Publications by authors named "Bing Chen"

1,484 Publications

  • Page 1 of 1

An Antibody from Single Human V-rearranging Mouse Neutralizes All SARS-CoV-2 Variants Through BA.5 by Inhibiting Membrane Fusion.

Sci Immunol 2022 Aug 11:eadd5446. Epub 2022 Aug 11.

Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.

SARS-CoV-2 Omicron sub-variants have generated a world-wide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of vaccination-induced antibodies. To manage Omicron sub-variants and prepare for potential new variants, additional means of isolating broad and potent humanized SARS-CoV-2-neutralizing antibodies are desirable. Here, we describe a mouse model in which the primary B cell receptor (BCR) repertoire is generated solely through V(D)J recombination of a human V1-2 heavy chain (HC) and, substantially, a human Vκ1-33 light chain (LC). Thus, primary humanized BCR repertoire diversity in these mice derives from immensely diverse HC and LC antigen-contact complementarity-region-3 (CDR3) sequences generated by non-templated junctional modifications during V(D)J recombination. Immunizing the human V1-2/Vκ1-33-rearranging mouse model with SARS-CoV-2 (Wuhan-Hu-1) spike protein immunogens elicited several V1-2/Vκ1-33-based neutralizing antibodies that bound RBD in a different mode from each other and from those of many prior human patient-derived V1-2-based neutralizing antibodies. Of these, SP1-77 potently and broadly neutralized all SARS-CoV-2 variants through BA.5. Cryo-EM studies revealed that SP1-77 bound RBD away from the receptor-binding-motif via a CDR3-dominated recognition mode. Lattice-light-sheet-microscopy-based studies showed that SP1-77 did not block ACE2-mediated viral attachment or endocytosis, but rather blocked viral-host membrane fusion. The broad and potent SP1-77 neutralization activity and non-traditonal mechanism of action suggest this antibody might have therapeutic potential. Likewise, the SP1-77 binding epitope may further inform on vacccine strategies. Finally, the general class of humanized mouse models we have described may contribute to identifying therapeutic antibodies against future SARS-CoV-2 variants and other pathogens.
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http://dx.doi.org/10.1126/sciimmunol.add5446DOI Listing
August 2022

A distributed nanocluster based multi-agent evolutionary network.

Nat Commun 2022 Aug 10;13(1):4698. Epub 2022 Aug 10.

National Key Laboratory of Science and Technology on Micro/Nano Fabrication, School of Integrated Circuits, Peking University, 100871, Beijing, China.

As an important approach of distributed artificial intelligence, multi-agent system provides an efficient way to solve large-scale computational problems through high-parallelism processing with nonlinear interactions between the agents. However, the huge capacity and complex distribution of the individual agents make it difficult for efficient hardware construction. Here, we propose and demonstrate a multi-agent hardware system that deploys distributed Ag nanoclusters as physical agents and their electrochemical dissolution, growth and evolution dynamics under electric field for high-parallelism exploration of the solution space. The collaboration and competition between the Ag nanoclusters allow information to be effectively expressed and processed, which therefore replaces cumbrous exhaustive operations with self-organization of Ag physical network based on the positive feedback of information interaction, leading to significantly reduced computational complexity. The proposed multi-agent network can be scaled up with parallel and serial integration structures, and demonstrates efficient solution of graph and optimization problems. An artificial potential field with superimposed attractive/repulsive components and varied ion velocity is realized, showing gradient descent route planning with self-adaptive obstacle avoidance. This multi-agent network is expected to serve as a physics-empowered parallel computing hardware.
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http://dx.doi.org/10.1038/s41467-022-32497-5DOI Listing
August 2022

Population Pharmacokinetics and Pharmacodynamics of Isoniazid and its Metabolite Acetylisoniazid in Chinese Population.

Front Pharmacol 2022 19;13:932686. Epub 2022 Jul 19.

Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmacy, Fudan University, Shanghai, China.

We aimed to establish a population pharmacokinetic (PPK) model for isoniazid (INH) and its major metabolite Acetylisoniazid (AcINH) in healthy Chinese participants and tuberculosis patients and assess the role of the 2 genotype on the transformation of INH to AcINH. We also sought to estimate the INH exposure that would achieve a 90% effective concentration (EC) efficiency for patients with various genotypes. A total of 45 healthy participants and 157 tuberculosis patients were recruited. For healthy subjects, blood samples were collected 0-14 h after administration of 300 mg or 320 mg of the oral dose of INH; for tuberculosis patients who received at least seven days therapy with INH, blood samples were collected two and/or six hours after administration. The plasma concentration of INH and AcINH was determined by the reverse-phase HPLC method. genotypes were determined by allele-specific amplification. The integrated PPK model of INH and AcINH was established through nonlinear mixed-effect modeling (NONMEM). The effect of genotype and other covariates on INH and AcINH disposition was evaluated. Monte Carlo simulation was performed for estimating EC90 of INH in patients with various 2 genotypes. The estimated absorption rate constant (K), oral clearance (CL/F), and apparent volume of distribution (V/F) for INH were 3.94 ± 0.44 h, 18.2 ± 2.45 L⋅h, and 56.8 ± 5.53 L, respectively. The constant of clearance (K) and the volume of distribution (V/F) of AcINH were 0.33 ± 0.11 h and 25.7 ± 1.30 L, respectively. The fraction of AcINH formation (F) was 0.81 ± 0.076. genotypes had different effects on the CL/F and F. In subjects with only one copy of NAT2 *5, *6, and *7 alleles, the CL/F values were approximately 46.3%, 54.9%, and 74.8% of *4/*4 subjects, respectively. The F values were approximately 48.7%, 63.8%, and 86.9% of *4/*4 subjects, respectively. The probability of target attainment of INH EC in patients with various NAT2 genotypes was different. The integrated parent-metabolite PPK model accurately characterized the disposition of INH and AcINH in the Chinese population sampled, which may be useful in the individualized therapy of INH.
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http://dx.doi.org/10.3389/fphar.2022.932686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343941PMC
July 2022

Does Plant Identity Affect the Dispersal of Resistomes Above and Below Ground?

