Publications by authors named "Tingting Yu"

355 Publications

The Impact of Legal Recycling Constraints and Carbon Trading Mechanisms on Decision Making in Closed-Loop Supply Chain.

Int J Environ Res Public Health 2022 Jun 16;19(12). Epub 2022 Jun 16.

Department of Industrial and Systems Engineering, The University of Tennessee, Knoxville, TN 37996, USA.

To investigate how legal constraints on the recycling rate of used products and carbon trading mechanisms affect the profits and other decisions of supply chain system members, this paper develops and solves a two-cycle game model in which the manufacturer dominates while the retailer takes a secondary position; the manufacturer produces only non-low-carbon new products in the first cycle and both new and low-carbon remanufactured products in the second cycle. Simultaneously, the effects of parameters such as recovery rate, unit carbon trading price, and carbon emission reduction factor on the decision making of members of the supply chain system are also discussed. Finally, the conclusions are verified by numerical analysis: (1) When carbon reduction is low, the manufacturer will choose the highest recycling rate to obtain the highest profit, and when carbon reduction is high, manufacturers tend to choose not to recycle when the minimum recycling rate bound by law harms the interests of manufacturers. (2) Under the implementation of the carbon trading mechanism, the unit carbon trading price affects the profits of the members of the supply chain system depending on the size of the carbon emission reduction, and the two are negatively correlated at lower carbon emission reductions and positively correlated at higher carbon emission reductions. (3) From the perspective of supply chain system members' interests, legal constraints and the existence of carbon trading mechanisms are not always conducive to increasing the margins of members of the supply chain system, both relevant to the size of carbon emission reductions. (4) From the perspective of environmental benefits, supply chain members do not need to pay economic costs in all cases to contribute to environmental benefits, and the existence of minimum recycling rate constraints and carbon trading mechanisms are conducive to achieving carbon reduction targets.
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http://dx.doi.org/10.3390/ijerph19127400DOI Listing
June 2022

Giant intrathyroidal parathyroid carcinoma: A case report and literature review.

Asian J Surg 2022 Jun 17. Epub 2022 Jun 17.

Department of Radiation Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, Liaoning Province, China.

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http://dx.doi.org/10.1016/j.asjsur.2022.06.003DOI Listing
June 2022

Predicting Global Functional Outcomes Among Post-traumatic Epilepsy Patients After Moderate-to-Severe Traumatic Brain Injury: Development of a Prognostic Model.

Front Neurol 2022 30;13:874491. Epub 2022 May 30.

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

Objective: The development of post-traumatic epilepsy (PTE) following traumatic brain injury (TBI) is associated with unfavorable functional outcomes, and the global function of PTE patients might change dynamically overtime. Predicting the long-term functional outcomes of patients with PTE may help to develop accurate rehabilitation programs and improve their quality of life. Based on this, the objective of this study is to use clinical data to derive and validate a model for predicting the functional outcomes of patients with PTE after moderate-to-severe TBI.

Methods: This study retrospectively analyzed 721 patients with PTE after moderate-to-severe TBI in the Epilepsy Centre, Beijing Tiantan Hospital, from January 2013 to December 2018. All patients had favorable global function as indicated by the Glasgow Outcome Scale-Extended (GOSE) at the time of their first late post-traumatic seizure (PTS) onset, and the 5-year global function after the first late PTS onset was chosen as the principal outcome of interest. To identify possible predictors for the global functional outcomes, univariate and multivariate logistic regression techniques were used. A prognostic model was established using these identified predictors, the internal validation with the bootstrapping method was performed, and the model was then visualized as a graphical score chart.

Results: The 5-year global functional outcome of 98 (13.59%) patients was unfavorable, and the temporal lobe lesion was found as the strongest predictor of unfavorable outcomes. The final prognostic model also included the following other predictors: gender, age at TBI, multiple injuries, the severity of TBI, and latency of PTE. Discrimination was satisfactory with C-statistic of 0.754 (0.707 - 0.800), the goodness-of-fit test indicated good calibration ( = 0.137), and the C-statistic was 0.726 for internal validation. A graphical score chart was also constructed to provide the probability of an unfavorable 5-year global functional outcomes more readily.

Conclusions: Clearer treatment strategies are essential to help ameliorate the global functional outcomes of patients with PTE. Our proposed prognostic model has significant potential to be used in the clinic for predicting global functional outcomes among patients with PTE after moderate-to-severe TBI.
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http://dx.doi.org/10.3389/fneur.2022.874491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197334PMC
May 2022

Use of a specialty endoscopy online platform for continuing medical education for clinical endoscopists during the COVID-19 pandemic.

BMC Med Educ 2022 Jun 15;22(1):458. Epub 2022 Jun 15.

The Second Hospital of HeBei Medical University, Shijiazhuang, People's Republic of China.

Background: To explore the use of a digestive endoscopy professional online platform by domestic endoscopists and its application effect on endoscopists' continuing medical education, analyse the related problems of continuing medical education using this method, and propose targeted improvement suggestions.

Methods: Based on the "Doctor's Circle" app, a questionnaire was sent to all members who successfully registered on the Hebei Biliary and Pancreatic Endoscopy Diagnosis and Treatment Alliance online platform. The questionnaire was available for 30 days. The questionnaire survey results were collected and counted for a grouping comparison.

Results: By the deadline, 703 completed questionnaires had been received. After the registered doctors joined the platform, 469 (66.7%) experienced a significant influence on their own endoscopic operation ability level, and 354 (50.3%) felt a significant improvement in their ability to diagnose biliary- and pancreatic-related diseases. The application effect of the platform on members' continuing medical education was affirmed by the vast majority of registered doctors. The clinical specialty of registered doctors, the length of time they joined the platform, the length of time they participated in the platform activities each time, and whether they played back course videos after the live broadcast of the course on the platform were the main factors affecting the application effect on continuing medical education (P < 0.05). Registered doctors who benefited significantly from the platform used it for 6-12 months, participated in activities for 1-2 hours each time, and often played back course videos.

