Publications by authors named "Fei Liu"

2,952 Publications

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Impacts of anthropogenic groundwater recharge (AGR) on nitrate dynamics in a phreatic aquifer revealed by hydrochemical and isotopic technologies.

Sci Total Environ 2022 May 23:156187. Epub 2022 May 23.

Ministry of Education Key Laboratory of Groundwater Circulation and Environmental Evolution, China University of Geosciences (Beijing), Beijing 100083, China. Electronic address:

Although anthropogenic groundwater recharge (AGR) can either elevate or decline the concentration of the nitrate (NO) in the phreatic aquifer with high hydraulic conductivity, the long-term impact of AGR on NO dynamics in the phreatic aquifer and its reason is seldom disclosed. In this study, the hydrogen and oxygen stable isotopes (δH-HO and δO-HO) combined with mixing stable isotope analysis in R (MixSIAR) were used to group the study area into the dominant area of AGR by surface water (AGRSW) and the dominant area of natural groundwater recharged by precipitation (NGRP). Hydrochemical parameters and multiple stable isotopes, including δH-HO, δO-HO, δN-NO, δO-NO, and δC-DIC, were applied to explore the impacts of AGR on the concentration, biogeochemical processes, and main sources of nitrate. The results showed that AGR by surface water with low nitrate content can reduce nitrate pollution in groundwater. The characteristic of δO-NO value revealed nitrification was the primary biogeochemical process of nitrogen in groundwater. AGR may enhance nitrification as indicated by the δO-NO value closer to the nitrification theoretical line. Dual nitrate stable isotopes and MixSIAR revealed that chemical fertilizer, soil nitrogen, and surface water contributed 10.88%, 49.92%, and 27.64% to nitrate in AGRSW groundwater, respectively, which is significantly larger than their nitrogen contribution to NGRP groundwater (p < 0.05). Notably, AGR significantly increased the contribution of SW but decreased the contribution of CF and SN in groundwater. This study provided a basis and guidance for groundwater quality assessment and pollution control in the phreatic aquifer with high hydraulic conductivity.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156187DOI Listing
May 2022

Accumulation of Lipid Droplets in a Novel Bietti Crystalline Dystrophy Zebrafish Model With Impaired PPARα Pathway.

Invest Ophthalmol Vis Sci 2022 May;63(5):32

Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

Purpose: Bietti crystalline dystrophy (BCD) is a progressive retinal degenerative disease primarily characterized by numerous crystal-like deposits and degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. CYP4V2 (cytochrome P450 family 4 subfamily V member 2) is currently the only disease-causing gene for BCD. We aimed to generate a zebrafish model to explore the functional role of CYP4V2 in the development of BCD and identify potential therapeutic targets for future studies.

Methods: The cyp4v7 and cyp4v8 (homologous genes of CYP4V2) knockout zebrafish lines were generated by CRISPR/Cas9 technology. The morphology of photoreceptor and RPE cells and the accumulation of lipid droplets in RPE cells were investigated at a series of different developmental stages through histological analysis, immunofluorescence, and lipid staining. Transcriptome analysis was performed to investigate the changes in gene expression of RPE cells during the progression of BCD.

Results: Progressive retinal degeneration including RPE atrophy and photoreceptor loss was observed in the mutant zebrafish as early as seven months after fertilization. We also observed the excessive accumulation of lipid droplets in RPE cells from three months after fertilization, which preceded the retinal degeneration by several months. Transcriptome analysis suggested that multiple metabolism pathways, especially the lipid metabolism pathways, were significantly changed in RPE cells. The down-regulation of the peroxisome proliferator-activated receptor α (PPARα) pathway was further confirmed in the mutant zebrafish and CYP4V2-knockdown human RPE-1 cells.

Conclusions: Our work established an animal model that recapitulates the symptoms of BCD patients and revealed that abnormal lipid metabolism in RPE cells, probably caused by dysregulation of the PPARα pathway, might be the main and direct consequence of CYP4V2 deficiency. These findings will deepen our understanding of the pathogenesis of BCD and provide potential therapeutic approaches.
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http://dx.doi.org/10.1167/iovs.63.5.32DOI Listing
May 2022

Quantitative and ultrasensitive in situ immunoassay technology for SARS-CoV-2 detection in saliva.

Sci Adv 2022 May 25;8(21):eabn3481. Epub 2022 May 25.

Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

The coronavirus disease 2019 (COVID-19) pandemic has become an immense global health crisis. However, the lack of efficient and sensitive on-site testing methods limits early detection for timely isolation and intervention. Here, we present a quantitative and ultrasensitive in situ immunoassay technology for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in saliva (QUIT SARS-CoV-2). Our nanoporous membrane resonator generates a rapid oscillating flow to purify and concentrate fully intact SARS-CoV-2 virus in saliva by 40-fold for in situ detection of viral antigens based on chemiluminescent immunoassay within 20 min. This method can not only achieve a detection sensitivity below 100 copies/ml of virus, comparable to the bench-top PCR equipment; it can also improve detection specificity via direct monitoring of viral loads. The integrated portable QUIT SARS-CoV-2 system, which enables rapid and accurate on-site viral screening with a high-throughput sample pooling strategy, can be performed in primary care settings and substantially improve the detection and prevention of COVID-19.
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http://dx.doi.org/10.1126/sciadv.abn3481DOI Listing
May 2022

Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25.

Parasit Vectors 2022 May 23;15(1):175. Epub 2022 May 23.

Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, Liaoning, China.

Background: The Plasmodium zygote-to-ookinete developmental transition is an essential step for establishing an infection in the mosquito vector, and antigens expressed during this stage are potential targets for transmission-blocking vaccines (TBVs). The secreted ookinete protein 26 (PSOP26) is a newly identified ookinete surface protein. The anti-PSOP26 serum has moderate transmission-blocking activity, indicating the benefit of further investigating this protein as a target for TBVs.

Methods: The function of psop26 was analyzed by targeted gene disruption. A chimeric PSOP25-PSOP26 protein was expressed in the Escherichia coli system. The PSOP25-PSOP26 fusion protein, along with mixed (PSOP25 + PSOP26) or single proteins (PSOP26 or PSOP25), were used for the immunization of mice. The antibody titers and immunogenicity of individual sera were analyzed by enzyme-linked immunoassay (ELISA), indirect immunofluorescence assay (IFA), and Western blot. The transmission-blocking activity of sera from different immunization schemes was assessed using in vitro and in vivo assays.

Results: PSOP26 is a surface protein expressed in Plasmodium gametes and ookinetes. The protein is dispensable for asexual blood-stage development, gametogenesis, and zygote formation, but is essential for the zygote-to-ookinete developmental transition. Specifically, both the prevalence of infections and oocyst densities were decreased in mosquitoes fed on psop26-null mutants. Mixtures of individual PSOP25 and PSOP26 fragments (PSOP25 + PSOP26), as well as chimeras (PSOP25-PSOP26), elicited high antibody levels in mice, with no immunological interference. Antisera against the mixed and fusion proteins elicited higher transmission-reducing activity (TRA) than antisera against the single PSOP26 antigen, but comparable to antisera against PSOP25 antigen alone.

