Publications by authors named "Min Fan"

306 Publications

Traditional Chinese medicine extracts as novel corrosion inhibitors for AZ91 magnesium alloy in saline environment.

Sci Rep 2022 May 5;12(1):7367. Epub 2022 May 5.

National Engineering Research Center of Light Alloy Net Forming, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

Zingiber officinale Roscoe extract, Raphanus sativus L. extract, Rheum palmatum extract, Coptis chinensis extract, Glycyrrhiza uralensis extract (GUE), Potentilla discolor extract (PDE) and Taraxacum officinale extract (TOE) were screened for the green corrosion inhibitors of AZ91 alloy in saline environment. The experiment results demonstrated that GUE, PDE and TOE can significantly enhance the corrosion resistance of AZ91 alloy by 73.4, 87.6 and 84.6%, respectively. Surface characterization using FTIR, UV-Vis and XPS revealed that the organic compounds of GUE, PDE and TOE can interact with the alloy surface to form a protective physisorbed film, effectively mitigating the corrosion process of AZ91 alloy. The present results may be helpful to discover the new green inhibitors with high inhibition efficiency for AZ91 alloy.
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http://dx.doi.org/10.1038/s41598-022-10900-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072390PMC
May 2022

Cross-sectional associations between cortical thickness and independent gait domains in older adults.

J Am Geriatr Soc 2022 May 5. Epub 2022 May 5.

State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China.

Background: Although the prevalence of gait disturbance is increasing with population aging, our understanding of its underlying neural basis is still limited. The precise brain regions linked to specific gait domains have not been well defined. In this study, we aim to investigate the associations of cortical thickness and different gait domains, and to explore whether these associations could be explained by cerebral small vessel disease.

Methods: A total of 707 community-dwelling participants from the Taizhou Imaging Study (mean age: 60.2 ± 3.0 years, 57.4% female) were involved. All participants underwent brain MRI and gait assessment. We obtained quantitative gait parameters using wearable devices and then summarized them into three independent gait domains through factor analysis. Cortical thickness was analyzed and visualized using FreeSurfer and Surfstat.

Results: Three independent domains (pace, rhythm, and variability) were summarized from 12 gait parameters. Among gait domains, poorer pace was associated with the thinner cortical thickness of multiple regions, which included areas related with motor function (e.g., the primary motor cortex, premotor cortex, and supplementary motor area), sensory function (e.g., the postcentral gyrus and paracentral lobule), visuospatial attention (e.g., the lateral occipital cortex and lingual gyrus), and identification and cognition (e.g., the fusiform gyrus and entorhinal cortex). Such a relationship was only slightly attenuated after adjustment for cerebrovascular risk factors and cerebral small vessel disease. No statistically significant association was found between cortical thickness and the rhythm or variability domains.

Conclusions: Poorer pace is independently associated with thinner cortical thickness in areas important for motor, sensory, cognitive function, and visuospatial attention. Our study emphasizes the importance of cortical thickness in gait control and adds value in investigating neural mechanisms of gait.
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http://dx.doi.org/10.1111/jgs.17840DOI Listing
May 2022

Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis.

Sci Adv 2022 04 27;8(17):eabm8965. Epub 2022 Apr 27.

Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.

Circulating lactate levels are a critical biomarker for sepsis and are positively correlated with sepsis-associated mortality. We investigated whether lactate plays a biological role in causing endothelial barrier dysfunction in sepsis. We showed that lactate causes vascular permeability and worsens organ dysfunction in CLP sepsis. Mechanistically, lactate induces ERK-dependent activation of calpain1/2 for VE-cadherin proteolytic cleavage, leading to the enhanced endocytosis of VE-cadherin in endothelial cells. In addition, we found that ERK2 interacts with VE-cadherin and stabilizes VE-cadherin complex in resting endothelial cells. Lactate-induced ERK2 phosphorylation promotes ERK2 disassociation from VE-cadherin. In vivo suppression of lactate production or genetic depletion of lactate receptor GPR81 mitigates vascular permeability and multiple organ injury and improves survival outcome in polymicrobial sepsis. Our study reveals that metabolic cross-talk between glycolysis-derived lactate and the endothelium plays a critical role in the pathophysiology of sepsis.
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http://dx.doi.org/10.1126/sciadv.abm8965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045716PMC
April 2022

Evaluation of a recombinant five-antigen Staphylococcus aureus vaccine: The randomized, single-centre phase 1a/1b clinical trials.

Vaccine 2022 May 23;40(23):3216-3227. Epub 2022 Apr 23.

Third Military Medical University, Chongqing 400038, China. Electronic address:

Background: Staphylococcus aureus is an important pathogen that causes hospital and community infections. To control Staphylococcus aureus infection and reduce the usage of antibiotics, we evaluated the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in healthy adults.

Methods: We conducted a randomized, double-blind, placebo-controlled phase 1a study and a randomized, open-label phase 1b study. In phase 1a, we randomly allocated 144 healthy participants in a ratio of 1:1:1:1 to receive the low-(60 μg), middle-(120 μg), and high-dose (240 μg) vaccine or placebo at day 0, 3, 7 and 14. In phase 1b, 144 healthy participants were randomly allocated at a ratio of 1:1:1:1 to receive 0-3-7, 0/0-7, 0/0-3-7, 0/0-7-14 regimens to estimate the optimal strategy. The primary study endpoint was the incidence of solicited adverse events post-vaccination. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as the cellular immune responses and functional antibodies.

Results: There were 31 (86%), 30 (83%), and 32 (89%) of 36 participants in the low-, middle-, and high-dose group reported solicited adverse events, respectively, most of the adverse events were mild or moderate. In phase 1b, the dose-adjusted rFSAV (90 μg) showed a better safety profile in the four immune procedures, and no vaccine-related serious adverse events were reported. The antigen-specific binding antibodies started to increase at day 7 and reached the peak around day 14 to 21. The cellular immune responses and functional antibodies also were substantially above background levels.

Conclusions: rFSAV is safe, well tolerated in healthy adults, elicits rapid and robust specific humoral and cellular immune responses with unconventional immunization procedure in phase 1a and 1b. It deserves to be noted and further explored.