Environ Sci Technol 2022 Aug 2. Epub 2022 Aug 2.

Key Laboratory of Urban Environment and Health, Ningbo Observation and Research Station, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.

Resistomes are ubiquitous in natural environments. Previous studies have shown that both the plant phyllosphere and soil-borne nematodes were reservoirs of above- and below-ground resistomes, respectively. However, the influence of plant identity on soil, nematode, and phyllosphere resistomes remains unclear. Here, a microcosm experiment was used to explore the characteristics of bacterial communities and resistomes in soil, nematode, and phyllosphere associated with six different plant identities (, , , , , and ). A total of 222 antibiotic resistance genes (ARGs) and 7 mobile genetic elements (MGEs) were detected by high-throughput quantitative PCR from all samples. Plant identity not only significantly affected the diversity of resistomes in soil, nematode, and phyllosphere but also influenced the abundance of resistomes in nematodes. Shared bacteria and resistomes indicated a possible pathway of resistomes transfer through the soil-nematode-phyllosphere system. Structural equation models revealed that plant identity had no direct effect on phyllosphere ARGs, but altered indirectly through complex above- and below-ground interactions (soil-plant-nematode trophic transfer). Results also showed that bacteria and MGEs were key factors driving the above- and below-ground flow of resistomes. The study extends our knowledge about the top-down and bottom-up dispersal patterns of resistomes.
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http://dx.doi.org/10.1021/acs.est.1c08733DOI Listing
August 2022

Comparative freezing study of broccoli and cauliflower: Effects of electrostatic field and static magnetic field.

Food Chem 2022 Jul 20;397:133751. Epub 2022 Jul 20.

State Key Laboratory of Food Science and Technology, Jiangnan University, 214122 Wuxi, Jiangsu, China.

The effects of 1, 3, 5 kV/cm electrostatic field (EF) and 2, 5, 8 mT static magnetic field (MF) on the quality of frozen broccoli and cauliflower (B and C) were studied. The freezing parameters were significantly improved by 3, 5 kV/cm EF or 8 mT MF treatment (P < 0.05), a maximum reduction of nucleation time and phase transition time by 20.14 % and 32.09 % was found in 5 kV/cm EF treated cauliflower. EF or MF treatment improved sample quality to some extent, the overall effect of 3 kV/cm EF was the best, which led to a maximum drip loss reduction of 64.3 % in cauliflower, accompanied by lower relative conductivity, higher ascorbic acid and less cell rupture. EF or MF did not significantly reduce the damage of the flavor. MF was less effective than EF in improving the quality of frozen B and C.
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http://dx.doi.org/10.1016/j.foodchem.2022.133751DOI Listing
July 2022

Adsorption of Methylene Blue from Aqueous Solution Using Gelatin-Based Carboxylic Acid-Functionalized Carbon [email protected] Framework Composite Beads.

Nanomaterials (Basel) 2022 Jul 23;12(15). Epub 2022 Jul 23.

College of Mechanical and Electrical Engineering, Qingdao University, 308 Ningxia Road, Qingdao 266071, China.

A novel gelatin-based functionalized carbon [email protected] framework ([email protected]@Gel) adsorbent was prepared by the green and simple method for the adsorption of methylene blue (MB). Cu-BTC (also known as HKUST-1) was selected as the MOF type. [email protected] particles were fixed by gelatin, thus avoiding the secondary pollution of carbon nanomaterial particles to the environment. CNTs were used as the connecting skeleton to make more effective adsorption sites exposed on the surface of the internal pore structure of the adsorbent. In this paper, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), thermogravimetry (TGA) and BET analysis methods were used to characterize the new adsorbent. The effects of time, temperature, pH, dosage and initial concentration on the adsorption process were investigated by batch adsorption experiments. The adsorption mechanism was further analyzed by several commonly used kinetic and isotherm models, and the reliability of several fitting models was evaluated by the Akaike information criterion (AIC), Bayesian information criterion (BIC) and Hannan information criterion (HIC). After five regeneration experiments, the adsorbent still had 61.23% adsorption capacity. In general, the new adsorbent studied in this paper has an optimistic application prospect.
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http://dx.doi.org/10.3390/nano12152533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332057PMC
July 2022

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease.

Front Aging Neurosci 2022 7;14:949083. Epub 2022 Jul 7.

Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China.

Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.
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http://dx.doi.org/10.3389/fnagi.2022.949083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300955PMC
July 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

Overnutrition Induced Cognitive Impairment: Insulin Resistance, Gut-Brain Axis, and Neuroinflammation.

Front Neurosci 2022 6;16:884579. Epub 2022 Jul 6.