Conclusions: PSOP26 plays a critical role in the zygote-to-ookinete developmental transition. PSOP25 is a promising TBV candidate that could be used alone to target the ookinete stage.
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http://dx.doi.org/10.1186/s13071-022-05294-8DOI Listing
May 2022

Patients with gastroenteric tumor after upper abdominal surgery were more likely to require rescue analgesia than lower abdominal surgery.

BMC Anesthesiol 2022 May 23;22(1):156. Epub 2022 May 23.

Department of Anesthesiology, Institute of Neurological Disease, West China Hospital, Chengdu, 610041, Sichuan, China.

Objectives: To find out the reasons why patients still need to use rescue analgesics frequently after gastrointestinal tumor surgery under the patient-controlled intravenous analgesia (IV-PCA), and the different abdominal surgery patients using the difference of analgesics.

Methods: A total of 970 patients underwent abdominal operation for gastrointestinal tumors were included. According whether patients used dezocine frequently for rescue analgesics within 2 days after surgery, they assigned into two groups: RAN group (Patients who did not frequently use rescue analgesia, 406 cases) and RAY group (Patients who frequently used rescue analgesia, 564 cases). The data collected included patient's characteristics, postoperative visual analogue scale (VAS), nausea and vomiting (PONV), and postoperative activity recovery time.

Results: No differences were observed in the baseline characteristics. Compared with the RAN group, patients in the RAY group had a higher proportion of open surgery, upper abdominal surgery, VAS score at rest on the first 2 days after surgery and PONV, and a slower recovery of most postoperative activities. Under the current use of IV-PCA background, the proportion of rescue analgesics used by patients undergoing laparotomy and upper abdominal surgery was as high as 64.33% and 72.8%, respectively. Regression analysis showed that open surgery (vs laparoscopic surgery: OR: 2.288, 95% CI: 1.650-3.172) and the location of the tumor in the upper abdomen (vs lower abdominal tumor: OR: 2.738, 95% CI: 2.034-3.686) were influential factors for frequent salvage administration.

Conclusions: In our patient population, with our IV-PCA prescription for postoperative pain control, patient who underwent open upper abdominal surgery required more rescue postoperative analgesia.
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http://dx.doi.org/10.1186/s12871-022-01682-wDOI Listing
May 2022

kngMap: Sensitive and Fast Mapping Algorithm for Noisy Long Reads Based on the -Mer Neighborhood Graph.

Front Genet 2022 5;13:890651. Epub 2022 May 5.

Key Laboratory of Information Fusion Technology of Ministry of Education, School of Automation, Northwestern Polytechnical University, Xi'an, China.

With the rapid development of single molecular sequencing (SMS) technologies such as PacBio single-molecule real-time and Oxford Nanopore sequencing, the output read length is continuously increasing, which has dramatical potentials on cutting-edge genomic applications. Mapping these reads to a reference genome is often the most fundamental and computing-intensive step for downstream analysis. However, these long reads contain higher sequencing errors and could more frequently span the breakpoints of structural variants (SVs) than those of shorter reads, leading to many unaligned reads or reads that are partially aligned for most state-of-the-art mappers. As a result, these methods usually focus on producing local mapping results for the query read rather than obtaining the whole end-to-end alignment. We introduce kngMap, a novel -mer neighborhood graph-based mapper that is specifically designed to align long noisy SMS reads to a reference sequence. By benchmarking exhaustive experiments on both simulated and real-life SMS datasets to assess the performance of kngMap with ten other popular SMS mapping tools (e.g., BLASR, BWA-MEM, and minimap2), we demonstrated that kngMap has higher sensitivity that can align more reads and bases to the reference genome; meanwhile, kngMap can produce consecutive alignments for the whole read and span different categories of SVs in the reads. kngMap is implemented in C++ and supports multi-threading; the source code of kngMap can be downloaded for free at: https://github.com/zhang134/kngMap for academic usage.
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http://dx.doi.org/10.3389/fgene.2022.890651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117619PMC
May 2022

3D Bioprinting of Living Materials for Structure-Dependent Production of Hyaluronic Acid.

ACS Macro Lett 2022 04 17;11(4):452-459. Epub 2022 Mar 17.

School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Guangming District, Shenzhen, Guangdong 518107, P. R. China.

3D bioprinting of living materials represents an interesting paradigm toward the efficacy enhancement for the biosynthesis of various functional compounds in microorganisms. Previous studies have shown the success of 3D-printed bioactive systems in the production of small molecular compounds. However, the feasibility of such a strategy in producing macromolecules and how the geometry of the 3D scaffold influences the productivity are still unknown. In this study, we printed a series of 3D gelatin-based hydrogels immobilized with fermentation bacteria that can secrete hyaluronic acid (HA), a very useful natural polysaccharide in the fields of biomedicine and tissue engineering. The 3D-printed bioreactor was capable of producing HA, and an elevated yield was obtained with the system bearing a grid structure compared to that either with a solid structure or in a scaffold-free fermentation condition. As for the grid structure, bioreactors with a 90° strut angel and a median interfilament distance displayed the highest HA yield. Our findings highlighted the significant role of 3D printing in the spatial control of microorganism-laden hydrogel structures for the enhancement of biosynthesis efficiency.
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http://dx.doi.org/10.1021/acsmacrolett.2c00037DOI Listing
April 2022

Long non-coding RNA H19X promotes tumorigenesis and metastasis of colorectal cancer through regulating the miR-503-5p/KANK1 axis.

Genes Genomics 2022 May 14. Epub 2022 May 14.

Department of General Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, People's Republic of China.

Background: It has been well established that the long non-coding RNAs (lncRNAs) plays a critical role in tumor progression. However, the function of these transcripts and mechanisms responsible for their deregulation in colorectal cancer (CRC) remain to be investigated.

Objective: To explore the potential effect and regulation mechanism of lncRNA H19X in colorectal cancer.

Methods: We predicted and validated long non-coding RNA H19X from microarray data of colorectal cancer tissues. In addition, the biological behaviors of H19X and miR-503-5p on CRC were examined in vitro and in vivo, including MTT, colony formation assay, Hoechst33342 and transwell assay. The mRNA and protein levels of KN Motif and Ankyrin Repeat Domains 1 (KANK1) were analyzed by Quantitative real-time PCR (qRT-PCR), western blotting (WB) assay. Moreover, bioinformatics tools and dual-luciferase reporter assay were applied to demonstrate the relationship between KANK1 and miR-503-5p.

Results: H19X was remarkably up-regulated in CRC tissues. Its expression related to tumor size (p = 0.041), lymph node metastasis (p = 0.037), distal metastasis (p = 0.028), advanced TNM stage (p = 0.034) and poor survival in CRC. H19X acted as an oncogenic lncRNA that induced CRC cell proliferation, invasion and metastasis. Through a number of functional studies, we found that H19X silencing inhibited the malignance phenotype of cancer cells through loss of miR-503-5p. Further studies demonstrated that miR-503-5p was involved in the progression of CRC by directly regulating the downstream target KANK1.