Conclusion: The new model of continuing medical education based on an online platform breaks through the constraints of traditional models and meets the individualized needs of every medical worker to improve their comprehension level. At present, the global outbreak of COVID-19 makes this learning mode increasingly popular among medical workers. We should constantly improve the organization of the content and methods of continuing medical education courses, make the online platform better serve the majority of medical workers, and effectively improve the comprehension levels of clinicians.
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http://dx.doi.org/10.1186/s12909-022-03516-2DOI Listing
June 2022

In vivo tissue optical clearing assisted through-skull targeted photothrombotic ischemic stroke model in mice.

J Biomed Opt 2022 Jun;27(6)

Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan, China.

Significance: Photothrombotic stroke is an important and widely used model for ischemic stroke research. However, the significant scattering of the skull during the procedure limits the light's ability to penetrate and focus on its target. Targeted photothrombosis uses surgery-based skull windows to obtain optical access to the brain, but it renders the brain's environment unnatural even before a stroke is established.

Aim: To establish a targeted, controllable ischemic stroke model in mice through an intact skull.

Approach: The in vivo skull optical clearing technique provides a craniotomy-free "optical window" that allows light to penetrate. Alongside the local photodynamic effect, we have established targeted photothrombosis without skull removal, effectively controlling the degree of thrombotic occlusion by changing the light dose.

Results: Ex vivo and in vivo results demonstrated that skull optical clearing treatment significantly enhanced light's ability to penetrate the skull and focus on its target, contributing to thrombotic occlusion. The skull optical clearing window was also used for continuous blood flow mapping, and the relationship between light dose and injury degree was evaluated over 14 days of monitoring. Per our findings, increasing the light dose was accompanied by more severe infarction, indicating that the model was easily controllable.

Conclusions: Herein, a targeted, controllable ischemic stroke model was established by combinedly running an in vivo skull optical clearing technique and a photothrombotic procedure, avoiding unnecessary damage or environmental changes to the brain caused by surgery on the skull. Our established model should offer significant value to research on ischemic stroke.
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http://dx.doi.org/10.1117/1.JBO.27.6.065001DOI Listing
June 2022

Effects of childhood obesity and related genetic factors on precocious puberty: protocol for a multi-center prospective cohort study.

BMC Pediatr 2022 May 27;22(1):310. Epub 2022 May 27.

Sanya Women and Children's Hospital, managed by Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 339 Yingbin Road, Sanya, 572022, China.

Background: Childhood obesity has important effects on the onset and development of puberty. Although a number of studies have confirmed the relationship between obesity and precocious puberty, little is known about the pleiotropic genes of obesity and precocious puberty and the interaction between genes and environment. There are four objectives: (1) to analyze the incidence of precocious puberty in the general population in China; (2) to verify the direct effect of obesity on children's precocious puberty using a variety of methods; (3) to verify the effect of obesity and its risk gene polymorphism on precocious puberty in a prospective cohort study; and (4) to analyze the interaction effect of genes and environment on pubertal development.

Methods: We will conduct a multi-center prospective cohort study in three cities, which are selected in southern, central, and northern China, respectively. Primary schools in these cities will be selected by a stratified cluster random sampling method. Primary school students from grade 1 to grade 3 (6 to 10 years old) will be selected for the cohort with extensive baseline data collection, including assessment of pubertal development, family demographic information, early development, sleep pattern, dietary pattern, and physical activity. Participants will be followed up for at least three years, and long-term follow-up will depend on future funding.

Discussion: The findings of this multicenter prospective population-based cohort study may expand previous related puberty development research as well as provide important information on the mechanism of early puberty. Targeted interventions can also be developed to improve adolescent health problems related to puberty development based on the available evidence.

Trial Registration: ClinicalTrials.gov Identifier: NCT04113070 , prospectively registered on October 2, 2019.
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http://dx.doi.org/10.1186/s12887-022-03350-xDOI Listing
May 2022

Site-Specific and Degree-Controlled Alkyl Deuteration via Cu-Catalyzed Redox-Neutral Deacylation.

J Am Chem Soc 2022 Jun 25;144(22):9570-9575. Epub 2022 May 25.

Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United States.

Deuterated organic compounds have become increasingly important in many areas; however, it remains challenging to install deuterium site-selectively to unactivated aliphatic positions with control of the degree of deuteration. Here, we report a Cu-catalyzed degree-controlled deacylative deuteration of diverse alkyl groups with the methylketone (acetyl) moiety as a traceless activating group. The use of -methylpicolino-hydrazonamide (MPHA) promotes efficient aromatization-driven C-C cleavage. Mono-, di-, and trideuteration at specific sites can be selectively achieved. The reaction is redox-neutral with broad functional group tolerance. The utility of this method has been demonstrated in forming a complete set of deuterated ethyl groups, merging with the Diels-Alder reaction, a net devinylative deuteration, and the synthesis of the -analogue of Austedo.
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http://dx.doi.org/10.1021/jacs.2c04382DOI Listing
June 2022

Primary mixed large cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder: A case report and literature review.

Asian J Surg 2022 May 19. Epub 2022 May 19.

Department of Radiation Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, Liaoning Province, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.05.036DOI Listing
May 2022

Factors predicting neuronal surface antibodies in the elderly with new-onset and unknown seizures.

Ann Clin Transl Neurol 2022 May 22. Epub 2022 May 22.

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

Objective: To investigate risk factors of neuronal surface antibodies (NSAbs) and develop a nomogram that could identify patients at the odds of NSAbs among the elderly (aged 60 years or older) with new-onset seizures of unknown etiology.

Methods: Clinical data for aged ≥60 years diagnosed with new-onset seizures of unknown etiology were retrospectively reviewed. A nomogram based on multivariable logistic regression was constructed. Model performance of nomogram was evaluated using area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC). Meanwhile, it was internally validated by bootstrap validation in current cohort.

Results: Of 147 patients included in final analysis, 68 (46.3%) had NSAbs-mediated encephalitis. Six factors were identified: duration of seizures less than 3 months (OR:14.259; 95% CI: 4.480-45.386), focal-onset seizures (OR:12.457; 95% CI: 2.710-57.261), psychiatric deficits (OR:10.063; 95% CI: 3.231-31.343), sleep disorders (OR:3.091; 95% CI: 1.011-9.454), hyponatremia (OR:6.252; 95% CI: 1.445-27.043), and medial temporal lobe (MTL) lesions on MRI (OR:4.102; 95% CI: 1.382-12.169). The nomogram had a good discrimination with an AUC of 0.916 and with a corrected AUC of 0.881 after the bootstrapping validation, our model also exhibited a better predictive performance than scoring systems commonly used clinically. Additionally, the calibration curve showed that predicted NSAbs-positive rates of nomogram were closely aligned with actual observed results. Moreover, the nomogram achieved well on clinical utility by using the DCA and CIC.

