Publications by authors named "Lin Guo"

895 Publications

Multivariate Analysis of Electrophysiological Signals Reveals the Time Course of Precision Grasps Programs: Evidence for Non-hierarchical Evolution of Grasp Control.

J Neurosci 2021 Sep 22. Epub 2021 Sep 22.

Department of Psychology at Scarborough, University of Toronto Scarborough, ON, Canada, M1C1A4

Current understanding of the neural processes underlying human grasping suggests that grasp computations involve gradients of higher- to lower-level representations and, relatedly, visual to motor processes. However, it is unclear whether these processes evolve in a strictly canonical manner from higher to intermediate, and to lower levels given that this knowledge importantly relies on functional imaging which lacks temporal resolution. To examine grasping in fine temporal detail here we used multivariate EEG analysis. We asked participants to grasp objects while controlling the time at which crucial elements of grasp programs were specified. We first specified the orientation with which participants should grasp objects and only after a delay we instructed participants about which effector(s) to use to grasp, either the right, or the left hand. We also asked participants to grasp with both hands because bimanual and left-hand grasping share intermediate level grasp representations. We observed that grasp programs evolved in a canonical manner from visual representations that were independent of effectors to motor representations that distinguished between effectors. However, we found that intermediate representations of effectors that partially distinguished between effectors arose after representations that distinguished between all effector types. Our results show that grasp computations do not proceed in a strictly hierarchically canonical fashion, highlighting the importance of the fine temporal resolution of EEG for a comprehensive understanding of human grasp control.A longstanding assumption of the grasp computations is that grasp representations progress from higher- to lower-level control in a regular, or canonical, fashion. Here, we combined EEG and multivariate pattern analysis to characterize the temporal dynamics of grasp representations while participants viewed objects and subsequently cued to execute an unimanual or bimanual grasp. Interrogation of the temporal dynamics revealed that lower-level effector representations emerged before intermediate levels of grasp representations, thereby suggesting a partially non-canonical progression from higher to lower, and then to intermediate level grasp control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.0992-21.2021DOI Listing
September 2021

Diagnostic value of serum tumor-associated autoantibodies in esophageal cancer.

Biomark Med 2021 Sep 20. Epub 2021 Sep 20.

Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.

To explore the application value of serum autoantibodies in the early diagnosis of esophageal cancer. A total of 130 patients with esophageal cancer and 110 controls were included and tested by ELISA. According to the receiver operating characteristic curve, total sensitivity is 83.08%, total specificity is 72.73%. A nomogram was established based on the positive judgment standard, the area under the receiver operating characteristic curve was calculated to be 0.880 after verification with the calibration curve. A 2-week follow-up analysis found compared with the preoperative control, the postoperative model integral value will significantly decrease. The combination of serum autoantibody groups has certain clinical application value in the early diagnosis of esophageal cancer and can be used as an auxiliary index for early diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm-2021-0351DOI Listing
September 2021

Accuracy of MRI and X-Ray Measurement of Displacement Distance of Humeral Lateral Condyle Fractures.

Orthop Surg 2021 Sep 19. Epub 2021 Sep 19.

Tianjin Hospital, Tianjin, China.

Objective: To investigate the accuracy of X-ray and magnetic resonance imaging (MRI) measurements in evaluating the displacement of humeral lateral condyle fracture (HLCF) in different positions of the forearm based on human cadaveric HLCF models.

Methods: Three human cadaveric elbow HLCF fracture models were successfully established. The wrist joint was fixed, and the forearm was rotated forward along the mid-axis. The maximum distance between the two segments of the lateral fracture gap was defined as LFS (lateral fracture space) distance, and the maximum distance between the two segments of the fracture gap at the anterior and posterior margins of the fracture model was defined as PFS (posterior fracture space). The LFS and PFS distances of the human cadaveric elbow HLCF fracture models were measured during forearm rotation at 0º, 45º, 90º, and 135º rotation using a Capture Motion System (CMS), positive and lateral elbow X-ray, coronal and sagittal MRI scans, respectively, and the CMS measurements were considered as the true fracture gap distances. The values obtained by CMS, X-ray, and MRI measurements for both LPS and PFS distances in the HLCF fracture model at each position during rotation were recorded. The LFS and PFS distances were measured by two independent orthopaedic and joint imaging physicians. The data were measured three times by each physician, and the final values were the average of the two measurements. The outcomes were determined by whether a statistical difference exists in the LFS and PFS among the CMS, X-ray, and MRI groups.

Results: The interobserver agreement tests between the two observers showed good agreement in the measurements. A multiple sample ANOVA showed statistical differences in the LFS distances of HLCF measured at 0º, 45º, 90º, and 135º rotated by three radiographic measurements (P < 0.05). The LFS distances obtained by MRI and CMS measurements were greater than those obtained by X-ray measurement in all positions using the LSD test (P < 0.05), and no statistical difference was found between the CMS and MRI methods in each position (P > 0.05). The same results were observed in terms of PFS values obtained by CMS, X-ray, and MRI measurements at 0º, 45º, 90º, and 135º pronation. It was statistically different among the three groups as shown by multiple sample ANOVA (P < 0.05). The CMS and MRI measurements were greater than the X-ray measurements (P < 0.05), while no statistical difference was observed between the CMS and MRI measurements (P > 0.05).

Conclusion: X-rays often underestimate the degree of displacement of HLCF fractures; MRI measurements are closer to the true values compared with X-ray.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/os.13116DOI Listing
September 2021

Up-regulation of GSTT1 in serous ovarian cancer associated with resistance to TAXOL / carboplatin.

J Ovarian Res 2021 Sep 17;14(1):122. Epub 2021 Sep 17.

Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, No.270, Dong'An Road, Xuhui District, Shanghai, 200032, China.

