Publications by authors named "Zhipeng Li"

446 Publications

Chrysin alleviates lipopolysaccharide-induced neuron damage and behavioral deficits in mice through inhibition of Fyn.

Int Immunopharmacol 2022 Aug 10;111:109118. Epub 2022 Aug 10.

The Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. Electronic address:

Fyn, a non-receptor tyrosine kinase, plays an important role in microglial-mediated neuroinflammation and may serve as a candidate therapeutic target for neuropsychiatric diseases. In this study, we discovered that chrysin, a natural flavonoid compound, suppressed the activation of Fyn kinase and further alleviated neuroinflammation-induced neuron damage and behavior deficits. Functionally, chrysin improved lipopolysaccharide (LPS)-induced memory impairment and depressive behaviors in mice, it also protected against LPS-induced neuronal degeneration and loss and synaptic defects in mice. Our study demonstrated that chrysin inhibited the activation of microglia and reduced the expression of NLRP3 and IL-1β. Furthermore, our data indicated that chrysin blocked phosphorylation of Fyn and activation of NF-κB. Transfection with siRNA-Fyn validated that knockdown of Fyn partly abolished the inhibitory effect of chrysin on the expression of the NLRP3 inflammasome and NF-κB activation. Taken together, our findings revealed that chrysin alleviated LPS-induced neuron damage and behavioral deficits by inhibiting the expression of the NLRP3 inflammasome and NF-κB pathway, which might be mediated by inhibition of Fyn.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2022.109118DOI Listing
August 2022

Rupture-related quantitative hemodynamics of the supratentorial arteriovenous malformation nidus.

J Neurosurg 2022 Aug 12:1-10. Epub 2022 Aug 12.

1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing.

Objective: The hemodynamics of a brain arteriovenous malformation (AVM) nidus may be closely related to clinical presentation. The authors of this study aimed to explore the hemorrhagic quantitative hemodynamic indicators of the nidus through quantitative digital subtraction angiography (QDSA).

Methods: The quantitative hemodynamic parameters were generated from QDSA. Three data sets were used to explore independent quantitative hemodynamic indicators associated with AVM rupture. The training data set was exploited to discover independent quantitative hemodynamic indicators of AVM rupture by performing univariate and multivariate logistic regression analyses. The authors plotted receiver operating characteristic curves to validate the diagnostic performance of the hemorrhagic hemodynamic indicators using the training and two external validation data sets. Kaplan-Meier survival analysis was adopted to verify the predictive power of these risk indicators of future hemorrhage in the external prospective validation data set.

Results: A total of 151 patients were included in this study, 91 in the training set and 30 in each of the two validation sets. A higher stasis index and slower transnidal relative velocity (TRV) of the nidus were significantly correlated with AVM rupture. The areas under the curve (AUCs) of the stasis index (nidus) were 0.765 and 0.815 and those of the TRV (nidus) were 0.735 and 0.796, respectively, in the training and retrospective external validation sets. Kaplan-Meier survival analysis confirmed the validity of the stasis index and TRV in predicting future rupture risk in the prospective validation data set (p = 0.008 and 0.041, respectively, log-rank test).

Conclusions: A higher stasis index (nidus) and slower TRV (nidus) in QDSA were associated with AVM rupture and were effective indicators of future hemorrhage, suggesting that the core mechanisms underlying AVM rupture could be intravascular blood stasis and occlusive hyperemia of the nidus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2022.6.JNS212818DOI Listing
August 2022

Association between secondhand smoke and cancers in adults in the US population.

J Cancer Res Clin Oncol 2022 Aug 9. Epub 2022 Aug 9.

Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5 Haiyuncang Hutong, Dongcheng district, Beijing, China.

Background: Tobacco use is the leading preventable cause of cancer and premature death, smoking has a clear causal relationship with a variety of cancers. However, the relationship between exposure to secondhand smoke (SHS) and other cancers besides lung cancer is not clear. In this study, we intend to investigate the cancers mortality risks especially other cancers besides lung cancer associated with exposure to SHS.

Methods: The National Health and Nutrition Examination Survey is a longitudinal population-based, nationally representative health survey and mortality rates linked to the National Death Index (NDI) database. In this study, the participants completed a questionnaire assessing sociodemographic data, anthropometry, and lifestyle information, including smoking and alcohol consumption, meanwhile, all the participants were screened for serum cotinine. First, Spearman correlation analysis was performed to confirm the correlation between serum cotinine level and exposure status. And then, exposure to SHS was divided into two groups: low exposure group (serum cotinine level between 0.015 and 10) and high exposure group (serum cotinine level ≥ 10), Cox proportional hazards regression modeling was used to evaluate the association between exposure to SHS and eight different types of smoke-related cancer.

Results: In this study, we evaluated a cohort of 25,794 US residents older than 19 years from 2005 to 2016 and were followed for mortality through the February 2019. We conducted Spearman correlation analysis to confirm the correlation between serum cotinine level and exposure status (including smoking and exposure to SHS), it demonstrated the correlation coefficient between serum cotinine level and exposure to smoke was 0.976, p < 0.00001. By Cox proportional hazards regression modeling, high exposure group were found to be positively associated with all neoplasms with a total Hazard Ratio (HR) of 1.748 (95% Confidence Interval (CI), 1.415-2.159), had higher all-cause mortality risks than non-exposure to tobacco smoke. Regarding the specific types, we found the following associations: cancer of the lung (HR, 1.484; 95% CI, 1.191-1.849), stomach (HR, 1.491; 95% CI, 1.199-1.854), bladder (HR, 1.487; 95% CI, 1.198,1.846), esophageal (HR, 1.487; 95% CI 1.194-1.852), kidney (HR, 1.497; 95% CI, 1.201-1.865), pancreatic (HR, 1.479; 95% CI 1.189-1.841), leukemia (HR, 1.479; 95% CI 1.190-1.839), cervical (HR, 1.490; 95% CI 1.198-1.853). However, low exposure group were non-existent statistically significant with a Hazard Ratio (HR) of 1.062 (95% Confidence Interval (CI), 0.953-1.183).