Interpretation: Our nomogram may provide a convenient and useful tool for identifying the elderly with new-onset seizures of unknown etiology who are at risk of NSAbs-mediated encephalitis, which would allow these patients receive earlier immunotherapy.
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http://dx.doi.org/10.1002/acn3.51597DOI Listing
May 2022

Short- and Long-term Outcomes of Postoperative Intrauterine Application of Hyaluronic Acid Gel: A Meta-analysis of Randomized Controlled Trials.

J Minim Invasive Gynecol 2022 May 13. Epub 2022 May 13.

Department of bstetrics and Gynecology of the 75th Army Medical Hospital, People's Liberation Army of China, Dali municipality Yunnan, China (Dr. Liu). Electronic address:

Objective: To systematically evaluate the role of hyaluronic acid (HA) gel and its derivatives in the postoperative prevention of intrauterine adhesions (IUA) and to assess whether HA gel could improve the pregnancy rate.

Data Sources: A structured search was performed in PubMed, Cochrane, Scopus, Web of Science, and Embase on February 2, 2022.

Methods Of Study Selection: We chose medical subject headings and relevant terms from other articles for the database search. The following intervention was selected: HA gel or related derivatives vs placebo in randomized controlled trials (RCTs). The following outcomes were selected: the rate and severity of IUA after intrauterine operations and pregnancy rate. After the full-text screening, 12 articles were included in the final analysis. The study quality and risk of bias were assessed with the Cochrane tool (www.training.cochrane.org/handbook).

Tabulation, Integration, And Results: Data from 12 articles on 1579 patients were extracted and analyzed by 2 independent reviewers. According to the meta-analysis, HA gel could decrease the risk of IUA (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.37-0.67; p = .005; I = 59%) after intrauterine operations. Subgroup analysis revealed a significant positive impact of HA gel on both groups receiving dilatation and curettage (RR, 0.42; 95% CI, 0.30-0.59; p = .86; I = 0) or hysteroscopic surgery (RR, 0.55; 95% CI, 0.38-0.80; p = .007; I = 66%). The sensitivity analysis showed that heterogeneity could be improved significantly by removing one study. The severity of IUA (mean difference = -0.92; 95% CI, -1.49 to -0.34; p <.00; I = 89%) was lower in the intervention group. Subgroup and sensitivity analyses did not significantly improve the heterogeneity. When the studies are classified by the volume of HA gel, 10 mL (RR, 0.40; 95% CI, 0.27-0.60; p = .96; I = 0) and 5 mL (RR, 0.34; 95% CI, 0.14-0.82; p = .36; I = 0) were effective in treating IUA. In contrast, HA gel <5 mL was not sufficient to prevent IUA (RR, 0.66; 95% CI, 0.43-1.01; p = .02; I = 71%; p = .05). The pregnancy rate was also improved by the use of HA gel (RR, 1.39; 95% CI, 1.13-1.72; p = .37, I = 0).

Conclusion: HA gel helps prevent IUA and decreases the severity of IUA after intrauterine surgery. A greater volume (≥5 mL) of HA gel is recommended to prevent IUA, according to this analysis. Moreover, HA gel can increase the pregnancy rate after intrauterine surgery. However, these conclusions should be interpreted with caution because of the inadequate quality of some RCTs with relatively small sample sizes and sample heterogeneity. Large RCTs are required to verify these conclusions in the future.
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http://dx.doi.org/10.1016/j.jmig.2022.05.006DOI Listing
May 2022

Proteomic Investigation of Molecular Mechanisms in Response to PEG-Induced Drought Stress in Soybean Roots.

Plants (Basel) 2022 Apr 26;11(9). Epub 2022 Apr 26.

College of Life Sciences, Jilin Agricultural University, Changchun 130118, China.

Roots are generally the critical drought sensors, but little is known about their molecular response to drought stress. We used the drought-tolerant soybean variety 'Jiyu 47' to investigate the differentially expressed proteins (DEPs) in soybean roots during the seedling stage based on the tandem mass tag (TMT) proteomics analysis. Various expression patterns were observed in a total of six physiological parameters. A total of 468 DEPs (144 up-regulated and 324 down-regulated) among a total of 8687 proteins were identified in response to drought stress in 24 h. The expression of DEPs was further validated based on quantitative real-time PCR of a total of five genes (i.e., , , k , and ) involved in the glutathione biosynthesis. Results of enrichment analyses revealed a coordinated expression pattern of proteins involved in various cellular metabolisms responding to drought stress in soybean roots. Our results showed that drought stress caused significant alterations in the expression of proteins involved in several metabolic pathways in soybean roots, including carbohydrate metabolism, metabolism of the osmotic regulation substances, and antioxidant defense system (i.e., the glutathione metabolism). Increased production of reduced glutathione (GSH) enhanced the prevention of the damage caused by reactive oxygen species and the tolerance of the abiotic stress. The glutathione metabolism played a key role in modifying the antioxidant defense system in response to drought stress in soybean roots. Our proteomic study suggested that the soybean plants responded to drought stress by coordinating their protein expression during the vegetative stage, providing novel insights into the molecular mechanisms regulating the response to abiotic stress in plants.
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http://dx.doi.org/10.3390/plants11091173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100407PMC
April 2022

Study of novel variants in patient of combined oxidative phosphorylation deficiency 24.

Transl Pediatr 2022 Apr;11(4):448-457

Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: catalyzes the attachment of asparagine amino acids to mitochondrial tRNA and is critical for efficient mitochondrial protein synthesis. Biallelic variants in are associated with combined oxidative phosphorylation deficiency 24 (COXPD24) and autosomal recessive deafness-94.

Methods: Patient information was obtained after recruitment. Genetic tests were performed using whole exome sequencing (WES) and Sanger sequencing. Structure prediction was based on the RaptorX and SWISS-MODEL platforms. The mRNA analysis of paternal variant was performed. Expression levels and dimerization of wild-type (WT) and mutant were detected in human embryonic kidney (HEK) 293T cells. Mitochondrial localization of variants was determined using immunofluorescence staining.