Serous ovarian cancer (SOC) is the most common women cancer and the leading cause of cancer-related mortality among the gynaecological malignancies. Although effective chemotherapeutics combined with surgery are developed for the treatment, the five-year survival rate is unsatisfactory due to chemoresistance. To overcome this shortcoming of chemotherapy, we established taxol and carboplatin resistant SOC cell lines for the understandings of the molecular and cellular mechanisms of chemoresistance. Here, we found that these chemoresistant cell lines showed less viability and proliferation, due to more cells arrested at G0/G1 phase. Glutathione-S-transferases-theta1 (GSTT1) was significantly upregulated in these chemoresistant cells, along with other chemoresistant genes. Meanwhile, GSTT1 expression was also significantly upregulated in the SOC patient tissues after taxol treatment, indicating this upregulation was physiologically relevant to chemotherapy. Further, suppression of GSTT1 expression by shRNA in SOC cell lines led to more sensitivity to drug treatment, through increasing divided cells and promoting cell death. Moreover, the expression of DNA topoisomerase 1 (Topo I) was in synergy with that of GSTT1 in the chemoresistant cells, and GSTT1 can bind to Topo I in vitro, which suggested GSTT1 could function through DNA repair mechanism during chemoresistance. In summary, our data imply that GSTT1 may be a potential biomarker or indicator of drug resistance in serous ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-021-00873-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447655PMC
September 2021

Investigation of Diagnostic Biomarkers for Osteoporosis Based on Differentially Expressed Gene Profile with QCT and mDixon-Quant Techniques.

Orthop Surg 2021 Sep 13. Epub 2021 Sep 13.

Department of Biomedical Engineering, School of Precision Instrument and Optoelectronic Engineering, Tianjin University, Tianjin, China.

Objective: To develop a comprehensive differential expression profile for osteoporosis based on two independent data sources.

Methods: Using a hindlimb unloading (HLU) rat model to mimic osteoporosis syndrome in humans (animal experiments), the significant differentially expressed mRNAs in osteoporosis were analyzed using RNA-seq. The enriched GO terms as well as KEGG signaling pathways were also deeply investigated. Using clinical specimens to verify the functions of potential hub genes (biomarkers) for osteoporosis (clinical experiments), 128 suspected cases for osteoporosis from January 2019 to December 2020 were randomly selected and analyzed by quantitative computed tomography (QCT) as well as modified Dixon quantification (mDixon-Quant) techniques in the Tianjin hospital. Among these, 80 patients out of 128 suspected cases were finally diagnosed as the osteoporosis group. Meanwhile, 48 patients were selected for osteopenia group. There was no significant age and gender difference across participant subgroups. The protein levels of potential hub genes (FST, CCL3, and RAPGEF4) were determined by ELISA double antibody sandwich method for osteopenia and osteoporosis groups from peripheral blood.

Result: In the RNA-seq analysis, compared with control group, a total of 803 differentially expressed mRNAs were identified, including 288 up-regulated and 515 down-regulated mRNAs. Of these, FST, CCL3, CPE, RAPGEF4, IL6, MDFI, PDZD2, and GATM were primary hub genes (biomarkers) for osteoporosis. These differentially expressed genes were significantly enriched in GO terms related to extracellular matrix process and KEGG signaling pathways including osteoclast differentiation. In the functional experiments, the protein expression level of FST, CCL3, and RAPGEF4 displayed a specific expression pattern between osteoporosis patients and control group. The protein concentration of FST was 23.63 ± 6.39 ng/mL in osteoporosis patients compared as 48.36 ± 9.12 ng/mL in osteopenia group (P < 0.01). Meanwhile, CCL3 was 1.03 ± 0.64 ng/mL in osteoporosis patients vs 0.56 ± 0.24 in osteopenia group (P < 0.01) and RAPGEF4 was 53.58 ± 11.42 ng/mL in osteoporosis patients vs 66.47 ± 13.28 ng/mL in osteopenia group (P < 0.05), respectively.

Conclusion: This study has identified potential gene biomarkers (the genes with most significantly differential expression and useful for distinguishing osteoporosis from other bone disorders) and established a differential expression profile for osteoporosis, which is a valuable reference for future clinical research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/os.13094DOI Listing
September 2021

Single cell DNA sequencing reveals punctuated and gradual clonal evolution in hepatocellular carcinoma.

Gastroenterology 2021 Sep 2. Epub 2021 Sep 2.

Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Translational Cancer Research Center, Peking University First Hospital, Beijing 100034, China. Electronic address:

Background & Aims: Copy number alterations (CNAs), elicited by genome instability, is a major source of intratumor heterogeneity. How CNAs evolve in hepatocellular carcinoma (HCC) remains unknown.

Methods: We performed single cell DNA sequencing (scDNA-seq) on 1275 cells isolated from 10 HCC patients, ploidy-resolved scDNA-seq of 356 cells from 1 additional patient, and single cell RNA sequencing (scRNA-seq) on 27344 cells from 3 additional patients. Three statistical fitting models were compared to investigate the CNA accumulation pattern.

Results: Cells in the tumor were categorized into three subpopulations: euploid, pseudoeuploid, and aneuploid. Our scDNA-seq analysis revealed that CNA accumulation followed a dual-phase copy number evolution (DPCNE) model, i.e. a punctuated phase followed by a gradual phase. Patients exhibited prolonged gradual phase showed higher intratumor heterogeneity and worse disease-free survival. Integrating bulk RNA-seq of 17 HCC patients, published datasets of 1196 liver tumors, and immunohistochemical staining of 202 HCC tumors, we showed that high expression of CAD, a gene involved in pyrimidine synthesis, was correlated with rapid tumorigenesis and reduced survival. The DPCNE model was validated by our scRNA-seq data and published scDNA-seq datasets of other cancer types. Furthermore, ploidy-resolved scDNA-seq revealed the common clonal origin of diploid- and polyploid-aneuploid cells, suggesting that polyploid tumor cells were generated by whole genome doubling of diploid tumor cells.

Conclusions: Our work revealed a novel DPCNE model, showed HCC with longer gradual phase were more severe, identified CAD as a promising biomarker for early recurrence of HCC, and supported the diploid origin of polyploid HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.08.052DOI Listing
September 2021

Systematic Review of Approaches to Preserve Machine Learning Performance in the Presence of Temporal Dataset Shift in Clinical Medicine.