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

Overnutrition-related obesity has become a worldwide epidemic, and its prevalence is expected to steadily rise in the future. It is widely recognized that obesity exerts negative impacts on metabolic disorders such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases. However, relatively fewer reports exist on the impairment of brain structure and function, in the form of memory and executive dysfunction, as well as neurogenerative diseases. Emerging evidence indicates that besides obesity, overnutrition diets independently induce cognitive impairments multiple mechanisms. In this study, we reviewed the clinical and preclinical literature about the detrimental effects of obesity or high-nutrition diets on cognitive performance and cerebral structure. We mainly focused on the role of brain insulin resistance (IR), microbiota-gut-brain axis, and neuroinflammation. We concluded that before the onset of obesity, short-term exposure to high-nutrition diets already blunted central responses to insulin, altered gut microbiome composition, and activated inflammatory mediators. Overnutrition is linked with the changes in protein expression in brain insulin signaling, leading to pathological features in the brain. Microbiome alteration, bacterial endotoxin release, and gut barrier hyperpermeability also occur to trigger mental and neuronal diseases. In addition, obesity or high-nutrition diets cause chronic and low-grade systematic inflammation, which eventually spreads from the peripheral tissue to the central nervous system (CNS). Altogether, a large number of unknown but potential routes interact and contribute to obesity or diet-induced cognitive impairment. The challenge for future research is to identify effective interventions involving dietary shifts and personalized therapy targeting the underlying mechanisms to prevent and improve cognition deficits.
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http://dx.doi.org/10.3389/fnins.2022.884579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298971PMC
July 2022

Shrimp-waste based dispersant as oil spill treating agent: Biodegradation of dispersant and dispersed oil.

J Hazard Mater 2022 Jul 16;439:129617. Epub 2022 Jul 16.

Northern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University of Newfoundland, St. John's, NL A1B 3×5, Canada.

The emerging demand for the enhancement of biodegradation of persistent organic pollutants from marine oil spills using oil-treating agents to minimize the environmental impacts promotes the development of green dispersants. Shrimp waste is a potential raw material to generate green dispersants. The biodegradability of dispersed oil and dispersants themselves are key factors for the national consideration of the approval, stockpile, and usage of dispersants. However, it is unknown whether shrimp-waste-based dispersant (SWD) has high bioavailability or facilitates the biodegradation of dispersed oil. In this study, we tackled the biodegradation of oil dispersed by a purified SWD. Furthermore, the SWD biodegradability was evaluated by exploring the degradation genes via metagenomic sequencing, analyzing the enzymatic activities for dispersant biodegradation by molecular docking, and discussing the SWD toxicity. We discovered that the SWD facilitated the biodegradation of two crude oils (Alaska North Slope and Marine Fuel-No.6). The metagenomic analysis with molecular docking showed that fresh seawater had feasible enzymes to degrade the SWD to safety components. Additionally, the SWD was low toxic and high bioactive. The findings helped confirm that the purified SWD is an effective and eco-sustainable marine oil spill treating agent and tracked the biodegradation of dispersed oil and the SWD.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129617DOI Listing
July 2022

Identification and fine-mapping of Xo2, a novel rice bacterial leaf streak resistance gene.

Theor Appl Genet 2022 Jul 24. Epub 2022 Jul 24.

Guangdong Provincial Key Laboratory of High Technology for Plant Protection, Plant Protection Research Institute of Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China.

Key Message: A novel rice resistance gene, Xo2, influencing pathogenesis of the bacterial leaf streak disease, has been identified, and candidate genes for Xo2 in the fine mapping region have been shown to be involved in bacterial leaf streak resistance. Rice (Oryza sativa) bacterial leaf streak, caused by Xanthomonas oryzae pv. oryzicola (Xoc), is one of the most serious rice bacterial diseases. The deployment of host resistance genes is an effective approach for controlling this disease. The cultivar BHADOIA 303 (X455) from Bangladesh is resistant to most of Chinese Xoc races. To identify and map the resistance gene(s) involved in Xoc resistance, we examined the association between phenotypic and genotypic variations in two F populations derived from crosses between X455/Jingang 30 and X455/Wushansimiao. The segregation ratios of the F progeny were consistent with the action of a single dominant resistance gene, which was designated as Xo2. Based on rice SNP chip (GSR40K) assays of X455, Jingang 30, and resistant and susceptible pools thereof, we mapped Xo2 to the region from 10 Mb to 12.5 Mb on chromosome 2. The target gene was further finely mapped between the markers RM12941 and D6-1 within an approximately 110-kb region. The de novo sequencing and gene annotation of X455 and Jingang 30 revealed nineteen predicted genes within the target region. RNA-seq and expression analysis showed that four candidate genes, including Osa002T0115800, encoding an NLR resistance protein, were distinctly upregulated. Differential sequence and synteny analysis between X455 and Jingang 30 suggested that Osa002T0115800 is likely the functional Xo2 gene. This study lays a foundation for marker-assisted selection resistance breeding against rice bacterial leaf streak and the further cloning of Xo2.
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http://dx.doi.org/10.1007/s00122-022-04179-9DOI Listing
July 2022

The mutation features and geographical distributions of the surface glycoprotein (S gene) in SARS-CoV-2 strains: A comparative analysis of the early and current strains.

J Med Virol 2022 Jul 24. Epub 2022 Jul 24.

Center for Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.

The surface glycoprotein (S protein) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to develop coronavirus disease 2019 (COVID-19) vaccines. However, SARS-CoV-2, especially the S protein, has undergone rapid evolution and mutation, which has remained to be determined. Here, we analyzed and compared the early (12 237) and the current (more than 10 million) SARS-CoV-2 strains to identify the mutation features and geographical distribution of the S gene and S protein. Results showed that in the early strains, most of the loci were with relative low mutation frequency except S: 23403 (4486 strains), while in the current strains, there was a surge in the mutation strains and frequency, with S: 23403 constantly being the highest one, but tremendously increased to approximately 1050 times. Furthermore, D614 (S: 23403) was one of the most highly frequent mutations in the S protein of Omicron as of March 2022, and most of the mutant strains were still from the United States, and the United Kingdom. Further analysis demonstrated that in the receptor-binding domain, most of the loci with low mutation frequency in the early strains, while S: 22995 was nowadays the most prevalent loci with 3 122 491 strains in the current strains. Overall, we compare the mutation features of the S region in SARS-CoV-2 strains between the early and the current stains, providing insight into further studies in concert with emerging SARS-CoV-2 variants for COVID-19 vaccines.
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http://dx.doi.org/10.1002/jmv.28023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350160PMC
July 2022

SARS-CoV-2 Achieves Immune Escape by Destroying Mitochondrial Quality: Comprehensive Analysis of the Cellular Landscapes of Lung and Blood Specimens From Patients With COVID-19.

