesses an origin equilibrium point, which is always unstable. Numerical results uncover that the HNN can present complex dynamic behaviors, evolving from regular motions to chaotic motions and finally to regular motions, as the memristors' coupling strength changes. In particular, coexisting bifurcations will appear with respect to synaptic weights, which means bi-stable patterns. In addition, some physical results obtained from breadboard experiments confirm Matlab analyses and Multisim simulations.
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http://dx.doi.org/10.1063/5.0095384DOI Listing
July 2022

The Provincial Baseline of PM in China and Its Hierarchical Management Strategy.

Front Public Health 2022 12;10:908760. Epub 2022 Jul 12.

School of Information and Safety Engineering, Zhongnan University of Economics and Law, Wuhan, China.

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http://dx.doi.org/10.3389/fpubh.2022.908760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314856PMC
August 2022

Recent advances in metabolism and toxicity of tyrosine kinase inhibitors.

Pharmacol Ther 2022 Jul 25;237:108256. Epub 2022 Jul 25.

Laboratory of Metabolomics and Drug-induced Liver Injury, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Small molecule tyrosine kinase inhibitors (TKIs) are widely used as anticancer drugs approved by U.S. FDA. However, the toxicities of TKIs to multiple organs have greatly limited their clinical applications. The metabolism of TKIs generates several potentially toxic metabolites in vivo, that can disturb the endogenous metabolism as well as cellular function, leading to organ damage. Therefore, it is essential to identify the toxic metabolites and elucidate the underlying mechanism of TKI-induced toxicity. Metabolomics is a powerful tool for the identification of the xenobiotic metabolites and metabolic derangement associated with xenobiotic exposure, that is helpful to understand the toxicity of TKIs. The study using metabolomics approach has revealed that the reactive metabolites/intermediates (e.g., N-oxide metabolite, primary amine metabolite, 1,4-benzoquinone intermediate) and adducts with glutathione, cysteine and mercapturic acid can be derived from TKIs. Fourteen metabolic pathways could be affected following the TKI treatment, including lipid metabolism, bile acid metabolism, and gut microbiota-related pathway. Modulation of xenobiotic receptor signaling, inhibition of xenobiotic metabolism, and supplementation of endogenous metabolites are potential strategies to protect against TKI-induced toxicity. In this review, studies on the metabolism of TKIs and the alterations of endogenous metabolism are discussed, and the potential preventions against TKI-induced toxicity are summarized.
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http://dx.doi.org/10.1016/j.pharmthera.2022.108256DOI Listing
July 2022

Cerebellar primary central nervous system lymphoma: Case series report.

Int J Surg Case Rep 2022 Jul 21;97:107440. Epub 2022 Jul 21.

Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China. Electronic address:

Introduction And Importance: Primary central nervous system lymphoma (PCNSL) is a rare cranial malignant haematological tumour. PCNSL in the cerebellar region is less common than PCNSL in other encephalic regions. A diagnosis of cerebellar PCNSL is relatively difficult to make due to its diverse imaging manifestations. The aim of this case series report is to determine whether surgery could be used to confirm the diagnosis of cerebellar PCNSL and the effect of surgical treatment.

Methods: We report 3 cases of cerebellar PCNSL that underwent neuronavigation microsurgery under general anaesthesia. The operation was performed by author 3 and author 5. One patient underwent left lateral ventricular drainage on the fourth and tenth days after the operation due to postoperative obstructive hydrocephalus. All patients received chemotherapy or radiotherapy after histological confirmation.

Outcomes: All patients' tumours were completely removed. One patient developed obstructive hydrocephalus twice during the perioperative period after the operation, was given drainage, and then recovered from the hospital. The other two patients recovered and were discharged smoothly without complications. One patient died 9 months after the operation, and the other two patients survived. The prognosis of 3 patients was related to tumour size and timely follow-up chemo-radiation therapy.