Appl Clin Inform 2021 08 1;12(4):808-815. Epub 2021 Sep 1.

Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada.

Objective: The change in performance of machine learning models over time as a result of temporal dataset shift is a barrier to machine learning-derived models facilitating decision-making in clinical practice. Our aim was to describe technical procedures used to preserve the performance of machine learning models in the presence of temporal dataset shifts.

Methods: Studies were included if they were fully published articles that used machine learning and implemented a procedure to mitigate the effects of temporal dataset shift in a clinical setting. We described how dataset shift was measured, the procedures used to preserve model performance, and their effects.

Results: Of 4,457 potentially relevant publications identified, 15 were included. The impact of temporal dataset shift was primarily quantified using changes, usually deterioration, in calibration or discrimination. Calibration deterioration was more common ( = 11) than discrimination deterioration ( = 3). Mitigation strategies were categorized as model level or feature level. Model-level approaches ( = 15) were more common than feature-level approaches ( = 2), with the most common approaches being model refitting ( = 12), probability calibration ( = 7), model updating ( = 6), and model selection ( = 6). In general, all mitigation strategies were successful at preserving calibration but not uniformly successful in preserving discrimination.

Conclusion: There was limited research in preserving the performance of machine learning models in the presence of temporal dataset shift in clinical medicine. Future research could focus on the impact of dataset shift on clinical decision making, benchmark the mitigation strategies on a wider range of datasets and tasks, and identify optimal strategies for specific settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1735184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410238PMC
August 2021

Inhibition of Noncanonical Ca Oscillation/Calcineurin/GSK-3β Pathway Contributes to Anti-Inflammatory Effect of Sigma-1 Receptor Activation.

Neurochem Res 2021 Sep 1. Epub 2021 Sep 1.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221000, Jiangsu Province, China.

Further understanding the mechanism for microglia activation is necessary for developing novel anti-inflammatory strategies. Our previous study found that the activation of sigma-1 receptor can effectively inhibit the neuroinflammation, independent of the canonical mechanisms, such as NF-κB, JNK and ERK inflammatory pathways. Thus, it is reasonable that an un-identified, non-canonical pathway contributes to the activation of microglia. In the present study, we found that a sigma-1 receptor agonist of 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) suppressed lipopolysaccharide (LPS) elevated nitric oxide (NO) content in BV-2 microglia culture supernatant and LPS-raised mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) in BV-2 microglia. Moreover, PRE-084 alleviated LPS-increased Ser 9 de-phosphorylation of glycogen synthase kinase-3 beta (GSK-3β), LPS-elevated catalytic activity of calcineurin, and LPS-raised percent and frequency of Ca oscillatory BV-2 cells. We further found that the inhibitory effect of PRE-084 was reversed by a calcineurin activator of chlorogenic acid and a GSK-3β activator of pyrvinium. Moreover, an IP receptor inhibitor of 2-aminoethoxydiphenyl borate mimicked the anti-inflammatory activity of PRE-084. Thus, we identified a noncanonical pro-neuroinflammary pathway of Ca oscillation/Calcineurin/GSK-3β and the inhibition of this pathway is necessary for the anti-inflammatory activity of sigma-1 receptor activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-021-03439-2DOI Listing
September 2021

Activating Metal Oxides Nanocatalysts for Electrocatalytic Water Oxidation by Quenching-Induced Near-Surface Metal Atom Functionality.

J Am Chem Soc 2021 Sep 27;143(35):14169-14177. Epub 2021 Aug 27.

Guangdong Provincial Key Lab of Nano-Micro Materials Research, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

Developing a reliable strategy for the modulation of the texture, composition, and electronic structure of electrocatalyst surfaces is crucial for electrocatalytic performance, yet still challenging. Herein, we develop a facile and universal strategy, quenching, to precisely tailor the surface chemistry of metal oxide nanocatalysts by rapidly cooling them in a salt solution. Taking NiMoO nanocatalysts an example, we successfully produce the quenched nanocatalysts offering a greatly reduced oxygen evolution reaction (OER) overpotential by 85 mV and 135 mV at 10 mA cm and 100 mA cm respectively. Through detailed characterization studies, we establish that quenching induces the formation of numerous disordered stepped surfaces and the near-surface metal ions doping, thus regulating the local electronic structures and coordination environments of Ni, Mo, which promotes the formation of the dual-site active and thereby affords a low energy pathway for OER. This quenching strategy is also successfully applied to a number of other metal oxides, such as spinel-type CoO, FeO, LaMnO, and CoSnO, with similar surface modifications and gains in OER activity. Our finding provides a new inspiration to activate metal oxide catalysts and extends the use of quenching chemistry in catalysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.1c04737DOI Listing
September 2021

Longitudinal changes of laboratory measurements after discharged from hospital in 268 COVID-19 pneumonia patients.

J Xray Sci Technol 2021 Aug 10. Epub 2021 Aug 10.

Guangzhou Eighth People's Hospital, Guangdong, China.

Background And Objective: Monitoring recovery process of coronavirus disease 2019 (COVID-19) patients released from hospital is crucial for exploring residual effects of COVID-19 and beneficial for clinical care. In this study, a comprehensive analysis was carried out to clarify residual effects of COVID-19 on hospital discharged patients.

Methods: Two hundred sixty-eight cases with laboratory measured data at hospital discharge record and five follow-up visits were retrospectively collected to carry out statistical data analysis comprehensively, which includes multiple statistical methods (e.g., chi-square, T-test and regression) used in this study.