Conclusion: Collectively, the findings of the present study indicate H19X/miR-503-5p/KANK1 axis has critical role in the progression of colorectal cancer, providing an effective prognostic indicator and promising target in treatment of colorectal cancer.
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http://dx.doi.org/10.1007/s13258-022-01259-4DOI Listing
May 2022

STAT3 regulates SRGN and promotes metastasis of nasopharyngeal carcinoma through the FoxO1-miR-148a-5p-CREB1 axis.

Lab Invest 2022 May 13. Epub 2022 May 13.

Department of Otolaryngology & Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, PR China.

Nasopharyngeal carcinoma (NPC), which is marked by a distinct distribution, is a common subtype of epithelial carcinoma arising from the nasopharyngeal mucosal lining. SRGN acts as an important and poor prognostic factor of NPC through multiple different mechanisms. However, the biological role and mechanism of SRGN in NPC remain unknown. Expression levels of miR-148a-5p, CREB1, FoxO1, and SRGN in NPC tissues and cell lines were tested by qRT-PCR or/and Western blot. The impacts of miR-148a-5p, CREB1, FoxO1, and SRGN on NPC cell viability, proliferation, migration, and invasion were estimated in vitro by CCK-8, colony formation, wound healing and Transwell experiments, and in vivo by a xenograft tumor model. JASPAR analysis was used to predict the binding activity of Foxo1 (CREB1) with the miR-148a-5p (SRGN) promoter, and the interaction was validated by EMSA and ChIP assays. The miR-148a-5p-CREB1 interaction was validated by a dual-luciferase reporter and RIP assays. CREB1 and SRGN were increased while miR-148a-5p was decreased in NPC. Silencing of SRGN and CREB1, as well as miR-148a-5p overexpression, repressed NPC tumor progression in vitro and in vivo. CREB1 promoted SRGN expression in NPC by targeting the promoter area of SRGN. Silencing of FoxO1 facilitated NPC tumor progression, while silencing of STAT3 repressed NPC tumor progression. FoxO1 bound to and regulated miR-148a-5p in NPC, and miR-148a-5p targeted CREB1. Additionally, FoxO1 knockdown abolished the downregulation of CREB1 and SRGN induced by STAT3 silencing. Our results suggest that STAT3 regulates SRGN and promotes the growth and metastasis of NPC through the FoxO1-miR-148a-5p-CREB1 axis.
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http://dx.doi.org/10.1038/s41374-022-00733-7DOI Listing
May 2022

Description of the Molecular and Phenotypic Spectrum of Lesch-Nyhan Disease in Eight Chinese Patients.

Front Genet 2022 26;13:868942. Epub 2022 Apr 26.

Department of Nephrology, Children's Hospital, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Zhejiang University School of Medicine, Hangzhou, China.

Lesch-Nyhan disease (LND) is a rare disorder involving pathogenic variants in the gene encoding the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) that result in hyperuricemia, intellectual disability, dystonic movement disorder, and compulsive self-mutilation. The purpose of the present study was to characterize the genetic basis of LND and describe its phenotypic heterogeneity by identifying the variation in the gene in a cohort of Chinese LND patients. The median age at diagnosis was 31 mo (interquartile range (IQR): 7-76 mo), and the initial manifestations were mainly head control weakness and motor development delay. The median age of self-mutilation behavior onset was 19 mo (IQR: 17-24 mo), and all patients were required to travel in a wheelchair and fall into the predicament of compulsive self-harm behavior. There were two patients whose blood uric acid levels were normal for their high urinary acid excretion fraction without taking uric acid-lowering drugs. Seven different pathogenic variants of the gene were identified among eight independent pedigrees, including four novel mutations [c.299 (exon 3) T > A; loss (exon: 6) 84 bp; c.277_281delATTGC; c.468_470delGAT]. The pathogenic variant sites were mainly concentrated in exon 3, and truncating mutations (including frameshift mutations and nonsense mutations) were the most common genetic variant types (5/7, 71.4%). The present study described the phenotypic and molecular spectrum of LND in eight Chinese families, including four novel mutations, which expands our understanding of LND.
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http://dx.doi.org/10.3389/fgene.2022.868942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086273PMC
April 2022

The dual effect of shellac on survival of spray-dried Lactobacillus rhamnosus GG microcapsules.

Food Chem 2022 Sep 18;389:132999. Epub 2022 Apr 18.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China. Electronic address:

Heat shock and hygroscopicity are two main factors that resulted in low viability of probiotics in spray-dried microcapsules during storage. Hydrophobic polyester shellac was combined with whey protein isolate (WPI) to solve this problem. The results suggested that although the survival rate after drying decreased from 20.63% to 0.01% with increased shellac to WPI ratio, the 1:1 shellac-WPI provided the best protection among all samples during storage. The consistence between moisture-adsorption-isotherm and bacterial inactivation constants confirmed the moisture barrier effect of shellac under moderate humidity. Single-droplet drying and differential scanning calorimeter revealed that shellac addition reduced the drying rate and glass transition temperature of microcapsules, which in turn decreased the membrane integrity and growth capability of the probiotics after drying. This study revealed the dual effect of hydrophobic material on instant and long-term survival of spray-dried probiotic microcapsules, which provided new sight to the design of composite wall materials.
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http://dx.doi.org/10.1016/j.foodchem.2022.132999DOI Listing
September 2022

Prevalence and relevant factors of micronutrient deficiencies in hospitalized patients with inflammatory bowel disease.

Nutrition 2022 Mar 31;99-100:111671. Epub 2022 Mar 31.

Department of Gastroenterology, Shanghai East Hospital, Medicine School of Tongji University, Shanghai, China; Department of Gastroenterology, Ji'an Hospital, Shanghai East Hospital, Ji'an, Jiangxi, China. Electronic address:

Objectives: Micronutrient deficiencies are common in hospitalized patients with inflammatory bowel disease (IBD). We aimed to investigate the prevalence of micronutrient deficiencies, and explore relevant factors in hospitalized patients with IBD.

Methods: A total of 52 hospitalized patients with IBD were included. Overall malnutrition and quality of life were evaluated with questionnaires, and micronutrient deficiencies were evaluated with serologic indices. Univariate and bivariate analyses were performed, and regression was applied to explore factors associated with micronutrient deficiencies.

Results: The most common micronutrient deficiency was 25-hydroxyvitamin D3 (25[OH]D; 76.9%). Folate deficiency was more common in recently diagnosed than in previously diagnosed patients (37.0% vs. 8.0%; P = 0.013), but iron deficiency was the opposite (29.6% vs. 60.0%; P = 0.028). 25(OH)D interacted with folate (r = 0.292; P = 0.036), vitamin B12 (r = 0.292; P = 0.035), and calcium (r = 0.415; P = 0.002), and ferritin interacted with folate (r = -0.288; P = 0.038) and magnesium (r = -0.333; P = 0.016). Calcium-deficient patients had longer hospital stays than those with normal calcium levels (P = 0.016). Low 25(OH)D levels increased the risk of overall malnutrition (odds ratio [OR]: 0.866; 95% confidence interval [CI], 0.744-0.982; P = 0.025), and low ferritin and calcium suggested a poorer quality of life (P = 0.043 and 0.011, respectively). In addition, hemoglobin (OR: 0.930; 95% CI, 0.870-0.993; P = 0.034) and folate (OR: 0.708; 95% CI, 0.545-0.922; P = 0.037) were independent protective factors against 25(OH)D deficiency.

