Publications by authors named "Cheng Zhang"

3,011 Publications

  • Page 1 of 1

High Performance Flip-Structure Enhancement-Mode HEMT with Face-to-Face Double Gates.

Nanoscale Res Lett 2022 Aug 11;17(1):73. Epub 2022 Aug 11.

The State Key Laboratory of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, Chengdu, 610054, China.

A novel double gates flip-structure enhancement-mode (E-mode) high electron mobility transistor with step field plate (DFF HEMT) is proposed. It features face-to-face double gates, including a top trench MIS gate with a step field plate and a bottom planar MIS gate, which is shorted together. In the on-state, the double gates not only can restore the 2DEG by the higher electric potential, but also can form the electron accumulation layers, and thus increase the saturation output current and reduce the on-resistance. The face-to-face double gates together deplete the 2DEG by using the work function difference to realize E-mode, instead of by etching the AlGaN layer under the gate for the conventional MIS gate E-mode HEMT. The double-gate structure not only avoids etch damage, but also maintains both high threshold voltage and low on-resistance. Meanwhile, the step gate field plate modulates E-field distribution to increase the BV. In order to easily fabricate, the trench gate with step field plate must be located on the top of device, forming the flip-structure. The flip-structure is also beneficial to decrease the leakage current in the substrate. The simulated V, BV and I of the DFF HEMT are 0.8 V, 465 V and 494 mA/mm, respectively. The FOM of the DFF HEMT is 79.8% and 444.2% higher than those of the conventional MIS-FP HEMT and MIS HEMT.
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http://dx.doi.org/10.1186/s11671-022-03713-4DOI Listing
August 2022

Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages and Trophoblasts.

Circ Res 2022 Aug 11:101161CIRCRESAHA122320771. Epub 2022 Aug 11.

Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences (J.J., Y.Z., Z.Z., Z.T., X.W., C.Z., Q.Z.).

Background: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated.

Methods: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development.

Results: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of , and short-chain fatty acids that could accurately diagnose preeclampsia.

Conclusions: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.
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http://dx.doi.org/10.1161/CIRCRESAHA.122.320771DOI Listing
August 2022

Development of a SETD2-related immune prognostic signature in clear cell renal cell carcinoma.

Medicine (Baltimore) 2022 Aug;101(31):e29561

Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Background: Renal cell carcinoma (RCC) is a malignant tumor of urinary system, and clear cell RCC (ccRCC) is the major pathological subtype. A high-frequency mutation in SETD2 gene is related to the occurrence, development, and poor prognosis of RCC.

Objective: The research of immune-related genes (IRGs) is important to the success of immunotherapy in RCC. The aim of this study was to develop SETD2-related immune prognostic signature (IPS) potentially useful in the prognosis prediction of ccRCC.

Methods: The expression profile, mutation profile, and clinical data related to ccRCC were obtained from the TCGA (Cancer Genome Atlas) and cBioPortal databases. The data of IRGs were downloaded from the ImmPort database.

Results: An IPS with 5 genes (PDIA2, PAEP, AMELX, GREM2, and INHA) was constructed by analyzing the correlation between prognosis data and IRGs associated with ccRCC patients with wild type and mutant SETD2 genes. The clinical utility of the IPS and its relationship with immune microenvironment were also studied.

Conclusions: According to the results of this study, the IPS can be a promising biomarker of ccRCC to guide its prognosis and treatment.
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http://dx.doi.org/10.1097/MD.0000000000029561DOI Listing
August 2022

Overexpression of Protein Phosphatase 2 Regulatory Subunit B"Alpha Promotes Glycolysis by Regulating Hexokinase 1 in Hepatocellular Carcinoma.

Biomed Environ Sci 2022 Jul;35(7):622-632

Department of Organ Transplantation, The Third Medical Center of PLA General Hospital, Beijing 100039, China.

Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( ) and hexokinase 1 ( ) in glycolysis of hepatocellular carcinoma (HCC).

Methods: In HepG2 and Huh7 cells, expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The -related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of and . Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by .

Results: RNA sequencing data revealed that siRNA significantly downregulated the expression of . gene overexpression promotes, while gene silencing suppresses, the level of and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by overexpression in liver cancer cells.

Conclusion: Our findings showed the correlation of and in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of in cancer.
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http://dx.doi.org/10.3967/bes2022.082DOI Listing
July 2022

False-negative and false-positive outcomes of computer aided detection on brain metastasis: secondary analysis of a multicenter, multireader study.

Neuro Oncol 2022 Aug 9. Epub 2022 Aug 9.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center, for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Errors have seldom been evaluated in computer-aided detection on brain metastases. This study aimed to analyze false negatives (FNs) and false positives (FPs) generated by a brain metastasis detection system (BMDS) and by readers.

Methods: A deep learning-based BMDS was developed and prospectively validated in a multicenter, multireader study. Ad hoc secondary analysis was restricted to the prospective participants (148 with 1,066 brain metastases and 152 normal controls). Three trainees and three experienced radiologists read the MRI images without and with the BMDS. The number of FNs and FPs per patient, jackknife alternative free-response receiver operating characteristic figure of merit (FOM), and lesion features associated with FNs were analyzed for the BMDS and readers using binary logistic regression.