Results: The patient presented early onset generalized epilepsy, myoclonic seizures, severe bilateral hearing impairment and affected liver and heart. WES identified two compound heterozygous variants in : c.1141A>G/p.Asn381Asp and c.1290G>C/p.Trp430Cys. In silico analysis predicted that both variants would cause significant and pathogenic changes in secondary structure. c.1290G>C is a variant at the first nucleotide of an exon, a location thought to affect mRNA splicing. Although transcriptional experiments did not identify aberrant splicing, we observed a lower proportion of transcripts from the 2 c.1290G>C variant. An experiment showed that both variants impaired expression, while mitochondrial localization and dimerization remained unaffected.

Conclusions: The patient was diagnosed with COXPD24 caused by novel variations. The cardiac dysfunction is identified for the first time. study revealed impairment of variants on expression. These data enrich our knowledge regarding the phenotypic and genotypic spectra of .
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http://dx.doi.org/10.21037/tp-21-570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9085945PMC
April 2022

Exposure to antibiotics and precocious puberty in children: A school-based cross-sectional study in China.

Environ Res 2022 Sep 29;212(Pt C):113365. Epub 2022 Apr 29.

Department of Clinical Epidemiology and Biostatistics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; School of Public Health, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Foods and water can be contaminated with antibiotics in China, which may affect children's health, but evidence on antibiotic exposure with precocious puberty (PP) is limited. This study explored the association of antibiotic exposure with PP in a school-based setting. A cross-sectional study with multistage stratified cluster random sampling was conducted in Zhongshan City, Guangdong Province and Qufu City, Shandong Province in China from October 11 to December 5, 2019. A first-morning urine sample was collected to detect antibiotic exposure. We detected 33 of 45 types of antibiotics from eight categories in 928 primary school children aged 6-12 years using HPLS-MS/MS. Detection rate of antibiotics was stratified by sex, study site, and BMI. The Tanner stages were assessed by professional pediatricians from local hospitals. PP is defined as the onset of secondary characters before 8-year-old or menarche before 10-year-old for girls and before 9-year-old for boys. Multivariable logistic regression was performed to examine the association between antibiotic exposure and PP after adjusting potential confounders. The overall detection rate of antibiotics was 93.0% in 928 children. We found the detection rate of tetracyclines and fluoroquinolones in children with PP was significantly higher than that of children with normal puberty (41.4% vs 29.9%, 56.8% vs 50.6%, respectively, all p < 0.05). Both fluoroquinolones (odds ratio (OR): 1.835, 95% confidence interval (CI): 1.066-3.158) and tetracyclines (OR: 2.120, 95% CI: 1.175-3.825) were associated with increased OR of PP after adjusting sex, age, BMI, study site, and family income. Specifically, compared to the values less than the limits of detection, low concentration of ofloxacin from fluoroquinolones (OR: 2.056, 95% CI: 1.091-3.875) and high concentration of chlortetracycline (OR: 3.027, 95% CI: 1.126-8.140) and tetracycline from tetracyclines (OR: 2.756, 95% CI: 1.167-6.506) were associated with increased OR of PP. Exposure to antibiotics, especially fluoroquinolones and tetracyclines was positively associated with precocious puberty.
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http://dx.doi.org/10.1016/j.envres.2022.113365DOI Listing
September 2022

Effects of dietary restriction on cognitive function: a systematic review and meta-analysis.

Nutr Neurosci 2022 Apr 25:1-11. Epub 2022 Apr 25.

Department of Psychiatry and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: Potential positive link between cognitive function and dietary restriction has been widely concerned. The present study describes a systematic review and preliminary meta-analysis to assess the efficacy of dietary restriction on cognitive function. We classified dietary restrictions as Calories Restriction (CR) and Intermittent Fasting (IF).

Method: This systematic review and meta-analysis conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement (PRISMA) Checklist, Databases including PubMed, Embase, Web of Science, and the Cochrane Library were searched for randomized controlled trials (RCTs) assessing the cognition effectiveness of dietary restriction from database inception to Sep 2021.

Result: Eleven RCTs met the inclusion criteria in the systematic review and meta-analysis. The overall effect of dietary restriction on cognitive function is SMD = 0.22 (95% CI: 0.09-0.34,  < 0.01). The effect on global function SMD = 0.35 (95% CI: 0.04-0.65,  < 0.05) and memory SMD = 0.18 (95% CI: 0.00-0.35,  = 0.05) is significant. MCI showed the best effectiveness SMD = 0.36 (95% CI: 0.05-0.68,  < 0.05), followed by the normal weight population SMD = 0.28 (95% CI: 0.03-0.52,  < 0.05) and overweight population SMD = 0.20 (95% CI: 0.06-0.34,  < 0.01). No statistically significant difference showed between IF and CR ( > 0.05).

Conclusion: Our study demonstrated that dietary restriction has varying degrees of positive effect on cognitive function in overweight/normal-weight people and MCI. However, it should be cautious when generalizing to other populations. Additional high-quality, large-scale, cohort and intervention studies are needed to further assess the effectiveness of dietary restriction on cognition.
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http://dx.doi.org/10.1080/1028415X.2022.2068876DOI Listing
April 2022

Novel RARS2 Variants: Updating the Diagnosis and Pathogenesis of Pontocerebellar Hypoplasia Type 6.

Pediatr Neurol 2022 Jun 15;131:30-41. Epub 2022 Apr 15.

Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China. Electronic address:

Background: Pontocerebellar hypoplasia type 6 (PCH6) is an early-onset encephalopathy with/without mitochondrial respiratory complex defects caused by recessive mutations in mitochondrial arginyl-tRNA synthetase (RARS2). Highly heterogeneous clinical phenotypes and numerous missense variations of uncertain significance make diagnosis difficult. Pathogenesis of PCH6 remains unclear.