Front Immunol 2022 1;13:946731. Epub 2022 Jul 1.

Department of Anesthesiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Mitochondria get caught in the crossfire of coronavirus disease 2019 (COVID-19) and antiviral immunity. The mitochondria-mediated antiviral immunity represents the host's first line of defense against viral infection, and the mitochondria are important targets of COVID-19. However, the specific manifestations of mitochondrial damage in patients with COVID-19 have not been systematically clarified. This study comprehensively analyzed one single-cell RNA-sequencing dataset of lung tissue and two bulk RNA-sequencing datasets of blood from COVID-19 patients. We found significant changes in mitochondrion-related gene expression, mitochondrial functions, and related metabolic pathways in patients with COVID-19. SARS-CoV-2 first infected the host alveolar epithelial cells, which may have induced excessive mitochondrial fission, inhibited mitochondrial degradation, and destroyed the mitochondrial calcium uniporter (MCU). The type II alveolar epithelial cell count decreased and the transformation from type II to type I alveolar epithelial cells was blocked, which exacerbated viral immune escape and replication in COVID-19 patients. Subsequently, alveolar macrophages phagocytized the infected alveolar epithelial cells, which decreased mitochondrial respiratory capacity and activated the ROS-HIF1A pathway in macrophages, thereby aggravating the pro-inflammatory reaction in the lungs. Infected macrophages released large amounts of interferon into the blood, activating mitochondrial IFI27 expression and destroying energy metabolism in immune cells. The plasma differentiation of B cells and lung-blood interaction of regulatory T cells (Tregs) was exacerbated, resulting in a cytokine storm and excessive inflammation. Thus, our findings systematically explain immune escape and excessive inflammation seen during COVID-19 from the perspective of mitochondrial quality imbalance.
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http://dx.doi.org/10.3389/fimmu.2022.946731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283956PMC
July 2022

The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer.

Adv Sci (Weinh) 2022 Jul 17:e2201701. Epub 2022 Jul 17.

Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.

Estrogen receptor alpha (ER-α) action is critical for hormone-dependent breast cancer, and ER-α dysregulation can lead to the emergence of resistance to endocrine therapy. Here, it is found that TRIM4 is downregulated in tamoxifen (TAM)-resistant breast cancer cells, while the loss of TRIM4 is associated with an unfavorable prognosis. In vitro and in vivo experiments confirm that TRIM4 increased ER-α expression and the sensitivity of breast cancer cells to TAM. Mechanistically, TRIM4 is found to target SET, and TRIM4-SET interactions are mediated by the RING and B-box domains of TRIM4 and the carboxyl terminus of SET. Moreover, it is determined that TRIM4 catalyzed the K48-linked polyubiquitination of SET (K150 and K172), promoting its proteasomal degradation and disassociation from p53 and PP2A. Once released, p53 and PP2A are able to further promote ESR1 gene transcription and enhance mRNA stability. Moreover, univariate and multivariate Cox proportional hazards regression analyses confirm that TRIM4 expression is an independent predictor of overall survival and recurrence-free survival outcomes in patients with ER-α positive breast cancer. Taken together, the data highlights a previously undiscovered mechanism and suggest that TRIM4 is a valuable biomarker that can be analyzed to predict response to endocrine therapy in breast cancer patients.
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http://dx.doi.org/10.1002/advs.202201701DOI Listing
July 2022

Recent advances in cellular optogenetics for photomedicine.

Adv Drug Deliv Rev 2022 Jul 16;188:114457. Epub 2022 Jul 16.

Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China; City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, China. Electronic address:

Since the successful introduction of exogenous photosensitive proteins, channelrhodopsin, to neurons, optogenetics has enabled substantial understanding of profound brain function by selectively manipulating neural circuits. In an optogenetic system, optical stimulation can be precisely delivered to brain tissue to achieve regulation of cellular electrical activity with unprecedented spatio-temporal resolution in living organisms. In recent years, the development of various optical actuators and novel light-delivery techniques has greatly expanded the scope of optogenetics, enabling the control of other signal pathways in non-neuronal cells for different biomedical applications, such as phototherapy and immunotherapy. This review focuses on the recent advances in optogenetic regulation of cellular activities for photomedicine. We discuss emerging optogenetic tools and light-delivery platforms, along with a survey of optogenetic execution in mammalian and microbial cells.
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http://dx.doi.org/10.1016/j.addr.2022.114457DOI Listing
July 2022

High genetic diversity and low population differentiation of a medical plant Ficus hirta Vahl., uncovered by microsatellite loci: implications for conservation and breeding.

BMC Plant Biol 2022 Jul 12;22(1):334. Epub 2022 Jul 12.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.

Background: Wuzhimaotao (Radix Fici Hirtae) originates from the dry root of Ficus hirta (Moraceae), which is widely known as a medical and edible plant distributed in South China. As the increasing demand for Wuzhimaotao, the wild F. hirta has been extremely reduced during the past years. It is urgent to protect and rationally develop the wild resources of F. hirta for its sustainable utilization. However, a lack of genetic background of F. hirta makes it difficult to plan conservation and breeding strategies for this medical plant. In the present study, a total of 414 accessions of F. hirta from 7 provinces in southern China were evaluated for the population genetics using 9 polymorphic SSR markers.