Results: Study found that 13 of 21 hematologic parameters in laboratory measured dataset and volume ratio of right lung lesions on CT images highly associated with COVID-19. Moderate patients had statistically significant lower neutrophils than mild and severe patients after hospital discharge, which is probably caused by more efforts on severe patients and slightly neglection of moderate patients. COVID-19 has residual effects on neutrophil-to-lymphocyte ratio (NLR) of patients who have hypertension or chronic obstructive pulmonary disease (COPD). After released from hospital, female showed better performance in T lymphocytes subset cells, especially T helper lymphocyte%(16%higher than male). According to this sex-based differentiation of COVID-19, male should be recommended to take clinical test more frequently to monitor recovery of immune system. Patients over 60 years old showed unstable recovery process of immune cells (e.g., CD45 + lymphocyte) within 75 days after discharge requiring longer clinical care. Additionally, right lung was vulnerable to COVID-19 and required more time to recover than left lung.

Conclusions: Criterion of hospital discharge and strategy of clinical care should be flexible in different cases due to residual effects of COVID-19, which depend on several impact factors. Revealing remaining effects of COVID-19 is an effective way to eliminate disorder of mental health caused by COVID-19 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/XST-210920DOI Listing
August 2021

Role of MicroRNA-155 in Triptolide-induced hepatotoxicity via the Nrf2-Dependent pathway.

J Ethnopharmacol 2021 Aug 4;281:114489. Epub 2021 Aug 4.

Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. Electronic address:

Ethnopharmacological Relevance: Triptolide (TP), the main bioactive and toxic ingredient of Tripterygium wilfordii Hook F, causes severe toxicity, particularly for hepatotoxicity. However, the underlying mechanisms for its hepatotoxicity are not entirely clear.

Aim Of The Study: The purpose of the study was to explore the role of miR-155, a microRNA closely related to various liver injuries and a regulator of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, in TP-induced liver injury in vitro and in vivo.

Materials And Methods: First, in vitro L02 cells were treated with different concentrations of TP. The protein levels of Nrf2 and its downstream genes Heme oxygenase1 (HO-1) were determined by Western blot. The mRNA expression of miR-155, Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1) and HO-1 were measured using qRT-PCR. And we transfected miR-155 inhibitor and miminc before TP treatment to determine the mRNA and/or protein levels of miR-155, Nrf2 and HO-1. Then, we further confirmed the interaction between miR-155 and Nrf2 pathway in TP-induced hepatic injury in BALB/C mice. The degree of liver injury was determined by HE staining and serum biochemical. The mRNA expression of miR-155 was examined with qRT-PCR and Nrf2 and HO-1 gene expression in liver were evaluated by immunohistochemistry and/or Western blot.

Results: The results showed that TP significantly induced the expression of miR-155 both in L02 cells and in rodents liver tissue, and the inhibition of miR-155 could mitigate the hepatic damages caused by TP. Further experiments demonstrated that the inhibition of miR-155 reversed the down-regulation of Nrf2 and HO-1 by TP, while the miR-155 mimic enhanced the effects of TP. Animal experiments also showed that the inhibition of miR-155 by miR-155 antagomir reversed the decrease of Nrf2 induced by TP administration.

Conclusions: These results indicated that miR-155 played an important role in TP-induced hepatotoxicity by regulating the Nrf2 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114489DOI Listing
August 2021

Visible-Light-Induced Multicomponent Synthesis of γ-Amino Esters with Diazo Compounds.

Org Lett 2021 Aug 5;23(16):6278-6282. Epub 2021 Aug 5.

State Key Lab of Urban Water Resource and Environment, School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China.

A visible-light-induced multicomponent reaction of ethyl diazoacetate, diarylamines, and styrene-type alkenes is described. This novel 1,2-difunctionalization of alkenes can be readily achieved under a simple operation and mild conditions, affording γ-amino esters as major products. The reaction proceeds through the generation of carbon-centered radicals from diazo compounds by a visible-light-promoted proton-coupled electron transfer (PCET) process. The carbon radicals then add to diverse alkenes, delivering new carbon radical species, and the final products are formed with -centered radicals via a radical-radical coupling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c02071DOI Listing
August 2021

[Effect of robotic-arm assisted total knee arthroplasty on femoral rotation alignment and its short-term effectiveness].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jul;35(7):807-812

Center for Joint Surgery, the First Affiliated Hospital (Southwest Hospital), Army Medical University, Chongqing, 400038, P.R.China.

Objective: To investigate the improvement of femoral rotation alignment in total knee arthroplasty (TKA) by robotic-arm assisted positioning and osteotomy and its short-term effectiveness.

Methods: Between June 2020 and November 2020, 60 patients (60 knees) with advanced osteoarthritis of the knee, who met the selection criteria, were selected as the study subjects. Patients were randomly divided into two groups according to the random number table method, with 30 patients in each group. Patients were treated with robotic-arm assisted TKA (RATKA) in trial group, and with conventional TKA in control group. There was no significant difference in gender, age, side and course of osteoarthritis, body mass index, and the preoperative hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), posterior condylar angle (PCA), knee society score-knee (KSS-K) and KSS-function (KSS-F) scores between the two groups ( >0.05). The clinical (KSS-K, KSS-F scores) and imaging (HKA, LDFA, MPTA, PCA) evaluation indexes of the knee joints were compared between the two groups at 3 months after operation.

Results: All patients were successfully operated. The incisions in the two groups healed by first intention, with no complications related to the operation. Patients in the two groups were followed up 3-6 months, with an average of 3.9 months. KSS-K and KSS-F scores of the two groups at 3 months after operation were significantly higher than those before operation ( <0.05), but there was no significant difference between the two groups ( >0.05). X-ray re-examination showed that the prosthesis was in good position, and no prosthesis loosening or sinking occurred. HKA, MPTA, and PCA significantly improved in both groups at 3 months after operation ( <0.05) except LDFA. There was no significant difference in HKA, LDFA, and MPTA between the two groups ( >0.05). PCA in trial group was significantly smaller than that in control group ( =2.635, =0.010).

Conclusion: RATKA can not only correct knee deformity, relieve pain, improve the quality of life, but also achieve the goal of restoring accurate femoral rotation alignment. There was no adverse event after short-term follow-up and the effectiveness was satisfactory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7507/1002-1892.202102043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311216PMC
July 2021

The changes of triacylglycerol and inflammatory factors during dialysis treatment of hypertriglyceridemia during pregnancy and analysis of nursing countermeasure.