Clinical Trials Registration: NCT02804711 and NCT03966040.
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http://dx.doi.org/10.1016/j.vaccine.2022.04.034DOI Listing
May 2022

Optimization of Nanofiltration Hollow Fiber Membrane Fabrication Process Based on Response Surface Method.

Membranes (Basel) 2022 Mar 29;12(4). Epub 2022 Mar 29.

School of Environment and Resources, Southwest University of Science and Technology, Mianyang 621000, China.

Layer-by-layer (LBL) self-assembly technology has become a new research hotspot in the fabrication of nanofiltration membranes in recent years. However, there is a lack of a systematic approach for the assessment of influencing factors during the membrane fabrication process. In this study, the process optimization of LBL deposition was performed by a two-step statistical method. The multiple linear regression was performed on the results of single-factor experiments to determine the major influencing factors on membrane performance, including the concentration of Poly (allylamine hydrochloride) (PAH), glutaraldehyde, and the NaCl concentration in PAH solution. The Box-Behnken response surface method was then used to analyze the interactions between the selected factors, while their correlation with the membrane performance was obtained by polynomial fitting. The R value of the regression models (0.97 and 0.94) was in good agreement with the adjusted R value (0.93 and 0.86), indicating that the quadratic response models were adequate enough to predict the membrane performance. The optimal process parameters were finally determined through dual-response surface analysis to achieve both high membrane permeability of 14.3 LMH·MPa and MgSO rejection rate of 90.22%.
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http://dx.doi.org/10.3390/membranes12040374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032820PMC
March 2022

Electrospun Polysaccharides for Periodontal Tissue Engineering: A Review of Recent Advances and Future Perspectives.

Ann Biomed Eng 2022 Apr 15. Epub 2022 Apr 15.

Nanchang Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, 637000, China.

Periodontitis is the leading cause of tooth loss among the adult population. Indeed, conventional treatment modalities have specific challenges such as scar tissue infiltration, the formation of long epithelium junctions, and aesthetic limitations. Therefore, the development of alternative strategies is highly demanded. In this regard, periodontal tissue engineering has shed new light on the next generation of treatment methods. The essence of this technology is the use of appropriate biomaterials, bioactive agents, and fabrication technologies to mimic the natural extracellular matrix (ECM) of periodontal tissue. Among different candidates, the use of electrospun polysaccharides has gained significant attention. These structures possess a solid resemblance to native periodontal tissue's ECM in physicochemical, biological, and structural properties. The current review discusses the recent progress, challenges, and future perspectives of electrospun polysaccharides in periodontal tissue engineering.
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http://dx.doi.org/10.1007/s10439-022-02952-xDOI Listing
April 2022

Cardiovascular Dysfunction in COVID-19: Association Between Endothelial Cell Injury and Lactate.

Front Immunol 2022 23;13:868679. Epub 2022 Mar 23.

Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.

Coronavirus disease 2019 (COVID-19), an infectious respiratory disease propagated by a new virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has resulted in global healthcare crises. Emerging evidence from patients with COVID-19 suggests that endothelial cell damage plays a central role in COVID-19 pathogenesis and could be a major contributor to the severity and mortality of COVID-19. Like other infectious diseases, the pathogenesis of COVID-19 is closely associated with metabolic processes. Lactate, a potential biomarker in COVID-19, has recently been shown to mediate endothelial barrier dysfunction. In this review, we provide an overview of cardiovascular injuries and metabolic alterations caused by SARS-CoV-2 infection. We also propose that lactate plays a potential role in COVID-19-driven endothelial cell injury.
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http://dx.doi.org/10.3389/fimmu.2022.868679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984030PMC
April 2022

Comparison between Traditional Chinese Medicine Constitution and Blood Biochemical Markers Associated with Left and Right Mammary Hyperplasia in Rural Areas of Southwest China.

J Healthc Eng 2022 23;2022:9274060. Epub 2022 Mar 23.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: Hyperplasia of mammary glands (HMG) is the breast disease with the highest clinical incidence. Many traditional Chinese medicine (TCM) doctors suggest that the treatment of HMG should be based on the left and right breast pain difference. However, these views are based on case reports, and an objective basis has not been established for treatment according to left-side and right-side differences.

Methods: We enrolled 150 patients who met the clinical diagnostic criteria of HMG. The incidence bias was determined according to the score difference between bilateral breast pain and mass in patients with HMG. A left group, right group, and bilateral group were included, and TCM constitution was investigated in each group. Blood biochemical indicators were measured for 120 fasting patients. We conducted a network pharmacology study of the key herb qingpi and chenpi, which are used by TCM doctors to treat different lateral HMG.

Results: In patients with biased onset of HMG, the results showed that the frequency and constitution score of stagnant blood in the group were higher than those of the group, and the frequency and constitution score of phlegm-dampness in the group were higher than those of the group. Both the and groups had high proportion of stagnant Qi. The results indicated that the concentration of coagulation factor VIII (FVIII) was higher in the group than that in the group, and the concentration of lipoprotein a (Lp-) was higher in the group than that in the group. The results showed that sinensetin and neohesperidin contained in qingpi might interfere with platelet activation, thrombogenesis, prolactin signaling pathway, and atherosclerosis process, in removing "blood stasis" and eventually treating the left-leaning group of HMG patients. Sitosterol and citromitin contained in chenpi could regulate lipid metabolism by interfering with regulation of lipolysis in adipocytes, salivary secretion, estrogen signaling pathway, and thyroid hormone signaling pathway. Chenpi could eliminate "phlegm turbidity" and treat HMG patients in the right-leaning group.

Conclusions: We preliminarily confirmed that the clinical pathogenesis of HMG is not a left-right equilibrium and TCM constitution, coagulation function, and lipid metabolism may be used as the objective basis for the difference between the left and right in HMG pathogenesis. For left-sided HMG patients, the doctor can consider qingpi, herb of activating blood and removing stasis, to treat HMG. However, for right-sided HMG, we think doctors should apply herb of activating Qi and eliminating phlegm, such as chenpi.
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http://dx.doi.org/10.1155/2022/9274060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967519PMC
March 2022

Selective Extraction of Transition Metals from Spent LiNi Co Mn O Cathode via Regulation of Coordination Environment.