Results: A mean of 17.1 alleles per locus was observed. The expected heterozygosity (He) varied from 0.142 to 0.861 (mean = 0.706) in nine SSR loci. High genetic diversity (H = 0.706, ranged from 0.613 to 0.755) and low genetic differentiation among populations (G' = 0.147) were revealed at population level. In addition, analysis of molecular variance (AMOVA) indicated that the principal molecular variance existed within populations (96.2%) was significantly higher than that among populations (3.8%). Meanwhile, the three kinds of clustering methods analysis (STRUCTURE, PCoA and UPGMA) suggested that the sampled populations were clustered into two main genetic groups (K = 2). Mantel test showed a significant correlation between geographic and genetic distance among populations (R = 0.281, P < 0.001). Pollen flow, seed flow and/or geographical barriers might be the main factors that formed the current genetic patterns of F. hirta populations.

Conclusions: This is a comprehensive study of genetic diversity and population structure of F. hirta in southern China. We revealed the high genetic diversity and low population differentiation in this medicinal plant and clarified the causes of its current genetic patterns. Our study will provide novel insights into the exploitation and conservation strategies for F. hirta.
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http://dx.doi.org/10.1186/s12870-022-03734-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277808PMC
July 2022

COL1A1: A novel oncogenic gene and therapeutic target in malignancies.

Pathol Res Pract 2022 Aug 5;236:154013. Epub 2022 Jul 5.

Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China. Electronic address:

Collagen type I alpha 1 (COL1A1), a member of the collagen family, is involved in epithelial-mesenchymal transition, which is closely linked to malignant tumorigenesis. COL1A1 is highly expressed in various cancers and regulates various cellular processes, including cell proliferation, metastasis, apoptosis, and cisplatin resistance. COL1A1 is also associated with cancer progression and prognosis; elevated COL1A1 expression is associated with poor prognosis in cancer patients. However, the main role of COL1A as a cancer-promoting factor in specific tumors has not been reported. Additionally, the protein levels and mechanisms of action of this protein differ among tumor types. This review discusses current research progress concerning COL1A1 in different tumor types, and then summarizes its contributions to cancer progression, thus providing a basis for follow-up research and potential targets for cancer treatment.
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http://dx.doi.org/10.1016/j.prp.2022.154013DOI Listing
August 2022

Unexpected Branch Malformation of the Facial Nerve during Stapes Surgery: Comparison between Intraoperative and Radiographic Findings.

ORL J Otorhinolaryngol Relat Spec 2022 Jul 7:1-8. Epub 2022 Jul 7.

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

The aim of this study was to determine the prevalence of facial nerve (FN) bifurcation in patients who undergo stapes surgery, and to ascertain the correlation between the intraoperative and radiographic findings in cases where an unexpected branch malformation for patients undergoing stapes surgery. Patients who underwent stapes surgery were retroactively examined for confirmed FN bifurcation. Among the 887 patients, 10 had a bifurcated FN confirmed during surgery and had a preoperative high-resolution computed tomography (HRCT) scan. The HRCT scans were examined by two radiologists who were blinded to the operational findings. The diagnostic accuracy of HRCT imaging was examined along with their preoperative audiometry. In total, 887 patients underwent stapes surgery and among them the prevalence of FN bifurcation was 1.13%. These 10 patients had a 1:1 male-female ratio with a mean age of 17.9 ± 7.0 years. From a surgical review, all cases had bifurcation at the horizontal segment of FN, including 1 case of FN trifurcation. The diagnostic difference between HRCT imaging and intraoperation observations for malformations in the middle ear varies widely depending on the location, ranging from 0% to 90%. The prevalence of incus and stapes malformations was high in both imaging and operation findings (≥60%). The detection rate of abnormal positioning and bifurcation of the FN during HRCT imaging was 30% and 0%, respectively. The mean air-bone gap hearing threshold for patients was significantly improved from 42.3 dB preoperatively to 15.6 dB postoperatively without any complications. These results showed that it is extremely difficult to predict the FN bifurcation prior to surgery with a detection rate of 0%. The diagnostic difference between HRCT imaging and intraoperation observations for malformations of different parts of the middle ear varies widely. These results highlight the importance of being vigilant in regard to FN anatomical variation during stapes surgery for any unexpected malformations that are not detected during HRCT evaluation. In addition, the surgical outcomes for these patients were optimal when treatment was performed by senior surgeons.
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http://dx.doi.org/10.1159/000523926DOI Listing
July 2022

Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1-Adiponectin Axis.

Front Endocrinol (Lausanne) 2022 17;13:907984. Epub 2022 Jun 17.

Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China.

Empagliflozin (EMPA) is a novel sodium-glucose cotransporter 2 inhibitor (SGLT2i) that produces protective cardiovascular-renal outcomes in patients with diabetes. However, the effects of EMPA on obesity-related kidney disease have not been determined. The heme oxygenase-1 (HO-1)-adiponectin axis is an essential antioxidant system with anti-apoptotic and anti-inflammatory properties. This study explored whether EMPA improves obesity-related kidney disease through regulation of the renal HO-1-mediated adiponectin axis. C57BL/6J mice were assigned to control, high-fat diet (HFD) groups, and EMPA (10 mg/kg) groups. HFD mice showed metabolic abnormality and renal injury, including increased urinary albumin excretion, morphologic changes, and lipid accumulation. EMPA treatment improved metabolic disorders and attenuated lipotoxicity-induced renal injury. Furthermore, EMPA treatment ameliorated renal NLRP3 inflammasome activity and upregulated the HO-1-adiponectin axis. Our findings indicate that EMPA improves obesity-related kidney disease through reduction of NLRP3 inflammasome activity and upregulation of the HO-1-adiponectin axis, suggesting a novel mechanism for SGLT2i-mediated renal protection in obesity.
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http://dx.doi.org/10.3389/fendo.2022.907984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248377PMC
June 2022

Research on the Impact of Marketing Strategy on Consumers' Impulsive Purchase Behavior in Livestreaming E-commerce.

