Publications by authors named "Chen Yang"

4,251 Publications

  • Page 1 of 1

SC2sepsis: sepsis single-cell whole gene expression database.

Database (Oxford) 2022 Aug;2022

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No.197 Ruijin Er Road, Shanghai CN 200025, China.

Sepsis, one of the major challenges in the intensive care unit, is characterized by complex host immune status. Improved understandings of the phenotypic changes of immune cells during sepsis and the driving molecular mechanisms are critical to the elucidation of sepsis pathogenesis. Single-cell RNA sequencing (scRNA-seq), which interprets transcriptome at a single-cell resolution, serves as a useful tool to uncover disease-related gene expression signatures of different cell populations in various diseases. It has also been applied to studies on sepsis immunopathological mechanisms. Due to the fact that most sepsis-related studies utilizing scRNA-seq have very small sample sizes and there is a lack of an scRNA-seq database for sepsis, we developed Sepsis Single-cell Whole Gene Expression Database Website (SC2sepsis) (http://www.rjh-sc2sepsis.com/), integrating scRNA-seq datasets of human peripheral blood mononuclear cells from 45 septic patients and 26 healthy controls, with a total amount of 232 226 cells. SC2sepsis is a comprehensive resource database with two major features: (i) retrieval of 1988 differentially expressed genes between pathological and healthy conditions and (ii) automatic cell-type annotation, which is expected to facilitate researchers to gain more insights into the immune dysregulation of sepsis.

Database Url: http://www.rjh-sc2sepsis.com/.
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http://dx.doi.org/10.1093/database/baac061DOI Listing
August 2022

Prostate-specific membrane antigen targeted, glutathione-sensitive nanoparticles loaded with docetaxel and enzalutamide for the delivery to prostate cancer.

Drug Deliv 2022 Dec;29(1):2705-2712

Department of Pharmacy, Wuxi Mental Health Center, Wuxi214000, Jiangsu Province, China.

Prostate cancer (PCa) is the most common malignant tumor in men. Chemotherapy with docetaxel (DTX) and novel hormonal agents such as enzalutamide (EZL) and abiraterone are the preferred first-line therapeutic regimens. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of PCa cells. This study aimed to prepare a PSMA targeted (Glutamate-Urea-Lysine, GUL ligand modified), glutathione (GSH)-sensitive (Cystamine, SS), DTX and EZL co-loaded nanoparticles (GUL-SS DTX/EZL-NPs) to treat PCa. Polyethylene glycol (PEG) was conjugated with oleic acid (OA) using a GSH-sensitive ligand: cystamine (PEG-SS-OA). GUL was covalently coupled to PEG-SS-OA to achieve GUL-PEG-SS-OA. GUL-PEG-SS-OA was used to prepare GUL-SS DTX/EZL-NPs. To evaluate the and efficiency of the system, human prostate cancer cell lines and PCa cells bearing mice were applied. Single drug-loaded nanoparticle and free drugs systems were utilized for the comparison of the anticancer ability. GUL-SS DTX/EZL-NPs showed a size of 143.7 ± 4.1 nm, with a PDI of 0.162 ± 0.037 and a zeta potential of +29.1 ± 2.4 mV. GUL-SS DTX/EZL-NPs showed high cancer cell uptake of about 70%, as well as higher cell growth inhibition efficiency (a maximum 79% of cells were inhibited after treatment) than single drug-loaded NPs and free drugs. GUL-SS DTX/EZL-NPs showed the most prominent tumor inhibition ability and less systemic toxicity. The novel GUL-SS DTX/EZL-NPs could be used as a promising system for PCa therapy.
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http://dx.doi.org/10.1080/10717544.2022.2110998DOI Listing
December 2022

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study.

Front Cell Infect Microbiol 2022 1;12:925982. Epub 2022 Aug 1.

Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Naval Medical University, Shanghai, China.

This study aimed to obtain further in-depth information on the value of metagenomic next-generation sequencing (mNGS) for diagnosing pulmonary aspergillosis in non-neutropenic patients. We did a retrospective study, in which 33 non-neutropenic patients were included, of which 12 were patients with pulmonary aspergillosis and 21 were diagnosed with non-pulmonary aspergillosis. Fungi and all other co-pathogens in bronchoalveolar lavage fluid (BALF) (27 cases), blood (6 cases), and/or pleural fluid (1 case) samples were analyzed using mNGS. One of the patients submitted both BALF and blood samples. We analyzed the clinical characteristics, laboratory tests, and radiologic features of pulmonary aspergillosis patients and compared the diagnostic accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value of mNGS with conventional etiological methods and serum (1,3)-β-D-glucan. We also explored the efficacy of mNGS in detecting mixed infections and co-pathogens. We further reviewed modifications of antimicrobial therapy for patients with pulmonary aspergillosis according to the mNGS results. Finally, we compared the detection of in BALF and blood samples from three patients using mNGS. In non-neutropenic patients, immunocompromised conditions of non-pulmonary aspergillosis were far less prevalent than in patients with pulmonary aspergillosis. More patients with pulmonary aspergillosis received long-term systemic corticosteroids (50% vs. 14.3%, p < 0.05). Additionally, mNGS managed to reach a sensitivity of 91.7% for diagnosing pulmonary aspergillosis, which was significantly higher than that of conventional etiological methods (33.3%) and serum (1,3)-β-D-glucan (33.3%). In addition, mNGS showed superior performance in discovering co-pathogens (84.6%) of pulmonary aspergillosis; bacteria, bacteria-fungi, and bacteria-PJP-virus were most commonly observed in non-neutropenic patients. Moreover, mNGS results can help guide effective treatments. According to the mNGS results, antimicrobial therapy was altered in 91.7% of patients with pulmonary aspergillosis. The diagnosis of detected in blood samples, which can be used as a supplement to BALF samples, seemed to show a higher specificity than that in BALF samples. mNGS is a useful and effective method for the diagnosis of pulmonary aspergillosis in non-neutropenic patients, detection of co-pathogens, and adjustment of antimicrobial treatment.
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http://dx.doi.org/10.3389/fcimb.2022.925982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376315PMC
August 2022

Intraneuronal sortilin aggregation relative to granulovacuolar degeneration, tau pathogenesis and sorfra plaque formation in human hippocampal formation.