Angew Chem Int Ed Engl 2022 Mar 19:e202202558. Epub 2022 Mar 19.

CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Centre for Excellence in Molecular Sciences, Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

The complexity of chemical compounds in lithium-ion batteries (LIBs) results in great difficulties in the extraction of multiple transition metals, which have similar physicochemical characteristics. Here, we propose a novel strategy for selective extraction of nickel, cobalt, and manganese from spent LiNi Co Mn O (NCM) cathode through the regulation of coordination environment. Depending on adjusting the composition of ligand in transition metal complexes, a tandem leaching and separation system is designed and finally enables nickel, cobalt, and manganese to enrich in the form of NiO, Co O , and Mn O with high recovery yields of 99.1 %, 95.1 %, and 95.3 %, respectively. We further confirm that the combination of different transition metals with well-designed ligands is the key to good selectivity. Through our work, fine-tuning the coordination environment of metal ions is proved to have great prospects in the battery recycling industry.
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http://dx.doi.org/10.1002/anie.202202558DOI Listing
March 2022

Impact of environmental regulation on green total factor productivity: a new perspective of green technological innovation.

Environ Sci Pollut Res Int 2022 Mar 15. Epub 2022 Mar 15.

School of Economics and Management, Xinjiang University, Urumqi, 830047, China.

Green total factor productivity (GTFP) is an essential indicator to measure economic and environmental efficiency. Moreover, formulating a reasonable environmental regulation system and promoting green technological innovation is a systematic way to improve GTFP. However, previous related studies lack to investigate the impact of environmental regulation on GTFP from the perspective of green technological innovation. For this purpose, this paper aims to examine the specific impact of environmental regulation on GTFP based on the perspective of green technology innovation, so as to provide some policy insights for the formulation of more effective implementation of environmental regulation, improve green technology innovation level, and achieve a win-win situation for both economic growth and environmental protection. Furthermore, epsilon-based measure (EBM), which includes both radial and non-radial distance functions, is used to measure the GTFP. The spatial autoregressive method is also employed to quantify the impact of environmental regulation on GTFP from the perspective of green technological innovation using panel data of 269 prefecture-level cities in China from 2004 to 2018. The main findings indicate that there is a significant spatial autocorrelation between environmental regulation and GTFP. Environmental regulation has a significant positive effect on GTFP. Environmental regulation in the local regions also significantly contributes to GTFP in neighboring regions. Besides, environmental regulation indirectly promotes GTFP by enhancing green technological innovation level. Regional heterogeneity results show that environmental regulation can not only directly promote GTFP but also indirectly significantly promote GTFP through green technological innovation in the eastern and central regions, but insignificant in the western region. Based on the above findings, we conclude that policymakers should not only develop differentiated environmental regulation standards and steadily improving the intensity and rationality of environmental regulation but also add green innovation funds supply, enhance green innovation factor allocation efficiency, and strengthen R&D talents, funds, and policies to green technology innovation, so as to drive GTFP improvement.
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http://dx.doi.org/10.1007/s11356-022-19576-2DOI Listing
March 2022

Weaning critically ill patients from mechanical ventilation: a protocol from a multicenter retrospective cohort study.

J Thorac Dis 2022 Jan;14(1):199-206

Foresea Life Insurance Guangzhou General Hospital, Guangzhou, China.

Background: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort.

Methods: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study.

Discussion: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).
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http://dx.doi.org/10.21037/jtd-21-1217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828530PMC
January 2022

MicroRNAs in Alzheimer's disease: Potential diagnostic markers and therapeutic targets.

Biomed Pharmacother 2022 Apr 15;148:112681. Epub 2022 Feb 15.

School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China; Anhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, Hefei, China. Electronic address:

Alzheimer's disease (AD) is the most common neurodegenerative disease, with cognitive decline as the primary clinical feature. According to epidemiological statistics, 50 million people worldwide are currently affected by Alzheimer's disease. Although new drugs such as aducanumab have been approved for use in the treatment of AD, none of them have reversed the progression of AD. MicroRNAs (miRNAs) are small molecule RNAs that exert their biological functions by regulating the expression of intracellular proteins, and differential abundance and varieties are found between the central and peripheral tissues of AD patients and healthy controls. This article will summarise the changes of miRNAs in the AD process, and the potential role of diagnostic markers and therapeutic targets in AD will be explored.
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http://dx.doi.org/10.1016/j.biopha.2022.112681DOI Listing
April 2022

The molecular mechanism of kinesin family member 2A (KIF2A) underlying non-small cell lung cancer: the effect of its knockdown on malignant behaviors, stemness, chemosensitivity, and potential regulated signaling pathways.

Am J Transl Res 2022 15;14(1):68-85. Epub 2022 Jan 15.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center Shanghai, China.

Kinesin family member 2A (KIF2A) represents an oncogene in several cancers, however, its involvement in non-small cell lung cancer (NSCLC) is limitedly investigated. Therefore, the present study aimed to explore potential molecular mechanism of KIF2A knockdown in repressing NSCLC malignant behaviors. The effect of KIF2A knockdown on cell proliferation, apoptosis, invasion, epithelial-mesenchymal transition (EMT) markers, stemness, chemosensitivity was detected after transfecting KIF2A short hairpin RNA (ShRNA) plasmids into A549 and NCI-H1975 cells. Moreover, KIF2A knockdown mediated signaling pathways were analyzed by RNA sequencing (RNA-seq), and then validated by western blot assay. Both KIF2A mRNA and protein expressions were increased in A549, NCI-H650, NCI-H358, NCI-H2106, NCI-H1299, NCI-H1650 and NCI-H1975 cells compared with BEAS-2B cells. KIF2A knockdown inhibited proliferation, invasion, EMT, stemness, but enhanced chemosensitivity to cisplatin and paclitaxel in both A549 and NCI-H1975 cells. Meanwhile, it only promoted apoptosis in NCI-H1975 cells but not in A549 cells. Moreover, after KIF2A knocking down, RNA-seq data indicated that 356 accordant differentially expressed genes (DEGs) in both A549 and NCI-H1975 cells, and these DEGs were enriched in PI3K-Akt, Wnt and Notch signaling pathways. Further western blot disclosed that KIF2A knockdown indeed inactivated PI3K-Akt, Wnt and Notch signaling pathways in both A549 and NCI-H1975 cells. In conclusion, KIF2A knockdown suppresses NSCLC cell malignant behaviors, EMT and stemness, but enhances chemosensitivity via inactivating PI3K-Akt, Wnt, and Notch signaling pathways, which proposes it as a potential therapeutic target for NSCLC treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829653PMC
January 2022

Self-reported reactogenicity of CoronaVac (Sinovac) compared with Comirnaty (Pfizer-BioNTech): A prospective cohort study with intensive monitoring.