Conclusion: The histology of all patients showed diffuse large B-cell lymphoma (GCB phenotype). Suspicious cerebellar PCNSL patients should undergo surgery to confirm the diagnosis, followed by radiotherapy and chemotherapy.
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http://dx.doi.org/10.1016/j.ijscr.2022.107440DOI Listing
July 2022

Preparation of transmittance-switchable composites from a coexistent system of polymer-dispersed and polymer-stabilized cholesteric liquid crystals.

Phys Chem Chem Phys 2022 Aug 10;24(31):18703-18712. Epub 2022 Aug 10.

Research Center for Humanoid Sensing, Zhejiang Laboratory, Hangzhou, 311121, P. R. China.

Polymer-dispersed and polymer-stabilized liquid crystals (PD&PSLCs) are the coexistent systems of PDLCs and PSLCs, in which a mesogenic polymer network forms in the LC droplets to construct the PSLC system and the combination of the LC domains and the isotropic polymer matrix makes up the PDLC system. In this work, a PD&PS cholesteric LC (PD&PSCLC) system, where the isotropic polymer walls make up the PDCLC microstructure and the liquid crystalline polymer network in the CLC droplets constructs the PSCLC system, is fabricated successfully. The CLCs are composed of a negative dielectric anisotropy nematic LC and a chiral dopant. Owing to the stabilizing effect of the liquid crystalline polymer network, the planar texture of the CLCs can be retained after the preparation process, and the PD&PSCLC sample is in a large-transmittance state. The action of a low-frequency electric field induces the disordered texture of the CLCs and the light-scattering (low-transmittance) state because of the electro-hydrodynamic effect and dynamic scattering effects. After the removal of the low-frequency electric field, the stabilizing effect of the liquid crystalline polymer network induces the CLC molecules to return to the homogeneous orientation state, and the sample also re-obtains the large transmittance. This work may provide a facile approach to fabricating polymer/CLC composites with switchable transmittance for reverse-mode smart windows.
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http://dx.doi.org/10.1039/d2cp01963aDOI Listing
August 2022

High-Temperature Oxidation Behavior of Cr-Ni-Mo Hot-Work Die Steels.

Materials (Basel) 2022 Jul 25;15(15). Epub 2022 Jul 25.

School of Materials Science and Engineering, Henan University of Science and Technology, Luoyang 471003, China.

The oxidation of 3Cr3Mo2NiW and 3CrNi3Mo steels was studied at 600 °C in air, and the test results suggest that the parabolic rate law fitted the oxidation kinetics of both steels. The microstructure, morphology, structure, and phase composition of the oxide film cross-sectional layers of the two Cr-Ni-Mo hot-work die steels were analyzed using scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), and X-ray diffraction (XRD). The influences of Cr, Ni, and Mo on the high-temperature oxidation resistance of the two Cr-Ni-Mo hot-work die steels are discussed, and the oxidation mechanism is summarized. Heat-treated samples were analyzed using electron backscattered diffraction (EBSD) to obtain inverse pole figures (IPFs) and average sample grain sizes, and the percentages of twin grain boundaries (TGBs) (θ = 60°) were also measured. After heat treatment, recrystallization was observed in both steels with a large portion of twin grain boundaries. After 10 h of oxidation, the dense chromium-rich oxide layer that formed in the inner oxide layer of 3Cr3Mo2NiW steel effectively prevented the continuation of oxidation. The inner oxide layer in 3CrNi3Mo steel formed an adhesion layer with a network structure composed mainly of Ni- and Cr-rich spinel oxide, without forming a barrier to prevent oxidation.
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http://dx.doi.org/10.3390/ma15155145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331425PMC
July 2022

Multisystem Langerhans Cell Histiocytosis in Younger Infants First Presenting in Skin: A Case Series.

J Pers Med 2022 Jun 22;12(7). Epub 2022 Jun 22.

Department of Pediatrics, Northwest Women and Children's Hospital, Xi'an 710061, China.