Front Aging Neurosci 2022 1;14:926904. Epub 2022 Aug 1.

Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, China.

Extracellular β-amyloid (Aβ) deposition and intraneuronal phosphorylated-tau (pTau) accumulation are the hallmark lesions of Alzheimer's disease (AD). Recently, "sorfra" plaques, named for the extracellular deposition of tilin c-terminal gments, are reported as a new AD-related proteopathy, which develop in the human cerebrum resembling the spatiotemporal trajectory of tauopathy. Here, we identified intraneuronal sortilin aggregation as a change related to the development of granulovacuolar degeneration (GVD), tauopathy, and sorfra plaques in the human hippocampal formation. Intraneuronal sortilin aggregation occurred as cytoplasmic inclusions among the pyramidal neurons, co-labeled by antibodies to the extracellular domain and intracellular C-terminal of sortilin. They existed infrequently in the brains of adults, while their density as quantified in the subiculum/CA1 areas increased in the brains from elderly lacking Aβ/pTau, with pTau (i.e., primary age-related tauopathy, PART cases), and with Aβ/pTau (probably/definitive AD, pAD/AD cases) pathologies. In PART and pAD/AD cases, the intraneuronal sortilin aggregates colocalized partially with various GVD markers including casein kinase 1 delta (Ck1δ) and charged multivesicular body protein 2B (CHMP2B). Single-cell densitometry established an inverse correlation between sortilin immunoreactivity and that of Ck1δ, CHMP2B, p62, and pTau among pyramidal neurons. In pAD/AD cases, the sortilin aggregates were reduced in density as moving from the subiculum to CA subregions, wherein sorfra plaques became fewer and absent. Taken together, we consider intraneuronal sortilin aggregation an aging/stress-related change implicating protein sorting deficit, which can activate protein clearance responses including enhanced phosphorylation and hydrolysis, thereby promoting GVD, sorfra, and Tau pathogenesis, and ultimately, neuronal destruction and death.
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http://dx.doi.org/10.3389/fnagi.2022.926904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376392PMC
August 2022

Characterization of Pleurotus citrinopileatus hydrolysates obtained from Actinomucor elegans proteases compared with that by commercial proteases.

J Food Sci 2022 Aug 17. Epub 2022 Aug 17.

Shandong Tianbo Food Inredients Co., LTD, Jining, China.

Pleurotus citrinopileatus, a nutritious and palatable edible mushroom, can be used as an appropriate material to prepare high-grade flavoring agents. Based on this, the current study aimed to investigate the feasibility of a productive protease system from Actinomucor elegans to prepare P. citrinopileatus hydrolysate (PCH). The Actinomucor elegans crude protease (AECP) was prepared from the solid-state fermentation product of P. citrinopileatus by A. elegans. AECP and four commercial proteases (alcalase, neutrase, papain, and protamex) were applied to acquire five kinds of PCHs. The physical-chemical properties of PCHs as well as its concentration and composition of nonvolatile compounds were comparatively analyzed. Sensory evaluation and electronic tongue analysis were utilized to evaluate sensory characteristics. AECP was found to be the most effective protease, with the highest hydrolysis degree (35.91%) and protein recovery (81.46%). The result of molecular weight distribution indicated that peptides below 500 Da were the main fraction of AECP hydrolysates, while AECP hydrolysates showed the highest content of monosodium glutamate-like (20.23 ± 0.16 mg/g) and flavor 5'-nucleotide (4.30 ± 0.07 mg/g) peptides. In summary, the AECP hydrolysate had superior sensory profiles compared with other hydrolysates. In addition, AECP hydrolysates exhibited favorable kokumi taste in which peptides below 500 Da showed the highest correlation with kokumi by the results of partial least-squares regression. These results indicated the feasibility of applying PCHs as flavor additives or seasoning in the food industry. AECP might be used as an alternative enzyme choice because of its low cost and high hydrolysis efficiency. PRACTICAL APPLICATION: Pleurotus citrinopileatus served as a potential raw material for natural seasonings because of its high protein content and appropriate ratio of umami amino acids to total amino acids. Enzymatic hydrolysis was an efficient approach to improve the flavor of P. citrinopileatus, where the choice of enzyme was one of the most critical factors. The research indicated that P. citrinopileatus hydrolysate prepared by A. elegans crude protease (AECP) exhibited an acceptable flavor, which provided theoretical support for the high-value utilization of P. citrinopileatus as food seasoning. AECP might be applied as an alternative enzyme resource because of its low cost and high hydrolysis efficiency.
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http://dx.doi.org/10.1111/1750-3841.16256DOI Listing
August 2022

Reconstructing distant interactions of multiple paths between perceptible nodes in dark networks.