Results: The FNs, FPs, and the FOM of the stand-alone BMDS were 0.49, 0.38, and 0.97, respectively. Compared with independent reading, BMDS-assisted reading generated 79% fewer FNs (1.98 vs. 0.42, P <0.001); 41% more FPs (0.17 vs. 0.24, P <0.001) but 125% more FPs for trainees (P <0.001); and higher FOM (0.87 vs. 0.98, P <0.001). Lesions with small size, greater number, irregular shape, lower signal intensity, and located on non-brain surface were associated with FNs for readers. Small, irregular, and necrotic lesions were more frequently found in FNs for BMDS. The FPs mainly resulted from small blood vessels for the BMDS and the readers.

Conclusions: Despite the improvement detection performance, attention should be paid to FPs and small lesions with lower enhancement for radiologists, especially for less-experienced radiologists.
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http://dx.doi.org/10.1093/neuonc/noac192DOI Listing
August 2022

Role of the rhizosphere of a flooding-tolerant herb in promoting mercury methylation in water-level fluctuation zones.

J Environ Sci (China) 2022 Sep 20;119:139-151. Epub 2022 May 20.

Interdisciplinary Research Center for Agriculture Green Development in Yangtze River Basin, College of Resources and Environment, Southwest University, Chongqing 400715, China. Electronic address:

The water-level fluctuation zone (WLFZ) has been considered as a hotspot for mercury (Hg) methylation. Flooding-tolerant herbs are gradually acclimated to this water-land ecotone, tending to form substantial root systems for improving erosion resistance. Accompanying rhizosphere microzone plays crucial but unclear roles in methylmercury (MeHg) formation in the WLFZ. Thus, we conducted this study in the WLFZ of the Three Gorges Reservoir, to explore effects of the rhizosphere of a dominant flooding-tolerant herb (bermudagrass) on MeHg production. The elevated Hg and MeHg in rhizosphere soils suggest that the rhizosphere environment provides favorable conditions for Hg accumulation and methylation. The increased bioavailable Hg and microbial activity in the rhizosphere probably serve as important factors driving MeHg formation in the presence of bermudagrass. Simultaneously, the rhizosphere environments changed the richness, diversity, and distribution of hgcA-containing microorganisms. Here, a typical iron-reducing bacterium (Geobacteraceae) has been screened, however, the majority of hgcA genes detected in rhizosphere, near-, and non-rhizosphere soils of the WLFZ were unclassified. Collectively, these results provide new insights into the elevated MeHg production as related to microbial processes in the rhizosphere of perennial herbs in the WLFZ, with general implications for Hg cycling in other ecosystems with water-level fluctuations.
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http://dx.doi.org/10.1016/j.jes.2022.05.008DOI Listing
September 2022

Distribution of mercury and methylmercury in river water and sediment of typical manganese mining area.

J Environ Sci (China) 2022 Sep 29;119:11-22. Epub 2021 Dec 29.

College of Resources and Environment, Southwest University, Chongqing 400715, China. Electronic address:

Manganese (Mn) ores contain substantial concentrations of mercury (Hg), and mining and smelting of Mn ores can bring Hg into the surrounding aquatic environment through atmospheric deposition, leaching of electrolytic Mn residue and Mn gangue dump. However, limited is known that how these processes influence the environmental behaviors of Hg in waterbody. Therefore, the seasonal distribution and existing form of Hg in water and sediment in one Mn ore area in Xiushan County, Chongqing were investigated. Our results showed that the mean Hg and methylmercury (MeHg) concentrations in water (n=35) were 5.8 ± 4.6 ng/L and 0.22 ± 0.14 ng/L, respectively. The mean Hg concentrations in retained riverbed and fluvial bank sediment (n=35) were 0.74 ± 0.26 mg/kg and 0.63 ± 0.27 mg/kg, respectively (the mean MeHg concentrations were 0.64 ± 0.40 µg/kg and 0.51 ± 0.30 µg/kg, respectively). It indicated that the mining and smelting of Mn ores were the main sources of anthropogenic Hg, and Mn may inhibit Hg methylation in rivers in Mn ore areas. Mercury in the bound to iron/ Mn (Fe/Mn) oxides of low crystallinity fraction (Hg-OX) accounted for 4.01% and 5.25% of the total Hg concentrations in the retained riverbed and fluvial bank sediment, respectively. The amount of Hg bound to Fe/Mn oxides in sediment increased significantly due to the manganese mining activities in the investigated area. Therefore, it could be hypothesized that high Hg concentrations in river sediment in Mn mining areas are closely related to high Mn concentration in sediment.
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http://dx.doi.org/10.1016/j.jes.2021.12.011DOI Listing
September 2022

Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity.

Cell Syst 2022 Jul 8. Epub 2022 Jul 8.

The Systems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, 141 52 Stockholm, Sweden; Manipal Institute of Virology (MIV), Manipal Academy of Higher Education, Manipal, 576104 Karnataka, India. Electronic address:

The clinical outcome and disease severity in coronavirus disease 2019 (COVID-19) are heterogeneous, and the progression or fatality of the disease cannot be explained by a single factor like age or comorbidities. In this study, we used system-wide network-based system biology analysis using whole blood RNA sequencing, immunophenotyping by flow cytometry, plasma metabolomics, and single-cell-type metabolomics of monocytes to identify the potential determinants of COVID-19 severity at personalized and group levels. Digital cell quantification and immunophenotyping of the mononuclear phagocytes indicated a substantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and personalized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as α-ketoglutarate, succinate, malate, and butyrate could play a crucial role in COVID-19 severity. Metabolic perturbations targeting the central metabolic pathway (TCA cycle) can be an alternate treatment strategy in severe COVID-19.
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http://dx.doi.org/10.1016/j.cels.2022.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263811PMC
July 2022

Alfalfa-grass mixtures reduce greenhouse gas emissions and net global warming potential while maintaining yield advantages over monocultures.