Front Psychol 2022 16;13:905531. Epub 2022 Jun 16.

School of Business, Guilin University of Electronic Technology, Guilin, China.

Livestreaming e-commerce has emerged as a highly profitable e-commerce that has revolutionized the retail industry, especially during the COVID-19 pandemic. However, research on livestreaming e-commerce is still in its infancy. This study sheds new light on impulsive purchase behavior in livestreaming e-commerce. Based on stimulus-organism-response (SOR) theory, this study introduces the "People-Product-Place" marketing strategy for livestreaming e-commerce from the perspective of consumer perception and aims to understand the impact of marketing strategy on impulsive purchase behavior in e-commerce livestreaming shopping scenes, and to examine the mediating effect of involvement. The study conducted SEM analysis, in Amos, on 437 response sets from an online anonymous survey. The results show that e-, , and positively influence impulsive purchase behavior; that "People-Product-Place" marketing strategy is important; and that effective marketing triggers impulsive purchase. , and positively influence , which positively influences impulsive purchase. mediates between e-, and , and impulsive purchase. These findings guide marketers to improve the profitability of livestreaming e-commerce and provide some references of economic recovery for many other countries that also suffered from the impact of the COVID-19 pandemic.
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http://dx.doi.org/10.3389/fpsyg.2022.905531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245792PMC
June 2022

Genomic Landscape of Metastatic Lymph Nodes and Primary Tumors in Non-Small-Cell Lung Cancer.

Pathol Oncol Res 2022 16;28:1610020. Epub 2022 Jun 16.

The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

To investigate the genetic mutation characteristics of non-small cell lung cancers (NSCLC) with and without lymph node metastasis. Primary lesions and metastatic lymph node lesions of 36 Chinese NSCLC patients were tested for somatic mutations, tumor mutation burden, phylogenetic and clonal evolutional analysis using a 1021-gene panel by next-generation sequencing (NGS) with an average sequencing depth of 671X. In this study, eighteen patients with lung adenocarcinoma (LUAD) and 18 with lung squamous cell carcinoma (LUSC) were included. Different groups had distinct characteristics of gene mutations. CTNNB1 gene mutations were only present in Nome_LC LUAD patients ( < 0.05). ARID1A mutation was however the only gene with significant alterations ( < 0.05) in Nome_LC in LUSC. Phylogenetic trees of mutated genes were also constructed. Linear and parallel evolutions of metastatic lymph nodes were observed both in LUAD and LUSC. LUSC exhibited more genetic mutations than LUAD. Intriguingly, there was significant difference in gene mutations between Meta_LC and Nome_LC. CTNNB1 gene alteration was the key mutation in LUAD that seems to promote proliferation of the tumor and then determine T stage. On the other hand, proliferation of the tumor was characterized by ARID1A missense mutation in LUSC, thus influencing the T stage as well. Lymph node metastasis could display both linear and parallel evolutionary characteristics in NSCLC. Different metastatic lymph nodes might have exactly the same or different mutated genes, underlining the heterogeneous genomic characteristics of these cancer types.
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http://dx.doi.org/10.3389/pore.2022.1610020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243222PMC
July 2022

[Two cases of coagulation factor Ⅺ deficiency caused by compound heterozygous mutations].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jun;39(6):597-601

Department of Hematology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.

Objective: To investigate the molecular pathogenesis of two coagulation factor Ⅺ (FⅪ) deficiency patients.

Methods: Coagulant assays: activated partial thromboplastin time (APTT), normal pooled-plasma corrected APTT test, PT, PT-INR and one-stage assay of coagulation factors activities were validated to diagnose coagulation factor Ⅺ deficiency. The patients' DNA samples were extracted and all exons and flanking sequences of F11 gene were amplified using PCR. After purified, the products of PCR were sequenced directly, the mutations were detected by comparing with wild sequences and analyzed using some bio-informatics softwares.

Results: The two patients were diagnosed with coagulation factor Ⅺ deficiency due to prolonged APTT, corrected APTT and low activities of coagulation factor FⅪ. The results of APTT, FⅪ: C were 88.1s, 1.1% and 107.1s, 3.8%, and the prolonged APTT could be corrected to normal range 32.9 s and 31.5 s, respectively. Through genetic analysis, we discovered compound heterozygous mutations g.1305-1G>A and g.1325delT in patient 1 and the sequencing results of TA plasmid clones showed that the two mutations were located on different strands of chromosomes. Compound heterozygous mutations g.1124A>G and g.1550C>G were detected in patient 2 resulting in Lys357Arg and Cys482Trp. Software analysis indicated the mutations probably brought amino acid sequence changed, protein features affected and splice site changed.

Conclusion: Compound heterozygous mutations g.1305-1G>A, g.1325delT and g.1124A>G, g.1550C>G had been identified in two coagulation factor Ⅺ deficiency patients which might be responsible for their prolonged APTT and low FⅪ: C. To the best of our knowledge, g.1325delT and g.1550C>G have been reported, while g.1124A>G and g.1305-1G>A are reported for the first time in the literature.
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http://dx.doi.org/10.3760/cma.j.cn511374-20201112-00793DOI Listing
June 2022

Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia.

BMC Genomics 2022 Jun 24;23(1):467. Epub 2022 Jun 24.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: T cell acute lymphoblastic leukemia (T-ALL) defines a group of hematological malignancies with heterogeneous aggressiveness and highly variable outcome, making therapeutic decisions a challenging task. We tried to discover new predictive model for T-ALL before treatment by using a specific pipeline designed to discover aberrantly active gene.