Phys Rev E 2022 Jul;106(1-1):014302

School of Science, Beijing University of Posts and Telecommunications, Beijing 100876, China.

Quantitative research of interdisciplinary fields, including biological and social systems, has attracted great attention in recent years. Complex networks are popular and important tools for the investigations. Explosively increasing data are created by practical networks, from which useful information about dynamic networks can be extracted. From data to network structure, i.e., network reconstruction, is a crucial task. There are many difficulties in fulfilling network reconstruction, including data shortage (existence of hidden nodes) and time delay for signal propagation between adjacent nodes. In this paper a deep network reconstruction method is proposed, which can work in the conditions that even only two nodes (say A and B) are perceptible and all other network nodes are hidden. With a well-designed stochastic driving on node A, this method can reconstruct multiple interaction paths from A to B based on measured data. The distance, effective intensity, and transmission time delay of each path can be inferred accurately.
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http://dx.doi.org/10.1103/PhysRevE.106.014302DOI Listing
July 2022

ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage.

Signal Transduct Target Ther 2022 Aug 15;7(1):288. Epub 2022 Aug 15.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, 100700, Beijing, China.

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using multi-omics, arachidonic acid 15-lipoxygenase-1 (ALOX15) was identified as the primary mediator of ischemia-provoked phospholipid peroxidation, which was further confirmed using chemogenetic approaches. Collectively, our results reveal that ALOX15 induction in the ischemia phase acts as a "burning point" to ignite phospholipid oxidization into ferroptotic signals. This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of I/R injury.
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http://dx.doi.org/10.1038/s41392-022-01090-zDOI Listing
August 2022

Sensitive detection and intracellular imaging of free copper ions based on DNA-templated silver nanoclusters aggregation-inducing fluorescence enhancement effect.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Aug 10;283:121734. Epub 2022 Aug 10.

Key Laboratory for Analytical Science of Food Safety and Biology of MOE, Fujian Provincial Key Lab of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China. Electronic address:

Free copper ions (Cu and Cu) have critical toxicity to cells, although copper is an essential element for human body. Hence, sensitive monitoring is crucial to avoid over intake of Cu/Cu. We herein designed a ssDNA sequence (A) for synthetizing A-templated silver nanoclusters (AgNCs), and demonstrated that Cu/Cu can induce the aggregation of A-templated AgNCs and thus greatly enhanced the fluorescence emission of A-templated AgNCs. Based on Cu/Cu-induced fluorescence enhancement effect of A-templated AgNCs, a label-free and signal-on fluorescent sensing platform was developed for the specific and sensitive detection of Cu/Cu in biological samples and intracellular imaging of Cu/Cu in cells. The signal-on fluorescent sensing platform could be used to rapidly detect Cu and Cu with a detection limit of 0.1 µM within 30 min., and to perform the intracellular imaging of Cu and Cu in cells with good cell permeability and biocompatibility. By using the signal-on fluorescent sensing platform, we have successfully detected Cu and Cu in cells fluids and human serum with a recovery of 90-104% and a RSD (n = 5) < 5%, and performed the imaging of Cu/Cu in Hela cells. The developed fluorescent sensing platform has obvious analytical and imaging advantages such as signal-on, simple operation, short analysis time, both Cu and Cu detection, similar or higher sensitivity, good cell permeability and biocompatibility, which promising a reliable approach for the rapid and on-site detection or imaging of free copper ions in biological samples in clinical diagnosis.
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http://dx.doi.org/10.1016/j.saa.2022.121734DOI Listing
August 2022

Clinical outcomes and potential therapies prediction of subgroups based on a ferroptosis-related long non-coding RNA signature for gastric cancer.

Aging (Albany NY) 2022 Aug 14;14(undefined). Epub 2022 Aug 14.

Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Gastric cancer (GC) is one of the most aggressive malignant tumors worldwide. Ferroptosis is a kind of iron-dependent cell death, which is proved to be closely related to tumor progression. In this study, we aim at constructing a ferroptosis-related lncRNAs signature to predict the prognosis of GC and explore potential therapies.

Methods: Ferroptosis-Related LncRNAs Signature for GC patients (FRLSG) was constructed through univariate Cox regression, the LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, receiver operating characteristic curves, and risk score plot were applied to verify the predictive power of FRLSG. Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses were conducted to explore the potential clinical value of the FRLSG. In addition, drug sensitivity prediction was applied to identify chemotherapeutic drugs with potential therapeutic effect.

Results: Five ferroptosis-related lncRNAs (AC004816.1, AC005532.1, LINC01357, AL355574.1 and AL049840.4) were identified to construct FRLSG, whose expression level in GC were confirmed by experimental validation. Kaplan-Meier curve and ROC curve proved the reliability and effectiveness of the FRLSG in predicting the prognosis for GC patients. Several immune-related pathways were enriched in the high-FRLSG group, and further immune infiltration analyses demonstrated the high immune infiltration status of the high-FRLSG group. In addition, 19 and 24 candidate drugs with potential therapeutic effect were identified for the high- and low-FRLSG groups, respectively.

Conclusions: FRLSG was an effective tool in predicting the prognosis of GC, which might help to prioritize potential therapeutics for GC patients.
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http://dx.doi.org/10.18632/aging.204227DOI Listing
August 2022

Strain Releasing of Flexible 2D Electronics through van der Waals Sliding Contact.

ACS Nano 2022 Aug 15. Epub 2022 Aug 15.

Key Laboratory for Micro-Nano Optoelectronic Devices of Ministry of Education, School of Physics and Electronics, Hunan University, Changsha 410082, China.