Sci Total Environ 2022 Aug 1:157765. Epub 2022 Aug 1.

State Key Laboratory of Grassland Agroecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China. Electronic address:

Improving forage productivity with lower greenhouse gas (GHG) emissions from limited grassland has been a hotspot of interest in global agricultural production. In this study, we analyzed the effects of grasses (tall fescue, smooth bromegrass), legume (alfalfa), and alfalfa-grass (alfalfa + smooth bromegrass and alfalfa + tall fescue) mixtures on GHG emissions, net global warming potential (Net GWP), yield-based greenhouse gas intensity (GHGI), soil chemical properties and forage productivity in cultivated grassland in northwest China during 2020-2021. Our results demonstrated that alfalfa-grass mixtures significantly improved forage productivity. The highest total dry matter yield (DMY) during 2020 and 2021 was obtained from alfalfa-tall fescue (11,311 and 13,338 kg ha) and alfalfa-smooth bromegrass mixtures (10,781 and 12,467 kg ha). The annual cumulative GHG emissions from mixtures were lower than alfalfa monoculture. Alfalfa-grass mixtures significantly reduced GHGI compared with the grass or alfalfa monocultures. Furthermore, results indicated that grass, alfalfa and alfalfa-grass mixtures differentially affected soil chemical properties. Lower soil pH and C/N ratio were recorded in alfalfa monoculture. Alfalfa and mixtures increased soil organic carbon (SOC) and soil total nitrogen (STN) contents. Importantly, alfalfa-grass mixtures are necessary for improving forage productivity and mitigating the GHG emissions in this region. In conclusion, the alfalfa-tall fescue mixture lowered net GWP and GHGI in cultivated grassland while maintaining high forage productivity. These advanced agricultural practices could contribute to the development of climate-sustainable grassland production in China.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157765DOI Listing
August 2022

TFIIB-related factor 1 is a nucleolar protein that promotes RNA polymerase I-directed transcription and tumour cell growth.

Hum Mol Genet 2022 Aug 4. Epub 2022 Aug 4.

School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan, 430081, China.

Eukaryotic RNA polymerase I (Pol I) products play fundamental roles in ribosomal assembly, protein synthesis, metabolism and cell growth. Abnormal expression of both Pol I transcription-related factors and Pol I products causes a range of diseases, including ribosomopathies and cancers. However, the factors and mechanisms governing Pol I-dependent transcription remain to be elucidated. Here, we report that transcription factor IIB-related factor 1 (BRF1), a subunit of transcription factor IIIB required for RNA polymerase III (Pol III)-mediated transcription, is a nucleolar protein and modulates Pol I-mediated transcription. We showed that BRF1 can be localized to the nucleolus in several human cell types. BRF1 expression correlates positively with Pol I product levels and tumour cell growth in vitro and in vivo. Pol III transcription inhibition assays confirmed that BRF1 modulates Pol I-directed transcription in an independent manner rather than through a Pol III product-to-45S pre-rRNA feedback mode. Mechanistically, BRF1 binds to the Pol I transcription machinery components and can be recruited to the rDNA promoter along with them. Additionally, alteration of BRF1 expression affects the recruitment of Pol I transcription machinery components to the rDNA promoter and the expression of TBP and TAF1A. These findings indicate that BRF1 modulates Pol I-directed transcription by controlling the expression of selective factor 1 subunits. In summary, we identified a novel role of BRF1 in Pol I-directed transcription, suggesting that BRF1 can independently regulate both Pol I- and Pol III-mediated transcription and act as a key coordinator of Pol I and Pol III.
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http://dx.doi.org/10.1093/hmg/ddac152DOI Listing
August 2022

A Questionnaire-Based Ensemble Learning Model to Predict the Diagnosis of Vertigo: Model Development and Validation Study.

J Med Internet Res 2022 Aug 3;24(8):e34126. Epub 2022 Aug 3.

Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Background: Questionnaires have been used in the past 2 decades to predict the diagnosis of vertigo and assist clinical decision-making. A questionnaire-based machine learning model is expected to improve the efficiency of diagnosis of vestibular disorders.

Objective: This study aims to develop and validate a questionnaire-based machine learning model that predicts the diagnosis of vertigo.

Methods: In this multicenter prospective study, patients presenting with vertigo entered a consecutive cohort at their first visit to the ENT and vertigo clinics of 7 tertiary referral centers from August 2019 to March 2021, with a follow-up period of 2 months. All participants completed a diagnostic questionnaire after eligibility screening. Patients who received only 1 final diagnosis by their treating specialists for their primary complaint were included in model development and validation. The data of patients enrolled before February 1, 2021 were used for modeling and cross-validation, while patients enrolled afterward entered external validation.

Results: A total of 1693 patients were enrolled, with a response rate of 96.2% (1693/1760). The median age was 51 (IQR 38-61) years, with 991 (58.5%) females; 1041 (61.5%) patients received the final diagnosis during the study period. Among them, 928 (54.8%) patients were included in model development and validation, and 113 (6.7%) patients who enrolled later were used as a test set for external validation. They were classified into 5 diagnostic categories. We compared 9 candidate machine learning methods, and the recalibrated model of light gradient boosting machine achieved the best performance, with an area under the curve of 0.937 (95% CI 0.917-0.962) in cross-validation and 0.954 (95% CI 0.944-0.967) in external validation.