Objectives-To investigate the clinical characteristics, managements, outcome, and evaluate the risk factors of Multisystem (MS) Langerhans Cell Histiocytosis (LCH) with diverse skin lesions as the first sign in four young infants. Methods-Their clinical features, disease progression, therapy, and outcomes were reviewed and analyzed retrospectively. Results-The average onset age of skin lesions was about 2 months. Cases 1 and 2 had risk organs involved (RO+) and a lack of bone lesions, and progression could not be reversed by systemic chemotherapy. They both died eventually. Cases 3 and 4 (RO-) had bone involvement and were given systemic chemotherapy for a prolonged duration. Unluckily, Case 3 had a recurrence 2 years later, while Case 4's recurrence happened nearly one year later, and diabetes insipidus one and a half years later. They both survived and are still in remission. Conclusion-MS-LCH infants with a low age of the first presentation in the skin are prone to dissemination, while RO+ is associated with high mortality. In addition, bone involvement may be a protective factor. Immunohistochemical examination of skin tissue facilitates correct early diagnosis, and adequate follow-up is necessary.
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http://dx.doi.org/10.3390/jpm12071024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315804PMC
June 2022

Characterization and Comparative Genomics Analysis of a New Bacteriophage BUCT610 against and Efficacy Assessment in Larvae.

Int J Mol Sci 2022 Jul 21;23(14). Epub 2022 Jul 21.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

The spread of multidrug-resistant (MDR-KP) has become an emerging threat as a result of the overuse of antibiotics. Bacteriophage (phage) therapy is considered to be a promising alternative treatment for MDR-KP infection compared with antibiotic therapy. In this research, a lytic phage BUCT610 was isolated from hospital sewage. The assembled genome of BUCT610 was 46,774 bp in length, with a GC content of 48%. A total of 83 open reading frames (ORFs) and no virulence or antimicrobial resistance genes were annotated in the BUCT610 genome. Comparative genomics and phylogenetic analyses showed that BUCT610 was most closely linked with the phage pYD38-A and shared 69% homology. In addition, bacteriophage BUCT610 exhibited excellent thermal stability (4-75 °C) and broad pH tolerance (pH 3-12) in the stability test. In vivo investigation results showed that BUCT610 significantly increased the survival rate of -infected larvae from 13.33% to 83.33% within 72 h. In conclusion, these findings indicate that phage BUCT610 holds great promise as an alternative agent with excellent stability for the treatment of MDR-KP infection.
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http://dx.doi.org/10.3390/ijms23148040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321532PMC
July 2022

Transcriptomic and Metabolomic Analyses Provide Insights into the Formation of the Peach-like Aroma of Schlecht. Fruits.

Genes (Basel) 2022 Jul 20;13(7). Epub 2022 Jul 20.

Horticulture Institute (Guizhou Horticultural Engineering Technology Research Center), Guizhou Academy of Agricultural Sciences, Guiyang 550006, China.

Schlecht. is a wild diploid strawberry species. The intense peach-like aroma of its fruits makes an excellent resource for strawberry breeding programs aimed at enhancing flavors. However, the formation of the peach-like aroma of strawberry fruits has not been comprehensively characterized. In this study, fruit metabolome and transcriptome datasets for (HA; peach-like aroma) and its interspecific hybrids PA (peach-like aroma) and NA (no peach-like aroma; control) were compared. In total, 150 differentially accumulated metabolites were detected. The K-means analysis revealed that esters/lactones, including acetic acid, octyl ester, δ-octalactone, and δ-decalactone, were more abundant in HA and PA than in NA. These metabolites may be important for the formation of the peach-like aroma of fruits. The significantly enriched gene ontology terms assigned to the differentially expressed genes (DEGs) were fatty acid metabolic process and fatty acid biosynthetic process. Twenty-seven DEGs were predicted to be associated with ester and lactone biosynthesis, including , , , , , , , , and cytochrome P450 subfamily genes. Thirty-five transcription factor genes were predicted to be associated with aroma formation, including , , , , , , and . Moreover, we identified differentially expressed , , and cytochrome P450 family genes and , , and transcription factor genes that were correlated with δ-octalactone and δ-decalactone. These findings provide key insights into the formation of the peach-like aroma of fruits, with implications for the increased use of wild strawberry resources.
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http://dx.doi.org/10.3390/genes13071285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318527PMC
July 2022

A Multicenter Clinical Study of the Automated Fundus Screening Algorithm.

