Publications by authors named "Yun Wang"

3,097 Publications

  • Page 1 of 1

Role of the cation-chloride-cotransporters in the circadian system.

Asian J Pharm Sci 2021 Sep 7;16(5):589-597. Epub 2020 Dec 7.

Institute of Biomedical and Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, Hatherly Laboratories, Exeter EX4 4PS, UK.

The circadian system plays an immense role in controlling physiological processes in our body. The suprachiasmatic nucleus (SCN) supervises this system, regulating and harmonising the circadian rhythms in our body. Most neurons present in the SCN are GABAergic neurons. Although GABA is considered the main inhibitory neurotransmitter of the CNS, recent studies have shown that excitatory responses were recorded in this area. These responses are enabled by an increase in intracellular chloride ions [Cl] levels. The chloride (Cl) levels in GABAergic neurons are controlled by two solute carrier 12 (SLC12) cation-chloride-cotransporters (CCCs): Na/K/Cl co-transporter (NKCC1) and K/Cl co-transporter (KCC2), that respectively cause an influx and efflux of Cl. Recent works have found altered expression and/or activity of either of these co-transporters in SCN neurons and have been associated with circadian rhythms. In this review, we summarize and discuss the role of CCCs in circadian rhythms, and highlight these recent advances which attest to CCC's growing potential as strong research and therapeutic targets.
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http://dx.doi.org/10.1016/j.ajps.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609385PMC
September 2021

Perioperative ctDNA-based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1).

Clin Cancer Res 2021 Nov 29. Epub 2021 Nov 29.

Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital of Sichuan University.

Purpose: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC).

Experimental Design: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3-day and 1-month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis.

Results: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS) (HR=4.2; <0.001). The presence of MRD (ctDNA positivity at postoperative 3-day and/or 1-month) was a strong predictor for disease relapse (HR=11.1; <0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathological variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR=0.3; =0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR=3.1; <0.001). After adjusting for clinicopathological variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (=0.002) but not in the MRD-negative population (=0.283).

Conclusions: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-3044DOI Listing
November 2021

A Layer-Dependent Analytical Model for Printability Assessment of Additive Manufacturing Copper/Steel Multi-Material Components by Directed Energy Deposition.

Micromachines (Basel) 2021 Nov 13;12(11). Epub 2021 Nov 13.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

Copper/steel bimetal, one of the most popular and typical multi-material components (MMC), processes excellent comprehensive properties with the high strength of steel and the high thermal conductivity of copper alloy. Additive manufacturing (AM) technology is characterized by layer-wise fabrication, and thus is especially suitable for fabricating MMC. However, considering both the great difference in thermophysical properties between copper and steel and the layer-based fabrication character of the AM process, the optimal processing parameters will vary throughout the deposition process. In this paper, we propose an analytical calculation model to predict the layer-dependent processing parameters when fabricating the 07Cr15Ni5 steel on the CuCr substrate at the fixed layer thickness (0.3 mm) and hatching space (0.3 mm). Specifically, the changes in effective thermal conductivity and specific heat capacity with the layer number, as well as the absorption rate and catchment efficiency with the processing parameters are considered. The parameter maps predicted by the model have good agreement with the experimental results. The proposed analytical model provides new guidance to determine the processing windows for novel multi-material components, especially for the multi-materials whose physical properties are significantly different.
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http://dx.doi.org/10.3390/mi12111394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618872PMC
November 2021

Discrepancies between Parent and Teacher Reports of Motor Competence in 5-10-Year-Old Children with and without Suspected Developmental Coordination Disorder.

Children (Basel) 2021 Nov 9;8(11). Epub 2021 Nov 9.

NTU Psychology, Nottingham Trent University, Nottingham NG1 4FQ, UK.

Parents and teachers have knowledge of children's daily motor performance yet may make different judgments about the levels of competence observed at home and school. The current study aimed to examine the discrepancies between parent and teacher reports using the Movement ABC-2 Checklist and the Developmental Coordination Disorder Questionnaire (DCDQ) on children with and without suspected Developmental Coordination Disorder (DCD). The Movement ABC-2 Test was administered to 1276 children aged 5-10 years in China. The Movement ABC-2 Checklist and DCDQ were completed by both parents and teachers of all children. A total of 172 children achieving a score below the 15th percentile on the Movement ABC-2 Test were identified as children with suspected DCD. Both parents and teachers showed suitable agreement in judging children's motor competence but low sensitivity in identifying children with DCD. Parent scores of children's motor competence were more closely associated with test performance scores compared to teacher scores. Teachers tended to over-rate children's motor competence. The motor difficulties identified by parents were associated with low Movement ABC-2 Test scores on Manual Dexterity and Balance components, while motor difficulties identified by teachers were associated with the Balance component only. The results demonstrated discrepancies between parent and teacher reports, suggesting the importance of using a range of measures to identify and describe motor difficulties in children.
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http://dx.doi.org/10.3390/children8111028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622880PMC
November 2021

Trends in Transcatheter and Surgical Aortic Valve Replacement Among Older Adults in the United States.

J Am Coll Cardiol 2021 Nov;78(22):2161-2172

Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA; Section of Cardiology, Yale School of Medicine, New Haven, Connecticut, USA; Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA. Electronic address:

Background: Recent trends, including survival beyond 30 days, in aortic valve replacement (AVR) following the expansion of indications for transcatheter aortic valve replacement (TAVR) are not well-understood.

Objectives: The authors sought to characterize the trends in characteristics and outcomes of patients undergoing AVR.

Methods: The authors analyzed Medicare beneficiaries who underwent TAVR and SAVR in 2012 to 2019. They evaluated case volume, demographics, comorbidities, 1-year mortality, and discharge disposition. Cox proportional hazard models were used to assess the annual change in outcomes.