Vaccine 2022 03 7;40(10):1390-1396. Epub 2022 Feb 7.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; Laboratory of Data Discovery for. Health (D(2)4H), Hong Kong Science and Technology Park, Hong Kong, China. Electronic address:

Objective: CoronaVac (Sinovac) Covid-19 vaccine has recently been approved for emergency use by the World Health Organization. However, data on its reactogenicity in real-world settings is scant. This study aimed to compare self-reported post-vaccination adverse reactions between CoronaVac and Comirnaty (Pfizer-BioNTech).

Methods: We adopted a prospective cohort study design using online surveys from the day of first-dose vaccination with intensive follow-up through two weeks after the second dose (11 time points). The primary outcome was adverse reactions (any versus none) and secondary outcomes were the sub-categories of adverse reactions (local, systemic, and severe allergic reactions). Potential effect modification across multimorbidity status, older age, and sex was examined.

Results: In total, 2,098 participants who were scheduled to complete the 14th-day survey were included, with 46.2% receiving Comirnaty. Retention rate two weeks after the second dose was 81.0% for the CoronaVac group and 83.6% for the Comirnaty group. Throughout the follow-up period, 801 (82.7%) of those receiving Comirnaty and 543 (48.1%) of those receiving CoronaVac reported adverse reactions. Adjusted analysis suggested that compared with Comirnaty, CoronaVac was associated with 83%-reduced odds of any adverse reactions [adjusted odds ratio (AOR) = 0.17, 95% confidence interval (CI) 0.15-0.20], 92%-reduced odds of local adverse reactions (AOR = 0.08, 95% CI 0.06-0.09), and 76%-reduced odds of systemic adverse reactions (AOR = 0.24, 95% CI 0.16-0.28). No significant effect modification was identified.

Conclusion: This post-marketing study comparing the reactogenicity of Covid-19 vaccines suggests a lower risk of self-reported adverse reactions following vaccination with CoronaVac compared with Comirnaty.
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http://dx.doi.org/10.1016/j.vaccine.2022.01.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818394PMC
March 2022

Competitive Doping Chemistry for Nickel-Rich Layered Oxide Cathode Materials.

Angew Chem Int Ed Engl 2022 May 24;61(21):e202116865. Epub 2022 Mar 24.

CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS, Research/Education Center for Excellence in Molecular Sciences, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing, 100190, P. R. China.

Chemical modification of electrode materials by heteroatom dopants is crucial for improving storage performance in rechargeable batteries. Electron configurations of different dopants significantly influence the chemical interactions inbetween and the chemical bonding with the host material, yet the underlying mechanism remains unclear. We revealed competitive doping chemistry of Group IIIA elements (boron and aluminum) taking nickel-rich cathode materials as a model. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen. Density functional theory calculations reveal, Al is preferentially bonded to oxygen and vice versa, and shows a much lower diffusion barrier than B . In the case of Al-preoccupation, the bulk diffusion of B is hindered. In this way, a B-rich surface and Al-rich bulk is formed, which helps to synergistically stabilize the structural evolution and surface chemistry of the cathode.
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http://dx.doi.org/10.1002/anie.202116865DOI Listing
May 2022

Exosomes derived from bone-marrow mesenchymal stem cells alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology.

J Neuroinflammation 2022 Feb 7;19(1):35. Epub 2022 Feb 7.

School of Pharmacy, Anhui Medical University, 81 Meishan Road, Anhui, 230032, Hefei, People's Republic of China.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognitive ability. Exosomes derived from bone-marrow mesenchymal stem cells (BMSC-exos) are extracellular vesicles that can execute the function of bone-marrow mesenchymal stem cells (BMSCs). Given the versatile therapeutic potential of BMSC and BMSC-exos, especially their neuroprotective effect, the aim of this study was to investigate the potential effect of BMSC-exos on AD-like behavioral dysfunction in mice and explore the possible molecular mechanism.

Methods: BMSC-exos were extracted from the supernatant of cultured mouse BMSCs, which were isolated from the femur and tibia of adult C57BL/6 mice, purified and sorted via flow cytometry, and cultured in vitro. BMSC-exos were identified via transmission electron microscopy, and typical marker proteins of exosomes were also detected via Western blot. A sporadic AD mouse model was established by intracerebroventricular injection of streptozotocin (STZ). Six weeks later, BMSC-exos were administered via lateral ventricle injection or caudal vein injection lasting five consecutive days, and the control mice were intracerebroventricularly administered an equal volume of solvent. Behavioral performance was observed via the open field test (OFT), elevated plus maze test (EPM), novel object recognition test (NOR), Y maze test (Y-maze), and tail suspension test (TST). The mRNA and protein expression levels of IL-1β, IL-6, and TNF-α in the hippocampus were measured via quantitative polymerase chain reaction (qPCR) and Western blot, respectively. Moreover, the protein expression of Aβ, BACE, IL-1β, IL-6, TNF-α, GFAP, p-Tau (Ser396), Tau5, synaptotagmin-1 (Syt-1), synapsin-1, and brain-derived neurotrophic factor (BDNF) in the hippocampus was detected using Western blot, and the expression of GFAP, IBA1, Aβ and DCX in the hippocampus was measured via immunofluorescence staining.