Methods: Facial characteristics of patients were assessed. Genetic tests were performed. Structure prediction was based on the template from AlphaFold Protein Structure Database. Expression of mutant RARS2 was tested in HEK293T cells. Patient-derived induced pluripotent stem cells (iPSCs) were detected for human mitochondrial tRNA (hmtRNA) steady-state level, mitochondrial respiratory complex (MRC) activity, oxygen consumption rate (OCR), extracellular acidification rate (ECAR), mitochondrial membrane potential (MMP), reactive oxygen species (ROS) abundance, and apoptosis level.

Results: The three pedigrees were diagnosed as PCH6 caused by compound heterozygous RARS2 variations. Five RARS2 variants were identified: c.3G>C(p.M1?), c.685C>T(p.R229∗), c.1060T>A(p.F354I), c.1210A>G(p.M404V), and c.1369G>A(p.G457R). RARS2 c.3G>C disrupted protein expression. RARS2 c.685C>T created a truncated protein lacking complete catalytic core and anticodon-binding domain. RARS2 c.1060T>A and c.1369G>A were predicted to cause structural abnormality. The hmtRNA steady-state abundance in a patient's iPSCs was unaffected. Mitochondrial energy metabolism was normal, including MRC activity, OCR, ECAR, and MMP, while mitochondria-related cellular characteristics, including ROS (P < 0.001) and apoptosis levels (P < 0.001), increased.

Conclusions: This study reports five RARS2 variations among which c.3G>C and c.1060T>A are novel. Summarized facial features of PCH6 patients will facilitate diagnosis. Defective mitochondrial energy metabolism may not be key points, but mitochondria-related abnormal cellular physiology, including apoptosis, may be an underlying pathogenesis.
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http://dx.doi.org/10.1016/j.pediatrneurol.2022.04.002DOI Listing
June 2022

Heat shock factor 2-binding protein promotes tumor progression via activation of MAPK signaling pathway in lung adenocarcinoma.

Bioengineered 2022 04;13(4):10324-10334

Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China.

Lung adenocarcinoma (LUAD) is a malignant tumor that causes a serious public health burden. The biological functions and potential mechanism of heat shock factor 2-binding protein (HSF2BP) in LUAD have not been studied. This study aimed to explore the HSF2BP expression pattern and its potential biological function in LUAD. The transcriptome data and relevant clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database. The mRNA levels and prognosis of HSF2BP were determined using TCGA datasets. The protein and mRNA expression levels of HSF2BP were identified by conducting western blot analysis and quantitative real-time polymerase chain reaction in tissues and cells, respectively. To determine whether HSF2BP affected the biological function of LUAD cell lines, a series of functional experiments were performed in vitro and in vivo. In addition, gene set enrichment analysis was applied to determine the pathways that HSF2BP regulated, which was further confirmed by western blotting, and the high expression of HSF2BP was observed in LUAD, which was correlated with the unfavorable prognosis in LUAD patients. Clinical correlation analysis revealed that tumor stage was positively correlated with high HSF2BP expression. Furthermore, HSF2BP could serve as an independent risk factor for overall survival. In vitro, HSF2BP knockdown suppressed the proliferation and migration of A549 and H1299 cells. We observed the same results in vivo experiments. Mechanistically, the HSF2BP regulates the mitogen-activated protein kinase signaling pathway to perform its biological function. The HSF2BP plays a role in the development of LUAD and could be a useful anticancer target for the treatment of LUAD.
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http://dx.doi.org/10.1080/21655979.2022.2063561DOI Listing
April 2022

EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model.

J Exp Med 2022 05 14;219(5). Epub 2022 Apr 14.

Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Natural killer (NK) cells exhibit antifibrotic properties in liver fibrosis (LF) by suppressing activated hepatic stellate cell (HSC) populations. Prostaglandin E2 (PGE2) plays a dual role in innate and adaptive immunity. Here, we found that E-prostanoid 3 receptor (EP3) was markedly downregulated in NK cells from liver fibrosis mice and patients with liver cirrhosis. NK cell-specific deletion of EP3 aggravated hepatic fibrogenesis in mouse models of LF. Loss of EP3 selectively reduced the cytotoxicity of the CD27+CD11b+ double positive (DP) NK subset against activated HSCs. Mechanistically, deletion of EP3 impaired the adhesion and cytotoxicity of DP NK cells toward HSCs through modulation of Itga4-VCAM1 binding. EP3 upregulated Itga4 expression in NK cells through promoting Spic nuclear translocation via PKC-mediated phosphorylation of Spic at T191. Activation of EP3 by sulprostone alleviated CCL4-induced liver fibrosis in mice. Thus, EP3 is required for adhesion and cytotoxicity of NK cells toward HSCs and may serve as a therapeutic target for the management of LF.
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http://dx.doi.org/10.1084/jem.20212414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014794PMC
May 2022

ALKBH5 Promotes Multiple Myeloma Tumorigenicity through inducing mA-demethylation of SAV1 mRNA and Myeloma Stem Cell Phenotype.

Int J Biol Sci 2022 6;18(6):2235-2248. Epub 2022 Mar 6.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

N6-methyladenosine (mA) is the most prevalent modification to RNA in higher eukaryotes. ALKBH5 is an RNA demethylase that impacts RNA export and metabolism, and its aberrant expression is associated with the generation of tumours. In this study, we found that ALKBH5 was highly expressed in both primary CD138 plasma cells isolated from multiple myeloma (MM) patients and MM cell lines. Downregulation of ALKBH5 inhibited myeloma cell proliferation, neovascularization, invasion and migration ability, and promoted the apoptosis . MeRIP-seq identified the SAV1 gene as main target gene of ALKBH5. Inhibiting ALKBH5 in MM cells increased SAV1 mA levels, decreased SAV1 mRNA stability and expression, suppressed the stem cell related HIPPO-pathway signalling and ultimately activates the downstream effector YAP, exerting an anti-myeloma effect. Additionally, MM stem cell phenotype was suppressed in ALKBH5-deficient cells and the expression of pluripotency factors NANOG, SOX2 and OCT4 were also decreased. Altogether, our results suggest that ALKBH5 acts as an oncogene in MM and might serve as an attractive potential biomarker and therapeutic target.
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http://dx.doi.org/10.7150/ijbs.64943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990482PMC
March 2022

Predicting the functional outcomes of anti-LGI1 encephalitis using a random forest model.

Acta Neurol Scand 2022 Apr 4. Epub 2022 Apr 4.