Results: Per 100,000 beneficiary-years, AVR increased from 107 to 156, TAVR increased from 19 to 101, whereas SAVR declined from 88 to 54. The median [interquartile range] age remained similar from 77 [71-83] years to 78 [72-84] years for overall AVR, decreased from 84 [79-88] years to 81 [75-86] years for TAVR, and decreased from 76 [71-81] years to 72 [68-77] years for SAVR. For all AVR patients, the prevalence of comorbidities remained relatively stable. The 1-year mortality for all AVR decreased from 11.9% to 9.4%. Annual change in the adjusted odds of 1-year mortality was 0.93 (95% CI: 0.92-0.94) for TAVR and 0.98 (95% CI: 0.97-0.99) for SAVR, and 0.94 (95% CI: 0.93-0.95) for all AVR. Patients discharged to home after AVR increased from 24.2% to 54.7%, primarily driven by increasing home discharge after TAVR.

Conclusions: The advent of TAVR has led to about a 60% increase in overall AVR in older adults. Improving outcomes in AVR as a whole following the advent of TAVR with increased access is a reassuring trend.
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http://dx.doi.org/10.1016/j.jacc.2021.09.855DOI Listing
November 2021

Volatiles Induced from (Dennstaedtiaceae) by Herbivores Attract (Hemiptera: Reduviidae): Clear Evidence of Indirect Defense in Fern.

Insects 2021 Oct 28;12(11). Epub 2021 Oct 28.

Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai Chenshan Botanical Garden, Shanghai 201602, China.

Plants have evolved various self-defense mechanisms against insect feeding. There are many reports regarding both direct and indirect defense mechanisms in seed-plant. However, only direct defenses on ferns were considered and the indirect defense mechanism has never been reported. In this study, it was observed that the fern can attract the assassin bug in the field. We collected and analyzed volatiles from healthy individuals and the ones wounded by , using dynamic headspace and GC-MS. We recorded the electroantennogram responses of antennae of to different standards of volatile compounds identified from the GC-MS analysis. We also analyzed the behavior of male and female adults in response to volatiles collected from using a Y-tube olfactometer. The results showed that a number of volatile compounds were produced when the fern was damaged by . Electroantennography and Y-tube olfactometer results showed that some herbivore-induced volatiles and volatiles from undamaged leaves could attract . Our research suggests that can attract insect predators by releasing herbivory-induced volatile organic compounds, and for the first time we found ferns may also have indirect defense mechanisms using volatile organic compounds.
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http://dx.doi.org/10.3390/insects12110978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618567PMC
October 2021

Isolating and culturing of single microbial cells by laser ejection sorting technology.

Appl Environ Microbiol 2021 Nov 24:AEM0116521. Epub 2021 Nov 24.

State Key laboratory of Applied Optics, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, P. R. China.

Single cell isolation and cultivation play an important role in studying physiology, gene expression and functions of microorganisms. A series of single-cell isolation technologies have been developed, among which single-cell ejection technology is one of the most promising. Single cell ejection technology has applied Laser Induced Forward Transfer Technique (LIFT) to isolate bacteria but the viability (or recovery rate) of cells after sorting has not been clarified in the current research progress. In this work, to keep the cells alive as much as possible, we propose a three-layer LIFT system (top layer: 25-nm aluminum film; second layer: 3 μm agar media; third layer: liquid containing bacterial) for the isolation and cultivation of single Gram-negative (), Gram-positive ( GG, LGG), and eukaryotic microorganisms (). The experiment results showed that the average survival rates for ejected pure single cells were 63% for , 22% for DH5α, and 74% for LGG. In addition, we successfully isolated and cultured the GFP expressing JM109 from the mixture containing complex communities of soil bacteria by fluorescence signal. The average survival rate of JM109 was demonstrated to be 25.3%. In this study, the isolated and cultured single colonies were further confirmed by colony PCR and sequencing. Such precise sorting and cultivation technique of live single microbial cells could be coupled with other microscopic approaches to isolate single microorganisms with specific functions, revealing their roles in the natural community. We developed a laser induced forward transfer (LIFT) technology to accurately isolate single live microbial cells. The cultivation recovery rates of the ejected single cells were 63% for , 22% for DH5α, and 74% for GG (LGG). Coupled LIFT with fluorescent microscope, we demonstrated that single cells of GFP expressing JM109 were sorted according to fluorescence signal from a complex community of soil bacteria, and subsequently cultured with 25% cultivation recovery rate. This single cell live sorting technology could isolate single microbes with specific functions, revealing their roles in the natural community.
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http://dx.doi.org/10.1128/AEM.01165-21DOI Listing
November 2021

Effects of long-term soft contact lens wear on corneal epithelial thickness after small incision lenticule extraction.

Exp Ther Med 2022 Jan 28;23(1). Epub 2021 Oct 28.

Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

The present study investigated changes in corneal epithelial thickness after small incision lenticule extraction (SMILE) in patients with long-term preoperative soft contact lens (SCL) wear, the impact of SCL wear on the efficacy of surgical outcomes and the effects of long-term SCL wear on postoperative corneal aberrations. Patients were assigned to three groups according to the duration of SCL wear: Group A, the non-SCL-wearing group; group B, those with SCL wear ≤1 year; and group C, those with SCL wear >1 year. Epithelial thickness was recorded in nine zones by anterior segment optical coherence tomography across a 5-mm diameter before surgery and at 1 week, and 1, 3 and 6 months post-surgery. Corneal epithelial thickness and corneal aberrations among the three groups were compared, as well as the effects of changes in corneal epithelial thickness on postoperative visual acuity and manifest refraction. No significant differences were noted with regard to age or preoperative spherical equivalent among groups A (22 eyes), B (17 eyes) and C (18 eyes). Preoperative corneal epithelial thickness in the inferonasal, inferior and inferotemporal zones was thinner in group B compared with that in group A, and corneal epithelial thickness was thinner in all nine zones in group C compared with that in group A (P<0.05). At all follow-up time points, in the central, nasal, inferonasal, inferior, inferotemporal and temporal areas, the epithelial thickness was thinner in group C compared with that in group A (P<0.05). At 3 months postoperatively, the epithelial thickness was thinner in the inferonasal and inferior sectors in group C compared with that in group B (P<0.05), and at 6 months postoperatively, the epithelial thickness in the inferior region was thinner in group C compared with that in group B (P<0.05). There were no significant differences in visual acuity or manifest refraction among the three groups at all postoperative time points. The total higher-order aberrations were greater in group C compared with those in group A for all time points (P<0.05) and were greater in group C at 1 and 3 months postoperatively compared with those in group B (P<0.05). The spherical aberrations at 3 and 6 months postoperatively were greater in group C compared with those in group A (P<0.05). The coma aberrations were greater in group C compared with those in groups A and B for all time points (P<0.05). In conclusion, long-term SCL wear will result in corneal epithelial thinning, which does not impact visual acuity or manifest refraction after SMILE.
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http://dx.doi.org/10.3892/etm.2021.10930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593870PMC
January 2022

Interferometric microscope with a confocal focusing for inner surface defect detection of ICF capsule.

Opt Express 2021 Nov;29(23):38924-38938

Inner surface defects of inertial confinement fusion (ICF) capsule are a key factor leading to ignition failure; however, there are still no effective and non-destructive detection methods available. To solve this problem, we propose the first interferometric microscope with confocal focusing (CFIM). CFIM first uses confocal technology to achieve accurate axial positioning of both capsule and the camera, thereby ensuring that the inner surface of the capsule is precisely and clearly imaged at the camera. Then, phase-shifting interferometry based on a short-coherence source and a spherical reference is applied to obtain inner defects result from null inner surface interferograms. In addition, in-situ focusing is realized by the axial adjustment of camera, but not by the capsule, to ensure that the outer defects and the fake inner defects caused by it have the same pixel coordinates, thereby solving the confusion of fake inner defects. The comparative experimental results of the CFIM and the scanning electron microscope (destructive detection) prove the feasibility of the proposed method. With unique precision confocal focusing and in-situ focusing ability, CFIM provides the first approach for non-destructive detection of inner surface defects of ICF capsule to the best of our knowledge.
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http://dx.doi.org/10.1364/OE.444117DOI Listing
November 2021

Diagnostic Improvements of Deep Learning-Based Image Reconstruction for Assessing Calcification-Related Obstructive Coronary Artery Disease.

Front Cardiovasc Med 2021 3;8:758793. Epub 2021 Nov 3.

State Key Laboratory of Complex Severe and Rare Diseases, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The objective of this study was to explore the diagnostic value of deep learning-based image reconstruction (DLR) and hybrid iterative reconstruction (HIR) for calcification-related obstructive coronary artery disease (CAD) evaluation by using coronary CT angiography (CCTA) images and subtraction CCTA images. Forty-two consecutive patients with known or suspected coronary artery disease who underwent coronary CTA on a 320-row CT scanner and subsequent invasive coronary angiography (ICA), which was used as the reference standard, were enrolled. The DLR and HIR images were reconstructed as CTA and CTA, and, based on which, the corresponding subtraction CCTA images were established as CTA and CTA, respectively. Qualitative images quality comparison was performed by using a Likert 4 stage score, and quantitative images quality parameters, including image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated. Diagnostic performance on the lesion level was assessed and compared among the four CCTA approaches (CTA, CTA, CTA, and CTA). There were 166 lesions of 86 vessels in 42 patients (32 men and 10 women; 62.9 ± 9.3 years) finally enrolled for analysis. The qualitative and quantitative image qualities of CTA and CTA were superior to those of CTA and CTA, respectively. The diagnostic accuracies of CTA, CTA, CTA, and CTA to identify calcification-related obstructive diameter stenosis were 83.73%, 69.28%, 75.30%, and 65.66%, respectively. The false-positive rates of CTA, CTA, CTA, and CTA for luminal diameter stenosis ≥50% were 15%, 31%, 24%, and 34%, respectively. The sensitivity and the specificity to identify ≥50% luminal diameter stenosis was 90.91% and 83.23% for CTA. Our study showed that deep learning-based image reconstruction could improve the image quality of CCTA images and diagnostic performance for calcification-related obstructive CAD, especially when combined with subtraction technique.
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http://dx.doi.org/10.3389/fcvm.2021.758793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595262PMC
November 2021

HLA-DR Expression Level in CD8 T Cells Correlates With the Severity of Children With Acute Infectious Mononucleosis.

Front Immunol 2021 3;12:753290. Epub 2021 Nov 3.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: This study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM).

Methods: Twenty-eight pediatric patients with IM aged 3-8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected.

Results: The percentages and absolute numbers of CD3 and CD8 T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve CD4 and CD8 T cells were decreased but with increased percentages of memory CD4 and CD8 T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-αβ, and inhibitory receptors PD-1, TIGIT in CD8 T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-γ, IL-2, and TNF-α) secretion capability of CD4 and CD8 T cells after stimulation with PMA/ionomycin . Multivariate analysis revealed that the percentage of HLA-DR CD8 T cells was an independent prognostic marker for IM. The percentage of HLA-DR CD8 T cells was significantly correlated with high viral load and abnormal liver function results.

Conclusion: Robust expansion and upregulation of HLA-DR in CD8 T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR CD8 T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.
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http://dx.doi.org/10.3389/fimmu.2021.753290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596082PMC
November 2021

Robot-assisted thoracic surgery for apical located neurogenic tumors.