Conclusions: The research demonstrated that serum cotinine has a significant correlation with smoke exposure status, which confirmed serum cotinine can be used as an indicator to reflect human smoke exposure. What's more, our results confirmed high exposure of SHS (serum cotinine level ≥ 10) has a significant effect on lung, stomach, bladder, esophagus, kidney, pancreatic, leukemia, cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-022-04266-wDOI Listing
August 2022

A bifunctional exolytic alginate lyase from Microbulbifer sp. ALW1 with salt activation and calcium-dependent catalysis.

Enzyme Microb Technol 2022 Aug 2;161:110109. Epub 2022 Aug 2.

College of Ocean Food and Biological Engineering, Jimei University, Xiamen 361021, China; Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen 361021, China; Research Center of Food Biotechnology of Xiamen City, Xiamen 361021, China. Electronic address:

Alginate lyases can depolymerize alginate to oligomers with potential applications in many fields. Here a new alginate lyase, namely AlgL6, was characterized from Microbulbifer sp. ALW1, phylogenetically classified into the polysaccharide lyase family 6 (PL6). The recombinant alginate lyase AlgL6 exerted enzymatic activities towards polymannuronate, polyguluronate, and sodium alginate in an exolytic manner. AlgL6 had an optimum temperature of 35 °C and good stability at 30 °C or below. Its optimum pH was 8.0, and it had good stability over the pH range of 5.0-9.0. AlgL6 exhibited excellent halo-stability against Na, and its activity can be increased up to about 1.8 times by 0.5 M NaCl. AlgL6 also showed strong stability in the presence of some nonionic detergents such as Tween 20 and Tween 80. The degradation products of sodium alginate by AlgL6 exhibited more effective antioxidant activities than the undigested polysaccharides. Structure analysis illustrated the catalytic mechanism defined by the coordination of the acid/base residues Arg269 and Lys248 of AlgL6. The replacement of Ca-interacting amino acid residues in AlgL6 and depletion of Ca suggested the involvement of Ca in the enzyme's catalytic activity. These properties of AlgL6 supply support to its industrial application for development of alginate bioresource.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.enzmictec.2022.110109DOI Listing
August 2022

Discovery of potential active ingredients of Er-Zhi-Wan, a famous traditional Chinese formulation, in model rat serum for treating osteoporosis with kidney-yin deficiency by UPLC-Q/TOF-MS and molecular docking.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Jul 28;1208:123397. Epub 2022 Jul 28.

School of Pharmacy, Nanjing University of Chinese Medicine & Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization & National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing, Jiangsu Province 210023, China. Electronic address:

Er-Zhi-Wan (EZW), a classical traditional Chinese formulation, has attracted more and more attention. This study was carried out to analyze the constituents of EZW absorbed into blood and find out the potential active ingredients for treating osteoporosis (OP) with kidney-yin deficiency (KYD). The rat model of OP with KYD was achieved by ovariectomies and using the mixture of thyroxine and reserpine. Then ultra-high performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer (UPLC-Q/TOF-MS) combined with statistical analysis was used to analyze the constituents of EZW absorbed into blood and differential components between the normal and OP with KYD rats. Finally, the components identified in OP with KYD rats were docked with targets of OP with KYD found in online databases. The results of molecular docking were adopted to find the potential active ingredients and further verified in vitro experiment. A total of 21 prototype compounds and 69 metabolites were identified in serum. Among them, 63 components in model rats and 50 components in normal rats were summarized, respectively. Most of the identified metabolites in serum of model rats were produced by hydrolysis, oxidation or glucuronidation, while in serum of normal rats were produced by hydrolysis, oxidation and methylation. According to the results of molecular docking, specnuezhenide, salidroside, tyrosol, echinacoside and verbascoside could be classified as potential active ingredients. The activity of salidroside and a metabolite was verified by pharmacodynamics analysis. In summary, UPLC-Q/TOF-MS system was combined with molecular docking to search the potential active ingredients from model rats of OP with KYD, which provided a new idea for the research on the pharmacodynamic material basis of other traditional medicine. Moreover, the result of this study lays the foundation for further study regarding the mechanism of EZW in treating OP with KYD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2022.123397DOI Listing
July 2022

NQO-1 Enzyme-Activated NIR Theranostic Agent for Pancreatic Cancer.

Anal Chem 2022 Aug 2. Epub 2022 Aug 2.

School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325035, China.

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, which is usually diagnosed in the advanced stage and is highly resistant to traditional chemotherapy, radiotherapy, and immunotherapy. Therefore, there is an urgent need for developing new PC-specific imaging and treatment. In this study, an quinone oxidoreductase 1 (NQO-1)-activated near-infrared (NIR) agent, , was synthesized. is almost nonemissive, while its NIR emission at 705 nm is triggered by NQO-1-induced reduction in the PC cells. In addition, the reduction product, , is specifically enriched in mitochondria and lysosomes and acts as an effective chemotherapeutic agent to selectively induce pancreatic cancer cell death the cell pyroptosis pathway. Further studies have shown that is suitable for imaging of clinical PC sections and solid tumors from patients. We expect this study will be helpful in the future for the design of targeted theranostic agents for PC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.2c01189DOI Listing
August 2022

Ammonia for post-healing of formamidinium-based Perovskite films.

Nat Commun 2022 Jul 29;13(1):4417. Epub 2022 Jul 29.

Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, P. R. China.