Am J Transl Res 2021 15;13(6):6745-6751. Epub 2021 Jun 15.

Department of Critical Care Medicine, The Third Hospital of Shandong Province Jinan, Shandong, China.

Objective: To investigate the changes of triacylglycerol and inflammatory factors after hypertriglyceridemia acute pancreatitis (HTG-AP) dialysis during pregnancy and to analyze the nursing strategies.

Methods: 50 patients treated with HTG-AP dialysis in our hospital from February 2017 to June 2019 were selected. The patient's vital signs, triglyceride (TG), total cholesterol (TC), TG and TC decline rates before treatment, 1, 3, and 5 days after treatment and inflammatory factors [tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-10 (IL-10) level changes] were measured, as well as the acute physiological and chronic health evaluation II (APACHEII), multiple organ dysfunction syndromes (MODS), systemic inflammatory response syndrome (SIRS) and maternal treatment outcomes.

Results: There was no significant change in body temperature before and after treatment (P>0.05); The heart rate, WBC, CRP before and after treatment were statistically different (P<0.05); Compared with before treatment, serum levels of TG and TC significantly decreased after treatment, and the rate of decrease was significantly increased (P<0.05); Compared with before treatment, the levels of inflammatory factors (TNF-α, IL-1β, IL-6, IL-10) gradually decreased after treatment, and the serum levels of patient's TNF-α, IL-1β, IL-6, IL-10 after 5 days of treatment were more significant (P<0.05); Compared with before treatment, APACHEll, MODS and SIRS scores significantly decreased after treatment, and APACHEll, MODS and SIRS scores were better after 5 days of treatment (P<0.05); The mortality rate during treatment was 2.00%; the complication rate was 32.00%, including 5 cases of acute respiratory distress syndrome, 4 cases of pleural effusion, 4 cases of lung infection, 2 cases of acute renal insufficiency and 1 case of shock.

Conclusion: Dialysis treatment can promote the recovery of HTG-AP patients promptly, improve triglycerides, and reduce inflammation. After the targeted nursing intervention, the treatment efficacy significantly improved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290644PMC
June 2021

Genetic Polymorphism of rs13306146 Affects Expression and Associated With Postpartum Depressive Symptoms in Chinese Women Who Received Cesarean Section.

Front Genet 2021 7;12:675386. Epub 2021 Jul 7.

Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha, China.

Postpartum depressive symptom (PDS) is a common psychological and mental disorder after giving birth. Our previous studies showing the application of dexmedetomidine, an α-AR agonist, can significantly improve maternal sleep, as well as relieve and reduce the incidence of PDS. This study investigated the association between α AR gene polymorphisms and PDS. A total of 568 cesarean section patients were enrolled; the incidence of PDS is 18.13% (103 with PDS, 465 with non-PDS). The Edinburgh Postpartum Depression Scale score ≥10 was used to diagnose PDS at 42 days after delivery. The single-nucleotide polymorphisms of αR were sequenced by pyrosequencing. The effect of rs13306146 A > G polymorphism on αR transcription and the regulation of miR-646 on αR expression were assessed by dual luciferase reporter assays or gene transfection. Increased stress during pregnancy, poor relationship between mother-in-law and daughter-in-law, spousal relationship, domestic violence, antenatal depression, self-harm ideation, and stressful life events were all associated with increased PDS incidence ( < 0.05). The logistic regression analysis found that the αAR rs13306146 polymorphism was associated with PDS after adjusting confounding variables. The transcriptional function of the αAR rs13306146 A allele was decreased compared with the G allele, and the αAR expression level was correspondingly decreased ( < 0.05), as the strongest binding ability of miR-646 to the αAR rs13306146 AA genotype. The effect of αAR rs13306146 A > G polymorphism may change the binding ability of miR-646 at the 3'UTR of the αAR gene, affecting the expression of αAR. This study supports the involvement of the norepinephrine system in the pathogenesis of PDS. Genotypes of αAR may be novel and useful biomarkers for PDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.675386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294467PMC
July 2021

Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation.

JCI Insight 2021 Jul 22;6(14). Epub 2021 Jul 22.

Translational Neurosciences, Faculty of Medicine and Health Sciences, and.

Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, TDP-43, hnRNPA1, hnRNPA2B1, and TIA1, underlie ALS, IBM, and other neurodegenerative diseases. Here, we characterize 4 potentially novel HNRNPA1 mutations (yielding 3 protein variants: *321Eext*6, *321Qext*6, and G304Nfs*3) and 2 known HNRNPA1 mutations (P288A and D262V), previously connected to ALS and MSP, in a broad spectrum of patients with hereditary motor neuropathy, ALS, and myopathy. We establish that the mutations can have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics. P288A accelerated fibrillization and decelerated SG disassembly, whereas *321Eext*6 had no effect on fibrillization but decelerated SG disassembly. By contrast, G304Nfs*3 decelerated fibrillization and impaired liquid phase separation. Our findings suggest different underlying pathomechanisms for HNRNPA1 mutations with a possible link to clinical phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.148363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410042PMC
July 2021

Near-Infrared Fluorescent Agent for Screening of Endometrial Cancer and Precancerous Lesions.

Front Oncol 2021 1;11:713583. Epub 2021 Jul 1.

Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for diagnosis of endometrial cancer and precancerous change by using ZW-FA.

Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.713583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281888PMC
July 2021

Maximizing metal utilization by coupling cross-linked PtRu multi-atom on an atomically dispersed ZnFeNC support.

Dalton Trans 2021 Aug;50(30):10354-10358

The state Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing Key Laboratory of Chemical Process for Clean Energy and Resource Utilization, School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China.