Results: The expression of 18 genes was significantly associated with shorter survival, including ACTRT2, GOT1L1, SPATA45, TOPAZ1 and ZPBP (5-GEC), which were used as a basis to design a prognostic classifier for T-ALL patients. The molecular characterization of the 5-GEC positive T-ALL unveiled specific characteristics inherent to the most aggressive T leukemic cells, including a drastic shut-down of genes located on the mitochondrial genome and an upregulation of histone genes, the latter characterizing high risk forms in adult patients. These cases fail to respond to the induction treatment, since 5-GEC either predicted positive minimal residual disease (MRD) or a short-term relapse in MRD negative patients.

Conclusion: Overall, our investigations led to the discovery of a homogenous group of leukemic cells with profound alterations of their biology. It also resulted in an accurate predictive tool that could significantly improve the management of T-ALL patients.
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http://dx.doi.org/10.1186/s12864-022-08688-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233359PMC
June 2022

Hepatitis C is associated with more adverse pregnancy outcomes than hepatitis B: A 7-year national inpatient sample study.

Hepatol Commun 2022 Jun 24. Epub 2022 Jun 24.

Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Prior international studies have shown mixed results regarding the association of hepatitis B and hepatitis C with adverse pregnancy outcomes. We performed an updated evaluation of the prevalence of associated adverse pregnancy outcomes and evaluated trends over time of diagnosis of chronic hepatitis B (HBV) and chronic hepatitis C (HCV) in pregnant women in a national database. All pregnant women with HBV and HCV were identified from the National Inpatient Sample database 2012 to 2018. Multivariate logistic regression analyses were performed to compare pregnancy-related complications, including rates of preeclampsia/eclampsia, gestational diabetes, intrauterine growth restriction, antepartum/intrapartum hemorrhage, preterm labor, and Cesarean section. We evaluated all-cause in-hospital mortality, length of stay, and total cost of hospitalizations. A total of 28.7 million pregnancy-related hospitalizations that met our eligibility criteria were identified, including 51,200 with HBV and 131,695 with HCV. In comparison with the uninfected controls, the HBV group was significantly more likely to develop gestational diabetes (12.94% vs. 6.94%, p < 0.001). The HCV group was more likely to have preterm labor (9.63% vs. 6.27%, p < 0.001), intrauterine growth restriction (6.04% vs. 2.89%, p < 0.001), longer length of stay (3.4 days vs. 2.7 days, p < 0.001), and higher hospitalization cost (15,052 dollars vs. 14,258 dollars, p < 0.001). These findings should inform counseling of women who are found to have HBV or HCV during pregnancy regarding the risk of adverse pregnancy outcomes and support the need for an interdisciplinary approach to optimize maternal and neonatal outcomes.
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http://dx.doi.org/10.1002/hep4.2002DOI Listing
June 2022

Recent advances in chemical and biological degradation of spilled oil: A review of dispersants application in the marine environment.

J Hazard Mater 2022 08 2;436:129260. Epub 2022 Jun 2.

Northern Region Persistent Organic Pollutant Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John's, NL A1B 3×5, Canada. Electronic address:

Growing concerns over the risk of accidental releases of oil into the marine environment have emphasized our need to improve both oil spill preparedness and response strategies. Among the available spill response options, dispersants offer the advantages of breaking oil slicks into small oil droplets and promoting their dilution, dissolution, and biodegradation within the water column. Thus dispersants can reduce the probability of oil slicks at sea from reaching coastal regions and reduce their direct impact on mammals, sea birds and shoreline ecosystems. To facilitate marine oil spill response operations, especially addressing spill incidents in remote/Arctic offshore regions, an in-depth understanding of the transportation, fate and effects of naturally/chemically dispersed oil is of great importance. This review provides a synthesis of recent research results studies related to the application of dispersants at the surface and in the deep sea, the fate and transportation of naturally and chemically dispersed oil, and dispersant application in the Arctic and ice-covered waters. Future perspectives have been provided to identify the research gaps and help industries and spill response organizations develop science-based guidelines and protocols for the application of dispersants application.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129260DOI Listing
August 2022

Development of advanced oil/water separation technologies to enhance the effectiveness of mechanical oil recovery operations at sea: Potential and challenges.

J Hazard Mater 2022 09 10;437:129340. Epub 2022 Jun 10.

Northern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Memorial University of Newfoundland, St. John's, NL A1B 3X5, Canada.

Mechanical oil recovery (i.e., booming and skimming) is the most common tool for oil spill response. The recovered fluid generated from skimming processes may contain a considerable proportion of water (10 % ~ 70 %). As a result of regulatory prohibition on the discharge of contaminated waters at sea, vessels and/or storage barges must make frequent trips to shore for oil-water waste disposal. This practice can be time- consuming thus reduces the overall efficiency and capacity of oil recovery. One potential solution is on-site oil-water separation and disposal of water fraction at sea. However, currently available decanting processes may have limited oil/water separation capabilities, especially in the presence of oil-water emulsion, which is inevitable in mechanical oil recovery. The decanted water may not meet the discharge standards and cause severe ecotoxicological impacts. This paper therefore comprehensively reviews the principles and progress in oil/water separation, demulsification, and on-site treatment technologies, investigates their applicability on decanting at sea, and discusses the ecotoxicity of decanted water in the marine environment. The outputs provide the fundamental and practical knowledge on decanting and help enhance response effectiveness and consequently reducing the environmental impacts of oil spills.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129340DOI Listing
September 2022

Integrating transcriptome and physiological analysis to reveal the essential responses of Daphnia magna to antimony trioxide nanoparticle.

J Hazard Mater 2022 09 6;437:129303. Epub 2022 Jun 6.

Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding 071002, China.