Solvents employed for perovskite film fabrication not only play important roles in dissolving the precursors but also participate in crystallization process. High boiling point aprotic solvents with O-donor ligands have been extensively studied, but the formation of a highly uniform halide perovskite film still requires the participation of additives or an additional step to accelerate the nucleation rate. The volatile aliphatic methylamine with both coordinating ligands and hydrogen protons as solvent or post-healing gas facilitates the process of methylamine-based perovskite films with high crystallinity, few defects, and easy large-scale fabrication as well. However, the attempt in formamidinium-containing perovskites is challenged heretofore. Here, we reveal that the degradation of formamidinium-containing perovskites in aliphatic amines environment results from the transimination reaction of formamidinium cation and aliphatic amines along with the formation of ammonia. Based on this mechanism, ammonia is selected as a post-healing gas for a highly uniform, compact formamidinium-based perovskite films. In particular, low temperature is proved to be crucial to enable formamidinium-based perovskite materials to absorb enough ammonia molecules and form a liquid intermediate state which is the key to eliminating voids in raw films. As a result, the champion perovskite solar cell based on ammonia post-healing achieves a power conversion efficiency of 23.21% with excellent reproducibility. Especially the module power conversion efficiency with 14 cm active area is over 20%. This ammonia post-healing treatment potentially makes it easier to upscale fabrication of highly efficient formamidinium-based devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-32047-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338283PMC
July 2022

Effect of Scan Pattern on the Accuracy of Complete-Arch Digital Implant Impressions with Two Intraoral Scanners.

Int J Oral Maxillofac Implants 2022 Jul-Aug;37(4):731-739

Purpose: To evaluate the effect of six scan patterns on the accuracy and speed of digital impressions with two different intraoral scanners for complete-arch implant rehabilitation.

Materials And Methods: A master model containing six parallelly placed implant analogs was fabricated, and six scan bodies were connected to the analogs. Reference scan was obtained with a laboratory scanner. Test scans were obtained by intraoral scanning with six scan patterns using 3Shape TRIOS 3 and Carestream CS 3600 intraoral scanners. Scanning time was recorded. Trueness and precision were assessed with an inspection software. Two-way analysis of variance (ANOVA) was performed to examine the effect of scan pattern, scanner, and their interaction on accuracy and scanning time. Differences between the six scan patterns with each scanner were tested by one-way ANOVA. Differences between the two scanners were evaluated by t test. The level of significance was set at α = .05.

Results: For trueness, the effects of scanner, scan pattern, and their interaction were significantly different in both linear and angular discrepancy. For precision, the scanner and scan pattern each had a significant effect on linear discrepancy independently, while their interaction did not. Only the effects of scanners were significantly different in angular discrepancy. For each of the two scanners, significant differences were detected in accuracy and speed between the patterns.

Conclusion: Scan pattern significantly influenced the accuracy and speed of digital impressions for complete-arch implant rehabilitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11607/jomi.9248DOI Listing
August 2022

Number 2 Feibi Recipe Ameliorates Pulmonary Fibrosis by Inducing Autophagy Through the GSK-3β/mTOR Pathway.

Front Pharmacol 2022 12;13:921209. Epub 2022 Jul 12.

Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Number 2 Feibi Recipe (N2FBR) is a traditional Chinese medicine formula for treating idiopathic pulmonary fibrosis. N2FBR inhibits HO-mediated oxidative stress damage in alveolar epithelial cells by increasing autophagy, as we previously demonstrated. However, it is unknown if similar mechanisms occur . We established a pulmonary fibrosis model by instilling bleomycin (BLM) from the airway to examine the effects of N2FBR on pulmonary fibrosis and investigate its probable mechanism in this work. We discovered that N2FBR treatment effectively alleviated interstitial fibrosis as well as collagen deposition, primarily in upregulating SOD, GSH-Px, T-AOC and downregulating MDA content. N2FBR also increased the expression of LC3B, Beclin-1, LAMP1, TFEB and downregulated the expression of p62, legumain. N2FBR treatment boosted the production of autophagosomes, according to the results of the TEM observation. Furthermore, we explored that N2FBR exerted its anti-oxidative stress and pro-autophagy effects via GSK-3β/mTOR signalling pathway. Therefore, these results provide further evidence for the protective effect of N2FBR in pulmonary fibrosis. Our findings could have ramifications for the development of antifibrosis therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.921209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315309PMC
July 2022

Long-term outcomes of Spetzler-Martin grade IV and V arteriovenous malformations: a single-center experience.

Neurosurg Focus 2022 Jul;53(1):E12

1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing.

Objective: This study aimed to explore whether intervention can benefit Spetzler-Martin (SM) grade IV-V arteriovenous malformations (AVMs).

Methods: Eighty-two patients with SM grade IV-V AVMs were retrospectively reviewed from 2015 to 2018. Patients were divided into two groups: those who received conservative management (22 cases [26.8%]) and intervention (60 cases [73.2%], including 21 cases of microsurgery, 19 embolization, and 20 hybrid surgery). Neurofunctional outcomes were assessed with the modified Rankin Scale (mRS). The primary outcome was long-term neurofunctional status, and the secondary outcomes were short-term neurofunctional status, long-term obliteration rate, seizure control, and risk of subsequent hemorrhage.

Results: Regarding the primary outcome, after an average of 4.7 years of clinical follow-up, long-term neurofunctional outcomes were similar after conservative management or intervention (absolute difference -0.4 [95% CI -1.5 to 0.7], OR 0.709 [95% CI 0.461-1.090], p = 0.106), whereas intervention had an advantage over conservative management for avoidance of severe disability (defined as mRS score > 3) (1.7% vs 18.2%, absolute difference 16.5% [95% CI -23.6% to 56.6%], OR 0.076 [95% CI 0.008-0.727], p = 0.025). Regarding the secondary outcomes, intervention was conducive to better seizure control (Engel class I-II) (70.0% vs 0.0%, absolute difference 70.0% [95% CI 8.6%-131.4%], p = 0.010) and avoidance of subsequent hemorrhage (1.4% vs 6.0%, absolute difference 4.6% [95% CI -0.4% to 9.6%], p = 0.030). In the subgroup analysis based on different intervention modalities, microsurgery and hybrid surgery achieved higher complete obliteration rates than embolization (p < 0.001), and hybrid surgery resulted in significantly less intraoperative blood loss than microsurgery (p = 0.041).

Conclusions: Intervention is reasonable for properly indicated SM grade IV-V AVMs because it provides satisfactory seizure control with decreased risks of severe disability and subsequent hemorrhage than conservative management. Clinical trial registration no.: NCT04572568 (ClinicalTrials.gov).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2022.4.FOCUS21648DOI Listing
July 2022

Hot Formability Study of Cr5 Alloy Steel by Integration of FEM and 3D Processing Maps.