Conclusions: Hospitalized patients with IBD were at risk of multiple micronutrient deficiencies, even those with a recent diagnosis or in remission. There were interactions between micronutrients and nutritional indices. Early identification and correction of micronutrient deficiency, as well as relevant factors, may improve clinical outcomes.
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http://dx.doi.org/10.1016/j.nut.2022.111671DOI Listing
March 2022

miR-626 Inhibition Enhanced the Radiosensitivity to Oral Squamous Cell Carcinoma via the Downregulation of Nuclear Factor Kappa-B Signaling.

Cancer Biother Radiopharm 2022 May 12. Epub 2022 May 12.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medical Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, P.R. China.

The effect of miR-626 on the radiosensitivity to oral squamous cell carcinoma (OSCC) was evaluated in this study. The level of miR-626 in OSCC patients was determined by analyzing the data of miRNA microarray GSE113956. miR-626 was overexpressed by miR-626 mimics and knockdown were performed by miR-626 inhibitor. The level of miR-626 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were used to detect the effect of miR-626 on the growth of OSCC cells. Flow cytometry was used to detect the apoptosis of OSCC cells. Western blot and dual luciferase reporter assays were used to explore the underlying mechanism of miR-626 regulating the radiosensitivity to OSCC. The effect of miR-626 on the radiosensitivity to OSCC were examined in an xenograft model. The serum miR-626 level of OSCC patients was significantly higher than that of healthy controls. miR-626 mimics significantly promoted the OSCC cell growth, but the miR-626 inhibitor significantly suppressed the OSCC cell growth. Radiation combined with the miR-626 inhibitor significantly suppressed the cell proliferation and promoted the apoptosis of SCC-4 and HSC4 cells. Moreover, miR-626 regulates the nuclear factor kappa-B (NF-κB) signaling mediated by TRAF-interacting protein with forkhead-associated domain B. Furthermore, inhibition of miR-626 enhances the radiosensitivity to OSCC in nude mice. miR-626 inhibition enhanced the radiosensitivity to OSCC through the downregulation of NF-κB signaling.
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http://dx.doi.org/10.1089/cbr.2021.0344DOI Listing
May 2022

Hsa_circ_0000345 inhibits cell proliferation, migration and invasion of nasopharyngeal carcinoma cells via miR-513a-3p/PTEN axis.

J Physiol Sci 2022 May 12;72(1):10. Epub 2022 May 12.

Department of Otorhinolaryngology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, No 195 Tongbai Road, Zhengzhou, 450007, China.

Background: Hsa_circ_0000345 has been reported to be down-regulated in nasopharyngeal carcinoma (NPC). Whether hsa_circ_0000345 can exert antitumor effect in NPC remains unclear. This study aimed to investigate the possible biological role of hsa_cic_0000345 in suppressing the progression of NPC.

Methods: Hsa_circ_0000345 expression was detected in normal nasopharynx epithelial cells (NP69) and NPC cell lines (SUNE1, HONE1, 6-10B and HNE1). The influence of hsa_circ_0000345 on cell proliferation, migration and invasion of NPC cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays. Quantitative real-time PCR and western blot were performed to examine gene and protein expression, respectively. Luciferase reporter assay was carried out to verify the relationship among hsa_circ_0000345, miR-513a-3p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN).

Results: Compared with NP69 cells, hsa_circ_0000345 was down-regulated in NPC cells. Moreover, hsa_circ_0000345 overexpression repressed cell proliferation, migration and invasion of SUNE1 cells, whereas hsa_circ_0000345 knockdown promoted cell proliferation, migration and invasion of 6-10B cells. Furthermore, hsa_circ_0000345 promoted PTEN expression by sponging miR-513a-3p. Both miR-513a-3p overexpression and PTEN knockdown promoted cell proliferation, migration and invasion of SUNE1 cells, which were effectively abolished by hsa_circ_0000345 up-regulation.

Conclusion: Hsa_circ_0000345 inhibits cell proliferation, migration and invasion of NPC cells via miR-513a-3p/PTEN axis, thereby suppressing the progression of NPC. Thus, this work suggests that hsa_circ_0000345 may be a potential biomarker for diagnosis and treatment of NPC.
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http://dx.doi.org/10.1186/s12576-022-00834-4DOI Listing
May 2022

Activation of the N-methyl-D-aspartate receptor contributes to orofacial neuropathic and inflammatory allodynia by facilitating calcium-calmodulin-dependent protein kinase II phosphorylation in mice.

Brain Res Bull 2022 May 7;185:174-192. Epub 2022 May 7.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Neuropathic and inflammatory pain are major clinical challenges due to their ambiguous mechanisms and limited treatment approaches. N-methyl-D-aspartate receptor (NMDAR) and calcium-calmodulin-dependent protein kinase II (CaMKII) are responsible for nerve system sensation and are required for the induction and maintenance of pain. However, the roles of NMDAR and CaMKII in regulating orofacial pain are still less well known. Here, we established a neuropathic pain model by transecting a mouse inferior alveolar nerve (IAN) and an inflammatory pain model by injecting complete Freunds adjuvant (CFA) into its whisker pad. The Cre/loxp site-specific recombination system was used to conditionally knock out (KO) NR2B in the trigeminal ganglion (TG). Von Frey filament behavioral tests showed that IANX and CFA-induced mechanical allodynia were altered in NR2B-deficient mice. CFA upregulated CaMKIIα and CaMKIIβ in the mouse TG and spinal trigeminal caudate nucleus (SpVc). CaMKIIα first decreased and then increased in the TG after IANX, and CaMKIIβ decreased in the TG and SpVc. CFA and IANX both greatly enhanced the expression of phospho (p)-NR2B, p-CaMKII, cyclic adenosine monophosphate (cAMP), p-ERK, and p-cAMP response element binding protein (CREB) in the TG and SpVc. These neurochemical signal pathway alterations were reversed by the conditional KO of NR2B and inhibition of CaMKII. Similarly, IANX- and CFA-related behavioral alterations were reversed by intra-ganglionic (i.g.) -application of inhibitors of CaMKII, cAMP, and ERK. These findings revealed novel molecular signaling pathways (NR2B-CaMKII-cAMP-ERK-CREB) in the TG- and SpVc-derived latent subsequent peripheral and spinal central sensitization under nerve injury and inflammation, which might be beneficial for the treatment of orofacial allodynia.
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http://dx.doi.org/10.1016/j.brainresbull.2022.05.003DOI Listing
May 2022

The Ameliorative Effect of Mahuang Fuzi and Shenzhuo Decoction on Membranous Nephropathy of Rodent Model is Associated With Autophagy and Wnt/β-Catenin Pathway.