Minimizing noble-metal (NM) usage by exposing all metal atoms on surfaces for catalysis has been a longstanding goal in the development of highly efficient NM catalysts. Here, we realized the full utilization of Pt and Ru atoms by anchoring the cross-linked PtRu multi-atom on the surface of atomically dispersed Zn, Fe and N tri-doped carbon nanomaterials through Pt-N and Ru-N bonds. This supported bimetallic PtRu multi-atom catalyst has extremely high atom efficiency and shows excellent stability and high activity towards the methanol oxidation reaction (MOR). Density functional theory (DFT) calculations reveal that the strongly coupled Pt-N and Ru-N bonds are critical for stabilizing multi-atom PtRu.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1dt01683kDOI Listing
August 2021

S-Decorated Porous Ti C MXene Combined with In Situ Forming Cu Se as Effective Shuttling Interrupter in Na-Se Batteries.

Adv Mater 2021 Aug 9;33(33):e2008414. Epub 2021 Jul 9.

School of Chemistry, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, 100191, China.

Given natural abundance of Na and superior kinetics of Se, Na-Se batteries have attracted much attention but still face the problem of shuttling effect of soluble intermediates. The first-principle calculations reveal the S-decorated Ti C exhibits increased binding energy to sodium polyselenides, suggesting a better capture and restriction on intermediates. The obtained [email protected] porous Ti C ([email protected] C ) exhibits a high reversible capacity of 765 mAh g at 0.1 A g (calculated based on Se), ≈1.2, 1.3, and 1.7 times of [email protected] Ti C ([email protected] C ), [email protected] C , and Se, respectively. It gives considerable capacity of 664 mAh g at 20 A g and impressive cycling stability over 2300 cycles with an ultralow capacity decay of 0.003% per cycle. The excellent electrochemical performance can be ascribed to the S-modified porous Ti C , which provides effective immobilization toward polyselenides, makes full use of nanosized Se, and alleviates volume expansion during sodiation/desodiation. Additionally, in situ forming Cu Se can generate Cu nanoparticles through discharge process and then transform polyselenides into solid-phase Cu Se, further suppressing the shuttling effect. This work provides a practical strategy to immobilize and transform sodium polyselenides for high-capacity and long-life Na-Se batteries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202008414DOI Listing
August 2021

miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway.

Anticancer Agents Med Chem 2021 Jul 6. Epub 2021 Jul 6.

Department of General surgery, ShengJing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang City, Liaoning Province, China.

Background: Gastric cancer (GC) accounts for high mortality, which seriously threatens people's health. This study set out to probe into the effect and mechanism of miR-27b-3p on invasion and migration of GC.

Methods: The miRNA sequence data of GC was acquired from The Cancer Genome Atlas (TCGA) database. The differential expression of miRNAs (DEMis) was acquired through R packages "edgeR" and "limma." TargetScan, picTar, RNA22, PITA, and miRanda were performed to predict the target gene of miR-27b-3p. Western-blot and RT-PCR were applied to detect the expression level of the selected candidate. Transwell assays evaluated the effect of miR-27b-3p and runt-related transcription factor 1 (RUNX1) on cell migration and invasion. The rescue assay was achieved by co-culture with mimics of miR-27b-3p and vector of RUNX1. The psiCHECK2 vector was used in the luciferase report assay.

Results: We found miR-27b-3p was down-regulated in GC and associated with GC patients' poor survival based on the TCGA data and bioinformatics analysis. Furthermore, RUNX1 was the target gene of miR-27b-3p, which was proved by the luciferase report assay. miR-27b-3p and RUNX1 jointly participate in the regulation of the Hippo pathway. The up-regulated miR-27b-3p could inhibit epithelial-mesenchymal transition (EMT) as well as invasion and migration. However, an overexpressed RUNX1 could weaken this phenomenon.

Conclusion: miR-27b-3p was down-regulated in GC, and it could regulate the Hippo pathway and affect EMT by inhibiting RUNX1 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871520621666210707095833DOI Listing
July 2021

Karyopherin-βs play a key role as a phase separation regulator.

J Biochem 2021 Sep;170(1):15-23

Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, USA.

Recent studies have revealed that cells utilize liquid-liquid phase separation (LLPS) as a mechanism in assembly of membrane-less organelles, such as RNP granules. The nucleus is a well-known membrane-bound organelle surrounded by the nuclear envelope; the nuclear pore complex on the nuclear envelope likely applies LLPS in the central channel to facilitate selective biological macromolecule exchange. Karyopherin-β family proteins exclusively pass through the central channel with cargos by dissolving the phase separated hydrogel formed by the phenylalanine-glycine (FG) repeats-containing nucleoporins. Karyopherin-βs also exhibit dissolution activity for the phase separation of cargo proteins. Many cargos, including RNA-binding proteins containing intrinsically disordered regions (IDRs), undergo phase separation; however, aberrant phase separation is linked to fatal neurodegenerative diseases. Multiple weak interactions between karyopherin-βs and phase separation-prone proteins, such as FG repeats-containing nucleoporins or IDR-containing karyopherin-β cargos, are likely to be important for passing through the nuclear pore complex and maintaining the soluble state of cargo, respectively. In this review, we discuss how karyopherin-βs regulate phase separation to function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jb/mvab072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457648PMC
September 2021

Severe bleeding following off-pump coronary artery bypass grafting: predictive factors and risk model.

J Geriatr Cardiol 2021 Jun;18(6):449-461

Department of Surgery, Hebei Medical University, Shijiazhuang, China.

Background: Severe bleeding following cardiac surgery remains a troublesome complication, but to date, there is a lack of comprehensive predictive models for the risk of severe bleeding following off-pump coronary artery bypass grafting (OPCABG). This study aims to analyze relevant indicators of severe bleeding after isolated OPCABG and establish a corresponding risk assessment model.

Methods: The clinical data of 584 patients who underwent OPCABG from January 2018 to April 2020 were retrospectively analyzed. We gathered the preoperative baseline data and postoperative data immediately after intensive care unit admission and used multifactor logistic regression to screen the potential predictors of severe bleeding, upon which we established a predictive model. Using the consistency index and calibration curve, decision curve, and clinical impact curve analysis, we evaluated the performance of the model.