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

Objectives: To establish a model in order to predict the functional outcomes of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis and identify significant predictive factors using a random forest algorithm.

Methods: Seventy-nine patients with confirmed LGI1 antibodies were retrospectively reviewed between January 2015 and July 2020. Clinical information was obtained from medical records and functional outcomes were followed up in interviews with patients or their relatives. Neurological functional outcome was assessed using a modified Rankin Scale (mRS), the cutoff of which was 2. The prognostic model was established using the random forest algorithm, which was subsequently compared with logistic regression analysis, Naive Bayes and Support vector machine (SVM) metrics based on the area under the curve (AUC) and the accuracy.

Results: A total of 79 patients were included in the final analysis. After a median follow-up of 24 months (range, 8-60 months), 20 patients (25%) experienced poor functional outcomes. A random forest model consisting of 16 variables used to predict the poor functional outcomes of anti-LGI1 encephalitis was successfully constructed with an accuracy of 83% and an F1 score of 60%. In addition, the random forest algorithm demonstrated a more precise predictive performance for poor functional outcomes in patients with anti-LGI1 encephalitis compared with three other models (AUC, 0.90 vs 0.80 vs 0.70 vs 0.64).

Conclusions: The random forest model can predict poor functional outcomes of patients with anti-LGI1 encephalitis. This model was more accurate and reliable than the logistic regression, Naive Bayes, and SVM algorithm.
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http://dx.doi.org/10.1111/ane.13619DOI Listing
April 2022

Affects Cell Apoptosis by Regulating Intestinal Flora and Metabolites to Promote the Development of Colorectal Cancer.

Front Microbiol 2022 18;13:841157. Epub 2022 Mar 18.

Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Background/aims: Intestinal flora, especially , can affect the development of colorectal cancer (CRC). In this study, we examined the composition of intestinal flora and their metabolites in the tissues, serum and feces of CRC patients.

Materials And Methods: CRC tissues, adjacent normal colonic tissues, fecal and serum samples were collected from CRC patients who received surgical treatment between January 2018 and January 2020. Fecal and serum samples were collected from healthy individuals for comparison. In addition, fecal samples were collected from BALB/c female mice. SW480, a human CRC cell line, was utilized for studies. The experiments involved H-NMR-based metabolomics analysis, targeted and untargeted mass spectrometry analysis, and intestinal flora 16S rDNA V4 region sequencing.

Results: The abundance of and propionic acid concentration were decreased and that of and lactic acid concentration were increased in CRC tissues. In addition, the abundances of , , and were decreased in CRC patients. The levels of leucine and isoleucine were decreased in the serum and tumor tissues of CRC patients. Aspartate, glutamate and glutathione levels were elevated in the tissues of CRC patients only. The serum glutamine, tyrosine, valine, alanine, and histidine levels were decreased significantly. Lactic acid inhibited and propionic acid promoted apoptosis among SW480 CRC cells.

Conclusion: affected the apoptosis of CRC cells and promoted the progression of CRC by affecting the distribution of intestinal flora, which altered the concentrations of metabolites such as lactic acid, propionic acid. Intestinal flora could regulate amino acid metabolism.
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http://dx.doi.org/10.3389/fmicb.2022.841157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971960PMC
March 2022

Ceramic Toughening Strategies for Biomedical Applications.

Front Bioeng Biotechnol 2022 7;10:840372. Epub 2022 Mar 7.

National Engineering Laboratory for Digital and Material Technology of Stomatology and Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Aiming at shortage of metal materials, ceramic is increasingly applied in biomedicine due to its high strength, pleasing esthetics and good biocompatibility, especially for dental restorations and implants, artificial joints, as well as synthetic bone substitutes. However, the inherent brittleness of ceramic could lead to serious complications, such as fracture and disfunction of biomedical devices, which impede their clinical applications. Herein, several toughening strategies have been summarized in this review, including reinforcing phase addition, surface modification, and manufacturing processes improvement. Doping metal and/or non-metal reinforcing fillers modifies toughness of bulk ceramic, while surface modifications, mainly coating, chemical and thermal methods, regulate toughness on the surface layer. During fabrication, optimization should be practiced in powder preparation, green forming and densification processes. Various toughening strategies utilize mechanisms involving fine-grained, stress-induced phase transformation, and microcrack toughening, as well as crack deflection, bifurcation, bridging and pull-out. This review hopes to shed light on systematic combination of different toughening strategies and mechanisms to drive progress in biomedical devices.
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http://dx.doi.org/10.3389/fbioe.2022.840372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940218PMC
March 2022

A Novel Compound Heterozygous Mutation in the DNAH11 Gene Found in Neonatal Twins With Primary Ciliary Dyskinesis.

Front Genet 2022 28;13:814511. Epub 2022 Feb 28.

Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Primary ciliary dyskinesia (PCD) is a rare genetically heterogeneous disorder of motile cilia. Common features of PCD include upper and lower respiratory tract disease, secretory otitis media, situs inversus and fertility problems. To date, although several PCD-associated genes have been identified, the genetic causes of most PCD cases remain elusive. In this case study, we analyzed the clinical and genetic data of one case of monochorionic diamniotic twins which were suspected of having PCD on the basis of clinical and radiological features including situs inversus, recurrent wet cough and sinusitis as well as varying degrees of respiratory distress. Whole-exome sequencing was performed to identify variants of the gene in the twins. Sanger sequencing and real-time quantitative polymerase chain reaction (RT-qPCR) were used for validation of variants both in the patient and the twins. In the twins, we found a novel mutation at c.2436C > G (p.Y812 *) and a pathogenic deletion encompassing 2.0 Kb of 7P15.3 ([GRCh38] chr7: g.21,816,397-21,818,402). The deleted region included exons 64 and 65 of . Sanger sequencing also revealed that the twins' father was a carrier of heterozygous C.2436C > G and a heterozygous deletion was detected in the mother. No other clinically relevant genetic variants were identified. We describe a novel gene compound heterozygous mutation in newborn twins with PCD and recommend that PCD diagnosis should be considered in newborns presenting with respiratory distress and/or situs inversus. Early diagnosis and treatment of PCD will help control disease progression and improve the patient's quality of life.
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http://dx.doi.org/10.3389/fgene.2022.814511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919259PMC
February 2022

Real-time three-dimensional echocardiography and two-dimensional speckle tracking imaging in the evaluation of left atrial function in patients with triple-vessel coronary artery disease without myocardial infarction.