Results: Lateral ventricle administration, but not caudal vein injection of BMSC-exos improved AD-like behaviors in the STZ-injected mouse model, as indicated by the increased number of rearing, increased frequency to the central area, and increased duration and distance traveled in the central area in the OFT, and improved preference index of the novel object in the NOR. Moreover, the hyperactivation of microglia and astrocytes in the hippocampus of the model mice was inhibited after treatment with BMSC-exos via lateral ventricle administration, accompanied by the reduced expression of IL-1β, IL-6, TNF-α, Aβ and p-Tau and upregulated protein expression of synapse-related proteins and BDNF. Furthermore, the results of the Pearson test showed that the preference index of the novel object in the NOR was positively correlated with the hippocampal expression of BDNF, but negatively correlated with the expression of GFAP, IBA1, and IL-1β. Apart from a positive correlation between the hippocampal expression of BDNF and Syt-1, BDNF abundance was found to be negatively correlated with markers of glial activation and the expression of the inflammatory cytokines, Aβ, and p-Tau, which are characteristic neuropathological features of AD.

Conclusions: Lateral ventricle administration, but not caudal vein injection of BMSC-exos, can improve AD-like behavioral performance in STZ-injected mice, the mechanism of which might be involved in the regulation of glial activation and its associated neuroinflammation and BDNF-related neuropathological changes in the hippocampus.
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http://dx.doi.org/10.1186/s12974-022-02393-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822863PMC
February 2022

Risk Identification of Heavy Metals in Agricultural Soils from a Typically High Cd Geological Background Area in Upper Reaches of the Yangtze River.

Bull Environ Contam Toxicol 2022 Jan 30. Epub 2022 Jan 30.

Chongqing Engineering Research Center for Soil Contamination Control and Remediation, Chongqing, 400067, China.

This study adopted two risk assessment models to estimate the potential risk of heavy metals (HMs) in agricultural soils from a high Cd geological background area. Results were as follows: HMs posed an extremely high potential ecological risk (PER) (PER = 2051 > 1200) ascribed to Cd contribution. The overall non-carcinogenic risk (HI) of HMs for children (HI > 1) was unacceptable. Contributions of HMs to HI generally decreased in the order of Cr > As > Pb > Cd > Ni > Cu > Zn. The total carcinogenic risk (TCR) value for adults (2.1 × 10) and children (2.2 × 10) surpassed the reference value (1.0 × 10), indicating that the risks were unacceptable. Contributions of HMs to TCR generally decreased in the order of Cr ≈ Ni > Cd > As > Pb. These results suggested that risk control policies should not only consider the potential ecological risk of Cd but also take into consideration of the carcinogenic and non-carcinogenic risk of Cr and Ni in a typically high Cd geological background area.
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http://dx.doi.org/10.1007/s00128-021-03417-yDOI Listing
January 2022

COVID-19 vaccines and risks of hematological abnormalities: Nested case-control and self-controlled case series study.

Am J Hematol 2022 04 9;97(4):470-480. Epub 2022 Feb 9.

Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong Special Administrative Region, China.

Several studies reported hematological abnormalities after vaccination against the coronavirus disease 2019 (COVID-19). We evaluated the association between COVID-19 vaccines (CoronaVac and BNT162b2) and hematological abnormalities. We conducted nested case-control and self-controlled case series analyses using the data from the Hong Kong Hospital Authority and the Department of Health, HKSAR. Outcomes of interest were thrombocytopenia, leukopenia, and neutropenia. Adjusted odds ratios (aORs), incidence rate ratios (IRRs), and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In total, 1 643 419 people received COVID-19 vaccination (738 609 CoronaVac; 904 810 BNT162b2). We identified 457 and 422 cases after CoronaVac and BNT162b2 vaccination, respectively. For CoronaVac, the incidence of thrombocytopenia, leukopenia, and neutropenia was 2.51, 1.08, and 0.15 per 10 000 doses. For BNT162b2, the corresponding incidence was 1.39, 1.17, and 0.26 per 10 000 doses. The incidence per 10 000 COVID-19 cases were 1254, 2341, and 884, respectively. We only observed an increased risk of leukopenia following the second dose of BNT162b2 (aOR 1.58, 95% CI 1.24-2.02; day 0-14, IRR 2.21; 95% CI 1.59-3.08). There was no increased risk of any hematological abnormalities after CoronaVac vaccination. We observed an increased risk of leukopenia shortly after the second dose of BNT162b2. However, the incidence was much lower than the incidence following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. There was no association between CoronaVac and hematological abnormalities. The benefits of vaccination against COVID-19 still outweigh the risk of hematological abnormalities.
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http://dx.doi.org/10.1002/ajh.26478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011752PMC
April 2022

TOR and SnRK1 fine tune SPEECHLESS transcription and protein stability to optimize stomatal development in response to exogenously supplied sugar.

New Phytol 2022 04 8;234(1):107-121. Epub 2022 Feb 8.

The Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Science, Shandong University, Qingdao, 266237, China.

In Arabidopsis, the differentiation of epidermal cells into stomata is regulated by endogenous and environmental signals. Sugar is required for plant epidermal cell proliferation and differentiation. However, it is unclear how epidermal cells maintain division and differentiation to generate proper amounts of stomata in response to different sugar availability. Here, we show that two evolutionarily conserved kinase Snf1-related protein kinase 1 (SnRK1) and Target of rapamycin (TOR) play critical roles in the regulation of stomatal development under different sugar availability. When plants are grown on a medium containing 1% sucrose, sucrose-activated TOR promotes the stomatal development by inducing the expression of SPEECHLESS (SPCH), a master regulator of stomatal development. SnRK1 promotes stomatal development through phosphorylating and stabilizing SPCH. However, under the high sucrose conditions, the highly accumulated trehalose-6-phosphate (Tre6P) represses the activity of KIN10, the catalytic α-subunit of SnRK1, by reducing the interaction between KIN10 and its upstream kinase, consequently promoting SPCH degradation and inhibiting stomatal development. Our findings revealed that TOR and SnRK1 finely regulate SPCH expression and protein stability to optimize the stomatal development in response to exogenously supplied sugar.
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http://dx.doi.org/10.1111/nph.17984DOI Listing
April 2022

Ratiometric fluorescent nanoprobes based on carbon dots and multicolor CdTe quantum dots for multiplexed determination of heavy metal ions.