Results: This study is the first to establish a risk assessment and prediction model for severe bleeding following isolated OPCABG. Eight independent risk factors were identified: male sex, aspirin/clopidogrel withdrawal time, platelet count, fibrinogen level, C-reactive protein, serum creatinine, and total bilirubin. Among the 483 patients in the training group, 138 patients (28.6%) had severe bleeding; among the 101 patients in the verification group, 25 patients (24.8%) had severe bleeding. Receiver operating characteristic (ROC) curve analysis for the internal training group revealed a convincing performance with a concordance index (C-index) of 0.859, while the area under the ROC curve for the external validation data was 0.807. Decision curve analysis showed that the model was useful for both groups.

Conclusions: Although there are some limitations, the model can effectively predict the probability of severe bleeding following isolated OPCABG and is therefore worthy of further exploration and verification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11909/j.issn.1671-5411.2021.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220385PMC
June 2021

Deep learning assistance for tuberculosis diagnosis with chest radiography in low-resource settings.

J Xray Sci Technol 2021 Jun 29. Epub 2021 Jun 29.

The First People's Hospital of Kashi, Xinjiang, China.

Tuberculosis (TB) is a major health issue with high mortality rates worldwide. Recently, tremendous researches of artificial intelligence (AI) have been conducted targeting at TB to reduce the diagnostic burden. However, most researches are conducted in the developed urban areas. The feasibility of applying AI in low-resource settings remains unexplored. In this study, we apply an automated detection (AI) system to screen a large population in an underdeveloped area and evaluate feasibility and contribution of apply AI to help local radiologists detect and diagnose TB using chest X-ray (CXR) images. First, we divide image data into one training dataset including 2627 TB-positive cases and 7375 TB-negative cases and one testing dataset containing 276 TB-positive cases and 619 TB-negative cases, respectively. Next, in building AI system, the experiment includes image labeling and preprocessing, model training and testing. A segmentation model named TB-UNet is also built to detect diseased regions, which uses ResNeXt as the encoder of U-Net. We use AI-generated confidence score to predict the likelihood of each testing case being TB-positive. Then, we conduct two experiments to compare results between the AI system and radiologists with and without AI assistance. Study results show that AI system yields TB detection accuracy of 85%, which is much higher than detection accuracy of radiologists (62%) without AI assistance. In addition, with AI assistance, the TB diagnostic sensitivity of local radiologists is improved by 11.8%. Therefore, this study demonstrates that AI has great potential to help detection, prevention, and control of TB in low-resource settings, particularly in areas with scant doctors and higher rates of the infected population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/XST-210894DOI Listing
June 2021

CALD1 is a prognostic biomarker and correlated with immune infiltrates in gastric cancers.

Heliyon 2021 Jun 9;7(6):e07257. Epub 2021 Jun 9.

Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, 200032, China.

Background: Caldesmon gene (CALD1) plays an important role in many cellular functions. Some researchers have found the correlation between CALD1 expression and prognosis of gastrointestinal cancer (GI), but the association with tumor-infiltrating lymphocytes (TILs) still unclear.

Methods: The expression of CALD1 in different human tumor was analyzed by Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The correlations between CALD1 and prognosis in types cancer were explored by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The association between CALD1 expression and tumor immune cell infiltration was further analyzed via TIMER and GEPIA databases.

Results: The CALD1 expressions in types cancer between tumor tissues and adjacent normal tissues were significantly different. The high expression of CALD1 was related with poor overall survival (OS) of patients with gastric cancer, especially in gastric cancer patients at N1, N2 and N3 stages. The expression of CALD1 was positively associated with immune-infiltrated, such as CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells (DCs) in gastric cancer.

Conclusions: CALD1 was considerably a key role in prognosis of patients with gastric cancer. The expression level of CALD1 is significantly associated with immune-infiltrated in gastric cancer. Furthermore, CALD1 expression may be involved in regulating tumor-associated macrophages (TAMs), dendritic cells, exhausted T cells and regulatory T cells in gastric cancer. These findings suggest that CALD1 could be utilized as a marker of prognosis and immune infiltration in gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2021.e07257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219766PMC
June 2021

A Polymorphic FeS Cathode Enabled by Copper Current Collector Induced Displacement Redox Mechanism.

ACS Nano 2021 Jun 28. Epub 2021 Jun 28.

School of Chemistry, Beihang University, Beijing 100191, P. R. China.

In this contribution, we fabricated a composite consisting of two polymorphs of FeS, pyrite (P-FeS) and marcasite (M-FeS), for high-performance Li-FeS battery. A series of electrochemical, microscopic, and spectroscopic characterizations indicate that the introduction of metastable M-FeS into P-FeS enables the four-electron reduction between FeS and lithium to generate Fe and LiS, providing a high specific capacity of 894 mAh/g with specific energy over 1300 Wh/kg. Moreover, it is verified that the electrochemical irreversibility of this composite toward lithium storage is mainly rooted in the shuttle effect, caused by the elemental sulfur which is inevitably produced during the oxidation process of LiS and Fe. To tackle this issue, copper (Cu) current collector is adopted to chemically immobilize the soluble lithium polysulfides and fundamentally alter the reaction pathway. It is shown that compared with Fe, LiS prefers to react with Cu current collector to generate CuS through the thermodynamically facile displacement reaction mechanism benefiting from the similar lattice framework between CuS and LiS. Such displacement reaction without lattice reconstruction renders the composite superior rate capability (∼730 mAh/[email protected] A/g) and long lifespan (89.7% capacity retention after 3200 cycles). Present work allows for the fabrication of high-performance electrodes based on metal chalcogenides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.1c02438DOI Listing
June 2021

AP-1 activity is a major barrier of human somatic cell reprogramming.

Cell Mol Life Sci 2021 Aug 28;78(15):5847-5863. Epub 2021 Jun 28.

CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.