Materials (Basel) 2022 Jul 9;15(14). Epub 2022 Jul 9.

School of Materials Science and Engineering, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang 471023, China.

Microstructure is an important factor that affects the mechanical properties and service life of forgings. Through the full study of the formability of the material, the internal microstructure of the material can be effectively controlled. In order to accurately describe the formability of materials during thermal processing, 3D hot processing maps containing strains were established in this paper, and the 3D hot processing maps were coupled with the finite element method for simulation calculation. The Cr5 alloy steel was subjected to unidirectional thermal compression at a strain rate of 0.005-5 s and temperature range of 900-1200 °C on a Gleeble-1500D thermal simulation machine, in order to obtain the date of true stress and strain. Based on the dynamic material model (DMM), the 3D processing maps of Cr5 alloy steel was established, and the 3D processing maps were associated with the analysis of microstructure evolution during hot deformation. The results show that the optimum thermal deformation conditions are as follows: temperature of 1000-1125 °C, strain rate of 0.01-0.2 s, and peak power dissipation of 0.41. The 3D processing maps were coupled with the finite element software FORGE to simulate the hot working process, and the distribution and change of power dissipation and flow instability domain on the metal deformation under different thermal deformation conditions were obtained. The comparison between the simulation results and metallographic images of typical regions of metal deformation shows that they are in good agreement. This method can effectively predict and analyze the formability of materials during hot processing and provide guidance for practical industrial production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma15144801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320613PMC
July 2022

RNA-Seq Reveals the Underlying Molecular Mechanism of First Cleavage Time Affecting Porcine Embryo Development.

Genes (Basel) 2022 Jul 15;13(7). Epub 2022 Jul 15.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530004, China.

The selection and evaluation of high-quality embryos are the key factors affecting in vitro embryo development and pregnancy outcome. The timing of first embryonic cleavage has been considered a positive indicator of the in vitro developmental potential of embryos, while the underlying molecular mechanism is still not fully understood. In this study, the embryos generated by parthenogenetic activation (PA) or in vitro fertilization (IVF) were monitored and recorded every 2 h and divided into two groups (early cleavage or late cleavage) based on the cleavage rate and blastocyst formation data. RNA sequencing was used to analyze the gene expression pattern of the embryos. We identified 667 and 71 different expression genes (DEGs) in early cleavage and late cleavage porcine PA and IVF embryos, respectively. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs are mainly enriched in pathways concerning the proteasome, DNA repair, cell cycle arrest, autophagy, and apoptosis, suggesting that severe endoplasmic reticulum stress (ERS) and DNA damage may be the key factors that led to the low development potential of late cleavage embryos. This study provides a theoretical basis for the following application and offers important information about the understanding of the timely manner of porcine embryo development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes13071251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320770PMC
July 2022

mTOR-FABP4 signal is activated in brain arteriovenous malformations in humans.

J Mol Med (Berl) 2022 Jul 25. Epub 2022 Jul 25.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Arteriovenous malformations (AVMs) are the most common types of cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. The dysfunction of endothelial cells has been postulated to play a role in the pathogenesis of brain AVMs. mTOR-FABP4 signal enhances the angiogenic responses of endothelial cells and is not activated in the normal cerebral vasculature. Herein, we investigated the hypothesis that the mTOR-FABP4 signal may be activated in brain AVMs. The abundance of molecules in mTOR-FABP4 signal expression was detected by immunohistochemistry and Western blotting; special expressing cells were further characterized by double immunofluorescence using antibodies against various cell-specific markers. Next, several functional assays were performed to analyze the influence of the mTOR-FABP4 signal on proliferation, apoptosis, migration, and vascular tube formation of endothelial cells in human umbilical vein endothelial cells (HUVECs) using rapamycin and L-leucine. The expression of mTOR, p-mTOR, and FABP4 was increased in endothelial cells of human brain AVMs. Endothelial cell mTOR and p-mTOR expression were present in 70% and 55% of brain AVMs, respectively. Moreover, a population of FABP4-positive endothelial cells was detected in 80% of brain AVMs. The mTOR-FABP4 signal was activated and inhibited by L-leucine and rapamycin in HUVECs. The proliferation, apoptosis, migration, and vascular tube formation of endothelial cells could be inhibited by rapamycin. The mTOR-FABP4 signal was activated in human brain AVMs, and the mTOR-FABP4 signal was involved in proliferation, apoptosis, migration, and the vascular tube formation of endothelial cells. Taken together, whether rapamycin has therapeutic potential for treating human brain AVMs is worthy of further study. KEY MESSAGES : We confirmed that the mTOR- FABP4 pathway is activated in human brain arteriovenous malformations. We confirmed that mTOR signaling pathway affects endothelial cell function by regulating proliferation, migration, apoptosis, and tube formation of endothelial cell. Our study can provide theoretical support for mTOR pathway inhibitors in the treatment of human brain arteriovenous malformations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00109-022-02237-9DOI Listing
July 2022

The effect of sex differences on complications and 90-day outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis.

Neurosurg Rev 2022 Jul 23. Epub 2022 Jul 23.

Department of Neurosurgery, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Beijing, 100070, China.