Front Pharmacol 2022 21;13:820130. Epub 2022 Apr 21.

Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

The increased incidence of membranous nephropathy (MN) has made it the most common pathological type of primary nephrotic syndrome in adults in China. According to the theory of Traditional Chinese Medicine (TCM), Mahuang Fuzi (Chinese ephedra and Radix Aconiti Lateralis Preparata) and Shenzhuo Decoction (MFSD) could be used to treat such diseases. We treated patients of MN with MFSD, and observed comparable efficacy to glucocorticoid and/or immunosuppressants. In this study, we observed the therapeutic effect of MFSD on the rat model of passive Heymann nephritis (PHN), a classical MN model. Our results showed that MFSD treatment significantly reduced urinary protein level and podocyte injury in PHN rats, and correspondingly improved renal pathology, with the improvement effect on MN comparable to that of Cyclosporine A (CsA) alone. To explore the potential therapeutical mechanism of MFSD, the main chemical components of MFSD were determined by High-performance liquid chromatography-mass spectrometry (HPLC-MS). There were about 30 active components of MFSD. Next, based on network pharmacology methods, we screened related targets of MSFD on MN, which provided a preliminary understanding of the MFSD bioactive compounds. The clustering analysis showed that its active site might be in the autophagy-related protein and Wnt/β-catenin pathway, which was related to podocyte injury. Finally, we observed an improvement in renal autophagy and a down-regulation of the Wnt/β-catenin pathway after MSFD treatment in a PHN rat model. According to this study, autophagy and Wnt/β-catenin pathway may be potential targets for MFSD in the treatment of MN.
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http://dx.doi.org/10.3389/fphar.2022.820130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068930PMC
April 2022

Expression of Cre recombinase in chondrocytes causes abnormal craniofacial and skeletal development.

Transgenic Res 2022 Jun 8;31(3):399-411. Epub 2022 May 8.

Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave, Ann Arbor, MI, 48109, USA.

The cranial base synchondroses are growth centers that drive cranial and upper facial growth. The intersphenoid synchondrosis (ISS) and the spheno-occipital synchondrosis (SOS) are two major synchondroses located in the middle of the cranial base and are maintained at early developmental stages to sustain cranial base elongation. In this study, we report unexpected premature ossification of ISS and SOS when Cre recombinase is activated in a chondrocyte-specific manner. We used a Cre transgenic line expressing Aggrecan enhancer-driven, Tetracycline-inducible Cre (ATC), of which expression is controlled by a Col2a1 promoter. Neonatal doxycycline injection or doxycycline diet fed to breeders was used to activate Cre recombinase. The premature ossification of ISS and/or SOS led to a reduction in cranial base length and subsequently a dome-shaped skull. Furthermore, the mice carrying either heterozygous or homozygous conditional deletion of Tsc1 or Fip200 using ATC mice developed similar craniofacial abnormalities, indicating that Cre activity itself but not conditional deletion of Tsc1 or Fip200 gene, is the major contributor of this phenotype. In contrast, the Col2a1-Cre mice carrying Cre expression in both perichondrium and chondrocytes and the mice carrying the conditional deletion of Tsc1 or Fip200 using Col2a1-Cre did not manifest the same skull abnormalities. In addition to the defective craniofacial bone development, our data also showed that the Cre activation in chondrocytes significantly compromised bone acquisition in femur. Our data calls for the consideration of the potential in vivo adverse effects caused by Cre expression in chondrocytes and reinforcement of the importance of including Cre-containing controls to facilitate accurate phenotype interpretation in transgenic research.
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http://dx.doi.org/10.1007/s11248-022-00308-8DOI Listing
June 2022

Vasorelaxant effect of curcubisabolanin A isolated from Curcuma longa through the PI3K/Akt/eNOS signaling pathway.

J Ethnopharmacol 2022 May 5;294:115332. Epub 2022 May 5.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Ethnopharmacological Relevance: Curcuma longa L. (Zingiberaceae) is a known blood-activating and stasis-removing traditional Chinese medicine and has relevant pharmacological properties. The rhizomes of C. longa have been used for the treatment of cardiovascular disease (CVD) in China. Previous studies have shown that sesquiterpenoids from C. longa have significant vasorelaxant effects, which are closely associated with the prevention and treatment of CVD.

Aim Of The Study: To explore the sesquiterpenoids with vasorelaxant effects from C. longa and investigate the underlying mechanisms.

Materials And Methods: The compound was isolated from C. longa by multiple chromatography technologies. Its structure was determined by extensive spectroscopic analyses, nuclear magnetic resonance (NMR) data calculations, electronic circular dichroism (ECD) data calculations, and optical rotation (OR) data calculations. The vasorelaxant effect of the isolated compound was evaluated by KCl- or phenylephrine (PHE)-inducing contraction of the rat thoracic aortic rings. Endothelial removal and L-NAME pretreatment experiments were used to verify the endothelium-dependent vasorelaxant effect of the isolated compound in rat thoracic aortic rings. NO production was monitored in human umbilical vein endothelial cells (HUVECs). Western blot was carried out in HUVECs to elucidate the potential mechanisms.

Results: A new bisabolane-type sesquiterpenoid, curcubisabolanin A [(+)-(1S,7S,9E)-bisabola-2(3),4(15),9(10)-trien-11-ol], was isolated from the rhizomes of C. longa. curcubisabolanin A exhibited endothelium-dependent relaxation on rat thoracic aortic rings, while pre-treatment of intact aortic rings with an eNOS inhibitor (L-NAME) attenuated the vasorelaxant response of curcubisabolanin A. In addition, curcubisabolanin A induced intracellular NO production and significantly increased the levels of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), and phosphorylated eNOS (p-eNOS) in HUVECs. LY294002 (a blocker of PI3K) and MK-2206 (a highly selective inhibitor of Akt) significantly decreased these effects of curcubisabolanin A.

Conclusions: These findings demonstrated that the vasorelaxant effect of curcubisabolanin A was partially endothelium-dependent and was related to regulation of NO production in vascular endothelial cells through the PI3K/Akt/eNOS signaling pathway.
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http://dx.doi.org/10.1016/j.jep.2022.115332DOI Listing
May 2022

Modified Protocol for Establishment of Intracranial Arterial Dolichoectasia Model by Injection of Elastase Into Cerebellomedullary Cistern in Mice.

Front Neurol 2022 18;13:860541. Epub 2022 Apr 18.

School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China.

Background And Purpose: This study aimed to construct an animal model of intracranial arterial dolichoectasia (IADE) applying the modified modeling protocol.