Antimony (Sb) pollution has already posed a severe threat to the aquatic ecosystem. However, the toxicity mechanisms of Sb on aquatic organisms are far from being elucidated. One of the crucial questions remaining unresolved is the characterization of molecular toxicity of Sb(III). Transcriptomics profiling combined with physiological characterizations was applied to investigate the response of Daphnia magna to nano-size antimony trioxide (nATO) and its soluble Sb(III) counterpart antimony potassium tartrate (APT) in the present study. Both nATO and APT induced the formation of oxidative stress, enhanced the activities of anti-oxidative enzymes, altered the metabolism of xenobiotics, increased the concentration of hydrogen sulfide (HS) and nitric oxide (NO), and triggered the self-protection mechanisms such as ubiquitin-mediated proteolysis. In addition, nATO and APT caused damage to the nervous system of D. magna, inhibited its locomotion and nutrient uptake in a concentration-dependent manner. Moreover, nATO exposure enhanced the autophagy activity, reflected by the up-regulated expression of hypoxia-inducible factor-1α, calmodulin-dependent protein kinase-β, and inositol-requiring enzyme 1. The present study, for the first time, depicted a global map of cellular response to nATO, provided essential information on Sb(III) toxicity to aquatic organisms, and is of great significance to the development of Sb management strategies.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129303DOI Listing
September 2022

Label-free detection and enumeration of rare circulating tumor cells by bright-field image cytometry and multi-frame image correlation analysis.

Lab Chip 2022 Jun 16. Epub 2022 Jun 16.

School of Information Engineering, Zhengzhou University, Zhengzhou 450001, China.

Identification and enumeration of circulating tumor cells (CTCs) in peripheral blood are proved to correlate with the progress of metastatic cancer and can provide valuable information for diagnosis and monitoring of cancer. Here, we introduce a bright-field image cytometry (BFIC) technique, assisted by a multi-frame image correlation (MFIC) algorithm, as a label-free approach for tumor cell detection in peripheral blood. For this method, images of flowing cells in a wide channel were continuously recorded and cell types were determined simultaneously using a deep neural network of YOLO-V4 with an average precision (AP) of 98.63%, 99.04%, and 98.95% for cancer cell lines HT29, A549, and KYSE30, respectively. The use of the wide microfluidic channel (400 μm width) allowed for a high throughput of 50 000 cells per min without clogging. Then erroneous or missed cell classifications caused by imaging angle differences or accidental misinterpretations in single frames were corrected by the multi-frame correlation analysis. This further improved the AP to 99.40%, 99.52%, and 99.47% for HT29, A549, and KYSE30, respectively. Meanwhile, cell counting was also accomplished in this dynamic process. Moreover, our imaging cytometry method can readily detect as few as 10 tumor cells from 100 000 white blood cells and was unaffected by the EMT process. Furthermore, CTCs from 8 advanced-stage cancer clinical samples were also successfully detected, while none for 6 healthy control subjects. Although this method is implemented for CTCs, it can also be used for the detection of other rare cells.
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http://dx.doi.org/10.1039/d2lc00190jDOI Listing
June 2022

Network Pharmacology and Molecular Docking Analysis of the Mechanism Underlying Yikunyin's Therapeutic Effect on Menopausal Syndrome.

Evid Based Complement Alternat Med 2022 6;2022:7302419. Epub 2022 Jun 6.

Department of Gynaecology and Obstetrics, The First Peoples Hospital of Wuhu City, Wuhu 241001, Anhui Province, China.

Objective: Yikunyin is an empirical prescription that exhibits good efficacy in the clinical treatment of menopausal syndrome; however, its underlying mechanism remains unclear. This study investigates the mechanism implicated in the therapeutic effect of Yikunyin by identifying its hub genes, central pathways, and key active ingredients.

Method: The active ingredients and targets of Yikunyin were obtained from the Traditional Chinese Medicine Systems Pharmacology database, whereas the targets related to menopausal syndrome were obtained from GeneCards, PharmGKB, Therapeutic Target Database (TTD), and Comparative Toxicogenomics Database (CTD). To reveal the pharmacological mechanism, the component-target and the intersecting protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Finally, molecular docking was carried out to assess the strength of binding between the key active ingredients and key targets.

Results: A total of 418 targets and 121 active ingredients were identified in Yikunyin. The intersection of Yikunyin's 418 targets with the 2822 targets related to menopausal syndrome shows that there are 247 common targets that can be considered potential targets of Yikunyin in the treatment of menopausal syndrome. The topology analysis of the constructed PPI network conducted using the Cytoscape software shows that there are 15 hub genes implicated in the therapeutic effect of Yikunyin: AKT1, PRKCA, TLR9, CXCL10, PRKCD, PARP1, ABCB1, TP53, CAV1, MAPK8, PPARA, GRB2, EGFR, IL-6, and JAK2. Moreover, the key active components acting on these genes are paeoniflorin, luteolin, quercetin, beta-sitosterol, and kaempferol. GO and KEGG analyses indicate that Yikunyin can treat menopausal syndrome by regulating cellular response to chemical stress (GO:0062197), cellular response to oxidative stress (GO:0034599), phosphatase binding (GO:0019902), cytokine receptor binding (GO:0005126), PI3K-Akt signaling (hsa04151), lipid and atherosclerosis (hsa05417), and hepatitis B (hsa05161). Finally, the results of molecular docking suggest that the key active ingredients and key targets can bind well, with binding energies of less than -5 kJ/mol.

Conclusion: The research conducted herein reveals that Yikunyin treats menopausal syndrome by targeting AKT1 and IL-6 and by regulating the PI3K-Akt signaling pathway. Moreover, it provides a new idea for understanding the therapeutic effects of traditional Chinese medicines.
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http://dx.doi.org/10.1155/2022/7302419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192326PMC
June 2022
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