Transl Vis Sci Technol 2022 Jul;11(7):22

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.

Purpose: To evaluate the effectiveness of automated fundus screening software in detecting eye diseases by comparing the reported results against those given by human experts.

Results: There were 1585 subjects who completed the procedure and yielded qualified images. The prevalence of referable diabetic retinopathy (RDR), glaucoma suspect (GCS), and referable macular diseases (RMD) were 20.4%, 23.2%, and 49.0%, respectively. The overall sensitivity values for RDR, GCS, and RMD diagnosis are 0.948 (95% confidence interval [CI], 0.918-0.967), 0.891 (95% CI, 0.855-0.919), and 0.901 (95% CI-0.878, 0.920), respectively. The overall specificity values for RDR, GCS, and RMD diagnosis are 0.954 (95% CI, 0.915-0.965), 0.993 (95% CI-0.986, 0.996), and 0.955 (95% CI-0.939, 0.968), respectively.

Methods: We prospectively enrolled 1743 subjects at seven hospitals throughout China. At each hospital, an operator records the subjects' information, takes fundus images, and submits the images to the Image Reading Center of Zhongshan Ophthalmic Center, Sun Yat-Sen University (IRC). The IRC grades the images according to the study protocol. Meanwhile, these images will also be automatically screened by the artificial intelligence algorithm. Then, the analysis results of automated screening algorithm are compared against the grading results of IRC. The end point goals are lower bounds of 95% CI of sensitivity values that are greater than 0.85 for all three target diseases, and lower bounds of 95% CI of specificity values that are greater than 0.90 for RDR and 0.85 for GCS and RMD.

Conclusions: Automated fundus screening software demonstrated a high sensitivity and specificity in detecting RDR, GCS, and RMD from color fundus imaged captured using various cameras.

Translational Relevance: These findings suggest that automated software can improve the screening effectiveness for eye diseases, especially in a primary care context, where experienced ophthalmologists are scarce.
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http://dx.doi.org/10.1167/tvst.11.7.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339691PMC
July 2022

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network.

Toxins (Basel) 2022 Jul 14;14(7). Epub 2022 Jul 14.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, China.

Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration ( < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.
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http://dx.doi.org/10.3390/toxins14070486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322933PMC
July 2022

Design, synthesis, biological evaluation and molecular docking studies of novel pleuromutilin derivatives containing nitrogen heterocycle and alkylamine groups.

J Enzyme Inhib Med Chem 2022 Dec;37(1):2078-2091

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

A series of pleuromutilin derivatives containing alkylamine and nitrogen heterocycle groups were designed and synthesised under mild conditions. The antibacterial activity of these semisynthetic derivatives against four strains of (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were evaluated by the broth dilution method. Compound was found to have excellent antibacterial activity against MRSA (MIC = 0.0625 μg/mL). Furthermore, compound was further studied by the time-killing kinetics and the post-antibiotic effect approach. In the mouse thigh infection model, compound exhibited superior antibacterial efficacy than that of tiamulin. Meanwhile, compound showed a lower inhibitory effect than that of tiamulin on RAW264.7 and 16HBE cells at the concentration of 10 μg/mL. Molecular docking study revealed that compound can effectively bind to the active site of the 50S ribosome (the binding free energy = -9.66 kcal/mol).
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http://dx.doi.org/10.1080/14756366.2022.2104267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318235PMC
December 2022

Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201).

Front Oncol 2022 7;12:925236. Epub 2022 Jul 7.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.