Conclusions: The questionnaire-based light gradient boosting machine was able to predict common vestibular disorders and assist decision-making in ENT and vertigo clinics. Further studies with a larger sample size and the participation of neurologists will help assess the generalization and robustness of this machine learning method.
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http://dx.doi.org/10.2196/34126DOI Listing
August 2022

Changes in Rat Scleral Collagen Structure Induced by UVA-Riboflavin Crosslinking at Various Tissue Depths in Whole Globe Versus Scleral Patch.

Transl Vis Sci Technol 2022 Aug;11(8)

Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.

Purpose: To investigate structural changes in scleral collagen fibers at various tissue depths before and after photosensitized crosslinking (CXL) both isolated scleral patch versus whole globe using second-harmonic generation (SHG) imaging.

Methods: Scleral tissues were harvested from Sprague-Dawley rats and separated into three groups: untreated sclera (control), full-thickness scleral patch for CXL (Free Scleral CXL group), and sclera in intact globe for CXL (Globe CXL group). The CXL groups were soaked in 0.1% riboflavin and irradiated with 365 nm ultraviolet-A light (power, 0.45 mW/cm2) for 30 minutes. SHG images were acquired every 5 µm between 10 and 60 µm from the outer scleral surface. Collagen fiber waviness was calculated as the ratio of the total length of a traced fiber and the length of a straight path between the fiber ends.

Results: In the Free Scleral CXL group, collagen waviness was significantly increased compared to the control group at 35 to 50 µm (P < 0.05). In the Globe CXL group, collagen waviness was decreased compared to control at all depths with statistical significance (P < 0.05) achieved from 10 to 45 µm.

Conclusions: Depending upon its initial state (i.e., free scleral patch versus mechanically loaded intact globe under pressure), collagen may experience different structural changes after CXL. In addition, the extent of the CXL effects may vary at different depths away from the surface.

Translational Relevance: Understanding the CXL effects on collagen structure may be important in optimizing the scleral crosslinking protocol for future clinical applications such as preventing myopic progression.
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http://dx.doi.org/10.1167/tvst.11.8.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351595PMC
August 2022

A Knowledge-Based Discovery Approach Couples Artificial Neural Networks With Weight Engineering to Uncover Immune-Related Processes Underpinning Clinical Traits of Breast Cancer.

Front Immunol 2022 14;13:920669. Epub 2022 Jul 14.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.

Immune-related processes are important in underpinning the properties of clinical traits such as prognosis and drug response in cancer. The possibility to extract knowledge learned by artificial neural networks (ANNs) from omics data to explain cancer clinical traits is a very attractive subject for novel discovery. Recent studies using a version of ANNs called autoencoders revealed their capability to store biologically meaningful information indicating that autoencoders can be utilized as knowledge discovery platforms aside from their initial assigned use for dimensionality reduction. Here, we devise an innovative weight engineering approach and ANN platform called artificial neural network encoder (ANNE) using an autoencoder and apply it to a breast cancer dataset to extract knowledge learned by the autoencoder model that explains clinical traits. Intriguingly, the extracted biological knowledge in the form of gene-gene associations from ANNE shows immune-related components such as chemokines, carbonic anhydrase, and iron metabolism that modulate immune-related processes and the tumor microenvironment play important roles in underpinning breast cancer clinical traits. Our work shows that biological "knowledge" learned by an ANN model is indeed encoded as weights throughout its neuronal connections, and it is possible to extract learned knowledge a novel weight engineering approach to uncover important biological insights.
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http://dx.doi.org/10.3389/fimmu.2022.920669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330471PMC
August 2022

The potential mechanism of Longsheyangquan Decoction on the treatment of bladder cancer: Systemic network pharmacology and molecular docking.

Front Pharmacol 2022 14;13:932039. Epub 2022 Jul 14.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Our goal was to explore the bioactive constituents of Longsheyangquan (LSYQ) Decoction and elucidate its mechanisms on the treatment of bladder cancer (BCa). A total of 38 compounds were selected based on their pharmacokinetic properties in three large traditional Chinese medicine (TCM) databases. 654 putative targets of LSYQ Decoction were predicted using a structure-based, reverse-docking algorithm online, of which 343 overlapped with BCa-related protein-coding genes. The protein-protein interaction (PPI) network was constructed to perform module analysis for further Gene Ontology (GO) annotations and Kyoto Encyclopedia Genes and Genomes (KEGG) pathway enrichment analysis, which identified and as hub targets. The TCM-compound-target network and compound-target-pathway network together revealed that quercetin, diosmetin, enhydrin and luteolin were the main components of LSYQ Decoction. Finally, molecular docking showed the affinity between the key compounds and the hub target proteins to verify the accuracy of drug target prediction in the first place. The present study deciphered the core components and targets of LSYQ Decoction on the treatment of BCa in a comprehensive systemic pharmacological manner.
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http://dx.doi.org/10.3389/fphar.2022.932039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330057PMC
July 2022

Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice.