Anal Chim Acta 2022 Jan 20;1191:339251. Epub 2021 Nov 20.

School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an, 710021, PR China.

Owing to the high risk to human and environmental health, heavy metal pollution has become a global problem. Rapid, accurate and multiplexed determination of heavy metal ions is critical. In this work, we reported a promising approach to designing ratiometric fluorescent nanoprobes for multiplexed determination of Hg, Cu, and Ag ions. The nanoprobes (CDs-QDx) were designed by mixing the CDs and multicolor CdTe QDs without the involvement of recognition elements. The CDs were insensitive to heavy metal ions while CdTe QDs showed the size-dependent fluorescence response to different heavy metal ions, thereby establishing a ratiometric detection scheme by measuring the fluorescence intensity ratios of CDs-QDx systems. By evaluating the detection performance, the CDs-QDx (x = 570, 650, and 702) were successfully used for differentiation and quantification of Hg, Cu, and Ag ions. In addition, we also carried out the detection of heavy metal ions in actual samples with acceptable results. We believed that this work offers new insight into the design of ratiometric fluorescent nanoprobe for multiplexed determination of not only heavy metals but also some other analytes by combining the CDs with CdTe QDs with fine-tuned sizes.
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http://dx.doi.org/10.1016/j.aca.2021.339251DOI Listing
January 2022

Mesenchymal Stem Cell-Derived Exosomes Attenuate Epithelial-Mesenchymal Transition of HK-2 Cells.

Tissue Eng Part A 2022 May 19. Epub 2022 May 19.

Department of Urology, The Third Affiliated Hospital of Soochow University, Jiangsu, China.

Renal fibrosis (RF) predisposes patients to an increased risk of progressive chronic kidney disease, and effective treatments remain elusive. Mesenchymal stem cell (MSC)-derived exosomes are considered a new treatment for tissue damage. Our study aimed to investigate the effects of bone marrow MSC-derived exosomes (BM-MSC-Exs) on transforming growth factor-β1 (TGF-β1)-induced fibrosis in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. Herein, we found BM-MSC-Exs could inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells, and may involve autophagy activation of BM-MSC-Exs. Moreover, we first reported that after ceria nanoparticles (CeNPs) treatment, the improvements induced by BM-MSC-Ex on EMT were significantly enhanced by upregulating the expression of Nedd4Lof MSCs and promoting the secretion of exosomes, which contained Nedd4L. In addition, Nedd4L could activate autophagy in HK-2 cells. In conclusion, BM-MSC-Ex prevents the TGF-β1-induced EMT of renal tubular epithelial cells by transporting Nedd4L, which activates autophagy. The results of this experiment may extend to RF, whereby BM-MSC-Ex may also be used as a novel treatment for improving RF.
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http://dx.doi.org/10.1089/ten.TEA.2021.0190DOI Listing
May 2022

Prevalence and Characteristics of Acquired Coronary Fistulas After Successful Revascularization of Chronic Total Occlusion.

Front Cardiovasc Med 2021 22;8:690890. Epub 2021 Dec 22.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Acquired coronary fistulas (ACFs) are rare coronary artery abnormalities in patients with chronic total occlusion (CTO). It has been found after revascularization, and it may cause fluster during the CTO percutaneous coronary intervention (CTO PCI). How to distinguish between ACFs and coronary perforation (CP) is very important for CTO operators. Chronic total occlusion reopening may reveal the microchannel of the adventitial vascular layers. Some of ACFs have been seen after revascularization. This study aimed to investigate the characteristics of ACFs after successful CTO PCI. The clinical and procedural characteristics, medical history, and findings in electrocardiography (ECG), echocardiography, and coronary angiography were collected from 2,169 consecutive patients undergoing CTO PCI between January 2018 and December 2019 and analyzed retrospectively. About 1,844 (85.02%) underwent successful CTO PCI with complete revascularization. Acquired coronary fistulas were found in 49 patients (2.66%): the majority of patients with ACFs were men (81.63 vs. 60.78%; = 0.016) and younger (62.8 vs. 66.69 years; = 0.003), and had a history of myocardial infarction (MI) or Q-wave (69.39 vs. 54.21%; = 0.035); 38 (77.55%) patients had multiple fistulas (≥3), and ACFs affected multiple branches of the CTO vessel (≥3) in 29 (59.18%) patients. None had pericardial effusion, tamponade, and hemodynamic abnormality before or after PCI. Acquired coronary fistulas after successful CTO PCI are mainly present in young and male patients with a history of MI, and they often involve multiple fistulas and distal CTO vessels.
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http://dx.doi.org/10.3389/fcvm.2021.690890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727748PMC
December 2021

An Air-Stable High-Nickel Cathode with Reinforced Electrochemical Performance Enabled by Convertible Amorphous Li CO Modification.

Adv Mater 2022 Mar 7;34(12):e2108947. Epub 2022 Feb 7.

CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

High-nickel (Ni ≥ 90%) cathodes with high specific capacity hold great potential for next-generation lithium-ion batteries (LIBs). However, their practical application is restricted by the high interfacial reactivity under continuous air erosion and electrolyte assault. Herein, a stable high-nickel cathode is rationally designed via in situ induction of a dense amorphous Li CO on the particle surface by a preemptive atmosphere control. Among the residual lithium compounds, Li CO is the most thermodynamically stable one, so a dense Li CO coating layer can serve as a physical protection layer to isolate the cathode from contact with moist air. Furthermore, amorphous Li CO can be transformed into a robust F-rich cathode electrolyte interphase (CEI) during cycling, which reinforces the cathode's interfacial stability and improves the electrochemical performance. The assembled coin cell with this modified cathode delivers a high discharge capacity of 232.4 mAh g with a superior initial Coulombic efficiency (CE) of 95.1%, and considerable capacity retention of 90.4% after 100 cycles. Furthermore, no slurry gelation occurs during the large-scale electrode fabrication process. This work opens a valuable perspective on the evolution of amorphous Li CO in LIBs and provides guidance on protecting unstable high-capacity cathodes for energy-storage devices.
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http://dx.doi.org/10.1002/adma.202108947DOI Listing
March 2022

Postmarketing safety of orphan drugs: a longitudinal analysis of the US Food and Drug Administration database between 1999 and 2018.