Asian J Surg 2021 Nov 17. Epub 2021 Nov 17.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.11.014DOI Listing
November 2021

Anterior quadratus lumborum block at the lateral supra-arcuate ligament versus transmuscular quadratus lumborum block for postoperative analgesia in patients undergoing laparoscopic nephrectomy: A randomized controlled trial.

J Clin Anesth 2021 Dec 19;75:110561. Epub 2021 Oct 19.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. Electronic address:

Study Objective: The analgesic efficacy of transmuscular quadratus lumborum block (TQLB) to decrease the need for opioid consumption after laparoscopic nephrectomy has been demonstrated in several studies. However, the effect of an anterior QLB approach at the lateral supra-arcuate ligament (QLB-LSAL) in this surgical context is unclear. Here, we aimed to compare postoperative analgesic effects of the two block approaches in laparoscopic nephrectomy.

Design: A single-center, randomized controlled trial.

Setting: University-affiliated tertiary care hospital.

Patients: A total of 106 patients with American Society of Anesthesiologists (ASA) physical status of I-III scheduled to undergo elective laparoscopic nephrectomy under general anesthesia.

Interventions: Patients were randomly allocated to receive preoperative TQLB or QLB-LSAL with 0.5% ropivacaine (25 mL). Postoperatively, patient-controlled analgesia with intravenous sufentanil was administered.

Measurements: The primary outcome was postoperative intravenous morphine equivalent consumption within the first 24 h postoperatively. Secondary outcomes included pain scores, satisfaction scores, levels of sedation, and incidence of nausea or vomiting.

Main Results: Patients who underwent preoperative QLB-LSAL used a significantly lower intravenous morphine equivalent dose than those who underwent preoperative TQLB within the initial 24 h after surgery (34.3 ± 6.3 mg vs 23.5 ± 3.2 mg, P < 0.001). No significant differences were observed in pain scores, satisfaction scores, sedation scores, or incidence of nausea or vomiting between the groups.

Conclusions: The results indicate that, compared to TQLB, QLB-LSAL is a beneficial nerve block that can reduce postoperative opioid consumption, making it a potentially superior approach to achieve multimodal analgesia after laparoscopic nephrectomy.
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http://dx.doi.org/10.1016/j.jclinane.2021.110561DOI Listing
December 2021

Adjuvant Chemotherapy for Gastric Cancer Patients with Mismatch Repair Deficiency or Microsatellite Instability: Systematic Review and Meta-Analysis.

Ann Surg Oncol 2021 Nov 18. Epub 2021 Nov 18.

Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status serves as a predictor of a poor response to adjuvant chemotherapy among stage 2 colon cancer patients. This study aimed to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC).

Methods: Clinical studies comparing adjuvant chemotherapy and surgery alone in dMMR/MSI-H GCs through June 2021 were retrieved to assess the survival of patients managed with both treatments. Two approaches were used to pool the hazard ratio (HR) of survival: (1) if Kaplan-Meier curves and number of patients at risk were provided, individual patient data were extracted. Cox models were used to calculate the HR with its 95% confidence interval (CI); (2) for study-level data, pooled HR was estimated using fixed/random-effects models.

Results: Seven clinical studies were assessed. For dMMR/MSI-H versus mismatch repair-proficient (pMMR)/microsatellite stable (MSS)/microsatellite instability-low (MSI-L) status, the estimated 5-year disease-free survival (DFS) rate was 74.2% versus 51.5% (HR, 0.44; 95% CI, 0.32-0.62; P < 0.001) and the estimated 5-year OS rate was 60.5% versus 49.1% (HR, 0.71; 95% CI, 0.60-0.85; P < 0.001). The study-level data showed pooled HRs of 0.42 for DFS (95% CI, 0.31-0.57; P < 0.001) and 0.65 for OS (95% CI, 0.38-1.11; P = 0.114). For adjuvant chemotherapy versus observation of dMMR/MSI-H, the estimated 5-year DFS rate was 76.1% versus 73.3% (HR, 0.72; 95% CI, 0.45-1.15; P = 0.171) and the estimated 5-year OS rate was 73.5% versus 59.7% (HR, 0.62; 95% CI, 0.46-0.83; P = 0.001). Significant survival differences also were observed at study level.

Conclusions: The study findings confirm the benefit of adjuvant chemotherapy for dMMR/MSI-H GC patients.
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http://dx.doi.org/10.1245/s10434-021-11050-6DOI Listing
November 2021

Biomimetic and immunomodulatory baicalin-loaded graphene oxide-demineralized bone matrix scaffold for bone regeneration.

J Mater Chem B 2021 Nov 17. Epub 2021 Nov 17.

Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center of Stomatology, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.

The use of an artificial bone substitute is a potential strategy for repairing bone defects; however, the inadequate consideration of repair-immune system interactions, resulting in significant pathological changes in the microenvironment, is a major barrier to achieving effective regenerative outcomes. Here, we evaluated a biomimetic baicalin (BAI)-incorporating graphene oxide-demineralized bone matrix (GO-BAI/DBM) hybrid scaffold, which was beneficial for bone regeneration. First, by considering that bone is a kind of organic-inorganic composite, a biomimetic GO/DBM bone substitute with enhanced physiochemical and osteoinductive properties was fabricated. Furthermore, inherently therapeutic GO was also used as a drug delivery carrier to achieve the sustained and prolonged release of BAI. Notably, a series of experiments showed that the GO-BAI nanocomposites could transform inflammatory M1 macrophages into pro-healing M2 macrophages, which was beneficial for angiogenesis and osteogenesis. By using a rat subcutaneous model, it was revealed that the GO-BAI nanocomposites proactively ameliorated the inflammatory response, which was coupled with decreased fibrous encapsulation. Notably, obvious calvarial bone regeneration was achieved using the GO-BAI/DBM hybrid scaffold. These findings demonstrated that the bifunctional GO-BAI/DBM scaffold, by enhancing beneficial cross-talk among bone cells and inflammatory cells, might be utilized as an effective strategy for bone regeneration.
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http://dx.doi.org/10.1039/d1tb00618eDOI Listing
November 2021

Combination of aqueous two-phase flotation and inverse transition cycling: Strategies for separation and purification of recombinant β-glucosidase from cell lysis solution.