Signal Transduct Target Ther 2022 Aug 1;7(1):259. Epub 2022 Aug 1.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

Angiotensin-converting enzyme 2 (ACE2) has proven beneficial in attenuating diabetic cardiomyopathy (DCM) but has been found to be a substrate of a disintegrin and metalloprotease protein-17 (ADAM17). However, whether ADAM17 plays a role in the pathogenesis and intervention of DCM is obscure. In this study, we created cardiomyocyte-specific knockout of ADAM17 (A17) mice, and left ventricular dimension, function, pathology and molecular biology were assessed in ADAM17 control, A17 control, ADAM17 diabetic and A17 diabetic mice. Both differentiated H9c2 cells and neonatal rat cardiomyocytes (NRCMs) were used to explore the molecular mechanisms underlying the effect of ADAM17 on DCM. The results showed that protein expression and activity of ADAM17 were upregulated whereas the protein expression of ACE2 was downregulated in the myocardium of diabetic mice. Cardiomyocyte-specific knockout of ADAM17 mitigated cardiac fibrosis and cardiomyocyte apoptosis and ameliorated cardiac dysfunction in mice with DCM. Bioinformatic analyses detected a number of genes enriched in metabolic pathways, in particular the AMPK signaling pathway, expressed differentially between the hearts of A17 and ADAM17 diabetic mice. The mechanism may involve activated AMPK pathway, increased autophagosome formation and improved autophagic flux, which reduced the apoptotic response in cardiomyocytes. In addition, hypoxia-inducible factor-1α (HIF-1α) might act as an upstream mediator of upregulated ADAM17 and ADAM17 might affect AMPK signaling via α1 A-adrenergic receptor (ADRA1A). These results indicated that ADAM17 activity and ACE2 shedding were enhanced in DCM, which was reversed by cardiomyocyte-specific ADAM17 knockout. Thus, inhibition of ADAM17 may provide a promising approach to the treatment of DCM.
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http://dx.doi.org/10.1038/s41392-022-01054-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339545PMC
August 2022

Toxic Effect of Combined Exposure of Microplastics and Copper on Goldfish (Carassius auratus): Insight from Oxidative Stress, Inflammation, Apoptosis and Autophagy in Hepatopancreas and Intestine.

Bull Environ Contam Toxicol 2022 Jul 31. Epub 2022 Jul 31.

College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.

The enhancement of the toxic effect of microplastics (MPs) on heavy metals and its mechanism needs more in-depth and systematic research. In this study, the copper (Cu) accumulation, histological injury, and expression of genes involved in oxidative stress, inflammation, apoptosis, and autophagy of goldfish after single or combined exposure of MPs (1 mg/L) and Cu (0.1 mg/L) for 7 days were determined. The results demonstrated that MPs enhanced the Cu accumulation in hepatopancreas and intestine of goldfish and induced more severe oxidative stress in the hepatopancreas and intestine of goldfish. Additionally, combined exposure of MPs and Cu induced inflammation, excessive apoptosis and insufficient autophagy in the hepatopancreas. Contrary, the inflammation and apoptosis were depressed in the intestine after combined exposure of MPs and Cu, which still requires further exploration. Hence, these findings provide further evidence for the threat of MPs and its adsorbed heavy metals.
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http://dx.doi.org/10.1007/s00128-022-03585-5DOI Listing
July 2022

Impacts of Forest Fire Ash on Aquatic Mercury Cycling.

Environ Sci Technol 2022 Jul 29. Epub 2022 Jul 29.

College of Environmental Science, Sichuan Agricultural University, Chengdu 611130, China.

Mercury (Hg) is a ubiquitous contaminant in the environment and its methylated form, methylmercury (MeHg), poses a worldwide health concern for humans and wildlife, primarily through fish consumption. Global production of forest fire ash, derived from wildfires and prescribed burns, is rapidly increasing due to a warming climate, but their interactions with aqueous and sedimentary Hg are poorly understood. Herein, we compared the differences of wildfire ash with activated carbon and biochar on the sorption of aqueous inorganic Hg and sedimentary Hg methylation. Sorption of aqueous inorganic Hg was greatest for wildfire ash materials (up to 0.21 μg g or 2.2 μg g C) among all of the solid sorbents evaluated. A similar Hg adsorption mechanism for activated carbon, biochar made of walnut, and wildfire ash was found that involves the formation of complexes between Hg and oxygen-containing functional groups, especially the -COO group. Notably, increasing dissolved organic matter from 2.4 to 70 mg C L remarkably reduced Hg sorption (up to 40% reduction) and increased the time required to reach Hg-sorbent pseudo-equilibrium. Surprisingly, biochar and wildfire ash, but not activated carbon, stimulated MeHg production during anoxic sediment incubation, possibly due to the release of labile organic matter. Overall, our study indicates that while wildfire ash can sequester aqueous Hg, the leaching of its labile organic matter may promote production of toxic MeHg in anoxic sediments, which has an important implication for potential MeHg contamination in downstream aquatic ecosystems after wildfires.
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http://dx.doi.org/10.1021/acs.est.2c01591DOI Listing
July 2022

Proteomic and Metabolomic Characterization of SARS-CoV-2-Infected Cynomolgus Macaque at Early Stage.

Front Immunol 2022 12;13:954121. Epub 2022 Jul 12.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.

Although tremendous effort has been exerted to elucidate the pathogenesis of severe COVID-19 cases, the detailed mechanism of moderate cases, which accounts for 90% of all patients, remains unclear yet, partly limited by lacking the biopsy tissues. Here, we established the COVID-19 infection model in cynomolgus macaques (CMs), monitored the clinical and pathological features, and analyzed underlying pathogenic mechanisms at early infection stage by performing proteomic and metabolomic profiling of lung tissues and sera samples from COVID-19 CMs models. Our data demonstrated that innate immune response, neutrophile and platelet activation were mainly dysregulated in COVID-19 CMs. The symptom of neutrophilia, lymphopenia and massive "cytokines storm", main features of severe COVID-19 patients, were greatly weakened in most of the challenged CMs, which are more semblable as moderate patients. Thus, COVID-19 model in CMs is rational to understand the pathogenesis of moderate COVID-19 and may be a candidate model to assess the safety and efficacy of therapeutics and vaccines against SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fimmu.2022.954121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315341PMC
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

Resveratrol Attenuates Heat Stress-Induced Impairment of Meat Quality in Broilers by Regulating the Nrf2 Signaling Pathway.