Materials And Methods: Twenty five milliunits elastase and inactivated elastase were, respectively, injected into the cerebellomedullary cistern of 60 C57/BL6 mice which were divided into experimental group (EG, = 30) and control group (CG, = 30) by using a computer-based random order generator. The modified modeling protocol clarified these aspects including brain three-dimensional parameters of mouse head fixation, angle of head inclination, fixed position of taper ear, needle holding technique, needle entry depth, prevention of liquid drug back flow, and storage conditions of elastase. And it was observed for the following parts such as mortality, inflammatory factors, craniocerebral arteries scanning, vascular tortuosity index, artery diameter, pathology of the cerebrovascular.

Results: Within differently surveyed stage, the total mortality of mice in EG was 20%. ELISA illustrated that the levels of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor α (TNF-α) in peripheral blood were increased significantly after modeling. Angiography indicated that 100% of IADE in EG were observed and the diameter and tortuosity index of the basilar artery were significantly increased ( < 0.01). EVG histological processing and staining showed the disrupted internal elastic lamina, the atrophied muscle layer, and the hyalinized connective tissue of the basilar artery with the vascular wall tunica media in EG. Micro-computed tomography reported that the craniocerebral arteries of the mice in EG were outstandingly elongated, tortuous, and dilated.

Conclusion: The modified modeling protocol can reduce the mortality, improve the success rate, and provide a stable animal model for IADE.
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http://dx.doi.org/10.3389/fneur.2022.860541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062172PMC
April 2022

Atrial cardiomyopathy markers and new-onset atrial fibrillation risk in patients with acute myocardial infarction.

Eur J Intern Med 2022 May 2. Epub 2022 May 2.

Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, No.193, Lianhe Road, Dalian, Liaoning 116000, China. Electronic address:

Background: New-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is common and independently correlated with poor prognosis. The purpose of this study is to explore whether atrial cardiomyopathy (ACM) markers improve NOAF risk assessment and contribute to therapy decision-making to improve prognosis.

Methods: We retrospectively analyzed 4713 patients with AMI without a documented history of atrial fibrillation (AF). We measured markers of ACM including P-wave terminal force in ECG lead V1 (PTFV1), Left atrial dimension (LAD), and B-type natriuretic peptide (BNP). Patients were stratified into tertiles of PTFV1, LAD, and BNP levels. Associations between markers and NOAF were evaluated using logistic regression analysis.

Results: Overall, 222 (4.71%) patients had NOAF out of 4713 patients. The prevalence of NOAF increased gradually with PTFV1, LAD, and BNP tertiles. On multivariable regression analysis with potential confounders, elevated PTFV1, LAD, and BNP markers were significantly associated with an increased risk of NOAF. The addition of PTFV1, LAD, and BNP to the AF risk factors recommended by the 2020 ESC Guidelines significantly improved risk discrimination for NOAF.

Conclusion: Atrial cardiomyopathy markers including PTFV1, LAD, and BNP were strongly associated with NOAF after AMI. The prediction performance of the clinical model for NOAF was increased by the addition of these markers.
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http://dx.doi.org/10.1016/j.ejim.2022.04.019DOI Listing
May 2022

Effect of Pore Size of Porous-Structured Titanium Implants on Tendon Ingrowth.

Appl Bionics Biomech 2022 25;2022:2801229. Epub 2022 Apr 25.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China.

Purpose: The reconstruction of a tendon insertion on metal prostheses is a challenge in orthopedics. Of the available metal prostheses, porous metal prostheses have been shown to have better biocompatibility for tissue integration. Therefore, this study is aimed at identifying an appropriate porous structure for the reconstruction of a tendon insertion on metal prostheses.

Methods: Ti6Al4V specimens with a diamond-like porous structure with triply periodic minimal surface pore sizes of 300, 500, and 700 m and a porosity of 58% (designated Ti300, Ti500, and Ti700, respectively) were manufactured by selective laser melting and were characterized with micro-CT and scanning electron microscopy for their porosity, pore size, and surface topography. The porous specimens were implanted into the patellar tendon of rabbits. Tendon integration was evaluated after implantation into the tendon at 4, 8, and 12 weeks by histology, and the fixation strength was evaluated with a pull-out test at week 12.

Results: The average pore sizes of the Ti300, Ti500, and Ti700 implants were 261, 480, and 668 m, respectively. The Ti500 and Ti700 implants demonstrated better tissue growth than the Ti300 implant at weeks 4, 8, and 12. At week 12, the histological score of the Ti500 implant was 13.67 ± 0.58, and it had an area percentage of type I collagen of 63.90% ± 3.41%; both of these results were significantly higher than those for the Ti300 and Ti700 implants. The pull-out load at week 12 was also the highest in the Ti500 group.

Conclusion: Ti6Al4V implants with a diamond-like porous structure with triply periodic minimal surface pore size of 500 m are suitable for tendon integration.
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http://dx.doi.org/10.1155/2022/2801229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061050PMC
April 2022

Photoelectrochemical oxygen evolution with interdigitated array electrodes: the example of TiO.

Nanotechnology 2022 May 17;33(32). Epub 2022 May 17.

International Research Center for Renewable Energy, State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, 28 West Xianning Road, Xi'an, Shaanxi 710049, People's Republic of China.

The catalytic reactions of photoelectrochemical water splitting attracts tremendous attention as a promising strategy for clean energy production. And the research on reaction mechanism is particularly important in design and developing new catalysts. In this work, the special electrochemical tool of interdigitated array (IDA) electrodes was utilized in investigating the photoelectrochemical oxygen evolution reaction process and detecting the reaction productwith the generation-collection mode. TiOwas taken as a model catalyst and was decorated onto the IDA generator electrode through an electrophoresis method, so that the photoelectrochemical water splitting can take place on the IDA generator and the reaction product can be detected directly with the IDA collector in real time. It is found that TiOcan be successfully decorated onto the surface of IDA electrode with the expected photoelectrochemical activity, and the generation-collection mode reveals and distinguishes the production of Ofrom the overall photoelectrochemical current on TiOgenerator. The mass transfer process of Ofrom the TiOgenerator to the collector could be observed as well. Large overall current at high potential range indicates the possible increasing production of the byproducts or nonfaradaic current.
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http://dx.doi.org/10.1088/1361-6528/ac6c33DOI Listing
May 2022

Suberoylanilide hydroxamic acid suppresses axonal damage and neurological dysfunction after subarachnoid hemorrhage via the HDAC1/HSP70/TDP-43 axis.

Exp Mol Med 2022 May 2. Epub 2022 May 2.

Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, Changsha, China.