Background: Nearly all anti-PD-1 antibodies are of the IgG4 isotype, and thus possess residual FcR effector functions. Such anti-PD-1 antibodies are also associated with immune tolerance and escape due to instability of the CH3 domain and Fc-Fc interaction. In this trial, we examined the efficacy and safety of penpulimab, a novel IgG1 anti-PD-1 antibody that does not bind to the Fc receptor, in patients with refractory or relapsed classical Hodgkin lymphoma (R/R cHL).

Methods: Adult patients (≥18 years of age) with R/R cHL received 200 mg penpulimab once biweekly until disease progression or unacceptable toxicities for a maximum of 24 months. The primary endpoint was objective response rate (ORR) based on the Independent Radiology Review Committee per Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs).

Results: A total of 94 patients were enrolled. The median follow-up was 15.8 months. The ORR was 89.4% (95% CI 80.8%, 95.0%) in the full analysis set (85 patients). Forty (47.1%) patients achieved complete remission, 36 (42.4%) patients achieved partial remission. The 12-month PFS rate was 72.1% (95% CI 60.5%, 80.8%) and the 18-month OS rate was 100%. Totally 97.9% (92/94) of patients experienced at least one TRAE. The rate of grade 3 and above TRAEs was 26.6% (25/94). In addition, 51 (54.3%) patients experienced an irAE, and 4 (4.3%) patients developed grade 3 or above irAEs. No irAE-related death occurred.

Conclusions: Penpulimab was effective and safe in patients with R/R cHL.
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http://dx.doi.org/10.3389/fonc.2022.925236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301139PMC
July 2022

Differential Gene Analysis of Trastuzumab in Breast Cancer Based on Network Pharmacology and Medical Images.

Front Physiol 2022 8;13:942049. Epub 2022 Jul 8.

Shanghai Eighth People's Hospital, Shanghai, China.

The purpose of this study was to use network pharmacology, biomedical images and molecular docking technology in the treatment of breast cancer to investigate the feasible therapeutic targets and mechanisms of trastuzumab. In the first place, we applied pubchem swisstarget (http://www.swisstargetprediction.ch/), (https://pubchem.ncbi.nlm.nih.gov/) pharmmapper (http://lilab-ecust.cn/pharmmapper/), and the batman-tcm (http://bionet.ncpsb.org.cn/batman-tcm/) database to collect the trastuzumab targets. Then, in NCBI-GEO, breast cancer target genes were chosen (https://www.ncbi.nlm.nih.gov/geo/). The intersection regions of drug and disease target genes were used to draw a Venn diagram. Through Cytoscape 3.7.2 software, and the STRING database, we then formed a protein-protein interaction (PPI) network. Besides, we concluded KEGG pathway analysis and Geen Ontology analysis by using ClueGO in Cytospace. Finally, the top 5 target proteins in the PPI network to dock with trastuzumab were selected. After screening trastuzumab and breast cancer in databases separately, we got 521 target genes of the drug and 1,464 target genes of breast cancer. The number of overlapping genes was 54. PPI network core genes include GAPDH, MMP9, CCNA2, RRM2, CHEK1, etc. GO analysis indicated that trastuzumab treats breast cancer through abundant biological processes, especially positive regulation of phospholipase activity, linoleic acid metabolic process, and negative regulation of endothelial cell proliferation. The molecular function is NADP binding and the cellular component is tertiary granule lumen. The results of KEGG enrichment analysis exhibited four pathways related to the formation and cure of breast cancer, containing Drug metabolism, Glutathione metabolism, Pyrimidine metabolism and PPAR signaling pathway. Molecular docking showed that trastuzumab has good binding abilities with five core target proteins (GAPDH, MMP9, CCNA2, RRM2, CHEK1). This study, through network pharmacology and molecular docking, provides new pieces of evidence and ideas to understand how trastuzumab treats breast cancer at the gene level.
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http://dx.doi.org/10.3389/fphys.2022.942049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304584PMC
July 2022
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