Orphanet J Rare Dis 2022 01 4;17(1). Epub 2022 Jan 4.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.

Background: Information about the specific regulatory environment of orphan drugs is scarce and inconsistent. Uncertainties surrounding the postmarketing long-term safety of orphan drugs remain. This study aimed to evaluate the labelling changes of orphan drugs and to identify postmarketing safety-associated approval factors.

Methods: This retrospective cohort study includes all drugs with orphan drug designation approved by the Center for Drug Evaluation and Research of the US Food and Drug Administration between 1999 and 2018. Main outcomes are safety-related labelling changes up to 31 December 2019. We defined any safety-related labelling changes as postmarketing safety events (PMSE). Safety-related withdrawals, suspensions, and boxed warnings were further categorised as severe postmarketing safety events (SPSE). Outcome measurements include frequencies of PMSE, SPSE, and association between approval factors and the occurrence of safety events.

Results: Amongst the 214 drugs identified with orphan drug designation (25.7% biologics), 83.6% were approved through at least one expedited programme, and 29.4% were approved with boxed warnings. During a median follow-up of 6.74 years since approval, 69.2% and 14.5% of the analysed orphan drugs had PMSE and SPSE, respectively. Safety-related withdrawal (0%, 0/214), suspended marketing (0.46%, 1/214) and new boxed warnings are uncommon (3.7%, 8/214). The safety-related labelling changes were more frequent in the drugs approved with boxed warnings [Incidence rate ratio (IRR): 1.95 (1.02-3.73)] and approved for long-term use [IRR: 2.76 (1.52-5.00)].

Conclusions And Relevance: In this long-term postmarketing analysis, approximately 70% of FDA-approved orphan drugs had safety-related labelling changes although severe safety events were rare. While maintaining early access to orphan drugs, the drug regulatory body has taken timely regulatory action with postmarketing surveillance to ensure patient safety.
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http://dx.doi.org/10.1186/s13023-021-02166-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728968PMC
January 2022

O3-Type NaNiTiO Layered Oxide as a Stable and High-Rate Anode Material for Sodium Storage.

ACS Appl Mater Interfaces 2022 Jan 23;14(1):677-683. Epub 2021 Dec 23.

CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China.

Sodium-ion batteries (SIBs) are currently the most promising candidates for large-scale energy storage devices owing to their low cost and abundant resources. Titanium-based layered oxides have attracted widespread attention as promising anode materials due to delivering a safe potential of about 0.7 V (vs Na/Na) and a small volume contraction during cycles; P2-type Ti-based layered oxides are typically reported, due to the challenging synthesis of the O3-type counterpart resulting from the high percentage of unstable Ti. Herein, we report an anomalous O3-NaNiTiO layered oxide as an ultrastable and high-rate anode material for SIBs. The anode material delivers a reversible capacity of 112 mA h g after 300 cycles at 0.1 C, a good capacity retention rate of 91% after 1400 cycles at 2 C, and, in particular, a capacity of 52 mA h g even at a high rate of 20 C (1780 mA g). Furthermore, the X-ray diffraction monitoring reveals no phase transitions and almost zero strain both underlie the good long-cycle stability. The measured high apparent Na diffusion coefficient (2.06 × 10 cm s) and the low migration energy barrier (0.59 eV) from density functional theory calculations are responsible for the superior rate capability. Our results promise advanced high-performance O3-type Ti-based layered oxides as promising anode materials toward application for SIBs.
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http://dx.doi.org/10.1021/acsami.1c17554DOI Listing
January 2022

TOR promotes guard cell starch degradation by regulating the activity of β-AMYLASE1 in Arabidopsis.

Plant Cell 2022 03;34(3):1038-1053

The Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao 266237, China.

Starch is the main energy storage carbohydrate in plants and serves as an essential carbon storage molecule for plant metabolism and growth under changing environmental conditions. The TARGET of RAPAMYCIN (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrient, hormone, and stress signaling to regulate growth in all eukaryotes. Here, we demonstrate that TOR promotes guard cell starch degradation and induces stomatal opening in Arabidopsis thaliana. Starvation caused by plants growing under short photoperiod or low light photon irradiance, as well as inactivation of TOR, impaired guard cell starch degradation and stomatal opening. Sugar and TOR induce the accumulation of β-AMYLASE1 (BAM1), which is responsible for starch degradation in guard cells. The plant steroid hormone brassinosteroid and transcription factor BRASSINAZOLE-RESISTANT1 play crucial roles in sugar-promoted expression of BAM1. Furthermore, sugar supply induced BAM1 accumulation, but TOR inactivation led to BAM1 degradation, and the effects of TOR inactivation on BAM1 degradation were abolished by the inhibition of autophagy and proteasome pathways or by phospho-mimicking mutation of BAM1 at serine-31. Such regulation of BAM1 activity by sugar-TOR signaling allows carbon availability to regulate guard cell starch metabolism and stomatal movement, ensuring optimal photosynthesis efficiency of plants.
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http://dx.doi.org/10.1093/plcell/koab307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894947PMC
March 2022

The influence of social pain experience on empathic neural responses: the moderating role of gender.

Exp Brain Res 2022 Jan 2;240(1):53-69. Epub 2021 Dec 2.

Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, South China Normal University, Guangzhou, China.