Aneurysmal subarachnoid hemorrhage (aSAH) is the most devastating form of stroke. Up to now, little is known about the effect of sex differences on complications and outcomes. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). Baseline characteristics, in-hospital complications, and outcomes were compared after 1:1 propensity score matching (PSM). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) analysis was calculated to measure each independent risk factor's prediction ability. A total of 833 patients were included. After PSM, 109 male patients were compared with 109 female patients. Female patients had a higher incidence of anemia (47/109 [43.1%] vs. 30/109 [27.5%], p = 0.016) than male patients, while male patients had a higher incidence of pneumonia (36/109 [33.0%] vs. 19/109 [17.4%], p = 0.008) than female patients. No significant differences were found in the rate of unfavorable outcomes at discharge and 90-day outcomes (40/109 [36.7%] vs. 50/109 [45.9%], p = 0.169; 15/109 [13.8%] vs. 19/107 [17.8%], p = 0.420) between female and male patients. Pneumonia (AUC = 0.749, 95% confidence interval [CI] = 0.623-0.875, p < 0.001) and anemia (AUC = 0.753, 95% CI = 0.632-0.873, p = 0.002) showed good ability to predict 90-day unfavorable outcomes in male and female patients, respectively. Female patients had a higher incidence of anemia but a lower incidence of pneumonia during hospitalization. However, differences in in-hospital complications did not result in differences in outcomes between women and men. Clinical Trial Registration: NCT04785976. 2021/03/05, retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10143-022-01836-xDOI Listing
July 2022

Metagenomic insights into the microbe-mediated B and K vitamin biosynthesis in the gastrointestinal microbiome of ruminants.

Microbiome 2022 07 21;10(1):109. Epub 2022 Jul 21.

Centre for Ruminant Nutrition and Feed Technology Research, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Background: B and K vitamins, essential nutrients in host metabolism, can be synthesized by the rumen microbiome in ruminants and subsequently absorbed by the host. However, the B and K vitamin biosynthesis by the whole gastrointestinal microbiome and their abundances in different dietary strategies are largely unknown. Here, we reanalyzed our previous large-scale metagenomic data on the gastrointestinal microbiome of seven ruminant species and recruited 17,425 nonredundant microbial genomes from published datasets to gain a comprehensive understanding of the microbe-mediated B and K vitamin biosynthesis in ruminants.

Results: We identified 1,135,807 genes and 167 enzymes involved in B and K vitamin biosynthesis. Our results indicated that the total abundances of B and K vitamin biosynthesis were dominant in the stomach microbiome, while the biosynthesis of thiamine, niacin, and pyridoxine was more abundant in the large intestine. By examining 17,425 nonredundant genomes, we identified 2366 high-quality genomes that were predicted to de novo biosynthesize at least one vitamin. Genomic analysis suggested that only 2.7% of these genomes can synthesize five or more vitamins, and nearly half of genomes can synthesize only one vitamin. Moreover, we found that most genomes possessed cobalamin transporters or cobalamin-dependent enzymes to consume cobalamin directly, and only a few microbial genomes possessed a complete cobalamin biosynthesis pathway. Based on these genomic data, we examined the effect of the high-grain (HG) diet on the vitamin biosynthesis of the rumen microbiome of dairy cattle. We revealed that most vitamin biosynthesis was enhanced in the HG group, while only cobalamin synthesis was inhibited in the HG group, indicating that dietary fiber is vital for cobalamin biosynthesis.

Conclusions: We primarily provided a gene catalog and 2366 microbial genomes involved in B and K vitamin biosynthesis in ruminants. Our findings demonstrated the regional heterogeneity and dietary effect of vitamin biosynthetic potential in the ruminant gastrointestinal microbiome and interpreted the biosynthesis mechanisms of these microbes and their physiological adaptability. This study expands our understanding of microbe-mediated vitamin biosynthesis in ruminants and may provide novel targets for manipulation to improve the production of these essential vitamins. Video abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40168-022-01298-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306216PMC
July 2022

Host-versus-commensal immune responses participate in the rejection of colonized solid organ transplants.

J Clin Invest 2022 Jul 14. Epub 2022 Jul 14.

Department of Medicine, University of Chicago, Chicago, United States of America.

Solid organ transplantation is the preferred treatment for end-stage organ failure. Although transplant recipients takelife-long immunosuppressive drugs, a substantial percentage of them still reject their allografts. Strikingly, barrier organs colonized with microbiota have significantly shorter half-lives than non-barrier transplanted organs, even in immunosuppressed hosts. We previously demonstrated that skin allografts mono-colonized with the common human commensal Staphylococcus epidermidis (S.epi) are rejected faster than germ-free (GF) allografts in mice because the presence of S.epi augments the effector alloimmune response locally in the graft. Here, we tested whether host immune responses against graft-resident commensal microbes, including S.epi, can damage colonized grafts independently from the alloresponse. Naïve hosts mounted an anti-commensalT cell response to colonized, but not GF, syngeneic skin grafts. Whereas naïve anti-graft-commensal T cells modestly damaged colonized syngeneic skin grafts, hosts with prior anti-commensal T cell memory mounted a post-transplant immune response against graft-resident commensals that significantly damaged colonized, syngeneic skin grafts. Importantly, allograft recipients harboring this host-versus-commensal immune response resisted immunosuppression. The dual effectsof host-versus-commensal and host-versus-allograft responses may partially explain why colonized organs have poorer outcomes than sterile organs in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI153403DOI Listing
July 2022

Pre-Operative Predictors for Post-Operative Pneumonia in Aneurysmal Subarachnoid Hemorrhage After Surgical Clipping and Endovascular Coiling: A Single-Center Retrospective Study.

Front Neurol 2022 24;13:893516. Epub 2022 Jun 24.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Objective: Postoperative pneumonia (POP) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH) associated with postoperative mortality, prolonged hospitalization, and increased medical cost. Early recognition of pneumonia and more aggressive management may improve patient outcomes.

Methods: We retrospectively reviewed all patients with aSAH who were admitted to our institution between January 2015 and December 2020. Baseline clinical characteristics, imaging data, and inflammatory biomarkers were reviewed. The risk factors derived from multivariate logistic regression of surgical clipping (SC) and endovascular coiling (EC) were analyzed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to calculate each independent predictor's prediction ability.