Human induced pluripotent stem cells (iPSCs) technology has been widely applied to cell regeneration and disease modeling. However, most mechanism of somatic reprogramming is studied on mouse system, which is not always generic in human. Consequently, the generation of human iPSCs remains inefficient. Here, we map the chromatin accessibility dynamics during the induction of human iPSCs from urine cells. Comparing to the mouse system, we found that the closing of somatic loci is much slower in human. Moreover, a conserved AP-1 motif is highly enriched among the closed loci. The introduction of AP-1 repressor, JDP2, enhances human reprogramming and facilitates the reactivation of pluripotent genes. However, ESRRB, KDM2B and SALL4, several known pluripotent factors promoting mouse somatic reprogramming fail to enhance human iPSC generation. Mechanistically, we reveal that JDP2 promotes the closing of somatic loci enriching AP-1 motifs to enhance human reprogramming. Furthermore, JDP2 can rescue reprogramming deficiency without MYC or KLF4. These results indicate AP-1 activity is a major barrier to prevent chromatin remodeling during somatic cell reprogramming.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-021-03883-xDOI Listing
August 2021

VHL regulates the sensitivity of clear cell renal cell carcinoma to SIRT4-mediated metabolic stress via HIF-1α/HO-1 pathway.

Cell Death Dis 2021 06 16;12(7):621. Epub 2021 Jun 16.

Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.

Clear cell renal cell carcinomas (ccRCC) reprogram carbon metabolism responses to hypoxia, thereby promoting utilization of glutamine. Recently, sirtuin 4 (SIRT4), a novel molecular has turned out to be related to alternating glutamine metabolism and modulating the tumor microenvironment. However, the role of SIRT4 in ccRCC remains poorly understood. Here, we illustrated that the expression of SIRT4 is markedly reduced in cancerous tissues, and closely associated with malignancy stage, grade, and prognosis. In ccRCC cells, SIRT4 exerted its proapoptotic activity through enhancing intracellular reactive oxygen species (ROS). Heme oxygenase-1 (HO-1) is part of an endogenous defense system against oxidative stress. Nevertheless, overexpression of SIRT4 hindered the upregulation of HO-1 in von Hippel-Lindau (VHL)-proficient cells and repressed its expression in VHL-deficient cells. This discrepancy indicated that competent VHL withstands the inhibitory role of SIRT4 on HIF-1α/HO-1. Functionally, overexpression of HO-1 counteracted the promotional effects of SIRT4 on ROS accumulation and apoptosis. Mechanistically, SIRT4 modulates ROS and HO-1 expression via accommodating p38-MAPK phosphorylation. By contrast, downregulation of p38-MAPK by SB203580 decreased intracellular ROS level and enhanced the expression of HO-1. Collectively, this work revealed a potential role for SIRT4 in the stimulation of ROS and the modulation of apoptosis. SIRT4/HO-1 may act as a potential therapeutic target, especially in VHL-deficient ccRCCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03901-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209205PMC
June 2021

Low temperature-boosted high efficiency photo-induced charge transfer for remarkable SERS activity of ZnO nanosheets.

Chem Sci 2020 Aug 13;11(35):9414-9420. Epub 2020 Aug 13.

Cixi Institute of Biomedical Engineering, Chinese Academy of Science (CAS) Key Laboratory of Magnetic Materials and Devices, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS 1219 Zhongguan West Road Ningbo 315201 P. R. China

Improving the photo-induced charge transfer (PICT) efficiency is the key factor for boosting the surface-enhanced Raman scattering (SERS) performance of semiconductor nanomaterials. Introducing plentiful surface defect states in porous ZnO nanosheets (d-ZnO NSs) effectively provides additional charge transfer routes for highly efficient PICT within the substrate-molecule system. Significantly, an interesting phenomenon of low temperature-boosted SERS activity of these d-ZnO NSs is consequently observed. The enhanced SERS activity can be attributed to the efficient PICT processes due to the significant reduction of non-radiative recombination of surface defects at a low temperature. This is carefully investigated through combining low-temperature SERS measurements with temperature-dependent photoluminescence (PL) emission spectroscopy. Our results clearly demonstrate that the weakened lattice thermal vibration at a low temperature effectively suppresses the phonon-assisted relaxation and reduces carrier traps, resulting in the increase of PL intensity. The decreased traps of photo-induced electrons at surface defect states effectively facilitate the PICT efficiency within the substrate-molecule system. An ultrahigh enhancement factor of 7.7 × 10 and low limit of detection (1 × 10 M) for a 4-mercaptopyridine molecule at a temperature of 77 K are successfully obtained. More importantly, the low temperature-enhanced SERS effect is also obtainable in other metal oxide semiconductors, such as d-TiO and d-CuO nanoparticles. To the best of our knowledge, this is the first time the low temperature-boosted SERS activity of semiconductors has been observed. This study not only provides a deep insight into the chemical SERS mechanism, but also develops a novel strategy for improving semiconductor SERS sensitivity. The strong SERS activity at a low temperature reported here may open new avenues for developing non-metal SERS substrates with new functionalities, especially for the research on cryogenic sensing and hypothermal medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sc02712jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162034PMC
August 2020

Baicalin-loaded macrophage-derived exosomes ameliorate ischemic brain injury via the antioxidative pathway.

Mater Sci Eng C Mater Biol Appl 2021 Jul 23;126:112123. Epub 2021 Apr 23.

School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, PR China. Electronic address:

Baicalin (BA), a strong free radical scavenger, has been demonstrated to exert neuroprotective effects in the treatment of ischemic stroke. However, its clinical application has been limited due to its inability to target the brain and its poor solubility. In this study, we designed novel brain-targeted BA-loaded macrophage-derived exosomes (Exo-BA) to induce neuroprotection against ischemic stroke in animal models. The results revealed that with the help of Exo, the solubility of BA was significantly enhanced. In addition, Exo-BA displayed better brain targeting ability than free BA, as they induced the transfer of more BA into the brain, in a transient middle cerebral artery occlusion/reperfusion (tMCAO) model and permanent middle cerebral artery occlusion (pMCAO) model. Compared with free BA, Exo-BA significantly reduced the generation of reactive oxygen species (ROS) and activated the Nrf2/HO-1 pathway in neurons, thus significantly alleviating cerebral ischemic injury in a stroke model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112123DOI Listing
July 2021
-->