Empathy for pain, the ability to share and understand the pain of others, plays an important role in the survival and development of individuals. Previous studies have found that social pain experience affects empathy for pain, but potential gender differences have not been considered. The stage of information processing during which gender is most likely to play a moderating role has yet to be clarified. In the current study, we set up two groups (social pain experience priming: social exclusion group; positive social interaction experience priming: social inclusion group) with a Cyberball game paradigm. We recorded the electrophysiological responses when participants were completing an empathy task. An early frontal P2 and N2 differentiation between painful stimuli and neutral stimuli was observed and females showed larger P2 amplitudes than males. At the P3 stage, in the social exclusion group, males showed similar parietal P3 amplitudes for painful and neutral stimuli, while females showed smaller P3 amplitudes for painful stimuli. At the central-parietal late positive potential (LPP) stage, females in the social inclusion group showed larger LPP amplitudes for painful stimuli than males. Our results suggest that gender plays a significant moderating role in how social pain experience affects empathy for pain during the late cognitive processing stage. Experiment 2 was designed to investigate the cognitive mechanism behind the results for the P3 component in females and the results partially confirmed our speculation. This study provides a neurophysiological basis for the dynamic gender differences in the effects of social pain experience on empathy for pain.
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http://dx.doi.org/10.1007/s00221-021-06279-2DOI Listing
January 2022

Comprehensive analysis of prognostic value of lymph node classifications in esophageal squamous cell carcinoma: a large real-world multicenter study.

Ther Adv Med Oncol 2021 5;13:17588359211054895. Epub 2021 Nov 5.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong-An Road, Shanghai 200032, China.

Background: We aim to assess the prognostic ability of three common lymph node-based staging algorithms, namely, the number of positive lymph nodes (pN), the lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in patients with esophageal squamous cell carcinoma (ESCC).

Methods: A total of 3902 ESCC patients treated at 10 Chinese institutions between 2003 and 2013 were included, along with 2465 patients from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic ability of the aforementioned algorithms was evaluated using time-dependent receiver operating characteristic (tdROC) curves, , Harrell's concordance index (C-index), and the likelihood ratio chi-square score. The primary outcomes included cancer-specific survival (CSS), overall survival (OS), and CSS with a competing risk of death by non-ESCC causes.

Results: LODDS had better prognostic performance than pN or LNR in both continuous and stratified patterns. In the multicenter cohort, the multivariate analysis showed that the model based on LODDS classification was superior to the others in predictive accuracy and discriminatory capacity. Two nomograms integrating LODDS classification and other clinicopathological risk factors associated with OS as well as cancer-specific mortality were constructed and validated in the SEER database. Finally, a novel TN classification which incorporates the LODDS classification was built and categorized patients in to three new stages.

Conclusion: Among the three lymph node-based staging algorithms, LODDS demonstrated the highest discriminative capacity and prognostic accuracy for ESCC patients. The nomograms and novel TN classification based on LODDS classification could serve as precise evaluation tools to assist clinicians in estimating the survival time of individual patients and improving clinical outcomes postoperatively in the future.
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http://dx.doi.org/10.1177/17588359211054895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573486PMC
November 2021

Evidence for hexasomic inheritance in Ramat. based on analysis of EST-SSR markers.

Genome 2022 Feb 10;65(2):75-81. Epub 2021 Nov 10.

Beijing Key Laboratory of Ornamental Plants Germplasm Innovation and Molecular Breeding, National Engineering Research Centre for Floriculture, College of Landscape Architecture, Beijing Forestry University, Beijing, China.

Chrysanthemums ( Ramat.) are ornamental flowers, which are famous worldwide. The mode of inheritance has great implications for the genetic analysis of polyploid species. However, genetic analysis of chrysanthemum has been hampered because of its controversial inheritance mode (disomic or hexasomic). To classify the inheritance mode of chrysanthemums, an analysis of three approaches was carried out in an F progeny of 192 offspring using 223 expressed sequence tag-simple sequence repeat (EST-SSR) markers. The analysis included segregation analysis, the ratio of simplex marker alleles linked in coupling to repulsion, as well as the transmission and segregation patterns of EST-SSR marker alleles. After segregation analysis, 204 marker alleles fit hexasomic inheritance and 150 marker alleles fit disomic inheritance, showing that marker alleles were inherited predominantly in a hexasomic manner. Furthermore, the results of the analysis of allele configuration and segregation behavior of five EST-SSR markers also suggested random pairing of chromosomes. Additionally, the ratio of simplex marker alleles linked in coupling to repulsion was 1:0, further supporting hexasomic inheritance. Therefore, it could be inferred that chrysanthemum is a complete or near-complete hexasome.
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http://dx.doi.org/10.1139/gen-2020-0155DOI Listing
February 2022

Transcriptome-wide N6-methyladenosine (mA) methylation in watermelon under CGMMV infection.

BMC Plant Biol 2021 Nov 8;21(1):516. Epub 2021 Nov 8.

Institute of Vegetables, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China.

Background: Cucumber green mottle mosaic virus (CGMMV) causes substantial global losses in cucurbit crops, especially watermelon. N6-methyladenosine (mA) methylation in RNA is one of the most important post-transcriptional modification mechanisms in eukaryotes. It has been shown to have important regulatory functions in some model plants, but there has been no research regarding mA modifications in watermelon.

Results: We measured the global mA level in resistant watermelon after CGMMV infection using a colorimetric method. And the results found that the global mA level significantly decreased in resistant watermelon after CGMMV infection. Specifically, mA libraries were constructed for the resistant watermelon leaves collected 48 h after CGMMV infection and the whole-genome mA-seq were carried out. Numerous mA modified peaks were identified from CGMMV-infected and control (uninfected) samples. The modification distributions and motifs of these mA peaks were highly conserved in watermelon transcripts but the modification was more abundant than in other reported crop plants. In early response to CGMMV infection, 422 differentially methylated genes (DMGs) were identified, most of which were hypomethylated, and probably associated with the increased expression of watermelon mA demethylase gene ClALKBH4B. Gene Ontology (GO) analysis indicated quite a few DMGs were involved in RNA biology and stress responsive pathways. Combined with RNA-seq analysis, there was generally a negative correlation between mA RNA methylation and transcript level in the watermelon transcriptome. Both the mA methylation and transcript levels of 59 modified genes significantly changed in response to CGMMV infection and some were involved in plant immunity.

Conclusions: Our study represents the first comprehensive characterization of mA patterns in the watermelon transcriptome and helps to clarify the roles and regulatory mechanisms of mA modification in watermelon in early responses to CGMMV.
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http://dx.doi.org/10.1186/s12870-021-03289-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574010PMC
November 2021
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