Results: A total of 843 patients were enrolled. Compared with patients in the EC group, the incidence of POP was higher in the SC group [143/414 (34.54%) vs. 114/429 (26.57%), = 0.015]. In the EC group, multivariate analysis revealed that age [ = 0.001; odds ratio (OR) = 1.04, 95% CI = 1.02-1.07], posterior circulation aneurysms ( = 0.021; OR = 2.07, 95% CI = 1.14-3.83), higher neutrophil (NEUT; < 0.001; OR = 1.13, 95% CI = 1.06-1.21), World Federation of Neurosurgical Societies (WFNS) grade 4 or 5 ( < 0.001; OR = 4.84, 95% CI = 2.67-8.79), modified Fisher Scale (mFS) grade 3 or 4 ( = 0.022; OR = 2.60, 95% CI = 1.15-5.89), and acute hydrocephalus ( = 0.048; OR = 1.74, 95% CI = 1.01-3.00) were independent risk factors for POP. In the SC group, multivariate analysis revealed that age ( = 0.015; OR = 1.03, 95% CI = 1.01-1.05), WFNS grade 4 or 5 ( = 0.037; OR = 1.76, 95% CI = 1.03-3.00), heart disease ( < 0.001; OR = 5.02, 95% CI = 2.03-12.45), higher white blood cell (WBC; < 0.001; OR = 1.13, 95% CI = 1.07-1.20), and mFS grade 3 or 4 ( = 0.019; OR = 2.34, 95% CI = 1.15-4.77) were independent risk factors for POP.

Conclusion: Patients treated with SC are more likely to develop POP. Comprehensive preoperative evaluation of patients may help physicians to better predict POP and implement preventive measures to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2022.893516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263125PMC
June 2022

An improved iterative neural network for high-quality image-domain material decomposition in dual-energy CT.

Med Phys 2022 Jun 23. Epub 2022 Jun 23.

School of Electronic & Electrical Engineering and Department of Artificial Intelligence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 16419, Republic of Korea.

Purpose: Dual-energy computed tomography (DECT) has widely been used in many applications that need material decomposition. Image-domain methods directly decompose material images from high- and low-energy attenuation images, and thus, are susceptible to noise and artifacts on attenuation images. The purpose of this study is to develop an improved iterative neural network (INN) for high-quality image-domain material decomposition in DECT, and to study its properties.

Methods: We propose a new INN architecture for DECT material decomposition. The proposed INN architecture uses distinct cross-material convolutional neural network (CNN) in image refining modules, and uses image decomposition physics in image reconstruction modules. The distinct cross-material CNN refiners incorporate distinct encoding-decoding filters and cross-material model that captures correlations between different materials. We study the distinct cross-material CNN refiner with patch-based reformulation and tight-frame condition.

Results: Numerical experiments with extended cardiac-torso phantom and clinical data show that the proposed INN significantly improves the image quality over several image-domain material decomposition methods, including a conventional model-based image decomposition (MBID) method using an edge-preserving regularizer, a recent MBID method using prelearned material-wise sparsifying transforms, and a noniterative deep CNN method. Our study with patch-based reformulations reveals that learned filters of distinct cross-material CNN refiners can approximately satisfy the tight-frame condition.

Conclusions: The proposed INN architecture achieves high-quality material decompositions using iteration-wise refiners that exploit cross-material properties between different material images with distinct encoding-decoding filters. Our tight-frame study implies that cross-material CNN refiners in the proposed INN architecture are useful for noise suppression and signal restoration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mp.15817DOI Listing
June 2022

A lymphatic route for a hyperbranched heteroglycan from Radix Astragali to trigger immune responses after oral dosing.

Carbohydr Polym 2022 Sep 27;292:119653. Epub 2022 May 27.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.

Gut barrier makes a huge research gap between in vivo and in vitro studies of orally bioactive polysaccharides: whether/how they contact the related cells in vivo. A hyperbranched heteroglycan RAP from Radix Astragali, exerting antitumor and immunomodulatory effects in vitro and in vivo, is right an example. Here, we determined first that RAP's antitumor activity is immune-dependent. Being undegraded and non-absorbing, RAP quickly entered Peyer's patches (PPs) in 1 h where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was further delivered to mesenteric lymph node, bone marrow, and tumor. By contrast, the control Dendrobium officinale polysaccharide did not enter PPs. These findings revealed a blood/microbiota-independent and selective lymphatic route for orally administrated RAP to directly contact immune cells and trigger antitumor immune responses. This route bridges the research gap between the in vitro and in vivo studies and might apply to many other bioactive polysaccharides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2022.119653DOI Listing
September 2022

Longitudinal study of irradiation-induced brain functional network alterations in patients with nasopharyngeal carcinoma.

Radiother Oncol 2022 Aug 16;173:277-284. Epub 2022 Jun 16.

Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China. Electronic address:

Background: To investigate radiotherapy (RT)-related brain network changes in patients with nasopharyngeal carcinoma (NPC) over time and develop least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) models to predict RT-related brain network changes.

Methods: 36 NPC patients were followed up at four timepoints: baseline, within 3 months (acute), 6 months (subacute), and 12 months (delayed) post-RT. 15 comparable healthy controls (HCs) were finally included and followed up in parallel. Functional neuroimaging data, dose-volume parameters of bilateral temporal lobes and Montreal Cognitive Assessment (MoCA) were acquired. Graph theoretical analysis and mixed-design analysis of variance were performed to investigate how the brain global and nodal changes were affected by RT. Multivariate logistic regression NTCP models were developed. LASSO with nested cross-validation strategy was used to select features. The relationships between network changes and MoCA changes were also examined.

Results: Significant changes were detected in nodal efficiency (NE) in NPC patients but not in HCs over time. Altered NE was distributed in the bilateral frontal, temporal lobes and the right insula, which showed a "decrease-increase/recovery" pattern over time. Among all models, the model for predicting NE changes of STG.R showed a relatively good performance (area under the receiver operating curve: 0.68), and D and V to right temporal lobe outperformed in this model.

Conclusion: Our findings indicate that RT-induced brain injury begin at the acute period and follow a recovery over time. Furthermore, our study presents prediction models for brain dysfunction based on the dosimetric and clinical parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2022.06.008DOI Listing
August 2022

Chromosome-level and haplotype-resolved genome provides insight into the tetraploid hybrid origin of patchouli.

Nat Commun 2022 06 18;13(1):3511. Epub 2022 Jun 18.