Two-dimensional (2D) materials have demonstrated promising potential for flexible electronics, owning to their atomic thin body thickness and dangling-bond-free surface. Here, we report a sliding contact device structure for efficient strain releasing. By fabricating a weakly coupled metal-2D junction with a van der Waals (vdW) gap in between, the applied strain could be effectively released through their interface sliding; hence minimized strain is transferred to the 2D lattice. Therefore, we observed stable device behavior with electrodes stretching over 110%, much higher than 2D devices using evaporated metal contacts. Furthermore, through multicycle straining-releasing measurements, we found the electrodes still form intimate contact with nearly constant contact resistance during sliding, confirming the optimization of device flexibility and electrical properties at the same time. Finally, we demonstrate this vdW sliding contact is a general device geometry and could be well-extended to various 2D or 3D bulk materials, leading to devices with much higher strain tolerance.
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http://dx.doi.org/10.1021/acsnano.2c06214DOI Listing
August 2022

Antibiotic-Induced Primary Biles Inhibit SARS-CoV-2 Endoribonuclease Nsp15 Activity in Mouse Gut.

Front Cell Infect Microbiol 2022 28;12:896504. Epub 2022 Jul 28.

Department of Biotechnology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids.
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http://dx.doi.org/10.3389/fcimb.2022.896504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366059PMC
August 2022

Mesh Exposure and Prolapse Recurrence Following Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Sacrocolpopexy: Over 24 months of Follow-Up Data.

J Minim Invasive Gynecol 2022 Aug 11. Epub 2022 Aug 11.

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 128 Shenyang RD, Shanghai 200090, China. Electronic address:

Study Objective: To describe the results of mesh exposure and prolapse recurrence of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) for sacrocolpopexy after more than 24 months of postoperative follow-up.

Design: A retrospective cohort study.

Setting: A university hospital.

Patients: Women with uterine prolapse who underwent vNOTES sacrocolpopexy with an ultra-lightweight polypropylene mesh between May 2018 and March 2020.

Interventions: vNOTES sacrocolpopexy.

Measurements And Main Results: Of 57 women, 55 (96.5%) women were included in the final analysis. The mean follow-up duration was 35.5±7.6 (24-46) months. The total incidence of mesh exposure was 3 of 55 (5.5%). The total incidence of prolapse recurrence was 3 of 55 (5.5%). The changes in the pelvic organ prolapse quantification system (POP-Q) scores, including Aa, Ba, C, Ap, Bp and TVL values, showed significant improvement after surgery (P<0.05 for all).

Conclusions: The study demonstrates that vNOTES sacrocolpopexy appears to be an effective option with low risks of mesh exposure and prolapse recurrence. Studies including more patients and longer follow-up periods should be performed before a clear conclusion can be reached.
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http://dx.doi.org/10.1016/j.jmig.2022.08.001DOI Listing
August 2022

Luteolin restricts ASFV replication by regulating the NF-κB/STAT3/ATF6 signaling pathway.

Vet Microbiol 2022 Aug 4;273:109527. Epub 2022 Aug 4.

Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, PR China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, PR China; Research Center for African Swine Fever Prevention and Control, South China Agricultural University, Guangzhou, PR China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong, PR China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, PR China; National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, PR China. Electronic address:

African swine fever (ASF) is a devastating infectious disease that causes significant economic losses to the pig industry worldwide. Luteolin is abundant in onion leaves, carrots, broccoli, and apple skin and exerts various biological activities, including anti-cancer and anti-virus effects. Our aim was to demonstrate the mechanism of action and potent antiviral activity of luteolin against ASF virus (ASFV) in porcine alveolar macrophages. We performed cell viability, hemadsorption, indirect immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction assays to investigate the effect of luteolin on ASFV. Notably, luteolin restricted ASFV replication in a dose-dependent manner. The anti-ASFV activity of luteolin was maintained for 24-72 h. Subsequent experiments revealed that luteolin could block multiple stages of the ASFV replication cycle, including those at 6-9 h and 12-15 h after infection, instead of directly interacting with ASFV. Moreover, ASFV infection stimulated the expression of phosphorylated nuclear factor (NF)-κB, interleukin (IL)- 6, and phosphorylated signal transducer and activator of transcription 3 (STAT3). However, luteolin downregulated ASFV-induced NF-κB, IL-6, and STAT3 expression. Importantly, NF-κB agonist CU-T12-9 weakened the inhibitory effects of luteolin on NF-κB and STAT3. Moreover, CU-T12-9 partially restored the inhibitory effect of luteolin on ASFV. Similarly, luteolin reduced ASFV-induced activating transcription factor 6 (ATF6) expression, and CU-T12-9 weakened the inhibitory effect of luteolin on ATF6. Our findings suggested that luteolin inhibited ASFV replication by regulating the NF-κB/STAT3/ATF6 signaling pathway and might provide a rationale for anti-ASFV drug development.
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http://dx.doi.org/10.1016/j.vetmic.2022.109527DOI Listing
August 2022

Evaluation of decompressive craniectomy in mice after severe traumatic brain injury.

Front Neurol 2022 26;13:898813. Epub 2022 Jul 26.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.