Food Chem 2021 Nov 8:131543. Epub 2021 Nov 8.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China. Electronic address:

This work was developed to solve the problems of the restriction of non-specific adsorption and time-dependent denaturation in the purification of recombinant proteins by multistage chromatographic procedures. A novel purification method (ATPF-ITC) which combining aqueous two-phase flotation (ATPF) with inverse transition cycling (ITC) was established and used to efficiently purify recombinant β-glucosidase (GLEGB) from cell lysis solution. First, GLEGB would preferentially adsorb on the nitrogen bubble interface relied on the hydrophobic property of the graphene-binding (GB) tag and enter into the top phase of ATPF. Second, GLEGB was achieved further purification by one-round ITC method based on the thermosensitive of the elastin-like polypeptide (ELP) tag. Consequently, the enzymatic activity recovery of GLEGB was 124.92% ± 0.83%, and the purification factor reached 24.26 ± 0.22. The purification results remained stable after six polymer cycles, and the process of ATPF-ITC had no negative effect on the structure of recombinant protein.
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http://dx.doi.org/10.1016/j.foodchem.2021.131543DOI Listing
November 2021

Evolution and Emerging Trends in Depression Research From 2004 to 2019: A Literature Visualization Analysis.

Front Psychiatry 2021 29;12:705749. Epub 2021 Oct 29.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Depression has become a major threat to human health, and researchers around the world are actively engaged in research on depression. In order to promote closer research, the study of the global depression knowledge map is significant. This study aims to map the knowledge map of depression research and show the current research distribution, hotspots, frontiers, and trends in the field of depression research, providing researchers with worthwhile information and ideas. Based on the Web of Science core collection of depression research from 2004 to 2019, this study systematically analyzed the country, journal, category, author, institution, cited article, and keyword aspects using bibliometric and data visualization methods. A relationship network of depression research was established, highlighting the highly influential countries, journals, categories, authors, institutions, cited articles, and keywords in this research field. The study identifies great research potential in the field of depression, provides scientific guidance for researchers to find potential collaborations through collaboration networks and coexistence networks, and systematically and accurately presents the hotspots, frontiers, and shortcomings of depression research through the knowledge map of global research on depression with the help of information analysis and fusion methods, which provides valuable information for researchers and institutions to determine meaningful research directions.
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http://dx.doi.org/10.3389/fpsyt.2021.705749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585938PMC
October 2021

Comparing the cycling behaviours of Australian, Chinese and Colombian cyclists using a behavioural questionnaire paradigm.

Accid Anal Prev 2021 Nov 10;164:106471. Epub 2021 Nov 10.

Queensland University of Technology (QUT), Centre for Accident Research and Road Safety-Queensland (CARRS-Q), Institute of Health and Biomedical Innovation (IHBI), Kelvin Grove, Queensland 4059, Australia.

Cyclists are vulnerable road users and face disproportionately high rates of road trauma, especially in low- and middle-income countries. Behaviour of road users is a system outcome, and thus studying cyclist behaviours can identify problems in the whole road transport system and assist in generating long-lasting, cost-effective solutions to promote cyclist safety. This study aims to investigate the similarities and disparities of cycling behaviour among countries with different income levels and cycling prevalence, and the relationships among cyclist demographic characteristics, behaviours and crash involvement. It applies the Cycling Behaviour Questionnaire (CBQ) to measure the behaviour of cyclists in three countries: Australia (high-income, emerging cycling country), China (mid-income, traditional cycling country) and Colombia (low-income, emerging cycling country). A total of 1094 cyclists (Australia 347, China 368, and Colombia 379) with a mean age of 31.8 years completed the online questionnaire. Confirmatory Factor Analysis was used to examine the factorial structure of the CBQ. The results showed that the three-factor CBQ (i.e., Traffic Violations, Errors and Positive Behaviours) had a stable and uniform factorial structure across all three countries. Cyclists reported more frequent positive behaviours than risky behaviours across all three countries. The Australian cyclists reported more positive behaviours and fewer violations than cyclists from the other countries, which is likely to reflect the road environment, policy and enforcement differences. Male cyclists tended to engage in more risky riding than females and reported more crash involvement. Older cyclists reported less risky riding and less involvement in crashes than younger cyclists. Cyclists who rode more often reported more frequent risky riding. The study helps understand the prevalence of risky/positive cyclist behaviours among countries and provides insights for developing systematic countermeasures to improve cycling environment and cyclist safety.
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http://dx.doi.org/10.1016/j.aap.2021.106471DOI Listing
November 2021

Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells.

PLoS One 2021 12;16(11):e0259644. Epub 2021 Nov 12.

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.

Background: Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes.

Methods: We introduce two new methods for diagnosing S. pneumoniae infections by measuring the presence of newly activated, pathogen-specific, circulating Antibody Secreting Cells (ASC). First, ASC were detected by ELISpot assays that measure cells secreting antibodies specific for signature antigens. Second, the antibodies secreted by isolated ASC were collected in vitro in a novel matrix, MENSA (media enriched with newly synthesized antibodies) and antibodies against S. pneumoniae antigens were measured using Luminex immunoassays. Each assay was evaluated using blood from S. pneumoniae and non-S. pneumoniae-infected adult patients.