Institute of Medicinal Plant Physiology and Ecology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Patchouli (Pogostemon cablin (Blanco) Benth.), a member of the Lamiaceae family, is an important aromatic plant that has been widely used in medicine and perfumery. Here, we report a 1.94 Gb chromosome-scale assembly of the patchouli genome (contig N50 = 7.97 Mb). The gene annotation reveals that tandem duplication of sesquiterpene biosynthetic genes may be a major contributor to the biosynthesis of patchouli bioactivity components. We further phase the genome into two distinct subgenomes (A and B), and identify a chromosome substitution event that have occurred between them. Further investigations show that a burst of universal LTR-RTs in the A subgenome lead to the divergence between two subgenomes. However, no significant subgenome dominance is detected. Finally, we track the evolutionary scenario of patchouli including whole genome tetraploidization, subgenome divergency, hybridization, and chromosome substitution, which are the key forces to determine the complexity of patchouli genome. Our work sheds light on the evolutionary history of patchouli and offers unprecedented genomic resources for fundamental patchouli research and elite germplasm development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-31121-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206139PMC
June 2022

Competing endogenous RNA analysis reveals the regulatory potency of CKAP5 in HPV+ HNSCC.

Oral Dis 2022 Jun 16. Epub 2022 Jun 16.

Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.14282DOI Listing
June 2022

Comprehensive Transcriptome Sequencing Analysis of in Different Growth Periods.

Front Physiol 2022 25;13:897458. Epub 2022 May 25.

Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Life Science and Engineering, Foshan University, Foshan, China.

Medical leeches are widely been used in biochemical and clinical medical studies, helping to restore blood circulation to grafted or severely injured tissue. Mostly, adult leeches are being used in the traditional pharmacopeia, but the gene expression profiling of leeches in different growth periods is not well-reported. So, in this study, we used transcriptome analysis to analyze the comparative gene expression patterns of () in different growth periods, including larval, young, and adult stages. We constructed 24 cDNA libraries from larval, young, and adult stages, and about 54,639,118 sequences were generated, 18,106 mRNA transcripts of which 958 novel mRNAs and 491 lncRNAs were also assembled as well. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially upregulated genes from the larval to adult stages were enriched in pathways such as cilium, myofibril, contractile fiber, cytoskeleton proteins, dilated cardiomyopathy, adrenergic signaling in cardiomyocytes, etc. Moreover, in the adult stages, a significant increase in the expression of the Hirudin-HM () genes was detected. In addition, our comparative transcriptome profiling data from different growth stages of also identified a large number of DEGs and DElncRNAs which were tentatively found to be associated with the growth of ; as it grew, the muscle-related gene expression increased, while the lipid metabolism and need for stimulation and nutrition-related genes decreased. Similarly, the higher expression of might attribute to the high expression of protein disulfide isomerase gene family (PDI) family genes in adulthood, which provides an important clue that why adult leeches rather than young leeches are widely used in clinical therapeutics and traditional Chinese medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2022.897458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174698PMC
May 2022

Divergent white matter changes in patients with nasopharyngeal carcinoma post-radiotherapy with different outcomes: a potential biomarker for prediction of radiation necrosis.

Eur Radiol 2022 Jun 10. Epub 2022 Jun 10.

Department of Radiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China.

Objectives: To investigate the effects of standard radiotherapy on temporal white matter (WM) and its relationship with radiation necrosis (RN) in patients with nasopharyngeal carcinoma (NPC), and to determine the predictive value of WM volume alterations at the early stage for RN occurrence at the late-delay stage.

Methods: Seventy-four treatment-naive NPC patients treated with standard radiotherapy were longitudinally followed up for 36 months. Structural MRIs were collected at multiple time points during the first year post-radiotherapy. Longitudinal structural images were processed using FreeSurfer. Linear mixed models were used to delineate divergent trajectories of temporal WM changes between patients who developed RN and who did not. Four machine learning methods were used to construct predictive models for RN with temporal WM volume alterations at early-stage.

Results: The superior temporal gyrus (STG) had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. Patients with RN showed more rapid atrophy than those with NRN. A predictive model constructed with temporal WM volume alterations at early-stage post-radiotherapy had good performance for RN; the areas under the curve (AUC) were 0.879 and 0.806 at 1-3 months and 6 months post-radiotherapy, respectively. Moreover, the predictive model constructed with absolute temporal volume at 1-3 months post-radiotherapy also presented good performance; the AUC was 0.842, which was verified by another independent dataset (AUC = 0.773).

Conclusions: NPC patients with RN had more sharp atrophy in the STG than those with NRN. Temporal WM volume at early-stage post-radiotherapy may serve as an in vivo biomarker to identify and predict RN occurrence.

Key Points: • The STG had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. • Although both groups exhibited time-dependent atrophy in the STG, the patients with RN showed a more rapid volume decrease than those with NRN. • Temporal WM volume alteration (or absolute volume) at the early stage could predict RN occurrence at the late-delay stage after radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-022-08907-zDOI Listing
June 2022

Additively manufactured macroporous chambers facilitate large volume soft tissue regeneration from adipose-derived extracellular matrix.

Acta Biomater 2022 08 6;148:90-105. Epub 2022 Jun 6.

Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan 430022, China. Electronic address:

Breast tissue engineering is a promising alternative intervention for breast reconstruction. Due to their low immunogenicity and well-preserved adipogenic microenvironment, decellularized adipose tissue (DAT) can potentially regenerate adipose tissue in vivo. However, the volume of adipose tissue regenerated from DAT can hardly satisfy the demand for breast reconstruction. Tissue engineering chamber (TEC) is an effective technique for generation of large adipose tissue volumes. However, TEC applications necessitate reoperation to remove non-degradable plastic chambers and harvest autologous tissue flaps, which prolongs the operation time and causes potential damage to donor sites. We improved the TEC strategy by combining bioresorbable polycaprolactone (PCL) chambers and decellularized adipose tissues (DAT). A miniaturized porous PCL chamber was fabricated based on scaling differences between human and rabbit chests, and basic fibroblast growth factor (bFGF)-loaded DAT successfully prepared. In rabbit models, a highly vascularized adipose tissue that nearly filled up the PCL chamber (5 mL) was generated de novo from 0.5 mL bFGF-loaded DAT. The newly formed tissue had significantly high expressions of adipogenic genes, compared to the endogenous adipose tissue. The concept described here can be exploited for breast tissue engineering. STATEMENT OF SIGNIFICANCE: Decellularized adipose tissue (DAT), which provides infiltrated cells adipogenic microenvironment, can potentially regenerate adipose tissue in vivo. Nevertheless, the volume of regenerated adipose tissue is insufficient to repair large sized tissue defect. Tissue engineering chamber (TEC) could provide a protective space for in situ regeneration of large volume tissue. Herein, a new strategy by combining biodegradable polycaprolactone chambers and basic fibroblast growth factor-loaded decellularized adipose tissue is proposed. In rabbit model, newly formed adipose tissue regenerated from DAT successfully filled the dome shaped chamber with ten folds higher volume than DAT, which is proportionally similar to women breast. This work highlighted the importance of adipogenic microenvironment and protective space for adipose tissue regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2022.05.053DOI Listing
August 2022

Generation of Heritable Prominent Double Muscle Buttock Rabbits via Novel Site Editing of Myostatin Gene Using CRISPR/Cas9 System.

Front Vet Sci 2022 20;9:842074. Epub 2022 May 20.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China.

Rabbits have been domesticated for meat, wool, and fur production, and have also been cherished as a companion, artistic inspiration, and an experimental model to study many human diseases. In the present study, the muscle mass negative regulator gene myostatin () was knocked out in rabbits at two novel sites in exon3, and the function of these mutations was determined in subsequent generations. The prominent double muscle phenotype with hyperplasia or hypertrophy of muscle fiber was observed in the -KO rabbits, and a similar phenotype was confirmed in the F1 generation. Moreover, the average weight of 80-day-old KO rabbits (2,452 ± 63 g) was higher than that of wild-type rabbits (2,393.2 ± 106.88 g), and also the bodyweight of -KO rabbits (3,708 ± 43.06g) was significantly higher ( < 0.001) at the age of 180 days than wild-type (WT) rabbits (3,224 ± 48.64g). In -KO rabbits, fourteen rabbit pups from the F1 generation and thirteen from the F2 generation stably inherited the induced gene mutations. Totally, 194 pups were produced in the F1 generation of which 49 were -KO rabbits, while 47 pups were produced in the F2 generation of which 20 were edited rabbits, and the ratio of edited to wild-type rabbits in the F2 generation was approximately 1:1. Thus, we successfully generated a heritable double muscle buttocks rabbits via myostatin mutation with CRISPR/Cas9 system, which could be valuable in rabbit's meat production and also a useful animal model to study the development of muscles among livestock species and improve their important economic traits as well as the human muscle development-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fvets.2022.842074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165342PMC
May 2022

The Difference in Body Type May Modify the Relationship Between Dietary Mineral Intake and Hypertension Among Korean Adults.

Biol Trace Elem Res 2022 Jun 4. Epub 2022 Jun 4.

School of Medicine, Taizhou University, No. 1139, Shifu Avenue, Jiaojiang District, Taizhou, 318000, Zhejiang, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-022-03310-7DOI Listing
June 2022

Microbiota and adipocyte mitochondrial damage in type 2 diabetes are linked by Mmp12+ macrophages.

J Exp Med 2022 07 3;219(7). Epub 2022 Jun 3.

College of Pharmacy, Oregon State University, Corvallis, OR.

Microbiota contribute to the induction of type 2 diabetes by high-fat/high-sugar (HFHS) diet, but which organs/pathways are impacted by microbiota remain unknown. Using multiorgan network and transkingdom analyses, we found that microbiota-dependent impairment of OXPHOS/mitochondria in white adipose tissue (WAT) plays a primary role in regulating systemic glucose metabolism. The follow-up analysis established that Mmp12+ macrophages link microbiota-dependent inflammation and OXPHOS damage in WAT. Moreover, the molecular signature of Mmp12+ macrophages in WAT was associated with insulin resistance in obese patients. Next, we tested the functional effects of MMP12 and found that Mmp12 genetic deficiency or MMP12 inhibition improved glucose metabolism in conventional, but not in germ-free mice. MMP12 treatment induced insulin resistance in adipocytes. TLR2-ligands present in Oscillibacter valericigenes bacteria, which are expanded by HFHS, induce Mmp12 in WAT macrophages in a MYD88-ATF3-dependent manner. Thus, HFHS induces Mmp12+ macrophages and MMP12, representing a microbiota-dependent bridge between inflammation and mitochondrial damage in WAT and causing insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20220017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170383PMC
July 2022

Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability.

Nat Chem Biol 2022 07 30;18(7):751-761. Epub 2022 May 30.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.

The selenoprotein glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid peroxides into nontoxic lipid alcohols. GPX4 has emerged as a promising therapeutic target for cancer treatment, but some cancer cells are resistant to ferroptosis triggered by GPX4 inhibition. Using a chemical-genetic screen, we identify LRP8 (also known as ApoER2) as a ferroptosis resistance factor that is upregulated in cancer. Loss of LRP8 decreases cellular selenium levels and the expression of a subset of selenoproteins. Counter to the canonical hierarchical selenoprotein regulatory program, GPX4 levels are strongly reduced due to impaired translation. Mechanistically, low selenium levels result in ribosome stalling at the inefficiently decoded GPX4 selenocysteine UGA codon, leading to ribosome collisions, early translation termination and proteasomal clearance of the N-terminal GPX4 fragment. These findings reveal rewiring of the selenoprotein hierarchy in cancer cells and identify ribosome stalling and collisions during GPX4 translation as ferroptosis vulnerabilities in cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41589-022-01033-3DOI Listing
July 2022

Types of endoscopic surgical approaches for benign parapharyngeal space tumors.

Oral Oncol 2022 07 13;130:105875. Epub 2022 May 13.

Department of Otolaryngology Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2022.105875DOI Listing
July 2022
-->