Decompressive craniectomy (DC) is of great significance for relieving acute intracranial hypertension and saving lives after traumatic brain injury (TBI). In this study, a severe TBI mouse model was created using controlled cortical impact (CCI), and a surgical model of DC was established. Furthermore, a series of neurological function assessments were performed to better understand the pathophysiological changes after DC. In this study, mice were randomly allocated into three groups, namely, CCI group, CCI+DC group, and Sham group. The mice in the CCI and CCI+DC groups received CCI after opening a bone window, and after brain injury, immediately returned the bone window to simulate skull condition after a TBI. The CCI+DC group underwent DC and contused tissue removal 6 h after CCI. The mice in the CCI group underwent the same anesthesia process; however, no further treatment of the bone window and trauma was performed. The mice in the Sham group underwent anesthesia and the process of opening the skin and bone window, but not in the CCI group. Changes in Modified Neurological Severity Score, rotarod performance, Morris water maze, intracranial pressure (ICP), cerebral blood flow (CBF), brain edema, blood-brain barrier (BBB), inflammatory factors, neuronal apoptosis, and glial cell expression were evaluated. Compared with the CCI group, the CCI+DC group had significantly lower ICP, superior neurological and motor function at 24 h after injury, and less severe BBB damage after injury. Most inflammatory cytokine expressions and the number of apoptotic cells in the brain tissue of mice in the CCI+DC group were lower than in the CCI group at 3 days after injury, with markedly reduced astrocyte and microglia expression. However, the degree of brain edema in the CCI+DC group was greater than in the CCI group, and neurological and motor functions, as well as spatial cognitive and learning ability, were significantly poorer at 14 days after injury.
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http://dx.doi.org/10.3389/fneur.2022.898813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360741PMC
July 2022

Prediction Model of Rice Seedling Growth and Rhizosphere Fertility Based on the Improved Elman Neural Network.

Comput Intell Neurosci 2022 31;2022:2151682. Epub 2022 Jul 31.

Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, China.

Rice developing prognostication is a key part of precise agricultural management, and its advancement is an intricate course of events involving the interplay of breed and environmental element. The traditional research method is based on data analysis of rice growth prediction modeling, mining the concealed rapport between rice productivity and circumstance element, for instance, weather, sunlight, and water, and then predicting its yield and analyzing the complex rapport between the circumstance element and growth in every developing phase. In this dissertation, the improved ElmanNN is accustomed to establish a prediction model, and the ElmanNN is accustomed to determine the rapport between the circumstance element and growth in every developing phase simultaneously so as to avoid the arithmetic falling into local optimum easily. In this dissertation, the improved genetic arithmetic is accustomed to optimize the initial weight and threshold of Elman neural network, and the range of weight value multitudinous layers in the mould are obtained by training the network with samples that have been tested in the last few years. Finally, the rapport between growth and yield in six different periods is independently modeled, and the training samples are build up separately one by one based on physiological parameters and environmental indicators of rice at every level. The experiments show that the accuracy for the prediction model in the light of the improved ElmanNN has been beneficial.
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http://dx.doi.org/10.1155/2022/2151682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357766PMC
August 2022

A signature based on m6A pattern and tumor microenvironment infiltration in clear cell renal cell carcinoma.

Am J Transl Res 2022 15;14(7):4931-4947. Epub 2022 Jul 15.

Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University Xiamen 361003, Fujian, China.

Background: RNA N6-methyladenosine (m6A) has been found to have a critical impact on clear cell renal cell carcinoma (ccRCC) by affecting the tumor microenvironment (TME) and immune cell (IC) infiltration and is related to the treatment and survival rate of patients with ccRCC. However, the mechanism of m6A in TME and IC infiltration remained unclear.

Methods: Nonnegative Matrix Factorization (NMF) clustering was performed on 650 ccRCC cases from the Cancer Genome Atlas (TCGA) and the Gene-Expression Omnibus (GEO) datasets. The immune infiltration was generated by the single-sample gene-set enrichment analysis (ssGSEA) algorithm. Survival analyses were performed using the Kaplan-Meier method, and the significance of the differences was determined using the log-rank test. The m6A score was constructed based on the expression of m6A regulators to quantify m6A modification. The package "survminer R" was employed to layer patients' low and high scores groups and predict the immunotherapy response.

Results: Three different patterns of m6A modification were established, and significant differences in TME and IC infiltration features were found in these three patterns. Survival analysis demonstrated that m6A cluster A and m6A gene cluster A experienced a longer survival time. Evaluation of m6A modification patterns in individual tumors was initiated by the m6A score. The low m6A score subtype was characterized by increased tumor mutation burden (TMB) and immune infiltration, whereas a high m6A score with a lack of immune cell infiltration showed significantly better overall survival. m6A score was also associated with the expression of programmed cell death protein 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Patients in the high m6A score group had high PD-L1 expression and low CTLA-4 expression. Significant differences in prognosis were identified among types of different TMB and m6A scores, where low TMB and high m6A score had longer survival time.

Conclusions: This research indicated that m6A modification greatly affected TME and IC infiltration. Physicians can develop practical immunotherapy strategies for patients with ccRCC by evaluating m6A-associated genes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360897PMC
July 2022

Van der Waals Epitaxy of c-Oriented Wurtzite AlGaN on Polycrystalline Mo Substrates for Enhanced Heat Dissipation.

ACS Appl Mater Interfaces 2022 Aug 11. Epub 2022 Aug 11.