J Clin Ultrasound 2022 May 8;50(4):445-454. Epub 2022 Mar 8.

Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Objective: To evaluate left atrial function in patients with triple-vessel disease (TVD) without myocardial infarction by real-time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle tracking imaging (2D-STE).

Methods: Sixty patients with coronary artery disease (CAD) without myocardial infarction were classified into two groups in accordance with the coronary angiography results: group B (all triple-vessel stenosis ≥ 50% and < 75%) and group C (all triple-vessel stenosis ≥ 75%). Thirty healthy individuals were selected as group A. LA volume related parameters including left atrial maximum volume index (LAVImax), LA passive and active ejection fraction (LAPEF, LAAEF) and LA total ejection fraction (LATEF) were measured by RT-3DE. The global peak atrial longitudinal systolic strain (LASRs), early and late diastolic LA strain (LASRe and LASRa) rates were measured by 2D-STE.

Results: We found statistically significant differences between 2D-STE and RT-3DE related parameters of these three groups. Furthermore, in groups B and C, N-terminal fragment brain natriuretic peptides (NT-pro-BNP) and left ventricular end-diastolic pressure (LVEDP) were found to be significantly correlated with LASRs and LASRa. And NT-pro-BNP had a moderate correlation with LVEDP.

Conclusions: 2D-STE and RT-3DE can assess the LA function in patients with TVD without myocardial infarction. And LA strain values may provide additional information for predicting increased LVEDP and NT-pro-BNP.
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http://dx.doi.org/10.1002/jcu.23188DOI Listing
May 2022

Passive repetition-rate stabilization for a mode-locked fiber laser by electro-optic modulation.

Opt Lett 2022 Mar;47(5):1178-1181

We report a passive stabilization of the repetition rate for a mode-locked fiber laser by using an electro-optic modulator in a phase-biased nonlinear amplifying loop mirror. The underlying mechanism, in contrast to active feedback operations, lies in the cross-phase modulation between electrical and optical pulses within an electro-optic crystal. The resulting spectral shift can automatically compensate for the cavity-length drift via the group velocity dispersion. Consequently, the artificial actuator enables a capture range up to 2.3 mm, much longer than that achieved by index changes of the modulator. A robust and tight locking for the repetition rate is then realized with a standard deviation as low as 9 Hz with a 1-s sample time over 11 hours, corresponding to a fractional instability of 4.3 × 10. Furthermore, a dynamic optical sampling by repetition-rate tuning has been manifested with a fast refresh rate at 100 kHz and a broad scanning range over 305 ps. The demonstrated passive servo action may provide a simple yet effective way to stabilize the repetition rate with high precision, large bandwidth, and wide tunability.
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http://dx.doi.org/10.1364/OL.450771DOI Listing
March 2022

Suppression of the magnetic noise response caused by elliptically polarized light in an optical rotation detection system.

Opt Express 2022 Jan;30(3):3854-3865

We analyze and suppress the magnetic noise response in optical rotation detection system (ORDS) in atomic magnetometers in this study. Because of the imperfections of the optical elements, the probe light is actually elliptically polarized in ORDS, which can polarize the atom ensemble and cause the responses to the three-axis magnetic noise. We theoretically analyze the frequency responses to the magnetic noise, and prove that the responses are closely associated with the DC magnetic field. The values of the DC magnetic fields are calculated with special frequency points, called 'break points', in the transverse responses. We reveal the relationships between the DC magnetic field and the sensitivities of ORDS, and effectively suppress the magnetic noise responses with the residual magnetic field compensation. Finally, the sensitivity of ORDS is improved by approximately two times at 10-20 Hz.
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http://dx.doi.org/10.1364/OE.449951DOI Listing
January 2022

A hypothesis-driven study to comprehensively investigate the association between genetic polymorphisms in EPHX2 gene and cardiovascular diseases: Findings from the UK Biobank.

Gene 2022 May 18;822:146340. Epub 2022 Feb 18.

Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Epoxyeicosatrienoic acids (EETs) are protective factors against cardiovascular diseases (CVDs) because of their vasodilatory, cholesterol-lowering, and anti-inflammatory effects. Soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, degrades EETs into less biologically active metabolites. EPHX2 is highly polymorphic, and genetic polymorphisms in EPHX2 have been linked to various types of CVDs, such as coronary heart disease, essential hypertension, and atrial fibrillation recurrence.

Methods: Based on a priori hypothesis that EPHX2 genetic polymorphisms play an important role in the pathogenesis of CVDs, we comprehensively investigated the associations between 210 genetic polymorphisms in the EPHX2 gene and an array of 118 diseases in the circulatory system using a large sample from the UK Biobank (N = 307,516). The diseases in electronic health records were mapped to the phecode system, which was more representative of independent phenotypes. Survival analyses were employed to examine the effects of EPHX2 variants on CVD incidence, and a phenome-wide association study was conducted to study the impact of EPHX2 polymorphisms on 62 traits, including blood pressure, blood lipid levels, and inflammatory indicators.

Results: A novel association between the intronic variant rs116932590 and the phenotype "aneurysm and dissection of heart" was identified. In addition, the rs149467044 and rs200286838 variants showed nominal evidence of association with arterial aneurysm and cerebrovascular disease, respectively. Furthermore, the variant rs751141, which was linked with a lower hydrolase activity of sEH, was significantly associated with metabolic traits, including blood levels of triglycerides, creatinine, and urate.

Conclusions: Multiple novel associations observed in the present study highlight the important role of EPHX2 genetic variation in the pathogenesis of CVDs.
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http://dx.doi.org/10.1016/j.gene.2022.146340DOI Listing
May 2022

Characteristics of Epileptiform Spike-wave Discharges and Chronic Histopathology in Controlled Cortical Impact Model of Sprague-Dawley Rats.

Neurochem Res 2022 Feb 1. Epub 2022 Feb 1.

Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

Post-traumatic epilepsy (PTE) is a serious complication that can occur following traumatic brain injury (TBI). Sustained secondary changes after TBI promote the process of PTE. Here, we aim to evaluate changes in behavior, electrocorticogram, and histomorphology in rats following chronic TBI models. We observed intensive 7-8 Hz spike-wave-discharges (SWDs) at frontal recording sites and quantified them in SD rats with different degrees of TBI and compared them with age-matched sham rats to evaluate the association between SWDs and injury severity. Notably, although SWDs were even presented in the sham group, the number and duration of events were much lower than those in the TBI groups. SWDs have numerous similarities to absence seizures, such as abrupt onset, termination, and lack of postictal suppression, which may be the nonconvulsive characteristics of PTE. Retigabine, a novel antiepileptic drug, is ineffective in reducing SWDs. In addition, we examined chronic histopathological changes in TBI rats. Rats subjected to moderate and severe TBI exhibited significantly impaired neurological function, which was accompanied by marked cortical injury, hippocampus deformation, reactive gliosis, and mossy fiber sprouting. Long-term progressive structural changes in the brain are one of the characteristics of epileptogenesis after TBI. Our study provided the potential value of epileptiform SWDs in reflecting the nonconvulsive characteristic of PTE and highlighted the vital role of chronic pathological changes, such as reactive gliosis, in promoting the epileptogenesis following TBI.
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http://dx.doi.org/10.1007/s11064-022-03542-yDOI Listing
February 2022

Genome-wide analysis of VPE family in four Gossypium species and transcriptional expression of VPEs in the upland cotton seedlings under abiotic stresses.

Funct Integr Genomics 2022 Apr 21;22(2):179-192. Epub 2022 Jan 21.

College of Life Science, Anhui Agricultural University, Hefei, 230036, China.

Vacuolar processing enzymes (VPEs) play important roles in plant development, programmed cell death, and the responsiveness to biotic and abiotic stresses. To characterize the VPEs in upland cotton (Gossypium hirsutum), the VPE gene family within four Gossypium species, consisting of G. hirsutum, G. barbadense, G. arboreum, and G. raimondii, together with Arabidopsis thaliana, was comparatively analyzed at the genome-wide level. As a result, a total of 43 VPEs were identified, including 13 GhVPEs, 12 GbVPEs, 7 GaVPEs, and 7 GrVPEs, which are evenly distributed with one gene on a chromosome from four Gossypium species, respectively. The phylogenetic tree showed that the identified VPEs within the four Gossypium species could be categorized into β-type, δ-type, and γ-type VPE clades. Collinearity analysis presented 36 of intraspecies VPE-pairs and 152 of interspecies VPE-pairs, respectively, which are included in synteny blocks on chromosome. These results indicate that VPE duplication events have accorded well with the whole genome duplication. And expression profiles of GhVPEs in G. hirsutum seedlings demonstrated that the GhVPEs from the same clade are not necessarily identical in the pattern of transcriptional expression. Upon abiotic stresses (i.e., waterlogging and salt treatments), three GhVPEs (i.e., Ghir_A05G004610, Ghir_A09G011870, and Ghir_D09G011410) were significantly upregulated in their expression amounts, respectively. The GhVPE genes that presented inducible expression under some abiotic stresses may be applied to the improvement of resilience to abiotic stresses for the cultivated cottons.
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http://dx.doi.org/10.1007/s10142-021-00818-4DOI Listing
April 2022

Functional Analysis of Genes and Encoding Dihydroflavonol 4-Reductase (DFR) in L. Var. (M. Laínz) M. Laínz.

Biomed Res Int 2022 10;2022:1382604. Epub 2022 Jan 10.

School of Life Sciences, Changchun Normal University, Changchun 130031, China.

Anthocyanins are important pigments for flower color, determining the ornamental and economic values of horticultural plants. As a key enzyme in the biosynthesis of anthocyanidins, dihydroflavonol 4-reductase (DFR) catalyzes the reduction of dihydroflavonols to generate the precursors for anthocyanidins (i.e., leucoanthocyanidins) and anthocyanins. To investigate the functions of DFRs in plants, we cloned the and genes from the petals of var. and transformed both genes into by -mediated leaf disc method. We further investigated the molecular and phenotypic characteristics of T1 generation transgenic tobacco plants selected based on the hygromycin resistance and verified by both PCR and semiquantitative real-time PCR analyses. The phenotypic segregation was observed in the flower color of the transgenic tobacco plants, showing petals darker than those in the wild-type (WT) plants. Results of high-performance liquid chromatography (HPLC) analysis showed that the contents of gentiocyanin derivatives were decreased in the petals of transgenic plants in comparison to those of WT plants. Ours results revealed the molecular functions of and in the formation of coloration, providing solid theoretical foundation and candidate genes for further genetic improvement in flower color of plants.
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http://dx.doi.org/10.1155/2022/1382604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763498PMC
January 2022

Grass Carp () KAT8 Inhibits IFN 1 Response Through Acetylating IRF3/IRF7.

Front Immunol 2021 3;12:808159. Epub 2022 Jan 3.

School of Life Science, Nanchang University, Nanchang, China.

Post-translational modifications (PTMs), such as phosphorylation and ubiquitination, , have been reported to modulate the activities of IRF3 and IRF7. In this study, we found an acetyltransferase KAT8 in grass carp (KAT8, MW286472) that acetylated IRF3/IRF7 and then resulted in inhibition of IFN 1 response. KAT8 expression was up-regulated in the cells under poly I:C, B-DNA or Z-DNA stimulation as well as GCRV(strain 873) or SVCV infection. The acetyltransferase domain (MYST domain) of KAT8 promoted the acetylation of IRF3 and IRF7 through the direct interaction with them. So, the domain is essential for KAT8 function. Expectedly, KAT8 without MYST domain (KAT8-△264-487) was granularly aggregated in the nucleus and failed to down-regulate IFN 1 expression. Subcellular localization analysis showed that KAT8 protein was evenly distributed in the nucleus. In addition, we found that KAT8 inhibited the recruitment of IRF3 and IRF7 to ISRE response element. Taken together, our findings revealed that grass carp KAT8 blocked the activities of IRF3 and IRF7 by acetylating them, resulting in a low affinity interaction of ISRE response element with IRF3 and IRF7, and then inhibiting nucleic acids-induced innate immune response.
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http://dx.doi.org/10.3389/fimmu.2021.808159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761793PMC
February 2022
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