Increased focus has been placed on the role of histone deacetylase inhibitors as crucial players in subarachnoid hemorrhage (SAH) progression. Therefore, this study was designed to expand the understanding of SAH by exploring the downstream mechanism of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in SAH. The expression of TDP-43 in patients with SAH and rat models of SAH was measured. Then, western blot analysis, immunofluorescence staining, and transmission electron microscope were used to investigate the in vitro effect of TDP-43 on a neuronal cell model of SAH established by oxyhemoglobin treatment. Immunofluorescence staining and coimmunoprecipitation assays were conducted to explore the relationship among histone deacetylase 1 (HDAC1), heat shock protein 70 (HSP70), and TDP-43. Furthermore, the in vivo effect of HDAC1 on SAH was investigated in rat models of SAH established by endovascular perforation. High expression of TDP-43 in the cerebrospinal fluid of patients with SAH and brain tissues of rat models of SAH was observed, and TDP-43 accumulation in the cytoplasm and the formation of inclusion bodies were responsible for axonal damage, abnormal nuclear membrane morphology, and apoptosis in neurons. TDP-43 degradation was promoted by the HDAC1 inhibitor SAHA via the acetylation of HSP70, alleviating SAH, and this effect was verified in vivo in rat models. In conclusion, SAHA relieved axonal damage and neurological dysfunction after SAH via the HSP70 acetylation-induced degradation of TDP-43, highlighting a novel therapeutic target for SAH.
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http://dx.doi.org/10.1038/s12276-022-00761-9DOI Listing
May 2022

Prognostic Value of Heterogeneity Index Derived from Baseline F-FDG PET/CT in Mantle Cell Lymphoma.

Front Oncol 2022 14;12:862473. Epub 2022 Apr 14.

Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.

Objectives: Mantle cell lymphoma (MCL) represents a group of highly heterogeneous tumors, leading to a poor prognosis. Early prognosis prediction may guide the choice of therapeutic regimen. Thus, the purpose of this study was to investigate the potential application value of heterogeneity index (HI) in predicting the prognosis of MCL.

Methods: A total of 83 patients with histologically proven MCL who underwent baseline fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) were retrospectively enrolled. The clinicopathologic index and PET/CT metabolic parameters containing maximum and mean standard uptake value (SUV and SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and HI were evaluated. Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal cutoff values of the parameters for progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression were used to assess relationships between risk factors and recurrence. Kaplan-Meier plots were applied for survival analyses.

Results: In univariate analyses, age [HR = 2.51, 95% CI = 1.20-5.24, = 0.041 for body weight (BW)] and HI-BW (HR = 4.17, 95% CI = 1.00-17.38, = 0.050) were significantly correlated with PFS. In multivariate analyses, age (HR = 2.61, 95% CI = 1.25-5.47, = 0.011 for BW) and HI-BW (HR = 4.41, 95% CI = 1.06-18.41, = 0.042) were independent predictors for PFS, but not for OS. B symptoms (HR = 5.00, 95% CI = 1.16-21.65, = 0.031 for BW) were an independent prognostic factor for OS, but not for PFS. The other clinicopathologic index and PET/CT metabolic parameters were not related to outcome survival in MCL.

Conclusion: The age and HI derived from baseline PET/CT parameters were significantly correlated with PFS in MCL patients.
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http://dx.doi.org/10.3389/fonc.2022.862473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047855PMC
April 2022

Influential Factors, Treatment and Prognosis of Autoimmune Encephalitis Patients With Poor Response to Short-Term First-Line Treatment.

Front Neurol 2022 14;13:861988. Epub 2022 Apr 14.

Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Objective: This study was performed to assess the potential factors for poor short-term first-line treatment response, the appropriate further treatment options, and the prognosis in patients with autoimmune encephalitis (AE).

Methods: This retrospective study consisted of 135 patients with AE. According to their short-term first-line treatment response, patients were divided into the response group and the non-response group. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and outcomes of patients were compared between the two groups. Univariate and multivariate logistic regression models were used to analyze whether non-responders have poor long-term outcomes. Further treatment and prognosis of non-responders were also analyzed.

Results: Of the 128 patients who were treated with first-line immunotherapy, 59 (46.1%) were non-responders. Patients in the non-response group had more symptoms and exhibited a higher proportion of mental behavior disorder, central hypoventilation, and autonomic nervous dysfunction. The modified Rankin scale (mRS) scores and neutrophil-to-lymphocyte ratio (NLR) levels were significantly higher and albumin, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (apoA) levels were significantly lower in the non-response group ( < 0.05, all). Multivariate logistic regression analysis showed that the number of clinical symptoms, mental behavior disorder, central hypoventilation, maximum mRS score, and albumin level was independently associated with non-response to short-term first-line treatment. Non-responders had poor long-term outcomes compared with the responders at all times of followed-up ( < 0.05, all). In multivariable analysis, initial first-line treatment response was independently associated with the long-term prognosis, both at 12-month [odds ratio (OR), 4.74, 95% CI, 1.44-15.59, and =0.010] and 24-month follow-ups (OR, 8.81, 95% CI, 1.65-47.16; and = 0.011). Among the non-responders, a higher improvement of mRS scores was observed in those who received second-line treatment than those who had no further treatment or repetition of first-line immunotherapy in the follow-up. However, the rate of a good outcome and median mRS scores were not significantly different among the three groups.

Conclusion: Disease severity, clinical features, anti-N-methyl-D-aspartate receptor subtypes, antibody titers, NLR, albumin, HDL-C, and apoA levels were all associated with non-response to short-term first-line treatment. The short-term first-line treatment response is a valuable predictor of long-term outcomes in patients with AE. Second-line immunotherapy may be a more aggressive treatment option for patients who failed short-term first-line immunotherapy.
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http://dx.doi.org/10.3389/fneur.2022.861988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046540PMC
April 2022

Mining and characterization of oxidative stress-related binding proteins of parthenolide in Xanthomonas oryzae pv. oryzae.

Pest Manag Sci 2022 May 1. Epub 2022 May 1.

The Jiangsu Provincial Platform for Conservation and Utilization of Agricultural Germplasm, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China.

Background: Lack of control agents and development of bacterial resistance are emergent problems in the chemical control of rice bacterial blight, therefore novel bactericides against Xanthomonas oryzae pv. oryzae (Xoo, the causal agent of rice bacterial blight) are urgently needed. We previously found that parthenolide (PTL) is a potential lead against Xoo, and PTL inhibits Xoo growth via oxidative stress. However, the mechanism of action of PTL against Xoo needs further elucidation.

Results: In this study, a biotinylated PTL probe was synthesized, and two important subunits in the respiratory chain (NuoF of complex I and SdhB of complex II) of Xoo were captured with the probe and identified with liquid chromatography tandem mass spectrometry (LC-MS/MS). The binding between them was verified with pull-down and drug affinity responsive target stability technologies. In addition, purified proteins of NuoF and SdhB greatly lowered the antibacterial activity of PTL, and PTL evidently inhibited the enzyme activities of complexes I and II. Moreover, knockout of nuoF and sdhB in Xoo caused elevated reactive oxygen species (ROS) levels and increased sensitivity to PTL. Furthermore, molecular simulations indicated that PTL may form covalent bonds with Cys105 and Cys187 in NuoF and Cys106 in SdhB.

Conclusion: PTL can directly bind to NuoF and SdhB, which impairs the enzyme functions of complexes I and II in the respiratory chain, leading to ROS accumulation in Xoo. This study will provide deep insight into the mechanism of action of PTL against Xoo. © 2022 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6961DOI Listing
May 2022

Automated synthesis of (R)-[ F]MH.MZ on the iPhase Flexlab reaction platform.

J Labelled Comp Radiopharm 2022 May 1. Epub 2022 May 1.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.