Results: We enrolled 23 patients with culture-confirmed S. pneumoniae infections and 24 controls consisting of 12 non-S. pneumoniae infections, 10 healthy donors and two colonized with S. pneumoniae. By ELISpot assays, twenty-one of 23 infected patients were positive, and all 24 controls were negative. Using MENSA samples, four of five S. pneumoniae-infected patients were positive by Luminex immunoassays while all five non-S. pneumoniae-infected patients were negative.

Conclusion: Specific antibodies produced by activated ASC may provide a simple diagnostic for ongoing S. pneumoniae infections. This method has the potential to diagnose acute bacterial infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259644PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589192PMC
November 2021

Correction to: Pharmacological stimulation of sigma-1 receptor promotes activation of astrocyte via ERK1/2 and GSK3β signaling pathway.

Naunyn Schmiedebergs Arch Pharmacol 2021 Nov 10. Epub 2021 Nov 10.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.

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http://dx.doi.org/10.1007/s00210-021-02180-5DOI Listing
November 2021

Tumoral Morphologic Features From Cervical Biopsies That Are Predictive of a Negligible Risk for Nodal Metastasis and Tumor Recurrence in Usual-type Cervical Adenocarcinomas: A Multi-institutional Study.

Am J Surg Pathol 2021 Nov 11. Epub 2021 Nov 11.

Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan Province Departments of Pathology Gynecologic Oncology, Sun Yat-Sen University Cancer Center Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai Department of Pathology, Women's Hospital, School of Medicine Zhejiang University, Hangzhou, Zhejiang Province Department of Pathology, Sheng Jing Hospital of China Medical University, Shenyang, Liaoning Province Department of Pathology, Shandong University School of Basic Medical Sciences Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University School of Medicine, Jinan, Shandong Province Department of Pathology, The Seventh Medical Center of Chinese PLA General Hospital Department of Pathology, The First Medical Center of Chinese PLA General Hospital, Beijing, China Departments of Pathology Obstetrics and Gynecology Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX Department of Pathology, Women & Infants Hospital & Alpert Medical School of Brown University, Providence, RI Department of Pathology, University of California San Diego, La Jolla, CA Archway Health, Boston, MA.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P<0.0001) and TR (odds ratio for TNG1=0.225, 95% CI: 0.051-0.987, P=0.0479; for NTD=0.367, 95% CI: 0.171-0.786, P=0.0099) independent of depth of stromal invasion, lymphovascular invasion, tumor size, FIGO stage, and Silva pattern. Overall, 73/379 (19%) cases were both TNG1 and NTD-negative on the biopsy, and none of these 73 cases showed NM (0%), but a single case (1.4%) showed TR. In contrast, among the 324 biopsies with TNG2/3 and/or presence of NTD, 62 (19.1%) had NM, and 41 (12.9%) had TR. In summary, 2 variables in combination (ie, TNG1 and NTD-negative) identified a subset of HPVA EAC patients-∼19%-with a 0% frequency of nodal metastases and only 1.4% frequency of recurrence. Biopsies highly but imperfectly predicted these features. Nonetheless, these findings may potentially be of clinical utility in the risk stratification of patients with HPVA EACs. This may allow some patients with a minimal risk of nodal metastases and TR to be identified at the biopsy phase, thereby facilitating more personalized, possibly less aggressive treatment.
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http://dx.doi.org/10.1097/PAS.0000000000001833DOI Listing
November 2021

Phosphorylation of MICAL2 by ARG promotes head and neck cancer tumorigenesis by regulating skeletal rearrangement.

Oncogene 2021 Nov 8. Epub 2021 Nov 8.

Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

The actin cytoskeletal architecture provides the structural underpinnings for crucial cellular behaviors. In cancer cells, changes in the actin cytoskeleton may serve as prerequisites for proliferation, invasion, and metastatic dissemination. However, the underlying mechanisms remain largely unknown. Here, we show that MICAL2, which is increased in head and neck squamous cell carcinoma (HNSCC) and inversely associated with patient survival, promotes HNSCC growth, invasion, and migration. MICAL2 serves as a flavoprotein monooxygenase and directly induces actin filament depolymerization by specifically oxidizing the methionine 44 and 47 residues of F-actin. The kinase ARG interacts with MICAL2 and augments MICAL2-mediated actin disassembly. Direct phosphorylation assay and mass spectrometry confirmed that ARG phosphorylates MICAL2 at Tyr445, Tyr463, and Tyr488. Substitution of the Tyr445 or Tyr463 residue of purified recombinant MICAL2-redox with phenylalanine (generating a non-phosphorylatable mutant) abolishes the enhanced MICAL2-mediated F-actin disassembly induced by ARG. Consistently, ectopic expression of non-phosphorylatable MICAL2 mutants (MICAL2 and MICAL2, not MICAL2) failed to ameliorate HNSCC cell growth, whereas expression of wild-type MICAL2 or MICAL2 rescued the impaired proliferation induced by MICAL2 knockdown. Moreover, CCG-1423, an inhibitor of MICAL2, was shown to inhibit HNSCC cell proliferation, invasion, and migration. Taken together, our findings indicate that phosphorylation of MICAL2 at Tyr445 and Tyr463 by ARG mediates F-actin disassembly and promotes HNSCC progression.
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http://dx.doi.org/10.1038/s41388-021-02101-zDOI Listing
November 2021

The Association of Parent-Child Communication With Internet Addiction in Left-Behind Children in China: A Cross-Sectional Study.

Int J Public Health 2021 10;66:630700. Epub 2021 Sep 10.