Animals (Basel) 2022 Jul 25;12(15). Epub 2022 Jul 25.

Department of Animal Science, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.

Studies have indicated that dietary resveratrol (RES) improves the meat quality of broilers subjected to heat stress (HS), but the mechanism of action remains unclear. Therefore, the main purpose of this study was to investigate the effect of RES on meat quality, muscle antioxidant status, and its mechanism of action in broilers under HS. A total of 162 male AA broilers at 21 days old with similar weight were randomly assigned to 3 treatment groups with 6 replicates each. The control group (ambient temperature: 22 ± 1 °C) and HS group (ambient temperature: 33 ± 1 °C for 10 h a day from 8:00 to 18:00 and 22 ± 1 °C for the remaining time) were fed a basal diet and the HS + RES group was fed a basal diet with 400 mg/kg RES. The feeding was conducted for 21 continuous days. The results indicated that HS decreased final body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), breast and leg muscle yield, a*, pH, the activities of catalase (CAT), glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px), and mRNA levels of nuclear factor erythroid 2-related factor 2 (), heme oxygenase-1 (), NADPH quinone oxidoreductase 1 (), and ( < 0.05). HS also increased b*, L*, drip loss, malondialdehyde (MDA) content, and kelch-like epichlorohydrin-associated protein 1 () mRNA level ( < 0.05). Compared with the HS group, the HS + RES group exhibited a higher ADG, breast and leg muscle yield, a*, pH, activities of GST and GSH-Px, and mRNA levels of , and but had lower drip loss and Keap1 mRNA level ( < 0.05). RES can improve meat quality and the muscle antioxidant ability of heat-stressed broilers by activating the Nrf2 signaling pathway.
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http://dx.doi.org/10.3390/ani12151889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330235PMC
July 2022

Research Progress on the Preparation and Applications of Laser-Induced Graphene Technology.

Nanomaterials (Basel) 2022 Jul 7;12(14). Epub 2022 Jul 7.

School of Mechanical and Power Engineering, Nanjing Tech University, Nanjing 211816, China.

Graphene has been regarded as a potential application material in the field of new energy conversion and storage because of its unique two-dimensional structure and excellent physical and chemical properties. However, traditional graphene preparation methods are complicated in-process and difficult to form patterned structures. In recent years, laser-induced graphene (LIG) technology has received a large amount of attention from scholars and has a wide range of applications in supercapacitors, batteries, sensors, air filters, water treatment, etc. In this paper, we summarized a variety of preparation methods for graphene. The effects of laser processing parameters, laser type, precursor materials, and process atmosphere on the properties of the prepared LIG were reviewed. Then, two strategies for large-scale production of LIG were briefly described. We also discussed the wide applications of LIG in the fields of signal sensing, environmental protection, and energy storage. Finally, we briefly outlined the future trends of this research direction.
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http://dx.doi.org/10.3390/nano12142336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317010PMC
July 2022

Investigation on the Air Permeability and Pore Structure of Concrete Subjected to Carbonation under Compressive Stress.

Materials (Basel) 2022 Jul 7;15(14). Epub 2022 Jul 7.

State Key Laboratory of Green Building Materials, China Building Materials Academy, Beijing 100024, China.

Concrete structures have to withstand the combined effects of external load and environmental factors. Therefore, it is meaningful to study the durability of concrete under compression and carbonation. The air permeability coefficient () and pore structure of concrete under uniaxial compression and carbonation were measured by the Autoclam method and mercury intrusion porosimetry (MIP). The Autoclam test results showed that the concrete changed in a concave parabolic manner with the compressive stress level, and the inflection point of the stress level was 45%. The MIP results showed that the characteristic pore structural parameters (porosity, average pore diameter, median pore diameter by area, and median pore diameter by volume) first decreased and then increased with the stress level change. The change in concrete microstructure was a result of the combined effect of pore filling, decalcification, and densification, as well as the split effect. The key pore structural parameters affecting were confirmed using gray relational analysis (GRA). The top three parameters with the highest correlation with the carbonated concrete were porosity (gray relational grade = 0.789), median pore diameter by volume ( = 0.763), and proportion of transition pore volume ( = 0.827). Furthermore, the regression analysis showed a good linear relation between and the important pore structural parameters.
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http://dx.doi.org/10.3390/ma15144775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321981PMC
July 2022

Understanding of Hormonal Regulation in Rice Seed Germination.

Life (Basel) 2022 Jul 9;12(7). Epub 2022 Jul 9.

Liaoning Rice Research Institute, Shenyang 110115, China.