State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

The epitaxy of III-nitrides on metallic substrates is competitive due to the advantages of vertical carrier injection, enhanced heat dissipation, and flexible application in various III-nitride-based devices. However, the serious lattice mismatch, atom diffusion, and interface reaction under the rigorous growth conditions have caused enormous obstacles. Based on the thermal and chemical stability of the graphene layer, we propose the van der Waals epitaxy of c-oriented wurtzite AlGaN on the polycrystalline Mo substrate by high-temperature metal-organic chemical vapor deposition. The insertion of a graphene layer interrupts the chaotic epitaxial relationship between the polycrystalline metal and epilayers, resulting in the single-crystalline orientation along the wurtzite (0002) plane and residual stress release in AlGaN because of the weak van der Waals interaction. We also demonstrate that the epitaxy of AlGaN on Mo metal possesses enhanced heat dissipation ability, in which the epilayer temperature is controlled at only 28.7 °C by the heating of a ∼54 °C hot plate. The heat dissipation enhancement for the present epitaxial structures provides a desirable strategy for the fabrication of efficient ultraviolet devices with excellent stability and lifetime.
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http://dx.doi.org/10.1021/acsami.2c10039DOI Listing
August 2022

Analysis of Pressure Fluctuation Characteristics of Central Swirl Combustors Based on Empirical Mode Decomposition.

Sensors (Basel) 2022 Jul 27;22(15). Epub 2022 Jul 27.

Key Laboratory of Aero-Engine Thermal Environment and Structure, Ministry of Industry and Information Technology, College of Energy and Power Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

In order to study the characteristics of pressure fluctuation during unstable combustion, experimental studies had been conducted on the mechanism model of the swirl combustor and the industrial swirl combustor. The signal of dynamic pressure, heat release rate, and the high-speed flame image in the two combustors were synchronously collected by using dynamic pressure sensors, a photoelectric sensor, and a high-speed camera under normal temperature and pressure. After empirical mode decomposition of the dynamic pressure signal, several intrinsic mode functions were obtained. It was found that the pressure pulsation energy is concentrated in the first three order intrinsic mode function. Through fast Fourier transform spectrum calculation, it was found that the first three order intrinsic mode function pulsation can characterize the changes of heat release rate and air flow pulsation under cold state and flame instability. It showed that the decomposition of the dynamic pressure in the combustor by this method can obtain the main physical processes in its connotation, and provide data processing methods for the induction mechanism of oscillating combustion and combustion diagnosis in an industrial combustor test.
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http://dx.doi.org/10.3390/s22155615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9371237PMC
July 2022

Metal Artifact Reduction Sequences MRI: A Useful Reference for Preoperative Diagnosis and Debridement Planning of Periprosthetic Joint Infection.

J Clin Med 2022 Jul 27;11(15). Epub 2022 Jul 27.

Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350000, China.

The diagnosis and treatment of periprosthetic joint infection (PJI) is complex and the use of MRI in PJI is gaining attention from orthopedic surgeons as MR technology continues to advance. This study aimed to investigate whether metal artefact reduction sequence (MARS) MRI could be used as an adjunct in the preoperative diagnosis of PJI and to explore its role in PJI debridement planning. From January 2020 to November 2021, participants with metal joint prostheses that needed to be judged for infection were prospectively enrolled. According to Musculoskeletal Infection Society standards, 31 cases were classified as infection, and 20 as non-infection. The sensitivity and specificity of MARS MRI for the diagnosis of PJI were 80.65% and 75%, respectively. In MARS MRI, the incidence of bone destruction, lamellar synovitis, and extracapsular soft tissue oedema were significantly higher in PJI than in non-PJI. Fourteen suspicious occult lesions were found in the preoperative MARS MRI in 9 cases, and the location of 9 infection lesions was confirmed intraoperatively. In conclusion, MARS MRI is an effective diagnostic tool for PJIand can provide a visual reference for preoperative surgical planning.
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http://dx.doi.org/10.3390/jcm11154371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369276PMC
July 2022

lncRNA2919 Suppresses Rabbit Dermal Papilla Cell Proliferation via -Regulatory Actions.

Cells 2022 Aug 6;11(15). Epub 2022 Aug 6.

College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

Hair follicles (HFs) are complex organs that grow cyclically during mammals' growth and development. Long non-coding RNAs (lncRNAs) cannot be translated into proteins and play crucial roles in many biological processes. In our previous study, candidate lncRNAs associated with HF cyclic regeneration were screened, and we identified that the novel lncRNA, lncRNA2919, was significantly expressed during catagen. Here, we identified that lncRNA2919 has no coding potentiality and is highly expressed in the cell nucleus, and downregulates HF growth and development-related genes, inhibits cell proliferation, and promotes cell apoptosis in rabbit dermal papilla cells. lncRNA2919 recruits STAT1 to form a compound. As a key transcription factor, STAT1 regulates the transcriptional expression of KRTAP11-1. Our study revealed that lncRNA2919 is involved in HF cyclic regeneration through the -regulatory lncRNA2919-STAT1-KRTAP11-1 axis. This study elucidates the mechanism through which lncRNA2919 regulates HF growth and development and the role of lncRNA2919 as a new therapeutic target in animal wool production and human hair-related disease treatment.
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http://dx.doi.org/10.3390/cells11152443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368379PMC
August 2022

Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology.

J Zhejiang Univ Sci B 2022 Aug;23(8):682-698

School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China.

Objectives: To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation.

Methods: The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-‍α (PFT-‍α) and GSK690693 for further investigation.

Results: The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-‍α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated.

Conclusions: Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
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http://dx.doi.org/10.1631/jzus.B2200038DOI Listing
August 2022

TRIM56 positively regulates TNFα-induced NF-κB signaling by enhancing the ubiquitination of TAK1.

Int J Biol Macromol 2022 Aug 8;219:571-578. Epub 2022 Aug 8.