The Institute of Social and Family Medicine, School of Medicine, Zhejiang University, Hangzhou, China.

Internet addiction has emerged as a growing concern worldwide. This study aimed to compare the prevalence of Internet addiction between left-behind children (LBC) and non-left-behind children (non-LBC), and explore the role of paternal and maternal parent-child communication on LBC. We conducted a cross-sectional survey in rural areas in Anhui, China. The complete data were available from 699 LBC and 740 non-LBC. Multivariable logistic regression was used to examine 1) whether LBC were more likely to develop Internet addiction, and 2) the association between parent-child communication and Internet addiction among LBC. LBC had a higher likelihood to report Internet addiction when compared to non-LBC (OR = 2.03, 95%CI = 1.43-2.88, < 0.001). Among LBC, parent-child communication (both mother-child and father-child) was protective factor for children's Internet addiction. The role of mother-child communication played well among male LBC. The lack of parental supervision may lead to Internet addiction. It is highly recommended for migrant parents to improve the quality of communication with their children. Also, gender-matching effects should be considered in the relationship between children's behavior and parental factors.
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http://dx.doi.org/10.3389/ijph.2021.630700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565268PMC
November 2021

Alleviation of Methamphetamine Sensitization by Partially Lesioning Dopaminergic Terminals with 6-Hydroxydopamine in Nucleus Accumbens.

Cell Transplant 2021 Jan-Dec;30:9636897211052300

Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.

Amphetamine-type stimulants have become important and popular abused drugs worldwide. Methamphetamine (Meth) sensitization, characterized by a progressive increase in behavioral responses after repeated administration, has been reported in rodents and patients. This behavioral effect has been used as a laboratory model to study drug addiction and schizophrenia. The mesolimbic dopaminergic pathway plays a significant role in the development of Meth behavioral sensitization. Previous studies have reported that the ablation of nucleus accumbens (NAc) by electrolytic or thermal lesioning attenuates addictive behavior to opioids in animals. However, these studies were only conducted in opioid addictive rodents. Furthermore, these ablation procedures also damaged the non-dopaminergic neurons and fibers passing through the NAc. The purpose of this study was to examine the therapeutic effect of NAc lesioning by a selective dopaminergic toxin in Meth-sensitized animals. Adult mice received repeated administration of Meth for 7 days. Open-field locomotor activity and stereotype behavior were significantly increased after Meth treatment, suggesting behavior sensitization. A partial lesion of dopaminergic terminals was made through stereotaxic administration of dopaminergic toxin 6-hydroxydopamine (6-OHDA) to the NAc in the Meth -sensitized mice. Meth behavioral sensitization was significantly antagonized after the lesioning. Brain tissue was collected for qRT-PCR analysis. Repeated administration of Meth increased the expression of tyrosine hydroxylase (TH), BDNF, and Shati, a marker for Meth sensitization, in the NAc. Treatment with 6-OHDA significantly antagonized the upregulation of TH and Shati. Taken together, these data suggest that local administration of 6-OHDA mitigated Meth sensitization in chronic Meth-treated animals. Our data support a new surgical treatment strategy for Meth abuse.
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http://dx.doi.org/10.1177/09636897211052300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579363PMC
November 2021

National Trends and Disparities in Hospitalization for Acute Hypertension Among Medicare Beneficiaries (1999-2019).

Circulation 2021 Nov 8;144(21):1683-1693. Epub 2021 Nov 8.

Center for Outcomes Research and Evaluation, Yale New Haven Hospital, CT (Y.L., Y.W., E.S.S., O.O. H.M.K.).

Background: In the past 2 decades, hypertension control in the US population has not improved and there are widening disparities. Little is known about progress in reducing hospitalizations for acute hypertension.

Methods: We conducted serial cross-sectional analysis of Medicare fee-for-service beneficiaries age 65 years or older between 1999 and 2019 using Medicare denominator and inpatient files. We evaluated trends in national hospitalization rates for acute hypertension overall and by demographic and geographical subgroups. We identified all beneficiaries admitted with a primary discharge diagnosis of acute hypertension on the basis of International Classification of Diseases codes. We then used a mixed effects model with a Poisson link function and state-specific random intercepts, adjusting for age, sex, race and ethnicity, and dual-eligible status, to evaluate trends in hospitalizations.

Results: The sample consisted of 397 238 individual Medicare fee-for-service beneficiaries. From 1999 through 2019, the annual hospitalization rates for acute hypertension increased significantly, from 51.5 to 125.9 per 100 000 beneficiary-years; the absolute increase was most pronounced among the following subgroups: adults ≥85 years (66.8-274.1), females (64.9-160.1), Black people (144.4-369.5), and Medicare/Medicaid insured (dual-eligible, 93.1-270.0). Across all subgroups, Black adults had the highest hospitalization rate in 2019, and there was a significant increase in the differences in hospitalizations between Black and White people from 1999 to 2019. Marked geographic variation was also present, with the highest hospitalization rates in the South. Among patients hospitalized for acute hypertension, the observed 30-day and 90-day all-cause mortality rates (95% CI) decreased from 2.6% (2.27-2.83) and 5.6% (5.18-5.99) to 1.7% (1.53-1.80) and 3.7% (3.45-3.84) and 30-day and 90-day all-cause readmission rates decreased from 15.7% (15.1-16.4) and 29.4% (28.6-30.2) to 11.8% (11.5-12.1) and 24.0% (23.5-24.6).

Conclusions: Among Medicare fee-for-service beneficiaries age 65 years or older, hospitalization rates for acute hypertension increased substantially and significantly from 1999 to 2019. Black adults had the highest hospitalization rate in 2019 across age, sex, race and ethnicity, and dual-eligible strata. There was significant national variation, with the highest rates generally in the South.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057056DOI Listing
November 2021

O-carboxymethyl chitosan based pH/hypoxia-responsive micelles relieve hypoxia and induce ROS in tumor microenvironment.