Seed germination is a critical stage during the life cycle of plants. It is well known that germination is regulated by a series of internal and external factors, especially plant hormones. In , many germination-related factors have been identified, while in rice, the important crop and monocot model species and the further molecular mechanisms and regulatory networks controlling germination still need to be elucidated. Hormonal signals, especially those of abscisic acid (ABA) and gibberellin (GA), play a dominant role in determining whether a seed germinates or not. The balance between the content and sensitivity of these two hormones is the key to the regulation of germination. In this review, we present the foundational knowledge of ABA and GA pathways obtained from germination research in . Then, we highlight the current advances in the identification of the regulatory genes involved in ABA- or GA-mediated germination in rice. Furthermore, other plant hormones regulate seed germination, most likely by participating in the ABA or GA pathways. Finally, the results from some regulatory layers, including transcription factors, post-transcriptional regulations, and reactive oxygen species, are also discussed. This review aims to summarize our current understanding of the complex molecular networks involving the key roles of plant hormones in regulating the seed germination of rice.
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http://dx.doi.org/10.3390/life12071021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324290PMC
July 2022

The Ethylene Response Factor ERF5 Regulates Anthocyanin Biosynthesis in 'Zijin' Mulberry Fruits by Interacting with and Genes.

Int J Mol Sci 2022 Jul 9;23(14). Epub 2022 Jul 9.

Academy of Agricultural Sciences, Industrial Crops Institute of Hubei, Wuhan 430064, China.

Ethylene promotes ripening in fruits as well as the biosynthesis of anthocyanins in plants. However, the question of which ethylene response factors (ERFs) interact with the genes along the anthocyanin biosynthesis pathway is yet to be answered. Herein, we conduct an integrated analysis of transcriptomes and metabolome on fruits of two mulberry genotypes ('Zijin', ZJ, and 'Dashi', DS, with high and low anthocyanin abundance, respectively) at different post-flowering stages. In total, 1035 upregulated genes were identified in ZJ and DS, including in the MBW complex and anthocyanin related genes such as . A KEGG analysis suggested that flavonoid biosynthesis and plant hormone signaling transduction pathways were significantly enriched in the upregulated gene list. In particular, among 103 genes, the expression of showed the most positive correlation with the anthocyanin change pattern across both genotypes and in the post-flowering stages, with a Pearson correlation coefficient (PCC) of 0.93. Electrophoresis mobility shift assay (EMSA) and luciferase assay suggested that ERF5 binds to the promoter regions of MYBA and F3H and transcriptionally activates their gene expression. We elucidated a potential mechanism by which ethylene enhances anthocyanin accumulation in mulberry fruits and highlighted the importance of the gene in controlling the anthocyanin content in mulberry species. This knowledge could be used for engineering purposes in future mulberry breeding programs.
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http://dx.doi.org/10.3390/ijms23147615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318412PMC
July 2022

Situs inversus totalis with local metastasis of gallbladder carcinoma and variation of the common hepatic artery.

BMC Gastroenterol 2022 Jul 26;22(1):357. Epub 2022 Jul 26.

Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Background: Situs inversus totalis (SIT) is a rare congenital anomaly characterized by a complete transposition of all the viscera. SIT cases were usually reported because of the presence of tumors, leading to false association between them. Therefore, any research that advances our understanding on SIT is highly required. This study firstly describes a very rare case of SIT with "jumping" metastasis to pancreas of gallbladder carcinoma.

Case Presentation: A 69-year-old female patient presented at our hospital with complaints of one month of epigastric pain was studied. She had not sought for treatment prior the visit. Imaging examinations of this patient revealed SIT and a variation of the common hepatic artery with concomitant tumors of gallbladder and pancreas. However, there was no evidence of distant metastases beyond the abdominal cavity. She underwent a combination of radical cholecystectomy, total pancreatectomy, splenectomy and hepatic artery-splenic artery reconstruction. Histological analyses revealed metastasis of the gallbladder carcinoma in to the pancreas. Although the patient opted against chemotherapy, she survived without tumor for 16 months following the surgery. A review of the current literature on association with SIT and tumor occurrence was presented.

Conclusions: It is a great surgical challenge for the resection of multicenter hepatobiliary and pancreatic tumors in such rare SIT anatomical abnormalities with vascular variants. A reliable surgical plan based on detailed preoperative imaging and intraoperative anatomical exploration is crucial to achieving radical resection.
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http://dx.doi.org/10.1186/s12876-022-02377-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327273PMC
July 2022

Dietary sea buckthorn polysaccharide reduced lipid accumulation, alleviated inflammation and oxidative stress, and normalized imbalance of intestinal microbiota that was induced by high-fat diet in zebrafish Danio rerio.

Fish Physiol Biochem 2022 Jul 25. Epub 2022 Jul 25.

College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.

The purpose of this study was to explore the beneficial effects of sea buckthorn polysaccharide (SP) on lipid metabolism, liver, and intestinal health in zebrafish fed with high-fat diet (HFD). The zebrafish were fed with regular diet (RD), HFD, and HFD supplemented with 2 g/kg (HFD_2SP) and 4 g/kg (HFD_4SP) of SP, respectively. Growth, serum biochemistry, histopathology, expression of genes involved in lipid metabolism, inflammation, oxidative stress and tight junction, and changes in intestinal microbiota were detected. Results showed that adding 2 and 4 g/kg of SP in the HFD significantly improved the survival rate of zebrafish; reduced the levels of serum triglyceride (TG), total cholesterol (TC), aspartate aminotransferase (AST), and alanine transaminase (ALT); and alleviated the lipid accumulation in the liver of zebrafish. Furthermore, SP significantly enhanced the antioxidant capacity of liver and intestine by up-regulating the expression of Nrf2 and Cu/Zn-SOD and alleviated liver and intestinal inflammation induced by HFD through up-regulating the expression of TGF-β1 and suppressing the expression of P38MAPK, IL-8, and IL-1β. Especially, dietary SP normalized intestinal microbiota imbalance caused by HFD and inhibited the proliferation of harmful bacteria, i.e., Mycobacterium, but promoted the proliferation of intestinal beneficial bacteria, i.e., Cetobacterium. In summary, 2 and 4 g/kg of dietary SP significantly reduced lipid accumulation, alleviated inflammation and oxidative stress, and normalized the imbalance of intestinal microbiota induced by HFD and consequently improved the survival rate of zebrafish.
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http://dx.doi.org/10.1007/s10695-022-01105-0DOI Listing
July 2022

Adenosine monophosphate deaminase modulates BIN2 activity through hydrogen peroxide-induced oligomerization.