(R)-[ F]MH.MZ ([ F]MH.MZ) is a promising positron emission tomography (PET) radiotracer for in vivo study of the 5-HT receptor. To facilitate clinical trials, a fully automated radiosynthesis procedure for [ F]MH.MZ was developed using commercially available materials on the iPhase Flexlab module. The overall synthesis time was 100 min with a radiochemical yield of 7 ± 0.9% (n = 3). The radiochemical purity was greater than 99% for [ F]MH.MZ with a molar activity of 361 ± 57 GBq/μmol (n = 3). The protocol described herein reliably provides [ F]MH.MZ that meets all relevant release criteria for a GMP radiopharmaceutical.
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http://dx.doi.org/10.1002/jlcr.3975DOI Listing
May 2022

Time series RNA-seq analysis identifies MAPK10 as a critical gene in diabetes mellitus-induced atrial fibrillation in mice.

J Mol Cell Cardiol 2022 Apr 27;168:70-82. Epub 2022 Apr 27.

Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, China.. Electronic address:

Atrial fibrillation (AF) is a major complication of type 2 diabetes mellitus (T2DM) and plays critical roles in the pathogenesis of atrial remodeling. However, the differentially expressed genes in atria during the development of AF induced by hyperglycemia have rarely been reported. Here, we showed time-dependent increased AF incidence and duration, atrial enlargement, inflammation, fibrosis, conduction time and action potential duration in db/db mice, a model of T2DM. RNA sequencing analysis showed that 2256 genes were differentially expressed in the atria at 12, 14 and 16 weeks. Gene Ontology analysis showed that these genes participate primarily in cell adhesion, cellular response to interferon-beta, immune system process, positive regulation of cell migration, ion transport and cellular response to interferon-gamma. Analysis of significant pathways revealed the IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway, chemokine signaling pathway, and cAMP receptor signaling. Additionally, these differentially expressed genes were classified into 50 profiles by hierarchical clustering analysis. Twelve of these profiles were significant and comprised 1115 genes. Gene coexpression network analysis identified that mitogen-activated protein kinase 10 (MAPK10) was localized in the core of the gene network and was the most highly expressed gene at different time points. Knockdown of MAPK10 markedly attenuated DM-induced AF incidence, atrial inflammation, fibrosis, electrical disorder and apoptosis in db/db mice. In summary, the present findings revealed that many genes are involved in DM-induced AF and that MAPK10 plays a central role in this disease, indicating that strategies targeting MAPK10 may represent a potential therapeutic approach to treat DM-induced AF.
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http://dx.doi.org/10.1016/j.yjmcc.2022.04.013DOI Listing
April 2022

Analgesic effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine after open gastrointestinal tumor surgery: a retrospective study.

BMC Anesthesiol 2022 04 29;22(1):130. Epub 2022 Apr 29.

Department of Anesthesiology, Institute of Neurological Disease, West China Hospital, Sichuan University, No. 37 Guoxue lane, Chengdu, 610041, Sichuan, China.

Background: To investigated the effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine for patient-controlled intravenous analgesia (PCIA) on patients after open gastrointestinal tumor surgery, and compared this combination with traditional PCIA with pure opioids or epidural analgesia (PCEA).

Methods: Patients (n = 640) who underwent open gastrointestinal tumor surgery and received patient-controlled analgesia (PCA) were included. According to the type of PCA, patients were assigned to three groups: MPCIA (PCIA with sufentanil, flurbiprofen axetil, dexmedetomidine and metoclopramide), OPCIA (PCIA with sufentanil, tramadol and metoclopramide) and PCEA group (PCEA with sufentanil and ropivacaine). The characteristics of patients, intraoperative use of analgesics, postoperative visual analogue scale (VAS), postoperative adverse reactions and postoperative recovery were collected. The primary outcome was postoperative VAS score. One-way ANOVA, Kruskal-Wallis H test, Fisher exact probability method, and binary logistic regression analysis were used for analysis.

Results: There were no significant differences in the characteristics of patients, operation time, tumor site and the use of postoperative rescue analgesics among the groups. In the first two days after open gastrointestinal tumor surgery, the VAS (expressed by median and interquartile range) of MPCIA (24 h, resting: 1,1; movement: 3,2. 48 h, resting: 0,1; movement: 2,1.) and PCEA (24 h, resting: 0,1; movement: 2,1. 48 h, resting: 0,1; movement: 2,2.) groups were significantly lower than those of OPCIA group (24 h, resting: 2.5,2; movement: 4,2. 48 h, resting: 1.5,1.75; movement: 3,1.) (all p <  0.01). The incidence of postoperative nausea and vomiting in MPCIA group was 13.6% on the first day after surgery, which was significantly higher than that in PCEA group. There was no significant difference in the incidence of other postoperative adverse events. Higher intraoperative sufentanil dosage (OR (95%CI) = 1.017 (1.002-1.031), p = 0.021), lower body mass index (OR (95%CI) = 2.081 (1.059-4.089), p = 0.033), and tumor location above duodenum (OR (95%CI) = 2.280 (1.445-3.596), p <  0.001) were associated with poor postoperative analgesia.

Conclusions: The analgesic effects of PCIA with sufentanil in combination with flurbiprofen axetil and dexmedetomidine on postoperative analgesia was better than that of traditional pure opioids PCIA, and similar with that of PCEA.
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http://dx.doi.org/10.1186/s12871-022-01670-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052469PMC
April 2022

CRL4-DCAF8L2 E3 ligase promotes ubiquitination and degradation of BARD1.

Biochem Biophys Res Commun 2022 Jun 23;611:107-113. Epub 2022 Apr 23.

Department of Cell Biology, Peking University Health Science Center, Beijing, 100191, China. Electronic address:

BARD1 is a tumor suppressor that is necessary for the functioning and stability of BRCA1, with which it forms a heterodimer and participates in the repair of DNA double-strand breaks. The cellular level of BARD1 and its interaction with BRCA1 are crucial for BRCA1/BARD1 function in homologous recombination and tumor suppression. However, the regulatory mechanism underpinning the stability of BARD1 is largely unclear. In this study, we identified DCAF8L2, a DDB1-Cullin associated factor (DCAF) associated with CRL4 E3 ligase, as a negative regulator of BARD1. Mechanistically, DCAF8L2 interacts with and targets BARD1 for ubiquitination and degradation. In addition, the interaction of DCAF8L2 with BARD1 through the RING domain could compete with the dimerization of BRCA1 and BARD1, leading to increased cellular uncoupling of BARD1 and BRCA1, subjecting the latter to degradation. The overexpression of DCAF8L2 compromises the homologous recombination process and confers cells with increased sensitivity to DNA damage. Furthermore, DCAF8L2 was aberrantly expressed in breast cancer cell lines. Our findings suggest that DCAF8L2 may play an oncogenic role in the pathogenesis of breast cancer, possibly by negative regulation of BARD1.
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http://dx.doi.org/10.1016/j.bbrc.2022.04.100DOI Listing
June 2022
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