Carbohydr Polym 2022 Jan 26;275:118611. Epub 2021 Aug 26.

XuZhou Central Hospital, XuZhou Clinical College, Xuzhou Medical University, China; School of Stomatology, Xuzhou Medical University, China. Electronic address:

The hypoxia in tumor microenvironment (TME) can upregulate the HIF-1α and PD-L1 expression and cause immunosuppression of tumor. In this study, a carboxymethyl chitosan-based pH/hypoxia-responsive and γ-FeO/isosorbide dinitrate carrying micelle was designed, and it could catalyze endogenous HO to generate oxygen and relieve hypoxia in TME, so as to relieve the overexpression of HIF-1α and PD-L1 in tumor; meanwhile, it could react with HO to release ROS via Fenton reaction and induce cytotoxicity in tumor. Along with these multiple effects, this carboxymethyl chitosan-based micelles could provide a comprehensive strategy for tumor treatment.
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http://dx.doi.org/10.1016/j.carbpol.2021.118611DOI Listing
January 2022

Regulation of mTORC1 by amino acids in mammalian cells: A general picture of recent advances.

Anim Nutr 2021 Dec 14;7(4):1009-1023. Epub 2021 Sep 14.

Key Laboratory of Ruminant Nutrition and Physiology, College of Animal Science and Technology, Shandong Agricultural University, No. 61, Daizong Street, Tai'an, Shandong, China.

The mechanistic target of rapamycin complex 1 (mTORC1) integrates various types of signal inputs, such as energy, growth factors, and amino acids to regulate cell growth and proliferation mainly through the 2 direct downstream targets, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1). Most of the signal arms upstream of mTORC1 including energy status, stress signals, and growth factors converge on the tuberous sclerosis complex (TSC) - Ras homologue enriched in brain (Rheb) axis. Amino acids, however, are distinct from other signals and modulate mTORC1 using a unique pathway. In recent years, the transmission mechanism of amino acid signals upstream of mTORC1 has been gradually elucidated, and some sensors or signal transmission pathways for individual amino acids have also been discovered. With the help of these findings, we propose a general picture of recent advances, which demonstrates that various amino acids from lysosomes, cytoplasm, and Golgi are sensed by their respective sensors. These signals converge on mTORC1 and form a huge and complicated signal network with multiple synergies, antagonisms, and feedback mechanisms.
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http://dx.doi.org/10.1016/j.aninu.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536509PMC
December 2021

Spindle and kinetochore-associated complex subunit 3 (SKA3) promotes stem cell-like properties of hepatocellular carcinoma cells through activating Notch signaling pathway.

Ann Transl Med 2021 Sep;9(17):1361

Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Cancer stemness contributes to hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance, and recurrence. The spindle and kinetochore-associated (SKA) complex has been shown to be involved in tumor progression; however, its effects on cancer stem cell-like properties have not yet been examined. This research sought to study each subunit of the SKA complex in HCC systematically.

Methods: Bioinformatic analyses were carried out to examine the expression and clinical data of the SKA complex's each subunit in HCC. The expression of the target genes was detected by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Clone formation and Transwell assays were performed to assess the proliferation and migration abilities of the SKA complex's each subunit. Sphere formation assays and subcutaneous xenograft experiments were performed to investigate the effects of SKA complex subunit 3 (SKA3) on the self-renewal and tumorigenic abilities of HCC.

Results: Each subunit of the SKA complex was highly expressed in HCC, but only SKA complex subunit 1 (SKA1) and SKA3 were associated with the poor overall survival of HCC patients. Additionally, the HCC cells overexpressing SKA3 exhibited increased migration, invasion, proliferation, self-renewal, Sorafenib resistance and tumorigenic abilities. Notch signaling played a vital role in the process by which SKA3 promoted HCC stemness.

Conclusions: SKA3 promotes HCC stem cell-like properties via the Notch signaling pathway. As SKA3 appears to act as a regulator of stemness in HCC, it might be a potential molecular target for HCC.
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http://dx.doi.org/10.21037/atm-21-1572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506556PMC
September 2021

A Comparative Transcriptional Landscape of Two Castor Cultivars Obtained by Single-Molecule Sequencing Comparative Analysis.

Front Genet 2021 18;12:749340. Epub 2021 Oct 18.

Agricultural College of Inner Mongolia Minzu University, Tongliao, China.

Castor ( L.) is an important non-edible oilseed crop. Lm-type female strains and normal amphiprotic strains are important castor cultivars, and are mainly different in their inflorescence structures and leaf shapes. To better understand the mechanisms underlying these differences at the molecular level, we performed a comparative transcriptional analysis. Full-length transcriptome sequencing and short-read RNA sequencing were employed. A total of 76,068 and 44,223 non-redundant transcripts were obtained from high-quality transcripts of Lm-type female strains and normal amphiprotic strains, respectively. In Lm-type female strains and normal amphiprotic strains, 51,613 and 20,152 alternative splicing events were found, respectively. There were 13,239 transcription factors identified from the full-length transcriptomes. Comparative analysis showed a great variety of gene expression of common and unique transcription factors between the two cultivars. Meanwhile, a functional analysis of the isoforms was conducted. The full-length sequences were used as a reference genome, and a short-read RNA sequencing analysis was performed to conduct differential gene analysis. Furthermore, the function of DEGs were performed to annotation analysis. The results revealed considerable differences and expression diversity between the two cultivars, well beyond what was reported in previous studies and likely reflecting the differences in architecture between these two cultivars.
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http://dx.doi.org/10.3389/fgene.2021.749340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558441PMC
October 2021
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