Plant Cell 2022 Jul 25. Epub 2022 Jul 25.

Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.

The Arabidopsis thaliana GSK3-like kinase, BRASSINOSTEROID-INSENSITIVE2 (BIN2) is a key negative regulator of brassinosteroid (BR) signaling and a hub for crosstalk with other signaling pathways. However, the mechanisms controlling BIN2 activity are not well understood. Here we performed a forward genetic screen for resistance to the plant-specific GSK3 inhibitor bikinin and discovered that a mutation in the ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD)/EMBRYONIC FACTOR1 (FAC1) gene reduces the sensitivity of Arabidopsis seedlings to both bikinin and BRs. Further analyses showed that AMPD modulates BIN2 activity by regulating its oligomerization in a hydrogen peroxide (H2O2)-dependent manner. Exogenous H2O2 induced the formation of BIN2 oligomers with a decreased kinase activity and an increased sensitivity to bikinin. By contrast, AMPD activity inhibition reduces the cytosolic reactive oxygen species (ROS) levels and the amount of BIN2 oligomers, correlating with the decreased sensitivity of Arabidopsis plants to bikinin and BRs. Furthermore, we showed that BIN2 phosphorylates AMPD to possibly alter its function. Our results reveal the existence of a H2O2 homeostasis-mediated regulation loop between AMPD and BIN2 that fine-tunes the BIN2 kinase activity to control plant growth and development.
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http://dx.doi.org/10.1093/plcell/koac203DOI Listing
July 2022

Direct photolysis of diclofenac under simulated sunlight: Transformation pathway and biological concerns.

Chemosphere 2022 Jul 19:135775. Epub 2022 Jul 19.

Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai, 519087, China.

Topical diclofenac gels are frequently applied on human skin and, consequently are exposed to sunlight during outdoor activities. The degradation of diclofenac (DCF) with sunlight exposure is known to occur but the detailed transformation characteristics and biological concerns have not been comprehensively investigated. In the present work, the transformation products during diclofenac photolysis were identified with the aid of ultra-performance liquid chromatography coupled with triple time-of-flight mass spectrometry (UPLC-TripleTOF). Biological concerns, including microtoxicity, genotoxicity, cytotoxicity and antiestrogenicity were examined with multiple in-vitro bioassays. Spearman correlation analysis was conducted to obtain further insight into the contributions of photolysis products to overall biological concerns. The results demonstrated that diclofenac was readily degraded under sunlight to form five main photolysis products via substitution, dechlorination, dehydroxylation, homodimerization and heterodimerization. Products P1, P2 and P5 were reported previously, while two dimer products (P3 and P4) are innovative products and have not been found in prior studies. A significant elevation in the microtoxicity was found during the photolysis of diclofenac, resulting mainly from the carbazole-containing photolysis products P2, P3, P4 and P5. Genotoxicity and antiestrogenicity declined along with the reduction of diclofenac, indicating that no photolysis products were genotoxic or anti-estrogenic. Modest cytotoxicity to the human skin epidermis cell line was observed and attributed to the formation of intermediate species. This outcome highlighted the biological concerns of diclofenac to human health when exposed to sunlight.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135775DOI Listing
July 2022

Depicting Developing Trend and Core Knowledge of Primary Open-Angle Glaucoma: A Bibliometric and Visualized Analysis.

Front Med (Lausanne) 2022 5;9:922527. Epub 2022 Jul 5.

National Clinical Research Center for Geriatric Diseases, Xiangya Hospital of Central South University, Changsha, China.

Objective: The prevalence of glaucoma is rising due to an increasing aging population. Because of its insidious and irreversible nature, glaucoma has gradually become the focus of attention. We assessed primary open angle glaucoma, the most common type of glaucoma, to study its present status, global trend, and state of clinical research.

Methods: Publications from 2000 to 2021 in Web of Science database were retrieved and analyzed by bibliometrics. VOSviewer and Citespace were used for analysis.

Results: A total of 6,401 publications were included in this review, and we found that the number of publications increased from 139 in 2000 to 563 in 2021. American researchers have published the most papers and had the highest h-index and the most citations, while the has published the most papers on this topic. Some key researchers, contributing institutions, their partnerships, and scientific masterpieces were identified. The publications we reviewed fall into seven categories: publications on intraocular pressure, normal tension glaucoma, risk factors, the trabecular meshwork, optical coherence tomography, surgery, and mutation. Clear study hotspots were described, which began with epidemiology and transitioned to pathogenesis and diagnosis and then to treatment.

Conclusion: Studies on primary open angle glaucoma extend well beyond ophthalmology to biochemistry molecular biology, general internal medicine, pharmacology, pharmacy, science technology, and other areas. Interest, research and publications on primary open angle glaucoma are on the rise.
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http://dx.doi.org/10.3389/fmed.2022.922527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294470PMC
July 2022
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