Henan International Joint Laboratory of Children's Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Children's Hospital, Zhengzhou, 450000, China. Electronic address:

Nuclear factor-κB (NF-κB) signaling participates in many biologic processes including immunity, inflammation, and cancer. Here we reported that tripartite motif-containing protein 56 (TRIM56), an E3 ligase enzyme, participated in TNFα-induced NF-κB signaling by interacting with TAK1. Overexpression of TRIM56 potentiated the activation of TNFα-induced NF-κB signaling, whereas knockdown of TRIM56 had an opposite effect. TRIM56 enhanced the ubiquitination of TAK1, specifically enhanced the M1-linked polyubiquitin chains to TAK1, leading to the tight interactions of the TAK1-IKKα complex. Consequently, the stimulation of TNFa and TRIM56 strengthened the interaction with TAK1. Furthermore, we found that the C terminal (CT) domain was the binding region of TRIM56, and the RING domain of TRIM56 was the E3 enzyme activity region which was important to the ubiquitination of TAK1. Together, these results reveal that TRIM56 positively regulates TNFα-induced NF-κB signaling by heightening the ubiquitination of TAK1 and provide new insight into the complicated mechanisms of the inflammatory and immune response.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.08.019DOI Listing
August 2022

CDK1 promotes the proliferation of melanocytes in Rex rabbits.

Genes Genomics 2022 Aug 11. Epub 2022 Aug 11.

College of Animal Science and Technology, Yangzhou University, 225009, Yangzhou, China.

Background: The fur color constitutes one of the most important economic characteristics of fur animals and is determined by the content of melanin. A previous study has shown that the cyclin-dependent kinase 1 (CDK1) is a member of the protein kinase family, involved in forming the color of the fur in Rex rabbits. However, its effect on the melanocytes remains unclear.

Objective: This study aimed to provide evidence for the role of CDK1 in melanogenesis.

Methods: This study measured the expression of CDK1 in Rex rabbit skins of six coat colors using qRT-PCR. The CDK1-mediated regulation of the pigmentation-related genes and cyclin-dependent kinases were analyzed. The melanin content, proliferation, and apoptosis of the melanocytes were analyzed using the NaOH, CCK8, and Annexin V-FITC methods.

Results: The CDK1 expression in the skin of the rex rabbits with different coat colors was found to be regular, and the expression level was found to be the highest in the skin of the black rex rabbits (P < 0.05). The overexpression/knockdown of CDK1 was found to significantly increase/decrease the melanin content in the melanocytes (P < 0.01). Besides, CDK1 was found to significantly promote the proliferation of the melanocyte and inhibit apoptosis (P < 0.01). Furthermore, the overexpression of CDK1 was found to significantly affect the expression of the other melanin-related genes like TYR, PMEL, DCT, as well as the mRNA expression of the cyclin-dependent kinases CDK4, CDK6, CDK8, CCNB1.

Conclusions: The results indicated that CDK1 can serve as a key gene regulating melanogenesis, melanocyte proliferation, and apoptosis, providing a new theoretical basis for studying the mechanism by which the different colors of the fur evolve in mammals.
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http://dx.doi.org/10.1007/s13258-022-01283-4DOI Listing
August 2022

Total Synthesis of Marine Alkaloids Cystodytins A-K.

J Org Chem 2022 Aug 10;87(16):11063-11072. Epub 2022 Aug 10.

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

The total synthesis of marine alkaloids cystodytins A-K has been accomplished in five to six steps starting from commercially available compounds. The highlights of the synthesis include an oxidative amination-cyclization of tryptamine and para-hydroquinones to build a tetracyclic pyridoacridinone ring with different side chains and a copper(II)-catalyzed enantioselective Henry reaction to construct an oxygenated stereogenic carbon center. For the first time, the absolute configuration of the stereogenic centers embedded in cystodytins D-I and K was established as . Moreover, the stereochemistry of the olefin unit in the side chain of cystodytins H and I was revised to the configuration from the originally assigned configuration.
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http://dx.doi.org/10.1021/acs.joc.2c01317DOI Listing
August 2022

Bibliometric and visual analysis of research on nutcracker syndrome from 1974 to 2021: A systematic review.

Medicine (Baltimore) 2022 Aug;101(31):e29939

School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: At present, researchers have obtained fruitful results in the study of nutcracker syndrome (NCS), but there is still a lack of systematic research on the overall status of this disease. This article aims to describe the past and current status of research into NCS, and predict future research trends and popular research topics.

Methods: Using bibliometric and visualization methods, 552 articles related to NCS collected from the Scopus database from 1974 to 2021 were analyzed from multiple perspectives.

Results: Overall, the amount of literature related to NCS is on the rise every year, and the number of citations is the turning point in 2006. The United States has the largest number of publications and has the most extensive cooperation with other countries. The main contents of the co-authored study focused on the symptoms, surgical procedures, and concomitant diseases of NCS. Keywords such as peak velocity, ultrasonography, orthostatic proteinuria, etc appeared earlier, whereas diagnosis, chronic pelvic pain, endovascular stents, etc appeared later.

Conclusions: The literature utilization rate of NCS is relatively insufficient. The pathogenesis and pathological mechanisms need to be further studied, and the diagnostic criteria and surgical methods will continue to be favored by clinicians.
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http://dx.doi.org/10.1097/MD.0000000000029939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351850PMC
August 2022

The relationship between the epigenetic aging biomarker "grimage" and lung function in both the airway and blood of people living with HIV: An observational cohort study.

EBioMedicine 2022 Aug 6;83:104206. Epub 2022 Aug 6.

Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH.

Methods: Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV/FVC<0.70, and FEV decline over 6 years in blood.

Findings: The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV/FVC
Interpretation: GrimAge may reflect lung and systemic epigenetic changes that occur with advanced airflow obstruction and may help to identify PLWH with a higher risk of developing COPD.

Funding: Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453.
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http://dx.doi.org/10.1016/j.ebiom.2022.104206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379521PMC
August 2022

Deciphering the focuses and trends in skin regeneration research through bibliometric analyses.

Front Med (Lausanne) 2022 22;9:947649. Epub 2022 Jul 22.

Department of Oral and Maxillofacial Surgery, Xi'an Daxing Hospital, Xi'an, China.

Increasing attention to skin regeneration has rapidly broadened research on the topic. However, no bibliometric analysis of the field's research trends has yet been conducted. In response to this research gap, this study analyzed the publication patterns and progress of skin regeneration research worldwide using a bibliometric analysis of 1,471 papers comprising 1,227 (83.4%) original articles and 244 (16.6%) reviews sourced from a Web of Science search. Publication distribution was analyzed by country/region, institution, journal, and author. The frequency of keywords was assessed to prepare a bibliometric map of the development trends in skin regeneration research. China and the United States were the most productive countries in the field: China had the greatest number of publications at 433 (29.4%) and the United States had the highest H-index ranking (59 with 15,373 citations or 31.9%). Author keywords were classified into four clusters: stem cell, biomaterial, tissue engineering, and wound dressing. "Stem cells," "chitosan," "tissue engineering," and "wound dressings" were the most frequent keywords in each cluster; therefore, they reflected the field's current focus areas. "Immunomodulation," "aloe vera," "extracellular vesicles," "injectable hydrogel," and "three-dimensional (3D) bioprinting" were relatively new keywords, indicating that biomaterials for skin regeneration and 3D bioprinting are promising research hotspots in the field. Moreover, clinical studies on new dressings and techniques to accelerate skin regeneration deserve more attention. By uncovering current and future research hotspots, this analysis offers insights that may be useful for both new and experienced scholars striving to expand research and innovation in the field of skin regeneration.
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http://dx.doi.org/10.3389/fmed.2022.947649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355679PMC
July 2022

Effects of 3-methylmethcathinone on conditioned place preference and anxiety-like behavior: Comparison with methamphetamine.

Front Mol Neurosci 2022 22;15:975820. Epub 2022 Jul 22.

National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China.

3-Methylmethcathinone (3-MMC), a drug belonging to synthetic cathinones family, raised public attention due to its harmful health effects and abuse potential. Although it has similar properties to other cathinone derivatives, the behavioral effects of 3-MMC remain largely unknown. In the present research, we evaluated the rewarding effect of 3-MMC using conditioned place preference (CPP) paradigm and its effect on anxiety-like behavior using elevated plus maze (EPM) and compared with methamphetamine (METH). Then, we performed a whole-brain c-Fos mapping to identify the specific brain regions in response to 3-MMC exposure and explored the changes of synaptic transmission in nucleus accumbens (NAc) using patch-clamp recording after chronic 3-MMC and METH exposure. 3-MMC induced CPP at higher doses of 3 or 10 mg/kg in rats and acute exposure of 3 mg/kg 3-MMC to rats produced anxiolytic-like effect, while anxiety-like behavior was increased after 7 days of injection with 3-MMC. Whole-brain immunostaining revealed increased c-Fos expression in anterior cingulate cortex (ACC), NAc and ventral tegmental area (VTA) after chronic 3-MMC injection compared with saline, which was similar to METH. Especially, 3-MMC induced more neural activation of VTA compared with METH. Finally, we found that amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) in NAc was decreased after chronic 3-MMC injection, while frequency of sIPSCs and spontaneous excitatory postsynaptic currents (sEPSCs) were not affected. Taken together, our results revealed the addictive potential of 3-MMC and its effect on anxiety-like behavior, which warn the risks of 3-MMC abuse and justify the control of synthetic cathinones. And 3-MMC selectively inhibit inhibitory but not excitatory transmission onto neurons in NAc, which may contribute to its effects.
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http://dx.doi.org/10.3389/fnmol.2022.975820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354685PMC
July 2022

Genetic and Functional Characterization of a Conjugative KpVP-2-Type Virulence Plasmid From a Clinical Strain.

Front Microbiol 2022 22;13:914884. Epub 2022 Jul 22.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.

The main mechanism of virulence in is the acquisition of virulence plasmids (KpVPs), which include two dominant types, namely, KpVP-1 (carrying 1, 1, , and ) and KpVP-2 (carrying 2, 2, and ). Both are non-conjugative and associated with different hypervirulent clones. In contrast to KpVP-1 reported in K1, K2, and other serotypes of , KpVP-2 was only reported in K2 strains and rarely characterized. In this study, we identified a conjugative KpVP-2-type virulence plasmid from a clinical hypervirulent strain. This plasmid was generated by the integration of conjugative transfer genes into the KpVP-2-type plasmid Kp52.145 II and could be readily conjugated to strain EC600 and strains of various types which are clinically existing, mediating hypervirulence. Furthermore, this kind of conjugative KpVP-2-type virulence plasmid has been disseminated in clinical settings in Hong Kong and other regions of the world. The generation of conjugative virulence plasmid may promote its transmission and explain the evolution of this type of virulence plasmid.
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http://dx.doi.org/10.3389/fmicb.2022.914884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354667PMC
July 2022
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